Patent GB-756937-A (GB)
Title: New derivatives of phenthiazine and their method of preparation
Filed: 1953-04-13
Abstract: The invention comprises phenthiazines containing the cation <FORM:0756937/IV(a)/1> wherein A is a saturated straight or branched chain divalent aliphatic hydrocarbon group comprising 2 or 3 carbon atoms, n is 2 or 3, R is methyl or ethyl, R1 is hydrogen, an alkyl radical comprising 1 to 4 carbon atoms, or a benzyl or acyl group, and Y is a hydrogen or halogen atom or a methyl, methoxy or phenoxy group.  The compounds are prepared (1) by heating an amine <FORM:0756937/IV(a)/2> with at least two molar proportions of a dialkylaminoalkylphenthiazine <FORM:0756937/IV(a)/3> to a temperature of 50 DEG -110 DEG  C. in a polar solvent; (2) by heating under conditions as in (1) a compound of formula <FORM:0756937/IV(a)/4> with at least one molar (preferably an equimolar) proportion of a dialkylaminoalkylphenthiazine as in (1); (3) by deacylating the reaction products from methods (1) and (2) when R1 is acyl; (4) by reducing the reaction products from methods (1) and (2) when R1 is acyl, thereby converting R1 to an alkyl or benzyl group; and (5) by converting the halogen anion in the reaction products of methods (1) to (4) to an anion of another acid by treatment with an alkali metal or silver salt of such acid.  The polar solvent mediums specified are alcohols, nitrobenzene or dimethylformamide, and preferably ethanol employed under reflux conditions.  The examples describe the preparation of 1 : 11-di-(31-chlorophenthiazinyl - 101) - 3 : 3 : 9 : 9 - tetramethyl-6 - ethyl - 6 - aza - 3 : 9 - diazanium - undecane dichloride; 1 : 11-di-(31-chloro- and 31-methylphenthiazinyl - 101) - 3 : 3 : 9 : 9 - tetramethyl - 6 - aza - 3 : 9 - diazanium - undecane dichloride hydrochloride; 1 : 11 - di - (31-chlorophenthiazinyl - 101) - 3 : 3 : 9 : 9 - tetramethyl - 6 - aza - 6 - formyl - 3 : 9 - diazanium-undecane dichloride; 1 : 11 - di - (phenthiazinyl - 101, 31 - chloro -, 31 - methyl -, 31-methoxy- and 31-phenoxyphenthiazinyl-101)-3 : 3 : 6 : 9 : 9 - pentamethyl - 6 - aza - 3 : 9-diazanium-undecane dichloride (the picrate, diperchlorate, bis-methanesulphonate, bis-paratoluenesulphonate and bis-benzoate of the 31-chloro derivative are also described); 1 : 11-di - (phenthiazinyl - 101 and 31 - chlorophenthiazinyl - 101) - 3 : 3 : 9 : 9 - tetramethyl-6 - butyl - 6 - aza - 3 : 9 - diazanium - undecane dichloride and di-iodide; 1 : 13-di-(31-chlorophenthiazinyl - 101) - 4 : 4 : 10 : 10 - tetramethyl - 7 - benzyl - 7 - aza - 4 : 10 - diazaniumtridecane dichloride; 1 : 13-di-(31-chlorophenthiazinyl - 101) - 7 - methyl - 4 : 4 : 10 : 10-tetraethyl - 7 - aza - 4 : 10 - diazanium - tridecane dichloride; 1 : 13-di-(31-chlorophenthiazinyl - 101) - 3 : 3 : 7 : 11 : 11 - pentamethyl - 7 - aza - 3 : 11 - diazanium - tridecane dichloride; 1 : 13 - di - (phenthiazinyl - 101,31-methyl-, 31-methoxy- and 31-chlorophenthiazinyl - 101) - 4 : 4 : 7 : 10 : 10 - pentamethyl-7 - aza - 4 : 10 - diazanium - tridecane dichloride; and 1 : 15-di-(31-chlorophenthiazinyl - 101) - 4 : 4 : 8 : 12 : 12 - pentamethyl-8 - aza - 4 : 12 - diazanium - pentadecane dichloride.  The amine starting materials used in method (2) are prepared from the reactants specified in method (1), using the same solvents but employing temperatures below 50 DEG  C.  2 : 21 - Dichlorotriethylamine, N : N - di-(2 - chloroethyl) - benzylamine, N : N - di - (3-chloropropyl) - methylamine and N : N - di-(2-chloroethyl)-formamide are prepared by reacting thionyl chloride with N-ethyldiethanolamine, N-benzyldiethanolamine, di-(3-hydroxypropyl)-methylamine and N : N-di-(2-hydroxyethyl)-formamide respectively.  N-Ethyldiethanolamine is prepared by reacting ethylamine with ethylene oxide. N-Benzyldiethanolamine is prepared by reacting benzyl chloride with diethanolamine.  Di-(3-hydroxypropyl)-methylamine is prepared by lithium aluminium hydride reduction of di - (2 - methoxycarbonylethyl) - methylamine.  N : N - Di - (2 - hydroxyethyl) - formamide is prepared by prolonged boiling of diethanolamine with excess of formamide.