GB833473A - - Google Patents

Abstract

833,473. Phenathiazines. SCHERICO Ltd. Dec. 18, 1956 [Jan. 3, 1956; Sept. 18, 1956], No. 38571/56. Class 2 (3). [Also in Group VI] The invention comprises compounds of the general formula and their salts with pharmaceutically acceptable acids, wherein A is S, SO or SO 2 ; X is a halogen or a hydrogen atom, a lower alkyl or a lower alkoxy group; Y is a lower alkylene group; Z is a hydrogen atom or a lower alkyl group; R is an unsaturated lower alkyl group, a hydroxyalkyl, an alkoxyalkyl, a hydroxyalkoxyalkyl, an acyloxyalkyl (except acetoxyalkyl), or a lower alicyclic group (" lower " in the foregoing definitions indicating that the said groups contain less than 7 carbon atoms), and the preparation thereof by reacting a compound of the general formula with a compound of the general formula wherein of P and Q one is attached directly to the relevant nitrogen atom and the other is connected to the relevant nitrogen atom through a divalent group Y<SP>1</SP>, R<SP>1</SP> and Y<SP>1</SP> standing for R and Y respectively, or for groups convertible into R and Y, respectively, and P and Q being atoms or groups of opposite polarity capable of being eliminated as the compound PQ in the course of the reaction, preferably in the presence of an acceptor for PQ, and if desired, converting the base into a salt with a pharmaceutically acceptable acid. 10-(3-Chloropropyl)-2-chloro-, -2-methyl-, and -2- methoxy - phenothiazines, 10 - (3 - chloropropyl)- phenothiazine and -2-chlorophenothiazine-5-dioxides, and 10-(5-chloropentyl}-2-methylphenothiazine are prepared from the appropriate phenothiazine and 1,3- or 1,5-bromo-chloropropane or pentane; 1-(2-chloroethyl)- and 1-(2- chloropropyl) - 4 - [3 - (10 - phenothiazyl) - propyl]-piperazines from the corresponding 1-(2- hydroxyethyl) and 1-(2-hydroxypropyl) compounds with thionyl chloride; 1-(3-chloropropyl - 4 - (2 - ethoxyethyl) - piperazine from 1- (2-ethoxyethyl)-piperazine and 3-chloropropanol after reacting the 1-(2-ethoxyethyl)-4-(3-hydroxypropyl)-piperazine so formed with thionyl chloride; 1 - (2 - hydroxyethyl) - 2,5 - dimethylpiperazine from 2,5-dimethylpiperazine and ethylene oxide; 1 - (2 - propynyl) - piperazine from properazine and propynyl bromide; 1-crotonyl- 4 - [3 - (2. chloro . 10 - phenothiazinyl) - propyl]- piperazine from the appropriate phenothiazine and crotonyl chloride; 1-(2-methylallyl)- and 1 - (3 - methyl - 2 - butenyl} - piperazines from 3 - chloro - 2 - methyl - propene or 1 - chloro- 3-methyl butene-2 and 1-carbethoxypiperazine, and hydrolysing off the carbethoxy group; and and 2 - chloro - 10 - (3 - chloropropyl) - phenothiazine - 5 - oxide by oxidation of the parent phenothiazine with hydrogen peroxide.