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[CONTRIBUTION FROM TH E DEPARTMENTF CHEMISTRY, COLUMBIA UNIVERSITY]Cashew Nut Shell Liquid. E. The Chromatographic Separation and StructuralInvestigation of the Olefinic Components of Methylcardanoll

BYWILLIAM . SYMES~ND CHARLES . DAWSONRECEIVED PRIL8, 1953

Cardanol, the monophenolic component of commercial cashew nut shell liquid, has an olefinic unsaturation of about twodouble bonds and possesses the carbon skeleton of 3-pentadecylphenol. I t has been found tha t the methyl ether can beseparated by chromatography on alumina into four pure components which vary only in their degree of unsaturation in theside chain. The four th component hasthe saturated side chain. The structuresof the three olefins have been established by methods of oxidative degradation.A monoolefin, diolefin and triolefin account for about 95% of the methylcardanol.There is no evidence of a component containing more than three double bonds.

It has been known for several years tha t cardanol,the main component of commercial cashew nutshell liquid, is a mixture of olefins, each having thecarbon skeleton of 3-pentadecylphenol. It hasalso been demonstrated that anacardic acid, thealkenyl salicylic acid derivative from which carda-no1 is derived by decarboxylation, is also hetero-olefinic in comp o~ it io n. ~ ecause of i ts commercialuses5 and it s structural similarity to the toxicprinciple of the poison ivy plant,6 the olefiniccomposition of cardanol has been a matter of con-siderable interest.The earlier investigations in this Laboratory oncardanol and anacardic acid were concerned withtreating the methyl ethers of these alkenyl phenols,with the hydroxylating agents silver iodobenzo-ate and performic acid. Mixtures of crystallineglycols were obtained which could be partially sep-arated by fractional crystallization or moleculardistillation. In each case a pure monoglycol wasreadily obtained, but the di- and higher glycolswere not satisfactorily separated. Degradation ofthe monoglycol from methylcardanol established thestructure of the monoolefinic component as 3-(pen-tadecenyl-8)-phenol. In a similar manner the posi-tion of the double bond in the monoolefinic compo-nent of anacardic acid was also found to be in the s-position.4In view of the difficulties encountered in at tempt-ing to separate and characterize the glycol deriva-tives of the higher olefinic components of methyl-cardanol, it seemed advisable to investigate thepossibility of separating the various olefinic compo-nents directly, i.e., without prior chemical altera-tion of the olefinic bonds. Attention was turned,therefore, to an investigation of chromatographica d s ~ r p t i o n ~ , ~s a means of obtaining the variousolefinic components of methylcardanol in pureform.Preliminary experiments with activated alumina

(1: For the eighth article in this series, see D. Wasserman a n dC. li. Damson, Tm s JOURFAL,2, 4994 (19.50).( 2 ) This paper is based on a portion of the thesis submitted by Wil-liam F. Symes in 1951 to Columbia University in partial fulfillment of

the requirements for the P h.D . degree in chemistry.(3 ) RI. Sletzinger an d C. R. Dawson, THIS OURNAL, 68, 45 (19413);J . O?g. Che m. , 1 4 , 670 (1949).(4 ) P. T . I z z o an d C. R. Dawson, i b i d . , 14 , 1039 (1949); 1 5 , 707:194!4).f 5 l M. 1.Harvey and S. Caplan, I n d . Eng. Ch o n . , 32, 1306 (1940) .(6 1 H. Keil, D. Wasserman and C. R. Dawsou, Sc i r i iLe , 1 4 , 279

(1945); I n d . M e d . , 1 4 : 1 1 , 825 (1946).(7 ) H. H. Strai n, Chromatographic Adsorption Analysis, Inter-science Publishers, Inc., New York, N. Y., 1942, p. 15.( 8 ) H. ondo, J . Pharm. Soc. (Japan) , 67, 218 (1937).

and the free phenol, cardanol, indicated that thevery strong adsorption of the phenolic hydroxylgroup tended to mask the small differences inadsorption of the various olefinic components andthereby hinder their separation. Conversion of thecardanol into it s methyl ether resulted in better de-velopment on the alumina column and a t the sametime made the material less hazardousg to handle.Furthermore, the separation of the olefinic compo-nents in their anisole form facilitated the subse-quent degradative work necessary to determine thepositions of the double bonds in the side chains.In an early experiment it was observed that therefractive indices of the fractions taken from thealumina column varied progressively from aboutn 2 5 ~.4900 to about 1.5100. The unsaturationvalues of several of these fractions, determined bycatalytic hydrogenation, showed a linear increasewith increase in refractive index. This circum-stance made it possible to estimate in advance therefractive indices of the saturated, mono-, di- andtriolefinic components of methylcardanol. Thedegree of separation achieved in a given chromato-gram became apparent by plotting the refractiveindices of the fractions against their cumulativeweights. The resulting curves showed plateauregions of constant refractive index correspondingto one or more of the olefinic components depend-ing on the olefinic composition of the start ing ma-terial and the degree of separation achieved (seeFig. 1).Fractions having refractive indices between anytwo plateaus were combined and rechromato-graphed until no further separation was indicated.The resulting fractions were then combined withthose of the appropriate plateau region and re-chromatographed until the refractive indices ofsuccessive fractions varied over a range of no morethan three or four parts in the fourth decimal place.In this way chromatographically pure mono-,di- and triolefins, having refractive indices ( n Z 6 ~ )of 1.4933, 1.5027 and 1.5110, respectively, were ob-tained. In addition to these a saturated component(XZ5D 1.4850) was isolated from the earliest fractionsof the first chromatogram. A sample of each of thepurified olefinic components was catalytically hy-drogenated and in each case absorbed the calcu-lated amount of hydrogen and gave the saturatedcomponent in pure form. No fraction with a dou-

(9 ) Cardanol is commonly contaminated with small amounts ofcardol, an alkenyl resorcinol tha t is very effective i n producing a poisonivy-like dermatitis. Methylation of such phenols makes t h em essen-tially innocuous.

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Oct. 20, 1953 SEPARATIONND STRUCTUREF OLEFINICCOMPONENTSF METHYLCARDANOL953

0.5

ble bond value exceeding 3.0 was obtained from anyof the chromatograms. It may be concluded,therefore, that no component with more thanthree double bonds is present in cardanol.

-

-

i'iiolefinr

I 2 3 4 5 6 7 8 9 / O / / / Z / S N NGmms .Fig. 1.-Chromatogram showing how the refractive in-

dices of successive fractions indicate the degree of separationof t he olefinic components of methylcardanol on alumina.

One chromatographic separation was conductedin as nearly quantitative manner as possible in or-der to estimate the composition of methylcardanol.All intermediate fractions of the first chromato-gram (see Fig. 1)were carefully rechromatographeduntil the fractions representing mixtures were re-duced to a minimum. The results of these chromat-ographic separations are given in Table I.RECOVERED OMPONENTSF 15 G. F METHYLCARDANOL

TABLE(1.84DOUBLE ONDS) TotalAmount (grams) recov- DoubleCom- Iso- Addi- ered, bondponent n 1 5 ~ lated tional'l Total % value

Saturated 1.4850 0.60 0.00 0.60 4.3 0.00Monodlefin 1.4935 5.94 .35 6.29 45.1 .45Diolefin 1.5032 2.35 .37 2.72 19.4 -38Triolefin 1.5112 4.19 .18 4.37 31 2 .93Recovery (total) 13.08 .90 13.98 100 0 1 .7SbRecovery, % 87.0 6.0 93.0b 96.7

Obtained as intermediate fractions which were not sepa-rated but the relative amounts of t he components of whichwere estimated from refractive indices. The 7% of mate-rial not recovered must have had an average double bondvalue of approximately 2.5 in order to account for the 3%loss in unsaturation (1.84 o 1.78 double bonds). It there-fore consisted mainly of triolefin, the most highly absorbedcomponent. It seems likely tha t some of t he saturatedcomponent was also not recovered. It is of in terest to notethat 1.02 g. of unrecovered material in the form of 0.17 g.of saturated and 0.85 g. of triolefin would have an unsatura-tion of 2.5 double bonds. The percentage of triolefin inthe starting material, therefore, may have been as high as34.8% (5.22/15.0).The Component Structures of MethylcardanolUltraviolet Spectra.-It is well known that con-

jugated trienes have a strong absorption band atabout 2700 k l 0 and conjugated dienes have a band(10) M. G. Mellon, "Analytical Absotption Spbctroscopy," JohdWileg and Sans, nc., New Yor t, N . Y . , 1950, D 462.

in the region of 2170 to 2400 8 . 10 , 11 Since the tri-olefinic and the saturated components of methyl-cardanol have the same molecular extinction coef-ficient in the region of 2700 A. (see Fig. 2), it maybe concluded tha t the triolefin is not a conjugatedtriene.E'O 4.0Fig. 2.-Ultraviolet absorption spect ra of the chromato-

graphically purified components of methylcardanol.It is important to note th at the intensities of ab-sorption of the di- and triolefins in the region of2170 to 2400 A. are only slightly greater than thoseof the saturated and monoolefinic components. Ifthe di- and triolefins were conjugated dienes amuch greater intensity of absorption would be ex-pected in this region.All of the olefinic components represented in Fig.2 were "chromatographically pure" as judged byconstancy of refractive index. Since it is known

th at conjugated olefins of this carbon skeletonhave higher refractive indices and are more stronglyadsorbed to alumina than non-conjugated isomers, 2the increased absorption in the region of 2170 to2400 b. cannot be attributed to contamination ofthe di- and triolefins with isomers containing con-jugated diene groups. The increased absorptionin this region may be due to very small amounts ofautoxidation products.Saturated Component.-The saturated compo-nent was proven to be identical with the catalyti-cally reduced methylcardanol(3-pentadecylanisole) .MonoS1elin.-Although the structure of themonoolefin was known as the result of earlier workon its glycol deri~ative,~he olefin itself had notpreviously been available for confirmation of thestructure. Ozonization of a sample of the chromato-graphically pure material, followed by catalyticreduction of the ozonide, gave the expected heptal-dehyde. Oxidation of the aromatic fragment withpotassium permanganate in acetone gave a goodyield of an acid melting and analyzing correctly forw- (3-methoxyphenyl) caprylic acid. The structureof the monoolefin was therefore confirmed as 3-(pentadecenyl-8') -anisole

OCH,fi[~/)-(CH~),CH=CH--(CH~)~CH,(li) R. B. Woodward, THIS OURNAL, 64, 72 (1942).(12) Observatlbns df 9. v. Stlnthankar, this Laboratory (to be pub-

lishkd).

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4954 WILLIAM . SYMES AND CHARLES , DAWSON VOl . 75Dioleib.-Ozonization of the diolefin followedby catalytic reduction of the ozonide and recoveryof the volatile aliphatic aldehyde fragment yieldedbutyraldehyde. The aromatic fragment resultingfrom the ozonolysis was oxidized and recovered as

w-(3-methoxyphenyl)-caprylic cid.Oxidation of the diolefin with potassium perman-ganate in acetone gave in addition to w-(3-methoxy-phenyl)-caprylic acid, a 58% yield of oxalic acid.Olefinic systems in which a methylene group is lo-cated between two double bonds, --CH==CH-CHS-CH=CH-, are known to give oxalic acid asan oxidation product under these conditions.It niay be concluded, therefore, tha t the structureof the diolefin is that of l-methoxy-3-(pentadeca-dienyl-8', 11)-benzene5/ (CH~)~~H=CH-CHFCH=CH-( CH2)2CH*Trio1efin.-Ozonization of the triolefin andcatalytic reduction of the ozonide resulted in theformation of formaldehyde. Oxidation of thearomatic aldehyde fraction yielded w-(a-methoxy-phenyl)-caprylic acid. When the original ozonidewas decomposed with peracetic acid,16 the w-(3-methoxypheny1)-caprylic acid was again recoveredand a small amount of malonic acid was obtained.16Oxidation of the pure triolefin with potassiumpermanganate in acetone gave a 49% yield of oxalicacid based on two moles of oxalic acid per mole oftriolefin. A good yield of the inethoxyphenylca-prylic acid was also obtained.On the basis of the above degradation products

and the fact tha t the ultraviolet spectrum indicatedthe absence of conjugation, the triolefin of methyl-cardanol may be assigned the structure of l-meth-oxy-3- (pentadecatrienyl-S', 11, 4')-benzeneOCHa

U,J-(CH~)~CH=CHCH~CH=CHCH~CH=CH~Experience indicated that the terminal olefinicbond of the triolefin coufd be selectively hydrogen-ated in part. Additional evidence for the locationof the third double bond in the 11'-position wastherefore obtained when ozonolysis of such a par-tially reduced sample of the triolefin yielded somebutyraldehyde.

E~perimental'~~*,I9Th e commercial cardanol used in this investigation, pro-vided by the Irvington Varnish and Insulator Company ofIrvington, N. J., had been obtained by a rapid vacuumdistillation of the crude shell liquid from Indian cashew nuts.I t was reported to contain 643% of th e resorcinol compo-(13) R. Haworth, J . Chem. Soc., 1458 (1929).(14) D. T. Mowry, W. R. Brode and J. B. Brown, J . Bi d . Chcm. ,(15) H. Wilms, A n n . , 567, 97 (1950).( l e ) V. Arreguine,R e c . U n i u . Aiacl. Cordoba,7-8, (1941); C. A , ,36,(17) All melting points are corrected.(18) Microanalyses were performed by Clark Microanalytical Lab-

oratories, Urbana, Ill., and Schwarzkopf Microanalytical Laboratory,Middle Village, L. I. , N. Y.(19) All activated alumina was prepared by beating aluminum hy-drovide (Mall.iackrodt) fo r four hours at 276-3OOu w i t h slow stirring.

142, 679 (19421.

4059 (1942).

nent, cardol, and possessed an unsaturation equivalent to2.0 double bonds as determined by quantitative catalytichydrogenation over 10% palladium-on-carbon using ethylacetate as solvent.Preparation of Methylcardano1.-To a 600-g. (2.0 moles)sample of cardanol contained in a 5-1. round-bottom flaskwas added 123 g. (2 .2 moles) of KOH dissolved in 500 cc. ofmethyl alcohol. After removing most of the alcohol inwucuo he reaction mixture was chilled in an ice-bath and 277g. (2.2 moles) of dimethy l sulfate was slowly added. Afterwarming on the steam-bath for one hour,zO the liquid wasdecanted , the insoluble salt washed thoroughly on a buchnerfunnel with ligroin (b.p. 60-90'), and the filtrate and de-canted liquid combined. The resulting solution (1 l.) wasshaken with an equal volume of Claisen solution (50%aqueous KOH with an equal volume of methanol) to removeunmethylated cardanol, and the ligroin layer was distilledin vacuo to remove the solvent. The residual oil was washedwith 600 ml. of methanol and then taken u p in 300 ml. ofligroin an d dried over 30 g. of calcium chloride. After de-colorizing with 15 g. of Norite and removing the solvent bydistillation in uucuo a residue of 245 g. of crude methyl car-danol was obtained as a light reddish oil.Purification by Chromatography.-The above methvl-cardanol was dissolved in 500 ml. of ligroin (b .p . 60-90")and passed through a bed of 500 g. of activated alumina con-tained in an 11.5-cm. buchner funnel. The "column" wasthen eluted with 17 1. of ligroin (approximately 5 1. perhour) collected in two fractions, followed by a 3-1. portionof benzene and finally 2.5 1. of diethyl ether. The solventwas removed from each of the four fractions b y distillationin vacuo on the steam-bath. Fraction 1 (7 1. of ligroin)gave 220 g. of colorless oil of double bond value 2.07. Frac-tion 2 (10 1. of ligroin) gave 6 g. of colorless oil of doublebond value 2.63. Fraction 3 (3 1. of benzene) gave 3 g. ofyellow oil. Frac tion 4 (2.5 1. of ether) gave 3 g. of a vis-cous red oil. The double bond values of fractions 1 and 2were determined b y catalyt ic hydrogenation a nd th e reduc-tion products were recovered by evaporating the ethyl ace-ta te solvent. A sample of the reduction product of frac-tion 1 melted a t 10-15' and was found by chromatographyon alumina to be a mixture of 3-pentadecylanisole (m.p. 28-29') with about 6-7% of 1,3-dimethoxy-5-pentadecylben-zene (m.p . 47.5-48.5') the reduction product of dimethyl-cardol.21 Th e reduced material from the hydrogenation ofa sample of fraction 2 melted a t 43-46' and on one recrystal-lization from petroleum ether melted a t 47.5-48.5'.In order to further separate the dimethylcardanol fromdimethylcardol, the 230 g. of fraction 1 was redissolved inligroin an d rechromatographed on 650 g. of alumina in a11.5-cm. buchner funnel. Four fractions mere taken byelution with ligroin, benzene and ether as before. Fraction1' (5 1. of ligroin), containing most of t he methvlcardanol,was reduced in volume by distillation to 500 ml. and usedin the next chromatogram. Fraction 2' ( 5 1. of ligroin)gave 7.2 g. of colorless oil of double bond value 2.60. Thereduction product melted at 15-20' indicating a mixture ofdimethylhydrocardanol and dimethylhydrocardol. Frac-tion 3' (2 1. of benzene) gave 8.0 g. of colorless oil of doublebond value 2.67. The reduction product melted a t 44-46',indicative of essentially pure dimethylcardol. Fraction 4'(2 1. of ether) gave 1.0 g. of oil which was not further inves-tigated.To obtain methylcardanol completely free of dimethyl-cardol the 500-ml. sample of fraction 1' was rechromato-graphed on 1200 g. of alumina in an 18.5-cm. buchner fun-nel. Six fractions were taken by elution with ligroin, ben-zene and ether. Fraction 1" (5 1. of ligroin) contained 165g. of colorless methylcardanol of double bond value 1.87.The reduction product melted a t 28-29', indicative of essen-tially pure 3-pentadecylanisole. Fraction 2" (5 1. of lig-roin) gave 12.0 g. of oil which was not further investigated .Frac tion 3" (5 1. of ligroin) gave 10.0 g. of oil of double bondvalue 2.60. The reduction product melted a t 28-29', indi-cating this fraction t o be free of dimethylcardol a nd consist-ing of the more highly unsaturated components of dimethyl-

(20) To facilit ate the subsequent removal of tbe cardol componentby chromatography it seemed advisable to only partially methylatethe commercial cardanol. The usual further treatment with dimethylsulfate wa4 therefore omitted.(21' T) \V'nsserman and C . R. Duwson. THISJOURNAL, 70 , 3675( J W R ; .

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Oct. 20, 1953 SEPARATIONND STRUCTURE F OLEFINICCOMPONENTSF METHYLCARDANOL985cardanol. Fract ion 4" (5 1. of ligroin) gave 1 .5 g. of oil notfurther investigated. Fraction 5" (2 1. of benzene) gave8.0 g. of oil of double bond value 2.80 bu t containing somedimethylcardol as revealed by t he melting point of t he re-duction product (m.p. 9-16'). Fraction 6" (2 1. of ether)contained 1.0 g. of oil not fur ther investigated.The methylcardanol of 1.87 double bonds, fraction l " ,and another sample of 1.84 double bonds prepared in a simi-lar manner, were used as the starting material for thechromatographic separation of methylcardanol into itsolefinic components. On the basis of the quan titative yieldand sharpness of melting point of their reduction product(3-pentadecylanisole) these samples of methylcardanol werejudged to be free of dimethylcardol. Fractions 2' and 3"proved subsequently to be a source of the triolefinic com-ponent of methylcardanol.Chromatographic Analysis of MethylcardanoL-A 15.0-g.sample of colorless methylcardanol of 1.84 double bonds waschromatographed on a column, 5.5 X 63 cm., of 1200 g.of alumina, 6.3 liters of ligroin under a pressure of approxi-mately 5 Ib. of nitrogen being required for developmentuntil the first non-volatile residue was detected in the ef-fluent. Th e residual solvent was forced from the columnwhich was then extruded, c ut in to 27 sections and each sec-tion extracted with 175-250 ml. of diethyl ether . Distilla-tion of t he ether gave residues, th e refractive indices andweights of which are recorded in Table I11 and plotted inFig. 1. The first fract ion was obtained on distillation of theresidual solvent forced from the column just prior to ex-truding the alumina.Fractions 17-20 of Table I1 were combined, 2.46 g., andchromatographed on a column, 4 X 28 cm., of 280 g. ofalumina, 3.5 liters of ligroin being required for development.The column was cut i nto 13 sections and extracted with di-ethyl ether as before to give a second chromatogram.

TABLE1

12345678910

0.10.0 8.09.34.38.80.70

1oo0.94

.9 7

1.4870 111.4885 121.4885 131.4888 141.4900 151.4920 161.4935 171.4935 181.4935 191.4935

0.53.50.38.81.54.7 5.62.54.6 6

1.49381.49401.4950I .49851.50201.50281,50351 50401.5060

202122232425262728

0.64.7 0.56.51.45.4 8.48.36

nI1.50801.51111.51121.51111.51121.51111.51131.5115....

Fractions 10-13 of the second chromatogram (@D 1.5108-1.5112) and fractions 21-27 of t he fist chromatogram(Table 11) gave 4.19 g. of triolefin (see Table I) .Fractions 1-7 (1.22 g.) of the second chromatogram (#D1.5025-1.5035) were combined with fractions 13-16 of thefirst chromatogram (Table 11) and chromatographed on acolumn, 5.5 X 30 cm., of 500 g. of alumina. The columnwas cut into 11 sections and extracted as before to give athird chromatogram.Fractions 4-9 (+D 1.5032-1.5036) of the third chromato-gram yielded 2.35 g. of diolefin.Fractions 1-6 of Table I1 were combined and yielded 0.60g. of pure saturated component (3-pentadecylanisole) onthree crystallizations from acetone. The filtrate from thefirst crystallization was evaporated to give an additional0.95 g. , n s D 1.4935, which was combined with fractions 7-12 of the &st chromatogram (Table 11) and fraction 1 of t hethird chromatogram (0.35 g., nuD 1.4935) to give 5.94 g. ofmonoolefin (see Table I).Chromatographic Purification of the Olefinic Components.-By a procedure similar to that described for the above&st chromatogram (see Table 11), except tha t t he elutiontechnique was employed, a sample of the methylcardanolof 1.87 double bonds and % ~ J D .5012 was separated into 26fractions.'* Selected fract ions were recombined so as to(22) The experimental detail s and chromatogram data are availablein the dissertation of W. F. Symes, a microfilm copy of which may be

obtained from the Columbia University Library.

give samples composed mainly of monoolefin, diolefin andtriolefin.The Mono6leiinicComponent.-A 6.0-g. sample of mono-olefin, made up of fractions between %*% 1.4929 and 1.4942,was subjected to a series of three more chromatograms,employing the extrusion technique and using selected frac-tions of each preceding chromatogram** to yield 2.4 g. ofpure monoolefin of f lSD 1.4933. The seven fractions mak-ing up this component on th e last chromatogram showed avaria tion of 2 par ts in th e fourth decimal place in refractiveindex. A sample adsorbed an amount of hydrogen corre-sponding to 1.0 double bonds and a quantitative yield of 3-pentadecylanisole was obtained (m.p. 28.5-29.5') withoutrecrystallization.The Diolefinic Component.-A 7.2-g. sample of diolefin,made up of fractions between n26.6~ .4957 and 1.5056, wassubjected to three more chromatograms22 to yield 3.1 g. ofpure diolefin in the form of a colorless oil, TPD.5027. Theseven fractions making up this component on the last chro-matogram varied in refractive index from 1.5023 to 1.5030.A sample taken for catalytic hydrogenation absorbed hy-drogen corresponding to a double bond value of 2.0. Thecolorless oil obtained afte r filtration of t he catalyst and re-moval of t he solvent by evaporation solidified on chillingto give crystals of m.p. 28-28.5'. On one recrxstalli-zation from methanol fine needles of m.p. 29-30 wereobtained.The Triolefinic Component .-The last nine fractions ofthe first chromatogram, varying in ~ ~ 2 6 . 6 ~rom 1.5075 to1.5116, when combined and subjected to further chroma-tography** yielded pure triolefin of T Z ~ ~ D.5110. A sampleof the pure triolefin also was obtained by further chromato-graphic separations carried out on the combined materialfrom fractions 2' and 3" obtained during the chromato-graphic purification .of methylcardanol. A 6.0-g. portionof the triolefin was distilled in a Hickman molecular sti ll.After a very slight forerun, five successive fractions weretaken at temperatures of 1 561 65' at 1 mm. pressure. Therefractive index of each fraction was the same, nZ6.%1.5105.These fractions were combined and used in the structuralwork. A sample of the combined fractions analyzed cor-rectly for triolefin and absorbed an amount of hydrogencorresponding to 3.0 double bonds. The reduced productmelted at 28-29.5' without recrystallization.Anal. Calcd.for C22&?0(triolefin):C, 84.55; H, 10.31.Found: C, 84.45; H, 9.99.

Saturat ed Component .-Fractions with refractive indicesbelow ?zZ6+J 1.4931, obtained from several chromatograms,were combined and a 6.0-g. sample was dissolved in 60 ml.of ethyl acetate and chilled in an acetone-Dry Ice-bath at-30'. Well defined crystals were obtained which on twofurthe r recrystallizations from ethyl ace tate or acetone werecolorless and melted at 29-30'. A mixed melting pointwith 3-pentadecylanisole obtained by catalyt ic hydrogena-tion of purified methylcardanol did not depress. The re-ported melting point of methylhydrocardanol (3-penta-decylanisole) is 29-30.*s,24Anal . Calcd. for Czz&O: C, 82.76; H, 12.00. Found:C, 82.75; H. 11.97.Ozonolysis of th e Mono6lefin.-A stream of ozonized

oxygen containing approximately 4% ozone was bubbledthrough a solution of 1.0 g. (0.0032 mole) of t he chromato-graphically pure monoolefin ( n s D 1.4933) in 25 ml. of ethylacetate at a ra te of 150-180 ml. per minute while th e solu-tion was maintained a t -60 to -80' by means of an ace-tone-Dry Ice-bath. The gas was passed directly from theozonization tube into a 10% aqueous potassium iodidesolution. Th e ozonization was stopped when the potassiumiodide solution turned yellow, a development which oc-curred abruptly and was easily detected.26 Th e solution ofozonide was brought to O ', transferred to a 100-ml. hydro-genation flask surrounded by cracked ice and hydrogenatedat atmospheric pressure employing 10% palladium-on-(23) I). Wassuman and C. R. Dawson, Ind . E ng . Chcm., 87, 396

(1945).(24) M. Sletzinger and C. R. Dawson, J . Org. Chcm., 14, 849

(1949).(25) I t was found n a control experiment employing the saturatedcomponent, 3-pentadecylanisole, that some ozonization of the benzenering occurred when the ozonization waa continued beyond the appear-

ance of yellow color in the potassium iodide solution.

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carbon as the catalyst in an Adams shaker.2G After filteringfrom the catalyst and removing the ethyl acetate by dis-tillation, the pale yellow residual oil was steam distilled andthe distillate (100 ml.) was extracted with ether. The ex-tract yielded a small oily residue which was taken up in 25ml. of 95% ethanol and treated with 2,4-dinitrophenylhy-drazine. The crystalline hydrazone melted at 103-104.5".When mixed with an authen tic sample of heptaldehyde 2,4-dinitrophenylhydrazone of m.p. 103.5-104.5 no depressionin melting point was observed.The oily aromatic aldehyde residue remaining after thesteam distillation was extracted with ether. Attempts toobtain crystalline dimedon and 2,4-dinitrophenylhydrazonederivatives were unsuccessful and consequently the materialwas oxidized to the corresponding carboxylic acid. Forthis purpose potassium permanganate in acetone gave betteryields than ammoniacal silver nitrate or 3% hydrogen per-oxide. The ether solution was evaporated, the residue takenup in 50 ml. of acetone, and 1.1 g. of potassium perman-ganate was added in small portions at 35-45'. After a pe-riod of about 15minutes, 50 ml. of water was added, and thereaction mixture was treated with sulfur dioxide to give acolorless cloudy solution which was then extracted exhaus-tively with ether. The ether extract was thoroughlywashed with water to remove acetone and then with 10%aqueous sodium hydroxide to recover the desired acid.Acidification, extraction with ether and drying over mag-nesium sulfate gave 0.70 g. (87%) of a n oily acid which solid-ified on chilling in an ice-bath (m.p. 44-50'). On one re-crystallization from aqueous ethanol 0.385 g. (48%) ofcolorless needles of m.p. 50-52" was obtained. Further re-crystallization from aqueous ethanol and from petroleuyether gave needles of constant melting point , 52.5-54 .Analysis was correct for the expected ~-(3-methoxyphenyl)-caprylic acid.

Anal. Calcd. for C15H2203: C, 71.96; H, 8.85; neut.equiv., 250. Found: C, 72.08; H, 8.90; neut. equiv.,251.Ozonolysis of th e Diolefin.-A 0.55-g. (0.0018 mole)sample of the chromatographically pure diolefin (%25D1.5027) was dissolved in 20 ml. of ethyl acetate and ozonizeda t -80' as described above. The ozonide was catalyti-cally reduced and the solvent was removed by distillation.

The ethyl acetate distillate, containing volatile aldehyde,was treated with 15 ml. of 50%aqueous ethanol containing0.90 g. of dimedon. A yield of 0.220 g. (36% of theory) ofcolorless crystals of m.p. 128-130' was obtained. Threerecrystallizations from aqueous ethanol produced colorlesscrystalline plates of constant melting point , 133-134'.LVhen mixed with an authentic sample of butyraldehydedimedon of m.p . 133-134" no depression in melting pointwas observed.Anal . Calcd. for C20Ha00: C, 71.83; H, 9.04. Found:C, 71.77; H, 8.95.The oily residue remaining after distilling the ethyl ace-ta te from the reduced ozonide was taken u p in 50 ml. of ace-tone and treated with 1.2 g. of potassium permanganate asdescribed in the case of the monoolefin. The acid obtainedfrom this oxidation amounted to 0.40; g. (90% of theory)of pale yellow crysta ls of m.p. 47-51 . Recrystallization

from aqueous ethanol and petroleum ether gave 0.270 g.(6!% of theory) of colorless crystals of m.p . 53-54". Amixed melting point with the w-(3-methoxyphenyl)-caprylicacid obtained from the ozonization of the monoolefin showedno depression.A,nal. Calcd. for C16H2203: C, 71.96; H , 8.85; neut.equiv., 250. Found: C, 72.17; H, 8.71; neut . equiv.,253.Ozonolysis of the Tr io le h-A 1.0-g. (0.0032 mole)sample of th e chromatographically pure triolefin (n%1.5110) was ozonized in 25 ml. of ethyl acetate a t -70"and the solution of the resulting ozonide was catalyticallyreduced using the procedures previously described. Thereduction catalyst was removed and the solvent ethyl ace-ta te was distilled directly into 200 ml. of a n aqueous solutionof 0.8 g. of dimedon. The mixture was shaken vigorouslyfor ten minutes and then allowed to stand a t room tempera-tur e for three hours. The ethyl acetate was removed by

distillation and the white crystalline precipitate, whichformed in the residual aqueous solution, on recrystallization(26, F. 0. isher, H . Dull rand 12.Frtei, B s r . , 66, 467 ( 1 9 32 ) .

from 95% ethanol gave 0.290 g. (31%) of fine needles ofm.p. 185-187'. One additional recrystallization p m 5%ethanol raised the melting point to 190.5-191 . Whenmixed with an authentic sample of formaldehyde dimedonof m.p. 189-190" no depression in the melting point was ob-served.Ana l . Calcd. for C17H2404: C , 69.83; H, 8.27. Found:C, 70.14; H, 8.02.An attempt to oxidize the aromatic aldehyde with am-moniacal silver nitrate was unsuccessful.The ozonolysis was repeated using a 0.70-g. (0.00225mole) sample of the triolefin. A yield of 0.210 g. (32%) offormaldehyde dimedon was obtained. The aromatic alde-hyde was oxidized with 2 .5 g. of potassium permanganateas previously described and a 0.360-g. (64%) yield of theacid of m.p. 52-53.5" was obtained. Recrystallization fromaqueous ethanol gave colorless needles of constant meltingpoint 52.5-54'. A mixed melting point determination withth e w-(3-methoxyphenyl)-caprylicacid obtained from theozonization of the monoolefin showed no depression.The ozonization was repeated using a 1.5-g. (0.0048 mole)sample of the pure triolefin and the ozonide was decomposedwith peracetic acid as described by Wilms.16 From a petro-leum ether extract of the reaction mix ture was obtained 0.50g. (42%) of w-(3-methoxyphenyl)-caprylic cid identified by

analysis and mixed melting point. The aqueous layer, re-maining from the petroleum ether extraction, yielded onevaporation to dryness under a stream of a ir a t room tem-perature a brownish semi-solid which could not be recrys-tallized from ethyl acetat e, ether or ethanol. On sublima-tion a small amount of solid was obtained which melted a t120-124'. On recrystallization from diethyl ether themelting point rose to 126-128'. A mixed melting pain:with an authentic sample of malonic acid of m .p . 132melted a t 126.5130'. A 2-mg. sample was treated withfour drops each of pyridine and acetic anhydride . Afterwarming the solution on a steam-bath for one minute, duringwhich a reddish-brown color developed, 10 ml. of 95% eth-anol was added to give a clear solution with a bright yellow-green fluorescence.16 A similar test using the same quanti-ties of reagents with an authentic sample of malonic acidgave a solution with comparable fluorescence both in inten-sity and color. Succinic, adipic and oxalic acids failed togive this test.Ozonolysis of the Partially Reduced Trio1efh.-A 1.6-g.(0.00513 mole) sample of pure triolefin was dissolved in 35m1. of ethyl acetatk and-catalytica lly hydrogenated over10% palladium-on-carbon a t 23' and 758 mm. until 1.2moles (145 ml.) of hydrogen had been absorbed. The re-action was stopped an d after removing the catalyst t he solu-tion of partially reduced triolefin was ozonized in the usualmanner. The solution of ozonide was then catalyticallyhydrogenated over palladium-on-carbon as previously de-scribed.One-half (30 ml.) of th e solution of reduced ozonide wasused in a preliminary experiment which indicated thepresence of formaldehyde, butyraldehyde and heptaldehydeamong th e ozonolysis products. The remaining 30 ml. ofsolution of reduced ozonide was then fractionally distilledusing a 19-inch Fenske column packed with glass helices.Five fractions of d isti llate (each of about 4-5 ml. ) were col-lected a t 76-78' over a period of one hour and the residuewas set aside for recovery of heptaldehyde as described be-low. Each fraction was refluxed for five minutes with 8 ml.of 50% aqueous ethanol containing 0.5 g. of dimedon andone drop of piperidine. Fractions 1, 3 and 4 yielded crys-talline derivatives, the dat a on which are given in Table 111.

TABLE11Frac- M.P.of derivative, O C .tion Crude Recryst. Mixed m.p. determination

1 185-187 189-190 No depress. with formaldehydedimedon of m.p. 190-191'3 118-121 122-1254 128-130 133-134 No depress. with butyraldehydedimedon of m.p. 133-134'The Fenske column had a strong odor of heptaldehyde.It was washed with 30 ml. of ethyl acetate which was thencombined with the heptaldehyde residue mentioned above.Most of the ethyl acetate and the remaining traces of bu tyr-

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Oct. 20, 1953 SUBSTITUTEDHENYLNAPHTHALENEELATEDO PODOPHYLLOTOXINCID 4957aldehyde were removed by careful distillation through thecolumn. The residue, 5 ml., was then steam distilled until8 ml. of a two-phase distillate had been collected. Theupper ethyl acetate layer was separated, the solvent evap-orated and th e residue taken up in 10 ml. of 95% ethanolcontaining 100 mg. of 2,4-dinitrophenylhydazine an d 3drops of 12 M hydrochloric acid. On chilling the solution,after refluxing for five minutes, a yellow crystalline solid wasobtained, m.p. 94-98, which on eight recrystallizationsfrom aqueous ethanol melted at 103-104.5. A mixed melt-ing point with heptaldehyde 2,4-dinitrophenylhydrazone ofm.p. 104-105 showed no depression.Oxidation of the Diolefin with Potassium Permanganate.-A 0.46-g. (0.00146 mole) sample of the pure diolefin dis-solved in 10 ml. of acetone was treated with 2 .5 g. of finelypowdered potassium permanganate in small portions over aperiod of four hours at 0-5 in an ice-bath.13 After adding10 ml. of water, t he manganese dioxide and excess potas-sium permanganate were reduced by treatment with sulfurdioxide. The colorless cloudy solution was made stronglyacid by t he addition of 3 ml. of 12 M hydrochloric acid andextracted exhaustively with diethyl ether. The combinedextracts were in tur n extracted with several 10-15-ml. por-tions of water unt il no further evidence of oxalic acid couldbe obtained as described below.In one of the potassium permanganate oxidation experi-ments the ether solution obtained a t this stage was extractedwith 10% sodium bicarbonate. Acidification of the extractgave a pale yellow oil the volatile components of which wereremoved by steam distillation. The residual oil, on crys-tallization from ethanol , gave a 22% yield of w(3-methoxy-phenyl)-caprylic acid, identified by analysis and mixedmelting point .The combined aqueous extracts were made basic to l itmuswith 6 M ammonium hydroxide and treated with a solutionof 2 g. of calcium chloride in 5 ml. of water. The precipi-tate of calcium oxalate was filtered, washed with 30 ml. of

hot dilute acetic acid and then with 10 ml. of water, anddried. The resulting 0.40 g. of white solid was dissolved in200 ml. of 0.45 M sulfuric acid by heating on the steam-bathand rapidly titr ated with a s tp d a r d solution of 0.200 M po-tassium permanganate at 70 . The titer (17.08 ml.) corre-sponded to 0.00086 mole of oxalic acid representing a 58%yield.In another experiment, a 20% yield of t he oxalic acidpresent in the aqueous extracts was recovered in the form ofthe dihydrate.Oxidation of the Triolefin with Potassium Permanganate.-A 0.50-g. (0.0016 mole) sample of t he pure triolefin wasdissolved in 20 ml. of acetone and oxidized with 3 .5 g. of po-tassium permanganate as above except that the tempera-ture of the reaction was maintained at 10-15. The oxida-tion required 90 minutes. The calcium oxalate, 0.55 g. ,isolated as described above, required 31.4 ml. of 0.200 Mpotassium permanganate for titration, corresponding to0.00157 mole of oxalic acid, or a yield of 49% based on twomoles of oxalic acid per mole of triolefin.In another experiment a 35% yield of oxalic acid dihy-dra te (m.p. 100-101), identified by analysis and mixedmelting point, was obtained. The aromatic fragment fromthe oxidation, O-( 3-methoxyphenyl)-caprylic acid was iso-lated in 40% yield and identified by analysis and mixedmelting point.Ultraviolet Absorption Spectra.-The ultraviolet spectraof the four components of methylcardanol were determinedusing a Carey recording photoelectric spectrophotometerwith 0.00010 M solutions in 95% ethanol.

Acknowledgment.-The authors are indebted tothe Irvington Varnish and Insulator Company ofIrvington, New Jersey, for the supply of cardanol,and for their helpful interest in this investigation.NEWYORK 7, S .Y.

[CONTRIBUTION FROM THE CHEMISTRY DEPARTMENTF THE UNIVERSITY OF MARYLAND]

Synthesis of a Substituted Phenylnaphthalene Related to PodophyllotoxinBYWILKINSREEVE ND HERBERTMYERSRECEIVEDUGUST4, 1952

The synthesis of a phenylnaphthalene derivative I11 closely related t o podophyllotoxin is described.In attempting to synthesize one of the isomers ofthe podophyllotoxin-picropodophyllin series I,we have prepared a substituted l-phenylnaph-thalene (111) differing from podophyllotoxin orpicropodophyllin only in that it has a naphthalenering instead of a tetralin ring, is a methyl ester in-stead of a lactone, and is missing a hydroxymethyl

group.The methyl ester I1 was prepared by methylatingthe corresponding keto acid with diazomethane.The keto acid was best prepared by the oxidationof the corresponding styrene. The aldehyde,3,4,5- trimethoxy -4 ,5 - methylenedioxybenzophe-none-2-carboxaldehyde, was also obtained when thereaction was carried out on a 50-g . scale.The sodium hydride-catalyzed Stobbe condensa-tion of I1 with methyl succinate gave a 16% yieldof the naphthol I11 and a 65% yield of a crudeitaconic acid mixture. When potassium t-butoxidewas used as a catalyst, none of the naphthol wasObtained. The structure assigned to I11 is based onanalytical data, the assumption the reaction pro-ceeds by the accepted mechanism of the Stobbe(1081),

(1) W. J. Gender and C. M. Samour, THISJOURNAL, 18, 5555

condensation2 (which requires an intermediatelactone and thereby excludes the carbomethoxygroup from the 2-position), and the fact that analcohol solution of i t couples with a cold aqueoussolution of diazotized $-toluidine at a PH of 8 to givea red dye. The fact that the itaconic acid mixtureis the predominant product suggests that theStobbe reaction occurs more rapidly than theClaisen reaction. Once a salt of the itaconic acidis formed, the Claisen reaction would not beexpected to occur.

ExperimentalAll melting points are corrected. Analyses are by Mrs.Mar y Aldridge and Mr. Byron Baer of th is Laboratory.Intermediates leading to the synthesis of the substitutedstyrene were prepared a s described earlier.33,4,5-Trimethoxy~,5-methylenedioxybenzophenone-2-carboxylic Acid.-The procedure employed differs somewhatfrom that of Gender and Samourl and is given here becausethe aldehyde also was obtained. Fif ty grams of 2-(3,4,5-trimethoxybenzoyl)-4,5-methylenedioxystyrenel and 42 g.(2) W. S. Johnson and G. H. Daub in Organic Reactions, R .

Adama, editor, Vol. VI, John Wiley and Sons, nc., New York, N. Y.,1951, p. 4.(3) W. Reeve and W. M. Eareckoon, THISOURNAL, 7P , 5195

(1050).