Patent GB-340237-A (GB)
Title: A process for manufacturing 1.2.4.-triazoles
IPC: C07D249/08
Filed: 1929-09-16
Abstract: 1 : 2 : 4-Triazoles; imido compounds; oxime esters; hydrazidines.  1 : 2 : 4-Triazoles are prepared by interaction of mono-acyl-hydrazines with imido compounds of the type <FORM:0340237/IV/1> , wherein R1 and R2 represent hydrocarbon radicles, which may be connected together when aliphatic, and X is a radicle capable of combining with one of the hydrogen atoms of the acyl-hydrazine, e.g. a halogen, an ether group or an acylated hydroxy group.  Instead of the imido compounds may be employed oximes, oxime esters and monosubstituted acid amides in conditions under which they undergo intramolecular conversion into the imido compounds.  In the reaction the residue X of the imido compound is first eliminated with a hydrogen atom of the primary amino group of the acylhydrazine and the 1 : 2 : 4-triazole is then formed by elimination of water from the resulting primary hydrazidine reacting in its tautomeric form.  The reaction is preferably effected in an organic solvent or suspending agent at ordinary or elevated temperature.  The intramolecular conversion (Beckmann transformation) of the oximes, oxime esters and monosubstituted acid amides is effected with inorganic or organic acid halides, such as phosphorus oxychloride, phosphorus pentachloride, benzene sulphonic chloride and thionyl chloride. In the case of oxime esters, the Beckmann transformation may be effected after the introduction of the acyl-hydrazine; with oximes or monosubstituted acid amides, the process is advantageously effected in presence of basic substances such as pyridine. According to the Examples, (1) methylacetamide dissolved in pyridine and chloroform is first treated with phosphorus oxychloride and then with benzoylhydrazine, yielding 3 : 4-dimethyl-5 - phenyl - 1 : 2 : 4-triazole; (2) acetophenone oxime is esterified with benzene sulphonic acid chloride in chloroform solution and the ester heated with propionyl hydrazine to form 3-methyl-4-phenyl-5-ethyl-1 : 2 : 4-triazole; the same triazole is also obtained by treating acetophenone oxime in chloroform with thionyl chloride, adding propionyl hydrazine to the solution and decomposing with water, or by treating acetanilide in chloroform solution with phosphorus pentachloride, adding propionyl hydrazine, precipitating the resulting hydrazidine with caustic soda and finally decomposing the latter by heat; (3) 5-methyl-4-phenyl-1 : 2 : 4-triazole results when formanilide is treated with benzene sulphonic acid chloride in the presence of pyridine and chloroform, acetylhydrazine in alcohol added, and the mixture treated with water, neutralized and evaporated; the same triazole is also obtained by causing the imido ester of acetanilide to react with formyl hydrazine; (4) acetocyclohexylamine dissolved in pyridine and chloroform is treated with benzene sulphonic acid chloride, the resulting imido ester introduced into a solution of isovaleryl hydrazine in chloroform, and the hydrazidine formed then isolated and heated to split off water and yield 3 - methyl - 4 - cyclohexyl - 5 - isobutyl - 1 : 2 : 4 - triazole; similarly, from aceto-2 : 4-dimethylaniline and isobutyryl hydrazine, 3-methyl-4-m-xylyl-5-isopropyl-1 : 2 : 4-triazole is obtained; (5) a solution of the p-toluenesulphonic acid ester of cyclohexanone oxime is treated with acetyl hydrazine to give 3 : 4-pentamethylene-5-methyl - 1 : 2 : 4 - triazole; (6) o-methylcyclohexanone oxime is esterified with benzene sulphonic acid chloride and added to diethylacetyl hydrazine in chloroform solution; the resulting hydrazidine is isolated and heated above its melting-point to give 3 : 4 - o - methylpentamethylene-5-#c-pentyl-1 : 2 : 4-triazole; (7) benzene sulphonic acid chloride is added to a solution of e -leucine lactam in pyridine and chloroform and the lactim ester formed then added to isovaleryl hydrazine; on decomposition with water, 3 : 4-pentamethylene-5-isobutyl-1 : 2 : 4-triazole is obtained; (8) 3 : 4-diphenyl-5-methyl-1 : 2 : 4-triazole is prepared by heating phenylbenzimido ethyl ether with acetyl hydrazine; the same triazole is also obtained from the benzene sulphonic acid ester of acetophenone oxime by treatment with benzoyl hydrazine, or from the benzene sulphonic acid ester of benzophenone oxime by treatment with acetyl hydrazine; (9) propionylcyclohexylamine is treated in presence of pyridine and benzene or chloroform with benzene sulphonic acid chloride and the lactim ester produced then added to a solution of formyl hydrazine in alcohol; 3 - ethyl - 4 - cyclohexyl-1 : 2 : 4-triazole is extracted from the product; similarly, formylcyclohexylamine and propionyl hydrazine yield the same triazole; by the same process, 3-methyl-4-cyclohexyl-1 : 2 : 4-triazole is obtained from acetocyclohexylamine and formyl hydrazine, and 3-methyl-4-hexahydro-m-tolyl-1 : 2 : 4-triazole from acetohexahydro-m-toluidine and formyl hydrazine; (10) acetocyclohexylamine is treated in chloroform solution with phosphorus pentachloride and then with acetyl hydrazine in alcohol solution; 3 : 5-dimethyl-4-cyclohexyl-1 : 2 : 4-triazole is obtained; (11) acetyl-o- or -p-hexahydro-toluidine is esterified with benzene sulphonic acid chloride in the presence of pyridine and chloroform, and treated with propionyl hydrazine in chloroform; 3-methyl-4-o- or p-hexahydrotolyl-5-ethyl-1 : 2 : 4-triazole is thereby obtained. Diethylacetyl hydrazine is prepared by heating diethylacetic acid methyl ester with hydrazine.  Acyl cyclic amines.-Formylcyclohexylamine is obtained by heating cyclohexylamine with formic acid.  Similarly, acetyl-o-, -m-, and -p-hexahydrotoluidines are prepared from the corresponding amine and glacial acetic acid.