Patent GB-641452-A (GB)
Title: Improvements in or relating to the preparation of derivatives of phenthiazine
Filed: 1947-11-20
Abstract: Phenthiazine derivatives of the general formula <FORM:0641452/IV (b)/1> (in which R1 and R2 are hydrogen or methyl groups, R3 and R4 are the same and are methyl or ethyl groups or together represent part of a heterocyclic ring, R5 is an alkyl or aralkyl group, X is the anion of an acid, n is 2 or 3, and the total number of carbon atoms in the group (CR1R2)n does not exceed 3) are prepared either (I) by the action of R5X on the compound <FORM:0641452/IV (b)/2> or (II) by the action of NR3R4R5 on the compound <FORM:0641452/IV (b)/3> The benzene rings may contain a 3-methoxy group.  The quaternary salts obtained may be converted to the quaternary salts of other acids, e.g. by treatment in aqueous solution with an acid or salt giving a less soluble quaternary salt.  Examples are given of the preparation of the following compounds by method (I) above, 2-(phenthiazinyl-101)-1-methylethyl - trimethylammonium iodide, 2-(phenthiazinyl-101)-1 - methylethyl - trimethylammonium methosulphate, 2 - (phenthiazinyl - 101) - 1 - methylethylethyl - dimethylammonium ethosulphate, 2-(phenthiazinyl-101)-ethyl-trimethylammonium iodide, 2 - (phenthiazinyl - 101) - ethyl - trimethylammonium methosulphate, 2 - (phenthiazinyl-101) - ethyl - benzyldimethylammonium chloride, 2 - (phenthiazinyl - 101) - ethyl - methyldiethylammonium iodide, 2-(phenthiazinyl-101)-ethyltriethylammonium iodide, 2-(phenthiazinyl-101)-propyl - trimethylammonium chloride, 2-(phenthiazinyl - 101) - ethyl - trimethylammonium p-toluene sulphonate, 2-(phenthiazyl-101)-ethyltriethylammonium p-toluene sulphonate, 2-(phenthiazinyl - 101) - ethyl - triethylammonium benzene sulphonate, 2-(phenthiazinyl-101)-ethylmethylpiperidinium iodide, 2 - (phenthiazinyl-101)-ethyl-ethylpiperidinium benzene sulphonate, 2-(phenthiazinyl-101)-ethyl-ethylmorpholinium benzene sulphonate and 2-(phenthiazinyl-101)-ethyl-allylpiperidinium bromide. Examples are given also of the preparation of the following compounds by method (II) above, 2-(phenthiazinyl - 101) - ethyl - trimethylammonium iodide, 2-(phenthiazinyl-101)-ethyl-triethylammonium iodide, and 2-(phenthiazinyl-101)-ethyl-methylpiperidinium iodide. Examples are given also of the replacement of the methosulphate anion in 2 - (phenthiazinyl - 101) - 1 - methylethyl (and ethyl)-trimethylammonium methosulphate by treatment with sodium iodide in aqueous solution. Halogenoalkyl-N-phenthiazines may be prepared by the action of the lithium derivative of phenthiazine on b -chloroethyl-p-toluene sulphonate and analogous compounds. 21-Piperidinoethyl-N-phenthiazine is prepared by the action of 2-piperidino-1-chloroethane on phenthiazine in the presence of sodamide.  Specifications 608,208 and 632,277 are referred to.  The Specification as open to inspection under Sect. 91 refers also in general terms to the preparation of quaternary ammonium compounds of the above general formula in which R1 and R2 are alkyl, R3 and R4 are alkyl, R5 is a hydrocarbon group and n is an integer greater than one.  The benzene rings of the phenthiazine may be substituted by alkyl or alkoxy groups.  This subject-matter does not appear in the Specification as accepted.