Patent GB-705310-A (GB)
Title: 5-aralkylamino-9-dialkylamino benzo (a) phenoxazine compounds and method of preparing same
Filed: 1951-08-28
Abstract: The preparation of a number of intermediates in the manufacture of 5-aralkylamino-9-dialkylaminobenzo (a) phenoxazines (see Group IV (c)) is described.  2- Nitroso-5-dipropylaminophenol hydrochloride is made by heating m-aminophenol with n-propyl bromide in ethanol solution to yield m-dipropylaminophenol which on treatment with sodium nitrite in hydrochloric acid yields the required hydrochloride.  2-Amino-5-dipropylaminophenol dihydrochloride is made by treating 2-nitroso-5-dipropylaminophenol hydrochloride with an acidic solution of stannous chloride and hydrogen chloride. 3-Dibutyl-and 3-diamylaminophenols are made by heating an ethanol solution of m-aminophenol with n-butyl or n-amyl bromides respectively.  3-Ethylpropylaminophenol is made by heating an ethanol solution of 3-ethylaminophenol with propyl bromide and is converted to 2-nitro-5-ethylpropylaminophenol hydrochloride by treatment with sodium nitrite in hydrochloric acid solution. m-Ethylhexylaminophenol is made by heating an ethanol solution of m-aminophenol with hexyl bromide, isolating and heating the product in ethanol solution with ethyl bromide. 3-Ethylpropylamino-4-methylbenzene sulphuric acid is made by treating N-ethyl-o-toluidine with n-propyl bromide, isolating and treating the product with oleum. 2- Nitroso-4-methyl-5-ethylpropylamino phenol hydrochloride is made by adding the sulphuric acid of the last sentence to a melt of potassium hydroxide at 290-310 DEG C., diluting, acidifying with hydrochloric acid and treating with sodium nitrite and a saturated alcoholic solution of hydrogen chloride.ALSO:The invention comprises benzo (a) phenoxazines of formula <FORM:0705310/IV(c)/1> where R1 is an alkyl group of 3-6 C atoms, R2 i an alkyl group of 2-5 C atoms, R3 is phenyl or halogen, alkyl, alkoxy, and alkylenedioxy substituted phenyl and R4 and R5 are H or alkyl radicles containing up to 6 C atoms, and their addition salts with acids.  Hydrochloric, hydrobromic, nitric, sulphuric and phosphoric acids are specified for salt formation.  Substituted phenyl radicals specified are 3-methoxy-, 2, 3-amethylene-dioxy-, 1, 3-dichloro-, 3-bromo- and 1-chloro-phenyl.  The salts may be made by heating under acid conditions to effect ring closure the appropriate 2-amino-5-dialkylaminophenol acid addition salt with a 4-benzylamino-1, 2-naphthol quinone, or preferably the appropriate 2-nitroso-5-dialkylamino-phenol with an N-benzyl-a -naphthylamine. The free base may be liberated from the salts.  The compounds have antituberculor activity.  In Examples (1) and (6) 5-benzylamino-, (2) 5-(4-methylbenzylamino)-, (3) 5-(4-chlorbenzylamino)-, (4) 5-(3, 4-methylenedioxybenzylamino)- and (5) 5-(2-chlorbenzylamino)-, 9-dipropylaminobenzo (a) phenoxazonium chloride, (7) 5-benzylamino-, (8) 5'-(4-methylbenzylamino)-and (9) 5-(4-chlorobenzylamino)-9-dibutylaminobenzo (a) phenoxazonium chloride, (10) 5-(3, 4-methylenedioxybenzylamino)-9-dibutylaminobenzo (a) phenoxazonium nitrate, (11) 5-benzylamino-9-diamylaminobenzo (a) phenoxazonium chloride and (12) the corresponding free base, (13) 5-(4-chlorobenzylamino)-9-diamylaminobenzo (a) phenoxazonium chloride and (14 the free base, (15) 5-(4-methylbenzylamino)-9-diamylaminobenzo (a) phenoxazonium nitrate, (16) 5-(4-methoxybenzylamino)-9-diamylaminobenzo (a) phenoxazonium chloride (17) 5-benzylamino-9-ethyl-propylaminobenzo (a) phenoxazonium chloride, (18), 5-(4-chlorobenzylamino)-9-ethylpropylaminobenzo (a) phenoxazonium chloride, (19) 5-benzylamino-9-ethyl-hexylaminobenzo (a) phenoxazonium chloride, (20) 5-(chlorobenzylamino)-9-ethylhexylaminobenzo (a) phenoxazonium chloride, (21) 5-(4-chlorobenzylamino)-9-ethylpropylamino-10-methylbenzo (a) phenoxazonium chloride and (22) 5-benzylamino-9-ethylpropylamino-10-methylbenzo (a) phenoxazonium chloride are made by the methods outlined above.  Specification 680,496 is referred to.