Patent GB-899014-A (GB)
Title: New derivatives of phenoxazine and processes for their production
Inventor: GIRARD ANDRE
IPC: C09B19/00
Filed: 1960-03-14
Abstract: The invention comprises compounds of the formula <FORM:0899014/IV (b)/1> (wherein R1 and R2 are alkyl groups of 2 to 5 carbon atoms and R3 and R4 are alkyl groups of 2 to 5 carbon atoms or together with the adjacent-nitrogen atom form a piperidine or pyrrolidine ring) and acid addition salts thereof; and their preparation by reducing a 2-nitroso-5-NR3R4-phenol to the corresponding 2-amino-5-NR3R4-phenol, condensing this with a 1 : 3-dihalogeno - 4 : 6 - dinitrobenzene to form a 3 - halogeno - 4 : 6- dinitro - 21 - hydroxy - 4 1 - NR3R4-diphenylamine, aminating this to yield a 3 - NHR1 - 4 : 6 - dinitro - 21 - hydroxy - 41 - NR3R4-diphenylamine, reducing and cyclizing this to form a 2-amino-2-NHR1-7-NR3R4-phenoxazine, oxidising this to a compound of the formula <FORM:0899014/IV (b)/2> and alkylating this to give the desired product.  The phenoxazine is advantageously oxidized in solution by bubbling air therethrough and the final alkylation may be achieved either by aminolysis, e.g. treating a salt of the phenoxazine with an excess of the appropriate amine R2NH2, or, where R2 is a branched chain alkyl group of 3 to 5 carbon atoms, by condensing the phenoxazine with a ketone r-CO-r1 (r and r1 being methyl or ethyl groups) to give a compound of the formula <FORM:0899014/IV (b)/3> and cleaving the imidazole ring of this by hydrogenation.  The invention also comprises an alternative process for the preparation of the compounds of the invention wherein 6-nitro-benz-imidazole is alkylated to obtain 6-nitro-N1-alkylbenzimidazole, this, preferably as the sodium or potassium derivative, is reacted with alkyl halide to give a compound of the formula <FORM:0899014/IV (b)/4> (X being a halogen atom), this is treated with a strong alkali to yield a 1-NHR1-2-NHR2-4-nitro-benzene, this is reduced to a 1-NHR1-2-NHR2-4-amino-benzene and this is condensed with a 2-nitroso-5-NR3R4-phenol to yield the desired product.  Examples are given.  N - (3 - hydroxy - 4 - nitroso - phenyl) - piperidine hydrochloride is prepared by nitrosation of N-(3-hydroxyphenyl)-piperidine.ALSO:The invention comprises compounds of the formula <FORM:0899014/IV (c)/1> (wherein R1 and R2 are alkyl groups of 2 to 5 carbon atoms and R3 and R4 are alkyl groups of 2 to 5 carbon atoms or together with the adjacent nitrogen atom form a piperidine or pyrrolidine ring) and acid-addition salts thereof; and their preparation by a process the last two stages of which comprise oxidizing a compound of the formula <FORM:0899014/IV (c)/2> to give a compound of the formula <FORM:0899014/IV (c)/3> and alkylating this either directly by aminolysis with the appropriate amine R2NH2 or, where R2 is a branched alkyl group of 3 to 5 carbon atoms, by condensing the phenoxazine with a ketone r-CO-r1 (r and r1 being methyl or ethyl) to give a compound of the formula <FORM:0899014/IV (c)/4> and cleaving this by hydrogenation.  Alternatively, they may be prepared by condensing an appropriate 1, 2 - di (monoalkylamino) - 4 - amino - benzene with an appropriate 2-nitroso-5-dialkylamino-phenol.  Examples are given.