FUNCTIONAL GROUP INTERCONVERSIONS 119

Functional Group Interconversions

C&S Chapter 3 #1; 2; 4a,b, e; 5a, b, d; 6a,b,c,d; 8

1 sulfonates
2 halides
3 nitriles
4 azides
5 amines
6 esters and lactones
7 amides and lactams

Sulfonate Esters
- reaction of an alcohols (1° or 2°) with a sulfonyl chloride
R'SO2Cl O R'= CH3 mesylate
R OH R O S R'
O CF3 triflate

sulfonate ester
CH3 tosylate

- sulfonate esters are very good leaving groups. Elimination is often a

competing side reaction

Halides
- halides are good leaving groups with the order of reactivity in SN2 reactions
being I>Br>Cl. Halides are less reactive than sulfonate esters, however
elimination as a competing side reaction is also reduced.

- sulfonate esters can be converted to halides with the sodium halide in acetone
at reflux. Chlorides are also converted to either bromides or iodides in the same
fashion (Finkelstein Reaction).
O
X-
R O S R' R X X= Cl, Br, I
O

NaI, acetone
reflux
R Cl R I

- conversion of hydroxyl groups to halides: Organic Reactions 1983, 29, 1

R OH R X

- R-OH to R-Cl
- SOCl2
- Ph3P, CCl4
- Ph3P, Cl2
- Ph3P, Cl3CCOCCl3
 FUNCTIONAL GROUP INTERCONVERSIONS 120

- R-OH to R-Br
- PBr3, pyridine
- Ph3P, CBr4
- Ph3P, Br2

- R-OH to R-I
- Ph3P, DEAD, MeI

Nitriles
- displacement of halides or sulfonates with cyanide anion
KCN, 18-C-6
R X DMSO
R C N
- dehydration of amides
O
R C N
R NH2
- POCl3, pyridine
- TsCl, pyridine
- P2O5
- SOCl2

- Reaction of esters and lactones with dimethylaluminium amide

TL 1979, 4907
Me H 3C
Me2AlNH2 OH
O JOC 1987, 52, 1309
NC
Ar
O Ar

- Dehydration of oximes
OH
H2NOH•HCl N
P2O5
R CHO R C N
R H

- Oxidation of hydrazones
O
O
N C Tetrahedron Lett.
NMe2 (97%) 1998, 39, 2009
N

- Reduced to aldehydes with DIBAL.

DIBAL
RC≡N RCHO
 FUNCTIONAL GROUP INTERCONVERSIONS 121

Azides
- displacement of halides and sulfonates with azide anion
LDA, THF O
O NaN3 O
NBS
O O O
Br
SO2N(C6H11)2 SO2N(C6H11)2 SO2N(C6H11)2 N3

O O
TL 1986, 27, 831
O HO
NH2 NH2
SO2N(C6H11)2
- activation of the alcohol

+ + R N3 +
R OH +
N F N OR N O
Me Me Me
TsO -
+
EtO2C PPh3
Ph3P, NaN3
R OH + EtO2C N N CO2Et N N
_ CO2Et
DEAD
activated alcohol

+
R-OH R N3 +
R O PPh3 Ph3P=O
JOC 1993, 58, 5886

HO N3
O
(PhO)2P(O)-N3 P(OPh)2 SN2
O + -
DBU, PhCH3 + DBU-H + N3 (91 %) O
O
(99.6 % ee) Ar (97.5 % ee)

- Photolyzed to aldehydes

Amines
- Gabriel Synthesis
O O

R X H2NNH2
N - K+ N R R NH2

O O
- reduction of nitro groups
R NO2 R NH2
H2, Pd/C
Al(Hg), H2O
NaBH4
LiAlH 4
Zn, Sn or Fe and HCl
H2NNH2
sodium dithionite
 FUNCTIONAL GROUP INTERCONVERSIONS 122

- reduction of nitriles
R C N R CH2 NH2
H2, PtO 2/C
B2H6
NaBH4
LiAlH 4
AlH3
Li, NH3

- reduction of azides
R N3 R NH2
H2, Pd/C
B2H6
NaBH4
LiAlH 4
Zn, HCl
(RO)3P
Ph3P
thiols

- reduction of oximes (from aldehydes and ketones)

OH
N NH2

R R' R R'
H2, Pd/C
Raney nickel
NaBH4, TiCl4
LiAlH 4
Na(Hg), AcOH

- reduction of amides
O
R'
R' R N
R N
R'' R''

H2, Pd/C
B2H6
NaBH4, TiCl4
LiBH4
LiAlH 4
AlH3

- Curtius rearrangement
O O O
NaN3 •• ∆ ••
••
R Cl R N N N R N
••
••

+ - N2
nitrene
R N O H2O
R NH2
isocyanate
 FUNCTIONAL GROUP INTERCONVERSIONS 123

- reductive aminations of aldehydes and ketones

- Borsch Reaction
- Eschweiler-Clark Reaction

- alkylation of sulfonamides
Tf Tf Tf
N HN K2CO3, DMF N N NH HN
Tf 110°C Na, NH3 TL 1992, 33 , 5505
Tf
N HN Br N N NH HN
Tf Br Tf Tf
cyclam

- transaminiation
O N Ph N Ph NH2
PhCH2NH2 Can. J. Chem.
tBuOK H3O +
H+ 1970, 48, 570

Esters and Lactones

- Reaction of alcohols with "activated acids"
- Baeyer-Villigar Reaction Organic Reactions 1993, 43, 251
- Pd(0) catalyzed carboylation of enol triflates
OTf CO, DMF CO2R
Pd(0), ROH TL 1985, 26 , 1109

- Arndt-Eistert Reaction Angew. Chem. Int. Ed. Engl. 1975, 15, 32.
O O O
CH2 N2 hν
N2 ••
R Cl Et2 O R ROH R CH
diazo ketone
Wolff R O
Rearrangement C O R'OH
R
H OR'
ketene
O TsN3, Et3N O
CO2Me N2
R R

- Diazoalkanes: carbene precursors

1) NH2NH2
2) Pb(OAc)4, DMF
R-CHO R-N2 JOC 1995, 60, 4725
R3N
H 2N
N TsN3 N2

R R R R

- Halo Lactonizations review: Tetrahedron 1990, 46 , 3321

I
+ I
I2-KI
CO2H O O
H2O, NaHCO3
H
O O
 FUNCTIONAL GROUP INTERCONVERSIONS 124

Pd(OAc)2
(5 mol %)
CO2H O JOC 1993, 58, 5298
DMSO, air O
(86%)

- Selenolactonization
PhSe
O PhSeCl, CH2Cl2 O H 2O 2 O
O JACS 1985,
O
107 , 1148
OH

- Mitsunobu Reaction Synthesis 1981 , 1; Organic Reactions, 1991, 42, 335

Mechanism: JACS 1988, 110 , 6487
O

OH DEAD, Ph3P O R'' Inversion of alcohol

stereochemistry
R R' R''CO2H R R'

Amides and Lactams

- reaction of an "activated acid" with amines
- Beckman Rearrangement Organic Reactions 1988, 35, 1
OH
O N PCl5 O

R R' R R' R NR'

- Schmidt rearrangement
O O
HN3
R R' H+ R NR'
- others
O NR2
OTf CO, DMF
Pd(0), R2NH
TL 1985, 26 , 1109

O OH
O
O
PhCH2NH2 N Ph TL 1977, 4171
AlMe3 H

OTHP OTHP

-Weinreb amide Tetrahedron Lett. 1981, 22, 3815

DIBAL O
O O
H3CNH(OCH3) •HCl R H
OCH3
R OR' R N
AlMe3 O
CH3
R1-M R R1