493
~,&DIARYLPROPIONIC ACIDSAND NITRILES
Jan. 20, 1958
[CONTRIBUTION FROM THE DANIELSIEFF RESEARCH INSTITUTE, THE WEIZMANN INSTITUTE
OF SCIENCE]
Reduction and Benzylation by Means of Benzyl Alcohol. V. A New Synthesis of a,@-DiarylpropionicAcids and the Corresponding Nitriles' BY MOSHEAVRAMOFF AND Y A ~ SPRINZAK R RECEIVED JUNE 17, 1957 cu,@Diphenylacrylonitrile is converted t o a,@-diphenylpropionicacid on heating with henzyl alcoholic potassium hydroxide. The reaction involves reduction of the ethylenic bond (eq. 2), followed by hydrolysis of the cyano group (eq. 3). With other &aryl substituents, the corresponding propionic acids are formed, accompanied by a,p-diphenylpropionic acid. The presence of the latter can be accounted for by a reverse aldol condensation of the acrylonitrile (eq. 6). This side reaction is avoided by performing the reduction under anhydrous conditions. The procedure makes possible the isolation of the intermediate propionitrile in good yield. The corresponding acid can be obtained directly by adding water to the reduction mixture and refluxing to effect hydrolysis.
A method frequently used for the preparation of a,p-diphenylpropionitrile consists in treating benzyl chloride with phenylacetonitrile under anhydrous conditions2 in the presence of a strong base such as sodium amide or a metal alkoxide (eq. 1).
activated ethylenic bond are capable of being reduced by benzyl alcoholic potassium hydroxide. It was consequently thought likely that a$diarylacrylonitriles would exhibit the same property owing to the presence of the cyano group. In fact, when a-phenylcinnamonitrile was heated with the NaNHz PhCHZCl PhCHzCN PhCHzCHPhCN (1) above reagent, a,@-diphenylpropionicacid was obYields are usually low3or else the purity of the prod- tained in 7oy0yield. The reaction may be repreuct leaves much to be d e ~ i r e d . ~Few other a,@- sented by the equations diarylpropionitriles have been prepared by this KOH method.6 Several a-phenyl-@-arylpropionitriles PhCHECPhCN PhCH20H PhCHzCHPhCN PhCHO (2) have been obtained, in unspecified yields, by reduction of the corresponding acrylonitriles, readily (2PhCHO KOH +PhCHiOH PhCOzK) prepared from aromatic aldehydes and phenyl- PhCHzCHPhCN PhCHzOH 2KOH ----t acetonitrile, with sodium amalgam.6 Catalytic PhCH&!HPhCOiK PhCHzOK 4- NHs (3) hydrogenation also has been used, but the product A similar result was obtained when a-phenylseems to be of a low purity.' Hydrolysis of alp-diarylpropionitriles proceeds cinnamonitrile was replaced by an equimolecular with diEculty and requires high reaction tempera- mixture of benzaldehyde and phenylacetonitrile. tures8 An alternative route to a,@-diarylpre Under alkaline conditions these compounds conpionic acids consists in reducing the appropriate dense readily (eq. 4) to form the unsaturated niacrylic acids, prepared by the Perkin condensaKOH tion of arylacetic acids and aromatic aldehydes, PhCHO PhCHzCN -+ PhCH=CPhCN HzO (4) with sodium amalgam.6*g High yields of the saturated acids have been obtained by hydrogenating trile. Moreover, the benzaldehyde can be omitted. the acrylic acids in the presence of Raney nickel.1° In this case reaction is initiated by a small It has been shown in previous parts of this series" amount of aldehyde formed by dehydrogenation of that certain types of compounds containing an benzyl alcohollla and possibly also by its oxidation (1) Part IV, M. Avramoff and Y.Sprinzak. J . Org. Chcm., 2 2 , 571 by the cyano group.12 The quantity of benzal(1957). dehyde required for transforming the bulk of (2) Recently the remarkable observation was made t h a t a,& phenylacetonitrile into the intermediate unsatudiphenylpropionitrile could be obtained in a 50% yield by interaction rated nitrile (eq. 4) is then gradually generated in of benzyl chloride and phenylacetonitrik in the presence of aqueous sodium hydroxide and triethylamine [J. Jarrousse, Compt. rend., 832, the subsequent reduction of the latter (eq. 2). 1424 (195l)j. However, under these conditions the yield of di(3) (a) H. Janssen, A n n . , 250, 125 (1889): (b) D. Shapiro, J. Org. Chem., 14, 839 (1949); (c) C. R. Hauser and W,R . Brasen, THIS phenylpropionic acid is appreciably lower (450j0), possibly because of the self-condensation of phenylJOURNAL, 78, 494 (1956). (4) (a) M . Protiva, J. 0. Jilek and J. Pliml, Chcm. Listy, 46, 640 acetonitrile. l 3 (1951); C. A . , 47, 8069 (1953); (b) N. Campbell and E. Ciganek, The assumption that reduction of the double J . Chcm. Soc., 3834 (1956). bond precedes hydrolysis of the cyano group is (5) (a) Ng. Ph. Buu-Hoi and P. Cagniant, Rec. h a w . chim., 64, borne out by the isolation of the saturated nitrile 355 (1945); (b) H.Lettrk, W. Haede and L. Schafer, Hoppe-Seyler's 2. physiol. Chem., P89, 298 (1952). in good yield (see below). That only a negligible (6) P.C.Jocelyn, J. Chcm. Soc., 1640 (1954). amount of the saturated acid could be produced by (7) A. Dobrowsky, Monatsh.. 88, 140 (1951). an alternative sequence as shown in equation 5 is (8) D.Libermann and L. Hengl, Bull. SOC. chim. France, 974 (1951); confirmed by the observation that little a,@-diS. Rovira, Ann. chim. ( P a r i s ) . Ill] 20, 660 (1845); ref. 4h, cf. also ref.
+
___f
+
+ +
+
5a.
(9) B. B. D a y and V. S. Ramanathan, Proc. Nail. Inst. Sci. India, 9, 193 (1943); C. A . , 43, 5025 (1949). (10) (a) D. Papa, H. Breiger and V. Peterson, J. Org. Chem., 14, 362 (1948); (b) W.D. McPhee and E. S. Erickson, Jr., THIS JOURNAL, 68, 624 (1946). (11) (a) Y . Sprinzak, ibid., 78, 466 (1956); (b) M. Avramoff and Y . Sprinzak, ibid., 78, 4090 (1956); cf. also P. Mastaglli, Ann. chim. ( P a r i s ) . I111 10, 281 (1988).
PhCHECPhCN
+
+ +
+
+
+PhCH=CPhCOZH + PhCHzCHPhCOzH
(5)
(12) Reduction products, including benzylamine, dibenzylamine and lophine, have been obtained in experiments with benzonitrile (unpublished results). (13) E. F. I. Atkinaon and J. F. Thorpe, 1.Chem. Soc., 89, 1906 (1906).
MOSHEAVRAMOFF AND YAYRSPRINZAK
494
phenylpropionic acid was formed when a-phenylcinnamic acid was used as the starting material. Applying Doering's hydride ion mechanism for the reduction of carbonyl compounds by metal alkoxidesr4to the reduction of the ethylenic bond in the unsaturated nitrile, the following scheme may be written [PhCH=CPhC=N
$ 8
f)
PhCHCPhCIN
f--)
e
+ PhCH208 --+ e [PhCHpCPhCrN +-+PhCH*CPh=C=h]eT + PhCHO 63
PhCHCPh=C=N]
e
[PhCHZCPhCE-N t+ PhCHzCPh=C=h] ?
VOl. 80
ends were achieved. The procedure thus corstitutes a convenient method for the preparation of both a,@-diarylpropionitriles (Table I) and the corresponding acids (Table 11). When the latter are desired, the requisite amount of water is added to the reaction mixture after termination of the reduction, and refluxing is continued uritil the evolution of ammonia is complete. Obviously, when the starting compound is a p-phenyl-cr-arylacrylonitrile and the acid alone is required, 3 separate reduction step is not necessary, and the reaction is carried out in one step as in the case of a,@diphenylpropionic acid (see Special Procedure in the Experimental).
+ PhCHpOH --++ PhCH2CHPhCzN
TABLE1
+
8 PhCHzO
RI
\
PREPARATION OF PROPIOXITRILESCHCHCK
Resonance forms in which a carbon atom is doubly linked to carbon and nitrogen have previously been postulated for the anion of phenylacetonitrile.l6 Zwitterionic structures for the anion of a-phenylcinnamic acid, such as 03 63
PhCHCPh=C"
\
08
are apparently much less likely. "hen a-phenyl-p-methoxycinnamonitrilewas submitted to the same reaction, the expected aphenyl-@-(p-methoxypheny1)-propionic acid was formed; it was, however, accompanied by a considerable amount of a,@-diphenylpropionic acid. The latter presumably results from the liberation of phenylacetonitrile from the starting compound by a reverse aldol condensation, induced by competition of the hydroxide ions with the (reducing) benzylate ions (eq. 6). The liberated phenylaceP-CH30C6HaCH=CPhCN
/
I
R2'
r
O--CH=CH-CH=C1-CloH7 CaHa CaH6 CsHr
I
