GB797628A - 10-dialkylaminoalkylphenothiazine-9-oxide derivatives and a process for their production - Google Patents

Abstract

The invention comprises 3-halogeno-9-oxyphenthiazines of the formula <FORM:0797628/IV (b)/1> (wherein X represents chlorine or bromine, A is a divalent hydrocarbon radical containing 2 to 4 carbon atoms, and R1 and R2 represent methyl or ethyl radicals), acid addition salts thereof, and processes for their preparation by: (a) oxidation of an acid addition salt of the corresponding 3 - halogeno - 10 - dialkylamino - alkylphenthiazine with hydrogen peroxide or an organic peracid; (b) oxidation of a 3-halogenophenthiazine with hydrogen peroxide or an organic peracid and reaction of the resulting 9-oxide with an amino-alkyl halide of formula Y.A.NR1R2 (Y represents a halogen atom) in the presence of a hydrogen halide acceptor. Specified acid addition salts include those with hydrochloric, sulphuric, hydrobromic, phosphoric, nitric, picric, maleic, tannic, acetic, oxalic, succinic, tartaric, citric, and malonic acids. The oxidation is preferably effected between 50 DEG and 100 DEG C. in methanol, ethanol, acetic acid, acetone, aqueous acetone or mixtures of these solvents, using hydrogen peroxide, peracetic or perbenzoic acid, and in neutral or acid conditions when a 10-substituent is present. The reaction with Y.A.NR1R2 is preferably carried out in benzene, toluene or xylene in the presence of sodamide, or an alkali alkoxide, alkali metal, or alkali metal hydroxide. In examples: (1) 3-chlorophenthiazine in methanol or ethanol is treated with 35 per cent hydrogen peroxide yielding 3-chlorophenthiazine-9-oxide, which is treated with sodamide and then refluxed with dimethylamino-g -chloropropane in xylene to give 10-(31-dimethylaminopropyl)-3-chloro-phenthiazine-9-oxide, characterized as its picrate, hydrochloride, oxalate, maleate, citrate and tartrate; (2) 10-(31-dimethylaminopropyl) - 3 - chlorophenthiazine hydrochloride in boiling methanol is treated dropwise with hydrogen peroxide, the mixture concentrated, basified and 10 - (31 - dimethylaminopropyl) - 3 - chlorophenthiazine - 9 - oxide extracted with benzene; (3) and (4) as in (2), commencing with the sulphate and oxalate salts respectively.