Patent GB-1265333-A (GB)
IPC: C07D501/24
Filed: 1969-02-07
Abstract: 1,265,333. Preparing #<SP>3</SP>-cephalosporins from #<SP>2</SP>-cephalosporins. ELI LILLEY & CO. 7 Feb., 1969 [7 Feb., 1968; 13 Jan., 1969 (2)], No. 33268/70. Heading C2A. #<SP>3</SP>-Cephalosporin compounds are prepared by treating a corresponding #<SP>2</SP>-cephalosporin with an oxidizing agent to convert it to the #<SP>3</SP>- cephalosporin-1-sulphoxide and then reducing the sulphoxide. The #<SP>3</SP>-cephalosporins produced have the Formula I wherein R is hydrogen, a group of formula  where X is amino, protected amino, hydroxy, C 1  to C 3  alkoxy, carboxyl or C 1  to C 3  alkanoyloxy; or R is a group of formula where X is oxygen, sulphur or a chemical bond, y is 0-2 and z is 1-3; or R is a group of formula  and Q in each of the aforesaid groups is hydrogen, CN, NO 2 , OH, Cl, Br, F, CF 3 , C 1  to C 3  alkyl, C 1  to C 3  alkoxy, α-amino-C 1  to C 3  alkyl, carboxymethyl or carboxamidomethyl; or R is a group of formula  where Y is sulphur or oxygen and each Z is hydrogen or Z and Z together with the carbons to which they are bonded complete a benzoring; or R is a group of formula where each of R<SP>1</SP> and R<SP>2</SP> is hydrogen, methyl, 2-sydnone-3-C 1  to C 3  alkanoyl, C 1  to C 10  alkanoyl, C 3  to C 10  alkenoyl, C 3  to C 7  alkyl-X-C 1  to C 3  alkanoyl where X is O or S, C 3  to C 7  alkenyl-XC 1  to C 3  alkanoyl where X is O or S, C 2  to C 10  haloalkanoyl where halo is Cl, Br or F, or C 2  to C 10  cyanoalkanoyl; and R<SP>1</SP> is cyano or -OY where Y is C 1  to C 10  alkyl, C 3  to C 10  alkenyl, C 3  to C 10  alkynyl, C 6  to C 7  cycloalkyl, C 5  to C 7  cycloalkyl-C 1  to C 3  alkyl, C 2  to C 10  haloalkyl, C 3  to C 10  haloalkenyl or C 3  to C 10  haloalkynyl, C 1  to C 3  alkyl-X-C 2  to C 6  alkyl where X is O or S, C 2  to C 4  alkanoyloxy-C 2  to C 6  alkyl, C 2  to C 4  alkanoyl-C 2  to C 6  alkyl, furyl-C 1  to C 3  alkyl, thienyl-C 1  to C 3  alkyl, 31-tetrahydrofuryl, tetrahydrofuryl-C 1  to C 3  alkyl, or phenyl, benzyl or phenethyl optionally substituted on ring carbons with C 1  to C 3  alkyl, C 1  to C 3  alkoxy, C 1  to C 3  alkoxycarbonyl, F, Cl, Br, NO 2 , CN or CF 3 ; and R<SP>11</SP> is hydrogen, a zwitterionic charge, a cation, C 4  to C 6  tert. alkyl, C 5  to C 7  tert. alkenyl, C 5 -C 7  tert. alkynyl, benzyl, methoxybenzyl, nitrobenzyl, benzhydryl, phthalimidomethyl, succinimidomethyl, trimethylsilyl or a phenacyl ester group. The corresponding #<SP>2</SP>-cephalosporin starting materials may be prepared by the process of Specification 1,265,332. The present process preferably employs oxidation with a per-acid, e.g. m-chloroperbenzoic acid, followed by reduction with sodium bisulphite or dithionite in the presence of an activator, e.g. acetyl chloride. Examples also are given for an alternative process wherein the #<SP>2</SP>-cephalosporin is partially isomerized with a base, e.g. pyridine, to give a mixture of #<SP>2</SP>- and #<SP>2</SP>-cephalosporins. Among the compounds prepared according to the invention are novel cephalosporins having the Formula I (as above), wherein R is 2-sydnone- 3-C 1  to C 3  alkanoyl, R<SP>1</SP> is -OY where Y is C 1  to C 10  alkyl, and R<SP>11</SP> is hydrogen.