Studies related to penicillins. Part 23. Preparation of the N-phenylacetyl and N-triphenylmethyl derivatives of (3R,4R)-3-amino-4-t-butylthioazetidin-2-one

Abstract

Addition of hypobromous acid to the alkene moiety of the 6-substituent of (1S, 5R)-3-benzyl-6-(2-methylprop-1-enyl)-4-oxa-2,6-diazabicyclo[3.2.0]hept-2-en-7-one (7a) was effected by the action of N-bromoacetamide in aqueous acetone. On the basis of ¹H n.m.r. spectroscopy, the resultant bromohydrin (14d) was partially converted by triethylamine in deuteriochloroform into a mixture of (1S,5R)-3-benzyl-4-oxa-2,6-diazabicyclo[3.2.0]hept-2-en-7-one (7b) and 2-bromo-2-methyl-propanal, but attempts to isolate compound (7b) were without avail.

The bromohydrin (14d) was treated with 2-methylpropane-2-thiol in dichloromethane containing triethylamine to give 2-methyl-2-t-butylthiopropanal and a 4:1 mixture of (3R,4R)-4-phenylacetamido-4-t-butylthioazetidin-2-one (6a) and its (3R,4S)-diastereoisomer (8b).

(3R,4R)-4-Methylsulphinyl-3-triphenylmethylaminoazetidin-2-one (23b) underwent thermolysis in 2-methylpropane-2-thiol to give 1-triphenylmethylimidazol-2(3H)-one (28). However, treatment of (3R,4R)-4-methylsuIphonyl-3-triphenylmethylaminoazetidin-2-one (23c) with 2-methylpropane-2-thiol and potassium t-butoxide gave a ca. 1.5:1 mixture of (3R,4R)-4-t-butylthio-3-triphenylmethylaminoazetidin-2-one (6b) and its (3R,4S)-diastereoisomer (8c). Compound (6b) was converted into the phenylacetyl derivative (6a) by a hydrolysis and phenylacetylation sequence.