SOME STUDIES ' N FATTY ACID SER ES
PART TWO CO-OLEFINIC FATTY ACIDS
NATIONAL CHEMICAL LABORATORY, POONA- 8. - (1965 ) C 0 T E T S
Page
CHAPTER I limOiXJCTION 25-34
w-Olefinic fatty acids 25
Methods of synthesis 25
Methods utilising components 28 in which the co-olefinic group is already present.
Methods in which the w-olefinic 30 group is produced by an elimiaation reaction.
Other methods 31
References 33
CHAPTER II PYROLYSIS OF MAiiY-MEMBERED 36 - 130 LACTONESj A UEJJHIAL METHOD 1T(B THE SYNTHESIS OF «-0LEFiiac f a t t y a c i d s .
Preliminary investigations 36
Pyrolysis of many-membered 43 lactones
Preparation of ^J^-hydroxy 45 fatty acids
Preparation of lactones 52
Pyrolysis of lactones 62
Discussion 67
Experimental 75
Summary 126
References 127 Page
CHAPTER III SYSrmTIC 131 - 153 CHAM-SHOHTENIiia OF W-OLEb*INIC f a t t y a c id s
Chain-shortening by 132 one carbon
Chain-shortening 133 two carbons
Chain-shortening by 136 three carbons
Experimental 141
Summary 150
References 151 CHAPTER I
INTRODUCTION 2 5
oj-OLH^’INIC FATTY AGIDS
I.{TRQJUCTIQN
The work described in this Part deals with the development of general method for the preparation of long chain co-olefinic fatty acids. cu-Olefinic acids offer an unique opportunity for degrading the molecule from one end in bits of one or more carbon atoms at a time. This work was of interest in comiection with the possible utilization of kamlolenic acid:
H0CH2(CH2)3CH=CHCH=CH-CH=CH(CH2)7C00H the major component of the o il from the seeds of Mallotus phllippinensis. ’
It appears relevant, in connection with this work, to describe very briefly the state of our knowledge with regard to to-olefinic acids. Unlike the other saturated and unsaturated acids, terminally unsaturated fatty acids are not at all wide spread in nature,though 9-decenoic acid has either been detected, isolated or identified in 1 —8 human milk fat , in butter and milk fats of various animals , 9 * and in sperm head oil .
METiiOJo Qi*'
Table 1 summarises the properties of the known co-olefinic acids. 20
TABLE 1 : PHOPERTILS OF w-OLEt‘'Ii;aC FATTY ACIDS
CH2=CH(CH2)nC00H
Jo. n= ni.p. b .p . P r . H e f. mra °c
1 0 1 2 . 3 1 4 1 .9 1 .0 6 2 1 ^ ^ 1 0 ,1 2 i 65 30 - I 12
!i 3 .5 1 .0 4 5 ^ ^ 1 .4 8 5 ^ ^ ; 13
2 1 1[-39 163 1 .0 1 3 ^ ^ 1 .4 2 5 7 ^ ^ 1 0 ,1 4 ] [ 72-72 .5 14 - - ] 16 1 3 2 ,<-18 189 0.9843^® 1.434l'^’ ^ s 1 0 ,1 1 ,1 4 r 1 186-87 745 0 .9 9 8 7 ^ i 11 f w« 187-89 0 .9 8 4 1 6 ^ ^ - 1 15
4 3 !f 203 0 .J 6 1 0 ^ ° 1 .4 3 4 3 ^ ^ ] 1 0 ,1 1 [+1 107 16 0 .9 6 1 0 ^ ° 1.4385^'° ] 17 17 5 4 ;-6.5 225 0.952"^^ 1.4425^® 1 10
• 225-27 1 18
;-6.5 125 15 0.3515^^-9 1.4404^^*^ J 19,11
( Lthyl ester 210- 12) - 20,11
7 6 116-18 1 0.il46^^*® 1.4492^^ 19 20 8 7 143-48 15 0.9238^^ 1 .4 4 8 8 10,11
-0.5 155-60 14 1 .4 4 6 2 4
4 ] 2
8 124.5 275 0.3075^^ 1.4464^"^^^ 10 [24-25 165 15 11 2 4 ^2-23 131 1 0 .9 0 7 2 19
. . . .contd. ^ (
TABLE 1 (Gontd.)
iN[o. n= m .p . b .p . P r. ^ R e f. mm °C
10 9 ( 143-44 3 0 .9 0 3 0 ^ ° 1 .4 5 1 0 ^ ^ ; 10,11,21
Cf .P .1 9 171-72 13 0.907^° - 22
11 10 192 2 5 a 10 «
'38-39 192 20 9 21 162 S ;S8-38.2 18 5 15 1 22,11
12 11 Not reported r 13 12 1 198 8 I 10
[49.8- 195 8 - 3 22 [50
14 IS Ilot reported
1 5 14 Not reported
16 15 [55-55.5 ] 2 3 ,2 5 .55,5- ] 24 [56.1
Several methods have been used for the prepara- tion of these compounds , and these may be broadly divided into three groups.
A. Methods utilising componeats in which
the fl>-olefinic group is already present
B. Methods in whicsh the w-olefinic group
is produced by an elimination reaction.
G. Other methods. o 8
A. Methods ut il l sing coigponents ia which the
ui~oleflnlc group is already present.
A number of compounds have been synthesized
by chain extension of a suitable starting material by
several of the available methods (Grrignard reaction,
exchange with cyanide, malonic acid synthesis etc.)*
Starting from vinyl ajagnesium and allyl aagnesiuia h alid es,
acrylic and vinyl acetic acids have been prepared res pect ively^^*^^. From allyl bromide, vinyl acetic acid^^ and allyl acetic acid^^*^^ have been synthesized. Vinyl
ethyl bromide has been used to prepare 5-hexenoic acid^"^*^^, vinyl propyl bromide was used to prepare 6-heptenoic acid^^, v/hich in turn, was elaborated to 8-nonenoic acid, which was, next, used as a starting material for 10-uudecenoic acid synthesis . The ready availability of 10-undecenoic 10 11 acid from castor oil cracking * * made possible its further elaboration into 11-dodecenoic acid^^, l2-tri- decenoic acid^^*^^, and 14-pentadeceiioic acid*^^. 17-octa- decenoic acid has been prepared from 10-undecenoic acid 23 24 by the following two routes * 2 9
•CH2= C H (C H 2;q c o o h
!• EtOH, H2SO4 S0 ( 2:LiAIH4 ,et-tier
CH2=CH(CH2/8C0CI CH2=CH(CH2)0CH2OH
Anhyd- Et.OH PBrj S-CH^COCHgCOOEt, NaOEt, BrCH2( C COOEt
3 Na,ether CH2=CH(CH2 )gCH2Br
4 CH3C0CNa L(CH2)5 COOEt COOEt 1 Mg ,CdCl2 _ 2 EtOCO(CH2)5COCI, COCH. CeHg CH2=CH(CH2)qCC C (CH2,5CCOEt 3- Aq' NaOH + 4 H COCEt
I-Aq- KOH CH= CH(CH2)gCH2C0(CH2)5C00H 2H^ 1 • Wolf -Kishner CH2=CH(CH2)gC0CH2(CH2)5C00Et reduction 2 K0H,Et0 H 1 Aq.NaOH 3 h" 2-H'^ 3 W olf-K1 shner reduction 3 0
B. ^Mettyids ia which the a)>oleriaic gruup j,a_ .MrodftftlA by aa ellmliiation reaction
Several types of elimination reactions have been used.
a) Jehydrohalo r enat 1 on
Acrylic acid (2-propeaolc acid) has beea prepared
by dehydrohalogenation of p-chloroproplonlc acid^^*^^.
Similarly vinyl acetic acid has been synthesized from
1 ,2 -dlbromopropionitr il e^*^.
b) Deamination
5-hexenoic acid and 6-heptenoic acid were prepared
by deamination of 6-arainocaproic acid and 7-arainoheptanolc
acid respectively, using nitrous acid for the pui’pose^^*^^.
c) Electrolytic decarboxylation
The Kolbe electrolysis of the half esters of several
dicarboxylic acids has been shown to produce an co-olefinic
acid ''ith one carbon less. Thus 5-hexenoic, 6-heptenoic,
7-octenoic and 8-nonenoic acids have been obtained by the
electrolytic decar bo-K.yl at ion of the potassium salts of
the half esters from pimelic^^, suberic^® azelaic^^’^^
and sebacic acids^^ respectively.
d) Pyrolysis of polyesters
Acrylic acid is being prepared commercially by the
pyrolysis of polyesters obtainable from the poljnnerization 13 of B-propiolactone . 3i
e) Psrrolysls of 8-hydroxy olefi.aic acid
10-Uadeceaoic acid is comiaerdally prepared by the pyrolysis of castor oil. The mechanism of this reaction has been investigated by Arnold and iraolins'tcy, who have profitably exploited this reaction for a variety 31-33 of purposes
C. Jther methoas.
Some specific methods are available for the synthesis of certain co-olefinic acids. Thus, for example, acrylic acid is being manufactured commercially by "carbonyl reaction" for which basic raw materials are acetylene, fiarboa monoxide (supplied as such or in the form of nickel IS carboiiyl) and water . This acid has also been prepared 13 by decarboxylation of maleic acid a*id catalytic "hydrolysis” of maleic anhydride^°»^^.
Vinyl acetic acid has been synthesized from 3-butynoic acid by converting it to allenic acid followed by reduction 1 4 with lithium alumixiium hydride .
Allyl acetic acid was prepared by the reduction of 27 methyl 4-pentynoate with sodium and alcohol
5-Hexenoic acid was obtained by decarboxylation of 28 A p-butenyl malonic acid . It has also been prepared from cyclohexanone through formation of 5-hexanal by ring-rupture 33
aad conversion of the aldehyde to hydroxamic acid followed by treatment with sulphuric acid^*^*^^. 33
REFERESiCES
1 A.W. Bosworth, J. Biol. Ghem, 106, 235 (1934),
2 I. Smedley, Bioehem. J. 6, 451 (1912).
3 A. Grriin and T. Wirth, Ber. 55, 2197 (1922).
4 I.P, Hilditch, Checiical Constitution of Natural Fats, Chapman and Hall Ltd. London (1956),125,319,513,514.
5 A.W. Bosworth and J.B. Brown, J. Biol. Chem. 103, 115 (1933).
6 R.W. Hisaouschneider and N.R. ELlis, ibid. 113, 219 (1936).
7 T.P. Hilditch and H.Jasperson, Bioehem. J. 38, 443 (1944).
8 X.T. Achaya and T.P. Hilditch, ?roc. Hoy. 3oc.(London) 137B. 187 (1950).
9 Y. Toyama and T. Tsuchiya, J. Chem. See. Japan, 56, 1313 (1935).
10 K .S , I4arld.ey, Fatty Acids, Part I , p p .1 1 2 , 110-136, Interscience Publishers Inc. New York (1J60),
11 A.W. Ralston, "Fatty Acids and their Derivatives" pp.81-95, John Wiley and i3ons, New York (1948).
12 R.E. Kirk and D.F, Othiaer, Encyclopedia of chemical Technology. First Ea. Vol.I, p.176,177, Interscience Encyclopedia Inc. New York (1947).
13 R.E. Kirk and J.F. Othmer, ibid. Second edition. Vol.I, pp.285, 293-295, Interscieace fiiblishers Inc, New York (1 9 6 3 ).
14 L.F. Fieser and M. Fieser, Advanced Organic Chemistry, p.240,360,575, Asia Publishing House, Bombay (1961).
15 J.F. Thorpe and M.A. V/hiteley, Thorpe’s Dictionary of Applied Chemistry, Fourth edition, Vol.I, p .256, Longmans Green and Co., London (1937).
16 A.I. Vogel, *Text Book of Practical Organic Chemistry', p.465, Longmans Green and Co., London (1956). 3 4
17 R.A. Letch and H.P. Linstead, J. Chem. Soc, 1994 (1934).
18 Wallach, Ann. 312. 171,207 (1900); 3 ^ , 40 (1905).
19 R .P . Linstead and H.x'i. ziydon, J . Ghem. i o c . 79 , 1197 (1901).
20 M. Carmichael, ibid. 121. 2545 (1922).
2 1 G .G . Tomecko and R , Adams, J . Ai:i. Chetri. 3oe. 4 9 » 522 (1927).
22 P. Chuit, F. Boelslng, J. Ilausser and G. Malet, Helv. Chlm. Acta. 10, 113 (1927).
2 3 R. Kapp and A. Knoll, J . Ara. Ghem. 3oc. 6 5 , 2062 (1 9 4 3 ).
24 W.F. Huber, Ibid. 73 . 2730 (1951).
25 S.C. Gupta, J. scl. industr. Res. India ISBj 885 (1954).
26 P.Gaubert, R.P. Linstead and H.N. Rydon, J. Chaa. 3oc. 1971 (1937).
27 Perkin and Simonsen, ibid. 91, 816 (1907).
28 Fr. Fichter and ¥. Langguth, Ber. 30, 2050 (1897); .^in. 313, 375 (1900).
29 Fr. Fichter, ibid. 2370 (1896).
30 A.3.Gupta and J .3.Aggarwal, J. sci. industr. Res. India 13B, 277 (1954).
31 R .T . Arnold and G, .Jmolirisky, J . /im. Ghem. 3oc. 8 1 , 6443 (1959).
32 R.T. Arnold and G. 3molinsky, J. Ori;. Ghem. 25, 129(1960)
33 R.T. Arnold and G. 3molinsky, J. Am. Gheia.3oc. 82, 4918 (1960). CHAPTER II
PYROLYSIS OF MANY-MEMBER E D LACTONES: A GENERAL METHOD FOR THE SYNTHESIS OF to -OLEFINIC FATTY ACIDS 3 5
PYaOLYdlJ OF LACTOSES: A Gii^iiiAL METHOD FOR THE 3Yi'fTHiiil3 OF w-OLH?MIC FATTY ACIDS
The purpose of the present worlc was to evolve a simple procedure for the preparation of 17-octadecenoic acid ( I ) from 18-l^droxy stearic acid ( I I ) , a compound readily available by the hydrogenatioxi of the naturally occurring kamlolenic acid (III), the main fatty acid com ponent of Kamala seed oil obtained from Kamala seels
(1-iallotus phillppinensis) , This Chapter describes the successful conclusion of this phase of work, v/hile the next Chapter deals with the methods adopted for the further chain shortening of the 17-octadecenoic acid.
CHg =CH (CH2),5 COOH HO H2C( CH2),6C00H
I J I
H0H2C(CH2)3CH = CHCH=CHCH = CH(CH2)7C00H
111 3r>
PREL IMIiUiiY IWEdTIGATIQiJS*
Of the various methods available for the
dehydration of primary alcohols the method of pyro- 2 lytic cis-elimlnations appeared promising. For this purpose, pyrolysis of the metaborate ester of methyl-18- hydroxy stearate (IV), was investigated in the first instance.
0=B-0-CH2(CH2)|6 c o o Me
rv
Pyrolysis of borate esters derived from a variety of alcohols has been investigated by several workers*' , and good yields of the olefins have been obtained. O‘ co.inor 4 and Nace suggested that this reaction proceeds via the
Gupta in a preliminary communication reported the preparation of 17-octadecenoic acid (I) from 18-hydroxy stearic acid (II). The hydroxy acid was converted to the corresponding w-chlorostearic acid by treatment with thionyl chloride, which was then deliydrohalogenated by heating with alcoholic potassium hydroxide solution (2 ^ ). The product which was obtained in aii unspecified yield was shown to have the melting point of 17-octadecenoic acid (55-56.5°C), and'was further characterized by its oxidation to 1,17-heptadeca^ioic acid and to stearic acid by catalytic hydrogenation of the unsaturated acid. Details of this work have not been published so fa r . 3 7
unstable metaborate ester which unaergoes els- elimination to yield an olefin and, in analogy vith the well-accepted mechanism of pyrolytic cis-elimina- tions, the borate pyrolysis was assumed to proceed as in V : / H , f — C ) f O — C H— 0^ a + B — C - C ^ 0 ' ^ I / Y
However, it has beea pointed out by De Puy^ that the pyrolysis of borate esters may not, in fact, be a cis~ elimination reaction as the metaborate esters are linear and are consequently unfavourable for a cyclic elimina tio n .
Methyl-18-hydroxy stearate, and boric acid were refluxed in toluene with continuous removal of water when the corresponding borate (IV) was readily obtained. This on pyrolysis at elevated temperature (free flame), and pressures of 0,5 to 0.6 mm gave only a poor yield of pyrolysate and a lot of polymeric material was obtained as a residue. Further modification in the design of the distillation flask (vide experimental), did not make axiy difference in the yields of the pyrolysate. The pyrolysate was found to be a mixture containing a liquid 3 8 compound which analysed for G]_3^^34^2*
give any colour with tetranltromethane and in the
infrared (Fig.l) displayed its at 1738 cm*’^ and did not exhibit any strong band around 910 or 990 cm where terminal vinyl group displays its characteristic out-of-plane CH deformations°j the absence of hydroxyl group is also clear from the IR spectrum. On hydrolysis it yielded 18-hydroxy stearic acid (II). On the basis of these data the compound is formulated as the lactone ( V I ) .
HgC- (CH2)|5 —C = 0
HgC
VI
This was confirmed by its compai’ison (lii) with an authentic sample of the lactone (VI) prepared according 9 to the method described by Gupta et a l .
The pyrolysis of the borate was, next, investi
gated in a colu.nn reactor (F i g .2) so as to minimise the period of stay of the product in the pyrolysis zone.
However, in this case also none of the expected w-olefinic
acid was obtained and the only identifiable products were
the lactone (VI) and the dilactone (VII) (m.p. 110-112°),
identified by comparison (Ili, mixed m.p.) with an authentic
4 1 sample . The results of these experiments are
0 • c= o
■0
VII summarised la Table 1.
The formation of the many-membered lactone (VI) during borate pyrolysis would appear to be due to the possibility of ester exchange between two moles of the borate ester to give methyl borate and polyesters (Vlllj;
• n 0=B — 0— CH2(CH2)|6C00Me
0 0 I— // // —\ n Me0-B = 0 + n/2 -O-CH 2 (CH2)|g C - 0-CH 2(CH2)i6C- 0-J vrn which under pyrolytic conditions are imox^n to yield lactones^^. The ester exchange reaction could have been initiated by a trace of boric acid present in the starting material or formed in the anticipated pyrolytic elimina tion (to give olefinic ester). Alternatively it is possible that the lactone (VI) could have originated directly by the pyrolytic cleavage: Hl>* O n Cij 1 © ‘4 0) •H © PS 3 S) fl c! c a o • ctf !3 o © 4J 0 0) ts-PM 01 O M 01 H O OcS > m ca > Q) M a,H v-^ liii-l 5 -If—ir—li—I . g "V—nr—ti—ir—n Q) H a 01 H iH CO « fn H W B 0 M \ • 00 -H W C fH CO o H H H t=4 aJ E- a, bO 0) ^ IN !0 H nj rH CO 10S3 I' • lO lO W O . ho 10 • •H W O ? Q, G) o O CO C\3• lO
I 01 a 5? % 01 «5 o I CS5 •p m H r S O S5 03 CO 10 13 .CHc XH 0 — B = 0 0 (CH2)|5 -> (CH2)|5 + Meo -B= 0 C— 0 - M e ,C = 0 CH. CH, ■3ZL In this cooiiectlon it may be mentioned that when the acetate [CH2 C''~0-GH2 (Gii.^)^gC00Me] was subjected to the same conditions of continuous pyrolysis as the borate eater (IV), the acetate was recovered unchanged. PYaOLZolS OF LACTQi^ES As raentionea earlier it is well recognised now that pyrolysis of esters to yield olefins proceeus through a cyclic transition state: \ / \C-rC- 0 OH \ / W / o j C c + c / " k It was argued that if instead of an ester a lactone be subjected to these conditions one should end up with cu-olefinic fatty acids, provided the lactone ring-size is such as to allow the attainment of planarity of the 1 4 concerned atoms in the transition state: H HoC HgC ■CH CH- 0 // (H2 0 , CH, (HoC)^ CH- C --OH The method, appeared all the more attractive because isomerisation of olefinic linkages under these pyrolytic conditions normally does not take place^. A preliminary experiment with the lactone (VI) After this preliminary worls had been completed, a review article on ^jjS-eliminations was published by De Puy et a l » LGhem, Hev. 60 , 431 (I 9 6 0 )] v;herein it is mentioned that 3ird and Bailey [Abstracts of papers presented before the Division of Organic Chemistry, at the ISlst Meeting of the American Chemic^ Society, Miami, ilorida, April 1957, p . 4 4 -0 ], studied the pyrolysis of some lactone of the type; CH2 (CH2)n C = 0 H3 C- CH 0 n = 1 and 3 Details of this work have not appeared so far, 45 described earlier, showed great potentialities for the reaction. It was decided to prepare a series of lactones of varying ring-sizes and study their pyrolysis. For this purpose a series of w-hydroxy acids had to be synthesiiied and the following two sections describe the preparation of various co-hydroxy acids and the lactones derived from them. PHgilRATIOM OF co»dYDHQXY FAl'TY AGIi>3 [H0-(CH2)^G00H; n = 17, 16, 14, 12, 11, 10 and 9] The to-hydroxy fatty acids, required for our investi gation, have all been described iu the literature. Several methods are available for the preparation of w-hydroxy 11 12 acids ’ . Special mention must be made of the procedures 13 developed by Chuit et al,. in which use has beea made of the half esters of dicarboxylic acids which by Bouveault- Blanc reduction yielded the hydroxy acids. These authors also u t il iz e d several o(,a)-bromohydrins for synthesizing 14 co-hydroxy acid s. Lycan axid Adams synthesized several u>-hydroxy acids by the ozonolysis of suitable olefinic fatty acids followed by reduction of the resulting aldehydic acids with hydrogen, and platinum oxide, using miimte quantities of ferrous sulphate as catalyst activator; Diaper et al.^^ and Benton et al. have recently used sodium borohydride for the direct reduction of the ozonides to give u>-hydroxy 4r> 17-1 9 acids. The Hussian group of workers have developed the .Colbe' s electrolytic reaction for the syntheses of these hydroxy acids. Another important route to the synthesis of w-hydroxy acids involves the reaction of 20 carbontetrachloride and ethylene (Telomerization; . The telomers or the tetrachloroalkanes [Cl(CH2 .GH.^)j^CClgJ 3JL 22 have been hydrolyzed to give a variety of co-hydroxy acids ’ For the purpose of the present work, 18-hydroxy stearic (II), 16«hydroxy palmitic (I/O, and 15-hydroxy- pentadecanoic (X) acids were prepared essentially according to the proceaures described in the literature, with suitable modifications whereever necessary. For the preparation of the remaining acids [n = 12,11,10 and 9] new and more con- veaient proceaures have been worked out. 1 . 1 8 -Hydroxy stearic acid ( H ) Q A S , 2 3 18-Hydroxy stearic acid (II) could be prepared in excellent yields by the catalytic hydrogenation of kamlolenic 9 acid (III) over Haney Nickel in alcohol . 2 . 16-xiydroxy palmitic acid (I X )^ ^ 1 6 -Hydroxy palm itic a c id , also knovm as juniperic acid, was prepared starting from almretic acid (XI) (obtained by hydrolysis of shellac) according to the pro- 24 ceiure described by Mathur et a l . 4 7 HOHj^ G C CHg ) gCHOH. CHOH ( OOH (XI) 96% HBr, AcOH BrH^C( ) gGHBr.cHBr(CH^) OOH (XII) 97% Et.0H,CgHg,a^304 BrH^ G(CH^) gCH. 3 r . CHBr( CHg) ^GOO Et (XIII) 96% Zn.dust, EtOH,HBr Brii^G (CH^ ) gGH=GH( GH^ ) ^GOOEt (XIV) 96% AcONa, Ac OHjAc^O AcOH^ G (Gii^) gCH=CH( GH^ ) ^GOO Et (XV) 96% 1 . KOH, Et OH 2. HOH^G (GH,^ ) gCH==GH (GH^ ) ^COOH (XVI) 95% rJi-Al alloy, aq.ITaOH H(XI^G(GH^)^^COOH (IX) The modification introiuced in this synthesis is the 4 8 hydrogenation of 16-hydroxy hexadec-9-eaoic acid (a VI) using aaney Nickel alloy, and aqueous alkali according to the method described by schwenk et al»^^ 3. 15-Hydroxypentadecanoic acid (X)^^ 15-Hydroxy pentadecanoic acid was prepared essen- tially by the method described by Bhattacharyya et al. with slight modifications. Thus, reduction of erucic acid (a VII) to the correspondixig alcohol was carried out profitably by Hansley's modification of Bouveault-Blanc reduction. Likewise, the hydrogenation of the unsaturated acid HOH^C(CHj^)^j^GH=CH COOH(a XII) was conveniently accom plished by Haney Nickel alloy and aqueous alkali. Erucic acid (XVII) required for this synthesis was isolated from mustard seed oil. CH3(GH.^)^0H=CH(CIi2>^j_ CUOH (XVII) Me0H,GQHQ,H2304 GH3 (GH2 ) 7CH=:GH(GH^)i1 GOOMe (XVIII) 94% Na, Tert.BuOH, GgHg.GHg GH3(CH2)7Gii=CH(GH^)^j_ GH^OH (XIX) 93^ 1. H.,0„,Ao3H,H„30/®>^® 2. KOH: EtOH 413 CH3(CH2)7GH0H.GH0H(CH2)iiCa^0H (XX) B6% Aq.IfalO^, Eton \f CH2(CH2)^CH0 + 0HC(CH^)^^CH20H (XXI) 91^ 1. CH2(C0^H)2, \f 2. iV H0Hj^C(CH2)^^CH=GHG00H (XXII) '^5 955^ iU-Al. alloy aq. iilaOH (X) 4, 13"Hydroxy trldecaaolc acid (x:s.lix) 13-Hydroxy tridecanoic acid could be conveniently made by the peracid oxidation of the aldehydic alcohol (XXI), an intermediate in the synthesis of 15-hydroxy pentadecanoic acid (X), described earlier. HO H2C(CH^)^^ CHO (XXI) 80% \f HgOg, AcOH" H0H2G(GH2)^j_C0aH ( m i l ) This acid has beexi prepared previously by different 1'^ 14 methods 5 . 1 2 -Hydroxy 1 auric acid (XXIV) A new method for the synthesis of 12-hydroxy lauric 50 acid (XXIV), also known as sabinlc acid was worked out. The schcane followed for the preparation of this acid is shown below. The route was preferred as the intermediate aldehydic alcohol (XXIX) could also be utilized for the synthesis of 10-hydroxydecanoic acid (XXXIV), The starting material 10-undecenoic acid (}J».V) was readily available as a product of pyrolysis of castor oil. CH^=CH(GH2)g GOOH (.av) MeOH, Cq Hq , rigSO^ CH^=Gh(GHj^)q OOOlie (XXVI) 93^ Na, Tert.BuOH, GgHs.GHg GH2=GH(CH^)g GH^OH (XXVII) 1. HgO^, Ac0II,H^30^ 90^ 2 . iCOH, ttOH CHj^OH.CHOH(GH^}g Gii^OH (..XV I I I ) 87^ Aq.i^aIO^,EtOH \/ H.GHO + OHC(GH^)g GHgOH (x:ax) 83^ 1. CH^(C0^d)^,G5H5.^ 2 . H+ 5i (XXX) iJiiil. alloy, aq.NaOH (iaiv) lii-hydroxy lauric acid has been prepared previously by 13—15 several workers , but by different methods. 6. 11-iIydroxy undecaaoic acid (.iwJwl) 1 1 -Hydroxy uadecaxioic acid (Xa XI) could readily be maae by the procedure shown below, starting with 10-undecenoic acid (XXV^), (Xa V) SO 70% H3r,3i5.^0^, Pet.ether 3rCH^(ca^)9GOOH (xxjai) AcOi'fa, AcOH, Ac^O Ac0CH2(CH^)gG00H (XXXIII) 97% 1 . KOH, i.tOH 2. H H0Cli2(CH^)gC00H (XXXI) The procedure is more coiiveaient than the various methods 12-14 of its synthesis described by others 52 7. lQ-:iydroxy decanolc acid (X^IV) 10-Hyiroxy decanoic acid OJJCIV), or lO-hydrojty caprlc acid, as indicated previously was made by the peracid oxidation of the aldehydic alcohol (XXIX), obtained earlier in connection with the synthesis of 12-hydroxy lauric acid (XXIV). HOGHg (GH.^) gCao ( a XIX) 78^ H ^ O ^ , A c OH H0CH2(CH2)gQ00H (iDQ.lV) The preparation of 10-hydroxy decaaoic acid by other X3**X6 methods has been described PREPAdATIQi^ OF LACTQi^£3 The lactones required for the purposes of our study are all higher than ^ -lactones. For the prepara tion of such lactones several methods are available, depending on the siae of the ring'*'. In the following pages ♦ The classification of the ring compounds into small rings (S- and 4-meinbered), common rings (5-, 6- and 7-membered), medium rAngs (8- to 12- membered), axid large rings (IS-membered or larger) has been suggested by Brown and Prelog Lj . Am.Chem.3oc. 215 (1951); footnote 21]. For our purposes this aomenclature will be used, the oxygen atom of the ring being counted as one o f the members of the cycle. 5 3 a brief introductory survey of the available methods is given followed by a aiscussion of the methods used for the present work. Available methods of synthesis Basically the various methods of synthesis may be divided into two groups, A. Ring expansion of a cyclic ketone to a lactone. B, Methods vrtilch involve cyclization of acids or esters through a suitably placed functional group (hydroxyl, halogen, ester). A. Hing expansion of a cyclic ketone to a lactone 3 1 32 The Baeyer-Villiger * oxidation of cyclanones to lactones by interaction with a peracid is especially ST useful for the preparation of coitunon (6-, 7-membered ) and medium ring * lactones. The method has also been used for the preparation of large membered lactones, 39 for example exaltolide (1,15-pentadecaiiolide) . The 40 method has been discussed in a review article . The chief limitation of this method for the preparation of higher-membered lactones is the availability of the re quired cyclic ketones which, in any case, have to be prepared from longchain o(,w-dicarboxylic acids. B. Methods which involve cyclization of acids or esters through a suitably placed functional group (hydroxyl, halogen, ester). The intramolecular cyclization of hydroxy acids to lactoaes constitutes an important 4 l and flexible method. 3toll and Rouve studied the cyclization of hydroxy acids [H0(GH2)_jjC00H; n = 3 to 17 and 22] under special conditions of high dilution and obtained lactones in yields of 40 to 75fa for large- membered (14 to 19) lactones and 2 to 15^ for the meiium-ring (10 to IS) lactones. Others^*"^ have also reported the preparation of various lactones through high dilutioii technique. The w-hydroxy acids (as formates) have been cyclized in vapour phase over titaiiium- dioxide at about 300°C^^. 44 45 Stoll and Hunsdieker and coworkers effected ring-closure of cu-bromo-, and oj-iodo fatty acids in the presence of potassium carbonate in methyl ethyl ketone, and have reported excellent yields for several lactones 46 (10 to 18-membered). Allen et al. reported a modified dilution head for the purpose. Carothers and coworkers^^ discovered that poly esters of hydroxy fatty acids can be slowly depolymerized in high vacuum at 2 7 0 °C using magnesium chloride as a catalyst, to furaish lactones in good yields. The method has the advantage of speed and simplicity over the high dilution method, and is suited for large scale preparations. Jeveral catalysts for the depolymerization step have been described and modifications of the original procedure have 55 47 48 been reported * A. number of monocyclic lactones of different 49 ring sizes have also been prepared from telomers • Present work For the present work cyclization of w-hydroxy fatty acids in the presence of an acid catalyst was selected. The chief drawback of the high-dllution technique (use of large volumes of solvents) has been offset by use of the special apparatus (Fig.3), in which advantage has been taken of the refluxiag solvent to dilute the hydroxy acid. The apparatus has been auopted one gQ from the/described by Cope and Herrick for effecting reactions unaer high dilution. Jince ia the lactonization reaction the equilibrium is forced in favour of the lactone by continuous retaoval of the water formed in the reaction, it was necessary to modify the apparatus of 50 Cope and Herrick » so that the water formed in the reaction is constantly reuoved during the recycling of the solvent; incorporation of a tube filled with activated silica gel in the path of returning solvent, [Fig.(S)], effectively answered the purpose. By using this method, several w-hydroxy acids [H0H^G(GH2 )^G 00H; n = 16,14,13,10,9 and 8] have been cyclized and'Table 2 summarizes these results. The last 5() 5 i TABLE 2 - GYCLI3ATI0W OF w-dYDHOXY FATTY ACIDS ^ ( H0CH2(CH2)n COOH CH2)n-- C = 0 HgC Conditions! of cyclisation No. n=5 % y ield obtained Moles of M oun t Solvent % yield acid* of cata- by 3toll ' and Rouve'^ lyst+ l i t . ^ • 1 16 0 .0 1 6 6 2 ,5 2 81 76 2 14 II m II 81 67 II 3 If « It 80 - ti 4 13 « If 79 23-76 5 11 M II 65 41 6 n 0 .0 3 3 2 n 59 « 7 10 0 .0 1 6 6 ft 24 16 8 n 0 .0 4 9 8 M n 14 - 9 9 0 .0 1 6 6 H II 18 11 10 M H tf n 18 - 11 fl 0 .0 0 8 3 1 .2 5 n 20 - 12 n II II n 22 - 13 8 0 .0 1 6 6 2 .5 n 4 1 .4 14 « 0 .0 0 8 3 1 .2 6 ft » - 15 « H fl « — The hydroxy acid was dissolved in 500 :nl benaene and the solution was added to the systen through the dropping fu n n el. %-Toluene sulphonic acid has beeii used as catalyst, ^ ;3toll and Rouve used 5 to 10 lit. benzene as solvent (for similar amounts of hyoroxy acid), and benzene sulphonic acid as cyclization catalyst. 58 entry in the Table shows the yields of the lactones as obtained by the usual high-dilution technique, for purposes of comparison} i?‘ig.(4) gives a graphical repre sentation of this comparison, and as can be seen from these, the yields of the lactones have not been sacrificed by the use of this new apparatus, which avoids the use of large bulks of solvent and has the further advantage of simplicity of operation. T&e sudden decrease in the yields of the lactones as we enter the zone of medium ring-size, is as expected and has been discussed by several workers. Table S records the properties of various lactones obtained by this procedure in the present work. The literature does not record the carbonyl stretching frequencies data for many lactones larger than seven-membered, except for exaltolide (C^g lactone), for -1 46 which a value of 17S8 cm has beea reported . The values obtained in the present work are those expected for an unstrained lactone. A point of special interest is that the medium ring lactones show a double carbonyl stretching frequency (Fig*5), which could possibly be attributed to the presence of two distinct conformers. The PMR spectra of these lactones are charac terized by three sets of sign^s 80, 130 and 240 cps 5 0 FIG. 4. 7o YIELDS OF MANY-MEMBERED LACTONES. 60 TABLE 3 - PH0PMTIE3 0¥ LACTONES (CH 2 )n C = 0 CH- 0 No. n=: m .p. b .p . , c=o T °C ^ om-l 1 16 36.5- 147-48/0.8-0.9 1.4666 1740 37 2 14 34-35 126-27/0.6 1.4678 1740 2 13 - 1 2 0 /0 .3 1 .4 6 9 2 1748 4 11 - 101-102/1.0 1 ,4 6 8 4 1748 5 10 mm 8 5 - 8 6 /0 .3 1 .4 6 9 0 17 40 ,1 7 5 0 6 9 m* 73-80/0.4 1.4694 17 40 ,1 7 5 0 7 8 - 66-56/0.9 1.4663 1748,1752 61 1800 1750 1700 1650 ■|G. 5. IR SPECTRA (CARBONYL STRETCHING) OF 1,11 - UN DECANOLIDE ' ' 6 2 0 // assignable^respectively to -CJi^-G-0-; and Table 4 suiiunariaes the PMd data of these lactoaes. As can be expected the PMa spectra of the homologous lactones differ very slightly from each other and Fig.6 shows the PMa spectrum of ^15 lactone (exaltolide) which is typical of these series. e~Caprolactone and ^ -enaiitho lactone were obtained by the action of perbenaoic acid on cyclo- 35 *^7 hexanone and cycloheptanone respectively ’ , in good y ie ld s. PiaOLYJX3 OF LACT0WE3 Pyrolysis of lactoaes was studied La vertical reactor packed with pyrex glass pieces. Fig.2, gives the details of the apparatus. Pyrolysis of C^g lactone (1,18-octadecanolide)VI, was investigated in the first instance, at different tem peratures in order to arrive at some workable yields of the unsaturated acid. As can be seen from the Table 5 the yield of the unsaturated acid per pass goes up with the rise in the pyrolysis temperature, but the yields based on the unrecovered lactone falls due to greater carbonization at higher temperatures. 6 3 TABLE 4 - PMR i)ATA OF MAi^Y-M^MBEaED LACTOSES (CH2 )n C = 0 HgC- " 7 ------C H g ■G-O- N o . n= cps l-^lti- cps m it i- cps Itilti- p lic ity p llcity p lic ity 1 16 7 9 .5 iinglet 1 S S .5 jissentid” 2 4 1 .2 Essen tial l y doublet ly triplet 2 14 7 9 .6 If 1 3 3 .5 ff 2 4 1 .6 ff 3 13 79 « 1 3 3 .7 ft 2 4 2 .2 ff 4 11 81 n 1 3 6 .S 41 2 4 2 .7 It 5 10 8 1 .9 t* 1 3 4 .1 " triplet 2 4 4 .1 ff 6 9 8 1 .7 If 1 3 6 .2 " quartet 245.2 ff 7 8 8 2 .1 n 1 3 5 .0 n 11 24 6 .2 n G4 -vO ■vO LiJ Q _J O < X LJ UJ 9 _1 o < 0 UJ Q < I- Z LiJ Q_ 1 10 Ll o Z) q : h- O LiJ Q- CO q: CL co o Ix. 65 TABLE 5 - PYilOLYSiS OF 1,18-OCTAJlCiA.IOLIDE (VI)* No. Tonp, Lactone % yield of acid recovered As such Based on unrecovered lactone. 1 450 89 10 84 2 500 84 13 87 3 525 67 16 50 1 g of the lactone was pyrolyzed per pass at the respective temperatures, and pressure of 150 mm and under nitrogen atmosphere. The lactone was dropped into the reactor at the rate of two drops per minute. On account of this, temperatures higher thaxi 525°C were not studied, and this t&nperature was, selected for the pyrolysis of the v/hole aeries of lactones. Table 6 gives the results of such a study which has been carried out under identical conditions, using 1 g of the lactone for pyrolysis. Yields are superior when larger amounts are pyrolysed at a time, as this reduces the losses due to hold up etc. (cf. entries in Table 6, show where 2 and 5 g of lactones have been pyrolysed. Also see Chapter III). The stmzcture of the acids obtained were established as the corresponding w-olefinic acid by a study of the infrared and NMH spectra of the methyl esters derived from (u; TABLE 6 - PYROLYSIS OF MA.^Y-MMBiaEL) LACTONES (CH2 )n COOH CH. CH' 'CH, i^o. n= Yield of the Yield of the acid pyrolysate based on unrecovered lactone. % $ 1 16 83 50 2 If 89 79 ♦ 3 14 9S 69 4 f« 92 67 5 IS 90 73 6 96 85 + 7 11 98 89 8 10 98 83 9 9 91 70 10 5 74 55 5 g of the lactone was pyrolyzed. 2 g. of the lactone was pyrolyzed. t) /' these acids. As expected, the methyl esters displayed absorption bands due to out-of-plane deformations of vinylic CH^ at 910 cm Table 7 records the carbonyl stretching frequency and the olefinic proton deformation frequency of the various esters and acids obtained in this work. Figs.7 and 8 show the infrared spectra of 15-pentadecenoic acid and its methyl ester respectively and these spectra are typical of these series; while Fig,9 shows the infrared spectrum of the neutral fraction obtained from the pyrolysis of lactone which is typical of the spectra of the neutral fractions in the series. The PMR spectra of the esters is characterized by four sets of protons occurring ~ 75, 125, 215 and 285-360 cps regions, and assignable respectively to 0 0 -GHg-G-OCHg, -GHg-G-OCHg and C^^=Cii-. Table 8 summarizes the PMR data of these esters, while Fig.10 shows a typical spectrum of the series. The work described above was carried out with the twin purpose of evolving a method for the preparation of o)-olefinic fatty acids and to determine the ring size of the lactone which would permit the attainment of B8 planarity of the concerned atoms for the pyrolytic els-elimination step. As has been demonstrated the Cy cyclic lactone (eight-membered) is capable of undergoing this elimination reaction. When the c'-capro- lactoae (seven-manbered) was subjected to the same reaction, none of the to-olefinic acid was formed and the only product isolated after the work up was the corresponding hydroxy acid (o-hydroxy caproic acid). Thus the steric requirements of this reaction can be met in the eight-member ed lactone cycle which represents the lowest limit of the lactones capable of undergoing this reaction. TABLE 7 - IJi-’riAHEJ SPECTRJiL JATA OF w-OLE&’XiaC ACIDS AiiD THKIR &3THi3 CH2 = CH (CHg)^ COOR R = H , C H 3 1)C= o ^c=c S-CH= J-CH= fo. n= Acid iiater ilcid Ester Acid i^ter Acid Ester 1 15 1700- 1750 1650 1650 317 913 995 935 1715 2 13 1705- 1750 1647 1650 919 913 993 995 1710 3 12 1695- 1750 1643 1645 917 913 995 996 1710 4 10 1725 1750 1645 1645 915 915 995 335 5 9 1705 1750 1643 1645 910 913 935 995 6 8 1717 1750 1633 1645 912 913 990 395 7 4 1709 1745 1639 1643 915 920 1000- 371 1020 O o o o 'tin CD N 7l o o . CO LJ 1- < o z Ld o O o LU (J) Q < h- 2 o UJ o Q- o 1 lO _ l >- T X >- LU o 5 Ll O 2 3 c r o I— o . o lO LU •— Q- c n c r 00 o o o o CM u_ o o o o o ? rO ^ lO CD N 3DNVeaOS9V LU tu □ 0 < u liJ Q cr I- 1 ro o o £r Q- O cr Li- O I— O < cn u_ _J < cr h- 3 UJ Li_ o 3 (T h- (J UJ Q_ CO cr 0^ 3DNV9dOSaV 73 TABLE 8 - p m JATA OF METHYL EdTiE3 OF u>-OLEF‘JiJlC AGIUS CH 2 = C H (C H 2 )n C O O C H 3 0 0 -CH^. -C-OGHg CIi^=Gxl. n= ♦ cps I'iulti- cps i'iulti- cps l»fiilti- cps i'iulti- p licity p lid ty plicJ;y p liclty 1 15 77 dinglet 128 iissen- 216 3inglet 285- itilti- tia lly 358 plet quartet 2 13 77 129 n 216.5 " 286- •• 349 3 12 7 7 .5 H 129 II 216 " 287- ” 359 4 10 78 H 128,,5 « 2 1 7 .5 « 287- 363 5 9 7 8 .5 It 127..5 « 216.5 " 285- " 365 6 8 80 fi 129 « 22B.5 288.5- « 3 6 8 .5 7 4 80 129 n 219 ” 288- ” 068 * indicates in cps the first aad. the last lines of the multiplet. cn O "D :d CO “D m o H c o■n m H X -< cn I T3 m 2: H > o m o m o > H m »-M r- ro EXP EHIMENTAL All melting points and boiling points are uncorrected. All solvent extracts were finally washed with saturated brine before drying (over anhydrous For tetranitromethane {THA) test, equal amounts of undiluted compound (liq u id ) 5 in chloroform (solid), and 10% solution of the reagent ia chloroform were mixed. IH spectra were recorded on Grubb-Parson's double beam, model S3} Perkin-ilmer Infracord, model 1S7E or pericin-Elmer, model 221 spectrometers, equipped with i^aCl optics, either as smear (liquid) or in xYujol (s o l id s ). 3ome of the Iii spectra were kindly recorded by ^^/s. Samuel P. viadtler and 30ns Inc. (1517 Vine Street, Philadelphia) in KBr on Beckman IH 4 spectrometer. Maxima are reported in cm All PMii spectra were taken in a 20^ solution in CCl^ with tetramethylsilane as internal standard, on a Varian Associates A-60 spectrometer; peaks are reported in cps. All ijLC reporter herein were carried out on Perkin- ilmer Vapor Fractometer model 154j Aerograph Gas Chromato graphy Dual Column, model A-350-B, at 160-200° (column temp.) over 'P' Column (2 meters) using hydrogen as carrier gas. 7G Kamala seed oil Fresh Kamala seeas* (4630 g) were soaked in dilute HaOH solution (O.SJaj 7 ,5 l i t ) for 45 minutes with occasional 51 stirring . The resultaxat dark coloured thick syrupy liquid (pxi 7,65)^ was drained off and collected separately. Treated seeds on washing free of alkali, resinous and fibrous material and sun drying weighed 3583 g. (2 1 ^ loss in weight). 3olve.it Extract ion: Cleanea seeds (3583 g) were crushed gently through a roller mill and the seed meal was extracted thrice with benzene (6 , 3, 3 lit) at room temperature. The solvent extract after filtration and flashing off the solvent gave a clear light yellowish orange viscous oil (1300 g, 30^). ^oupplied by The Chief Forest Utilisation Officer, Govt, of Bihar, Hinoo, Bihar State, India. '*'The alkali wash on extraction with ether-pet. ether (40-60'*) mixture (1:1) yielded a fatty product ( 'v. 1,5^; on volume) which was further separated into the neutral {2^%) and acid (68^) components by the usual methods. The acid fraction on analysis (isolation, saponification equivalent and identification by IE and VPC of the methyl esters against authentic samples) was found to be rich in palmitic, oleic and linoleic acids. The neutral fraction b.p* 160-205°/0.6 to 0.1 mm giving pleasant smell (lit ii895 , 2670 , 2360, 1827, 1748, 1723, 1461, 1422, 1377, 1354, 1258, 1237, 1163, 1117, 109^, 1028, 970, 810 and 724 cm"! by smear) was not investigated further. Solvent extracted alkali wash, on acidification, filtra tion, washing and drying yielded Kamala dye. 77 i^amlolenlc acid III i’otal fatty acids Kamala seed oil (120 0 g) was heated under reflux (Ng) with ethaaolic KOH (2.5 lit; 12^) for 3 hrs. After concentration in vacuo at reduced temperature (75-80^ of the alcohol by volume used was d i s t i l l e d ) , . the soap was dissolved in water (3 lit) and the fatty acids were libe rated by the addition of phosphoric acid to the soap solu tion, taking care xiot to allow the liberated acids coming into contact with atmospheric oxygen, by maintaining a layer of nitrogen in the system. The total fatty acids were taken in benzene (2 lit.) washed free from mineral acid, then with brine and dried. iaatimation of Karalolenic acid Methyl esters were prepared by reacting above fatty acids (2 .6 g) with ether aiid working up. Crude methyl esters (2 g) were chromatographed over activated alumina grade III (60 g). The column (0.25 x 51 cm; alumine column height 20 cm) was eluted successively with pet. ether (40-60°), ether, ether-methanol mixture (1,10 and 25^ methanol) and methanol. In all fifty fractions of 20 ml each were collected, and after preliminary studies, were combined to form three main fractions as shovm in Table 9. 78 TAaLii 9 - UHiiOi^ATOGHAPHi: Oi' MiiTHYL Eiil'IiRS OF TOTAL AGIiJS FROM KAMALA SEiJ) OIL No. ELuent Frac W eight Final Appearance tions & fr a c tions g. 1 . Pet. ether 8 X 20 ml 0 .5369 0 .5 3 6 9 I Liq uid. (40-60°) 2 . Ether 1 2 x20 1 .0 6 1 4 ; Sefnisolid. 1 .1 2 7 0 n 3 . Ether MeOH 6 X 20 0 .0 6 5 6 i It ( 1 ^) N 4 X 20 0.0306 ■ so lid . 4 . Ether + MeOH 8 X 20 0 .0 8 6 1 ] n (10 ^) 1 0 .1 3 8 1 III 5. Ether + MeOH 8 X 20 0 .0 4 0 4 “ If (25^t) 6 . MeOH 4 X 20 0 .0 3 1 0 ; ft JraCtioa 1 (Pet, ether solublej. The product was distilled to yield clear liquid (0.52 gj b.p. 85-155°/l mni). IR , spectrum; GOOMe 1745, 1205, 1176, 1124; C=G 1650; peak for hydroxyl group completely absent. Analysis by GLG (Perltin- HLmer Vapor Fractometer, model 154; 200'^C, Column *P '; flow rate 70 cc/mt attenuation 1 ; Chart speed 15 irxyhr; and ester injected 1 /-fl), showed peaks and retention time for methyl esters of lauric, myristic, palmitic, oleic, linoleic and stearic acids, in which lauric and myristic 70 acids were found to be ia mlriute quaxititiea. The peaks were xurther confirmed by injecting separately, authentic samples of methyl esters of the respective fatty acids along with the mixture of total esters. Fraction II (ether soluble;. The fraction was distilled ixi vacuo to yield very pale leiaon coloured liquid (1 . 1 g) b.p. 186°/1 mm, which became slightly waxy at room temp, m ,p .25-26^. IR spectrum: OH 333S, I055j GX>Me 17 51 , 1205, 1178, 1119; CaC 1645; cis-, trans- C=G 991, 971, 930 cm'^. The spectrum was superimposable with that of methyl eleo- stearate except for the peak for hydroxyl group wiiich is absent in the latter one. PMR signals: 211.5 (t); -OCH3 216 ( s ) ; 6 vinylic H 336-373 (m); two and one -a^-C=0 128-140 (o-H, m ) 71-110 (14H; m ). (Foundj C, 73.76; H, 10.4; C^9H3203 requires: G, 73.98; H, 10.46)^). fraction 1X1. The product was crystallized from acetonitrile to yield white crystalline product (0.16 g) m,p. 31-31.5®C. IH spectrum; Ox^ 3344, 1064; COOMe 1745, 1203, 1176, 1124; C=C 1650 , 995, 984 , 929 cm"^. Higher m.p. indicates the presence of p-isomer in sufficient quantity. Trials for the analysis of fractions II and III either by Perkin-Elmer Vapor Fractometer, or by Aerograph Gas Chromatography Dual Golumii at 200, 225 and 250°C, Column *P’ ; flow rate 70 cc/mt Hg, attenuation 1, Chart speed 15"/hr; 80 and ester (in acetone) injected 1 « 1 gave broad and irregular peaks, exibiting the possibility of decomposition or polymerisation of the higiily unsaturated compound. Hence the content of Kamloleiiic acid in Kamala seed oilv«es 6 5 .8 ^* Isolation of Ka^oleaic acid* Benzene extract of the total kamala fatty acids was kept at 16® overnight. The crystallized material was filtered and washed with cold benzene (2 x 150 ml) to y ie ld shining light cream coloured crystalline acid (650 g) m .p. 74- 75°, Recry stall isat ion from bexizene (1 l i t ) afforded i^amlolexiic acid m.p, 75-76°. 18-hydroxy stearic acid II Kamlole-iic acid (550 g) m .p. 75-76° dissolved in alcohol (2 lit) was hydrogenated in presence of Raney nickel (5.5 g) initially at 90° and finally at 100-110°/600 Ibs/sq.in. dnring 1 2 hrs when no more hydrogen gas was further absorbed. The filtered solution was cooled and white *This is modified and improved method for the isolation of kamlolenic acid over other methods o 2 reported previously. Gupta et al. reported the isolation of the acid by precipitation (twice) with addition of pet. ether (40-6QO) to the ether solution of the total fatty acids, followed by crystallisation from benzene and ethyl acetate respectively, while 0©ombie et al^ obtained the acid by chilling ether solution at 0 , in low yields. In the present modi fied method solvent losses are low axid yield of acid is high. 8i crystalline 18-hydroxy stearic acid (450 g) m.p. 36.6 - 97,6® was filtered off. Recrystallisation from alcohol gave acid m.p. 37-98°. ^lother liquors on con centration, crystallisation and recrystallisation furaished second crop of acid (30g), total yield (.96%), IH spectrum (in KBr): OH 3281, 1059j COOH 2618, 1715 cm"^. (Foundx C, 71,8; H, 11.94; requires* C, 71.95; H, 12,08jg). Methyl-18-hydroxy stearate 18-Hydroxy stearic acid (50 g), anhydrous methanol (250 ml), dry beazene (250 ml), and sulphuric acid G.P. sp. gr. 1.84 (5 ml) were heated under reflux for 4 hrs. \ After distilling off the solvent mixture (75^ by volume) the reaction product was poured into water (200 ml) and was ta'ien into ether (250 ml). Ether solution was extracted with sodium carbonate solution (3 x 50 ml; 7^), washed free of alkali and dried. Flashing off the solvent afforded white shining crystalline product (52 g, 99^) m.p, ol-62°. The ester on crystallisation from ether-pet.ether (40-60°) mixture (1:1) furnished white shining flakes (47.6 g) m.p. 62-62.5°. Conceutration of the mother liquor furnished a second crop of the ester (3.1 g) m.p. 61.5 - 62°. (Keported Aggarwal e»t nl.^^ 62°; Beilstein 61.5 - 62°). IR spectrum* (in KBr)* OH 3356, 1057; COOCH3 1742, 1214, 1198, 1176 cm"^. (Found: G, 72.42; H, 12.1; C^gHggO^ requires: C, 72.56; H,12.18^) Mletaborate ester of methyl 18-hydroxy stearate (IV) Methyl 18-hydroxy stearate (1 1 . 8 g), boric acid (2.4 g slight excess over the molar proportion) and dry xylene (50 ml) hea'I^ed to reflux in a system fitted with modified moisture trap. Four hours heating gave out water of reaction (1.S5 ml). Xylene (20 ml) was drawn from the trap. Removal of rest of solvent and traces under reduced pressure yielded light cream coloured brittle metaborate ester (12.7 g) m.p. 76-15o'^G. IK spectrum: COOMe 1732, 1216, 1197, 1182 cm~^. Several lots of the borate ester were prepared as and when required. Methyl-18-acetoxy stearate To a chilled solution of methyl 18-hydroxy stearate (20 g) in dry benisene-ether mixture (60 m l), pyridine (20 ml) was added with stirring. This was followed by the addition of acetyl chloride (20 ml) in five lots. The reactants were mixed thoroughly and allowed to remain in ice bath for 15 minutes. After slowly bringing to room temperature, the reaction was kept overnight. Excess acetyl chloride was decomposed in cold with ice-cold water aad the reaction product was taken in ether (100 ml), washed free from acid and dried. Removal of solvent and traces under suction gave white shining material (2 1 .6 g; 95^) m.p. 50-52°, which on crystallisation from benzene-pet. ether mixture (50 ml) in cold yielded white pearly 8 Li shining crystalline product (19.4 g) m,p. 51-52°. IR spectrum: (in SBr): ester groups, 1748, 1250, 1212, 1196, 1168 cm”^. (Found: C, 70.6j H, 11.19; requires: C, 70.74j H, 11.31^). Pyrolysis of metaborate ester IV Metaborate ester (5.02 g) was pyrolyzed in a flask fitted with a short distillation head, using free flame. Pyrolyzed product b.p. 150-180V o .5-0.8 mm (1.37 g; 39.25^) was obtained while rest of the ester gelled in the flask. Pyrolysate was taken in hexane (25 ml), extracted with sodium carbonate solution (3x5 mlj 5^), washed free of a lk a li aad dried. He.aoval of solvent gave waxy product (1,6 g). The product was triturated with pet. ether success ively (S X 10 ml) and solids separated by filtration. Solid product was crystallized from benzene to yield white crystal line material (0.21 g) m.p. 111-112°. Liquid fraction on distillation gave water white liquid (0.51 g; 10.12^) b.p. 139-143°/0.5-0.4 mm, n^^ 1,4615 which did not give TMM test. The product solidified at room temperature. IR spectrum: 2^G=0 1738 cm"^ (Found: G, 76.62; H, 12.09; requires: C, 76.54; H, 1 2 ,1 3 % ). pyrolysis of metaborate in a modified flask Metaborate ester (5,01 g) x^as pyrolysed in a modified flask with the side arm fused at the bottom the flask neck, using free flame, Pyrolysed product (1,85 g; 36.94j^) b.p. ' ■ f '• 84 150-185°/0*4-1 mm was obtained while rest of the ester gelled in the flask. Pyrolysate on woriclng in the usual fashion afforded solid (0.025 g) ra.p. 110-112®, and liquid fraction (0.61 gj 12.13^) b.p. 138-141°/0.4-0.5 mm, n^^ 1.4619; also did not give test. IR spectrum: ^0-0 1738 cm"^. (Found: C, 76.58} H, 11.38; ^^3^3402 requires: C, 76.54; H, 12.13^). 3everal experiments were carried out with similar results. pyrolysis of metaborate ester through reactor 'i) Metaborate ester (5.01 g) was pyrolyzed through an electrically heated vertical furnace as shown in Fig.2 at 350°/0.5-0.6 mm. Borate ester melt was dropped in 1 hr followed by further heating for 0.5 hr, and pyrolysate (2 .5 2 g; 5 0 ,2 % ) was obtained which on working up in the usual manner gave solid crystalline material (0.053 g) m.p. 110-112° and clear liquid component (0.44 g; 8.7^0 b.p. 142°/0.4 mm, n^^ 1.4591, did not give TNM test and solidified at room temperature. IR spectrum:^C=0 1736 cm”^. (Found: C, 76.42; H, 11.3; ^18^34^2 72.54; H, 12.13^). (ii) Pyrolysis of metaborate ester (5.01 g) was carried out through the furnace at 350°/0.5-0.6 mm by dropping the ester melt in 0.5 hr (to minimise the time of contact) followed by subsequent heating for 0.5 hr. This run furnished 85 semi-liquid pyrolysate (2.41 gj 48.11JS), which on processing by the usual methoa gave solid crystallized product (0.053 g) m.p. 110-112° and a colourless mobile liquid (1.32 g; 26.36^) b.p. 140-14l°/0.s-0.4 mm. n^^ 1.4660. Did not give TMM test. IR spectrum:j^C=o 1740 cm“^. (iii) Metaborate ester (4.6 g) was pyrolysed through the furnace at 400*^/0.5 mm by adding the ester melt in 15 minutes and subsequent heating for 5 minutes to obtain semi-liquid pyrolysate (2.79 gj 60.6^), which on working up in the usual fashion fur^ilshed white crystalline solid (0.053 g) m .p. 110-112*^ and a liq u id fraction (0 .7 1 g; 1 5 ,5 1 % ) b .p . 136-138^0.25 - 0.3 m>a. 1.4649, also did not give Ti-iM test. IH spectrumjj^ = 0 1740 cm”^. Without exception the liquid fractions obtained from all the pyrolyses gave faint pleasant odour characteristic of large ring lactones. Several experiments were carried out in each case with similar results. * Q Lactonisation of 18-hydroxystearic acid (VI) Dry benzene (2 lit.) and benzene sulphonic acid (2.5 g) * 9 This method adopted by Gupta et al. is a modification 41 of Stoll and Rouves' method and was first reported by 42 Toyama and Hirai for lactonising juniperic acid (16-hydroxy palmitic acid). were placed in a flask (3 lit. cap.) and the solution was refluxed on a waterbath. A 0.15^' solution of 18-hydroxy stearic acid (10 g) in benzene (6 .S 3 l i t ) was added dropwise at a rate of 100 ml per SO min. Juring this treatment a portion of benzene in the flask was distilled off so as to keep the volume of the benzene in the flask at about 2 lit. After the completion of the addition (C2 hrs) of 18-hydroxy stearic acid solution, the contents were re fluxed for another 30 min. The solution was then washed with water in order to remove benzene sulphonic acid and driea. Benzene was distilled off and the residue (9.26 g; 48.42^) was dissolved in hot hexane (100 ml). On cooling the hexane solution the crystalline solid was separated by filtration and the filtrate was concentrated, chilled and filtered. The filtrate was diluted to 100 ml with hexane and was washed with ailute sodium carbonate solution 25 ml X 5), washed free from alkali and dried. After removal of solvent the product was distilled to furnish monolactone (1,18-octadecanolide, 7.59 g 81^) b.p. 140-4sV 4 mm, n^ 1.4662, single peak (GLC), having faint pleasant odour and which solidified at room temperature m.p. 37°. IR spectrum:^C=0 1740 cm”^ (Found: C, 76.52} H, 12.19; ^18^^*=4^2 '76.54; H, l2.13jg). Total solids on crystallisation from benzene furnished dilactone (1.64 g) 9 41 m.p. 112-113° (reported 113° and 114° ). IR spectrum* f' b ( yC=o 1745 cm*’^, mix. m.p. with dilactoae (VII) obtaixied from pyrolyses 111-112®. IR spectrum of dilactones from pyrolyses^GsO 1745 iiydrolysla of lactoae Lactoae (VI) (1 g) from the pyrolyses was refluxed with alcoholic potassium hydroxide solution (lOjtfj 15 ml) on a waterbath for 4 hrs. The soap solution on acidification (after removal of solvent) with dilute hydrochloric acid, liberated white powdery solid, which was then washea free from acid, dried and crystallised from benaene to furnish jJhite solid m.p. 37-98°, mix. m.p. (with authentic sample of 18-hydroxystearic acid) 97-98°. Li spectrum: OH 3300, COOH 2618, 1715 cm”^. pyrolysis of methyl-18-acetoxy stearate Methyl-18-acetoxy stearate (5 g) was pyrolyzed at 400V 0 .5 mm through the column reactor (Fig.2) by dropping the ester melt in SO min. The pyrolysate on working up in the usual fashion did not furnish axiy liquid fraction. The crude product, m.p. 49-51° on crystallisa tion from benzene-pet. ether mixture, furnished white pearly shining crystalline product (4.5 g) m.p. 51-52°, mix. m.p. (with authentic sample of methyl-18-acetoxy stearate) 51-52°. IR spectrum: was identical with that of the authentic sample of the acetoxy ester. 88 PRHP.^TiATIOii OF co-dYJaOAY FATTY ACIDS 16-Hydi-oxy palmitic acid CIX) Aleuritic acid (XI) Jewaxed blonde shellac (1000 g) was saponified by boiling for 4 hrs with aqueous caustic soda solution (20%i 1 l i t . ) . The mixture was diluted with coamon salt solution (2 0 % ’f 2 l i t . ) a*id kept at room temperature for 48 hrs, when sodium aleuritate separated la granular form. It was filtered off, washed with salt solution (2 llt .> and decomposed with dilute hydrochloric acid to liberate dfr aleuritic acid, which was^colourised in alcoholic solution with activated charcoal and crystallised from alcohol. The first crop of aleuritic acid was again decolourised and recrystallised to yield sharp melting acid (159 g) m.p. 100-101°. From the mother liquors, a second crop was obtained (16 g) m.p. 97.5-99°j total yield 17%, St f-*" IR spectrum: Od SSIO, COOH 17 15 , 1 6 5 6 ,/ l l l 6 , 1058 and 10i^4 cm"^, (Found; G, 6 S .3 5 j H, 1 0 .4 ; C, 63.12; H, 10.6^). 9tlO,16-tribromo-hexadeeaQolc a d d (XXI) Aleuritic acid (100 g) was heated with a solution of hydrogen bromide in glacial acetic acid (15jb W/V; 1.5 lit.) on a water bath for 8 hrs under antiydrous conditions. Hyoro- bromlc acid solution was recovered by distillation under 8n reduced pressure. The product obtained as residue was dissolved la ether and washed free from acid, dried and decolourised with activated carbon. Ether was distilled to obtain the crude 9,10,16-tribrorao hexadecanoic acid (156 g; 36^0. (Found: C, 40.2; H, 5.3; Br, 46.9} requires: C, 39.0; H, 5.9j Br, 48.6^). i^thyl"9ilQ,16-tribromo-hexadecanoate (a III) The crude tribromo acid XII was esterified azeo- tropically by refluxing with absolute alcohol (100 ml) and be.izeae (400 ml) containing sulphuric acid (1 ml, sp.gr.1.84), until water separation ceased (20 hrs). Solvent was distilled off under reduced pressure and the product poured in ice-cold water, extracted with ether and washed with sodium carbonate solution (5^; 3 x 50 ml) to remove free acid. The ether solution was washed free of alkali, dried and ether flashed off to obtain crude ethyl-9,10,16-tribromo-hexadecanoate P 5 (160 g; 97^), n^ * 1.5030. (Found: G, 42.8; H, 6 . 6 ; Br, 44.5. ^18^"^S3^^3®2 C, 4 1 .5 ; H, 6 .4 ; B r, 4:6,0%). Ethyl ~16-bromo-hexadec-9~enoat e CAN ) Zinc dust (105 g) was suspended by mechanical stirring in absolute alcohol (1 . 2 lit.) containing hydrobromic acid solution (3 ml), and the mixture boiled for 20 min. The reactants were cooled (ca. 50°) and to the warm suspension of zinc aust, the tribromo ester M il (160 g) was gradually 90 added la 30 min. The mixture was refluxed with stirring for 1 hr to complete the reaction, zinc dust was filtered off, and from the filtrate alcohol was recovered under reduced pressure. The resioue was dissolved in ether, washed and processed as described earlier to obtain the crude u)-bromo ester (106 g; 96^), which was distilled to yield pure ethyl-16-bromo-hexadec-9-enoate (94 g) b.p. 152-153°/iJ»l 1.4679. IH spectrum: COOCgHg 1724, 12S5, trans- CH=CH 966 cm . (i-ound: C, 60.Ij H, 9.3j Br, 21.8; C^gH^gBrOg requires* C, 59.8; H, 9.2; Br, 22.1JS). Ethy 1 “16 >a c et oxy -h exad e c -9 » enoat e (XV) Lthyl-16-bromo-hexadec-9-enoate (92 g) was refluxed under stirring with glacial acetic acid (184 ml) acetic anhydride (10 ml) aud fused sodium acetate (92 g) for 12 hrs. Acetic acid was recovered by distillation under reduced pressure and the product was poured in cold water, extracted V7ith n-hexane (250 rul) and washed free from acid and dried. The solvent was recovered and the residue was distilled to obtain ethyl-16-acetoxy-hexadec-9-enoate (82.8 g; ^6% ). b.p. 140Vo.016 mm; 1.4565 (Found* C, 70.6; H, 10.8; *^20^36^4 10 *7$^). 16-hydrQxy"hexadec-9--enoic acid (XVI) The acetoxy ester (XV) (82 g) was saponified by refluxing with alcoholic potash (10^; 600 ml) for 4 hrs. 9 i Ijccess alcohol was d is t ille d o ff (75^ by volume), residue was dissolved in water (500 ml) and acidified with dilute hydrochloric acid to liberate the hydroxy acid, filtered, washed free from mineral acid and dried. The crude hydroxy acid on crystallisation from benzene furnished pure 16-hydro3 963 cm”^. (Found: C, 71,2| H, 11.3; ^1 5 ^ 30^3 requires: C, 71.1; H, 11.2^). 16~Hydroxypalmitlc acid ( IX) 16-Hydroxy hexadec-9-enoic acid (10 g) was dissolved in aqueous NaOH solution (10^; 300 ml) and heated to 90® with stirring. To it was added Raaey-Hickel alloy (30 g) in small lots taking care that the succeeding lot was added only whei the evolution of gas from the previous addition of alloy stopped. Addition was completed in 1 hr. The reaction mixture was stirred for an additional hour, the temperature being maintained at 90°. The original volume was maintained by the addition of water as and when needed. The hot solution was filte re d and the residue was washed thoroughly with warm water. Filtrate was cooled and acidified by pouring into hydroci^oric acid with stirring. The liberated hydroxy acid was filtered, washed and dried. Crystallisation from alcohol afforded pure 16-hydroxy palmitic acid [oynonym: Juniperic acid (9.6 g; 95^)3 m.p, 94,5-95.0°. IR spectrum: OH 3226; GOOH 2604, 133g> 1695 cm"^. (Foundj G, 7 0 .4 5 j |j H, 1 2 .0 ; ^ 1 5 ^ 32^3 requires: C, 70.5; H, 11.8^). Several lots of this hydroxy acid have beea prepared with similar re su lts. 15-Hydroxy pentadecaiiolc acid (X) Methyl erucate CXVIII)* mstard seed oil (952 g), methanol (250 g) and anhydrous potassium carbonate (95 g) were refluxed over waterbath for '6 hrs when the whole reaction mixture formed a single layer. After cooling to room temperature, it was poured into water (2 lit.) and the resultant turbid mixture was extracted with ether (4 x 500 ml) combined ether extracts were further extracted with potassium carbo nate solution (7^; S x 150 ml), washed free of alkali and dried. Recovery of solvent and removal of traces under reduced pressure afforded crude mixed fatty esters (428 g). Alkaline aqueous layer was acidified with dilute hydrochloric acid aad the liberated fatty acids were taken in ether (4 x 250 ml), washed free from acid and dried. The solvent was distilled to obtain mixed fatty acids (450 g)^, Methanolysis of mustard seed oil was accomplished according to the procedure reported by :iartman^2 on fat, coconut and linseed oils. Excessive formation of soap is due to free fatty acids present in the starting unrefined mustard oil. Experiments v;ith refined oil gave high yield of methyl esters. which were iurther refluxed with dry methanol (200 m l ), beazeae (800 ml) and conc. sulphuric acid (15 ml, sp. gr. 1.84) for 6 hrs. Excess solvent mixture was distilled (75^c by volume) and the reaction product was poured into water (1.5 lit.) Methyl esters were taken in ether (4 x 250 ml) and the solvent extract was washed with sodium carbonate solution (7 ^ ; 3 X 150 ml), washed free from alkali and dried, iolvent was flashed off to obtain a second lot of crude methyl esters of the mixed fatty acids (473 g). The total methyl esters (900 g) on straight distillation yielded pale lemon coloured mixture of methyl esters (851 g) b.p. 115-205°/0.3-l mm. The distilled methyl esters were carefully fractionated through Todd's Precise Fractionation Assembly, model 'A*, and in all 19 fractions were collected (798 g total). Fractions 10 to 16, b.p. 170-175°/0.9~1 mm aftesr testing their purity by GLC were combined (389 g) and refractionatea to obtain methyl erucate (375 g; 44^0» h.p. 170-172°/l mm, TNM, GLC tested, nj^ 1.450JB. IR spectrum: GOOCHj^ 1750j C=C 1670, 972 cm"^. (Found: C, 78.12; H, 12.4j ^^23^44^2 G, 78.34; H, I2.58®i), i^rucyl alcoiiol (Xl^i) Shining sodium metal (75 g; 3.25 g atom) was finely pulverized in dry toluene (150 ml) at reflux temp, using efficient Hers-hberg stirrer in a three-necked flask. Methyl erucate (228 g; O.o5 M) dissolved in a*ih/drous tert-butyl 9 4 alcohol (144 g; 1.3524) and tolueiie (500 ml) was then let in during 45 minutes with stirring. Juring the exothermic reaction the bath temperature was maintained at 120° + 5®. After the addition, it v/as stirred and heated for another SO minutes, cooled, finally in ice-water and carefully treated with small quantities of ice-water with swirling, vihen 800 ml of water had thus been added, the toluene layer was separated and washed with water (4 X 250 ml). The alkaline washings and previous aqueous portions were combined and extracted with ether (3 x 300 ml). The combined toluene and ether extracts were washed once with dilute acetic acid (5^0 and finally with brine. After drying, the solvents were fractionated off and obtained crude erucyl alcohol (202 g; 9 6 *7 7 % ), The product was fractionated under vacuum toj^ield pure erucyl alcohol (197 gj 94J6) , b.p. 2l5“21vVl*o iam, m.p. 34'^j (positive Ti'JM test and GLG, single peak). IH spectrum: 3350; C=G 1660, 728 cm~^. (Found* C| 81.2j H, 13.6; requires? G, 81.41; H, 13.65^) 13,14-dihydroxy behenyl alcohol (Xa ) Erucyl alcohol (284 g. 0 .88M;, glacial acetic acid (120 0 ml) and conc. sulphuric acid ( 1 1 ml) were taken in a three necked flask and cooled to 20 °. Hydrogenperoxide (100 volumes; 150 g; l.lM 20^ excess) v/as let i'n quickly while stirring the reactants. After stirring for 10 minutes 9t: the temperature was brought to room temperature and slowly raised to 40° and the reaction was allowed to proceed overnight. At the completion of the reaction contents were poured into water (3 lit.) at 20°G and the acetoxy-hydroxy derivative was vmshed free from acid. The derivative was refluxed with ethanolic potassium hydroxide solution iJQO ml} 10^) for 4 hrs and worked it up in the usual fashion. Solid 13,14-dihydrobehenyl alcohol was washed and dried (yield 311 g; 99^). The crude glycol so obtained was crystallised from alcohol and 13,14-dihydroxybehenyl alcohol resulted in a white crystalline form (290 g) m.p, 91.5 - 92^ (reported 92°). IR spectrum* OH 3413, 1344, 1263, 1124, 1070, 1035 cm"^. (Found: C, 73.9j H, 12.8; 022^46^3 73.68; H, 12.93^). Oxidation of 15tl4~dihyarobehexiyl alcohol. 13,14-dihydroxy b&henyl alcohol (54 g; 0 .1 ^ ) was taken in absolute alcohol (750 ml) and was treated with 4c 10% aqueous sodiuni meta periodate solution (375 ml) by letting in the meta periodate solution during 30 minutes witl'^efficient stirring at 35°. Stirring was coatinued for * Prepared in the laboratory accordiiig to the method reported by H.H. Willard tlnorg?. Syntheses Vol.I, p.168 (1 9 3 9 )3 . 1 hour more during which period the temperature was raised to S?'^. At the end of the reaction the contents were tested for excess of sodium meta periodate with potassium iodide solution (lOjD. ileaction mixture was filtered through No.4 sintered funnel and the sodium iodate residue was washed with alcohol (S x 50 ml). Filtrate was poured into water (5 lit.) and the turbid solution was extracted with ether (4 x 500 ml). Ether extract was washed, dried and flashed off the solvent. The crude product (53 g) m.p, 56-58*^ was fractioiiated under reduced pressure, to give pelargonic aldehyde (20 g ), b.p. 70 /lO mm, n^. l,4i^07, aiid 13-hydroxy tridecaaql XX.I (21.0 gj b.p. 153-155^^/0.3 mm, m.p. 74®. El spectrum: OH 3320; GIIO 2690, 1730, 364 cm"^. (Founds C, 72.7; H, 1 2 .Ij Cj_s^26^2 C, 72.84J H, I 2 . 2 3 f ) . 13- hyoroxy tridecanql has also been prepared with 100 g. lot of 13,14-dihydroxy beheayl alcohol with similar yields. 15-Hydroxy geat5 dec»2-enoic acid (>JCII) 13-hydroxy tridecanql (30 g) dissolved in pyridine (25 g) was added to a cooled solution of malonic acid (23 g) in pyridine (70 g) by means of a dropper in about 10 minutes while the reaction mixture was kept swirling. The contents were mixed thoroughly at the completion of addition of aldeliyde solution and kept at room temperature for 36 hrs, then heated over a water bath for 3 hrs. After removal of 97 pyridine in vacuo the lii^ht reddish liquid residue was extracted with ether (3 x 40 ml)j the extract was washed with dilute hydrochloric acid, water and aqueous sodium carbonate solution (7^; 4 x 25 ml). The carbonate extract was acidified with phosphoric acid, oolid acid was filtered and washed free of mineral acid and dried in vacuo to give 16-liydroxy pentadec-2-eaoic acid (32 g) m.p. 77-79^ which on crystallisation from alcohol afforded white crystalline unsaturated acid (29 g) m.p. 80°. la spectrum: OH 3380} COOH 2645, 1438, -C-C-COOH; 1690 C=C 1675, 1019, 994, 959 cm"^. (x-ound: G, 70.1; H, 10.9; ^15^28^3 C, 70.27; H, 11.01^). 15~Hydroxy pentadecanoic acid (X) In a three necked flask fitted with Herschberg stirrer (slip sleeve), 15-hydroxypentadec-2-enoic acid (20 g) was dissolved in aqueous sodium hydroxide solution (10%'f 600 ml) and the solution was heated to 90° and stirred for 15-20 minutes when clear soap solution resulted. Heating was stopped and itaney Hickel-aluminium alloy (60 g) was added to the hot solution in very small lots taking care that the next lot was added only when the evolution of gas from the previous addition of alloy stopped completely. Addition was accomplished i n 2 hrs. When the frothing stopped, finally the contents were heated at 85-95° for 5 hrs with vigorous stirring. The 08 reaction mixture was dilutea with water to filterable consistency, and filtered through cotton padded Bucliner f'uxinel. Washed the catalyst several times with sciall portions of warm water. The filtrate was chilled and poured into concentrated hydrochloric acid with stirring. VJhite precipitate was filtered and washed free from acid and dried in vacuo. Crude hydroxy acid (20 g) m.p, 82-84°, was crystallised from ethyl acetate to yield white 15- hydroxy pentadecanoic acid (19 g, 96^J) m.p. 84.5-85'^. IH spectrum: OH 3333, COOH 2604, 1709. (Found: C, 70.0} H, 1 1 . 8 j ^ 1 ^ 2 0 ^ 2 C, S9.7; H, 11.7^). 13-IIydroxy tridecanoic acid OJCIII) To 13-hydroxy tridecanol XXI (20 g) was added peracetic acid (132 ml, prepared by mixing 100 ml glacial acetic acid and 32 ml hydrogen peroxide, 100 volumes) and the contents were heated at 85'^C for 15 minutes. The resulting clear solution was cooled to 40° and kept over night at that temperature with stirring. At the completion of reaction the solution was cooled to room temperature and poured into cold water (1500 ml). The white precipitate was filtered and washed free from acid. The crude acid (2 1 .0 g> was refluxed with alcoholic potassium hydroxide solution (10%'f 75 ml) for 3 hrs and after removal of excess alcohol and working up in the usual fashion afforded white crystalline hydroxy acid (17 g) which on crystallisation 913 from benzene yielded 13-hydroxy tridecanoic acid (16 g) m.p. 78,0-78,5°. IR spectrums OH 3344, COOH 2632, 1706 cm"^. (Founds C, 67.72} H, 11.36; requires: C, 67.78j H , 11,38% )> Oxidation o f 1 3 -hydroxy trldecanal with a lk ali 13-hydroxy tridecanal (1 g) was kept in a tiiree necked flask and to it was added aqueous sodium hydroxide solution (5^; 26,5 ml) and hydrogen peroxide (SJbj 40 ral prepared by diluting 6 ml H^Og 100 volumes to 50 ml with distilled water). Initially the hydroxy aldehyde floated on the surface of the reaction mixture. Reactants were slowly heated to 65-75^ in 15 minutes and maintained for another 15 minutes with stirring. The aldehyde gradually disappeared and a turbid soapy solution resulted. The solution was filtered through a sintered funnel (No,2), cooled and acidified with dilute sulfuric acid. The white precipitate was filtered, washed free from acid and dried in vacuo. The crude product (1 g) m.p, 55-57^ was saponi fied with alcoholic potassium hydroxide solution (10^; 5 ml) and was worked up in the usual fashion and dried, ilesultant acid (0,6 g) m.p, 7 5 -77 °C was crystallised from benzene to afford IS-hydroxy tridecanoic acid (0,4 g) m,p, 78.0-78,5. mix, m.p, with the previous sample of 13-hydroxy tridecanoic acid 78,0-78.5°. liiO 1 2 -riydroxy laurlc acid (.jvIV') IQ-Undecenolc acid (XXV) 10~Undecenoic acid prepared in this Laboratory 54 by castor oil cracking has been used for the preparation of and tu-hydroxy fatty acids. lO-'Jndecenoic acid was purified by careful fractionation and the purity was tested by ?PC and a n aly sis, b .p , 131- 1S2°/1 nim, m .p. Sl°, n^^ 1,4489. positive TilM test. IK spectrum; GOOH 2 6 0 0 , 1716; C=C 16 35 , 390, 916 cm”^. (Found: C, 71.8; H, 11.2J requires; C, 71.69; H, 10.94^0. Methyl 10-undecenoate (XX^I) 10-Undecenoic acid (500 g ) , axihydrous methanol (1000 m l); dry ben;aene (1000 ml) and concentrated sulphuric acid (10 ml) were refluxed for 6 hrs, and excess solvent mixture was distilled under reduced pressure. The reaction product was poured into water (2 lit.). Esters were takea in ether (S x 400 ml), washed free from acid, extracted with sodium carbonate solution (7^; S x 50 ml), washed free from alkali and dried, solvent was recovered and the traces were removed under reduced pressure a^id crude methyl 1 0 - undecenoate (520 g; 99^) was obtained. The crude ester was distilled carefully to give water white pure methyl ester (500 g), b.p. 104-105°/0.7 mm (TWM and GLG tested); 1^' 1.4383. IR spectrum; COOCH^ 1748, C=C 1645, 994, 919 cm'^. (Found: C, 72.5; H, 11.3; 72.68; H, 11.18^). Th. MIQ 1 0 1 lQ»UnaecenoI ( i C v V I I ) Bright sodium (75 gj 2 .2 5 g atom; 25fi excess) was placed in a dry three-necked flask fitted with a Hers-hberg stirrer (slipseal), an eificient reflux con denser and a dropping fUiinel. ioaiuai was immediately covered with anhydrous toluene (150 ml) and heated on an oil bath at 12 0 ° and stirred to somewhat disperse the sodium, A mixture of methyl ester (126 g, 0.65M), anhy drous tert.butyl alcohol (144 g; 1,95m) and toluene (500 ml) was added in 45 mimtes with stirring, Juring the exothermic reaction the bath temperature was main tained at 120® + 5°, After the addition, the reactants were heated with stirring for another SO minutes, cooled, finally in ice-water, and carefully treated with small quantity of ice-water with swirling while maintaining nitrogen atmosphere in the flask. isfhe:i 500 ml of water had beexTi added, the toluene layer was separated and washed with water (4 x 150 ml). The alkaline washings and pre vious aqueous portions were combixied and extracted with ether (3 x 300 ml), The combined toluene and ether extracts were washed once with dilute acetic acid (5^) and finally with brine and dried. The solvents were distilled off and crude 10-undecenol (109 g; 98,5^) was obtained,on caret*ul fractionation it afforded pure 10-undeceiiol (102 g; 93^0; h-P« 125°/S mm (TJM and GLC K'lrJ te s te d ), 1.45 G=C S095, 1820, 1640, 991, 912 cm"^. (Found: C, 77.46j H, 1 2 .9 ; ^1x^22^ requires: G, 77.58; H, lS. 02Ji;; . Few more batches of 1 0 -iindeceaol were prepared with similar y ie ld s . 10«ll-.^ihydroxy undeca-iol (X V II) lO-Undeceuol (UO g; l.llM); glacial acetic acid (1200 ml) and sulphuric acid (11.5 ml, sp. gr. 1«84) were takea in a three-necked flask and chilled to 20 '^. iiyorogen peroxide (195 g; 100 volumes) was quickly added to the reactants v/hile stirring and the reaction was con tinued at 20*^ for 5 minutes. The contexts v/ere slowly brought to room temperature and gradually raised to 40^^ aid kept overnight. Reaction mixture was poured into water (S lit.) at 20^ and extracted with ether (4 x 200 ml), washed free from acid, dried and distilled off the solvent. The acetoxy-hydroxy-derivative was refluxed with 10^ ethanolic potassium hydroxide solution (lo oo ml) for 4 hrs. Excess alcohol was flashed off and the product was worked up in the usual manner to afford crude 1 0 , 1 1 -dihydroxy undecanol (225 g; 98.77^) which was crystallised from alcohol to yield a first crop of the glycol (156 g; 70»3fj) m.p. 73-74°. I'lother liquors on concentration, crystallisation and re- crystallisation from alcohol afforded a second crop of 10,11-dihydroxy undecanol (44 g; 20^') m.p. 7S-7S.5®. IH 103 spectrum: OH 3333, lo50, 1130, 1069 cm"^. (Found: G, 64.74; H, 11.77; requires: C, 64.66; a, 11.84^;). 1 0 -Hydroxy aecanal In a three aecked flask fitted with efficient stirrer (slipseal) condenser and dropping llinnel, 1 0 , 1 1 - dihyiroxy undecanol (2 g) was dissolved in absolute alcohol (25 ml) and treated with freshly prepared 10^ aqueous sodium meta periodate (,H5 ml) during 45 minutes at 35°. stirring was continued for another one hour and after testing the reactatts for excess of metaperiodate, the reaction mixture was filtered through a sintered funnel (:^o.4), washed the residue with alcohol (3x5 ml) and the filtrate was poured into cold water (250 m l). The liberated compound was extracted with ethyl acetate, washed, dried and solvent was distilled off under reduced pressure. Crude 10- hydroxydecanal (1.76 g; theoretical) m.p. 68-70° was crystal lised from alcohol to afford first crop of the pure com- pound(1.26 g; 7A,Q%) m.p. 76-77°. i4>ther liquors on con centration, and crystallisation afforded a second crop of 10-hydroxy decanal (0.21 g; IQ f) m.p. 75-76°. IR spectrum: OH 3460; CHO 1724 cm'^. (Found: C, 69.4; H, 11.5; requires: G, 69.72; H, 1 1 ,7 % ) , The 2,4-dinitropheayl hydrazone prepared in alcohol and acid, crystallised from 1 0 ‘1 dilute alcohol had a m.p, 98-39°. IR spectrum: OH 3460, 1059; CHO 288Sy 17^4, 1458, 980, 964 cm"^. (Foundz C, 54.7; H, 6 . 6 ; 15,7; requires: C, 54.53; H, 6.87; W, 15.9^j). The semicarbazoxie prepared in pyridine and crystallised from methyl alcohol had a m.p. 106.5*^. More quantity of 1 0 -hydroxy decanal was prepared in 10 g lots also with similar results. 1^-iiydroxy dodec-2 -erioic acid (XXX) To a cooled solution of malonic acid (8.20 g) in dry pyridine (SO ml), 10-hydroxydecanal (10 g) in pyridine (15 ml) was added drop by drop i n 15 minutes with shaking. The reactants were kept at room temperature for 36 hrs, then heated on a waterbath for 3 hrs. Pyridine was removed under reduced pressure and the residue was extracted with ether (2 X 50 ml), the extract was washed with dilute hyaro- chloric acid, water and aqueous sodium carbonate (7jl, 5 X 25 ml). The combined carbdnate extracts on acidification with dilute hydrociiloric acid gave 1 2 -hydroxy iodec-2 -eaoic acid ( 1 2 . 2 g; 6 6 ,6 % ) which crystallised from alcohol yielded the acid (8 g) m.p. 67-67,5®. Mother liquors on concentration and recrystallisation afforded a second crop (2 g, 16.7^) m.p, 66.5-67®. IH spectrum; OH So48, 1053; COOH 2620, 1440; C=C-COOH 1705, 1580 cm‘ ^ . (Found; G, 6 7 .2 6 ; H, 1 0 .4 7 ; Ci 2^22^3 67.25; H, 10.SS^^). More quantity of 105 the acid was prepared in batches with similar results. 12-xiyaroxy lauric acid (XXIV) (i) 12-Hydroxy dodec-2 -eaoic acid (0.5 g) dissolved in glacial acetic acid (15 ml, E.Merck; v/as hydrogenated in the presence of palladium-carbon (lOJ^j 0 .0 5 2 g) at room temperature. The compound absorbed hyarogen gas (65 al> in the first hour of reaction and no farther perceptible absorption of gas was observed even after stirring for 3 hrs. The catalyst was separated by filtration, washed with acetic acid (3x2 ml) and the acetic acid was removed from the filtrate under reduced pressure. The residue on saponification and hydrolysis afforded crude 12-hydroxy lauric acid (0,5 g) m.p, 82° C , which on crystal lisation from benzene gave pure acid (0.4S g) m.p. 83-84°. I la spectrum: OH 3333, 1054; GOOH 2571,(19^ 1684, 1316 cm“^. (Found: C, 3 6 ,4 ; H, 1 1 .1 } ^i2^^24*^3 6 6 .6 3 ; H, 11.18^). ( i i ) l 2 -Hydroxy aodec-2 -enoic acid (13.3 g) was dis solved in aqueous NaM solution (10^; 400 ml) and heated to 90^^. Raney-nicicel alloy (40 g) was added to the hot solution in small lots taking all care as described pre viously. Addition was accomplished in ^ one and half hour and the reaction mixture was heated for axiother hour at 90°C with stirring. Insoluble material was filtered off 1.0B and the filtrate was worked up ia the usual maimer to obtain crude 12-hydroxy lauric acid (13.2 g) ra.p, 79-81°, which on crystallisation from ethyl acetate afforaed pure acid (12 g; 90;^’) m.p. 83-84°. There was no depression in melting point with l 2 -hydroxy lauric acid from the previous batch. IR spectrum: Qii 3333, COOH 2571, 1923, 1684 cm”^. efficient quantity of the hyaroxy acid was prepared in batches with similar yields. 11-bromoundecanoic acid (XXXII) 1 0 -Undecenoic acid (50 g) was dissolved in pet.ether (40-60°, sulphuric acid washed, distilled, 350 ml) in a three necked flask fitted with thermometer, wide bored inlet tube and caicium chloride guard tube. After adding freshly crystallised benzoyl peroxide (1 g) to the solution, cooled to 0° and hydrogen bromide (evolved by dropping 53 ml of bromine into 51 g of tetralin) was rapidly passed into the solution. Solids started appearing after 5 minutes and as solids separated the flask was shaken and process was continued till all the hyarogen bromide passed into the reaction mixture ('^25-30 minutes). The temperature was maintained at 0° throughout. The contents were shaken for a further 20 minutes. The pink precipitate was chilled to -1 2 ° and filtered off and transferred to a porous plate and dried. When dry it was colourless and 1.07 shining (57 g; 72%) m.p, 47-49°. The crude product was crystallised from pet. ether (40-60°; 100 ml) twice at -15°. Filtered and dried in vacuo to obtain 1 1 -bromo undecaaoic acid (54 g) m.p. 50.5-51°C, white shining flaky crystalline material. 11-Acetoxy undecaaoic acid (JQCvIII) 11-bromo undecaaoic acid (50 g ) , freshly fused sodium acetate (55 g), glacial acetic acid (100 ml), and acetic anhydride were refluxed over a controlled hot oil bath for 12 hrs. The reaction mi/ture was cooled and poured into water (250 ml) and the- contents were extracted with ether (4 x 50 ml). The combined ether extracts were washed free from acid, finally with brine and dried. Recovery of the solvent gave crude 11-acetoxy undecaaoic acid (4 2 .4 gj 96%) which was distilled fractionally to obtain pure acetoxy derivative (35.5 g) b.p. 176-177°/0.7 ram. About 2 g forerun of the distillate was collected separately. IR spectrum: COOH 2660, 1718, 1686j CHgCOO-j 1234 cm'^. (Found; C, 63.7; H, 9.8; requires* C, 63.90; H, 9 . 9 ^ ) . 1 1 -Hydroxy undecaaoic acid (X}QLI) 11-acetoxy undecanoic acid (34 g) was refluxed with alcoholic potassium hydroxide solution (10^; 150 ml) for 6 hrs. Excess alcohol was distilled off and the residue after dissolving in water (200 ml) was acidified with dilute 1.08 hydrochloric acid. The precipitated acid on filtration, washing and drying afforded crude ll-hydroay undecanoic acid (28 g; theoretical); m.p, 65-67°, which was crystal lised from ethyl acetate gave pure acid (27 g} 97%) m .p. 67-67.5°. IK spectrums OH 3o20} COOE 2626, 1711 cm'^. (Found: C, 65.1; H, 10.9; requires; C, 65,31; H, 10.96^). IQ-Hydroxy decanoic acid (XX^.IY) 10-Hydroxy decanal (XXIX) (10 g) and peracetic acid (67 ml, prepared by mixing 51 ml glacial acetic acid and 16 ml hydrogen peroxide, 100 volura.es) were heated on a waterbath at 85° for 15 minutes and left overnight. The reaction mixture was filtered, pourea into water and ex tracted with ethyl acetate (S x 50 ml), solvent extract was washed free from acid, dried, and flashed off the solvent to obtain a slimy product was refluxed with alcoholic potassium hydroxide solution (10^; 50 ml) for 4 hrs. Alcohol was distilled off and the product was worked up in the usual maiiner to obtain crude 1 0 -hydroxy decanoic acid (10.9 g) m.p. 68-70°. Crystallisation from benzene- ethyl acetate afforded pure hyaroxy acid (8.5 gj 78^), m.p. 75.5-76.0°. IR spectrum; OH 33S3, 1060; COOH 2646, 1698 cm'^. (Found: C, 63.9; H, 10.81; I requires: C, 63.79; H, 1 0 ,7 1 % ), 1. 0!3 CYCLISATIQi^ OF ca-HXiUQXY FATTY ACIDS l«18-Qctaciecaaollde Thiophene free dry benzene (2, lit.) and p-toluene sulphonic acid (2.5 g) were taken in the flask shown in the set up (Fig.2 ) heated to gentle distillation and allowed the distilled solvent to circulate through the system for one hour. 18-Hydroxy stearic acid (5 g; 0.0166 M) dissolved in dry benzene (500 rrilj 0.008S Vi/l) was dropped into the set up, tiirough the cropping fuiinel in 32. hr s. Hate of additioxi of the hydroxy acid solution was controlled by adjusting the tungston wire tipped plunger fitted in the capillary tube fused at the bottom of the dropping furmel and efficient dilution was ensured through steady distillation of solvent and recirculation. Solvent was stripped of,water of reaction while passing through the drying tube filled with activated indicating silica gel which was changed as and when needed. Hydroxy acid was kept dissolved in the dropping funnel and horizontal tube where dilution was accomplished, with the help of a heating tape. At the completion of addition, the reaction mixture was refluxed for another one hour, cooled to roam temperature, washed free from a c id , followed by washing with aqueous sodium carbonate solution (7%; 3 X loo ml), washed free from alkali and aried. Benzene was recovered under reduced pressure, and the residue was 110 dissolved in n-hexane (50 ml), chilled. Solids were separated by filtration. Filtrate was concentrated and cooled. The process was continued till no solids separated. Hexane was recovered and the product on distillation afforded colourless 1,18-octadecanolide (3.46 g; 81.1^) b.p. 147.5-148/ 0.8-0.9 mraj m.p. 36.6-37°, n^^ 1.4666; (GIa J single peak). lii spectrum:^G=0 1740} Pi-IH signals: (s), /? /? -CHg-C-O- 1 3 3 .5 ( d ) , -CH^-G-O-CHg- 2 4 1 .2 ( t ) . (Found; C, 76.52; H, 12.19; requires: C, 76.54; H, 12.13%). Dilactone m .p. 1 1 1 -1 1 2 ° . I,16-Hexadecanolide 16-:iydroxy palmitic acid (4.53 g; 0.0116 M) dissolved in dry beazene (500 ml; 0 .0 0 8 3 H /l ) was cyclised in the same manner as described previously, by adding the hydroxy acid solution to the reaction mixture (benzene 2 lit, p-toluene sulphonic acid 2.5 g) in 33 hrs. on working up ia the usual fashion and distillation it afforded colourless 1,16-hexa- decanolide (synonym: dihydro ambrettolide) (3.42 g; 80.9Jfc); b .p . l 2 6 -1 2 7 ° / 0 .6 ram; m.p. 34-36°; n^^ 1.4678 (GLC tested). IH spectrumiyC=0 1740; PI© signals: 79.6 (s); 133.5(d); -GHg-G^-O-Ciig- 241.6 (t) cps. (Found* C, 75.71; H, 11.85; requires: C, 75.53; H, 11.89^). 1,15-p exitadecanolide 15-Hydroxy pentadecaaoic acid (4.28 g; 0.0166 M) 111 dissolved in benzene (500 ml; 0,0083 1^1) was laotonised in the usual manner. Addition of the hydroxy solution to the reaction mixture (beazene 2 lit., p-toluene sulphonic acid 2.5 g) was completed in £2.5 hrs. Working up of the reaction product ana distillation gave colourless pleasant smelling 1,15-peatadecanolide (synonym; exaltolide) (2.79 g; 78.9^) b.p. 120V o .3 mmj 1.4692; (GLC single peak), lil spectrura:^C=3 1748; PMH signals; Crig-C-O- 1 S S .7 (d ); -GH^-G-O-Cii^- 2 4 2 .2 (t; cps. (Found: G, 75.21; H, 11.8; Cjl5^28^2 G, 74.95; H, 11.74^i>. 1.13-Trldecanolide IS-Hydroxy tridecanoic acid (3.82 g; 0.0166 M) dissolved in benzene (500 ml; 0.0083 M /1) was cyclised accordingly. Addition of the hydroxy acid solution to the reaction mixture (beazene 2 lit.; p-toluene sulphonic acid 2.5 g) was accomplished in 33.5 hrs. The product was worked up as described previously and distilled to obtain colourless pleasant smelling 1 ,13-tridecanolide (2.3 g; 65,4^'); b.p. 101-102*^/1.0 iQ2i; 1.4684; (GLC tested); IH spectrum* // ^C=0 17^; PM signals: 81(s); -Ca^-G-O- 136.3(d); -GHg-O-O-Ggg- 24^.7 (t) cps. (Found: G, 73.39; H, 11.53; ^13^24^2 requires: G, 73.53; H, 11.39%). 1 , 1 2 -dod ecaaolide 12-Hydroxy lauric acid (3.53 g; 0.0166 M) dissolved 112 in benzene (500 ml; O.OOSS m/ 1 ) was lactonlsed in the usual man.ier. Addition of the hydroxy acid solution to the reaction medium (beazene 2 lit,, p-toluene sulpho.iic acid 2.5 g) was carried out in c3 hrs. The reaction product was processed in the same fashion as described previously, distilled and redistilled to afford colourless strong smelling 1,12-dodecanolide (0.78 g; 2 B .7 ^ ) b.p. 85-86^0.3 mm; r- ^ nj^ 1.46^0; (GLG single peak). IH spectrum:);C=0 1740, If Q 1750; signals: 81.3(s); 134.1(d); -CHj^-C'O-GH,^- 244.1 (t) cps. (Found: C, 72.54; H, 11.1; ^12^22^2 72.68; H, 11.18%), 1 ,1 1 -Undecanol ide 1 1 -Hydroxy undecanoic acid (3 .3 5 g; 0 .0 1 6 6 M) d i s solved in benzene (500 ml; 0.0083 iVl) was cyclised by adding to benzene (2 lit.), p-toluene solphonic acid (2.5 g) in the usual manner in 33 hrs. The reaction product on working up according to the usual method and distillation yielded colourless strong s|aelling 1,11-undecanolide (0.56 g; 18.33^); b.p. 7^-80°/0.4 mm; n^® 1.4694; (GLG tested); IH spectruffl:yC=0 1740, 1750; PMa signals: -CHg-CJi^-GH^" 81.7(s); -CHj^-G-0-, 1 3 6 .2 ( d ) ; -CH^-C-O-Giig-, 2 4 5 .2 (t ) cps. (Found: C, 72.0; H, 11.04; requires: C, 71.69; H, 10.94^i) . ItlO-decanolide 10-Hydroxy decanoic acid (3.12 g; 0.0166 M) dissolved II 3 in beazeiie (500 ml; 0.0083 iVl) was lactonised by lettin g it into the reaction medium (benzene 2 lit., p-toluene sulphonic acid 2 . 5 g) in the same manner as described pre viously in SZ hrs. The reaction product was worked up in the usual fashion and distilled to give 1 , 1 0 -decanolide (0.114 gj 4.03fJ); b.p. 65-66°/0.a mia, n§° 1.4663; (GLG tested). IR spectrum: yG=0 1748, 1752; P MR signals: CHg- 8 2 .1 ( s ) ; -CH^-0-0- 1 3 5 .0 (d ); -GHg-G-O-Oii^- 2 4 6 .2 ( t ) cps. (Found: G, 70.9; H, 10.8; C3_QHj_g02 requires: G, 70.54; H, 1 0 . 66?:). 55 l«7-Heptanolide C 4 -eaantholactone);cycloheptaiioae ; In a three-necked flask fitted with efficient stirrer, dropping funnel and thermometer, cyclohexaiione (45 g; b.p, 154-156^), methyl alcohol (36 g; acetone free) and dry analar potassium carbonate (catalytic amount) were cooled to 20° with stiri-ing and the agitation was continued for 10 minutes. Jitroso- methylurethane (56 g; prepared in the laboratory;was slowly added to the reactants through the dropping funnel at such a rate that temperature of the reaction mixture did not rise above 20°« After completion of addition, reactants were stirred for another 30 minutes, brought to room tenpera- ture and kept overnight. The product after filtration was carefully fractionated and compound d is tillin g at 179-181° was collected aad refractionated to afford cycloheptaaone (31 g; 60^) b.p. 179.5 - 180.5°; n]]^ 1.4566; IE spectrum: 111 ^C=0 1701 cm"^. preparation of lactone; Cycloheptaaone (5,6 g) and per- benzoic acid (3,3 g; ca. 250 ml chloroform, prepared according 57 to the procedure of Braun ) were mixed thoroughly by shalcing in a flask covered with t)lack paper and kept in dark, at room temperature. Jame volume of perbenzoic acid solution in chloroform was also kept side by side in a separate flask as a control. Aliquots of the reaction mixture and blank solution (5 ml each) were rmoved at Intervals of 48 hrs and titrated iodometrically in the 57 normal manner . After 17 days ( ^ 8 hrs) the ketone con sumed perbenzoic acid (6.5 g), Heaction mixture was ex tracted several times with sodium bicarbonate solution ( 3^ ) , washed free from alkali and dried. After ranoval of solvent at reduced pressure the product (5,4 gj 84.S7^o) was frac tionally distilled in vacuo, keeping the receiver in ice-salt mixture to yield 1,7-heptanolide (3.7 g; 60%) b.p. 81-83°/ 1 mm, n^^ l,466ii.IS 3pectrumjyC=o 1742, 1786 cm“^, g-Caprolactone A mixture of cyclohexanone (7 g; b.p, 154-156'^) and perbenzoic acid (12 g; ca. 130 ml chloroform) solution; was mixed thoroughly and kept at room tenperature for 8 hrs with occasional swirling. The reaction mixture was processed as described already, dried and solvent was removed under reduced 1,15 pressure. The product was carefully distilled to give e-caprolactoae (S’5 gj QB>%) b.p, 80-81°/l»^ 1.4665. IR spectrum:j;C=0 17S5 cm”^. PYHQLY3I3 0¥ LACTQNE3 17>3ctaaeceaoic acid (I) (CIj^=aH(GH^)j^gCOQH) 1,18-Octadecanollde (1 g) was pyrolysed in a vertical reactor shown in Fig.2. The reactor consists of an inner tube (1,4 O.D. x 30 cm) fused at the bottom with another tube (8 mm O.D. x 21 cm). Rest three outer tubes form the electrically heated furnace. The reactor tube was filled with pyrex glass pieces (1.5 to 2 mm cubes approx.) to a height of 15 cm. Rirnace was heated to 450° and after fitting the micro dropping funnel containing lactone to the reactor tube, the system was flushed several times with oxygen-free dry nitrogen, by means of a nitrogen system, at 150 mm pressure. Te mperature was gradually raised to 525°, and when it stabilised, lactone was dropped on the hot bed of glass pieces (one drop every half minute; maintaining the pressure at 150 mm. Pyrolysis was completed in one hour. Reactor was heated for another 15 minutes and the system was brought to room temperature. Pyrolysate (0.83 g, 83^) was dissolved in ether (20 ml) and ether solution was extracted with aqueous sodium carbonate solution (5^j 6 x 5 ml). The combined alkali extract was further extracted with ether (2 x 15 ail). Ethereal solution was 1.1 n washed free from aln:ali, oriea said recovered the solvent to afford neutral fi?action (0.67 g), which on distillation afforded colourless liquid (0 .6 g) b .p . 140-141 ° / 6 mm. IK spectrum:^ 1740 cm” , and similar to the IR curve of the starting lactone (1,18-octa- decanolide). Allcali extracts were combined and acidi fied with dilute hydrochloric acid. Liberated acid was talcen in ether (3 x 20 ml), washed free from acid, dried and recovered the solvent to afford 17-octa- decenoic acid (0.162 gj 50fJ feased on the unrecovered lactone) m.p. 52-54° which on crystallisation from acetoaitrile afforded white shining crystalline urisatu- rated acid (0.155 g) m.p. 54.5-55°, gave THM test. IH spectrumjj;C=0, 1700-1715;^C=C 1650 S 917j S-GH =: CH^ 935. (Found: C, 76.76; H, 12.27; requires: C, 76.54; H, 12,1356). Methyl-17-0ctadecenoate fCri^=GH(GH^)^ ^COOCH^ ) : 17-Qcta- decenoic acid (85 mg) was esterified by reacting with aiazomethane in ether, worked up and jlstilled (in bulb) in vacuo to yield methyl, 17-octadecenoate, b.p, 143-44^(bath)/ 0.2-0.3 mm, 1.4469 (Gave TiilM test and single peak GLC); IH spectrum: COOGH^ 1750; ^ G=G 1650; 5 -CH^Cag 913; ^ S-G|i =Cii^ 995; PMH sign als: 7 7 ( s ) ; -Ga^c'^-OGHg 129 ( q ) ; -CHg-c'^-O GH^ 2 1 6 ( s ) ; -GH2 =GIi- 285-358(m). (Found: 1.17 v l C, 76.63; H, 12.33} requires: C, 76.37; H, 12.24;^), :tore of 17-octaciecenoic acid was prepared by pyrolyziag 6 g lots of 1 ,18-octadeGanolide. Ijj^drogexiatioa of 17»octadeceaoic acid: Methyl, 17-octa- decenoate (0.5 g) was hyorogenated in alcohol (10 inl) in the presence of Pd on calcium carbonate catalyst (0.25 g; lOJ^) at room temperature. Reaction was con tinued for S hr s. Whe.i no absorption of hydrogen gas was observed, the catalyst was filtered and washed with alcohol (3x3 al), iolveat was removed from the filtrate at room temperature under suction. Residue was heated with alcoholic potassium hydroxide (10 ^ ; 10 ml) under reflux, removed solvent and soap was hydrolysed with dilute hydrochloric acid. Liberated solid acid was filtered, washed free from acid, dried to afford stearic acid (0.48 g; 100^); m.p. 63-69°. Crystallised from .onitrile, and obtained pure shining stearic acid (0.45 g; 96^^') m.p. 69-69.5'^; mix. m.p. with authentic sample of stearic acid 69-69.5*^. IR spectrumj COOH 26S2, 1698 cm“^ . 15-Hexadeceaoic acid (CJio=CII( GHoji^COOHj 1,16-Hexadecanolide (1 g) was pyrolyzed at 525°/150 mm in one hour. Pyrolysate (0.93 g; 93fJ) was separated into -leutral and acid fractions in the usual 1.18 fashion. Neutral product (0.G7 g). IR spectrum: ^0=0 1740 cm was very siinilcir to the starting lactone. Acid fraction (0,23 g; 6'^% based on the unrecovered lactone) ra.p. 45-47° was crystallised from acetonitrile to afford pure 16-hexadeceaoic acid (0.2 g) m.p. 48-48.5®. Gave TiJM test. IE spectrum: ^0=0 1705-1710; 1647; ScH=ca^ 919; S-Ca-GHg 993; (Found: C, 75.61; H, 11.74; ^16'^^S0*^2 C, 7 5 .5 3 ; H , 11.89fjj. Methyl-15-hexadeceaoate (CH^= JH(CH^j j : 16-hexa- decexioic acid (90 mg; was esterified by reacting with diazo- methane in ether. Methyl ether, after working up, dis tilled (blilb) in vacuo to give pure methyl 17-hexadecenoate b.p. 140-145° (bath)/0.6 mm; n ^ 1.4445 (positive TNM test, single peak uLC). IR spectrum: yC=0 1750; j>G=C 1650; S-CH=cao 913; S-G|i=CH, 995; PMd sign als: -CH,-Cii,-GH- 7 7 (s ); -GH^-C-OCH^ 12? (q ); -GH^-c'^-OGH^ 2 1 6 .5 ( s ) ; Gii^=Ga - 286-349(m) cps. (Found: G, 7 6 .2 1 ; H , 1 2 .0 9 ; Gj^^H^^Og requires: C, 7 6 .0 6 ; H, 1 2 . 02^ ) . 14-Pentadeceaoic acid (CH^=CH(ai^)j^^GOOH) 1,15-pelitadecanolide (1 g) was pyrolysed at 525°/l50 mm in one hour and pyrolysate (0 .9 0 3 g ; 90fi) was as usual separated into neutral (0.65 g) , IR spectrum of which was similar to that of the starting lactone, and acid fraction (0.26 g; 73^u, based on unrecovered lactone) m.p 45-47°, crystallise! from acetonitrile gave crystalline 15-pex\tadecenoic 1.1 n acid (0.13 g) m.p. 50-50.5'^; (positive TNM test). IR spectrum; ^C = 0 1695-1710; j;C=G 16 43 ; S-QH^qHg 917; S-Cii=CH^ 935.cm'^. (Found; C, 75.06; H, 11.85; ‘^15'^28^2 G, 74.i5; H, 11.74^U, Methyl «-14>g eataaeceaoat e ( GxH^=CHC j^^COOCH^) j 1 5 -p ent a - deceaoic acid (100 mg) esterified with diazomethaae in ether and after processing distilled (bulb) gave methyl 15»pentadecenoate, b.p. 120-125°(bath)/0.4-0.5 mm; SO Uj 1.4426, gave T*'iM test. uLG testea. IR spectrum: j;C =0 1750; j;G=:C 1645; S-GH=CI^ 91S; S~Ca=GIi^ 996; p m sig n a ls: 7 7 . 5 ( s ) ; -GH,^-G^'-OCHg 1 2 9 (q ); -CHg-C-OGHg 2l6(s); CH,^=CK- 287-359(m) cps. (Found; C, 75.68; H, 11.85; C^qH^q O^ requires: C, 75.53; H, 11.89^). 12-tridecenoic acid. CIi^=CH(CiU)j_QCOOHj ; 1,13-tridecanolide (1 g) was pyrolysed at 525^/150 mm in one hour. Pyrolysate (0 .9 8 g; 98^) on woricing up by usual procedure afforded neutral fraction (0.68 g), IR spectrum of which was very similar to the one obtained for the starting lactone; and acid fraction (0.29 gj 89^ based on unrecovered lactone); m.p. (double capillary) 35-37°, which on crystallisation from acetonitrile in cold afforded first crop of 13-tridecenoic acid (62 mg), m.p. 38^^. Mother liquor on conceiitration and chilling gave a second crop, reerystallised from aceto nitrile to give unsaturated acid (46 mg>, m.p. 38® (positive 120 TMM t e s t ), sixigle peak (GLG). iiest of the product after removal of solveat was distilled (bulb), b.p. 135-140^(bath)/l nm; m.p. 3 7 .5 -3 8 ^; IR spectrums j;C=0 1725j I645j S-CH=Cii^ 915j S-GH^CHg J95; (Found: C, 73.1; H, 11.58; ^ 1 3 ^ 04^2 G, 7 3 .5 3 ; H, 11.39J^). Methyl»12>trldecenoate (CH^=aH(ai^)j_QCOOCH^) : is-tri- decenolc acid (90 mg) esterified with diazomethane in ether, processed and distilled (bulb) to give methyl 13-tridecenoate, b.p. 120-125°(bath)/l mm, n|° 1.4395; gave T'JM test, GLC tested. IH spectruiu: ^0=0 1750; j;C=C 1645; S-CH=CHj^ 915; 995; PMH signals: 7 S ( s ) ; 1 2 8 .5 ( q ) ; -GH.^-C-OCiig 217.5(s); G|^= CH- 287-363 C^)cps. (Fouad: C, 74.61; H, 11,67; requires: C, 74.28; H, 11.58^). 11-Jodecenoic acid (GlI^=GiI(Glio> ^COv^H) : 1,12-dodecanolide (1 g) was pyrolysed at S^5®/l50 mm in 1 hr. Pyrolysate (0.98 g; 98^) was separated into neutral component (0 ,7 3 g ) , IK spectrum of v/hich was observed to be very similar to the spectrum of 1,12-dodecanolide and acid fraction (0,23 g; 83% based on unrecovered lactone), by usual method, which on distillation (Ixilb) gave 12-dode- ce-ioic acid, b.p. 125-130°(bath)/0.8 mm, n^® 1.4398. Positive TNM test, single peak (QLC). IR spectrum: ^0=:0 1705; 1 2 1 ^C=C 164S; S-CH=CH^ aiO; 99 5. (Found: G, 72.49; H, 11.27; i*eq^i^es! G, 72.68; H, 11.18^). Methyl-11-dodecenoate CCH^=^CH(Gii^)gQOQCH^) ; l2-dodeceiioic acid (91 mg) was esterifled with diazoraethane In ether, processed and distilled to afford methyl 1 2 -dodecenoate, b.p. 80-85®(bath)/0.6 mm; n ^ 1.4362, positive WM test (GLG tested). IR spectrum; ^ Q=0 1 750; 1645; ^-Ga = CHg 9^5; P m sign als: -CE^-Cag-GH^- 7 8 .5 ( s ) ; -Ca^-C-OGEg 1 2 7 .5 ( q ); -Grl^-G^'-DGilg 2 1 6 .5 ( s ) ; GHj^=C:H- 285-S65(m) cps. (B’oundjc,7S.9S; H, 11.42; requires: G, 73.53; H, 11.39^0* IQ-Undecenoic acid (GH^aCH(CHo)QGQOH 1,11-Undecanolide (0.75 g) was pyrolysed at 525^ 150 aua in 45 minutes and pyrolysate (0.68 g; 91^0 was pro cessed to give neutral fraction (0 .5 1 g) and acid componeat (0.17 g; 70^ based on unrecovered lactone). Heutral portion, IR spectrum of which was similar to the one obtained for starting lactone, on distillation (bulb) afforded 1^1-undecanolide b.p. 115-125°(bath ) / 2 mm. IR spectrumjy G=0 1740, 1750, super imp o sable on the IH spectrum of authentic sample of lactone. (Found: G, 71.73; H, 10.96; ^11^20^2 r®Q.^i2?es: G, 71.69; fl, 10.94). Acid fraction was distilled(tailb) to obtain 1 1 -undecenoic acid, b.p. 130-135(bath)/l mm; n^^ 1.4462; positive TI^M test, QLG tested. 12 Id IR spectrum: yC=0 1717; j;G=G 1339; ^-CH=C2^ 912; S-ClT=GHj^ 990 cm"^. (Found: C, 71.73; H, 11.0; requires: C, 71.69; H, 10.94ji)« Methyl >10-undeceaoat e (CH^=GH( CH^) '^OCH^) ; 11-Undecenoic acid (93 rag) esterified with diazoiaethane iii ether, was distilled (bulb) to afford methyl 11-undecenoate, b.p, 90-35°(bath)/0.5 mm; 1.4360; gave positive TmM test, GLG single peak. IH spectrum: y 0=0 1750; j;G=C 1645; S-aH=GH^ 913; S-CII=qi^ 995; PMH sig n a ls: -Gil^-CH^- 8 0 ( s ) ; -CH^-G-OCH^ I 2 9 ( q ) ; -CH^-G^'-OGHg, 2]J 8 .5 (s ); CH^=Gii- 288.5-368.5(m) cps. (Found: G, 72.44; H, 11.24; ^12^22^2 C, 72.68; H, Ix.lS^'). 6-:ieptenoic acid (GH^=GH(GH^) ^COOH) 1 ,7-hepta-iolide (0.9 g) was pyrolysed at ^ s V l^ o nun in 45-50 min. Pyrolysate (0.67 g; 74^.) when processed gave neutral component (0 .3 5 g ) , IH spectrum of which was similar to that of 1,7-heptaaolide, and acid fraction ( 0 .3 g; 55^ based on the unrecovered lactone). On dis tillation (bulb) this afforded 7-heptenoic acid, b.p. ,110-115°(bath)/6 ram; gave TNM test. IH spectrum: j; G=o 1709; j^C=G 1639; S-CH=sCH^ 915; S-Ga=CH^ 1000-1020 cm'^. Methyl 6-hepteaoate CGH.^=GH(CH^) ^GOOCH^) : 6-hepteaoic acid (95 rag) was esterified with diazomethane in ether in cold, 123 processed Ander cold co/iditions, distilled quicicly to obtain methyl 6 -hepte.ioate b.p. 100-110(bath)/9 mm; positive Ti'^M test. IK spectrum: ^0=0 1745; yC=C 1642; S-GH-CH^ 920; 971. P m sig n a ls: -CH^-CH^' 80 (s); -G-OGHg 129 (q); -CH^ -C-OCH^ 219 (s); -CHg= Cii- 288-368 cps. Pyrolysis of fc-caprolactone f-Gaprolactone (1 g) was pyrloysed at 525°/150 lam * in 1 hr. Pyrolysate (0.9 g; 90^) on working up in cold yielded a liquid neutral fraction (0.13 g ), IR spectrum: yC=0 1724 cm~^; similar to that of starting lactone in every respect; and an acid component (0 .6 9 g; 80 ^ based on the unrecovered lactone which did not give positive TM test). IH spectrum: OH 3344, GOOH 2632, 1695 cm”^ and any peak for vinylic unsaturation in the region of 910-920 was completely absent, and it did not give Ti'iM test. iugteriftcatlon of acid fraction; Above acid fraction (u.58 g) was esterified with diazomethane in ether, in cold, pro cessed and fractionated. Fraction I (0.37 g) b.p. 87-39^10 mm. IR spectrum: OH 3430; COXiig 1740; and Fraction II (.16 g) b.p. 110-115^8 mm. IH spectrum: OH 3410; GOOCHg 1738 cm”^. Fractionation by YPC: Methyl esters (0.68 g) preparea from *■ the acid fraction obtained from a second pyrolysis of e-caprolactone were fractionated through Perlcin-Elmer Vapor 124 x’factoraeter, model 154 (Colum *P', length 6 'j temp. 160°; pressure (hydrogen gas) 15 Ibsj attenuation 4; material injected 20xfl/i^jection, total number of injections S3). Two distinct fractions were collected, first being in minute quantity and the second forming the major fraction. Fraction I distilled (bulb), b.p, 80-S5°(bath)/8 ram, IH spectrum j OH 3430; C jOCH^ 1740 cm*"^. Fraction II distilled (’cRilb>, b.p, 110-115°/8 ram, IR spectruia: O^i, 34ki0; COOCHg 1745 cm”^ . (Found: C, 5 8 ,0 2 ; H, 9,45; requires: C, 57.51; H, 9.65J-); PMii signals: -GH^-CH2-C2i^-(6H) 74-114(m); (2H) 1 3 5 .5 ( t ) ; :)H(1H) 1 8 0 ( s ) ; GHj^-0 (2 H) 210,5 (t); COOCH^ (3H) 217 (s) cps. Several pyrolyses were carried out with similar results. Hyorolysis of e-caprolactone; C-Caprolactone (0,37 g) was refluxed with alcoholic potassium hydroxide solution (10^; 15 ml) for 3 hr. Alcohol was removed, soaps dis solved in water (25 ml), and carefully acidified in cold with dilute hyarochloric acid, maintaining a layer of nitrogen in the flask, Liberatea acids were taken in ether (3 x 15 ml) (after saturating the aqueous layer with ammonium sulphate), washed with brine, dried, solvent was flashed off and the product after drying under reduced pressure was immediately esterified with diazomethane in ether. Methyl esters, on careful distillation afforded 125 two fractions. Fraction I, b.p. 80-85^(bath)/8 ram. IR spectrum* OH 3400; CCWCH^ 1740 cm“^j superimposable on the spectrum obtained for the firs t fraction from VPG* Fraction II, b.p, 110-115‘^(bath)/8 ram. IR spectrum: OH 34S0j COOCiig 1746 cm”^j superimposable on the spectrum obtained for the second fraction from VPG. PMH signals: 7S.5-114.5(m); Gii^-G=0 (2H) 135.5(t); OHCH) 182(s); 210.5(t); COOC^^ (ai) 2l7(s) cps, 1 .2 B 3U14MAHY A general procedure for the synthesis of co-olefinic fatty acids involving pyrolytic ois-elimina- tion of lactones having eight or more members in the ring is described. The method which gives high overall yields has been applied for the synthesis of (Gj^g, C^g, *^13’ ^ 1 2 ’ ^ 1 1 ^ 7 ^ tu-olefinic acids. In con*iection with the above work new proceaures for the synthesis of the following acids have been worked out (^ 2^5 * ^ 1 3 * ^1 2 » ^ 1 1 ^1 0 ^* A simplified procedure for the lactoniaation of u)-hydro2y acids to give large-rneinbered lactones is described. spectral data (IH , NMK) of many-membered lactones o)-olefinic acids and their methyl esters have been presented and discussed. 127 HEi EilEaCES 1 S.C .u u p ta , J« 3g1. liidustr. lies. India» 13B, 885 (1954), 2 C.H. JePuy and ii.W.King, Chem. Rev. 60, 431 (I960). 3 W. Brandenberg and A. aalat, J. Am. Chem. 3oc. 72, 3275 (1950). 4 G.L.O’Goiinor and H.R. Nace, Ibid. 75, 2118 (1953) j 77, 1578 (1955). 5 3ukh Dev, J . Indian Ghem. 3oc. 3 S i 769 (1 9 5 6 ). 6 L.J. Bellamy, The Infrared Spectra of Complex Molecules, p.o4, John Wiley and dons Inc. Jew York (1960). 7 H.W.Thompson, J . Chem. 3oc. 328 (1943). 8 V, W illiam s, flev. S c i. Instruments 1 9 , 135 (1 9 4 8 ), 9 A.S. Gupta and J.o, Aggarwal, J. Indian Chem. ooc. 33« 804 (1956). 10 E.W , 3panagel and W .H , Carothers, J . Am. Chem. Soc. 5 8 ^ 654 (1936). 11 K,3. I'larld.ey, Fatty Acids, Part I, p.65-82, Interscience Publishers Inc. iJew York (I960). 12 A.W. xialston. Fatty Acids and their Derivatives, p. 171-187, Joiin Wiley and oons, x^ew York (1948), 13 P. Chuit and J. Hausser, Helv. Chim. Acta 12, 463 (1929), 14 W.H. Lycan and H. Adams, J. Am. Ghem, 3oc. 51, 625 (1929) 15 D.G.iM. Diaper and D.L. Mitchell, Gan. J. of Chem. 38. 1976 (1960), 16 F.L. Benton and A.A. Kiess, J. Org. Chem. 25, 470 (1960). 17 G.E. i^'-adkovskaya, 3.A. Voitkevich, Ye.K.imol*yttninova, and V.N, Bellov, ^ur. obschei. IChim. 27, 2146 (1957); C .A . 58 . 6192" (1 9 5 8 ). 1 2 8 18 V.^l* Bellov, :^ur. obschei Khlm. 28« 2268(1958); G.A. 5^ 208SS C1959). 19 V.il. Bellov, Ye K. Smol'yanlnova, Ye. A. Ogorodaikova, V.M. Hodioaov, x^.P. 3oloveva, u.E. avadkovskaya and i'f.ii, ohevyakova, Trudy Vsesavuz Nauch-Issledovatel Inst. Sintet-i~Matural i)U3histykh Veshchestv No.4 . ^958); G^A. 5 3 f 15969^ (1959). 20 Joyce, W.n-. Hanford and J. Harmon, J. Am.Chem. 3oc. 70, 2529 (1948). 21 A.N. Nesmeyanov, L.-C. Zakharia, T. a . ICost and ii.rCh. Freidllna, Izvest. Akad. Nauk. 3.S.3.H. Qldel iChlm. ilauk, 21i (1960); C.A. 54, 20864^ (1960). 22 R. iih. Freidlina and 3h.A. Karapetyaa, Teloraerlzation and Hew synthetic Materials, Pergamon Press, London (1961), 48 , 52. 23 3 .C . liupta, V.l'J. Sharma and J . 3 . Aggarwal, J . scl. Industr. Res. India lOB, 76 (1951), 24 H.H, iMathur and 3.C, Bhattacharyya, J. Che u Joe. 3505 (1963). 25 E. Schwenk, i). Papa, W. Whitraan axid H.F. uiasberg, J . )rK. Chem. ^ 175 (1 9 4 4 ). 26 V.V. Jhekne, 3.B. Uhatge, U.G. Jayak, K.K.Chakravarty and 3.C. Bhattacharyya, J. Chem. 3oc. 2348 (1962). 27 \f.L. Hansley, Ind. Eng. Chem. 39, 56 (1947). 28 D. owern, G.N. Bilien, T.vJ. Findley and J.T.3canlan, J. /J3i. Cherfl. 3oG. 67. 1786 (1945); C. Doree and A.C. Pepper, J. Ghein. 3oc. 477 (1942). 29 J. Ross, A.I. Gebhart and J.F. Gerecht, J. Aia.Gheii.3oc. 67, 1275 (19&5); G.V.T. Campbell, A, Dick, J. Ferguson and J.J. London, J. Chem. 3oc. 749 (1941); J. Svrern, Chem. .^ev. 4 5 « 38 (1 9 4 9 ). 30 R. Ashton and J.C.Smith, J. Chem. 3oc. 435 (1934); R .G . Jones, J . Am. Chem. 3oc. 6 9 , 2350 (1 9 4 7 ). 31 A. Baeyer and V.Villiger, to. 3635 (1899). 32 A. Baeyer and V.Villiger, Ber. 33. 858 (1900). 120 33 R, Hobinsoa and L.H. imith, J. Chem. Joe. 371 (1937). 34 W.W, Westerfield, J. Biol. Ghem.143, 177 (1942). 35 S.L. Friessj J. Am. Chem. Joe. 71, 2571 (1949). 36 H .W . Heine and H. Jones, J . Am. Chem. Joe. 73, 1 3 6 1 (1 9 5 1 ). 37 3 .L . Friess and P .E . i.-'Yankenberg, J . M, Chem. 3oc. 7 4 , 2679 (1 9 5 2 ). 38 P.i. Starcher and B. phillips, J. Am. Chem. Soc. 80, 4079 (1958). 39 L. Kuzica and M. otoll, Helv. Ghim. Acta 11, 1159(1928). 40 Organic Heaetions, Vol.IX, p.78, John Wiley and ions Inc. i:^ew York (1957). 41 M. 3toll and A. Rouve, Helv. Ghim. Acta. 17, 1283, 1289 (1934); 18, 1087 (1935). 42 ToyaiHa and Hirai, Res. Rept. Ja^oya lad. Jci. Res.Inst. 5 , 36 U 9 & 1 ) , 43 M. Stoll and P. 3olle, Helv. Ghim. Acta, 31, 98(1948). 44 M. Stoll, ibid. 1393 (1947). 45 H. Hunsdiecker and H.E. i^rlbach, Ber. 80, 129 (1947). 46 C.F.H. Allen and J.A. van Allan, J. 0r,c^. Chem. 14, 754 (1949). 47 L.L. Carabalona, Brit. Pat. 655, 428 (1951), 48 M .g . j . Beets ana H.V. Essen, Ger. Pat. 1,025,861 (1958); U.S. Pat. 2,936,310 (I960;; I'J.V'. Polak and Schwarz's Essenfabrieken, Brit. Pat. 793,555 (1958). 49 A.N. I’Jesmeyaaov, R. Kh. Freidliaa, V.J. Belov, 3h. A. Karapetyan. Ye. K. Smol'yaainova, Ye. A.Ogoradnikova, Ye.I. Vasil'yeva, L. I. Zakharia and Shevyakova, Patent No.113687, 12/IV (1957). 50 A.C.Cope and E.G. Herrick, J. ^1m. Chem. 3oc. 72 , 983 (1950); N.J. Leonard and R.G. Sentz, J. .\m.Ghem. 3oc. 74, 1704 (1952). 51 V,ii. Ojhai P.G. iharma and J.d. Aggarwal» J. sci. industr. Res. India< 15B« 551 (1956). 52 L. Crombie and J.ij. Tayler, J. Che u Joe. 2816 (1954), 52 L. Hartman, J. Am. Oil Cheai. ooc. 129 (1956). 54 A.J, Gupta and J.3. Aggarwal, J. scl. Industr. Hes.India 13B. 277 (1954). 55 E.P. Kohler, M. Tishler, H. Potter and H.T. Thompson, J . Affl. Che.Ti. ooe. 6 1 , 1057 (19S9) . 56 W.W. Hartman and M.ii.Brethen, Q-g. d.yn. GoIj.. Vol. II, 278 (194S); W.W. Jartman and R. Phillips, ibid. 464 (1943). 57 G. Braun, 3yn,.. Coll. '/ol.I, p.431 (1947). 58 K.J. Jones, P. Humphries, F. Herling and K. Jobriner, J . Am, Ghem. Soc. ;M, 2820 (1952). 59 H.H. Zeiss and M.Tsutsui, ibid. 75, 897 (1953). 60 D. Chapman, J. Am. Oil Gheaists* 3oc. 73 (1960), and references cited therein. CHAPTER III SYSTEMATIC CHAIN - SHORTENING OF VJO-OLEFINIC FATTY ACIDS 1:31 oYiTEMATIC CHAIH-SHOiiTMIi^G OF w-oLEb“iiac f a t t i a c i d s The previous Chapter describes the development of a general method for the preparation of w-olefinlc fatty acids froa the corresponding w-hydroxy acids by the pyrolysis of their lactones. As indicatea earlier, this woric was uadertalcen to explore the utilisation of 18-hydroxy stearic acid, readily accessible from .vamlolenic acid (I). Li the present Chapter we report on the systematic chain- shortening of 17-octadecenoic acid (II) by one, two or three carbons at a stretch, Tiiis work has lead to a simple preparation of 15-hydroxy pentaaecaaoic acid, a necessary 1 -19 intermediate for the preparation of exaltolide (III) , 20-33 a valuable perfumery chemical (CH^ ) gCHs GH. CH=CH. Cfl=CH (GH^ ) ^GOOH CH^=CH(CH^)^gCOOH II G= 0 CH. 0 III 1 2 2 Obviously the chain-shortening methods described in tais Chapter can be applieu. to any other cu-olefiaic fatty acid, and by the application of these methods in combination with the work described in the previous Chapter, it should be possible, in principle, to convert 17~octadecenoic acid (XI) to lower ui-olefinic fatty acids including the chain- length. CHAM-3xi0aiMXi-ju BY ONfc GArtflON Jhaii-shortening of an u)-olefinic fatty acid by one carbon atom is evidently a straightforvm-d procedure. Of the various p o s s ib ilitie s available the method of sodium- Ii4-27 borohydride reduction of an ozoaide was selected as the resulting product would be an a>-hydroxy acid (ester), which can be lactonised and pyrolysed to yield the next lower u)-olefinic fatty acid. GH^=CH(CH,^)^GOOii 0 OH,, CH (CH..) OOJH I ^ I ^ XI 0- 0 iiOGH..(GH.,)„COOH Two steps CH^=CH(CH2)^^^C00H r s ‘3 Ozonolysis of 17-octadecenoic acid (II) was best carried out in methanolic solution and the resulting solution containing the ozoniae was straightaway treated with i'iaBH^ and workea up to itirnish 17-hydroxy heptadecanoic acid in an overall yield of 25%, Its IH spectrum is ihown in F i g .l . GHAXW^iiiORTMING BI TWO GAtiBONd The scheme successfully developed for chain-shortening by two carbons is shown in F i g ,2 . CH^=CH(GH^)_L5G00H (II) GH^.iii,, ether GH^=CH(CH2)3_5G00CH2 (IV) NB3, GCl. CH^=CHGx£Br(CH^)^^G0XH2 (V) Li^COg, aq.dioxan CH^=CHCH0H(CH2 )j_4G00GH2 (V ia) + iiOCH^GH=CH(GH^;^^GOOCHg (VIb) KMnO^, acetone H 0 0 C ( C H ^ ) jL4G00GH j^ ( Y l i ) 1 . KOH, lit OH 2 . HOOC(Ca^)3_4COOH (VIII) Fig.2 135 Methyl-17-octaclecenoate (IV) was treated with i'ifBS and the resultiag allylic bromide (V) without further puri fication was hydrolysed in aqueous dioxan in presence of eg Li^GOs*'' . The crude product resulting from the above reaction was chromatographed to furnish a mixture (TLC) of alcohols (Fig.3), formulated as (Via and VIb). The alcohol mixture, without further separation, was smoothly oxidised with KMnO^ to yield the half-ester (VII). The final product, which could be obtained in an overall yield of from 17-octadecenoic acid (II), was identified by its hydrolysis to l,lo-hexadecanedioic acid (synonym thapsic acid) (VIII), and comparison (mixed m.p.; IR) with an authentic sample of the acid and their esters (Fig.4). GHAIi^-jriQHTEijMG BY THREi^ CAHBOHS The sequence adopted for this purpose is outlixied in F i g .5, CH2=CH(CH^)^gG00CH3 (IV) AB3, CCI \/ 4 GH^=GHGiI3r(CH2)^^C00CH2 (V) AgNO.,, JM30 OH^=GiiCH=GH (GH^) 1. O3 2 . NaBH^ *Thin-layer Chromatography. r s b HXH2(GH^)^2COOCH2 (X) J£DH, KtOH H0GH2(CH^)^3G00H (XI) 2 steps CH^=CH(GH^)3_2G00H (XII) F i g .5 This reaction sequence is an adaptation of modified CtQ 4Q Barbier-V^ieland de^jradation first introduced by Wettstein'" * The debroraination step is normally carried out by heating 41 42 with quinoline or a pyridine base . when this debromi- nation sequence was used on the allylic bromide (V) only poor yields of the diene (IX) resulted. This aifficulty was successfully overcome by the use of Agi'JO^ and dimethyl- sulphoxide, a reagent recently developed in our laboratory. The resulting diene (IX) 222.5 mw, t: = 9300) was ozonised and the resulting ozoniae reduced with essentially as described earlier, to y ield methyl-15-hydroxy pentadecaaoate (X) whiA was identified by its hydrolysis to the 15-hyoroxy pentadecanoic acid (XI) obtained in an * Worlc by G, Mehta, 3.A. Patwarohan and K.C.irivastava. 137 overall yield of 70^i, and its comparison (mixed m.p.j IR) with an authentic sample of the acid (Fig,6), 1 3 if) iij I- < o Q LjJ 'Z. < 0 llJ Q < X LJ X 1 to X h- LlI U_ o < OL I— u LJ CL o Li. I . i 0 CO Q U < U O z < o LU Q < y~ z LU CL X 0 q: Q > X 1 to l l o CD < (T h- O LU Q- CO q: CD O Li_ il l h X P KKlMEx^TAL For geaeral remarks see page 75 . IR spectra were recoraed on Perkin-Elaier Infracord model 137E, Spectrometer, equipped with I'faCl optics, either as smear (liq u id s) or la liujol or as KBr pellets (solids), llaxima are reported in cm CJV j-ata were obtained on Perkin-Elmer, model 350, arid Beckman, uK-2 iiatio Recording, ipectrophotometer. 1 .1 8 -QCTAijia.OAgQL IDE The lactone (1,18-octadecanolide) required for its pyrolysis to 17-octadecenoic acid was more conveniently prepared by the application of Garothers'depolymerisa- tion method. 1 8 -hydroxy stearic acid (50 g) was heated in a distillation flask (100 ml cap.) fitted with air con denser and drying tube in an o il bath at 5:200-210°(bath) f for 2 hrs; at 2 2 0 -230 ° (bath) for 1 hi* and finally at 230-240° (bath)/l mm for 1 hr. To the product, I'igCl.^ (1 g) was added and depoly/nerisation carried out at 280°/0.01 mm, to give crude 1,18-octadecanolide (37.2 g; 80^5) which soli d ifie d at/toom temperature. Light browxiish coloured residue * was discarded . The cruae lactone taken ixi ether (300 ml) * Atternpts to recover 18-hydroi^y stearic acid from the residue did not succeed as a considerable quantity remained insoluble even after boiling; in aqueous alkali or alcoholic potassium hydroxiae solution for a nuiiber of hours, i'fegli- gible amount . hich got saponified was lot workea up. extractea with aqueous sodium carbonate solution (SJfaj 3 X 50 ml), washed I'ree from alkali, and dried. Ax'ter re:noviag the solvent completely, the product was dissolved in n-hexane (300 ml), chilled and filtered to give white precipitate (0.62 g) ra.p. 110-112^ (di lactone). Filtrate was next conceatratea to 150 ml; no precipitate separated on chilling, indicating the absence of ailactoae. After recovering the solvent, cruae mono-lactone was fractionally distilled to afford 1,18-octadecanolide (£4.1 g; 7 2 ,4 % ) y colourless liquid, b.p. 147-148*^/0.8-0.9 mm. m.p. 36*^. 1.4659; IR spectrum: ^0=0 1740 cm”^. (Found: G, 76.4; H, 12.20; ^ 1 3 ^ 34^2 C, 76.52; H, 12.13^e). 17-Octadecenoic acid (II; Pyrolysis of 1^18-octadecanolide The lactone (1,18-octadecanolide) was pyrolysed as described in Chapter II. 5 g were passed through a bed maintained at 525® at reduced pressure (150 mm) during 5 hrs. Resultant pyrolysate (4.5 g; 90^) on wording up Alicali extractioxi has to be carried out carefully without much shalcing in the in it ia l stages, otherwise a thick emulsion results, and large volume of solvent becomes necessary for working up the product. Starting with dilute alkali solution and gradually increasing the concentration was found convenient. 1 1 u in the usual fashion to I'urnish neutral fraction (1,2 g ; IR spectrum:^C=0 1738 and very similar to that of starting lactone) and a solid acid (3.1 g; 79^ based on the unre covered la cto n e), m .p. 52-54*^; mixed m .p, with authentic sample of 17-octadecenoic acid, 52.5-54.5^. IE spectrumj COOH 1700} -CH=CH^ 1650, 916, 936 cm"^. In a second experiment, when 10 g of the lactone were passed through the reactor in 10 hrs, the pyrolysate (8,2 g; 82^) on processing gave neutrul fraction (0,81 g)"*^ and uasaturated acid (6.3 g; 70^ based on the unrecovered lactone) m.p. 51.5-53.5°. The combined crude acid (9 g) on crystallisation from acetonitrile afforded shini.ig crystalliue 17-octadecenoic acid (6,2 g ), m.p. 55-55.5°; mixed m.p, with an authentic Sample of the acid 55-55.5°. Intense yellow colour with THM, Mother liquors were concentrated and crystallized to obtain a second crop of the acid (1.5 g) m.p, 55°. Methyl 17-octadecenoate (IV) 17-Octadecenoic acid II (3 g) was esterified by reacting with diazomethane in ether, processed and frac tionally distilled to give colourless methyl 17-octadecenoate Low yield of neutral fraction might be due to carboni sation and decomposition on the pyrolysis bea in the reactor in view of long duration. 144 (3 g; 95^), b.p. 149-150°/4 ram. CHAlN-iiHORTKi^ING Eg 0H£ C M B Qi^ 17-iiyaroxy heptadecaaolc acid from 17-octacieceaoic acid Qzonolyslst 17-Octadecenoic acid {2 g) dissolved ia absolute methyl alcohol (10 ml) was treated with ozonized oxygen at 0° till ozone passed freely (tested with acidi fied aqueous potassium iodide solution), reduction of the ozoaide; Methanolic solution of the ozoaide was then added aropwise to an ice-cold solution of sodium hydroxide (0.5 g) and sodiumborohydride (0.6 g) in 50% aqueous ethyl alcohol (10 fill), kept stirred magne tically. A gentle evolution of hydrogen resulted. The reaction mixture was slowly brought to room temperature and stirring was continued overnight. Solvent was removed under reduced pressure at room temperature and the residue after diluting with water (15 ml) v/as then added dropwise to an excess of ice-cold dilute hydrochloric acid (50 ml; under inert atmosphere with stirring. Precipitated acid was filtered, washed free from mineral acid with ice-cold water and dried under reduced pressure to furnish crude hydroxy acid (1.82 g; , m.p. 8 1 Crystallisation (twice) from benzene afforded pure white 17-hydroxy- heptadecanoic acid (1.7 g; 90^) m.p. 87.5-88'^ (Lit. m.p. 87.5-88^)^*^*^. Combined mother liquors on concentration and crystallisation furnished second crop of the hydroxy 145 acid (0.095 g; dfi,), m.p, 87-88°. IH spectrum; OH 3226j COOH 2604, 16^8 cra“^. (Found: G, 71.1} H, 11.84; requires: C, 71.28; H, 11.J6^). CHAIii-SilORTmNG 3Y I>;J CAHBOiiJ 1 .lo^hexaiecanedlolG acid (Thapslc acidj (yill) from 17~octaiecenolc acid /illylic bromixiatlon of methyl 17-octadecenoate and hyorolysis; Methyl 17-octadeceaoate (1 g) freshly crystallised O Co.66 g; 1:1.1 molar ratio) GCl^ (40 ml), and benz^ylperoxide (ixi catalytic amount) were refluxed over waterbath till succinimide floated on the surface (~£0 minutes) (guard tube), iolid succinimide was filtered off and the filtrate was washed with 5^ sodium carbonate solution (25 ml x 3), brine and dried. The solvent was then flashed off, when viscous liquid bromide (V) (1.28 g) was obtained. IR spectrum: -GHsCH^ 917, 969; C-Br 699 cm"^. The crude bromo compound ( 1 .2 g) was stirred with dioxan (3S ml), water (11 ml) and Li^GO^ (i>00 mg) over a waterbath for 5 hrs. The product was filtered and the filtrate concentrated (suctio-Vwarra waterbath) to 15 lal, diluted with water (20 ml) extracted with ether (25 x 3) and washed with brine and dried. The solvent was flashed off when a viscous liquid (1.1 g) vras obtaiaed. lil spectrum: OH 3390 cm’^. Preliminary test (I’LC) showed the product to be a mixture and hence was fractionated chromatographically 11 r> over an alu.:iiaa column. CiaOMATQax^AM Alumi-ia graae I I I ; 30 g Height of the bed : 19 cm x 1,6 cm Wt, of the product: 1 g. No. Eluent Fractions Wt. Final Appearance ml (g) Frn. 1 Pet. ether (40-60^) 9 X 20 0 .2 2 6 1 I Liquid 2 Lther 1 4 X 20 0 .7 6 0 1 II Thick v i s cous liquid. 3 Ether + i4eOH (5^) 8 X 20 0 .0 0 6 8 III demisolid. After prelimlaary Investigations (-TLG; 3ilicagel-Agi^0^ 15^;^; 44 solvent syston: benaene: ethyl acetate, 9:1) the fractions were combined accordingly to form three main fractions. l*'raction I: IR spectrum: bands for hydroxyl group were absent. Fraction II: Yellow colouration by TilM. In TLG (conditions same as described earlier) the compound gave two spots partially overlapping. IR spectrum: OH 3448; COOCHg 1739j C=C 970 cm”^. Formulated as mixture of Via + VIb (Fig,3). KMnQ^ oxidation of iraction II to I«16-hexadecanedloic acid(V'III). The above mixture of hyaroxy esters (0.48 g) was dissolved in aistilled dry acetone (10 ml) and to it, finely powdered KMnO^ was added in small lots, with stirring till 1.-17 pink colour persisted in the reaction mixture. Stirring was contiaued for 4 hrs. lixcess permanganate was de composed with addition of aqueous solution of sodium bisulphite (5 inl), followed by dropwise addition of dilute sulphuric acid till the black precipitate dissolved and the mixture was acidic to Congo red. The liberated half ester was taken ixi ethyl acetate, washed free from acid and dried, flashing off the solvent fur.iished crude h a lf ester (0.4 solution of potassium hydroxide (5 ml} 10%) for S hrs. Joap solution on acidification, working up and orying in vacuo gave a solid acid (0.4 gj 91^ on the basis of hyoroxy esters and 66% on the starting methyl-17-octadecenoate) m.p. 118-121°. Crystallisation I’rom acetone afforded white crystals of 1,16-hexadecanedioic acid (VIII; (0.39 g) m.p. 123-124°, mixeu m.p. with an autheiitic sample (m.p. 124.5-125°; Lit./125, 126.1°;^“^ 123.5-124.5°. IR spectrum: COOH 2710, 1708 cm'^j superimposable on the spectrum obtained for the authentic sample (Found; C, 66.78; H, 10.42; re quires: C, 67.03; H, 10.56^'). The dicarboxylic acid (62 mg; was esterified by re acting with CH.^A^2 in ether, worked up and aistilled (bulb) b.p. 130-165°/0.2 Eim m.p. 51-51.5°, mixed m.p. with authentic ester (m.p, 51.5; Lit. 51,6°) 51.5°. IH spectrum: COOCilg, 1755 cm“^. (Fig.4). 1.48 CHAIi^-SHOxiTMIi^G BY THK££ CAHBQ.J3 ;t,,5TjijL4ga??y J3et?.taA§sa-^9iiz, ..,l^jiLji.7.T9ctaa^(??n9J.s,,,,asU Allyllc bromlxiatloa of methyl»17~octadecenoate /J l y l i c broffiiaation was carried out by reacting methyl“17-0ctadeceaoate (0.5 g), freshly crystallised NBo (0 .3 3 g ) , GCl^ (HO ml) and be-izoyl peroxide (catalytic amount), according to the method described previously and on working up the reaction mixture furnished bromo compound (¥) ( 0 .6 4 g ) . x^ehydrobromlnation of bromo ester iV) To a solution of silvernitrate (0.34 g) in dimethyl- sulphoxide (1 ml) (dissolveu by warmiiig), the aoove bromo ester aissolved in JM30 (2 ial) was aaded dropwise at 15°, when light yellow precipitate separated i.nmedlately. The reactants were mixed thoroughly by shaking and kept in aark at 15° for 1 hr with occasional shaking. The precipitate was separated by filtration and washed with benzene (5 ml). Filtrate was poured into cold water (25 ml), followed by extraction with chloroform (5 ml x 3). The solvent extract washed with water, brine and dried. Removal of the solvent in cold at reduced pressure furxiished the liquid diene ester (IX) (0.5 g). UV spectrum; 222.5 m/U f = 9300. 15~hydroxy pentadecaxiolc acid (XI) The above diene egter (0.48 g), dissolved in absolute 1\U methanol (5 ml), was ozo;iised ia the usual fashioa at 0°. The ozonide was reduced by adalng Its methanolic solutioii (oropwise) to a solution of sodium hydroxide (0.4 g), NaBd^ (0.45 g) ia 50^ aqueous ethanol (5 ml) at 0*^. After stirring the reaction mixture overnight at room temperature, the product was processed according to the procedure des cribed previously, and the resultant hydroxy ester on hydrolysis in the usual way afforded solid acid (0.42 g) m,p. 77-81°. Repeated crystallisation from acetone-aceto- nitrile lurnished white crystalline 15-hydroxypexitadecanoic acid (X I) (O .S g; 70^0 m .p. 83-34*^; mixed m .p. with authentic sample (m.p. 84.5-85^; Lit. 84.5-85®) 84-36®. IH spectrum; (in KBr): OH 3400j GOOH 2676, 1726 cm"^, superimposable on the spectrum obtained for the authentic sample (Fig.6). (Found: C, 69.3; H, 11.9} requires: C, 69.7; H, 1 1 .7 ^ ) . 1 50 i Conversion of 17-octadecenoic acid into, 17-hydroxy• heptadecanoic, 1,16-hexadecaaedioic acid and 15-hydroxy pentadecanoic acid by methods enabling the cleavage of one carbon, two carbons axid three carbons at a time, res pectively has been described. The methods are obviously general in character. 151 aEFEdR^CES 1 L. Buzicka aad M. Jtoll, Helv. Chim. Acta 11, 1159 (1928); M, i^aef and Co., Jwlss Pat. 128,466 (1927); Brit. Pat. 294,60L (1927); Fr. Pat. 657,371 (1928). 2 M, Stoll and A. Kouve, Helv. Chlia. Acta 17, 128S (1934); 18, 1087 (1935). 3 E.W, 3panagel and W.H. Garothers, J. Am. Cheia. 3oc. 5 8 f 664 (1936). 4 M. Stoll, Helv. Ghlm. Acta 30. 1393 (1947). 5 H. Hunsdiecker and H. itlbach, Ber. 80, 129 (1947). 6 M. Stoll and P. Bolle, Helv. Ohlm. Acta 31. 98 (1948). 7 G.F.H. Allen and J.A. Van iUlan, J. Jrg. Ghem. 14, 756 (1343) 8 L.L.Carabalona, Brit. Pat, 655,428 (1951). 9 M .g .J.B eets and H.V.Essen, ^er. Pat. 1,025,861 (1958); U.S.Pat. 2,936,310 (1960); N.V. Polak and Schwarz's Essencefabrieken, ^ it . Pat. 793,555 (1958). 10 Fi.U. Lemieux, Perfum. Essent. Oil, necord 44, 136 (1953). 11 A.N. Nesiaeyanov, ll.Kh.Preidlina, B.N. Belov, Sh.A. ICarapetyaxi, E.K. Smol’yanlnova, E.A. Ogorodnikova, E.I.Vasil* eva, L.I.Zakharin and W.^j.siievyakova, U.S.3.a. Pat. 113,687 (1957-58); G.A. 53, 6090b (1959). 12 G.E. Svadkovskaya, S.A.Voitkeyich, E.K.Smol'yaninova and /.iiJ.Belov, ihur. Obschei ivhim 27. 2146 (1957); G.A. 52, 6192c (1958). 13 Q.E.Svadkovskaya, E.K. Smol'y^ininova and V.N.Belov, ibid. 28, 2268 (1958); G.A. 53y 2083g (1959). 14 Belov, E.K. Smol'yaninova, E.A. Ogorodnikova, V.M. Rodionov, N.P. Solov’ eva, G.E. Svadkovskaya and N.ii. Shevyakova, Trudy Vsesoyuz i'iauch. - Issxedovatel Inst. Sintet.l.Natural, jushistylch Veshchestv, i‘jo.4, 3 (1958); G.A. 15969a (1959); C ^ .^ , 3189b (1960). 15 A.N. Nesmeyanov, L.I.Zakharin, T.A. Kost and ii.Kh. Freidlina, Izvest Akad. i^tauk S.S.S.R .. Oldel Khim. ^^auk 211 (I960) ;~'(I7I7~5Cr~2Q854~I (1960). 15*^ 16 G. Egliaton, a.J. Harailtoa, R. Hoages and. H.A. Haptiael, Chem. and lad» 955 (1959). 17 J.Carnauff, G, Eglintoa, W. McCrae and xi.A, Raphael Ibid. 559 (1960). 18 L.D. Berg el son, J.G. Molotkovsky and M.M.Siierayakin, ibid. 558 (1960). 19 V.J. Belov and 3.G. Polyakova, U.^.3.H. Pat. 135,483 (1961); C^. 18598 i (1961). 20 G. Ciamiclan and P. oilber, 29, 1811 (1896). 21 M. Kerschbaufa, ibid. 60B, 902 (1927). 22 M. otoll, Mfg. Perfum. 1, 107 (1937). 23 M. 3};oll and W. Scherrer, Helv. Giilsi. Acta 19. 735(1936) j A. Muller and A.F.3chutz, Ber. 71. 692 (l938); G.M, Bennett and II. Gudgeon, J. Ghea. Soc. 1891 (1938), 24 J.P, Fourneau, Ind. Perfum. 3, 109 (1948)j C.A. 42. 6991 e (1948). 25 E. Schinidt, Chem. Tech (Berlin), 5, 441 (1953); G.A. 6977 c (1954). 26 P.Z. Bedoukian “Perfumery iynthetics andlsolates" p.325, J. van xiostrand Go, Inc. Hew York (1950). 27 H.G.J. Beets, Syraposium on Organoleptic Quality and ^"lolecular Structure, oociety of Chemical Industry, Geneva, 2-3 I4ay, 1957. 28 M.H. iClouwen, Perfum. fcssent. Oil aecord. Jubilee Uo.XXVIl (1959). 29 R.Kh. Freidlina a^id 3h. A. Karapetyan, Telomerisation and New Synthetic Materials, p.48, 52, Pergamon Press, London (1961). 30 B.B. Ghatge, U.G.Nayak, K.K.Chakravarti and S.G. Bhattacharyya, Cheia. and Ind. 1334 (1960); Indian Pat. 59419 (1957). 31 V.V.ahekne, B.B.Ghatge and S.G.Bhattacharyya, Indian Pat. 73702 (1960). 153 32 V.V.Dhekae, B.B.Ghatge, U.u. Nayak, K.K.Ghaicravarti and 3 .C . Bhattacharya, J . Ghem. aoc. 2348 (1 9 6 2 ). 33 U.H. Mathur and S.G. Bhattacharyya, J» Ghem. 3oc« 3505(1963). 34 areenwood, J. Qr^. Chen. 20, 803 (1955). 35 J.A. Sousa and A.L. Bluhm, J. Ori^. Ghem. 25, 108 (1960). 36 F.L.Beaton and A.A. fCiess, J. Qrg. Ghem. 470 (1360). 37 J.G.M. Diaper aad D.L. Mitchell, Can. J. of Ghem. 38, 1976 (1960). 38 J.j.Roberts, E.H. Trumbull Jr., W. Bennett and R.Armstrong, J. Am. Chen. 3oc. 72. 3116 (1950). 39 von J. Heer and A. Weltstei-i, Helv. Ghlm. Acta 36, 891 (1953). 40 P .M .a . Bavin, Gan. J . of Ghem. 3 8 , 1103 (1 9 6 0 ). 41 A.G.Gope and L.L. Estes Jr., J. Am. Ghem. 5oc. 72, 1128(1950). 42 W.ii. Nes, R.B. Kostic and E. Mosettig, J. iUn. Ghem. 3oc. 78, 436 (1956). 43 P.Chuit aiid J. Hausser, Helv. Chim. Aeta 12, 463 (1929;. 44 A.3.Gupta and Sukh Jev, J. Chroaiatog. 12, 189 (1963). 45 A.W. Ralston, Fatty Acids and their derivatives, p.327, John Wiley and Sons, Inc. New York (1948). 46 K .3 . iMarkley, Fatty Acids, Part I , p . 96 , 321, Inter- science Publishers Inc. I'iew iTork u 960). 47 M. Carmichael, J. Ghea. 3oc. 121, 2545 (1922). 48 P. Ghuit, Helv. Ghim. Acta 9. 264 (1926).