RU2380363C2 - METHOD OF PRODUCING 1-(β-PHENYLETHYL)-4-(para-DIMETHYLAMINOBENZYLIDENAMINO)-1,2,4-TRIAZOLE BROMIDE - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: there is described a single-step method for synthesis of 1-(β-phenylethyl)-4-(para-dimethylaminobenzylidenamino)-1,2,4-triazole bromide with high output without release of intermediate products using one solvent. In accordance with the described method, 4-amino-1,2,4-triazole is dissolved in butanol, a solution of β-bromoethylbenzene is added to the butanol, the mixture is boiled for 6-8 hours, cooled to 50-60°C, a solution of para-dimethylaminobenzaldehyde is added, as well as a catalytic amount of concentrated hydrobromic acid, the mixture is kept at 50-60°C for 3-5 hours with subsequent cooling to room temperature; the precipitate is filtered, washed with diethyl ether or butanol and dried in air.

EFFECT: design of an efficient method of producing heterocyclic compounds.

2 cl, 1 ex

Description

The invention relates to the field of medicine and pharmacy, in particular to a technology for the production of heterocyclic compounds.

A known method of producing a heterocyclic compound disclosed in the description of the patent of Ukraine No. 23260, class. 6 C07D 249/08 on the biologically active compound “1-pentyl-4- (n-methoxybenzylidenamino) -1,2,4-triazolium bromide". The method described in the description includes, in a first step, mixing equivalent amounts of 4-amino-1,2,4-triazole and pentane bromide and boiling in ethanol for 7 hours, evaporating the reaction mixture in a boiling water bath, followed by isolation of 1-pentyl-4 bromide amino-1,2,4-triazolium (intermediate), which is recrystallized from ethanol.

In the second stage, the obtained intermediate product is dissolved in ethanol, n-methoxybenzaldehyde and concentrated hydrobromic acid are added to the solution, stirred, kept at room temperature for one day, the precipitate is filtered off, washed with ether and the target product is recrystallized from aqueous ethanol.

The disadvantages of this method are: obtaining the target product in two stages; the need for the operation of evaporation and isolation of the intermediate product in the first stage, as well as the need for aging the solution of the reaction mixture during the day in the second stage. All this increases production costs and reduces the percentage yield of the target product - 1-pentyl-4- (n-methoxybenzylideneamino) -1,2,4-triazolium bromide.

A known method for producing a heterocyclic compound disclosed in the description of the patent of Ukraine No. 28494, 6 C07D 249/08, А61К 31/41 for the biologically active compound "1- (β-Phenylethyl) -4- (n-dimethylaminobenzylidenamino) -1,2 4-triazolium. "

The method described in the description, as in the above analogue, includes, at the first stage, mixing and boiling in the solvent of two starting components - 4-amino-1,2,4-triazole and β-bromoethylbenzene, but nitromethane is used as the solvent and boiled in mute the reaction mixture for 8 hours. Then the solvent is distilled off and an intermediate product is isolated - 1- (β-phenylethyl) -4-amino-1,2,4-triazolium bromide, which is recrystallized from butanol.

At the second stage, the obtained intermediate product is dissolved in ethanol, an alcohol solution of n-dimethylaminobenzaldehyde is added to the resulting solution, and it is kept at a temperature of 20-25 ° С for 20-24 hours, concentrated hydrochloric acid is used as a catalyst. The reaction mixture was left for a day, the precipitate formed was filtered off and recrystallized from aqueous ethanol to obtain the desired product 1- (β-phenylethyl) -4- (n-dimethylaminobenzylideneamino) -1,2,4-triazolium bromide. The latter is of interest as a cardiotonic drug.

By the identity of the obtained target product, this method is taken as a prototype.

The disadvantages of the prototype are inherent in the analogue of the use of two solvents in the reaction process instead of one with a significant consumption, in addition, the time of the chemical process is more than 30 hours.

The basis of the invention is the task to develop a one-stage method for obtaining the target product, providing a reduced number of technological operations using a single solvent in the main chemical process and reducing its consumption, increasing the yield of the target product.

The solution of this problem provides a method for producing 1- (β-phenylethyl) -4- (n-dimethylaminobenzylideneamino) -1,2,4-triazolium bromide, which includes a reaction when the active components of 4-amino-1,2,4- are heated in an organic solvent triazole, β-bromoethylbenzene and n-dimethylaminobenzaldehyde, due to the fact that 4-amino-1,2,4-triazole is dissolved in n-butyl alcohol (butanol), then β-bromoethylbenzene dissolved in n-butyl alcohol is added to the solution and the reaction mixture is boiled for 6-8 hours, after cooling the mixture to 50-60 ° C, a solution of n-dimethyls is introduced into it of aminobenzaldehyde in n-butyl alcohol and concentrated hydrobromic acid in a catalytic amount is added as a catalyst, then the resulting mixture is heated at 50-60 ° C for 3-5 hours, cooled to room temperature (15-20 ° C), the precipitate is filtered off and washed on the filter with butanol, then diethyl ether and dried.

The reaction used 4-amino-1,2,4-triazole, β-bromoethylbenzene and n-dimethylaminobenzaldehyde in equimolar ratios of 1: 1: 1.

Technical and economic effect when using the proposed method:

- reducing the time of the process and the direct cost of obtaining the target product by obtaining it in one stage and eliminating intermediate operations - distillation of the solvent, isolation, purification and drying of the intermediate product of 1- (β-phenylethyl) -4-amino-1,2 4-triazolium;

- reducing the cost of solvents by using one solvent instead of two by analogy and reducing its consumption due to the fact that the solvent introduced into the reaction process, only one;

- increase in the percentage of yield of the target product due to the exclusion of losses in the allocation of the intermediate product of the prototype.

The invention is illustrated by the following description of the proposed method and its chemical-technological scheme.

The whole process is carried out in one continuous cycle according to the scheme below:

The method for producing 1- (β-phenylethyl) -4- (n dimethylaminobenzylideneamino) -1,2,4-triazolium bromide can be illustrated by the following example.

Example

In a 2.5 L reactor equipped with a mechanical stirrer and reflux condenser, 168 g (2 mol) of 4-amino-1,2,4-triazole are added, 1.2 L of n-butyl alcohol is added and heated until dissolved. To the resulting solution was added 380 g (2.05 mol) of β-bromoethylbenzene in 200 ml of n-butyl alcohol. The reaction mass is boiled for 8 hours. After that, the mixture is cooled to 50-60 ° C and a solution of 372.6 g (2.2 mol) of n-dimethylaminobenzaldehyde in 500 ml of n-butyl alcohol and 2 ml of concentrated hydrobromic acid is added to it as a catalyst. The reaction mixture is heated at 50-55 ° C for 3-5 hours. Then it is cooled to 15-20 ° C, the precipitate is filtered off, washed on the filter with butanol, then 200 ml diethyl ether and dried in air.

Obtain 702 g ± 8 (87.8%) of the target product, which is a yellow crystal with a melting point of 174-180 ° C (from 60% aqueous ethanol or propanol).

Found,%: C 56.9; H 5.5; Br 20.0; N, 17.5.

C ₁₉ H ₂₂ BrN ₅ .

Calculated,%: C 57.0; H 5.5; Br 20.0; N, 17.4.

IR spectrum: 1610 cm ^-1 (√C = N); 3000 cm (γ CP ar).

With increased industrial production of the target product, the number of components used will vary taking into account the technological capabilities of the enterprise, but their ratio, sequence and execution modes should correspond to the above specific example.

Claims (2)

1. The method of producing 1- (β-phenylethyl) -4- (p-dimethylaminobenzylideneamino) -1,2,4-triazolium bromide, including the reaction of 4-amino-1,2,4-triazole with β-bromoethylbenzene, using an organic solvent boiling the reaction mass, adding p-dimethylaminobenzaldehyde and using a catalyst, characterized in that 4-amino-1,2,4-triazole is heated in n-butyl alcohol to dissolve, a solution of β-bromoethylbenzene in n-butyl alcohol is added, then the reaction the mass is boiled for 6-8 hours, cooled to 50-60 ° C, a solution of p-dimethylaminobenzald is introduced a hydride in n-butyl alcohol, a catalytic amount of concentrated hydrobromic acid is added, then the resulting mixture is heated at 50-60 ° C for 3-5 hours, cooled to 15-20 ° C, the precipitate is filtered off, washed on the filter with butanol, then diethyl ether . 2. The method according to claim 1, characterized in that the reaction uses 4-amino-1,2,4-triazole, β-bromoethylbenzene and p-dimethylaminobenzaldehyde in equimolar ratios of 1: 1: 1.