DK129166C

1314628 Preparing penicillin sulphoxides ELI LILLY & CO 5 Aug 1971 [10 Aug 1970] 36912/71 Heading C2A Pencillin sulphoxides of formula, wherein R is hydrogen, a unit negative charge or a non-oxidizable ester forming group, R 2 is methyl or C 2 to C 5 alkanoyloxymethyl, and R 1 is NH+ 3 , protected amino, phthalimido or an acylamino group of formula wherein X is hydrogen, methyl or ethyl, Y is hydrogen, methyl, hydroxy, NH+ 3 or protected amino, P is phenyl or substituted phenyl or C 1 to C 5 alkyl, n is 0 or 1, and when n is 1, P is phenyl or substituted phenyl and Y is hydrogen or methyl and when n is 0 and Y is hydrogen, hydroxy, NH+ 3 or protected amino, X is hydrogen, with the limitation that when R 1 does not include an NH+ 3 group, then R is hydrogen or a non-oxidizable ester forming group, are prepared by oxidizing a penicillin of formula wherein R, R 1 and R 2 are as previously defined, with ozone in a reaction-inert solvent at - 10‹ to 35‹ C. The term "non-oxidizable ester forming group" is defined as a conventionally employed carboxylic acid protecting group which is unreactive with ozone under the specified reaction conditions, e.g. benzyl, benzhydryl, p-nitrobenzyl, 2,2,2-trichloroethyl, t-butyl and methyl. "Substituted phenyl" refers to a group of formula in which R 3 is C 1 to C 4 alkyl, C 1 to C 4 alkoxy, halogen, hydroxy, nitro, NH+ 3 or protected amino, and m is 1 or 2. Suitable inert solvents are water, aqueous or non-aqueous acetone, methanol or ethanol, chlorinated hydrocarbons, and esters such as ethyl and isopropyl acetate. The ozone is provided as ozonized oxygen produced by a conventional electrical discharge procedure. The oxidation yields a mixture of the α- and #-sulphoxides in varying proportions; these isomers may be separated from each other by chromatography on silica gel. The sulphoxides may be converted to analogous cephalosporin compounds by heating under acid conditions according to a known process.