GB762711A - New phenthiazine derivatives and process for their preparation - Google Patents

Abstract

The invention comprises phenthiazine derivatives of the formula <FORM:0762711/IV(b)/1> and their salts, including quaternary ammonium derivatives, wherein X represents a hydrogen or halogen atom or a methyl, methoxy, aryl or aryloxy group, R represents a hydrogen atom or a methyl, methoxy, ethyl, b -chloroethyl or benzyl group and A represents a saturated divalent straight or branched aliphatic radical containing 2 or 3 carbon atoms. Such compounds are obtained by reacting the corresponding mono- or di-N-(b -hydroxyethyl) derivative with any known reagent for replacing a hydroxy group in an aliphatic chain by a chlorine atom. Thionyl chloride, phosphorus oxychloride and phosphorus chlorides are specified. Salts, quaternary compounds and addition compounds, e.g. with 8-chloro-theophyllinates are mentioned. In Example (1) 10 - [2 - (N - b - chloroethyl - N - ethyl) - aminoethyl]-phenthiazine hydrochloride is prepared by reacting thionyl chloride with 10-[2-(N-b -hydroxyethyl - N - ethyl) aminoethyl] - phenthiazine, which is itself obtained by treating 10-(2-chlorethyl) - phenthiazine with N - ethylmonoethanolamine and copper powder. Further examples describe similar compounds having in some cases a 3-chlorine substituent and in the 10-position groups selected from 3-(N-b -chlorethyl-N-ethyl) aminopropyl, 2-(N-b -chloroethyl-N - ethyl) aminopropyl, 3 - (di - N - b - chloroethyl) aminopropyl, 2-(N-b -chloroethyl) aminopropyl, 3 - (N - b - chloroethyl) aminopropyl, 2 - (N - b - chloroethyl - N - methyl) aminopropyl, 3 - (N - b - chloroethyl - N - benzyl) aminopropyl and 2-(N-b -chloroethyl-N-benzyl) aminoethyl groups. The preparation of the N-hydroxyalkyl compounds used as starting materials by reaction of the appropriate N-chloralkylphenthiazine with a substituted ethanolamine is described. Compounds with methyl, methoxy, phenyl and phenoxy groups in the 3 position are also referred to. Other starting materials. 10-(2-Hydroxypropyl)-phenthiazine is obtained by the hydrochloric acid hydrolysis of 10-(2-tetrahydropyranyloxypropyl) phenthiazine, itself obtained by the action of 2-(2-tetrahydropyranyloxy)-1-chloropropane on phenthiazine in the presence of sodamide. 3 - Chloro - 10 - (3 - hydroxypropyl)-phenthiazine is obtained from 3-chlorophenthiazine and 3-(2-tetrahydropyranyloxy)-1-chloropropane. 3 - Chloro - 10 - (2 - hydroxypropyl)-phentiazine is obtained by the acid hydrolysis of 3-chloro-10-(2-tetrahydropyranyloxypropyl-phenthiazine, itself obtained by the reaction of 2 - (2 - tetrahydropyranyloxy) - 1 - chloropropane on phenthiazine in the presence of sodamide.