Patent GB-797061-A (GB)
Title: Improvements in or relating to azaphenthiazine derivatives and their preparation
IPC: C07D513/04
Filed: 1956-06-26
Abstract: The invention comprises azaphenthiazine derivatives of the formula <FORM:0797061/IV (b)/1> which may carry nuclear halogen substituents and acid addition salts thereof (wherein <FORM:0797061/IV (b)/2> represents a dimethylamino, diethylamino, pyrrolidino, piperidino, piperazino, N1-alkyl piperazino or morpholino group, and [A] is a saturated aliphatic straight or branched chain hydrocarbon radical having a valency of 2 or 3, one valency linking it to the 10-N atom of the azaphenthiazine nucleus, said radical containing from 2 to 6 carbon atoms of which only 2 or 3 are in a straight chain between the 10-N atom and a nitrogen atom of an <FORM:0797061/IV (b)/3> group, the number of <FORM:0797061/IV (b)/4> groups being sufficient to satisfy the valencies of [A]; also processes for their preparation (a) by reacting a 10-M-substituted azaphenthiazine with a compound <FORM:0797061/IV (b)/5> where one of P and M is a hydrogen atom and the other is the grouping [A]-[X]m, X being the residue of a reactive ester, e.g. a halo atom, and n and m are both unity, or n is one when m is two, or n is two and m is one; (b) by dehydrohalogenation of a compound of formula <FORM:0797061/IV (b)/6> wherein one of W and Y is a halogen atom and the other represents the grouping <FORM:0797061/IV (b)/7> or <FORM:0797061/IV (b)/8> A is a saturated divalent aliphatic hydrocarbon radical of from 2 to 6 carbon atoms, at least 2 and at most 3 of such atoms being in a straight chain between the nitrogen atoms, and A1 is a trivalent grouping of structure <FORM:0797061/IV (b)/9> (x being 0, 1, 2, or 3).  In certain types of process (a), i.e. when [A] represents a branched chain, isomerization of the chain may take place during the reaction.  In examples: (1) 1-azaphenthiazine is treated with sodamide in boiling xylene, 1-diethylamino-2-chloroethane added and after refluxing, the mixture is acidified, the aqueous phase basified and 10-(21-diethylaminoethyl) - 1 - azaphenthiazine isolated by ether extraction and distillation, and characterized as its oxalate and picrate; (2) to (6), (9) to (11), (16), (17), (19), (21), (23), and (24) similarly are obtained the following phenthiazines: 10 - (31 - dimethylaminopropyl) - 1 - aza -, 10 - (21 - dimethylaminopropyl) - 2 - aza -, 10 - (21 - diethylaminoethyl) - 3 - aza -, 10 - (31 - dimethylaminopropyl) - 3 - aza -, 10 - (21 - dimethylaminopropyl) - 3 - aza -, 10 - (21 - diethylaminoethyl) - 6 - chloro - 3 - aza -, 10 - (31 - dimethylamino - 21 - methylpropyl) - 3 - aza -, 10 - (31 - pyrrolidinopropyl) - 3 - aza -, 10 - [31 - (411 - methyl - 111 - piperazinyl) propyl] - 3 - aza -, 10 - (31 - dimethylaminopropyl) - 4 - aza -, 10 - (21 - diethylaminoethyl) - 4 - aza -, 10 - (31 - dimethylaminopropyl) - 6 - chloro - 4 - aza -, 10 - (21 - diethylaminoethyl) - 6 - chloro - 4 - aza -, and 10 - (31 - morpholinopropyl) - 4 - aza -; (7) 3 - azaphenthiazine in xylene is treated with sodamide and then refluxed with 1,3-bis(dimethylamino) - 2 - chloropropane to yield 10-[21,31 - bis - (dimethylamino) propyl] - 3 - azaphenthiazine; similarly (8), (18), (20) and (22) are prepared the following phenthiazines: 10 - (21,31 - bis - piperidinopropyl) - 3 - aza -, 10 - (21 - dimethylaminopropyl) - 4 - aza -, 10 - [21,31-bis - (dimethylamino) propyl] - 4 - aza -, and 10 - (21 - dimethylaminopropyl) - 6 - chloro - 4 - aza-; (12) 3-(31-dimethylaminopropyl) amino-4 - (21 - bromophenyl) - mercaptopyridine, potassium carbonate and copper powder are refluxed in dimethylformamide under nitrogen to give 10-(31-dimethylaminopropyl)-3-azaphenthiazine; likewise (13) to (15) are prepared the following phenthiazines: 10-(21-dimethylaminopropyl) - 3 - aza -, 10 - (31 - dimethylaminopropyl) - 6 - chloro - 3 - aza -, and 10 - (21 - dimethylaminopropyl)-6-chloro-3-aza-.  Starting materials.  1-Aza-phenthiazine is prepared from 2-bromophenyl mercaptan and 2-chloro-3-nitropyridine via 3-nitro-2-(21-bromophenyl) mercaptopyridine, reduction of the nitro group and cylization with HBr; 3-azaphenthiazine is similarly obtained from 3-nitro-4-chloropyridine; 2-azaphenthiazine is prepared by reacting 2-aminophenylmercaptan with 3-nitro-4-chloropyridine and cyclizing the resulting 3-nitro-4-(21-mercaptophenyl) aminopyridine with KOH; 3-(31-dimethylaminopropyl) amino - 4 - (21 - bromophenyl) mercaptopyridine is obtained by condensation of 1-dimethylamino-3-chloropropane with 3-amino-4-(21 - bromophenyl) mercapto - pyridine in the presence of sodamide; 3-(21-dimethylaminopropyl) amino - 4 - (21 - bromophenyl) mercaptopyridine, 3 - (31 - dimethylaminopropyl) amino - 4 - (21 - bromo - 41 - chlorophenyl) - mercapto - pyridine, and 3 - (21 - dimethylaminopropyl)-amino - 4 - (21 - bromo - 41 - chlorophenyl) mercapto-pyridine are likewise prepared.