[COKTRIBUTION FROM CHEMICAL RESEARCHLABORATORY O F SCHERING CORPORATION]
REDUCTIONS WITH NICKEL-ALUMINUM ALLOY AND AQUEOUS ALKALI. IV. T H E CARBON-CARBON DOUBLE BOND ERWIN SCHWENK, DOMEKICK PAPA, BRADLEY WHITMAN, GINSBERG
AND
HELEN F.
Received November 1 7 , 1948
In previous work from this laboratory (1) the reduction of several compounds conhining carbon-to-carbon double bonds was reported. This reaction was further studied and examples are given in Table I for the reduction not only of conjugated double bonds but of isolated and ring double bonds as well. TABLE I REDUCTIONS WITH NICKEL-ALUMINUM ALLOY COMPOUND
1. Cinnamic acid 2. Maleic acid 3. Crotonic acid 4. Oleic acid 5. Sorbic acid 6. p-Hydroxystilbene 7. a-Phenyl-p-hydroxycinnamic acid
REDUCTION PRODUCT
Hydrocinnamic acid Succinic acid Butyric acid Stearic acid Caproic acid 1- (p-Hydroxyphenyl) -2-phenylethane p- (p-Hydroxypheny1)a-phenylpropionic acid 8. a..Phenyl-p-methoxycinnamic acid p-(p-Methoxypheny1)e-phenylpropionic acid 9 . a-(p-Methoxypheny1)cinnamic acid a-(p-Methoxyphenyl)-8-phenylpropionic acid 10. a-(p-Hydroxypheny1)cinnamic acid a-(p-Hydroxypheny1)-8-phenylpropionic acid 11. AWyclohexenylacetic acid Cyclohexanacetic acid 12. Cyclohexylidenacetic acid Cyclohexanacetic acid 13. a-(A1-Cyclohexeny1)cinnamicacid 8-Phenyl-a-cyclohexylpropionicacid 14. a-(AI-Cyclohexeny1)p-hydroxycin- 6-(p-Hydroxypheny1)-a-cyclohexylnamic acid propionic acid 15. Chaulmoogric acid Dihydrochaulmoogric acid Hexostrol, n1.p. 184-185" 16. Stilbestrol (m.p. 170-171") Hexostrol, m.p. 126-128" 17. Phenylpropiolic acid Hydrocinnamic acid 18. ~~-3(p)-Hydroxyetiocholenic acid Recovered unchanged
95 90 80 100 80 85 95 90 90 95 15 80 90 90 100 30 50
80
In all the compounds containing aliphatic chain double bonds, and a chain and alicyclic double bond in conjugation, the reduction proceeded smoothly and in good yields. An anomalous behavior was observed in the reduction of isolated ring double bonds. A6-3(~)-Hydroxyetiocholenicacid' was recovered unchanged 1 We have experienced no difficulty in reducing A4-3-ketoetiocholenic acid. A report on the reduction of this and other steroid compounds is forthcoming. 175
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SCHWENK, PAPA, WHITMdN, AND GINSBERG
and there was only about 15% reduction2 of A'-cyclohexenylacetic acid even though five times the normal amount of Raney nickel-aluminum alloy was used. That A'-cyclohexenylacetic acid reduces a t all may be due to an initial isomerization to cyclohexylidenacetic acid, which has been shown (2) to take place in an alkaline environment. In sharp contrast t o the resistance to reduction of the double bond in the two aforementioned compounds, the cyclopentene ring of chaulmoogric acid underwent quantitative reduction. \T7ith Raney nickel catalyst in alcohol, stilbestrol is hydrogenated quantitatively to the lower-melting isomer (3). However, with the nickel-aluminum alloy reduction method, both isomeric hexostrols are obtained, the higher-melting in 3091, yield, the lower-melting in 50% yield. One triple bonded compound was studied and was found to undergo complete reduction. EXPERIMENTAL
General procedure The reductions of the compounds in Table I mere carricd out as previously described (1). The yields of the reduction products are based on the reduction of 10 g. of compound and represent products purificd by distillation and/or recrystallization. All melting points are corrected. 0-(p-Methoxyphenyl)-a-phenylpropionicacid was obtained by the reduction of a-phenylp-inethoxycinnamic acid (4) as white needles from alcohol melting a t 119-120". Anal. Calc'd for Cl6Hl6Oa: C, 74. 86; H , 6.29. Found: C , 74.66; H , 6.31. cu-(p-MethoxyphenyZ)-~-pheny~propionic acid was obtained from a-(p-niethoxyphenyl) cinnamic acid as white needles melting a t 108-109" from benzene-petroleum ether. Anctl. Calc'd for C16Hl603: C, 74.86; H, 6.29. Found: C, 74.41; H , 6.45. The a-(p-methoxypheny1)cinnamicacid was prepared by heating for 6 hours a t 105-110" equimolecular proportions of potassium p-methoxyphenylacetate and benzaldehyde in acetic anhydride. The excess acetic anhydride was decomposed with water, the semisolid residue extracted with ether and the ether extracts washed free of acetic acid. The a-(p-methoxypheny1)einnamicacid was then extracted from the ether with 10% sodium carbonate. Acidification of the sodium carbonate extract gave an 80% yield. On recrystallization from benzene-petroleum ether the acid melted a t 152-153". Anal. Calc'd for C16H1103: C, 75.56; H , 5.55. Found: C, 75.22; H , 5.36. This compound has previously been prepared by another method and has been reported to melt a t 132-133" (5). a-(p-Hydroxyphenyl)-0-phenylpropionicacid was obtaincd from w(p-hydroxyphenyl) cinnamic acid and melted a t 158-159" on recrystallization from acetone and water mixture. Anal. Calc'd for C~SHIIOJ: C, 74.20; €1, 5.82. Found: C, 73.99; H , 5.79. The a-(p-hydroxypheny1)cinnamicacid was prepared as described for the corresponding methoxy compound and on recrystallization from acetone and water melted a t 221-222". Anal. Calc'd for ClbHlrOa: C, 74.96; H, 5.06. Found: C, 74.62; H, 5.11. Ten grams of A1-cyclohexenyZacetic acid was reduced using 30 g. of nickel-aluminum alloy and 500 cc. of 10% sodium hydroxide. After the reaction, the product was isolated in the usual manner and was found to be unchanged. I t was then treated with 100 g. of nickelaluminum alloy and 2 liters of 10% sodium hydroxide. After isolation of the reduction product a bromine titration showed that 85% of the material was recovered unchanged. a
Extent of reduction determined by bromine titration.
REDUCTIONS WITH NICKEL-ALUMINUM ALLOY
177
p-Phenyl-ar-cyclohoxylpropionic acid was obtained from a-(A1-cyclohexeIiyl)cinnamic asid (6) in the form of long white needles from petroleum ether and melted a t 70-71". Anal. Calc'd for C16H2002: C, 77.53;H, 8.68. Found: C, 76.99;H, 8.63. p-(p-I€ydroxyphenyl)-a-cyclohexylpropionic acid was obtained from u-(A'-cyclohexeny1)-p-hydroxycinnamic acid (6) and melted a t 180-181" after recrystallization from a mixture of acetone and water. Anal. Calc'd f o r C1~H*0OP: C, 72.53;H, 8.12. Found: C, 72.36;H , 8.08. SUMMARY
1. Examples are given of the reduction of conjugated, isolated, and cyclic double bonds using nickel-aluminum alloy and aqueous alkali. 2. An anomalous behavior was observed in the reduction of isolated cyclic double bonds. 3. An example of the reduction of a triple bond is given. 4. The reduction of stilbestrol yielded a mixture of both low-melting and highmelting isomers of hexostrol. BLOOMFIELD, N. J REFERENCES (1) For the previous publications on the use of this reduction method see: J. Org. Chem., 7 , 587 (1942);J . Org. Chem., 9,1 (1944); Znd.Eng. Chem., Anal. Ed., 16,576 (1943). (2) BEESLEY, INGOLD, A N D THORPE, J. Chem. soc., 107, 1099 (1915). AND SPIELMAN, J . Am. Chem. soc., 62, 2163 (1940). (3) DOCKEN
Gazz. chim. ital., 9, 533 (1879). (4) OGLIALORO, (5) SCHULEMANN, Bey., 60,413 (1917). AND PAPA,in manuscript. (6) SCHWENK
