9

OZONOLYSIS OF FATTY ACIDS AND

THEIR DERIVATIVES

Richard G. Kadesch

CONTENTS
I.INTRODUCTION . . . . . . . . . . . . . . . . . 292

II.NATURE OF THE OZONIZATION REACTION ...... 292

A. Structure of ozone ................ 292
B. The ozonization reaction .............. 293
C. Mechanism of ozonization .............. 294

III.USE OF OZONOLYSIS FOR STRUCTURE DETERMINATION 296

A. General ................... 296
B. Mono-unsaturated compounds ............. 296
C. Di-unsaturated compounds ............. 299
1). Tri-unsaturated compounds ............. 299
E. Tetra-unsaturated compounds ............. 301
F. Pent&-and hexct-unsaturated compounds .......... 302
G. Miscellaneous compounds .............. 302

IV. USE OF OZONIZATION AND OZONOLYSIS FOR COMPOUND

PREPARATION ................. 304
A. General ................... 304
B. Ozonides ................... 304
C. Aldehydes and ketones ............... 304
D.Acids ................... 305
E. Miscellaneous ozonolysis products ........... 306

V. APPLICATIONS FOR OZONIZATION AND OZONOLYSIS

PRODUCTS. .................. 306
8. Ozonides .- .................. 306
B. Monofunctional ozonolysis products ........... 306
C. Difunctionel ozonolysis products ............ 307

REFERENCES ................. 307

20 Progress 291
 9

OZONOLYSIS OF FATTY ACIDS AND

THEIR DERIVATIVES

Richard G. Kadesch

I. INTRODUCTION

DURIXG the last 6fty years ozonolysis has been an extremely useful and ver-
satile tool for establishing complex unsaturated structures and for obtaining
useful products. Ozonolysis techniques have been particularly useful in deal-
ing with the long chain unsaturated structures commonly present in fats and
other lipids. This review covers primarily the ozonization of lipids and ma-
terials derived from them, such as fatty acids and their simple esters. In some
cases work on closely related long chain compounds is included.
The general reaction of ozone with unsaturated compounds has been
known for about one hundred years. It was poorly understood until Harries
did his ‘pioneer work on ozonization beginning in 1901. The first clear cut
ozonolysis of a fatty compound and examination of the cleavage products
appears to have been by Molinari in 1903 with oleic acid.u-4) Somewhat
earlier in 1898 the use of unsaturated fatty acid ozonides as disinfectants was
patented by Weyl.@)

II. NATURE OF THE OZONIZATION REACTION

A. Structure of ozone

Early studies of ozone structure soon ruled out the symmetrical linear and
equilateral triangle structures in favour of an isosceles triangle. However,
determinations of the apex angle varied from 38” to 140”. More recent stu-
dies are in better agreement. Electron d&action@) indicates an apex angle of
127 ’ and 0 - 0 distance 1.26 8. Microwave spectrum (71s)indicates an apex
angle of 117” and O-O distance l-28 8. The principal resonance contribu-
Cons to the structure of ozone a,re made by
0+ 0
/X ‘\ A A
-0 0 0 o- f0 o- -0 o+
(1) (TI) (III) (IV)

292
 Nature of the Ozonization Reaction

with I and II being the most important. The double bond character of the
O-O bond has been calculated to be 30 per cent@) and 50 per cent.@) These
st,ructures explain the small dipole moment of O-5 D.(lO)

B. The oxonization reaction

Reaction with ozone is a general reaction of compounds containing carbon-to-’
carbon double or triple bonds. A negative group, such as halogen or carboxyl,
slows the reaction when attached directly to the double bond. Several such
groups can prevent the reaction entirely. Three atoms of oxygen add to the
multiple linkage to form an ozonide. This is called ozonization.
The ozonide is relatively unstable and is easily decomposed by various
means. The result is cleavage of the chain at the point of the original mul-
tiple Linkage. The term, ozonolysis, is used here to describe the overall process
of ozonization and subsequent cleavage. The ozonide cleavage, either thermal
or hydrolytic, yields a mixture of aldehydes and acids. The aldehydes can be
made to predominate by decomposing under reducing conditions, and acids
under oxidizing conditions.
Since natural fats and oils contain unsaturation almost entirely of the
-CH=CH- and -(EC- type, they undergo ozonization readily. Actually
the component fatty acids, or simple esters derived from them, are usually
used. Generally some inert volatile solvent is used such as chloroform, carbon
tetrachloride, methylene chloride, acetic acid or ethyl acetate. The tempera-
ture of ozonization should be low, preferably not above 0”. Often even better
results are obtained at - 60”.
The very early work on the ozonization of oleic acid involved a polemic be-
tween Harries and Molinari. Based on ozonization by ozonized oxygen, Harries
contended that two types of .ozonides could be obtained.(11-14) He found
that in acetic acid a fluid “normal” ozonide was formed initially, containing
three itoms of added oxygen. In chloroform four atoms of oxygen added to
give a viscous “perozonide” which could be converted to the “normal” ozo-
nide and hydrogen peroxide by washing with sodium bicarbonate. Several
perozonides were described, varying in the amount of added oxygen, depend-
ing on conditions of time, temperature, solvent and ozone concentration.(14)
Later workers found that the initial fast absorption of ozone by oleic acid is
followed by a second stage of slow absorption.(16) This was attributed to
perozonide formation involving the ozonide group rather than the carboxyl
group. Molinari claimed that decomposition of the ozonide did not form
hydrogen peroxide and that acids were produced rather than aldehydes(16*17).
This work utilized the lower concentration of ozone present in ozonized air.
Molinari also differed by finding two C,, acids among the products. These
were later shown(12g16) to arise from the self-condensation of azelaic half
aldeh yde .
Much of the older work on the decomposition of fatty ozonides has been
reviewed by Rieche.(le6)

293
 Ozonolysis of Fatty Acids and their Derivatives

Ozone adds very rapidly in acetic acid to the cis and trans isomers, oleic
acid and elaidio acid, at about the same rate. (ls) Eleostearic acid, with three
conjugated double bonds, adds the first mole of ozone rapidly but the remain-
ing ozone slowly. The relative rate of ozonization of elaidic acid has been
determined by competition experiments involving mixtures with various
other unsaturated compounds.(lQ~eo) In this way elaidic acid was found to
ozonize more rapidly than ethyl cinnamate or ethyl acrylate, containing a
conjugated double bond.
Infrared study showed several new bands after ozonization of oleic acid
or methyl oleate. The heats of ozonization are 117 and 121 calories per mole,
respectively.(21)
The triple bond of stearolic acid adds ozone more slowly than the double
bond of oleic acid.(4*ss) This probably explains why Molinari.contended that
stearolic acid does not form an ozonide(4*23*24) whereas Harries, using higher
ozone concentration, got normal results. (86126)
The formation of a yellow colour
accompanies the ozonization of stearolic acid. This was at.tributed to 9, 10-d&
ketostearic acid, which was present both before and after the hydrolysis of
the ozonide. The diketo acid is formed in either acetic acid or carbon tetra-
chloride, probably by the direct action of ozone.(2s)

C. Mechanism of ozonization

Staudinger was the first to propose an ozonide structure which was reason-
ably consistent with the facts. He suggested t2’) that most ozonides have struc-
ture I which he called an “isozonide”.

/O\
RsC( >cs R&-CR,
I I
o-o o-o=0
(1) (II)
Structure II (named a “molozonide”) was believed to form initially but, being
unstable, rearranges immediately to I. Rieche supported structure I by
synthesizing a simple ozonide by an alternate route. Later he obtained III
(R = n-octyl or -(CH&,COOH) by the partial

RCH-0-0-CHR
I I
OH OH
(III)

fission of oleic acid ozonide in acetic acid. (*) It was concluded that the first
step in ozonide fission is cleavage of the ether linkage ; the second step cleav-
age of the peroxide linkage and recombination.

294
 Nature of the Ozonization Reaction

The rearrangement of II to I has been explained by Leffler@) and by

Criegee@O)as follows :
R&-CR, + R&-CR, --f R&-O-CR, -+ I
I I I I +
o-o + 1-o 0 ci
I I .
O- O- o-

Criegee(s”*sl) also postulated that IV actually undergoes scission to a new

zwitterion (VI) which can react in various
IV-+ R,C + + CR,
II I
0 0
I
o-
(V) (VI)
ways. Normal reaction involves V and VI recombining to give I. This is the
usual situation with the aliphatic RCH=CHR linkage commonly present in
fats and oils because V is an aldehyde which is sufficiently reactive to recom-
bine. VI can dimerize or react with the solvent depending on conditions. The
two mechanisms are similiar but the latter appears to explain better all the
observations(s1~32) and is now widely accepted.
The initial attack of ozone on the unsaturated compound to form II is
still not fully understood. The ozone functions as an electrophilic reagent*
but whether initial attack involves the central or terminal oxygen atom is
not known. Attack by the central oxygen seems to be preferred(s3). Criegee
has hally observed an unstable compound, existing only at low temperature,
which may be II.(3s) Structure VIII must also be considered.@OO)
More recently several authors have suggested that initial attack involves
the terminal oxygen atom of ozone. (107-100)Bailey proposes a pi complex
(VII) from the initial attack while suggesting that neither II or VIII is in-
0
/‘\ /O\
00 00 0 0
,I--.‘\
R&CR, Pi&&
(VW (VIII)

volved.(les) Contrarily, Blair and Maggiolo (19s)deduce from steric considera-

tions that initial attack proceeds in one step to form VIII, which immedi-
ately breaks down to V and VI.
* This haa been more clearly shown for the ozonization of aromatic compounds. Here alumi-
num chloride increases the rate by enhancing the electrophilic character of ozone.(34- %)

295
 Ozonolysis of Fatty Acids their and Derivatives

III. USE OF OZONOLYSIS FOR STRUCTURE DETERMINATION

A. Genera.!
Ozonolysis has been the preferred method for establishing the structure of
polyunsaturated fatty acids.(s7~3s~17Q)
It h as been extremely useful because
of the mild conditions involved. For mono-unsaturated fatty acids the use
of potassium permanganate is considered to be as good(assi’s) or better (37)
than ozonolysis. About 5 per cent of degradation products are formed during
ozonolysis.Qs) Extensive abnormal reaction does occur with LY,b-unsaturated
carbonyl compounds and other compounds containing an immediately ad-
jacent group with an unshared electron pair (OH, OR, NR,, OCOCH,).(ss)
Since such structures seldom, if ever, occur in lipids, this is no problem. Re-
ports of peculiar behavior during the ozonolysis of systems containing
-CHzCH=CHCH,- or -CH=CH-CH=CH- groups are extremelyrare.
It is claimedc40) that brassidyl acetate, CHs(CH,),CH=CH(CH,)1,0COCH3,
when ozonized, hydrogenated and distilled, gives lauryl acetate. Apparently
carbon monoxide is lost, either from the ozonide or OHC(CH&OCOCHs.
Identification of ozonolysis products from mono- and poly-unsaturated
fatty acids has been facilitated by oxidizing them to acids and applying
chromatographic analysis to the acids(fl,179) or to the hydroxamic acids ob-
tained from them.(m) A variation involves treating the paper chromato-
gram of the unsaturated fatty acid itself with ozone followed by fuchsin-
sulphur dioxide. (4s)
Titration with ozone has been used to determine quantitatively the amount
of unsaturation present.u80) The method has been refined and applied to
oleic acid, methyl oleate and tall oil fatty acids.oel) The authors point out
several advantages that such determination of ‘Lozone number” or “double
bond equivalent” has over the conventional determination of unsaturation
using bromine, iodine chloride or hydrogen.

B. Mono-unsaturated compounds

The fact that alkali fusion of oleic acid gives palmitic acid and acetic acid*
caused early workers to assign it the structure CH,(CH,),,CH=CHCOOH. It
was not until much later that ozonolysis of oleic acid showed its double bond
to be at the 9,10-position. Ozonolysis also showed elaidic acid to be the
trans-isomer of the naturally occurring cis-compound, oleic acid.(@) A large
number of other mono-unsaturated fatty compounds have been subjected to
structure determination by ozonolysis (Table 1). Early workers used Harries’
method of decomposing the ozonide in boiling water or aqueous alkali and
had to contend with a complex mixture of acids and aldehydes. Later workers
* This is the Varrentrapp reaction, first observedin 1MO. The double bond shifte to the
2. j-position followed by cleavage.

296
 Use of Ozonolysis for Structure Determination

Table 1. Ozonolysis of mono-unsaturated fatty acids and their derivatives

- -
Carbon 1hbk bond,
unaaturukd ConupotLnd Source Reference
NO. poeition
_- --
Decene 10 I-6 Barium Undeoenoate + NaOEt 46
Undecenoic acid 11 10 Castor oil 46,67 .
Undecenoic acid 11 9 9-Undeoynoic acid + I& 68
Methyl undecenoate 11 10 Castor oil 69
Tetradecenoic acid 14 4 Tsuzu oil 60,61
Tetradecenoio
Palmitoleic acid
acid
I 14
16
5
9
Sperm oil
Cod liver oil
62
63
Methyl pelmitoleate 16 9 Lyoopodium oil 64
Heptadecene 17 - Barium oleata + NaOEt 4.5
Petroselinic acid 18 6 Parsley seed oil 66-68
Petroselinic acid 18 .6 Ivy seed oil 69
Taririo acid* 18 6 Picramnia sow IO
Oleic acid 18 9 - 1, 17, 44
Methyl okate 18 9 - 179,201
Elaidic acid 18 9 Oleic acid 44,69
Ricinoleio acid 18 9 Castor oil 46
Methyl rioinoleak** 18 9 Castor oil 71
Stearolio acid* 18 9 9, lo-Dibromstearic acid 26,72
Octadecenoic acid 18 a10 Press staarin 46
Octadecenoic acid 18 S-10 Dehydration of oleio acid 47
sulfation product
Ootadecenoio acid 18 8.9 Dehydration of hydrogenated 73
hydroxyacid from isano oil
Octadecenoic acid 18 9-12 Partially hydrogenated sun- 48
flower seed oil
Octadecenoio acid 18 9-12 Partially hydrogenated Na soap! 182
of safflower acids
Octadecenoic acid 18 12 Partially hydrogenated liuoleic 60
acid (linseed oil)
Ootadeoenoic acid 18 11 Partially hydrogenated a-eleo- 61
steario acid (linseed oil)
Methyl ootadecenoate 18 7-11 Partial hydrogenation of methyl 183, 184
oleate
Dibromoctadecenoio acid 18 9 Linoleic acid + bromine 63
Dithiocyano-octadecen-
oio acid 18 12 Linoleio acid + (SCN), 52
Tetrabromoctadeoenoic
acid 18 9 Linolenic acid + bromine 63
Tetrathiocyano
octadecenoic acid 18 16 Linolenic acid + (SCN), 62
Methyl linoleate-
HSCHJOOH adduct 18 9, 12 Methyl linoleate 54
Sterculio acid*** 19 9 Steroulia oil 66,74,
186,186
Gadoleio acid 20 9 Sardine or herring oil 15
I
-
* Triple bond present.
** p-Hydroqpelargonio aoid isolated indicating hydroxyl group at C,,.
*** Not a straight-chain compound.

297
 . Ozonolysis of Fatty Acids and their Derivatives

Table l-continued
- -
Carbon. Do,uble bond
Unsaturated Compound Sor1rce Reference
h’o. / position
.- ___-
Gadoleic acid 20 ’ 9 Cod liver oil 76
Cetoleic acid 22 ; 11 Sei-whale oil 71
Cetoleic acid (?) 22(?) 1 11 Lycopodium oil 64
EI ucic acid 22 13 Wallflower seed oil 78, 79
Braasidic acid 22 13 Erucic acid 78
Methyl oleate-maleic
anhydride adduct* 22 8-10 Methyl oleak 49
Selacholeic acid 24 15 Alizame liver oil 80
Hydrocarbon from
phthiocerol 35 I 3,4 Tubercle bacillus 51
-
* Not a straight-chain compound.

decomposed the ozonide under oxidizing or reducing conditions to obtain

predominately acids or aldehydes, respectively.
Double bond shifting during various chemical reactions has been demon-
strated by ozonolysis studies. Reaction of sodium ethoxide with barium un-
decenoate or barium oleate produces decene and heptadecene, respectively,
with the double bond extensively shifted. (45) The 9, lOdouble bond of oleic
acid shifts to both the EL and lo-positions when heated for long periocls(J6)
or when undergoing sulphation.@7) The unsaturated material remaining after
partial hydrogenation of oleic acid or methyl oleate (the trans-isomer, elaidic
acid, behaves similarly) over nickel contains isomers resulting from double
bond shifting to an equal extent in both directions.(1*s*184) This corrected an
earlier report which erroneously claimed that the double bond shifted pre-
ferentially away from the ester group. Partial hydrogenation of the 9, 12-
diene system in sunflower seed nil or safflower fatty acid soaps(ls2) is ac-
companied by shifting of the remaining double bond. The succinic anhydride
group in maleic anhydride-methyl oleate adduct is attached about equally at
the 8-, 9-, lo- and Il-positions with the double bond being distributed among
the 8-, 9- and lo-positions.(49) This supports a reaction mechanism involving
initial attack at the Lu-methylene group of methyl oleate with the formation
of a resonating allylic radical, analogous to the free radical mechanism of
autotidation.
Based on ozonolysis, it has been claimed that addition reactions to poly-
unsaturated fatty acids can occur preferentially. HyclrogencsO) and thiocya-
nogen(52) appear to add first at the 9, lo-double bond of linoleic or linolenic
acid*. Bromine is reported as the opposite,(b3) adding first, at the 12,13-
double bond of linoleic acid and at the 12,13- and 15,16double bonds of

* On the other hand, later work involving hydrogenation of the sodium soaps of safflower
fatty acids showed no very strong preference for reaction at the 9, lo-double bond over the
12, Is-double bond (182).

298
 Use of Ozonolysis for Structure Determination

linolenic acid. In contrast, recent work indicates that mercaptoacetic acid

adds to methyl linoleate about equally at the 9, IO- and 12, 13-positions.(s)
Structure I has been proposed for sterculic acid.(56) Various methodsof
oxidation, including ozonolysis, give only azelaic and pelargonic acids. Ozono-
lysis under very mild conditions -yields a C,, acid believed to be IV@5~~s5~1*6)

CH,(CH&C=C(CH&COOH CH,(CH&Z?H-CHCH=CH(CH1),COOH *
‘J “\/
CH, CH,
(1) (II)

CH,(CH,),CH-C=CH(CH,),COOH 0 0
II II
CH, CH,(CH,),CCH,-C(CH,),COOH
(III) Iv
Structure II is preferred by other workers, primarily on the basis of infrared
data.c56) A third structure (III) has been proposed as a possibility@7) since
methylenecyclopropanes have been found to ozonize abnormally.

C. Di-unsaturated compounds

The structures established by ozonolysis for various dienoic fatty acidsare

given in Table 2. The first report appears to have been in 1906 for ordinary
linoleic acid (9, 12-octadecadienoic acid), but no details are given.(l’)
The cou;se of various addition reactions to more highly unsaturated com-
pounds was also studied. The point of preferential addition to linolenic acid
is claimed to be the 9, IO-double bond for hydrogen(“) and the 15, 16-double
bond for bromine.(53)
The dehydration of ricinelaidic acid (IS-hydroxy-trans-9-octadecenoic
acid) gives the conjugated 9, 11-octadecadienoic acid rather than the non-
conjugated 9, 12-acid.(51)
A little shifting of multiple bond position accompanies the hydrogenation
of 10,12-octadecadiynoic acid to 10, 12-octadecadienoic acid.(s2) The only di-
basic acid resulting from ozonolysis of the former is sebacic acid, whereas the
dibasic acids from the latter contain 8 per cent of C,, C,, and C,, dibasic
acids.
D. Tri-unsaturated compounds

The structures established by ozonolysis for various naturally occurring

triply unsaturated fatty acids are given in Table 3. The lirst report in 1909
dealt with linolenic acid from linseed oil .fg4) Eleostearic acid from tung oil
is a triply conjugated acid, C4HgCH=CHCH=CHCH=CH(C&),COOH.
However, it was first believed to be
C,H,CH = CHClX$H,CH=CH( CH,),COOH
because the glyoxal in the ozonolysis products was overlooked.

299
 Ozonolysis of Fatty Acids and their Derivatives
.
Table 2. Ozonolysis of &-unsaturated fatty acids and their derivatives
- -
Carbon POS.
Sowce Reference
NO. of unmt.
-- .-
Tridecadienoic acid 13 5, 9 Synthesis 188
Linoleic acid 18 9,12 - 11,83
Linoleic acid 18 9, 12 Carnation oil 61
Linoleic acid 18 * Soya or rice bran oil 84
Ethyl linoleate 18 9, 12 Corn oil 86
Ethyl linoleate 18 9, 12 Wallflower seed oil 79
Methyl linoleate 18 9, 12 Pumpkin seed oil 86, 179
Dibromlinoleio acid 18 9,12 Linolenic acid + bromine 63
Octadecadienoic acid 18 9,11 Dehydration of ricinelaidic acid 61
Ximenynic acid** 18 9, 11 Ximenia oil 87,88
Ootadecadiynoic acid 18 10, 12 C,H,,CzCH + lo-undecynoic
acid 82
Octadecadienoic acid 18 10,12 10, 12-octadecadiynoic acid +
hydrogen 82
9,14-Dihydroxyoctadeca-
dienoic acid 18 10, 12 Tung oil 89
Octadecadienoic acid 18 12,15 Partially hydrogenated linolenic
acid (linseed oil) 50
Tetmthiocyano-
octadecadienoic acid 18 12,15 Moroctic acid (sardine oil)
+ (SW, 90
Methyl nonadecadienoate 19 10,13 Liuoleic acid 83
Eiooeadienoic acid 20 5, 14 Arachidonic acid + hydrogen . 91
Hexabromdocosadienoic
acid 22 4, 8 Clupanodonic acid + bromine 92
Methyl docosadienoate 22 - Methyl clupanodonate + & 93
-
* The author assigned the structure 9.14-octadecadienoic acid, but later workers (85)
believed it actually to be 9,12-octadecadienoic acid, ordinary linoleic acid.
** Octadec-11-en-9-ynoic acid.

An interesting acetylenic acid is isanic acid from isano oil, containing two
triple bonds and one double bond. Two of the multiple bonds are conjugated.
CH,=CHC&(CH,),C=C(CH,),COOH (I)

CH,=CH(CH,),C=CC=C(CH,),COOH (II)

At first it was not possible to decide between structures I and II since form-
aldehyde, adipic acid and azelaic acid would be produced by the ozonolysis
of either one.(QQ)Additional information indicated II as the actual struc-
ture.(Q6s97)
or-Kamlolenic acid from kamala oil is another interesting acid. Hydrogen-
ation to w-hydroxystearic acid along with the ozonolysis data indicated the
structure to be related to eleostearic acid:(QQQQ)
HO(CH2),CH=CHCH=CHCH=CH(CH&COOH

300
 Use of Ozonolysis for Structure Determination

Table 3. Ozonolysis of tri-unsaturated fatty acids and their derivatives

Carbon 9ouble bond

Unsaturated Compound Reference
number P-.
-
Methyl
hexadecatrienoate* 16 6, 10, 14 Bonito oil 100 *
Methyl
hexadecatrienoate* 16 6, 10, 14 Japanese sardine oil 101
Linolenic acid 18 9, 12, 15 Linseed oil 94
Ethyl linolenate 18 9, 12, 16 Linseed oil 94
Octadecatrienoic acid 18 6, 9, 12 Evening primrose seed 65, 102
a-Eleostearic acid 18 9, 11, 13 Chinese tung oil 103
j3-Eleosteario acid 18 9, 11, 13 Chinese tung oil 103
Eleostearic aoidttt 18 9, 11, 13 Japanese tung oil 104
Eleostearic acid 18 9, 11, 13 Po-Yoak oil 105
Punicic acid** 18 9, 11, 13 Pomegranate seed oil 106
Methyl punioat.e** 18 9, 11, 13 Pomepranate seed oil 106
Isanic acid*** 18 9, 11, 17 Ieano-oil 96
Ethyl issnate*** 18 9, 11, 17 Ran0 oil Q&97,
107
Lioanic acid 18 9, 11, 13 Po-Yoak oil 105
Licanic aoidt 18 9, 11, 13 Oitioica oil 108
Ethyl lioanatet 18 9, 11, 13 Oitioica oil 108
Methyl a-kamlolenatett 18 9, 11, 13 Kamala oil 98,QQ
Eicosatrienoic acid 20 5, 8, 11 Beef liver phosphatides 189
Methyl docosatrienate 22 3 isomers Methyl clupanodonate + H, 109
Tetrabromdocosatrien-
oic acid 22 4, 8, 12 Clupanodonic acid (sardine oil)
+ bromine 92
I -
* Methyl hiragonate.
** Punioio acid is an authenticated isomeride of the more common a- and ,%eleosteario
acids.
*** Triple bond at the Q- and 11-positions.
t The name s-eleosteario acid was assigned to a supposed new isomer of 9, 11, 13-ootade-
catrienoic acid. Later workers (110) found a keto group and assigned the name, lioanio acid,
4-keto-9, 11, I3-octadecatrienoio acid.
tt Hydroxyl group at the IS-position.
otLJrt Concluded structure to be 9, 13-octadeoadienoic acid, but this has not been supported by

E. Tetra-unsaturated compounds

The more highly unsaturated fatty acids, containing four double bonds or
more, occur principally in fish oils. Conjugation does not occur in these oils
and linkages of the type
RCH=CH- (R=C,H,, CsH,)
=CHCH,CH=
=CHCH,CH,CH=
=CHCH,CH,COOH

301
 Ozonolysis of Fatty Acids and their Derivatives
.
are the most common. If conditions are used which decompose malonic acid,
the =CHCH&H= is readily determined quantitatively from the amount of
carbon dioxide evolved. If the fatty acid is ozonized, it is not possible to dis-
tinguish between =CHCH,CH,CH= and =CHCH,CH,COOH, both giving
rise to succinic acid. Therefore, the ester is often used, enabling the latter
grouping to be identified by the formation of succiuic acid half ester. Table 4
contains information on the ozonolysis of tetra-unsaturated compounds.

F. Penta- and hera-unsaturated compounds

The ozonolysis of various fish fatty acids and their esters, containing five
and six double bonds, is covered by Table 5. These acids are similiar to the
tetraenoic acids in that conjugation is absent and the first double bond is at
the 4- or B-position. Since the chain lengths are about the same, the result is
an increase in the percentage of =CHCH,CH= groups and greater proximity
of unsaturation to the end of the chain.

G. Miscellaneous compounds

Ozonolysis of the fatty acid or methyl ester mixture (C,,C,,), obtained

directly from a fish oil, is not very satisfactory for structure determin-
ation. WW1%)
Dimers and trimers are believed to form by a thermal polymerization of
linolenic acid esters involving a Diels-Alder mechanism. A large number of
complex structures are produced. One of the simplest structures of the type
proposed is :
C8H,,CH-CH(CH,),COOH
/ \
C,H,CH CHCH,CH=CH(CH,),COOH
\ /
CH=CH

This contains three external double bonds and one in the ring. In such a
structure a significant part of the double bond on the right does not shift,
since azelaic acid is the principal dibasic acid identified after ozonolysis.
Double bond shifting is also prevalent since ozonolysis produces succinic acid
and monobasic acids of various chain lengths.(12a-129)
Based on ozonolysis, the presence of a four-membered ring structure in
polymerized methyl linoleate is claimed. (lso)

302
 Table 4. Ozonolysis of tetra-unsaturated fatty acids and their derivative.s

Carbon Double bond

Reference
mmber posn.

Methyl octadeca-
tetraenoate 18 4, 8. 12, 15 Sardine oil 90
Methyl octadeca-
tetraenoate* 18 4, 8, 12, 15 Bonito oil 100 ,
Parinaric acid** 18 9, 11, 13, 15 Makita oil 111
Methyl Eicosatetraenoate. 20 4, 8, 12, 16 Bonito oil 169
Amy1 eicosatetraenoate 20 4. 8, 12, 16 Sardine oil 112
Methyl arachidonate* 20 5, 8, 11, 14 Animal phosphatide 85, 91,
113,189
Dibromdecosatetraenoic 22 4, 8, 12, 16 Dooosapentaenoio acid loo,92
acid + bromine

* A partially hydrogenated derivative was also ozonized. *

** At first mistaken for an isomer of eleostearic acid but later (114) shown to contain four
double bonds.

Table 5. Ozonolysis of penta- and hem-unsaturated fatty acids and their

derivatives
-
Carbon Double bond
Umatumted Compound Source
number posn.***
--
Amy1 eicosapentaenoate 20 4, 8, 12, 15, 18 Bonito oil 115
Amy1 eicosapentaenoate 20 4, 8, 12, 15, 18 Sardine oil 116
Eicosapentaenoio acid 20 5, 8, 11, 14, 17 Beef liver phosphatides 189
Clupanodonio acid 22 I 4, 7, 11, 15, 19 Sardine oil 117,118
or
Amy1 clupanodonat.e* 22 ** Sardine oil, bonito oil 92, 100,
or 117, 118
I 4, 8, 11,
12, 15, 19
Docosapentaenoio acid 22 5, 8, 11, 14, 17 S. African pilchard oil 83
Amy1 dooosahexaenoate 22 4, 8, 12, 15, 18, 21 Sardine oil 119
or
4, 8, 11, 14, 17,20
Amy1 dooosahexaenoate* 22 4, 8, 12, 15, 18,21 Bonito oil 120
Methyl dooosahexaenoati 22 5 possible isomers Cod liver oil 121,122
Methyl tricosapenta-
enoate 23 6, 9, 12, 15, 18 C, Ea. from pilchard oil 83
(above)
Amy1 nisinate 24 4,8, 12, 15, 18, 21 Sardine oil 123
-
* A partially hydrogenated derivative was also ozonized.
** The authors do not agree on the structure. Actually, “clupanodonio acid” does not
appear to occur naturally, but is rather the result of heat alteration of a hexaenoio acid. No
doooaapentaenoio aoid product wae found in sardine or cod liver oil when low temperature
molecular distillation was used (121, 122).
*** Becent work (188) indicates disagreement with Toyama’s conclusions about l,d-diene
structures being present in certain unsaturated fish fatty acids. This attitude is based on ozono-
lysia of the model compound 6,9-tridecadienoio acid.

303
 Ozonolysis of Fatty Acids and their Derivatives

IV. USE OF OZONIZATION AND OZONOLYSIS FOR COMPOUND

PREPARATION

A. Geneml

The ozonization of fatty compounds is a valuable synthetic tool. Since a

carboxyl or ester group (or other group which has replaced it) is initially pre-
sent at the l-position, the method readily affords 01, o-difunctional straight
chain compounds, often difficult to obtain by other means. The w-group,
which arises from the original point of unsaturation, is generally an aldehyde
or carboxyl group. Such reactive groups lend themselves well to the syn-
thesis of a variety of longer chain compounds by chain extension.
The original method of Harries for decomposing ozonides involved hy-
drolysis by boiling water. Molinari showed that thermal decomposition could
be used also. Either method produces large amounts of aldehydes and acids.
Therefore, a modified decomposition method is used for synthetic purposes
to produce a single functiona, group.

B. Ozonides

Ozonides are usually intermediates for the preparation of other compounds.

In a few cases the ozonides themselves are desired.
A quantitative study of ozone absorption by various vegetable oils was
made and the constants compared with iodine value.(13i) The ozonides of
linseed oil, (17) camelia ~il(‘~s,133) and glyceryl tri-oleate(134) are described.
Ozonides from glyceryl tri-oleate were made containing 9, 12 or 15 atoms
of added oxygen and the compressibility of their unimolecular films studied.(135)
These ozonide films form in two stages. (136-138)This was interpreted as ad-
dition of ozone to the double bond and to the ester group, forming per-
ester*. Ozonide formation from unimolecular films of oleic acid on water was
studied by Nasini and Mattei.(136)

C. Aldehydes and ketones

The technique of decomposing the ozonide in the presence of sodium bi-

sulphite may aid the isolation of aldehydes. 03’) In order to favour aldehyde
formation and avoid excessive contamination with acids, reductive decom-
position of the ozonide is used. This most commonly involves catalytic hydro-
genation over palladium at low temperature(“‘$ i4’, *“) or chemical reduction
using zinc. Zinc and water(5e*1J”) or zinc and acetic acid(143) may be used.
Over-ozonization should be avoided for best results. Fatty ozonides also can
be reduced by potassium ferrocyanide,(r4’) sodium sulphite(145s190)or sodium
bisulphite.uW)
* Compare with Harries’ early ideas. (lp) Also compare with the conclusion that perozonide
formation from oleic acid involves the ozonide group.t”)

304
 Use of Ozonization and Ozonolysis for Compound Preparation

Fatty compounds which have been subjected to ozonolysis, to obtain al-

dehydes for subsequent synthesis, are oleic acid,(13D-141~143~145~146,lDo) erucic
acid,oQQ) undecylenic acid,(leQ) sodium oleate,04’) methyl or ethyl oleate,(sQ*
142*148,1Do*202)met.hyl undecenoate,(sQ* 14~) methyl enmate, oleyl alcoho1(14211QQ)
oleyl esters, (la’) oleonitrile oD3) pentadecyl 3-butenyl ketone(161) and penta-
decyl 3-butenyl carbinol .(lh) The o-substituted aldehydes produced are par-
ticularly useful, yielding, for example, 1,16-hexadecanedialdehyde,(1M) ‘a
cyclic hemi-acetal(142) and 9-aminononanoic acid.(141s 145*14’, IDo) The latter can
be obtained from oleic acid without isolation of the %formyloctanoic acid by
hydrogenating its oxime or by direct reductive amination.
When dealing with naturally occurring compounds, the unsaturation is
generally of the type RCH=CHR, and aldehydes result when using the
methods just described. If a structure of the type RCH=CR, or R,C=CR,
is present, ketones are produced.(56~*l,ls2,16s) .

D. Acids

Oxidation, either during or after ozonide decomposition, enables the produc-

tion of acids only. Probably the most convenient method for laboratory use
utilizes hydrogen peroxide in acetic acid as the oxidant(lM). This has been
widely used. Oxidation by air or oxygen containing ozone is described in a
patent.os5) High yields are claimed when alkaline silver oxide is the oxid-
ant.(15Q-15s) A complete telescoping of all three steps of ozonization, cleavage
and oxidation into one simultaneous operation is claimed in a patent(15Q).
The oxidation conditions, which are also the ozonization conditions, typically
involve hydrogen peroxide in aqueous acetic acid at 90”.
The preparation of azelaic acid by such methods is described using oleic
acid,(154*1sQ--1QQ) linoleic acid,(iQQ) ricinoleic acid,(lsQ) sperm fatty acids,(155,191)
and tall oil fatty acids.(201)
The ozonolysis of oleic acid is being carried out commercially by Emery
Industries, Inc. The process is conducted to produce azelaic and pelargonic
acids.oQ3) lo-Undecenoic acid yields sebacic acid.(159) Half esters are produced
from methyl oleate(isQ) and methyl 21-docosenoate.(la4) Hydroxy acids result
from oleyl alcohol,(isQ~iQQ)

and

and hydroxyketo acids from l-(w-hydroxyalkyl)cycloalkenes.(iQQ~15Q) Brassidyl

acetate (trans) and erucyl acetate (cis) gave 13-acetoxytridecanoic acid and
its ethyl ester, respectively.(m) The ethyl ester formation seems to be due to
some sort of participation of the ethyl acetate solvent in the scission of the
ozonide. lo-Acetoxy decanoic acid is obtained from lo-undecenyl acetate.(166)

305
 Ozonolysis of Fatty Acids and their Derivatives

Other substituted acids are conveniently obtained by ozonolysis. Oleyl

amine gives 9-aminononanoic acid and lo-undecenyl amine (as the forma-
mide) is converted to lo-aminodecanoic acid.oQr) The decomposition of
oleonitrile ozonide yields g-cyan0 octanoic acid.(lQ*~lQQ)

E. Miscellaneous ozonolysis products

Compounds other than aldehydes or acids may be obtained by working up
the ozonide under still different conditions. Alcohols are formed by catalytic
hydrogenation of the ozonide under more severe conditions than those used
when aldehydes are desired. Thus, 1-(lo-undecenyl) cyclohexanol is con-
verted to l-( IO-hydroxydecyl) cyclohexanol. (15~)Ozonization of oleic acid
or methyl oleate and hydrogenation over copper chromite gives alcohols.(162)
The’reaction of oleic acid ozonide with ammonia is merely described as
giving a crystalline product.
An unusual reaction involves the decomposition of oleic acid ozonide in
the presence of salicylaldehyde, converting the latter to catechol.(16g) Hydro-
gen peroxide arising from the oleic acid ozonide may be responsible. The con-
version of salicylaldehyde to catechol by reaction with hydrogen peroxide in
alkaline solution is known as the Dakin reaction.

V. APPLICATIONS FOR OZONIZATION AND OZONOLYSIS PRODUCTS

A. Ozonides

In 1898 the use of unsaturated fatty acid ozonides as disinfecting agents was
patented.cs) Germicidal and fungicidal properties possessed by the ozonides
of cod-liver oil(ivQ) and olive oil(i7Q*ivi) were attributed to the liberation of
active oxygen. Ozonized glyceryl tri-oleate has been patented for use in oint-
ments and for treating burns. (172)Another patent covers the use of ozonized
ethyl oleate internally as a vermicide. (173)The ozonides of oleic acid(174~175)
and of ethylene oxide condensation products (from tall oil, oleic acid or
abietic acid) (17s~
~6) are effective germicides toward S. aureus. An important
factor in this activity is the pelargonic acid which arises from slow ozonide
decomposition. The results with unsaturated triglyceride ozonides should be
considered in the light of this observation, since most of them are capable of
yielding pelargonic acid on cleava.ge.

B. Monofunctional oxonolysis products

Pelargonic acid, produced commercially by Emery Industries Inc. using the
ozonolysis of oleic acid, has found use in ore flotation and alkyd-type surface
coatings. It is effective as a germicide, fungicide and nematocide. Heavy metal
salts of pelargonic acid are useful as heat-stabilizers for chlorine-containing

306
 References

resins. Esters of pelargonic acid are used as resin plasticizers, synthetic oils
and lubricating grease bases. Examples are diethylene glycol clipelargonate,
dipropylene glycol dipelargonete, triethylene glycol dipelargonate and iso-
decyl pelargonate.
The potentially available pelargonaldehycle is a versatile raw material
and can be converted to a great number of useful products such as nonyl
alcohol and nonyl amine. Reaction of the aldehyde with polyvinyl alcohol
gives polyvinyl nonanal which, as a yarn, has good elastic recovery.(l&)

C. Difunctiond ozonolysis products

Azelaio acid, the other product from the commercial ozonolysis of oleic acid,
gives di-esters and polyesters useful as resin plasticizers and as lubricants.
The di-octyl azelates are widely used. These uses, along with many others for
azelaic acid have been reviewed .(177*17s)Polyester coatings and plastics con-
taining azelaic acid are of interest.
The polyamide from 9-aminononanoic acid is convertible to an oriented
fibre having good strength, resistance to water and chemicals, and heat
stability.(145p147) B-Amino-octanoic acid is also of interest as a polyamide
intermediate.(ls3) Azelaic acid, produced by ozonolysis, and hexamethylene
diamine give nylon 6-9, M.pt. 212”C.(1s1)
A Japanese process involves the production of a polyurea fibre
[ -(CH,),NHCONH-1, from nonamethylene diamine and urea.(ls4) Dutch
workers have obtained the same fibre from nonamethylene diamine and car-
bon oxydphide. ~9~)Advantages over ordinary 6-6 Nylon are higher melting
point and better water and chemical resistance.

REFERENCES

(1) MOLINARI E. (1903) Ann .aoc. chim., dlilano 9, 145.

le) RALSTON A.W. (1948) Fatty Acids and their Derivativea, New York: John Wiley,
p. 419.
(8) HILDITCH T.P. (1956) The Chemical Constitution of Natural Fate, 3rd ed., New
York: John Wiley, p. 495.
t4) MOLINARI E. (1908) Ber. dtsch. them. Bee. 41, 585.
6) WEYL T. (1906) Ber. dtsch. them. t&s. 39, 3347.
@) SHAND W. Jr. and SPURR R.A. (1943) J. Amer. them. Sot. 65, 179.
('1 TRAMBARVLO R.F., GHOSH S.N., BURRUS C.A. Jr. and GORDY W. (1953) J. them.
Phys. 21, 851.
(*) HUQHES R.H. (1956) J. them. Phye. 24, 131.
@) PENNEY W.G. and SUTHERLAND G.B.B.M. (1936) Proc. Roy. Sot. A 166, 654.
(10) SMYTH C.P. and LEWIS G.L. (1939) J. Amer. them. Sot. 61, 3063.
(11) HARRIES C. and THIEME C. (1906) Ber. dtsch. them. Ues. 39. 2844, 3728.
(1%)HARRIES C. and TURK H.O. (1906) Ber. dtsch. them. Gee. 39, 3732.
(Ia) HARRIES C. and FRANOK W. (1909) Ber. dtsch. them. &8. 42, 447.

21 progress 307
 Ozonolysis of Fatty Acids and their Derivatives
.
(1’) HARRIES C. and FRANCE W. (1910) Liebig’s Ann. 374, 356.
(16) BRUS G. and PEYRESBLANQUES G. (1930) Corn@. rend. 190,501.
(16) MOLINARI E. end BAROSI C. (1908) Ber. dtsch. them. Qes. 41, 2794.
(17) MOLINARI E. end SONCINI E. (1906) Ber. dtsch. them. Be.s. 39, 2735.’
(I*) NOLLER C.R., CARSON J.F., MARTIN H. and HAWKINS K.S. (1936) J. A,mer.
&em. Sot. 68,24.
(lo) YAKUBCHIE A.I., KASATKINA N.G. end PAVLOVSHAYA T.E. (1955) J. Appl.
Chem. (U.S.S.R.) 26, 1473; (1955) J. Cen. Chem. (U.S.S.R.) 26, 1419.
(aa) YAEUBCHIK A.I. and KASATEINA N.G. (1956) J. AppZ. Chem. (U.S.S.R.) 26,699.
(80 CHASTONAY PH. DE and BRINER E. (1954) Helv. chim. acta 37, 1561.
(a*) KHAN N.A. and NEWMAN M.S. (1952) J. org. Chem. 17, 1063.
@*) MOLINARI E. (1907) Ber. dtsch. them. aes. 40, 4154.
ta4) MOLINARI E. (1908) Ber. dtech. them. @ea. 41, 2782.
ca6)HARRIES C. (1907) Ber. d&h. them. Qes. 40, 4905.
tas) HARRIES C. (1908) Ber. dtach. them. @es. 41, 1227.
ca7) STAUDINQER H. (1925) Ber. dtsch. them. Ges. 58, 1088.
@) RIEOHE A., MEISTER R., SAUTHOFF H. and PFEIFFER H. (1942) Liebig’s Ann.
663, 187.
(*@ LEFFLER J.E. (1949) Chem. Rev. 46, 399.
(So) CRIEQEE R. (1948) Liebig’s Ann. 560, 127.
(sl) CRIE~EE R. (1953) Liebig’s Ann. 683, 1.
ta2) CRIEQEE R., BLUST G. snd ZINE~ H. (1954) Ber. dtsch. them. Ues. 87, 766.
ts8) Various papers presented et the International Ozone Conference, Chicago, Nov.
28-30, 1956, Advances in Chemistry Series, No. 21. “Ozone Chemistry and Tech-
nology”.
ta4) WIBAUT J.P., SIXMA F.L.J., KAMPSCHMIDT L.W.F. and BOER H. (1950) Rec.
truv. chim. 69, 1355.
@s)SIXMA F.L.J., BOER H. and WIBAUT J.P. (1951) Rec. trav. chim. 70, 1005.
(w) CRIE~EE R. (1956) paper presented at the International Ozone Conference, Chicago,
Nov. 28-30, Advances in Chemistry Series, No. 21. 133.
ts7) MARKLEY K.S. (1947) Fatty Acids, Interscience Publishers, Inc., New York.
pp. 424-8.
@a) HAVERKAMP BE~EMANN P., KEPPLER J.G. and BOEKENOO~EN H.A. (1950) Rec.
trav. chim. 69, 439.
@go)YOUNG W.G., MCKINNIS A.C., WEBB I.D. and ROBERTS J.D. (1946) J. Amer.
them. Sot. 68, 293.
(‘O) STOLL M. and ROUVE A. (1944) HeZw. chim. acta 27, 950.
(‘l) KLENE E. and BON~ARD W. (1952) 2. physio2. Chem. 290, 181.
(‘*) INOUE Y., NODA M. and HAMURO Y. (1952) J. Agr. Chem. Sot. Japan 26, 491;
(1952) Chem. Abstr. 46, 6408.
(4s) FRIES J., HOLASEE A. and LIEB H. (1956) blikrochim. Acta 1722.
(“) HARRIES C. and THIEME C. (1905) Liebig’a Ann. 343, 354.
f4~) NOORDUYN A.C. (1919) Rec. traw. chim. 38, 317.
(‘O) STEQER A., VAN LOON J. and PENNEEA~P B. (1940) Rec. trav. chim. 59,952.
(“’ STEQER A., VAN LOON J., VELLENGA B.R.N. and PENNEKAMP B. (1938) Rec.
trav. chim. 67, 25.
(48) BOELHOUWER C., LIE O.T. and WATERMAN H.I. (1953) Research Correspondence
6,41 S.

308
 References

(OQ) BICKFORD W.G., FISHER G.S., KYAME L. and SWIFT C.E. (1948) J. Amer. Oil
Chem. Sot. 26, 254.
(50) BAUER K.H. and ERMANN F. (1939) Chem. U~machuu 37,241.
(50 BOESEEEN J., HOO~LAND J.J.. V.D.BROEI~ A.G. and SMIT W.C. (1927) Rec. trav.
chim. 46, 619.
taa) TOYAMA Y. and TSUCIIIYA T. (1935) J. Sot. Chem. Ind. Japan 38, Suppl. binding
35.
tss) TOYAMA Y. end TSUCHIYA T. (1935) J. Sot. Chem. Id Japan 38, Suppl. binding
36.
(~1 FORE S.P., O’CONNOR R.T. and GOLDBLATT L.A. (1958) J. Amer. Oil Chem. Sot.
35, 225.
(55) NUNN J.R. (1952) J. Chem. Sot. 313.
(56) VERMA J.P., GUPTA S., NATH B. end A~QARWAL J.S. (1956) J. Indian Chem. Sot.
33, 111 and earlier references given there.
(57) HARQREAVES G.H. and OWEN L.N. (1947) J. Chem. Sot. 753.
(5@ COLLAUD C. (1943) Helv. chim. a.& 26, 1064.
(59) NOLLER C.R. end ADAMS R. (1926) J. Amer. them. Sot. 48, 1074.
(50) TSUJIMOTO M. (1928) Chem. Ulnschaw 35,225.
(El) TSUJIMOTO M. (1928) Bull. Inst. Tokyo Ind. Rea. Lab. (3) 23,53; (1929) Chem. Abstr.
23, 1109.
(82) TSUJIMOTO M. (1925) Chem. Utnxhuu 32, 202.
(63) TOYAMA Y. (1927) J. Sot. Chem. Ind. Japan 30, 603; (1928) Chem. Abstr. 22, 575.
@*) RIEBSOMER J.L. and JOHNSON J.R. (1933) 66, J. Amer. them. Sot. 3352.
(65) EIBNER A., WIDENMAYER L. and SCHILD E. (1927) Chem. Umechau 34,312.
(66) HILDITCH T.P. and JONES E.E. (1927) J. Sot. Chem. Ind. 46,174 T.
(67) VAN LOON J. (1927) Rec. trav. chim. 46, 492.
(a*) VONQERICHTEN E. and KOHLER A. (1909) Ber. dtsch. them: Ges. 42, 1638.
(68) STEQER A. and VAN LOON J. (1928) Rec. trav. chim. 47, 471.
(70) STEGER A. and VAN LOON J. (1933) Rec. trav. chim. 52, 593.
(71) HALLER A. and BROCHET A. (1910) Compt. rend. 160,496.
(72) KHAN N.A., DEATHERAQE F.E and BROWN J.B. (1951) J. Amer. Oil Chem. Sot.
28, 27.
t’s) STEQER A. and VAN LOON J. (1941) Rec. trav. chim. 60, 106.
(74) STEQER A. and VAN LOON J. (1943) Fette u. Seifen 60, 305.
(‘6) TOYAMA Y. and TSUCHIYA T. (1934) J. Sot. Chem. Id Japan 37, Suppl. binding

(7e) TOYAMA Y. and TSUCHIYA T. (1934) J. Sot. Chem. Ind. Japan 37, Suppl. binding
14.
(77) TOYAMA Y. (1927) J. Sot. Chem. Ind. Japan 30, 597; (1928) Chem. Abstr. 22, 575.
(‘8) HOLDE D. and ZADEE F. (1923) Ber. dtsch. them. Ues. 66, 2052.
(7~ VAN LOON J. (1930) Rec. trav. chim. 49, 745.
(*O) TSUJIYOTO M. (1927) J. Sot. Chew Znd. Japan 30, 868; (1928) Chem. Abstr. 22,
1326.
(81) HALL J.A., LEWIS J. W. and POLQAR N. (1955) J. Chem. Sot. 3971.
(82) ALLEN R.R. (1956) J. org. Chem. 21, 143.
(88) WHITCUTT J.M. and SUTTON D.A. (1956) Biochsm. J. 63,469. .
(8~ TAKAHASHI K. (1921) J. Chem. Sot. Japan 42, 130; (1921) Chem. Abstr. 16, 2273.
186) ARCUS C.L. and SMEDLEY-MACLEAN I. (1943) Biochem. J. 37, 1.
(86) RIEBSOMER J.L. and NESTY G.A. (1934) J. Amer. them. Sot. 66, 1784.

309
 Ozonolysis of Fatty Acids and their Derivatives

@7) HATT H.H. and SZUMNER A.Z. (1954) Chem. Ind. 962.
(**I LwrHELnf S.P., SCHWARTZ H.M. and VON HOLDT M.M. (1952) J. Chem. Sot. 1088.
w DAVIS S.B., CONROY E.A. and SHAKESPEARE N.E. (1950) J. Amer. them. Sot. 72,
124.
@O)TOYAMA Y. and TSUCHIYA T. (1935) Bull. Cl&em. Sot. Japan. 16, 232.
w MOWRY D.T., BRODE W.R. and BROWN J.B. (1942) J. biol. Chem. 142,679.
@*I TOYAnlA Y. and TS~CHIYA T. (1935) Bull. Chem. Sot. Jnpan 10, 441.
@S)TAEANO M. (1937) J. Sot. Chem. Ind. Japan. 40, Suppl. binding 165.
tp4) E~DMANN E., BEDFORD F. and RASPE F. (1909) Ber. dtsch. them. Ues. 42, 1334.
@5) CASTILLE A. (1939) Liebig’a Ann. 643, 104.
(06) FAUVE M. (1948) Peintures, pigments, wernis. 24, 110. 6, 183.
(@'ISTEQER A. and VAN LOON J. (1940) Rec. tram. chim. 69, 1156.
(WI CROMBIE L. and TAYLER J.L. (1954) J. Chem. Sot. 2816.
@O)CALDERWOOD R.C. and GUNSTONE F.D. (1954) J. Sci. Food Agr. 5, 382.
(loo) MA-&DA S. (1942) J. Sot. Chem. Ind. Japan 45, Suppl. binding 3, 4, 8, 134.
(~1) TOYAMA Y. and TSUCHIYA T. (1935) Bull. Chem. Sot. Japan 10, 192.
(102) HILDITCH T.P. (1956) The Chemical Constitution of Nntural Fats, 3rd ed.. John Wi-
ley, New York, p. 521.
(103) EIBNER A. and ROSSMANN E. (1928) Chem. lJ7,tich.o.u 35. 197.
(IO') MAJInlA R. (1909) Ber. dtsch. them. Qes. 42, 674.
(106) STEQER A. and VAN LOON J. (1938) Rec. tram. cl&m. G7, 620.
t106) TOYAMA Y. and TSUCHIYA T. (1935) J. Sot. Chem. Ind. Japan 3& Suppl. binding
182.
(lo') STEOER A. and VAN LOON J. (1937) Fette u. Seifen 44, 243.
(lo*) VAN LOON J. and STE~ER A. (1931) Rec. trav. chim. 50, 936.
(loo) TAKANO M. (1937) Bull. Chem. Sot. Japan 12, 395.
(110) BROWN W.B. and FARMER E.H. (1935) Biochena. J. 29, 631.
(w) TSUJIMOTO M. and KOYANACI H. (1933) J. Sot. Japan 36, Suppl. Chem. Ind.
binding 673.
(112) TOYAMA Y. and TSUCHIYA T. (1935) Bull. Ch,enz. Sot. Japan 10, 296.
(lls) SHINOWARA G.Y. and BROWN J.B. (1940) J. biol. Chew 134, 331.
(l") FARMER E.H. and SUNDERLAND F. (1935) J. Chem. Sot. 759.
t115) MATSUDA S. (1942) J. Sot. Chem. Ind. Japan 45, Suppl. binding 49.
ale) TOYANA Y. and TSUCHIYA T. (1935) Bull. Chena. Sot. Japan 10, 301.
(11') TSUJInIOTO M. (1928) Bull. Inat. Tokyo Ind. Res. Lab. (3) 23, 1; (1929) Chem. Abstr.
23, 1108.
cla) TSUJINOTO M. (1928) Bull. Chem.. Sot. Japan 3, 299.
(119)TOYANA Y. and TSUCHIYA T. (1935) BUZZ. Chem. Sot. Japan 10, 539.
ozo) MATSUDA S. (1942) J. Sot. Chem. Ind. Japan 45, Suppl. binding 158.
(121) FARNER E.H. end VAN DEN HEUVEL F.A. (1938) J. Sot. Chem. Ind. 57, 24.
(122) FARMER E.H. and VAN DEN HEUVEL F.A. (1938) J. Chem. Sot. 427.
(lZ3) TOYANA Y. and TSUCHIYA T. (1935) Bull, Chem. Sot. Japan 10, 547.
(12() KLENK E. and BONQARD W. (1953) 2. physiol. Ch,em. 292, 51.
(126) MCGREQOR R.R. and BEAL G.D. (1926) J. Amer. chew Sot. 48, 3150.
(12~) KINO K. (1937) Sci. Papers Inst. Phys. Chem. Research (Tokyo) 31, 244; (1937)
Chem. Abetr. 31, 6196.
(le7' PETIT J. (1946) Peintures, pigntents, vernis. 22, 3.
(12') CHanrPETrER G. and PETIT J. (1945) Compt. rend. 226, 748.
(u9) CHANPETIER G. and PETIT J. (1945) Bull. sot. chim. (5) 12,680.

310
 References

~~9) RALSTON A.W. (1948) Fatty Acids and their Derivatives, John Wiley, New York,
p. 471.
(131) FENAROLI P. (1906) Gaze. chim. ital. 36, II 292.
os2) IZUMI G. (1951) J. Chem. Sot. Japan., Ind. Chem. Sec. 54, 546, 548; (1953) Chem.
Abstr. 47, 6678.
(1a3) ~ZUMI G. (1954) J. Chetn. Sot. Japan, Ind. Chem. Sect. 57,499; (1955) Chem. Abstr.
49, 5861.
oa4) MOLINARI E. and FENAROLI P. (1908) Ber. dtsch. them. Ges. 41, 2789.
(135) NASINI A. and MATTEI G. (1941) Gazz. chi,m. ital. 71, 422.
(136) NASINI A. and MATTEI G. (1941) Gazz. chim. ital. 71, 302.
(137) NASINI A. and MATTEI G. (1943) Chem. Abatr. 37,2244.
03*) NASINI A. and MATTEI G. (1942) Kolloid 2. 101, 113.
(la83 ISI~A~A S. and MIYATA A. (1940) Chem. Abstr. 34, 981.
(140) FISCHER F.G., DULL H. and ERTEL L. (1932) Ber. dtsch. them. Ges. 65, 1467.
(141) CARPENTER A.S. end REEDER F. (1956) Brit. Pat. 743 491 to Conrtaulds, Ltd.
(14*) HELFERICH B. and SCHAFER W. (1924) Ber. dtsch. them. Ges. 57, 1911.
(14a) KOBATA Y. (1935) J. 9gr. Chem. Sot. Japan 11, 709; (1935) Chem. Abstr. 29, 7279.
(lr4) HARRIES C. Ger. Pat. 321 567 (1918).
(145) OTSUKI H. and FUNAEASHI H. (1956) paper presented at the International Ozone
Conference, Chicago, Nov. 28-30, Advances in Chemistry Series, No. 21,205.
(146) HARRIES C. and TURK H.O. (1907) Ber. dtsch. them. Ges. 40, 2756.
(147) OTSUEI H. and FUNAHASHI H. (1954) Japan. Pat. 8417 to Nippon Ozone Co.
(149) STOLL M. and ROUVE A. (1937) HeZv. chim. acta 20, 525.
(l(9) H~RDINQ V.J., WALSH G.M. and WEIZMANN C. (1911) J. Chem. Sot. 99,448.
b”) IZUMI G. (1955) J. Chem. Sot. Japan, Id Chem. Sect. 68, 803; (1956) Chem. Abstr.
50, 11936.
osl) HELFZRICH 13. and KOSTER H. (1923) Ber. dtsch. them. Ges. 56, 2088.
05?) COLLAUD C. (1942) HeZv. chim. acta 26, 965.
(15a) COLLAUD C. (1943) HeZv. chim. acta 26, 1155.
w4) RIEBSOYER J.L. and TALLMAN R.C. (1934) Proc. Indiana Acud. Sci. 43, 136.
(~5) KOBAYASHI T. and MIYAZAKI S. (1954) Japan Pat. 5079 to Bureau of Industrial
Technics.
flse) BSINQER F. PB Report 95601.
(157) Ger. Pat. 868 148 (1953).
(Isa) .&INCER F. (1942) Ber. dtsch. them. Ges. ii, 656.
(159) RIECHE A. (1932) Ger. Pat. 565 158.
060) HARRIES C. and TANK L. (1907) Ber. dtsch. them. Ges. 40, 4555.
(lG1) KINO K. (1939) Ch,em. Rev. (Japan) 5, 475; (1941) Chem. Abstr. 36, 7943.
(lez)Izum G. (1956) J. Chem. Sot. Japan, Id. Chem. Sect.; 59, 1129.
(193) GOEBEL C.G., BROWN B.C., OEHLSCHLAEGER H.F. and ROLFES R.P. (1957)
Brit. Pat. 757355 to Emery Industries, Inc.; (1957) U.S. Pat. 2813 113.
os4) RUZIOEA L., STOLL M. and SCHINZ H. (1928) HeZv. chim. actu 11, 670.
(le5) COLLAUD C. (1943) Helv. chim. acta 26, 849.
(x6) MOTTIER M. (1931) Helv. chim acta 14, 1080.
(167) OTSUKI H. and FUNlHASHI H. (1956) Japan. Pat. 4117 to Nippon Ozone Co.
(leg) CARPENTER A.S. and REEDER F. (1955) Brit. Pat. 741739 to Courtanlds, Ltd.
(I-59) WACEK A., EPPINQER H.O. and BEZARD A. (1940) Ber. dtsch. them. GM. 73, 521.
two) STEVENS (1936) J. Bad. 32, 47.
(171) CRONHEIM (1947) J. Am. Phnrm. Assoc., ~5%. Ed. 36, 274, 278.

311
 . Ozonolysis of Fatty Acids and their Derivatives

(l’*) JOHNSON (1844) U.S.Pet. 2366062 (1944) to Letimer LabOretOry, Inc.

(lT8) BUTZ end LALANDE (1937) U.S. Pet. 2097 115 to D.Jeyne and Son, Inc.
(17’) KAEABINOS J.V. end FERLIN H.J. (1964) J. Amer. Oil Chem. Sot. 31, 228.
(l7b) FERLIN H.J. end KA~ABINOS J.V. (1955) Xrane. Ill. State Ad. Sci. 47, 86.
(176) FERLIN H.J., BALLUN end KARABINOS J.V. (1964) J. Amer. Oil Chem. Sot. 31,
103.
(177) KADESOH R.G. (1954) J. Amer. Oil Chem. Sot. 31, 568.
(17@) KADESOH R.G. (Aug. 1962) &fcdern Plaetim 29, 111.
(17@) KEPPLER J.G. (1957) Rec. trav. chim. 76,49.
(lao) BOER H. end KOOYMAN H.C. (1961) And. chim. acta 6, 550.
(Ial) KNESBAOH S. end MAQQIOLO A. (1958) paper given at 134th meeting, Amer.
Chem. Soo., Chicago, Ill., Sept. 7-12.
(la4) SCIHOLFIELD C.R., JONES E.P., STOLP J.A. and COWAN J.C. (1958) J. Amer. Oil
Chem. Sot. 36, 44%.
(les) KNEQTEL J.T., BOELHOUWER C., TELS M. and WATERMAN H.I. (1967) J. Amer.
Oil Chem. Sot. 34, 336.
(la’) ALLEN R.R. and KIESS A.A. (1955) J. Amer. Oil Chem. Sot. 32,400.
(18s) FAURE P.K. end SMITH J.C. (1956) J. Chem. Sot. 1818.
(lee) BROOKE D.G. end SMITH J.C. (1957) Chem. Id. 1508.
(Is7) CROYBIE L. and HALSALL T.G. (1956) Ann,. Rep. Chem. Sot. 63, 180.
(le*) DE SURVILLE B.M.A., RIVETT D.E.A. and SUTTON D.A. (1957) J. Chem. Sot.
3304.
(la@ MONTAQ W., KLENK E., HAYES H. end HOLMAN R.T. (1957) J. biol. Chem. 63,
227.
(loo) OTSUKI H. and FUNAHASHI H. (1957) Brit. Pat. 789575 to Nippon Ozone Co.
(ln) HATTORI H. and AOKI M. (1957) Chem. Abstr. 61, 10948.
(19*) IZUMI G. (1955) J. Chem. Sot. Japan, Ind. Chem. Sect. 68, 803.
(lo’) CARPENTER A.S. end REEDER F. (1958) Caned. Pet,. 552 623 to Courteulds, Ltd.
(lo’) (1958) Chem. Engr. Jun. 13 73; (1957) Brit. Pat. 773964-5 to Toyo Koatsu Indus-
tries, Inc.
(l”) VAN DER KERE G.J.M., OVERMARS H.G.J. end VAN DER WANT G.M. (1955) Rec.
trav. chim. 74, 1301.
(lB6) RIEOHE A. (1931) Alkylperoxyyde and Ozon.ide, Theodor Steinkopff, Dresden and
Leipzig, pp. 150-159.
(lw) BAILEY P.S. end BATH S.S. (1957) J. Amer. them. Sot. 79, 3120.
(198) BAILEY P.S. (1957) Chem. Ind. 1148.
(lw) BLAIR E.A. and MAQQIOLO A. (1958) p&per given et 134th meeting, Amer. Chem.
Sot., Chicago, Ill., Sept. 7-12.
(*O”) CRIEQEE R. (1957) Record of Chem. Progress 18, 111.
(*01) MAQQIOLO, A. (1958) U.S. Pet. 2, 865,937 to Welsbech Corp.
(*O*) PRYDE E.N., ANDERS D.E., TEETER N.M. and COWAN J.C. (1960) J. Org. Chem.
26,618.

312