1

TECHNICAL BULLETIN
REACTION SOLVENT
DIMETHYL SULFOXIDE (DMSO)


H
3
C
S
CH
3
O




CAS Name: Methane, sulfinylbis
CAS Registry Number: 67- 68- 5



Dimethyl sulfoxide as manufactured by Gaylord Chemical, is a water-white almost odorless liquid, boiling at
189°C. and melting at above 18.2° C. It is relatively stable and easy to recover, miscible in all proportions with
water and most common organic solvents and has a low order of toxicity.









Gaylord Chemical Company, L.L.C.
P.O. Box 1209
Slidell, LA 70459-1209
(985) 649-5464
2


TABLE OF CONTENTS

Page
INTRODUCTION 5
PART I. PROPERTIES OF DMSO 6
Physical Properties 6
Thermal and Chemical Stability 6
Recovery from Aqueous Solutions 12

PART II. SOLVENCY CHARACTERISTICS OF DMSO 12
Solubility of Salts 13
Solubility of Resins and Polymers 14
Solubility of Miscellaneous Materials 15
Solubility of Gases 16

PART III. REACTIONS OF DMSO 17
1. Oxidation of DMSO 17
2. Reduction of DMSO 17
3. Reaction with Metals 17
4. Reaction with Strong Bases-Dimsyl Ion 17
5. Reaction with Acid Halides 18
6. Reaction with Acid Anhydrides 18
7. Halogenation of DMSO 19
8. Reaction with Phenols and Aniline 19
9. Alcohol Oxidation with DMSO 20
a) Acetic Anhydride 21
b) Trifluoroacetic Anhydride 21
c) Dicyclohexylcarbodiimide 21
d) Phosphorus Pentoxide 22
e) Sulfur Trioxide-Pyridine 22
f) Oxalyl Chloride 23
10. Kornblum Reaction 23
11. Mehoxydimethylsulfonium Salts and 23
Trimethyloxosulfonium Salts

PART IV. DMSO AS A REACTION SOLVENT 24
A. DISPLACEMENT REACTIONS IN DMSO 24
Anions-Nucleophiles (Bases):
1. Acetylide Ion 24
2. Alkoxide Ion 24
3. Amides 26
4. Amines 28
5. Ammonia 30
6. Azide Ion 30
7. Carbanions 32
8. Carboxylate Ion 34
9. Cyanate Ion 35
10.Cyanide Ion 35
11.Halogen Ion 39
12.Hydroxide ion 40
13.Mercaptide (or Thiopenoxide) Ion 42
14.Nitrite Ion 43
15.Phenoxide Ion 44
16.Sulfide (or Hydrosulfide) and Thiosulfate Ions 46
17.Thiocyanate Ion 47
B. BASES AND BASE CATALYZED REACTIONS IN DMSO 48
Bacities in DMSO 48
Proton Removal 48

ELIMINATION REACTIONS 51
1. Cope Elimination 51
2. Decarboxylatoin and Decarbalkoxylation 51
3. Dehalogenation 52
4. Dehydrohalogenation 54
5. Nitrogen Elimination 57



3
Page

6. Sulfenate Elimination 59
7. Sulfonate Elimination 59
8. Water Elimination-dehydration 60

ISOMERIZATION REACTIONS 62
1. Acetylene Isomerization 62
2. Allyl Group Isomerization 63
3. Diene, Triene Isomerization 63
4. Olefin Isomerization 64
5. Racemization 65

C. OTHER REACTIONS IN DMSO
ADDITION REACTIONS 66
a) Additions to acetylenes 66
b) Additions to olefins 67
c) Additions to nitriles 69
d) Additions to isocyanates 69
CONDENSATION REACTIONS 69
a) Aldol-type condensations 69
b) Ester condensations 70
c) Dieckmann condensation-cyclization 71
d) Mannich reaction 72
e) Michael condensation 72
f) Reformatsky reaction 73
g) Thorpe-Ziegler condensation 73
h) Ullmann-type condensations 73
i) Wittig reaction 73
OXIDATION REACTIONS 74
a) Autoxidation 74
b) Chemiluminescence 76
c) Other oxidations involving oxygen 77
d) Dehydrogenation 77
e) Hypohalite oxidations 78
f) Lead tetraacetate oxidations 78
g) Silver compound oxidations 79
h) Superoxide and peroxide oxidations 80
REDUCTION REACTIONS 80
1. Reduction of Alkyl Halides and Sulfonates 81
a) Reductions with sodium borohydride 81
b) Reductions with chromous ion 82
c) Reductions with dimsyl ion 82
d) Reductions with hydrazine 82
e) Reductions by electrolysis 82
2. Reduction of Carbonyl Compounds 82
a) Reductions with borohydrides 82
b) Catalytic reduction 83
c) Electrochemical reduction 83
d) Wolff-Kishner reduction 83
3. Reduction of Nitroaromatics 83
4. Reduction of C=C Systems 84
SOLVOLYTIC REACTIONS 85
1. Hydrolysis 85
a) Aliphatic halide hydrolysis 85
b) Aromatic halide hydrolysis 85
c) Amide hydrolysis 86
d) Epoxide hydrolysis 86
e) Ether hydrolysis 86
f) Nitrile hydrolysis 86
g) Saponification 87
2. Alcoholysis, Aminolysis 87
3. Transesterification (Ester Interchange) 88







4
Page
PART V. USES OF DMSO 88
1. Polymerization and Spinning Solvent 88
Polymerization Solvent for Heat-Resistant Polymers 88
2. Extraction Solvent 89
3. Solvent for Electrolytic Reactions 89
4. Cellulose Solvent 89
5. Pesticide Solvent 90
6. Cleanup Solvent 90
7. Sulfiding Agent 90
8. Integrated Circuits 90
PART VI. TOXICITY, HANDLING, HAZARDS, ANALYSIS 90
1. Toxicity and Handling Precautions 90
2. Comparative Toxicity of Commercial Solvents 91
3. Chemical Reactions to be Avoided with DMSO 91
4. Analytical Procedures 92
a) Gas chromatographic analysis of DMSO 92
b) DMSO freezing point 92
c) Water by Karl Fischer titration 92
PART VII. BIBLIOGRAPHY 93



TABLES AND FIGURES


Page
Table I Physical Properties of DMSO 6
Table II Results of Reflux of DMSO for 24 Hours with Various Compounds 9
Table III Refluxing of DMSO and Mixtures for Shorter Periods 9
Table IV Effect of Heating DMSO with Concentrated Acids 10
Table V Solubility of Salts in DMSO 13
Table VI Solubility of Resins and Polymers in DMSO 14
Table VII Solubility of Miscellaneous Materials in DMSO 15
Table VIII Solubility of Gases in DMSO 16
Table IX Solubility of Various Bases in DMSO 24
Table X Solubility of Sodium Azide in Four Solvents 31
Table XI Acidities in DMSO 50
Table XII Single-Dose Toxicity (Rats) of Some Common Solvents 91
Table XIII Single-Dose Toxicities to Mice of 4M Solvents 91

Figure 1 Vapor Pressure-Temperature DMSO 7
Figure 2a Freezing Point Curve for DMSO-Water Solutions (Wt % water) 8
Figure 2b Freezing Point Curve for DMSO-Water Solution (Wt % water) 8
Figure 3 Viscosity of DMSO 8
Figure 4 Viscosity of DMSO-Water Solutions 8
Figure 5 Thermal Stability of DMSO 11
Figure 6 DMSO Recovery from Aqueous Solutions 12
Figure 7 Solubility of NaCN in DMSO 36
Figure 8 Solubility of NaCl in DMSO-H2O Mixtures 36
Figure 9 Solubility of Hydroxides in Aqueous DMSO 41
Figure 10 Acidity Functions of Bases in DMSO 49


5
INTRODUCTION



Dimethyl sulfoxide or DMSO is a highly polar, high boiling, aprotic, water miscible, hygroscopic organic liquid. It is essentially odorless,
water white and has a low order of toxicity.
Chemically, DMSO is stable above 100° C in alkaline, acidic or neutral conditions. Prolonged refluxing at atmospheric pressure will
cause slow decomposition of DMSO. If this occurs, it can be readily detected by the odor of trace amounts of methyl mercaptan and
bis(methylthio)methane. The rate of decomposition is a timetemperature function that can be accelerated by the addition of acids and
retarded by some bases.
DMSO is a versatile and powerful solvent that will dissolve most aromatic and unsaturated hydrocarbons, organic nitrogen
compounds, organo-sulfur compounds and many inorganic salts. It is miscible with most of the common organic solvents such as
alcohols, esters, ketones, lower ethers, chlorinated solvents and aromatics. However, saturated aliphatic hydrocarbons are vi rtually
insoluble in DMSO.
As a reaction solvent, DMSO is valuable for displacement, elimination, and condensation reactions involving anions. In DMSO, the
rates of these reactions are often increased by several orders of magnitude. In free radical polymerizations, higher average molecular
weights have been reported when DMSO was used as the reaction solvent.
The dominant characteristics of DMSO most important in its usefulness as a reaction solvent are its high polarity, its essentially
aprotic nature, and its solvating ability toward cations. The high dipole moment of the sulfur-oxygen bond (4.3) and the high dielectric
constant (approx. 48) for bulk DMSO suggest the solvating properties and ability to disperse charged solutes. DMSO is not a
hydrogen donor in hydrogen bonding and poorly solvates anions except by dipolar association to polarizable anions. The hydrogen
atoms of DMSO are quite inert, although they are replaceable under sufficiently severe conditions (bulk pKa = 35.1). The oxygen of
DMSO is somewhat basic and participates strongly as a hydrogen bond acceptor. DMSO forms isolatable salts with several strong
acids.
Owing to its chemical and physical properties, DMSO can be efficiently recovered from aqueous solutions. Commercial users of
DMSO employ a variety of processing schemes in their recovery systems. All of these are based on evaporation or fractional
distillation because of simplicity of design and operation. Unlike some other solvents, DMSO can be easily separated from water by
distillation in substantially pure form. For example, DMSO containing less that 500 ppm water can be recovered from a solution
containing 50 weight percent water with only 15 column plates at a reflux ratio of 1:1.
Dimethyl sulfoxide occurs widely in nature at levels of 3 ppm or less. It has been found in spearmint oil, corn, barley, malt, alfalfa,
beets, cabbage, cucumber, oats, onions, swiss chard, tomatoes, raspberries, beer, coffee, milk and tea. DMSO is a common
constituent of natural waters. It has been identified in seawater in the zone of light penetration where it may represent an end product
of algal metabolism. Its occurrence in rainwater may result from oxidation of atmospheric dimethyl sulfide which in turn occurs as part
of the natural transfer of sulfur of biological origin.
No attempt has been made in this bulletin to present a complete literature survey of all the uses of DMSO as a reaction solvent,
solvent, or reactant. A few carefully chosen references have been selected to illustrate the most important areas of DMSO chemistry.
For persons wishing to learn more about DMSO as a reaction solvent, ir any other information in this bulletin, please write or call:











P.O. Box 1209
Slidell, LA 70459-1201
(985) 649-5464
6
PART I. PROPERTIES OF DMSO
TABLE I. Physical Properties of DMSO

Reference
Molecular Weight 78.13
Boiling Point at 760 mm Hg 189 °C (372°F) (342)
Freezing point 18.45°C (65.4°F) (342)
Molal freezing point constant, °C/(mol)(kg) 4.07 (2151)
Refractive index nD25 1.4768 (581)
Surface tension at 20°C 43.53 dynes/cm (2223)
Vapor pressure, at 25°C 0.600 mmHg (372)
Density, g/cm3, at 25°C 1.099 (581)
Viscosity, cP, at 25°C 2.0 (see Figs. 3 & 4) (581)
Specific heat at 29.5°C 0.47+/- 0.015 cal/g/°C (3215)
Heat capacity (liq.), 25°C 0.47 cal/g/°C (2900)
Heat capacity (ideal gas) Cp(T°K)=6.94+5.6x10 ÷2T-0.227x10-4T2 (353)
Heat of fusion 41.3 cal/g (232)
Heat of vaporization at 70°C 11.3 kcal/mol (260 BTU/lb)
Heat of solution in water at 25°C -54 cal/g, @ f dilution (3215)
Heat of combustion 6054 cal/g; (473 kcal/mole) (342)
Flash point (open cup) 95°C (203°F)
Auto ignition temperature in air 300-302°C (572-575°F)
Flammability limits in air
lower (100°C)

3-3.5% by volume

upper 42-63% by volume
Coefficient of expansion 0.00088/°C (342)
Dielectric constant, 10MHz 48.9 (20°C) (342)
45.5 (40°C)
Solubility parameter Dispersion 9.0 (8070)
Polar 8.0
H-bonding 5.0
Dipole moment, D 4.3 (342)
Conductivity, 20°C 3x108(ohm ÷1cm-1) (342)
80°C 7x108(ohm ÷1cm-1)
PKa 35.1 (10411)

Thermal and Chemical Stability of DMSO
As shown in Figure 5, DMSO is highly stable at temperatures below 150° C. For example, holding DMSO at 150° C for 24 hours, one
could expect a loss of between 0.1 and 1.0%. Retention times even in batch stills are usually considerably less than this, and
therefore, losses would be correspondingly less.. It has been reported that only 3.7% of volatile materials are produced during 72
hours at the boiling point (189° C) of DMSO (1). Slightly more decomposition, however, can be expected with the industrial grade
material. Thus, about 5% DMSO decomposes at reflux after 24 hours (3921). Almost half of the weight of the volatile materials is
paraformaldehyde. Dimethyl sulfide, dimethyl disulfide, bis(methylthio)methane and water are other volatile products. A small amount
of dimethyl sulfone can also be found. The following sequence of reactions explains the formation of these decomposition
products (1):









DMSO is remarkably stable in the presence of most neutral or
basic salts and bases (3922). When samples of DMSO (300g) are
H
3
CSOCH
3
H
3
CSH + HCHO (HCHO)
x
2H
3
CSH + HCHO (H
3
CS)
2
CH
2
+ H
2
O
2H
3
CSH + CH
3
SOCH
3
H
3
CSSCH
3
+ H
3
CSCH
3
+ H
2
O
2H
3
CSOCH
3
H
3
CSO
2
CH
3
+ H
2
CSCH
3
H
3
C
S
CH
3
O
7
refluxed for 24 hours with 100g each of sodium hydroxide, sodium carbonate, sodium chloride, sodium cyanide, sodium acetate and
sodium sulfate, little or no decomposition takes place in most cases. The results are shown in Table II below (3922):






FREEZING POINT CURVES FOR DMSO-WATER SOLUTIONS

8



9
TABLE II
Results of Reflux of DMSO for 24 Hours with Various Compounds

Compound (1008)
in 300 g DMSO
Reflux
Temp.,° C.
DMSO Recovered
% of Original
DMS
(a)
% of Decomposition Products, M Md
DMDS
(b)
BMTM
(c)
HCHO
NaOH 185-140e 93.7 63 31
Na2CO3 190 96.3 14
NaCI 190 98.7 15
NaCN 148-164f 100.0
NaOAc 182-187 97.0 22 33 8 20
Na2SO4 181-148g 85.4 66 11
DMSO only 189 98.0 15 30 30


(a) Dimethyl sulfide
(b) Dimethyl disulfide
(c) Bis(methylthio)methane
(d) Methyl mercaptan
(e) Reflux temp. decreased from 185°C to 140°C over the first 16 hours.
(f) Reflux temp. was 148°C for 20 hours; increased to 164° C during the last 4 hours.
(g) Reflux temp. decreased gradually from 181°C to 148° C.
DMSO does not seem to be hydrolyzed by water and very little decomposition of DMSO takes place when it is heated under reflux for
periods of 5 to 16 hours. The following tests, shown in Table III, have been performed: 1)10 parts DMSO + 1 part water, 2) 60 parts DMSO
+ 5 parts water + 1 part sodium hydroxide, 3) 60 parts DMSO + 12 parts water + 1 part sodium bicarbonate, 4) DMSO alone (3922):



TABLE III
Refluxing of DMSO and Mixtures For Shorter Periods
Composition of Sample,
Parts
10 DMSO:1 H2O
Reflux
Time,°C.
152
Time
Hr.
5
DMSO
100
Organic Product Composition, BMTM
0
DMS
0
DMDS
0
15 99.7 0.15 0 0.15
60 DMSO:5 H2O:1 NaOH 155 5 99.8 0.1 0.1 0
8 99.3 0.6 0.1 0
60 DMSO:12 H2O:1 NaHCO3 131 6 99.9 0.1 0 0
12 99.8 0.2 0 0
DMSO only 191 5 99.8 0.1 0.1 0
9 99.1 0.2 0.2 0.5
16 99.0 0.2 0.2 0.6

























DMSO is also stable in the presence of concentrated sulfuric or hydrochloric acid at 100° C for up to 120 minutes of heating at atmospheric
10
pressure. Phosphoric acid causes more rapid decomposition of DMSO than does sulfuric or hydrochloric acid. Detected decomposition
products are dimethyl sulfide, dimethyl disulfide, and, in smaller quantity, formaldehyde. The results are shown in Table IV (3920):


TABLE IV
Effect of Heating DMSO with Concentrated Acids - (200g DMSO with 20g of concn. acid)


Acid Conc. Temp.,
° C.
Time,
Min.
DMSO Left,
%
% of
Decomposition Products
H2SO4 36N 100 15 99 DMS
(a)

100
DMDS
(b)
HCHO
30 99 100
120 98 100
H2SO4 36N 125 - 15 86 7 93
150 86 7 93
210 80 10 90
H3 P04 85% 100 15 92 25 75
30 89 45 55
45 89 45 55
60 87 46 54
120 87 46 54
150 86 50 50 some
H3 P04 85% 125 15 84 25 75
60 82 33 67
150 82 33 67
HCI 12N 95 15 99 100
30 99 100
60 99 100
120 98 100
HCI 12N 115 15 93 100
30 92 100
45 87 100
60 87 100
120 87 100 some
(a) Dimethyl Sulfide
(b) Dimethyl Disulfide
11



12


FIGURE 6


Recovery from Aqueous Solutions

Many chemical processes using DMSO require the addition of water to stop the reaction or to separate the product from the solvent
(DMSO). DMSO can be separated efficiently and cleanly from this water and other impurities by distillation. DMSO distillations are not
complicated by any known azeotropes.
A typical feed to a recovery operation is relatively weak in DMSO - 10 to 20%. There would usually be two vacuum distillation steps in
the recovery:
1) Evaporation of the DMSO-water solution overhead to eliminate less volatile impurities, if any are present, and
2) Fractional distillation of the DMSO-water solution to recover pure DMSO.
Recovery may be done batchwise or continuously, employing moderate conditions. An operating pressure of about
100 mm Hg abs. would allow the use of 85 psig steam and normally available cooling water.

PART II
SOLVENCY CHARACTERISTICS OF DMSO
The solvent characteristics of DMSO derive mainly from its being highly polar and aprotic. Because of its high polarity it forms
association bonds with other polar and polarizable molecules, including itself. Thus, it is miscible with water and almost all types of
organic liquids except the saturated alkanes. It has a high solvency for the large organic molecules containing polar groups. DMSO has
also exhibited an ability to dissolve many inorganic salts, particularly those of the transition metals or those which have nitrates,
cyanides or dichromates as their anions.
The following tables of solubilities are offered as a guide and an easy reference.

13
Solubility of salts ----------- -----------------------------------------------------------------------------------------Table V
Solubility of resins and polymers -------------------------------------------------------------------------------- Table V I
Solubility of miscellaneous materials --------------------------------------------------------------------------- Table VII
Solubility of gases -------------------------------------------------------------------------------------------------- Table VIII

The difficulty of predicting solubility characteristics suggests that each specific compound be checked for its solubility in DMSO rather
then generalizing from reported solubilities. Because of the variability of resins and polymers from one manufacturer to another,
tradenames and companies have been used to identify accurately the materials in Table VI.
The study of co-solvent possibilities utilizing DMSO has not been included as the complexity and diversity of this field are too broad to
give adequate coverage. It will be noted however from Table VII that DMSO is compatible with most of the common solvents. This
compatibility and the strong solvency properties of DMSO indicate numerous possibilities for co-solvent systems to perform given tasks
efficiently and economically.




TABLE V
Solubility of Salts in DMSO (794)

Solubility Grams/100 cc DMSO Solubility Grams/100 cc DMSO
25°C. 90-100°C. 25°C. 90-100°C
Aluminum sulfate (18H2O) Insol. 5 Lithium dichromate (2 H2O) 10 -
Ammonium borate (3H2O) 10 - Lithium nitrate 10
Ammonium carbonate (H2O) 1 - Magnesium chloride (6 H2O) 1 -
Ammonium chloride Insol. 10 Magnesium nitrate (6 H2O) 40 -
Ammonium chromate 1 - Manganous chloride (4 H2O) 20 -
Ammonium dichromate 50 - Mercuric acetate 100 -
Ammonium nitrate 80 - Mercuric bromide 90 -
Ammonium thiocyanate 30 - Mercuric iodide 100 -
Barium nitrate 1 - Molybdenum bromide 1 Reacts
Beryllium nitrate (4 H2O) 10 - Nickel chloride (6 H2O) 60 -
Bismuth trichloride 1 - Nickel nitrate (6 H2O) 60 -
Cadmium chloride 20 - Potassium iodide 20 20
Cadmium iodide 30 - Potassium nitrate 10 -
Calcium chloride Insol. 1 Potassium nitrite 2 -
Calcium dichromate (3 H2O) 50 - Potassium thiocyanate 20 50
Calcium nitrate (4 H2O) 2 30 - Silver nitrate 130 180
Ceric ammonium nitrate 1 - Sodium dichromate (2 H2O) 10 -
Cobaltous chloride (6 H2O) 30 Misc. m.p. 86°C. Sodium iodide 30 -
Cupric acetate (H2O) Insol. 6 Sodium nitrate 20 -
Cupric bromide 1 20 150°C. Sodium nitrite 20 -
Cupric chloride (2 H2O) Insol. 27 Sodium thiocyanate 1 -
Cuprous iodide 1 - Stannous chloride (2 H2O) 40 -
Ferric ammonium sulfate (12 H2O) Insol. Misc. m.p. 40° C. Strontium bromide (6 H2O) 5 -
Ferric chloride (6 H2O) 30 90 Strontium chloride (2 H2O) 10 -
Ferrous chloride (4 H2O) 30 90 Tungsten hexachloride 5 -
Gold chloride 5 - Uranyl nitrate (6 H2O) 30
Lead chloride 10 - Vanadium chloride - 1
Lead nitrate 20 60 Zinc chloride 30 60
Zinc nitrate (6 H2O) 55 -

14
TABLE VI
Solubility of Resins and Polymers in DMSO

Grams Soluble in 100 cc DMSO
Material 20-30°C 90-100°C Comments
Polyacrylics
Orlon (du Pont) - 20 Viscous soln.
Acrilan (Monsanto) >25 -
Verel (Eastman) >5 25 at 130°C with some
decompostion
Creslan (Am. Cyanamid) 5 25 at 130°C
Zefran (DOW) - Insol.
Polyamides
Nylon 6 - Insol. 40 at 150°C
Nylon 6/6 - Insol. 25 at 150°C
Nylon 6/10 - Insol. 40 at 150°C
Cellulose
Cellulose triacetate 10 20
Viscose rayon - <1
Cellophane - Insol.
Carboxymethyl cellulose - Insol.
Epoxies
Epon 1001 (Shell) 50 -
Epon 1004 (Shell) 50 -
Epon 1007 (Shell) 50 -
Methacrylates
Lucite 41, 45 (du Pont) - <1
Plexiglass (Rohm & Haas) - <1
Polycarbonates
Lexan (General Electric) - >5
Merlon (Mobay) - Insol.
Polyesters
Dacron (du Pont) - >1 Dissolves at 160°C ppts.
130°C CX 1037 (Goodyear) - 7
Atlac (ICI-America) - 50
Silicones
Dow Corning 803 soln. Miscible -
Dow Corning 805 soln. Miscible -
Dow Corning "Sylkyd 50¨ Miscible -
Dow Corning Z6018 (flake) 70 -
Urethanes
Vithan (Goodyear) - 100
Vinyls ± Polymers & Co-polymers
Butvar B-76 (Monsanto) - 20 Very viscous
Formvar 7/70 E (Montsanto) - 42 Very viscous
Elvanol 51-05 (du Pont) - 90 Viscous
Elvanol 52-22 (du Pont) - 15 Viscous
Elvanol 71-24 (du Pont) - 30 Viscous
Polyvinyl pyrrolidone (GAF) 30 >100
Geon 101 (PVC Goodrich) - 10
Vinylite VYHH (Union Carbide) 2 30
Teslar (du Pont) - - Partially sol. at 160-170°C

15
Vinylidenes
Darvan (Goodrich) 5 - Soln. Cloudy and viscous
Saran film (Dow) - 30
Geon 200 x 20 (Goodrich) - 20
DNA (Goodrich) >5 - 25 at 130°C
Other Resinous Materials
Melmac 405 (Am. Cyanamid) 70 -
Neoprene Insol. Insol.
Polyethylene Insol. Insol.
Polystyrene - - Sol. At 150°C ppts at 130°C
Rosin (Hercules) >100 -
Penton (chlorinated polyether)
(Hercules) - 5
Teflon (du Pont) Insol. Insol.
Vinsol (Hercules) 50 >100



TABLE VII
Solubility of Miscellaneous Materials in DMSO

Solubility
Grams/100 cc DMSO
Solubility
Grams/100 cc DMSO
Material 20-30°C 90-100°C Material 20-30°C 90-100°C
Acetic acid Miscible - Glycerine Miscible -
Acetone Miscible - Glycine <0.05 0.1
Acrawax <1 >1 Hexane 2.9 -
Acrawax B Insol. 4 Hy-wax 120 - <1
Aniline Miscible - Iodine Soluble -
Beeswax - <1 Isoprene Miscible -
Benzene Miscible - Kerosene 0.05 (0.5% DMSO soluble in 11 (gets cold)
Benzidine Soluble - Lanolin, hydrated (Lanette O)
Benzidine methane sulfonate Insol. - Lauryl amide (Amid 12) 10 >20
Bromine Reacts - Lorol 5 Miscible -
Lubricating oil 0.4 -
Butenes 2.1 - Methionine 0.1 0.3
Clacium methyl sulfonate Soluble - Methyl borate Miscible -
Camphor Soluble Soluble Methyl caprate - Miscible
Candelilla wax - <1 Methyl iodide Miscible Reacts
Carbon Insol. - Methyl laurate 7 Miscible
Carbon disulfide 90 - Methyl mercaptan 40 -
Carbon tetrachloride Miscible - N-methyl morpholine Miscible -
Carbowax 600 Miscible - Methyl palmitate Immiscible Misc. 130-180°
Carbowax 6000 Insol. 8 Methyl salicylate Miscible -
Carnauba wax - <1 Methyl sulfonic acid Miscible -
Castor oil Miscible - Methylene chloride Miscible -
Ceresin wax - <1 Microcrystalline wax - <1
Chlorine Reacts - Morpholine Miscible Miscible-
Chloroform Miscible - Naphthalene 40 Insol.
Chlorosulfonic acid Reacts - Neoprene Insol. -
Citric acid >70 - Nitrobenzene Miscible -
Coconut oil 0.3 1.3 Oleic acid Miscible -
Misc.-160°C Ouricuri wax - 1
Cork Softens Softens Oxalic acid 38 -
Cresylic acid Miscible - Paint (dried) Softens & dissolves
Cumene Miscible - Palmitic acid 100
Cyclohexane 4.67 - Paraffin Insoluble -
Cyclohexylamine Miscible - Paraformaldehyde Insoluble Slightly soluble
Decalin 4.5 - Pentaerythritol 5-10 30
n-Decane 0.7 - n-Pentane 0.35 -
Di-n-butylamine 11 - Pentene 1 & 2 7.1 -
o-Dichlorobenzene Miscible - Perchloric acid Reacts violently -
p-Dichlorobenzene Very Soluble - Petroleum ether 3 (DMSO soluble 0.3-0.5% in petroleum
ether) Dicholorodiphenyltrichloroethane 4 100
Dicyandiamide 40 - Phenol Soluble -
Dicyclohexylamine 4.5 - Phosphoric acid Miscible -
Diethylamine Miscible - Phosphorus trichloride Reacts vigorously -
Diethyl ether Miscible - Phthalic acid 90 -
bis-(2-ethylhexyl)amine Miscible - Isophthalic acid 68 76
Diethyl sulfide 0.7 - Terephthalic acid 26 33
Di-isobutyl carbinol Miscible Picric acid Soluble -

16
Di-isobutylene 3.3 (0.6% DMSO soluble in
di-isobutylene)
Pyridine Miscible -
- Pyrogallol 50 -
Dimethyl ether 4.4 - Rosin >100 -
Dimethyl formamide Miscible - Rosin soap Slightly soluble 0.9
Dimethyl sulfide Miscible - (Hercules Dresinate X)
Dimethyl sulfone 33.9 Miscible Sevin 50 -
Dioxane Miscible - Shellac, white, dried - 80
Diphenyl Very Soluble - Silicon tetrachloride Reacts vigorously
Dipentene 10 - Sodium - Reacts
n-Dodecane 0.38 - Sorbitan sesquioleate 2.5 -
Dodecylbenzene (Neolene 400) 3.5 - Sorbitan trioleate - Miscible
Dyes - Sorbitol 60 >180
Burnt Sugar Soluble - Soybean oil 0.6 -
FD&C Blue Soluble - Starch, soluble >2 -
Pistachio Green B Soluble - Stearic acid 2 Miscible
Ethyl benzoate Miscible - Succinic acid 30 -
Ethyl alcohol Miscible - Sugar (sucrose) 30 100
Ethyl bromide Miscible Reacts Sulfamic acid 40 -
Ethyl ether Miscible - Sulfur - <1
Ethylene dichloride Miscible - Sulfuric acid Miscible -
Formalin (37%) Miscible - Tallow Insol. 1.9
Formamide Miscible - Tallow amide, hydrogenated Insol. >40
Formic Acid Miscible - (Armour Armide HT)
Tetrahydrophthalic anhydride 50 -
Thiourea 40 85
Toluene Miscible -
Toluene di-isocyanate Miscible -
Tributylamine 0.9 -
Tricresyl phosphate Miscible -
Triethanolamine laurylsulfate Soluble -
Triethanolamine Miscible -
Triethylamine 10 -
Trinitrotoluene Soluble -
Turpentine 10 -
Urea 40 110
Water Miscible -
Xylene Miscible -


TABLE VIII
Solubility of Gases in DMSO at Atmospheric Pressure and 20°C
(from pure gases in each case)

Grams Gas per
100 Grams Solution

Gas Volume per
Volume of DMSO
Acetylene 2.99 28.1
Ammonia 2.6 40.0
Butadiene 4.35 -
Mixed butylenes 2.05 -
Carbon dioxide 0.5 3.0
Carbon monoxide 0.01
Ethylene 0.32 2.8
Ethylene oxide 60.0 306.0
Freon 12 1.8 3.7
Helium Insol.
Hydrogen 0.00
Hydrogen sulfide 0.5 (reacts)
Isobutylene 2.5-3.0 -
Methane 0.00
Nitric oxide (NO) 0.00
Nitrogen 0.00 -
Nitrogen dioxide (NO2, N2O4) Miscible (possible reaction) 0.06
Oxygen 0.01
Ozone Reacts
Sulfur dioxide 57.4 (reacts)




17

PART III
REACTIONS OF DMSO
1. Oxidation of DMSO
DMSO reacts with strong oxidizing agents to give dimethyl sulfone, CH3SO2CH . Ozone gives a good yield of the sulfone (825)(8923).
Both dichromate oxidation (321) and permanganate oxidation (9222) have been used for quantitative determination of DMSO (1612).
Aqueous chlorine under acidic conditions gives dimethyl sulfone and
methanesulfonyl chloride (1273)(8548), but under alkaline conditions the oxidation is accompanied by chlorination to give an 80% yield
of hexachlorodimethyl sulfone (905):
CH
3
SOCH
3
+ NaOCl CCl
3
SO
2
CCl
3

Sodium hypobromite similarly gives a 75% yield of hexabromodimethyl sulfone (229). DMSO reacts with hydrogen peroxide (10224),
organic peroxides (1515), or hydroperoxides (8105), particularly in the presence of catalysts (4136), to give the sulfone. It has been
reported that the persulfate ion can remove an electron from the sulfur of DMSO to give a radical cation, which is a suitable
polymerization catalyst for acrylonitrile (1271). DMSO is also oxidized by peroxydiphosphate (9563) and chloramine-T (9678).

2. Reduction of DMSO
DMSO is reduced to dimethyl sulfide, CH SCH , by a number of strong reducing agents, including aluminum hydrides (1024)(1022)
and boranes (1138)(3429)(3816)(8885). Mercaptans reduce acidified DMSO and are oxidized to the disulfides
(428)(1373)(2532)(2779)(8054)(8095)(8405)(9949):
2RSH + CH
3
SOCH
3
RSSR + CH
3
SCH
3
+ H
2
O
acid

3. Reaction with Metals
The reaction of DMSO with sodium and potassium metals does not lead to simple removal of a hydrogen, but occurs by cleaving the
carbon-sulfur bond (206):
CH
3
SOCH
3
+ 2M
CH
3
SO
-
M
+
+ CH
3
-
M
+
CH
3
SOCH
3
+ CH
3
-
M
+
CH
3
SOCH
2
-
M
+
+ CH
4

The electrolytic reduction of sodium chloride or sodium iodide in DMSO similarly leads to a mixture of hydrogen and methane gases at the
cathode (1508).

4. Reaction with Strong Bases - Dimsyl Ion
Methylsulfinyl carbanion, dimsyl ion, H2CSOCH3.
The activating influence of the sulfinyl group on Į-hydrogens is considerably less than that of a carbonyl group but
still sufficient to give a pKa of 35.1 for DMSO (10411). Consequently, strong bases such as sodium hydride or sodium amide react with
DMSO to produce solutions of sodium methylsulfinyl carbanion (dimsyl ion) which have proved to be synthetically useful (634):
CH
3
SOCH
3
+ NaH NaCH
2
SOCH
3
+ H
2
+ -

As the base, the dimsyl sodium solution can be employed to remove protons from carbohydrates, amines, amides, acetylenes, weakly
acidic hydrocarbons and many other compounds. The dimsyl ion has also been used to prepare salts of carbonyl compounds, and for
eliminations producing olefins, aromatics and cyclopropane derivatives. There are numerous applications of the dimsyl ion in the
isomerization of alkynes and formation of phosphorus ylides in preparing Wittig reagents.
The dimsyl ion solutions provide a strongly basic reagent for generating other carbanions. The dimsyl ion shows the expected
nucleophilicity of carbanions and serves as a source of methylsulfinylmethyl groups (634).
Thus, with alkyl halides or sulfonate esters, sulfoxides are obtained; carbonyl compounds yield ȕ-hydroxysulfoxides and esters give ȕ-
ketosulfoxides (624):
n-C
4
H
9
Br + :CH
2
SOCH
3
-
n-C
4
H
9
CH
2
SOCH
3
(C
6
H
5
)
2
CO + :CH
2
SOCH
3
-
(C
6
H
5
)
2
C(OH)CH
2
SOCH
3
C
6
H
5
COOEt + :CH
2
SOCH
3
C
6
H
5
C(O)CH
2
SOCH
3
-

Zinc and sulfuric acid have been used to reduce DMSO (86). Quantitative procedures for determining DMSO have been based on its
reduction using stannous chloride and hydrochloric acid (982), or titanium trichloride in dilute hydrochloric acid (272). DMSO is
reduced only very slowly with hypophosphorus acid unless catalyzed by dialkyl selenides (1005). Hydroiodic acid reduces DMSO
(7073), and the kinetics of the reaction have been examined (84)(85)(1687)(1544). Hydrogen bromide, on the other hand, reduces
DMSO only at temperatures about 80° C (1579). DMSO has also been reduced with iodine-sulfur dioxide or bromine-sulfur dioxide
complexes (9464), cyclic phosphoranes derived from catechol (9944), silanes (10085)(10127), thiophosphoryl bromide (10139) and
other reagents. Quantitative or almost quantitative yields of dimethyl sulfide are claimed in some of these reductions.
The dimsyl ion also adds to carbon-carbon double bonds, and if the mixture is heated for several hours, the initial adduct eliminates
methanesulfenic acid. The overall result is methylation and with compounds such as quinoline or isoquinoline, yields are nearly
quantitative (202):

18
N
H
2
CSOCH
3
N
H CH
2
SOCH
3
N
CH
3
isoquinoline

Care is required in running these reactions because the decomposition of the intermediate sulfoxide anion (and also dimsyl sodium)
during the heating in the strongly alkaline system is exothermic and also produces a precipitate which can interfere with heat removal.
Explosions have been observed which were not detonations but were due to a pressure build-up by an uncontrolled exotherm (8).

5. Reaction with Acid Halides
DMSO has long been known to react with chlorine or acid chlorides, such as sulfur monochloride, S2Cl2, to give chloromethyl methyl
sulfide, whereas with sulfuryl chloride, SO2Cl2, only 13% of the chloromethyl methyl sulfide is obtained (720). Aromatic sulfonyl chlorides
(463), thionyl chloride (595), and organic acid chlorides also give chloromethyl methyl sulfide (467)(8601). With thionyl chloride, it has
been suggested that the reaction, in a simplified form, can be represented as follows:
CH
3
SOCH
3
+ SOCl
2
CH
3
SCH
2
Cl + SO
2
+ HCl









The reaction in many cases proceeds by way of initial attack of the chlorinating agent upon the oxygen of DMSO, followed by removal of
a proton to give an ylide which is finally attacked by chlorine (459):
CH
3
SOCH
3
+ Z-M-X
[(CH
3
)
2
SOMZ]
+
X
-
X
-
(e.g. Cl
-
)
-
OMZ + CH
3
SCH
2
X [CH
2
SOCH
2
:]
M-Z +HX
M= an atom (such as S) to which the halogen atom X is attached
Z=the remaining portion of the molecule


The kinetics of the reaction between DMSO and acetyl chloride has been studied using NMR spectroscopy. The decay of DMSO and
acetyl chloride follows mainly 2nd order kinetics. The growth of the main products, acetic acid and chloromethyl methyl sulfi de is mainly
second order. The overall reaction is complicated by several side reactions, which generate acetoxymethyl methyl sulfide, acetic
anhydride and chlorodimethylsulfonium chloride (9773):




This displacement of a reactive chloride by the DMSO oxygen has been used to introduce hydroxyl groups into compounds that are
sensitive toward water (459)(294)(1016)(1383)(3152). Thus, DMSO reacts with cyanuric chloride to give cyanuric acid and with benzoyl
chloride to give benzoic acid, (1383):




The ability of suIfoxides to react with acid chlorides can be used for the quantitative determination of DMSO. When DMSO is reacted with
acetyl chloride in the presence of iodide the following reaction, involving formation of the acyloxysulfonium salt, can be represented as
follows:





The iodine is then titrated with sodium thiosulfate (1805).
The reaction of DMSO with reactive acid chlorides is vigorous and exothermic and should be conducted with care (669)(8601)(10470).

6. Reaction with Acid Anhydrides
Carboxylic acid anhydrides react with DMSO in a manner similar to that of acid halides. With acetic anhydride, the final product is
acetoxymethyl methyl sulfide, CH3CO2CH2SCH3 (290)(291). Several mechanisms of the reaction, the Pummerer rearrangement, have
been proposed. There seems to be little doubt that the first step in the reaction of DMSO with acetic anhydride is the formation of the
acetoxysulfonium salt (2643)(2896). Various possible pathways of the rearrangement from the sulfonium salt have been proposed, but
CH
3
SOCH
3 CH
3
SCH
2
Cl + CH
3
CO
2
H + (CH
3
CO)
2
O +CIS(CH
3
)
2
+Cl
-
OCH
3
CCl
N
3
C
3
Cl + 3CH
3
SOCH
3
N
3
C
3
O
3
H
3
+ 3CH
3
SCH
2
Cl
PhCOCl + CH
3
SOCH
3
PhCO
2
H + CH
3
SCH
2
Cl
CH
3
SOCH
3
+ CH
3
COCl [(CH
3
)
2
SOCOCH
3
]+ + Cl-
[(CH
3
)
2
SOCOCH
3
]
+
+ 2l
-
CH
3
SCH
3
+ l
2
+ CH
3
CO
2
-

19
the one going through the ylide seems likely (2643)(4820). The Pummerer rearrangement can then be represented by the following
reactions













DMSO also reacts with trifluoroacetic anhydride to give the acetoxysulfonium salt. When this intermediate is reacted with aromatic
amines, amides or sulfonamides the corresponding iminosulfuranes are obtained (7044). When aliphatic carboxylic acids are treated
with DMSO activated by tert-butylbromide in the presence of NaHCO3 the corresponding methylthiomethyl esters are obtained in a
Pummerer like reaction (10032). A Pummerer type rearrangement is also suggested in the reaction of diphenylphosphinic anhydride-
DMSO reaction (4128):
[Ph
2
PO]
2
O + CH
3
SOCH
3 P
O
OCH
2
SCH
3
Ph
Ph
+ Ph
2
PO
2
H




Inorganic anhydrides also attack the DMSO oxygen. The sulfur trioxide-DMSO complex reacts easily with cellulose to give cellulose
sulfate esters with a high degree of substitution (1474).
Reactions of DMSO wlth some acid anhydrides, both organic and lnorganic, can be vigorous and should be conducted with care. Thus,
acetic anhydride and benzoic anhydride react with DMSO even at room temperature (290), although higher temperatures, e.g. 85-90° C,
are needed for faster reactions (7613).

Complex formation between DMSO and sulfur trioxide is an exothermic reaction. To avoid overheating with consequent darkening and
violent boiling of the mixture, sulfur trioxide should be added slowly to a cool well stirred and cooled DMSO (1474).
DMSO cannot be dried with phosphorus pentoxide because this may lead to an explosive mixture (354).

7. Halogenation of DMSO
DMSO can be halogenated with chlorine or bromine in the presence of a base. Thus, stirring a solution of DMSO, pyridine, and
bromine in chloroform results in the formation of bromomethyl methyl sulfoxide (3148):
CH
3
SOCH
3
Br
2
, pyridine, CCl
4
0
o
C
3 hr.
CH
3
SOCH
2
Br
48%

Similarly, bubbling chlorine into a DMSO, pyridine and methylene chloride solution at 0° C for over 30 minutes produces chloromethyl
methyl sulfoxide in a 77% yield (6268).
Chlorination of DMSO in the presence of triethylamine yields chloromethyl methyl sulfoxide. Further chlorination in the presence of
pyridine yields methyl trichloromethyl sulfoxide (4802):
CH
3
SOCH
3
Cl
2
, Et
3
N, CCl
4
-5 to 5
o
C
3 hrs.
CH
3
SOCH
2
Cl
60%
Cl
2
, pyridine, CHCl
3
below 5
o
C
CH
3
SOCCl
3
30%

Bromination of DMSO with elemental bromine leads to the formation of trimethylsulfonium bromide. Methanesulfonic acid,
paraformaldehyde, dimethyl disulfide, and hydrogen bromide are formed as by-products (4802):
CH
3
SOCH
3
Br
2
20-50
o
C
(CH
3
)
3
S
+
Br
-
75%


A small amount of hydrogen halides or halogens, especially bromine or hydrogen bromide, catalyze the decomposition of DMSO in the
absence of a base. This catalytic decomposition takes place sluggishly. The reaction of bromine proceeds via the initial Į-bromination to
afford Į-bromethyl methyl sulfoxide which is oxidized (Kornblum reaction) to afford the products listed above [(4802)]. These consecutive
reactions form an oxidation-reduction cycle between Br2-HBr and DMSO-dimethyl sulfide (8400).

8. Reaction with Phenols and Aniline
CH
3
SOCH
3
+ (CH
3
CO)
2
O
H
3
C
S
CH
3
O
O
CH
3
O
O
CH
3
H
3
C
S
CH
2
O
O
CH
3
+CH
3
CO
2
H
H
3
CSH
2
CO CH
3
O
O
O
CH
3
H
3
CS CH
2

20

a) Acid chloride or hydrogen chloride catalysis.
When a solution of phenol in DMSO is treated with an acid chloride, such as thionyl chloride, or saturated with hydrogen chloride, the
initially formed adduct of DMSO reacts by electrophilic attack on the phenol to form the sulfonium salt. The sulfonium salt can be
decomposed by heating to give hydroxyaryl methylthioethers (2075)(302)(296):













Up to 60% yields are obtained, depending on the structure of the phenol. p-Hydroxyaryl methylthioethers are also obtained when phenols
are suspended in 70% perchloric acid and DMSO is added, followed by heating of sulfonium salts in hot, saturated potassium chloride
solution (1268):

OH
R
+ CH
3
SOCH
3
HClO
4
15-20
o
C
2-3 hours
OH
R
S(CH
3
)
2
+
ClO
4
H
2
O, KCl-
-
reflux
4-5 hrs.
OH
R
SCH
3
65-68%

Similarly, hydroxyaryl thioethers can be prepared by reacting phenols with DMSO in sulfuric acid, and heating the crude reaction mixture
with aqueous sodium chloride (6335) (6674)(6613).
N,N-dimethylaniline can be reacted with DMSO using phosphoryl chloride catalysis. However, the yield of the aryl thioether is lower in
this case (348). Other aromatic amines and hydrazine derivatives also react with DMSO and dicyclohexylcarbodiimide (4651).

b) Dicyclohexylcarbodiimide or acid anhydride catalysis
The reaction of phenols with DMSO and dicyclohexylcarbodiimide in the presence of phosphoric acid or pyridinium trifluoroacetate
affords a mixture of the products consisting mainly of 2-methylthiomethyl phenol and 2,6-bis(methylthiomethyl)phenol
(540)(1234)(4898)(4891). It has been suggested that the mechanism proceeds according to the following steps (540)(1234)(4898):
CH
2
SOCH
3
+ H+ + C
6
H
11
-N=C=N-C
6
H
11
C
6
H
11
-N-C=N-C
6
H
5
H
O
S(CH
3
)
2
phenol
O
S
CH
2
CH
3
(CH
3
)
2
SO
-
base
+
C
6
H
11
N
C
C
6
H
11
N
H H
O
O
H
Ch
2
SCH
3
OH
H
3
CSCh
2
2-thiomethoxymethyl phenol
+
+

A similar reaction takes place when acetic anhydride (849)(1055) or the pyridine-sulfur trioxide complex (4636) is used to polarize
the DMSO molecule instead of dicyclohexylcarbodiimide.
Finally, it has been found that phenols can be methylthiomethylated by boiling with excess DMSO. A mixture of isomeric
methylthiomethylation products are obtained, but o-methylthiomethylation is preferred (4636)(4772).

9. Alcohol Oxidation with DMSO
A breakthrough in the preparation of carbonyl compounds from alcohols has been achieved with the development of reagents based on
CH
3
SOCH
3
+ HCl
CH
3
SCH
3
OH
Cl
+ Phenol
OH S(CH
3
)
2
R
+
+
Cl-
heat
OH SCH
3
+ CH
3
Cl
4-(methylthio)phenol

21
DMSO (8551)(1503)(4820)(16359).
Several procedures have been developed which permit the selective oxidation of structurally diverse primary are secondary alcohols to
the corresponding carbonyl compounds, i.e. aldehydes and ketones, respectively. Most of these reactions take place at room
temperature or above. Nucleophilic attack occurs on the DMSO sulfur atom. Most reactions in which the nucleophilic attack takes place
on sulfur are aided by prior electrophilic attack on the oxygen atom (10720):
CH
3
SCH
3
+ E
O
+
O E
+
CH
3
SCH
3


The electrophilic reagents which activate DMSO include acetic anhydride, trifluoroacetic anhydride, and other acid anhydrides, the sulfur
trioxide-pyridine complex, thionyl chloride, oxalyl chloride, acetyl chloride, and other, acid chlorides, bromine, chlorine, t-butyl
hypochlorite, dicyclohexylcarbodiimide, and others.
The labile intermediate, the DMSO-electrophile complex, can now be attacked by a nucleophile, such as an alcohol, to perform a
displacement on sulfur with oxygen as the departing group:
H
3
C
S
CH
3
O
E
H
3
C
S
CH
3
Nu
+ Nu
+ OE
-




Several of the above-mentioned activating agents and their use in the oxidation of alcohols are described below.

a) Acetic anhydride
In this procedure an alcohol is treated with a mixture of acetic anhydride and DMSO at room temperature (1127) (9926). DMSO first
reacts with acetic anhydride to form the acyloxysulfonium salt which in turn reacts with the alcohol to give the alkoxydimethylsulfonium
intermediate which decomposes to the carbonyl compound and dimethyl sulfide (DMS)(1127):
CH
3
SCH
3
+ (CH
3
CO)
2
O
[(CH
3
)
2
S-O-COCH
3
]
+
CH
3
COO
-
acyloxysulfonium salt
CH
3
SCH
3
+ RR'C=O
[(CH
3
)
2
S-O-CHRR']
+
+CH
3
COO
-


A number of side reactions take place when using the acetic anhydride-DMSO procedure. The usual side products are acetates and
methylthiomethyl ethers, RR'CHOCH2SCH3. The advantage of the acetic anhydride-DMSO method is the fact that highly hindered
alcohols, which would be inert to other DMSO-activator systems, are oxidized (4820).

b) Trifluoroacetic anhydride
Trifluoroacetic anhydride and DMSO react exothermally at -60° C. in methylene chloride to produce a white precipitate, presumably an
ion pair, trifluoroacetoxydimethylsulfonium trifluoroacetate.
[(CH
3
)
2
S-O-COCF
3
]
-
OCOCF
3
+

This reacts rapidly with alcohols, even sterically hindered ones (e.g. 2-adamantol and neopentyl-type alcohols) to give the
corresponding carbonyls (7943)(8455). Trifluoroacetic anhydride is an excellent activator for DMSO because of short reaction times and
high yields of carbonyl compounds with minimal by-product formation. The major drawback is the need to work at very low temperatures
(-30 to -60° C) (10720).

c) Dicyclohexylcarbodiimide
This method of oxidation is generally referred to as the "Pfitzner-Moffatt" technique, after its originators (1503). The reaction involves
addition of an alcohol substrate to a solution of dicyclohexylcarbodiimide (DCC) in DMSO with an acid, such as phosphoric aci d or
pyridinium trifluoroacetate (172), present as a proton source. This results in reaction conditions near neutrality at room temperature. The
oxidation technique is applicable to primary or secondary alcohol groups in an almost unlimited variety of compounds, includi ng
alkaloids, steroids (173), and carbohydrates (4349). Steric effects are not important except in highly hindered systems (1503). In the
reaction, the DMSO molecule is first converted to a labile intermediate which is susceptible to attack at the sulfur by an alcohol group to
produce an alkoxysulfonium salt which undergoes base-catalyzed decomposition to the carbonyl compound (3049):

22
C
6
H
11
-N=C=N-C
6
H
11
+ H+OS(CH
3
)
2
C
6
H
11
HN C N C
6
H
11
O
CH
3
SCH
3
HOHCRR'
(CH
3
)
2
S-O-CRR'
H
+
-H
+
:CH
2
alkoxysulfonium salt
(CH
3
)
2
S-O-CRR'
H
+
N
H
N
H
O
C
6
H
11
C
6
H
11
O
R'
R
SH
CH
3
H
R R'
O
+ CH
3
SCH
3



Protecting groups such as isopropylidene, benzylidene, acetate, benzoate, and sulfonate esters and ethers are stable in the conditions
used for oxidation (3602)(175).

d) Phosphorus pentoxide
It has been found that DMSO containing phosphorus pentoxide rapidly oxidizes the alcoholic groups of carbohydrates and other
compounds at room or elevated temperatures to the corresponding aldehydes or ketones (208). In general, oxidations proceed most
efficiently in the presence of 3-4 molar equivalents of DMSO and 1.2-2.0 molar equivalents of phosphorus pentoxide (2327). The
carbohydrate oxidation with DMSO-P4O10 should be run at about 60-65°C. This system catalyzes carbohydrate polymerization at
temperatures below 35° C (5296) (6079). DMSO, DMF and pyridine seem to be the best solvents for this reaction (3602)(2327)(6691).

e) Sulfur trioxide-pyridine
The combination of DMSO with S03-pyridine complex in the presence of triethylamine yields a reagent that rapidly oxidizes primary and
secondary alcohols in good yield at room temperature to aldehydes and ketones, respectively (9926)(10720). An attractive feature of this
reagent is its property of effecting oxidation of allylic alcohols to the corresponding Į , ȕ-unsaturated carbonyl compounds (1752).
The S03-pyridine complex in DMSO can be used to oxidize acid-labile trans-diols (4037) or cis-diols (8033) to quinones. This reagent has
also been used to oxidize alkaloid hydroxyl groups to ketone groups (2749)(8017). Application of the DMSO-S03-pyridine reagent to
partially acetylated carbohydrates leads to oxidation as well as elimination of the elements of acetic acid, thus providing a high yield to
novel unsaturated carbohydrates (2652):



























O
O
O
OR
1
OR
2
R
3
OH
2
C
OAc
OR
OAc
O
O
CH
2
OAc
R
3
= H
SO
3
, DMSO R
1
=H
R
2
=H
O
OR
1
OR
2
OAc
OAc
R
3
OH
2
C
OHC

23
f) Oxalyl chloride
Oxalyl chloride is an efficient and useful activator, superior to trifluoroacetic anhydride, for the conversion of alcohols to their
alkoxysulfonium salts which, upon basification, result in generally higher and frequently quantitative yields of the corresponding carbonyl
compounds (9786)(9926). The unstable intermediate formed at low temperatures (usually-60° C) instantaneously loses carbon dioxide
and carbon monoxide. The new intermediate is the same as that proposed for the dimethyl sulfide-chlorine reagent. This product has been
reacted with a wide variety of alcohols to convert them to the carbonyl compounds (10084):
CH
3
SOCH
3
+ (COCl)
2
CH
2
Cl
2
-60
o
[(CH
3
)
2
S O C C Cl]
O O
Cl
-CO
2
, -CO
[(CH
3
)
2
S-Cl] Cl
-
RR'CHOH
+
[(CH
3
)
2
SOCHRR']
Cl
-
(Et)
3
N
RR'C=O + CH
2
SCH
3


10. Kornblum Reaction
Kornblum and co-workers have demonstrated that in DMSO Į -bromoketones at room temperature and primary alkyl tosylates on heating
afford the corresponding carbonyl compounds, presumably through an oxysulfonium intermediate (273)(8551):
CH
3
SOCH
3
+ XCHRR'
[(CH
3
)
2
S-O-CHRR']X
-
RR'C=O + BH
+
B:
+


Some reactive alkyl halides, such as methyl iodide, also react with DMSO to form the oxosulfonium intermediate (the O-alkyl derivative).
However, this intermediate rearranges readily to the more stable oxosulfonium salt, i.e. (CH3)3S+Ol-, and no oxidation takes place (324).
Some reactive halides, such as benzyl, can also be oxidized to the corresponding carbonyl compounds but higher reaction temperatures
are necessary. An acid acceptor, e.g. sodium hydrogen carbonate, is frequently used (105).
The relatively unreactive alkyl halides, such as 1 -chloroheptane, can be oxidized by DMSO if the chloride is first converted to the tosylate
(106).
The DMSO oxidation of the primary allylic chloride, 4-chloro-3-methyl-2-buten-1-ol acetate, does not proceed well when sodium hydrogen
carbonate is used as the acid acceptor. However, this reaction runs well when a dibasic metal phosphate, Na2HPO4 or K2HPO4, is used
(9960):
H
2
CCl C
CHCH
2
OCOCH
3
CH
3
DMSO
M
2
HPO
4
, 80
o
C
OHC C
CH
3
CHCH
2
OCOCH
3

This particular reaction is catalyzed by sodium bromide (9960)(10066).

11. Methoxydimethylsulfonium Salts and Trimethyloxosulfonium Salts
Alkylating agents, such as methyl iodide, react initially with DMSO at the oxygen to give methoxydimethylsulfonium iodide (see the
previous section, Kornblum Reaction). These alkoxysulfonium salts are quite reactive and with continued heating either decompose to
give the carbonyl compounds or rearrange to the more stable trimethyloxosulfonium salts. In the case of methyl iodide
trimethylsoxosulfonium iodide is produced (324):
(CH
3
)
2
SO + CH
3
I
methoxydimethylsulfonium
iodide
trimethyloxosulfonium
iodide
[(CH
3
)
2
SOCH
3
]+I-
[(CH
3
)
3
SO]+I
-


Trimethyloxosulfonium iodide is of interest because treatment with sodium hydride or dimsyl sodium produces dimethyloxosulfonium
methylide which is an excellent reagent for introducing a methylene group into a variety of structures (632)(2463)(4820):
[(CH
3
)
3
SO]
+
I
-
+ NaH (CH
3
)
2
S CH
2
+ NaI + H
2
O
dimethyloxosulfonium
methylide


Many aldehydes and ketones react with the ylide to give better than 75% yields of epoxides (632):
(CH
3
)
2
S CH
2
O
+C
6
H
5
CH=CHC(O)C
6
H
5
CH
2
+ (CH
3
)
2
SO
H
C
90 % yield
(C
6
H
5
)
2
C

In a similar case, the dimethyloxosulfonium methylide reacts with carbon-carbon double bonds that are conjugated with carbonyl groups to
give cyclopropane derivatives (4820)(7361):

24
(CH
3
)
2
S CH
2
O
+C
6
H
5
CH=CHC(O)C
6
H
5
C
6
H
5
CH CHC(O)C
6
H
5
H
2
C




PART IV. DMSO AS A REACTION SOLVENT
A. DISPLACEMENT REACTIONS IN DMSO
These are reactions in which reactive groups are replaced by nucleophilic ions or molecules.
The largest category of reactions in which DMSO has been used as a solvent is that in which labile groups are replaced by nucleophilic
ions or molecules. The reason for the particular utility of DMSO in these reactions has not always been established and derives from a
number of factors. DMSO as one of the most polar of the common aprotic solvents. It is a favored solvent for displacement reactions
because of its high dielectric constant and because anions are less solvated in it (9488). The high dielectric constant of a solvent insures
that dissolving species or a solute bearing opposite charges do not come together to agglomerate. E.g. when sodium hydroxide is
dissolved in DMSO, the interaction between Na' and OH- is minimized. Due to the polarity of the sulfoxide bond and the electron density at
the oxygen, cations are much more solvated by DMSO than the anions. Conversely, the aprotic nature of DMSO precludes the solvation of
anions by hydrogen bonding so that these are solvated only by dipolar attraction and thereby are more reactive. In other cases, the
controlling influence is suggested to the ability of highly polar DMSO molecules to stabilize transition state structures and thereby lower the
activation energy (22) (471)(399). This latter effect is evident in the cases where comparatively minor additions of DMSO cause significant
enhancement of reaction rates (1262).



A great variety of displacement reactions can be run in DMSO and suitable nucleophiles include:
1. Acetylide ion 10. Cyanide ion
2. Alkoxide ion 11. Halogen ion
3. Amides 12. Hydroxide ion
4. Amines 13. Mercaptide (or Thiophenoxide) ion
5. Ammonia 14. Nitrite ion
6. Azide ion 15. Phenoxide ion
7. Carbanions 16. Sulfide (or Hydrosulfide) and Thiosulfate ions
8. Carboxylate ion 17. Thiocyanate ion
9. Cyanate ion

1. Acetylide Ion
The usual reactions of sodium acetylide may be accomplished in good yield by stirring a slurry of sodium acetylide in DMSO sl ightly below
room temperature with reagents such as alkyl halides, epoxides or carbonyl compounds (544). Displacement of halides with the ethylene-
diamine complex of lithium acetylide is also easily effected in DMSO (3178)(4175). Thus, the reaction of 1-bromo-5-chloropentane with
lithium acetylide-ethylene diamine complex in DMSO gives 7-chloro-1 -heptyne (1826):
Cl (CH
2
)
5
Br + HC CLi
+
-
DMSO
Cl (CH
2
)
5
C CH

The use of lithium acetylide-ethylene diamine in DMSO has given higher yields of the desired products than sodium acetylide in liquid
ammonia (4175).
The addition of lithium acetylide as the ethylene-diamine complex to 7-bromoheptanol tetrahydropyranyl ether in DMSO gives non-8-yn-1-
ol tetrahydropyranyl ether in higher than 90% yield (4333).

2. Alkoxide Ion
The high activity of alkoxide ions in DMSO shows up in their enhanced basicity. The basicity of alkoxides reaches a maximum in DMSO
when the mixture is substantially free of hydroxylic material. In this case, the acidity of the alcohols in dilute solutions is about 103 times
that of DMSO so that only a minor equilibrium quantity of the DMSO anion is present (734). The reactivity of the alkoxide ion in DMSO is
influenced by the cation and is greater with cesium and with lithium less (606)(1162). The vastly enhanced activity of alkoxide ions in
DMSO over their activity in alcohols is attributed to the absence of alkoxide-solvent hydrogen bonds in DMSO which are present in the
hydroxylic solvents (434).
The basicity of alkoxides in DMSO is conveniently expressed n terms of acidity functions, and a number of these are plotted in Figure 10
for bases n DMSO-water and DMSO-methanol systems.
Alkoxides differ in their solubilities n DMSO. Thus, potassium t-butoxide is more soluble than some lower alkoxides (17). The solubilities
of these hydroxylic bases are also shown in Table IX for comparative purposes.

A review article on potassium t-butoxide and its use in nucleophilic displacements has been published (6815).

TABLE IX

Substance

Solubilities of Various Bases in DMSO

moles/liter Reference

25
NaOH 7.6 x 10'° (725)
KOH 1 x 10'3 (17)
(CH ) NOH 1 x 10' (17)
NaOCH3 1.6 x 10'3 (725)
NaOEt 2 x 10'2 (17)
iso-PrONa 7 x 10'3 (17)
n-BuONa 5 x 10'3 (17)
t-BuOK 1 x 10'2 (17)

a) Aliphatic halide displacement
The rate of reaction of alkoxide ions with alkyl halides in alcohol-DMSO mixtures to form ethers increases with the increasing amount of
DMSO. This is illustrated in the reaction of methyl iodide with methoxide ion or with ethoxide ion to make dimethyl- or methyl ethyl ethers,
respectively (329), and in the reaction between benzyl chlorides and methoxide ion to make the corresponding benzyl methyl ethers
(433). The rate increase at high DMSO concentrations is attributed to an increased activity of the methoxide ion caused by reduced
solvation, but other factors are probably more important at low DMSO concentrations. The activation energy decreases continuously as
the DMSO concentration increases (433). The Williamson ether synthesis from alcohols and alkyl halides (chlorides) with sodium
hydroxide as the base can be considerably improved by using DMSO as the solvent in place of the excess alcohol (2924):
ROH + CIR'
NaOH, DMSO
100
o
C
6-14 hrs.
ROR'

Secondary alkyl chlorides and primary alkyl bromides give little etherification, elimination being the major reaction.
The use of alkoxides in DMSO in some cases involves elimination n addition to displacement, followed by the addition of the alkoxide to
the double bond in alicyclic compounds (1798).

b) Aromatic halide displacement
As with alkyl halides, the use of alkoxides in DMSO can involve both the displacement and elimination reactions with aromatic halogen
compounds. Thus, when a solution of 3-bromo-tropolone in DMSO is heated with sodium methoxide, an almost 1:1 mixture of 3-
methoxytropolone and 4-methoxytropolone is obtained in 96% yield (3572):
Br
OH
O
NaOCH
3,
DMSO
O
-
O
benzyne-type
intermediate
OCH
3
OH
O
3-methoxy
tropolone
+
OH
O
H
3
CO
4-methoxy
tropolone
NaOCH
3,
DMSO


Aromatic halogens in nitroaryl halides can be displaced by the methoxide ion in DMSO-methanol. The reaction rate increases some
1000-fold when the DMSO concentration is increased to 80% (399):
+
-
OR F NO
2
DMSO
k
1
N
OR
F
O-
O
+
DMSO
k
2
OR NO
2

R = C2H5 or t-Bu
p-Nitrochlorobenzene also reacts with alkoxides. When 2-alkylamino-ethanol is first treated with dimsyl sodium to make the oxyanion
base followed by the addition of p-nitrochlorobenzene, the preferential nucleophilic attack by oxygen (rather than the amino group) is
insured (8399):





The reaction of monoiodo-, monobromo-, monochloro- and monofluoro-naphthalenes with potassium butoxide in butyl alcohol-DMSO
has been examined (4058)(4059). The major products observed in the bromo-, iodo- and chloronaphthalene reactions are 1- and 2-butyl
naphthyl ethers, 1- and 2-naphthols and 1-methylmercapto-2naphthol. This suggests that 1,2-dehydrohaphthalene is an intermediate in
each of these reactions, and 1-methyl-mercapto-2-naphthol is probably the benzyne intermediate-DMSO reaction product (4059). The
RHN(CH
2
)
2
OH +
NO
2
NaH
2
CSOCH
3
, DMSO
+
RHN(H
2
C)
2
O NO
2
Cl

26
fluoronaphthalenes undergo only direct nucleophilic substitution with no formation of 1,2-dehydronaphthalene, i.e. no benzyne-type
intermediate (4058)(5244):










2,3-Dichloranisole can be prepared by reacting 1,2,3-trichlorobenzene with sodium methoxide in DMSOmethanol (9107).
The kinetics of the reaction of 2-bromo-, 2-bromo-3-methyl-, and 2-bromo-5-methylpyridine and methoxide ion in DMSO containing small
amounts of methanol have been determined (2125). The ortho:para ratio is higher at lower temperatures (2.5 at 40° C vs 1.44 at 110* C):
N
R R'
Br
+
-
OCH
3
DMSO
40-110
o
C
N
R R'
OCH
3
+
N
R R'
OCH
3

2-Bromopyridine reacts with potassium methoxide in DMSO containing 1 % of methanol 3000 times faster than it does with the same
reagent in pure methanol at 110°C.
A number of 4-alkoxypyridines is prepared by reacting 4-chloropyridine with sodium alkoxides in DMSO in moderate to high yields
(5038).
5-Bromo-3-methyl-4-nitroisothiazole reacts smoothly with sodium alkoxides in alcohols-DMSO to give the appropriate 5-alkoxy-3-methyl-
4-nitroisothiazoles (4098):
N
S
CH
3
NO
2
+ NaOR
DMSO
60-100
o
C
N
S
CH
3
NO
2
OR Br

c) Nitro group displacement
When sodium methoxide or sodium ethoxide is added to p-nitro- or p,p'-dinitrobenzophenone in DMSO, almost quantitative yields of p-
alkoxy- or p,p'-dialkoxybenzophenone are obtained (470):
NO
2
C NO
2
O
+NaOR
ROH-DMSO
20
o
C
24 hrs.
OR C OR
O



Sulfonamides are also alkylated in DMSO.4,6-Dichloropyrimidine reacts with the sodium salt of p-nitrobenzenesulfonamide in DMSO to
give 4-chloro-6-(p-nitrobenzenesulfonamido)pyrimidine (42):
With 2,2'-dibromo-4,4'-dinitrobenzophenone, there is no displacement of bromide ion, and 2,2'-dibromo-4,4'dimethoxybenzophenone
(90%) is obtained. No reaction occurs in any instance when dioxane is used instead of DMSO (470).


d) Sulfinate displacement
When ȕ-styrylsulfones are treated with one molar equivalent of sodium alkoxides in DMSO, ȕ-alkoxystyrenes are formed by
nucleophilic substitution (9761):
CH=C
R"
R'
R
SO
2
Ph
R'"
NaOR
iv DMSO
room temp.
CH=C
R"
R'
R
OR
R'"
iv

10-68%
e) Sulfonate displacement
Benzene sulfonates of common primary and secondary alcohols react rapidly with sodium methoxide in DMSO to give high yields of alkyl
methyl ethers and/or alkenes. The ether-alkene ratio is significantly higher in reactions with sodium methoxide than with potassium t-
butoxidesulfonyl ester groups from carbohydrate derivatives, the conversion to the ether with sodium methoxide or sodium e. More olefins
are formed from secondary sulfonate esters than from primary esters (580)(592). In the displacement of methane thoxide in DMSO occurs
by the attack on the sulfur, leading to the retention of configuration, rather than by the usual attack on carbon with inversion (1119)(653).

3. Amides
F
+ t-BuOK
t-BuOK-DMSO
70
o
C
14 hours
O
+
OH
38%
27%
(degradation
product of the ether)

27
The N-alkylation of amides can take place in DMSO. The reaction of various Ȧ-haloamides with the dimsyl ion in DMSO can be used to
obtain good to high yields of 4-, 5- and 6-membered lactams. However, the reaction with dimsyl ion fails to produce the seven-membered
heterocyclic ring (888):
X
N C (CH
2
)
n
Br
H O
H
2
CSOCH
3
, DMSO
-
X
N (CH
2
)n
O

X = Br, Cl, F, I;
N = 2, 3, 4

The readily available base, dimsyl ion, could be more convenient to work with than sodium in liquid ammonia (888). The alkylation of the
sodium salt of saccharin with a benzyl chloride also proceeds well in DMSO to give a high yield of N-benzyl saccharin (947):
7-Oxo-7,8-dihydro-s-triazolo[4,3-a]pyrimidine can be alkylated as above using p-chlorobenzyl chloride in DMSO. In this case, however a
mixture of the N-benzyl- and the O-benzyl deriviatives results (3885):









It has been found that the N-alkylation of carboxylic acid amides proceeds well in DMSO by using dry potassium hydroxide as the base.
Good yields can be obtained even at room temperature (4355):





With DMSO as the solvent, the use of stronger bases, such as sodium hydride or potassium alkoxides, is not necessary.
When the sodium salt of an acetamidonitrile in DMSO is treated with chloramine, a smooth N-amination is achieved (4382):










Peptides and proteins can also be N-alkylated with methyl iodide and benzyl bromide using DMSO as the solvent and the dimsyl ion as
the base (4945).

A number of amides, such as acetanilide, have been N-alkylated with dialkyl sulfates using potassium hydroxide as the base and DMSO
as the solvent (8276):





The sodium salt of an amide can displace a methoxy group from a benzene nucleus. Thus, the treatment of 2-acetamido-2'-
methoxybenzophenone with sodium hydride in DMSO gives the 9-acridone (8564):










R NHR'
O
+ R"X
R NR'R"
O
54-90%
KOH, DMSO
RT
N
N
O
N
N
H
+ RCl
NaOH, DMSO
N
N
O
N
N
R
+
N
N
O
N
N
H
CH
2
Cl R =
H
3
CO
OCH
3
CN
NNa
H
3
COC
+ ClNH
2
DMSO
H
3
CO
OCH
3
CN
NNH
2
H
3
COC
NHCCH
3
O
+
(RO)
2
SO
2
KOH, DMSO
20
o
C
N CCH
3
R O
NH OCH
3
O
N
O
COCH
3
COCH
3
68%
NaH, DMSO
room temp

28

4. Amines
In most displacement reactions, the nucleophiles are negatively charged. However, displacements can also take place involving
uncharged nucleophiles, namely, amines (3433). Amines, like ammonia, do not hydrolyze DMSO. The presence of DMSO in the
displacement reaction involving amines allows the reagents to surmount the energy barrier easier than in hydroxylic solvents, irrespective
of the charge type of the reagents. The effect of DMSO, then, must be the decrease in- the energy of the transition state. It could also be
said that DMSO polarizes a substrate (399). For a reaction involving neutral reactants, such as amines, and going through a charged
transition state, it appears that DMSO can solvate the cationic part of the reacting system at the point of attack of the amine reagent
(1240). Thus, displacement reactions by amines in DMSO generally proceed at a good rate. A catalytic effect is seen by adding DMSO to
an alcohol system containing amines and aryl halides (399)(1262).
a) Aliphatic halide displacement-primary amines
Alkylation of weak aromatic amines with alkyl bromides (e.g. 2-aminofluorenone with ethyl bromide) in DMSO gives ring brominated N-
alkyl derivatives (211). However, aralkylation of 2-aminofluorenone with aralkyl bromide, such as benzyl- and para-substituted benzyl
bromides in DMSO leads to azomethines as the main products (264):











DMSO also catalyzes the reaction between 2-substituted carboxylic acids and amines. Thus, ethylenediamine reacts with chloroacetic
acid to give ethylenediaminetetraacetic acid (EDTA) (4910):

H
2
NCH
2
CH
2
NH
2
+ 4ClCH
2
CO
2
H
DMSO
80
o
C
(HO
2
CCH
2
)
2
NCH
2
CH
2
N(CH
2
CO
2
H)
2


b) Aliphatic halide displacement-secondary amines
Ȧ -Bromoalkylbenzofuranones react with morpholine in DMSO to give high yields of the N-alkylation products (613):
O
O
(CH
2
)
n
Br +
Ph
NH O
DMSO
O
O
(CH
2
)
n
Ph
N- O
n=1,2,3,4
yield almost quantitive if n=1 or 2

The morpholinoethylbenzofuranone is formed by direct halogen displacement and no rearrangement reactions take place.


c) Aliphatic halide displacement-tertiary amines
The reaction between triethylamine and ethyl iodine has been investigated in benzene, DMSO and various benzene-DMSO mixtures.
The reaction rate increases with increasing DMSO concentration in the solvent. Although DMSO reacts slowly with alkylating agents,
quaternizations, such as the reaction of triethylamine and ethyl iodide, proceed much more rapidly to give a high yield of
tetraethylammonium iodide (585):
(C
2
H
5
)
3
N + C
2
H
5
I
DMSO
20-50
o
C
(C
2
H
5
)
4
N+I
-

Similarly, when p-nitrocumyl chloride is treated with quinuclidine in DMSO, a 90% yield of pure quaternary ammonium chloride can be
isolated (3433):











N
O
2
C
(CH
3
)
2 Cl
+
N
DMSO
room temperature
10 hours
N
O
2
C (CH
3
)
2
N
Cl
-
+
90%
O
O
NH
2
BrH
2
C X
DMSO
+
100
o
C
1.5 hrs
N
Br
HC X


29


d) Aromatic halide displacement - primary amines
A series of primary amines has been reacted with 4-nitrofluorobenzene in DMSO to determine the rate constants. DMSO was selected as
the solvent because of its relatively high boiling point and the fact that most nucleophilic reactions in DMSO proceed at a fast rate (1638).
These reactions are run in the presence of an excess of amines:
NO
2
F
+ 2RHN
2
DMSO
NO
2
NHR + RNH
3
F
-
+

Similarly, benzylamine reacts with 2,4-dinitrochlorobenzene (399):
C
6
H
5
CH
2
NH
2
+ CIC
6
H
3
(NO
2
)
2
DMSO
C
6
H
5
CH
2
NHC
6
H
3
(NO
2
)
2

e) Aromatic halide displacement - secondary amines
The displacement of aromatic halides by secondary amines in DMSO has been studied rather extensively. The fluoro compounds undergo
substitution by various nucleophiles, such as secondary aliphatic and alicyclic amines, at rates 100 to 1000 times faster than their chloro
analogs. The rate of displacement of fluorine is further enhanced by the order of 103 to 105 in dipolar aprotic solvents, such as DMSO, as
compared with reactions in aprotic solvents (471). Thus, 4-fluoroacetophenone undergoes a very rapid displacement of the halogen by
amines, such as morpholine, in DMSO and affords in high yields the corresponding 4-amino derivatives, which are otherwise difficult to
prepare (398):
OCCH
3
X
+
NH
DMSO
OCCH
3
N

X = F, Cl, Br
The yields of products obtained in DMSO are higher than those obtained with DMF under comparable conditions.

The reaction of 2,4-dinitrochlorobenzene with piperidine, which is known to be insensitive to base catalysis, is nevertheless accelerated by
DMSO (538).

The rate constants for the reaction of 4-nitrofluorobenzene in DMSO with 19 secondary amines have also been determined. This reaction
is the fastest with pyrrolidine, azacyclobutane and dimethylamine, and slowest with methylanisidine, diisobutylamine and diethanolamine
(1639).

The dechlorination of 2- and 4-chloroquinolines, as well as 6- and 8-alkyl-substituted 4-chloroquinolines with piperidine in DMSO and
other solvents has been studied (1240)(1239)(1238).

f) Nitro group displacement
In some cases, activated nitro groups can be displaced by amines. Thus, 2,5-dinitro-1 -methylpyrrole undergoes nucleophilic aromatic
substitution by piperidine (7756):
N
O
2
N
NO
2
CH
3
+
NH
DMSO
N
O
2
N
N
CH
3

The reaction with the amine is favored by the accelerating effect of DMSO in aromatic substitutions by neutral nucleophiles.

g) Alkoxide and phenoxide displacement
The reaction of n-butylamine or t-butylamine with 2,4-dinitro-1 -naphthyl ethyl ether gives the corresponding 2,4-dinitro-1 -
naphthylamines in high yields (3445):

OC
2
H
5
NO
2
NO
2
+ RNH
2
DMSO
room temp
NHR
NO
2
NO
2


1-Piperidino-2,4-dinitronaphthalene can be prepared by reacting 1-methoxy-2,4-dinitronaphthalene with piperidine in DMSO. 1 -
Dimethylamino-2,4-dinitronaphthalene is prepared similarly (8408). The kinetics of the reaction of piperidine, n-butylamine, morpholine
and benzylamine with 2,4-dinitrophenyl phenyl ether in DMSO has been studied as a function of amine concentration. The reactions of

30
the secondary amines are base catalyzed; those of the primary amines are not (9138).

5. Ammonia
DMSO is stable to ammonia. Displacement reactions with ammonia and amines are examples where the nucleophile is uncharged
(3433). The solubility of ammonia is 40 liters per liter of DMSO at 1 atmosphere or 2.6% by weight (5033).

a) Aliphatic halide displacement
Reaction of methyl 2-bromo-3-phenyl-3-butenoate with ammonia in DMSO gives the desired Į-amino ester (10134):
Ph C CHCO
2
CH
3
+ NH
3
CH
2
Br
DMSO
room temp.
1.5 hrs.
Ph C CHCO
2
CH
3
CH
2
NH
2
88%

Secondary amine by-products are not found in any significant amounts in the above reaction. Somewhat similarly, isopropyl 2,3-dibromo-
2,3-dihydrocinnamate reacts with ammonia to give isopropyl 2-phenyl 3-aziridine-carboxylate (10143):








High yields of nitrilotriacetic acid are claimed when ammonia is reacted with chloroacetic acid in DMSO (4910):
4NH
3
+ 3ClCH
2
CO
2
H N(CH
2
CO
2
H)
3
+ 3NH
4
Cl

b) Aromatic halide displacement
2,4-Dinitrochlorobenzene reacts with ammonia to give 2,4-dinitroaniline (402):

Cl
NO
2
NO
2
+ NH
3
(aq.)
DMSO
room temp.
several hrs.
NH
2
NO
2
NO
2
93%


Similarly, p-aminotrifluoroacetophenone reacts with ammonia in DMSO (3399):







When DMF is used as the solvent in the above
reaction, p-dimethylaminotrifluoroacetophenone results, apparently due to the hydrolysis of DMF to dimethylamine:






c) Alkoxide displacement
Displacement of an -OMe group by ammonia produces 3-amino-2-heteroarylpropenenitriles (10458):





6. Azide Ion
Rate constants for displacement reactions by the azide ion in DMSO are up to about 10,000 times greater than for the same reaction in
protic solvents, such as methanol (471). Reactions are frequently run with an excess solid sodium azide, making it a pseudo first-order
PhCHCHCO
2
CH(CH
3
)
2
+ NH
3
Br Br
DMSO
room temp.
3 hours
N
H
PhCHCHCO
2
CH(CH
3
)
2
Ar C
CHOCH
3
+ NH
3
CN
DMSO
Ar C
CH-NH
2
CN
84-95%
F
O
+ NH
3
DMSO
135
o
C.
24 hrs.
NH
2
O
42%
F
3
CC
F
3
CC
+ NH
3
+(H
3
C)
2
NCHO
(NCH
3
)
2
O
F
O
F
3
CC
F
3
CC

31
process. Under these conditions, the rate is also a function of the solubility of the reagent. Measurements of solubility show that sodium
azide is much more soluble in DMSO than in some other solvents, and the solubility increases slightly with the addition of water (7527).

TABLE X
__________________________________Solubility of Sodium Azide in Four Solvents______________________
Solubility, mol/l.
Dry 1% H2O 5% H2O 10% H2O
______________ (110°) (110°) (110°)_________
2-Methoxyethanol 0.31 (124°)
DMF 0.10-0.12 0.17 0.28 0.48 (25-150°)
DMSO 1.5-1.6 1.6 1.8 1.9 (95-150°)
HMPA 0.43 0.45 0.48 0.51 (110-150°)
a) Aliphatic halide displacement
Some aliphatic halides are easily displaced by the azide ion in DMSO (4815). Thus, the reaction of 2-(2nitrophenyl)ethyl bromide with a
3-fold excess of sodium azide gives a 95% yield of 2-(2-nitrophenyl)ethyl azide (4360):
CH
2
CH
2
Br
NO
2
+ NaN
3
DMSO
CH
2
CH
2
N
3
NO
2

b) Aromatic halide displacement
Treatment of 4-fluoro- or 4-iodonitrobenzene with sodium azide in DMSO produces a quantitative yield of 4-nitrophenyl azide (471):
NO
2
X
+ NaN
3
DMSO
100
o
C.
NO
2
N
3
100 %

X = F or I
When 4-chloro-3-nitrobenzoic acid is treated with sodium azide in DMSO, the 5-carboxybenzofuroxan results (1007):

CO
2
H
NO
2
Cl
+ NaN
3
DMSO
CO
2
H
N
+
N
O
O
-


Reaction of 2-chloroquinoxzline 1-oxide with sodium azide in DMSO at room temperature gives 2-azidoquinoxaline (9767):
N
N
O
Cl
+ NaN
3
DMSO
N
N
O
N
3
52%


c) Nitro group displacement
The aromatic nitro group can also be displaced by dry sodium azide in DMSO (6572). Thus, 2,3-dinitroacetanilide with sodium azide
gives the monoazido-derivative (4600):








d) Sulfonate displacement
Sulfonates, such as toluenesuIfonates and methanesuIfonates are also readily displaced by the azide ion in DMSO (4920)(8339). A high
yield of the 2,3-diazidobutane is obtained when meso-1,4-di-0-acetyl-2,3-di-0-(methylsulfonyl)erythrol is reacted with a slight excess of
sodium azide (7692):



HNOAc
NO
2
NO
2
+ NaN
3
DMSO
90
o
C
HNOAc
N
3
NO
2
87%
OMes OMes
OAc OAc
+ 2 NaN
3
DMSO
60-100
o
C
N
3
N
3
OAc OAc
96%

32





The above described displacements are frequently used to prepare amino sugar derivatives by reducing the azido to the corresponding
amino group (5481)(7071).

e) Other displacements
Treatment of fumaronitrile with sodium azide in DMSO with subsequent acidification leads to 1,2,3-triazole-4-carbonitrile (4249):





7. Carbanions
The majority of carbanions which are usually prepared as reaction intermediates or as transistory species in chemical reactions are
readily obtained in DMSO.

a) Aliphatic halide displacement
The alkylations of 2,4-pentanedione with alkyl iodides and sodium hydride as the base may be more conveniently and rapidly achieved
when DMSO is used in place of the usual alcohols or non-polar solvents (4261):
CH
3
C
H
2
C CCH
3
+ 2RX
O
NaH, DMSO
CH
3
C C CCH
3
O
R
R
O
X= I or Br

Similar results are obtained with malononitrile (599).

Alkylation of malonic esters in DMSO can be faster than in DMF, dimethoxyethane, THF and benzene. This alkylation is strongly
accelerated by comparatively minor additions of DMSO to benzene. This could mean that DMSO disperses the ion aggregates
(611)(612).

With ambient anions where either carbon or oxygen alkylation is possible, DMSO favors oxygen alkylation (690):
O
O
+ PhCH
2
Br
DMSO
O Ph
95%

This is also demonstrated in the alkylation of ȕ -ketoesters, where a proper choice of alkylating agent, temperature, and alkali metal can
lead to significant amounts of O-alkylation (773)(1114)(1229).
Interaction of the potassium salt of 2-carbethoxy-cyclopentanone with an alkyl halide in DMSO at room temperature provides good yields
of alkylated keto esters and probably constitutes the best method of alkylating this ȕ-ketoester (1823):
O
CO
2
C
2
H
5
O
CO
2
C
2
H
5
Br
+
K
+
DMSO
room temperature
6 hrs.
78%



b) Aromatic halide displacement
Substituted o-nitrohalobenzenes reaction DMSO in the presence of powdered KOH with deoxybenzoin to form the corresponding
nitroarylated deoxybenzoins (9439):
Cl
NO
2
R
NO
2
R
Ph
Ph
O
+
Ph
Ph
O
KOH, DMSO

DMSO
[NC CH CH N
3
]
N
N
H
N
C CH CN
NC CN
+

N
3

33
c) Nitro and sulfinate group displacement
Ìt has been discovered that aliphatic nitro and sulfone groups can be displaced at tertiary carbon. Thus, the treatment of Į,-p-
dinitrocumene with the lithium salt of 2-nitropropane in DMSO gives the alkylation product (1237):
NO
2
NO
2
NO
2
NO
2
CH3
NO
2
H
3
C
Li
+
+ 71%
DMSO
25
o
C

Nitrobenzenes substituted by an electron withdrawing group, such as p-dinitrobenzene, readily undergo displacement by the lithium salt of
2-nitropropane in DMSO (8436):
NO
2
NO
2
NO
2
NO
2
NO
2
H
3
C
CH3
Li
+
+
DMSO
25
o
C
75%

The sulfone group of Į-nitrosulfones is also easily displaced by carbanions, e.g. the lithium salt of 2-nitropropane or the lithium salt of
nitrocyclohexane (7108):
R'
R
NO
2
SO
2
Ar
+
NO
2
"R
R"
Li
+
DMSO
room temperature
R
R'
O
2
N
R"
NO
2
R"

d) Other displacement reactions
Treatment of 2-cyanomethyl-2',4'-dimethoxybenzophenone with sodium methoxide in DMSO gives 9-cyano-2-methoxyanthracen-10-ol
(3112):
O
NC
H
3
CO
CN
OH
OCH
3
OCH
3
95%
NaOCH
3
, D MSO
140
o
C, 10 min.

When p-nitrobenzylidene diacetate is reacted with the lithium salt of 2-nitropropane in DMSO, a compound in which one of the acetate
groups is replaced by the C(CH3)2,NO2, group is obtained (7657):
O
2
N CH(OCOCH
3
)
2
+ (CH
3
)
2
CNO
2
Li
+
DMSO
room temp
3 hrs.
O
2
N CH(OCOCH
3
)
2
(CH
3
)
2
NO
2

Treatment of (p-cyanobenzyl)trimethylammonium chloride with the lithium salt of 2-nitroprprane gives the carbon alkylate (10399):
O
2
N
NO
2
DMSO
25
o
C
82%
CH
2
N(CH
3
)
3
Cl
-
NC
+
+
[(CH
3
)
2
CNO
2
}Li
+

e) Use of aqueous sodium hydroxide as the base
It has been found that nitriles containing sufficiently activated methylene groups, such as phenylacetonitrile, can be conveniently alkylated
in excellent yields and selectivities by using aqueous sodium hydroxide as the base and DMSO as the reaction solvent (3951):
PhCH
2
CN + RX
Ph
CN
R
R'
Ph
CN
R
R'X
NaOH(aq), DMSO

Previously, these reactions have usually been carried out by treating the nitrile with a strongly basic reagent, such as a metal amide,
hydride, or alcoholate, followed by addition of the appropriate alkyl- or aryl hydride. These latter methods are generally cumbersome and

34
the selectivities are poor (3951).
Similarly, 50% aqueous sodium hydroxide in DMSO can be used as a base to induce an essentially quantitative cyclization of 5-chloro-2-
pentanone to give cyclopropyl methyl ketone (3398):
Cl(H
2
C)
3
O
CH
3
O
CH
3
NaOH (aq), DMSO
30
o
C, 15 min
96%

O- and C-alkylation of benzoins is also easily achieved by the reaction of alkyl halides in aqueous sodium hydroxide in DMSO at ambient
temperatures (4699):
Ph
O
Ph
OH
Ph
O
Ph
OH
Ph
O
Ph
OR
RX +
R
R
NaOH (aq), DMSO
RX



f) Use of calcium oxide as the base
In some cases, calcium oxide has been used as a base to produce carbanions. Diethyl malonate can be alkylated with benzyl bromide to
yield diethyl benzylmalonate (3931):
!
"
#$%
"
$
"
!
&
'
"
(
$)
$%
"
$
"
!
&
$
"
!
&
%
"
$
*+,
$-%.//012%



The use of lime in the dimethylation of 2,4-pentanedione gives a 73% yield of 3,3-dimethyl-2, 4-pentanedione (3931).

8. Carboxylate Ion
Alkylation of carboxylate ions with alkyl halides in DMSO or DMSO-water is an efficient method of esterification (7950)(365)(8809).
Carboxylate ions have also been used to displace sulfonates (8254). In aqueous DMSO systems, the reaction rate increases as the
concentration of DMSO increases both for intramolecular and intermolecular displacment (407).

a) Aliphatic halide displacement
Simple alkyl halides, such as n-decylbromide, react with disodiurn phthalate in DMSO tog ive, e.g. didecylphthalate in 91 % yield
(2597). Carboxylic acid esters are prepared by reacting an organic halide and potassium or sodium acetate in DMSO (574)(6847).
Carboxylic acid esters are also prepared by reacting an acid with an organic halide in the presence of an alkali metal hydroxide in
DMSO or DMSO-water, e.g. to obtain benzyl acetate (2969):
Cl
CO
2
CH
3
+ CH
3
CO
2
H
70-81%
NaOH
DMSO


Potassium and sodium methacrylates react in DMSO with xylylene dichlorides in DMSO to give unsaturated, polymerizable
compounds (487):
CH
3
Cl
Cl
H
3
C
H
2
C
CH
3
H
3
C
O
CH
2
CH
3
O
CO
2
Na
O
CH
2
DMSO
140-145
o
C
nearly quantitative
+ 2


A convenient procedure for preparing pyruvic acid esters utilizes an organic halide as the starting material rather than the
corresponding alcohol (9657). Thus, the reaction of sodium pyruvate with n-octyl iodide or phenacyl bromide in DMSO yields the esters:
CO
2
Na
O
CO
2
(CH
2
)
7
CH
3
O
+I(CH
2
)
7
CH
3
DMSO
50
o
C, 3.5 hrs
95%




35
O
CO
2
Na
O
DMSO
50
o
C, 3.5 hrs
Br
Ph
O
+
O
O
Ph
O
85%


A ring opening and displacement reaction takes place when E and Z 2-phenylcyclopropyl bromides react with potassium acetate in
DMSO in the presence of a crown ether (1 8-crown-6) (10465):

R
Br CHCH
2
OCOCH
3
R
DMSO
85
o
C
+ CH
3
CO
2
K

b) Sulfonate displacement
When the sodium or potassium 2-methanesulfonoxybicyclo[3.3.1 ]nonane-1 -carboxylate is heated in DMSO, the corresponding ȕ-
lactone is produced (6347):

9. Cyanate Ion
Sodium and potassium cyanates in DMSO can displace reactive halogens (26). When alkyl halides are reacted with cyanates, either
isocyanates or isocyanurates result, depending on the reaction conditions and the solvent (440). DMSO plays a superior role in the
displacement reaction and also in the subsequent trimerization of isocyanates. These reactions may be written as follows (386):
RX +KCNO
DMSO
70-80
o
C
an isocyanate.
RNCO + KX
3 hrs.


3RNCO
N
N
N
O
R R
O
O
R
DMSO
100-150
o
C
an isocyanurate
X = Br, I; R = ethyl, n-propyl
1-2 hours


If an organic dihalogen compound is reacted with either potassium cyanate or sodium cyanate, the following reactions take place (9408):

XRX + MNCO XR NCO+ MX
DMSO
70 - 200
o
C
X-R-NCO + MCO
OCN
R
NCO + MX
M= sodium or potassium


Under conditions causing trimerization, the products can be converted to the corresponding cyanurates:
N
N
N
O
R R
O
O
R
N
N
N
O
R R
O
O
R
X X
X
OCN NCO
OCN
or

10. Cyanide Ion
Perhaps the most widely used of the displaycement reactions in DMSO are those involving the cyanide ion. Halogen atoms and sulfonate
(tosyl) groups are displaced rapidly by cyanide ion. Often the yields of the desired products are higher and side reactions are minimized in
DMSO. Many products are more easily isolated from reaction mixtures containing DMSO.
Certain inorganic cyanides are more soluble in DMSO than in other organic solvents. Thus, DMSO can be used advantageously in
systems where water is undesirable. At 95°C, about 10 g of sodium cyanide and/or 2 g of potassium cyanide will dissolve in 100 cc of
DMSO. At 25°C, 1 g of either is soluble (964)(1924).
The solubility of sodium cyanide in DMSO at various temperatures is shown in Figure 7 below. The solubility of sodium chloride, the usual
inorganic by-product when reacting sodium cyanide with organic chlorine compounds, is illustrated in the phase diagram, Figure 8.
Also soluble in DMSO are mercury cyanide, cadmium cyanide, and mixtures of potassium cyanide with copper, nickel, zinc, cobalt, or
silver cyanides. These mixtures appear to be complex salts (801).
In many cases it is not necessary to have a complete solubility of sodium cyanide in DMSO. Reactions can be run using an agitated,
stirred slurry of sodium cyanide with DMSO. Yields are commonly good with primary aliphatic halides, but somewhat lower with
secondary ones due to dehydrohalogenation (475)(577)(8843).



36


37
a) Aliphatic halide displacement
The reaction of sodium cyanide with ethyl 6-chlorohexanoate in DMSO gives a high yield of 6-cyanohexanoate (474):

Cl(CH
2
)
5
CO
2
C
2
H
5
+ NaCN
DMSO
95-100
o
C, 1hr.
CN(CH
2
)
5
CO
2
C
2
H
5
+ NaCl
90%

Similarly, ethylene dichloride reacts with sodium cyanide to give acrylonitrile (473):
ClCH
2
CH
2
Cl + 2 NaCN
H
2
C CHCN + HCN + 2NaCl
DMSO
100
o
C

In the above case, both the displacement and elimination reactions take place.
The use of DMSO allows the cyanide ion to displace halides from neophyl and neopentyl compounds without rearrangement
(475)(7547):
CH
2
Cl
+NaCN
DMSO
26%
neophyl chloride
120
o
C, 24hrs


The displacement reactions of alkyl chlorides and bromides with potassium cyanide occur much more slowly when compared with
sodium cyanide (475). This could be due to the lower solubility of potassium cyanide in DMSO. The yields are also lower and longer
reaction times are required with DMF, sulfolane and dimethyl sulfolane as solvents (475). It has also been established that both primary
and secondary alkyl chlorides react with sodium cyanide in DMSO to give high yields of the corresponding nitriles in shorter reaction
times than have been obtained with bromides or iodides in aqueous alcohol solvent (577).
When 1-chloro-17-fluoro-8-heptadecyne is reacted with sodium cyanide in DMSO, 1-cyano-17-fluoro-8heptadecyne is produced in high
yield (2189):
F(H
2
C)
8
C C(CH
2
)
7
Cl
F(H
2
C)
8
C C(CH
2
)
7
CN + NaCl
+ NaCN
DMSO
135
o
-140
o
C
50 min.
93.5%

The difference in the reactivity of halogens is also illustrated in the reaction of 1,1-dichloro-2-(bromomethyl)-2methylbutane with
potassium cyanide (2769):
Br
Cl
2
CN
Cl
2
+ KCN
DMSO
50%

The use of sodium cyanide in the above reaction gives some undesirable by-products.
The enolate salt of ethyl 4-bromo-3-oxobutyrate reacts with the cyanide ion in DMSO (9135):
Br
O
CO
2
C
2
H
5
NC
O
CO
2
C
2
H
5
DMSO
81%
+ CN
-

Ȧ-Cyano N,N-disubstituted amides are conveniently prepared from halogenated amides by treatment with alkaline cyanides (9985):
Cl
R O
N
CH
3
CH
3
NC
R O
N
CH
3
CH
3
n n DMSO, 80
o
C
+ NaCN


Poly[3,3-bis(chloromethyl)oxocyclobutane] reacts with sodium cyanide in DMSO to give the bis(cyanomethyl) derivative (6847):

CH
2
Cl
CH
2
Cl
O
CH
2
CN
CH
2
CN
O
DMSO
120-130
o
C
+ 2nNaCN
n n



b) Aromatic halide displacement
Aromatic halides, particularly those not activated by electron withdrawing groups, are best displaced by using cuprous cyanide
(1593)(1774)(1946). Thus, p-halophenol reacts with cuprous cyanide in DMSO to give p-hydroxybenzonitrile (1946):


38
OH
X
OH
CN
+ CuCN
DMSO
reflux 2-5 hrs.
X = Cl, Br, I

Cuprous cyanide and 9-bromoanthracene in DMSO give 9-cyanoanthracene in 91% yield (3247).
A procedure for the separation of isomers of dihalonitrobenzene consists of treating them with an alkali metal cyanide or cuprous cyanide
in DMSO. When a mixture of 2,3- and 3,4-dichloronitrobenzene is thus treated, only the 2,3-isomer reacts, whereas the 3,4-isomer is
recovered unchanged (1455):
NO
2
Cl
Cl
NO
2
CN
Cl
+ NaCN
DMSO

Sodium cyanide and o-fluoronitrobenzene in DMSO form 2-hydroxy-isophthalonitrile (8065):
F
NO
2
OH
CN NC
+ NaCN
60%
DMSO
120
o
C, 2hrs.

c) Hydrogen displacement
When o-nitrobenzonitrile is heated with sodium cyanide in DMSO hydroxy-isophthalonitrile is produced (8065).
NO
2
CN
OH
CN
+ NaCN
DMSO
120
o
C
1 hour
CN
55%

d) Quarternary ammonium salt displacement
When 2-pyrrolylmethylammonium salts are reacted with sodium cyanide both pyrrole-2-acetonitrile and "abnormal¨ nitrile are produced
(8759):
N
CH
3
CH
2
N
+
(CH
3
)
3
X
-
N
CH
3
CN
N
CH
3
CN
+ Na CN +
NC
DMSO
80-85
o
C

e) Sulfinate displacement
1-Chloro-4-(methylsulfonyl)benzene (I0 and cuprous cyanide fail to react to give the desired 1-cyano-4-(methylsulfonyl)benzene when
refluxed for 24 hours in DMF. However, when equimolar amounts of I and potassium cyanide are allowed to react in DMSO for 30
minutes, a 1:1 mixture of 1,4-bis(methylsulfonyl)benzene (II) and terephthalonitrile (III) is obtained in about 80% yield (1711):
Cl SO
2
CH
3
H
3
CO
2
S SO
2
CH
3
NC CN +KCN
DMSO
reflux
I.
II. III.
+


When 4- (methylsulfonyl)cinnoline and potassium cyanide are reacted in DMSO, 4-cinnolinecarbonitrile is produced quantitatively (1721):
N
N
SO
2
CH
3
N
N
CN
+ KCN
DMSO
20
o
C
100%





f) Sulfonate displacement
Sulfonates (e.g. tosylates) or disulfonates are converted in high yields to the corresponding nitriles or dinitriles with cyanides
in DMSO (477)(2525)(10044). Thus, azulene-1,3-bis(hexanenitrile) and azulene-1, 3-bis-(pentanenitrile) are prepared
by treating the corresponding tosylates (or chlorides) with sodium cyanide (2783).
A neopentyl substitution product can be obtained by treating the corresponding tosylate with potassium cyanide in DMSO
(8255):



39
O
CH
2
OTs
O
CH
2
CN
DMSO
70
o
C
3 hrs.
+ KCN
61%

g) Other displacement reactions
Reacting a chloromethyl-1,2,3,4-tetrahydropyrimidine-2-one or4-(1-chlorethyl)- 4-dihydropyridine with sodium cyanide gives the ring-
expansion products (4739)(9986). Thus, the above-mentioned pyrimidine produces a 7 membered ring compound (4739):
O
CH
2
OTs
O
CH
2
CN
DMSO
70
o
C
3 hrs.
+ KCN
61%

Displacement of primary or secondary hydroxyl groups by nitrile groups is accomplished by a short refluxing of the alcohol and
triphenylphosphine in carbon tetrachloride, followed by the addition of DMSO and sodium cyanide to obtain 70-85% yields of the
corresponding nitriles (872).


11. Halogen Ion
Displacement of halogen or other groups by halide ions is frequently easy in DMSO. Exchange reactions between halogens often
require high temperatures and because of its boiling point of 189° C, DMSO is the solvent of choice.
a) Aliphatic halide displacement
The kinetics of homogeneous isotope exchange between 36Cl in cyclic compounds (e.g. cyclopentyl chloride, cyclohexyl chloride,
cycloheptyl chloride, cyclooctyl chloride) and lithium chloride has been studied in DMSO. This exchange is a bimolecular SN2 reaction
(109)(651):
RCl
36
+ Cl
-
RCl + Cl
36 -

Similar exchange reactions between n-hexyl chlorides (containing36CI) and n-hexyl bromides (containing "Br) and lithium chloride and
bromide have also been studied in DMSO (650).
By exchanging two bromine atoms in the 1,4-positions with lithium chloride in DMSO, 1,4-di-p-tolyl-1,4-dichloro2,3-dibromo-2-butene
can be obtained (2760):
OTs
Br
Br
Br
Br
OTs
OTs
Cl
Br
Br
Cl
OTs
+ LiCl
DMSO
Ts=tosyl

Nucleophilic reactions between halogeno(phenyl)acetylenes and halide ions have also been examined in DMSO (10394), eg.
CPh CBr
PhC CCl
dry DMSO
95
o
C, 125 hrs.
+ (C
2
H
5
)
4
N
+
Cl
-
15%

b) Aromatic halide displacement
The chloride ion in chloro nitrobenzenes can be replaced by fluoride with potassium fluoride in DMSO (438):
Cl
NO
2
F
NO
2
+ KF
DMSO
190
o
C
14 hrs
72%




40
Quantitative studies are reported for substitution of the type ArHal + CuX Æ ArX + CuHal in DMSO and other polar solvents
(541)(1593)(1214). Ease of replacement follows the order: H a I= I, Br, CI, F; X =CI,Br,I. The reaction rates are the highest in DMSO
among the solvents examined. Thus [1-36Cl]chloronaphthalene can be prepared from 1 - bromonaphthalene and radioactive cuprous
chloride (1593):

c) Sulfonate displacement
Br
Cl
36
+ CuCl
36
DMSO
reflux 1 hr.
nearly quantitative

Sulfonates (e.g. tosylates, nosylates = p-O2N-Ph-S03) can be displaced by halogens by reacting them with lithium chloride, lithium
iodide (4066)(5836), lithium bromide (4066) or sodium bromide (1027) in DMSO. Pure secondary alcohols can be converted to bromides
without rearrangement by first preparing the tosylates and then reacting them with sodium bromide in DMSO at room temperature
(1027).
Treatment of endo-5,6-bis(p-toluenesulfonyloxy-methyl)-2-norbornene with cesium chloride in DMSO gives the endo-5,6-
bis(chloromethyl)-2-norbornene (10002):

d) Displacement of diazonium ion
CH
2
OTs
CH
2
OTs
CH
2
Cl
CH
2
Cl
+ 2CsCl DMSO
100
o
C, 12 hrs
50%

p-Nitrobenzenediazonium tetrafluoroborate in DMSO reacts with iodides, bromides and chlorides to give the corresponding p-
halonitrobenzene (99), e.g.:
N
2
+
BF
4
-
NO
2
Br
NO
2
70%
DMSO
room temp


12. Hydroxide Ion
The basicity of hydroxides in DMSO closely parallels that obtainable with alkoxides, as shown in Figure 10 in which acidity functions up to
26 are obtained with 0.01 tetramethylammonium hydroxide in DMSO (1172). The solubility of the hydroxides is generally low, ranging
from 7 x 103 mol/liter for sodium hydroxide (725) to 0.12 for tetramethylammonium hydroxide at room temperature (1172) (see Table IX).
Additions of water increase the solubility of alkali metal hydroxides, but the increased solubility is accompanied by a decrease in the
activity of the dissolved hydroxide ion. Figure 9 is a phase diagram of the water-DMSO-metal hydroxide systems for NaOH and KOH.
Potassium hydroxide is consistently more soluble than sodium hydroxide at a given water content. In spite of the low solubility of alkali
metal hydroxides in DMSO, satisfactory use of the strong basicity of the hydroxide ion is sometimes achieved by using a slurry of the
powdered base in the reaction.

a) Aliphatic halide displacement
When the alkaline hydrolysis of methyl iodide is studied in the presence of hydroxyl ion in DMSO-water, the rate of hydrolysis increases
with increasing DMSO content (329):
CH
3
I + NaOH
DMSO-H
2
O
CH
3
OH + NaI

Similar results are obtained with other primary alkyl halides (iodides, bromides, chlorides)(913).
The rate constants for the reaction of hydroxide ion with ring substituted benzyl chlorides in acetone-water and DMSO-water mixtures are
reported as a function of both solvent composition and temperature. The reaction rate increases with increasing DMSO concentration but
decreases with increasing acetone concentration (432).

b) Aromatic halide displacement
The reaction of 2,4-dinitrofluorbenzene and 4-nitrofluorobenzene with hydroxide ion in DMSO-water are strongly accelerated by DMSO
(328).


41
Hydrolysis of o- and p-nitrochlorobenzenes with caustic soda in DMSO produces o- and p-nitrophenols (3925):
Cl
NO
2
OH
NO
2
DMSO, air
80-115
o
C
3 hours
+ NaOH (aq)

Nucleophilic substitution reactions have also been carried out on a variety of mono- and dihalogen-1,2,3Denzothiadiazoles, e.g. 6-
chloro-4-fluoro-1,2,3-benzothiadiazole, with potassium hydroxide in aqueous DMSO to give the corresponding phenol (4425):


F
Cl
S
N
N
OH
Cl
S
N
N
92%
DMSO (aq), KOH
reflux 2 hrs.







42
c) Nitro group displacement
The nitro group in 4-nitropyridine N-oxide, p-nitrobenzophenone and 1-nitroxanthone can be replaced with aqueous sodium hydroxide to
give the corresponding phenols or 1-hydroxyxanthone, resp. (409)(470).
When p-dinitrobenzene is reacted with hydroxide ion in aqueous DMSO, one nitro group is displaced (6937).

13. Mercaptide (or Thiophenoxide) Ion
The mercaptide or thiophenoxide ions are known as good nucleophiles, and significant rate increases have been observed in DMSO when
compared to the same reaction in alcohols (399).

a) Aliphatic halide displacement
A number of alkyl halide displacements with mercaptides or thiophenoxides have been studied in DMSO (680) (712)(8779). Thus, the
reaction of Į, Į' - dibromo- Į, Į, Į', Į'-tetrafluoro-p-xylene with sodium ethyl mercaptide gives the corresponding
Į
,

Į'-bis(ethylthio)xylene
(3386):










Methyl perfluoroalkyl sulfides may be prepared by reaction of the perfluoroalkyl iodides with sodium methyl mercaptide and dimethyl
disulfide in DMSO (4792), e.g.:







A derivative of poly-3,3-bis(chloromethyl)oxacyclobutane is prepared by reacting it with sodium benzyl mercaptide in DMSO (6847):








b) Aromatic halide displacement
Aromatic halogens are replaced by mercaptide or thiophenoxide ions in DMSO (541), particularly when the aromatic ring contains
electron withdrawing groups in the ortho- or para-positions to the halogen (8344)(399). Thus, potassium benzyl mercaptide reacts with
p-fluoronitrobenzene in DMSO-methanol under mild conditions (399):






The reaction rate of the above reaction increases significantly with increasing DMSO concentration.
The reactions of 4-methyithiophenoxide with 3- or4-halo-substituted phthalimide derivatives have been studied in DMSO (9771):









Nucleophilic substitution reactions have been carried out with mercaptide or thiophenoxide ions on a variety of mono- and dihalogen-
1,2,3-benzothiadiazoles (4425).

c) Nitro group displacement
The nitro group at certain tertiary carbon atoms can be displaced by thiophenoxide in DMSO-methanol (1237) or
CF
2
Br
CF
2
Br
CF
2
SC
2
H
5
CF
2
SC
2
H
5
+ 2 C
2
H
5
SNa
NaOCH
3
, DMSO
50-60
o
C
2hrs.
n-C
6
F
13
I + CH
3
SNa
CH
3
SSCH
3
, DMSO
105
o
C
20-40 hrs.
n-C
8
H
13
SCH
3
88%
H
2
C
H
2
C O
H
2
C
H
2
C O
SCH
2
Ph
PhH
2
CS
Cl
Cl
NaSH
2
C
DMSO
n
n 110-120
o
C
5 hrs.
26-40
o
C
few min.
SK
NO
2
DMSO
O
2
N
H
2
C
S
NR
NR
O
O
X
O
O
CH
3
NaS
H
3
C
+
DMSO

43
methyl mercaptide ions in DMSO (10008). The yields of the tertiary sulfides are very high in both cases, e.g. (10008):
SO
2
Ph
(H
3
C)
2
C NO
2
SO
2
Ph
(H
3
C)
2
C SCH
3
+ NaSCH
3
DMSO
15 min.


The nitro group in substituted nitrobenzenes is displaced by the thiophenoxide ion (9771) or mercaptide ion (4068) (9771) to give the
diaryl or alkyl aryl sulfides, respectively, e.g. (4068):






d) Sulfonate group displacement
The reactions of the tosylate of 2,2,2-trifluoroethanol with the sodium salts of methyl, ethyl or 2-hydroxyethyl mercaptides in DMSO
give the expected thio ethers (589):




14. Nitrite Ion
Sodium nitrite has good solubility in DMSO. Thus, in a few minutes, 100 cc of DMSO dissolves 19.2 g of sodium nitrite, whereas only
1.88 g dissolves in 100 cc of DMF at room temperature after 24 hours. In DMSO it is not necessary to add urea to increase the
solubility of sodium nitrite, as is the case with DMF (685). Displacement reactions involving the nitrite ion have been studied rather
extensively in DMSO.
a) Aliphatic halide displacement
The displacement of aliphatic iodide, bromide or chloride to give the corresponding nitro compound is readily accomplished in DMSO
with yields ranging from 50-91 %, depending on the structures involved (684)(3686) (4562). Primary and secondary alkyl bromides and
iodides react with sodium nitrite to produce the corresponding nitro compounds (486), e.g. 1 -bromooctane gives 1 -nitrooctane (685):

CH
3
(CH
2
)
7
Br + NaNO
2
CH
3
(CH
2
)
7
NO
2
66%

Lower nitroparaffins are prepared by treating the corresponding C1-3 alkyl chlorides with alkali metal nitrites in DMSO (10286):
CH
3
Cl + NaNO
2
CH
3
NO
2
DMSO
85%

When Į -haloesters are reacted with sodium nitrite in DMSO, the nitro ester initially formed is quickly converted to the Į-nitrite ester
(684):







However, by adding phloroglucinol to the reaction mixture, the formation of nitrite ester is prevented and pure - nitroesters are produced
in excellent yields (682)(684)(691).
When 1,3-dihalogen compounds, such as 3-bromo-l-chloropropane, are reacted with sodium nitrite, a heterocyclic compound is
obtained, e.g. 3-nitro-2-isoxazole (366)(988):








Other substitutions at tertiary carbon atoms involving the nitrite ion have been studied (2565)(2566)(3490). The reaction of 1 -iodo-
4-heptyne with sodium nitrite in DMSO produces 1 -nitro-4-heptyne (4384)(6692):
NO
2
R
SR'
R
+ NaSR'
DMSO
CF
3
CH
2
OTs + RSNa
CF
3
CH
2
SR
DMSO
R
Br
CO
2
C
2
H
5
R
O
2
N
CO
2
C
2
H
5
R
ONO
CO
2
C
2
H
5 +NaNO
2
DMSO
room temperature
D-nitroester
D-nitrite ester
Br(CH
2
)
3
Cl + 2NaNO
2
N
O
O
2
N
53%
DMSO
0-30
o
C
18 hrs

44







b) Aromatic halide displacement
Aromatic halides can also be displaced by the nitrite ion (8063). When 2,4-dinitrochlorobenzene is reacted with sodium nitrite in DMSO,
2,4-dinitrophenol is formed (402)(4562):










c) Sulfonate displacement
The reaction of the tosylate of the secondary alcohol (in the steroid or prostaglandin series) with potassium nitrite in DMSO affords the
inverted alcohol as the main product together with the corresponding nitroalkane, ketone, and alkene (10454):
R
R'
OTs
H
R
R'
H
OH
R
R'
H
NO
2
R R'
O
+
+ + alkene
DMSO
+ KNO
2


15. Phenoxide Ion
DMSO enhances the rate at which halides are displaced by phenoxides (phenol, catechol, hydroquinone) almost as much as it does for
alkoxides or mercaptides (399). With ions such as naphthoxide, where a choice exists between carbon and oxygen alkylation, the reaction
in DMSO gives almost exclusively oxygen alkylation (690). DMSO is a good solvent for phenoxide ions. Thus, the polymerizations of the
dipotassium salt of bisphenol A with dihaloaromatic compounds proceeds best in DMSO when compared to other dipolar aprotic solvents
(6026). The alkylation of phenoxide is enhanced more than the alkylation of amino groups in DMSO. The phenoxide group in tyrosine can
be selectively etherified without blocking the amino group (442). DMSO is also a good solvent in the nucleophilic displacement of activated
aromatic nitro groups by phenoxides for the synthesis of aromatic ethers (10434).

a) Aliphatic halide displacement
DMSO can be used as the solvent in alkylation of sterically hindered phenols (884)(3631)(3830)(4573). When 2,6-di-tert-butyl-4-
methylphenoxide is reacted with ethyl iodide, the major product is the corresponding ether (517):
OH
CH
3
C
2
H
5
O
CH
3
O
CH
3
O
CH
3
NaH, DMSO
room temp., 10 min.
77% 23% 0%
C
2
H
5
C
2
H
5

With tert-butyl alcohol as the solvent, the corresponding product distribution is 19%, 73%, 8%, and the reaction takes several days instead
of 10 minutes, as in DMSO.
When 2-t- butyl-5-methyl phenol is alkylated with allyl bromide in DMSO with sodium methoxide as a base, a 97% yield of allyl-t-butyl-5-
methylphenyl ether is obtained (885).
Reaction of polychloroethanes with sodium phenoxide in DMSO gives phenoxychloroethylenes (8410):



CH
3
CH
2
C C(CH
2
)
3
I
H
3
CH
2
CC C(CH
2
)
3
NO
2
+ NaNO
2
45%
DMSO
room temp.
1hr
Cl
NO
2
NO
2
OH
NO
2
NO
2
+ NaNO
2
DMSO
room temp.
several minutes.
80%
ONa
O
Cl
Cl
DMSO, 70
o
C
5 hrs.
+
Cl
2
CHCHCl
2

45
Sodium methyl salicylate and diiodomethane in DMSO give formaldehyde disalicyl acetal (6460):







Alkylation reactions of the bifunctional Ȧ -bromo-1,2-epoxyalkanes have been found to be markedly dependent upon the solvent. In
alcoholic media, phenoxides react by opening the epoxide ring to give ȕ-hydroxy- Ȧ- bromoalkyl derivatives. In DMSO, these same
compounds react by displacement of bromide ion to give epoxylalkyl derivatives (3395). Polyhydroxyethers can be synthesized from
mono-alkali metal salts of bisphenols, such as 4,4'sulfonyldiphenol, and 1-halo-2,3-epoxyalkanes in a one-step reaction in DMSO
(10437):







A number of catechol ethers have been prepared by using DMSO as the solvent (9145). Catechol reacts with methylene chloride in
DMSO with sodium hydroxide as the base to give 1,2-methylenedioxybenzene (2887):
OH
O
O

+ CH
2
Cl
2
NaOH, DMSO
OH
91%



b) Aromatic halide displacement
The phenoxide ions in DMSO have been used in many aromatic halide displacement reactions (399)(690). Activated fluorobenzenes
react with alkali metal salts of divalent phenols to give aryloxy compositions (8683):








Phenoxides also react with halo-substituted phthalimide derivatives in DMSO to produce high yields of ether imides (9096):









The dipotassium salt of 3-hydroxybenzoic acid reacts with 3,4-dichlorobenzotrifluoride in DMSO to yield 3-(2-chloro-4-
trifluoromethylphenoxy)-benzoic acid (10320):








The ability of phenoxide ions in DMSO to displace aromatic halogens and the solubility of the phenoxide ions in DMSO are used in
polycondensation reactions to obtain linear, high molecular weight aromatic polyethers (6026)(6830)(7699). Thus, bisphenol A can be
polymerized with 4,4'-dichlorodiphenyl sulfone in DMSO to prepare a polyether sulfone (6831):
ONa
CO
2
CH
3
O
CO
2
CH
3
O
CO
2
CH
3
+ CH
2
I
2
2
DMSO, 145
o
C
24 hrs.
n (
-
O-Ar-OH)+
O
Cl
R
OH
R
O
O Ar
n
DMSO
130-140
o
C
2.5 hrs.
n
S
OH
HO
+
CN
F
O
S
OH
CN
NaOH, DMSO
100
o
C, 18hrs
N
O
O
R
N
O
O
R
NaO
+
X
O
DMSO
OK
KO
2
C
O
Cl
CO
2
H
CF
3
Cl
Cl CF
3
K
2
CO
3
, DMSO
138-144
o
C, 22 hrs
+

46







The dipotassium or disodium salt of catechol in DMSO reacts smoothly with some polyhalogenated benzenes (or heterocycles) to
give good yields of the corresponding dibenzo-p-dioxins (7553)(8311 ), e.g. (7047):









c) Nitro group displacement
Some activated nitro groups are displaced with ease by phenoxide ions (8984)(8350)(8685):








Nucleophilic displacement of activated aromatic nitro groups with aryloxy anions in DMSO is a versatile and useful reaction for the
synthesis of aromatic ethers (10434). This reaction has also found applications in polymers, particularly in the preparation of polyimides
(7710)(8287).

d) Phenoxide displacement
Polyetherimides can be made by effecting an interchange reaction, in the presence of an alkali phenoxide, between aryloxy-substituted
bisphthalimide and disodium salt of, e.g., bisphenol A in DMSO (8714):
N R'
O
O
O
O PhO
OPh
N
R'
N
O
O
O
O
O
O
Ar
Ar
N
n
+ HOArOH
NaOPh, DMSO
160
o
C, 1 hr

e) Sulfonate displacement
The monotosylate of 2-t-butyl-1,3-propane can be transformed to phenoxyalcohol with sodium phenoxide in DMSO 6315):
HOH
2
C
CH
2
OTs
HOH
2
C
ONa
O
83%
DMSO
50-60
o
C, 3 hrs
+


16. Sulfide (or Hydrosulfide) and Thiosulfate Ions
The sulfide and hydrosulfide ions act as nucleophiles and both these ions can be alkylated and/or arylated in DMSO. Water seems to be
a necessary component for thiosulfate solubility. The rate constant for the reaction of thiosulfate in aqueous DMSO is at least an order
of magnitude larger than in other solvents (656).

a) Aliphatic halide displacement
Polymercaptans can be produced by reacting polyhalo compounds with sodium sulfhydrate (sodium hydrogen sulfide) in DMSO, e.g.,
1,2,3-trichlorpropane and sodium sulfhydrate give the corresponding trimercaptan (6192):


S
OH
HO SO
2
Cl
Cl
O
S
O
+
KOH , DMSO
n
O O
OH
OH
Cl Cl
Cl Cl
O
O Cl
Cl
+
KOH, DMSO
reflux
81%
H
3
C
N
O
O
CH
3
H
3
C
ONa
O
2
N
N
CH
3
O
O
+
DMSO
room temp.
O

47





A mixture of either an aryl isothiocyanate or an aryl isocyanide dichloride, methylene bromide, and a sulfide source, such as ammonium
sulfide or sodium sulfide, can be reacted in DMSO to provide a one-step synthesis of aromatic 2-imino-1,3-dithietanes (7528):

N=CCl
2
+ CH
2
Br
2
+2 (NH
4
)
2
S
DMSO
40
o
C
1 hour
N C
S
S
CH
2
77%


The ȕ-activated diethyl sulfides can be prepared by reacting the appropriate chloride with sodium sulfide in DMSO (6398):






Sodium thiosulfate and benzyl chloride react to yield sodium benzylthiosulfate which forms dibenzyl disulfide
(472):






b) Aromatic halide displacement
Sodium sulfhydrate can also displace aromatic halogens from activated nuclei, as in the reaction with chloro-4-nitro-3-
trifluorotoluene in DMSO. The major product is a disulfide (4123):







c) Sulfonate displacement
Sulfonates (tosylates) can be displaced by using either sodium sulfydrate or sodium sulfide in DMSO. Thus, 1,1-dihydrotrifluoroethyl p-
toluene sulfonate reacts with sodium sulfide to give bis(1,1-dihydrotrifluoroethyl) sulfide (489):





17. Thiocyanate Ion
Sodium and potassium thiocyanates are very soluble in DMSO, and in most cases, the rate constants in displacement reactions are
considerably greater than for reactions in protic solvents, e.g. methanol (471).

a) Aliphatic halide displacement
The reaction of 2-bromooctane with potassium thiocyanate yields 2-octyl thiocyanate (472):





3-Bromocyclohexene reacts with potassium thiocyanate in DMSO to form 3-thiocyanocyclohexene which is labile and rearranges to 3-
isothiocyanocyclohexene (390):






Ammonium thiocyanate and 2-chloromethylbenzimidazole in DMSO react to form thiocyanic acid (2benzimidozolyl)methyl ester (7173):
2 CH
2
Cl + 2Na
2
S
2
O
3
DMSO (aq.)
30
o
C
2 days
CH
2
S
2
O
3
Na
CH
2
S
2
NO
2
2 Cl
F
3
C
+ NaSH
DMSO
20-25
o
C
8 hours
NO
2
F
3
C
S S NO
2
CF
3
45%
CF
3
CH
2
OTs + Na
2
S.9H
2
O
S, H
2
O, DMSO
70-80
o
C
2 hours
CF
3
CH
2
SCH
2
CF
3
+ CF
3
CH
2
S-S-CH
2
CF
3
29%
43%
H
3
C CH(CH
2
)
5
CH
3
+ KSCN
Br
DMSO
74
o
C
2 hrs.
H
3
C CH(CH
2
)
5
CH
3
SCN
50%
+ KSCN
DMSO, 5% H
2
O
0
o
C
Br
SCN
NCS
distill
2H
3
CO
2
CCH
2
CH
2
Cl + Na
2
S.9H
2
O
DMSO
10
o
C
2 hrs.
H
3
CO
2
CCH
2
Ch
2
CO
2
CH
3
62%
CH
2
ClCHClCH
2
Cl + 3 NaHS
HSH
2
C
SH
SH
DMSO
50
o
C , 50 min.

48
N
CCH
2
Cl
N
H
+ NH
4
SCN
DMSO
room temp
15 minutes
N
CCH
2
SCN
N
H
41%


b) Aromatic halide displacement
Nitrotrifluoromethylchlorobenzenes react with sodium thiocyanate in DMSO to yield the corresponding phenylthiocyanates
(4123)(7158):
Cl
NO
2
CF
3
+ NaSCN
DMSO
45-50
o
C (22 hrs.)
120
o
C (3 hrs.)
NO
2
CF
3
70%


c) Sulfonate displacement
Potassium thiocyanate in DMSO displaces the sulfonate groups from 2,4-pentane di-p-bromobenzenesulfonate to
give 2,4-dithiocyanopentane (515):
OBs
OBs
DMSO
70-75
o
C, 50 hr
+ KCN
SCN
SCN
68%




Similarly, 2-methylbutyl p-toluenesulfonate and potassium thiocyanate in DMSO yield (62.5%) 2-methylbutyl thiocyanate (5435).

B. BASES AND BASE-CATALYZED REACTIONS IN DMSO

Basicities in DMSO
The reactivity of nucleophiles in DMSO mixtures with water or alcohols consistently increases as the content of DMSO in the mixture
increases. When the nucleophile is the hydroxide ion in the aqueous system, or the alkoxide ion in the alcoholic system, the activities of
the bases can be presented in terms of acidity function, shown in Figure 10. Since the acidity function is a logarithmic scale measuring
the ability of the system to remove a proton from the reference indicator, the data show the basicity to be enhanced some 10
14
fold
upon going from water or alcohol to 99% DMSO. Such a protic-aprotic system offers a means of adjusting the basicity of a reaction
medium over a wide range.
In the highly basic systems, obtained when the concentration of water or alcohol is low, an equilibrium amount of the DMSO anion will
be present. The simple aliphatic alcohols are about 1,000 times as acidic as DMSO and they have about the same acidity as
triphenylmethane (734)(1558). One chemical consequence of this effect shows up in the alkoxide-catalyzed autoxidation of fluorene
where the oxidation rate is controlled by the rate of carbanion formation (1728). The reaction rate increases 220-fold upon changing the
solvent from t-butanol to an 80:20 DMSO-t-butyl alcohol mixture. However, in the 80:20 mixture the concentration of DMSO anion is
sufficient to react with the product so that instead of a 91 % yield of fluorenone a 78% yield of the DMSO adduct of fluorenone is
obtained.
Although the equilibrium amount of DMSO anion produced by alkoxide ion in this system is small, the rate at which the protons transfer
is fast (1758)(1759) so that a steady pool of DMSO anion is available for reaction.
Proton Removal
A number of different reactions require the removal of protons from carbon with the resultant formation of carbanions. The proton removal
can be either an initial or the rate-determining step. Carbanions are formed in racemizations, in isomerizations and in a wide variety of
elimination reactions. Just as the equilibrium basicity of alkoxides and hydroxides is enormously enhanced in DMSO versus in hydroxylic
solvents, so also is the rate at which proton removal or hydrogen exchange reactions occur in DMSO. The rate of potassium t-butoxide-
catalyzed hydrogen-deuterium exchange at a benzyllic carbon atom is 10
6
times greater in DMSO than in t-butanol (606).
A similar rate enhancement is observed in racemizations using ammonia as the base, with the reaction being 10
6
-10
7
times faster in
DMSO than in t-butanol (622)(524). The influence of the cation is greater in DMSO than in t-butanol. For example, in t-butanol, sodium
and potassium t-butoxides are about equally effective in prompting hydrogen exchange, whereas in DMSO the potassium salt gives a
reaction rate one hundred times that of the sodium salt (606).


49



50
The table below (Table XI) lists the acidities (pKa) values of 132 organic compounds in DMSO, starting with the most acidic-
protonated pyridine, and ending with the least acidic-propionitrile (10569). The pKa of DMSO is 35 (10411).
TABLE XI
Acidities in DMSO

COMPOUND pKa COMPOUND pKa
Protonated pyridine 3.5 Nitromethane 17.2,16.5
2,6-Dinitro-4-chlorophenol 3.6 Diphenylacetonitrile 17.5
Protonated analine 3.7 Į, Į, Į', Į'-Tetraphenylacetone 17.6
Protonated 2-methylpyridine 4.0 Phenyl benzyl ketone 17.7
Protonated 2,4-dimethylpyridine 4.5 Bis(2-nitrophenyl)amine 17.7
Protonated o-phenylenediamine 4.8 Nitrocyclobutane 17.8
Thiosalicylic acid 5.2 9-Phenylfluorene 17.9
Phthalic acid I 6.2 Nitrocyclohexane 17.9
Oxalic acid I 6.2 Nitroneopentane 18.1
Sulfamic acid 6.5 Į, Į-Diphenylacetophenone 18.7
Salicylic acid 6.8,6.6 Į-Thiophenylaceton 18.7
Thioacetic acid 6.7 Methyl trifluoromethyl sulfone 18.8
Thiocyanuric acid 6.7 4-Chloro-2-nitroanaline 18.9
Bromocresol green 7.0 4-Nitroanaline 19.2
2,5-Dihydroxybenzoic acid 7.1 a, a-Diphenylacetone 19.4
Phenylsulfonylnitromethane 7.2 Methyl benzyl ketone 19.8
3,5-Dinitrobenzoic acid 7.3 2-Bromofluorene 20.0
2,4-Dihydroxybenzoic acid 7.5 Ethyl trifluoromethyl sulfone 20.4
Rhodanine 7.7 Thiourea 20.5
Nitromethyl phenyl ketone 7.7 Thiophenylacetonitrile 20.8
9-Cyanofluorene 8.3 Bis(n-chlorophenyl)amine 21.4
2,5-Dihydrophthalic acid 8.3 Phenylacetonitrile 21.9
Protonated tributylamine 8.3 9-Methylfluorene 22.3
Protonated diphenylguanidine 8.6 Phenylacetylene 22.6,28.8
Chloroacetic acid 8.9 2,6-Dichloroanaline 22.6
p-Nitrobenzoic acid 9.0 Fluorene 22.6
Ethyl nitroacetate 9.2 Trithiophenylmethane 22.8
Thiophenol 9.8 Phenyldithiophenylmethane 23.0
Protonated dibutylamine 10.0 1 -Phenyl-1 -cyanoethane 23.0
Bromo thymol blue 10.2 3-Methylfluorene 23.1
p-Chlorobenzoic acid 10.2 2,4 Dichloroanaline 23.4
9-Carboxymethylfluorene 10.2' 3-Methoxy-1 -propyne 23.5
9-Phenylsulfonylfluorene 10.3 Formamide (N-H) 23.5
Protonated piperidine 10.6 Diphenylamine 23.5,23.6
Protonated pyrrolidone 10.8 Dibenzyl sulfone 23.9
Benzoic acid 10.8,10.9 N,N-Dimethylprop-2-ynylamine 24.2
o-Toluic acid 11.0 9-tert-Butyl-fluorene 24.3
m-Toluic acid 11.0 Ethyl phenyl ketone 24.4
Malononitrile 11.1 Diphenylmethylphenyl sulfone 24.5
p-Toluic acid 11.2 2,5-Dichloroanaline 24.6
3-Nitro-l-propene 11.2 Acetophenone 24.7
Phenylacetic acid 11.6 Urea 25.1
Thiophenylnitromethane 11.8,11.9 2,4-Dichloroanaline 25.3
Phenylnitromethane 12.2 Acetamide (N-H) 25.5
Methylmalononitrile 12.4 Methyl benzyl sulfone 25.6
Acetic acid 12.6 1,3,3-Triphenylpropene 25.6
2-Thiohydantoin I 12.8 Isopropyl phenyl ketone 26.3
Acetylacetone 13.6 Acetone 26.5
Hydrogen cyanide 13.7 9-(3-Chlorophenyl)xanthene 26.6
Bis(ethylsulfonyl)methane 14.4 3-Chloroanaline 26.7
2,4-Dinitroanaline 14.8 Diphenylthiophenylmethane 26.7
Oxalic acid II 14.9 Nitrocyclopropane 26.9
Resorcinol 15.3 Diethyl ketone 27.1
9-Phenylthiofluorene 15.4 9-Phenylxanthene 27.9
2,5-Dihydrophthalic acid II 15.6 Water 28.0
Nitrocycloheptane 15.8 Benzyl methyl sulfoxide 29.0
Nitrocyclopentane 16.0 Methyl phenyl sulfone 29.0
p-Chlorophenol 16.1 Diphenylyldiphenylmethane 29.4
2,5-Dichloro-4-nitroanaline 16.2 Triphenylmethane 30.0,30.6
Nitromethylcyclopropane 16.5 Phenylthiophenylmethane 30.8
Nitroethane 16.7 Ethyl phenyl sulfone 31.0
1,1 Bis(ethylsulfonyl)ethane 16.7 Dimethyl sulfone 31.1
1 -Nitropropane 16.8 Acetonitrile 31.3
2-Nitropropane 16.9 Diphenylmethane 32.3
Phenol 16.9 Propionitrile 32.5
m-Cresol 17.0 DMSO 35


51


ELIMINATION REACTIONS
These are base-catalyzed reactions in which two atoms or groups are removed or eliminated, usually from one or two carbon atoms. A
double bond is frequently formed as the result of this elimination.
1. Cope Elimination
The pyrolysis oft-amine oxides (Cope elimination) in dry DMSO proceeds at a convenient rate at 25°C to give 80-90% yields of olefins.
Temperatures of 132-138° are usually required in water. In addition, the rates in DMSO are 10,000 times faster than in water (495):

Ph
N
O (CH
3
)
3
DMSO
25
o
C
Ph CH
3
+
Ph
80-90%

The rate is higher in wet DMSO than in dry THF because DM SO acts as an internal drying agent and competes with amine oxide for the
water present (578).
5 Į-Stigmasta-7,22,25-trien-3 ȕ-ol, a steroid alcohol, is obtained by heating the appropriate t-amine oxide in DMSO (3481):
H
3
C
R
N
O (CH
3
)
2
H
3
C
R
61%
DMSO
120-130
o
C


2. Decarboxylation and Decarbalkoxylation
DMSO promotes the decomposition of malonic (640), oxalic (604), and oxamic (643) acids at elevated temperatures, e.g. 140-160
°
C.
Pyridylacetic acid hydrochloride decarboxylates in DMSO at moderate temperatures. The only product of this decarboxylation is 4-
methyl-pyridine hydrochloride (2343)(3743):


ClHN
ClHN
CH
2
CO
2
H
CH
3
DMSO
30
o
C
95+%


The decarboxylation of trichloroacetic acid also occurs as low as 25.0
°
C in the presence of DMSO and water. The reaction rate constant
increases by a factor of 6-7 with a change in concentration of DMSO from 50 to 86%. Dramatic rate accelerations result in the
decarboxylation of benzisoxazole-3-carboxylic acids if water is replaced by DMSO (3447):

O
N
CO
2
H
X
Y
CN
OH
X
Y
CO
2
DMSO, 30
o
C
+




Some acids, such as optically pure (+)-2-benzenesulfonyl-2-methyl-octanoic acid, decarboxylate more readily in the presence of base
to give, in this case, (+)-2-octylphenylsulfone in 98% optical purity (631):

Ph
O
2
S
CO
2
H
n-C
6
H
13
H
3
C Ph
O
2
S
CH
3
n-C
6
H
13
KOCH
3
, DMSO
90
o
C, 148 hrs.
83%



Tetrahalophthalic acids in DMSO in the presence of alkali and alkaline earth chlorides undergo double decarboxylation to form 1,2,3,4-
tetrahalobenzenes, whereas, in the presence of other chlorides (e.g. CoCl2, NiCl2, CuCI2) or no salts at all mostly single decarboxylation
occurs to give 2,3,4,5-Cl4(or Br4)C6HCO2H (4602). Lead tetraacetate has been used in DMSO to decarboxylate dicarboxylic acids (5081).
Thus, the treatment of 3,3-dimethylcyclohex-4-ene-1,2-dicarboxylic acid yields 3,3-dimethyl-1,4-cyclohexadiene (7533):

52
CO
2
H
CO
2
H
Pb(OAc)
4
, DMSO-pyridine


Rates of decarboxylation are reported for several phenylmalonic acids and esters in DMSO at 55.4°C. Only those compounds bearing at
least one carboxylic proton are labile, which establishes that intramolecular proton transfer is an integral part of the reaction mechanism
(7655).

Benzaldehydes can be prepared from the phenylacetic acids by electrolytic decarboxylation and oxidation in DMSO in the presence
of sodium hydride. The yields are good in most cases (8766):
CH
2
CO
2
H
R
CHO
R
electrolysis
NaH



Decarbalkoxylation (mostly decarbethoxylation) is related to decarboxylation in that the -CO2R group, instead of CO2
(decarboxylation) is eliminated. Thus, geminal dicarboxy groups are eliminated when malonic ester derivatives are heated in DMSO
(942):
C
2
H
5
O
2
C
C
2
H
5
O
2
C
C
2
H
5
O
2
C
H
NaCN, DMSO
160
o
C, 4 hrs.
60-80%



The treatment of ethyl trichloroacetate with sodium methoxide in DMSO at 0
°
C produces dichlorocarbene which is oxidized by
DMSO (1040).
Decarboxylation of geminal diesters, ȕ-keto esters, and Į-cyanoesters to the corresponding monoesters, ketones and nitriles can
be accomplished in excellent yields (85-95%) in wet DMSO in the presence of sodium chloride at 140-186°C (6102)(7022)(9769).
Other dipolar aprotic solvents, such as DMF, are less effective in the case of substrates with lower activity because of lower boiling
points of these solvents (6102).
The alkylative decarboxylation of N-carbalkoxypyrozoles has been shown to require a polar aprotic solvent, such a DMSO, and to
be subject to catalysis by nucleophiles, e.g. halide ions (7285):

N
N
CO
2
R
N
N
R
CO
2
X
-
, DMSO +


The decarbalkoxylation of methyl or ethyl isohexylmalonates in DMSO in the presence of various alkali metal salts gives methyl or
ethyl 6-methylheptanoates. The best results are obtained in the presence of 1 equivalent of salt and 2 equivalents of water (8861).
Salts such as KCN, NaCl, or LiCl dramatically enhance the decarbalkoxylation rates of geminal diesters, ȕ-keto esters, and Į-
cyanoesters by DMSO-water (9769).

3. Dehalogenation
By a proper choice of reaction conditions or nucleophile in DMSO, one can obtain elimination of either bromine or hydrogen bromide
in cases where both paths are available (454):
Br
Br
Br
71%
H
2
CSOCH
3,
DMSO
61%
H
2
CSOCH
3,
DMSO



In the presence of excess dimsyl sodium in DMSO at room temperature, the debrominated intermediate results, while the use of a
larger excess of dimsyl sodium and longer reaction times yield 1,2-cyclononadiene.
In the reaction of 3 ȕ-chloro-5 Į-bromo-6 ȕ-bromocholestane with excess dimsyl sodium in DMSO, bromine elimination occurs.
When this intermediate is treated with potassium t-butoxide in DMSO, HCl elimination occurs (455):

53

Br
Cl
Br
Cl
H
2
CSOCH
3,
DMSO
room temperature
t-BuOK, DMSO
43%
77%



Pure olefins from their dibromides can be obtained by using sodium thiosulfate in DMSO as the debrominating agent. Thus,
stilbene dibromide yields stilbene (6496):
Br
Br
+ Na
2
S
2
O
2
DMSO
60
o
C, 8 hrs.
99%


Treatment of 8,9-dibromodispiro[2.0.2.4]decane with potassium t-butoxide in DMSO gives spiro[2.0.2.4]dec-8
ene (7153):
Br
Br
t-BuOK, DMSO
room temperature, 20 hrs



Another dibromide can be dehalogenated by heating with zinc dust in DMSO (7184):
OAc
OAc
OAc
OAc
Br
Br
DMSO, Zn
90
o
, 2.5 hrs
100%




Heating trans- Į, ȕ-dibromo derivatives of diphenylethylene and meso-stilbene with potassium fluoride and cesium fluoride in
DMSO afford quantitative yields of diphenylacetylene and trans-stilbene, resp., via the intermediacy of dimsyl ion. These
reactions do not occur in N-methylpyrrolidone, DMF, or sulfolane (9338):
Ph
Br
Ph
Br
PhC CPh
DMSO
KF or CsF
Ph
Br
Ph
Br DMSO




The action of zinc-copper couples on perfluoroiodoalkanes, C 4 F 9I, C6 H33I and CsF17I, has been studied in aprotic solvents,
such as DMSO. A mixture of perfluoroolefins results (9928),
'
e. g.
C
4
F
9
I
F
F
3
C
CF
3 F
CF
3
F
F
3
C
F
+ C
4
F
9
H
+
Zn-Cu, DMSO
80
o
C
39% 21%
20%




54
Some dehalogenation reactions using potassium t-butoxide as the base have been reviewed (6815).

4. Dehydrohalogenation
A variety of bases have been used in the dehydrohaloge nation reaction. The most frequently used base has beer potassium t-butoxide,
followed by other alkoxides. Other bases used include: sodium and potassium hydroxide the carbonate and bicarbonate ions, quaternary
ammonium hydroxide, dimsyl ion, sodium cyanide and some relatively weak organic bases, such as ammonia and amines.
The effects of base strength and size upon the orientation in base-promoted ȕ-elimination reactions have beer studied
(6234)(6378)(6818)(8582)(10011).
Ionic association in base-promoted ȕ-elimination reactions has been reviewed (8050).

a) Potassium t-butoxide in dehydrohalogenations
The enhanced basicity of potassium t-butoxide in DMSO has been suggested as the dominant factor which causes dehydrobrominations
to occur much more readily in DMSO than in t-butanol (652).

The reaction of benzhydryl chloride with potassium t-butoxide in t-butanol occurs slowly by displacement giving benzhydryl t-butyl ether,
whereas the base in DMSO causes a very rapid elimination( Į-elimination) giving nearly quantitative yields of tetraphenyl ethylene (696).
The rapid reaction is suggested to occur by an initial formation of the carbanion which eleminates chloride ion to give a carbene
intermediate, as shown below:
[Ph
2
CCl]
-
K
+
PhC: + Cl
-
+K
+
Ph
2
C: + Ph
2
C: (or [Ph
2
CCl
-
])
Ph
Ph
Ph
Ph
DMSO
DMSO



The rate of dehydrobromination of 2-arylethyl bromides with potassium t-butoxide in t-butanol-DMSO mixtures increases with
increasing DMSO concentration at a much faster rate than the increase of acidity function (833).
The strongly basic reaction medium obtainable with potassium t-butoxide in DMSO in the case of aromatic bromine compounds
produces aryne intermediates (434)(514) (see also Displacement reactions Alkoxide Ion, Aromatic halide displacement, p. 20).
2,7-Dichlorobicyclo[2.2.1 ]heptane on treatment with potassium t-butoxide in DMSO gives 7-chlorobicyclo[2.2.1] heptene (3360):
Cl
Cl
t-BuOK, DMSO
room temperature
3.5 days
Cl
96%



Olefinic products from reactions of a series of 2-bromoaIkanes with potassium t-butoxide are produced. The transcis 2-alkene ratio is
dependent upon the alkyl group of the 2-bromoalkane (3368):
H
2
CR
Br
CH
3
RH
2
CHC CH
2
CHCH
3
RHC
+
t-BuOK, DMSO
30-90
o
C


The trans-1 -iodocyclopropylpropene reacts at least ten times faster with potassium t-butoxide in DMSO than the cis isomer to yield 1
-cyclopropyl-2-methylacetylene (3503)(4176):
H CH
3
I
H
CH
3
I
CH
3
t-BuOK, DMSO
t-BuOK, DMSO
slow
fast
trans
cis



Six or seven-membered trans-cycloolefins may be transformed into the corresponding 3-alkoxycycloalkynes by reaction with
potassium t-butoxide in DMSO (3707):
Br
OR
(CH
2
)n
OR
(CH
2
)n
t-BuOK, DMSO
20
o
C, few seconds
or minutes
60-74 %


n = 5 or 6

55
The reaction of 1,1 -dichloro-1 -cyclopropylethane with potassium t-butoxide in DMSO gives 1 -cyclopropylacetylene
(5594):
Cl
Cl
CH
3
t-BuOK, DMSO
room temperature
34%



Similarly, treatment of pinacolone dichloride with potassium t-butoxide in DMSO produces tert-butylacetylene in high yield (7608):

(H
3
C)
3
CC Cl
H
3
C
Cl
(H
3
C)
3
C CH
95+%
t-BuOK, DMSO
below 40
o
C


3,3-Dimethylcyclopropene is easily produced from 1 -bromo-2,2-dimethylcyclopropane (7028):

CH
3
H
3
C
CH
3
H
3
C
H
Br
t-BuOK, DMSO
90
o
C, 3hrs
84%



1-Bromo-2-chloro-2,2-difluoro-l-phenylethane reacts with potassium t-butoxide to give Į-bromo- ȕ, ȕdifluorostvrene (5980):
Ph
Br
F
Cl
F
Ph
Br
F
F
t-BuOK, DMSO
50
o
C, 4 hrs.




cis-3-Bromocyclodiene is easily dehydrobrominated to 1,2-cyclodecadiene (8960):

C (CH
2
)
7
78%
Br
t-BuOK, DMSO
20
o
C, 5 min.



Dehydrofluorinations can also be accomplished with potassium t-butoxide in DMSO (5118):
H
F H
F
F
H
t-BuOK, DMSO
120
o
C, 24 hrs.




b) Other alkoxides in dehydrohalogenations
Other alkoxides, such as sodium and potassium methoxides or ethoxides, have been used with good results in dehydrohalogenation
reactions.
The olefinic products observed in reactions of sodium ethoxide or 2,2,2-trifluoroethoxide with 2-butyl iodide, bromide and chloride in
DMSO are reported (3853):
X
CH
3
H
3
CH
2
CHC CH
2
CHCH
3
H
2
CHC
NaOC
2
H
5
(or NaOCH
2
CF
3
), DMSO
25
o
C, 10 min
+
2-butene
1-butene


X = I, Br, Cl

In all cases in the above reaction, the change from ethoxide to 2,2,2-trifluoroethoxide results in a decrease in the percent 1 -butene
(3853).
Treatment of 3-chloro-3,4-dihydro-2,2-dimethoxypyrans with an excess of sodium ethoxide in DMSO produces the corresponding Į-
pyrones (5834). (7737):

56
O R
3
R
2
R
1
O R
3
R
2
R
1
OCH
3
OCH
3
Cl
O
NaOCH
3
, DMSO
room temp., few hours



The addition of DMSO to the NaOCH -CH3OH medium causes a significant increase in the rate of dehydrochlorination of Ph2CHCH2Cl
(9142)(9143). Although double dehydrobromination of 2,6,6-bis-(ethylidenedioxy)-3,7-dibromobicyclo[3.3.0]octane with ethanolic
potassium hydroxide requires refluxing for several days for complete reaction, the elimination may be effected in several hours with
sodium methoxide in DMSO (9604):
O
O
O
O
O
O
O
O
Br
Br
NaOCH
3
, DMSO
60-70
o
C, 2.5 hrs
89-92%



c) Dimsyl ion in dehydrohalogenations
Treatment of 1-acetylnaphth-2-yl 2'-chloroallyl ether with dimsyl ion in DMSO yields 1-acetylnaphthyl-2-yl propargyl ether which cyclizes
to 2-methyl- l,4-phenanthrenequinone (7552):
O
O
O
O
O
O DMSO
CH
2
SOCH
3
30% 55-60%



Reaction of 2,2-dimethyl-3-dimethyl-3-chloro-3-butenoic acid with dimsyl sodium in DMSO gives 2,2-dimethyl-3-butynoic acid (7865):

Cl
CH
3
CH
3
CO
2
H
CH
3
CH
3
CO
2
H
CH
2
SOCH
3
DMSO 50
o
C, 5 hrs
88%


In some cases, potassium t-butoxide is a better dehydrohalogenating agent than the dimsyl ion. Thus, the dimsyl ion can act as a
dehalogenating agent for vicinal dibromides (455):
Br Br
Br Br
CH
2
SOCH
3,
DMSO
t-BuOK, DMSO
37%
78%
+ styrene
22%


d) Hydroxylic bases in dehydrohalogenations
Hydroxylic bases, such as sodium hydroxide, potassium hydroxide and tetraalkylammonium hydroxide have been used for ȕ -
dehydrohalogenation reactions (8050). Tetra methylammonium hydroxide is more soluble in DMSO than either sodium hydroxide
or potassium hydroxide (see Table IX). Thus, 1,1,1 -chlorodifluoroethane can be dehydrochlorinated to vinylidene fluoride in high
yield in heterogeneous DMSO suspensions or aqueous DMSO suspensions or solutions in the presence of sodium hydroxide,
potassium hydroxide or tetramethylammonium hydroxide (5279), e.g.:
H
3
CCClF
2
+ NaOH
H
2
C CF
2
DMSO + H
2
O (5%)
50
o
C
69.8 % conversion
99.5% selectivity


DMSO is a better reaction medium for the above reaction than some other solvents.
Methyl halogenated ethyl sulfides can be dehydrohalogenated with potassium hydroxide in DMSO (3142), e.g.


57
S
F
F
H
F
Cl
+ KOH H
3
CFSC CFCl
DMSO
room temperature





6-Hydroxy-2-isopropenyl-5-acetylcoumaran can be obtained from the corresponding vinyl bromide by dehydrohalogenation with
potassium hydroxide and cyclization in DMSO (4892):
O
Br
OH
O
OH
O
O
42%
KOH, DMSO
20
o
C



Relatively high yields of alkynes can be obtained from Į, ȕ-dihalides or Į, Į-dihalides in short reaction times at moderate temperatures
in DMSO using moderately strong bases, such as potassium hydroxide, without isolation of the intermediate olefin (8238), e.g.:
Cl
Br
(H
3
C)
3
CHC CHCl
(H
3
C)
3
C CH
DMSO, KOH
130-160
o
C
91%



e) Weak bases in dehydrohalogenations
Although potassium t-butoxide in DMSO is an extremely strong and reactive base-solvent system, sometimes undesirable reactions take
place after dehydrohalogenations. Thus, the freshly formed olefins tend to isomerize, and carbanions can be generated which can
decompose in various ways (4180)(6163).
Dehydrohalogenations without olefin isomerization can sometimes be accomplished by using weaker bases, such as carbonates,
cyanides, or amines.
Thus, the treatment of 1,3-dibromo-1,3-diphenylcyclobutane with sodium cyanide in DMSO produces 1,3diphenylcyclobut-2-enyl
cyanide (4077):
Br
Ph
Br
Ph
Ph
CN
DMSO-CH
3
CN
NaCN
Ph


In the above reaction, both the ȕ-elimination and displacement (substitution) reactions take place.
3,3-Dibromo-6-dibromomethyl-5-carbethoxy-2,3-dihydro-2-methyl-4H-pyran-4-one with sodium carbonate in DMSO yields 3-bromo-6-
dibromomethyl-5-carbethoxy-2-methyl-4H-pyran-4-one (6215):
O
CO
2
C
2
H
5
H
3
C
Br
Br
CHBr
2
O
CO
2
C
2
H
5
H
3
C CHBr
2
Br
+ Na
2
CO
3
DMSO
20
o
C, 3 hrs
55%



3-Alkylthio- or3-arylthio-4-chlorothiolane 1,1-dioxide can be dehydrohalogenated when warmed with triethyl. amine in DMSO (385):








5. Nitrogen Elimination
Elemental nitrogen can be eliminated from a number of compounds by heating in DMSO in the presence or absence of bases. Usually
these are compounds that contain the nitrogen-nitrogen bond, such as hydrazones, hydrazides, carbazides, azo compounds,
O
SR
O
SR
Cl
60-90%
DMSO
90
o
C, 2 hrs.
+(C
2
H
5
)
3
N

58
diazomethane derivatives, azides, diazonium salts and others.
Addition of hydrazones of aldehydes and ketones to a solution of potassium t-butoxide in DMSO produces an immediate evolution of
nitrogen and formation of the corresponding hydracarbons in 60-90% yields. The reaction of the benzophenone hydrazone is typical
(495).
Ph
2
C NNH
2
PH
2
CH
2
+ N
2
t-BuOK, DMSO
25
o
C



The above reaction, the so-called Wolff-Kishner reduction in DMSO, can be run even at room temperature.
The rate of the Wolff-Kishner reaction of benzophenone hydrazone in mixtures of butyl carbinol and DMSO in the range of 100-190°C
increases as the concentration of DMSO is increased, but this effect passes through a maximum. The maxima tend to drift
toward higher DMSO concentrations as the temperature is lowered (377).
The thermal decomposition of norbornan-2-one and norborn-5-en-2-one tosylhydrazone sodium salts has been studied over the
temperature range 100-150
°
C in DMSO and two other solvents. First order kinetics have been observed in all cases (8955):

N-N-OTs + N
2
+ OTs
-
DMSO
117.5
o
C


Treatment of 1-acylsemicarbazides in DMSO with air or oxygen gives rise to carboxamides in good yields (3721):

R'
O
N
H
H
N
O
H
N
R"
R' N
H
R"
O
+ N
2
+ CO
O
2
, KOH, DMSO
100-110
o
C



Thermal decomposition of two azobisamidines and their conjugate acids has been studied in DMSO (4748).
Rate coefficients are reported for the reaction of diazodiphenylmethane with benzoic acid and its orthosubstituted derivatives in DMSO
and other solvents (2765):
Ph
2
CN
2
+ RCO
2
H RCO
2
CHPh
2
+ N
2
DMSO
30
o
C


Thermal decomposition of several diazirines has also been investigated in DMSO (4906)(5635), e.g.
N
N
Cl
Ph
NN
Cl
Ph
DMSO
60-90
o
C
N
2
+ PhClC
diazirine
Ph
Cl


Sodium azide in DMSO reacts with Į-bromophenylacetonitrile to yield benzonitrile (10077):

Ph
Br
CN
+ N
3
-
PhCN + N
2
+ CN
- DMSO
90%


Diazonium salts can be prepared in DMSO by diazotizing primary amines with sodium nitrite. In the case of benzylamine, benzaldehydes
can be prepared in good yields (167), e.g.:
R
NH
2
R
CH
2
DMSO
-N
2
, H
2
O
+ OS(CH
3
)
2
+ NaNO
2
+ H
+


R
C
H
2
S
CH
3
CH
3
R
CHO
+ CH
3
SCH
3


Benzenediazonium tetrafluoroborate in DMSO decomposes instantaneously with evolution of nitrogen upon addition of a DMSO solution
of choline or tetramethylammonium hydroxide (5124):

N
2
+
X
X
+N
2
+
OH
-
, DMSO
20
o
C


59
When p-nitrobenzenediazonium tetrafluoroborate is decomposed in the presence of DMSO-benzene or DMSOnitrobenzene systems, the
respective biphenyl derivatives are obtained in good yields (5642).
The dediazotization of aromatic diazonium ions has been reviewed in various solvents, including DMSO (9423).

6. Sulfenate Elimination
The t-butoxide ion or dimsyl ion in DMSO has been used to eliminate sulfenates from sulfoxides to produce olefins in moderate to high
yields (501)(203)(672). When a number of 3-phenyl-2-alkylpropyl sulfoxides is allowed to react in DMSO with a large excess of dimsyl
sodium, cyclopropanes and olefins are formed (396)(2842):
+ H
2
CSOCH
3
DMSO
60-70
o
C, 48 hrs.
CH
3
SO
-
Ph
R
Ph
R
CH
2
SOCH
3
+

When isomeric 2-phenylsulfinyl-1,2-diphenyl-l-ethanols are pyrolyzed in DMSO in the presence of trace quantities of pyridine,
deoxybenzoin is formed (4776):
PhCHCHPh
S
OH
Ph O
pyridine, DMSO
119
o
C
PhC=CHPh
OH
PhCCH
2
Ph + PhSOH
O


3-Phenylindole is obtained from ȕ-hydroxysulfoxide on treatment of the latter with dimsyl ion in DMSO (5300):
OH
Ph
SOCH
3
NH
2
N
Ph
H
+ H
2
CSOCH
3
DMSO


7. Sulfonate Elimination
Various bases have been used in the reaction of sulfonate esters of primary and secondary alcohols to give alkenes. Some of these
bases are potassium t-butoxide, sodium methoxide, potassium ethoxide, phenoxides, and others. In a few cases, elimination reactions
involving sulfonate esters have been achieved without the presence of a base by the action of heat alone.

a) Potassium t-butoxide in sulfonate elimination
Most ȕ-eliminations involving sulfonate esters seem to have been investigated with potassium t-butoxide as the base. Sulfonate esters
of cyclic and secondary acyclic alcohols react rapidly with potassium t-butoxide in DMSO at 20-25°C to give about 80% yields of alkenes
and no appreciable quantities of ethers. Esters of normal primary alcohols and of cyclohexylcarbinol give only 20-25% alkenes and 60-
70% ethers, as the result of displacement reactions in the latter case (491).
Mesylate and tosylate derivatives of cholesterol, all easily prepared, undergo facile reactions in DMSO at room temperature to afford
excellent yields of dienic materials (965).

Treatment of the tosylate of (+)-(S)-3-methyl-7-deutero-octen-4-ol-7 with potassium t-butoxide in DMSO yields (+)-(S)-cis,trans-3-
methyl-7-deuterooctadiene-4,6 (3482):

D H
3
C
OTs
CH
3
D
t-BuOK, DMSO
80
o
C



The tosylate of cyclohexanol-2,2,6,6-d4 on treatment with potassium t-butoxide gives cyclohexene-1,3,3-d3 (3584) :
D
D
OTs
H
D
D
D
D
D
t-BuOK, DMSO
room temperature
36%


5,6 Dimethylenebicyclo[2.2.0]hexene-2, the Dewar o-xylylene, can be obtained by reacting the corresponding ditosylate with potassium
t-butoxide in DMSO (3827):

60
OTs
OTs
CH
2
CH
2
t-BuOK, DMSO
room temp.
40%

When 4- hydroxy-trans-bicyclo[5.1.0] octane p-bromobenzene-sulfonate is treated with potassium t-butoxide in DMSO, it is rapidly
converted to trans-bicvclo[5.1.0]oct-3-ene (4039):
OBs
H
t-BuOK, DMSO
20-25
o
C, 30 min.


When 2-butyl and 2-pentyl halides or tosylates are treated with tetraethylammonium fluoride in acetonitrile, an olefin forming elimination
takes place and an overwhelming Saytzeff orientation is observed. These results are compared with results of the elimination in other
base-solvent systems, including potassium t-butoxide in DMSO (4524).
The reaction of trans-2-methylcyclooctyl tosylate with potassium t-butoxide in DMSO for 30 min at 25
°
C yields cis-3-methylcyclooctene,
93%, and cis-1 -methylcyclooctene, 4%. With t-butenol as the solvent, the ratio of the isomers is 2:1.
An approximately equimolar mixture of bicyclo[5.2.0]non-1 (9)-ene and bicyclo[5.2.0]non-8-ene is obtained by treatment of 8-
methanesulfonyloxybicyclo[5.2.0]nonane with potassium 1-butoxide in DMSO (9727).

t-BuOK, DMSO
20
o
C, 15 hrs.
OMs
65% total


b) Sodium methoxide in sulfonate elimination
Benzenesulfonates of typical primary and secondary alcohols react rapidly at room temperature with sodium methoxide in DMSO to
give high yields of alkenes and/or alkyl methyl ethers. Except for cyclohexyl benzenesulfonate, the ether-alkene ratio is higher in
reactions with sodium methoxide than with potassium t-butoxide. This indicates that the displacement reactions are favored over
elimination reactions with sodium methoxide in most cases (580).
1,3 -Dimethoxypropene can be obtained from p-toluenesulfonate of 1,3-dimethoxy-2-propanol by means of sodium methoxide in DMSO
in good yield with cis/trans ratio of 2.1:1. Evidently little of the displacement reaction goes on (3875):
CH
2
OCH
3
CH
2
OCH
3
TsO
CH
2
OCH
3
CHOCH
3
NaOCH
3
, DMSO
71%



A double bond in a cyclic system, a precursor of dl-juvabione, is introduced by treatment of a tosylate with sodium methoxide in
refluxing methanol containing 10% DMSO (6947).

c) Other bases in sulfonate elimination
When cyclohexyl tosylate is reacted with potassium t-butylmercaptide in DMSO, cyclohexene is the major product. However potassium
t-butoxide reacts much more ranidly than the mercaptide (496).
The effect of base strength upon orientation in base prompted elimination reactions has been studied. 2-Butyl p-toluenesulfonate is
reacted with the following bases in DMSO: potassium t-butoxide, potassium ethoxide, potassium phenoxide, potassium 4-
methoxyphenoxide, potassium 4-nitrophenoxide and potassium 2nitrophenoxide. The results are completely consistent with a correlation
between orientation and base strength (882).
The trans:cis olefin ratios have been determined for the elimination reactions of 1-benzylethyl tosylate, PhCH2CH(OTs)CH3, in different
base-solvent systems. The basicity of the nucleophile does not appear to significantly affect the trans:cis ratio (8372).

d) Sulfonate elimination without a base
DMSO has been found to be an excellent non-reacting solvent for the decomposition of (-)-menthyl, ȕ-cholestanyl, cyclohexyl and 2-
octyl aryl-sulfonates to the corresponding olefins. The sulfonates are heated at 89-91°C for 6 hours without a base (408).
The elimination reactions of some secondary acyclic and medium sized ring cyclic alcohol tosylates carried out in DMSO at 50
°
C and
90-95
°
C show that olefins are formed, especially with secondary alcohol tosylates.

8. Water Elimination-dehydration
Many alcohols can be dehydrated in DMSO to olefins. Certain diols when heated in DMSO lead to cyclic ethers. A group of tertiary
alcohols, such as 2-alkylcycloalkanes, at 160-190
°
C for several hours in DMSO give endocyclic olefins, 1 -alkylcycloalkenes, as the
major products. Thus, 1 -methylcyclopentanol gives only 1 -methylcyclopentene (394):

61
CH
3
OH
DMSO
160
o
C
6 hours
CH
3
88%


When certain diols are heated in DMSO, cyclic ethers result instead of the expected dienes (395). When 1,4-butanediol, 1,5-pentanediol
and 1,6-hexanediol are heated, using 2 moles of alcohol per mole of DMSO, the corresponding heterocycles, tetrahydrofuran (70%),
tetrahydropyran (47%), and oxepane (24%) are formed (394):
HOCH
2
(CH
2
)nCH
2
OH
DMSO
190
o
C
14-24 hrs.
(nH
2
C)
H
2
C
O
C
H
2
24-70%
n=2, 3, 4
2,4-Di(2-hydroxy-2-propyl)cyclohexene can be selectively dehydrated to 2-(2-propenyl)-4-(2-hydroxy-2-propyl)1-cyclohexene in DMSO
(4775):
DMSO
190
o
C
1.5 hrs. 80%
HO OH
OH



Heating of 2,2,3,3-tetramethylbutane-1,4-diol in a sublimation apparatus in DMSO gives the tetrahydrofuran (4934) :
CH
2
OH C C CH
2
OH
CH
3
CH
3
CH
3
CH
3
DMSO
160
o
C
16 hrs.
H
2
C
CH
2
O
42%
H
3
C
CH
3
H
3
C
H
3
C



In the dehydration of 1,4-diols, a cyclic transition state with DMSO has been postulated (395)(6098):
O
O
S
O
H
CH
3
CH
3
H
3
C
CH
3
H



When sec- or tert-benzylic alcohols or tert-aliphatic alcohols are heated in DMSO at 160-185° C for 9-16 hours, dehydration produces
olefins in 70-85% yields (405), e.g.
PhCHCH
2
CH
3
OH
DMSO
160
o
C
16 hrs.
PhCH=CHCH
3
79%


2,2-Dimethyl-3(2H)-furanone can be obtained by dehydrating the corresponding 5-hydroxy compound on heating in DMSO (4755):
O
O
HO
O
O
DMSO



2-Methoxy-4,5-dimethylstilbene is obtained by heating 2-methoxy-4,5-dimethylphenylbenzylcarbinol in DMSO (9605):

62
OCH
3
CH
2
OH
CH
3
H
3
C
OCH
3
CH
3
H
3
C
Ph
Ph
DMSO
150
o
C
9.5 hrs
80%




One of the key features of the stereoselective and regioselective total synthesis of two naturally occurring fungitoxic hydroquinones (±)-
zonarol and (±)-isozonarol is the dehydration of a tertiary alcohol to an alkene without rearrangement (9780):
H
HO
H
DMSO
155
o
C, 16 hrs
77%



In some cases, the dehydration is achieved in DMSO in the presence of an inorganic acid. Thus, the lactonization of a hydrolyzed
terpolymer can be carried out by reacting the polymer in the presence of a very small quantity of concentrated sulfuric acid in DMSO
(2265):
HO
H
3
C
CH
2
OH
HO
2
C
CO
2
H
HO
2
C
HO
H
3
C
CO
2
H
HO
2
C
O
O
H
2
SO
4
, DMSO
65
o
C, 100 hrs


Potassium hydrogen sulfate in DMSO is an effective medium for elimination of water from some intermediate hydroxy derivatives in the
preparation of various C19 analogs of retinoic acid (4235):
R
OH
R
KHSO
4
, DMSO
140-160
o
C
18-40 min


Dehydration of 4-(1 -hydroxyethyl) biphenyl in DMSO in e presence of a small amount of potassium hydrogen sulfate and hydroquinone
gives p-phenyl-styrene (7867):
190C
several hours
OH
KHSO
4
, DMSO
82%


Dehydration of a diol can also be accomplished by using the triethylamine-sulfur trioxide complex in DMSO (7080):

OH
OH
O
Et
3
N / SO
3,
DMSO
15
o
C, 15 minutes




ISOMERIZATION REACTIONS
These are base-catalyzed reactions that convert olefins and other unsaturated compounds into molecules with different atomic
arrangement. Included are also racemization reactions: the conversion of half a given quantity of an optically active compound into one
enantiomer.
1. Acetylene Isomerization
The enhanced rate of base catalyzed isomerization in DMSO can be used to control the direction of a cyclization of acetylenes (600).
When propargyloxyethanol is cyclized in DMSO in the presence of sodium hydroxide, 2-vinyl -1,3-dioxolane and 2-methyl-l,4-dioxene
are the major products (101):


63
HC CCH
2
OCH
2
CH
2
OH H
2
C C CHOCH
2
CH
2
OH
HC COCH
2
CH
2
OH
O
O
O
O
DMSO
NaOH

Treatment of an acetylenic compound with potassium tert-butoxide in DMSO gives the corresponding allenic compounds (2239):
R
H
C C C(A)-R'
t-BuOK, DMSO
30
o
C
R C C CH(A)-R'

R = Alkyl or phenyl, R'= H, alkyl or phenyl, A=Alkoxy, phenoxy, alkylthio, phenylthio, dialkyulamino, etc.


3-Phenylpropyne undergoes in DMSO a dimsyl ion-catalyzed isomerization with very little H-D exchange with the solvent (2987):
PhH
2
CC CH
D
2
CSOCD
3,
(CD
3
)
2
SO
PhHC C CH
2


4-Alkoxy-4-alkyl-1 -t-butoxy-2- butyne, when heated with catalytic amounts of potassium t-butoxide in DMSO, is isomerized to allenic
diethers (4257):
C CCH
2
OtBu
R'
RO
C CHOtBu
R'
RO
50-78%
t-BuOK , DMSO


Similarly, 3-alkoxy-l -phenylpropynes are isomerized in DMSO under the catalytic influence of potassium tert-butoxide to give 3-alkoxy-1
-phenylallenes (4258):
Ph
OC
2
H
5
R
t-BuOK , DMSO
C Ph
OC
2
H
5
R
PhHC
H
O
R
40-67%




The rates of base-catalyzed isomerization of a series of 1,3,3-triphenyl- prop-1-yne and [3-
2
H]-1,3,3-triphenylprop1-yne, have been
measured in aqueous DMSO containing tetramethylammonium hydroxide and give linear correlations with the acidity function for the
medium (5864).
Pure 2-alkynes are obtained upon heating 1-alkynes with sodamide in DMSO (6510):
CH RH
2
C
CH
3
R
NaNH
2
, DMSO
65-70
o
C, 21 hrs. 90-94%
R=alkyl



2. Allyl Group Isomerization
The isomerization of allyl ethers to propenyl ethers occurs 1000 times faster in DMSO than in dimethoxyethane and 10,000 times faster
than in dimethoxyethane-t-butanol mixtures (481). This facile isomerization of allyl to easily hydrolyzed propenyl groups.enables the use
of allyl groups as blocking agents (10043). For example, 9-allyladenine is isomerized with potassium t-butoxide in DMSO to the propenyl
compound which is then easily hydrolyzed to regenerate the amino group (941):
N
N
N
N
N
N
N
N
t-BuOK , DMSO
100
o
C, 20 min.
82%



The allyl group of a glycoside can be isomerized to the prop-1 -enyl group by the action of potassium t-butoxide in DMSO, without
affecting phenyloxazine group (8951):
O
O N
R OCH
2
CH
Ph
O
O N
R OCH
Ph
t-BuOK , DMSO
20
o
C, 26 hrs.
CHCH
3
77%
CH
2

3. Diene, Triene Isomerization
Unconjugated dienes can be converted to the conjugated isomers by treating them with a strong base in DMSO. Thus, the treatment of 2-
bromo-1,3-cyclohexadiene (I) with potassium t-butoxide in DMSO yields a mixture of 79% 1-bromo-l,3-cyclohexadiene (II) and 21 % of I.

64
The difference in free energy between I and II appears to be the result of greater conjugation of bromine with cyclohexadiene system in 11
(596):
Br
Br
t-BuOK , DMSO
75
o
C, 8 hrs.
II.
I.



Several unconjugated dienamines on treatment with potassium t-butoxide in DMSO produce the conjugated dienamine by a pivoting of
the double bond around the carbon carrying the nitrogen atom (4018):

OCH
3
OCH
3
t-BuOK , DMSO
N
N


2-Methyl-1 -(tetramethylcyclopropylidene)propene is isomerized with potassium t-butoxide in DMSO to give 2methyl-3-
(tetramethylcyclopropylidene)propane (4126):

C
H
3
C
H
3
C
CH
3
CH
3
CH
3
CH
3
H
3
C
CH
3
CH
3
CH
3
CH
3
64%
t-BuOK , DMSO
100
o
C , 2hr.

Unsaturated fatty acid esters containing conjugated double bonds are manufactured by isomerization from the esters with
unconjugated double bonds by heating them with alkali metal alkoxides in DMSO (8906).

Steroids have been isomerized with a base in DMSO (3272)(2323). Thus, 19-hydroxy- ǻ
4,6
-3-keto steroids are deconjugated to ǻ
4,7
-3
ketones by treatment with sodium methoxide in DMSO (4311):
O
HOH
2
C
O
HOH
2
C
NaOCH
3
, DMSO
room temp.
several min.



Sodium methoxide catalyzed deconjugation of cholesta-1,4-6-trien-3-one in DMSO to cholesta-1,5,7-trien-3-one is a key step in a
reported route to 1- Į -hydroxy-vitamin D3 (10048).
1,3,6-Octatrienes and 1,3,7-octatrienes are isomerized to 2,4,6-octatriene in 70-85% yields with hydroxide bases in DMSO (3379).

4. Olefin Isomerization
The isomerizations of simple alkenes (e.g. pentene-1,hexene-1) with potassium t-butoxide do not occur in tert-butanol, THF or 1,2-
dimethoxyethane. However, in DMSO with potassium tert-butoxide as the base, 1-olefins can be converted to 2-olefins, e.g. 2-
methylpentene to 2-methylpentene-2 (579):
H
3
C
H
3
CH
2
CH
2
C
H
3
CH
2
CHC
CH
3
CH
3 t-BuOK , DMSO




S-(2-propenyl)-L-cysteine is isomerized to cis-S-(1 -propenyl)-L-cysteine by reaction in potassium tert-butoxide and DMSO (1001):


H
2
C CHCH
2
SCH
2
CH(NH
2
)CO
2
H
t-BuOK , DMSO
H
3
CHC CHSHCH
2
CH(NH
2
)CO
2
H
60%
25
o
C , 18 hrs.


Į-Pinene can be converted to ȕ -pinene by using potassium hydroxide and DMSO (480)(7229):
KOH , DMSO
110-190
o
C
0.5 - 6 hrs.
4-6%


65
Similarly, (+)-sabinine isomerizes to an equilibrium mixture of 91 % (-)- Į-thujene and 9% (+)-sabinine under the influence of
potassium t-butoxide in DMSO (2998):
t-BuOK ,DMSO
90
o
C, 2 hrs.
(-)-D-thujine (+)-sabinine






Isomerization of a mixture consisting of 17.4% 1 -methylcyclopropene and 81.3% methylenecyclopropane with potassium t-butoxide
and t-butanol in DMSO produces a 98% pure methylenecyclopropane (4262):
t-BuOK ,DMSO
50-60
o
C
70%



5. Racemization
In the racemization of saturated compounds by exchange of hydrogen at an asymmetric carbon, the rate of racemization correlates
well with the acidity function of the reaction system containing DMSO (944). Similarly, the base-catalyzed rate of hydrogen-deuterium
exchange correlates well with the racemization rate (1501). In solvents of high dissociating power which are not proton donors, e.g.
DMSO, the carbanion (obtained with potassium t-butoxide) is long enough lived to become symmetrically solvated, and electrophilic
substitution gives a racemic product (1161).
A variety of active functional groups can be attached to the saturated asymmetric carbon atom.
a) Alcohols
When optically pure tertiary alcohols with an asymmetric carbon atom are treated with a strong base in DMSO, the predominant
steric course is racemization (1162)(2589).
b) Alkyl halides
The reduction of optically active tertiary alkyl halides with sodium borohydride in DMSO proceeds with racemization presumably via
an elimination mechanism (3519):
H
3
C
H
3
C
CH
3
H
3
C
Cl
CH
3
C
2
H
5
DMSO
8 NaBH
4
H
3
C
H
3
C CH
3
H
3
C
H
CH
3
C
2
H
5
Racemic 2,7-dimethyl-octane
(-)-(R)-3-chloro-3,7-dimethyloctane



c) Amides, amino acids
D- Į -Acetamide- Į -vanillylpropionitrile is racemized using sodium cyanide as the base and DMSO as the solvent to give 96-97%
pure DL- Į -acetamido- Į -vanillylpropionitrile (7772)(7984):
H
3
CO
HO
NH
H
3
C
CN
O
CH
3


Optically active N-acylamino acids are racemized nearly quantitatively by heating with DMSO (8418).

d) Esters
The racemization and solvolysis of (+)-methyl 1 -cyano-2, 2-diphenyl-cyclopropane carboxylate has been studied in DMSO and six
other solvents. In DMSO, racemization is the dominant reaction (6287).

e) Ethers
Potassium t-butylmercaptide in DMSO is a weaker kinetic base system than potassium t-butoxide in DMSO or than dimsyl sodium in
DMSO in the racemization of optically pure (-)-1-methoxyphenylethane (496):





Rate constants for racemization of (-)-4-biphenyl-methoxyphenylmethane in methanol-0-d-DMSO-d6 catalyzed by potassium
methoxide have been measured (2007).
Ph
H
H
3
CO
CH
3
Ph
C
CH
3
H
3
CO
Ph H
H
3
CO
CH
3
DMSO
B
-
DMSO
BH
+ B
-

66

f) Hydrocarbons
The results of H-D exchange and racemization of (-)-9-deuterio-9-methyl-2-trimethylammonium fluorene iodide in t-butanol-DMSO
catalyzed by tripropylamine are reported. Exchange (69%) and racemization (69%) take place
(5339):
H(D)
CH
3
N(CH
3
)
3
I


D-tetramisole or its 1 -tetramisole enantiomer is racemized in DMSO solution in the presence of a catalytically effective amount of
potassium hydroxide (10315):
N
N S
Ph




g) Nitriles
Racemization of 2-methyl-3-phenylpropionitrile in DMSO can proceed 1,000,000 times faster than in tert-butanol in the presence of the
same base (434)(944).
The mechanism of base-catalyzed racemization of Į-acetamidonitriles bearing no enolizable Į-hydrogen has been studied in DMSO
and found to proceed via elimination and readdition of the elements of HCN (2013).
The base catalyzed racemization of 2,2-diphenylcyclopropylnitrile (1) has been studied in solvents containing various amounts of
DMSO. With sodium methoxide as the base and nitrile 1 as a substrate, the rate for racernization in 1.5 mole % methanol-98.5 mol %
DMSO is 3.6 x 10
8
times that observed in methanol (7282):

Ph
Ph
CN
H
Ph
Ph
H
CN
-OCH
3
, DMSO
(-) -1
(+) -1


h) Sulfones
When the 2,2-dimethyl-1-phenylsulfonylcyclopropane is heated in DMSO for 6 hours at 175
°
C the material is 88% racemized (2035):

H
3
C
H
3
C
CO
2
CH
3
SO
2
Ph



C. OTHER REACTIONS IN DMSO ADDITION REACTIONS
These are additions of nucleophilic compounds to carbon-carbon double bonds, carbon-carbon triple bonds, carbon-nitrogen triple
bonds and others.
In a number of cases the use of DMSO improves the rate of addition of nucleophiles to olefins, such as acrylonitrile. The rate of
addition of the glycine anion to acrylonitrile in an aqueous buffer is increased 200-fold by adding an equal amount of DMSO to the
buffer (1233). Similarly, the cyanoethylation of methanol using potassium methoxide catalysis in methanol-DMSO occurs at a rate
greater than in several other aprotic solvents. The order of effectiveness of the solvents for this reaction is also the order of their
hydrogen bonding strength (1591).

a) Additions to acetylenes (carbon-carbon triple bonds)
The DMSO anion (dimsyl sodium) adds to diphenyl acetylene to give a 95% yield of a cis-trans mixture of the expected
unsaturated sulfoxide (203):

PhC CPh
H
Ph
Ph
CH
2
SOCH
3
H
Ph
CH
2
SOCH
3
Ph
+ Na
+
CH
2
SOCH
3
DMSO
room temp.
95%
+

When the addition is conducted at 40
°
C, the reaction consumes 2 moles of the DMSO anion with elimination of two methane
sulfenate groups to give 2,3-diphenyl-1,3-butadiene (203):
PhC CPh
+ Na
+
CH
2
SOCH
3
DMSO
40
o
C
Ph
CH
2
Ph
CH
2
28%


67
Ethyl phenylpropiolate reacts readily with dimethyloxosulfonium methylide to give 91 % of a stable ylide (217):
PhC CO
2
C
2
H
5 PhC
HCO
2
C
2
H
5
C
(H
3
C)
2
SOCH
2
SO(CH
3
)
2
91%

The addition of alkoxides to triple bonds in DMSO has been examined in structures where the intramolecular addition can
occur(600)(101)(429). The rapid rearrangement of the triple bond to the allenic compound seems to precede the cyclization (600):

N
CH
2
CH
2
OH
CH
3
C
N
CH
2
CH
2
OH
CH
3
N
O
CH
3
NaOH , DMSO
DMSO


Dinitrophenylhydrazine reacts with dimethylacetylenedicarboxylate in DMSO-methanol to yield a 1:1 adduct which exists as an imine-
emamine tautomer (3387):
PhNHNH
2
+
CO
2
CH
3
CO
2
CH
3
PhNHN
CO
2
CH
3
CH
2
CO
2
CH
3
PhHNHNHC
CO
2
CH
3
DMSO
room temp. , 15 hr
CO2CH3
53%




The reaction of alkynes with sodium azide in DMSO, followed by hydrolysis, affords 1,2,3-triazoles (3456):
RC CR'
C
N
N
N
C
+ NaN
3
DMSO
R R'
11-54%



DMSO has been one of the solvents studied in the reaction of 1 -propyl-sulfones and sulfoxides with ethylenimine. The greatest amount
of trans product (cis addition) is formed in DMSO. This may be explained on the basis that DMSO can stabilize the zwitterionic
intermediate best (3660):
H
3
CC CSO
2
C
2
H
5
NH
N
H
3
C SO
2
C
2
H
5
H
N
H
3
C H
SO
2
C
2
H
5
DMSO
+
room temp.
6 hrs
trans 84% cis 16%



b) Additions to olefins (carbon-carbon double bonds)
Aliphatic conjugated dienes add the dimsyl ion in DMSO to give sulfoxides. These unsaturated sulfoxides isomerize spontaneously and
eliminate methanesulfenate upon continued warming in the strongly basic medium to produce the overall effect of methylation (411):

SOCH
3
SOCH
3
+ H
2
CSOCH
3
DMSO
55
o
C
BH
E-elimination
50%
+ H
3
CSO
-
+B
-




Although the yields of the aliphatic dienes are 50% or less, the yields using polynuclear aromatic compounds or some heterocyclic
compounds, such as quinoline, are high (202):
N N
CH
3
+ H
2
CSOCH
3
DMSO
70
o
C, 4 hrs.
96%





68
The dimsyl ion also adds to aryl conjugated olefins, such as styrene or 1,1-diphenylethylene, in DMSO to give the corresponding methyl 3-
arylpropyl sulfoxides in almost quantitative yield (423):
Ph
2
C CH
2
+ H
2
CSOCH
3
Ph
2
CCH
2
CH
2
SOCH
3
Ph
2
CHCH
2
CH
2
SOCH
3
+ H
2
CSOCH
3
DMSO
25
o
C


One stage sequential double methylation of the C=C bonds in stilbene, 2-methylstilbene and 4,4'-dimethoxystilbene with the dimsyl ion in
DMSO leads to methyl diarylbutyl sulfoxides (7234):
CH
3
Ph
2H
2
CSOCH
3
DMSO
CH
3
Ph
CH
2
CH
2
SOCH
3
+




Kinetic rate measurements of the alkoxide catalyzed addition of methanol and ethanol to methyl esters of acrylic and methacrylic acid
have been investigated in the mixed solvent alcohol-DMSO (3249).
1-Alkenecarbonitriles react with aromatic or heteroaromatic aldehydes in DMSO under the catalytic influence of cyanide ions to give Ȋ-
oxonitriles (6172)(7582):

RCHO
R'HC
R"
CN
R
O
R'
CN
R"
54-91%
CN
-
, DMSO
+


Alkyl esters of Į , ȕ - and ȕ , Ȋ -unsaturated carboxylic acids can be carboxylated at the Į- or ȕ - position using sodium phenoxide in
DMSO (3506):
H
2
C
CO
2
CH
3
CO
2
CH
3
H
3
C
CO
2
CH
3 H
3
C
NaO
2
CH
2
C
CO
2
CH
3
CO
2
Na
or or
+ CO
2
PhO
-
, DMSO
25
o
C, 3 hrs



Sodium azide adds to Į , ȕ -unsaturated nitro compounds in DMSO to form 1,2,3-triazoles (4452):

RPh
NO
2
N
N
H
N
RPh
DMSO
room temp.
NaN
3
+
60%


Phenacyl bromide and its derivatives in the presence of zinc or a zinc-copper couple undergo anti-Markownikow additions to terminal
olefins (6627):
X-PhCOCH2Br + H
2
C Ar
2
X-PhCO(CH
2
)
2
CHAr
2
54%
Zn-Cu , DMSO
140
o
C



Phenacyl bromide in DMSO in the presence of the zinc-copper couple also adds to conjugated enynes and dienes (7536).
When olefins are treated with N-bromosuccinimide in DMSO containing a small quantity of water, the corresponding bromohydrins can be
obtained after a short reaction time in high yields (705)(4026)(4817):
BrN
Br
OH
78%
H
2
O , DMSO
20
o
C , 15 min.
+



A variety of alkylaromatic compounds undergo nucleophilic addition to conjugated olefins (3384). Particularly when the reaction is
performed in dipolar aprotic solvents, using potassium t-butoxide as a catalyst. The effectiveness of the solvents decreases in the
following order. DMSO, HMPA, N-methyl-2-pyrrolidone, DMF, sulfolane, tetramethylurea (4339).





69
c) Additions to nitriles (carbon-nitrogen triple bond)

The reaction of sodium azide with nitriles, such as benzonitrile, occurs readily in DMSO to give 5-phenyl tetrazole (550):
PhCN + NaN
3
NH
4
Cl, DMSO
123-127
o
C, 7 hrs
N
NH
N
N
Ph
87%

The reaction of anthranilonitrile with sodium hydride in DMSO yields 4-amino-2-(2-aminophenyl)quinazoline (8576):
R= H orBr
R CN
NH
2
R CN
NH
2
R CN
NH
2
N
N
NH
2
NH
2
R
R
NaH , DMSO
DMSO
+
0
o
C, 3hrs
25
o
C, 21hrs
nearly quantitative

Phthalodinitriles react with dicyandiamide in DMSO in the presence of basic compounds, such as potassium hydroxide, to
produce phthalo-bis-guanamines (8008):
CN
CN
2H
2
N
NH
CN
H
+
N
N N
N
N
N
NH
2
NH
2
NH
2
H
2
N
97%
KOH, DMSO
85
o
C, 3hr




d) Additions to isocyanates
The reactions of organic isocyanates and diisocyanates are catalyzed by DMSO, and they run at good rates in this solvent
(392)(312)(1360). Thus, diisocyanates react in DMSO with active hydrogen compounds such as dihydrazides (450), polyols
(449), or even with the hydroxyl groups of carbohydrates (cellulose) (443). In the last instance, DMSO is also used as an
effective swelling agent for cellulosic rayon fibers.
Diisocyanates, such as bis(4-isocyanatophenyl)methane or 2,2-bis(4-isocyanatophenyl)propane, react with ethylene glycol in
DMSO. Polyurethane filaments can then be spun from the reaction mixture (1880):
OCN NCO
+ HOCH
2
CH
2
OH
N
H
N
H
O O
OH
2
CH
2
CO
n
a ketone
DMSO

Dry DMSO is inert to alkyl or aryl isocyanates but it does react with isocyanates having electron withdrawing groups such as
acyl (714) or sulfonyl (308)(391).
A number of synthetic polymers containing sugar residues, such as D-cellobiose (10116)(10439) and Į , Į -trehalose (10123),
have been prepared by direct addition polymerization of the carbohydrate with diisocyanates, such as 4,4'-
methylenedi(phenylisocyanate) in DMSO.
CONDENSATION REACTIONS
These are mostly specific reactions (e.g. aldol condensation, Mannich reaction) in which two or more molecules combine,
usually with the separation of water or some other simple molecule.
Most of the ordinary reactions of carbonyl compounds can be accomplished in DMSO. Good results are often obtained either
because of the greater solubility of generally insoluble reactants or because of enhanced reactivity of nucleophiles.
a) Aldol-type condensations
Alkyl aryl ketones react easily and at a high rate with paraformaldehyde in DMSO in the presence of base to yield
hydroxymethyl compounds. The high reaction rates may be attributed to the high reactivity of the anionic catalyst in the DMSO
medium (1099). Thus, 1-indanone and formaldehyde react rapidly in DMSO to yield 2,2-bis(hydroxymethyl)-1-indanone:
O O
CH
2
OH
CH
2
OH
KOH, DMSO
room temperature
5 min.
70%


Fluorene and o- and p-nitrotoluene react similarly with paraformaldehyde in an aldol like addition in DMSO under the
influence of a strong base to give hydroxymethyl compounds (1100).


70
Racemic 2-(o-formylphenoxy)propiophenone can be prepared in 79% yield from equivalent amounts of a sodium salt of salicylaldehyde
and 2-bromopropiophenone in DMSO. When the reaction product is kept in DMSO in the presence of quinine, two optically active
diastereomeric ketols result (5613):
CHO
ONa
Br
H
3
C
O
Ph
CHO
OC
+
CH
3
O
Ph
OC
CH
3
O
Ph
OH
H
DMSO DMSO
79%


The reaction of 1-hydroxy-2,2,5-trimethyl-3,4-hexadione with paraformaldehyde in DMSO in the presence of potassium hydroxide gives
1,6-dihydroxy-2,2,5,5-tetramethyl-3,4-hexadione (6028):
O O
+ 2HCHO
O O
HO OH
KOH, DMSO
20
o
C, 24 hrs
85%


2-Carbomethoxycyclohexanone condenses with 3-pent-2-one in DMSO in the presence of sodium methoxide to give methyl 4-methyl-1
(9)-octal-2-one-1O-carboxylate (4048):
O
H
3
CO
2
C
O
CO
2
CH
3
O
NaOCH
3
, DMSO
29
o
C
+


The reaction of pentafIuoracetophenone with methyl benzoate in the presence of sodium hydride in DMSO is the best way to the
diketone (3376):
C
6
F
6
COCH
3
C
6
F
6
COCH
2
C
6
F
6
COCH
2
COPh
60%
PhCO
2
R NaH, DMSO
35
o
C, 24hrs


b) Ester condensation
The esters of carboxylic acids react with the dimsyl ion in DMSO to yield ȕ -keto sulfoxides (639)(1651):
+ RCOCHSOCH
3
+
R'O
-
+DMSO
R
O
SOCH
3
H
2H
2
CSOCH
3
RCO
2
R'

This condensation reaction has found a fairly wide application in the synthesis of useful intermediates. Thus, a number of benzoic acid
esters can be reacted with the dimsyl ion in
-
DMSO to give the corresponding ȕ -keto sulfoxides (9150):
2H
2
CSOCH
3
H
3
CO
H
3
CO
H
3
CO
CO
2
CH
3
+
OCH
3
OCH
3
OCH
3
O
S
O
H
3
C
70%
20-25
o
C, 0.5 hr
DMSO


Ethyl salicylate reacts with 3.2 equivalents of dimsyl ion to give the ȕ -keto sulfoxides (9196):
OH
CO
2
C
2
H
5
+
2H
2
CSOCH
3
OH
O
S
O
CH
3
92%
DMSO


A number of ȕ-keto sulfoxides have been prepared by condensing the dimsyl ion with substituted phenyl or naphthyl esters
(9249)(9402). Thus, ethyl 1-hydroxy-2-naphthoate reacts with the dimsyl ion to give 3'-hydroxy-2-(methylsulfinyl)-2'-acetonaphthone
(9244):

OH
CO
2
C
2
H
5
+
2H
2
CSOCH
3
OH O
S
O
CH
3
64%


71!
Ethyl isovalerate gives methyl sulfinyl methyl isobutyl ketone (9825):
(H
3
C)
2
CHCH
2
CO
2
C
2
H
5
+ H
2
CSOCH
3
DMSO
0
o
C
1/2-1 hr.
(H
3
C)
2
CHCH
2
CCH
2
SCH
3
O O


The preparation and synthetic applications of ȕ-keto-suIfoxides have been reviewed (4820)(8529).
Symmetrical ȕ -diketones are readily prepared by reacting methyl esters with methyl ketones in DMSO with sodium hydride as the base
(193) :
RCOCH
3
+ RCO
2
CH
3
+ 2NaH
DMSO
CR CH
2
CR
O O
75-83%


The yield is increased from 36% to 83% by using sodium hydride in DMSO instead of sodium methoxide in toluene.
In the presence of zinc-DMSO, 2,2,2-trichloroethyl esters of Į -substituted ȕ -keto acids react stereospecifically at the Į -carbon to the
ester carbonyl with aldehydes to give aldols in good yields (8833):
R
C CH
CO
2
CH
3
CCl
3
O R'
Zn, DMSO
25
o
C
48-92%
R CHR"
OH O
R'
+ OHCR"


Cyclohexanediones-1,3 are prepared in good selectivity by reacting an Į , ȕ-unsaturated carboxylic acid ester with a ketone in the
presence of a strong base in DMSO (8717):

H
2
C=CHCO
2
CH
3
+ CH
3
COC
2
H
5
NaOCH
3
50
o
C, 1/2 hr.
CH
3
O
O

c) Dieckmann condensation-cyclization
The Dieckmann condensation of dimethyl-l -methylcyclohexane 1,2-diacetate with sodium hydride in DMSO furnishes a crystalline keto
ester (6593):
CO
2
CH
3
CO
2
CH
3
CH
3
NaH, DMSO
85
o
C
4 hrs.
CH
3
O
CO
2
CH
3
68%



Reaction of diethyl Ȋ-ketopimelate with an excess of methylenetriphenylphosphorane in DMSO provides for the introduction of an
exocyclic methylene group and subsequent Dieckmann condensation to the carbethoxycyclohexanone (6648):
CO
2
C
2
H
5
C
2
H
5
O
2
C
O
Ph
3
PCH
2
, DMSO
- +
CH
2
CO
2
C
2
H
5
O
60%

!
72!
d) Mannich reaction
A ȕ -keto carboxylic acid reacts with formaldehyde-piperidine hydrochloride in DMSO to give the corresponding Į ÷methylene ketone in
excellent yield (6463)(8888):













The first step in the reaction is probably decarboxylation. The Mannich reaction product is most likely formed, but it loses piperidine
hydrochloride in the highly polar reaction medium.
The "Mannich reagent", dimethyl (methylene)ammonium iodide, reacts with enol borinates in DMSO-THF to provide excellent yields of ȕ -
dimethylamino ketones (6671):
DMSO-THF
Room temp.
3 hours
R'
(R)
2
BO
+ N
CH
3
CH
3
R'
O
R
N
CH
3
CH
3
R
I
-
80-100%

e) Michael condensation
The reaction of methyl Į-bromo- ȕ-methoxypropionate (I) with sodium nitrite in DMSO in the presence of phloroglucinol gives dimethyl
Į -methoxymethyl- Į , Į'-dinitrogluturate (IV), which is formed from methyl Į - nitro - ȕ cnethoxypropionate (II) and methyl Į -
nitroacrylate (III) by Michael addition (664):
H
3
COCH
2
CHCO
2
CH
3
+ NaNO
2
Br
phloroglucinol.
DMSO
H
3
COCH
2
CHCO
2
CH
3
-MeOH
NO
2
CH
2
C CO
2
CH
3
O
2
N
+ II
H
3
COCH
2
C
H
2
C CHCO
2
CH
3
CO
2
CH
3
NO
2
III
IV
NO
2
I
II


Double Michael reaction of 3-methyl-4-methylene-cyclohex-2-enone with dimethyl 3-oxoglutarate in DMSO in the presence of potassium
fluoride as a catalyst gives a mixture of the stereomeric diketodiesters (9746):
O
CH
2
+ H
2
C CHCO
2
CH
2
CH
2
OH
KF, DMSO
55-60
o
C
2 days
CO
2
CH
3
OH
CO
2
CH
3
O

Michael addition of carbazole to 2-hydroxyethyl acrylate in DMSO in the presence of 1,8-diazobicyclo[5.4.0]-7undecene (DBU) takes
place under mild conditions (10091):
DBU, DMSO
room temp.
48 hours
N
CH
2
CH
2
CO
2
CH
2
CH
2
OH
N
H
+ H
2
C=CHCO
2
CH
2
CH
2
OH


Michael-type polyaddition of dithiols to divinylsulfoxide in DMSO leads to the formation of poly(sulfinylethylene-thioalkene (or
arylene)thioethylene)s (10443):



O
CO
2
H
O
+ HCHO +
NH
2
Cl
+ - DMSO
20
o
C
2 hrs.
O
CH
2
O
N HCl
65%
O
CH
2
O

!
73!



H
2
C CH-SO-CH=CH
2
+ HSRSH
Et
3
N, DMSO
60
o
12hrs.
[CH
2
CH
2
-SO-CH
2
CH
2
-S-R-S]
n



f) Reformatsky reaction
Bromonitriles, when treated with zinc in DMSO-THF, yield an intermediate organozinc compound. ȕ - Hydroxynitriles are then prepared
from this intermediate and aliphatic aldehydes and ketones (4767):
R' C
R
Br
C+Zn
DMSO-THF
R' C
R
ZnBr
CN
"R C R'"
O
"R C C CN
R'" R'
OH R
30-66%

g) Thorpe-Ziegler condensation
1,4-Dinitriles, which can be prepared from dihalides or ditosylates and sodium cyanide in DMSO, can be cyclized directly to ȕ-enamino
nitriles in very high yields (477)(6163):
OTs
OTs
+ NaCN
DMSO
95
o
C
1 hr.
CN
CN
NaH, DMSO
95
o
C
1 hr.
NH
2
92%
CN



The cyclization of 1,2-di-(cyanomethoxy) benzene with dimsyl ion (sodamide + DMSO) in DMSO produces 3-amino-4-cyano-2H-1,5-
benzodioxepin (8690)(9145):
OCH
2
CN
OCH
2
CN
H
2
CSOCH
3
, DMSO
room temp.
3 hours
O
O
CN
NH
2
92%


h) Ullmann-type condensations
lodofluoroalkanes react with aryl iodides in DMSO in the presence of copper to give arylfluoroalkanes (5185)
(7293):
R
I
+ IR'
Cu, DMSO
100-150
o
C.
R
R'
45-70%
R = CF
3
, n-C
3
F
7
, etc.



i) Wittig reaction
The reaction of a tertiary phosphine (usually triphenylphosphine) with an alkyl halide to yield a phosphonium salt can be done in DMSO
(4669). DMSO also seems to be a good solvent for these salts. In these phosphonium salts, the Į C-H bonds are sufficiently acidic
(5551) for the hydrogen to be removed by a strong base in DMSO, e.g. an organolithium compound (4110), sodium hydride or the dimsyl
ion (8360), to produce a phosphorus ylide (a phosphorane), the so-called Wittig reagent. Subsequent reactions of these ylides with
aldehydes, ketones or hemiacetals in DMSO offer a useful synthesis for olefins. The overall reaction can be written as follows
(49)(240)(5551):

Ph
3
P + RCH
2
X
DMSO
Ph
3
P
+
CH
2
RX
-
DMSO
base
Ph
3
P-CHR
R
2
CO, DMSO
R
2
C=CHR
+ -


As mentioned above, the Wittig reaction converts carbonyl compounds to olefins. Thus, the reaction of formaldehyde and the
phosphorane derived from 1 ,5-bis(triphenylphosphoniomethyl)naphthalene dibromide in DMSO gives 1,5-divinylnaphthalene (7641):

!
74!
CH
2
PPh
3
Br
-
CH
2
PPh
3
Br
-
room temperature
2.5 hours
CH=PPh
3
CH=PPh
3
+ HCHO
DMSO
room temperature
overnight
CH=CH
2
CH=CH
2
64%
CH
2
SOCH
3
, DMSO
+


Ketones react with phosphoranes in a way similar to aldehydes. Verbinone with methylidenetriphosphorane in DMSO yields
methylenedihydroterpine (7476):
Ph
3
PCH
3
I
-
+
n-BuLi, DMSO
Ph
3
P=CH
2
+
O
DMSO
reflux
overnight
CH
2



Lactols (hemiacetals) can also be reacted with a Wittig reagent (7691). Treatment of a lactol with a Wittig reagent derived from 5-
triphenylphosphovalerate ion in DMSO gives the corresponding hydroxy acid (7729):
O
OH
R
+ Ph
3
P=CH(CH
2
)
3
CO
2
H
DMSO
OH
CH
2
CH
R
(CH
2
)
3
CO
2
H


It has also been found that aromatic and aliphatic esters can be directly converted to the corresponding isopropenyl compounds by
reaction with methylenetriphenylphosphorane in DMSO (10078):
R C OR'
O
+ 4PH
3
P=CHR" +3Na
+
CH
2
-
SOCH
3
DMSO
R C CH
2
R"
CHR"


OXIDATION REACTIONS
These are reactions in which oxygen combines chemically with another substance or reactions in which electrons are transferred from
one substance to another. DMSO in these reactions, with a few exceptions, is a solvent and not a reactant, i.e. it gets neither reduced
nor oxidized.
Many different reactions using oxygen have been conducted in DMSO, such as autoxidation (also chemiluminescence),
dehydrogenation, hypohalite reactions, lead tetraacetate oxidation, silver compound oxidations, superoxide and peroxide oxidations and
others not discussed here (e.g. electrooxidation, periodic acid oxidations, manganese dioxide oxidations, sulfur dioxide oxidations).
a) Autoxidation
The base-catalyzed oxidation of a number of compounds by oxygen in DMSO-t-butanol mixtures has been studied extensively.
Formation of the carbanion of the substrate usually precedes the oxidation. The rate of carbanion formation and oxidation increases as
the DMSO content is increased (728).

In the solution DMSO-t-butanol-potassium t-butoxide, a number of hydrocarbons can be oxidized easily. Thus, triphenylmethane
reacts with oxygen in the above system to form triphenylcarbinol (479):
Ph
3
CH + O
2
DMSO-t-BuOH-t-BuOK
Ph
3
COH
room temp.
20 min.
96%



Aniline under the above conditions gives azobenzene (469):
DMSO-t-BuOH-t-BuOK
room temp.
1 hr.
PhNH
2
+ O
2 PhN=NPh



Ketones in DMSO-potassium t-butoxide are oxidized to semidiones (1787):
!
75!
H
R
H
R
O + O
2
t-BuOK, DMSO
O
O
.
-




Some ketones can also be oxidized to the carboxy compounds (9707).
When nitrotoluenes are oxidized in DMSO-potassium t-butoxide, dimers or acidic products can be formed (568). Thus, the autoxidation of
o- and p-nitrotoluene in DMSO under basic conditions result in the formation of 1,2-di(nitrophenyl)ethanol, presumably via the
corresponding nitrobenzaldehydes (4812):
CH
3
NO
2
+ O
2
KOH, DMSO
O
2
N
NO
2
OH


The above dimers can be further oxidized to ketones, or dehydrated to nitrostilbenes (4812).
The autoxidation of 1- and 3-arylpropenes has been induced with the DMSO-t-butanol system containing potassium t-butoxide. The
autoxidation of safrole gives piperonylic acid. Without DMSO, no oxidation takes place (1140):
O
O
+ O
2
DMSO-t-BuOH-t-BuOK
O
O
CO
2
H
42%


In the presence of alkali metal hydroxides, it is possible to oxidize various substituted methanes, such as Į, Į-diphenyl-2-pyridenemethane,
to the corresponding alcohols using air or oxygen and DMSO as the sole solvent (6971):

R' C H + O
2
R
R"
NaOH, DMSO
R' C OH
R
R"



1,2,5,6-Dibenzanthracene and several other aromatic hydrocarbons are oxidized to the corresponding quinone derivatives in basic
DMSO (5587).
Autoxidation of 1 -methyl-2-isopropyl-5-nitroimidozole in DMSO with air or oxygen in the presence of a base gives 2-(2-hydroxy-2-
propyl)-1-methyl-5-nitroimidazole (8867):
N
N
NO
2
C
+ O
2
KOR, DMSO
CH
3
CH
3
CH
3
N
N
NO
2
C
CH
3
CH
3
CH
3
OH


Base catalyzed autoxidation of ethyl 2-cyano 3,3-disubstituted carboxylates in DMSO gives good yields of the 2-oxo esters (3662):

R' C CHCO
2
C
2
H
5
R
R
CN
+ O
2
DMSO, t-BuOH, T-BuOK
R'C CHCO
2
C
2
H
5
R
R
C
O



The system cobalt (II) and/or (III) acetylacetonate-t-butyl hydroperoxide has been used to initiate autoxidation of polyvinyl alcohol) in
DMSO (8043).
9,10-Dihydroanthracene can be oxidized to anthraquinone with oxygen in DMSO containing an inorganic base, such as sodium
hydroxide (2940).


!
76!
b) Chemiluminescence
Chemiluminescence reactions are very similar to autoxidation. Both these reactions require oxygen and the presence of a strong base.
Chemiluminescence reactions can be classified as special autoxidation reactions that produce light emissions. As the basicity of
alkoxides and hydroxides is enormously enhanced in DMSO over the value of hydroxylic solvents, it has also been observed with
chemiluminescence reactions that the emission periods have been increased and the light intensities enhanced in DMSO containing a
base (1025).
A bright green light is observed on the treatment of a solution of 2,3-dimethylindoie and its hydroperoxide in DMSO with a base, e.g.
potassium t-butoxide or granular potassium hydroxide (2140)(2218):

N
H
CH
3
CH
3
+ O
2 KOH, DMSO
N
CH
3
CH
3
base, DMSO OOH
CCH
3
N
H
CCH
3
O
+ light
O




When DMSO, luminol, water and caustic solution are shaken in the presence of oxygen from air, an oxidation reaction produces
considerable bright blue-green light. The reaction sequence can be represented as follows (3241):

NH
NH
NH
2
O
O
+ 2NaOH
DMSO
N
-
N
-
H
2
N O
O
+ O
2
DMSO
N
N-
NH
2
O
O
O
2

-
O
-
O
-
NH
2
O
O
+
N
2 + light




Some derivatives of luminol, containing methoxyl groups, are more efficient in chemiluminescence in DMSO solution than luminol itself
(1668).


The reaction of potassium cyanide with N-methylacridinium chloride in 90% DMSO-10% water produces Nmethyl-90-cyanoacridan. With
excess cyanide, the red N-methyl-9-cyanoacridanide ion is produced which, in the presence of oxygen, produces N-methylacridone and
potassium cyanate with light emissions (3653):

N
+
+ KCN
DMSO-H
2
O
N
CH
3
N
CH
3
CN
O
+ O
2
KCN, DMSO
+ HOCN + light
CH
3
Cl
-


The chemiluminescence emission spectra of two efficient chemiluminescent linear hydrazides in DMSO with potassium t-butoxide and
oxygen suggest that the corresponding acid anion is the light emitter (5116):
!
77!
R CNHNN
2
O
t-BuOK, DMSO
R C-N
-
HNN
2
O
O
2
, DMSO
R CNNH
O
t-BuOK, DMSO
RCN=N
-
O
RC- + light
O


c) Other oxidations with oxygen
Carbonyl compounds can be manufactured by oxidation of olefins, such as ethylene, propylene, styrene, and cyclohexane, in water-
DMSO mixture in the presence of a catalyst to give acetaldehyde, acetic acid, acetone, propanol, acetophenone and others (5800).
DMSO can be used as a catalyst component in the oxidation of olefins, e.g. DMSO can be a coordinate in complexes such as
Cu(ClO4)2(DMSO)4, or Fe(ClO4),(DMSO)4, (9412).
3-Oxo- ǻ
4
-(19)-norsteroids react with oxygen in DMSO to afford 1,3,5-(10)-oestratrien-6-ones (5912):
O
+ O
2
KOAc, DMSO
100-120
o
C
4 hours
OH
O
15-48%


The liquid phase oxidation of s-butanol with oxygen under pressure has been examined in various solvents using vanadium pentoxide-
molybdenum trioxide catalyst While no reaction occurs in water, benzene, or chlorobenzene, the oxidation in DMSO at 125
°
C for 13 hours
converts 10.8% of s-butanol to methyl ethyl ketone with a selectivity of 89% (9434).
Terpenes can be oxidized with dry air in DMSO. Thus, Į -longipinene is oxidized at 125-135
°
C to longiverbone as the major product
(9871), and p-mentha-1,4(8)- and -2,4(8)- dienes at 100
°
C give p-methylacetophenone (9874).
In neutral solution, benzyl alcohols can be oxidized by oxygen in the presence of ultraviolet light to give the corresponding aldehydes
(737)(1118):

C
6
H
5
CH
2
OH + O
2
UV, DMSO
room temp.
C
6
H
5
CHO + C
6
H
5
CO
2
H
48.7% 12.6%


The oxidation of benzoin by cupric sulfate and oxygen in DMSO occurs to give a high yield of benzil (945):
CuSO
4
, DMSO
90-100
o
C
1 hour
Ph
O
Ph
O
97% Ph
HO
Ph
O
+ O
2



d) Dehydrogenation
In the dehydrogenation reaction, oxidation (i.e., the removal of hydrogen) can take place without the presence of oxygen.
Several platenoid metal catalysts in DMSO promote dehydration, disproportionation and dehydrogenation of diarylcarbinols (10422). The
dehydrogenation can be the main reaction when DMSO is used as the solvent instead of Į -methylnaphthalene (8838):


R
2
CHOH
RuCl
2
(PPh
3
)
3
, DMSO
R
2
C=O + H
2


Dihydroarenes, e.g. 1,2-dihydronaphthalene, can be converted into the corresponding aromatic compounds, e.g. naphthalene, by
deprotonation with potassium fencholate, followed by dehydration with fenchone (2-oxo-1,3,4-trimethylbicyclo [2.2.1 ]-heptane) (9707):
+
O
H
O
-
, DMSO
90
o
95%
+
H
OH

!
78!
5,7,4'-Trimethoxyflavanone, when heated with DMSO in the presence of a catalytic amount of iodine and concentrated sulfuric acid,
gives 5,7,4'-trimethoxyflavone in almost quantitative yield (10,000):

O
OCH
3
OCH
3
OCH
3
O
I
2
, H
2
SO
4
, DMSO
O
OCH
3
OCH
3
OCH
3
O

A solution of sodium dichromate and sulfuric acid in DMSO oxidizes primary alcohols to aldehydes and secondary alcohols to ketones. In
these oxidations, DMSO acts as a solvent and not as a reactant (7609):

CH-OH
R
R
Na
2
Cr
2
O
7
, DMSO, H
2
SO
4
C=O
R
R
80-90%


e) Hypohalite oxidations
Halogenations with sodium hypohalites of alkyl - or arylamidines and isoureas in DMSO solution afford the corresponding alkyl-, aryl- or
alkoxy-3-halodiazirines in practical yields (843):
R-C-HN
2
NaOX, DMSO
25-55
o
C
R
C
N
X N
3-haloazirine, 60%
NH


Oxidative cyclization of trifluoroacetamidine with hypochlorite and chloride ion in aqueous DMSO gives the corresponding diazirine
(8108):
F
3
C-C-HN
2
-OCl. LiCl. DMSO-H
2
O
NH CF
3
C
N
Cl N




f) Lead tetraacetate oxidations
Polysaccharides, such as dextran and amylose, can be oxidized by lead tetraacetate in DMSO if 15-20% of glacial acetic acid is added
to prevent oxidation of the solvent. This oxidation proceeds at a rate which is several times faster than the periodate oxidation in
aqueous solution. Polysaccharides oxidized by lead tetraacetate contain free aldehyde groups. Oxidation follows the normal gl ycol-
cleavage pattern (615).

Oxidation of 1 -amino-3,4,5,6-tetraphenyl-2-pyridone with lead tetraacetate in DMSO gives the corresponding 5,5-dimethyl-N-
sulfoximide, indicating that DMSO is an efficient trap for N-nitrenes (4987):
N
Ph
Ph
Ph
Ph
O
N
Pb(OAc)
4
. DMSO
room temp.
1 hour
N
Ph
Ph
Ph
Ph
O
N:
DMSO
N
Ph
Ph
Ph
Ph
O
N S(CH
3
)
2
O


Similarly, lead tetraacetate oxidation of N-aminolactams in the presence of DMSO gives the sulfoximides in good yields (5846):
R
2
N-NH
2
¹ DMSO
R
2
N-N S O
H
3
C
H
3
C
Pb(OAc)
4
. DMSO



Oxidation of aminonaphth[2,3-b]azet-2(1 H) -one by lead tetraacetate in DMSO leads to 2-naphthoic acid
(6243):
!
79!
NR
O
Pb(OAc)
4
. DMSO
CO
2
H


Treatment of a dicarboxylic acid (prepared from the Diels-Alder adduct of dimethyl - cyclobut-1-ene-1,2dicarboxylate with butadiene) with
lead tetraacetate in DMSO containing pyridine gives a product which is mainly bicyclo [4,1,0]octa-1(6),3-diene, with a small amount of
benzocyclobutene (7533):
CO
2
H
CO
2
H
Pb(OAc)
4
, DMSO, pyridine
+



g) Silver compound oxidations
A number of alcohols, e.g. methanol, ethanol, n-propanol, isoborneol, can be oxidized by argentic picolinate to yield the corresponding
aldehydes or ketones, i.e., formaldehyde, acetaldehyde, propionaldehyde, camphor. The rate of reaction is influenced by the solvent,
and the use of DMSO leads to a more rapid reaction (2915):
R'RCHOH + 2Ag(pic)
2
DMSO
40-70
o
C
10-15 min.
66-80%
R'RC=O + 2Ag(pic) + 2 pic-H



Oxidation of menaquinol-1 dimethyl ether with silver picolinate in DMSO gives the desired alcohol (4653):
OCH
3
CH
3
R
OCH
3
OCH
3
CH
2
OH
R
OCH
3
Ag++ picolinate, DMSO
80
o
C
30 min.
25%



Reaction of 1,2-diphenyl-2-[(phenyl)methylamino]vinyl chloride with silver (II) oxide in DMSO gives benzil (5843):

reflux
1 1/2 hr.
95%
PhMeN
Ph
Ph
Cl
O
Ph
O
Ph
Ag
2
O, DMSO



In boiling nitromethane with silver tetratluoroborate, the yield of benzil is only 60% (5843).
Bromoalkyl formates are easily converted to protected secondary hydroxyaldehydes by treatment with silver tetrafluoroborate in DMSO
in the presence of triethylamine (7507):
OCHO
H
3
C-CH-(CH
2
)
n
CH
2
Br
AgBF
4
, DMSO, Et
3
, N
-5 to -20
o
C
24 - 120 hrs.
OCHO
H
3
C-CH-(CH
2
)
n
CHO
50-90%



The use of silver nitrate in DMSO on a 3-chloro-7-hydroxy-1 7-oxo-androstane accomplishes two purposes. It oxidizes the 7-hydroxy
group to the 7-oxo group, and it dehydrohalogenates the steroid (8340):
!
80!
Cl OH
AgNO
3
, DMSO
reflux
O
52%




17 Į-Ethynyl-17 ȕ-hydroxysteroids are converted quantitatively to the corresponding 17-ketones by treatment with excess silver
carbonate or silver oxide in DMSO (7460):
OR
OH
C C-R'
Ag
2
CO
3
, DMSO
O




Dimethyl esters of monoalkylated malonic acids and ȕ-keto esters are easily oxidatively dimerized by silver oxide in DMSO (8830),
e.g.:
R-CH
CO
2
R'
CO
2
R''
70-80
o
C
Ag
2
O, DMSO
R C C R
R'O
2
C CO
2
R'
CO
2
R'
CO
2
R'
70-90 %



h) Superoxide and peroxide oxidations
Secondary amines are instantaneously oxidized to dialkylnitroxides by potassium superoxide in DMSO (6293):
R
2
NH+O
2
-
DMSO
R
2
N-O + OH
-


Alcohols are the major end products resulting from the reaction of alkyl halides and tosylates with an excess of potassium superoxide in
DMSO in a rapid process in which the C-O bond-forming step proceeds with inversion of configuration (8030):
C
6
H
13
C
CH
3
H X
KO
2
, DMSO
25
o
C
75 min.
C
6
H
13
C
CH
3
OH H
X = Cl, Br, I, OTs



With 1 -bromooctane, the yield of 1 -octanol is 63%.
Phenolic compounds are prepared by oxidation of aromatic hydrocarbons with organic hydroperoxides in the presence of boron oxide,
meta- or orthoboric acid ortheir lower alkyl esters, and DMSO. Thus, DMSO is added to a mixture of m-xylene, tetralin hydroperoxide and
boron oxide to give 38:62 ratio of 2,6- and 2,4-xylenol, dihydronaphthalene and tetralone (8658).



REDUCTION REACTIONS
These are reactions in which hydrogen is added or oxygen or a halogen is removed. DMSO can be either a solvent or a catalyst
component.
Although DMSO can be either oxidized or reduced, it is comparatively stable toward both changes and hence can be used as a solvent
for many oxidation-reduction reactions. In polarography studies using tetraethylammonium perchlorate electrolyte, the usable potentials
range from +0.3 volts anode potential to-2.8 volts cathode potential (both relative to the standard calomel electrode) (553)(772). In
general, the halfwave potentials for inorganic ions in DMSO are quite similar to those in aqueous solutions (553). However, a more
negative cathode potential is usable in DMSO as shown by the observation of the magnesium wave at -2.20 volts. Lithium metal is inert
toward DMSO (206). The electrodeposition of cerium cannot be accomplished in aqueous solution because the metal is too positive but it
can be deposited from a DMSO solution of cerium chloride (1744). The transfer of electrons between molecules of redox systems
sometimes occurs very readily in DMSO as observed for isotope exchange between ferrous and ferric perchlorates (1036)(923) and in
!
81!
the base-catalyzed transfer of electrons between unsaturated organic molecules and their dihydro derivatives (722).

1. Reduction of Alkyl Halides and Sulfonates

a) Reduction with sodium borohydride
the selective substitution of hydrogen for primary, secondary or, in certain cases, tertiary halogen (or sulfonate) in alkyl halides without
reduction of other functional groups present in the molecule may be effected by reduction with sodium borohydride in DMSO
(2980)(3248):
C-X
R
R
1
R
11
NaBH
4
, DMSO
25-100
o
C
C-H
R
R
1
R
11
X=Cl, Br, I, tosylate



Sodium borohydride in DMSO is a convenient source of a nucleophilic hydride which may be used for the reductive displacement of
primary and secondary alkyl halides, or sulfonate esters (e.g. tosylates). The mildness of borohydrides allows a number of chemoselective
transformations without damage to groups (e.g. COOR, COOH, CN, NO2) normally affected by harsher reagents such as lithium aluminum
hydride (9783).
The reduction of optically active tertiary alkyl halides with sodium borohydride in DMSO proceeds with racemization, presumably via an
elimination-addition mechanism (3519):
R-Cl
NaBH
4
, DMSO
R(ene)
BH
3
/H
+
, DMSO
RH



4-Nitro-2-chloromethyl-1-isopropylbenzene can be reduced with sodium borohydride in DMSO in good yield (4602):

(H
3
C)
2
HC
CH
2
Cl
NO
2
NaBH
4
, DMSO
room temp.
3 1/2 hrs.
(H
3
C)
2
HC
NO
2
CH
3
82%




An iodo-tosylate can be reduced with sodium borohydride in DMSO to give one major product, a cyclopentadiene (6502):

CH
2
I CH
3
OTs
NaBH
4
, DMSO
100
o
C.
27 hrs.

In the above case, both reduction of the iodide and elimination of the tosylate take place.
Sodium borohydride in DMSO selectively reduces 2-chloro-4-chloromethyl naphthalene to 1-chloro-4methylnaphthalene (6785):
Cl
Cl
NaBH
4
, DMSO
CH
2
Cl
72%
CH
3
room temp.
2 hours


Sodium borohydride in DMSO-water reacts with Į , Į , Į , Į', Į', Į'-hexachloro-p-xylene to give an insoluble polymer (7205):
!
82!
CCl
3
CCl
3
NaBH
4
, DMSO-H
2
O
C C
Cl
Cl
Cl
Cl
C C
Cl
Cl
Cl
Cl 25
o
C
n

c) Reductions with chromous ion
Reduction of Į, Į-dichlorobenzyl benzyl sulfoxide to a mixture of diastereomeric Į-chlorobenzylbenzyl sulfoxide can be carried out by
chromous ion in aqueous DMSO (6972):
Ar
Cl S
O
Ar
Ar
Cl S
O
Ar
Cl
CrCl
2
, aq. DMSO
room temp



The use of n-butanethiol and chromium (II) acetate in DMSO in the reduction of a 5 Į-bromo-6 ȕ-hydroxysteroid permits the removal of
the bromine and the isolation of the 6 ȕ-hydroxy-steroid (6825)(6970):
OAc
Br
OH
OAc
OH
H
Cr(OAc)
2
, n-BuSH, DMSO



c) Reduction with dimsyl ion
Treatment of 8,8-dibromobicyclo[5,1,0]octane with dimsyl sodium in DMSO produces exo-8-bromobicyclo [5,1,0]octane (454)(3009):
Br
Br
H
2
CSOCH
3
, DMSO
Br
H


d) Reductions with hydrazine
Hydrazine can reduce meso-1,2-stilbene dibromide in DMSO to Į -bromostilbene and some bibenzyl (6509):
PhCHBrCHBrPh + N
2
H
4
DMSO
PhCH=CBrPh + PhCH
2
CH
2
Ph
66% 18%



e) Reductions by electrolysis
Controlled potential electrolysis of 2,4-dibromopentanes in DMSO containing tetraethylammonium bromide (TEAB) gives cis- and trans-
dimethylcyclopropanes and small quantities of 1-pentene, 2-pentene and n-pentane (4492)(6659):
2e
-
, TEAB, DMSO
H
3
C CH
3
+
CH
3
CH
2
CH
2
CH=CH
2
+ CH
3
CH
2
CH=CHCH
3
+ CH
3
(CH
2
)
3
CH
3
H
3
C
Br
Br
H
3
C
Br
Br
H
3
C



2. Reduction of Carbonyl Compounds
Carbonyl compounds, aldehydes and ketones in DMSO can be reduced by electrochemical means or by Wolff-Kishner reduction of the
corresponding hydrazones.

a) Reductions with borohydrides
The kinetics of the reduction of acetone, pivalaldehyde, (H3C)3CCHO, and benzaldehyde by sodium borohydride and
tetramethylammonium borohydride have been determined in DMSO-water systems. The reactions obey 2nd order kinetics (8953):

4R
2
CO + BH
4
- + H
2
O
DMSO
R
2
CHOH + B(OH)
4
-

!
83!

The reduction product of benzaldehyde in DMSO is NaB(OCH2Ph)4, which is readily hydrolyzed to benzyl alcohol, PhCH2OH (8953).
When benzaldehyde is reduced in DMSO and DMSO-water mixtures of tritiated sodium borohydride, the reduction is accompanied by
the incorporation of tritium into the aldehyde group of unchanged benzaldehyde (8954).


b) Catalytic reduction
The mechanism of reduction of cyclic ketones by the system iridium(III) salt-sulfoxide-isopropyl alcohol has been investigated. With 4-t-
butyl cyclohexanone, a 97% conversion to 4-t-butylcyclohexanol, with a cis/trans ratio of 1.50, can be achieved with DMSO as the
sulfoxide (4436):
O
IrCl
3
-i-Pr-DMSO
OH
97% conversion

An unusually selective hydrogenation of Į , ȕ-unsaturated aldehydes to the unsaturated alcohols has been accomplished catalytically
under mild conditions using the iridium complex HlrCl2(DMSO)3 in isopropanol, the solvent being the source of hydrogen (9752):
RCH=CHCHO + H
2
HlrCl
2
(DMSO)
2
RCH=CHCH
2
OH



c) Electrochemical reduction
The electrochemical reduction of carbonyl compounds, particularly ketones and diketones, has been studied in DMSO (2567)(3217).
The reduction of 1,3-diphenyl-1,3-propanedione in DMSO proceeds by an overall 0.5 electron process (5971):
4Ph-C=CH-C-Ph +2e
OH
O
DMSO
Ph C
H
2
C C Ph
O OH
C Ph
H
2
C Ph
OH O
Ph2 C
H
C C Ph
O OH
+
dimeric pinacol enolate anion


d) Wolff-Kishner reduction
The Wolff-Kishner reduction, the reaction of hydrazones of aldehydes and ketones with a base to produce the corresponding
hydrocarbons, has been run in DMSO (495)(377):
Ph
2
C=NNH
2
t-BuOK, DMSO
Ph
2
CH
2
+N
2
25
o
C
8 hours
benzophenone
hydrazone
diphenyl methane
90%


The Wolff-Kishner reduction in DMSO has been carried out in the presence of potassium t-butoxide, dimsyl sodium, and other base
catalysts, and the activation parameters have been determined (8735). The Wolff-Kishner reaction mechanism in DMSO has been
reviewed (1942)(3048).

3. Reduction of nitroaromatics
The reduction of aromatic nitro compounds with sodium borohydride in DMSO initially produces the azoxy compounds which, in most
cases, are subsequently reduced to the corresponding azo derivatives and amines (4946), e.g.:

PhNO2
NaBH4, DMSO
85-100
o
C
Ph-N=N-Ph Ph-N=N-Ph PhNH
2
nitrobenzene
azoxybenzene azobenzene aniline
O


In the case of o-nitroanisole, 63% of o-methoxyaniline and 23 % of the azobenzene are produced.
Nitroaromatics are selectively hydrogenated in neutral media in the presence of precious metal catalysts and DMSO to produce N-
arylhydroxyamines in high yield. Thus, nitrobenzene in the presence of platinum on carbon and DMSO yields hydroxylamine and phenyl
aniline (5663):
!
84!


PhNO
2
+ [H]
Pt/C-DMSO
ethanol
room temp.
PhNHOH+PhC
6
H
4
NH
2
86% 13%


Catalysts of noble metals on activated carbon can be subjected to the action of DM SO together with hydrazine or its derivatives. The
hydrogenation of 2-chloronitrobenzene in the presence of platinum on carbon and DMSO gives a high yield of 2-chloroaniline (8118):
Cl
NO
2
+ [H]
Pt/C-DMSO
hydrazine
Cl
NH
2

Similarly, the reduction of nitrobenzene with hydrogen over platinum oxide in alcohol (methanol or ethanol)sulfuric acid in the
presence of DMSO produces p-alkoxyaniline (9294)(9581):
+ [H]
PtO
2
, DMSO
ROH- H
2
SO
4
OR NH
2
NO
2


4. Reduction of C=C Systems
The electrochemical reduction of several aryl Į , ȕ -unsaturated ketones, C6H5CH=CHCOR, has been studied at mercury cathodes by the
techniques of polarography, controlled potential coulometry and cyclic voltammetry. Conditions have been established under which a
dimer of the Į, ȕ-unsaturated ketones is formed by coupling at the ȕ-carbon atoms in good yields. A suitable medium for the reduction is
tetra-n-butylammonium perchlorate in DMSO with added lithium perchlorate (4253), e.g.:
LiCO
4
, DMSO-H
2
O
R = t-butyl
H
COR
Ph
H
Ph CH
2
COR
Ph CH
2
COR
75%

Diimide, generated by the sodium metaperiodate oxidation of hydrazine in DMSO, is a particularly useful reducing system for olefins or
compounds which contain readily oxidized functional groups (4392), e.g. maleic anhydride can be reduced to succinic anhydride:

HC
HC
C
C
O
O
O
HN=NH, DMSO
H
2
C
H
2
C
C
C
O
O
O
95%

A thiophene derivative is reduced the same way (4392):
S
SCH
3
CO
2
C
2
H
5
S
SCH
3
CO
2
C
2
H
5
HN=NH, DMSO


Allylbenzene can be hydrogenated by chloro(DMSO)palladium complexes (5526):
PhCH
2
CH=CH
2
+ [H]
(DMSO)
2
PdCl
2
PhCH
2
CH
2
CH
3




In the presence of the same catalyst, 1 -pentene is converted to isomers more rapidly than without the catalyst and the bond migration of
the pentene is more rapid than its hydrogenation (5630).
Double bonds in some Į, ȕ-unsaturated ketones are reduced by propen-2-ol in the presence of soluble iridium-DMSO catalysts (7031):

PhCOCH=CHPh
i-PrOH, H[IrCl
4
(DMSO)
2
]
73
o
C
PhCOCH
2
CH
2
Ph
95%


Acrylic acid and its derivatives can be dimerized in high yields by means of alkali metal amalgam in DMSO-water. Acrylonitrile gives
adiponitrile (4907):


!
85!
2 CH
2
=CHCN
Na amalgam, DMSO-H
2
O
NC(CH
2
)
4
CN
95%


Diethyl fumarate, C2H5O2CCH=CHCO2C2H5, can be dimerized by electrochemical reduction (7331).

SOLVOLYTIC REACTIONS
These are reactions in which the elements of water (also alcohols or amines) are added, usually with the formation of two new
substances.
1. Hydrolysis
The DMSO-water system has been used in many hydrolysis reactions. The rates of base catalyzed reactions usually increase as the mole
fraction of DMSO in the mixture increases, and the increase is particularly rapid above 0.7 mole fraction of DMSO
(336)(367)(369)(464)(726)(730). The opposite is sometimes true in the case of hydrolysis in the presence of acids. The rate of acid
hydrolysis decreases as the mole fraction of DMSO is increased, particularly above 25-30% DMSO (368). A similar decrease is seen for
the acid catalyzed hydrolysis of acetals (742) and the reaction of tert-butyl chloride with aqueous DMSO (431)(1028)(1521).

a) Aliphatic halide hydrolysis
The alkaline hydrolysis of alkyl halides has been studied in DMSO-water (329)(432)(2583)(4846). In the alkaline hydrolysis of methyl
iodide, DMSO exerts a strong accelerating effect. The rate of the hydroxyl ion catalyzed reaction in DMSO is up to 10
6
-10
7
times the rate in
water (329).
The rate constants for the reaction of hydroxyl ion with benzyl chlorides in acetone-water decrease with increasing acetone concentration
while the rates increase with increasing DMSO concentration in DMSO-water (432).
The rate of alkaline hydrolysis of chloroacetic acid increases with increasing concentration of the organic component in acetone-water,
THF-water, dioxane-water and DMSO-water. However, the increase is greatest in DMSO-water (2583).
Alcohols can be prepared from alkyl halides in DMSO-water in the presence of a base. Thus, octanol is obtained from octyl chloride and
calcium hydroxide in DMSO-water at reflux (4846):
Octyl chloride +Ca(OH)
2
DMSO-H
2
O
reflux
4 hrs.
Octanol
92%

Solvolysis of 2-adamantyl bromide and Į-chloroethylbenzene decreases with increasing DMSO content (2194)(3766)(2196).
The Diels-Alder adduct, obtained by reacting 5-methoxymethyl-1,3-cyclopentadiene with chloroacrylonitrile, is converted with aqueous
potassium hydroxide in DMSO to the anti-bicyclic ketone (3033):
CN
Cl
H
3
COH
2
C
KOH, DMSO-H
2
O
25-30
o
C
14 hours
H
3
COH
2
C
O

b) Aromatic halide hydrolysis
Aromatic halogens can be hydrolyzed from activated nuclei by aqueous bases in DMSO. The rate coefficients for the alkaline hydrolysis of
a series 1-halogen substituted 2,4-dinitrobenzenes have been measured in aqueous DMSO. These rates have been correlated with the
acidity function of medium (4467)(4520).
The aryl polyether that is prepared by the reaction of the disodium salt of bisphenol A with 4,4'-dichlorodiphenyl sulfone in DMSO depends
on the moisture content of the polymerizing system. In the presence of water, hydrolysis of 4,4'-dichlorodiphenyl sulfone monomer occurs
concomitant with the polymerization (4704).
The reaction of 2,8-dibromo-5,5-dioxodibenzothiophene with aqueous potassium hydroxide in DMSO gives 8-bromo-2-hydroxy-5,5-
dibenzothiophene (7709):
S
O
2
Br
Br
+ KOH
aq. DMSO
110
o
C
3 hours
S
O
2
Br
OH


Several 4-halogenophenyl sulfonylphenols, useful for the synthesis of poly(arylene ether sulfones), have been prepared by partial
hydrolysis of the corresponding dihalides in DMSO (8825):

X
R
SO
2 X + 2KOH
aq. DMSO
60
o
C
24 hrs.
X
R
O
2
S
R
OK + KX
x=halogens

!
86!
c) Amide hydrolysis

The rates of base catalyzed hydrolysis of anilides have been studied in DMSO-water (3820)(7573)(8696). Even a very small amount of
DMSO (less than 1 %) facilitates the kinetic measurements in the hydrolysis of p-nitro- and pformylacetanilide (3820). Some increase
with increasing DMSO has been found in the hydrolysis rate of trifluoroacetanilide (7573).

The reaction of İ-caprolatam with barium hydroxide in DMSO-water gives İ -aminocaproic acid on acidification
(4972):
N
+H
2
O
Ba (OH)
2
, DMSO
O
95-103
o
C
4 hrs.
H
2
N(CH
2
)
5
CO
2
H
H

d) Epoxide hydrolysis
The most commonly encountered reactions of epoxides are those in which the ring is opened by a nucleophile. Such reactions are
advantageously performed in DMSO because DMSO is inert to the epoxides and it also provides maximum reactivity for the nucleophile.
When the relatively unreactive 1 -phenylcyclohexene oxide is heated with potassium hydroxide in aqueous DMSO, the corresponding
trans-glycol is obtained in fairly good yield (334):
O
Ph
+ H
2
O
KOH, DMSO
100
o
C
6 hrs
OH
Ph
OH
60%

In the presence of acids a mixture of cis- and trans glycols results. The same reaction in aqueous dioxane after48 hours at 150
°
C gives
only a 10% yield (334).

Treatment of 8,9-epoxyundec-5-en-ol with potassium hydroxide in refluxing aqueous DMSO produces undeca-4,6-diene-3,9-diol (8261):
CH
2
H
5
CH-CHCH
2
CH=CHCH
2
CH
2
H
5
+H
2
O
O
OH
KOH, DMSO C
2
H
5
CCH
2
CH=CHCH=CHCC
2
H
5
OH OH


The same treatment of the saturated epoxide, 8,9-epoxy-undecan-3-ol, leads to simple cleavage of the epoxy ring giving undecane-
3,4,9-triol (8261):
C
2
H
5
CH-CH(CH
2
)
4
CHC
2
H
5
+H
2
O
KOH, DMSO
HO
C
2
H
5
-CH-CH(CH
2
)
4
CHC
2
H
5
OH OH



1 -(ȕ, Ȋ -Epoxypropyl)cyclohexan-1 -ol, when treated with base in 75% aqueous DMSO, gives the corresponding oxetan as the main
product (8306):
OH
+H
2
O
OH
-
, DMSO
CH
2
OH
49%

e) Ether hydrolysis
When water, strong acid, and ethyl vinyl ether are all solutes in DMSO, the rate of hydrolysis of the vinyl ether is still controlled by the rate
of proton transfer to the carbon. The rate decreases with increasing DMSO concentration (2492)(7643):
CH
2
=CHOC
2
H
5
+ H
2
O
H
+
, DMSO
CH
3
CHO+C
2
H
5
OH

The rate coefficients for the alkaline hydrolysis of 4-substituted 1-methoxy-2-nitrobenzenes and 1-alkoxy 2,4dinitrobenzenes have been
measured in aqueous DMSO. These rates have been correlated with the acidity function of the medium (4467)(4520):
NO
2
OR
NO
2
+ OH
-
OH OR
NO
2
NO
2
aq. DMSO
OH
NO
2
NO
2

A similar study has been done with substituted 2-alkoxytropones in 40% aqueous DMSO (4521).
2,4,6-Trinitroanisole and 2,4,6-trinitrophenyl phenyl ether react with DMSO to give 2,4,6-trinitrophenol and methanol and phenol, resp.
(6878):
!
87!
NO
2
OR
NO
2
NO
2
DMSO
NO
2
OH
NO
2
NO
2
+ ROH
R= Me, Ph

f) Nitrile hydrolysis
Powdered anhydrous sodium hydroxide and potassium hydroxide in DMSO can be used to convert nitriles to amides, e.g. benzonitrile to
benzamide, at a reaction rate that is approximately 10,000 times that in aqueous caustic. However, the solubility of the dry caustic in
DMSO is very low which reduces the speed of converting the nitrile (725).
The reaction of 5-chloro-1,4-diphenyl-1,2,3-triazole with sodium cyanide in moist DMSO gives 1,4-diphenyl1,2,3-triazole-5-carboxamide
due to hydrolysis of the nitrile (7115):
N
N
N
Cl + NaCN + H
2
O
Ph
Ph
N
N
N
COHN
2
Ph
Ph
DMSO


g) Saponification
In the base catalyzed hydrolysis of esters in aqueous DMSO, the rate of hydrolysis increases as the mole fraction of DMSO in the mixture
increases. This increase is particularly rapid above 0.7 mol fraction of DMSO (336)(367)(369) (464)(726)(730).
The use of DMSO-water as a solvent for saponification increases the reaction rate difference between the first and second group of
diesters. In 50% aqueous DMSO (v/v) the first ester group can be hydrolyzed more than nine times faster than the second one (1694).
There is a considerable rate enhancement for both steps in alkaline hydrolysis of a series of dicarboxylic acid esters in DMSO-water. The
rates increase with increasing amount of DMSO and these rates are larger in aqueous DMSO than in aqueous ethanol (5969)(6543) or
aqueous acetonitrile (5459).
When the saponification of glycol monobenzoates are carried out in 80% aqueous DMSO, 80% aqueous ethanol and 80% aqueous
acetone, the rates are up to 1000 times faster in 80% aqueous DMSO than in the other two solvent systems (5622):
CH
2
OH
Ph-CO
2
H
2
C
+ H
2
O
30
o
C
OH
-
, DMSO
CH
2
OH
CH
2
OH
+ HO
2
C-Ph

Similarly, the saponification rates of unsaturated esters in DMSO-water are faster than in ethanol-water (3356) (7540). Increased transition
state solvation, not increased hydroxyl ion desolvation, is the major cause of rate enhancement in DMSO (6822).
The rate coefficients of neutral hydrolysis of methyl trifluoroacetate and chloromethyl dichloroacetate in DMSOwater are greater than in
acetone-water and acetonitrile-water (6477).
With hydrolysis on the acid side, however, the reaction rate decreases as the mole fraction of DMSO increases above 25-30% DMSO,
as is the case with ethyl acetate (368).
The cleavage of highly hindered esters can be accomplished in DMSO using potassium t-butoxide as the base and heating until the
cleavage is accomplished. In this case, the cleavage occurs by alkyl-oxygen fission (490). Esters are also cleaved by sodium
superoxide in DMSO to give carboxylic acids in excellent yield, as is the case of
ethyl p-cyanobenzoate (10086).
NC CO
2
Et + O
2
-
DMSO
5 min.
H
2
NC
O
CO
2
H
96%


2. Alcoholysis, Aminolysis
In the basic methanolysis of some aryl substituted N-methyl-2,2,2-trifluoroacetanilides in DMSO-methanol rate increases with increasing
amount of DMSO (6474):
R-C
6
H
4
NCOCF
3
+ CH
3
O
-
CH
3
OH
9
DMSO
CH
3
CH
3
OH
CH
3
R-C
6
H
4
-NH + F
3
CCOCH
3
O
O
-
OCH
3
CF
3
N
R
C
6
H
4
H
3
C

!
88!


N-Methyl-4'-nitroanilides undergo basic methanolysis by way of rate determining methoxide addition to the amide, as shown above. The
addition of DMSO produces a rate increase in each case (7844).
The mechanism of basic methanolysis of a series of N-aryl-N-phenylbenzamides in methanol and in 80% DMSOmethanol has been
studied. In methanol the rate determining step seems to be the solvent assisted C-N bond breaking, while in 80% DMSO-methanol the
rate determining step is methoxide attack (10409).
Markedly increased alcoholysis rates are obtained by the addition of DMSO to ethylene-vinyl ester interpolymer alcohol mixtures in the
presence of either alkaline or acidic mixtures (7156).
DMSO is an effective catalyst for the n-butylaminolysis of p-nitrophenyl acetate in chlorobenzene (6988).
NO
2
25
o
C
O
O
+NH
2
(CH
2
)
3
CH
3
NO
2
O
OH
chlorobenzene, DMSO
H
3
C
NH(CH
2
)
3
CH
3
O
+
-
O NO
2



The aminolysis of polymeric macronet N-hydroxy-succinimide esters of Boc-amino acids by free amino acids and peptides in DMSO has
been studied, both in the presence and in the absence of organic bases (8832).
3. Transesterification (Ester Interchange)
The reported work concerning the base catalyzed transesterification of fatty acid esters mainly describes esterification of carbohydrates
and other polyhydroxylic materials. DMSO is a particularly suitable solvent in this area because of the enhanced activity of the base
catalyst in DMSO and also because of the excellent solubility of most carbohydrate and polyhydroxylic substances in DMSO. A number of
the reports are concerned with sucrose esters (160)(161)(181)(162)(164)(165). Others report esterifying hexitols and hexoses (1257) and
inositols (166). The reaction of 1,2-0-isopropylidene-6-tosyl-glucose under the conditions of the Kornblum oxidation with potassium
bicarbonate as the base gives none of the expected aldehyde but only the 5,6-carbonate ester(183) in a transesterification.
Alkylation of methyl 0-(tetrahydropyran-2-yl) mandelate using alkyl halides and sodium hydride in DMSO at 80
°
C produces
transesterification products (4278):
C
H
O
O
CO
2
CH
3
+ RX
80
o
C
H
2
CSOCH3, DMSO CHCO
2
R
OH
R = benzyl, isopropyl, allyl, n-pentyl or cyclopentyl


Dimethyl terephthalate can be polymerized with ethylene glycol in the presence of a tin chloride-DMSO complex and trimethylphosphate
to give a poly(ethylene terephthalate) (7255).
Thermoplastic polymers derived from natural products have been prepared by interesterifying starch with methyl palmitate in DMSO with
potassium methoxide as the catalyst (8227).



PART V USES
1. Polymerization and Spinning Solvent
DMSO is used as a solvent for the polymerization of acrylonitrile and other vinyl monomers, e.g. methyl methacrylate (9638) and styrene
(5192). Acrylonitrile is readily soluble in DMSO and the polymerization is carried out by the addition of initiators (8184)(8185). The low
incidence of transfer from the growing chain to DMSO leads to high molecular weights. Copolymerization reactions of acrylonitrile with
other vinyl monomers can also be run in DMSO. Monomer mixtures consisting of acrylonitrile, styrene, vinylidene chloride, methallyl
sulfonic acid, styrene sulfonic acid, etc. are polymerized in DMSO-water (6713). In some cases, the fibers are spun from the reaction
solution into DMSO-water baths (8501)(8603).
DMSO can also be used as a reaction solvent for other polymerizations. Thus, ethylene oxide is rapidly and completely polymerized in
DMSO (9652). Diisocyanates and polyols and polyamines can be dissolved and reacted in DMSO to form solutions of polyurethanes
(8677).

Polymerization Solvent for Heat Resistant Polymers. Poly(ether sulfones) are a family of polymers from which a series of tough
thermoplastics can be selected for use under continuous stress in the temperature range of 150-250
°
C (7196)(7619). These poly(ether
sulfones) are prepared by reacting dialkali metal salts of a bisphenol, such as bisphenol A or 4,4'-sulfonyldiphenol with 4,4'-
dihyalodiphenyl sulfones by the displacementetherification reaction in DMSO (7104)(9961), e.g.:
!
89!
SO
2
Cl Cl
+ NaO SO
2
ONa
DMSO
O
S
O
2
n

Interest in heat-resistant polymers has also lead to the development of polyetherimides. These polymers are prepared by the reaction of
a dialkali metal salt of a bisphenol, such as bisphenol A or 4,4'-sulfonyl diphenol, with bis(halophthalimide) in DMSO as the solvent
(9686). In place of bis(halophthalimides), certain bis(nitrophthalimides) in DMSO can be used (10434):
N
O
O
N
O
O
N
X
O
N
O
O
+
S
O O
NaO
ONa
DMSO
X
X
O
S
O
O O
X= halogen or NO
2.
n


Somewhat similar polyetherimides can be prepared by reacting an aromatic bis(ether dicarboxylic acid) component with a diamine in
DMSO-water (10762):
O
HO
2
C
HO
2
C
X
O
CO
2
H
CO
2
H
+
X
H
2
N
NH
2
N
O
X
O
N
O
O
O
O
X X= S; SO
2
, CH
2
, C(CH
3
)
2
, etc.
x-S; SO2; CH2; C(CH3)2, etc


2. Extraction Solvent
DMSO is immiscible with alkanes but a good solvent for most unsaturated and polar compounds. Thus it can be used to separate olefins
from paraffins (10771). DMSO is used in the Institute Francais du Petrole (IFP) process for extracting aromatic hydrocarbons from
refinery streams (8554). DMSO is also used in the analytical procedure for determining polynuclear hydrocarbons in food additives of
petroleum origin (2371).

3. Solvent for Electrolytic Reactions
DMSO has been widely used as a solvent for polarographic studies and it permits the use of a more negative cathode potential than in
water. In DMSO cations can be successfully reduced to form metals that would react with water. Thus, the following metals have been
electrodeposited from their salts in DMSO: cerium (1749), actinides (2520), iron, nickel, cobalt, manganese ÷ all amorphous deposits;
zinc, cadmium, tin, bismuth ÷ all crystalline deposits; (5488); chromium (6672), silver (7459), lead (9175), copper (9396), titanium
(7260). Generally, no metal less noble than zinc, such as magnesium or aluminum, can be deposited from DMSO.

4. Cellulose Solvent
Although DMSO by itself does not dissolve cellulose, the following binary and ternary systems are listed as cellulose solvents: DMSO-
methylamine, DMSO-sulfur trioxide, DMSO-carbon disulfide-amine, DMSO-ammoniasodamide, DMSO-dinitrogen tetroxide, DMSO-
paraformaldehyde (8970)(10368), DMSO-sulfur dioxide-ammonia (9541). A least a ratio of 3 moles of active agent per mole of glucose unit
is necessary for complete dissolution (8970). While only 80% of cellulose dissolves in DMSO-methylamine under cold anhydrous
conditions (10368), DMSO-nitrogen tetroxide is a better solvent, particularly when a small quantity of water is added (9170). Most of these
systems are capable of producting cellulose fibers. The recently discovered DMSO-paraformaldehyde system does not degrade cellulose
and it can form solutions containing up to 10% cellulose (7763)(8506)(9850). It is believed that a methylol-cellulose compound forms which
is stable for extended periods of storage at ambient conditions (9850). Regenerated cellulose articles such as films and fibers can be
prepared by contacting the DMSO-paraformaldehyde solution with methanol and water (9850)(9895).
!
90!

5. Pesticide Solvent
Many organic fungicides, insecticides and herbicides are soluble in DMSO, including such difficultly soluble materials as the substituted
ureas and carbamates. DMSO forms cosolvent systems of enhanced solubility properties with many solvents.
6. Cleanup Solvent
DMSO is used to remove urethane polymers and other difficultly soluble materials from processing equipment. Hard crusts of poly(vinyl
chloride) resin can be dissolved by using 85:15 ethyl acetate-DMSO mixture (8927).

7. Sulfiding Agent
DMSO (ENVIRO-S) can be used as a sulfiding agent in refineries because of its low odor, low toxicity and ease of handling.

8. Integrated Circuits
DMSO solutions are useful for etching resists in integrated circuit manufacture.












PART VI
TOXICITY, HANDLING, HAZARDS, ANALYSIS



1. Toxicity and Handling Precautions
Dimethyl sulfoxide is a relatively stable solvent of low toxicity. The LD50, for single dose oral administration to rats is about 18,000 mg/kg.
For comparison, the LD50 for ethyl alcohol is about 13,700 mg/kg. DMSO by itself presents less hazard than many chemicals and solvents
commonly used in industry. However, DMSO has the ability to penetrate the skin and may carry with it certain chemicals with which it is
combined under certain conditions.
The toxicity of DMSO solutions will depend, in part, on the nature and toxicity of the other chemicals used and the degree of penetration.
The degree of penetration is determined by the concentration of DMSO and water in the solution and the length of time of skin contact.
Not all chemicals will be carried through the skin even though the DMSO may penetrate. A 10% solution of DMSO in water causes only
slight increase in skin penetration over the same solution without DMSO.
Conventional industrial safety procedures and practices should be observed when working with DMSO as with any organic solvent.
Protective clothing is not necessary when handling DMSO in containers or in small amounts on limited occasions. However, when working
with DMSO on a prolonged basis or in combinations with other materials, protective clothing is recommended, including suitable gloves or
eye protectants. Butyl rubber gloves are suggested for DMSO service.
Contacts with DMSO Alone
Skin: Undiluted DMSO may have a mildly irritating effect on the skin and should be washed off promptly with cold water. As is the case
with other organic solvents, dimethyl sulfoxide tends to dehydrate and de-fat the skin. Repeated skin contact overextended periods should
be avoided since the effects of such contact, if any, are not yet known.
Eyes: DMSO in contact with the eye may cause temporary irritation but will not result in eye damage if washed out promptly with cold
water.
Vapors: The normal ambient airborne DMSO concentration is low. (DMSO has a high boiling point, 189
°
C or 372
°
F, and a low vapor
pressure.) Inhalation of vapors of hot DMSO or DMSO aerosol mists may be harmful and should be avoided.
Contact with DMSO solutions: When handling solutions of possibly toxic substances in DMSO, care must be taken to avoid contact with
the skin and to wash such solutions off immediately and thoroughly with soap and water. If toxic substances penetrate into the system,
serious harm may occur. Clothing contacted by such solutions should be removed and washed before reusing.

91!


2. Comparative Toxicity of Commercial Solvents
All solvents are toxic to some extent, but DMSO is much less so than many in common usage. Toxicity, as measured by dermal and
oral LD50 in rats, is shown for a number of common solvents. They are listed in order of increasing oral toxicity.
TABLE XII
Single-Dose Toxicity (Rats) of Some Common Solvents
LD50, mg/kg
Solvent Oral Dermal
Glycerine 31600 10000
DMSO 17400 40000
Ethanol 13700 -
Acetone 9750 -
Dimethylacetamide 7500 5000
Ethylene glycol 7200 -
N-methyl-2-pyrrolidone 7000 -
Trichloroethylene 5860 -
Lsopropanol 5840 -
n-Propanol 4300 -
Benzene 4080 -
Diacetone alcohol 4000 -
Methyl ethyl ketone 3980 -
Xylene 3830 10000
Cyclohexanone 3460 -
Acetic acid 3310 -
n-Butenol 2610 5620
2-Heptanol 2580 -
Butyl cellosolve 2380 -
Dimethylformamide 2250 442
Sodium lauryl sulfate 1650 10000
Pyridine 891 1120
Aniline 442 1540
Phenol 14* -
* Approximate lethal dose.
Most of the solvents in the above table were chosen because, like DMSO, they are polar.
Several studies have been made in comparing the toxicity of DMSO with other solvents. Table XIII shows the results of
one of these studies.

TABLE XIII
Single-Dose Toxicities to Mice of 4M Solutions
LD50, mg/kg (mice)
Compound Intravenous Intraperitoneal
DMSO 7176 14664
Glycerine 6164 6900
Dimethyl formamide 3650 6570
Dimethyl acetamide 3915 5916
N-methyl pyrrolidone 1980 3564


3. Chemicals and Reactions to be Avoided with DMSO
DMSO can react vigorously and even explosively with iodine pentafluoride, periodic acid, potassium permanganate, silver fluoride and
other strong oxidizing agents such as magnesium perchlorate and perchloric acid.
DMSO cannot be used in Friedel-Crafts reactions or with Ziegler-Natta catalysts.
DMSO reacts vigorously with acid chlorides. These reactions proceed with about the same vigor as the reaction between acid
chlorides and ethyl alcohol, and suitable precautions should be taken.
DMSO also reacts with carboxylic acid anhydrides, such as acetic anhydride, the major product being the
acyloxymethyl methyl sulfide, RCO2CH2SCH3.
Adequate heat removal should be provided when reacting DMSO with sodium hydride or potassium hydride when making the
DMSO anion (dimsyl ion) (Please see PART III, Reactions of DMSO, 4. Reaction with Strong
Bases).
An uncontrolled reaction took place when DMSO was heated with methyl bromide to prepare trimethyloxosulfonium bromide. This

92!
reaction should be run in the presence of compounds that remove HBr or Br2, such as methyl or ethyl orthoformate or tetramethyl
orthocarbonate. These esters act as scavengers of HBr and Br2, produced as byproducts in the reaction. Thus, the possible
violent exothermic decomposition of the reaction mixture can be prevented with little, if any, loss in the yield of the product (9964).
4. Analytical Procedure
a) Gas chromatographic analysis of DMSO
Apparatus
Gas chromatograph with flame ionization detector and a 4 ft. x 1/8 inch o.d. stainless steel column packed with 15% FFAP
(Varian Aerograph) on Chromosorb T (Johns-Manville), 40/60 mesh.
1.0 microliter syringe.
Chromatograph Conditions
Temperatures: Column - 150°C, Detector - 220°C, Inlet - 210°C Carrier gas flow -
30 ml/min
Adjust the instrument sensitivity so that a 0.5 microliter sample will give a DMSO peak between 75 and 100% of recorder full
scale.
Procedure
Inject 0.5 microliters of the DMSO. Record the DMSO peak at the sensitivity determined above. Record the period before and
after the DMSO peak at 100 times this sensitivity. Record the chromatogram for 20 minutes. Sum the areas of any extraneous
peaks.

Calculations


b) DMSO Freezing Point
Pour 30-50 ml of DMSO into a clean, dry test tube, approximately 2.5x20 cm in size and fitted with a stopper
containing thermometer and also containing a small magnetic stirring bar.
Cool the test tube in water at 15
°
C while agitating with a magnetic stirrer until crystallization starts. Once crystallization has
begun read the thermometer while both liquid and solid DMSO are present. Purified DMSO - 18.3
°
C minimum (See Figure
2b, page 5)
c) Water Determination by Karl Fischer Titration
Discussion
Water is determined by Karl Fischer titration. Karl Fischer procedures other than the one described below may be used provided
that their accuracy in this analysis has been determined.
Scope
This procedure may be used with all grades of DMSO.
Reagents
1. Pyridine-SO2-methanol.
Mix 300 ml. C.P. pyridine and 300 ml anhydrous methanol. Bubble in 60 grams of SO2. This can be done
with the solution on a platform balance to weigh directly the SO2 added.
2. Anhydrous methanol.
3. Karl Fischer Reagent - stablilized.
Fischer Scientific SO-K-3
4. Water-methanol standard.
1 ml = 1 mg of water. Can be obtained commercially.
Apparatus
Titration Assembly
The titration is contained in a screwcap glass jar of 100-200 ml capacity. The cap is drilled to admit2 platinum electrodes and one
burette tip. During the titration the jar is mounted over a magnetic stirrer with the electrodes extending through the cap into the solution
to be titrated. Reagents and sample are added through the third hole and a micro burette containing Karl Fischer Reagent is mounted
above the third hole.
A preferred alternate to the above assembly can be constructed from both halves of a large diameter glass ball and socket joint.
End-Point Detecting Assembly
The end-point detecting assembly is of the "dead stop" type, which depends upon the depolarization of the electrodes on reaching the
end-point of the titration.


93!
Procedure
End-Point Detection
With the equipment set up as described and the material to be titrated in the bottle, start the magnetic stirrer. Adjust the variable
resistance to produce a microammeter deflection of 1 or 2 microamps. Titrate with Karl Fischer Reagent. As the end-point is neared,
the ammeter needle starts to swing with each addition of titrant, but returns to the original point of deflection after each swing. When
the end-point is reached the needle will remain permanently displaced up scale.
Standardization of Reagents



The Karl Fischer solution must be standardized daily. Add 20 ml of anhydrous methanol and 5 ml of the pyridine-SO2-methanol
solution to the titration bottle (Note 1). Add Karl Fischer Reagent dropwise from a microburette to the end-point. Accurately pipette 20
ml of the water-methanol standard (a weighed amount of pure water may be used) into the titration bottle and titrate with Karl Fischer
Reagent to the end-point. Record the volume of titrant used in the second titration and calculate its water equivalence.
Determination of Water



Add 20 ml of anhydrous methanol and 5 ml of the pyridine-SO2-methanol solution to a clean titration bottle. Add Karl Fischer Reagent
dropwise to the end-point. Add 2 to 3 grams (accurately weighed) of the DMSO to be tested (Notes 2, 3, and 4). Titrate with Karl
Fischer Reagent to the end-point. Record the volume of titrant used in the second titration and calculate the water content of the
dimethyl sulfoxide.
Notes
1. Response tends to be slow with the stabilized Karl Fischer Reagent. A sharper end-point is obtained with the addition of the
pyridine-SO2-methanol solution to the titration vessel.
2. DMSO is extremely hydroscopic. Exposure of the sample to atmospheric moisture must be kept to a minimum.
3. Samples larger than 2-3 grams of DMSO produce low results.
4. For convenience, with a sacrifice of accuracy, a 2 or 3 ml. volume of DMSO can be sampled with a volumetric pipette. The weight
of DMSO samples is calculated by multiplying the volume in ml. by 1.10 (the specific gravity of pure DMSO @ 20°C.).
5. A titration assembly such as a Beckman Model KF-2 Aquameter may be used for the titration.





















PART VII
BIBLIOGRAPHY

1 Traynelis, V.J.; Hergenrother, W.L. J. Org. Chem. 29, 221-222 (1964).
8 French, F.A. Chem. & Eng. News, 48 (April 11, 1966).
17 Allen, F.M. Crown Zellerbach, results unpublished.
22 Parker, A.J. Sci. & Technol. (August 1965).
26 Turner, H.S.; Warne, R.J. Brit. Patent 946,989 (CO7D) (Jan. 15, 1964).
42 Daiichi Seiyaku Co. Ltd. Japan 10051/65; CA 63 5659B (1965).
49 Fuqua, S.A.; Duncan, W.G.; Silverstein, R.M. Tetrahedron Lett., No. 9, 521-523 (1965).

94!
84 Modena, G.; Scorrano, G.; Landini, D.; Montanari, F. Tetrahedron Lett., No. 28, 3309-3313
(1966).
85 Krueger, J.H. Inorg. Chem. 5, 132-135 (1966).
86 Saytzeff, A. Ann. 144, 148-156 (1967).
99 Johnson, M.D. J. Chem. Soc. 805-806 (1965).
101 Bottini, A.T.; Corson, F.P.; Bottner, E.F. J. Org. Chem. 30, 2988-2994 (1965).
105 Nace, H.R.; Monagle, J.J. J. Org. Chem. 24, 1792-1793 (1959).
106 Kornblum, N.; Jones, W.J.; Anderson, G.J. J. Am. Chem. Soc. 81, 4113-4114 (1959).
109 Elias, H.; Krutzik, S. Ber. 99, 1026-1031 (1966).
160 D'Amato, V. U.S. 3,054,789 (C1. 260-234) (Sept. 18, 1962).
161 Osipow, L.I.; York, W.C. U.S. 2,903,445 (C1. 260-211.5) (Sept. 8, 1959).
162 Hass, H.B.; Snell, F.D.; York, W.C.; Osipow, L.I. U.S. 2,893,990 (C1. 260-234) (July 7,
1959).
164 Distillers Co., Ltd. Brit. Pat. 859, 305 (CO7C) (Jan. 13, 1961).
165 Hass, H.B. U.S. 2,970,142 (C1. 260-234) (Jan. 31, 1961).
166 Huber, W.F. U.S. 2,997,490 (C1. 260-410) (Aug. 22, 1961).
167 Scheidt, K.H.; Kampe, W. Angew. Chem. Int. Ed. 4, 787 (1965).
172 Pfitzner, K.E.; Moffatt, J.G. J. Am. Chem. Soc. 87, 5661-5670 (1965).
173 Pfitzner, K.E.; Moffatt, J.G. J. Am. Chem. Soc. 87, 5670-5678 (1965).
175 Pfitzner, K.E.; Moffatt, J.G. J. Am. Chem. Soc. 85, 3027-3028 (1965).
181 Huber, W.F.; Tucker, N.B. U.S. 2,812,324 (C1. 260-234) (Nov. 5, 1957).
183 Brousse, E.; Lefort, D. Compt. Rend. 261, GP8, 1990-1991 (1965).
193 Bloomfield, J.J. J. Org. Chem. 27, 2442-2746 (1962).
202 Russell, G.A.; Weiner, S.A. J. Org. Chem. 31, 248-251 (1966).
203 Iwai, I.; Ide, J. Chem. Pharm. Bull. (Tokyo) 13(6), 663-672 (1965).
206 O'Connor, D.E.; Lyness, W.Ì. J. Org. Chem. 30, 1620-1623 (1965).
208 Onodera, K.; Hirano, S.; Kashimura, N. J. Am. Chem. Soc. 87, 4651-4652 (1965).
211 Fletcher, T.L.; Pan, H.L. J. Am. Chem. Soc. 78, 4812 (1965).
217 Izzo, P.T. J. Org. Chem. 28, 1713-1715 (1963).
229 Johnston, H. U.S. 3,051,757 (C1. 260-607) (Aug. 28, 1962).
232 Weaver, E.E.; Keim, W. Proc. Indiana Acad. Sci. for 1960, Vol. 70, 123-131 (1961).
240 Greenwald, R.; Chaykovsky, M.; Corey, E.J. J. Org. Chem. 28, 1128-1129 (1963).
264 Fletcher, T.L.; Pan, H-L. J. Org. Chem. 24, 141-142 (1959).
272 Legault, R.R.; Groves, K. Anal. Chem. 29, 1495-1496 (1957).
273 Kornblum, N.; Powers, J.W.; Anderson, G.J.; Jones, W.J.; Larson, H.O.; Levand, O.;
Weaver, W.M. J. Am. Chem. Soc. 79, 6562 (1957).
290 Horner, L.; Kaiser, P. Liebigs, Ann. Chem. 626, 19-25 (1959).
291 Pae, S.; Kitao, T.; Kawamura, S.; Kitaoka, Y. Tetrahedron 19, 817-820 (1963).
294 Ratz, R.; Sweeting, O.J. Tetrahedron Lett. No. 8, 529-532 (1963).
296 Goethals, E.; DeRadzitzky, P. Bull. Soc. Chim. Belg. 73 546-559 (1964).
302 Claypool, D.C.; Lard, E.W. Chem. Eng. News 38, 46-47 (Nov. 21, 1960).
308 King, C. J. Org. Chem. 25, 352-356 (1960).
312 Kuryla, W.C. J. Appl. Polymer Sci. 9, 1019-1040 (1965).
321 Soczewinski, E. J. Chromatog. 11, 275-277 (1963).
324 Smith, S.G.; Winstein, S. Tetrahedron 3, 317-319 (1958).
328 Murto, J.; Hiiro, A.M. Suomen Kemistilehti B37, 177-180 (1964).
329 Murto, J. Suomen Kemistilehti B34, 92-98 (1961).
334 Berti, G.; Macchia, B.; Macchia, F. Tetrahedron Lett. No. 38, 3421-3427 (1965).
336 Tommila, E. Suomen Kemistilehti 37B, 117-120 (1964).
342 Schlafer, H.L.; Schaffernicht, W. Angew. Chem. 72, 618-626 (1960).
348 Thomas, R.; Eriks, K. Dissertation Abstracts 26, No. 6, 3069-3070 (Dec. 1965).
353 Mackle, H.; O'Hare, P.A.G. Trans. Farad. Soc. 58, 1912-1915 (1962).
154 Lindberg, J.J. Finska Kemistsamfundets Medd 70, 33-39 (1961).
365 Webb, R.L. U.S. 3,280,177 (C1. 260-489) (Oct. 18, 1966).
366 Bay, P.G. U.S. 3,270,761 (C1. 260-307) (Sept. 21, 1965).
367 Tommila, E.; Murto, M.-L. Acta Chem. Scand. 17, 1947-1956 (1963).
368 Tommila, E.; Murto, M.-L. Acta Chem. Scand. 17, 1957-1970 (1963).
369 Tommila, E.; Palenius, I. Acta Chem. Scand. 17, 1980-1984 (1963).
372 Douglas, T.B. J. Am. Chem. Soc. 70, 2001-2002 (1948).
377 Szmant, H.H.; Roman, M.N. J. Am. Chem. Soc. 88, 4034-4039 (1966).

95!
385 Gundermann, K.D.; Holtmann, P. Angew. Chem. Int. Ed. 5, 668 (1966).
386 Fukui, K.; Tanimoto, f.; Kitano, H. Bull. Chem. Soc. Japan 38, No. 10, 1586-1589 (1965).
390 Emerson, D.W.; Booth, J.K. J. Org. Chem. 30, No. 7, 2480-2481 (1965).
391 Appel, R.; Rittersbacher, H. Ber. 97, 852-856 (1964).
392 Dyer, E.; Glenn, J.F.; Lendrat, E.G. J. Org. Chem. 26, 2919-2925 (1961).
394 Traynelis, V.J.; Hergenrother, W.L.; Hanson, H.T.; Valicenti, J.A. J. Org. Chem. 29, 123-
129 (1964).
396 Baker, R.; Spillett, M.J. Chem. Comm. 757-758 (1966).
398 Bader, H.; Hansen, A.R.; McCarty, F.J. J. Org. Chem. 31, 2319-2321 (1966).
399 Kingsbury, C.A. J. Org. Chem. 29, 3262-3270 (1964).
402 Murto, J. Suomen Kemistilehti B38, 49-50 (1965).
405 Traynelis, V.J.; Hergenrother, W.L.; Livingston, J.R.; Valicenti, J.A. J. Org. Chem. 27,
2377-2383 (1962).
407 Kingsbury, C.A. J. Am. Chem. Soc. 87, 5409-5416 (1965).
408 Nace, H.R. J. Am. Chem. Soc. 81, 5428-5430 (1959).
409 Kaiser, C.; Trost, B.M.; Beeson, J.; Weinstock, J. J. Org. Chem. 30, 3972-3975 (1965).
411 Argabright, P.A.; Hofman, J.E.; Schriesheim, A. J. Org. Chem. 30, 3233-3235 (1965).
423 Walling, C.; Bollyky, L. J. Org. Chem. 29, 2699-2701 (1964).
428 Wallace, T.J. J. Am. Chem. Soc. 86, 2018-2021 (1964).
429 Bottini, A.T.; Bottner, E.F. J. Org. Chem. 31, 389-391 (1966).
431 Tommila, E. Acta Chem. Scand. 20, 923-936 (1966).
432 Tommila, E.; Pitkanen, I.P. Acta Chem. Scand. 20, 937-945 (1966).
433 Tommila, E.; Savolainen, M. Acta Chem. Scand. 20, 946-962 (1966).
434 Cram, D.J.; Rickborn, B.; Knox, G.R. J. Am. Chem. Soc. 82, 6412-6413 (1960).
438 Finger, G.C.; Kruse, C.W. J. Am. Chem. Soc. 78(12), 6034-6037 (1956).
440 Argabright, P.A.; Rider, H.D.; Sieck, R. J. Org. Chem. 30, 3317-3321 (1965).
442 Solar, S.L.; Schumaker, R.R. J. Org. Chem. 31, 1996-1997 (1966).
443 Adams, A.R. U.S. 3,007,763 (C1. 8-11602) (Nov. 7, 1961).
449 Wyart, J.W.; Vona, J.A.; Cunningham, R.R. U.S. 3,061,629 (C1. 260-471) (Oct. 30, 1962).
450 Farago, J. U.S. 3,004,945 (C1. 260-30.8) (Oct. 17, 1961).
454 Osborn, C.L.; Shields, T.C.; Shoulders, B.A.; Cardenas, C.G.; Gardner, P.D. Chem. & Ind.
766-767 (1965).
455 Cardenas, C.G.; Khafaji, A.N.; Osborn, C.L.; Gardner, P.D. Chem. & Ind. 345-346 (1965).
459 Amonoo-Neizer, E.H.; Ray, S.K.; Shaw, R.A.; Smith, B.C. J. Chem. Soc. 6250-6252
(1965).
463 Boyle, R.E. J. Org. Chem. 31, 3880-3882 (1966).
464 Roberts, D.D. J. Org. Chem. 31, 4037-4041 (1966).
467 Michelot, R.; Tchoubar, B. Bull. Soc. Chem. France 3039-3040 (1966).
469 Russell, G.A.; Janzen, E.G.; Becker, H-D.; Smentowski, F.J. J. Am. Chem. Soc. 84, 2652-
2653 (1962).
470 Gorvin, J.H. Chem. Ind. 1525-1526 (1967).
471 Miller, J.; Parker, A.J. J. Am. Chem. Soc. 83, 117-123 (1961).
472 Fuchs, R.; McCrary, G.E.; Bloomfield, J.J. J. Am. Chem. Soc. 83, 4281-4284 (1961).
473 Ham, G.E. U.S. 3,206,499 (C1. 260-465.9) (Sept. 14, 1965).
474 Freure, B.T.; Decker, H.J. U.S. 3,024,266 (C1. 260-464) (Mar. 6, 1962).
475 Friedman, L.; Shechter, H. J. Org. Chem. 25, 877-879 (1960).
477 Bloomfield, J.J.; Fennessey, P.V. Tetrahedron Lett. No. 33, 2273-2276 (1964).
479 Anonymous Chem. & Engr. News 50-51 (Sept. 24, 1962).
480 Webb, R.L. U.S. 3,264,362 (C1. 260-675.5) (Aug. 2, 1966).
481 Price, C.C.; Snyder, W.H. J. Am. Chem. Soc. 83, 1773 (1961).
486 Hardies, D.E.; Kornblum, N.; Powers, J.W. U.S. 3,014,972 (C1. 206-644) (Dec. 26, 1961).
487 Fekete, F. U.S. 2,830,078 (C1. 260-486) (Apr. 8, 1958).
489 Oesterling, R.E. U.S. 3,006,964 (C1. 260-608) (Oct. 31, 1961).
490 Chang, R.C.; Wood, N.F. Tetrahedron Lett. No. 40, 2962-2973 (1964).
491 Snyder,C.H.; Soto, A.R. J. Org. Chem. 29, 742-745 (1964).
495 Cram, D.J.; Sahyun, M.R.V.; Knox, G.R. J. Am. Chem. Soc. 84, 1734-1735 (1962).
496 Mac, Y.C.; Parker, A.J. Australian J. Chem. 19, 517-520 (1966).
501 Hofmann, J.E.; Wallace, T.J.; Argabright, P.A.; Schriesheim, A. Chem. & Ind. (London)
1243-1244 (1963).
514 Cram, D.J.; Day, A.C. J. Org. Chem. 31, 1227-1232 (1966).

96!
515 Overberger, C.G.; Kurtz, T. J. Org. Chem. 31, 288-291 (1966).
517 Miller, B.; Margulies, H. J. Org. Chem. 30, 3895-3897 (1965).
524 Cram, D.J.; Gosser, L. J. Am. Chem. Soc. 86, 5457-5465 (1964).
526 Stewart, R.; O'Donnell, J.P. Can. J. Chem. 42, 1681-1693 (1964).
538 Bernasconi, C.F.; Kaufmann, M.; Zollinger, H. Helv. Chem. Acta. 49, 2563-2570 (1966).
540 Burdon, M.G.; Moffatt, J.G. J. Am. Chem. Soc. 88, 5855-5864 (1966).
541 Bacon, R.G.R.; Hill, H.A.O. Proc. Chem. Soc. 113-114 (1962).
544 Blumenthal, J.H. U.S. 3,028,423 (C1. 260-533) (Apr. 3, 1962).
550 Cisney, M.E. Crown Zellerbach, unpublished results (Jan. 12, 1967).
553 Kolthoff, I.M.; Reddy, T.B. J. Electrochem. Soc. 108, 980-985 (1961).
568 Russell, G.A.; Moye, A.J.; Janzen, E.G.; Mak, S.; Talaty, E.R. J. Org. Chem. 32, 137-146
(1967).
574 Ayres, J.T.; Mann, C.K. Polymer Letters 3, 505-508 (1965).
577 Smiley, R.A.; Arnold, C. J. Org. Chem. 25, 257-258 (1960).
578 Sahyun, M.R.V.; Cram, D.J. J. Am. Chem. Soc. 85, 1263-1268 (1963).
579 Schriesheim, A.; Hofmann, J.E.; Rowe, C.A., Jr. J. Am. Chem. Soc. 83, 3731-3732 (1961).
580 Snyder, C.H.; Soto, A.R. J. Org. Chem. 30, 673-676 (1965).
581 LeBel, R.g.; Goring, D.A.I. J. Chem. Engr. Data 7, 100-101 (1962).
585 Tommila, E.; Hamalainen, L. Acta. Chem. Scand. 17, 1985-1990 (1963).
589 Terrell, R.C.; Ucciardi, T.; Vitcha, J.F. J. Org. Chem. 30, 4011-4013 (1965).
592 Wood, N.F.; Chang, F.C. J. Org. Chem. 30, 2054-2055 (1965).
595 Bordwell, F.G.; Pitt, B.M. J. Am. Chem. Soc. 77, 572-577 (1955).
596 Bottini, A.T.; Schear, W. J. Org. Chem. 30, 3205-3206 (1965).
599 Bloomfield, J.J. J. Org. Chem. 26, 4112-4115 (1961).
600 Bottini, A.T.; Mullikin, J.A.; Morris, C.J. J. Org. Chem. 29, 373-379 (1964).
604 Clark, L.W. J. Phys. Chem. 61, 699-701 (1957).
606 Cram, D.J.; Kingsbury, C.A.; Rickborn, B. J. Am. Chem. Soc. 83, 3688-3696 (1961).
611 Zaugg, H.E.; Horrom, B.W.; Borgwardt, S. J. Am. Chem. Soc. 82, 2895-2903 (1960).
612 Zaugg, H.E. J. Am. Chem. Soc. 83, 837-840 (1961).
613 Zaugg, H.E.; Chadde, F.E.; Michaels, R.J. J. Am. Chem. Soc. 84, 4567-4573 (1962).
615 Zitko, V.; Bishop, C.T. Can. J. Chem. 44, 1749-1756 (1966).
622 Cram, D.J.; Gosser, L. J. Am. Chem. Soc. 85, 3890-3891 (1963).
624 Cotton, F.A.; Francis, R.; Horrocks, W.D., Jr. J. Phys. Chem. 64, 1534-1536 (1960).
631 Cram, D.J.; Wingrove, A.S. J. Am. Chem. Soc. 85, 1100-1107 (1963).
632 Corey, E.J.; Chaykovsky, M. J. Am. Chem. Soc. 87, 1353-1364 (1965).
634 Corey, E.J.; Chaykovsky, M. J. Am. Chem. Soc. 87, 1345-1353 (1965).
639 Martin, D.; Niclas, H-J. Ber. 102, 31-37 (1969).
640 Clark, L.W. J. Phys. Chem. 60, 825-826 (1956).
643 Clark, L.W. J. Phys. Chem. 65, 1651-1652 (1961).
650 Elias, H.; Christ, O.; Rosenbaum, E. Ber. 98, 2725-2737 (1965).
651 Elias, H.; Lieser, K.H. Chem. Ber. 94, 3128-3134 (1961).
652 Eaton, P.E. J. Am. Chem. Soc. 84, 2344-2348 (1962).
653 Eades, E.D.M.; Ball, D.H.; Long, L., Jr. J. Org. Chem. 31, 1159-1162 (1966).
656 Fuchs, R.; Nisbet, A. J. Am. Chem. Soc. 81, 2371-2373 (1959).
664 Gundermann, K.D. Angew. Chem. Int. Ed. 3, 144 (1964).
669 Heininger, S.A.; Dazzi, J. Chem. Eng. News 35, No. 9, 87 (1957).
672 Hofman, J.E.; Wallace, T.J.; Schriesheim, A. J. Am. Chem. Soc. 86, 1561-1563 (1964).
680 Jaunin, R. Helv. Chim. Acta. 49, 412-419 (1966).
682 Kornblum, N.; Powers, J.W. U.S. 2,816,909 (C1. 260-478) (Dec. 17, 1957).
684 Kornblum, N.; Blackwood, R.K.; Powers, J.W. J. Am. Chem. Soc. 79, 2507-2509 (1957).
685 Kornblum, N.; Powers, J.W. J. Org. Chem. 22, 455-456 (1957).
690 Kornblum, N.; Seltzer, R.; Haberfield, P. J. Am. Chem. Soc. 85, 1148-1154 (1963).
691 Kornblum, N.; Blackwood, R.K. Organic Synthesis Coll. Vol. IV, Rabjohn, N.Ed., John
Wiley & Son, New York (1963), 454-456.
696 Ledwith, A.; Shih-Lin, Y. Chem. & Ind. 1867-1868 (1964).
705 Dalton, D.R.; Hendrickson, J.B.; Jones, D. Chem. Comm. 591-592 (1966).
712 Montgomery, J.A.; Temple, C., Jr. J. Am. Chem. Soc. 83, 630-635 (1961).
714 Neidlein, R.; Hausmann, W. Angew. Chem. Int. Ed. 4, 708-709 (1965).
720 Richtzenhain, H.; Alfredsson, B. Ber. 86, 142-148 (1953).
722 Russell, G.A.; Janzen, E.G.; Strom, E.T. J. Am. Chem. Soc. 84, 4155-4157 (1962).

97!
725 Roberts, W.; Whiting, M.C. J. Chem. Soc. 1290-1293 (1965).
726 Roberts, D.D. J. Org. Chem. 30, 3516-3520 (1965).
728 Russell, G.A.; Janzen, E.G.; Bemix, A.G.; Geels, E.J.; Moye, A.J.; Mak, S.; Strom, E.T.
Advances in Chem. Series, No. 51, 112-173 (1965).
730 Roberts, D.D. J. Org. Chem. 29, 2039-2040 (1964).
734 Steiner, E.C.; Gilbert, J.M. J. Am. Chem. Soc. 85, 3054-3055 (1963).
737 Sato, T.; Yamada, E-I.; Akiyama, T.; Inoue, H.; Hata, K. Bull. Chem. Soc. Japan 38, 1225
(1965).
742 Wolford, R.K. J. Phys. Chem. 68, 3392-3398 (1964).
772 Jones, J.L.; Fritsche, H.A., Jr. J. Electroanal. Chem. 12, 334-340 (1966).
773 LeNoble, W.J.; Puerta, J.E. Tetrahedron Lett. No. 10, 1087-1090 (1966).
786 Bowden, K.; Buckley, A.; Stewart, R. J. Am. Chem. Soc. 88, 947-949 (1966).
790 Allen, F.M. Crown Zellerbach, results unpublished (Jan. 20, 1965).
794 Allen, F.M. Crown Zellerbach, results unpublished (Aug. 12, 1960).
801 Dodd, R.E.; Gasser, R.P.H. Proceed. Chem. Soc. 415 (1964).
825 Maggiolo, A.; Blair, E.A. Advances in Chem. Series, No. 21, 200-201 (1959).
833 Cockerill, A.F.; Rottschaefer, S.; Saunders, W.H. J. Am. Chem. Soc. 89, 901-905 (1967).
843 Graham, W.H. J. Am. Chem. Soc. 87, 4396-4397 (1965).
849 Hayashi, Y.; Oda, R. J. Org. Chem. 32, 457-458 (1967).
872 Brett, D.; Downie, I.M.; Lee, J.B. J. Org. Chem. 32, 855-856 (1967).
882 Froemsdorf, D.H.; Robbins, M.D. J. Am. Chem. Soc. 89, 1737-1739 (1967).
884 Miller, B. J. Am. Chem. Soc. 89, 1685-1690 (1967).
885 Miller, B.; Margulies, H. J. Am. Chem. Soc. 89, 1678-84 (1967).
888 Manhas, M.S.; Jeng, S.J. J. Org. Chem. 32, 1246-1248 (1967).
905 DiSanto, C. U.S. 3,304,331 (C1. 260-607) (Feb. 14, 1967).
913 Bockmann, T.; Haanaes, E.; Ugelstad, J. Tidsskr. Kjemi. Bergv. Met. 24, No. 11, 209-215
(1964).
923 Wada, G.; Reynolds, W. Inorg. Chem. 5, 1354-1358 (1966).
941 Montgomery, J.A.; Thomas, H.J. J. Org. Chem. 30, 3235-3236 (1965).
942 Krapcho, A.P.; Glynn, G.A.; Grenon, B.J. Tetrahedron Lett. No. 3, 215-217 (1967).
944 Stewart, R.; O'Donnell, J.P.; Cram, D.J.; Rickborn, B. Tetrahedron 18, 917-922 (1962).
945 Bennett, C.F. Crown Zellerbach, results unpublished (Feb. 21, 1967).
947 Bennett, C.F. Crown Zellerbach, results unpublished (Aug. 16, 1966).
964 Cisney, M.E. Crown Zellerbach, results unpublished (Mar. 20, 1967).
965 Chang, F.C.; Wood, N. Steroids 5, 55-56 (1964).
982 Glynn, E. Analyst 72, 248-250 (1947).
988 Cisney, M.E. Crown Zellerbach, results unpublished (Mar. 8, 1967).
1001 Carson, J.F.; Boggs, L.E. J. Org. Chem. 31, 2862-2864 (1966).
1005 Gunther, W.H.H. J. Org. Chem. 31, 1202-1205 (1966).
1007 Boulton, A.J.; Ghosh, P.B.; Katritzky, A.R. J. Chem. Soc. (C) 971-976 (1966).
1016 Senning, A. Chem. Commun. 64 (1967).
1022 Brown, H.C.; Yoon, N.M. J. Am. Chem. Soc. 88, 1464-1472 (1966).
1024 Brown, H.C.; Weissman, P.M.; Yoon, N.M. J. Am. Chem. Soc. 88, 1458-1463 (1966).
1025 Sugiyama, N.; Akutagawa, M. Bull. Chem. Soc. Japan 40, 240 (1967).
1027 Cason, J.; Correia, J.S. J. Org. Chem. 26, 3645-3649 (1961).
1028 Tommila, E.; Virtanen, O. Suomen Kemistilehti 34B, 139-143 (1961).
1036 Manashi, J.; Reynolds, W.L.; Van Auken, G. Inorg. Chem. 4, 299-304 (1965).
1040 Oda, R.; Mieno, M.; Hayashi, Y. Tetrahedron Lett. No. 25, 2363-2365 (1967).
1055 Pettit, G.R.; Brown, T.H. Can. J. Chem. 45, 1306-1308 (1967).
1099 Wesslen, B. Acta. Chem. Scand. 21, 713-717 (1967).
1100 Wesslen, B. Acta. Chem. Scand. 21, 718-20 (1967).
1110 Chalmers, L. Specialties 2-6 (Dec. 1966).
1114 Rhoads, S.J.; Hasbrouck, R.W. Tetrahedron 22, 3557-3570 (1966).
1118 Sato, T.; Inoue, H.; Hata, K. Bull. Chem. Soc. Japan 40, 1502-1506 (1967).
1119 Ball, D.H.; Eades, E.D.M.; Long, L., Jr. J. Am. Chem. Soc. 86, 3579-3580 (1964).
1127 Albright, J.D.; Goldman, L. J. Am. Chem. Soc. 89, 2416-2423 (1967).
1138 Brown, H.C.; Rao, B.C.S. J. Am. Chem. Soc. 82, 681-686 (1960).
1140 Barton, D.H.R.; Jones, D.W. J. Chem. Soc. 3563-3570 (1965).
1161 Courtalds, Ltd. Brit. Pat. 928,114 (CO8F) (June 6, 1963).
1162 Cram, D.J.; Mateos, J.L.; Hauck, F.; Langmann, A.; Kopecky, K.R.; Nielsen, W.D.; Allinger,

98!
J. J. Am. Chem. Soc. 81, 5774-5784 (1959).
1172 Dolman, D.; Ross, S. Can. J. Chem. 45, 911-927 (1967).
1214 Kolling, O.W. Trans. Kansas Acad. Sci. 67(4), 635-639 (1964).
1229 Bram, G. Tetrahedron Lett. 41, 4069-4072 (1967).
1233 Nelsen, S.F.; Seppanen, E.D. J. Am. Chem. Soc. 89, 5740-5742 (1967).
1234 Burdon, M.G.; Moffatt, J.G. J. Am. Chem. Soc. 89, 4725-4735 (1967).
1237 Kornblum, N.; Davies, T.M.; Earl, G.; Greene, G.S.; Holy, N.L.; Kerber, R.C.; Manthey, J.W.;
Musser, M.T.; Snow, D.H. J. Am. Chem. Soc. 89, 5714-5715 (1967).
1238 Calligaris, M.; Illuminati, G.; Marino, G. J. Am. Chem. Soc. 89, 3518-3521 (1967).
1239 Genel, F.; Illuminati, G.; Marino, G. J. Am. Chem. Soc. 89, 3516-3518 (1967).
1240 Illuminati, G.; Marino, G.; Sleiter, G. J. Am. Chem. Soc. 89, 3510-3515 (1967).
1257 Howards of Ilford, Ltd. Brit. Pat. 872,293 (Aug. 3, 1956).
1262 Ross, S.D.; Barry, J.E.; Petersen, R.C. J. Am. Chem. Soc. 83, 2133-2136 (1961).
1268 Hirose, K.; Ukai, S. Yakugaku Zasshi 86(3), 187-191 (1966); CA 64 19466D (1966).
1271 Kitagawa, H. Kobunshi Kagaku 20 (213), 5-10 (1963); CA 61 1942E (1964).
1273 Bennett, C.F.; Goheen, D.W.; MacGregor, W.S. J. Org. Chem. 28, 2845-2846 (1963).
1360 Nicholas, L.; Gmitter, G.T. J. Cellular Plastics 1 (1), 85-89 (1965).
1373 Wallace, T.J.; Mahon, J.J. J. Am. Chem. Soc. 86, 4099-4103 (1964).
1383 Ray, S.K.; Shaw, R.; Smith, B.C. Nature 196, 372 (1962).
1417 Sears, P.G.; Siegfried, W.D.; Sands, D.E. J. Chem. Eng. Data 9(2), 261-263 (1964).
1455 Shell Res. Ltd. Fr. Pat. 1,326,419 (C1. C O7C) (May 10, 1963).
1474 Whitstler, R.L.; King, A.H.; Ruffini, G.; Lucas, F.A. Arch. Biochem. Biophys. 121, 358-363
(1967).
1501 Cram, D.J.; Rickborn, B.; Kingsbury, C.A.; Haberfield, P. J. Am. Chem. Soc. 83, 3678-
3687 (1961).
1503 Epstein, W.W.; Sweat, F.W. Chem. Rev. 67(3), 247-260 (1967).
1505 Evans, J.C.; Lo G. Y-S. Spectrochimica Acta 21, 33-44 (1965).
1508 Giordano, M.C.; Bazan, J.C.; Arvia, A.J. Electrochim. Acta. 11, 741-747 (1966).
1515 Horner, L.; Bruggemann, H. Ann. Chem. 635, 22-30 (1960), CA55 4401 (1961).
1521 Gallais, F.; Voigt, D. Bull. Soc. Chim. France 1935-1942 (1963).
1544 Landini, D.; Montanari, F. Tetrahedron Lett. 38, 26912696 (1964).
1558 Ritchie, C.D.; Uschold, R.E. J. Am. Chem. Soc. 89(12), 2960-2963 (1967).
1579 Tien, J.M.; Hunsberger, I.M. U.S. Dept. Com. Tech. Serv. AD264, 111 (1959).
1591 Feit, B-A.; Sinnreich, J.; Zilkha, A. J. Org. Chem. 32, 2570-2575 (1967).
1593 Bacon, R.G.R.; Hill, H.A.O. J. Chem. Soc. 1097-1107 (1964).
1612 Krull, L.H.; Friedman, J. J. Chromatog. 26, 336-338 (1967).
1638 Suhr, H. Ann. Chem. 687, 175-182 (1965); CA 63 17825C (1965).
1638 Suhr, H. Ann. Chem. 689, 109-117 (1965).
1651 Shilling, W.L. Crown Zellerbach, results unpublished.
1668 White, E.H.; Bursey, M.M. J. Am. Chem. Soc. 86, 941-942 (1964).
1687 Allenmark, S. Ark. Kemi. 24(4), 34-47 (1966).
1694 Venkatasubramanian, N.; Rao, G.V. Tetrahedron Lett. (52), 5275-5280 (1967).
1711 Ten Haken, P. Tetrahedron Lett. (8), 759-760 (1967).
1721 Hayashi, E.; Akahori, Y.; Watanabe, T. J. Pharmaceutical Soc. Jap. 87(9), 1115-1117
(1967).
1728 Martin, D.; Niclas, H.-J. Ber. 100, 187-195 (1967).
1744 Nichols, G.A. Appita 19(3), XXVII-XXX (1965); ABIPC 36, 8842.
1749 Porter, J.A. AEC Res. & Dev. Report DP-389 (July 1959).
1752 Parikh, J.R. J. Am. Chem. Soc. 89(21), 5505-5507 (1967).
1758 Brauman, J.I.; Nelson, N.J.; Kahl, D.C. J. Am. Chem. Soc. 90 (2), 490-491 (1968).
1759 Brauman, J.I.; Nelson, N.J. J. Am. Chem. Soc. 90 (2), 491-492 (1968).
1774 Zimmerman, H.E.; Grunewald, J.O. J. Am. Chem. Soc. 89, 5163-5172 (1967).
1787 Russell, G.A.; McDonnell, J.; Whittle, P.R. J. Am. Chem. Soc. 89, 5516-5517 (1967).
1798 Oth, J.F.M.; Merenyi, R.; Nielsen, J.; Schroder, G. Ber. 98, 3385-3400 (1965).
1805 Allenmark, S. Acta. Chem. Scand. 20, 910-911 (1966).
1823 Pond, D.M.; Cargill, R.L. J. Org. Chem. 32, 4064-4065 (1967).
1826 Peterson, P.E.; Bopp, R.J.; Chevli, D.M.; Curran, E.L.; Dillard, D.E.; Kamat, R.J. J. Am.
Chem. Soc. 89, 5902-5911 (1967).
1880 Lyman, D.J. U.S. 2,984,636 (C1. 260-30.8) (May 16, 1961).
1924 Cisney, M.E. Crown Zellerbach, unpublished results (Feb. 13, 1967).

99!
1942 Szmant, H.H. Angew. Chem. Int. Ed. 7(2), 120-128 (1968).
1946 Harriss, H.E.; Herzog, H.L. U.S. 3,259,646 (C1. 260-465) (July 5, 1966).
2007 Kollmeyer, W.D.; Cram, D.J. J. Am. Chem. Soc. 90, 1784-1791 (1968).
2013 Firestone, R.A.; Reinhold, D.F.; Gaines, W.A.; Chemerda, J.M.; Sletzinger, M. J. Org.
Chem. 33, 1213-1218 (1968).
2035 Cram, D.J.; Ratajczak, A. J. Am. Chem. Soc. 2198-2200 (1968).
2075 Farbenfabriken Bayer A.-G. Ger. Pat. 1,088,980 (C1. CO7C) (Sept. 15, 1960).
2125 Abramovitch, R.A.; Helmer, F.; Liveris, M. J. Chem. Soc. 492-496 (1968).
2140 Sugiyama, N.; Akutagaawa, M.; Yamamoto, H. Bull. Chem. Soc. Japan 41, 936-941
(1968).
2151 Garnsey, R.; Prue, J.E. Trans. Faraday Soc. 64(545), 1206-1219 (1968).
2189 Dear, R.E.A.; Pattison, F.L.M. J. Am. Chem. Soc. 85, 622-626 (1963).
2194 Delhoste, J.; Gomez, G.; Lamaty, G. Comptes Rendus 266(19), 1468-1470 (1968).
2196 Dahlgren, K.; Delhoste, J.; Lamaty, G. Comptes Rendus 266(15), 1180-1182 (1968).
2218 Berger, A.W.; Driscoll, J.S.; Pirog, J.A.; Linschitz, H. Photochem. Photobio. 7, 415-420
(1968).
2223 Tommila, E.; Pajunen, A. Suomen Kemi 41(5-6), 172-175 (1968).
2239 Normant, H. U. S. 3,390,186 (C1. 260-590) (June 25, 1968).
2265 Kawai, W. J. Polym. Sci. A-1 6, 1945-1954 (1968).
2323 Shapiro, E.; Legatt, T.; Weber, L.; Oliveto, E.P.; Tanake, M.; Crowe, D.F. Steroids 3, 183-
188 (1964).
2327 Onodera, K.; Hirano, S.; Kashimura, N. Carbohydrate Res. 6, 276-285 (1968).
2343 Jurch, G.R., Jr.; Ramey, K.C. Chem. Comm. 1211-1212 (1968).
2371 Haenni, E.O.; Joe, F.L., Jr.; Howard, J.W.; Leibel, R.L. J. Assn. Off. Agr. Chemists 45(1),
59-66 (1962).
2463 McCasland, G.E.; Naumann, M.O.; Durham, L.J. J. Org. Chem. 33, 4220-4226 (1968).
2492 Kreevoy, M.M.; Williams, J.M., Jr. J. Am. Chem. Soc. 90, 6809-6813 (1968).
2520 Handley, T.H.; Cooper, J.H. Anal. Chem. 41(2), 381-382 (1969).
2525 Schmid, G.H.; Fitzgerald, P.H. Can. J. Chem. 46, 3758-3762 (1968).
2532 Goethals, E.J.; Sillis, C. Makromol. Chemie 119, 249-251 (1968).
2565 Kornblum, N.; Davies, T.M.; Earl, G.W.; Holy, N.L.; Manthy, J.W.; Musser, M.T.; Swiger,
R.T. J. Am. Chem. Soc. 90, 6219-6221 (1968).
2566 Kornblum, N.; Earl, G.W.; Holy, N.L.; Manthey, J.W.; Musser, M.T.; Snow, D.H.; Swiger,
R.T. J. Am. Chem. Soc. 90, 6221-6223 (1968).
2567 Buchta, R.C.; Evans, D.H. Anal. Chem. 40(14), 2181-2186 (1968).
2583 Kohler, W.; Neuheiser, L. Z. Chem. 8(11), 425-426 (1968).
2589 Hoffman, T.D.; Cram, D.J. J. Am. Chem. Soc. 91, 1000-1008 (1969).
2597 Gustav, J.; Schulz, D.; Whitaker, A.C.; Winteler, P. U.S. 3,418,360 (C1. 260-475) (Dec. 24,
1968).
2643 Johnson, C.R.; Phillips, W.G. J. Am. Chem. Soc. 91, 682-687 (1969).
2652 Cree, G.M.; Mackie, D.W.; Perlin, A.S. Can. J. Chem. 47, 511-512 (1969).
2749 Milborrow, B.V.; Djerassi, C. J. Chem. Soc. C 417-424 (1969).
2760 Brownlee, R.T.C.; English, P.J.Q.; Katritzky, A.R.; Topsom, R.D. J. Phys. Chem. 73, 557-
564 (1969).
2765 Buckley, A.; Chapman, N.B.; Shorter, J. J. Chem. Soc. B 195-200 (1969).
2769 Landgrebe, J.A.; Thurman, D.E. J. Am. Chem. Soc. 91, 1759-1766 (1969).
2779 Toland, W.G. U.S. 3,428,671 (C1. 260-51.3) (Feb. 18, 1969).
2783 Anderson, A.G., Jr.; Breazeale, R.D. J. Org. Chem. 34(8), 2375-2384 (1969).
2842 Baker, R.; Spillett, M.J. J. Chem. Soc. B 581-588 (1969).
2887 Bonthrone, W.; Cornforth, J.W. J. Chem. Soc. C 1202-1204 (1969).
2896 Oae, S. Quart. Reports on Sulfur Chemistry 5(1), 53-66 (1970).
2900 Clever, H.L.; Westrum, E.F., Jr. J. Phys. Chem. 74, (6), 1309-1317 (1970).
2915 Clarke, T.G.; Hampson, N.A.; Lee, J.B.; Morley, J.R.; Scanlon, B. Can. J. Chem. 47, 1649-
1654 (1969).
2924 Smith, R.G.; Vanterpool, A.; Kulak, H.J. Can. J. Chem. 47, 2015-2019 (1969).
2940 Morgan, M.S.; Simon, A.W. U.S. 3,441,574 (C1. 260-369) (Apr. 29, 1969).
2969 Fierce, W.L. U.S. 3,461,156 (C1. 260-491) (Aug. 12, 1969).
2980 Hutchins, R.O.; Hoke, D.; Keogh, J.; Koharski, D. Tetrahedron Lett. 40, 3495-3498 (1969).
2987 Klein, J.; Brenner, S. Chem. Comm. 1020-1021 (1969).
2988 Acharaya, S.P.; Brown, H.C.; Suzuki, A.; Nozawa, S.; Itoh, M. J. Org. Chem. 34(10), 3015-

100!
3022 (1969).
3009 Baird, M.S.; Reese, C.B. J. Chem. Soc. C 1803-1807 (1969).
3033 Corey, E.J.; Weinshenker, N.M.; Schaaf, T.K.; Huber, W. J. Am. Chem. Soc. 91, 5675-
5677 (1969).
3048 Kharasch, N.; Szmant, H.H. Quart. Rep. Sulfur Chem. 3(2), 147-148 (1968).
3049 Kharasch, N.; MacGregor, W.S. Quart. Rep. Sulfur Chem. 3(2), 149-158 (1968).
3112 Davies, J.S.; Cavies, V.H.; Hassall, C.H. J. Chem. Soc. C 1873-1879 (1969).
3142 Terrell, R.C. U.S. 3,476,812 (C1.260-609) (Nov. 4, 1969).
3148 Iriuchijima, S.; Tsuchihashi, G.-I. Synthesis 588 (1970).
3152 Beninate, J.V.; Boylston, E.K. U.S. 3,480,381 (C1. 8-120) (Nov. 25, 1969).
3178 Gibson, T.W.; Erman, W.F. J. Am. Chem. Soc. 91, 4771-4777 (1969).
3215 Bennett, C.F. Crown Zellerbach, results unpublished (Sept. 15, 1970).
3217 Tallant, D.R.; Evans, D.H. Anal. Chem. 41(6), 835-838 (1969).
3241 Schneider, H.W. J. Chem. Ed. 47, 519-522 (1970).
3247 Whitaker, K.E.; Snyder, H.R. J. Org. Chem. 35, 30-32 (1970).
3248 Bell, H.M.; Vanderslice, C.W.; Spehar, A. J. Org. Chem. 34, 3923-3926 (1969).
3249 Feit, B.A.; Bigon, Z. J. Org. Chem. 34, 3942-3948 (1969).
3272 Irvine, D.S.; Kruger, G. J. Org. Chem. 35, 2418-2419 (1970).
3356 Blakrishnan, M.; Rao, G.V.; Venkatasubramian, N. Indian J. Chem. 8, 566-567 (1970).
3360 Weiss, R.G.; Snyder, E.I. J. Org. Chem. 35, 1627-1632 (1970).
3368 Bartsch, R.A. J. Org. Chem. 35, 1334-1338 (1970).
3376 Filler, R.; Rao, Y.S.; Biezais, A.; Miller, F.N.; Beaucaire, V.D. J. Org. Chem. 35, 930-935
(1970).
3384 Stalick, W.M.; Rines, H. J. Org. Chem. 35, 422-426 (1970).
3386 Chow, S.W.; Pilato, L.A.; Wheelwright, W.L. J. Org. Chem. 35, 20-22 (1970).
3387 Heindel, N.D.; Kennewel, P.D. J. Org. Chem. 35, 80-83 (1970).
3395 Cruickshank, P.A.; Fishman, M. J. Org. Chem. 34, 4060-4065 (1969).
3398 Bartsch, R.A.; Cook, D.M. J. Org. Chem. 35, 1714-1715 (1970).
3399 Klabunde, K.J.; Burton, D.J. J. Org. Chem. 35, 1711-1712 (1970).
3429 Brown, H.C.; Heim, P.; Yoon, N.M. J. Am. Chem. Soc. 92,1637-1646 (1970).
3433 Kornblum, N.; Stuchal, F.W. J. Am. Chem. Soc. 92, 1804-1806 (1970).
3445 Orvik, J.A.; Bunnett, J.F. J. Am. Chem. Soc. 92, 2417-2427 (1970).
3447 Kemp, D.S.; Paul, K. J. Am. Chem. Soc. 92, 2553-2554 (1970).
3456 Woerner, F.P.; Reimlinger, H. Ber. 103, 1908-1917 (1970).
3481 Sucrow, W.; Girgensohn, B. Ber. 103, 750-756 (1970).
3482 Roth, W.R.; Koenig, J.; Stein, K. Ber. 103, 426-439 (1970).
3490 Kornblum, N.; Swiger, R.T.; Earl, G.W.; Pinnick, H.W.; Stuchal, F.W. J. Am. Chem. Soc.
92, 5513-5514 (1970).
3503 Kelsey, D.R.; Bergman, R.G. J. Am. Chem. Soc. 92, 228-230 (1970).
3506 Bottaccio, G.; Chiusoli, G.P. Z. Nturforsch. (B) 23, 1016 (1968); Synthesis 1,33 (1970).
3519 Jacobus, J. J. Chem. Soc. (D) 338-339 (1970).
3572 Yamatani, T.; Yasunami, M.; Takase, K. Tetrahedron Lett. 1725-1728 (1970).
3584 Fahey, R.C.; Monahan, M.W. J. Am. Chem. Soc. 92, 2816-2820 (1970).
3602 Butterworth, R.F.; Hanessian, S. Synthesis 70-88 (1971).
3631 Miller, B. J. Org. Chem. 35, 4262-4264 (1970).
3653 Happ, J.W.; Janzen, E.G.; Rudy, B.C. J. Org. Chem. 35, 3382-3389 (1970).
3660 Truce, W.E.; Markley, L.D. J. Org. Chem. 35, 3275-3281 (1970).
3662 Rabjohn, N.; Harbert, C.A. J. Org. Chem. 35, 3240-3243 (1970).
3686 Baer, H.H.; Naik, S.R. J. Org. Chem. 35, 3161-3164 (1970).
3707 Reese, C.B.; Shaw, A. J. Chem. Soc. (D) 1172-1173 (1970).
3721 Lorkowski, H.J.; Pannier, R. J. Prakt. Chem. 311, 936 (1969).
3743 Dodd, D.; Johnson, M.D. J. Chem. Soc. (B), 1337-1343 (1970).
3766 Raber, D.J.; Bingham, R.c.; Harris, J.M.; Fry, J.L.; Schleyer, P.V.R. J. Am. Chem. Soc. 92,
5977-5981 (1970).
3816 Brown, H.C.; Bigley, D.B.; Arora, S.K.; Yoon, N.M. J. Am. Chem. Soc. 92, 7161-7167
(1970).
3820 Pollack, R.M.; Bender, M.L. J. Am. Chem. Soc. 92, 7190-7194 (1970).
3827 Farr, F.R.; Bauld, N.L. J. Am. Chem. Soc. 92, 6695-6696 (1970).
3830 Miller, B. J. Am. Chem. Soc. 92, 6252-6259 (1970).
3853 Bartsch, R.A.; Kelly, C.F.; Pruss, G.M. Tetrahedron Lett. 3795-3796 (1970).

101!
3875 Franck, B.; Petersen, U.; Hueper, F. Angew. Chem. Intern. Ed. Engl. 9, 891 (1970).
3885 Reimlinger, H. Ber. 103, 3278-3283 (1970).
3920 Bennett, C.F. Crown Zellerbach; results unpublished (Aug. 8, 1969).
3921 Bennett, C.F. Crown Zellerbach; results unpublished (Nov. 20, 1970).
3922 Bennett, C.F. Crown Zellerbach; results unpublished (Nov. 12, 1968).
3925 Tuemmler, W.B.; Linder, S.M. U.S. 3,506,724 (C1. 260-622) (Apr. 14, 1970).
3931 Orle, J.V. Crown Zellerbach; results unpublished (Jan. 14, 1969).
3951 Taranko, L.B.; Perry, R.H., Jr. J. Org. Chem. 34, 226-227 (1969).
4018 Birch, A.J.; Hutchinson, E.G.; Rao, G.S. J. Chem. Soc. (C) 637-642 (1971).
4026 Dalton, D.R.; Dutta, V.P. J. Chem. Soc. (B) 85-89 (1971).
4037 Marshall, J.A.; Cohen, G.M. J. Org. Chem. 36, 877-882 (1971).
4046 Hutchins, R.O.; Lawson, D.W.; Rua, L.; Milewski, C.; Maryanoff, B. J. Org. Chem. 36, 803-
806 (1971).
4048 Marshall, J.A.; Warne, T.M., Jr. J. Org. Chem. 36, 178-183 (1971).
4058 Hales, R.H.; Bradshaw, J.S.; pratt, D.R. J. Org. Chem. 36, 314-317 (1971).
4059 Bradshaw, J.S.; Hales, R.H. J. Org. Chem. 36, 318-322 (1971).
4066 Weiss, R.G.; Snyder, E.I. J. Org. Chem. 36, 403-406 (1971).
4068 Baumann, J.B. J. Org. Chem. 36, 396-398 (1971).
4077 Farnum, D.G.; Mostashari, A.; Hagedorn, III, A.A. J. Org. Chem. 36, 698-702 (1971).
4093 Walters, S.L.; Bruice, T.C. J. Am. Chem. Soc. 93, 2269-2282 (1971).
4098 Stocks, I.D.H.; Waite, J.A.; Wooldridge, K.R.H. J. Chem. Soc (C), 1314-1317 (1971).
4110 Bhalerao, U.T.; Rapaport, H. J. Am. Chem. Soc. 93, 105-110 (1971).
4123 Jacobs, R.L. J. Org. Chem. 36, 242-243 (1971).
4126 Poutsma, M.L.; Ibarbia, P.A. J. Am. Chem. Soc. 93, 440-450 (1971).
4128 Venezky, D.L. Anal. Chem. 43, 971 (1971).
4136 Seree, De Roch, I.; Menguy, P. French Pat. 1,540,284 (C1. CO7C) (Sept. 27, 1968); CA
71, 80944Q.
4175 Sherrod, S.A.; Bergman, R.G. J. Am. Chem. Soc. 93, 1925-1940 (1971).
4176 Kelsey, D.R.; Bergman, R.G. J. Am. Chem. Soc. 93, 1941-1952 (1971).
4180 Parker, A.J. Chem. Tech. 297-303 (1971).
4235 Augustyn, O.P.H.; DeWet, P.; Garbers, C.F.; Lourens, L.C.F.; Neuland, E.; Schneider, D.F.;
Steyn, K. J. Chem. Soc. (C) 1878-1884 (1971).
4249 Zefirov, N.S.; Chapovskaya, N.K. J. Org. Che. USSR 4, 1252 (1968).
4257 Mantione, R. Synthesis, 332-333 (1971).
4258 Mantione, R. Synthesis, 332 (1971).
4261 Shepherd, T.M. Chem. Ind. 567 (1970); Synthesis, 334 (1971).
4262 Koester, R.; Arora, S.; Binger, P. Synthesis, 322-323 (1971).
4278 Shepard, K.L. J. Chem. Soc. (D), 951-952 (1971).
4311 Kruger, G. J. Org. Chem. 36, 2129-2132 (1971).
4333 Cable, J.; Djerassi, C. J. Am. Chem. Soc. 93, 3905-3910 (1971).
4339 Pines, H.; Stalick, W.M.; Holford, T.G.; Golab, J.; Lazar, H.; Simonik, J. J. Org. Chem. 36,
2299-2301 (1971).
4349 Brimacombe, J.S. Angew. Chem. Intern. Ed. Engl. 10, 236-248 (1971).
4355 Isele, G.L.; Luttringhaus, A. Synthesis, 266-268 (1971).
4360 Muchowski, J.M. Can. J. Chem. 49, 2023-2028 (1971).
4382 Karady, S.; Ly, M.G.; Pines, S.H.; Slezinger, M. J. Org. Chem. 36, 1949-1951 (1971).
4384 McMurry, J.E.; Melton, J. J. Am. Chem. Soc. 93, 5309-5311 (1971).
4392 Hoffman, J.M., Jr.; Schlessinger, R.H. J. Chem. Soc. (D), 1245-1246 (1971).
4425 Davies, J.H.; Haddock, E.; Kirby, P.; Webb, S.B. J. Chem. Soc. (C), 2843-2846 (1971).
4436 Gullotti, M.; Ugo, R.; Colonna, S. J. Chem. Soc. (C), 2652-2656 (1971).
4452 Zefirov, N.S.; Chapovskaya, N.K.; Kolesnikov, V.V. J. Chem. Soc. (D), 1001-1002 (1971).
4467 Bowden, K.; Cook, R.S. J. Chem. Soc. (B), 1765-1770 (1971).
4492 Fry, A.J.; Britton, W.E. Tetrahedron Lett. 46, 4363-4366 (1971).
4520 Bowden, K.; Cook, R.S. J. Chem. Soc. (B), 1771-1778 (1971).
4521 Bowden, K.; Price, M.J. J. Chem. Soc. (B), 1784-1792 (1971).
4523 Gilmer, T.C.; Pietrzyk, D.J. Anal. Chem. 43, 1585-1592 (1971).
4524 Ono, N. Bull. Chem. Soc. Japan 44, 1369-1372 (1971).
4562 Russell, G.A.; Norris, R.K.; Panek, E.J. J. Am. Chem. Soc. 93, 5839-5845 (1971).
4573 Dunn, B.M.; Bruice, T.C. J. Am. Chem. Soc. 93, 5725-5731 (1971).
4600 Boulton, A.J.; Ghosh,k P.B.; Katritzky, A.R. J. Chem. Soc. (B), 1004-1011 (1966).

102!
4602 Chen, C.-T.; Yan, S.-J.; Wang, C.-H. Chem. Ind. (London) 895-896 (1970); CA 73,
55764Q.
4636 Claus, P.; Vavra, N.; Schilling, P. Monatsh. Chem. 102, 1072-1080 (1971).
4651 Lerch, U.; Moffatt, J.G. J. Org. Chem. 36, 3861-3869 (1971).
4653 Snyder, C.D.; Bondinell, W.E.; Rapoport, H. J. Org. Chem. 36, 3951-3960 (1971).
4669 McKinley, S.V.; Rakshys, J.W., Jr. J. Chem. Soc. Chem. Commun. 134-135 (1972).
4699 Heine, H.G. Synthesis 664 (1971).
4704 Johnson, R.N.; Farnham, A.G. J. Polymer Sci. A-1, 5, 2415-2427 (1967).
4739 Bullock, E.; Carter, R.A.; Gregory, B.; Shields, D.C. J. Chem. Soc., Chem. Commun. 97-98
(1972).
4748 Hammond, G.S.; Neuman, R.C., Jr. J. Am. Chem. Soc. 83, 1501-1508 (1963).
4755 Margaretha, P. Tetrahedron Lett. 4891-4892 (1971).
4767 Fomin, G.V.; Gurdzhiyan, L.N. Zh. Fiz. Khim. 44, 1820-1821 (1970); CA 73, 76458H.
4772 Doucet, J.; Gagnaire, D.; Robert, A. Synthesis, 556 (1971).
4775 Wharton, P.S.; Sundin, C.E.; Johnson, D.W.; Kluender, H.C. J. Org. Chem. 37, 34-38
(1972).
4776 Kingsbury, C.A. J. Org. Chem. 37, 102-106 (1972).
4792 Haszeldine, R.N.; Hewitson, B.; Higginbottom, B.; Rigby, R.B.; Tipping, A.E. J. Chem.
Soc., Chem. Commun. 249-250 (1972).
4802 Martin, D.; Berger, A.; Peschel, R. Synthesis, 598 (1971).
4812 Bakke, J. Acta. Chem. Scand. 25, 3509-3516 (1971).
4815 Hortmann, A.G.; Roberston, D.A.; Gillard, B.K. J. Org. Chem. 37, 322-324 (1972).
4817 Dalton, D.R.; Rodebaugh, R.K.; Jefford, C.W. J. Org. Chem. 37, 362-367 (1972).
4820 Durst, T. Advan. Org. Chem. 6, 285-388 (1969); CA 72, 21221Z.
4846 Komatsu, Y.; Furukawa, Y.; Shima, K. Japan. 70,00,496 (C1. 16 B 41) (Jan. 1970); CA 72,
110777C.
4891 Olofson, R.A.; Marino, J.P. Tetrahedron 27, 4195-4208 (1971).
4892 Bohlmann, F.; Buhmann, U. Ber. 105, 863-873 (1972).
4898 Marino, J.P.; Pfitzner, K.E.; Olofson, R.A. Tetrahedron 27, 4181-4194 (1971).
4906 Liu, M.T.H.; Toriyama, K. J. Phys. Chem. 76, 797-801 (1972).
4907 Arad, Y.; Levy, M.; Miller, I.R.; Vofsi, D. U.S. Patent 3,649,666 (C1. 250-465.8) (Mar. 14,
1972).
4910 Jackisch, P.F. U.S. Patent 3,642,887 (C1. 260-534 E) (Feb. 15, 1972).
4920 zu Reckendorf, W.M.; kamprath-Scholtz, U. Ber. 105, 686-695 (1972).
4934 Bates, R.B.; Kroposki, L.M.p; Potter, D.E. J. Org. Chem. 37, 560-562 (1972).
4945 Friedman, M.; Krull, L.H. Biochim. Biophys. Acta. 207, 361-363 (1970); CA 73, 35746G.
4972 Tandara, M. U.S. Patent 3,655,748 (C1. 260-634 R) (Apr. 11, 1972).
4987 Rees, C.W.; Yelland, M. J. Chem. Soc., Perkin I Trans. 77-82 (1972).
5033 Kharasch, N.; Ranky, W.O.; Nelson, D.C. Organic Sulfur Compounds. Dimethyl Sulfoxide,
Vol. I. Symposium Publication Division. Pergamon Press, New York Oxford, London, Paris,
170-182 (1961).
5038 Schmid, G.H.; Wolkoff, A.W. Can. J. Chem. 50, 1181-1186 (1972).
5116 Rapaport, E.; Cass, M.W.; White, E.H. J. Am. Chem.Soc. 94, 3153-3159 (1972).
5118 Tanner, D.D.; Van Bostelen, P. J. Am. Chem. Soc. 94, 3187-3195 (1972).
5124 Kamigata, N.; Kurihara, T.; Minato, H. Bull. Chem. Soc. Japan 44, 3152-3154 (1971).
5185 McLoughlin, V.C.R.; Thrower, J. Synthesis, 441 (1971).
5192 Bamford, C.H.; Ferrar, A.N. Proc. Roy. Soc., Ser. A 321, 425-443 (1971).
5244 Bradshaw, J.S.; Chen, E.Y.; Hales, R.H.; South, J.A. J. Org. Chem. 37, 2051-2052 (1972).
5279 Moyer, P.H.; Penner, S.E. Ger. Offen. 1,959,343 (C1. C O7 C) (Aug. 13, 1970); CA 73
98306X.
5296 Whistler, R.L.; BeMiller, J.N.; Onodera, K.; Kashimura, N. Oxidation of Carbohydrates with
Dimethyl Sulfoxide-Phosphorus Pentaoxide, Methods in Carbohydrate Chemistry, Vol. VI,
Academic Press, New York and London (1972), p. 331-336.
5300 Bravo, P.; Gaudiano, G.; Ponti, P.P. Chem. Ind. (London) 253-254 (1971);CA 74,
111854D.
5339 Chu, K.C.; Cramn, D.J. J. Am. Chem. Soc. 94, 3521-3531 (1972).
5435 Casey, J.P.; Martin, R.B. J. AM. Chem. Soc. 94, 6141-6151 (1972).
5459 Radhakrishnamurti, P.S.; Patro, P.C. Indian J. Chem. 9,1098-1101 (1971); CA 76,
13377X.
5481 zu Reckendorf, W.M.; Wassiliadou-Micheli, N. Ber. 105, 2998-3013 (1972).

103!
5488 Morisaki, S.; Baba, N.; Tajima, S. Denki Kagaku 38, 746-752 (1970).
5526 Nazarova, N.M.; Freidlin, L.K.; Kopyttsev, Y.A.; Varava, T.I. Isv. Akad. Nauk. SSSR, Ser.
Khim. 1422-1424 (1972); CA 77, 100943T.
5551 House, H.O. Modern Synthetic Reactions, 2nd Edition, W.A. Benjamin Inc., Menlo Park,
682-691 (1972).
5587 Haga, J.J.; Russell, B.R.; Chapel, J.F. Biochem. Biphys. Res. Commun. 44, 521-525
(1971); CA 75 86543N.
5594 Schoberth, W.; Hanack, M. Synthesis, 703 (1972).
5613 Benius, U.; Bergson, G. Acta. Chem. Scand. 26, 2546-2547 (1972).
5622 Balakrishnan, M.; Rao, G.V.; Venkatasubramanian, N. Tetrahedron Lett. 4617-4620
(1972).
5630 Freidlin, L.K.; Nazarova, N.M.; Kopyttsev, Y.A. Izv. Akad. Nauk. SSSR, Ser. Khim. 201-
203 (1972); CA 77, 4634X.
5635 Liu, M.T.H.; Toriyama, K. Can. J. Chem. 50, 3009-3016 (1972).
5642 Gloor, B.; Kaul, B.L.; Zollinger, H. Helv. Chim. Acta. 55, 1596-1610 (1972).
5663 Rylander, P.N.; Karpenko, I.M.; Pond, G.R. U.S. 3,694,509 (C1. 260-578) (Sept. 26, 1972).
5800 David, Estienne, J. Brit. 1,219,599 (C1. C O7C 27/12, 45/34, 51/32) (Jan. 20, 1971).
5834 Belanger, A.; Brassard, P. J. Chem. Soc. Chem. Commun. 863-864 (1972).
5836 Johnston, D.B.R.; Schmitt, S.M.; Firestone, R.A.; Christensen, B.G. Tetrahedron Lett.
4917-4920 (1972).
5843 Capozzi, G.; Modena, G.; Ronzini, L. J. Chem. Soc. Perkin Trans. I, 1136-1139 (1972).
5846 Anderson, D.J.; Horwell, D.C.; Stanton, E.; Gilchrist, T.L.; Rees, C.W. J. Chem. Soc.
Perkin Trans. I, 1317-1321 (1972).
5864 Bowden, K.; Cook, R.S. J. Chem. Soc. Perking Trans. II, 1407-1411 (1972).
5912 Hofmeister, H.; Laurent, H.; Wiechert, R. Ber. 106, 723-726 (1973).
5969 Rao, G.V.; Venkatasubramaniam, N. Aust. J. Chem. 24, 201-203 (1971).
5971 Buchta, R.C.; Evans, D.H. J. Electrochem. Soc. 117, 1492-1500 (1970).
5980 Norris, R.D.; Binsch, G. J. Am. Chem. Soc. 95, 182-190 (1973).
6026 Gould, R.F.; Schulze, S.R.; Baron, A.L. Advances in Chemistry Series 91, American
Chemical Society, Washington, D.C. 692-702 (1969).
6028 Kruger, H.-R.; Weyerstahl, P.; Marschall, H.; Nerdel, F. Ber. 105, 3553-3565 (1972).
6079 Hirano, S.; Kashimura, N.; Kosaka, N.; Onodera, K. Polymer 13, 190-194 (1972); CA 77,
50489B.
6098 Jacobus, J. J. Org. Chem. 38, 402-404 (1973).
6102 Krapcho, A.P.; Lovey, A.J. Tetrahedron Lett. 957-960 (1973).
6163 Paquette, L.A.; Meisinger, R.H.; Wingard, R.E., Jr. J. Am. Chem. Soc. 95, 2230-2240
(1973).
6172 Stetter, H.; Schreckenberg, M. Tetrahedron Lett. 1461-1462 (1973).
6192 Michelotti, F.W.; Jordan, J.M.; Cook, N.P. U.S. 3,728,400 (C1. 260-609A) (Apr. 17, 1973).
6215 Sato, K.; Inoue, S.; Ohashi, M. Bull. Chem. Soc. Jap. 1288-1290 (1973).
6234 Bartsch, R.A.; Pruss, G.M.; Bushaw, B.A.; Wiegers, K.E. J. Am. Chem. Soc. 95, 3405-
3407 (1973).
6243 Bashir, N.; Gilchrist, T.L. J. Chem. Soc. Perkin Trans. I, 868-872 (1973).
6268 Iriuchijima, S.; Tsuchihashi, G. U.S. 3,732,318 (C1. 260-607) (May 8, 1973).
6287 Yankee, E.W.; Badea, F.D.; Howe, N.E.; Cram, D.J. J. Am. Chem. Soc. 95, 4210-4219
(1973).
6293 Poupko, R.; Rosenthal, I. J. Phys. Chem. 77, 1722-1724 (1973).
6315 Kabuto, K.; Kikuchi, Y.; Yamaguchi, S.; Inoue, N. Bull. Chem. Soc. Japan 46, 1839-1844
(1973).
6325 Cox, B.G.; Parker, A.J. J. Am. Chem. Soc. 95, 408-410 (1973).
6347 Marshall, J.A.; Faubl, H. J. Am. Chem. Soc. 92, 948-955 (1970).
6378 Bartsch, R.A.; Shelly, T.A. J. Org. Chem. 38, 2911-2913 (1973).
6398 DeJonge, C.R.H.I.; Hageman, H.J.; Huysmans, W.G.B.; Mijs, W.J. J. Chem. Soc. Perkin
Trans. II, 1276-1279 (1973).
6460 Anderson, E.; Fife, T.H. J. Am. Chem. Soc. 95, 6437-6438 (1973).
6463 Hajos, Z.G.; Parrish, D.R. J. Org. Chem. 38, 3244-3249 (1973).
6474 Broxton, T.J.; Deady, L.W. Tetrahedron Lett. 3915-3918 (1973).
6477 Cleve, N.J. Suom. Kemistilehti B 45, 385-390 (1972).
6496 Ibne-Rasa, K.M.; Tahir, A.R.; Rahman, A. Chem. Ind. (London) 232 (1973).
6502 Barrow, K.D.; Barton, D.H.R.; Chain, E.; Ohnsorge, F.W.; Sharma, P. J. Chem. Soc.

104!
Perkin Trans. I, 1590-1599 (1973).
6509 Gordon, J. E.; Chang, V. S. K. J. Org. Chem. 38, 3062-3064 (1972).
6510 Klein, J.; Gurfinkel, E. Tetrahedron 2127-2131 (1970); Synthesis 704 (1972).
6543 Findlay, J. A.; Kwan, D. Can. J. Chem. 51. 3299-3301 (1973).
6572 DiNunno, L.; Florio, S.; Todesco, P. E. J. Chem. Soc. Perkin Trans. I, 1954-1955 (1973).
6593 Coates, R. M.; Chung, S. K. J. Org. Chem. 38, 3740-3741 (1973).
6613 Pilgram, K. H.; Medema, D.; Soloway, S. B.; Gaertner, G. W. Jr. U.S. Pat. 3,775,485 (C1.
260-609 F) (Nov. 27, 1973).
6627 Ghera, E.; Perry, D. H.; Shoua, S. J. Chem. Soc. Chem. Commun. 858-859 (1973).
6648 Matcha, R. L. J. Am. Chem. Soc. 95, 7508-7510 (1973).
6659 Fry, A.J.; Britton, W. E. J. Org. Chem. 38, 4016-4021 (1973).
6671 Hooz, J.; Bridson, J. N. J. Am. Chem. Soc. 95, 602 (1973); Synthesis 685 (1973).
6672 Bharucha, N. R. U.S. Pat. 3,772,170 (C1. 204/51) (Nov. 13, 1973).
6674 Pilgram, K. H.; Medema, D.; Soloway, S. B.; Gaertner, G. W. Jr. U.S. Pat. 3,772,391 (C1.
260-609 F) (Nov. 13, 1973).
6691 Stevens, C. L.; Balasubramanian, K. K.; Bryant, C. P.; Filippi, J. B.; Pillai, P. M. J. Org.
Chem. 38, 4311-4318 (1973).
6692 McMurry, J. E.; Melton, J. J. Org. Chem. 38, 4367-4373 (1973).
6713 Sakai, H.; Hamada, S.; Yamanaka, Y.; Ito, I.; Izumi, Z.; Kitagawa, H.; Mukoyama, E.;
Suzuki, Z.; Kato, T.; Hosaka, S. U.S. Pat. 3,781,248 (C1. 260-793 M) (Dec. 25, 1973).
6785 Renaud, R. N. Can. J. Chem. 52, 376-380 (1974).
6815 Pearson, D. E.; Buehler, C. A. Chem. Revs. 74, 45-86 (1974).
6818 Bartsch, R. A.; Wiegers, K. E.; Guritz, D. M. J. Am. Chem. Soc. 96, 430-433 (1974).
6822 Balakrishnan, M.; Rao, G. V.; Venkatasubramanian, N. J. Chem. Soc. Perkin Trans. II, 6-
10 (1974).
6825 Hanson, J. R. Sythesis, 1-8 (1974).
6830 Robinson, H. B.; Valley, D. J. U.S. Pat. 3,264,536 (C1. 317-258) (Aug. 2, 1966).
6831 Barth, B. P. U.S. Pat. 3,370,107 (C1. 260-901) (Feb. 20, 1968).
6847 Minoura, Y.; Shiina, K.; Yoshikawa, K. J. Polymer Sci. A-1, 5, 2843-2856 (1967).
6878 Byval'kevich, O. G.; Leshina, T. V.; Shein, S. M. Izv. Sib. Otd. Akad. Nauk. SSSR, Ser.
Khim. Nauk. 1973, 114-116; CA 80, 36780.
6937 Abe, T. Chem. Lett. (Japan), 1339-1342 (1973).
6947 Fincini, J.; D'Angelo, J.; Noire, J. J. Am. Chem. Soc. 96, 1213-1214 (1974).
6970 Akhtar, M.; Barton, D. H. R.; Sammes, P. G. J. Am. Chem. Soc. 87, 4601-4607 (1965).
6971 Kress, T. J. U.S. 3,794,642 (C1. 260-251R) (Feb. 26, 1974).
6972 Hauser, F. M.; Huffman, R. C. Tetrahedron Lett. 905-908 (1974).
6988 Su, C.-W.; Watson, J. W. J. Am. Chem. Soc. 96,1854-1857 (1974).
7022 Krapcho, A. P.; Jahngen, E. G. E. Jr.; Lovey, A. J.; Short, F. W. Tetrahedron Lett. 1091-
1094 (1974).
7028 Binger, P. Synthesis, 190-192 (1974).
7031 Henbest, H. B.; Trocha-Grimshaw, J. J. Chem. Soc. Perkins Trans. I, 601-603 (1974).
7044 Sharma, A. K.; Swern, D. Tetrahedron Lett. 1503-1506 (1974).
7047 Kende, A. S.; Wade, J. J.; Ridge, D.; Poland, A. J. Org. Chem. 39, 931-937 (1974).
7071 Zu Reckendorf, W. M.; Wassiliadou-Micheli, N. Ber. 107, 1188-1194 (1974).
7073 Baron, A. L. U.S. 3,532,677 (C1. 260-79.3) (Oct. 6, 1970); CA 73, 121223R.
7080 Ferland, J. M. Can. J. Chem. 52, 1652-1661 (1974).
7104 D'Alessandro, W. J. U.S. 3,455,866 (C1. 260-37, C 08G, F 16D) (July 15, 1969); CA 71,
62072Z (1969).
7108 Kornblum, N.; Boyd, S. D.; Ono, N. J.Am. Chem. Soc. 96,2580-2587 (1974).
7115 Smith, P. A. S.; Bruckmann, E. M. J. Org. Chem. 39, 1047-1054 (1974).
7153 DeMeijere, A. Ber. 107, 1684-1701 (1974).
7156 Hoyt, J. M.; Williams, M. Jr. U.S. 3,780,004 (C1. 260-87.3) (Dec. 18, 1973).
7158 Jacobs, R. L. U.S. 3,813,446 (C1. 260-622 R) (May 28, 1974).
7173 Haugwitz, R. D.; Maurer, B. V.; Narayanan, V. L. J. Org. Chem. 39, 1359-1361 (1974).
7184 Oda, M.; Kayama, Y.; Kitshara, Y. Tetrahedron Lett. 2019-2022 (1974).
7196 Rose, J. B. Polymer 15, 1456-465 (1974).
7205 St. Clair, T. L.; Bell, H. M. J. Polymer Sci. Polymer Chem. Ed. 12, 1321-1322 (1974).
7229 Ferro, A.; Naves, Y.-R. Helv. Chim. Acta. 57, 1152-1155 (1974).
7234 James, B. G.; Pattenden, G. J. Chem. Soc. Perkin Trans. I, 1204-1208 (1974).
7255 Segawa, H.; Itoi, K. Japan 73, 19,557 (C1. C08G, B 01 J) (June 14, 1973); CA 80,

105!
134072X.
7260 Santos, E.; Dyment, F. Plating (East Orange, N.J.) 60, 821-822 (1973); CA 79, 99733G.
7282 Youssef, A. A.; Sharaf, S. M. J. Org. Chem. 39, 1705-1707 (1974).
7285 Wilczynski, J. J.; Johnson, H. W. Jr. J. Org. Chem. 39, 1909-1915 (1974).
7293 Griffith, J. R.; O'Rear, J. G. Synthesis, 493 (1974).
7331 Ryan, M. D.; Evans, D. H. J. Electrochem. Soc. 121, 881-883 (1974).
7361 Krapcho, A. P. Synthesis 383-419 (1974).
7459 Nakagawa, S.; Takehara, Z.; Yoshizawa, S. Denki Kagaku 41, 880-883 (1973); CA 80 151,
952Q.
7460 Vitali, R.; Gladiali, S.; Gardi, R. Gazz. Chim. Ital. 102, 673-678 (1972); Synthesis 454
(1974).
7476 Mariano, P. S.; Watson, D. J. Org. Chem. 39, 2774-2778 (1974).
7507 Boeckman, R. K. Jr.; Ganem, B. Tetrahedron Lett. 913 (1974); Synthesis, 748 (1974).
7527 Wu, M.-C.; Anderson, L.; Slife, C. W.; Jensen, L. J. J. Org. Chem. 39. 3014-3020 (1974).
7528 Brand, W. W.; Bullock, M. W. U.S. 3,842,096 (C1. 260-327 M) (Oct. 15, 1974).
7533 Thummel, R. P. J. Chem. Soc. Chem. Commun. 899-900 (1974).
7536 Ghera, E.; Shoua, S. Tetrahedron Lett. 3843-3846 (1974).
7540 Balakrishnan, M.; Rao, G. V.; Venkatasubramanian, N. J. Indian Chem. Soc. 51, 537-539
(1974).
7547 Tokoroyama, T.; Matsuo, K.; Kanazawa, R.; Kotsuki, H.; Kubota, T. Tetrahedron Lett. 3093-
3096 (1974).
7552 Mully, M.; Zsindely, J.; Schmid, H. Chimia 28, 62 (1974); Synthesis, 604 (1974).
7553 Gulbenk, A. H.; Horne, D. J.; Johnston, H. U.S. 3,746,707 (C1. 260-243AN; CO 7D) (July
17, 1973); CA 79, 105301H.
7573 Meresaar, U. Acta. Chem. Scand. A28, 656-660 (1974).
7582 Stetter, H.; Schreckenberg, M. Ber. 107, 210-214 (1974); Synthesis, 63 (1975).
7608 Kocienski, P. J. J. Org. Chem. 39, 3285-3296 (1974).
7609 Rao, Y. S.; Filler R. J. Org. Chem. 39, 3304-3305 (1974); Synthesis, 543 (1975); CA 82,
16,473K.
7613 Varkey, T. E.; Whitfield, G. F.; Swern, D. J. Org. Chem. 39, 3365-3372 (1974).
7619 Rose, J. B. Chimia 28, 561-567 (1974).
7641 Fleming, R. H.; Quina, F. H.; Hammond, G. S. J. Am. Chem. Soc. 96, 7738-7741 (1974).
7643 Eliason, R.; Kreevoy, M. M. J. Phys. Chem. 78, 2658-2659 (1974).
7655 Challis, B. C.; Kerr, S. H.; McDermott, I. R. J. Chem. Soc. Perkin Trans. II, 1829-1832
(1974).
7657 Girdler, D. J.; Norris, R. K. Tetrahedron Lett. 431-434 (1975).
7691 Iguchi, Y.; Kori, S.; Hayashi, M. J. Org. Chem. 40, 521-523 (1975).
7692 Martin, R. L.; Norcross, B. E. J. Org. Chem. 40, 523-524 (1975).
7699 Thompson, R. M.; Duling, I. N. U.S. 3,738,960 (C1. 260-49) (June 12, 1973).
7709 Leslie, V. J.; Newton, A. B.; Rose, J. B. U.S. 3,775,368 (C1. 260-49) (Nov. 27, 1973).
7710 Heath, D. R.; Wirth, J. G. U.S. 3,869,499 (C1. 260-465 F) (March 4, 1975).
7729 Corey, E. J.; Shiner, C. S.; Volante, R. P.; Cyr, C. R. Tetrahedron Lett. 1161-1164 (1975).
7737 Belanger, A.; Brassard, P. Can. J. Chem. 53, 195-200 (1975).
7756 Doddi, G.; Mencarelli, P.; Stegel, F. J. Chem. Soc. Chem. Commun., 273-274 (1975).
7763 Johnson, D. C.; Nicholson, M. D.; Haigh, F. C. IPC Technical Paper Series No. 5 (April
1975).
7772 Reinhold, D. F.; Sletzinger, M.; Chemerda, J. M. U.S. Pat. 3,366,679 (C1. 260-519) (Jan.
30, 1968).
7844 Broxton, T. J.; Deady, L. W. J. Org. Chem. 40, 2906-2910 (1975).
7865 Schexnayder, M. A.; Engel, P. S. J. Am. Chem. Soc. 97, 4825-4836 (1975).
7867 Hanzlik, R. P.; Shearer, G. O. J. Am. Chem. Soc. 97, 5231-5233 (1975).
7943 Omura, K.; Sharma, A. K.; Swern, D. J. Org. Chem. 41, 957-962 (1976).
7950 Pfeffer, P. E.; Silbert, L. S. J. Org. Chem. 41, 1373-1379 (1976).
7984 Firestone, R. A.; Reinhold, D. F.; Sletzinger, M. U.S. 3,401,178 (C1. 260-340.5) (Sept. 10,
1968).
8008 Diem, H.; Dudeck, C.; Lehmenn, G. U.S. 3,966,727 (C1. 260-249.9) (June 29, 1976).
8017 Chinn, L. J.; Desai, B. N.; Zawadzki, J. F. J. Org. Chem. 40, 1328-1331 (1975).
8030 San Filippo, J. Jr.; Chern, C.-I.; Valentine. J. S. J. Org. Chem. 40, 1678-1680 (1975).
8033 Harvey, R. G.; Goh, S. H.; Cortez, C. J. Am. Chem. Soc. 97, 3468-3479 (1975).
8043 Auerbach, A.; Indictor, N.; Kruger, A. Macromolecules 8, 262-266 (1975).

106!
8050 Bartsch, R. A. Accounts Chem. Res. 8, 239-245 (1975).
8054 Lowe, O. G. J. Org. Chem. 40, 2096-2098 (1975).
8063 Broxton, T. J.; Muir, D. M.; Parker, A. J. J. Org. Chem. 40, 3230-3233 (1975).
8065 Chapas, R. B.; Knudsen, R. D.; Nystrom, R. F.; Snyder, H. R. Org. Chem. 40, 3746-3748
(1975).
8070 Barton, A. F. M. Chem. Revs. 75, 731-753 (1975).
8095 Lowe, O. G. J. Org. Chem. 41, 2061-2064 (1976).
8105 Gibian, M. J.; Ungermann, T. J. Org. Chem. 41, 2500-2502 (1976).
8108 Grayston, M. W.; Lemal, D. M. J. Am. Chem. Soc. 98, 1278-1280 (1976).
8118 Vollheim, G.; Troger, K.-J.; Lippert, G. U.S. 3,897,499 (C1. 260-580) (July 29, 1975).
8184 Kimura, K.; Inaki, Y.; Takemoto, K. Angew. Makromol. Chem. 49, 103-114 (1976).
8185 Kimura, K.; Hanabusa, K.; Inaki, Y.; Takemoto, K. Angew. Makromol. Chem. 52, 129-142
(1976).
8227 Rooney, M. L. Polymer 17, 555-558 (1976).
8238 Sowa, J. R.; Lamby, E. J.; Calamai, E. G.; Benko, D. A.; Gordinier, A. Organic Prep.
Proced. Int. 7, 137-144 (1975).
8254 Schmidt, U.; Gombos, J.; Haslinger, E.; Zak, H. Ber. 109, 2628-2644 (1976).
8255 Marschall, H.; Muehlkamp, W. B. Ber. 109, 2785-2792 (1976).
8261 Masamune, T.; Numata, S.; Matsue, H.; Matsuyuke, A.; Sato, T.; Murase, H. Bull. Chem.
Soc. Jap. 48, 2294-2302 (1975).
8276 Akerblom, E. B. U.S. Pat. 3,886,208 (C1. 260-518 R) (May 27, 1975).
8287 White, D. W. U.S. Pat. 3,852,242 (C1. 2060-4 CZ) (Dec. 3, 1974).
8306 Murai, A.; Ono, M.; Masamune, T. J. Chem. Soc. Chem. Commun. 864-865 (1976).
8311 Gray, A. P.; Cepa, S. P.; Solomon, Ì. J.' Aniline, O. J. Org. Chem. 41, 2435-2439 (1976).
8339 Brimacombe, J. S.; Da'Aboul, Ì.; Yuker, L. C. N. J. Chem. Soc. Perkin Trans. Ì, 979-984
(1975).
8340 Jones, E. R. H.; Meakins, G. D.; Miners, J. O.; Wilkins, A. L. J. Chem. Soc. Perkin Trans. I,
2308-2312 (1975).
8344 Cavazza, M.; Biggi, G.; DelCima, F.; Pietra, F. J. Chem. Soc. Perkin Trans. II, 1636-1638
(1975).
8350 Markezich, R. L. U.S. 3,992,406 (C1. 260-326 N) (Nov. 16, 1976).
8360 James, G. G.; Pattenden, G. J. Chem. Soc. Perkin Trans. I, 1476-1479 (1976).
8372 Alumni, S.; Baciocchi, E. J. Chem. Soc. Perkins Trans. 11, 488-491 (1976).
8399 Knipe, A. C.; Sridhar, N. Synthesis, 606-607 (1976).
8400 Aida, T.; Akasaka, T.;Furukawa, N.; Oae, S. Bull. Chem. Soc. Jap. 49, 1117-1121 (1976).
8405 Aida, T.; Akasaka, T.; Furukawa, N.; Oae, S. Bull. Chem. Soc. Jap. 49, 1441-1442 (1976).
8408 Sekiguchi, S.; Tsutsumi, K.; Shizuka, H.; Matsui, K.; Itagaki, T. Bull. Chem. Soc. Jap. 49,
1521-1523 (1976).
8410 Timoto, S.; Taniyasu, T.; Miyake, T.; Okano, M. Bull. Chem. Soc. 49, 1931-1936 (1976).
8418 Uzuki, T.; Takahashi, M.; Komachinya, Y.; Wakamatsu, H. U.S. 3,991,077 (C1. 260-326.14
T) (Nov. 9, 1976).
8436 Kornblum, N.; Cheng, L.; Kerber, R. C.; Kester, M.; Newton, B. M.; Pinnick, H. W.; Smith, R.
G.; Wade, P. A. J. Org. Chem. 41, 1560-1564 (1976).
8451 Padwa, A.; Au, A. J. Am. Chem. Soc. 98, 5581-5590 (1976).
8455 Huang, S. L.; Omura, K.; Swern, D. J. Org. Chem. 41, 3329-3331 (1976); Synthesis, 505
(1977); CA 85-142716S.
8501 Toray Inds. KK Japan. J7 6028-734 (C1. A14F01) (A32 A94) ( Aug. 20, 1976).
8506 Seymour, R. B.; Johnson, E. L. J. Appl. Polym. Sci. 20,3425-3429 (1976).
8529 Mozdzen, E. C. Purdue University Organic Seminar (Jan. 29, 1977).
8548 Grossert, J. S.; Langler, R. F. Can. J. Chem. 55, 407-420 (1977).
8551 Haines, A. H. Chem. Ind. (London), 883-887 (1976).
8554 Bailes, P. J. Chem. Ind. (London), 69-73 (1977).
8564 Adams, J. H.; Gupta, P.; Khan, M. S.; Lewis, J. R.; Watt, R. A. J. Chem. Soc. Perkin Trans
I, 2089-2093 (1976).
8576 Kennewell, P. D.; Taylor, J. B. Chem. Soc. Revs. 4, 189-210 (1975).
8582 Bartsch, R. A.; Roberts, D. K. Tetrahedron Lett. 321-322 (1977).
8601 Iwakura, Y.; Uno, K.; Nguyen, C. Makromol. Chem. 175, 2079-90 (1974); CA 81, 152729E
(1974).
8603 Kamino, J.; Okamoto, S. Japan. 73, 29,811 (C1. D 01F) (Sept. 13, 1973); CA81, 38758P
(1974).

107!
8658 Nakano, F.; Sugishita, M. Japan. 74 24,057 (C1. C 07C, B 01J) (June 20, 1974); CA 82,
111772R.
8677 Richardson, T.; Hustad, G. O. U.S. 3,658731 (C1. 260-2.5 BD) (April 25, 1972).
8683 Heath, D. R.; Wirth, J. G. U.S. 3,873,593 (C1. 260-465 F) (March 25, 1975).
8685 Heath, D. R.; Takekoshi, T. U.S. 3,879,428 (C1. 260-346.3) (April 22, 1975).
8690 Wasson, B. K.; Williams, H. W. R. U.S. 3,812,150 (C1. 260-326.15; C07D) (May 21,1974);
CA 81, 37585T (1974).
8696 Gani, V.; Viout, P. Tetrahedron 32, 2883-2889 (1976).
8714 Takekoshi, T. U.S. 4,024,110 (C1. 260-47 CZ) (May 17, 1977).
8717 Mueller, W. H. U.S. 4,028,417 (C1. 260-586 C) (June7, 1977).
8735 Szmant, H. H.; Birke, A.; Lau, M. P. J. Am. Chem. Soc. 99, 1863-1871 (1977).
8759 Carson, J. R.; Hortenstine, J. T.; Maryanoff, B. E.; Molinari, A. J. J. Org. Chem. 42, 1096-
1098 (1977).
8766 Mandell, L.; Daley, R. F.; Day, R. A. Jr. J. Org. Chem. 42, 1461-1462 (1977).
8779 Roedig, A.; Zaby, G.; Scharf, W. Ber. 110, 1484-1491 (1977).
8809 Galli, C.; Mandolini, L. J. Chem. Soc. Perkin Trans. II, 443-445 (1977).
8825 Attwood, T. E.; Barr, D. A.; Feasey, G. G.; Leslie, V. J.; Newton, A. B.; Rose, J. B. Polymer
18, 354-358 (1977).
8830 Ito, Y.; Fujii, S.; Konoike, T.; Saegusa, T. Synthetic Commun. 6, 429-433 (1976); Sythesis
283 (1977).
8832 Andreev, S. M.; Tsiryapkin, V A.; Samoilova, N. A.; Mironova, N. V.; Davidovich, Y. A.;
Rogozhin, S. V. Synthesis 303-304 (1977).
8833 Mukaiyama,T.; Sato, T.; Suzuki, S.; Inoue, T.; Nakamura, H. Chem. Lett. (1) 95-98 (1976);
Synthesis 433 (1977).
8838 Pri-Bar, I.; Buchman, O.; Blum J. Tetrahedron Lett. 1443-1446 (1977).
8843 Guenther, H. J.; Jaeger, V.; Skell, P. S. Tetrahedron Lett. 2539-2542 (1977).
8861 Markgraf, J. H.; Ibsen, M. S.; Kinny, J. B.; Kuper, J. W.; Lurie, J. B.; Marrs, D. R.; McCarthy,
C. A.; Pile, J. M.; Pritchard, T. J. J. Org. Chem. 42, 2631-2632 (1977).
8867 Hofheinz, W. U.S. 4,042,597 (C1. 548-339) (Aug. 16,1977).
8885 Kabalka, G. W.; Baker, J. D. Jr.; Neal, G. W. J. Org. Chem. 42, 512-517 (1977).
8888 Hajos, Z. G. U.S. 4,048,195 (C1. 260-345.9 S) (Sept. 13, 1977).
8906 Ritz, J.; Reese, J. Ger. Offen. 2,250,232 (C1. C 07C, C09D) (Apr. 25, 1974); CA 82,
113469W (1975).
8923 Razumovskii, S. D.; Shatokhina, E. L.; Malievskii, A. D.; Zaikov, G. E. Izv. Akad. Nauk.
SSSR, Ser. Khim. 543-546 (1975); CA 82, 169742X (1975).
8927 Carosello, T. F.; Weinberg, J. Ger. Offen. 2,432,685 (C1. C 08F, C 04B, A 01N) (Feb. 6,
1975); CA 82, 171903U.
8951 Gigg, R.; Conant, R. J. Chem. Soc. Perkin Trans. I, 2006-2014 (1977).
8953 Adams, C.; Gold, V.; Reuben, D. M.E. J. Chem. Soc. Perkin Trans. II, 1466-1472 (1977).
8954 Adams, C.; Gold, V.; Reuben, D. M. E. J. Chem. Soc. Perkin Trans. II, 1472-1478 (1977).
8955 Liu, M. T. H.; Jennings, B. M.; Yamamoto, Y.; Maruyama, K. J. Chem. Soc. Perkin Trans.
II, 1490-1492 (1977).
8960 Agarwal, S. K.; Moorthy, S. N.; Mahrotra, I.; Devaprabhakara, D. Synthesis 483 (1977).
8970 Philipp, B.; Schleicher, H.; Wagenknecht, W. Chemtech 702-709 (Nov. 1977).
8984 Relles, H. M.; Johnson, D. S.; Manello, J. S. J. Am. Chem. Soc. 99, 6677-6686 (1977).
9096 Williams, F. J.; Donahue, P. E. J. Org. Chem. 42, 3414-3419 (1977).
9107 Mendelson, W. L.; Webb, R. L. U.S. 4,057,585 (C1. 260-612 D) (Nov. 8, 1977).
9135 Troostwijk, C. B.; Kellogg, R. M. J. Chem. Soc. Chem. Commun. 932-933 (1977).
9138 Aydeiran, D.; Bamkole, T. O.; Hirst, J.; Onyido, I. J. Chem. Soc. Perkin Trans. II 1580-1583
(1977).
9142 McLennan, D. J. J. Chem. Soc. Perkin Trans. II, 1708-1715 (1977).
9142 Grout, A.; McLennan, D. J.; Spackman, I. H. J. Chem. Soc. Perkin Trans. II, 1758-1763
(1977).
9145 Wasson, B. K.; Williams, H. W. R. U.S. 3,944,560 (C1. 260-302H) (March 16, 1976); CA
85, 94415U.
9150 Cresswell, R. M.; Mentha, J. W. U.S. 3,878,252 (C1. 260-607A; C07C) (April 15, 1975);
CA 83, 78855R.
9170 Turbak, A. F.; Hammer, R. B.; Portnoy, N. A.; West, A. C. U.S. 4,076,933 (C1. 536-30)
(Feb. 28, 1978).
9175 Kuznetsov, V. V.; Grigor'ev, V. P.; Shpan'ko, S. P.; Bozhenko, L. G. Zashch. Met. 1, 631-

108!
634 (1975); CA 84, 10359X.
9196 Amick, D. R. J. Heterocycl. Chem. 12, 1051-1052 (1975); CA 84, 59082R.
9222 DeOliveira, L. A.; Toma, H. E.; Giesbrecht, E. Inorg. Nucl. Chem. Lett. 12, 195-203 (1976);
C. A. 84, 112283K.
9244 Von Strandtmann, M.; Shavel, J. Jr.; Klutchko, S. U.S. 3,892,739 (C1. 260-243R; C07D)
(July 1,1975); CA 84, 43632J.
9249 Von Strandtmann, M.; Shavel, J. Jr.; Klutchko, S.; Cohen, M. U.S. 3,937,704 (C1. 260-
250C; C07D) (Feb. 10, 1976); CA 84, 150650K.
9338 Kremley, M. M.; Fialkov, Y. A. Ukr. Khim. Zh. (Russ. Ed.) 42, 1058-1060 (1976); CA 86,
72048V.
9396 Kuznetsov, V. V.; Bozhenko, L. G.; Petrova, I. V. Izv. Sev.-Kavk. Nauchn. Tsentra Vyssh.
Shk., Ser. Estestv. Nauk. 4, 47-79 (1976); CA 86, 179414P.
9402 Von Strandtmann, M.; Shavel, J. Jr.; Klutchko, S.; Cohen, M. P. U.S. 3,843,730 (C1. 260-
592; C 07C) (Oct. 22, 1974), CA 82, 125172G.
9408 Handa, S.; Tanaka, Y.; Nishibata, A.; Ueda, S.; Inamoto, Y.; Saito, M.; Tanimoto, F.; Kitano,
H. U.S. 4,059,610 (C1. 544-193) (Nov. 22, 1977).
9412 Mimoun, H.; Thao, D.; Seree DeRochi, I. U.S. 4,085,145 (C1. 260-592) (April 18, 1978).
9423 Zollinger, H. Angew. Chem. Intern. Ed. Engl. 17, 141-150 (1978).
9434 Takita, Y.; Maehara, T.; Yamazoe, N.; Seiyama, T. Bull. Chem. Soc. Jap. 51, 669-670
(1978).
9439 Jawdosiuk, M.; Kmiotek-Akarzynska, I.; Wilczynski, W. Can. J. Chem. 56, 218-220 (1978).
9464 Tokura, N. Garasu Kogyo Gijutsu Shoreikai Kenkyu Hokoku 28, 85-94 (1976); CA 87,
39046R.
9488 Buncel, E.; Wilson, H. Advances in Physical Organic Chemistry, Academic Press, London,
New York, San Francisco, Vol. 14, 133-202 (1977).
9541 Wagenknecht, W.; Scheicher, H.; Philipp, B. Faserforsch. Textiltech. 28, 546-547 (1977);
CA 88, 75457B.
9563 Maruthamuthu, P.; Santappa, M. Indian J. Cham., Sect. A 16A, 43-45 (1978); CA 88,
126959E.
9567 Trofimov, B. A.; Mikhaleva, A. Ì.; Korostova, S. E.; Vakul'skaya, T. Ì.; Poguda, Ì. S.;
Voronkov, M. G. Zh. Prikl. Khim. (Leningrad) 51, 117-120 (1978); CA 137048H.
9581 Tsenyuga, V. A.; Nadezhina, N. A.; Ovchinnikov, p. N.; Timofeeva, E. Y. Zh. Org. Khim.
14, 337-339 (1978); C. A. 88, 169698M.
9604 Hagedorn III, A. A.; Farnum, D. G. J. Org. Chem. 42, 3765-3767 (1977).
9605 Marvel, E. N.; Reed, J. K.; Gaenzler, W.; Tong, H. J. Org. Chem. 42, 3783-3784 (1977).
9638 Ouchi, T.; Tatsumi, A.; Imoto, M. J. Polymer Sci. Polymer Chem. Ed. 16, 707-711 (1978).
9652 Kazanskii, K. S.; Solov'yanov, A. A.; Bubrovsky, S. A. Makromol. Chem. 179, 969-973
(1978); CA 88, 170564W.
9678 Radhakrishnamurti, P. S.; Padhi, S. C. Curr. Sci. 46, 517-518 (1977); CA 87, 183721Z.
9686 Wirht, J. G.; Heath, D. R. U.S. 3,787,364 (C1. 260-61) (Jan. 22, 1974).
9707 Reetz, M. T.; Eibach, F. Angew Chem. Intern. Ed. Engl. 17, 278-279 (1978).
9727 Salomon, R.G.; Sinha, A.; Salomon, M.F. J. Am. Chem. Soc. 100, 520-526 (1978).
9746 Irie, H.; Katakawa, J.; Mizuno, Y.; Udaka, S.; Taga, T.; Osaki, K J. Chem. Soc. Chem.
Comm. 717-718 (1978).
9752 James, B.R.; Morris R.H. J. Chem. Soc. Chem. Commun. 929-930 (1978).
9761 Julia, M.; Righini, A.; Uguen, D. J. Chem. Soc. Perkin Trans I, 1646-1651 (1978).
9767 Dirlam, J.P.; Cue, B.W. Jr.; Gombatz, K.J. J. Org. Chem. 43,76-79 (1978).
9769 Krapcho, A.P.; Weimaster, J. F.; Eldridge, J.M.; Jahngen, E.G.E. Jr.; Lovey, A.J.; Stephens,
W.P. J. Org. Chem. 43, 138-47 (1978); CA 88, 50032Z.
9771 Williams, F.J.; Donahue, P.E. J. Org. Chem. 43,250-254 (1978).
9773 Cocivera, M.; V.; Woo, K.W.; Effio, A. J. Org. Chem. 43, 1140-1145 (1978); CA 88,120237W.
9780 Welch, S.C.; Rao, A.S.C.P. J. Org. Chem. 43, 1957-1961 (1978).
9783 Hutchins, R.O.; Kandasamy, D.; Dux III, F.; Maryanoff, C.A.; Rotstein, D.; Goldsmith, B.;
Burgoyne, W.; Cistone, F.; Dalessandro, J.; Puglis, J. J. Org. Chem. 43,1140-1145 (1978).
9786 Mancuso, A.J.; Huang, S.-L.; Swern, D. J. Org. Chem. 43,2480-2482 (1978); CA 89,2369OT.
9825 Wendler, N.L.; Girota, N.N.; Zelawski, Z.S. U.S. Pat. 4,094,878 (Cl. 260-297Z) (June 13,
1978); CA89,163425U.
9850 Johnson, D.C.; Nicholson, M.D. U.S. Pat4,097,666 (Cl. 536-57) (June 27, 1978)
9871 Shieh, B.; Moriguchi, A.; Matsubara, Y. Nippon Kagaku Kaishi 1167-9 (1978); CA 90,6549R.
9874 Iwamuro, H.; Ohshio, T.; Matsubara, Y. Nippon Kagaku Kaishi, 909-11 (1978); CA 90,23267Q.

109!
9895 Hammer, R.B.; O'Shaughnessy, M.E.; Strauch, E.R. Turbak, A.F. J. Appl. Polym.Sci. 23,485-
94 (1979); CA90, 122862M.
9926 Omura, K.; Swern, D. Tetrahedron 34, 1651-1660 (1978).
9928 Blancou, H.; Moreau, P.; Commeyras, A. Tetrahedron 33,2061-2067 (1977).
9944 Savignac, P.; Breque, A.; Bartet, B.; Wolf, R. C.R.H. Acad. Sci. Ser. C, 13-16 (1978).
9949 Kim, J. K.; Lingman, E.; Caserio, M.C. J. Org. Chem. 43,4545-4546 (1978).
9960 Babler, J.H. W.S. 4,175,204 (Cl. 560-262) (Nov. 20, 1979).
9961 Johnson, R.N.; Farnham, A.G. U.S. 4,175,175 (Cl. 528-125) (Nov. 20, 1979).
9964 Dryden, H.L.Jr.; Sarcos, M.G. Westrich, J.P. U.S. 4,141,920 (Cl. 260-607B; C07C148/00)
(Feb. 27, 1979); CA 90 168063E.
9985 Larcheveque, M.; Mulot, P. Can. J. Chem. 57, 17-20 (1979).
9986 Gregory, B.; Bullock, E.; Chen, T.S. Can. J. Chem. 57,44-52 (1979).
10000 Fatma, W.; Iqbal, J.; Ismail, H.; Ishratullah, K.; Shaida, W.A.; Rahman, W. Chem. Ind.
(London), 315-316 (1979).
10002 Chollet, A.; Hagenbuch, J.P.; Vogel, P. Helv. Chim. Acta. 62,511-524 (1979).
10008 Kornblum, N.; Carlson, S.C.; Smith, R.G. J. Am. Chem. Soc. 101,647-657 (1979).
10011 Bartsch, R.A.; Read, R.A.; Larsen, D.T.; Roberts, D.K.; Scott, K.J.; Cho, B.R. J. Am. Chem.
Soc. 101, 1176-1181 (1979).
10032 Dossena, A.; Marchelli, R.; Casnati, G. J. Chem. Soc., Chem. Commun. 370-371 (1979); CA
91,211782Y.
10043 Gigg, R. J. Chem. Soc.; Perkin Trans I. 712-718 (1979).
10044 Tanaka, H.; Nagai, Y.; Irie, H.; Uyeo, S.; Kuno, A. J. Chem. Soc.; Perkin Trans. I, 874-878
(1979).
10048 Guest, D.W.; Williams, D.H. J. Chem. Soc.; Perkin TransI, 1695-1697 (1979).
10066 Babler, J. H.; Coghlan, M.J.; Feng, M.; Fries, P. J. Chem. 44,3157-3162 (1979).
10077 Jarvis, B.B.; Nicholas, P.E. J. Chem. 44, 2951-2952 (1979).
10078 Uijttewaal, A.P.; Jonkers, F.L.; Van der Gen, A. J. Chem. 44,3157-3162 (1979).
10084 Mancuso, A.J.; Brownfain, D.S.; Swern, D. J. Chem. 44, 4148-4150 (1979); C.A. 91,210384H.
10085 Detty, M.R. J. Chem. 44,4528-4531 (1979).
10086 Kornblum, N.; Singaram, S. J. Chem. 44,4727-4729 (1979).
10091 Kamogawa, H.; Koizumi, H.; Nanasawa, M. J. Polymer Sci.; Polymer Chem. Ed. 11,9-18
(1979).
10116 Kurita K.; Hirakawa, N.; Iwakura, Y. Makromol. Chem. 180,855-858 (1979).
10123 Kurita K.; Hirakawa, N.; Morinaga, H.; Iwakura, Y. Makromol. Chem. 180, 2769-2773 (1979).
10127 Olah, G.A.; Narang, S.C.; Gupta, B.G.; Malhotra, R.; Synthesis 61-2 (1979) CA 90, 103544T.
10134 Chari, R.V.J.; Reed, J.N.; Turnbull, K. Tetrahedron Lett. 1481-1484
10139 Still, I.W.J.; Reed, J.N.; Turnbull, K. Tetrahedron Lett. 1481-1484 (1979).
10143 Wade, T.N.; Gaymard, F.; Guedg, R. Tetrahedron Lett. 2681-2682 (1979).
10224 Morimoto, A.; Nanbu, N.; Nanby, T. Jpn Kokai Tokkyo Koho 79,44.611 (Cl. C07Cl47/02) (April
9, 1979); CA 91,91170Y.
10286 Takagi, U.; Tsumura, R.; Mazaki, T. Kokai Tokkyo Koho 79,125,604 (Cl. C07 C79/04) (Sept.
29, 1979); CA92, 110519H.
10315 Gibbio, V.; Omato, F. U.S. 4,206,118 (Cl. 548-155) (Jun. 3, 1980).
10320 Bayer, H.O.; Swithenbank, C.; Yih, H.R.Y. U.S. 4,220, 468 (Cl. 71-124) (Sept. 2, 1980).
10368 Turbak, A.F.; Hammer, R.B.; Davies, R.E.; Hergert, H.L. Chemtrech, 51-57 (1980).
10394 Tanaka, R.; Zheng, S.Q.; Kawaguchi, K.; Tanaka, T. J. Org. Chem. Soc.; Perkin Trans. II,
1714-1720 (1980).
10399 Kornblum, N.; Fifolt, M.J. J. Org. Chem. 45,2404-2408 (1980).
10409 Broxton, T.J.; Deady, L.W.; Rowe, J.E. J. Org. Chem. 45,2404-2408 (1980).
10411 Olmstead, W.N.; Margolin, Z.; Bordwell, F.G. J. Org. Chem.45,3295-3299 (1980).
10422 Pri-Bar, I.; Buchman, O. J. Org. Chem. 45,4418-4428 (1960).
10434 Takeshoni, T.; Wirth, J.G.; Heath, D.R.; Kochanowski, J.E.; Manello, J.S.; Webber, M.J. J.
Polymer Sci.; Polymer Chem. Ed. 18,3069-3080 (1980).
10437 Rokicki, G.; Kuran, W. Makromol Chem. 181,985-993 (1980).
10439 Kurita, K.; Hirakawa, N.; Iwakura, Y. Makromol. Chem. Rapid Commun. 1,695-662 (1980).
10443 Imai, Y.; Asamidori, Y.; Ueda, M. Makromol. Chem. Rapid Commun. 1, 659-662 (1980)
10454 Raduechel, B. Synthesis 292-295 (1980).
10458 Cariou, M. Synthesis 1045 (1980).
10465 Buchanan, D.H.; McComas, G. Tetrahedron Lett. 21,4317-4320 (1980).
10470 Manual of Hazardous Chemical Reactions 1971, National Fire Protection Association,

110!
International, Boston, MA 491M-100-101, (1971).
10569 Erickson, A.S. A Compilation of pKa's of 132 Organic Compounds, Crown Zellerbach, results
unpublished (1979).
10720 Mancuso, A.J.; Swern, D. Synthesis, 165-185 (1981).
10762 Boldebuck, E.M.; Banucci, E.G. U.S.4,255,471 (Cl. 427-385.5) (Mar. 10, 1981).
10771 Carter, C.O. U.S. 4,267,034 (Cl. 208-323) (May 12, 1981).
16359 Tidwell, T.T. Synthesis, 857-70 (1990).

TABLE OF CONTENTS INTRODUCTION PART I. PROPERTIES OF DMSO Physical Properties Thermal and Chemical Stability Recovery from Aqueous Solutions PART II. SOLVENCY CHARACTERISTICS OF DMSO Solubility of Salts Solubility of Resins and Polymers Solubility of Miscellaneous Materials Solubility of Gases REACTIONS OF DMSO 1. Oxidation of DMSO 2. Reduction of DMSO 3. Reaction with Metals 4. Reaction with Strong Bases-Dimsyl Ion 5. Reaction with Acid Halides 6. Reaction with Acid Anhydrides 7. Halogenation of DMSO 8. Reaction with Phenols and Aniline 9. Alcohol Oxidation with DMSO a) Acetic Anhydride b) Trifluoroacetic Anhydride c) Dicyclohexylcarbodiimide d) Phosphorus Pentoxide e) Sulfur Trioxide-Pyridine f) Oxalyl Chloride 10. Kornblum Reaction 11. Mehoxydimethylsulfonium Salts and Trimethyloxosulfonium Salts DMSO AS A REACTION SOLVENT A. DISPLACEMENT REACTIONS IN DMSO Anions-Nucleophiles (Bases): 1. Acetylide Ion 2. Alkoxide Ion 3. Amides 4. Amines 5. Ammonia 6. Azide Ion 7. Carbanions 8. Carboxylate Ion 9. Cyanate Ion 10.Cyanide Ion 11.Halogen Ion 12.Hydroxide ion 13.Mercaptide (or Thiopenoxide) Ion 14.Nitrite Ion 15.Phenoxide Ion 16.Sulfide (or Hydrosulfide) and Thiosulfate Ions 17.Thiocyanate Ion B. BASES AND BASE CATALYZED REACTIONS IN DMSO Bacities in DMSO Proton Removal 1. 2. 3. 4. 5. ELIMINATION REACTIONS Cope Elimination Decarboxylatoin and Decarbalkoxylation Dehalogenation Dehydrohalogenation Nitrogen Elimination Page 5 6 6 6 12 12 13 14 15 16 17 17 17 17 17 18 18 19 19 20 21 21 21 22 22 23 23 23 24 24 24 24 26 28 30 30 32 34 35 35 39 40 42 43 44 46 47 48 48 48 51 51 51 52 54 57

PART III.

PART IV.

2

Page 6. Sulfenate Elimination 7. Sulfonate Elimination 8. Water Elimination-dehydration ISOMERIZATION REACTIONS 1. Acetylene Isomerization 2. Allyl Group Isomerization 3. Diene, Triene Isomerization 4. Olefin Isomerization 5. Racemization C. OTHER REACTIONS IN DMSO ADDITION REACTIONS a) Additions to acetylenes b) Additions to olefins c) Additions to nitriles d) Additions to isocyanates CONDENSATION REACTIONS a) Aldol-type condensations b) Ester condensations c) Dieckmann condensation-cyclization d) Mannich reaction e) Michael condensation f) Reformatsky reaction g) Thorpe-Ziegler condensation h) Ullmann-type condensations i) Wittig reaction OXIDATION REACTIONS a) Autoxidation b) Chemiluminescence c) Other oxidations involving oxygen d) Dehydrogenation e) Hypohalite oxidations f) Lead tetraacetate oxidations g) Silver compound oxidations h) Superoxide and peroxide oxidations REDUCTION REACTIONS Reduction of Alkyl Halides and Sulfonates a) Reductions with sodium borohydride b) Reductions with chromous ion c) Reductions with dimsyl ion d) Reductions with hydrazine e) Reductions by electrolysis Reduction of Carbonyl Compounds a) Reductions with borohydrides b) Catalytic reduction c) Electrochemical reduction d) Wolff-Kishner reduction Reduction of Nitroaromatics Reduction of C=C Systems SOLVOLYTIC REACTIONS Hydrolysis a) Aliphatic halide hydrolysis b) Aromatic halide hydrolysis c) Amide hydrolysis d) Epoxide hydrolysis e) Ether hydrolysis f) Nitrile hydrolysis g) Saponification Alcoholysis, Aminolysis Transesterification (Ester Interchange) 59 59 60 62 62 63 63 64 65 66 66 67 69 69 69 69 70 71 72 72 73 73 73 73 74 74 76 77 77 78 78 79 80 80 81 81 82 82 82 82 82 82 83 83 83 83 84 85 85 85 85 86 86 86 86 87 87 88

1.

2.

3. 4. 1.

2. 3.

3

PART V.

PART VI.

PART VII.

USES OF DMSO 1. Polymerization and Spinning Solvent Polymerization Solvent for Heat-Resistant Polymers 2. Extraction Solvent 3. Solvent for Electrolytic Reactions 4. Cellulose Solvent 5. Pesticide Solvent 6. Cleanup Solvent 7. Sulfiding Agent 8. Integrated Circuits TOXICITY, HANDLING, HAZARDS, ANALYSIS 1. Toxicity and Handling Precautions 2. Comparative Toxicity of Commercial Solvents 3. Chemical Reactions to be Avoided with DMSO 4. Analytical Procedures a) Gas chromatographic analysis of DMSO b) DMSO freezing point c) Water by Karl Fischer titration BIBLIOGRAPHY

Page 88 88 88 89 89 89 90 90 90 90 90 90 91 91 92 92 92 92 93

TABLES AND FIGURES Page 6 9 9 10 13 14 15 16 24 31 50 91 91 7 8 8 8 8 11 12 36 36 41 49

Table I Table II Table III Table IV Table V Table VI Table VII Table VIII Table IX Table X Table XI Table XII Table XIII Figure 1 Figure 2a Figure 2b Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10

Physical Properties of DMSO Results of Reflux of DMSO for 24 Hours with Various Compounds Refluxing of DMSO and Mixtures for Shorter Periods Effect of Heating DMSO with Concentrated Acids Solubility of Salts in DMSO Solubility of Resins and Polymers in DMSO Solubility of Miscellaneous Materials in DMSO Solubility of Gases in DMSO Solubility of Various Bases in DMSO Solubility of Sodium Azide in Four Solvents Acidities in DMSO Single-Dose Toxicity (Rats) of Some Common Solvents Single-Dose Toxicities to Mice of 4M Solvents Vapor Pressure-Temperature DMSO Freezing Point Curve for DMSO-Water Solutions (Wt % water) Freezing Point Curve for DMSO-Water Solution (Wt % water) Viscosity of DMSO Viscosity of DMSO-Water Solutions Thermal Stability of DMSO DMSO Recovery from Aqueous Solutions Solubility of NaCN in DMSO Solubility of NaCl in DMSO-H2O Mixtures Solubility of Hydroxides in Aqueous DMSO Acidity Functions of Bases in DMSO

4

INTRODUCTION

Dimethyl sulfoxide or DMSO is a highly polar, high boiling, aprotic, water miscible, hygroscopic organic liquid. It is essentially odorless, water white and has a low order of toxicity. Chemically, DMSO is stable above 100° C in alkaline, acidic or neutral conditions. Prolonged refluxing at atmospheric pressure will cause slow decomposition of DMSO. If this occurs, it can be readily detected by the odor of trace amounts of methyl mercaptan and bis(methylthio)methane. The rate of decomposition is a timetemperature function that can be accelerated by the addition of acids and retarded by some bases. DMSO is a versatile and powerful solvent that will dissolve most aromatic and unsaturated hydrocarbons, organic nitrogen compounds, organo-sulfur compounds and many inorganic salts. It is miscible with most of the common organic solvents such as alcohols, esters, ketones, lower ethers, chlorinated solvents and aromatics. However, saturated aliphatic hydrocarbons are virtually insoluble in DMSO. As a reaction solvent, DMSO is valuable for displacement, elimination, and condensation reactions involving anions. In DMSO, the rates of these reactions are often increased by several orders of magnitude. In free radical polymerizations, higher average molecular weights have been reported when DMSO was used as the reaction solvent. The dominant characteristics of DMSO most important in its usefulness as a reaction solvent are its high polarity, its essentially aprotic nature, and its solvating ability toward cations. The high dipole moment of the sulfur-oxygen bond (4.3) and the high dielectric constant (approx. 48) for bulk DMSO suggest the solvating properties and ability to disperse charged solutes. DMSO is not a hydrogen donor in hydrogen bonding and poorly solvates anions except by dipolar association to polarizable anions. The hydrogen atoms of DMSO are quite inert, although they are replaceable under sufficiently severe conditions (bulk pKa = 35.1). The oxygen of DMSO is somewhat basic and participates strongly as a hydrogen bond acceptor. DMSO forms isolatable salts with several strong acids. Owing to its chemical and physical properties, DMSO can be efficiently recovered from aqueous solutions. Commercial users of DMSO employ a variety of processing schemes in their recovery systems. All of these are based on evaporation or fractional distillation because of simplicity of design and operation. Unlike some other solvents, DMSO can be easily separated from water by distillation in substantially pure form. For example, DMSO containing less that 500 ppm water can be recovered from a solution containing 50 weight percent water with only 15 column plates at a reflux ratio of 1:1. Dimethyl sulfoxide occurs widely in nature at levels of 3 ppm or less. It has been found in spearmint oil, corn, barley, malt, alfalfa, beets, cabbage, cucumber, oats, onions, swiss chard, tomatoes, raspberries, beer, coffee, milk and tea. DMSO is a common constituent of natural waters. It has been identified in seawater in the zone of light penetration where it may represent an end product of algal metabolism. Its occurrence in rainwater may result from oxidation of atmospheric dimethyl sulfide which in turn occurs as part of the natural transfer of sulfur of biological origin. No attempt has been made in this bulletin to present a complete literature survey of all the uses of DMSO as a reaction solvent, solvent, or reactant. A few carefully chosen references have been selected to illustrate the most important areas of DMSO chemistry. For persons wishing to learn more about DMSO as a reaction solvent, ir any other information in this bulletin, please write or call:

P.O. Box 1209 Slidell, LA 70459-1201 (985) 649-5464

5

PART I. PROPERTIES OF DMSO TABLE I. Physical Properties of DMSO Reference Molecular Weight Boiling Point at 760 mm Hg Freezing point Molal freezing point constant, °C/(mol)(kg) Refractive index nD25 Surface tension at 20°C Vapor pressure, at 25°C Density, g/cm3, at 25°C Viscosity, cP, at 25°C Specific heat at 29.5°C Heat capacity (liq.), 25°C Heat capacity (ideal gas) Heat of fusion Heat of vaporization at 70°C Heat of solution in water at 25°C Heat of combustion Flash point (open cup) Auto ignition temperature in air Flammability limits in air lower (100°C) upper Coefficient of expansion Dielectric constant, 10MHz Solubility parameter 78.13 189 °C (372°F) 18.45°C (65.4°F) 4.07 1.4768 43.53 dynes/cm 0.600 mmHg 1.099 2.0 (see Figs. 3 & 4) 0.47+/- 0.015 cal/g/°C 0.47 cal/g/°C Cp(T°K)=6.94+5.6x10 2T-0.227x10-4T2 41.3 cal/g 11.3 kcal/mol (260 BTU/lb) -54 cal/g, @ dilution 6054 cal/g; (473 kcal/mole) 95°C (203°F) 300-302°C (572-575°F) 3-3.5% by volume 42-63% by volume 0.00088/°C 48.9 (20°C) 45.5 (40°C) Dispersion 9.0 Polar 8.0 H-bonding 5.0 Dipole moment, D Conductivity, 20°C 80°C PKa 4.3 3x108(ohm 1cm-1) 7x108(ohm 1cm-1) 35.1 (10411) (342) (342) (8070) (342) (342) (3215) (342) (342) (342) (2151) (581) (2223) (372) (581) (581) (3215) (2900) (353) (232)

Thermal and Chemical Stability of DMSO As shown in Figure 5, DMSO is highly stable at temperatures below 150° C. For example, holding DMSO at 150° C for 24 hours, one could expect a loss of between 0.1 and 1.0%. Retention times even in batch stills are usually considerably less than this, and therefore, losses would be correspondingly less.. It has been reported that only 3.7% of volatile materials are produced during 72 hours at the boiling point (189° C) of DMSO (1). Slightly more decomposition, however, can be expected with the industrial grade material. Thus, about 5% DMSO decomposes at reflux after 24 hours (3921). Almost half of the weight of the volatile materials is paraformaldehyde. Dimethyl sulfide, dimethyl disulfide, bis(methylthio)methane and water are other volatile products. A small amount of dimethyl sulfone can also be found. The following sequence of reactions explains the formation of these decomposition products (1):

H3CSOCH3 2H3CSH + HCHO 2H3CSH + CH3SOCH3 2H3CSOCH3
DMSO is remarkably stable in the basic salts and bases (3922). When

H3CSH + HCHO (H3CS)2CH2 + H2O

(HCHO)x

H3CSSCH 3 + H3CSCH3 + H2O H3CSO 2CH3 + H2CSCH3
presence of most neutral or samples of DMSO (300g) are

6

sodium acetate and sodium sulfate. sodium chloride. sodium cyanide. little or no decomposition takes place in most cases.refluxed for 24 hours with 100g each of sodium hydroxide. The results are shown in Table II below (3922): FREEZING POINT CURVES FOR DMSO-WATER SOLUTIONS 7 . sodium carbonate.

8 .

9 99. 100 DMS DMDS 152 5 0 0 15 99. (b) (c) DMDS BMTM HCHO 31 14 15 33 30 8 30 20 M Md 22 66 15 11 (a) Dimethyl sulfide (b) Dimethyl disulfide (c) Bis(methylthio)methane (d) Methyl mercaptan (e) Reflux temp.0 97.7 96.8 99. 3) 60 parts DMSO + 12 parts water + 1 part sodium bicarbonate.15 0 155 131 191 5 8 6 12 5 9 16 99.15 0 0 0 0 0 0.2 0. 4) DMSO alone (3922): Composition of Sample.3 99.. was 148°C for 20 hours.2 BMTM 0 0.° C. DMSO does not seem to be hydrolyzed by water and very little decomposition of DMSO takes place when it is heated under reflux for periods of 5 to 16 hours. Parts 10 DMSO:1 H2O 60 DMSO:5 H2O:1 NaOH 60 DMSO:12 H2O:1 NaHCO3 DMSO only TABLE III Refluxing of DMSO and Mixtures For Shorter Periods Reflux Time DMSO Organic Product Composition.°C.3 98.1 0.2 0. shown in Table III. 185-140e 190 190 148-164f 182-187 181-148g 189 DMSO Recovered % of Original 93.2 0.5 0.6 DMSO is also stable in the presence of concentrated sulfuric or hydrochloric acid at 100° C for up to 120 minutes of heating at atmospheric 9 .6 0.8 99. (g) Reflux temp.1 99.2 0. 2) 60 parts DMSO + 5 parts water + 1 part sodium hydroxide.8 99.TABLE II Results of Reflux of DMSO for 24 Hours with Various Compounds Compound (1008) in 300 g DMSO NaOH Na2CO3 NaCI NaCN NaOAc Na2SO4 DMSO only Reflux Temp. The following tests. increased to 164° C during the last 4 hours.1 0 0 0. (f) Reflux temp.4 98.1 0.1 0.7 100. Time.0 DMS 63 (a) % of Decomposition Products. Hr.1 0.0 0.7 0. decreased from 185°C to 140°C over the first 16 hours. have been performed: 1)10 parts DMSO + 1 part water. decreased gradually from 181°C to 148° C.0 85.1 0.

acid) Acid H2SO4 Conc.. The results are shown in Table IV (3920): TABLE IV Effect of Heating DMSO with Concentrated Acids . formaldehyde. Phosphoric acid causes more rapid decomposition of DMSO than does sulfuric or hydrochloric acid.(200g DMSO with 20g of concn.15 150 210 15 30 45 60 120 150 15 60 150 15 30 60 120 15 30 45 60 120 DMSO Left. Detected decomposition products are dimethyl sulfide.pressure. % 99 99 98 86 86 80 92 89 89 87 87 86 84 82 82 99 99 99 98 93 92 87 87 87 % of Decomposition Products (a) (b) DMS DMDS 100 100 100 7 7 10 25 45 45 46 46 50 25 33 33 100 100 100 100 100 100 100 100 100 HCHO H2SO4 36N 125 H3 P04 85% 100 H3 P04 85% 125 93 93 90 75 55 55 54 54 50 75 67 67 some HCI 12N 95 HCI 12N 115 some (a) Dimethyl Sulfide (b) Dimethyl Disulfide 10 . Min. dimethyl disulfide. and. 15 30 120 . 100 Time. in smaller quantity. 36N Temp. ° C.

11 .

There would usually be two vacuum distillation steps in the recovery: 1) Evaporation of the DMSO-water solution overhead to eliminate less volatile impurities. would allow the use of 85 psig steam and normally available cooling water. cyanides or dichromates as their anions. and 2) Fractional distillation of the DMSO-water solution to recover pure DMSO. Because of its high polarity it forms association bonds with other polar and polarizable molecules.FIGURE 6 Recovery from Aqueous Solutions Many chemical processes using DMSO require the addition of water to stop the reaction or to separate the product from the solvent (DMSO). The following tables of solubilities are offered as a guide and an easy reference. if any are present. DMSO has also exhibited an ability to dissolve many inorganic salts. Thus. 12 .10 to 20%. including itself. it is miscible with water and almost all types of organic liquids except the saturated alkanes. DMSO distillations are not complicated by any known azeotropes. A typical feed to a recovery operation is relatively weak in DMSO . employing moderate conditions. particularly those of the transition metals or those which have nitrates. Recovery may be done batchwise or continuously. PART II SOLVENCY CHARACTERISTICS OF DMSO The solvent characteristics of DMSO derive mainly from its being highly polar and aprotic. An operating pressure of about 100 mm Hg abs. DMSO can be separated efficiently and cleanly from this water and other impurities by distillation. It has a high solvency for the large organic molecules containing polar groups.

The study of co-solvent possibilities utilizing DMSO has not been included as the complexity and diversity of this field are too broad to give adequate coverage. TABLE V Solubility of Salts in DMSO (794) Solubility Grams/100 cc DMSO Solubility Grams/100 cc DMSO 25°C. Because of the variability of resins and polymers from one manufacturer to another. m. 25°C. 5 Lithium dichromate (2 H2O) 10 Ammonium borate (3H2O) 10 Lithium nitrate 10 Ammonium carbonate (H2O) 1 Magnesium chloride (6 H2O) 1 Ammonium chloride Insol.Solubility of salts ----------. 86°C. 90-100°C Aluminum sulfate (18H2O) Insol. m.Table VIII The difficulty of predicting solubility characteristics suggests that each specific compound be checked for its solubility in DMSO rather then generalizing from reported solubilities. 10 Magnesium nitrate (6 H2O) 40 Ammonium chromate 1 Manganous chloride (4 H2O) 20 Ammonium dichromate 50 Mercuric acetate 100 Ammonium nitrate 80 Mercuric bromide 90 Ammonium thiocyanate 30 Mercuric iodide 100 Barium nitrate 1 Molybdenum bromide 1 Reacts Beryllium nitrate (4 H2O) 10 Nickel chloride (6 H2O) 60 Bismuth trichloride 1 Nickel nitrate (6 H2O) 60 Cadmium chloride 20 Potassium iodide 20 20 Cadmium iodide 30 Potassium nitrate 10 Calcium chloride Insol. 1 Potassium nitrite 2 Calcium dichromate (3 H2O) 50 Potassium thiocyanate 20 50 Calcium nitrate (4 H2O) 2 30 Silver nitrate 130 180 Ceric ammonium nitrate 1 Sodium dichromate (2 H2O) 10 Cobaltous chloride (6 H2O) 30 Misc. This compatibility and the strong solvency properties of DMSO indicate numerous possibilities for co-solvent systems to perform given tasks efficiently and economically. Strontium bromide (6 H2O) 5 Ferric chloride (6 H2O) 30 90 Strontium chloride (2 H2O) 10 Ferrous chloride (4 H2O) 30 90 Tungsten hexachloride 5 Gold chloride 5 Uranyl nitrate (6 H2O) 30 Lead chloride 10 Vanadium chloride 1 Lead nitrate 20 60 Zinc chloride 30 60 Zinc nitrate (6 H2O) 55 - 13 .p. 90-100°C. It will be noted however from Table VII that DMSO is compatible with most of the common solvents.-----------------------------------------------------------------------------------------Table V Solubility of resins and polymers -------------------------------------------------------------------------------. 40° C. Sodium iodide 30 Cupric acetate (H2O) Insol.Table V I Solubility of miscellaneous materials --------------------------------------------------------------------------.p. tradenames and companies have been used to identify accurately the materials in Table VI.Table VII Solubility of gases -------------------------------------------------------------------------------------------------. Sodium nitrite 20 Cupric chloride (2 H2O) Insol. 6 Sodium nitrate 20 Cupric bromide 1 20 150°C. Misc. 27 Sodium thiocyanate 1 Cuprous iodide 1 Stannous chloride (2 H2O) 40 Ferric ammonium sulfate (12 H2O) Insol.

Insol. 25 at 130°C with some decompostion 25 at 130°C Insol. 20 <1 Insol. Insol. Insol. >1 7 50 100 20 42 90 15 30 >100 10 30 Very viscous Very viscous Viscous Viscous Viscous Dissolves at 160°C ppts. Insol. Dow Corning Z6018 (flake) Urethanes Vithan (Goodyear) Vinyls Polymers & Co-polymers Butvar B-76 (Monsanto) Formvar 7/70 E (Montsanto) Elvanol 51-05 (du Pont) Elvanol 52-22 (du Pont) Elvanol 71-24 (du Pont) Polyvinyl pyrrolidone (GAF) Geon 101 (PVC Goodrich) Vinylite VYHH (Union Carbide) Teslar (du Pont) 20-30°C >25 >5 5 10 50 50 50 Miscible Miscible Miscible 70 30 2 - Partially sol. Dow Corning 805 soln. 45 (du Pont) Plexiglass (Rohm & Haas) Polycarbonates Lexan (General Electric) Merlon (Mobay) Polyesters Dacron (du Pont) CX 1037 (Goodyear) Atlac (ICI-America) Silicones Dow Corning 803 soln. at 160-170°C 14 .TABLE VI Solubility of Resins and Polymers in DMSO Grams Soluble in 100 cc DMSO 90-100°C Comments 20 Viscous soln. 130°C 40 at 150°C 25 at 150°C 40 at 150°C Material Polyacrylics Orlon (du Pont) Acrilan (Monsanto) Verel (Eastman) Creslan (Am. Cyanamid) Zefran (DOW) Polyamides Nylon 6 Nylon 6/6 Nylon 6/10 Cellulose Cellulose triacetate Viscose rayon Cellophane Carboxymethyl cellulose Epoxies Epon 1001 (Shell) Epon 1004 (Shell) Epon 1007 (Shell) Methacrylates Lucite 41. <1 <1 >5 Insol.

1 Reacts violently 3 (DMSO soluble 0.9 <1 Soluble Miscible 0.05 (0.1 Soluble Soluble Insol.3 Misc.3 Softens Miscible Miscible 4.05 0. 130-180° Miscible Miscible Miscible <1 Miscible Miscible40 Insol. Insol.5% in petroleum ether) Soluble Miscible Reacts vigorously 90 68 76 26 33 Soluble - 15 .5% DMSO soluble in 11 (gets cold) 10 >20 Miscible 0.3 Miscible Miscible Miscible Reacts 7 Miscible 40 Miscible Immiscible Misc.67 Miscible 4. 50 30 20 Insol.1 0.7 Miscible >1 4 <1 Soluble <1 8 <1 <1 1. 5 Insol. Miscible Miscible 1 38 Softens & dissolves 100 Insoluble Insoluble Slightly soluble 5-10 30 0.5 Miscible Miscible Miscible 0. Insol.4 0. 90 Miscible Miscible Insol.Vinylidenes Darvan (Goodrich) Saran film (Dow) Geon 200 x 20 (Goodrich) DNA (Goodrich) Other Resinous Materials Melmac 405 (Am. >100 Soln.5 0. Reacts 2.-160°C Softens 100 - Material Acetic acid Acetone Acrawax Acrawax B Aniline Beeswax Benzene Benzidine Benzidine methane sulfonate Bromine Butenes Clacium methyl sulfonate Camphor Candelilla wax Carbon Carbon disulfide Carbon tetrachloride Carbowax 600 Carbowax 6000 Carnauba wax Castor oil Ceresin wax Chlorine Chloroform Chlorosulfonic acid Citric acid Coconut oil Cork Cresylic acid Cumene Cyclohexane Cyclohexylamine Decalin n-Decane Di-n-butylamine o-Dichlorobenzene p-Dichlorobenzene Dicholorodiphenyltrichloroethane Dicyandiamide Dicyclohexylamine Diethylamine Diethyl ether bis-(2-ethylhexyl)amine Diethyl sulfide Di-isobutyl carbinol Material Glycerine Glycine Hexane Hy-wax 120 Iodine Isoprene Kerosene Lanolin. Miscible Reacts Miscible Reacts >70 0.35 7. hydrated (Lanette O) Lauryl amide (Amid 12) Lorol 5 Lubricating oil Methionine Methyl borate Methyl caprate Methyl iodide Methyl laurate Methyl mercaptan N-methyl morpholine Methyl palmitate Methyl salicylate Methyl sulfonic acid Methylene chloride Microcrystalline wax Morpholine Naphthalene Neoprene Nitrobenzene Oleic acid Ouricuri wax Oxalic acid Paint (dried) Palmitic acid Paraffin Paraformaldehyde Pentaerythritol n-Pentane Pentene 1 & 2 Perchloric acid Petroleum ether Phenol Phosphoric acid Phosphorus trichloride Phthalic acid Isophthalic acid Terephthalic acid Picric acid Solubility Grams/100 cc DMSO 20-30°C 90-100°C Miscible <0. Cyanamid) Neoprene Polyethylene Polystyrene Rosin (Hercules) Penton (chlorinated polyether) (Hercules) Teflon (du Pont) Vinsol (Hercules) 5 >5 70 Insol. Miscible Miscible Soluble Insol. >100 Insol.7 11 Miscible Very Soluble 4 40 4. At 150°C ppts at 130°C TABLE VII Solubility of Miscellaneous Materials in DMSO Solubility Grams/100 cc DMSO 20-30°C 90-100°C Miscible Miscible <1 Insol. Insol.1 2.3-0. Cloudy and viscous 25 at 130°C Sol.

Insol. 50 40 Miscible Miscible 0. 0.01 Reacts 57.5 60 0.7 0.1 40.8 Insol.00 0.32 60.0 0.00 0.5-3.00 Miscible (possible reaction) 0.8 306.38 3.9 Miscible Soluble Miscible 10 Soluble 10 40 Miscible Miscible 0. soluble Stearic acid Succinic acid Sugar (sucrose) Sulfamic acid Sulfur Sulfuric acid Tallow Tallow amide.0 1.6% DMSO soluble in di-isobutylene) 4.01 0.3 (0.Di-isobutylene 3.4 (reacts) Gas Volume per Volume of DMSO 28.6 4. hydrogenated (Armour Armide HT) Tetrahydrophthalic anhydride Thiourea Toluene Toluene di-isocyanate Tributylamine Tricresyl phosphate Triethanolamine laurylsulfate Triethanolamine Triethylamine Trinitrotoluene Turpentine Urea Water Xylene Miscible 50 >100 Slightly soluble 50 Reacts vigorously 2. N2O4) Oxygen Ozone Sulfur dioxide 2.4 Miscible Miscible 33.99 2.0 3.00 0.9 Miscible Very Soluble 10 0. dried Silicon tetrachloride Sodium Sorbitan sesquioleate Sorbitan trioleate Sorbitol Soybean oil Starch.0 2.5 (reacts) 2.06 16 .9 >40 85 110 - Dimethyl ether Dimethyl formamide Dimethyl sulfide Dimethyl sulfone Dioxane Diphenyl Dipentene n-Dodecane Dodecylbenzene (Neolene 400) Dyes Burnt Sugar FD&C Blue Pistachio Green B Ethyl benzoate Ethyl alcohol Ethyl bromide Ethyl ether Ethylene dichloride Formalin (37%) Formamide Formic Acid TABLE VIII Solubility of Gases in DMSO at Atmospheric Pressure and 20°C (from pure gases in each case) Grams Gas per 100 Grams Solution Acetylene Ammonia Butadiene Mixed butylenes Carbon dioxide Carbon monoxide Ethylene Ethylene oxide Freon 12 Helium Hydrogen Hydrogen sulfide Isobutylene Methane Nitric oxide (NO) Nitrogen Nitrogen dioxide (NO2.6 >2 2 30 30 40 Miscible Insol.35 2.0 3.5 0.5 Soluble Soluble Soluble Miscible Miscible Miscible Miscible Miscible Miscible Miscible Miscible Miscible Reacts - Pyridine Pyrogallol Rosin Rosin soap (Hercules Dresinate X) Sevin Shellac. white.05 0.9 80 Reacts Miscible >180 Miscible 100 <1 1.

yields are nearly quantitative (202): 17 . dimsyl ion. Ozone gives a good yield of the sulfone (825)(8923). Reaction with Metals The reaction of DMSO with sodium and potassium metals does not lead to simple removal of a hydrogen. The overall result is methylation and with compounds such as quinoline or isoquinoline. CH SCH . It has been reported that the persulfate ion can remove an electron from the sulfur of DMSO to give a radical cation. DMSO is also oxidized by peroxydiphosphate (9563) and chloramine-T (9678). Hydrogen bromide. H2CSOCH3. Mercaptans reduce acidified DMSO and are oxidized to the disulfides (428)(1373)(2532)(2779)(8054)(8095)(8405)(9949): CCl3SO2CCl3 2RSH + CH 3SOCH 3 acid RSSR + CH 3SCH 3 + H 2O 3. Aqueous chlorine under acidic conditions gives dimethyl sulfone and methanesulfonyl chloride (1273)(8548). including aluminum hydrides (1024)(1022) and boranes (1138)(3429)(3816)(8885). The dimsyl ion also adds to carbon-carbon double bonds. with alkyl halides or sulfonate esters. Reduction of DMSO DMSO is reduced to dimethyl sulfide. Consequently. The dimsyl ion solutions provide a strongly basic reagent for generating other carbanions. Quantitative or almost quantitative yields of dimethyl sulfide are claimed in some of these reductions. amines. Reaction with Strong Bases . DMSO has also been reduced with iodine-sulfur dioxide or bromine-sulfur dioxide complexes (9464).PART III REACTIONS OF DMSO 1. 2. aromatics and cyclopropane derivatives. amides. which is a suitable polymerization catalyst for acrylonitrile (1271). CH 3SO2CH . particularly in the presence of catalysts (4136). 4. Oxidation of DMSO DMSO reacts with strong oxidizing agents to give dimethyl sulfone. Quantitative procedures for determining DMSO have been based on its reduction using stannous chloride and hydrochloric acid (982). to give the sulfone. organic peroxides (1515). the dimsyl sodium solution can be employed to remove protons from carbohydrates. acetylenes. carbonyl compounds yield -hydroxysulfoxides and esters give ketosulfoxides (624): n-C4H9Br + :CH2SOCH3 n-C4H9CH2SOCH3 (C6H5)2C(OH)CH2SOCH3 C6H5C(O)CH2SOCH3 (C6H5)2CO + :CH2SOCH3 C6H5COOEt + :CH2SOCH3 Zinc and sulfuric acid have been used to reduce DMSO (86). but occurs by cleaving the carbon-sulfur bond (206): CH3SOCH3 + 2M CH3SOCH3 + CH3-M+ CH3SO -M+ + CH3-M+ CH3SOCH2-M+ + CH4 The electrolytic reduction of sodium chloride or sodium iodide in DMSO similarly leads to a mixture of hydrogen and methane gases at the cathode (1508). but under alkaline conditions the oxidation is accompanied by chlorination to give an 80% yield of hexachlorodimethyl sulfone (905): CH3SOCH3 + NaOCl Sodium hypobromite similarly gives a 75% yield of hexabromodimethyl sulfone (229). reduces DMSO only at temperatures about 80° C (1579). sulfoxides are obtained. on the other hand. The dimsyl ion shows the expected nucleophilicity of carbanions and serves as a source of methylsulfinylmethyl groups (634). or titanium trichloride in dilute hydrochloric acid (272). The activating influence of the sulfinyl group on -hydrogens is considerably less than that of a carbonyl group but still sufficient to give a pKa of 35. There are numerous applications of the dimsyl ion in the isomerization of alkynes and formation of phosphorus ylides in preparing Wittig reagents. DMSO reacts with hydrogen peroxide (10224). cyclic phosphoranes derived from catechol (9944). Hydroiodic acid reduces DMSO (7073). thiophosphoryl bromide (10139) and other reagents. and if the mixture is heated for several hours. Both dichromate oxidation (321) and permanganate oxidation (9222) have been used for quantitative determination of DMSO (1612). Thus. or hydroperoxides (8105). and the kinetics of the reaction have been examined (84)(85)(1687)(1544).1 for DMSO (10411). silanes (10085)(10127).Dimsyl Ion Methylsulfinyl carbanion. weakly acidic hydrocarbons and many other compounds. DMSO is reduced only very slowly with hypophosphorus acid unless catalyzed by dialkyl selenides (1005). the initial adduct eliminates methanesulfenic acid. and for eliminations producing olefins. by a number of strong reducing agents. The dimsyl ion has also been used to prepare salts of carbonyl compounds. strong bases such as sodium hydride or sodium amide react with DMSO to produce solutions of sodium methylsulfinyl carbanion (dimsyl ion) which have proved to be synthetically useful (634): CH3SOCH3 + NaH + NaCH2SOCH3 + H2 As the base.

can be represented as follows: CH3SOCH3 + SOCl2 CH3SCH2Cl + SO 2 + HCl The reaction in many cases proceeds by way of initial attack of the chlorinating agent upon the oxygen of DMSO. only 13% of the chloromethyl methyl sulfide is obtained (720).H2CSOCH3 N isoquinoline H N CH2SOCH3 N CH3 Care is required in running these reactions because the decomposition of the intermediate sulfoxide anion (and also dimsyl sodium) during the heating in the strongly alkaline system is exothermic and also produces a precipitate which can interfere with heat removal. The reaction of DMSO with reactive acid chlorides is vigorous and exothermic and should be conducted with care (669)(8601)(10470). the final product is acetoxymethyl methyl sulfide. in a simplified form. it has been suggested that the reaction. 5. With acetic anhydride. have been proposed.g. Various possible pathways of the rearrangement from the sulfonium salt have been proposed. When DMSO is reacted with acetyl chloride in the presence of iodide the following reaction. There seems to be little doubt that the first step in the reaction of DMSO with acetic anhydride is the formation of the acetoxysulfonium salt (2643)(2896). CH3CO2CH2SCH3 (290)(291). followed by removal of a proton to give an ylide which is finally attacked by chlorine (459): [(CH3)2 SOMZ] +XCH SOCH + Z-M-X 3 3 X-(e. and organic acid chlorides also give chloromethyl methyl sulfide (467)(8601). With thionyl chloride. acetic anhydride and chlorodimethylsulfonium chloride (9773): CH3SOCH3 OCH3CCl CH3SCH2Cl + CH3CO2H + (CH3CO)2O +CIS(CH3)2 +Cl- This displacement of a reactive chloride by the DMSO oxygen has been used to introduce hydroxyl groups into compounds that are sensitive toward water (459)(294)(1016)(1383)(3152). SO2Cl2. S2Cl2. The overall reaction is complicated by several side reactions. Reaction with Acid Anhydrides Carboxylic acid anhydrides react with DMSO in a manner similar to that of acid halides. such as sulfur monochloride. (1383): N3C3Cl + 3CH3SOCH3 PhCOCl + CH3SOCH3 N3C3O3H3 + 3CH3SCH2Cl PhCO2H + CH3SCH2Cl The ability of suIfoxides to react with acid chlorides can be used for the quantitative determination of DMSO. the Pummerer rearrangement. acetic acid and chloromethyl methyl sulfide is mainly second order. which generate acetoxymethyl methyl sulfide. whereas with sulfuryl chloride. Reaction with Acid Halides DMSO has long been known to react with chlorine or acid chlorides. DMSO reacts with cyanuric chloride to give cyanuric acid and with benzoyl chloride to give benzoic acid. but 18 . The growth of the main products. Cl -) - OMZ + CH3SCH2 X [CH2SOCH2:] M-Z +HX M= an atom (such as S) to which the halogen atom X is attached Z=the remaining portion of the molecule The kinetics of the reaction between DMSO and acetyl chloride has been studied using NMR spectroscopy. Explosions have been observed which were not detonations but were due to a pressure build-up by an uncontrolled exotherm (8). Aromatic sulfonyl chlorides (463). 6. Thus. involving formation of the acyloxysulfonium salt. The decay of DMSO and acetyl chloride follows mainly 2nd order kinetics. Several mechanisms of the reaction. can be represented as follows: CH3SOCH3 + CH3COCl [(CH3)2SOCOCH3]+ + 2l- [(CH3)2SOCOCH3]+ + ClCH3SCH3 + l2 + CH3CO2- The iodine is then titrated with sodium thiosulfate (1805). thionyl chloride (595). to give chloromethyl methyl sulfide.

although higher temperatures. dimethyl disulfide. pyridine. Further chlorination in the presence of pyridine yields methyl trichloromethyl sulfoxide (4802): CH3SOCH3 Cl2. CH3SOCH2Br 48% Similarly. Thus. 85-90° C. stirring a solution of DMSO. Halogenation of DMSO DMSO can be halogenated with chlorine or bromine in the presence of a base. e. Methanesulfonic acid. Reaction with Phenols and Aniline 19 . CCl4 -5 to 5 C 3 hrs. o CH3SOCH2Cl 60% Cl2. and hydrogen bromide are formed as by-products (4802): Br2 CH3SOCH3 (CH3)3S+Bro 20-50 C 75% A small amount of hydrogen halides or halogens. These consecutive reactions form an oxidation-reduction cycle between Br2-HBr and DMSO-dimethyl sulfide (8400). Complex formation between DMSO and sulfur trioxide is an exothermic reaction. Reactions of DMSO wlth some acid anhydrides. paraformaldehyde. both organic and lnorganic. 7. 8. pyridine and methylene chloride solution at 0° C for over 30 minutes produces chloromethyl methyl sulfoxide in a 77% yield (6268).g. Thus. sulfur trioxide should be added slowly to a cool well stirred and cooled DMSO (1474). CCl4 0oC 3 hr. When aliphatic carboxylic acids are treated with DMSO activated by tert-butylbromide in the presence of NaHCO3 the corresponding methylthiomethyl esters are obtained in a Pummerer like reaction (10032). This catalytic decomposition takes place sluggishly. DMSO cannot be dried with phosphorus pentoxide because this may lead to an explosive mixture (354). acetic anhydride and benzoic anhydride react with DMSO even at room temperature (290). amides or sulfonamides the corresponding iminosulfuranes are obtained (7044). To avoid overheating with consequent darkening and violent boiling of the mixture. The sulfur trioxide-DMSO complex reacts easily with cellulose to give cellulose sulfate esters with a high degree of substitution (1474). pyridine. CHCl3 below 5oC CH3SOCCl3 30% Bromination of DMSO with elemental bromine leads to the formation of trimethylsulfonium bromide. pyridine. A Pummerer type rearrangement is also suggested in the reaction of diphenylphosphinic anhydrideDMSO reaction (4128): O P [Ph2PO]2O + CH SOCH3 3 Ph Ph + OCH 2SCH3 Ph2PO2H Inorganic anhydrides also attack the DMSO oxygen. The reaction of bromine proceeds via the initial -bromination to afford -bromethyl methyl sulfoxide which is oxidized (Kornblum reaction) to afford the products listed above [(4802)]. especially bromine or hydrogen bromide. When this intermediate is reacted with aromatic amines. Et 3N. bubbling chlorine into a DMSO.the one going through the ylide seems likely (2643)(4820). can be vigorous and should be conducted with care. are needed for faster reactions (7613). and bromine in chloroform results in the formation of bromomethyl methyl sulfoxide (3148): CH3SOCH3 Br2. catalyze the decomposition of DMSO in the absence of a base. The Pummerer rearrangement can then be represented by the following reactions O O O CH3SOCH3 + (CH3CO)2O S H3C O H3CS CH 2 O CH 3 CH 3 CH 3 O O CH 3 O H3CSH2CO CH 3 O S H3C CH 3 CH 2 +CH3CO 2H DMSO also reacts with trifluoroacetic anhydride to give the acetoxysulfonium salt. Chlorination of DMSO in the presence of triethylamine yields chloromethyl methyl sulfoxide.

A mixture of isomeric methylthiomethylation products are obtained. 65-68% R R R Similarly. but o-methylthiomethylation is preferred (4636)(4772). Finally. When a solution of phenol in DMSO is treated with an acid chloride.N-dimethylaniline can be reacted with DMSO using phosphoryl chloride catalysis. However. the yield of the aryl thioether is lower in this case (348). the initially formed adduct of DMSO reacts by electrophilic attack on the phenol to form the sulfonium salt. hydroxyaryl thioethers can be prepared by reacting phenols with DMSO in sulfuric acid. followed by heating of sulfonium salts in hot. or saturated with hydrogen chloride. saturated potassium chloride solution (1268): ClO4H2O. 9.6-bis(methylthiomethyl)phenol (540)(1234)(4898)(4891). b) Dicyclohexylcarbodiimide or acid anhydride catalysis The reaction of phenols with DMSO and dicyclohexylcarbodiimide in the presence of phosphoric acid or pyridinium trifluoroacetate affords a mixture of the products consisting mainly of 2-methylthiomethyl phenol and 2. It has been suggested that the mechanism proceeds according to the following steps (540)(1234)(4898): H CH 2SOCH 3 + H+ + C6H11-N=C=N-C6H11 C6H11-N-C=N-C6H5 O S(CH3)2 phenol + O CH 3 S . and heating the crude reaction mixture with aqueous sodium chloride (6335) (6674)(6613). KClOH S(CH3)2 OH + CH3SOCH3 HClO4 15-20oC 2-3 hours + OH SCH3 reflux 4-5 hrs. p-Hydroxyaryl methylthioethers are also obtained when phenols are suspended in 70% perchloric acid and DMSO is added. The sulfonium salt can be decomposed by heating to give hydroxyaryl methylthioethers (2075)(302)(296): OH CH3SOCH3 + HCl CH3SCH3 + Cl Phenol + OH S(CH3)2 Cl+ R heat OH SCH3 + CH3Cl 4-(methylthio)phenol Up to 60% yields are obtained. N. Alcohol Oxidation with DMSO A breakthrough in the preparation of carbonyl compounds from alcohols has been achieved with the development of reagents based on 20 .CH 2 base (CH3)2SO H + N O C N H + C6H11 O H Ch2SCH3 OH C6H11 H3CSCh 2 2-thiomethoxymethyl phenol A similar reaction takes place when acetic anhydride (849)(1055) or the pyridine-sulfur trioxide complex (4636) is used to polarize the DMSO molecule instead of dicyclohexylcarbodiimide. Other aromatic amines and hydrazine derivatives also react with DMSO and dicyclohexylcarbodiimide (4651). such as thionyl chloride. depending on the structure of the phenol. it has been found that phenols can be methylthiomethylated by boiling with excess DMSO.a) Acid chloride or hydrogen chloride catalysis.

aldehydes and ketones. The usual side products are acetates and methylthiomethyl ethers. In the reaction. steroids (173). The reaction involves addition of an alcohol substrate to a solution of dicyclohexylcarbodiimide (DCC) in DMSO with an acid. Trifluoroacetic anhydride is an excellent activator for DMSO because of short reaction times and high yields of carbonyl compounds with minimal by-product formation. which would be inert to other DMSO-activator systems. can now be attacked by a nucleophile. to perform a displacement on sulfur with oxygen as the departing group: E O S + Nu CH3 H3C Nu S + OECH3 H3C Several of the above-mentioned activating agents and their use in the oxidation of alcohols are described below. the sulfur trioxide-pyridine complex. the DMSO-electrophile complex. DMSO first reacts with acetic anhydride to form the acyloxysulfonium salt which in turn reacts with the alcohol to give the alkoxydimethylsulfonium intermediate which decomposes to the carbonyl compound and dimethyl sulfide (DMS)(1127): CH 3SCH3 + (CH3CO) 2O [(CH3)2S-O-COCH3]+CH 3COO acyloxysulfonium salt CH 3SCH3 + RR'C=O [(CH3)2S-O-CHRR'] ++CH3COO - A number of side reactions take place when using the acetic anhydride-DMSO procedure.g.e. are oxidized (4820). presumably an ion pair. and others. + [(CH3)2S-O-COCF3]-OCOCF3 This reacts rapidly with alcohols. This results in reaction conditions near neutrality at room temperature.DMSO (8551)(1503)(4820)(16359). Most of these reactions take place at room temperature or above. a) Acetic anhydride In this procedure an alcohol is treated with a mixture of acetic anhydride and DMSO at room temperature (1127) (9926). chlorine. such as phosphoric acid or pyridinium trifluoroacetate (172). bromine. and carbohydrates (4349). and other acid anhydrides. 2-adamantol and neopentyl-type alcohols) to give the corresponding carbonyls (7943)(8455). trifluoroacetic anhydride. Several procedures have been developed which permit the selective oxidation of structurally diverse primary are secondary alcohols to the corresponding carbonyl compounds. such as an alcohol. Nucleophilic attack occurs on the DMSO sulfur atom. Steric effects are not important except in highly hindered systems (1503). b) Trifluoroacetic anhydride Trifluoroacetic anhydride and DMSO react exothermally at -60° C. t-butyl hypochlorite. The labile intermediate. and other. including alkaloids. trifluoroacetoxydimethylsulfonium trifluoroacetate. acetyl chloride. acid chlorides. after its originators (1503). oxalyl chloride. thionyl chloride. Most reactions in which the nucleophilic attack takes place on sulfur are aided by prior electrophilic attack on the oxygen atom (10720): O O E CH3SCH3 + E + CH3SCH3 + The electrophilic reagents which activate DMSO include acetic anhydride. present as a proton source. the DMSO molecule is first converted to a labile intermediate which is susceptible to attack at the sulfur by an alcohol group to produce an alkoxysulfonium salt which undergoes base-catalyzed decomposition to the carbonyl compound (3049): 21 . respectively. The major drawback is the need to work at very low temperatures (-30 to -60° C) (10720). The oxidation technique is applicable to primary or secondary alcohol groups in an almost unlimited variety of compounds. The advantage of the acetic anhydride-DMSO method is the fact that highly hindered alcohols. RR'CHOCH2SCH3. even sterically hindered ones (e. c) Dicyclohexylcarbodiimide This method of oxidation is generally referred to as the "Pfitzner-Moffatt" technique. in methylene chloride to produce a white precipitate. dicyclohexylcarbodiimide. i.

d) Phosphorus pentoxide It has been found that DMSO containing phosphorus pentoxide rapidly oxidizes the alcoholic groups of carbohydrates and other compounds at room or elevated temperatures to the corresponding aldehydes or ketones (208). DMSO R1=H OR2 R3OH2C O OR 1 O OAc OR 2 CH2 O R2=H OR OAc O 22 . This system catalyzes carbohydrate polymerization at temperatures below 35° C (5296) (6079). thus providing a high yield to novel unsaturated carbohydrates (2652): OHC R3 = H O OAc OR1 R3OH2C O OAc OAc SO3. DMSO. In general. benzylidene. oxidations proceed most efficiently in the presence of 3-4 molar equivalents of DMSO and 1.0 molar equivalents of phosphorus pentoxide (2327). e) Sulfur trioxide-pyridine The combination of DMSO with S03-pyridine complex in the presence of triethylamine yields a reagent that rapidly oxidizes primary and secondary alcohols in good yield at room temperature to aldehydes and ketones. This reagent has also been used to oxidize alkaloid hydroxyl groups to ketone groups (2749)(8017). An attractive feature of this reagent is its property of effecting oxidation of allylic alcohols to the corresponding . -unsaturated carbonyl compounds (1752). The S03-pyridine complex in DMSO can be used to oxidize acid-labile trans-diols (4037) or cis-diols (8033) to quinones. acetate. and sulfonate esters and ethers are stable in the conditions used for oxidation (3602)(175).2-2. Application of the DMSO-S03-pyridine reagent to partially acetylated carbohydrates leads to oxidation as well as elimination of the elements of acetic acid.C6H11 -N=C=N-C6H11 + H+OS(CH3)2 C6H11HN C O N C6H11 HOHCRR' CH3SCH3 H (CH3)2S-O-CRR' + C6H11 N H O C6H11 N H alkoxysulfonium salt R' O SH R H :CH2 CH3 + CH3SCH3 R R' H (CH3)2S-O-CRR' + -H+ O Protecting groups such as isopropylidene. DMF and pyridine seem to be the best solvents for this reaction (3602)(2327)(6691). benzoate. respectively (9926)(10720). The carbohydrate oxidation with DMSO-P4O10 should be run at about 60-65°C.

An acid acceptor. The new intermediate is the same as that proposed for the dimethyl sulfide-chlorine reagent. such as methyl iodide. Kornblum Reaction Kornblum and co-workers have demonstrated that in DMSO -bromoketones at room temperature and primary alkyl tosylates on heating afford the corresponding carbonyl compounds. Methoxydimethylsulfonium Salts and Trimethyloxosulfonium Salts Alkylating agents. This product has been reacted with a wide variety of alcohols to convert them to the carbonyl compounds (10084): O C O C CH3SOCH3 + (COCl)2 + [(CH3)2S-Cl] Cl - CH2Cl2-60o -CO2.g. Na2HPO4 or K2HPO4. presumably through an oxysulfonium intermediate (273)(8551): CH3SOCH3 + XCHRR' + [(CH3)2S-O-CHRR']X- B: RR'C=O + BH+ Some reactive alkyl halides. is frequently used (105). However. such as methyl iodide. also react with DMSO to form the oxosulfonium intermediate (the O-alkyl derivative). superior to trifluoroacetic anhydride. is used (9960): CH3 CH3 DMSO H2CCl C CHCH 2OCOCH3 M2HPO4. such as 1 -chloroheptane. -CO [(CH3)2S O Cl] Cl RR'CHOH [(CH3)2SOCHRR'] Cl (Et)3N RR'C=O + CH2SCH3 10. The relatively unreactive alkyl halides. Kornblum Reaction).f) Oxalyl chloride Oxalyl chloride is an efficient and useful activator. (CH3)3S+Ol-. result in generally higher and frequently quantitative yields of the corresponding carbonyl compounds (9786)(9926). the dimethyloxosulfonium methylide reacts with carbon-carbon double bonds that are conjugated with carbonyl groups to give cyclopropane derivatives (4820)(7361): 23 . However. this intermediate rearranges readily to the more stable oxosulfonium salt. react initially with DMSO at the oxygen to give methoxydimethylsulfonium iodide (see the previous section. 4-chloro-3-methyl-2-buten-1-ol acetate. The unstable intermediate formed at low temperatures (usually-60° C) instantaneously loses carbon dioxide and carbon monoxide. i. 80oC OHC C CHCH2OCOCH3 This particular reaction is catalyzed by sodium bromide (9960)(10066). e. does not proceed well when sodium hydrogen carbonate is used as the acid acceptor. such as benzyl. this reaction runs well when a dibasic metal phosphate. These alkoxysulfonium salts are quite reactive and with continued heating either decompose to give the carbonyl compounds or rearrange to the more stable trimethyloxosulfonium salts. Some reactive halides. upon basification. The DMSO oxidation of the primary allylic chloride. can also be oxidized to the corresponding carbonyl compounds but higher reaction temperatures are necessary. In the case of methyl iodide trimethylsoxosulfonium iodide is produced (324): (CH3)2SO + CH 3I [(CH3)2SOCH3]+I- [(CH3)3SO]+I - methoxydimethylsulfonium iodide trimethyloxosulfonium iodide Trimethyloxosulfonium iodide is of interest because treatment with sodium hydride or dimsyl sodium produces dimethyloxosulfonium methylide which is an excellent reagent for introducing a methylene group into a variety of structures (632)(2463)(4820): O [(CH3)3SO] I + NaH +- (CH 3)2S CH2 + NaI + H2 dimethyloxosulfonium methylide Many aldehydes and ketones react with the ylide to give better than 75% yields of epoxides (632): H C O (CH3)2S CH2 +C6H5CH=CHC(O)C 6H5 (C6H5)2C 90 % yield CH2 + (CH3)2SO In a similar case. can be oxidized by DMSO if the chloride is first converted to the tosylate (106).e. 11. for the conversion of alcohols to their alkoxysulfonium salts which. and no oxidation takes place (324). sodium hydrogen carbonate.

Carboxylate ion 17.is minimized. Cyanate ion 1. Mercaptide (or Thiophenoxide) ion 5. the interaction between Na' and OH. A review article on potassium t-butoxide and its use in nucleophilic displacements has been published (6815). DISPLACEMENT REACTIONS IN DMSO These are reactions in which reactive groups are replaced by nucleophilic ions or molecules. Phenoxide ion 7. Amides 12. and a number of these are plotted in Figure 10 for bases n DMSO-water and DMSO-methanol systems. Displacement of halides with the ethylenediamine complex of lithium acetylide is also easily effected in DMSO (3178)(4175). Due to the polarity of the sulfoxide bond and the electron density at the oxygen. cations are much more solvated by DMSO than the anions. Acetylide ion 10. E. The solubilities of these hydroxylic bases are also shown in Table IX for comparative purposes. It is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (9488). The high dielectric constant of a solvent insures that dissolving species or a solute bearing opposite charges do not come together to agglomerate. the acidity of the alcohols in dilute solutions is about 103 times that of DMSO so that only a minor equilibrium quantity of the DMSO anion is present (734). Halogen ion 3.g. TABLE IX Solubilities of Various Bases in DMSO Substance moles/liter Reference 24 . The vastly enhanced activity of alkoxide ions in DMSO over their activity in alcohols is attributed to the absence of alkoxide-solvent hydrogen bonds in DMSO which are present in the hydroxylic solvents (434). Thiocyanate ion 9. the reaction of 1-bromo-5-chloropentane with lithium acetylide-ethylene diamine complex in DMSO gives 7-chloro-1 -heptyne (1826): Cl(CH2)5Br + HC CLi+ DMSO Cl(CH2)5C CH The use of lithium acetylide-ethylene diamine in DMSO has given higher yields of the desired products than sodium acetylide in liquid ammonia (4175). potassium t-butoxide is more soluble than some lower alkoxides (17). In other cases. A great variety of displacement reactions can be run in DMSO and suitable nucleophiles include: 1. epoxides or carbonyl compounds (544). when sodium hydroxide is dissolved in DMSO. Alkoxide ion 11. The reason for the particular utility of DMSO in these reactions has not always been established and derives from a number of factors. Acetylide Ion The usual reactions of sodium acetylide may be accomplished in good yield by stirring a slurry of sodium acetylide in DMSO slightly below room temperature with reagents such as alkyl halides. This latter effect is evident in the cases where comparatively minor additions of DMSO cause significant enhancement of reaction rates (1262). Cyanide ion 2. Thus. Amines 13. Sulfide (or Hydrosulfide) and Thiosulfate ions 8. the aprotic nature of DMSO precludes the solvation of anions by hydrogen bonding so that these are solvated only by dipolar attraction and thereby are more reactive. DMSO AS A REACTION SOLVENT A. The addition of lithium acetylide as the ethylene-diamine complex to 7-bromoheptanol tetrahydropyranyl ether in DMSO gives non-8-yn-1ol tetrahydropyranyl ether in higher than 90% yield (4333). The largest category of reactions in which DMSO has been used as a solvent is that in which labile groups are replaced by nucleophilic ions or molecules. The reactivity of the alkoxide ion in DMSO is influenced by the cation and is greater with cesium and with lithium less (606)(1162). In this case. Conversely.O (CH 3)2S CH2 +C6H5CH=CHC(O)C 6H5 C6H5CH H2 C CHC(O)C 6H5 PART IV. Alkoxides differ in their solubilities n DMSO. 2. Nitrite ion 6. Alkoxide Ion The high activity of alkoxide ions in DMSO shows up in their enhanced basicity. DMSO as one of the most polar of the common aprotic solvents. Ammonia 14. The basicity of alkoxides reaches a maximum in DMSO when the mixture is substantially free of hydroxylic material. Hydroxide ion 4. the controlling influence is suggested to the ability of highly polar DMSO molecules to stabilize transition state structures and thereby lower the activation energy (22) (471)(399). Carbanions 16. Thus. The basicity of alkoxides in DMSO is conveniently expressed n terms of acidity functions. Azide ion 15.

The rate increase at high DMSO concentrations is attributed to an increased activity of the methoxide ion caused by reduced solvation.and 2-naphthols and 1-methylmercapto-2naphthol.6 x 10'° 1 x 10'3 1 x 10' 1. but other factors are probably more important at low DMSO concentrations. the preferential nucleophilic attack by oxygen (rather than the amino group) is insured (8399): + Cl RHN(CH2)2OH + NO2 NaH2CSOCH3.2-dehydrohaphthalene is an intermediate in each of these reactions. The activation energy decreases continuously as the DMSO concentration increases (433). DM SO ROR' ROH + CIR' 100oC 6-14 hrs. elimination being the major reaction. followed by the addition of the alkoxide to the double bond in alicyclic compounds (1798). DMSO OH benzyne-type intermediate O3-methoxy tropolone O NaOCH 3. and in the reaction between benzyl chlorides and methoxide ion to make the corresponding benzyl methyl ethers (433). the use of alkoxides in DMSO can involve both the displacement and elimination reactions with aromatic halogen compounds. DMSO RHN(H2C)2O NO2 The reaction of monoiodo-. The 25 .and monofluoro-naphthalenes with potassium butoxide in butyl alcohol-DMSO has been examined (4058)(4059). monochloro. Thus.and chloronaphthalene reactions are 1.6 x 10'3 2 x 10'2 7 x 10'3 5 x 10'3 1 x 10'2 (725) (17) (17) (725) (17) (17) (17) (17) a) Aliphatic halide displacement The rate of reaction of alkoxide ions with alkyl halides in alcohol-DMSO mixtures to form ethers increases with the increasing amount of DMSO. The use of alkoxides in DMSO in some cases involves elimination n addition to displacement.NaOH KOH (CH ) NOH NaOCH3 NaOEt iso-PrONa n-BuONa t-BuOK 7. The Williamson ether synthesis from alcohols and alkyl halides (chlorides) with sodium hydroxide as the base can be considerably improved by using DMSO as the solvent in place of the excess alcohol (2924): NaOH. iodo. b) Aromatic halide displacement As with alkyl halides. and 1-methyl-mercapto-2-naphthol is probably the benzyne intermediate-DMSO reaction product (4059). DMSO O H3CO + OH 4-methoxy tropolone O OH Aromatic halogens in nitroaryl halides can be displaced by the methoxide ion in DMSO-methanol. Secondary alkyl chlorides and primary alkyl bromides give little etherification. This is illustrated in the reaction of methyl iodide with methoxide ion or with ethoxide ion to make dimethyl.or methyl ethyl ethers. When 2-alkylamino-ethanol is first treated with dimsyl sodium to make the oxyanion base followed by the addition of p-nitrochlorobenzene. when a solution of 3-bromo-tropolone in DMSO is heated with sodium methoxide. respectively (329). 1. The reaction rate increases some 1000-fold when the DMSO concentration is increased to 80% (399): NO2 F + -OR DMSO k1 OO + N OR F DMSO k2 NO2 OR R = C2H5 or t-Bu p-Nitrochlorobenzene also reacts with alkoxides.and 2-butyl naphthyl ethers. This suggests that 1. monobromo-. The major products observed in the bromo-. an almost 1:1 mixture of 3methoxytropolone and 4-methoxytropolone is obtained in 96% yield (3572): Br OCH3 O NaOCH 3.

rather than by the usual attack on carbon with inversion (1119)(653). almost quantitative yields of palkoxy. Amides 26 .p'-dialkoxybenzophenone are obtained (470): O NO2 C NO2 +NaOR 20oC 24 hrs.6-Dichloropyrimidine reacts with the sodium salt of p-nitrobenzenesulfonamide in DMSO to give 4-chloro-6-(p-nitrobenzenesulfonamido)pyrimidine (42): With 2.3-Dichloranisole can be prepared by reacting 1. The kinetics of the reaction of 2-bromo-. R R' 10-68% R'" R" e) Sulfonate displacement Benzene sulfonates of common primary and secondary alcohols react rapidly with sodium methoxide in DMSO to give high yields of alkyl methyl ethers and/or alkenes. d) Sulfinate displacement When -styrylsulfones are treated with one molar equivalent of sodium alkoxides in DMSO. -alkoxystyrenes are formed by nucleophilic substitution (9761): iv CH=C OR CH=C SO Ph 2 R'" R R' R" iv NaOR DMSO room temp. no benzyne-type intermediate (4058)(5244): F + t-BuOK 70oC 14 hours O t-BuOK-DMSO + 38% 27% (degradation product of the ether) OH 2.4'dimethoxybenzophenone (90%) is obtained. the conversion to the ether with sodium methoxide or sodium e. 3. and 2.5 at 40° C vs 1.3-trichlorobenzene with sodium methoxide in DMSOmethanol (9107).2'-dibromo-4.2.4.2'-dibromo-4. i. there is no displacement of bromide ion.2-dehydronaphthalene.44 at 110* C): OCH3 R' R + -OCH3 40-110oC N Br N OCH3 R' R R' + N R DMSO 2-Bromopyridine reacts with potassium methoxide in DMSO containing 1 % of methanol 3000 times faster than it does with the same reagent in pure methanol at 110°C.e. leading to the retention of configuration. A number of 4-alkoxypyridines is prepared by reacting 4-chloropyridine with sodium alkoxides in DMSO in moderate to high yields (5038). and 2-bromo-5-methylpyridine and methoxide ion in DMSO containing small amounts of methanol have been determined (2125).or p.or p. More olefins are formed from secondary sulfonate esters than from primary esters (580)(592). In the displacement of methane thoxide in DMSO occurs by the attack on the sulfur. 5-Bromo-3-methyl-4-nitroisothiazole reacts smoothly with sodium alkoxides in alcohols-DMSO to give the appropriate 5-alkoxy-3-methyl4-nitroisothiazoles (4098): CH3 NO2 DM SO 60-100oC CH3 N S OR NO2 + NaOR N S Br c) Nitro group displacement When sodium methoxide or sodium ethoxide is added to p-nitro. The ether-alkene ratio is significantly higher in reactions with sodium methoxide than with potassium tbutoxidesulfonyl ester groups from carbohydrate derivatives.fluoronaphthalenes undergo only direct nucleophilic substitution with no formation of 1. 2-bromo-3-methyl-.4'-dinitrobenzophenone.p'-dinitrobenzophenone in DMSO. ROH-DMSO OR O C OR Sulfonamides are also alkylated in DMSO. No reaction occurs in any instance when dioxane is used instead of DMSO (470). The ortho:para ratio is higher at lower temperatures (2.

When the sodium salt of an acetamidonitrile in DMSO is treated with chloramine. DM SO + R"X NHR' O 54-90% R NR'R" R RT With DMSO as the solvent.and 6-membered lactams. However. F. the use of stronger bases. DM SO O NH OCH3 COCH3 room temp N COCH3 68% 27 . Good yields can be obtained even at room temperature (4355): O KOH. 4 H2CSOCH 3.8-dihydro-s-triazolo[4.The N-alkylation of amides can take place in DMSO. 3. such as acetanilide. could be more convenient to work with than sodium in liquid ammonia (888). A number of amides. a smooth N-amination is achieved (4382): CN + ClNH2 NNa H3CO OCH3 H3COC H3CO OCH3 H3COC CN NNH2 DM SO Peptides and proteins can also be N-alkylated with methyl iodide and benzyl bromide using DMSO as the solvent and the dimsyl ion as the base (4945). DM SO N R N N O N + H N N N N It has been found that the N-alkylation of carboxylic acid amides proceeds well in DMSO by using dry potassium hydroxide as the base. is not necessary. Cl. 5. DMSO (CH2)nBr X N O (CH2)n The readily available base. Thus. the reaction with dimsyl ion fails to produce the seven-membered heterocyclic ring (888): H O C N X X = Br. however a mixture of the N-benzyl. have been N-alkylated with dialkyl sulfates using potassium hydroxide as the base and DMSO as the solvent (8276): O NHCCH 3 + (RO)2SO2 KOH. DMSO 20oC R N O CCH 3 The sodium salt of an amide can displace a methoxy group from a benzene nucleus. In this case. The reaction of various -haloamides with the dimsyl ion in DMSO can be used to obtain good to high yields of 4-. I.and the O-benzyl deriviatives results (3885): H O N N N N R =CH2 Cl + RCl O NaOH. the treatment of 2-acetamido-2'methoxybenzophenone with sodium hydride in DMSO gives the 9-acridone (8564): O NaH. N = 2. The alkylation of the sodium salt of saccharin with a benzyl chloride also proceeds well in DMSO to give a high yield of N-benzyl saccharin (947): 7-Oxo-7.3-a]pyrimidine can be alkylated as above using p-chlorobenzyl chloride in DMSO. dimsyl ion. such as sodium hydride or potassium alkoxides.

must be the decrease in. c) Aliphatic halide displacement-tertiary amines The reaction between triethylamine and ethyl iodine has been investigated in benzene.2. Thus.3. like ammonia. namely. a) Aliphatic halide displacement-primary amines Alkylation of weak aromatic amines with alkyl bromides (e. when p-nitrocumyl chloride is treated with quinuclidine in DMSO. it appears that DMSO can solvate the cationic part of the reacting system at the point of attack of the amine reagent (1240). However.4. displacement reactions by amines in DMSO generally proceed at a good rate. quaternizations. such as the reaction of triethylamine and ethyl iodide. It could also be said that DMSO polarizes a substrate (399). ethylenediamine reacts with chloroacetic acid to give ethylenediaminetetraacetic acid (EDTA) (4910): H2NCH2CH2NH2 + 4ClCH2CO2H DMSO o (HO2CCH2)2NCH2CH2N(CH2CO2H)2 80 C b) Aliphatic halide displacement-secondary amines -Bromoalkylbenzofuranones react with morpholine in DMSO to give high yields of the N-alkylation products (613): O O O (CH2)nBr +NH O DM SO O (CH2)n NO Ph Ph yield almost quantitive if n=1 or 2 n=1. The effect of DMSO. a 90% yield of pure quaternary ammonium chloride can be isolated (3433): DMSO (C2H5)3N + C2H5I 20-50oC (C2H5)4N+I- (CH3)2 C Cl (CH3)2 DM SO N room temperature 10 hours C Cl+ N + N O2 N O2 90% 28 . Amines. The presence of DMSO in the displacement reaction involving amines allows the reagents to surmount the energy barrier easier than in hydroxylic solvents. Thus.and para-substituted benzyl bromides in DMSO leads to azomethines as the main products (264): Br + BrH 2C X DMSO 100oC 1. DMSO and various benzene-DMSO mixtures. then. The reaction rate increases with increasing DMSO concentration in the solvent. 2-aminofluorenone with ethyl bromide) in DMSO gives ring brominated Nalkyl derivatives (211). Amines In most displacement reactions. amines (3433). do not hydrolyze DMSO. irrespective of the charge type of the reagents. such as amines. aralkylation of 2-aminofluorenone with aralkyl bromide.5 hrs HC N X O NH2 O DMSO also catalyzes the reaction between 2-substituted carboxylic acids and amines. and going through a charged transition state. However.the energy of the transition state. proceed much more rapidly to give a high yield of tetraethylammonium iodide (585): Similarly. Although DMSO reacts slowly with alkylating agents.g. displacements can also take place involving uncharged nucleophiles. A catalytic effect is seen by adding DMSO to an alcohol system containing amines and aryl halides (399)(1262). such as benzyl. For a reaction involving neutral reactants. the nucleophiles are negatively charged.4 The morpholinoethylbenzofuranone is formed by direct halogen displacement and no rearrangement reactions take place.

This reaction is the fastest with pyrrolidine. The fluoro compounds undergo substitution by various nucleophiles.4-dinitronaphthalene can be prepared by reacting 1-methoxy-2. The reaction of 2. Thus. which are otherwise difficult to prepare (398): DM SO OCCH3 X + NH OCCH3 N X = F. 2. g) Alkoxide and phenoxide displacement The reaction of n-butylamine or t-butylamine with 2. such as morpholine. benzylamine reacts with 2. The rate of displacement of fluorine is further enhanced by the order of 103 to 105 in dipolar aprotic solvents. in DMSO and affords in high yields the corresponding 4-amino derivatives. such as DMSO.4-dinitrochlorobenzene (399): DMSO C6H5CH2NHC6H3(NO2)2 C6H5CH2NH2 + CIC 6H3(NO2)2 e) Aromatic halide displacement . These reactions are run in the presence of an excess of amines: DMSO NO2 F + 2RHN2 NO2 + NHR + RNH3F- Similarly. azacyclobutane and dimethylamine. Br The yields of products obtained in DMSO are higher than those obtained with DMF under comparable conditions. activated nitro groups can be displaced by amines. f) Nitro group displacement In some cases.secondary amines The displacement of aromatic halides by secondary amines in DMSO has been studied rather extensively.4-dinitrochlorobenzene with piperidine. The reactions of 29 . as well as 6. which is known to be insensitive to base catalysis.4-dinitronaphthalene with piperidine in DMSO. morpholine and benzylamine with 2.and 8-alkyl-substituted 4-chloroquinolines with piperidine in DMSO and other solvents has been studied (1240)(1239)(1238). n-butylamine.4-dinitro-1 naphthylamines in high yields (3445): OC2H5 NO2 DM SO + RNH2 room temp NO2 NO2 NHR NO2 1-Piperidino-2. is nevertheless accelerated by DMSO (538). The dechlorination of 2. such as secondary aliphatic and alicyclic amines. and slowest with methylanisidine. The rate constants for the reaction of 4-nitrofluorobenzene in DMSO with 19 secondary amines have also been determined.4-dinitro-1 -naphthyl ethyl ether gives the corresponding 2. 4-fluoroacetophenone undergoes a very rapid displacement of the halogen by amines.4-dinitronaphthalene is prepared similarly (8408). Thus. 1 Dimethylamino-2. Cl.and 4-chloroquinolines. The kinetics of the reaction of piperidine.4-dinitrophenyl phenyl ether in DMSO has been studied as a function of amine concentration. at rates 100 to 1000 times faster than their chloro analogs.5-dinitro-1 -methylpyrrole undergoes nucleophilic aromatic substitution by piperidine (7756): NO2 N CH3 + DM SO NH O2N N N CH3 O2N The reaction with the amine is favored by the accelerating effect of DMSO in aromatic substitutions by neutral nucleophiles.d) Aromatic halide displacement . diisobutylamine and diethanolamine (1639). as compared with reactions in aprotic solvents (471). DMSO was selected as the solvent because of its relatively high boiling point and the fact that most nucleophilic reactions in DMSO proceed at a fast rate (1638).primary amines A series of primary amines has been reacted with 4-nitrofluorobenzene in DMSO to determine the rate constants.

making it a pseudo first-order 30 . p-dimethylaminotrifluoroacetophenone results. isopropyl 2.3-dibromo2. p-aminotrifluoroacetophenone reacts with ammonia in DMSO (3399): O DMSO F + NH3 F3CC 135oC. NO2 NO2 93% Similarly. Somewhat similarly. O NH2 F3CC 42% When DMF is used as the solvent in the above reaction.the secondary amines are base catalyzed.3-dihydrocinnamate reacts with ammonia to give isopropyl 2-phenyl 3-aziridine-carboxylate (10143): 88% PhCHCHCO2CH(CH3)2 + NH3 Br Br 4NH3 + 3ClCH2CO2H DMSO room temp. Reactions are frequently run with an excess solid sodium azide.) room temp.000 times greater than for the same reaction in protic solvents. 24 hrs. Azide Ion Rate constants for displacement reactions by the azide ion in DMSO are up to about 10.5 hrs. The solubility of ammonia is 40 liters per liter of DMSO at 1 atmosphere or 2.4-dinitroaniline (402): Cl NO2 NH2 NO2 DMSO + NH3 (aq. 3 hours PhCHCHCO2CH(CH3)2 N H High yields of nitrilotriacetic acid are claimed when ammonia is reacted with chloroacetic acid in DMSO (4910): N(CH2CO2H)3 + 3NH4Cl b) Aromatic halide displacement 2. those of the primary amines are not (9138). 1. apparently due to the hydrolysis of DMF to dimethylamine: O O F F3CC + NH3+(H3C)2NCHO F3CC (NCH3)2 c) Alkoxide displacement Displacement of an -OMe group by ammonia produces 3-amino-2-heteroarylpropenenitriles (10458): Ar C CN CHOCH 3 + NH3 DMSO Ar C CH-NH 2 CN 84-95% 6. Ammonia DMSO is stable to ammonia. such as methanol (471).4-Dinitrochlorobenzene reacts with ammonia to give 2. 5.6% by weight (5033). Secondary amine by-products are not found in any significant amounts in the above reaction. a) Aliphatic halide displacement Reaction of methyl 2-bromo-3-phenyl-3-butenoate with ammonia in DMSO gives the desired -amino ester (10134): DMSO Ph C CH2 CHCO 2CH3 + NH3 Br Ph C CH2 CHCO 2CH3 NH2 room temp. several hrs. Displacement reactions with ammonia and amines are examples where the nucleophile is uncharged (3433).

43 0.6 1.3-di-0-(methylsulfonyl)erythrol is reacted with a slight excess of sodium azide (7692): HNOAc N3 OMes OMes + 2 NaN3 DMSO 60-100oC OAc N3 N3 31 OAc 96% OAc OAc .48 0.3-diazidobutane is obtained when meso-1. 100 % NO2 N3 X = F or I When 4-chloro-3-nitrobenzoic acid is treated with sodium azide in DMSO. such as toluenesuIfonates and methanesuIfonates are also readily displaced by the azide ion in DMSO (4920)(8339). Dry 1% H2O 5% H2O 10% H2O ______________ (110°) (110°) (110°)_________ 2-Methoxyethanol 0. Measurements of solubility show that sodium azide is much more soluble in DMSO than in some other solvents. TABLE X __________________________________Solubility of Sodium Azide in Four Solvents______________________ Solubility. the 5-carboxybenzofuroxan results (1007): CO2H DM SO + NaN3 NO2 Cl N N+ O OCO2H Reaction of 2-chloroquinoxzline 1-oxide with sodium azide in DMSO at room temperature gives 2-azidoquinoxaline (9767): N + NaN3 N O Cl DMSO N N O 52% N3 c) Nitro group displacement The aromatic nitro group can also be displaced by dry sodium azide in DMSO (6572).9 (95-150°) HMPA 0. mol/l.28 0. Thus.process.3-dinitroacetanilide with sodium azide gives the monoazido-derivative (4600): HNOAc NO2 DMSO + NaN3 NO2 90oC NO2 87% d) Sulfonate displacement Sulfonates.51 (110-150°) a) Aliphatic halide displacement Some aliphatic halides are easily displaced by the azide ion in DMSO (4815).8 1. Thus.31 (124°) DMF 0. and the solubility increases slightly with the addition of water (7527).45 0. the rate is also a function of the solubility of the reagent.6 1. the reaction of 2-(2nitrophenyl)ethyl bromide with a 3-fold excess of sodium azide gives a 95% yield of 2-(2-nitrophenyl)ethyl azide (4360): CH2CH2N3 CH2CH2Br DMSO + NaN3 NO2 NO2 b) Aromatic halide displacement Treatment of 4-fluoro.5-1. Under these conditions. A high yield of the 2.10-0.or 4-iodonitrobenzene with sodium azide in DMSO produces a quantitative yield of 4-nitrophenyl azide (471): DMSO NO2 X + NaN3 100oC. 2.17 0.48 (25-150°) DMSO 1.12 0.4-di-0-acetyl-2.

With ambient anions where either carbon or oxygen alkylation is possible. THF and benzene. temperature. and alkali metal can lead to significant amounts of O-alkylation (773)(1114)(1229). where a proper choice of alkylating agent.4-pentanedione with alkyl iodides and sodium hydride as the base may be more conveniently and rapidly achieved when DMSO is used in place of the usual alcohols or non-polar solvents (4261): O CH3 C H2 C CCH3 + 2RX NaH. dimethoxyethane. This could mean that DMSO disperses the ion aggregates (611)(612).3-triazole-4-carbonitrile (4249): DMSO [NC CH CH N3] CN C N N CH N NC CN + N3 H 7. This alkylation is strongly accelerated by comparatively minor additions of DMSO to benzene. Alkylation of malonic esters in DMSO can be faster than in DMF.The above described displacements are frequently used to prepare amino sugar derivatives by reducing the azido to the corresponding amino group (5481)(7071). DMSO O Ph R Ph NO2 32 . e) Other displacements Treatment of fumaronitrile with sodium azide in DMSO with subsequent acidification leads to 1. DMSO favors oxygen alkylation (690): O + PhCH2Br DM SO O O 95% Ph This is also demonstrated in the alkylation of -ketoesters.2. DM SO O C CH3 R O CCH3 X= I or Br C R Similar results are obtained with malononitrile (599). Interaction of the potassium salt of 2-carbethoxy-cyclopentanone with an alkyl halide in DMSO at room temperature provides good yields of alkylated keto esters and probably constitutes the best method of alkylating this -ketoester (1823): O + CO 2C2H5 Br + K O DMSO CO 2C2H5 room temperature 78% 6 hrs. a) Aliphatic halide displacement The alkylations of 2. b) Aromatic halide displacement Substituted o-nitrohalobenzenes reaction DMSO in the presence of powdered KOH with deoxybenzoin to form the corresponding nitroarylated deoxybenzoins (9439): Cl NO2 R + Ph O Ph KOH. Carbanions The majority of carbanions which are usually prepared as reaction intermediates or as transistory species in chemical reactions are readily obtained in DMSO.

can be conveniently alkylated in excellent yields and selectivities by using aqueous sodium hydroxide as the base and DMSO as the reaction solvent (3951): PhCH2CN + NaOH(aq). These latter methods are generally cumbersome and 33 . D MSO 140oC. CH(OCOCH3)2 (CH3)2 NO2 Treatment of (p-cyanobenzyl)trimethylammonium chloride with the lithium salt of 2-nitroprprane gives the carbon alkylate (10399): + CH2N(CH3)3Cl+ [(CH3)2CNO2}Li+ DMSO 25oC O2N 82% NO2 NC e) Use of aqueous sodium hydroxide as the base It has been found that nitriles containing sufficiently activated methylene groups. the lithium salt of 2-nitropropane or the lithium salt of nitrocyclohexane (7108): R' NO2 R SO 2Ar + R' DM SO R" Li+ R" "R NO room temperature R R" 2 O2N NO2 d) Other displacement reactions Treatment of 2-cyanomethyl-dimethoxybenzophenone with sodium methoxide in DMSO gives 9-cyano-2-methoxyanthracen-10-ol (3112): NC H3CO OCH 3 CN OCH 3 NaOCH3.-pdinitrocumene with the lithium salt of 2-nitropropane in DMSO gives the alkylation product (1237): NO2 Li CH3 + H C 3 NO2 + DM SO 25oC NO2 71% NO2 NO2 Nitrobenzenes substituted by an electron withdrawing group. O 95% OH When p-nitrobenzylidene diacetate is reacted with the lithium salt of 2-nitropropane in DMSO. such as a metal amide. a compound in which one of the acetate groups is replaced by the C(CH3)2. such as p-dinitrobenzene. such as phenylacetonitrile. 10 min.g. e.c) Nitro and sulfinate group displacement . group is obtained (7657): DMSO O2N CH(OCOCH3)2 + (CH3)2CNO2 Li + O2N room temp 3 hrs. hydride. or alcoholate.NO2. readily undergo displacement by the lithium salt of 2-nitropropane in DMSO (8436): NO2 + NO2 Li+ H3C CH3 DMSO 25oC NO2 NO2 75% NO2 -nitrosulfones is also easily displaced by carbanions. these reactions have usually been carried out by treating the nitrile with a strongly basic reagent. followed by addition of the appropriate alkyl. DMSO R R'X RX CN Ph Ph R R' CN Previously.or aryl hydride.

5 hrs CO2Na O 95% CO2(CH2)7CH3 34 . 50% aqueous sodium hydroxide in DMSO can be used as a base to induce an essentially quantitative cyclization of 5-chloro-2pentanone to give cyclopropyl methyl ketone (3398): O Cl(H2C)3 CH3 NaOH (aq).4-pentanedione gives a 73% yield of 3. $%"$"!& The use of lime in the dimethylation of 2. e. react with disodiurn phthalate in DMSO tog ive. Carboxylate ions have also been used to displace sulfonates (8254). DMSO 30oC. a) Aliphatic halide displacement Simple alkyl halides. Diethyl malonate can be alkylated with benzyl bromide to yield diethyl benzylmalonate (3931): !"#$%"$"!&'" ( $) $-%.g. 3. e. Carboxylic acid esters are also prepared by reacting an acid with an organic halide in the presence of an alkali metal hydroxide in DMSO or DMSO-water. DMSO O Ph Ph R OH RX Ph O Ph R OR f) Use of calcium oxide as the base In some cases. calcium oxide has been used as a base to produce carbanions. Carboxylic acid esters are prepared by reacting an organic halide and potassium or sodium acetate in DMSO (574)(6847). 8. the reaction rate increases as the concentration of DMSO increases both for intramolecular and intermolecular displacment (407). polymerizable compounds (487): CH3 O CH3 O CO2Na CH2 DMSO Cl 2H C + o 2 140-145 C CH3 H3C O nearly quantitative H3C CH2 Cl A convenient procedure for preparing pyruvic acid esters utilizes an organic halide as the starting material rather than the corresponding alcohol (9657). the reaction of sodium pyruvate with n-octyl iodide or phenacyl bromide in DMSO yields the esters: O DMSO +I(CH2)7CH3 50oC. didecylphthalate in 91 % yield (2597). Similarly. such as n-decylbromide.3-dimethyl-2.//012% $"!&%"$ *+. 15 min O CH3 96% O. Carboxylate Ion Alkylation of carboxylate ions with alkyl halides in DMSO or DMSO-water is an efficient method of esterification (7950)(365)(8809). to obtain benzyl acetate (2969): NaOH + CH3CO2H Cl CO 2CH 3 DMSO 70-81% Potassium and sodium methacrylates react in DMSO with xylylene dichlorides in DMSO to give unsaturated. 4-pentanedione (3931). Thus.the selectivities are poor (3951). In aqueous DMSO systems.and C-alkylation of benzoins is also easily achieved by the reaction of alkyl halides in aqueous sodium hydroxide in DMSO at ambient temperatures (4699): O RX + Ph Ph OH NaOH (aq).g.

either isocyanates or isocyanurates result. zinc. Reactions can be run using an agitated. 1 g of either is soluble (964)(1924). 3 hrs. Many products are more easily isolated from reaction mixtures containing DMSO. At 25°C.O + Br CO2Na O Ph DMSO 50oC. Halogen atoms and sulfonate (tosyl) groups are displaced rapidly by cyanide ion. and mixtures of potassium cyanide with copper. Cyanide Ion Perhaps the most widely used of the displaycement reactions in DMSO are those involving the cyanide ion.200o C MX R OCN NCO + M= sodium or potassium Under conditions causing trimerization. cobalt. Certain inorganic cyanides are more soluble in DMSO than in other organic solvents. DMSO plays a superior role in the displacement reaction and also in the subsequent trimerization of isocyanates. When alkyl halides are reacted with cyanates. about 10 g of sodium cyanide and/or 2 g of potassium cyanide will dissolve in 100 cc of DMSO. the following reactions take place (9408): DMSO 100-150o C 1-2 hours N N XRX + MNCO X-R-NCO + MCO DMSO XR NCO + MX 70 . The solubility of sodium chloride. Cyanate Ion Sodium and potassium cyanates in DMSO can displace reactive halogens (26). is illustrated in the phase diagram. Figure 8. but somewhat lower with secondary ones due to dehydrohalogenation (475)(577)(8843). I. The solubility of sodium cyanide in DMSO at various temperatures is shown in Figure 7 below.5 hrs O O O O 85% Ph A ring opening and displacement reaction takes place when E and Z 2-phenylcyclopropyl bromides react with potassium acetate in DMSO in the presence of a crown ether (1 8-crown-6) (10465): R + CH3CO2K Br DMSO 85oC R CHCH2OCOCH3 - b) Sulfonate displacement When the sodium or potassium 2-methanesulfonoxybicyclo[3.3. These reactions may be written as follows (386): RX +KCNO DMSO RNCO + KX 70-80oC an isocyanate. Yields are commonly good with primary aliphatic halides. nickel. At 95°C. the corresponding lactone is produced (6347): 9.1 ]nonane-1 -carboxylate is heated in DMSO. These mixtures appear to be complex salts (801). n-propyl R If an organic dihalogen compound is reacted with either potassium cyanate or sodium cyanate. cadmium cyanide. Also soluble in DMSO are mercury cyanide. 3. Thus. depending on the reaction conditions and the solvent (440). DMSO can be used advantageously in systems where water is undesirable. stirred slurry of sodium cyanide with DMSO. Often the yields of the desired products are higher and side reactions are minimized in DMSO. the products can be converted to the corresponding cyanurates: O O R R R R OCN N N NCO X N N X or N O O O O N R R OCN X 10. the usual inorganic by-product when reacting sodium cyanide with organic chlorine compounds. or silver cyanides. In many cases it is not necessary to have a complete solubility of sodium cyanide in DMSO. O R R 3RNCO O N O an isocyanurate X = Br. R = ethyl. 35 .

36 .

DMSO NC CO2C2H5 O 81% -Cyano N. particularly those not activated by electron withdrawing groups. p-halophenol reacts with cuprous cyanide in DMSO to give p-hydroxybenzonitrile (1946): 37 . 80oC n CH3 CH3 Poly[3.1-dichloro-2-(bromomethyl)-2methylbutane with potassium cyanide (2769): Cl2 Br+ KCN DMSO Cl2 CN 50% The use of sodium cyanide in the above reaction gives some undesirable by-products. Thus. 90% + NaCl Similarly. The yields are also lower and longer reaction times are required with DMF. 1hr. both the displacement and elimination reactions take place.5% The difference in the reactivity of halogens is also illustrated in the reaction of 1.a) Aliphatic halide displacement The reaction of sodium cyanide with ethyl 6-chlorohexanoate in DMSO gives a high yield of 6-cyanohexanoate (474): Cl(CH2)5CO2C2H5 + NaCN DMSO CN(CH2)5CO2C2H5 o 95-100 C.3-bis(chloromethyl)oxocyclobutane] reacts with sodium cyanide in DMSO to give the bis(cyanomethyl) derivative (6847): CH2Cl O n + CH2Cl DMSO 2nNaCN 120-130oC CH2CN O n CH2CN b) Aromatic halide displacement Aromatic halides. When 1-chloro-17-fluoro-8-heptadecyne is reacted with sodium cyanide in DMSO. The enolate salt of ethyl 4-bromo-3-oxobutyrate reacts with the cyanide ion in DMSO (9135): Br O CO2C2H5+ CN. This could be due to the lower solubility of potassium cyanide in DMSO. ethylene dichloride reacts with sodium cyanide to give acrylonitrile (473): ClCH2CH2Cl + 2 NaCN DMSO H C CHCN + HCN + 2NaCl 2 100oC In the above case.N-disubstituted amides are conveniently prepared from halogenated amides by treatment with alkaline cyanides (9985): R O R O Cl NC CH3 + NaCN CH3 N N n DMSO. 1-cyano-17-fluoro-8heptadecyne is produced in high yield (2189): DMSO 120oC. It has also been established that both primary and secondary alkyl chlorides react with sodium cyanide in DMSO to give high yields of the corresponding nitriles in shorter reaction times than have been obtained with bromides or iodides in aqueous alcohol solvent (577). o o F(H 2C)8C C(CH2)7CN + NaCl 93. 24hrs 26% DMSO F(H 2C)8C C(CH2)7Cl + NaCN 135 -140 C 50 min. The use of DMSO allows the cyanide ion to displace halides from neophyl and neopentyl compounds without rearrangement (475)(7547): CH2Cl +NaCN neophyl chloride The displacement reactions of alkyl chlorides and bromides with potassium cyanide occur much more slowly when compared with sodium cyanide (475). sulfolane and dimethyl sulfolane as solvents (475). are best displaced by using cuprous cyanide (1593)(1774)(1946).

3. When a mixture of 2. 3-bis-(pentanenitrile) are prepared by treating the corresponding tosylates (or chlorides) with sodium cyanide (2783). CN CN III.3-bis(hexanenitrile) and azulene-1. X = Cl. a 1:1 mixture of 1.OH + CuCN X DMSO reflux 2-5 hrs. Thus. only the 2.4-bis(methylsulfonyl)benzene (II) and terephthalonitrile (III) is obtained in about 80% yield (1711): Cl I. NO2 OH DMSO CN 120oC 1 hour 55% duced CN + NaCN CN d) Quarternary ammonium salt displacement When 2-pyrrolylmethylammonium salts are reacted with sodium cyanide both pyrrole-2(8759): CH2N+(CH3)3XCN CN N CH3 + Na CN DMSO 80-85o C N CH3 + NC N CH3 e) Sulfinate displacement 1-Chloro-4-(methylsulfonyl)benzene (I0 and cuprous cyanide fail to react to give the desired 1-cyano-4-(methylsulfonyl)benzene when refluxed for 24 hours in DMF.(methylsulfonyl)cinnoline and potassium cyanide are reacted in DMSO.g.and 3. OH CN 60% c) Hydrogen displacement When o-nitrobenzonitrile is heated with sodium cyanide in DMSO hydroxy-isophthalonitrile is produced (8065). 2hrs. whereas the 3. tosylates) or disulfonates are converted in high yields to the corresponding nitriles or dinitriles with cyanides in DMSO (477)(2525)(10044).3-isomer reacts. When 4.4-isomer is recovered unchanged (1455): NO2 Cl Cl + NaCN DMSO NO2 CN Cl Sodium cyanide and o-fluoronitrobenzene in DMSO form 2-hydroxy-isophthalonitrile (8065): F NO2 NC + NaCN DMSO 120oC. 4-cinnolinecarbonitrile is produced quantitatively (1721): SO2CH3 + N KCN DMSO 20oC N N N 100% f) Sulfonate displacement Sulfonates (e. Br. azulene-1. However.4-dichloronitrobenzene is thus treated. DMSO H3CO2S SO2CH3+KCN reflux + SO2CH3 NC II. I OH CN Cuprous cyanide and 9-bromoanthracene in DMSO give 9-cyanoanthracene in 91% yield (3247). A neopentyl substitution product can be obtained by treating the corresponding tosylate with potassium cyanide in DMSO (8255): 38 . when equimolar amounts of I and potassium cyanide are allowed to react in DMSO for 30 minutes. A procedure for the separation of isomers of dihalonitrobenzene consists of treating them with an alkali metal cyanide or cuprous cyanide in DMSO.

1.4-di-p-tolyl-1. followed by the addition of DMSO and sodium cyanide to obtain 70-85% yields of the corresponding nitriles (872). Halogen Ion Displacement of halogen or other groups by halide ions is frequently easy in DMSO.O O DMSO CH 2OTs + KCN 70o C 3 hrs.4-tetrahydropyrimidine-2-one or4-(1-chlorethyl). 11.3-dibromo-2-butene can be obtained (2760): OTs Br Br Br Br Ts=tosyl OTs + LiCl DMSO Cl OTs Br Br OTs Cl Nucleophilic reactions between halogeno(phenyl)acetylenes and halide ions have also been examined in DMSO (10394). the above-mentioned pyrimidine produces a 7 membered ring compound (4739): O O DMSO CH 2OTs + KCN 70o C 3 hrs. eg. 15% o dry DMSO b) Aromatic halide displacement The chloride ion in chloro nitrobenzenes can be replaced by fluoride with potassium fluoride in DMSO (438): F 72% NO2 39 .4-dihydropyridine with sodium cyanide gives the ringexpansion products (4739)(9986).g. cyclopentyl chloride. cycloheptyl chloride. 125 hrs. a) Aliphatic halide displacement The kinetics of homogeneous isotope exchange between 36Cl in cyclic compounds (e. DMSO is the solvent of choice. Exchange reactions between halogens often require high temperatures and because of its boiling point of 189° C. 61% CH 2CN Displacement of primary or secondary hydroxyl groups by nitrile groups is accomplished by a short refluxing of the alcohol and triphenylphosphine in carbon tetrachloride.4-dichloro2.2. This exchange is a bimolecular SN2 reaction (109)(651): 36 36 - RCl + Cl RCl + Cl Similar exchange reactions between n-hexyl chlorides (containing36CI) and n-hexyl bromides (containing "Br) and lithium chloride and bromide have also been studied in DMSO (650). cyclooctyl chloride) and lithium chloride has been studied in DMSO. 61% CH 2CN g) Other displacement reactions Reacting a chloromethyl-1.4-positions with lithium chloride in DMSO. CPh CBr + (C2H5)4N+ClCl + KF NO2 DMSO 190oC 14 hrs PhC CCl 95 C. By exchanging two bromine atoms in the 1. cyclohexyl chloride. Thus.3.

12 hrs CH2OTs d) Displacement of diazonium ion p-Nitrobenzenediazonium tetrafluoroborate in DMSO reacts with iodides. chlorides)(913). Treatment of endo-5. e. the rate of hydrolysis increases with increasing DMSO content (329): CH3I + NaOH DMSO-H2O CH3OH + NaI Similar results are obtained with other primary alkyl halides (iodides. The rate constants for the reaction of hydroxide ion with ring substituted benzyl chlorides in acetone-water and DMSO-water mixtures are reported as a function of both solvent composition and temperature.6-bis(p-toluenesulfonyloxy-methyl)-2-norbornene with cesium chloride in DMSO gives the endo-5. nosylates = p-O2N-Ph-S03) can be displaced by halogens by reacting them with lithium chloride.I.Quantitative studies are reported for substitution of the type ArHal + CuX ArX + CuHal in DMSO and other polar solvents (541)(1593)(1214). as shown in Figure 10 in which acidity functions up to 26 are obtained with 0.: CH2Cl CH2Cl 50% N2+BF4- Br DMSO room temp NO2 NO2 70% 12. Br. bromides and chlorides to give the corresponding phalonitrobenzene (99). Cl36 c) Sulfonate displacement Sulfonates (e.bromonaphthalene and radioactive cuprous chloride (1593): Br + CuCl36 DMSO reflux 1 hr. Additions of water increase the solubility of alkali metal hydroxides. X =CI. CI.12 for tetramethylammonium hydroxide at room temperature (1172) (see Table IX). Figure 9 is a phase diagram of the water-DMSO-metal hydroxide systems for NaOH and KOH. tosylates.g. Potassium hydroxide is consistently more soluble than sodium hydroxide at a given water content. In spite of the low solubility of alkali metal hydroxides in DMSO. Ease of replacement follows the order: H a I= I. Hydroxide Ion The basicity of hydroxides in DMSO closely parallels that obtainable with alkoxides. ranging from 7 x 103 mol/liter for sodium hydroxide (725) to 0. b) Aromatic halide displacement The reaction of 2. F. but the increased solubility is accompanied by a decrease in the activity of the dissolved hydroxide ion. The reaction rate increases with increasing DMSO concentration but decreases with increasing acetone concentration (432). The reaction rates are the highest in DMSO among the solvents examined. lithium bromide (4066) or sodium bromide (1027) in DMSO. satisfactory use of the strong basicity of the hydroxide ion is sometimes achieved by using a slurry of the powdered base in the reaction. bromides.01 tetramethylammonium hydroxide in DMSO (1172). Pure secondary alcohols can be converted to bromides without rearrangement by first preparing the tosylates and then reacting them with sodium bromide in DMSO at room temperature (1027). lithium iodide (4066)(5836). Thus [1-36Cl]chloronaphthalene can be prepared from 1 .Br. a) Aliphatic halide displacement When the alkaline hydrolysis of methyl iodide is studied in the presence of hydroxyl ion in DMSO-water.g.4-dinitrofluorbenzene and 4-nitrofluorobenzene with hydroxide ion in DMSO-water are strongly accelerated by DMSO (328).6bis(chloromethyl)-2-norbornene (10002): nearly quantitative + 2CsCl DMSO CH2OTs 100o C. 40 . The solubility of the hydroxides is generally low.

e. KOH N reflux 2 hrs. with potassium hydroxide in aqueous DMSO to give the corresponding phenol (4425): F N DMSO (aq).3-benzothiadiazole.Hydrolysis of o. air + NaOH (aq) 80-115oC 3 hours OH NO2 Nucleophilic substitution reactions have also been carried out on a variety of mono.3Denzothiadiazoles.2.g.and dihalogen-1. 6chloro-4-fluoro-1.2.and p-nitrochlorobenzenes with caustic soda in DMSO produces o. S Cl OH N 92% S N Cl 41 .and p-nitrophenols (3925): Cl NO2 DMSO.

H2 C S NO2 The reaction rate of the above reaction increases significantly with increasing DMSO concentration. CF2Br CF2SC2H5 Methyl perfluoroalkyl sulfides may be prepared by reaction of the perfluoroalkyl iodides with sodium methyl mercaptide and dimethyl disulfide in DMSO (4792). resp. . The reactions of 4-methyithiophenoxide with 3.dibromo. DMSO + CH3SNa n-C8H13SCH3 o 105 C 88% 20-40 hrs. potassium benzyl mercaptide reacts with p-fluoronitrobenzene in DMSO-methanol under mild conditions (399): SK O2N DMSO 26-40oC few min.3-bis(chloromethyl)oxacyclobutane is prepared by reacting it with sodium benzyl mercaptide in DMSO (6847): H2 C Cl Cl H2 C O n NaSH2C H2 DMSO o C 110-120 C 5 hrs. (409)(470). When p-dinitrobenzene is reacted with hydroxide ion in aqueous DMSO. c) Nitro group displacement The nitro group at certain tertiary carbon atoms can be displaced by thiophenoxide in DMSO-methanol (1237) or 42 .c) Nitro group displacement The nitro group in 4-nitropyridine N-oxide.: n-C6F13I CH3SSCH3. DMSO 50-60 C 2hrs. '-bis(ethylthio)xylene (3386): CF2Br CF2SC2H5 3 + 2 C2H5SNa NaOCHo .3-benzothiadiazoles (4425). SCH2Ph H2 C O A derivative of poly-3. Mercaptide (or Thiophenoxide) Ion The mercaptide or thiophenoxide ions are known as good nucleophiles. Thus. particularly when the aromatic ring contains electron withdrawing groups in the ortho. one nitro group is displaced (6937)..2.or4-halo-substituted phthalimide derivatives have been studied in DMSO (9771): O NR + X O NaS CH3 DMSO H3C O O NR Nucleophilic substitution reactions have been carried out with mercaptide or thiophenoxide ions on a variety of mono. '. e.or para-positions to the halogen (8344)(399). Thus.g. '-tetrafluoro-p-xylene with sodium ethyl mercaptide gives the corresponding . the reaction of . and significant rate increases have been observed in DMSO when compared to the same reaction in alcohols (399).and dihalogen1. PhH2CS n b) Aromatic halide displacement Aromatic halogens are replaced by mercaptide or thiophenoxide ions in DMSO (541). p-nitrobenzophenone and 1-nitroxanthone can be replaced with aqueous sodium hydroxide to give the corresponding phenols or 1-hydroxyxanthone. a) Aliphatic halide displacement A number of alkyl halide displacements with mercaptides or thiophenoxides have been studied in DMSO (680) (712)(8779). 13. ' .

In DMSO it is not necessary to add urea to increase the solubility of sodium nitrite. as is the case with DMF (685). by adding phloroglucinol to the reaction mixture. Primary and secondary alkyl bromides and iodides react with sodium nitrite to produce the corresponding nitro compounds (486).2. depending on the structures involved (684)(3686) (4562). are reacted with sodium nitrite.3-dihalogen compounds. bromide or chloride to give the corresponding nitro compound is readily accomplished in DMSO with yields ranging from 50-91 %. a) Aliphatic halide displacement The displacement of aliphatic iodide. When 1. the nitro ester initially formed is quickly converted to the -nitrite ester R Br DMSO CO2C2H5 +NaNO2 R O2N room temperature CO2C2H5 -nitroester However.methyl mercaptide ions in DMSO (10008).g. e. (4068): R NO2 + NaSR' DMSO SR' R d) Sulfonate group displacement The reactions of the tosylate of 2.g. ethyl or 2-hydroxyethyl mercaptides in DMSO give the expected thio ethers (589): CF3CH2OTs + RSNa DMSO CF3CH2SR 14.g. 3-nitro-2-isoxazole (366)(988): Br(CH2)3Cl + 2NaNO2 DMSO 0-30oC 18 hrs O2N O N 53% Other substitutions at tertiary carbon atoms involving the nitrite ion have been studied (2565)(2566)(3490).88 g dissolves in 100 cc of DMF at room temperature after 24 hours. Displacement reactions involving the nitrite ion have been studied rather extensively in DMSO.2 g of sodium nitrite. The yields of the tertiary sulfides are very high in both cases. in a few minutes. Ph SO2 Ph SO2 The nitro group in substituted nitrobenzenes is displaced by the thiophenoxide ion (9771) or mercaptide ion (4068) (9771) to give the diaryl or alkyl aryl sulfides. (10008): (H 3C)2C NO2 (H 3C)2C SCH3 + NaSCH3 DMSO 15 min. 100 cc of DMSO dissolves 19. whereas only 1. the formation of nitrite ester is prevented and pure . 1 -bromooctane gives 1 -nitrooctane (685): CH3(CH2)7Br + NaNO2 CH3(CH2)7NO2 66% Lower nitroparaffins are prepared by treating the corresponding C1-3 alkyl chlorides with alkali metal nitrites in DMSO (10286): CH3Cl + NaNO2 DMSO CH3NO2 85% R ONO CO2C2H5 -nitrite ester When (684): -haloesters are reacted with sodium nitrite in DMSO. e. Nitrite Ion Sodium nitrite has good solubility in DMSO. respectively.2-trifluoroethanol with the sodium salts of methyl. e. The reaction of 1 -iodo4-heptyne with sodium nitrite in DMSO produces 1 -nitro-4-heptyne (4384)(6692): 43 . e. such as 3-bromo-l-chloropropane.g. Thus. a heterocyclic compound is obtained.nitroesters are produced in excellent yields (682)(684)(691).

10 min. OH NO2 NO2 80% c) Sulfonate displacement The reaction of the tosylate of the secondary alcohol (in the steroid or prostaglandin series) with potassium nitrite in DMSO affords the inverted alcohol as the main product together with the corresponding nitroalkane. CH3 C2H5O O O C2H5 CH3 77% C2H5 CH3 23% CH3 0% With tert-butyl alcohol as the solvent. 73%. With ions such as naphthoxide. 8%. DMSO is also a good solvent in the nucleophilic displacement of activated aromatic nitro groups by phenoxides for the synthesis of aromatic ethers (10434). 70oC 5 hrs. where a choice exists between carbon and oxygen alkylation. several minutes. DMSO is a good solvent for phenoxide ions. a) Aliphatic halide displacement DMSO can be used as the solvent in alkylation of sterically hindered phenols (884)(3631)(3830)(4573). and the reaction takes several days instead of 10 minutes. catechol. DMSO room temp. the major product is the corresponding ether (517): OH NaH.6-di-tert-butyl-4methylphenoxide is reacted with ethyl iodide. When 2.4-dinitrochlorobenzene is reacted with sodium nitrite in DMSO.4-dinitrophenol is formed (402)(4562): Cl NO2 + NaNO2 NO2 DMSO room temp. The alkylation of phenoxide is enhanced more than the alkylation of amino groups in DMSO. Cl 44 . When 2-t. When 2. as in DMSO. the polymerizations of the dipotassium salt of bisphenol A with dihaloaromatic compounds proceeds best in DMSO when compared to other dipolar aprotic solvents (6026).butyl-5-methyl phenol is alkylated with allyl bromide in DMSO with sodium methoxide as a base. The phenoxide group in tyrosine can be selectively etherified without blocking the amino group (442). ketone. and alkene (10454): R R' OTs + KNO2 H DMSO R R' R H H + + R' NO2 OH O R R' + alkene 15. hydroquinone) almost as much as it does for alkoxides or mercaptides (399). Thus. Reaction of polychloroethanes with sodium phenoxide in DMSO gives phenoxychloroethylenes (8410): Cl ONa + O Cl2CHCHCl2 DMSO..CH3CH2C C(CH2)3I + NaNO2 DMSO H3CH2CC C(CH2)3NO2 room temp. the corresponding product distribution is 19%. Phenoxide Ion DMSO enhances the rate at which halides are displaced by phenoxides (phenol. the reaction in DMSO gives almost exclusively oxygen alkylation (690). 45% 1hr b) Aromatic halide displacement Aromatic halides can also be displaced by the nitrite ion (8063). 2. a 97% yield of allyl-t-butyl-5methylphenyl ether is obtained (885).

O CO2CH3 O CO2CH3 Alkylation reactions of the bifunctional -bromo-1.3-epoxyalkanes in a one-step reaction in DMSO (10437): n ( O-Ar-OH) + - n O R Cl DMSO 130-140oC 2. DMSO + CH2Cl2 OH O O 91% b) Aromatic halide displacement The phenoxide ions in DMSO have been used in many aromatic halide displacement reactions (399)(690). In DMSO.2-epoxyalkanes have been found to be markedly dependent upon the solvent. Polyhydroxyethers can be synthesized from mono-alkali metal salts of bisphenols.4'sulfonyldiphenol.bromoalkyl derivatives. DMSO F 100 C. and 1-halo-2. DMSO CF3 138-144 o C. such as 4. Catechol reacts with methylene chloride in DMSO with sodium hydroxide as the base to give 1.. Thus. 145 C 24 hrs. bisphenol A can be polymerized with 4. high molecular weight aromatic polyethers (6026)(6830)(7699).Sodium methyl salicylate and diiodomethane in DMSO give formaldehyde disalicyl acetal (6460): 2 + ONa CO2CH3 o CH2I2 DMSO.4-dichlorobenzotrifluoride in DMSO to yield 3-(2-chloro-4trifluoromethylphenoxy)-benzoic acid (10320): OK KO2C Cl + Cl Cl K2CO3. Activated fluorobenzenes react with alkali metal salts of divalent phenols to give aryloxy compositions (8683): HO S + OH O N R X O + CN NaOH. 22 hrs O CF3 CO2H The ability of phenoxide ions in DMSO to displace aromatic halogens and the solubility of the phenoxide ions in DMSO are used in polycondensation reactions to obtain linear. 18hrs o CN O S OH Phenoxides also react with halo-substituted phthalimide derivatives in DMSO to produce high yields of ether imides (9096): O NaO DMSO O N R O The dipotassium salt of 3-hydroxybenzoic acid reacts with 3. phenoxides react by opening the epoxide ring to give -hydroxy.2-methylenedioxybenzene (2887): OH NaOH.4'-dichlorodiphenyl sulfone in DMSO to prepare a polyether sulfone (6831): 45 . Ar O R OH O n A number of catechol ethers have been prepared by using DMSO as the solvent (9145). these same compounds react by displacement of bromide ion to give epoxylalkyl derivatives (3395). In alcoholic media.5 hrs.

in the presence of an alkali phenoxide. d) Phenoxide displacement Polyetherimides can be made by effecting an interchange reaction. DMSO reflux O O Cl 81% Cl c) Nitro group displacement Some activated nitro groups are displaced with ease by phenoxide ions (8984)(8350)(8685): H3C ONa O N 2 + O HC DMSO 3 N CH3 room temp. DMSO O O O S O n OH Cl The dipotassium or disodium salt of catechol in DMSO reacts smoothly with some polyhalogenated benzenes (or heterocycles) to give good yields of the corresponding dibenzo-p-dioxins (7553)(8311 ).2. (7047): OH OH + Cl Cl Cl Cl KOH. Sulfide (or Hydrosulfide) and Thiosulfate Ions The sulfide and hydrosulfide ions act as nucleophiles and both these ions can be alkylated and/or arylated in DMSO. between aryloxy-substituted bisphthalimide and disodium salt of. This reaction has also found applications in polymers. 1. Water seems to be a necessary component for thiosulfate solubility. e. a) Aliphatic halide displacement Polymercaptans can be produced by reacting polyhalo compounds with sodium sulfhydrate (sodium hydrogen sulfide) in DMSO.3-propane can be transformed to phenoxyalcohol with sodium phenoxide in DMSO 6315): OPh HOH2C CH2OTs + ONa DMSO 50-60oC.g.HO S + Cl SO2 KOH . 3 hrs HOH2C O 83% 16. O O N O O CH3 Nucleophilic displacement of activated aromatic nitro groups with aryloxy anions in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers (10434). DMSO 160oC.g.. 1 hr Ar O N R' N O O Ar n OO e) Sulfonate displacement The monotosylate of 2-t-butyl-1. The rate constant for the reaction of thiosulfate in aqueous DMSO is at least an order of magnitude larger than in other solvents (656). e.g. e.3-trichlorpropane and sodium sulfhydrate give the corresponding trimercaptan (6192): 46 .. bisphenol A in DMSO (8714): O PhO N R' N O O O + HOArOH O NaOPh. particularly in the preparation of polyimides (7710)(8287).

e. H3C 50% CH(CH2)5CH3 SCN 3-Bromocyclohexene reacts with potassium thiocyanate in DMSO to form 3-thiocyanocyclohexene which is labile and rearranges to 3isothiocyanocyclohexene (390): + KSCN Br DMSO. the rate constants in displacement reactions are considerably greater than for reactions in protic solvents. a) Aliphatic halide displacement The reaction of 2-bromooctane with potassium thiocyanate yields 2-octyl thiocyanate (472): H3C CH(CH2)5CH3 + KSCN Br DMSO 74oC 2 hrs. HSH2C SH SH A mixture of either an aryl isothiocyanate or an aryl isocyanide dichloride.1-dihydrotrifluoroethyl ptoluene sulfonate reacts with sodium sulfide to give bis(1. methanol (471). 5% H2O 0oC distill SCN NCS Ammonium thiocyanate and 2-chloromethylbenzimidazole in DMSO react to form thiocyanic acid (2benzimidozolyl)methyl ester (7173): 47 . Thiocyanate Ion Sodium and potassium thiocyanates are very soluble in DMSO. as in the reaction with chloro-4-nitro-3trifluorotoluene in DMSO. and a sulfide source.9H2O S. 50 min.g. H2O. 1. The major product is a disulfide (4123): DMSO NO2 2 F3C Cl + NaSH 20-25oC 8 hours NO2 F3C S 45% S NO2 CF3 c) Sulfonate displacement Sulfonates (tosylates) can be displaced by using either sodium sulfydrate or sodium sulfide in DMSO. methylene bromide.CH2ClCHClCH2Cl + 3 NaHS DMSO 50oC . o H3CO2CCH2Ch2CO2CH3 62% Sodium thiosulfate and benzyl chloride react to yield sodium benzylthiosulfate which forms dibenzyl disulfide (472): 2 CH2Cl + 2Na2S2O3 DMSO (aq.3-dithietanes (7528): DMSO N=CCl 2 + CH2Br 2+2 (NH4)2S 40oC 1 hour N 77% C S S CH 2 The -activated diethyl sulfides can be prepared by reacting the appropriate chloride with sodium sulfide in DMSO (6398): 2H3CO2CCH2CH2Cl + Na2S.1-dihydrotrifluoroethyl) sulfide (489): CF3CH2OTs + Na2S.) 30oC 2 days CH2S2O3Na CH2S 2 b) Aromatic halide displacement Sodium sulfhydrate can also displace aromatic halogens from activated nuclei. DMSO CF3CH2SCH2CF3 + CF3CH2S-S-CH2CF3 70-80oC 43% 29% 2 hours 17.9H2O DMSO 10 C 2 hrs. such as ammonium sulfide or sodium sulfide. and in most cases. can be reacted in DMSO to provide a one-step synthesis of aromatic 2-imino-1. Thus.

When the nucleophile is the hydroxide ion in the aqueous system. Since the acidity function is a logarithmic scale measuring 14 the ability of the system to remove a proton from the reference indicator. In the highly basic systems. 2-methylbutyl p-toluenesulfonate and potassium thiocyanate in DMSO yield (62. an equilibrium amount of the DMSO anion will be present. The influence of the cation is greater in DMSO than in t-butanol. shown in Figure 10.4-pentane di-p-bromobenzenesulfonate to give 2. Although the equilibrium amount of DMSO anion produced by alkoxide ion in this system is small. sodium and potassium t-butoxides are about equally effective in prompting hydrogen exchange. the data show the basicity to be enhanced some 10 fold upon going from water or alcohol to 99% DMSO. in isomerizations and in a wide variety of elimination reactions.000 times as acidic as DMSO and they have about the same acidity as triphenylmethane (734)(1558).) CF3 NO2 70% c) Sulfonate displacement Potassium thiocyanate in DMSO displaces the sulfonate groups from 2.4-dithiocyanopentane (515): OBs OBs + KCN DMSO o 70-75 C. the activities of the bases can be presented in terms of acidity function. The simple aliphatic alcohols are about 1. Proton Removal A number of different reactions require the removal of protons from carbon with the resultant formation of carbanions. The rate of potassium t-butoxide6 catalyzed hydrogen-deuterium exchange at a benzyllic carbon atom is 10 times greater in DMSO than in t-butanol (606). Carbanions are formed in racemizations. BASES AND BASE-CATALYZED REACTIONS IN DMSO Basicities in DMSO The reactivity of nucleophiles in DMSO mixtures with water or alcohols consistently increases as the content of DMSO in the mixture increases. One chemical consequence of this effect shows up in the alkoxide-catalyzed autoxidation of fluorene where the oxidation rate is controlled by the rate of carbanion formation (1728). with the reaction being 10 -10 times faster in DMSO than in t-butanol (622)(524). the rate at which the protons transfer is fast (1758)(1759) so that a steady pool of DMSO anion is available for reaction. obtained when the concentration of water or alcohol is low. However. 48 . Just as the equilibrium basicity of alkoxides and hydroxides is enormously enhanced in DMSO versus in hydroxylic solvents. in t-butanol.) 120oC (3 hrs. 6 7 A similar rate enhancement is observed in racemizations using ammonia as the base. 50 hr SCN SCN 68% Similarly. B. The reaction rate increases 220-fold upon changing the solvent from t-butanol to an 80:20 DMSO-t-butyl alcohol mixture. The proton removal can be either an initial or the rate-determining step.5%) 2-methylbutyl thiocyanate (5435). For example. whereas in DMSO the potassium salt gives a reaction rate one hundred times that of the sodium salt (606). or the alkoxide ion in the alcoholic system. in the 80:20 mixture the concentration of DMSO anion is sufficient to react with the product so that instead of a 91 % yield of fluorenone a 78% yield of the DMSO adduct of fluorenone is obtained.N CCH2Cl + NH4SCN N H DMSO room temp 15 minutes N CCH2SCN N 41% H b) Aromatic halide displacement Nitrotrifluoromethylchlorobenzenes react with sodium thiocyanate in DMSO to yield the corresponding phenylthiocyanates (4123)(7158): Cl NO2 + NaSCN CF3 DMSO 45-50oC (22 hrs. so also is the rate at which proton removal or hydrogen exchange reactions occur in DMSO. Such a protic-aprotic system offers a means of adjusting the basicity of a reaction medium over a wide range.

49 .

8 10.2.5 24.0.0 29.8 22.7 18.4 30.6 23.7 26.8 14.5 26.0 10.5 23.11. .5-Dinitrobenzoic acid 2.8 18.4 12.0 7. -Diphenylacetophenone -Thiophenylaceton Methyl trifluoromethyl sulfone 4-Chloro-2-nitroanaline 4-Nitroanaline a.2 12.N-Dimethylprop-2-ynylamine 9-tert-Butyl-fluorene Ethyl phenyl ketone Diphenylmethylphenyl sulfone 2.23.0 4.5 17.1 18.7 6.3 8.3.7 14.1 25. '-Tetraphenylacetone Phenyl benzyl ketone Bis(2-nitrophenyl)amine Nitrocyclobutane 9-Phenylfluorene Nitrocyclohexane Nitroneopentane .5 17.6 17.8 17.5 25. The pKa of DMSO is 35 (10411).4-Dichloroanaline Acetamide (N-H) Methyl benzyl sulfone 1.3 10.0 9.10.4 19.0 16.4 23.6 24.2 11.6.3 7.9 9.3 25. a-Diphenylacetone Methyl benzyl ketone 2-Bromofluorene Ethyl trifluoromethyl sulfone Thiourea Thiophenylacetonitrile Bis(n-chlorophenyl)amine Phenylacetonitrile 9-Methylfluorene Phenylacetylene 2.5.6 6.0 23.6 30.6 10.5 20.3 26.4-Dinitroanaline Oxalic acid II Resorcinol 9-Phenylthiofluorene 2.5 23.8 23. '.5 7.5-Dichloro-4-nitroanaline Nitromethylcyclopropane Nitroethane 1.2 10.9 16.8.2 19.6 22.8 20.6-Dinitro-4-chlorophenol Protonated analine Protonated 2-methylpyridine Protonated 2.3 15.1 16.9 11.2 11.8 5.7 18.6-Dichloroanaline Fluorene Trithiophenylmethane Phenyldithiophenylmethane 1 -Phenyl-1 -cyanoethane 3-Methylfluorene 2.9 15.8 10.3 8.6 8. starting with the most acidicprotonated pyridine.6 12.7 16.6 22.1 11.3-Triphenylpropene Isopropyl phenyl ketone Acetone 9-(3-Chlorophenyl)xanthene 3-Chloroanaline Diphenylthiophenylmethane Nitrocyclopropane Diethyl ketone 9-Phenylxanthene Water Benzyl methyl sulfoxide Methyl phenyl sulfone Diphenylyldiphenylmethane Triphenylmethane Phenylthiophenylmethane Ethyl phenyl sulfone Dimethyl sulfone Acetonitrile Diphenylmethane Propionitrile DMSO pKa 17.7 7.The table below (Table XI) lists the acidities (pKa) values of 132 organic compounds in DMSO.5 6.9 19.9 18.0 11.6 15.0 COMPOUND Nitromethane Diphenylacetonitrile .5-Dichloroanaline Acetophenone Urea 2.6 25.8 13.7 16.9 24.5 35 50 .28.9 28.2 6.4 21.5-Dihydroxybenzoic acid Phenylsulfonylnitromethane 3.4 Dichloroanaline 3-Methoxy-1 -propyne Formamide (N-H) Diphenylamine Dibenzyl sulfone N.1 7.0 31. TABLE XI Acidities in DMSO COMPOUND Protonated pyridine 2.6 3.2 6.0 11.9 17.3 22.7 17.16.8.2' 10.7 4.1 27.5 3.0 20.3 8.4 15.7 7.8.2 24.9 27. and ending with the least acidic-propionitrile (10569).0 29.1 23.2 9.3 24.4-dimethylpyridine Protonated o-phenylenediamine Thiosalicylic acid Phthalic acid I Oxalic acid I Sulfamic acid Salicylic acid Thioacetic acid Thiocyanuric acid Bromocresol green 2.8 21.6 26.8 16.4 20.0 23.3 32.0 29.6.1 31.8 16.7 17.4-Dihydroxybenzoic acid Rhodanine Nitromethyl phenyl ketone 9-Cyanofluorene 2.5-Dihydrophthalic acid II Nitrocycloheptane Nitrocyclopentane p-Chlorophenol 2.2 16.9 17.6 13.6 11.5 4.5-Dihydrophthalic acid Protonated tributylamine Protonated diphenylguanidine Chloroacetic acid p-Nitrobenzoic acid Ethyl nitroacetate Thiophenol Protonated dibutylamine Bromo thymol blue p-Chlorobenzoic acid 9-Carboxymethylfluorene 9-Phenylsulfonylfluorene Protonated piperidine Protonated pyrrolidone Benzoic acid o-Toluic acid m-Toluic acid Malononitrile p-Toluic acid 3-Nitro-l-propene Phenylacetic acid Thiophenylnitromethane Phenylnitromethane Methylmalononitrile Acetic acid 2-Thiohydantoin I Acetylacetone Hydrogen cyanide Bis(ethylsulfonyl)methane 2.8 31.2 6.6 26.7 26.30.9 12.7 25.3 32.9 22.2 7.5 16.4 24.4 14.1 Bis(ethylsulfonyl)ethane 1 -Nitropropane 2-Nitropropane Phenol m-Cresol pKa 3.7 8.2 10.

Temperatures of 132-138° are usually required in water. 30oC X Y CN + OH CO 2 Some acids. Thus. In addition.0 C in the presence of DMSO and water.25-trien-3 -ol. Ph O2 S CH3 83% n-C6H13 H3C n-C H 6 13 Tetrahalophthalic acids in DMSO in the presence of alkali and alkaline earth chlorides undergo double decarboxylation to form 1.4-cyclohexadiene (7533): 51 . decarboxylate more readily in the presence of base to give.4. The reaction rate constant increases by a factor of 6-7 with a change in concentration of DMSO from 50 to 86%.5-Cl4(or Br4)C6HCO2H (4602). usually from one or two carbon atoms.ELIMINATION REACTIONS These are base-catalyzed reactions in which two atoms or groups are removed or eliminated. and oxamic (643) acids at elevated temperatures.2. NiCl2.g. the treatment of 3. whereas.3. DMSO 90oC. CoCl2. CuCI2) or no salts at all mostly single decarboxylation occurs to give 2. Dramatic rate accelerations result in the decarboxylation of benzisoxazole-3-carboxylic acids if water is replaced by DMSO (3447): CO 2H X Y O N DMSO. 1. 5 -Stigmasta-7. The only product of this decarboxylation is 4methyl-pyridine hydrochloride (2343)(3743): ClHN CH2CO2H DMSO 30oC ClHN CH3 95+% ° The decarboxylation of trichloroacetic acid also occurs as low as 25.3. a steroid alcohol. Pyridylacetic acid hydrochloride decarboxylates in DMSO at moderate temperatures.22.4tetrahalobenzenes. Cope Elimination The pyrolysis oft-amine oxides (Cope elimination) in dry DMSO proceeds at a convenient rate at 25°C to give 80-90% yields of olefins.2-dicarboxylic acid yields 3.3-dimethylcyclohex-4-ene-1. 148 hrs. A double bond is frequently formed as the result of this elimination. in this case. Lead tetraacetate has been used in DMSO to decarboxylate dicarboxylic acids (5081). the rates in DMSO are 10. (+)-2-octylphenylsulfone in 98% optical purity (631): Ph O2 S CO 2H KOCH3. in the presence of other chlorides (e. Decarboxylation and Decarbalkoxylation ° DMSO promotes the decomposition of malonic (640). e. is obtained by heating the appropriate t-amine oxide in DMSO (3481): O R H3 C N (CH3)2 DMSO 120-130oC R H3C 61% 2. such as optically pure (+)-2-benzenesulfonyl-2-methyl-octanoic acid. 140-160 C.000 times faster than in water (495): O Ph N (CH3)3 DMSO 25oC Ph CH3 + 80-90% Ph The rate is higher in wet DMSO than in dry THF because DM SO acts as an internal drying agent and competes with amine oxide for the water present (578).g.3-dimethyl-1. oxalic (604).

Only those compounds bearing at least one carboxylic proton are labile. -keto esters. In the reaction of 3 -chloro-5 -bromo-6 -bromocholestane with excess dimsyl sodium in DMSO. DMSO N R N + CO2 The decarbalkoxylation of methyl or ethyl isohexylmalonates in DMSO in the presence of various alkali metal salts gives methyl or ethyl 6-methylheptanoates. Decarboxylation of geminal diesters.2-cyclononadiene.CO 2H Pb(OAc)4. and to be subject to catalysis by nucleophiles. or LiCl dramatically enhance the decarbalkoxylation rates of geminal diesters. NaCl.4°C. DMSO C2H5O2C 160oC. Benzaldehydes can be prepared from the phenylacetic acids by electrolytic decarboxylation and oxidation in DMSO in the presence of sodium hydride. e. 4 hrs. are less effective in the case of substrates with lower activity because of lower boiling points of these solvents (6102). geminal dicarboxy groups are eliminated when malonic ester derivatives are heated in DMSO (942): C2H5O2C C2H5O2C NaCN. -keto esters. one can obtain elimination of either bromine or hydrogen bromide in cases where both paths are available (454): Br Br H2CSOCH3. Other dipolar aprotic solvents. and -cyanoesters to the corresponding monoesters. such a DMSO. Salts such as KCN. while the use of a larger excess of dimsyl sodium and longer reaction times yield 1. Dehalogenation By a proper choice of reaction conditions or nucleophile in DMSO. The yields are good in most cases (8766): R CH2CO2H electrolysis NaH CHO R Decarbalkoxylation (mostly decarbethoxylation) is related to decarboxylation in that the -CO2R group. such as DMF. DMSO-pyridine CO 2H Rates of decarboxylation are reported for several phenylmalonic acids and esters in DMSO at 55. the debrominated intermediate results. Thus. The best results are obtained in the presence of 1 equivalent of salt and 2 equivalents of water (8861). ° H 60-80% The treatment of ethyl trichloroacetate with sodium methoxide in DMSO at 0 C produces dichlorocarbene which is oxidized by DMSO (1040). 3. ketones and nitriles can be accomplished in excellent yields (85-95%) in wet DMSO in the presence of sodium chloride at 140-186°C (6102)(7022)(9769). and cyanoesters by DMSO-water (9769). halide ions (7285): N CO2R N X-. HCl elimination occurs (455): 52 . The alkylative decarboxylation of N-carbalkoxypyrozoles has been shown to require a polar aprotic solvent. DMSO Br 61% In the presence of excess dimsyl sodium in DMSO at room temperature. bromine elimination occurs. When this intermediate is treated with potassium t-butoxide in DMSO. DMSO 71% H2CSOCH3.g. which establishes that intramolecular proton transfer is an integral part of the reaction mechanism (7655). instead of CO2 (decarboxylation) is eliminated.

8 hrs.2. 2. DMSO 43% Pure olefins from their dibromides can be obtained by using sodium thiosulfate in DMSO as the debrominating agent. 20 hrs Another dibromide can be dehalogenated by heating with zinc dust in DMSO (7184): OAc OAc Br DMSO.0. stilbene dibromide yields stilbene (6496): Br Br + Na2S2O2 DMSO 60oC. Zn 90o. These reactions do not occur in N-methylpyrrolidone. DMF.9-dibromodispiro[2. DMSO room temperature. C 4 F 9I.0. C6 H33I and CsF17I. A mixture of perfluoroolefins results (9928). -dibromo derivatives of diphenylethylene and meso-stilbene with potassium fluoride and cesium fluoride in DMSO afford quantitative yields of diphenylacetylene and trans-stilbene. ' such as DMSO.4]decane with potassium t-butoxide in DMSO gives spiro[2.. DMSO Cl Br room temperature Br Cl 77% t-BuOK.H2CSOCH3. C4F9I Zn-Cu. 99% Treatment of 8.2. g. e.. Thus. DMSO 80oC F3C F F + F3C F CF3 F 21% + C4F9H 20% 39% CF3 53 . has been studied in aprotic solvents.5 hrs Br OAc OAc 100% Heating trans. via the intermediacy of dimsyl ion. resp. or sulfolane (9338): Ph Br Ph Br Br Ph Br Ph DMSO KF or CsF DMSO PhC CPh The action of zinc-copper couples on perfluoroiodoalkanes.4]dec-8 ene (7153): Br Br t-BuOK.

Ionic association in base-promoted -elimination reactions has been reviewed (8050).1] heptene (3360): Cl t-BuOK. 20). p. a) Potassium t-butoxide in dehydrohalogenations The enhanced basicity of potassium t-butoxide in DMSO has been suggested as the dominant factor which causes dehydrobrominations to occur much more readily in DMSO than in t-butanol (652). The rapid reaction is suggested to occur by an initial formation of the carbanion which eleminates chloride ion to give a carbene intermediate. few seconds or minutes n = 5 or 6 OR (CH2)n 60-74 % 54 . followed by other alkoxides. The strongly basic reaction medium obtainable with potassium t-butoxide in DMSO in the case of aromatic bromine compounds produces aryne intermediates (434)(514) (see also Displacement reactions Alkoxide Ion.7-Dichlorobicyclo[2. The transcis 2-alkene ratio is dependent upon the alkyl group of the 2-bromoalkane (3368): H2CR CH3 t-BuOK.2.2. DMSO 20oC.1 ]heptane on treatment with potassium t-butoxide in DMSO gives 7-chlorobicyclo[2. Aromatic halide displacement.5 days Cl Cl 96% Olefinic products from reactions of a series of 2-bromoaIkanes with potassium t-butoxide are produced. such as ammonia and amines. The most frequently used base has beer potassium t-butoxide. 2.Some dehalogenation reactions using potassium t-butoxide as the base have been reviewed (6815). quaternary ammonium hydroxide. DMSO RH2CHC CH2 + RHC CHCH3 30-90oC Br The trans-1 -iodocyclopropylpropene reacts at least ten times faster with potassium t-butoxide in DMSO than the cis isomer to yield 1 -cyclopropyl-2-methylacetylene (3503)(4176): I t-BuOK. The reaction of benzhydryl chloride with potassium t-butoxide in t-butanol occurs slowly by displacement giving benzhydryl t-butyl ether. DMSO H CH3 trans fast CH3 t-BuOK. DMSO H slow cis I CH3 Six or seven-membered trans-cycloolefins may be transformed into the corresponding 3-alkoxycycloalkynes by reaction with potassium t-butoxide in DMSO (3707): Br OR (CH2)n t-BuOK. The effects of base strength and size upon the orientation in base-promoted -elimination reactions have beer studied (6234)(6378)(6818)(8582)(10011). dimsyl ion. sodium cyanide and some relatively weak organic bases. as shown below: [Ph2CCl]-K+ Ph2C: + DMSO PhC: Ph2C: (or [Ph2CCl-]) DMSO + ClPh Ph +K+ Ph Ph The rate of dehydrobromination of 2-arylethyl bromides with potassium t-butoxide in t-butanol-DMSO mixtures increases with increasing DMSO concentration at a much faster rate than the increase of acidity function (833). whereas the base in DMSO causes a very rapid elimination( -elimination) giving nearly quantitative yields of tetraphenyl ethylene (696). 4. Dehydrohalogenation A variety of bases have been used in the dehydrohaloge nation reaction. Other bases used include: sodium and potassium hydroxide the carbonate and bicarbonate ions. DMSO room temperature 3.

o (CH2)7 C 78% Dehydrofluorinations can also be accomplished with potassium t-butoxide in DMSO (5118): F H F t-BuOK.2.2-dimethylcyclopropane (7028): H3C CH3 H Br t-BuOK.2-cyclodecadiene (8960): Br t-BuOK. DMSO Ph 50oC. The olefinic products observed in reactions of sodium ethoxide or 2. DMSO o H 120 C. 10 min In all cases in the above reaction. such as sodium and potassium methoxides or ethoxides. Br F F cis-3-Bromocyclodiene is easily dehydrobrominated to 1. treatment of pinacolone dichloride with potassium t-butoxide in DMSO produces tert-butylacetylene in high yield (7608): Cl (H 3C)3CC Cl H3C t-BuOK.2-trifluoroethoxide with 2-butyl iodide. 5 min. bromide and chloride in DMSO are reported (3853): CH3 X X = I.3-Dimethylcyclopropene is easily produced from 1 -bromo-2.2. DMSO 20 C. DMSO 1-butene 25oC.The reaction of 1.2-trifluoroethoxide results in a decrease in the percent 1 -butene (3853).1 -dichloro-1 -cyclopropylethane with potassium t-butoxide in DMSO gives 1 -cyclopropylacetylene (5594): Cl t-BuOK. 24 hrs. have been used with good results in dehydrohalogenation reactions. difluorostvrene (5980): Ph Br Cl F F t-BuOK. 4 hrs. DMSO CH3 room temperature Cl 34% Similarly. Cl H3CH2CHC CH2+ H2CHC CHCH3 2-butene NaOC2H5 (or NaOCH2CF3). the change from ethoxide to 2. (7737): 55 .. DMSO H3C 90oC.2-dimethoxypyrans with an excess of sodium ethoxide in DMSO produces the corresponding pyrones (5834).2-difluoro-l-phenylethane reacts with potassium t-butoxide to give -bromo. F H b) Other alkoxides in dehydrohalogenations Other alkoxides. 3hrs CH3 84% 1-Bromo-2-chloro-2.4-dihydro-2. Treatment of 3-chloro-3. DMSO below 40oC (H 3C)3C CH 95+% 3. Br.

1.6.g.6-bis-(ethylidenedioxy)-3.2-dimethyl-3-butynoic acid (7865): Cl CH3 CO2H CH3 CH2SOCH3 DMSO 50oC.g. Thus. 56 .1.DMSO Br Br Br Br t-BuOK. Methyl halogenated ethyl sulfides can be dehydrohalogenated with potassium hydroxide in DMSO (3142).l. such as sodium hydroxide. Tetra methylammonium hydroxide is more soluble in DMSO than either sodium hydroxide or potassium hydroxide (see Table IX).1 -chlorodifluoroethane can be dehydrochlorinated to vinylidene fluoride in high yield in heterogeneous DMSO suspensions or aqueous DMSO suspensions or solutions in the presence of sodium hydroxide.2-dimethyl-3-dimethyl-3-chloro-3-butenoic acid with dimsyl sodium in DMSO gives 2.: H3CCClF2 + NaOH DMSO + H2O (5%) 50 C o H2C CF2 69. DMSO 60-70oC. DMSO R3 2 O O room temp. the elimination may be effected in several hours with sodium methoxide in DMSO (9604): O Br O O O Br O NaOCH 3. potassium t-butoxide is a better dehydrohalogenating agent than the dimsyl ion.0]octane with ethanolic potassium hydroxide requires refluxing for several days for complete reaction.5 hrs O O O 89-92% c) Dimsyl ion in dehydrohalogenations Treatment of 1-acetylnaphth-2-yl 2'-chloroallyl ether with dimsyl ion in DMSO yields 1-acetylnaphthyl-2-yl propargyl ether which cyclizes to 2-methyl.8 % conversion 99. 5 hrs CH3 CO2H 88% CH3 In some cases.. Although double dehydrobromination of 2. 2. few hours R R1 R1 The addition of DMSO to the NaOCH -CH3OH medium causes a significant increase in the rate of dehydrochlorination of Ph2CHCH2Cl (9142)(9143). potassium hydroxide and tetraalkylammonium hydroxide have been used for dehydrohalogenation reactions (8050). e. potassium hydroxide or tetramethylammonium hydroxide (5279).7-dibromobicyclo[3. DMSO 78% 37% + styrene 22% d) Hydroxylic bases in dehydrohalogenations Hydroxylic bases.5% selectivity DMSO is a better reaction medium for the above reaction than some other solvents.4-phenanthrenequinone (7552): O O DMSO CH2SOCH3 30% O O O O 55-60% Reaction of 2. e.3.R3 R2 O OCH3 OCH3 Cl NaOCH3. Thus. the dimsyl ion can act as a dehalogenating agent for vicinal dibromides (455): CH2SOCH3.

1-dioxide can be dehydrohalogenated when warmed with triethyl.3-dihydro-2-methyl-4H-pyran-4-one with sodium carbonate in DMSO yields 3-bromo-6dibromomethyl-5-carbethoxy-2-methyl-4H-pyran-4-one (6215): Br Br H3C O CO2C2H5 DMSO + Na2CO3 20oC. DMSO 20oC O OH O 42% Relatively high yields of alkynes can be obtained from . hydrazides. 2 hrs. 57 . amine in DMSO (385): Cl O SR DMSO +(C2H5)3N o 90 C. Dehydrohalogenations without olefin isomerization can sometimes be accomplished by using weaker bases.g. -dihalides in short reaction times at moderate temperatures in DMSO using moderately strong bases.or3-arylthio-4-chlorothiolane 1.F SF F Cl H + KOH H3CFSC CFCl room temperature DMSO 6-Hydroxy-2-isopropenyl-5-acetylcoumaran can be obtained from the corresponding vinyl bromide by dehydrohalogenation with potassium hydroxide and cyclization in DMSO (4892): O Br OH O KOH. SR O 60-90% 5. without isolation of the intermediate olefin (8238). carbazides. 3. or amines.3-diphenylcyclobutane with sodium cyanide in DMSO produces 1. -dihalides or . Thus. such as potassium hydroxide. Usually these are compounds that contain the nitrogen-nitrogen bond. azo compounds. cyanides.3diphenylcyclobut-2-enyl cyanide (4077): Br Ph Ph Br DMSO-CH3CN NaCN Ph Ph CN In the above reaction. the freshly formed olefins tend to isomerize. 3 hrs CHBr2 O Br H3C CO2C2H5 55% CHBr2 3-Alkylthio. Nitrogen Elimination Elemental nitrogen can be eliminated from a number of compounds by heating in DMSO in the presence or absence of bases. Thus. such as carbonates. the treatment of 1.: Cl Br DMSO. both the -elimination and displacement (substitution) reactions take place. and carbanions can be generated which can decompose in various ways (4180)(6163). sometimes undesirable reactions take place after dehydrohalogenations.3-dibromo-1.3-Dibromo-6-dibromomethyl-5-carbethoxy-2. such as hydrazones. e. KOH (H 3C)3CHC CHCl 130-160oC (H 3C)3C CH 91% e) Weak bases in dehydrohalogenations Although potassium t-butoxide in DMSO is an extremely strong and reactive base-solvent system.

: R NH2 + NaNO2 + H+ DMSO -N2. the so-called Wolff-Kishner reduction in DMSO. DMSO O R" + R" 100-110 oC R' N H N2 + CO Thermal decomposition of two azobisamidines and their conjugate acids has been studied in DMSO (4748). H2O R CH2 + OS(CH3)2 R CH3 C S H2 CH 3 R CHO + CH3SCH3 Benzenediazonium tetrafluoroborate in DMSO decomposes instantaneously with evolution of nitrogen upon addition of a DMSO solution of choline or tetramethylammonium hydroxide (5124): N2+ + X OH-. e. DMSO Ph2C NNH2 25oC PH2CH2 + N2 The above reaction.g. KOH. Rate coefficients are reported for the reaction of diazodiphenylmethane with benzoic acid and its orthosubstituted derivatives in DMSO and other solvents (2765): Ph2CN2 + RCO2H DMSO 30 C o RCO2CHPh2 + N2 Thermal decomposition of several diazirines has also been investigated in DMSO (4906)(5635). azides. In the case of benzylamine. The rate of the Wolff-Kishner reaction of benzophenone hydrazone in mixtures of butyl carbinol and DMSO in the range of 100-190°C increases as the concentration of DMSO is increased. DMSO 20oC X +N2 58 . can be run even at room temperature.g. Ph Cl N N DMSO 60-90oC N2 + PhClC Cl diazirine NN Ph Cl Ph Sodium azide in DMSO reacts with -bromophenylacetonitrile to yield benzonitrile (10077): Ph Br CN + N3 DMSO PhCN + N2 + CN90% Diazonium salts can be prepared in DMSO by diazotizing primary amines with sodium nitrite. but this effect passes through a maximum. Addition of hydrazones of aldehydes and ketones to a solution of potassium t-butoxide in DMSO produces an immediate evolution of nitrogen and formation of the corresponding hydracarbons in 60-90% yields. diazonium salts and others. e. The reaction of the benzophenone hydrazone is typical (495). The thermal decomposition of norbornan-2-one and norborn-5-en-2-one tosylhydrazone sodium salts has been studied over the ° temperature range 100-150 C in DMSO and two other solvents. First order kinetics have been observed in all cases (8955): N-N-OTs DMSO 117. t-BuOK.5oC + N2 + OTs- Treatment of 1-acylsemicarbazides in DMSO with air or oxygen gives rise to carboxamides in good yields (3721): O R' N H H N O H N O2. benzaldehydes can be prepared in good yields (167). The maxima tend to drift toward higher DMSO concentrations as the temperature is lowered (377).diazomethane derivatives.

Sulfonate Elimination Various bases have been used in the reaction of sulfonate esters of primary and secondary alcohols to give alkenes. cyclopropanes and olefins are formed (396)(2842): R Ph CH2SOCH3 + H2CSOCH3 DMSO Ph o 60-70 C. DMSO PhC=CHPh PhCHCHPh 119oC OH OH Ph OH NH2 PhCCH2Ph + PhSOH O 3-Phenylindole is obtained from -hydroxysulfoxide on treatment of the latter with dimsyl ion in DMSO (5300): SOCH3 + H2CSOCH3 Ph DMSO N H 7. Sulfenate Elimination The t-butoxide ion or dimsyl ion in DMSO has been used to eliminate sulfenates from sulfoxides to produce olefins in moderate to high yields (501)(203)(672).3.6 Dimethylenebicyclo[2. and others. the Dewar o-xylylene. including DMSO (9423). all easily prepared. The dediazotization of aromatic diazonium ions has been reviewed in various solvents. elimination reactions involving sulfonate esters have been achieved without the presence of a base by the action of heat alone. sodium methoxide. When a number of 3-phenyl-2-alkylpropyl sulfoxides is allowed to react in DMSO with a large excess of dimsyl sodium. as the result of displacement reactions in the latter case (491). potassium ethoxide. Some of these bases are potassium t-butoxide. DMSO 80oC H3C D OTs D CH3 The tosylate of cyclohexanol-2. Esters of normal primary alcohols and of cyclohexylcarbinol give only 20-25% alkenes and 6070% ethers.When p-nitrobenzenediazonium tetrafluoroborate is decomposed in the presence of DMSO-benzene or DMSOnitrobenzene systems. 48 hrs.0]hexene-2. + R CH3SO- When isomeric 2-phenylsulfinyl-1.6 (3482): t-BuOK. a) Potassium t-butoxide in sulfonate elimination Most -eliminations involving sulfonate esters seem to have been investigated with potassium t-butoxide as the base. Sulfonate esters of cyclic and secondary acyclic alcohols react rapidly with potassium t-butoxide in DMSO at 20-25°C to give about 80% yields of alkenes and no appreciable quantities of ethers. Treatment of the tosylate of (+)-(S)-3-methyl-7-deutero-octen-4-ol-7 with potassium t-butoxide in DMSO yields (+)-(S)-cis. can be obtained by reacting the corresponding ditosylate with potassium t-butoxide in DMSO (3827): 59 .6-d4 on treatment with potassium t-butoxide gives cyclohexene-1.6. deoxybenzoin is formed (4776): O S Ph pyridine.2. In a few cases. Mesylate and tosylate derivatives of cholesterol. undergo facile reactions in DMSO at room temperature to afford excellent yields of dienic materials (965).trans-3methyl-7-deuterooctadiene-4. phenoxides. the respective biphenyl derivatives are obtained in good yields (5642). 6.2. DMSO D D room temperature D D 36% 5.3-d3 (3584) : H D D OTs D t-BuOK.2-diphenyl-l-ethanols are pyrolyzed in DMSO in the presence of trace quantities of pyridine.

OMs 65% total b) Sodium methoxide in sulfonate elimination Benzenesulfonates of typical primary and secondary alcohols react rapidly at room temperature with sodium methoxide in DMSO to give high yields of alkenes and/or alkyl methyl ethers. potassium ethoxide. is introduced by treatment of a tosylate with sodium methoxide in refluxing methanol containing 10% DMSO (6947). 8.3-dimethoxy-2-propanol by means of sodium methoxide in DMSO in good yield with cis/trans ratio of 2. d) Sulfonate elimination without a base DMSO has been found to be an excellent non-reacting solvent for the decomposition of (-)-menthyl. -cholestanyl.3 -Dimethoxypropene can be obtained from p-toluenesulfonate of 1.0]nonane with potassium 1-butoxide in DMSO (9727). it is rapidly converted to trans-bicvclo[5. ° The reaction of trans-2-methylcyclooctyl tosylate with potassium t-butoxide in DMSO for 30 min at 25 C yields cis-3-methylcyclooctene. at 160-190 C for several hours in DMSO give endocyclic olefins. A group of tertiary ° alcohols.0]non-8-ene is obtained by treatment of 8methanesulfonyloxybicyclo[5. such as 2-alkylcycloalkanes. The effect of base strength upon orientation in base prompted elimination reactions has been studied. DMSO room temp. the ether-alkene ratio is higher in reactions with sodium methoxide than with potassium t-butoxide.0]non-1 (9)-ene and bicyclo[5. The basicity of the nucleophile does not appear to significantly affect the trans:cis ratio (8372).2.OTs t-BuOK. a precursor of dl-juvabione. OTs 40% CH2 CH2 When 4. cyclohexyl and 2octyl aryl-sulfonates to the corresponding olefins. potassium phenoxide.2. ° The elimination reactions of some secondary acyclic and medium sized ring cyclic alcohol tosylates carried out in DMSO at 50 C and ° 90-95 C show that olefins are formed. including potassium t-butoxide in DMSO (4524). an olefin forming elimination takes place and an overwhelming Saytzeff orientation is observed. potassium 4methoxyphenoxide. Except for cyclohexyl benzenesulfonate.2. in different base-solvent systems. 4%. Certain diols when heated in DMSO lead to cyclic ethers.1. Evidently little of the displacement reaction goes on (3875): TsO CH2OCH3 CH2OCH3 NaOCH3. DMSO 71% CH2OCH3 CHOCH3 A double bond in a cyclic system. When 2-butyl and 2-pentyl halides or tosylates are treated with tetraethylammonium fluoride in acetonitrile.0]oct-3-ene (4039): OBs t-BuOK. 1 -methylcyclopentanol gives only 1 -methylcyclopentene (394): 60 . The sulfonates are heated at 89-91°C for 6 hours without a base (408).0] octane p-bromobenzene-sulfonate is treated with potassium t-butoxide in DMSO. the ratio of the isomers is 2:1. With t-butenol as the solvent. c) Other bases in sulfonate elimination When cyclohexyl tosylate is reacted with potassium t-butylmercaptide in DMSO. DMSO o H 20-25 C.1:1.hydroxy-trans-bicyclo[5.1. as the major products. potassium 4-nitrophenoxide and potassium 2nitrophenoxide. PhCH2CH(OTs)CH3. Water Elimination-dehydration Many alcohols can be dehydrated in DMSO to olefins. and cis-1 -methylcyclooctene. This indicates that the displacement reactions are favored over elimination reactions with sodium methoxide in most cases (580). The results are completely consistent with a correlation between orientation and base strength (882). Thus. 1 -alkylcycloalkenes. An approximately equimolar mixture of bicyclo[5. 30 min. 15 hrs. However potassium t-butoxide reacts much more ranidly than the mercaptide (496). t-BuOK. cyclohexene is the major product. DMSO 20oC. 1. 93%. especially with secondary alcohol tosylates. These results are compared with results of the elimination in other base-solvent systems. 2-Butyl p-toluenesulfonate is reacted with the following bases in DMSO: potassium t-butoxide. The trans:cis olefin ratios have been determined for the elimination reactions of 1-benzylethyl tosylate.

80% OH Heating of 2. cyclic ethers result instead of the expected dienes (395).3. the corresponding heterocycles. H3C H3C H2C H3C CH3 CH2 42% CH3 CH3 O In the dehydration of 1. dehydration produces olefins in 70-85% yields (405).g. When 1.4-diol in a sublimation apparatus in DMSO gives the tetrahydrofuran (4934) : CH3 CH3 CH2OH C C CH2OH DMSO 160oC 16 hrs. o H2 C (nH2C) O n=2.4-butanediol. tetrahydropyran (47%).3-tetramethylbutane-1.6-hexanediol are heated. and oxepane (24%) are formed (394): HOCH 2(CH2)nCH2OH DMSO 190 C 14-24 hrs.5-pentanediol and 1.2-Dimethyl-3(2H)-furanone can be obtained by dehydrating the corresponding 5-hydroxy compound on heating in DMSO (4755): O DMSO HO O O O 2-Methoxy-4.5-dimethylphenylbenzylcarbinol in DMSO (9605): 61 .or tert-benzylic alcohols or tert-aliphatic alcohols are heated in DMSO at 160-185° C for 9-16 hours.5-dimethylstilbene is obtained by heating 2-methoxy-4.CH3 OH DMSO 160oC 6 hours CH3 88% When certain diols are heated in DMSO. tetrahydrofuran (70%). e. 4 2. a cyclic transition state with DMSO has been postulated (395)(6098): O H O S CH 3 CH 3 O H3C CH 3 H When sec. o PhCH=CHCH3 79% 2.4-diols.5 hrs.2. using 2 moles of alcohol per mole of DMSO. 3.4-Di(2-hydroxy-2-propyl)cyclohexene can be selectively dehydrated to 2-(2-propenyl)-4-(2-hydroxy-2-propyl)1-cyclohexene in DMSO (4775): C H2 24-70% DMSO 190oC HO OH 1. 1. OH PhCHCH2CH3 DMSO 160 C 16 hrs.

DMSO R 140-160oC OH 18-40 min Dehydration of 4-(1 -hydroxyethyl) biphenyl in DMSO in e presence of a small amount of potassium hydrogen sulfate and hydroquinone gives p-phenyl-styrene (7867): KHSO4. 1. When propargyloxyethanol is cyclized in DMSO in the presence of sodium hydroxide. Thus. the lactonization of a hydrolyzed terpolymer can be carried out by reacting the polymer in the presence of a very small quantity of concentrated sulfuric acid in DMSO (2265): H3C H2SO4.OCH3 OH CH2Ph H3C CH3 OCH3 DMSO 150oC H3C 9. DMSO OH 190C several hours 82% Dehydration of a diol can also be accomplished by using the triethylamine-sulfur trioxide complex in DMSO (7080): OH OH Et3N / SO3. the dehydration is achieved in DMSO in the presence of an inorganic acid. 2-vinyl -1.5 hrs CH3 Ph 80% One of the key features of the stereoselective and regioselective total synthesis of two naturally occurring fungitoxic hydroquinones (±)zonarol and (±)-isozonarol is the dehydration of a tertiary alcohol to an alkene without rearrangement (9780): HO DMSO H 155oC. 100 hrs HO HO CH2OH HO2C CO2H O O Potassium hydrogen sulfate in DMSO is an effective medium for elimination of water from some intermediate hydroxy derivatives in the preparation of various C19 analogs of retinoic acid (4235): R KHSO4. Included are also racemization reactions: the conversion of half a given quantity of an optically active compound into one enantiomer. 15 minutes O ISOMERIZATION REACTIONS These are base-catalyzed reactions that convert olefins and other unsaturated compounds into molecules with different atomic arrangement.4-dioxene are the major products (101): 62 . DMSO 15oC. Acetylene Isomerization The enhanced rate of base catalyzed isomerization in DMSO can be used to control the direction of a cyclization of acetylenes (600).3-dioxolane and 2-methyl-l. 16 hrs 77% H In some cases. DMSO H3C HO2CHO2C CO2H 65oC.

DMSO H R C C C(A)-R' 30oC 3-Phenylpropyne undergoes in DMSO a dimsyl ion-catalyzed isomerization with very little H-D exchange with the solvent (2987): PhH CC CH 2 D2CSOCD3. 3-alkoxy-l -phenylpropynes are isomerized in DMSO under the catalytic influence of potassium tert-butoxide to give 3-alkoxy-1 -phenylallenes (4258): Ph R t-BuOK . O N 77% Ph Ph 3. 20 min. DMSO CHCH3 CH 2 O N 20oC. when heated with catalytic amounts of potassium t-butoxide in DMSO. For example. 21 hrs. DMSO 100 C. Pure 2-alkynes are obtained upon heating 1-alkynes with sodamide in DMSO (6510): 2 NaNH2. 9-allyladenine is isomerized with potassium t-butoxide in DMSO to the propenyl compound which is then easily hydrolyzed to regenerate the amino group (941): N N N N t-BuOK . DMSO R CH3 RH2C CH o 65-70 C. Allyl Group Isomerization The isomerization of allyl ethers to propenyl ethers occurs 1000 times faster in DMSO than in dimethoxyethane and 10. This facile isomerization of allyl to easily hydrolyzed propenyl groups.enables the use of allyl groups as blocking agents (10043).H]-1. Diene. have been measured in aqueous DMSO containing tetramethylammonium hydroxide and give linear correlations with the acidity function for the medium (5864).3-cyclohexadiene (I) with potassium t-butoxide in DMSO yields a mixture of 79% 1-bromo-l. without affecting phenyloxazine group (8951): O O OCH CH R OCH R 2 t-BuOK . Triene Isomerization Unconjugated dienes can be converted to the conjugated isomers by treating them with a strong base in DMSO. Thus. 90-94% R=alkyl 2. (CD3)2SO P hHC C CH2 4-Alkoxy-4-alkyl-1 -t-butoxy-2. DMSO OC2H5 Ph C R P hHC OC2H5 R H O 40-67% The rates of base-catalyzed isomerization of a series of 1. is isomerized to allenic diethers (4257): t-BuOK . 26 hrs.3. DMSO R' R' C CCH2OtBu C CHOtBu RO RO 50-78% Similarly.3-cyclohexadiene (II) and 21 % of I.000 times faster than in dimethoxyethane-t-butanol mixtures (481).HC CCH2OCH2CH2OH DMSO NaOH O H2C C CHOCH2CH2OH O O O Treatment of an acetylenic compound with potassium tert-butoxide in DMSO gives the corresponding allenic compounds (2239): HC COCH2CH2OH R C C CH(A)-R' t-BuOK.prop-1-yne and [3.3.butyne. 63 .3-triphenylprop1-yne. the treatment of 2bromo-1. o N N N N 82% The allyl group of a glycoside can be isomerized to the prop-1 -enyl group by the action of potassium t-butoxide in DMSO.3-triphenyl.

DMSO N OCH3 2-Methyl-1 -(tetramethylcyclopropylidene)propene is isomerized with potassium t-butoxide in DMSO to give 2methyl-3(tetramethylcyclopropylidene)propane (4126): CH3 CH3 H3C t-BuOK .6 -3- 4. DMSO room temp. several min. t-BuOK .7-octatrienes are isomerized to 2.3. Br Several unconjugated dienamines on treatment with potassium t-butoxide in DMSO produce the conjugated dienamine by a pivoting of the double bond around the carbon carrying the nitrogen atom (4018): N OCH3 t-BuOK . DMSO H3C CH3 CH3 C CH3 100oC . 18 hrs. DMSO 75oC.5 .4.g. 2methylpentene to 2-methylpentene-2 (579): H3C CH3 t-BuOK .5. in DMSO with potassium tert-butoxide as the base. THF or 1. Steroids have been isomerized with a base in DMSO (3272)(2323). However. 2hr.3. e. 64 4-6% . II.-hydroxy-vitamin D3 (10048). Thus. DMSO 25oC . 4.2dimethoxyethane. Olefin Isomerization The isomerizations of simple alkenes (e. CH3 H3C CH3 64% CH3 Unsaturated fatty acid esters containing conjugated double bonds are manufactured by isomerization from the esters with unconjugated double bonds by heating them with alkali metal alkoxides in DMSO (8906).7 -3 Sodium methoxide catalyzed deconjugation of cholesta-1.The difference in free energy between I and II appears to be the result of greater conjugation of bromine with cyclohexadiene system in 11 (596): Br I. 1.g. O HOH2C 4.6 hrs. 1-olefins can be converted to 2-olefins.7-trien-3-one is a key step in a reported route to 1. 19-hydroxyketones by treatment with sodium methoxide in DMSO (4311): HOH2C O NaOCH3 .4-6-trien-3-one in DMSO to cholesta-1.6-Octatrienes and 1. DMSO 110-190oC 0. 8 hrs.hexene-1) with potassium t-butoxide do not occur in tert-butanol.6-octatriene in 70-85% yields with hydroxide bases in DMSO (3379). pentene-1. H3CHC CHSHCH2CH(NH2)CO2H 60% -pinene by using potassium hydroxide and DMSO (480)(7229): KOH . DMSO H3CH2CHC H3CH2CH2C CH3 S-(2-propenyl)-L-cysteine is isomerized to cis-S-(1 -propenyl)-L-cysteine by reaction in potassium tert-butoxide and DMSO (1001): H2C CHCH2SCH2CH(NH2)CO2H -Pinene can be converted to t-BuOK .

e.-vanillylpropionitrile is racemized using sodium cyanide as the base and DMSO as the solvent to give 96-97% pure DL. In DMSO. a) Alcohols When optically pure tertiary alcohols with an asymmetric carbon atom are treated with a strong base in DMSO.Similarly.3% methylenecyclopropane with potassium t-butoxide and t-butanol in DMSO produces a 98% pure methylenecyclopropane (4262): t-BuOK .-thujine Isomerization of a mixture consisting of 17. the predominant steric course is racemization (1162)(2589). In solvents of high dissociating power which are not proton donors. b) Alkyl halides The reduction of optically active tertiary alkyl halides with sodium borohydride in DMSO proceeds with racemization presumably via an elimination mechanism (3519): CH3 CH3 H3C H3C C2H5 H3C C2H5 H3C DMSO H Cl 8 NaBH4 CH3 CH3 H3C H3C Racemic 2. DMSO.-thujene and 9% (+)-sabinine under the influence of potassium t-butoxide in DMSO (2998): t-BuOK .DMSO 50-60oC 70% 5.DMSO 90oC.7-dimethyloctane c) Amides. d) Esters The racemization and solvolysis of (+)-methyl 1 -cyano-2.-Acetamide.7-dimethyl-octane (-)-(R)-3-chloro-3. racemization is the dominant reaction (6287). the rate of racemization correlates well with the acidity function of the reaction system containing DMSO (944). Similarly.-vanillylpropionitrile (7772)(7984): H3CO H3C CN NH CH HO 3 O Optically active N-acylamino acids are racemized nearly quantitatively by heating with DMSO (8418).g. the base-catalyzed rate of hydrogen-deuterium exchange correlates well with the racemization rate (1501). amino acids D. 2 hrs. 2-diphenyl-cyclopropane carboxylate has been studied in DMSO and six other solvents. 65 .-acetamido. the carbanion (obtained with potassium t-butoxide) is long enough lived to become symmetrically solvated. (+)-sabinine isomerizes to an equilibrium mixture of 91 % (-). and electrophilic substitution gives a racemic product (1161). e) Ethers Potassium t-butylmercaptide in DMSO is a weaker kinetic base system than potassium t-butoxide in DMSO or than dimsyl sodium in DMSO in the racemization of optically pure (-)-1-methoxyphenylethane (496): H3CO H Ph CH 3 DMSO B- H3CO C CH 3 Ph DMSO BH H3CO Ph CH3 + BH Rate constants for racemization of (-)-4-biphenyl-methoxyphenylmethane in methanol-0-d-DMSO-d6 catalyzed by potassium methoxide have been measured (2007).4% 1 -methylcyclopropene and 81. A variety of active functional groups can be attached to the saturated asymmetric carbon atom. (+)-sabinine (-). Racemization In the racemization of saturated compounds by exchange of hydrogen at an asymmetric carbon.

f) Hydrocarbons The results of H-D exchange and racemization of (-)-9-deuterio-9-methyl-2-trimethylammonium fluorene iodide in t-butanol-DMSO catalyzed by tripropylamine are reported. Similarly. OTHER REACTIONS IN DMSO ADDITION REACTIONS These are additions of nucleophilic compounds to carbon-carbon double bonds. Exchange (69%) and racemization (69%) take place (5339): H(D) CH3 N(CH3)3I D-tetramisole or its 1 -tetramisole enantiomer is racemized in DMSO solution in the presence of a catalytically effective amount of potassium hydroxide (10315): N Ph N S g) Nitriles Racemization of 2-methyl-3-phenylpropionitrile in DMSO can proceed 1. a) Additions to acetylenes (carbon-carbon triple bonds) The DMSO anion (dimsyl sodium) adds to diphenyl acetylene to give a 95% yield of a cis-trans mixture of the expected unsaturated sulfoxide (203): Ph CH2SOCH3 Ph Ph PhC CPh + Na+CH2SOCH3 DMSO + room temp. the rate for racernization in 1.000 times faster than in tert-butanol in the presence of the same base (434)(944). In a number of cases the use of DMSO improves the rate of addition of nucleophiles to olefins.2-diphenylcyclopropylnitrile (1) has been studied in solvents containing various amounts of DMSO. The rate of addition of the glycine anion to acrylonitrile in an aqueous buffer is increased 200-fold by adding an equal amount of DMSO to the buffer (1233). The order of effectiveness of the solvents for this reaction is also the order of their hydrogen bonding strength (1591).000. carbon-nitrogen triple bonds and others. carbon-carbon triple bonds.6 x 10 times that observed in methanol (7282): Ph Ph CN H (-) -1 -OCH3 . the cyanoethylation of methanol using potassium methoxide catalysis in methanol-DMSO occurs at a rate greater than in several other aprotic solvents. the reaction consumes 2 moles of the DMSO anion with elimination of two methane sulfenate groups to give 2. DMSO P h Ph H CN (+) -1 h) Sulfones ° When the 2.5 mole % methanol-98. H Ph H CH2SOCH3 95% ° When the addition is conducted at 40 C. such as acrylonitrile. The base catalyzed racemization of 2. With sodium methoxide as the base and nitrile 1 as a substrate. The mechanism of base-catalyzed racemization of -acetamidonitriles bearing no enolizable -hydrogen has been studied in DMSO and found to proceed via elimination and readdition of the elements of HCN (2013).5 mol % 8 DMSO is 3.3-butadiene (203): PhC CPh + Na+CH2SOCH3 DMSO 40oC Ph CH2 Ph CH2 28% 66 .2-dimethyl-1-phenylsulfonylcyclopropane is heated in DMSO for 6 hours at 175 C the material is 88% racemized (2035): H3C H3C CO2CH3 SO2Ph C.3-diphenyl-1.

6 hrs H3C N SO2C2H5 H trans 84% H3C N H SO2C2H5 cis 16% b) Additions to olefins (carbon-carbon double bonds) Aliphatic conjugated dienes add the dimsyl ion in DMSO to give sulfoxides. These unsaturated sulfoxides isomerize spontaneously and eliminate methanesulfenate upon continued warming in the strongly basic medium to produce the overall effect of methylation (411): + H2CSOCH3 DMSO 55oC -elimination SOCH3 BH SOCH3 +B- + H3CSO50% Although the yields of the aliphatic dienes are 50% or less. affords 1. the yields using polynuclear aromatic compounds or some heterocyclic compounds. followed by hydrolysis. such as quinoline. 4 hrs. This may be explained on the basis that DMSO can stabilize the zwitterionic intermediate best (3660): H3CC CSO2C2H5 + NH DMSO room temp.2. 15 hr CO2CH3 CO2CH3 53% CO2CH3 The reaction of alkynes with sodium azide in DMSO.Ethyl phenylpropiolate reacts readily with dimethyloxosulfonium methylide to give 91 % of a stable ylide (217): PhC CO2C2H5 (H3C)2SOCH2 HCO2C2H5 PhC C SO(CH3)2 91% The addition of alkoxides to triple bonds in DMSO has been examined in structures where the intramolecular addition can occur(600)(101)(429). N 96% 67 . DMSO C N CH2CH2OH DMSO O N CH3 CH3 CH3 Dinitrophenylhydrazine reacts with dimethylacetylenedicarboxylate in DMSO-methanol to yield a 1:1 adduct which exists as an imineemamine tautomer (3387): CO2CH3 CO2CH3 CH2CO2CH3 DMSO P hNHN PhHNHNHC PhNHNH2 + room temp. . The rapid rearrangement of the triple bond to the allenic compound seems to precede the cyclization (600): N CH2CH2OH NaOH . The greatest amount of trans product (cis addition) is formed in DMSO. are high (202): CH3 + H2CSOCH3 N DMSO 70oC.3-triazoles (3456): RC CR' + NaN3 R R' C C DMSO N N N 11-54% DMSO has been one of the solvents studied in the reaction of 1 -propyl-sulfones and sulfoxides with ethylenimine.

4'-dimethoxystilbene with the dimsyl ion in DMSO leads to methyl diarylbutyl sulfoxides (7234): CH3 Ph + 2H2CSOCH3 DMSO CH3 Ph CH2CH2SOCH3 Kinetic rate measurements of the alkoxide catalyzed addition of methanol and ethanol to methyl esters of acrylic and methacrylic acid have been investigated in the mixed solvent alcohol-DMSO (3249).The dimsyl ion also adds to aryl conjugated olefins.2.or .and -unsaturated carboxylic acids can be carboxylated at the . the corresponding bromohydrins can be obtained after a short reaction time in high yields (705)(4026)(4817): Br H2O . OH 78% A variety of alkylaromatic compounds undergo nucleophilic addition to conjugated olefins (3384). DMSO RCHO + R'HC R CN CN R' 54-91% Alkyl esters of . The effectiveness of the solvents decreases in the following order. sulfolane. such as styrene or 1. using potassium t-butoxide as a catalyst. DMSO (3506): . DMSO X-PhCO(CH )2CHAr2 X-PhCOCH2Br + H2C Ar2 2 140oC 54% Phenacyl bromide in DMSO in the presence of the zinc-copper couple also adds to conjugated enynes and dienes (7536). DMSO.. Particularly when the reaction is performed in dipolar aprotic solvents. -unsaturated nitro compounds in DMSO to form 1. tetramethylurea (4339). HMPA. 68 . N-methyl-2-pyrrolidone. 15 min.position using sodium phenoxide in H2C H3C NaO2CH2C CO2CH3 CO2CH3 PhO.3-triazoles (4452): RPh NO2 + NaN3 DMSO room temp. 2-methylstilbene and 4. in DMSO to give the corresponding methyl 3arylpropyl sulfoxides in almost quantitative yield (423): Ph2C CH2 + H2CSOCH3 DMSO Ph2CCH2CH2SOCH3 25oC Ph2CHCH2CH2SOCH3 + H2CSOCH3 One stage sequential double methylation of the C=C bonds in stilbene. RPh N N H N 60% Phenacyl bromide and its derivatives in the presence of zinc or a zinc-copper couple undergo anti-Markownikow additions to terminal olefins (6627): Zn-Cu . DMSO + BrN o 20 C . 3 hrs CO2Na Sodium azide adds to . When olefins are treated with N-bromosuccinimide in DMSO containing a small quantity of water. 1-Alkenecarbonitriles react with aromatic or heteroaromatic aldehydes in DMSO under the catalytic influence of cyan oxonitriles (6172)(7582): O R" R" CN-. DMF.1-diphenylethylene. DMSO or or + CO2 CO2CH3 CO2CH3 H3C 25oC.

Thus. Diisocyanates. Thus. diisocyanates react in DMSO with active hydrogen compounds such as dihydrazides (450). or even with the hydroxyl groups of carbohydrates (cellulose) (443). 69 . DMSO is also used as an effective swelling agent for cellulosic rayon fibers. aldol condensation. 1-indanone and formaldehyde react rapidly in DMSO to yield 2. A number of synthetic polymers containing sugar residues.g. CONDENSATION REACTIONS These are mostly specific reactions (e. DMSO PhCN + NaN3 Ph 123-127oC. and they run at good rates in this solvent (392)(312)(1360). DMSO room temperature 5 min. such as benzonitrile. 3hrs NH2 CN + NH2 R CN NH2 DMSO 25oC. occurs readily in DMSO to give 5-phenyl tetrazole (550): NH4Cl. 7 hrs N N NH 87% R R N N NH2 NH2 nearly quantitative N The reaction of anthranilonitrile with sodium hydride in DMSO yields 4-amino-2-(2-aminophenyl)quinazoline (8576): R CN NaH .4'methylenedi(phenylisocyanate) in DMSO. Good results are often obtained either because of the greater solubility of generally insoluble reactants or because of enhanced reactivity of nucleophiles. to produce phthalo-bis-guanamines (8008): NH2 CN + CN 2H2N N H CN NH KOH. have been prepared by direct addition polymerization of the carbohydrate with diisocyanates. polyols (449). -trehalose (10123). such as 4. usually with the separation of water or some other simple molecule. Polyurethane filaments can then be spun from the reaction mixture (1880): N N H H n Dry DMSO is inert to alkyl or aryl isocyanates but it does react with isocyanates having electron withdrawing groups such as acyl (714) or sulfonyl (308)(391). DMSO 85oC. 3hr N H2N N N NH2 N N NH2 97% d) Additions to isocyanates The reactions of organic isocyanates and diisocyanates are catalyzed by DMSO.2-bis(4-isocyanatophenyl)propane. such as D-cellobiose (10116)(10439) and . The high reaction rates may be attributed to the high reactivity of the anionic catalyst in the DMSO medium (1099). a) Aldol-type condensations Alkyl aryl ketones react easily and at a high rate with paraformaldehyde in DMSO in the presence of base to yield hydroxymethyl compounds.c) Additions to nitriles (carbon-nitrogen triple bond) The reaction of sodium azide with nitriles. DMSO R 0oC.and p-nitrotoluene react similarly with paraformaldehyde in an aldol like addition in DMSO under the influence of a strong base to give hydroxymethyl compounds (1100). react with ethylene glycol in DMSO. O CH2OH CH2OH 70% Fluorene and o. 21hrs R= H orBr Phthalodinitriles react with dicyandiamide in DMSO in the presence of basic compounds. such as potassium hydroxide. In the last instance. Most of the ordinary reactions of carbonyl compounds can be accomplished in DMSO.2-bis(hydroxymethyl)-1-indanone: OCN + HOCH2CH2OH NCO a ketone DMSO OH2CH2CO O O O KOH. Mannich reaction) in which two or more molecules combine. such as bis(4-isocyanatophenyl)methane or 2.

+ DMSO This condensation reaction has found a fairly wide application in the synthesis of useful intermediates.4-hexadione with paraformaldehyde in DMSO in the presence of potassium hydroxide gives 1.2. Thus. two optically active diastereomeric ketols result (5613): H CHO ONa + H3C Br O Ph DMSO CHO Ph OC 79% CH3 O DMSO OC CH3 OH Ph O The reaction of 1-hydroxy-2.5-tetramethyl-3.2 equivalents of dimsyl ion to give the -keto sulfoxides (9196): O O S CH3 CO2C2H5 + OH 2H2CSOCH3 DMSO OH 92% A number of -keto sulfoxides have been prepared by condensing the dimsyl ion with substituted phenyl or naphthyl esters (9249)(9402). a number of benzoic acid esters can be reacted with the dimsyl ion in DMSO to give the corresponding -keto sulfoxides (9150): OCH3 H3CO O DMSO O H3CO CO2CH3+ 2H2CSOCH3 OCH3 S 20-25oC.6-dihydroxy-2.Racemic 2-(o-formylphenoxy)propiophenone can be prepared in 79% yield from equivalent amounts of a sodium salt of salicylaldehyde and 2-bromopropiophenone in DMSO.4-hexadione (6028): O O O O KOH. ethyl 1-hydroxy-2-naphthoate reacts with the dimsyl ion to give 3'-hydroxy-2-(methylsulfinyl)-2'-acetonaphthone (9244): OH OH O O CO2C2H5 + 2H2CSOCH3 S 64% CH3 70 .5 hr H3C OCH3 70% H3CO Ethyl salicylate reacts with 3. Thus. DMSO 35 C. DMSO 29oC CO2CH3 O The reaction of pentafIuoracetophenone with methyl benzoate in the presence of sodium hydride in DMSO is the best way to the diketone (3376): C6F6COCH3 NaH. 24 hrs HO OH 85% 2-Carbomethoxycyclohexanone condenses with 3-pent-2-one in DMSO in the presence of sodium methoxide to give methyl 4-methyl-1 (9)-octal-2-one-1O-carboxylate (4048): H3CO2C + O O NaOCH3. 24hrs o C6F6COCH2 P hCO2R C6F6COCH2COPh 60% b) Ester condensation The esters of carboxylic acids react with the dimsyl ion in DMSO to yield -keto sulfoxides (639)(1651): O RCO2R' + 2H2CSOCH3 RCOCHSOCH3 R H SOCH3 + R'O.2. 0.5-trimethyl-3.5. When the reaction product is kept in DMSO in the presence of quinine. DMSO + 2HCHO 20oC.

O c) Dieckmann condensation-cyclization The Dieckmann condensation of dimethyl-l -methylcyclohexane 1. 1/2 hr. DM SO 25oC R 48-92% O OH CHR" R' Cyclohexanediones-1. -unsaturated carboxylic acid ester with a ketone in the CH3 O H2C=CHCO 2CH 3 + CH3COC 2H5 50oC.2-trichloroethyl esters of -substituted -keto acids react stereospecifically at the ester carbonyl with aldehydes to give aldols in good yields (8833): O C R CH R' + OHCR" CO2CH3CCl3 Zn.Ethyl isovalerate gives methyl sulfinyl methyl isobutyl ketone (9825): DMSO (H3C)2CHCH2CO2C2H5 + H2CSOCH3 0oC 1/2-1 hr. Symmetrical -diketones are readily prepared by reacting methyl esters with methyl ketones in DMSO with sodium hydride as the base (193) : RCOCH3 + RCO2CH3 + 2NaH DMSO O O CR CH2CR 75-83% -carbon to the The yield is increased from 36% to 83% by using sodium hydride in DMSO instead of sodium methoxide in toluene. DMSO C2H5O2C CO2C2H5 CH2 60% O CO2C2H5 71! .3 are prepared in good selectivity by reacting an presence of a strong base in DMSO (8717): NaOCH 3 .2. In the presence of zinc-DMSO. CH3 68% Re -ketopimelate with an excess of methylenetriphenylphosphorane in DMSO provides for the introduction of an exocyclic methylene group and subsequent Dieckmann condensation to the carbethoxycyclohexanone (6648): O +Ph3PCH2. O O (H3C)2CHCH2CCH2SCH3 The preparation and synthetic applications of -keto-suIfoxides have been reviewed (4820)(8529).2-diacetate with sodium hydride in DMSO furnishes a crystalline keto ester (6593): CO2CH3 O CO2CH3 CO2CH3 CH3 NaH. 2. DM SO 85oC 4 hrs.

8-diazobicyclo[5.cnethoxypropionate (II) and methyl nitroacrylate (III) by Michael addition (664): H3COCH2 Br I CHCO2CH3 + NaNO2 phloroglucinol. - R CH3 e) Michael condensation The reaction of methyl -bromo.-methoxypropionate (I) with sodium nitrite in DMSO in the presence of phloroglucinol gives dimethyl -methoxymethyl.nitro . The Mannich reaction product is most likely formed.. The "Mannich reagent". but it loses piperidine hydrochloride in the highly polar reaction medium. DMSO H3COCH2 CHCO2CH3 NO2 II CO2CH3 CH2 C O2N III CO2CH3 + II H3COCH2 C NO2 IV H2 C CHCO2CH3 NO2 -MeOH R' CH3 3 hours Double Michael reaction of 3-methyl-4-methylene-cyclohex-2-enone with dimethyl 3-oxoglutarate in DMSO in the presence of potassium fluoride as a catalyst gives a mixture of the stereomeric diketodiesters (9746): O CO2CH3 KF. DM SO CHCO2CH2CH2OH 55-60oC 2 days CH2 CO2CH3 O OH + H2C Michael addition of carbazole to 2-hydroxyethyl acrylate in DMSO in the presence of 1.0]-7undecene (DBU) takes place under mild conditions (10091): + H2C=CHCO 2CH 2CH 2OH N H DBU.d) Mannich reaction A -keto carboxylic acid reacts with formaldehyde-piperidine hydrochloride in DMSO to give the corresponding excellent yield (6463)(8888): ! methylene ketone in O O O DM SO + NH2Cl 20oC 2 hrs. reacts with enol borinates in DMSO-THF to provide excellent yields of dimethylamino ketones (6671): O CH3 (R)2BO R DM SO-THF CH3 + N IR' N 80-100% Room temp. '-dinitrogluturate (IV). dimethyl (methylene)ammonium iodide. which is formed from methyl . DMSO room temp.4. + HCHO + O CO2H O O CH2 N HCl CH2 65% The first step in the reaction is probably decarboxylation. 48 hours N CH 2CH 2CO 2CH 2CH 2OH Michael-type polyaddition of dithiols to divinylsulfoxide in DMSO leads to the formation of poly(sulfinylethylene-thioalkene (or arylene)thioethylene)s (10443): 72! .

yield an intermediate organozinc compound. Thus. DM SO H2C CH-SO-CH=CH2 + HSRSH 60o 12hrs.! Et3N. 100-150oC. DMSO OCH 2CN room temp. DMSO 95oC 1 hr. DMSO DMSO Ph3P-CHR R2C=CHR base As mentioned above.5-bis(triphenylphosphoniomethyl)naphthalene dibromide in DMSO gives 1. the Wittig reaction converts carbonyl compounds to olefins. the reaction of formaldehyde and the phosphorane derived from 1 .2-di-(cyanomethoxy) benzene with dimsyl ion (sodamide + DMSO) in DMSO produces 3-amino-4-cyano-2H-1. DMSO + IR' R R = CF3. an organolithium compound (4110). 3 hours NH2 92% O h) Ullmann-type condensations lodofluoroalkanes react with aryl iodides in DMSO in the presence of copper to give arylfluoroalkanes (5185) (7293): I Cu. R 45-70% R' i) Wittig reaction The reaction of a tertiary phosphine (usually triphenylphosphine) with an alkyl halide to yield a phosphonium salt can be done in DMSO (4669). Subsequent reactions of these ylides with aldehydes. can be cyclized directly to -enamino nitriles in very high yields (477)(6163): CN OTs OTs + NaCN DMSO 95oC 1 hr. the C-H bonds are sufficiently acidic (5551) for the hydrogen to be removed by a strong base in DMSO.5-divinylnaphthalene (7641): 73! .4-Dinitriles.R2CO. sodium hydride or the dimsyl ion (8360). OH R 30-66% NH2 92% The cyclization of 1. etc. DMSO also seems to be a good solvent for these salts.Hydroxynitriles are then prepared g) Thorpe-Ziegler condensation 1.5benzodioxepin (8690)(9145): CN OCH 2CN O H2CSOCH 3. the so-called Wittig reagent. e. from this intermediate and aliphatic aldehydes and ketones (4767): R DMSO-THF R' C Br C+Zn R' R C ZnBr "R CN O R'" C R'" "R C C CN R' . The overall reaction can be written as follows (49)(240)(5551): Ph3P + RCH2X DMSO Ph3P + CH2RX- + . [CH2CH2-SO-CH2CH2-S-R-S] n f) Reformatsky reaction Bromonitriles. when treated with zinc in DMSO-THF. which can be prepared from dihalides or ditosylates and sodium cyanide in DMSO. CN CN NaH. In these phosphonium salts. ketones or hemiacetals in DMSO offer a useful synthesis for olefins. n-C3F7. to produce a phosphorus ylide (a phosphorane).g.

is a solvent and not a reactant. Verbinone with methylidenetriphosphorane in DMSO yields methylenedihydroterpine (7476): O n-BuLi. lead tetraacetate oxidation.CH 2PPh3Br CH 2SOCH3. DMSO + Ph3P=CH2 + Ph3PCH3IDMSO reflux overnight CH 2 Lactols (hemiacetals) can also be reacted with a Wittig reagent (7691). dehydrogenation. 1 hr. DMSO room temperature 2. periodic acid oxidations.g. Many different reactions using oxygen have been conducted in DMSO. a) Autoxidation The base-catalyzed oxidation of a number of compounds by oxygen in DMSO-t-butanol mixtures has been studied extensively. sulfur dioxide oxidations). i. manganese dioxide oxidations. it gets neither reduced nor oxidized. with a few exceptions. hypohalite reactions. silver compound oxidations.5 hours CH 2PPh3Br - + ! CH=PPh 3 DMSO + HCHO room temperature overnight 64% CH=PPh 3 CH=CH 2 CH=CH 2 Ketones react with phosphoranes in a way similar to aldehydes. 20 min. electrooxidation. a number of hydrocarbons can be oxidized easily. Ketones in DMSO-potassium t-butoxide are oxidized to semidiones (1787): 74! . DMSO in these reactions. Formation of the carbanion of the substrate usually precedes the oxidation. triphenylmethane reacts with oxygen in the above system to form triphenylcarbinol (479): DM SO-t-BuOH-t-BuOK room temp. Ph3CH + O2 Ph3COH 96% Aniline under the above conditions gives azobenzene (469): PhNH2 + O2 DM SO-t-BuOH-t-BuOK PhN=NPh room temp. The rate of carbanion formation and oxidation increases as the DMSO content is increased (728). Thus. superoxide and peroxide oxidations and others not discussed here (e. Treatment of a lactol with a Wittig reagent derived from 5triphenylphosphovalerate ion in DMSO gives the corresponding hydroxy acid (7729): OH O + Ph3P=CH(CH 2)3CO 2H DMSO R R OH CH 2CH (CH2)3CO 2H It has also been found that aromatic and aliphatic esters can be directly converted to the corresponding isopropenyl compounds by reaction with methylenetriphenylphosphorane in DMSO (10078): O R C OR' + 4PH3P=CHR" +3Na+CH2-SOCH3 DMSO R CHR" C CH2R" OXIDATION REACTIONS These are reactions in which oxygen combines chemically with another substance or reactions in which electrons are transferred from one substance to another. such as autoxidation (also chemiluminescence).e. In the solution DMSO-t-butanol-potassium t-butoxide.

! H O + O2 R R H O t-BuOK. dimers or acidic products can be formed (568).3-disubstituted carboxylates in DMSO gives good yields of the 2-oxo esters (3662): R R' C R CN CHCO2C2H5+ O2 DMSO. T-BuOK R R'C R O C CHCO2C2H5 The system cobalt (II) and/or (III) acetylacetonate-t-butyl hydroperoxide has been used to initiate autoxidation of polyvinyl alcohol) in DMSO (8043). 9. presumably via the corresponding nitrobenzaldehydes (4812): CH3 + O2 NO2 OH KOH.2. it is possible to oxidize various substituted methanes. such as .and 3-arylpropenes has been induced with the DMSO-t-butanol system containing potassium t-butoxide. DMSO R' R C R" OH 1. The autoxidation of safrole gives piperonylic acid.5. the autoxidation of o. -diphenyl-2-pyridenemethane. Without DMSO. 75! . DM SO O2N NO2 The above dimers can be further oxidized to ketones.6-Dibenzanthracene and several other aromatic hydrocarbons are oxidized to the corresponding quinone derivatives in basic DMSO (5587). Autoxidation of 1 -methyl-2-isopropyl-5-nitroimidozole in DMSO with air or oxygen in the presence of a base gives 2-(2-hydroxy-2propyl)-1-methyl-5-nitroimidazole (8867): CH3 CH3 C N CH3 KOR. The autoxidation of 1.10-Dihydroanthracene can be oxidized to anthraquinone with oxygen in DMSO containing an inorganic base. or dehydrated to nitrostilbenes (4812). no oxidation takes place (1140): O + O2 O DM SO-t-BuOH-t-BuOK O O 42% CO2H In the presence of alkali metal hydroxides.2-di(nitrophenyl)ethanol. DM SO + O2 NO2 CH3 N N CH3 C N OH CH3 NO2 Base catalyzed autoxidation of ethyl 2-cyano 3. DM SO . When nitrotoluenes are oxidized in DMSO-potassium t-butoxide. Thus. such as sodium hydroxide (2940).and p-nitrotoluene in DMSO under basic conditions result in the formation of 1. t-BuOH. O Some ketones can also be oxidized to the carboxy compounds (9707). to the corresponding alcohols using air or oxygen and DMSO as the sole solvent (6971): R R' C R" H + O2 NaOH.

Chemiluminescence reactions can be classified as special autoxidation reactions that produce light emissions. With excess cyanide. The reaction sequence can be represented as follows (3241): O DM SO + 2NaOH O NN - NH NH + O2 DM SO NH2 O H2N O O O OO2 O - NN + N2 + light NH2 O NH2 O Some derivatives of luminol. in the presence of oxygen. DMSO + O2 O + KCN N + CH 3Cl- N CH 3 + HOCN + light N CH 3 The chemiluminescence emission spectra of two efficient chemiluminescent linear hydrazides in DMSO with potassium t-butoxide and oxygen suggest that the corresponding acid anion is the light emitter (5116): 76! . e. are more efficient in chemiluminescence in DMSO solution than luminol itself (1668). the red N-methyl-9-cyanoacridanide ion is produced which. an oxidation reaction produces considerable bright blue-green light. DM SO N O CCH3 OOH CH3 base. DMSO ! N H CCH3 O + light When DMSO.b) Chemiluminescence Chemiluminescence reactions are very similar to autoxidation. potassium t-butoxide or granular potassium hydroxide (2140)(2218): CH3 CH3 CH3 N H + O2 KOH. Both these reactions require oxygen and the presence of a strong base.g. it has also been observed with chemiluminescence reactions that the emission periods have been increased and the light intensities enhanced in DMSO containing a base (1025). A bright green light is observed on the treatment of a solution of 2. As the basicity of alkoxides and hydroxides is enormously enhanced in DMSO over the value of hydroxylic solvents. luminol. containing methoxyl groups. water and caustic solution are shaken in the presence of oxygen from air. produces N-methylacridone and potassium cyanate with light emissions (3653): CN DMSO-H2O KCN.3-dimethylindoie and its hydroperoxide in DMSO with a base. The reaction of potassium cyanide with N-methylacridinium chloride in 90% DMSO-10% water produces Nmethyl-90-cyanoacridan.

DMSO R O CNNH t-BuOK. oxidation (i.2-dihydronaphthalene.5-(10)-oestratrien-6-ones (5912): + O2 O KOAc. DMSO Ph HO + O2 90-100oC Ph 97% Ph Ph 1 hour O d) Dehydrogenation In the dehydrogenation reaction.7% 12. DMSO 100-120oC OH 4 hours O 15-48% The liquid phase oxidation of s-butanol with oxygen under pressure has been examined in various solvents using vanadium pentoxide° molybdenum trioxide catalyst While no reaction occurs in water. Thus.3. DMSO R CN=N - RC. in waterDMSO mixture in the presence of a catalyst to give acetaldehyde. naphthalene. DMSO can be used as a catalyst component in the oxidation of olefins. e. Several platenoid metal catalysts in DMSO promote dehydration.g.6% The oxidation of benzoin by cupric sulfate and oxygen in DMSO occurs to give a high yield of benzil (945): O O CuSO4.g.(DMSO)4.and -2. such as ethylene. and p-mentha-1. ° Terpenes can be oxidized with dry air in DMSO. or Fe(ClO4)..dienes at 100 C give p-methylacetophenone (9874). and cyclohexane. propylene. e.g. DMSO room temp.1 ]-heptane) (9707): H O-. e. C6H5CHO + C 6H5CO2H 48.+ light c) Other oxidations with oxygen Carbonyl compounds can be manufactured by oxidation of olefins. DMSO R O O C-N-HNN 2 O O2. the removal of hydrogen) can take place without the presence of oxygen. benzene.2.8% of s-butanol to methyl ethyl ketone with a selectivity of 89% (9434). (9412). DMSO R2C=O + H2 Dihydroarenes.4-trimethylbicyclo [2. In neutral solution.4(8). The dehydrogenation can be the main reaction when DMSO is used as the solvent instead of -methylnaphthalene (8838): R2CHOH RuCl 2(PPh3)3. or chlorobenzene. the oxidation in DMSO at 125 C for 13 hours converts 10. benzyl alcohols can be oxidized by oxygen in the presence of ultraviolet light to give the corresponding aldehydes (737)(1118): C6H5CH2OH + O2 UV. followed by dehydration with fenchone (2-oxo-1.-(19)-norsteroids react with oxygen in DMSO to afford 1. acetic acid. acetone. styrene.4(8). disproportionation and dehydrogenation of diarylcarbinols (10422).O R CNHNN 2 ! t-BuOK. -longipinene is oxidized at 125-135 C to longiverbone as the major product ° (9871). can be converted into the corresponding aromatic compounds. 1. by deprotonation with potassium fencholate. propanol. DMSO + O 90o OH 95% + H 77! . 4 3-Oxo. acetophenone and others (5800).e.3. DMSO can be a coordinate in complexes such as Cu(ClO4)2(DMSO)4.

/0( 134(5678*+. DMSO acts as a solvent and not as a reactant (7609): R R CH-OH R Na2Cr2O7.000): OCH 3 OCH 3 O OCH 3 I2. DMSO R-C-HN 2 25-55oC R C X N N 3-haloazirine./0( %"# C'&$& 0 ( %"# Oxidation of aminonaphth[2. H2SO4 R C=O 80-90% e) Hypohalite oxidations Halogenations with sodium hypohalites of alkyl .6-tetraphenyl-2-pyridone with lead tetraacetate in DMSO gives the corresponding 5. H2SO4. Oxidation of 1 -amino-3.-#)*+. indicating that DMSO is an efficient trap for N-nitrenes (4987): 12 12 12 134(567 8*+.+<=. 60% Oxidative cyclization of trifluoroacetamidine with hypochlorite and chloride ion in aqueous DMSO gives the corresponding diazirine (8108): &% !"#$#$%& ' #!" $(#)*+. DMSO. Polysaccharides oxidized by lead tetraacetate contain free aldehyde groups. DMSO O OCH 3 OCH 3 OCH 3 O O A solution of sodium dichromate and sulfuric acid in DMSO oxidizes primary alcohols to aldehydes and secondary alcohols to ketones./0( 9::. In these oxidations.5-dimethyl-Nsulfoximide. Oxidation follows the normal glycolcleavage pattern (615).4'-trimethoxyflavone in almost quantitative yield (10. such as dextran and amylose.5.>? ( @+2:A9 12 12 12 .or alkoxy-3-halodiazirines in practical yields (843): NH NaOX.3-b]azet-2(1 H) -one by lead tetraacetate in DMSO leads to 2-naphthoic acid (6243): 78! ./0( 12 & &B ( 12 & & ( 04#%"7' ( 12 12 12 12 & & Similarly.7. lead tetraacetate oxidation of N-aminolactams in the presence of DMSO gives the sulfoximides in good yields (5846): C'&$&%'+D+. aryl. This oxidation proceeds at a rate which is several times faster than the periodate oxidation in aqueous solution.4.or arylamidines and isoureas in DMSO solution afford the corresponding alkyl-. when heated with DMSO in the presence of a catalytic amount of iodine and concentrated sulfuric acid./0($% '( #) & & # f) Lead tetraacetate oxidations Polysaccharides.4'-Trimethoxyflavanone.7.! 5. can be oxidized by lead tetraacetate in DMSO if 15-20% of glacial acetic acid is added to prevent oxidation of the solvent. gives 5.

acetaldehyde.0]octa-1(6). DMSO Ph reflux 1 1/2 hr. n-propanol. i.( 134(5678*+. DMSO./0( &C ! #('% Treatment of a dicarboxylic acid (prepared from the Diels-Alder adduct of dimethyl .120 hrs. e. DMSO 80oC 30 min.g. propionaldehyde. ethanol. with a small amount of benzocyclobutene (7533): CO2H Pb(OAc)4. H3C-CH-(CH 2)nCHO 50-90% The use of silver nitrate in DMSO on a 3-chloro-7-hydroxy-1 7-oxo-androstane accomplishes two purposes. can be oxidized by argentic picolinate to yield the corresponding aldehydes or ketones. DMSO. camphor. isoborneol. formaldehyde. R'RC=O + 2Ag(pic) + 2 pic-H 66-80% Oxidation of menaquinol-1 dimethyl ether with silver picolinate in DMSO gives the desired alcohol (4653): OCH 3 CH3 Ag++ picolinate. N -5 to -20oC 24 .cyclobut-1-ene-1. methanol.3-diene. OCH 3 CH2OH R OCH 3 25% OCH 3 R Reaction of 1. and the use of DMSO leads to a more rapid reaction (2915): DMSO R'RCHOH + 2Ag(pic)2 40-70oC 10-15 min.. It oxidizes the 7-hydroxy group to the 7-oxo group. O Ph PhMeN Ph 95% O In boiling nitromethane with silver tetratluoroborate.2dicarboxylate with butadiene) with lead tetraacetate in DMSO containing pyridine gives a product which is mainly bicyclo [4. pyridine + CO2H g) Silver compound oxidations A number of alcohols.e. the yield of benzil is only 60% (5843).2-diphenyl-2-[(phenyl)methylamino]vinyl chloride with silver (II) oxide in DMSO gives benzil (5843): Ph Cl Ag 2O. Et3. and it dehydrohalogenates the steroid (8340): 79! . The rate of reaction is influenced by the solvent. Bromoalkyl formates are easily converted to protected secondary hydroxyaldehydes by treatment with silver tetrafluoroborate in DMSO in the presence of triethylamine (7507): OCHO H3C-CH-(CH 2)nCH 2Br OCHO AgBF 4.1.

tetralin hydroperoxide and boron oxide to give 38:62 ratio of 2. DMSO reflux Cl OH 52% O 17 -Ethynyl-17 -hydroxysteroids are converted quantitatively to the corresponding 17-ketones by treatment with excess silver carbonate or silver oxide in DMSO (7460): OH O C C-R' Ag 2CO3. Lithium metal is inert toward DMSO (206). DMSO is added to a mixture of m-xylene. dihydronaphthalene and tetralone (8658). The electrodeposition of cerium cannot be accomplished in aqueous solution because the metal is too positive but it can be deposited from a DMSO solution of cerium chloride (1744).8 volts cathode potential (both relative to the standard calomel electrode) (553)(772).or orthoboric acid ortheir lower alkyl esters. OH C CH3 H CH3 X = Cl. and DMSO. a more negative cathode potential is usable in DMSO as shown by the observation of the magnesium wave at -2. it is comparatively stable toward both changes and hence can be used as a solvent for many oxidation-reduction reactions.! AgNO 3. DMSO R'O2C R C C CO2R' R CO2R' 70-90 % CO2R'' 70-80oC CO2R' h) Superoxide and peroxide oxidations Secondary amines are instantaneously oxidized to dialkylnitroxides by potassium superoxide in DMSO (6293): R2NH+O 2- DMSO R2N-O + OH - Alcohols are the major end products resulting from the reaction of alkyl halides and tosylates with an excess of potassium superoxide in DMSO in a rapid process in which the C-O bond-forming step proceeds with inversion of configuration (8030): C6H13 C6H13 H C X KO 2. the usable potentials range from +0. In general. OTs With 1 -bromooctane. meta. Although DMSO can be either oxidized or reduced. DMSO OR Dimethyl esters of monoalkylated malonic acids and -keto esters are easily oxidatively dimerized by silver oxide in DMSO (8830). However. e. the yield of 1 -octanol is 63%.20 volts. the halfwave potentials for inorganic ions in DMSO are quite similar to those in aqueous solutions (553). DMSO 25oC 75 min. Phenolic compounds are prepared by oxidation of aromatic hydrocarbons with organic hydroperoxides in the presence of boron oxide. I.6. The transfer of electrons between molecules of redox systems sometimes occurs very readily in DMSO as observed for isotope exchange between ferrous and ferric perchlorates (1036)(923) and in 80! . Thus.3 volts anode potential to-2. Br. In polarography studies using tetraethylammonium perchlorate electrolyte.4-xylenol. REDUCTION REACTIONS These are reactions in which hydrogen is added or oxygen or a halogen is removed.and 2.g.: CO2R' R-CH Ag 2O. DMSO can be either a solvent or a catalyst component.

NO2) normally affected by harsher reagents such as lithium aluminum hydride (9783). OTs 27 hrs. Sodium borohydride in DMSO selectively reduces 2-chloro-4-chloromethyl naphthalene to 1-chloro-4methylnaphthalene (6785): Cl NaBH 4. tertiary halogen (or sulfonate) in alkyl halides without reduction of other functional groups present in the molecule may be effected by reduction with sodium borohydride in DMSO (2980)(3248): R R1 R 11 NaBH4. DMSO C-X 25-100oC R R1 R 11 C-H X=Cl. DMSO R-Cl R(ene) RH 4-Nitro-2-chloromethyl-1-isopropylbenzene can be reduced with sodium borohydride in DMSO in good yield (4602): CH 2Cl (H3C)2HC (H3C)2HC NaBH 4. secondary or. In the above case. DMSO room temp. presumably via an elimination-addition mechanism (3519): BH3/H+. a cyclopentadiene (6502): CH 2I CH 3 NaBH 4. COOR. NO2 82% CH 3 An iodo-tosylate can be reduced with sodium borohydride in DMSO to give one major product. NO2 3 1/2 hrs. COOH. Reduction of Alkyl Halides and Sulfonates a) Reduction with sodium borohydride the selective substitution of hydrogen for primary. or sulfonate esters (e.! the base-catalyzed transfer of electrons between unsaturated organic molecules and their dihydro derivatives (722). DMSO NaBH 4. tosylate Sodium borohydride in DMSO is a convenient source of a nucleophilic hydride which may be used for the reductive displacement of primary and secondary alkyl halides. . 1.g. DMSO 100o C. 2 hours CH 2Cl Cl 72% CH 3 Sodium borohydride in DMSO-water reacts with . The mildness of borohydrides allows a number of chemoselective transformations without damage to groups (e. DMSO room temp. Br.g. tosylates). I. . in certain cases. -hexachloro-p-xylene to give an insoluble polymer (7205): 81! . The reduction of optically active tertiary alkyl halides with sodium borohydride in DMSO proceeds with racemization. CN. both reduction of the iodide and elimination of the tosylate take place.

aq. DMSO OAc Br OAc OH H OH c) Reduction with dimsyl ion Treatment of 8.0]octane with dimsyl sodium in DMSO produces exo-8-bromobicyclo [5. DMSO room temp Ar Ar Cl S Cl Cl The use of n-butanethiol and chromium (II) acetate in DMSO in the reduction of a 5 -bromo-6 -hydroxysteroid permits the removal of the bromine and the isolation of the 6 -hydroxy-steroid (6825)(6970): Cr(OAc)2. DMSO Br H d) Reductions with hydrazine Hydrazine can reduce meso-1.! CCl 3 CCl 3 NaBH 4.2-stilbene dibromide in DMSO to DMSO -bromostilbene and some bibenzyl (6509): PhCHBrCHBrPh + N2H4 PhCH=CBrPh + PhCH2CH2Ph 18% 66% e) Reductions by electrolysis Controlled potential electrolysis of 2.0]octane (454)(3009): Br Br H2CSOCH 3.4-dibromopentanes in DMSO containing tetraethylammonium bromide (TEAB) gives cis. 2-pentene and n-pentane (4492)(6659): H3C H3C Br Br 2e .and transdimethylcyclopropanes and small quantities of 1-pentene. and benzaldehyde by sodium borohydride and tetramethylammonium borohydride have been determined in DMSO-water systems. (H 3C)3CCHO.8-dibromobicyclo[5.1. aldehydes and ketones in DMSO can be reduced by electrochemical means or by Wolff-Kishner reduction of the corresponding hydrazones. a) Reductions with borohydrides The kinetics of the reduction of acetone. pivalaldehyde. -dichlorobenzyl benzyl sulfoxide to a mixture of diastereomeric -chlorobenzylbenzyl sulfoxide can be carried out by chromous ion in aqueous DMSO (6972): O S Ar Ar O CrCl2. n-BuSH. DMSO-H2O Cl 25oC C Cl C Cl Cl Cl C Cl C Cl Cl n c) Reductions with chromous ion Reduction of .1. The reactions obey 2nd order kinetics (8953): 4R2CO + BH4. TEAB.+ H2O DMSO R2CHOH + B(OH) 482! . DMSO - H3C Br Br H3C CH3(CH2)3CH3 + CH3 CH3CH2CH2CH=CH 2 + CH3CH2CH=CHCH 3 + 2. Reduction of Carbonyl Compounds Carbonyl compounds.

The Wolff-Kishner reaction mechanism in DMSO has been reviewed (1942)(3048). a 97% conversion to 4-t-butylcyclohexanol. can be achieved with DMSO as the sulfoxide (4436): O IrCl3-i-Pr-DMSO 97% conversion OH An unusually selective hydrogenation of . When benzaldehyde is reduced in DMSO and DMSO-water mixtures of tritiated sodium borohydride. the solvent being the source of hydrogen (9752): HlrCl 2(DMSO)2 RCH=CHCHO + H 2 RCH=CHCH 2OH c) Electrochemical reduction The electrochemical reduction of carbonyl compounds.50. DMSO PhNO2 85-100 C o Ph-N=N-Ph O Ph-N=N-Ph PhNH2 nitrobenzene azoxybenzene azobenzene aniline In the case of o-nitroanisole. and the activation parameters have been determined (8735). has been studied in DMSO (2567)(3217). With 4-tbutyl cyclohexanone.: NaBH4. the reaction of hydrazones of aldehydes and ketones with a base to produce the corresponding hydrocarbons. PhCH 2OH (8953).5 electron process (5971): OH O DMSO Ph Ph OH C C O C 4Ph-C=CH-C-Ph +2e H2 C H2 C Ph Ph + Ph2 OH C H C O C Ph OH O dimeric pinacol enolate anion d) Wolff-Kishner reduction The Wolff-Kishner reduction. -unsaturated aldehydes to the unsaturated alcohols has been accomplished catalytically under mild conditions using the iridium complex HlrCl 2(DMSO)3 in isopropanol. dimsyl sodium.3-propanedione in DMSO proceeds by an overall 0.! The reduction product of benzaldehyde in DMSO is NaB(OCH2Ph)4. nitrobenzene in the presence of platinum on carbon and DMSO yields hydroxylamine and phenyl aniline (5663): 83! . 3. Nitroaromatics are selectively hydrogenated in neutral media in the presence of precious metal catalysts and DMSO to produce Narylhydroxyamines in high yield. the reduction is accompanied by the incorporation of tritium into the aldehyde group of unchanged benzaldehyde (8954). with a cis/trans ratio of 1. in most cases. particularly ketones and diketones. has been run in DMSO (495)(377): Ph2C=NNH 2 t-BuOK. DMSO 25o C 8 hours benzophenone hydrazone Ph2CH 2+N2 90% diphenyl methane The Wolff-Kishner reduction in DMSO has been carried out in the presence of potassium t-butoxide. Thus. The reduction of 1. 63% of o-methoxyaniline and 23 % of the azobenzene are produced. which is readily hydrolyzed to benzyl alcohol.g. e. are subsequently reduced to the corresponding azo derivatives and amines (4946). b) Catalytic reduction The mechanism of reduction of cyclic ketones by the system iridium(III) salt-sulfoxide-isopropyl alcohol has been investigated. and other base catalysts. Reduction of nitroaromatics The reduction of aromatic nitro compounds with sodium borohydride in DMSO initially produces the azoxy compounds which.3-diphenyl-1.

C6H5CH=CHCOR.! PhNO2 + [H] Pt/C-DMSO ethanol room temp. DMSO H2C C H2C C O O A thiophene derivative is reduced the same way (4392): SCH3 S 95% O SCH3 HN=NH. H[IrCl 4(DMSO)2] 73o C PhCOCH2CH2Ph 95% Acrylic acid and its derivatives can be dimerized in high yields by means of alkali metal amalgam in DMSO-water. Acrylonitrile gives adiponitrile (4907): 84! . Conditions have been established under which a dimer of the . is a particularly useful reducing system for olefins or compounds which contain readily oxidized functional groups (4392). A suitable medium for the reduction is tetra-n-butylammonium perchlorate in DMSO with added lithium perchlorate (4253). the reduction of nitrobenzene with hydrogen over platinum oxide in alcohol (methanol or ethanol)sulfuric acid in the presence of DMSO produces p-alkoxyaniline (9294)(9581): NO2 + [H] PtO2.g. Double bonds in some . 1 -pentene is converted to isomers more rapidly than without the catalyst and the bond migration of the pentene is more rapid than its hydrogenation (5630). e. generated by the sodium metaperiodate oxidation of hydrazine in DMSO. Reduction of C=C Systems The electrochemical reduction of several aryl .H2SO4 OR NH2 4. DMSO-H2O Ph CH 2COR R = t-butyl Diimide. controlled potential coulometry and cyclic voltammetry. has been studied at mercury cathodes by the techniques of polarography. DMSO S CO2C2H5 CO2C2H5 Allylbenzene can be hydrogenated by chloro(DMSO)palladium complexes (5526): PhCH2CH=CH 2 + [H] (DMSO)2 PdCl2 PhCH2CH2CH3 In the presence of the same catalyst.: H COR Ph CH 2COR 75% Ph H LiCO 4. -unsaturated ketones is formed by coupling at the -carbon atoms in good yields. PhNHOH+ PhC6H4NH2 86% 13% Catalysts of noble metals on activated carbon can be subjected to the action of DM SO together with hydrazine or its derivatives. DMSO ROH. -unsaturated ketones are reduced by propen-2-ol in the presence of soluble iridium-DMSO catalysts (7031): PhCOCH=CHPh i-PrOH.g. e. -unsaturated ketones. The hydrogenation of 2-chloronitrobenzene in the presence of platinum on carbon and DMSO gives a high yield of 2-chloroaniline (8118): Cl Cl NO2 + [H] Pt/C-DMSO hydrazine NH2 Similarly. maleic anhydride can be reduced to succinic anhydride: O HC HC C C O O HN=NH.

The rates of base catalyzed reactions usually increase as the mole fraction of DMSO in the mixture increases. DMSO-H2O ! NC(CH 2)4CN 95% Diethyl fumarate. C2H5O2CCH=CHCO2C2H5. Hydrolysis The DMSO-water system has been used in many hydrolysis reactions. obtained by reacting 5-methoxymethyl-1. useful for the synthesis of poly(arylene ether sulfones). The rate of the hydroxyl ion catalyzed reaction in DMSO is up to 10 -10 times the rate in water (329). is converted with aqueous potassium hydroxide in DMSO to the anti-bicyclic ketone (3033): H3COH2C H COH C 3 2 KOH. SOLVOLYTIC REACTIONS These are reactions in which the elements of water (also alcohols or amines) are added. DMSO-H 2O Cl CN 25-30 C 14 hours o O b) Aromatic halide hydrolysis Aromatic halogens can be hydrolyzed from activated nuclei by aqueous bases in DMSO.5-dioxodibenzothiophene with aqueous potassium hydroxide in DMSO gives 8-bromo-2-hydroxy-5. The Diels-Alder adduct. usually with the formation of two new substances. These rates have been correlated with the acidity function of medium (4467)(4520).8-dibromo-5. In the alkaline hydrolysis of methyl 6 7 iodide.4'-dichlorodiphenyl sulfone monomer occurs concomitant with the polymerization (4704). and the increase is particularly rapid above 0. The reaction of 2. octanol is obtained from octyl chloride and calcium hydroxide in DMSO-water at reflux (4846): Octyl chloride +Ca(OH)2 DMSO-H2O reflux 4 hrs. hydrolysis of 4. Alcohols can be prepared from alkyl halides in DMSO-water in the presence of a base. THF-water.4'-dichlorodiphenyl sulfone in DMSO depends on the moisture content of the polymerizing system. Thus. DMSO 60 C 24 hrs.7 mole fraction of DMSO (336)(367)(369)(464)(726)(730). In the presence of water. However. o SO2 X + 2KOH x=halogens X R O2 S R OK + KX 85! . The aryl polyether that is prepared by the reaction of the disodium salt of bisphenol A with 4.4-dinitrobenzenes have been measured in aqueous DMSO. particularly above 25-30% DMSO (368). a) Aliphatic halide hydrolysis The alkaline hydrolysis of alkyl halides has been studied in DMSO-water (329)(432)(2583)(4846).3-cyclopentadiene with chloroacrylonitrile. have been prepared by partial hydrolysis of the corresponding dihalides in DMSO (8825): X R aq. DMSO exerts a strong accelerating effect. The opposite is sometimes true in the case of hydrolysis in the presence of acids. 1.5dibenzothiophene (7709): Br Br OH Br aq. The rate of alkaline hydrolysis of chloroacetic acid increases with increasing concentration of the organic component in acetone-water. The rate coefficients for the alkaline hydrolysis of a series 1-halogen substituted 2. Octanol 92% Solvolysis of 2-adamantyl bromide and -chloroethylbenzene decreases with increasing DMSO content (2194)(3766)(2196). The rate of acid hydrolysis decreases as the mole fraction of DMSO is increased. A similar decrease is seen for the acid catalyzed hydrolysis of acetals (742) and the reaction of tert-butyl chloride with aqueous DMSO (431)(1028)(1521). the increase is greatest in DMSO-water (2583). DMSO + KOH 110o C S S 3 hours O2 O2 Several 4-halogenophenyl sulfonylphenols.2 CH2=CHCN Na amalgam. can be dimerized by electrochemical reduction (7331). dioxane-water and DMSO-water. The rate constants for the reaction of hydroxyl ion with benzyl chlorides in acetone-water decrease with increasing acetone concentration while the rates increase with increasing DMSO concentration in DMSO-water (432).

6-diene-3.9-epoxyundec-5-en-ol with potassium hydroxide in refluxing aqueous DMSO produces undeca-4. DMSO CH3CHO+C 2H5OH OH The rate coefficients for the alkaline hydrolysis of 4-substituted 1-methoxy-2-nitrobenzenes and 1-alkoxy 2. Some increase with increasing DMSO has been found in the hydrolysis rate of trifluoroacetanilide (7573). the rate of hydrolysis of the vinyl ether is still controlled by the rate of proton transfer to the carbon.c) Amide hydrolysis ! The rates of base catalyzed hydrolysis of anilides have been studied in DMSO-water (3820)(7573)(8696).9-epoxy-undecan-3-ol. the corresponding trans-glycol is obtained in fairly good yield (334): Ph KOH.9-diol (8261): O OH OH OH CH2H5CH-CHCH 2CH=CHCH 2CH2H5+H2O KOH. H2N(CH2)5CO 2H d) Epoxide hydrolysis The most commonly encountered reactions of epoxides are those in which the ring is opened by a nucleophile. These rates have been correlated with the acidity function of the medium (4467)(4520): OR NO2 + NO2 OHNO2 aq. Even a very small amount of DMSO (less than 1 %) facilitates the kinetic measurements in the hydrolysis of p-nitro. when treated with base in 75% aqueous DMSO.4.4dinitrobenzenes have been measured in aqueous DMSO.and pformylacetanilide (3820).6-trinitrophenyl phenyl ether react with DMSO to give 2.9-triol (8261): C2H5CH-CH(CH 2)4CHC 2H5+H2O KOH. leads to simple cleavage of the epoxy ring giving undecane3. DMSO 95-103o C 4 hrs.4. The rate decreases with increasing DMSO concentration (2492)(7643): CH2=CHOC 2H5 + H2O OR H+. gives the corresponding oxetan as the main product (8306): +H2O OH OH-. DMSO OH NO2 NO2 NO2 A similar study has been done with substituted 2-alkoxytropones in 40% aqueous DMSO (4521). (6878): 86! .4. Such reactions are advantageously performed in DMSO because DMSO is inert to the epoxides and it also provides maximum reactivity for the nucleophile. DMSO C2H5CCH 2CH=CHCH=CHCC 2H5 The same treatment of the saturated epoxide. DMSO O + H2O 100o C 6 hrs 60% Ph OH OH ° In the presence of acids a mixture of cis. strong acid.and trans glycols results.6-Trinitroanisole and 2. 2. When the relatively unreactive 1 -phenylcyclohexene oxide is heated with potassium hydroxide in aqueous DMSO. DMSO 49% CH2 OH e) Ether hydrolysis When water. DMSO OH HO OH C2H5-CH-CH(CH 2)4CHC 2H5 1 -( -Epoxypropyl)cyclohexan-1 -ol. Treatment of 8.4.6-trinitrophenol and methanol and phenol. -caprolatam with barium hydroxide in DMSO(4972): -aminocaproic acid on acidification H N O +H2O Ba (OH)2. and ethyl vinyl ether are all solutes in DMSO. resp. 8. The same reaction in aqueous dioxane after48 hours at 150 C gives only a 10% yield (334).

the cleavage occurs by alkyl-oxygen fission (490). the saponification rates of unsaturated esters in DMSO-water are faster than in ethanol-water (3356) (7540). When the saponification of glycol monobenzoates are carried out in 80% aqueous DMSO. the solubility of the dry caustic in DMSO is very low which reduces the speed of converting the nitrile (725). as is the case of ethyl p-cyanobenzoate (10086). DMSO CH2OH Similarly. In 50% aqueous DMSO (v/v) the first ester group can be hydrolyzed more than nine times faster than the second one (1694). the reaction rate decreases as the mole fraction of DMSO increases above 25-30% DMSO. The rate coefficients of neutral hydrolysis of methyl trifluoroacetate and chloromethyl dichloroacetate in DMSOwater are greater than in acetone-water and acetonitrile-water (6477). the rate of hydrolysis increases as the mole fraction of DMSO in the mixture increases. 80% aqueous ethanol and 80% aqueous acetone. This increase is particularly rapid above 0. e. not increased hydroxyl ion desolvation.3-triazole-5-carboxamide due to hydrolysis of the nitrile (7115): Ph Ph N N N Ph Cl + NaCN + H2O DMSO N N N COHN 2 Ph g) Saponification In the base catalyzed hydrolysis of esters in aqueous DMSO.4-diphenyl1. There is a considerable rate enhancement for both steps in alkaline hydrolysis of a series of dicarboxylic acid esters in DMSO-water. Alcoholysis. benzonitrile to benzamide. at a reaction rate that is approximately 10.OR NO2 NO2 DMSO NO2 NO2 OH ! NO2 + ROH NO2 R= Me. is the major cause of rate enhancement in DMSO (6822).2-trifluoroacetanilides in DMSO-methanol rate increases with increasing amount of DMSO (6474): CH3 Ph-CO2H2C + H2O 30o C + HO2C-Ph CO2H CH3OH9 DMSO O R O CH3OH R-C6H4NCOCF3 + CH3OCH3 R-C6H4-NH H3C N C6H4 CF3 OCH 3 + F3CCOCH3 87! .000 times that in aqueous caustic. With hydrolysis on the acid side. The cleavage of highly hindered esters can be accomplished in DMSO using potassium t-butoxide as the base and heating until the cleavage is accomplished. however.2. In this case. The reaction of 5-chloro-1. However.7 mol fraction of DMSO (336)(367)(369) (464)(726)(730).2.3-triazole with sodium cyanide in moist DMSO gives 1. The use of DMSO-water as a solvent for saponification increases the reaction rate difference between the first and second group of diesters. The rates increase with increasing amount of DMSO and these rates are larger in aqueous DMSO than in aqueous ethanol (5969)(6543) or aqueous acetonitrile (5459). as is the case with ethyl acetate (368). Esters are also cleaved by sodium superoxide in DMSO to give carboxylic acids in excellent yield. O H2NC 96% 2. the rates are up to 1000 times faster in 80% aqueous DMSO than in the other two solvent systems (5622): CH2OH CH2OH OH-.g. NC CO2Et + O2DMSO 5 min.4-diphenyl-1. Ph f) Nitrile hydrolysis Powdered anhydrous sodium hydroxide and potassium hydroxide in DMSO can be used to convert nitriles to amides. Increased transition state solvation.2. Aminolysis In the basic methanolysis of some aryl substituted N-methyl-2.

g. The reaction of 1. DMSO is a particularly suitable solvent in this area because of the enhanced activity of the base catalyst in DMSO and also because of the excellent solubility of most carbohydrate and polyhydroxylic substances in DMSO.! N-Methyl-4'-nitroanilides undergo basic methanolysis by way of rate determining methoxide addition to the amide. Thus. The low incidence of transfer from the growing chain to DMSO leads to high molecular weights. styrene sulfonic acid. Monomer mixtures consisting of acrylonitrile. as shown above.4'-sulfonyldiphenol with 4. Polymerization and Spinning Solvent DMSO is used as a solvent for the polymerization of acrylonitrile and other vinyl monomers. In some cases.6-carbonate ester(183) in a transesterification. 3. Transesterification (Ester Interchange) The reported work concerning the base catalyzed transesterification of fatty acid esters mainly describes esterification of carbohydrates and other polyhydroxylic materials. DMSO O NO2 O O H3C 25o C NH(CH 2)3CH3 + O OH NO2 The aminolysis of polymeric macronet N-hydroxy-succinimide esters of Boc-amino acids by free amino acids and peptides in DMSO has been studied. vinylidene chloride.g. allyl. are polymerized in DMSO-water (6713).2-0-isopropylidene-6-tosyl-glucose under the conditions of the Kornblum oxidation with potassium bicarbonate as the base gives none of the expected aldehyde but only the 5. The mechanism of basic methanolysis of a series of N-aryl-N-phenylbenzamides in methanol and in 80% DMSOmethanol has been studied. methyl methacrylate (9638) and styrene (5192).4'dihyalodiphenyl sulfones by the displacementetherification reaction in DMSO (7104)(9961). Copolymerization reactions of acrylonitrile with other vinyl monomers can also be run in DMSO. etc. In methanol the rate determining step seems to be the solvent assisted C-N bond breaking. A number of the reports are concerned with sucrose esters (160)(161)(181)(162)(164)(165). These poly(ether sulfones) are prepared by reacting dialkali metal salts of a bisphenol. Thermoplastic polymers derived from natural products have been prepared by interesterifying starch with methyl palmitate in DMSO with potassium methoxide as the catalyst (8227). DMSO 80o C CHCO 2R C CO CH 2 3 H R = benzyl. such as bisphenol A or 4. Polymerization Solvent for Heat Resistant Polymers. DMSO is an effective catalyst for the n-butylaminolysis of p-nitrophenyl acetate in chlorobenzene (6988). ° Alkylation of methyl 0-(tetrahydropyran-2-yl) mandelate using alkyl halides and sodium hydride in DMSO at 80 C produces transesterification products (4278): O OH O + RX H2CSOCH3. Others report esterifying hexitols and hexoses (1257) and inositols (166). ethylene oxide is rapidly and completely polymerized in DMSO (9652). e. Acrylonitrile is readily soluble in DMSO and the polymerization is carried out by the addition of initiators (8184)(8185). Markedly increased alcoholysis rates are obtained by the addition of DMSO to ethylene-vinyl ester interpolymer alcohol mixtures in the presence of either alkaline or acidic mixtures (7156). n-pentyl or cyclopentyl Dimethyl terephthalate can be polymerized with ethylene glycol in the presence of a tin chloride-DMSO complex and trimethylphosphate to give a poly(ethylene terephthalate) (7255). e. O NO2 +NH2(CH2)3CH 3 chlorobenzene. the fibers are spun from the reaction solution into DMSO-water baths (8501)(8603). isopropyl. PART V USES 1. Poly(ether sulfones) are a family of polymers from which a series of tough ° thermoplastics can be selected for use under continuous stress in the temperature range of 150-250 C (7196)(7619). DMSO can also be used as a reaction solvent for other polymerizations. methallyl sulfonic acid. The addition of DMSO produces a rate increase in each case (7844). while in 80% DMSO-methanol the rate determining step is methoxide attack (10409). styrene. both in the presence and in the absence of organic bases (8832).: 88! . Diisocyanates and polyols and polyamines can be dissolved and reacted in DMSO to form solutions of polyurethanes (8677).

Thus. actinides (2520). Cellulose Solvent Although DMSO by itself does not dissolve cellulose. nickel. with bis(halophthalimide) in DMSO as the solvent (9686). titanium (7260). O O O N O X x-S. DMSO-carbon disulfide-amine. the following metals have been electrodeposited from their salts in DMSO: cerium (1749). can be deposited from DMSO.! Cl SO2 O Cl + NaO SO2 ONa DMSO S n O2 Interest in heat-resistant polymers has also lead to the development of polyetherimides. cobalt. etc. DMSO-sulfur dioxide-ammonia (9541). (5488). chromium (6672). These polymers are prepared by the reaction of a dialkali metal salt of a bisphenol. SO2. C(CH3)2. zinc. In DMSO cations can be successfully reduced to form metals that would react with water. X O S O O n Somewhat similar polyetherimides can be prepared by reacting an aromatic bis(ether dicarboxylic acid) component with a diamine in DMSO-water (10762): X HO2C HO2C O O X CO2H + H2N CO2H NH2 X O N O X= S. While only 80% of cellulose dissolves in DMSO-methylamine under cold anhydrous conditions (10368). etc 2. A least a ratio of 3 moles of active agent per mole of glucose unit is necessary for complete dissolution (8970). In place of bis(halophthalimides). copper (9396). particularly when a small quantity of water is added (9170). DMSO-ammoniasodamide. DMSO-dinitrogen tetroxide. the following binary and ternary systems are listed as cellulose solvents: DMSOmethylamine. such as magnesium or aluminum.4'-sulfonyl diphenol. 4. It is believed that a methylol-cellulose compound forms which is stable for extended periods of storage at ambient conditions (9850). DMSO-sulfur trioxide. DMSOparaformaldehyde (8970)(10368). CH2. C(CH3)2. The recently discovered DMSO-paraformaldehyde system does not degrade cellulose and it can form solutions containing up to 10% cellulose (7763)(8506)(9850). CH2. DMSO is used in the Institute Francais du Petrole (IFP) process for extracting aromatic hydrocarbons from refinery streams (8554). Solvent for Electrolytic Reactions DMSO has been widely used as a solvent for polarographic studies and it permits the use of a more negative cathode potential than in water. bismuth all crystalline deposits. iron. cadmium. Extraction Solvent DMSO is immiscible with alkanes but a good solvent for most unsaturated and polar compounds. DMSO is also used in the analytical procedure for determining polynuclear hydrocarbons in food additives of petroleum origin (2371). DMSO-nitrogen tetroxide is a better solvent. Regenerated cellulose articles such as films and fibers can be prepared by contacting the DMSO-paraformaldehyde solution with methanol and water (9850)(9895). Generally. 89! . such as bisphenol A or 4. manganese all amorphous deposits. certain bis(nitrophthalimides) in DMSO can be used (10434): O O N O O N + NaO X O N O O N O O S O DMSO ONa X X= halogen or NO2. silver (7459). 3. lead (9175). Most of these systems are capable of producting cellulose fibers. SO2. Thus it can be used to separate olefins from paraffins (10771). no metal less noble than zinc. tin.

8. including suitable gloves or eye protectants. low toxicity and ease of handling. As is the case with other organic solvents. dimethyl sulfoxide tends to dehydrate and de-fat the skin. Integrated Circuits DMSO solutions are useful for etching resists in integrated circuit manufacture. (DMSO has a high boiling point. If toxic substances penetrate into the system. The toxicity of DMSO solutions will depend. protective clothing is recommended. and a low vapor pressure. PART VI TOXICITY. 189 C or 372 F. 6. Clothing contacted by such solutions should be removed and washed before reusing. insecticides and herbicides are soluble in DMSO. Conventional industrial safety procedures and practices should be observed when working with DMSO as with any organic solvent. the LD50 for ethyl alcohol is about 13. HANDLING. DMSO forms cosolvent systems of enhanced solubility properties with many solvents. Pesticide Solvent Many organic fungicides. Eyes: DMSO in contact with the eye may cause temporary irritation but will not result in eye damage if washed out promptly with cold water. However. Butyl rubber gloves are suggested for DMSO service. The LD 50. when working with DMSO on a prolonged basis or in combinations with other materials. DMSO by itself presents less hazard than many chemicals and solvents commonly used in industry.000 mg/kg. Contact with DMSO solutions: When handling solutions of possibly toxic substances in DMSO. Sulfiding Agent DMSO (ENVIRO-S) can be used as a sulfiding agent in refineries because of its low odor. if any. care must be taken to avoid contact with the skin and to wash such solutions off immediately and thoroughly with soap and water. However. The degree of penetration is determined by the concentration of DMSO and water in the solution and the length of time of skin contact.700 mg/kg. Cleanup Solvent DMSO is used to remove urethane polymers and other difficultly soluble materials from processing equipment. ANALYSIS 1. 7. are not yet known. in part. For comparison. serious harm may occur. DMSO has the ability to penetrate the skin and may carry with it certain chemicals with which it is combined under certain conditions. Protective clothing is not necessary when handling DMSO in containers or in small amounts on limited occasions. Hard crusts of poly(vinyl chloride) resin can be dissolved by using 85:15 ethyl acetate-DMSO mixture (8927). HAZARDS.) Inhalation of vapors of hot DMSO or DMSO aerosol mists may be harmful and should be avoided. for single dose oral administration to rats is about 18. on the nature and toxicity of the other chemicals used and the degree of penetration. A 10% solution of DMSO in water causes only slight increase in skin penetration over the same solution without DMSO. Repeated skin contact overextended periods should be avoided since the effects of such contact. ° ° Vapors: The normal ambient airborne DMSO concentration is low. 90! . Toxicity and Handling Precautions Dimethyl sulfoxide is a relatively stable solvent of low toxicity.! 5. Contacts with DMSO Alone Skin: Undiluted DMSO may have a mildly irritating effect on the skin and should be washed off promptly with cold water. Not all chemicals will be carried through the skin even though the DMSO may penetrate. including such difficultly soluble materials as the substituted ureas and carbamates.

silver fluoride and other strong oxidizing agents such as magnesium perchlorate and perchloric acid. These reactions proceed with about the same vigor as the reaction between acid chlorides and ethyl alcohol. DMSO cannot be used in Friedel-Crafts reactions or with Ziegler-Natta catalysts. Comparative Toxicity of Commercial Solvents All solvents are toxic to some extent.2. they are polar. RCO2CH2SCH3. 4. is shown for a number of common solvents. Reactions of DMSO. as measured by dermal and oral LD50 in rats. Table XIII shows the results of one of these studies. like DMSO. Reaction with Strong Bases). Toxicity. DMSO also reacts with carboxylic acid anhydrides. potassium permanganate. They are listed in order of increasing oral toxicity. TABLE XII Single-Dose Toxicity (Rats) of Some Common Solvents LD50. such as acetic anhydride. Several studies have been made in comparing the toxicity of DMSO with other solvents. An uncontrolled reaction took place when DMSO was heated with methyl bromide to prepare trimethyloxosulfonium bromide. the major product being the acyloxymethyl methyl sulfide. This 91! . TABLE XIII Single-Dose Toxicities to Mice of 4M Solutions LD50. Chemicals and Reactions to be Avoided with DMSO DMSO can react vigorously and even explosively with iodine pentafluoride. mg/kg Solvent Oral Dermal Glycerine 31600 10000 DMSO 17400 40000 Ethanol 13700 Acetone 9750 Dimethylacetamide 7500 5000 Ethylene glycol 7200 N-methyl-2-pyrrolidone 7000 Trichloroethylene 5860 Lsopropanol 5840 n-Propanol 4300 Benzene 4080 Diacetone alcohol 4000 Methyl ethyl ketone 3980 Xylene 3830 10000 Cyclohexanone 3460 Acetic acid 3310 n-Butenol 2610 5620 2-Heptanol 2580 Butyl cellosolve 2380 Dimethylformamide 2250 442 Sodium lauryl sulfate 1650 10000 Pyridine 891 1120 Aniline 442 1540 Phenol 14* * Approximate lethal dose. DMSO reacts vigorously with acid chlorides. and suitable precautions should be taken. Adequate heat removal should be provided when reacting DMSO with sodium hydride or potassium hydride when making the DMSO anion (dimsyl ion) (Please see PART III. Most of the solvents in the above table were chosen because. but DMSO is much less so than many in common usage. mg/kg (mice) Compound DMSO Glycerine Dimethyl formamide Dimethyl acetamide N-methyl pyrrolidone Intravenous 7176 6164 3650 3915 1980 Intraperitoneal 14664 6900 6570 5916 3564 3. periodic acid.

P. Sum the areas of any extraneous peaks. loss in the yield of the product (9964). produced as byproducts in the reaction. 3. Can be obtained commercially. Calculations b) DMSO Freezing Point Pour 30-50 ml of DMSO into a clean. dry test tube.18.210°C Carrier gas flow 30 ml/min Adjust the instrument sensitivity so that a 0.reaction should be run in the presence of compounds that remove HBr or Br2.stablilized.5x20 cm in size and fitted with a stopper containing thermometer and also containing a small magnetic stirring bar. Karl Fischer Reagent . Purified DMSO . Detector . Bubble in 60 grams of SO 2. Reagents 1. Fischer Scientific SO-K-3 4. Thus. such as methyl or ethyl orthoformate or tetramethyl orthocarbonate.0 microliter syringe. 40/60 mesh. if any. Chromatograph Conditions Temperatures: Column . Karl Fischer procedures other than the one described below may be used provided that their accuracy in this analysis has been determined. Reagents and sample are added through the third hole and a micro burette containing Karl Fischer Reagent is mounted above the third hole. 1 ml = 1 mg of water.d. page 5) c) Water Determination by Karl Fischer Titration Discussion Water is determined by Karl Fischer titration. C. Mix 300 ml. During the titration the jar is mounted over a magnetic stirrer with the electrodes extending through the cap into the solution to be titrated. End-Point Detecting Assembly The end-point detecting assembly is of the "dead stop" type. Record the period before and after the DMSO peak at 100 times this sensitivity.5 microliters of the DMSO. Anhydrous methanol. x 1/8 inch o. 2. Record the DMSO peak at the sensitivity determined above.220°C. 4. 1. ° Cool the test tube in water at 15 C while agitating with a magnetic stirrer until crystallization starts. pyridine and 300 ml anhydrous methanol. The cap is drilled to admit2 platinum electrodes and one burette tip. which depends upon the depolarization of the electrodes on reaching the end-point of the titration. the possible violent exothermic decomposition of the reaction mixture can be prevented with little. Water-methanol standard. Record the chromatogram for 20 minutes. Procedure Inject 0. Inlet . A preferred alternate to the above assembly can be constructed from both halves of a large diameter glass ball and socket joint. approximately 2. Pyridine-SO2-methanol.5 microliter sample will give a DMSO peak between 75 and 100% of recorder full scale. These esters act as scavengers of HBr and Br 2.150°C. stainless steel column packed with 15% FFAP (Varian Aerograph) on Chromosorb T (Johns-Manville).3 C minimum (See Figure 2b. 92! . Analytical Procedure a) Gas chromatographic analysis of DMSO Apparatus Gas chromatograph with flame ionization detector and a 4 ft. Once crystallization has ° begun read the thermometer while both liquid and solid DMSO are present. Scope This procedure may be used with all grades of DMSO. This can be done with the solution on a platform balance to weigh directly the SO2 added. Apparatus Titration Assembly The titration is contained in a screwcap glass jar of 100-200 ml capacity.

V. Exposure of the sample to atmospheric moisture must be kept to a minimum. Patent 946.G. 221-222 (1964). Duncan.989 (CO7D) (Jan. and 4). Response tends to be slow with the stabilized Karl Fischer Reagent. 521-523 (1965). Japan 10051/65.. Add Karl Fischer Reagent dropwise to the end-point. Daiichi Seiyaku Co. W. Accurately pipette 20 ml of the water-methanol standard (a weighed amount of pure water may be used) into the titration bottle and titrate with Karl Fischer Reagent to the end-point. 1966). Chem. 3. R.S.. Add Karl Fischer Reagent dropwise from a microburette to the end-point. Add 2 to 3 grams (accurately weighed) of the DMSO to be tested (Notes 2. For convenience. J. 48 (April 11. F.10 (the specific gravity of pure DMSO @ 20°C. Add 20 ml of anhydrous methanol and 5 ml of the pyridine-SO2-methanol solution to the titration bottle (Note 1). Allen. but returns to the original point of deflection after each swing. by 1. No. Parker. 5. The weight of DMSO samples is calculated by multiplying the volume in ml.A. Chem. W. Crown Zellerbach. Samples larger than 2-3 grams of DMSO produce low results.A. PART VII BIBLIOGRAPHY 1 8 17 22 26 42 49 Traynelis.J. the ammeter needle starts to swing with each addition of titrant. a 2 or 3 ml. 3.L. Titrate with Karl Fischer Reagent to the end-point. Standardization of Reagents The Karl Fischer solution must be standardized daily. DMSO is extremely hydroscopic. News. H. Determination of Water Add 20 ml of anhydrous methanol and 5 ml of the pyridine-SO2-methanol solution to a clean titration bottle.J. Adjust the variable resistance to produce a microammeter deflection of 1 or 2 microamps.M. Silverstein. 9. (August 1965). 4. S. 1964). Record the volume of titrant used in the second titration and calculate its water equivalence. & Technol.M.).J. results unpublished. When the end-point is reached the needle will remain permanently displaced up scale.. start the magnetic stirrer. Org. Notes 1. Brit.Procedure End-Point Detection With the equipment set up as described and the material to be titrated in the bottle. Warne. Turner. 29. French. As the end-point is neared. Fuqua. CA 63 5659B (1965). 93! . A titration assembly such as a Beckman Model KF-2 Aquameter may be used for the titration. A. 15. Titrate with Karl Fischer Reagent. Hergenrother. Sci. with a sacrifice of accuracy. F. volume of DMSO can be sampled with a volumetric pipette. 2. Record the volume of titrant used in the second titration and calculate the water content of the dimethyl sulfoxide.. Tetrahedron Lett. A sharper end-point is obtained with the addition of the pyridine-SO2-methanol solution to the titration vessel. R. Ltd.. & Eng.

L.-L. 1. Chem. 3309-3313 (1966). Horner. Saytzeff. Chem.. Moffatt. Org. Anderson.280. Acta Chem.J. J. DeRadzitzky. 261. 13.E. 24. J. M.B.A. 1959). Scand. Ann. Chem.. 2. Moffatt. A. 9. L. Chem. Macchia. 1128-1129 (1963). Goethals. 1495-1496 (1957). Corson.J.. Macchia. Soc.I. Lindberg. 21.B. Montanari. Chem. Belg. U. (Tokyo) 13(6).J. Acta Chem. Kuryla. 3421-3427 (1965). F. 260-607) (Aug. 92-98 (1961).I. Thomas. 24. Hiiro.S.B. 4113-4114 (1959). Am. Finska Kemistsamfundets Medd 70. U. A... 19-25 (1959)..270. G. Roman. J.990 (C1. 70. Soc. 4651-4652 (1965)..812. K... Lefort. Murto. Palenius. Jones. 2001-2002 (1948)..L. H.. Tetrahedron 19. 17. 248-251 (1966).. Chem. News 38. W. Chem. 5. Org. 805-806 (1965).757 (C1.T. Hass. Larson.. Rend. Pfitzner. Suomen Kemistilehti B34.A. Bay.. Tetrahedron Lett. 94! .. Kitao. Soc. Acta Chem. 29. Ltd. Chaykovsky.C. T. 1959).445 (C1..5) (Sept. 1990-1991 (1965). Corey. L. N. K.H. J. Schlafer. K.. J. Liebigs. Int. Am. Proc. 72. P. Eng.R. Murto. Org. 87. G.S. W.J. Soczewinski. J.S. 529-532 (1963). J.H.. B. Chromatog... Sci. Bull.G. Scand. Distillers Co. Chem. S. 38. E. G. 81. 1961). Webb. Szmant. York. E.. Pfitzner. 30. 4034-4039 (1966). 73 546-559 (1964). Chem. Kashimura. K.S. Org. T.J. H. 31. Snell. Chem. R. P. Soc.O.G. J. H. J. Org. 5670-5678 (1965). Soc.W.F. 88. Iwai... 275-277 (1963).M. Pae.. Scheidt.. 8.. J. J. Brousse. Am.-L. Chem. Brit. Huber. 87. R. 141-142 (1959). W. 260-234) (Sept. Sweeting. Hirano. S. Appl. Bottner. Greenwald.324 (C1.. R. 260-234) (Nov. J. Pan. H. 352-356 (1960). Monagle. Tucker. S. Am.L. Powers. U. E. 79. E. 1980-1984 (1963). Pan. S. Russell. J. No. Weaver..P. 4812 (1965). Anderson. W. G. U. S. S. E. 5661-5670 (1965). Kampe.. 2. Pfitzner. Chem. Nace. 1961). Tommila. Ed.903. Tommila.J. Angew. G. Krutzik. U. 177-180 (1964). Schaffernicht. Douglas. 22. J. Soc. J. T. 3.G. 2. Soc. Tommila. M. 99. 2988-2994 (1965). Soc.. Smith.. 260-234) (July 7.F. W. H. W. 6562 (1957). D.N.970.S. A. Ide. Tetrahedron Lett. W. 28... 260-211. Org. 663-672 (1965). J. Pharm.. J.. 117-120 (1964). D. 1026-1031 (1966). 1962). 1019-1040 (1965). Kornblum.D. J. Chem. Chem. 2. 46-47 (Nov. Winstein..B. for 1960. -1915 (1962). Weiner.R. L. Bottini. 1713-1715 (1963). J. I. Chem. 27. 3. J. Kornblum. 85. Fletcher. Polymer Sci. E. York.. Am. Keim. J. Chim. Scorrano. E. W. S. O.C. O. Chem. P... 2.S. Compt. W. K. 317-319 (1958).T. Kaiser.. Groves.893. J. Inorg. J.. Claypool.. 1947-1956 (1963). R. J. J.. E. U.E. Angew.C.J.490 (C1. 305 (CO7C) (Jan. F. 31. E.. Berti. Chem. J. GP8. 2442-2746 (1962). Ann. N.D.C. 1965). Suomen Kemistilehti 37B. J. J. Fletcher. J. 17. M. Izzo.761 (C1. 17. Am. Soc. 87. 1965). Krueger.051. Murto. N. No. 21.. I. M. F. N. W. 817-820 (1963). No. H. K. Soc. 1960). Chem. 3069-3070 (Dec. Am. Legault.E. Indiana Acad. Lard. Tetrahedron 3. 6. Ratz.J. Bull.M. 260-234) (Jan. Kawamura. Chem. 8. H. G. J..142 (C1.S. Anal.W. H. 30..F. Elias. 859. 5. Chem. 25. M. Scand. R.H.. Eriks. Johnston.177 (C1. Chem. 1957). Org. 28. No. K. 148-156 (1967). Osipow. Chem.. F. Murto. U. 132-135 (1966). 787 (1965).. Dissertation Abstracts 26. Ber.G.. Suomen Kemistilehti B37.G.997. Org. Osipow. Jones. 28. 33-39 (1961). Huber. Chem. Tommila. 1962). 4. 618-626 (1960). King. Chem. 18. Y.J. 123-131 (1961). 260-307) (Sept. D. 260-489) (Oct. C. Pat.E. P. 11.. Tetrahedron Lett. Chem.L.. H-L. Weaver. Am. Chem. Moffatt. Johnson. 3. 78. Bloomfield. E. 1961). J. 1620-1623 (1965). Am.84 85 86 99 101 105 106 109 160 161 162 164 165 166 167 172 173 175 181 183 193 202 203 206 208 211 217 229 232 240 264 272 273 290 291 294 296 302 308 312 321 324 328 329 334 336 342 348 353 154 365 366 367 368 369 372 377 Modena. 1792-1793 (1959). E. Levand. Vol. 144. Hass. H. Kitaoka.S. Soc. 18. Onodera. W. 1966). U. 70.. 28. Landini. 3027-3028 (1965). T. 626.L. 260-410) (Aug. 1957-1970 (1963).

49-50 (1965). Snyder. P. V. Argabright. 389-391 (1966). Hergenrother.E. 517-520 (1966). Am.. F. J. Sahyun. 6412-6413 (1960). 5409-5416 (1965). Beeson. Tommila. 6. J. 84... I.264. Janzen. C. J.T. Org.G. P. 6034-6037 (1956). Shechter.R. J. Org. J. Boyle. C.R... 1966). 10.H. Gardner.385 386 390 391 392 394 396 398 399 402 405 407 408 409 411 423 428 429 431 432 433 434 438 440 442 443 449 450 454 455 459 463 464 467 469 470 471 472 473 474 475 477 479 480 481 486 487 489 490 491 495 496 501 514 Gundermann. 668 (1966). J. 25. No. Hanson. 3972-3975 (1965).J. Angew. Shaw.C..D. 29. Bottner. U. G. 3.J. 3.W. B.D.A. J. 3880-3882 (1966). G. Soc. Friedman.. Chem. Hansen. Cram. H-D. M. 20. Chem. 31. Org.. Chem. J.9) (Sept. Ham. 86. U. 117-123 (1961). Acta Chem. 29. U. Shoulders. J. Chem. 3. Chem.G. Org. Osborn. Farago. 2319-2321 (1966). Gardner.. 123129 (1964). Am. J. J.R. Scand. Org. J. Soc. No. D. Glenn. M. S. 1227-1232 (1966). Tetrahedron Lett. McCrary. T. T. C. Livingston.A. Org. 742-745 (1964). Chem. Org. Ind. Tanimoto. 3. Michelot. Wyart.. Org. & Engr. Comm. 2018-2021 (1964). J. 95! . J.A. Traynelis. D. J. Fuchs. Kornblum.. Bader. W. 1965).C....D. Am. 83. Hofman. R.S. U. J. 5428-5430 (1959). Australian J. G. G.972 (C1.J. Smith. 260-471) (Oct. 2273-2276 (1964). Fennessey. Adams. Y. P. Japan 38. V. W. Chang. Bloomfield. A. U. Chem. Am.. Chem. Schumaker. K. Chem. J.S. 2699-2701 (1964).F.. Org. D. 81. 3233-3235 (1965). Cram. Snyder. Chem. Roberts. Rittersbacher.M. U.830. R. 7. Powers. 1525-1526 (1967). Parker. J.R. 29. H. 260-675. N.S. & Ind. Chem. 8-11602) (Nov. Soc.. Org. 1962). 24.H. Pitkanen. Hardies. A.E. Soc.J. Nace. Chem.024. Chem. Ber.L. E. J.964 (C1.R.362 (C1. 83. J. P. 30. 26. Bollyky. 3. U. E. 30. C. 6250-6252 (1965). McCarty. Org. E.J.E. D.. 7.. 1961). 30.A. D. R.206. F. Rider.. 946-962 (1966). A. 27.R. Ray.014.L.H. D.C. 260-608) (Oct.J.S.499 (C1. Kaiser.R. Baker. C. E.A. Kitano. Miller. Chem. J. A. 2.J..004. Finger.R. T.L. Org. Soc. 17. Chem. 1961).C. P.. Chem. Soc.G.A. Soc. Cunningham. R. 3317-3321 (1965). J. J. Knox. Chem. Rickborn. N. 40.J.. Parker. H.T.. Valicenti. M. J. Dyer.L. G.W. Bull. Ed... 877-879 (1960). 206-644) (Dec. Solar. J... Chem. B. Mac.. 2480-2481 (1965). A.P. 1962). Hergenrother. Schriesheim. Org. Trost. Appel.. Decker. 1961).E. Tommila. 31. Savolainen. A. B.J. Org. H. B. Cardenas.. Russell. R. Holtmann.763 (C1. J. G. 757-758 (1966). 3262-3270 (1964). Acta Chem.C. Chem.C. (London) 1243-1244 (1963). 923-936 (1966). Fukui. 4281-4284 (1961). Tommila. 31. Chem.S. J. R. J. 26522653 (1962).006.8) (Oct.D. 97. Smentowski.. Chem. 1961). 1962). Traynelis. 3. 31.T.K. J. 4037-4041 (1966). J. 31.. 19. 20. Becker.. 937-945 (1966). Am. W. C.S.. Kingsbury.S.629 (C1.. C. Org. Chem.J.S.C.. Chem. Wallace.N. Int. 30. Scand.. 2. 29. 84. E.A. & Ind. Soc. J.C. Chem.E. R. Chem.078 (C1.J.A. R. Lendrat. Bloomfield. Chem.K. Am. Argabright. J. J. Freure. Argabright. f.E.. E. Chem.A. Soc.F. 8. 852-856 (1964).. Bull. C. Kingsbury.5) (Aug.J. Sieck. 31.D. K.. C. Chem. J. Soc.J.. No. Am. R.J. P.. Acta Chem.R. P.. Murto. Oesterling. Soc. Soc. 14.. France 3039-3040 (1966).. J. A. Tchoubar. A. 31. Day. 2919-2925 (1961). 345-346 (1965). S. 3. Soc. Org.W.A. Suomen Kemistilehti B38.R. Knox. Bottini. 1734-1735 (1962). 83...L. Cardenas. C. J. 260-465.... Chem.W..J.266 (C1.. E. Khafaji. B. A. 2962-2973 (1964).A. Fekete. Wood. H. 5. Emerson. R.. 1586-1589 (1965).007. Price. Scand.E.F.. Amonoo-Neizer.L. J. 82. Gorvin.S.. Tetrahedron Lett. Schriesheim. U.061. J. J. Chem. U.. 30. Am. Hofmann.. Chem.. Anonymous Chem. 20.V. Chem. 78(12). H. Booth. Soto. 260-30. F.. Valicenti.. Chem. R. Vona. Chem. Walling.. A.. L. J. No.945 (C1. 260-486) (Apr.V. Org. L. Am. Wallace. 3. Chem.G. 1996-1997 (1966).. J. Chem. J.H. Kruse. Shields. Cram. 2377-2383 (1962). B. J. E. News 50-51 (Sept. 1958). H.. Spillett. 87. Weinstock. Osborn. J. H. J. & Ind. 1773 (1961). Chem. 260-464) (Mar. R. 33. 26. H. 766-767 (1965). J. Am. Webb.

Proc.. J.H. K. Org. Jr. 4112-4115 (1961). 1985-1990 (1963). E. R.. Mann. H. 83. R. 3.. J. Tommila.M. 87. 142-148 (1953). H. 1561-1563 (1964). Chem. A. C.. 30.K. Schriesheim. Cotton... E. D. Chem. Chem.E. Soc. Phys... 3205-3206 (1965).T. D.. 572-577 (1955).H.. Kaufmann. Reddy. Sahyun. Ber. Fuchs. Powers. G.T. 2. 64. Haberfield. 137-146 (1967). Miller..M. Powers. 17. Zitko. 44. Org. Mullikin.R. Chem.R. 2563-2570 (1966)..A. Chem. Am.. Soc. Crown Zellerbach.G. H-J. Comm. N.K. Chem.. 108. 3895-3897 (1965). Am. Bottini. Kornblum. Am.A. Soc. Phys. 84. 30. 1962). A. Soc.. Wood. Ed.. Org. Moye. Chem. 2507-2509 (1957). Kingsbury. & Ind. Chem. C.A.F. Blackwood.B.Ed. 454-456.E. Am.F. Zaugg. 31-37 (1969). Ayres. Wingrove. Bordwell. Elias.J. W. 3688-3696 (1961). Helv. Cram. Jaunin.. 84.g.909 (C1.I. 1651-1652 (1961). 3. Chem... 84. Soc.S.. -1693 (1964). Int. 2895-2903 (1960). Chadde. Rabjohn.A. 3128-3134 (1961). Soc. E. J. 2344-2348 (1962). Elias. Chem. Eades. 94.. E. Hill.. J. Clark. 32.. T.G. C. Gundermann. R. J.G. Heininger. Soto. Terrell. 98.J... Org. 30. Chem.. Michaels. 83.. L..R. N. J. Shih-Lin. Moffatt. J. Chem. 83.. M. H. J. F. J. Chem.B.H. Chem. C. 96! .A. R.. Chem. W. R.028. Am. 31. Chem. R.A.O. H. Gosser. C. J.A. Am. Burdon. John Wiley & Son. Margulies. Dazzi. Kurtz. L.. 77. C. Gosser. Strom. V. P.D. 257-258 (1960).. Russell.. Richtzenhain. Lieser. 2054-2055 (1965). 3731-3732 (1961). Chem. H. Chem. 86. T. J. Zaugg. Arnold. D. Soc. J. 1534-1536 (1960). Jr.. IV. Blackwood. Am. 1353-1364 (1965). Am. 65. 373-379 (1964).. 49. Org. 4. 102. T. L. 79. 86.E. 4011-4013 (1965). M. Data 7.H.. J.K. Kornblum. Neidlein. R.. 1957).T. Org.S. 3890-3891 (1963). 29. Nisbet. N. U. 4155-4157 (1962). 30. Snyder.J. Angew. Chem. 88. Chem..T. L. Ed. Russell. J. H. 1148-1154 (1963). Seltzer. J. 260-478) (Dec. 86. Soc.. Chem. 3. J. 31. 85. D. Chem. J. Chem. J.. J. Chem. 85..W.G. Engr. Wallace. S. J. B. Bloomfield. J. Niclas. I. 113-114 (1962). F. Zollinger. P. J.816.W. J. Kolthoff. Goring. LeBel. J. Francis. N.W. 22. F. J. Org. J. Am. Hamalainen.D. Hofman. A. Bottini.W.C. Soc. J. Chem. Chem. Org. Am. 61.. Bernasconi. Acta. News 35. Am. 2371-2373 (1959). Chem.G. Chem. Chem. Chang. L.. 25. Christ. Chem. Ucciardi.J. 412-419 (1966). Chem. J. Kornblum. Ball. Y. Org. Chem. 26. Morris. Can. Chem. Org. Soc. Long. H. J. A.. Angew. J. Phys.. Cram. Vitcha. Soc. E. M. J. Borgwardt. Smiley.515 517 524 526 538 540 541 544 550 553 568 574 577 578 579 580 581 585 589 592 595 596 599 600 604 606 611 612 613 615 622 624 631 632 634 639 640 643 650 651 652 653 656 664 669 672 680 682 684 685 690 691 696 705 712 714 720 722 Overberger. Chem. Blumenthal. N. 288-291 (1966).J. G... Schear. 49. C. Pitt.A. 83. D. Chem. 505-508 (1965). 100-101 (1962). H.J. Org. J. Chem. Bishop.. Temple. Clark.. Schriesheim. A. J. Chem. Clark. Vol. Jr. Rowe. Am.E. J. O. J. Corey. Soc. Chim. Hausmann.D.G.C. B. J. Am.A. Chaykovsky. Eaton. 9.. Soc. L. Bacon. Rosenbaum.. T. J. 85. J. R. Soc. D. Polymer Letters 3.S. 837-840 (1961). Ledwith. Zaugg. 673-676 (1965). B. Chem.. Jr. Am. Alfredsson. B.. R. Org.. J. J. 1100-1107 (1963). J. Cram. Acta.E. Soc. 630-635 (1961).W. Ber.A. 60. 1867-1868 (1964).. Am..J. Talaty. 1749-1756 (1966). 1159-1162 (1966). Soc. Horrocks. C. 87. 30. unpublished results (Jan. E. Kornblum. J.W.J. W. Hendrickson.. Cisney. 1967). N. A. A. Chem. Soc. S. J. Janzen. J. D..E.. N.F. C. 825-826 (1956).. Helv. R. 980-985 (1961). J. L.J. Phys. Ber. 144 (1964). Chem. 82. Soc. Am. 455-456 (1957). 1345-1353 (1965). 1263-1268 (1963). Mak.. Chem. J. 2725-2737 (1965). No. J. D. 5855-5864 (1966).W. S. 85. 260-533) (Apr.T. D. Int.. J. Soc..J.R.. A. Soc. U. E.A. M. Chem. Ber. C. H. Horrom. Montgomery. B. 591-592 (1966).E. Am. Electrochem. Organic Synthesis Coll. M.J. 699-701 (1957).. Chem. E. 5457-5465 (1964). Eng. 81. Scand. Chem. Corey. J. Acta. Hofmann. D.R. New York (1963).V. J. Am. Cram. Powers.. Chem. 708-709 (1965). A. Dalton. Am. F.. M. J.G. J. Jones. Chem. Soc.423 (C1.. Martin..M.E.J. Kornblum.. J. Chaykovsky. Soc. K. Janzen. 87 (1957). R. 12. R. Rickborn. Am. 17. E. Chem. Cram. 4567-4573 (1962).

Soc.. 24. No. K.. Soc. Series. J. Org. R. Scand. J. Weissman. D. Reynolds.. Tidsskr. Hata. Chem. Jr. Bennett. Org. G. Am. H.B. J..D. Janzen. Chem. Brown. Japan 38. M. 89.A. Soc.. Soc..M.J.. Rickborn. Chem. Commun. W.. F. Steroids 5.C. 1967). 855-856 (1967). 718-20 (1967). Chang. 2416-2423 (1967). E. Soc.R. Hata. C. J. K.. B. . Chem. Org. D. Robbins. Am. 20. 3392-3398 (1964).114 (CO8F) (June 6. D. Brown. J. J. 457-458 (1967). Chem. Downie. Soc. 1963).. 1967). J. Eades. M.. Crown Zellerbach. T. 5. 30... G. Cockerill. M.. Correia.M. No. Org. Chem. Hayashi. J. Chem. J. S. W.D.P.K. L. Am.J. J. Montgomery.C. Manhas. Wada. J.A. Tetrahedron 18. Chem.. A. Chem.. E. Russell. Crown Zellerbach. 3516-3520 (1965).. Soc.. 1966). J. J. F. 26. J. O. Chem. Cisney. 1290-1293 (1965). Chem.L. Margulies.G. J. Chem. Soc. 64 (1967).H. No. Reynolds. 97! ... J. Electroanal. Mateos. Kjemi.R.. Y. Chem.H. Bull. 14.S. Chem. Japan 40. Soc. Nielsen.G. 928. Akutagawa. 3645-3649 (1961). R. Kopecky.. Tetrahedron Lett. Virtanen. Puerta. 25.L.C. J. 3563-3570 (1965).A.M. Chem. S. Glynn. Van Auken. 1960). Suomen Kemistilehti 34B. Chem. 21. 16. E. 3. Katritzky. Saunders. B. Scand.. J. E. 3557-3570 (1966). 32. Chem. 3.E. 20... Tommila. 2862-2864 (1966). 21. Brit.. Soc.. J. D. 1502-1506 (1967).304. K.W. LeNoble. Oda. 2039-2040 (1964). L. Thomas. Acta... 88. J. Whiting. T.. Am. 917-922 (1962). Am. Soc.F. A. 1967).. Am. Y. P.R. Chem. Allen. Chem.C. Chem.F. J.. A. G. 3579-3580 (1964). J. Hasbrouck. Sato. Japan 40. Org. 1225 (1965). J. Cisney. results unpublished (Mar. H...331 (C1. J.. Chem. Chem.D. Yamada. Rao. Miller. 299-304 (1965). Goldman.D. Soc.. J. Miller. Org.E. D. Langmann. Org. S. B. 51. 1965).L. Ltd. W. Soc.M. 3054-3055 (1963). Chem. B. Grenon. B. Chem.. Chem. Wesslen. Am. 2363-2365 (1967). J. E. Bull. Analyst 72. Allen. 55-56 (1964)...H. Hauck.R.. Chem. Sugiyama. DiSanto. Soc.. Advances in Chem. N. Boulton. A. Geels.D. Brown. N. 248-250 (1947). 31.. Advances in Chem.M.. Chem. 112-173 (1965). E-I. 12. Am. H. Crown Zellerbach. G.. 200-201 (1959). J. S. 1678-84 (1967). 1087-1090 (1966). results unpublished (Aug.J. L. Chem. 1685-1690 (1967). 21.. 11. W. Soc. H. 88. Mieno. Ugelstad. Am. J. 334-340 (1966). Soc. Wolford.J.P..M. 32. W. 89. J.J. Bowden. 89. Allinger. Org. Am. I. H. R. J. A.H. Yoon. A. 29. Inorg. Chem. Bennett. K. No.J. Glynn. Graham. A.H. 1202-1205 (1966). results unpublished (Feb.C. Gilbert. 139-143 (1961). Chem. 8.T. 1967). J. Crown Zellerbach. Wesslen. A. R. Hayashi. 86. Inorg. 4396-4397 (1965). Carson.. F. Cram.. 21.H. Manashi. Steiner.J. results unpublished (Mar.W. 87. E. Ball. 89. Wood. T. A.. D. Tetrahedron Lett. B. D.. Sato.. Crown Zellerbach. 85. E. Soc. M. Inoue. Series.B. M. 89.. Chem. T. 1966). 681-686 (1960). Mak. Org. 30. Phys. Lee.F.S. H. T. 4. 713-717 (1967). Gunther. 901-905 (1967). W. W.J. Tetrahedron Lett. 1458-1463 (1966). J. J. N. 1737-1739 (1967). Rottschaefer. Proceed. A. G. W. 1246-1248 (1967). Chem. R. E.H.E. 45. Bull. (C) 971-976 (1966). 3235-3236 (1965). P. Blair. Stewart. 32.. Soc. Jones. Boggs. Brett. Chem. Maggiolo. Akiyama.H. Yoon. Bockmann. M. N. Barton. Gasser. 1464-1472 (1966). 415 (1964). Ghosh. 82.. Froemsdorf. results unpublished (Aug. D. J. Cason. Cram. Courtalds. 1306-1308 (1967). H. Jr. Long. Bemix.F.J. R. Met. J. Am. Dodd. Rhoads.E.M. 12. 10. Pat. Can. C.. Chalmers. Brown... Pettit. Krapcho. Inoue. 88.. J. Roberts. Roberts. Specialties 2-6 (Dec. Soc..J. Jones.S.M. Fritsche. Chem. Oda.. Moye. Am. L. 215-217 (1967). 240 (1967). Senning.C. No.E. 209-215 (1964). R. B. 1354-1358 (1966). Haanaes. 260-607) (Feb. 31.. D. Tetrahedron 22. C.. M. J.H.. Chem.A. Acta.. J. J. 68.C. Buckley. Jeng. H.S. U. F. E. Albright. 947-949 (1966). Crown Zellerbach. results unpublished (Jan. Chem. Strom. No.D. Bergv.A.725 726 728 730 734 737 742 772 773 786 790 794 801 825 833 843 849 872 882 884 885 888 905 913 923 941 942 944 945 947 964 965 982 988 1001 1005 1007 1016 1022 1024 1025 1027 1028 1036 1040 1055 1099 1100 1110 1114 1118 1119 1127 1138 1140 1161 1162 Roberts..

. Sears. Chem. France 1935-1942 (1963). G. Marino. Bacon. Soc. Brit. F. Am. I. J. H. G. Akahori. Haberfield. J.C. Sci. Soc. 1115-1117 (1967).M. J. CA 64 19466D (1966). 5163-5172 (1967). Hill. results unpublished. M. Goheen. Ten Haken. 2960-2963 (1967). G. D. J. J. J. R. Feit. Org.. Soc.. Chem. Shell Res. Ber. Crown Zellerbach. Wallace. J. Chem. N. 22-30 (1960).293 (Aug. Com. C. Am.. Soc. D. Nelson. R. 89. Brauman. N. Chem. unpublished results (Feb. 89(12). 89. AD264. 100.W. E. Dept. G. 4064-4065 (1967). Suhr. D. J. 187-191 (1966). 689. Acta. Dolman..W. Ber. Martin. U. R..C. J. B. Gallais.. Whitstler. Ann. A.M. 38. 98! . J. Allenmark. Am. Y-S. 635. Tetrahedron Lett. H. Evans. J. Ann. S.. Chem. Petersen. R. Kitagawa. 1967). J. Biochem. G. Uschold. 34-47 (1966). Am. Merenyi. R. Kobunshi Kagaku 20 (213). Moffatt. Chem.M. Brauman. H..W. H. J. Fr. 5505-5507 (1967). Kansas Acad. 3510-3515 (1967). 4725-4735 (1967). CA 61 1942E (1964). Cargill.. Am. Jap. G. Chem. G. J. Gmitter. C. Smith.. Soc. Russell. R.. 26912696 (1964). J. 260-30..E.. Chem. Bram.. G. Chim. J. Nicholas. Chem. Nelson. D. 32. Hunsberger. Kamat..C.. Seppanen. J. 3385-3400 (1965).A. H.A. Chem.. W. 24(4). Am. Chem. Zimmerman. Ross. 5275-5280 (1967). Davies.. Kemi. Soc. McDonnell. Crown Zellerbach. 89. Soc. F. 67(3). Landini.L. J.E. Lucas. Soc. Soc. Soc. Chromatog. G. 2570-2575 (1967). L. B.. 28. Chem.636 (C1. Whittle.. Greene. Org. Krull.C.E. Biophys. Am.I. J..L.R. Soc. 759-760 (1967).. M. R.L. Chem. Am. Dillard. 358-363 (1967). M. S. M... J. Am... Mahon.. Suhr. Marino. Bopp. C O7C) (May 10. D. G. Bruggemann. 33-44 (1965). Hayashi. J. 2. Can. Pharmaceutical Soc. Chem.H. Soc. 87(9). 83. Curran.E.. 687. J.A. T. U. Zilkha. 89.. 83. Acta. 121.V. King. C. Ltd. S.. Porter. Org. J.J. Kerber. Arvia.. Sinnreich. F. Rao. Tetrahedron Lett.. F. Illuminati.O. (52).H. Horner. Bazan. 2133-2136 (1961). 89(21). Chem..J. J.S.. Bennett. N. J. Chem.H.. D. Earl. Y. S. Chem.984. 261-263 (1964).A. Illuminati. Am. Allenmark. D. H.S. K. 941-942 (1964).L. Grunewald. S. Ltd. Am.J. Watanabe. Peterson. Soc. Sands. 1097-1107 (1964)..A. 67(4).. Manthey. Chem. 5902-5911 (1967). E. 90 (2). White... W. Marino. Soc. Siegfried.J. J. 32. 89. Soc.D.F.1172 1214 1229 1233 1234 1237 1238 1239 1240 1257 1262 1268 1271 1273 1360 1373 1383 1417 1455 1474 1501 1503 1505 1508 1515 1521 1544 1558 1579 1591 1593 1612 1638 1638 1651 1668 1687 1694 1711 1721 1728 1744 1749 1752 1758 1759 1774 1787 1798 1805 1823 1826 1880 1924 J.T. Lo G.M. Chem. Chem. Soc. 11. 491-492 (1968)..A.F.C. Chem. Tech. Kahl. Spectrochimica Acta 21. 247-260 (1967). Nelsen. 175-182 (1965). Nichols.D. CA55 4401 (1961). CA 63 17825C (1965).E. Genel. MacGregor. Howards of Ilford.G. AEC Res. Bull..T.... 81. Am. Tetrahedron Lett. Chem.M. Kornblum. J. 1961). Holy. Cisney. Ruffini. Shaw. ABIPC 36. Pat. L. Am. J. J.E.-J. (8)..G. D. 89. D. Am.. 45. Yakugaku Zasshi 86(3). & Dev. Am. 3. E.K. Snow. 5740-5742 (1967). J. Illuminati.W. 89.F.M. O. Soc. 5-10 (1963). Chem. 2845-2846 (1963). 41. Data 9(2). 85-89 (1965). N. Chem. Ray. Am. Ann. 336-338 (1967). J. 26. Chevli. Trans. P.D. Ross. J. Rev.. Ark. 8842..8) (May 16. Musser. 109-117 (1965). Pat.W. J. H.D. 5714-5715 (1967). Kingsbury. J.J. W.G. J. Chem. 89.. Report DP-389 (July 1959).I. Soc. J.S. Nielsen. 5774-5784 (1959).H.... Tetrahedron Lett. G. W.R.L.. Soc. E. Chem. Tien... Electrochim. Sleiter. J.C. A..J.J. 1. D. R. R. Montanari. Calligaris. 111 (1959). J. Am. G. 911-927 (1967). Eng. Arch.R. Chem. 86. Serv. J. Pond. G.. B-A. J. A. 36783687 (1961). Kolling. G.O. 1956). G. Hirose. J. P. 4099-4103 (1964). Parikh. Chem. 910-911 (1966). 86.. P. 90 (2). T. G. Sweat. Venkatasubramanian.. 3518-3521 (1967). 490-491 (1968). Barry.. D. 5516-5517 (1967).419 (C1. Scand. R.. Epstein. 20. Niclas. L.M. M. Am.. Friedman. T. Giordano. M. Nature 196. 4069-4072 (1967). Cellular Plastics 1 (1). Oth. Voigt.E.. Burdon.326. Shilling. 13. XXVII-XXX (1965). P. 872.C.S. Ukai. Chem. S.. 1963). Cram. J. 187-195 (1967). Ritchie. Rickborn. 372 (1962). 98. D. J. D. P. 741-747 (1966). S.J. N. 3516-3518 (1967). J. Lyman.J. Appita 19(3)... 635-639 (1964).G. Soc. F. Bursey. 89. Schroder.

418. Djerassi. Musser. Chem. Chem..E. J. Hampson. 3758-3762 (1968). Toland.. Chem.C. Soc. Reports on Sulfur Chemistry 5(1). Polym. Soc. Farbenfabriken Bayer A. Joe.J. J.. G. Chem. H. Delhoste. Makromol.980 (C1. 46. 3. Soc. T..3) (Feb.O. Berger. J. J. H. J. Normant.P. J. 260-465) (July 5. S. K.Q.T. Soc. L. Chem. Pajunen. 29..C.. 7. 1000-1008 (1969). Chemie 119. Steroids 3. 492-496 (1968). 90. Brown.1942 1946 2007 2013 2035 2075 2125 2140 2151 2189 2194 2196 2218 2223 2239 2265 2323 2327 2343 2371 2463 2492 2520 2525 2532 2565 2566 2567 2583 2589 2597 2643 2652 2749 2760 2765 2769 2779 2783 2842 2887 2896 2900 2915 2924 2940 2969 2980 2987 2988 Szmant. Chemists 45(1).J. 73.W. Soc. D. Photobio. D. 41(2). Kornblum. J.. 557564 (1969). J. A. CO7C) (Sept. 6809-6813 (1968). 4220-4226 (1968). G. Shorter. J. Am.A. 1968). Pattison. Buckley. Whitaker. Kawai. 90. Org. Chem. P. Mackie. Nozawa.. R. Kreevoy. 3495-3498 (1969). A. B. Gaines. Ed.088. Schmid.. 3. Clarke... Lamaty. 90. Ger. Hutchins. 3. Int. N. Jr. U. Anderson. 1. Org. R.L. M. 1213-1218 (1968).. Chem.S.. N.M. 90. Chapman. 1759-1766 (1969). Am. B. N. Soc... Cooper.S.L. H. 1960). 260-369) (Apr. M..L... Chem. J. C. Agr. English.F.. Sillis.J. Chem.. Chem. 1966).. W. Topsom. 53-66 (1970). D. 1969).H. Fierce..S. Angew.A. 47. 2181-2186 (1968). Westrum. 59-66 (1962). J. M. Chem. J.. J.461. 511-512 (1969). A. 47. 425-426 (1968).. J. Anal. 1468-1470 (1968). E. 15.. Acharaya.671 (C1. N.D. 260-51. P. H.. Am. Can. R.428. A.. Suzuki. D. Pat. 172-175 (1968). W. Buchta. Org.. J.. A-1 6. F. 415-420 (1968).L. Chem. 1968). D.W.. B 581-588 (1969). Carbohydrate Res.. T. Jr. G. Am. Perlin. J. Weber. Chem.. D. McCasland. Soc. 1784-1791 (1968).E. 8(11). 249-251 (1968). J. Shapiro. N. A.H. Fitzgerald. 1969). Bonthrone.. Winteler. 33. K. Comptes Rendus 266(15). Harriss. Soc. Kornblum.. 91. 1211-1212 (1968). T. U.. W. Cram. W. R. Leibel. J... Soc.W.M. Chem. Hoffman.E. M. Chem. Holy. U.. J. D.W. J. T.S. J.259. Chem. Tanake. S. Durham. S. Davies. 2198-2200 (1968).A. R. J. J. 682-687 (1969). J.J. Dear.574 (C1. (6). Jurch. Anal. Hoke.G. R. Comm. 33. A.. 622-626 (1963).B. C 1202-1204 (1969). M. L. P. Milborrow. M... Ratajczak. D. Yamamoto. Evans. S. 260-491) (Aug. S. R.. D.156 (C1.. Faraday Soc.. Suomen Kemi 41(5-6). Sci. Smith. C 417-424 (1969). F. Snow. K. Japan 41. Chem. R.. Goethals. Oliveto.J. Comptes Rendus 266(19). Crowe. 7(2). Klein. Photochem. E. Sugiyama.S.C. Chem..A. Katritzky. R.. Kashimura. F. Kulak.V. 2015-2019 (1969). Trans..O. Morley. Gustav.. H. Brenner. J..J. 24. 260-475) (Dec. 301599! . 6219-6221 (1968). A. J. Musser. J. 1309-1317 (1970).. N. Chem.F. E. W. Am. J.. Hirano. R. Phillips. Chem. Chemerda.W. Soc. Bull. D. J. 120-128 (1968)... Chem.J. Chem. Can. R. J.F. L.T.S. Chem.D. 1180-1182 (1968).R. E.390.H. Helmer. Schulz.. U...L. 34(10). 2375-2384 (1969). Onodera. 34(8). Cornforth. E.S. Driscoll. A.H. 6221-6223 (1968). Howard. Thurman. 276-285 (1968). 1969).. 3. Phys. 64(545). Tommila. Legatt. Liveris. G. T. H. R. Oae. 1020-1021 (1969).. Soc. A.O. Itoh.646 (C1. Sletzinger. Chem. Can.M. J.C. 12. J. Ramey.D. Soc. 260-590) (June 25. G.G.M. Landgrebe. Haenni. Kollmeyer. Handley. G. Can.L. Z. N.. M. Neuheiser. Swiger.. 3. Koharski... Delhoste..W. J. Kohler. Swiger.. Am. A. Chem.S. J. Akutagaawa.T. U. Quart. 936-941 (1968). Garnsey. Johnson. J. Cram. J. Am. Org. Manthey. Off.W.W.L.H. 18.J.A. J. Tetrahedron Lett. 1206-1219 (1968). J.M... R. Clever.. W.W.. B 195-200 (1969). G. H.B. Keogh.G. Chem.R. R.A.. 16491654 (1969).L. Brownlee.. M. Scanlon. W. Manthy. W. 85.E.H. C. E.. Chem. G.. Lamaty.-G. M. M. M. Earl.H. G. Am. Chem. 74... Assn. 91. Soc. Comm.A. Vanterpool. J. Naumann. S. Abramovitch. Firestone.M. 47.D. Soc. 40(14). Phys..P. H. J. Spillett.T.. J. 1945-1954 (1968). U. Jr. H. D. Chem. Linschitz. Cram... Am. Jr. J. C.. Dahlgren.. Baker. Breazeale. Lee. Cree.E. Morgan.R. 40. Pirog.186 (C1. Holy. N.T. Reinhold. A.G... Chem.R. Simon. 6. J. D.. Earl. Chem. Herzog.G.. Williams. J. 91. Soc. J.... Prue. 3.. 381-382 (1969).441.360 (C1. Jr.. 183188 (1964). Gomez.C.

M. H. Am.. Miller. G. L. Chem. Davies. 15.D. Baird. Anal. Hassall. Biezais.W. 92. S. F.S.M. J.A. H. Terrell. C. P. V. Bigon. 4060-4065 (1969). Markley. Schleyer. Kelsey. J.W. Soc. 930-935 (1970).33 (1970). 34.W. Sulfur Chem. J. T. E.. Org.K.. H.. Snyder. Chem. K. N. Bartsch. A. Chem. Chem.C.R. Schaaf. 3161-3164 (1970).W.R. 426-439 (1970). Chem. Kruger.C. Soc. 41(6). Am. Fry. Org. Soc. S.M. Kharasch. M.C... Wheelwright. D. 1970). Chem.-I. Beaucaire.. Ed.. Am. Chem. 228-230 (1970). W. 6695-6696 (1970). Org.A.R..V.W. (D) 338-339 (1970). 3(2). Rao. D. Kharasch. J.D.P. B. Chem.V. 1337-1343 (1970). Koenig. Feit. Y. G. Soc. Am. Kennewel. 35. D. Am. Pannier. C.G. R.R. Ber. Chem. Burton.M. Tetrahedron Lett. G. 1711-1712 (1970). 20-22 (1970). Yoon.812 (C1. Beninate. Soc. Vanderslice. Org. J. Pollack. C.. Kemp. 4771-4777 (1969). Szmant. (D) 1172-1173 (1970). H. 519-522 (1970). Heim. Chem. Bender. 3923-3926 (1969). Gibson. J. N. K.J. T. Takase. Chem.V. 1725-1728 (1970). Bell. Org. P. 6252-6259 (1970). Chem. J.M. Org. F. R. T. Schneider. N.I..S.L. Chem..E. Iriuchijima. D. Chem. Brown. Org. N. N. Baer. Nturforsch. J. Chem. 4. 92.1637-1646 (1970). Fishman. Huber. Paul.. 35. 92. P. 3275-3281 (1970). Soc. Soc. F..W.M.A. Weinshenker. 92.. Org.W. Chem. Earl. Chem. 35..A.R. Soc. 34. N. Rudy. N.R. 3240-3243 (1970).S. M.. 936 (1969). 3.c. 1334-1338 (1970). J. Sulfur Chem. Boylston. S. W..D. 92. 34. Am. Chem. Org. 47. J. J. 35. 3(2).. H. Cruickshank.. J.. Z. 2418-2419 (1970). D. B. J. Chem. Reese. Reese. L. D. Org. Indian J. Chem.. Blakrishnan. 422-426 (1970). J. 103. R. W. Bennett. Soc. Janzen. Rep. C. Org.381 (C1.. A.. Org.K.. M. Z. Chem. Chem. 30-32 (1970). 149-158 (1968).H. Reimlinger. Soc.K..F. Rep. Lorkowski. Filler. Naik.R. Soc. 3382-3389 (1970). J. Stuchal. J.480. Bartsch.M. 25. Evans. J. B. J. J. 1016 (1968).. S. J. Org. H. 4262-4264 (1970).H.. W.J. Chem.M. 311. Pruss. D.. C. Cook.S.L. Bingham..S. Am. U.. Org.B. Orvik. Ber..C. Chem.. Stalick. Soc.S. Brown. Yamatani. H. R.W. J. Happ.D. J. Chiusoli. Stein. J. Chem. J. 1969). Shaw.L.B.G. Quart. Chow. MacGregor. Soc. 103. Am. G.. 92. 1969). Chem. Am. D. 35. Irvine. Yoon. Soc. Miller.T.N. Miller. Dodd. 35. N. J.. 3.. Soc. Bottaccio. Am. N..A.P. J. Bigley. Chem. R.. Hanessian. M. R. J. 35. Kornblum. J. J.H. Bunnett. K. J. F..L. B. Synthesis 1. Chem.. results unpublished (Sept. Johnson.. Prakt. 2417-2427 (1970). Harris. Venkatasubramian.B. Soc.A.J.. C 1803-1807 (1969)..W. Roth. Chem.D. J. J. 35. 35.F. Farr.. G. E. C 1873-1879 (1969). Soc.. J. Rines. Am.F. W. Chem. Chem.M. (B). Bauld.. P. R. R.. Woerner.H.. U. J. Pinnick. 1804-1806 (1970). E. J.G.. W. Chem. Tsuchihashi.E. Klabunde.F. 35. Org.W. J. 92. Synthesis 588 (1970). G. J. 1714-1715 (1970). M.. Snyder. 5513-5514 (1970).. Kelly. Swiger. Monahan. Crown Zellerbach. Chem. Corey. Heindel. Erman. H. 7190-7194 (1970). Jacobus.. A. 91. Rabjohn.M. 35.. Soc. J. Chem. 35. Spehar. Tallant.S. K. K. Soc. Stuchal. D. Harbert. Kornblum. Cavies. W.. Org. Chem.3009 3033 3048 3049 3112 3142 3148 3152 3178 3215 3217 3241 3247 3248 3249 3272 3356 3360 3368 3376 3384 3386 3387 3395 3398 3399 3429 3433 3445 3447 3456 3481 3482 3490 3503 3506 3519 3572 3584 3602 3631 3653 3660 3662 3686 3707 3721 3743 3766 3816 3820 3827 3830 3853 3022 (1969). C. 8-120) (Nov. W. Chem.... 7161-7167 (1970). R. 750-756 (1970). C. J. Quart. Bergman. H. 92. 147-148 (1968). R.260-609) (Nov.C. 80-83 (1970). Butterworth. J. Chem.. Yasunami.. 5977-5981 (1970). 92..F. B. V. J. J. 92.. G.H. 3795-3796 (1970).A.J.. J. Truce. 8.. Am. H. 1908-1917 (1970). 3942-3948 (1969).. R. Arora. Girgensohn. Raber. 566-567 (1970).S. R. N. Chem. Chem.476. 1627-1632 (1970). N. J. Org.. S.A. J. 35. M. Chem. R. 835-838 (1969). 100! . D. F. Whitaker.. 56755677 (1969). Ber. 2816-2820 (1970).. 92.. Chem. 2553-2554 (1970). 103. 91. J. Am. E. (B) 23. 35. H. J. Pilato.J. Synthesis 70-88 (1971). Org. Rao. Weiss.. Am. 35. J. Sucrow. Tetrahedron Lett. Fahey. Bartsch. 92.

20. 1941-1952 (1971). Am. R. 803806 (1971).J. Brimacombe. C. Hutchins. Warne. 226-227 (1969). Bowden. Chem. Cable. 403-406 (1971). J. R. 951-952 (1971).L. U. J. J. P.H..J. pratt. Dunn. Schneider. J. 266-268 (1971). Lourens. 1771-1778 (1971). Chem. J. 178-183 (1971). Bennett. A.. Org. D. Chem. 891 (1970). Org. Fry. V. 1585-1592 (1971). Bowden.K. J. Chem.. Baumann. Soc. R. Gullotti. Soc. Marshall. Am. Soc. I.R.. A.R. Soc. Luttringhaus. 36. Chem. Cook. Chem. B. J..O. 14. 260-622) (Apr.C. O. C. Venezky. Org. Haddock.M. Reimlinger. T. Intern. Chem. G. Simonik.. N. W. 12. Am. Kirby. J. Davies. 318-322 (1971).. D. Chem. Webb. Jr. Hagedorn. 36. Soc. R.. Stocks. Kelsey. Gilmer. A. Arora. Walters.I. Soc.. Poutsma.C.L.A. A.M. (D). N.M. R. S.F. CO7C) (Sept.. Chem. Chapovskaya. Chem. Chem. Waite. Chem. Sherrod.A. Muchowski.S. 3278-3283 (1970). Ed. (B). J. M. Crown Zellerbach. Steyn.. T. Bradshaw. 5309-5311 (1971). K. R. Synthesis. U. R. Synthesis. results unpublished (Nov. R. 1969).P. Soc. E. Golab. 332-333 (1971). Soc. T. Chem. 93. 27. J. Seree. S. J. J. 93. Crown Zellerbach.R.J. S. Zefirov. Djerassi. (D). W. Bruice. Lawson.. S. N. 93. J. Chem.. Dalton.G. Bruice. Kolesnikov. results unpublished (Aug. Bergman.. J. J. Chem. 3905-3910 (1971). Tetrahedron Lett. L... Isele. J. Chem. 46. N. Synthesis.. 971 (1971). Melton. Snyder. J. CA 71. 105-110 (1971). Chem. De Roch. P.H. Mantione.. Boulton. J. Soc. J. Pines. 93. Cohen.. Ber.. (D).S. Chem. Bradshaw.P.B.. Org. 93..F. Bull..724 (C1. 36... Soc. C. R. Hutchinson. 36.B.F. Chem. 4363-4366 (1971). J.. 332 (1971). P. 2299-2301 (1971). D. H. Soc. Katritzky...M. Chapovskaya.A..540.K. Org. E. (C). Chem. Cook. S. Binger. Price. 49. F. Chem. M.. Soc.M. Chem. M. Org. 80944Q. B.S. 36. H.E.H.B.S. 2023-2028 (1971). Taranko.. 236-248 (1971). Crown Zellerbach..H.. J. Bennett.. 877-882 (1971).284 (C1.A. K. D. J.506. J. Anal. Bhalerao. Tech. Zefirov. K. Perry.. 93. Crown Zellerbach. J.V.. H.L. Marshall. Norris.B. J.J. Am. J. Org. 36. Maryanoff. Ibarbia. Shepard.G. 2129-2132 (1971). J. Parker. Britton. P. Chem. Milewski. 5839-5845 (1971). Russell. C.S. Shepherd. J. Org.K. Org. Hueper. J. Menguy. R. Ugo. K. 2652-2656 (1971). J. Bennett. Panek. Chem. (C) 1878-1884 (1971). J. Jr. R.. 3. Mantione. Angew. 1765-1770 (1971). Ed. J. M.G. 36.. J. Mostashari. French Pat. 5725-5731 (1971). 93. 1925-1940 (1971). 93. Kruger. (C) 637-642 (1971).M. C. T. G. Holford.R. R. Jr.. 1784-1792 (1971).J. E. Pines.J. Slezinger. 1969). A.. Ind. Jacobs. Engl. 1. 1949-1951 (1971). Soc. Hales. 101! . Karady. M. Soc. Org. J. Chem. 314-317 (1971). Dutta. III.. 396-398 (1971).R. Am. J. Ly. Che. Rua.. J. Colonna. 34. 9. Chem.. Neuland. Soc. Stalick. 334 (1971). 8.H. I. Bergman. J.. L. Chem. 36. J. Ono. A. Pietrzyk.3875 3885 3920 3921 3922 3925 3931 3951 4018 4026 4037 4046 4048 4058 4059 4066 4068 4077 4093 4098 4110 4123 4126 4128 4136 4175 4176 4180 4235 4249 4257 4258 4261 4262 4278 4311 4333 4339 4349 4355 4360 4382 4384 4392 4425 4436 4452 4467 4492 4520 4521 4523 4524 4562 4573 4600 Franck. Chem. A. results unpublished (Nov. Synthesis. Org. P. V.H. J. Bowden. Am. 1970). Soc. 1314-1317 (1971). Chem.L. Chem. Garbers.G.A.. 103. Chem. J.. Rapaport. Synthesis.H.. 698-702 (1971). Chem. H. Chem. DeWet.E. Anal. 43. Soc. 242-243 (1971).C. Chem. C. 297-303 (1971). Chem. 1968). K. 322-323 (1971).H. 2843-2846 (1971)... J.A. Birch... 1245-1246 (1971). J. J. L.J. J. 1252 (1968).D. (B). 36. Chem. Farnum.C.L. 1970). J. Chem.. J. Japan 44. B.. S. Org. Chem. R. J. Hoffman. 43. J.G.. D.. Angew.F. Can. Org.. G.G. N. Chem. Rao. Soc. 36. E. USSR 4. 1004-1011 (1966). Engl. Ghosh. 93. (B).. R..F..M.. McMurry. Chem.. Linder. Soc. S.F.T.W. 1369-1372 (1971). (B) 85-89 (1971).S. 567 (1970). G. G. 36. Am. Org...S.L.. 14. 1001-1002 (1971). K. E. 10.S. J. 440-450 (1971). Weiss. Chem. Chem. U. S. Koester. Petersen. R. Orle. D. D. Chem.M. Soc..k P.B. Intern. T.H. J. 36. 2269-2282 (1971). R. D. A..G. Augustyn. Soc. (C). W. Lazar. Soc. Hales. Tuemmler.. Wooldridge. J. J.S. Am. J. Am..V. Soc (C). 1968).A. Schlessinger. (B). T. results unpublished (Jan.

649. Organic Sulfur Compounds. Gagnaire. CA 73.H. 863-873 (1972).. 1970). Johnson.. Chem.. 207. Ferrar. Advan. 2998-3013 (1972). 83.. Martin.. P. W. Kingsbury.W. Chem. 3951-3960 (1971). J.V. New York Oxford. Polymer Sci. A. Rapaport.p.S.P.. Wang. Perkin I Trans. Am. L. McKinley... M.655. Cass. J..S. Chem.W. C. Schmid. Chem. G. 94.-J. U. A. Rakshys.E..A. R. Khim. Carter.B. 50. Bohlmann.. M. F. Symposium Publication Division. C. Dalton. Hewitson. 1972). S. C. 1820-1821 (1970).R. D. J. Patent 3. Ber. Hortmann. S. Scand.. K. Oxidation of Carbohydrates with Dimethyl Sulfoxide-Phosphorus Pentaoxide. J. Chem. 94. Marino. B. Robert.J. Soc.R. E. Doucet. D. 36. Bradshaw. Chu. P. D. A. CA 72. K.. 110777C. Johnson. D. S.M.. Ber. P. J. Y..G. Soc. Chem.B. Berger.S. Can. Pfitzner. Japan..G.CA 74. 4891-4892 (1971). J..N.T. 55764Q. 1501-1508 (1963). 94. Ponti.S.S.. C. 3153-3159 (1972). 14.. Kluender.. Patro.Y. P. Higginbottom. Moyer. T. 3861-3869 (1971). 37. Chem. 102! . K. CA 73 98306X.. Synthesis.E. Kroposki. Roy. Margaretha. Penner. G. 331-336.N.C. Wharton. P. B.N. Olofson. 170-182 (1961).. E. Onodera. Arad. Chem.. 4181-4194 (1971). Chen. Gillard. 3509-3516 (1971). 76458H.. New York and London (1972). Komatsu. M. 13377X.642. R. R. 3152-3154 (1971). E. J. J.W. 6. Chem. R. J.A. P. A 321. P. Snyder. 6141-6151 (1972). D. M. J. J.A. 102-106 (1972). Chem. Phys.. 77-82 (1972)..H.K. R. CA 72. Bullock. 134-135 (1972).. Chem.. J. London. R.. D.887 (C1. C.E. Farnham. Academic Press.W. 1072-1080 (1971).. J. Wassiliadou-Micheli. Ber. R. Heine. (London) 253-254 (1971).. p. Bakke... H. 598 (1971). I.1098-1101 (1971). J.H. 111854D. Monatsh.R. Soc. Chem. Bates. Commun. Tandara. Am.. 97-98 (1972). Soc. Vol. D. 34-38 (1972).C. J.. Toriyama.S. Bondinell. P. Chem. Fomin. Levy. Ser..8) (Mar. C.496 (C1. (London) 895-896 (1970).00. AM. Org. J. CA 73. N. W. Am. 560-562 (1972). Sundin.N. Shields. J. Olofson.. Acta. kamprath-Scholtz. Wolkoff. 1181-1186 (1972). 70. 15. 13. Rigby. zu Reckendorf. South. 2415-2427 (1967).A. U.C. 9. D.W. Org. Rapoport. Casey. N. U. J. 260-534 E) (Feb. Tetrahedron Lett. J. L.. 37. J. Org. T. McLoughlin. 35746G.. Zh.W. U. 105. Buhmann. K.4602 4636 4651 4653 4669 4699 4704 4739 4748 4755 4767 4772 4775 4776 4792 4802 4812 4815 4817 4820 4846 4891 4892 4898 4906 4907 4910 4920 4934 4945 4972 4987 5033 5038 5116 5118 5124 5185 5192 5244 5279 5296 5300 5339 5435 5459 5481 Chen.L. Hales. Kharasch.. D. R. Chem. White.. Chem. J. M. Bravo. 425-443 (1971).. Hammond. Chem. Commun.. Bamford. P.343 (C1. 105. Soc.P. J... M. 37. Soc. Chem. J. Org.N. Fiz.M.C.H. Am. R. K. C...G.. Tetrahedron 27. Ranky. CA 76. Chem. Radhakrishnamurti. 37. Ind. 16 B 41) (Jan. Org.S. 797-801 (1972). 686-695 (1972). Soc.. Yelland. Soc... Synthesis 664 (1971). Chem. Chem. 361-363 (1970). Miller. 1. Chem. Chem. B. Kamigata. Marino. J.V. Chem.. Y. 322-324 (1972)... 105..-H.O. 249-250 (1972).H.F. W. 260-634 R) (Apr. Minato. A-1. N.A.H.E. Whistler. Dimethyl Sulfoxide. Chem. Chem. P.. J. Thrower. CA 73. Lerch. H.. J. Proc... Yan. Biochim. Org. P. Kashimura.. Methods in Carbohydrate Chemistry. G. Soc. Biophys. Org.. 1970). G. Gurdzhiyan. I. E.A. Tetrahedron 27.D. Japan 44. 250-465. Jr. J.. 11..G. Furukawa.M. 37. Haszeldine. 2051-2052 (1972). 3521-3531 (1972). D. Roberston. 556 (1971). Org.B. zu Reckendorf. Patent 3. A.. A. A. 76. Pergamon Press. Neuman. Cramn. Jackisch. Shima. Kurihara. 1972). J. Van Bostelen.C. R.666 (C1. 37. B.C. Chem. Org. Jefford. 36. Gregory. 21221Z.. N.. R. L.-T. H. 44. Synthesis. Krull. 441 (1971). Chem. Soc. Tanner. Liu.P. Jr. Nelson. C O7 C) (Aug.. 4195-4208 (1971). J. VI. Offen. 25.H. N. Friedman. Tipping. Paris..D.. D..959. U. Chem. Bull. Claus. Potter. Ger.748 (C1. Chem. Ind. 1972). V. BeMiller. W. R. J. R. Moffatt. Acta. Peschel.Soc. Y. Commun. Gaudiano. A. 94. 5.. C. Vol. Martin. 3187-3195 (1972). 362-367 (1972). Schilling. Indian J. Patent 3. Rodebaugh.E. 285-388 (1969)..E.C. J.K. 102. U.P. Vavra. H. Vofsi. Durst. Synthesis. Rees.

5488 5526 5551 5587 5594 5613 5622 5630 5635 5642 5663 5800 5834 5836 5843 5846 5864 5912 5969 5971 5980 6026 6028 6079 6098 6102 6163 6172 6192 6215 6234 6243 6268 6287 6293 6315 6325 6347 6378 6398 6460 6463 6474 6477 6496 6502

Morisaki, S.; Baba, N.; Tajima, S. Denki Kagaku 38, 746-752 (1970). Nazarova, N.M.; Freidlin, L.K.; Kopyttsev, Y.A.; Varava, T.I. Isv. Akad. Nauk. SSSR, Ser. Khim. 1422-1424 (1972); CA 77, 100943T. House, H.O. Modern Synthetic Reactions, 2nd Edition, W.A. Benjamin Inc., Menlo Park, 682-691 (1972). Haga, J.J.; Russell, B.R.; Chapel, J.F. Biochem. Biphys. Res. Commun. 44, 521-525 (1971); CA 75 86543N. Schoberth, W.; Hanack, M. Synthesis, 703 (1972). Benius, U.; Bergson, G. Acta. Chem. Scand. 26, 2546-2547 (1972). Balakrishnan, M.; Rao, G.V.; Venkatasubramanian, N. Tetrahedron Lett. 4617-4620 (1972). Freidlin, L.K.; Nazarova, N.M.; Kopyttsev, Y.A. Izv. Akad. Nauk. SSSR, Ser. Khim. 201203 (1972); CA 77, 4634X. Liu, M.T.H.; Toriyama, K. Can. J. Chem. 50, 3009-3016 (1972). Gloor, B.; Kaul, B.L.; Zollinger, H. Helv. Chim. Acta. 55, 1596-1610 (1972). Rylander, P.N.; Karpenko, I.M.; Pond, G.R. U.S. 3,694,509 (C1. 260-578) (Sept. 26, 1972). David, Estienne, J. Brit. 1,219,599 (C1. C O7C 27/12, 45/34, 51/32) (Jan. 20, 1971). Belanger, A.; Brassard, P. J. Chem. Soc. Chem. Commun. 863-864 (1972). Johnston, D.B.R.; Schmitt, S.M.; Firestone, R.A.; Christensen, B.G. Tetrahedron Lett. 4917-4920 (1972). Capozzi, G.; Modena, G.; Ronzini, L. J. Chem. Soc. Perkin Trans. I, 1136-1139 (1972). Anderson, D.J.; Horwell, D.C.; Stanton, E.; Gilchrist, T.L.; Rees, C.W. J. Chem. Soc. Perkin Trans. I, 1317-1321 (1972). Bowden, K.; Cook, R.S. J. Chem. Soc. Perking Trans. II, 1407-1411 (1972). Hofmeister, H.; Laurent, H.; Wiechert, R. Ber. 106, 723-726 (1973). Rao, G.V.; Venkatasubramaniam, N. Aust. J. Chem. 24, 201-203 (1971). Buchta, R.C.; Evans, D.H. J. Electrochem. Soc. 117, 1492-1500 (1970). Norris, R.D.; Binsch, G. J. Am. Chem. Soc. 95, 182-190 (1973). Gould, R.F.; Schulze, S.R.; Baron, A.L. Advances in Chemistry Series 91, American Chemical Society, Washington, D.C. 692-702 (1969). Kruger, H.-R.; Weyerstahl, P.; Marschall, H.; Nerdel, F. Ber. 105, 3553-3565 (1972). Hirano, S.; Kashimura, N.; Kosaka, N.; Onodera, K. Polymer 13, 190-194 (1972); CA 77, 50489B. Jacobus, J. J. Org. Chem. 38, 402-404 (1973). Krapcho, A.P.; Lovey, A.J. Tetrahedron Lett. 957-960 (1973). Paquette, L.A.; Meisinger, R.H.; Wingard, R.E., Jr. J. Am. Chem. Soc. 95, 2230-2240 (1973). Stetter, H.; Schreckenberg, M. Tetrahedron Lett. 1461-1462 (1973). Michelotti, F.W.; Jordan, J.M.; Cook, N.P. U.S. 3,728,400 (C1. 260-609A) (Apr. 17, 1973). Sato, K.; Inoue, S.; Ohashi, M. Bull. Chem. Soc. Jap. 1288-1290 (1973). Bartsch, R.A.; Pruss, G.M.; Bushaw, B.A.; Wiegers, K.E. J. Am. Chem. Soc. 95, 34053407 (1973). Bashir, N.; Gilchrist, T.L. J. Chem. Soc. Perkin Trans. I, 868-872 (1973). Iriuchijima, S.; Tsuchihashi, G. U.S. 3,732,318 (C1. 260-607) (May 8, 1973). Yankee, E.W.; Badea, F.D.; Howe, N.E.; Cram, D.J. J. Am. Chem. Soc. 95, 4210-4219 (1973). Poupko, R.; Rosenthal, I. J. Phys. Chem. 77, 1722-1724 (1973). Kabuto, K.; Kikuchi, Y.; Yamaguchi, S.; Inoue, N. Bull. Chem. Soc. Japan 46, 1839-1844 (1973). Cox, B.G.; Parker, A.J. J. Am. Chem. Soc. 95, 408-410 (1973). Marshall, J.A.; Faubl, H. J. Am. Chem. Soc. 92, 948-955 (1970). Bartsch, R.A.; Shelly, T.A. J. Org. Chem. 38, 2911-2913 (1973). DeJonge, C.R.H.I.; Hageman, H.J.; Huysmans, W.G.B.; Mijs, W.J. J. Chem. Soc. Perkin Trans. II, 1276-1279 (1973). Anderson, E.; Fife, T.H. J. Am. Chem. Soc. 95, 6437-6438 (1973). Hajos, Z.G.; Parrish, D.R. J. Org. Chem. 38, 3244-3249 (1973). Broxton, T.J.; Deady, L.W. Tetrahedron Lett. 3915-3918 (1973). Cleve, N.J. Suom. Kemistilehti B 45, 385-390 (1972). Ibne-Rasa, K.M.; Tahir, A.R.; Rahman, A. Chem. Ind. (London) 232 (1973). Barrow, K.D.; Barton, D.H.R.; Chain, E.; Ohnsorge, F.W.; Sharma, P. J. Chem. Soc. 103!

6509 6510 6543 6572 6593 6613 6627 6648 6659 6671 6672 6674 6691 6692 6713 6785 6815 6818 6822 6825 6830 6831 6847 6878 6937 6947 6970 6971 6972 6988 7022 7028 7031 7044 7047 7071 7073 7080 7104 7108 7115 7153 7156 7158 7173 7184 7196 7205 7229 7234 7255

Perkin Trans. I, 1590-1599 (1973). Gordon, J. E.; Chang, V. S. K. J. Org. Chem. 38, 3062-3064 (1972). Klein, J.; Gurfinkel, E. Tetrahedron 2127-2131 (1970); Synthesis 704 (1972). Findlay, J. A.; Kwan, D. Can. J. Chem. 51. 3299-3301 (1973). DiNunno, L.; Florio, S.; Todesco, P. E. J. Chem. Soc. Perkin Trans. I, 1954-1955 (1973). Coates, R. M.; Chung, S. K. J. Org. Chem. 38, 3740-3741 (1973). Pilgram, K. H.; Medema, D.; Soloway, S. B.; Gaertner, G. W. Jr. U.S. Pat. 3,775,485 (C1. 260-609 F) (Nov. 27, 1973). Ghera, E.; Perry, D. H.; Shoua, S. J. Chem. Soc. Chem. Commun. 858-859 (1973). Matcha, R. L. J. Am. Chem. Soc. 95, 7508-7510 (1973). Fry, A.J.; Britton, W. E. J. Org. Chem. 38, 4016-4021 (1973). Hooz, J.; Bridson, J. N. J. Am. Chem. Soc. 95, 602 (1973); Synthesis 685 (1973). Bharucha, N. R. U.S. Pat. 3,772,170 (C1. 204/51) (Nov. 13, 1973). Pilgram, K. H.; Medema, D.; Soloway, S. B.; Gaertner, G. W. Jr. U.S. Pat. 3,772,391 (C1. 260-609 F) (Nov. 13, 1973). Stevens, C. L.; Balasubramanian, K. K.; Bryant, C. P.; Filippi, J. B.; Pillai, P. M. J. Org. Chem. 38, 4311-4318 (1973). McMurry, J. E.; Melton, J. J. Org. Chem. 38, 4367-4373 (1973). Sakai, H.; Hamada, S.; Yamanaka, Y.; Ito, I.; Izumi, Z.; Kitagawa, H.; Mukoyama, E.; Suzuki, Z.; Kato, T.; Hosaka, S. U.S. Pat. 3,781,248 (C1. 260-793 M) (Dec. 25, 1973). Renaud, R. N. Can. J. Chem. 52, 376-380 (1974). Pearson, D. E.; Buehler, C. A. Chem. Revs. 74, 45-86 (1974). Bartsch, R. A.; Wiegers, K. E.; Guritz, D. M. J. Am. Chem. Soc. 96, 430-433 (1974). Balakrishnan, M.; Rao, G. V.; Venkatasubramanian, N. J. Chem. Soc. Perkin Trans. II, 610 (1974). Hanson, J. R. Sythesis, 1-8 (1974). Robinson, H. B.; Valley, D. J. U.S. Pat. 3,264,536 (C1. 317-258) (Aug. 2, 1966). Barth, B. P. U.S. Pat. 3,370,107 (C1. 260-901) (Feb. 20, 1968). Minoura, Y.; Shiina, K.; Yoshikawa, K. J. Polymer Sci. A-1, 5, 2843-2856 (1967). Izv. Sib. Otd. Akad. Nauk. SSSR, Ser. Khim. Nauk. 1973, 114-116; CA 80, 36780. Abe, T. Chem. Lett. (Japan), 1339-1342 (1973). Fincini, -1214 (1974). Akhtar, M.; Barton, D. H. R.; Sammes, P. G. J. Am. Chem. Soc. 87, 4601-4607 (1965). Kress, T. J. U.S. 3,794,642 (C1. 260-251R) (Feb. 26, 1974). Hauser, F. M.; Huffman, R. C. Tetrahedron Lett. 905-908 (1974). Su, C.-W.; Watson, J. W. J. Am. Chem. Soc. 96,1854-1857 (1974). Krapcho, A. P.; Jahngen, E. G. E. Jr.; Lovey, A. J.; Short, F. W. Tetrahedron Lett. 10911094 (1974). Binger, P. Synthesis, 190-192 (1974). Henbest, H. B.; Trocha-Grimshaw, J. J. Chem. Soc. Perkins Trans. I, 601-603 (1974). Sharma, A. K.; Swern, D. Tetrahedron Lett. 1503-1506 (1974). Kende, A. S.; Wade, J. J.; Ridge, D.; Poland, A. J. Org. Chem. 39, 931-937 (1974). Zu Reckendorf, W. M.; Wassiliadou-Micheli, N. Ber. 107, 1188-1194 (1974). Baron, A. L. U.S. 3,532,677 (C1. 260-79.3) (Oct. 6, 1970); CA 73, 121223R. Ferland, J. M. Can. J. Chem. 52, 1652-1661 (1974). W. J. U.S. 3,455,866 (C1. 260-37, C 08G, F 16D) (July 15, 1969); CA 71, 62072Z (1969). Kornblum, N.; Boyd, S. D.; Ono, N. J.Am. Chem. Soc. 96,2580-2587 (1974). Smith, P. A. S.; Bruckmann, E. M. J. Org. Chem. 39, 1047-1054 (1974). DeMeijere, A. Ber. 107, 1684-1701 (1974). Hoyt, J. M.; Williams, M. Jr. U.S. 3,780,004 (C1. 260-87.3) (Dec. 18, 1973). Jacobs, R. L. U.S. 3,813,446 (C1. 260-622 R) (May 28, 1974). Haugwitz, R. D.; Maurer, B. V.; Narayanan, V. L. J. Org. Chem. 39, 1359-1361 (1974). Oda, M.; Kayama, Y.; Kitshara, Y. Tetrahedron Lett. 2019-2022 (1974). Rose, J. B. Polymer 15, 1456-465 (1974). St. Clair, T. L.; Bell, H. M. J. Polymer Sci. Polymer Chem. Ed. 12, 1321-1322 (1974). Ferro, A.; Naves, Y.-R. Helv. Chim. Acta. 57, 1152-1155 (1974). James, B. G.; Pattenden, G. J. Chem. Soc. Perkin Trans. I, 1204-1208 (1974). Segawa, H.; Itoi, K. Japan 73, 19,557 (C1. C08G, B 01 J) (June 14, 1973); CA 80, 104!

7260 7282 7285 7293 7331 7361 7459 7460 7476 7507 7527 7528 7533 7536 7540 7547 7552 7553 7573 7582 7608 7609 7613 7619 7641 7643 7655 7657 7691 7692 7699 7709 7710 7729 7737 7756 7763 7772 7844 7865 7867 7943 7950 7984 8008 8017 8030 8033 8043

134072X. Santos, E.; Dyment, F. Plating (East Orange, N.J.) 60, 821-822 (1973); CA 79, 99733G. Youssef, A. A.; Sharaf, S. M. J. Org. Chem. 39, 1705-1707 (1974). Wilczynski, J. J.; Johnson, H. W. Jr. J. Org. Chem. 39, 1909-1915 (1974). Ryan, M. D.; Evans, D. H. J. Electrochem. Soc. 121, 881-883 (1974). Krapcho, A. P. Synthesis 383-419 (1974). Nakagawa, S.; Takehara, Z.; Yoshizawa, S. Denki Kagaku 41, 880-883 (1973); CA 80 151, 952Q. Vitali, R.; Gladiali, S.; Gardi, R. Gazz. Chim. Ital. 102, 673-678 (1972); Synthesis 454 (1974). Mariano, P. S.; Watson, D. J. Org. Chem. 39, 2774-2778 (1974). Boeckman, R. K. Jr.; Ganem, B. Tetrahedron Lett. 913 (1974); Synthesis, 748 (1974). Wu, M.-C.; Anderson, L.; Slife, C. W.; Jensen, L. J. J. Org. Chem. 39. 3014-3020 (1974). Brand, W. W.; Bullock, M. W. U.S. 3,842,096 (C1. 260-327 M) (Oct. 15, 1974). Thummel, R. P. J. Chem. Soc. Chem. Commun. 899-900 (1974). Ghera, E.; Shoua, S. Tetrahedron Lett. 3843-3846 (1974). Balakrishnan, M.; Rao, G. V.; Venkatasubramanian, N. J. Indian Chem. Soc. 51, 537-539 (1974). Tokoroyama, T.; Matsuo, K.; Kanazawa, R.; Kotsuki, H.; Kubota, T. Tetrahedron Lett. 30933096 (1974). Mully, M.; Zsindely, J.; Schmid, H. Chimia 28, 62 (1974); Synthesis, 604 (1974). Gulbenk, A. H.; Horne, D. J.; Johnston, H. U.S. 3,746,707 (C1. 260-243AN; CO 7D) (July 17, 1973); CA 79, 105301H. Meresaar, U. Acta. Chem. Scand. A28, 656-660 (1974). Stetter, H.; Schreckenberg, M. Ber. 107, 210-214 (1974); Synthesis, 63 (1975). Kocienski, P. J. J. Org. Chem. 39, 3285-3296 (1974). Rao, Y. S.; Filler R. J. Org. Chem. 39, 3304-3305 (1974); Synthesis, 543 (1975); CA 82, 16,473K. Varkey, T. E.; Whitfield, G. F.; Swern, D. J. Org. Chem. 39, 3365-3372 (1974). Rose, J. B. Chimia 28, 561-567 (1974). Fleming, R. H.; Quina, F. H.; Hammond, G. S. J. Am. Chem. Soc. 96, 7738-7741 (1974). Eliason, R.; Kreevoy, M. M. J. Phys. Chem. 78, 2658-2659 (1974). Challis, B. C.; Kerr, S. H.; McDermott, I. R. J. Chem. Soc. Perkin Trans. II, 1829-1832 (1974). Girdler, D. J.; Norris, R. K. Tetrahedron Lett. 431-434 (1975). Iguchi, Y.; Kori, S.; Hayashi, M. J. Org. Chem. 40, 521-523 (1975). Martin, R. L.; Norcross, B. E. J. Org. Chem. 40, 523-524 (1975). Thompson, R. M.; Duling, I. N. U.S. 3,738,960 (C1. 260-49) (June 12, 1973). Leslie, V. J.; Newton, A. B.; Rose, J. B. U.S. 3,775,368 (C1. 260-49) (Nov. 27, 1973). Heath, D. R.; Wirth, J. G. U.S. 3,869,499 (C1. 260-465 F) (March 4, 1975). Corey, E. J.; Shiner, C. S.; Volante, R. P.; Cyr, C. R. Tetrahedron Lett. 1161-1164 (1975). Belanger, A.; Brassard, P. Can. J. Chem. 53, 195-200 (1975). Doddi, G.; Mencarelli, P.; Stegel, F. J. Chem. Soc. Chem. Commun., 273-274 (1975). Johnson, D. C.; Nicholson, M. D.; Haigh, F. C. IPC Technical Paper Series No. 5 (April 1975). Reinhold, D. F.; Sletzinger, M.; Chemerda, J. M. U.S. Pat. 3,366,679 (C1. 260-519) (Jan. 30, 1968). Broxton, T. J.; Deady, L. W. J. Org. Chem. 40, 2906-2910 (1975). Schexnayder, M. A.; Engel, P. S. J. Am. Chem. Soc. 97, 4825-4836 (1975). Hanzlik, R. P.; Shearer, G. O. J. Am. Chem. Soc. 97, 5231-5233 (1975). Omura, K.; Sharma, A. K.; Swern, D. J. Org. Chem. 41, 957-962 (1976). Pfeffer, P. E.; Silbert, L. S. J. Org. Chem. 41, 1373-1379 (1976). Firestone, R. A.; Reinhold, D. F.; Sletzinger, M. U.S. 3,401,178 (C1. 260-340.5) (Sept. 10, 1968). Diem, H.; Dudeck, C.; Lehmenn, G. U.S. 3,966,727 (C1. 260-249.9) (June 29, 1976). Chinn, L. J.; Desai, B. N.; Zawadzki, J. F. J. Org. Chem. 40, 1328-1331 (1975). San Filippo, J. Jr.; Chern, C.-I.; Valentine. J. S. J. Org. Chem. 40, 1678-1680 (1975). Harvey, R. G.; Goh, S. H.; Cortez, C. J. Am. Chem. Soc. 97, 3468-3479 (1975). Auerbach, A.; Indictor, N.; Kruger, A. Macromolecules 8, 262-266 (1975). 105!

992. S. N. C.. Revs. 38758P (1974). D. Grayston. 3. Chem. 260-326. 321-322 (1977). 3230-3233 (1975). Lewis. J. Lowe. (London)..242 (C1... M. L. Snyder. 1931-1936 (1976). K. Takemoto. Chem. Takahashi.S. Huang.. J. 9. K. G. Newton. J7 6028-734 (C1. P. 1976). 69-73 (1977)... KK Japan.. Chem. J.. M. Pat. Inaki. 137-144 (1975). C. Chem. T. 1976).208 (C1. J. Akasaka. M. C. D. M. 1974). Cavazza. R. N. E. Perkin Trans. Ind. Zak. J. Komachinya. Soc. A. 260-580) (July 29.. J.. Can. 1975). 189-210 (1975). B. Kester. 106! . I. Chem. G. 41. 103-114 (1976). M. S. 2079-90 (1974).. Chem. Bartsch. 2096-2098 (1975). Masamune. 488-491 (1976).. Aida. Itagaki. -2439 (1976). U. Angew. Rooney.Furukawa. II. Org.811 (C1. P. Res. Chem. T. B. Makromol. R. S. 407-420 (1977). 73. J. 1975). Chem. O. 49. 731-753 (1975). Takemoto. 175. E. R. Omura.. F. E. Padwa. Matsue. O. J. B. Soc. Chem. R. 20. L. T. White. Oae. Jap. 75. J. Marschall. J. R. 29. Muir.077 (C1. Pat. Nystrom. 2500-2502 (1976). Adams. A.14 T) (Nov. K. Chem. J. 3. B. R. 3329-3331 (1976). Synthesis. 40. C. 3. M. Bull. J. Watt. Japan. A. 13. Kamino. 260-326 N) (Nov. J.. Haslinger.. F. D. Chem. J..S. D. G. Uzuki. 5581-5590 (1976). Pietra. 52. Wakamatsu. Polym. Angew. M. 2060-4 CZ) (Dec. Chem. Chem. 48. Org. K. D. Soc. G. Wade. Sekiguchi. Soc. Chem.. Soc. Sowa. Sato. M. K... 1117-1121 (1976). D. T. J. R. 98. P. Bull. H. A. J. M. A14F01) (A32 A94) ( Aug. 1476-1479 (1976). N.. H. Pattenden. D. B. Jones. Inaki. 2061-2064 (1976). 41.. S. 49. 4. G.. Chem. 3.. Taylor. J. Tsutsumi. L. Knudsen. L. Troger. U. A.. Iwakura. 109. J. N. J. 7. 1521-1523 (1976). Soc. Au. U. 49. Timoto. Am.499 (C1. Lemal. Makromol. CA 81. A. Nguyen. Broxton.. J. Okano. A.. Pinnick. G.. K. T. Org. 49. U. Chem. Oae.. Alumni. 41. 40. Lowe. Sci. Polymer 17. Uno. Synthesis. A. Jap. Revs. K. J. R. A... Calamai. 49. T.. H.. Furukawa... H. B. W. 2308-2312 (1975). J. Org. T.. H. T. G. CA 85-142716S. Johnson. -984 (1975). Schmidt. Masamune.. 239-245 (1975). 20. Soc.. G.. S. P. 2785-2792 (1976). Chem. I. 864-865 (1976). W. F. Seymour.. Y.. 40. Appl. L. J.3425-3429 (1976). James. S. S. Sridhar.886. 1560-1564 (1976).. 55.. 606-607 (1976). Gibian. Chem. 152729E (1974).. G.S. Chem. Baciocchi. Chem. A. Ber. K. W. Chem.S. Knipe. T. Perkin Trans I. H. A. 1636-1638 (1975).S. Murai. Perkins Trans. E. H. Akasaka.. Makromol.. Mozdzen. T. Kerber.-J. M. Muehlkamp. Gombos. R. 260-518 R) (May 27. 16. 505 (1977). Barton. Soc. Markezich. E. Org. Org. Chem. Jap.. E. T. R. 8. J. Chapas. W. Akerblom. J. Miyake.. F. Chem. Murase. Soc. 41. Meakins. Numata. E. Am. Swern. 2294-2302 (1975). Grossert. Lippert. Shizuka. A. J. Vollheim. 11. U. 98. O.. Gordinier. A. E.991.8050 8054 8063 8065 8070 8095 8105 8108 8118 8184 8185 8227 8238 8254 8255 8261 8276 8287 8306 8311 8339 8340 8344 8350 8360 8372 8399 8400 8405 8408 8410 8418 8436 8451 8455 8501 8506 8529 8548 8551 8554 8564 8576 8582 8601 8603 Bartsch. 109. Bull. Ungermann. Wilkins.. 3.. R. Bull. Smith. T. 29. Ind. Lamby. 1976). Chem.897. DelCima. Kimura. Cheng. A.. Organic Prep. Y. H.. Tetrahedron Lett. Perkin Trans. Chem. Matsui. 1441-1442 (1976). Commun. G. L. Proced. R. U. 129-142 (1976). Purdue University Organic Seminar (Jan. J.. Soc. F. Khan. Biggi. A. 2089-2093 (1976).. Int. Jap.. Soc. 1278-1280 (1976). Accounts Chem.. S. Hanabusa. S. Bailes.. Org. 1977). Miners. Kornblum. Langler.. D 01F) (Sept.. D.. Aida. R. Bull.. Okamoto. Chem.852... M. Soc..406 (C1. H. Perkin Trans. Y. H. G. Ber. Benko. K. 3746-3748 (1975). Matsuyuke. R. 555-558 (1976)... R. Soc. CA81. Chem. Ono. S. Haines.. 1973)... Kennewell. Chem. Toray Inds. Soc. 3. Parker. Kimura. M. T.. 883-887 (1976). Roberts. Y.. K.. Gupta. M. 2628-2644 (1976). (London). H. J. D. Chem. J.. Taniyasu.. K.

R.. Ritz.. H. 16. 2006-2014 (1977).. Donahue. B. Jaeger. Cresswell. L.. Reese.S. R. J. 42.3) (April 22. Moorthy.. 1974). M. 1484-1491 (1977). H. Heath. 42.. C07C) (April 15. J. Mentha. R. Ger. Polymer 18. V. Razumovskii. W. Buchman. B. 1472-1478 (1977). Chemtech 702-709 (Nov. Grout. B. Ber..933 (C1. C 08F. H. V. 429-433 (1976). S. Tetrahedron Lett.. Chem. Gigg. 10961098 (1977). D. G. Soc. Soc. 1443-1446 (1977). Chem.. 260-346. Andreev. Org. West. C. J.. 2. Zaby. M. 1863-1871 (1977). F. 1976).. U. Philipp. R. J. 25. Org. Kellogg. 260-326. 4. D. Lau. SSSR. 1977). W. B..879. H. Perkin Trans. Ser.. 171903U. J. J. 3414-3419 (1977). W. Adams. K.. L. I. T. S. 354-358 (1977). 260-465 F) (March 25. J. 260-345. Soc. E. U. 1758-1763 (1977). R. Heath. Jr. J. Perkin Trans. Marrs.... T. Ibsen. J. R. Tetrahedron Lett. Synthesis 433 (1977). R. Saegusa. S... Agarwal. S. 99. T. 1708-1715 (1977). 37585T (1974).878.252 (C1. J. D. Baker.. E. Chem. 4. 2. A. C09D) (Apr.. J. D. T. Jennings. D. M. I. M. Org. Samoilova. 1975). H. J. T. F. J. Akad. Perkin Trans. Commun.. V. Bamkole. U. B. II.195 (C1. Rose. Izv. Chem. 4. D. Devaprabhakara. W. Am. J. Khim.. Perkin Trans. Chem.... Hortenstine.S. 42. B. Markgraf. Chem. A. 1466-1472 (1977). II. B. U.. E. E.S. Williams.. B. J. Y. T. Portnoy. D. Synthesis 483 (1977). G. Mandell. Sato. 110. Chem. P. G.E.042. Chem. Soc. J. B. R. W. 1974).S. E.232 (C1. O. H. J. 1977). II. Kuper.585 (C1. J. C 04B. 6...S. Sythesis 283 (1977). Maruyama. U. Soc. J. II. F.. Johnson.. Chem.658731 (C1. V. 3. 260-586 C) (June7. 1975).873. Offen. J.8658 8677 8683 8685 8690 8696 8714 8717 8735 8759 8766 8779 8809 8825 8830 8832 8833 8838 8843 8861 8867 8885 8888 8906 8923 8927 8951 8953 8954 8955 8960 8970 8984 9096 9107 9135 9138 9142 9142 9145 9150 9170 9175 Nakano. Lurie. Kinny. Liu. 3. C.. H.. J. J.. CA 82. Takekoshi. 42. R. H. 74 24. U. W. Gold. CA 82. Mahrotra.944. CA 82. Blum J. Chem.. A. Hammer. V. II. Y. C. V A. J.. J. Zaikov. Aydeiran. Williams. P. Wasson. S.. 932-933 (1977). Davidovich.. 260-607A. Org. Chem. Onyido.T.. A. I.S.150 (C1. A. 28. Chem. Feasey. Chem.560 (C1. Mukaiyama. Weinberg. 111772R. G. Org. B. J. CA 85. Yamamoto. Viout. McLennan.110 (C1... A. Tsiryapkin. 1978). N. G.028. Reuben. Nakamura. Takekoshi. Leslie. 548-339) (Aug. 543-546 (1975). Y. Maryanoff. M. Hofheinz. W. 536-30) (Feb. R. C07D) (May 21. Day.597 (C1.S.. C 07C... 1975). S. M. G. Perkin Trans. Galli. M.1977).428 (C1.. 6677-6686 (1977).076. J.048. Chem. 1975). 13.812. Am. (1) 95-98 (1976).. 3. Reuben.. M. Spackman. Pile. R. Gani... D. F. D. CA 81. I. Wagenknecht..432. G. Webb. 1490-1492 (1977).S. N. Synthesis 303-304 (1977). T. Soc. Perkin Trans... U. U. Mironova.. Japan. C. Chem.5 BD) (April 25. Sugishita.. J. D.15. J. T. Nauk. Relles.S.. Gold. R.. 1977). 42. II 1580-1583 (1977).057. Adams.. Richardson. J. Ger. 4. J. M. Carosello. 3.. U. D. Scharf. K. P. W. L. A. M. W.9 S) (Sept.. 78855R... Soc. Rogozhin. J. U. 3.S. A. J. 107! . S. S. T. Skell. Synthetic Commun. 1977). Barr.. F. V.593 (C1. Hirst. H. O.057 (C1. T. U. Carson. Soc. 1977). N. Tetrahedron 32. J. L. 1972). A. V. J. 169742X (1975). B. Daley. T. McLennan. Malievskii. Mandolini. C 07C. A. W.. M. Shatokhina. R. Lett. Inoue..417 (C1.. Perkin Trans.S.. H.. Conant. Roedig. Chem. 4. 99.. CA 82.1974). M.685 (C1. S.024. H.. D. Fujii. D.. Soc. CA 83. P. Suzuki. I.. Pri-Bar. E. McCarthy. C. Troostwijk. 2631-2632 (1977). Molinari. 94415U. G. W.. Mendelson. 3. Attwood. Perkin Trans. Szmant. K. Mueller. Kabalka. Turbak. A 01N) (Feb. 2539-2542 (1977). 1461-1462 (1977). T.. Williams. II. J. A. J. J. 6. Ito. S. Chem. Wasson. 260-612 D) (Nov. G. Z. T. Guenther. B 01J) (June 20. Manello.. Birke. C. 260-302H) (March 16. Hustad. H. J. A. 2883-2889 (1976).250.. Pritchard.. O. D.. K. Soc. U.S. Soc.. 443-445 (1977). A. Jr. 8. Newton. Schleicher. 260-47 CZ) (May 17. 113469W (1975). Hajos. Offen. 4. N. 260-2. Chem. Konoike. A. 512-517 (1977). S.. Wirth. J. Neal. L. R.

Y. J. 544-193) (Nov. 22. 1957-1961 (1978). Pat4. J. A. James. J.085. Stephens. Cohen. CA 86. DeOliveira. Jr.120237W.. J. Nadezhina. CA 84. M.. Org. Santappa. A. CA 90. C. D. K. V. CA 87. Takita. I. Chem. CA 86. Dalessandro.. S.9196 9222 9244 9249 9338 9396 9402 9408 9412 9423 9434 9439 9464 9488 9541 9563 9567 9581 9604 9605 9638 9652 9678 9686 9707 9727 9746 9752 9761 9767 9769 9771 9773 9780 9783 9786 9825 9850 9871 9874 634 (1975). F. Julia.G... Khim.094. 546-547 (1977). D... J. Chem. Chem.S. H. CA 84. I. K J. 4.. 260-592) (April 18.23267Q. Moriguchi. K. B. Taga. 43. A. M. 12.A. N. Org. Sci. (Leningrad) 51. Farnum. 43.C. Kuznetsov. F. 133-202 (1977). Advances in Physical Organic Chemistry. D. 278-279 (1978). Swern. Y.1975). Wirht. Org. S. A.. Zollinger. Cue. Makromol. Curr. J.250-254 (1978). J. Tsentra Vyssh.163425U. Bull. 179. A. Kitano.. N. 112283K.. Soc. 46. Girota. M.. Ed. Commun. A. 3783-3784 (1977). Tatsumi. 3.. Polymer Chem.. Khim. Jap. Ueda. Puglis. Chem. 1646-1651 (1978). Johnson. W. D. L. CA 88. 909-11 (1978). Nucl. Chem. Iwamuro. N. Seree DeRochi.892. Chem. Tokura. 170564W. Org. Kremley. Estestv. R. F. Nippon Kagaku Kaishi. Zh. Mimoun. R. 43.S. J. S. 85-94 (1976). Prikl.N.... E. R.J.D.W. J. Comm. Klutchko. Org. S. Sev. 10359X. Radhakrishnamurti. Wilson. Matsubara. Salomon.878 (Cl. V... Klutchko. Org. 72048V. D. Soc. Org. U. E.. M. M. Cistone. 1051-1052 (1975). Nauchn. Woo..C. Saito. 10. P. Tsenyuga. CA 88. H. 117-120 (1978).P.. Kandasamy. J. J.. Von Strandtmann. C. p. CA89.E. Katakawa. Shavel. Shk. M. U. Rotstein.6549R. Ed. Jr. 1974).. Chem. R. J. 14.... B.. Sinha. M.J.) 42. Chem. M.. 1978). 17. 50032Z.. Von Strandtmann. C07D) (Feb. L. F. Righini.L. CA 137048H. 260-243R. W... Williams. G. Yamazoe.. A. San Francisco. 47-79 (1976).S. Osaki. M. Cham. Wagenknecht. 43. 12. Chem. Thao. E. 1058-1060 (1976). J. Jr. Reetz.. Tanimoto. CA 88. Toma.059. 536-57) (June 27. D.. Tanaka. Timofeeva. Goldsmith. T. P. Jr. J.. Inamoto.1140-1145 (1978). B. M. H. Inorg. 126959E. 43-45 (1978). Vol. A. 22. Krapcho. T. Ovchinnikov. Uguen. Chem. Padhi.S. 43632J. N... E.704 (C1. U. 43.76-79 (1978). Petrova. (Russ... G. 717-718 (1978).666 (Cl.C. F. C 07C) (Oct.W.O. Cocivera. Morris R. Y. Polymer Sci. Huang. 218-220 (1978). Cohen. Khim. N. Tong. Y. 4. A. Rao. Soc. Wilczynski. B. A. 108! . Hutchins. 260-297Z) (June 13. J. W. K. D. 517-518 (1977). A. 669-670 (1978). S. Lovey. J. U.. Maryanoff. A. Shavel.. Ukr. 195-203 (1976). I.G. CA 88. U. J. Amick.. Mizuno. A. M. Gaenzler. H. Jr. Org. Burgoyne..H. A 16A. Am.2369OT. Pat. 43. Salomon. Engl.J. CA 84. 59082R. 141-150 (1978). Zh. Org. 22. Angew Chem. H. Irie.. 16. Zelawski. P. Academic Press. 3. Eibach..S. M.739 (C1. 260-61) (Jan. Y. Chem. S. CA 90...610 (C1. Buncel. Chem. Welch. J. S. Seiyama. E. E. Von Strandtmann. Marvel. S. D. Dux III... Perkin Trans I. Zh.097. Intern. Nippon Kagaku Kaishi 1167-9 (1978). 1974).P... 88... 125172G. C. Matsubara. Chem. 3. Nishibata. Voronkov. Donahue. Z. Philipp. Org. J.. J. Gombatz. 56. CA 89. 520-526 (1978)..-Kavk. V. 150650K. A.843. 14.. Kmiotek-Akarzynska. Soc. Udaka. D. Can. U. 17. Chem. J. T. Chem. 183721Z. 75457B. Weimaster.. Lett. 929-930 (1978). 1978) Shieh.M.. Chem. 260250C. 42. H. Intern... Garasu Kogyo Gijutsu Shoreikai Kenkyu Hokoku 28..E. Chem. 179414P.. A. Mancuso.. Ed. U. Hagedorn III. Wendler. A.J. Heath.. V. Eldridge. Izv. Imoto.-L. 43. Scheicher. CA 87. J. N. J. G. Ser. Indian J. M.. Nauk. Ohshio. A. F. Maruthamuthu. N. Chem. 4.787. 42. C07D) (July 1. 707-711 (1978). A. New York. Jawdosiuk. C. T.. Maehara. Faserforsch. Nicholson. Sect. H. Angew... W.R.P. S... 1977).. Handa... 28. S. H. Engl.S. Jahngen. J. 1140-1145 (1978). 51. Shavel. G.730 (C1. Ouchi.... Giesbrecht. V. Klutchko. J. J. W. Fialkov.. 969-973 (1978). Chem.937. M.. Chem.2480-2482 (1978). 4. M.S. U.P. M. Heterocycl. 3.. H.. Textiltech. Soc. Y. 337-339 (1978). Dirlam. CA 82. Effio. Y. 84. Y.145 (C1.S.364 (C1. 1976). London.S. 3765-3767 (1977). 260592.. M. Reed. Ed.. T.F. Chem. CA 88. P. 100.. 39046R. Bozhenko. T. 169698M. CA 84. 1978). B.S. 138-47 (1978)..

2404-2408 (1980). A.. 11. Commun. Carlson.L.. Chem. H. P.. Chollet.. J. Org.. Babler. Chim..211782Y. J. 1714-1720 (1980).... K.45.. Takagi. Chem.. Narang.S. Chem. Soc.. 1979).985-993 (1980).J. C07 C79/04) (Sept. 712-718 (1979). H. Kurita K. CA90.44.. Synthesis 61-2 (1979) CA 90.J.. Bordwell. N.F. Koizumi.. 1481-1484 Still. Chem. Takeshoni. Chem. A.. Reed. T. T. Gaymard.. D. Margolin. B. N. D. Jonkers. Wolf. U.S.P... 44. 20.. J.. Perkin TransI. Smith. J..4418-4428 (1960). F..604 (Cl. 101. 45. Olmstead. 51-57 (1980). 1481-1484 (1979). Davies.. Am. Z. G. Larsen. L.E.R. Turnbull. Nanasawa. Wirth. J. Commeyras. 4. Iqbal. T. F.R. J.G. Asamidori. D. Nagai. Morinaga. Hirakawa.L.9-18 (1979). Pri-Bar. Malhotra. Chem. H. Org. A... N. Y.9895 9926 9928 9944 9949 9960 9961 9964 9985 9986 10000 10002 10008 10011 10032 10043 10044 10048 10066 10077 10078 10084 10085 10086 10091 10116 10123 10127 10134 10139 10143 10224 10286 10315 10320 10368 10394 10399 10409 10411 10422 10434 10437 10439 10443 10454 10458 10465 10470 94 (1979). J. Savignac. Nanby. Polymer Sci.C. 2769-2773 (1979). CA92.B. Y.. Org.4317-4320 (1980).. T.. 1176-1181 (1979). 44. 315-316 (1979). I. Brownfain.. Farnham. C. K. J. Makromol. Casnati. Buchanan. Am. Tanaka.. K. U.. 57. Chem. 45.. 3.. I.N. 2951-2952 (1979). Scott. J.. Tanaka. W. P. D.V.204 (Cl.220. R. Coghlan. J.4727-4729 (1979). 874-878 (1979).A.695-662 (1980).J. 13-16 (1978). Kamogawa. Kuno.J. N. Chem. Manello. Mancuso. Kornblum. H.C. H. J. Imai. Kuran.E. M. 2. N.P.A. 181.. V.. 1. Westrich.L. C. 4. Y. J. M. Makromol. Deady. G. J. J.118 (Cl.G.91170Y. CA 90 168063E.. Wade. M. R. P. 1651-1660 (1978). Swithenbank. Fatma. 548-155) (Jun. A. Helv.. Y. M. Turbak. Buchman.N. G. J. Caserio. Jpn Kokai Tokkyo Koho 79. Chem.. M. B.. 1979).S... J.A. H. J. Rapid Commun. CA 91. Tetrahedron Lett. Babler. A. U. Polymer Sci. Bullock. Ind. Hammer. Swern. H. Soc. Kim. J.. B.N.J. Kornblum. Chem.175. J. Hagenbuch. 44. Chem. Jarvis. 62. II. Fifolt.. K.3157-3162 (1979).R. 1979). M. R.. Swern.855-858 (1979). Mulot. H..4528-4531 (1979).3069-3080 (1980).175. Omura. R.920 (Cl.B. Bartsch. Ed. Webber. R. Chen. Kawaguchi. Polymer Chem. P. A.3295-3299 (1980). M. Org. 1695-1697 (1979). 1980)... Ishratullah. Read. Acad. Rowe.44-52 (1979)...J... B.. D. S. Org. M.H. Y.. 4. CA 91.. Ser. Soc. Tetrahedron Lett.. D.. Kurita...G. P.. K. J.G. C07Cl47/02) (April 9. K. 109! . Rokicki. E.J. F.. D. 57. 370-371 (1979).E. Omato. Makromol. Johnson. Ueda. 260-607B. Makromol Chem. Dossena.. R. Bartet. Lingman. T.E. Soc. Chem. T.H. P. Chem.W. J. Van der Gen. C. Guest.125. W. Iwakura. E. Sarcos. Synthesis 1045 (1980). Chem.. Kochanowski. M. 1980). 180. J..O. Ed.. Can. Zheng. N. R. J.4545-4546 (1978). Dryden.. Reed.. W. R. A. Gigg.R. 21. Tetrahedron 34. McComas. H. Sci. J. Tsumura. J. R. A. Soc. Chem.T. Bayer.141. U. 45. B. 103544T.. M. Uijttewaal.. R. 560-262) (Nov.G.A..K. J. Tetrahedron Lett. Singaram. S.. Chem. Y. W. 4. Rapid Commun. A.H. Iwakura. S. Cariou. Chari. C07C148/00) (Feb.S. Cho. Chem. Shaida..206. J.P. J. Ismail. 44.. Chem.N. Broxton. Chem. N.. J. Chem. Gibbio. Kurita K. Detty..W.511-524 (1979). National Fire Protection Association. Perkin Trans I. R. S.3157-3162 (1979). Kornblum. Tanaka. Iwakura. Kokai Tokkyo Koho 79. H. 101. Mazaki.R. Nicholas.. Marchelli. Chem... R. Synthesis 292-295 (1980). 27. K.. 71-124) (Sept. Feng.175 (Cl. 91.W. Yih... Acta. D. 1979). W. 17-20 (1979).N. Perkin Trans.S. Larcheveque. Heath. Breque. Org. Chem. Perkin Trans. J. 20. Gregory. Manual of Hazardous Chemical Reactions 1971.. Chemtrech. Rahman. 122862M.. U.Q. 44. J. F.Jr. 44. Roberts. Hirakawa. R. A. Vogel. J. S. 2681-2682 (1979). Turnbull. 110519H.. R.S. Makromol.. A.S.. Morimoto. Chem. Can.647-657 (1979). B. K.. 528-125) (Nov. Fries. 1.. Blancou. Gupta.2404-2408 (1980). Hergert.J. Nanbu. O. Irie...S.. 29. 1979). G.C. 4. M. 43. 659-662 (1980) Raduechel.. W. (London). J. Polymer Chem.. Soc..210384H. Guedg. Tetrahedron 33.H.A. 468 (Cl. Uyeo. Hirakawa. Chem. Soc. Chem. D. Moreau. Chem. H. C. Tetrahedron Lett. 18.611 (Cl. Olah.G. T. 180. H. J. Williams...Y.2061-2067 (1977). I. 4148-4150 (1979).

G. Carter. 208-323) (May 12. MA 491M-100-101.471 (Cl. U. C. 1981). Synthesis.. Synthesis.5) (Mar. 10569 10720 10762 10771 16359 unpublished (1979).International.034 (Cl. 1981). A.O. Boldebuck.T. Banucci.M. 857-70 (1990).267.J.255. 165-185 (1981). U. Boston.S. 110! . 4..S. Mancuso. 10.4. E. D. T. Tidwell. E. 427-385. (1971). Swern.

Sign up to vote on this title
UsefulNot useful