Some hydrolytic reactions of beta-lactams

Abstract

This thesis describes the synthesis and alkaline ring fission of some β-lactams. Three series of β-lactams were studied: those of type (A) bearing a substituent on the ring nitrogen; 1,3,4-trisubstituted 3-lactams (B); and the spiro-3-lactams of type (C).

[See diagrams within thesis - Abstract.]

Three synthetic routes were used for the synthesis of the p-lactams, namely (a) the Reformatsky Reaction using an imine and a bromoacetate ester, (b) the cyclization of a 3-bromopropionamide, and (c) the addition of an acid chloride across an imino group. In the acid chloride-imine reaction it was shown that, contrary to previous reports, the reaction will proceed successfully with an U-benzyloxycarbonylaminoacyl chloride, and that conditions of high-dilution are not necessary in order to obtain high yields. The results of hydrolytic studies indicate that intramolecular assistance by an amido-group alpha to the β-lactam carbonyl is not of significance in the hydrolysis of these β-lactams in the conditions employed (0.1-1.0 M sodium hydroxide). Hydrolyses were also conducted in the presence of micelle forming agents and the results obtained show that the effect of these upon the rate of hydrolytic fission is dependent upon the nature of the substituenis present on the β-lactam ring.