GB701741A - Improvements in or relating to the preparation of phenthiazine derivatives - Google Patents

Abstract

The process of preparing the 10-dialkyl-aminoalkyl-phenthiazines of the parent Specification is carried out using as acid binding agent an alkali metal or its hydroxide, alkoxide, hydride or alkyl, aryl or aralkyl derivative. The process is particularly applicable to compounds where the 10-substituent is-(CR1R2)n -N(R3)2, R1 and R2 being hydrogen or methyl, R3 methyl or ethyl, n 2 or 3 and the grouping (CR1R2)n containing not more than 3 carbon atoms. The dialkylaminoalkyl halide which is reacted with the phenthiazine is preferably used as a solution in an aromatic hydrocarbon (e.g. benzene, xylene or toluene) and the reaction is carried out at the boiling point of the solvent. When the group (CR1R2)n forms a branched chain isomerization takes place during the reaction giving a mixture of two products; these can be separated by conversion into hydrochlorides, fractional crystallization from alcohol and re-conversion to free bases. In the examples, (1) N-dimethyl-aminoethylphenthiazine is made by heating phenthiazine with dimethylaminochloroethane, sodium and xylene; (2) as in (1) using caustic soda and toluene; (3) as in (2) using diethylaminochloroethane; (4) as in (2) using 1-dimethylamino - 2 - chloropropane in toluene; the resulting mixture of N-(21-dimethylaminopropyl) and N-(21-dimethylamino-isopropyl)-phenthiazines is separated by fractional crystallization of their hydrochlorides from ethanol; (5) as in (4) using 1-diethylamino-2-chloropropane; (6) N-dimethylaminoethylphenthiazine is made from phenthiazine, dimethylaminochloroethane and phenyl-lithium in xylene; (7) N-diethylaminoethylphenthiazine is prepared from phenthiazine, diethylaminochloroethane and sodium t-butoxide in xylene; (8) N-diethylaminoethylphenthiazine is made from phenthiazine, diethylaminochloroethane and lithium hydride in toluene. The phenthiazine nucleus may contain alkyl or alkoxy substituents. Other specified acid binding agents are n-butyl-lithium, phenylsodium and triphenylmethyl-sodium.