Preparation of 7-substituted amino-desacetoxycephalosporanic acid compounds

A process for the preparation of 7.beta.-acylamido-3-methyl-3-cephem-4-carboxylic acids by conversion of the corresponding 6.beta.-acylamido penicillanic sulfoxide acids comprising heating a 6.beta.-acylamidopenicillanic sulfoxide acid anhydride having the group --COOR.sub.3, selected from the group consisting of

• a. an acid anhydride group wherein R.sub.3 is ##STR27## wherein R.sub.4 and R.sub.5 are the same or different and each is selected from the group consisting of lower alkyl of 1 to 6 carbon atoms, cycloalkyl of 5 to 8 carbon atoms, phenyl, phenyl alkyl having 1 to 2 carbon atoms in the alkyl, lower alkoxy and lower alkylthio of 1 to 6 carbon atoms, phenoxy, phenylalkoxy containing 1 to 2 carbon atoms in the alkoxy, halogen and a 6.beta.-acylamido-penicillanylsulfoxide-3-carbonyloxy group, or R.sub.4 and R.sub.5 together form an alkylene group and M.sub.1 is selected from the group consisting of boron, aluminum and phosphorous atoms and
• b. an acid anhydride group wherein R.sub.3 has the formula ##STR28## wherein R.sub.4, R.sub.5 and R.sub.6 are the same or different and each is selected from the group consisting of lower alkyl of 1 to 6 carbon atoms, cycloalkyl of 5 to 8 carbon atoms, phenyl, phenylalkyl having 1 to 2 carbon atoms in the alkyl, lower alkoxy of 1 to 6 carbon atoms, lower alkylthio of 1 to 6 carbon atoms, phenoxy, phenylalkoxy group having 1 to 2 carbon atoms in the alkoxy, halogen and a 6.beta.-acylamidopenicillanyl sulfoxide-3-carbonyloxy group or R.sub.4 and R.sub.5 together form an alkylene group or R.sub.4 and R.sub.5 or R.sub.6 together are selected from the group consisting of =O and =S, and M.sub.2 is selected from the group consisting of silicon, sulfur, germanium and tin atoms, or a carbon atom when R.sub.4 and R.sub.6 together are selected from the group consisting of =O and =S.
• c. an acid anhydride group wherein R.sub.3 has the formula ##STR29## wherein R.sub.4 and R.sub.5 are the same or different and have the above definition, and R.sub.7 and R.sub.8 are the same or different and are selected from the group consisting of halogen and a 6.beta.-acylamido-penicillanyl sulfoxide-3-carbonyloxy group or R.sub.7 and R.sub.8 together form an alkylene group or together are selected from the group consisting of =S and =O, and M.sub.3 is selected from the group consisting of phosphorous and tungsten atoms,
• d. an acid anhydride group, wherein R.sub.3 has the formula ##STR30## wherein R.sub.9 is selected from the group consisting of lower alkyl of 1 to 6 carbon atoms, cycloalkyl of 5 to 8 carbon atoms, phenyl, phenylalkyl having 1 to 2 carbon atoms in the alkyl, lower alkoxy of 1 to 6 carbon atoms, lower alkylthio of 1 to 6 carbon atoms, phenoxy, or phenylalkoxy group having 1 to 2 carbon atoms in the alkoxy, and M.sub.4 is a sulfur atom and
• e. a group wherein R.sub.3 is selected from the group consisting of an alkali metal, alkaline earth metal ion and a cation derived from an amine in a dry inert organic solvent at a temperature up to 160.degree. C with an anhydrous acid capable of causing ring expansion of the penam ring to a .DELTA..sup.3 -cephem ring in the presence of at least one molar equivalent based on the compound of a silicon-containing compound having a formula selected from the group consisting of ##STR31## wherein X.sub.1, X.sub.2 and X.sub.3 are individually selected from the group consisting of halogen, lower alkyl of 1 to 6 carbon atoms, lower alkoxy of 1 to 6 carbon atoms, phenyl, phenylalkyl of 1 to 2 alkyl carbon atoms, cycloalkyl of 5 to 8 carbon atoms and when the X's are not halogen or alkyl, optionally substituted with a member of the group consisting of halogen, lower alkyl of 1 to 6 carbon atoms, lower alkoxy of 1 to 6 carbon atoms and di(lower)alkylamino of 1 to 6 carbon atoms, X.sub.4, X.sub.5, X.sub.6 and X.sub.7 are individually selected from the group consisting of hydrogen and hydrocarbon group of 1 to 8 carbon atoms, with no aliphatic unsaturation and X.sub.6 and X.sub.7 together with the nitrogen atom to which they are attached may form a 5- or 6-membered heterocyclic group which may contain a non-adjacent second hetero atom selected from oxygen and nitrogen, with the provisos that X.sub.6 and X.sub.7 together contain not more than 18 carbon atoms, and X.sub.6 is alkyl with a tertiary carbon atom linked to the depicted nitrogen atom, X.sub.7 is hydrogen, or X.sub.4 and X.sub.6 together with the nitrogen atoms to which they are attached and the carbonyl group complete a 5- or 6-membered heterocyclic group with an ethylene or tri-methylene group in the ring;
• X.sub.8 and X.sub.9 each are hydrocarbon of 1 to 8 carbon atoms, with no aliphatic unsaturation, X.sub.10 is selected from the group consisting of hydrogen, hydrocarbon of 1 to 8 carbon atoms with no aliphatic unsaturation and --Si.tbd.(X.sub.1, X.sub.2, X.sub.3);
• X.sub.11 is alkyl of 1 to 8 carbon atoms;
• Y is alkylene of 3 to 18 carbon atoms with 3 to 5 carbon atoms between the nitrogen atom and the carbonyl group to which Y is attached;
• and n is 1 or 2, the aforesaid acid being strong enough not to be substantially silylated under the reaction conditions employed;
• and hydrolyzing the resulting compound in situ to form a 7.beta.-acylamido-3-methyl-3-cephem-4-carboxylic acid.