Verfahren zur Herstellung von Derivaten von Cephalosporin C

1,208,015. Cephalosporins. GLAXO LABORATORIES Ltd. 12 March, 1968 [23 March, 1967], No. 13868/67. Heading C2A. [Also in Division A5] The invention comprises 3 - azido - methyl - 7 - arylglyoxamidoceph - 3 - em - 4 - carboxylic acids of formula in which Ar is a carbocyclic or heterocyclic aromatic group; their salts and α - carbonyl derivatives.- Ar may be thienyl, furyl, pyrrolyl, pyridyl thiazolyl, 1 - naphthyl, 2 - phenanthryl or where R is amino, substituted amino, halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkoxycarbonyl, nitro or cyano, n is zero or 1 to 4 and the groups R are the same or different when n is greater than 1. Typical compounds are 3 - azidomethyl - 7 - phenylglyoxamido ceph - 3 - em - 4 - carboxylic acid and 3 - azidomethyl - 7 - (p - acetamidophenylglyoxamido) - ceph - 3 - em - 4 - carboxylic acid. The α - carbonyl derivatives specified are the oxime, semicarbazone, thiosemicarbazone, isonicotinoyl hydrazone, hydrazone and methoxime. Salts are formed with alkali metals, alkaline earth metals, organic bases, acids (when Ar contains a basic group) and with resins e.g. polystyrene resin containing amino, quaternary amino or sulphonic acid groups or a resin containing carboxyl groups e.g. a polyacrylic acid resin. The cephalosporins are produced by reacting a compound of formula in which Y is H or ArCO.CO- and Ar is an aromatic or heterocyclic aromatic group, with a nucleophilic reagent serving to replace the acetoxy group by an azide group (e.g. as in Specification 1,012,943) and, when Y is hydrogen, acylating the resulting 3 - azidomethyl derivative with an aromatic or heterocyclic aromatic glyoxylic acid or a reactive derivative thereof e.g. acid halide, anhydride, mixed acid anhydride, activated ester or reactive azide. The cephalosporins are antibiotics which can be administered orally (see Division A5).