Studies related to penicillins. Part V. The conversion of 6β-phthalimidopenicillanic acid into cepham derivatives

Abstract

6β-Phthalimidopenicillanoyldiazomethane (5) reacts with hydrochloric acid, methanesulphonic acid, and toluene-p-sulphonic acid to give 6β-phthalimidopenicillanoylmethyl chloride, methanesulphonate, and toluene-p-sulphonate (6; X = Cl, OMs, or OTs), respectively. 6β-Phthalimidopenicillanoyl-methane and -methyl iodide (6; X = H or l) are formed in the reactions of compound (5) with hydriodic acid and iodine, respectively. The derivatives (6; X = leaving group) undergo tertiary-amine-induced ring expansions to give mixtures of 4-isopropylidene-3-oxo-7β- and -7α-phthalimidocephams [(19) and (20)]; the ratio (19) : (20) is sensitive to the leaving group, the base, and the solvent. Abstraction of the 3-proton of compound (6; X = Cl) represents the slow step in the rearrangement.