GB1162257A - 3-(5-Nitro-2-Furyl) Isoxazole Derivatives and methods of preparation thereof - Google Patents

Abstract

1,162,257. Nitrofuran derivatives. DAINIPPON PHARMACEUTICAL CO. Ltd. 20 Sept., 1966 [22 Sept., 1965], No. 41885/6. Heading C2C. Novel stable nitrofuran derivatives of formula in which R 1 represents a hydrogen atom, a C 1-4 alkyl, aryl, aralkyl, C 1-3 alkyl-carbonyl, aralkanoyl, arylcarbonyl or cyano group, a substituted or unsubstituted carbamoyl group, a C 1-3 alkoxy - carbonyl, acylamino, amino, nitro, cyanomethyl or halomethyl group, or a substituted or unsubstituted heterocyclic group of 5 or 6 ring atoms, at least one of which is a nitrogen atom; R 2 represents a hydrogen atom or a C 1-4 alkyl group; R 3 represents a hydrogen atom or a C 1-4 alkyl, C 1-3 alkoxy, C 1-4 alkylcarbonyloxy, C 1-3 , alkoxy-carbonyl or -NR<SP>1</SP>R<SP>11</SP> group, R<SP>1</SP> and R<SP>11</SP> each representing a hydrogen atom or a C 1-4 alkyl group, or R<SP>1</SP> and R<SP>11</SP> together with the nitrogen atom to which they are attached representing a substituted or unsubstituted heterocyclic ring; or R 2 and R 3 together represent a single bond; R 4 represents a hydrogen atom, a C 1-4 alkyl, aryl, aralkyl, C 1-3 alkyl-carbonyl or cyano group, a substituted or unsubstituted carbamoyl group, a C 1-3 alkoxycarbonyl, acylamino, amino, C 1-3 alkoxy, cyanomethyl or halomethyl group, a substituted or unsubstituted heterocyclic group of 5 or 6 ring atoms at least one of which is a nitrogen atom, or a C 1-3 alkoxy-methyleneamino or group; or R 1 and R 4 together with the carbon atoms to which they are attached represent a saturated ring of 5-7 carbon atoms which may contain one or more interrupting nitrogen, oxygen or sulphur ring atoms; are prepared by contacting (a) 5-nitrofuronitrile or (b) a 5-nitro- 2-furhydroxamoyl halide and a hydrogen halide acceptor, with an ethylenic compound of formula R 1 R 2 C = CR 3 R 4 in which R 1 to R 4 are as defined above except that R 2 and R 3 cannot together represent a single bond, at a temperature of 150‹ C., and optionally converting the compounds obtained into their #<SP>4</SP>'<SP>5</SP> - derivatives by elimination of hydrogen or an alcohol, carboxylic acid or amine. The #<SP>4</SP>'<SP>5</SP> -3-(5-nitro-2- furyl)isoxazoles of Formula I in which R 1 is a cyano, C 1-3 alkoxy-carbonyl or -COR group (R being C 1-3 alkyl, aralkyl or aryl) and R 4 is an amino, C 1-3 alkoxy, C 1-4 alkyl, aralkyl or aryl, are prepared by reacting a 5-nitro-2-furhydroxamoyl halide or 5-nitro-2-furonitrile oxide with at least an equimolar amount of a compound of formula Y-CH 2 -Y<SP>1</SP>, in which Y and Y<SP>1</SP> each represents a cyano, C 1-3 alkoxy-carbonyl or -COR group, in the presence of an alkali metal alkoxide or hydroxide, at a temperature of -5‹ to +100‹ C. 4,5-Dihydro-3-(5-nitro-2- furyl) - 4 - oxoisoxazole[5,4-d]pyrimidine and its 6-alkyl derivatives are prepared by reacting 5 - amino - 3 - (5 - nitro - 2 - furyl) - 4 - isoxazolecarbonamide with an alkyl orthocarboxylate of formula ZC(O-Alkyl) 3 , Z being hydrogen or alkyl. 5 - C 1-3 alkoxy - methyleneamino - 3 - (5 - nitro - 2 - furyl) - 4 - isoxazole - carbonitriles are prepared by reacting 5-amino-3-(5-nitro-2- furyl) - 4 - isoxazole - carbonitrile with a C 1-4 alkyl orthoformate. The 5-acylamino-isoxazoles of Formula I may be prepared by acylation of the corresponding 5-amino compounds. Compounds I are stated to have antiprotozoal and antibacterial activity. Ethyl 5 - amino - 3 - (5 - nitro - 2 - furyl) - 4 - isoxazole carboxylate is prepared by reacting 5-nitro-2-furhydroxamoyl chloride with ethyl cyanoacetate. 5 - Amino - 3 - (5 - nitro - 2 -furyl) - 4 - isoxazole carbonitrile is prepared by reacting 5-nitro- 2-furhydroxamoyl chloride with malonitrile. 5 - Amino - 3 - (5 - nitro - 2 - furyl) - 4 - isoxazole carbonamide is prepared by hydrolysis of the corresponding carbonitrile.