RU2394811C2 - Method of producing acetamidine hydrochloride - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing acetamidine hydrochloride which is used as raw material in organic synthesis. The method involves condensation of acetonitrile with lower alcohols in the presence of hydrogen chloride, where condensation of acetonitrile with methanol takes place in a dichloroethane medium in the presence of hydrogen chloride at temperature between -2 and +3°C, and subsequent addition of the obtained acetoiminoester suspension into methanol saturated with ammonia. Acetamidine hydrochloride is extracted through filtration from ammonium chloride and distillation of the solvent mixture until formation of a suspension, filtration and washing the residue with cold alcohol. Before distillation of the solvent mixture, the mother solution and the washing alcohol are returned to the reaction mixture.

EFFECT: high output of end product (over 91%).

1 cl, 3 ex

Description

The invention relates to the field of organic synthesis, in particular to a method for producing acetamidine hydrochloride (AA GC), which is used as a raw material in the production of explosives, as well as a highly reactive compound.

Traditionally, the starting compounds in the synthesis of amidines (2) are nitriles, which are transformed into amidines via intermediate imino esters (1). The latter are usually obtained by the Pinner reaction by the interaction of hydrogen chloride with nitriles in alcohol (Scheme 1).

Scheme 1

A known method of producing AA GC according to the Dox method (A.V. Doke. Acetamidine hydrochloride // Synthesis of organic preparations, Moscow, 1949, I, p.66). According to this method, dry hydrogen chloride (HC1) is passed through a solution of 2.44 moles of well-dried acetonitrile in 2.5 moles of absolute ethyl alcohol. Saturation with hydrogen chloride is continued until 2.6 mol of HCl is absorbed. At the end of saturation, the reaction mass is kept for 2–3 days until complete crystallization. Then, the obtained solid crystalline mass of hydrochloric acid acetoimino ester is broken with a spatula, triturated in a mortar and treated in the reaction flask with an excess of 9% alcohol solution of ammonia (500 ml).

After stirring for three hours, the solution of acetamidine hydrochloride is filtered from the precipitated ammonium chloride. The solvent is distilled off to a total volume of 200 ml, the reaction mass is cooled and acetamidine hydrochloride is filtered off. The product is dried in a desiccator over sulfuric acid. The output of AA GC is 80 ÷ 91%, T _pl = 164 ÷ 166 ° C.

The main disadvantages of this method of obtaining AA GC are:

- the use of expensive absolute ethyl alcohol;

- non-technological stage of obtaining acetoiminoether and, as a consequence, the inability to obtain a product on an industrial scale;

- the addition of alcohol saturated with ammonia to the solid product leads to a difficult to control exothermic reaction of the formation of AA GC and local overheating of the reaction mass and, accordingly, to the formation of by-products of the reaction;

- the duration of the process of obtaining AA GC.

A known method of producing amidines using the appropriate nitrile as a solvent for the reaction (A. Dinkulescu. Patent RO 59061. The method of producing amidines. Declared 04.10.71 g, publ. 07.07.75 g). To obtain iminoether to an excess of nitrile at a temperature of 50 ÷ 60 ° C, lower alcohol and dry hydrogen chloride are dosed in parallel for 3 ÷ 5 hours. HCl saturation control is carried out by periodically weighing the reaction flask.

Amidines are prepared by passing gaseous ammonia into the reactor to a pH of 8. After hot filtering the solution from ammonium chloride, the reaction mass is cooled and the amidine precipitated is filtered.

Acetamidine hydrochloride according to this method is obtained with a yield of 85% and a basic substance content of 99%. This method of obtaining AA GC adopted by us as a prototype.

When testing this method using methyl alcohol and acetonitrile as reagents, the following disadvantages were identified:

- the use as a solvent of the reaction of expensive acetonitrile;

- low-tech stage of obtaining AA GC due to the constant overgrowth of ammonium chloride tube (capillary) dosage of gaseous ammonia;

- low stability of acetoiminoether at temperatures above 30 ° C and, as a result, the formation of a by-product of the reaction of acetamide;

- low yield of less than 60%.

An object of the invention is to develop a technological method for producing AA GC, devoid of the above disadvantages and suitable for use on an industrial scale.

The technical result is achieved by condensation of acetonitrile with methyl alcohol in the presence of hydrogen chloride in dichloroethane at a temperature of -2 ÷ + 3 ° C and subsequent dosage of the resulting suspension of iminoether in ammonia saturated methyl alcohol and the isolation of AA GC is carried out with a loop of the mother liquor.

The method of producing acetamidine hydrochloride is illustrated by the following examples:

Example 1. According to the prototype

In a reaction flask equipped with a mechanical stirrer, thermometer and capillary for dosing hydrogen chloride, 101 g (2.46 mol) of dried acetonitrile were charged. Then, with stirring and a temperature in the flask of 50 ÷ 55 ° C, 20 g (0.62 mol) of methyl alcohol were dosed in parallel and hydrogen chloride was passed for 3 hours. A total of 26 g (0.71 mol) of HCl was absorbed. The reaction mass was kept for 5 hours at a temperature of 50 ÷ 55 ° C, cooled and saturated with gaseous ammonia at a temperature of 0 ÷ 35 ° C to a pH of 8.

Due to the low solubility of acetamidine hydrochloride in acetonitrile (less than 1 g in 100 ml at 80 ° C), ammonium chloride was not purified as described in the prototype.

After saturation of the reaction mass with ammonia and cooling to 10-15 ° C, AA GC was filtered off. The product was dried in a thermostat at a temperature of ~ 70 ° C to constant weight and analyzed by high performance liquid chromatography (HPLC).

The product yield was 47.5 g (80.4%). However, when analyzing the product by HPLC, the content of the basic substance in it was only 66%. The main impurity in AA GC was acetamide.

By reducing the exposure time and reaction temperature, a poor quality product was also obtained. The maximum yield of AA GC during the reaction at a temperature of 20 ÷ 30 ° C, considering the product as 100%, amounted to 57.0%.

Example 2. Obtaining AA GC using dichloroethane as medium

In a reaction flask equipped with a mechanical stirrer with a shutter, a thermometer and a capillary for dosing hydrogen chloride, 41.0 g (1.0 mol) of dried acetonitrile, 35.2 g (1.1 mol) of methyl alcohol and 46, 0 g of dichloroethane (1.12 parts by weight per 1 part by weight of acetonitrile). The resulting solution was cooled and about 41.0 g (1.12 mol) of dry hydrogen chloride was introduced at a temperature of -2 ÷ + 3 ° C. Then, over 3 hours, the temperature was gradually raised to 20 ° C and kept at this temperature for 20 hours. At the end of the exposure, a suspension of acetoimino ester at a temperature of about 20 ° C was dosed in 160 g of a saturated solution of ammonia in methyl alcohol (12 g of NH ₃ in 100 g of methanol) and after 15 minutes the reaction mass was heated to boiling. After heating, the pH of the medium was checked, which should be at least 8, and if necessary, an additional amount of alcohol saturated with ammonia was added. Then the reaction mass was kept at boiling for 10 minutes, filtered from ammonium chloride and the solvent mixture was distilled off until a stirred suspension was formed upon cooling. The precipitated AA GC was filtered off, washed twice with chilled alcohol, and dried in a thermostat at a temperature of 60–70 ° С.

The product yield was 62.2 g (65.8%), T _pl = 167 ÷ 170 ° C, the content of the main substance, determined by high performance liquid chromatography, was more than 98%.

In order to develop a technologically advanced method for product recovery, the mother liquor after AA GC filtration and washing alcohol from AA GC washing were used in the following AA GC synthesis.

Example 3. Obtaining AA GC using dichloroethane as a medium and cycling of mother liquors

The synthesis of AA GC was carried out similarly to the previous experiment, but before distillation of the solvent mixture, the mother liquor was added to the resulting reaction mass after filtering AA GC and washing alcohol from washing AA GC from the previous experiment.

The product yield was 95.7 g (101.2%), T _pl = 164 ÷ 167 ° C, the content of the basic substance, determined by high performance liquid chromatography, was more than 97%.

Similarly to experiment 3, two more syntheses were performed to obtain AA GC.

The product yield from experiment 4 was 93.5 g (98.9%), T _pl = 162 ÷ 167 ° C, the content of the basic substance, determined by high performance liquid chromatography, was more than 97%.

The product yield from experiment 5 was 94.0 g (99.4%), T _pl = 160 ÷ 165 ° C, the content of the basic substance, determined by high performance liquid chromatography, was more than 96%.

The average product yield from 4 experiments to obtain AA GC (op. 2-5) is 345.4 g (91.2%), T _pl = 162 ÷ 167 ° C, the content of the basic substance determined by high performance liquid chromatography is more than 97 %

Thus, the developed method for producing AA GC allows one to obtain a product with a high yield and can be implemented on an industrial scale.

Claims (1)

A method of producing acetamidine hydrochloride by condensation of acetonitrile with lower alcohols in the presence of hydrogen chloride, characterized in that the condensation of acetonitrile with methyl alcohol is carried out in dichloroethane in the presence of hydrogen chloride at a temperature of (-2) - (+ 3) ° C, followed by a dosage of the resulting suspension of acetoiminoether into methyl alcohol saturated with ammonia, and the isolation of acetamidine hydrochloride is carried out by filtration from ammonium chloride and distillation of the solvent mixture to form a suspension, by filtration and romyvaniem precipitate chilled alcohol, and distilling off the solvent mixture to conduct zatsiklovku wash liquor and alcohol to the reaction mixture.