Patent GB-1210602-A (GB)
Title: New furazan derivatives, processes for their production and compositions containing them
IPC: C07D233/54
Filed: 1968-02-06
Abstract: 1,210,602. 3-Amino-4-(substituted phenyl) furazans. J. R. GEIGY A.G. 6 Feb., 1968 [7 Feb., 1967], No. 5895/68. Heading C2C. Novel 3 - amino - 4 - (substituted phenyl)- furazans of the general formula wherein R 1  is a halogen atom or a nitro, trifluoromethyl, C 1-5  alkoxy or C 1-5  alkylthio group, R 2  is a hydrogen atom or a C 1-5  alkyl or alkoxy group and R 3  is a hydrogen atom or a C 1-5  alkoxy group, are prepared (a) by reaction of a substituted phenyl-glyxoalaldoxime of the general formula or an alkali metal salt thereof with 2 mol. equivalents of hydroxylamine; (b) by reaction of a substituted phenylglyoxylonitrile oxime of the general formula or an alkali metal salt thereof with 2 molequivalents of hydroxylamine; (c) by cyclisation of a 2-(substituted phenyl)-glyoxylamide oxime derivative of the general formula wherein X 1 , X 2  and X 3  are hydrogen atoms or carboxylic acyl radicals, and optional simultaneous hydrolysis; (d) by hydrolysis of a 4- (substituted phenyl)-furazan-3-carbamic acid ester or 4 - (substituted phenyl) - 3 - acylaminofurazans of the general formula wherein X 3 <SP>1</SP> is a carboxylic acyl, alkoxycarbonyl or aryloxycarbonyl radical; (e) by reaction of a 4-(substituted phenyl)-5-nitroso-imidazole derivative of the general formula wherein R 4  is a hydrogen atom or a low alkyl group, with hydroxylamine hydrochloride; (f) by heating in a strong mineral acid a 3-(substituted benzoyl) - 1 - oxa - 2,4 - diazole oxime derivative of the general formula wherein R 5  is a C 1-5  alkyl group; (g) by subjection of a 4-(substituted phenyl)-furazan-3- carboxamide of the general formula to a Hofmann degradation; and (h) by reduction of a 3-amino-4-(substituted phenyl)- furoxan of the general formula Pharmaceutical compositions having central nervous system depressant, anti-convulsive and muscle-relaxing activity comprise, as active ingredient, a 3-amino-4-(substituted phenyl)- furazan of the first general formula above, in combination with a pharmaceutically acceptable diluent or carrier, and may be administered orally, rectally or parenterally. Substituted phenyl-glyoxalaldoximes of the second general formula above are prepared by reaction of a substituted acetophenone with butyl nitrite in the presence of ethanolic sodium ethylate. Substitued phenyl-glyoxylonitrite oximes of the third general formula above are prepared by reaction of a substituted phenylacetonitrile with butyl nitrite in the presence of ethanolic sodium ethylate. 2 - (Substituted phenyl)- glyoxylamide oxime derivatives of the fourth general formula above are prepared, e.g. by treatment of a substituted phenyl-glyoxime with chlorine in acetic acid, reaction of the resulting 1-(substituted phenyl)-2-chloroglyoxime with benzoyl chloride in benzene and treatment of the resulting O<SP>1</SP> - benzoyl - 1 - (substituted phenyl) - 2 - chloroglyoxime with ammonia. 4 - (Substituted phenyl) - furazan - 3 - yl - carbamic acid esters of the fifth general formula above, wherein X 3 <SP>1</SP> is an alkoxycarbonyl radical, are prepared by reaction of a substituted benzoyl-acetic acid lower alkyl ester with hydroxylamine, reaction of the resulting 3-(substituted phenyl) - isoxasol - 5 - one with nitrous acid, heating the 3-(substituted phenyl)-isoxazol-4- oxime-5-one thus produced in a saturated sodium carbonate solution, treatment of the resulting 3- (substituted phenyl) -furazan 4 - carboxylic acid with thionyl chloride, reaction of the corresponding carboxylic acid chloride so obtained with an alkanol, treatment of the resulting carboxylic acid ester with hydrazine hydrate, reaction of the carboxylic acid hydrazide thus produced with nitrous acid and treatment of the resulting carboxylic acid azide with an alkanol according to the Curtius method. 4 - (Substituted phenyl)-3-amido-furazans of the fifth general formula above, wherein X3<SP>1</SP> is the formyl radical, are prepared by heating a 4- (substituted phenyl)-5-nitroso-imidazole with hydroxylamine in anaqueous-alkanolic medium. 3 - Acylamino - 4 - (substituted phenyl) - furazans of the fifth general formula above wherein X3<SP>1</SP> is an alkanoyl radical are obtained by treatment of a phenacyl chloride or bromide with an alkanoylamide and ammonia, reaction of the resulting 2 - alkyl - 4 - (substituted phenyl)- imidazole with butyl nitrite in ethanolic sodium ethylate and reaction of the 2-alkyl-4-nitroso-5- (substituted phenyl)-imidazole thus produced with hydroxylamine. 3-(Substituted benzoyl)-1- oxa-2,4-diazole oxime derivatives of the seventh general formula above are prepared by treatment of a substituted phenylglyoxime with chlorine in glacial acetic acid, reaction of the resulting 1 - (substituted phenyl) - 2 - chloroglyoxime with ammonia, acylation of the 1- (substituted phenyl) - 2 amino - glyoxime so produced and condensation of the resulting O,O - diacyl - 1 - (substituted phenyl) - 2 - aminoglyoxime by heating in concentrated hydrochloric acid. 4 - (Substituted phenyl) -furazans- 3-carboxamides of the eighth general formula above are prepared by treatment of the corresponding carboxylic acid chloride with ammonia. 3 - Amino - 4 - (substituted phenyl)- furoxans of the ninth general formula above are prepared by oxidation of the corresponding 1- amino-2-(substituted phenyl)-glyoxime with an aqueous solution of a halogen or with potassium ferricyanide and ammonia in an aqueous solution. Substituted phenylacetonitriles are prepared by treatment of the corresponding benzyl alcohol with thionyl chloride and reaction of the resulting benzyl chloride derivative with sodium cyanide. 1 - Amino - 2 - (substituted phenyl)-glyoximes are prepared by reaction of the corresponding substituted phenylglyoxylonitrile oxime with hydroxylamine.