GB774882A - Improvements in or relating to phenthiazine derivatives - Google Patents

Abstract

A process for the preparation of compounds of the formula: <FORM:0774882/IV(b)/1> and their salts including quaternary ammonium compounds wherein the -CH2- bridge is directly connected to a ring carbon atom of the piperidine nucleus, preferably in the 3- or 4-position, at least one of the benzene rings of the phenthiazine nucleus may contain a halogen, alkyl, alkoxy, phenyl or phenoxy substituent group, preferably in the 3-position and R represents a hydrogen atom or an alkyl group containing not more than 4 carbon atoms or a benzyl group, comprises reducing a phenthiazine compound of the general formula: <FORM:0774882/IV(b)/2> (wherein Hal represents a halogen atom and the phenthiazine nucleus may be substituted as aforesaid) by the application of known methods for the reduction of pyridine derivatives to the corresponding piperidine derivatives. The reduction may be effected catalytically, suitably with an Adams platinum catalyst in absolute ethanol (at ordinary or increased temperature and pressure) or in aqueous alcohol (at increased temperature and pressure). Substituents on the piperidine nitrogen atom may be present in the starting material or be introduced by alkylation processes. In Example (1): 1-methyl-3-(101-phenthiazinylmethyl)-pyridinium iodide is hydrogenated in absolute ethanol in presence of Adams platinum catalyst to give 1-methyl-3-(101-phenthiazinylmethyl)-piperidine hydriodide from which the free base, hydrochloride and picrate are prepared. Similarly obtained are 3-methyl - 10 - (1 - methyl - 3 - piperidyl) - methylphenthiazine; (3) 3 - chloro - 10 - (1 - methyl-3 - piperidyl) methylphenthiazine; (4) 3-methoxy - 10 - (1 - methyl - 3 - piperidyl) methylphenthiazine; (5) 10 - (1 - benzyl - 3 - piperidyl) methylphenthiazine; (6) 3 - chloro-10 - (1 - methyl - 4 - piperidyl) - methylphenthiazine; (7) 10 - (1 - methyl - 4 - piperidyl) methylphenthiazine. In Example (8): 10-(31-pyrdylmethyl)-phenthiazine hydrochloride is hydrogenated in an autoclave at 60-90 kg/cm.2 pressure and 60 DEG C. to give 10-(31-piperidylmethyl)-phenthiazine which is recovered as the methanesulphonate. Starting materials of the second formula above are obtained by the action of a halogenomethylpyridine, preferably in the presence of a condensing agent, on the appropriate phenthiazine and reaction of the product with a compound R Hal. In this manner are prepared 10 - (31 - pyridylmethyl) - phenthiazine and corresponding compounds having 3-methyl, chloro and methoxy substituents, 3-chloro-10-41 - pyridylmethyl) - phenthiazine and 10-(41-pyridylmethyl) - phenthiazine and quaternary compounds of these bases, for use in the above examples. Specification 774,883 is referred to.