A method of obtaining a bis-1,2-(1,2,4-triazole-1-yl)ethane

 

(57) Abstract:

The invention relates to the field of chemical technology, in particular to methods of producing bis-(1,2,4-triazole-1-yl)alkanes, and can be used for the production of biologically active substances. Describes how to obtain bis-1,2-(1,2,4-triazole-1-yl)ethane using alkylation of 1,2-dibromethane in the solvent by heating, characterized in that the alkylation is subjected to 4-amino-1,2,4-triazole at 95-105C, the solvent used is N, N'-dimethylformamide, followed by deamination. The technical result is the reduction of the process time while increasing the yield of the target product. 1 table, 1 Il.

The invention relates to the field of chemical technology, in particular to methods of producing bis-(1,2,4-triaal-1-yl)alkanes, and can be used for the production of biologically active substances.

Known methods for producing bis-1,1'-(1,2,4-triazole-1-yl)methane and bis-1,2-(1,2,4-triazole-1-yl)ethane [Julia S., Sala P., J. Mazo, M. Sancho N-Polyazolylmethanes. 1. Synthesis and NMR Study of N,N'-Diazolylmethanes //J. Heterocycl. Chem. - i982. - Vol. 19. - P. 1141 - 1145; J. Torres, Lavandera J. L., Cabildo P., Claramunt, R. M.; Elguero J. Synthesis and Physicochemical Studies on 1,2 - Bisazolylethanes //J. Heterocycl. Cliem. - 1988. - Vol. 2lyazolylmethanes. 1. Synthesis and NMR Study of N,N'- Diazolyhnethanes //J. Heterocycl. Chem. - 1982. - Vol. 19. - P. 1141-1145]. Use the method of phase transfer catalysis in the liquid - to-liquid (methylene chloride - water). The reaction is introduced 1,2,4-triazole in the presence of a catalyst, tetrabutylammonium bisulfate. The reaction mixture is kept under strong stirring for 8 hours. The layers are separated and the aqueous layer was extracted with ether, and together with the organic layer dried anhydrous MgSO4. The solvent pariveda under vacuum. So PL 127oC. Yield 61%.

The disadvantages are the counterpart: the low yield of the target product, a significant reaction time, complex selection of product, requiring large expenditures of solvent.

A prototype of the proposed method is [J. Torres, Lavandera J. L., Cabildo P., Claramunt, R. M.; Elguero J. Synthesis and Physicochemical Studies on 1,2-Bisazolylethanes //J. Heterocycl. Chem. - 1968. - Vol. 25. - P. 771763] , which describes a method for bis-1,2-(1,2,4-triazole-1-yl)ethane by the method of interfacial catalysis.

Example. A mixture of 29 mmol 1,2,4-triazole, 10 ml of 40% aqueous NaOH, 1.4 mmol tetrabutylammonium bromide, 14.5 mmol 1,2-dibromethane in 25 ml of toluene was heated (60 - 80oC) with vigorous stirring for 27 72 hours. After cooling, the aqueous phase ekstragirovanny, and the dry product was purified by recrystallization from dichloromethane. Exit 40 - 45%, So pl. 157 - 158oC.

The disadvantages of the prototype are the low yield of the target product, the long duration of the reaction.

The technical result of the proposed solutions is the reduction of the process time while increasing the yield of the target product.

The technical result is achieved by conducting the alkylation of 4-amino-1,2,4-triazole in a solution of N,N'- dimethylformamide 1,2-dibromethane at 95-105oC, followed by deamination.

Significant differences of the proposed method is used as the starting material 4-amino - 1,2,4-triazole, and the solvent N, N'-dimethylformamide under alkylation, which is carried out at a temperature of 95-105oC.

In the prior art it is known the use of 4-amino-1,2,4-triazole in producing monoalkylated Quaternary salts [Becker N. G.O., Boettcher N., Roethling So, Timpe N. J. Zur Alkylierung von 4-Amino-1,2,4-triazol // Wiss. Z. Tech. Hochsch. Chem. Leuna-Merseburg. - 1966. -Bd 8.-N 1.-S. 22-25. C. A. 1966. Vol. 64. 19596]. N,N'-dimethylformamide as a solvent known in the alkylation processes [U.S. Pat. 538700 Japan, C 07 D 249/08. Cotati N., Yasuda M, Fujita T. N westminste differences note, that these features together lead to a significant reduction of the process time without sacrificing the properties of the final product, with a simultaneous increase of the yield of the target product. This effect is due to the fact that the reaction proceeds by the mechanism of bimolecular nucleophilic substitution, as first revealed by us in the study of the kinetics of alkylation of 4-amino-1,2,4-triazole dihalogenoalkane (see chart).

The method is illustrated by examples of its implementation.

Example 1. To a solution of 8.4 g (0.1 mol) 4-amino-1,2,4-triazole in 40 ml of N, N'-dimethylformamide is added dropwise with stirring 9.4 g (0.05 mol) of 1,2-dibromethane. The reaction mixture is stirred at a temperature of 95oC for 2 hours. Then evaporated and under vigorous stirring spend deamination: connect with 125 ml of 2n. HCl containing 13.8 g (0.2 mol) NaNO2Stirred for 1 hour at 05oC. the Excess acid is neutralized under cooling soda. The aqueous solution extracted twice with ethyl acetate, the ethyl acetate is separated in a funnel, dried, evaporated. Recrystallized product from dioxane. Get 2.96 g (68%) of 1,2-bis(1,2,4-triazole-1-yl)ethane, so pl. 158oC (dioxane).

Found, %: C, 43.60, 43.77 , H 5.03, 5.09, N is combined with the melting temperature confirms the purity of the secreted product.

So plasma was determined on the device "PTP-1" (, Wedge) THAT 87524-87, elemental analysis was performed on the determinant of the elements "CHN-1 (manufactured Czechoslovakia) by known methods.

The examples are summarized in table (in comparison with the prototype).

From the table it is seen that compared with the prototype of the proposed method is workable: a time for 3 hours (prototype 27-72 hours) and the output 61-87% (45% - prototype), and more economical by reducing energy consumption. At lower temperature the output is reduced, with an increase above the optimal side hydrolysis of the initial 1,2-dibromethane leads to the same effect.

A method of obtaining a bis-1,2-(1,2,4-triazole-1-yl)ethane using alkylation of 1,2-dibromethane in the solvent by heating, characterized in that the alkylation is subjected to 4-amino-1,2,4-triazole at 95 - 105oWith, the solvent used is N,N-dimethylformamide, followed by deamination.

 

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