Vol. s1
6286 [CONTRIBUTION FROM
THE
RESEARCH LABORATORIUM DR.
c. JANSSEN]
Acylation and Tosylation of Substituted 3,3-Diphenyl-A1-pyrrolines BY PAULJ. A. DEMOEN, PAULA. J.
JANSSEN A N D JOZEF
L. h4. LOOXANS
RECEIVED APRIL 29, 1959 Acylation or tosylation of 2-alkyl-substituted 3,3-diphenyl-A1-pyrrolines gives N-acylated or N-tosylated exo-unsaturated pyrrolidines. Scid hydrolysis of these pyrrolidines results in the formation of open-chain amidoketones. Benzoylation of 2,3,3-triphenyl-A1-pyrroline in the presence of excess alkali immediately gives the corresponding amidoketone. The amidoketones can be considered as possible metabolites of normethadone and related basic ketones.
Introduction With the other reagents, the 2-alkyl-substituted The literature dealing with the acylation of pyr- A'-pyrrolines (I, K = CH3, C2H5)yielded crystalrolines is rather restricted and, moreover, is not in line products identified as exo-unsaturated, Nagreement as to the exact structure of the products. acylated or S-tosylated pyrrolidines (11) by infraKohler and Drake' reduced y-nitro-p-phenyl- red spectrophotometry. On the other hand, 2,3,3-triphenyl-A1-pyrroline butyrophenone catalytically and obtained oily did not react. products which could not be distilled. After treatThe pyrrolines I also were treated with benzoyl ment with benzoyl chloride in the presence of excess potassium hydroxide solution, a substance was chloride in the presence of excess sodium hydroxide , ~2,4formed with m.p. 179-1SOo, which was believed solution, as described by Kloetzel, et ~ l . for diphenyl-A'-pprroline. Again, the 2-alkyl-substito be N-benzoyl-2,4-diphenyl-A2-pyrroline. Rupe and Gisiger2 obtained the same product tuted A'-pyrrolines afforded the exo-unsaturated (m.p. 1SOO) from benzoyl chloride and the reduc- pyrrolidines I I , whereas 2,3,3-triphenyl-A1-pyrtion product of P-cyano-P-phenylpropiophenone. roline yielded a small amount of the arnidoketone (111, K = C6H5,R' = COCsH5),in addition to the Acetylation of the same reduction product gave the hydrochloride of the starting material (I, R = corresponding N-acetyl derivative, m.p. 105". Ce"). Kloetzel, et u Z . , ~ showed that a A1-pyrroline is The exo-unsaturated pyrrolidines (11) are riot formed by reduction of y-nitro-P-phenylbutyrobasic when titrated with perchloric acid in glacial phenone over Raney nickel. Benzoylation of 2,4acetic acid. Their infrared spectrum shows a diphenyl-A1-pyrroline, as above, afforded the amidoketone y-benzoylamino-/3-phenylbutyrophe- sharp absorption peak a t about 6.1 p (amide C=O), none, m.p. 182-183'. Acetylation of the same pyr- and no NH- stretching frequency around 3 p . roline gave the corresponding N-acetylaminoTABLE I ketone, m.p. 105O. From the similarity of the IXPKAKED SPECTRAa OF N-ACYLPYRKOLIDINES (11) melting points, Kloetzel, et al., concluded that the R' also had isolated the ainidoearlier I ketones. In the present paper, acylations and tosylation (C6H5)2 of 2-R-3,3-diphenyl-A1-pyrrolines (I, R = methyl, Ahsurpliun maxima ( H ) in the 5.5-7.0 p rcgioii ethyl and phenyl) are described. The A1-pyrrolines RIRsC= were prepared by Grignard reaction on 2,2-diSkeletal C = C CHRs or RiR?C= 1-Amide vibrations in phenyl phenyl-4bromobutyronitrile. K K' CHz carbonyl groups
m
COCHa 3.99 6.13 6.27* 6.73 6 . 9 2 COCIIB 5.96 6.06 6.30* 6.72 6.95 COC& 5.99 6.13 (3.31 6.75 6.97 SOzCsHaP-CHI 6.07 .. 6.30 6.74 6.94 a One mg. in a 300-mg. KBr dis.; thickness about 0.9 n m . * Shoulder.
CH2 CHsCI1 CI-IsCH CHaCfI
fJ \
I11
Results and Discussion 2-AIethyl- or 2-ethyl-3,3-diphenyl-A1-pyrroline and 3,3,3-tripheny1-A1-pyrroline were acylated at 100O with acetic anhydride, propionic anhydride, acetyl chloride, p-toluenesulfonyl chloride and benzoyl chloride in the presence of isopropyl alcohol or benzene or without a ~ o l v e n t . ~ With benzoyl chloride, no pure reaction products could be isolated. N.L. Drake, ' h i s JOURNAL, 45, 2144 (1923). (2) H. Rupe and F. Gisiger, Hels. Chim. A d a , 8, 338 (1925). (3) M. C . Kloetzel, J . L. Pinkus and R. M. Washburn, THISJ O U R NAI., 79, 4222 (1957). (4) P. J. A . Demoen and P. A. J. Jansscu, ibid., 81, 628i (1:JX). (1) E. P. Kohler and
The terminal methylene group was identified in K-acetyl-2-methylene-3,3-diphenylpyrrolidine (11, I< = CH2, R' = COCH3) by near-infrared spectrophotometry: a 10% solution of the colfipound in carbon tetrachloride showed a sharp absorption peak at 1.72 p ( E 0.40) and another one a t 2.22 p ( e 1.70). The starting material (I, R = CH,), on the other hand, showed nearly rectilinear background absorption between 1.70 and 1.75 /* (c1.7? 0.05), and an absorption peak at 2.23 1.1 ( E 1.50). The corrected molar absorption values for the pyrrolidine (11, I< = CH2, I
