GB1360006A - Process for producing 6-methylenetetracyclines and 6-deoxytetra cyclines - Google Patents

Abstract

1360006 6 - methylene and 6 - deoxy tetracyclines I VILLAX 28 June 1971 [3 July 1970 (3) 3 May 1971] 30120/71 Heading C2A In a process for dehalogenation or simultaneous dehalogenation and reduction at C6- of an 11a-chloro-6-doexy-6-demethyl-6-methyllenetetracycline, the 11a - chloro - derivative is dehalogenated at C11a by an equimolecular amount of hydrazine to yield the respective 6 - deoxy - 6 - demethyl - 6 - methylene - tetracyclines, or simultaneously dehalogenated at C11a and reduced at C6 by at least two equimolecular amounts of hydrazine to yield the respective 6 - deoxy - tetracyclines, in the presence of catalytic amounts of a noble metal catalyst such as palladium, platinum or rhodium in a reaction-inert medium, and the compounds thus formed are recovered subsequently from the reaction mixture. The 11a-chlorotetracyclines may be further substituted and suitable reaction-inert media are aliphatic alcohols and dialkyl formamides. If 5-hydroxy-tetracyclines are employed, it is preferable to use anhydrous conditions to avoid the formation of the degradation product 5-12a lactone. The starting tetracyclines may be in the form of free base, acid addition salts, e.g. hydrochloride, hydrofluoride, p-toluenesulphonate or N,N<SP>1</SP>- dibenzylethylene diamine or N,N<SP>1</SP> - dibenzylethylenediimine molecular complexes. The two last-mentioned complexes may be prepared by reacting 11a-chloro-6-deoxy-6-demethyl-6- methylenetetracyclines with N,N<SP>1</SP> - dibenzylethylenediamine or N - N<SP>1</SP> - dibenzylethylenediimine in a reaction inert medium at a pH adjusted to between 3À5 and 7À5 with ammonia; or the corresponding alkaline earth metal complexes may be prepared when the pH is adjusted with an alkaline earth metal hydroxide. The process for preparing 6-deoxy-tetracyclines is particularly suitable for obtaining predominantly the α-isomer.