3-methylene cephalosporanic acid derivatives and process for preparation

Abstract

Novel substituted hydrazide derivatives of 7-(substituted)amino-3-methylene-cepham-4-carboxylic acids expressed by the formula ##STR1## wherein R.sub.1 represents alkyl containing at least 3 carbon atoms, cycloalkyl, or optionally substituted aryl, and one of R.sub.2 and R.sub.3 represents hydrogen with the other being hydrogen or the same as R.sub.1 ; or R.sub.1 and R.sub.2 form a heterocyclic ring optionally through a hetero atom together with the attached nitrogen and R.sub.3 represents hydrogen atom; and Z.sub.1 represents amino or protected amino; and acid addition salts thereof, which are useful as intermediates for synthesizing cephalosporin antibiotics. These compounds can be prepared in high yields from the corresponding substituted hydrazide derivatives of 6-substituted amino-1-oxide-2, 2-dimethyl-penam-3-carboxylic acids, which are readily available at low costs, by heating them in the presence of a thermal rearrangement promotor such as organic sulfonic acids and optionally in the further presence of a tertiary nitrogen-containing cyclic compound, followed if desired by splitting off the amino-protecting group and converting the product to acid addition salts.