GB1355791A - Process for the preparation of cephalosporanic acid derivatives application - Google Patents

Abstract

1355791 Preparation of cephalosporanic acid compounds KONINKLIJKE NEDERLANDSCHE GIST-EN SPIRITUSFABRIEK NV 19 April 1971 [18 Feb 1970 23 July 1970] 7892/70 and 35796/70 Heading C2A [Also in Division C3] The invention comprises a process for the transformation of a 6-substituted aminopenicillanic sulphoxide in the form of an acid or a derivative thereof, including a thiocarboxylic acid derivative, salt, ester or amide, into a 7- substituted aminodesacetoxycephalosporanic derivative characterized in that the penicillanic sulphoxide compound is heated up to a temperature not greater than 160‹ C. under anhydrous conditions in the presence of at least one nitrogen containing organic base and a silicon compound having a silicon-halogen bond, at least 5 moles of base being present for each mole of penicillanic sulphoxide compound. The penicillanic sulphoxide starting material may be of the general Formula I and the 7-substituted amino-desacetoxycephalosporanic acid derivative obtained as product may be of the Formula II wherein R 1 represents a group linked to the nitrogen atom by a carbon or sulphur atom, R 2 represents a hydrogen or an alkyl or phenylalkyl group, or R 1 and R 2 together with the nitrogen atom to which they are attached represent a heterocyclic group which may carry one or more substituents, and R 3 represents (a) a radical linked to the carbon atom by nitrogen, the nitrogen atom having attached to it atoms or groups selected from hydrogen, alkyl and aryl groups or a combination of two carbonyl groups on the nitrogen atom may be joined through the agency of a phenyl group; or R 3 represents (b) a group -SR 4 wherein R 4 is hydrogen, alkyl or phenyl; or R 3 represents (c) a group -OR 5 wherein R 5 is hydrogen, a cation which is preferably pharmaceutically acceptable, an alkyl group, a cycloalkyl group containing 4 to 7 carbon atoms, phenyl, phenylalkyl or diphenylalkyl or aroylalkyl group, the alkyl radicals of which contain 1 or 2 carbon atoms, or a stannyl group (R 6 R 7 R 8 )#Snwherein R 6 , R, and R 8 each represent an alkyl group, a phenyl group or a phenylalkyl group containing 1 or 2 carbon atoms in the alkyl radical, or a silyl group (R 9 R 10 R 11 )#Siwherein R 9 , R 10 and R 11 each represent a halogen atom, an alkyl group, phenyl or phenylalkyl group containing one or two carbon atoms in the alkyl radical, or one of R 9 , R 10 and R 11 represents the group connected to symbol R 3 in Formula II and linked via oxygen to the silicon atom, the alkyl and aryl groups within the definitions of R 2 and R 3 optionally carrying as substituents halogen atoms and in the case of aryl groups, alkyl, alkoxy or dialkylamino groups. The invention also comprises 6-aminopenicillanic sulphoxide silyl esters of the general Formula III wherein R 1 and R 2 are as previously defined, Y 1 , Y 2 and Y 3 each may be the same or different and each represents a halogen atom, an alkyl group, or a phenyl or a phenylalkyl group containing one or two carbon atoms in the alkyl radical, the alkyl and phenyl groups optionally carrying substituents such as halogen atoms and, in the case of phenyl groups, alkyl, alkoxy, or dialkylamino groups or one of Y 1 , Y 2 and Y 3 represents the 6-aminopenicillanyl-carbonyloxy group attached to the silicon atom in the formula. Particular examples of these compounds are benzylpenicillin sulphoxide trimethylsilyl ester, benzylpenicillin sulphoxide dimethyl chlorosilyl ester, di-(benzylpenicillin sulphoxide)dimethylsilyl ester, phenoxymethyl. penicillin sulphoxide trimethylsilyl ester, phenoxymethylpenicillin dimethylchlorosilyl ester and di-(phenoxymethylpenicillin sulphoxide) dimethylsilyl ester. Reference has been directed by the Comptroller to Specification 1,174,335.