[CONTRIBUTION FROM
THE SCHOOL O F
CHEMISTRY, UNIVERSITY O F MINNESOTA]
The Reactions of Aldehydes with p-Anilinocrotonic Esters’ R Y JOHN G. ERICKSON~ While Knoevenage13 has studied the reactions of benzaldehyde with some 8-aminocrotonic esters, there appear to be no published studies of the reactions of aldehydes with p-anilinocrotonic esters alone. L a c h o ~ i c z however, ,~ has reported that the reaction of benzaldehyde with a mixture of ethyl 0-anilinocrotonate and ethyl acetoacetate l,-l-diphenyl-2,B-dimethvl-:i,3-dical’bethyields ;,xy-l,~-dihydropyridine(I )
acetate. Bertini, on the basis of his analytical results, assigned I11 the structure of a tetrahydropyrimidine derivative. On the basis of analytical results alone there are other formulas for I11 which are nearly as satisfactory as the molecular formula C32HmN202. Furthermore, plausible structures other than Rertini’s can be written for the formula C32H30r\;?OT. Accordingly, additional work was carried out in order to establish the structure of 111. 11 I? Benzaldehyde reacts with methyl p-anilinocrotonate, yielding a compound (V) whose analyC!H,OOC .;.‘~i-ciioc,a, sis is consistent with the formula C31H28N202. C“th)-CH3 ‘I Compound V can also be prepared by the action I , R = CBH, of benzalaniline on methyl acetoacetate or methyl 11, R = CHI c$13, tu-acetyl-8-anilinohydrocinnamate (VI). Since ‘The present study deals with the reactions of Schiff and Bertini’ have shown that ethyl acetoacetaldehyde and benzaldehyde with 8-anilino- acetate reacts with benzalaniline to yield IV, it crotonic esters. The reaction of acetaldehyde follows that the syntheses of Bertini and of Philwith ethyl p-anilinocrotonate was found to yield pott and Jones are equivalent and that in the I - phenyl - 2,4,6 - trimethyl - 3,s - dicarbethoxy- formation of I11 and V, the alpha carbon atom of 1,4-dihydropyridine, 11. The identity of 11 was the unsubstituted acetoacetic ester becomes atproved by analysis and by mixed melting point tached to the anilinobenzyl grouping. It has determination with an authentic sample of 11, been found that DroDvl acetoacetate reacts with prepared from aniline and ethyl ethylidene bis- berizalaniline to gives substance (VII) of molecular formula C33HaN202. Likewise, butyl acetoacetoacetate. CHICOCHCOOC,H, acetate reacts with benzalaniline to give a substance similar to 111, V and VII. I CH3CHO CeHsNH? CH3C=CHCOOC>Hj I1 f-CHCH? I t is apparent that, since the reactions I I of benzalaniline with each of four alkyl SHCsH6 CH3C0CHC00C2H5 acetoacetates give four similar but difFrom the reaction mixture of benzaldehyde ferent products, the ester grouping must be left with ethyl p-anilinocrotonate there were isolated intact in each of these reactions and all of the two products, I and another compound (111), oxygen present in 111, V and VI1 must be conwhose analysis corresponds most closely to the tained in carboalkoxy groupings. Furthermore, formula C32H30N202. Compound I11 has been attachment of the beta carbon atoms to nitrogen prepared by Bertini,6 who isolated it, as well as I, atoms is indicated. The validity of this latter from the reaction mixture of benzalaniline with statement is based upon the fact that ethyl and ethyl a-acetyl-P-anilinohydrocinnamate(IV). It methyl 6-anilinocrotonates react with benzalhas also been made by Philpott and Jonesa by aniline to yield I11 and V, respectively. treatment of benzalaniline with ethyl acetoI t was not found possible to cause ethyl a H C&S b y ‘
___f
CHaCOCHCOOR
I
CHCeHs
CeHsCH=I\;CsHb ______j
--
)i
~ 0 0 ~ N---CBH5 CsH&CH=KCsHs CH3COCHzCOOR I/ I .H
SHCeHs
i i ) Ahctracted from the P h D t h e v c of John Brickwn, M a y , 1944 (2) Present address, American Cyanamid Company, Stamford, Ennn ..~~~
(3) Knoevenagel, Ber.. 31, 7 3 8 - - i 4 8 (1898). ( 4 ) Lachowicz, Monoirk.. 17, :343-:36O ( I W R ) ( 5 ) Bertini, G a m c k t m tia!., 89, I1 :3Il :iT, 11899 ~ l i jPhilpntt and Jones J < !:.sa i , , c .3:ii :I11 \1!):4SJ.
methylacetoacetate to react with benzalaniline, A no; unreasonable conclusion from this result is that in the formation of 111, V and VII, the gamma carbon atoms of the acetoacetic or panilinocrotonic esters are not involved. Tt follows 1 7 ; :chiti
:iiiil
14~rt1111,
1h.r , DO, ( i l l l - ( d l 4 f I V O 7 , .
REACTIONS OF ALDEHYDESWITH ~~ANILINOCROTONIC ESTERS
.lug., 1945
from these considerations that the most likely structure for I11 is the one proposed by Bertini and that V and VI1 have analogous structures. The synthesis of I11 and V was attempted, using the reaction of benzaldehyde with ethyl and methyl cy-( a-anilinobenzy1)-8-anilinocrotonates (VIII and IX) CH,C=CCOOR
/
CsHdNH
I
CHCsHs
CsHsCHO
I
111 or V
NHCsH5
VIII, R IX,R
= CiHk =i
CBs
1383
anilino groups by hydroxyl groups and subsequent recyclization. This formulation of XI ,and XI1 is supported by syntheses which, although they yielded insufficient material for complete pudication, leave little room for doubt as to the structures of XI and XII. Compounds IV and VI, treated with benzaldehyde, yield small amounts of X I and XII. These latter reactions are analogous to the synthesis by Betti* of a naphthoxazine from benzaldehyde and 8-(cy-anilinobenzy1)-a-naphthol. It might be objected that X I and XII, obtained in this way from IV and VI, might actually be the products of acid degradation of I11 and V, these latter compounds being formed from IV and VI and benzalaniline resulting from decomposition of part of the IV and VI. This possibility seems unlikely since the small amounts of X I and XI1 this synthesis does afford are formed rapidly and prolonged standing does not improve the yield except after days. The use of stronger acid and shorter reaction periods converts 111 into an unstable material
Two syntheses of VI11 and I X presented themselves. However, one, the reaction of benzalaniline with 8-anilinocrotonic esters, gave only I11 or V, whether one or two moles of benzalaniline were used. The second proposed synthesis of VI11 and I X involved the action of aniline on IV and VI, Treatment of IV and VI with aniline gave viscous oils which could not be crystallized but which, in the case of the methyl ester onlv. on treatment with beizaldehyde gave a good yield of the desired prodHC1 uct. + The chemical nature of Ha0 111 (and V) is of some interest. Bertini stated CsHs that I11 is chemically very resistant. The present work has indicated that this statement should be CHaCOCHCOOR I modified. Heated at 250' CHCsHs CsHsCHO I I11 rapidly yields a small SHCsHa amount of s-dhhenvlurea, besides much resinous material. Two moles of XI, R = C*Hs XII,R = CHs methane are slowly formed when I11 or V is treated with methylmagnesium iodide, but there is no (XIII), m. p. 11&120.5°, instead of XI. Comevidence of any addition reaction occurring during pound XIII, treated with pyridine or a mixture of dioxane and aqueous hydrochloric acid, is conthis treatment. Compound I11 slowly dissolves in hot glacial verted into XI. The action of ethanolic sodium acetic acid to form a compound (X), m. p. 237- hydroxide upon XI11 appears to convert it into a 238', whose analysis is most consistent with the still more labile compound which, refluxed briefly formula C24HsN02. Since similar treatment of with alcohol after acidification with acetic acid, V gives a compound, m. p. 249-254', it would yields XI. No product analogous to XI11 could appear that in X the carbethoxy grouping has be isolated from reaction mixtures of V and acids been retained. Compound X is quite resistant of various concentrations. to the action of acids and bases. There is inI am deeply indebted to Dr. W. M. Lauer for sufficient evidence to warrant suggesting a struc- assistance in the performance of this research. I ture for X. also wish to thank Messrs. Chien-Pen Lo and While I11 and V are stable toward bases, they Vincent Webers for performing several of the are quite sensitive toward acids. The action of a analyses reported in t h i s paper. mixture of dioxane and aqueous hydrochloric Experimental9 acid u on I11 and V yields CzaH&JOa (XI)and CSHa 0 8 (XII), respectively, The formation The Reaction of Ethyl ,s-Anilinocrotbnate with Acetaldeof these compounds is vieked as o c c e n g by way hyde.-Twenty grams (0.0975 mole) of ethyl 8-anilinoof hydrolysis of the vinylamhe grou ings in I11 (8) Betti, Casr. chfm. ilaZ., Il, 379 (1901). and V, followed by replacement of t e resulting (9) All melting pointr are eswectrd valurr.
r
-
K
i
1.384
JOHN
G. ERICKSON
lro1. ( i i
best method of purification appears to be to dissolve the material in the minimum amount of hot benzene and then to reprecipitatc the product by the addition of several volumes of 95% ethanol, followed by cooling. After several applications of this procedure the product is colorless and melts a t about 150-155'. It is then recrystallized from 1:4 benzene-ethanol and finally from 95% ethanol, in which it is only slightly soluble. Crystallization from alcohol gives small rhombic crystals, melting a t 175-17ri which are stable in air. Crystallization from beruetie or xylene gives much larger crystals which, hokvever. cruinhlc. on exposure to air. Anal. Calcd. for C~zHaoN.0~:C, 80.98; H,6.37; S . 5.90; mol. wt., 474.6. Found: C, 80.75,81.31; H, li.iJ!i, 6.15;S , 6.00; mol. wt., 457,468 (benzene f . p , ) . Admixture of this product with samples of 1,2,3,4tetraphenyl - 5 - carbethoxy - 0 - methyl - 1,2,3,4 - tetrahydropyrimidine, prepared by the procedures of Bertini or of Philpott and Jones or by the following syntheses, did not produce a depression of the melting point. Syntheses of C3BIs~N2O1: (a) From Ethyl Acetoacetate, Benzaldehyde and Aniline.-Sixty-four grams (0.603mole) of benzaldehyde, 56.2 g. (0.604mole) of anil-Phenyl-2,4,6-trimethyl-3,5-dicarbethoxy-l,4-dihydro- line and 39.0 g. (0.302 mole) of ethyl acetoacetate were pyridine.-Ethyl ethylidene bisacetoacetate was prepared mixed and the mixture was dissolved in 100 cc. of 95% following the directions of Rabe and Elze.lo The ester ethanol. Three drops of concentrated hydrochloric acid (8.58g., 0.030mole) was dissolved in 10 cc. of 95% ethanol. was then added. An insoluble oil separated from the soluTo this solution were added 2.8 g. (0.030mole) of aniline tion after two hours. After standing for two weeks, this and four drops of concentrated hydrochloric acid. oil had changed to a light yellow solid. The mixture was After forty-eight hours large rhombic crystals had ap- then filtered. The product, after one recrystallization peared in the solution; disturbance of the.solution caused from benzene, weighed 82.3 g. and melted at 137-153". smaller crystals to appear. After five days, 5 cc. of water Two further recrystallizations from benzene yielded 24.0 was added t o the solution and the mixture was cooled to g. of product, m. p. 168-172'. 5" and maintained at this temperature For sixteen hours. (b,) From Ethyl p-Anilinocrotonate, Benzaldehyde and The mixture was then filtered and the precipitate washed Amline.-Sixty-two grams (0.30mole) of ethyl p-anilinowith a few cc. of dilute (1:1) ethanol. Pressing the prod- crotonate, 64.0g. (0.60mole) of benzaldehyde and 28.2g. pct on a porous plate gave 2.75 g. of material melting a t (0.30mole) of aniline were mixed and the mixture then 95-102 '. Recrystallization from dilute ethanol gave 2.42 dissolved in 100 cc. of 95% ethanol. Four drops of cong, (23.8% yield) of white needles, m. p. 104-105°. Ad- centrated hydrochloric acid was added to the mixture mixture with the reaction product of ethyl @-aiditio- which was then allowed to stand for nine days. The mixcrotonate and acetaldehyde resulted in no depression of the ture was filtered and the precipitate, a light yellow solid, melting point. was washed with ethanol. The weight of dry crude prodReaction of Ethyl p-Anilinocrotonate with Benzaldeuct, m. p. 135-145', was 130.0 g. Thiscorresponds to a hyde.-Forty-one grams (0.20 mole) of ethyl p-anilino- 91% yield of the crude product. crotonate and 21.2 g. (0.20 mole) of benzaldehyde were ( c j From Ethyl 8-Anilinocrotonate and Benzalaniline. mixed and threc drops of concentrated hydrochloric acid --Ethyl p-anilinocrotonate (2.05g., 0.01 mole) was mixed added to the mixture. A small amount of white solid, pre- with 3.62 g. (0.02 mole) of benzalaniline and 0.5 g. of sumably the hydrochloride of the amino ester, separated Drierite. Approximately 1 mg. of aniline hydrochloride immediately. After several minutes the mixture became was added to the mixture which was then heated on ihe cloudy and the white solid redissolved ill the mixture. steam cone for forty-eight hours. At the end of this period The temperature of the mixture rose from 25 to 47.5" the viscous liquid, while still hot, was separated by dewithin ten minutes of mixing. After fifteen minutes the caritation from the Drierite. The Drierite and flask were mixture was very cloudy and quite viscous. After five then washed with a mixture of 5 cc. of ethyl ether and 30 days the supernatant water layer was removed and the cc. of ethanol. Upon addition of these washings to the viscous oil was dissolved, with warming, in 200 cc. of 95% main body of the product, crystallization started immeethanol. diately. The mixture was filtered after fifteen minute:. Within a very few minutes a precipitate had begun to The weight of dry, light yellow product, m. p. 160-165 , form. .After four days the mixture was filtered and the was 2.0 g. After recrys:allization from ethanol the precipitate was washed with 50 cc. of 95% ethanol. The product melted at 172-173 . weight of the light yellow material obtained in this mdnner (d) Viu Ethyl a-(a-Anilinobenzyl)-p-anilinocrotonate. was 20.8 g. The combined filtrate and washings, after -Ethyl a-acetyl-~-anilinohydrocinnamate7 (0.93g., 0.003 standing forty-eight hours longer, deposited a further 0.30 mole) and aniline (0.28g., 0.003mole) were mixed and disg. The product thus obtained melted at 130-140'. solved in 3 cc. of benzene. After less than one hour the The alcoholic mother liquor was poured into 300 cc. of solution had become cloudy. After twenty-four hours a water. After the brown oil had separated completely, the considerable amount of water had formed. The benzene water was poured off and the oil was dried under reduced and water were removed by evaporation under reduced pressure and recrystallized from benzene and petroleum pressure at room temperature. There remained a rather ether. This procedure yielded a yellow material which was viscous yellow oil, soluble in benzene, alcohol and ether. recrystallized twice from 95% ethanol. There was ob- Attempts to cause this oil to crystallize failing, the oil was tained 0.85 g. of a solid possessing a faint greenish-yellow dissolved in 3 cc. of benzene and to this solution was added tinge, m. P. 156-158'. Admixture with an authentic 0.32 g. (0.003mole) of benzaldehyde. The solution besample of 1,4-diphenyl-2,6-dimethy1-3,5-dicarbethoxy-l,4came cloudy within one minute. After several hours, the dihydropyridine4 resulted in no depression of the melting benzene and water were removed by the use of reduced point. pressure and 5 cc. of ethanol was added to the viscous The yellow precipitate isolated above by virtue of its residue. A precipitate began to form in a few minutes. slight solubility in cold alcohol is not easily purified. The The mixture was filtered after two hours. The weight of dry crude product. melting at about 160", was 0.05 g. i t 0 ) R s b e and Elm, A n n . , 918, HQ (1902). crotonate and 4.3 g. (0.0975 mole) of freshly distilled acetaldehyde were mixed, the mixture cooled in an ice-bath and two drops of concentrated hydrochloric acid added to this mixture. Within five minutes the mixture became cloudy. The mixture was then allowed to stand a t room temperature. After six days a considerable amount of water had separated from the mixture. Removal of the water by the use of a vacuum desiccator left a dark viscous oil. Forty cubic centimeters of 95% cthanol was added and an attempt was made to crystallize the reaction mixture. This attempt failing, the mixture was put aside. After several months it was noticed that crystals had begun to form in the alcoholic solutio11 of the reaction mixture. After nineteen months the mixture had become transformed into a . number of large rhombic crystals covefed by a dark viscous oil which was only slightly soluble in alcohol. The crystals were picked out and washed with dilute ethanol.. The product from this ,treatment weighed 1.12 g. and melted at 100-105°. rhree recrystallizations from dilute ethanol gave long white needles, m. p. 104-105". Anal. Calcd. for Cl&I&04: C, 69.94; H,7.34; N, 4.08. Found: C, 70.32; H, 7.33; N, 4.17.
O,
Aug., 1945
REACTIONS OF ALDEHYDES WITH 0-ANILINOCROTONIC ESTERS
1385
It was dissolved, with warming, in 15 cc. of n-propanol. Rec:ystallized from ethanol, the product melted at 172After nine days the formation of precipitate had appar173 ently ceased. The precipitate was filtered off and reReaction of Methyl 8-AIlilinocrotonate with Benzaldehyde.-Methyl 8-anilinmotonate (47.8 g., 0.25 mole) crystallized three times from n-propanol; 2.29 g. of prodand 23.3 g. (0.25 mole) of benzaldehyde were mixed. uct, m. p. 146-147". was obtained. There was a definite cooling effect attending this mixing, A d . Calcd. for CSrHltN2Ot: C, 81.12; H , 6.60; N, the temperature of the mixturedropping to about seven 5.74. Found: C, 81.39; H, 0.50; N, 5.72. degrees below room temperature. The mixture was then Conversion of 111 into =.-Ten grams of 111 was diswarmed gently on the steam cone in order to achieve solved in 700 cc. of dioxane. T o this solution were added homogeneity and five drops of concentrated hydrochloric 8 )cc. of water and 80 cc. of concentrated hydrochloric acid. acid added to the mixture. The solution immediately became colored a bright greenishIn B very few minutes the mixture became quite turbid yellow upon addition of the acid. After standing twentybut never very warm. After several days the mixture eight hours a t room temperature, the solution, now colored had become a very viscous oil covered by a layer of water. a greenish-brown, was poured into 4 liters of water. After The water was removed and 150 cc. of methanol was added another twenty-eight hours, the suspension resulting from to the oil. A few minutes of gentle warming on the steam this treatment was filtered. One recrystallization of the cone caused the oil to dissolve in the methanol. This oily precipitate from ethanol gave 2.65 g. of pink needles, solution then rapidly precipitated a nearly white solid. m. p. 148-152'. The solid was filtered off after several hours and washed The removal of the pink co!or is a matter of some difiwith a small amount of methanol. The yield of crude dry culty as this color is strongly absorbed from solution by product obtained in this manner was 30.6 g. the crystals of XI and is apparently not absorbed a t all by The purification of this product is accomplished in very charcoal. Removal of the color was accomplished by dismuch the same fashion as is that of I11 except that meth- solving the pink needles in more than the minimum amount anol is used in place of ethanol in the procedure previously of hot alcohol, allowing the product to crystallize by cooldescribed. The purification of V was found, however, to ing, removing these crystals by filtration and then conbe more easily achieved than that of 111. Final re- centrating the filtrate under reduced pressure. The macrystallization from methanol or from benzene-methanol' terial, thus obtained from the filtrate, is, after another regives long white needles, m. p. 192-193 crystallization,from ethanol, very nearly white and melts Anal. Calcd. for CIIH~~NZOZ: C, 80.94; H, 6.00; .N, a t 148-160' with some softening at about 143 . 6.09; mol. wt., 460.6. Found: C, 81.14, 81.28; H, 5.62, Anal. Calcd. for G&IHpsNOs: C, 78.17; H, 6.31; N, 6.32; N, 6.23; mol. wt. (benzene f. p,), 416. 3.51. Found: C, 78.25; H, 6.35; N, 3.61. Admixture of this product with samples of 1,2,3,4-tetraSynthesis of XI.-Ethyl a-acetyl-8-anilinohydrccinnaphenyl - 5 carbomethoxy - 6 methyl 1,2,3,4 tetrahydropyrimidine, prepared by any of the following syn- mate (0.31 g., 0.001 mole) and 0.11 g. (0.001 mole) of benzaldehyde were mixed and the mixture dissolved with theses, did not produce a depression of the melting point. gentle warming in 2 cc. of ethanol. One drop of glacial Syntheses of CalH2J%02:(a) From Methyl a-Acetyl8-anilinohydrocinnamate.-Methyl a-benzalacetoacetate acetic acid was then added, the solution was warmed a few was prepared, following the direction of Knoevenagel.11 minutes longer and was then allowed to stand for an hour. It is a light yellow liquid, boiling at 158-162" under 12 *vera1 cubic centimeters of water was then added. An mm. of pressure. Following the procedure of Ruhemann oil separated wbich, after sevecal recrystallizations from and Watson," the benzalacetoacetic ester was converted ethanol, gave a small amount of pinkish-white crystals in good yield into methyl a-acetyl-p-anilinohydrocinna- melting at 126-130". There was insufficient material for further purification. A mixture of this product with X I , mate. This latter compoundDis a white solid, melting, with rapid heating, a t 119-122 I t may also be obtained prepared by degradation of 111, melted at 144-149'. Conversion of III into =.-Ten grams of I11 was disfrom the reaction of methyl acetoacetate with benzalsolved in a mixture of 100 cc. of dioxane, 15 cc. of water and aniline. Methyl a-acetyl-8-anilinohydrocinnamate(0.30 g., 0.001 25 cc. of concentrated hydrochloric acid. After standing two and one-half hours at room temperature, the yellow mole) was mixed with 0.18 g. (0.001mole) of benzalaniline. Three grams of benzene and about 1 mg. of aniline hydro- solution was poured into 850 cc. of water. After standing chloride were then added. After eight days the solvent for twenty-four hours a t room temperature, the suspension was removed under reduced pressure a t room temperature. thus obtained had deposited a considerable amount of Four grams of methanol was then added. Crystallization yellow nodules. These were filtered off and recrystallized of the product proceeded fairly rapidly. The wei ht of from ethanol. Two such recTstallizations gave 6.90 g. of the dry crude product, filtered off after twenty-five %ours, white needles, m. p. 116-119 . Three more recrystallizations from ethanol raised the melting point to 118-120.59. was 0.07 g. After recrystallization from methanol-benThe material is apparently unstable and the amount of zene the product melted at 187-190". (b) From Methyl 8-Aniinocrotonate and Benzalani- heating t o which alcoholic solutions are subjected during he.-This was done in a manner similar to that used with recrystallization appears to affect the melting point. Anal. Found: C, 78.51; H, 6.49; N, 3.82. the ethyl ester. Equivalent quantities and the same conditions were employed. The yield of crude dry product Conversion of III into X.-Five and six-tenths grams of was 2.10 g. Recrystallized from methanol-benzene, it 111 was warmed with 40'cc. of glacial acetic acid on the melted a t 191-193'. steam cone until solution was complete. This process (c) Viu Methyl ~1-(~~obenzyl)-8-anilinocroton-required about fifteen minutes. At this stage the solution ate.-This was done in amanner exactiyanalogous to that was dark red. Water was then-added dropwise until the employed with the ethyl ester, eqiuvalent quantities being turbidity persisted and the mixture was allowed to cool. used. There was obtained 0.61 g. of crude product. After After twenty-four hours a precipitate had appeared and three recrystallizations from methanol-benzene, the prod- was filtered off. The filtrate was warmed and to it was uct melted a t 18&192O.. Efforts to repeat this experiment added more water. After a second period of twenty-four were never successful. houri another crop of solid had appeared and was 6ltered Reaction of n-Prop 1 Acetoacetate with Benzalaniline.off and added to the first crop. The combined product Propyl acetoacetate fi.44 g., 0.010 mole) was mixed with was recrystallized twice from dilute ethanol. This treat3.62 g. (0.020 mole) of benzalaniline and the mixture was ment gave 0.9 g. of white flakes, m. p. 237-238". then melted by gentle heating. Approximately 1 mg. of Anal. Calcd. for G4HI8NO2: C, 80.64; H, 6.49; K, aniline hydrochloride was added. After forty-eight hours 3.92. Found: C, 80.52: H, 6.50; N.4.10. a t room temperature the mixture was a jelly-like mass. Pyrolysis of IXL-This was accomplished by placing the sample of 111, contained in an qlenmeyer flask,in a fusible (11) Knoevenagel, B e . , PI,.172 (1896). (12) Ruhcmonn and Watson, 1.Chrm. Soc., 86, 1170 (1904). alloy bath, preheated to 250 Within five minutes of
.
'.
-
-
-
-
.
.
heating, some inaterial had appeared 0 1 1 the cooler parts warniiiig O m drop of concentrated sulfuric acid was of the flask. Further heating had no effect. The sub- added and the solution warmed for a few minutes longer, limate was then scraped from the walls of the flask and then allowed to cool. After two hours a small amount of recrystallized from ethanol. Only a few milligrams of precipitate had appeared. This was filtered off and reproduct melting at 236-237" was obtained for each gram crystallized from dilute methanol; there was not enough of 111 used. Admixture with an authentic sample of s-di- material for two recrystallizations. There was obtained a 1)henylurea produced no depression of the melting point. white powder, m. p. 148-1,507°: admixture with XIT g a w Conversion of V into XU--Two grams of V was dis- a melting point of 152-164 . wlved in 125 cc. of dioxane and 10 cc. of water and 10 c ~ . of- concentrated hydrochloric was then added. There summarg was immediate formation of a yellow color upon addition 1. I t has been shown that the reaction uf of the acid. After standing for twenty-four hours, thr acetaldehyde with ethyl 0-anilinocrotonate yields holution was poured into 300 cc. of water. After standing for forty-eight hours, the suspension a dihydropyridine derivative. resulting from this treatment had deposited yellow leaves. 2. It has been shown that the reaction of These were removed by filtration and washed with water. benzaldehyde with ethyl p-anilinocrotonate yields There was obtained in this maimer 0.70 g. of dry yellow product, m. p. 1fX-176". Two recrystallizations from a dihydropyridine derivative and a tetrahydromethanol gave pink nwdles melting a t 175-177 ~ ' , pyrimidine derivative and that the reaction of T h e pink color accompaiiying this product is as difficult benzaldehyde with methyl 6-anilinocrotonate to remove as that accompanying XI ; its removal was accomplished by use of the same techiiique as that previously yields a tetrahydropyrimidine derivative. 3 . Several degradation products of these tetradescribed for XI. This treatment gave very nearly white needles, m. p. 177-178" hydropyrimidines have been isolated. The ac-4nal. Calcd. for C&diOa: C, 77.90; H , 6.01; S , tion of dilute hydrochloric acid upon these tetra3.63. Found: C, 78.00; H, 6.74; S , 3.71. hydropyrimidines yields compounds which are Synthesis of =I.-Four-tenths gram of methyl a- probably oxazines. acetyl-8-anilinohydrocinnatnate and 0.50 g. of benzaldeIiydc were mixed and disqolved in 1 cc. of methanol with MIWEAPOLIS, MINNESOTA RECEIVED MAY21, 1945
[ C u S y ' R I B U T I O x F R O M 'THE I)I\vISIOS O F PfIYSIOLOGICAI, CHEMISTRY, c : S I V E K S I T Y OF
MINNESOTA, MINNEAPOLIS]
Spectrophotometric Studies of the Oxidation of Fats. 11. The Oxidation of Dienoic Fatty Acids BY RALPHT. HOLMAN,' WALTER0. LUNDBERG~ AND GEORGE 0. BURR
The changes in fats which take place during autoxidation have been the subject of much study and many workers have proposed mechanisms for the oxidation of the component unsaturated fatty acids. Von Mikusch and Priest3 have summarized briefly the theories and proposed mechanisms by which oxygen may attack the double bond. The mechanism whereby a fourmembered ring peroxide is formed is favored with the more unsaturated fatty acids. The demonstration of oxido structures among the products of autoxidation of monoethylenic systems by Ellis4 and Deatherage and MattilP lends support to the mechanism leading to a threemembered ring peroxide containing tetravalent oxygen. Fahrions first proposed a rearrangement of peroxides to form a keto1 and MorrelP and co(1) This paper represents part of a thesis presented by Ralph T. Holman t o the Graduate Faculty of the University of Minnesota in partial fulfillment of the requirements for the P h . D . degree, June, 1944. The work was aided by grants from the Hormel Research Foundation, the National Live Stock and Ment Board, and the Sational Dairy Council. (2) Present address: Hormel Institute, Austin. Minaesota. 13) J. D . Von hIikusrh :and G . W Prie.st. Oil nird Ton,+ 18, XI I
1941). (4) G . W. Ellis, Biochrm. J , SO, 757 I lY:36). ( 5 ) F. E. Ueatherage ani1 FI , \ Xlattrii. I n d . b.tig.
(
I>?,,?
31,
1426 (1931). (6) W.Z.Fahrion, Angew. Chew,., 16, 665, 697 (1903). (7) B. S . Morrell and E . 0. Phillips, Feltr u . S e i f e n , 46,541 (1939).
workers have been able to identify ketols as products of oxidation of p-eleostearin. EllisBsuggested that the addition of oxygen to the double bond yields an ene-diol. Scheibergpostulated the addition of oxygen to the unconjugated diene system a t the active methylene group to form -CH===CH-CO-CH=CH--. Farrnerlo~ilproposed a mechanism whereby oxygen attacks the carbon between the double bonds of the linoleic acid type system to yield a hydroperoxide. It will be noted that in the last three mechanisms the system retains its unsaturation after the addition of oxygen. In disagreement with these mechanisms is the work of Paschke and Wheeler12who found the decrease in iodine value roughly parallel to the increase in peroxide value during the oxidation of fatty acid esters. Some work has been done relative to the spectroscopy of fat oxidations. Edisbury and c o - ~ o r k e r found. s ~ ~ an increase in the absorption of ling oil upon its exposure to air. In the oxidized sample there was an indication of an absorpi8) G. W.Ellis, J. SOC.Chcm. Ind.. 46, 193T (1926). (9) J. Scheiber, Z. nngcw. Them., 46, 643 (1938). (IO) E. H.Farmer, G. H. Bloomfield, A . Sundralingam and D. .k. Sutton,,Trans. Faraday SOC.,88, 348 (1942). ' 11) 13. 11. Farmer and D. 4 . Sutton, J , Chcm. SOC.,119 (1943). I 12) K.P. Paschke and D. H. Wheeler, O i l atid Soap, 21, 62 (1941). (13) J . K. Edisbury, K -4, hIorton and J . .4. Lovern. Biochem. J., as, 899 (1936).
