Cephalosporanic acids. Part VI. Action of primary and secondary aromatic amines on cephalosporanic acids

Abstract

Aniline and anisidine displace the acetate group from 7β-phenylacetamidocephalosporanic acid (I; R¹= NH·CO·CH₂Ph, R²= OH, R³= OAc); if the pH is not controlled, the products may cyclize to the γ-lactams (II). If the pH is kept at 7.5 this cyclization is prevented; the vinylamines (III), which resemble the penamaldic acids, are by-products. Formation of the lactams is avoided in reactions with N-substituted anilines as nucleophiles. We have observed no products of nucleophilic attack by carbon atoms of the aromatic molecules. 7-Phenylacetamido-cephalosporanic acid reacts in acetone at 50° with aniline, to give the lactam (V). This change represents initial nucleophilic attack at the 8-position; the dihydrothiazine (V) is protected by the stability of its γ-lactam system. The result is similar to the conversion of penicillanic acids into derivatives of the penicilloic acids.