RU2266278C2 - Method for preparing trisamine - Google Patents

Abstract

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to the improved method for preparing trisamine representing tri-(hydroxymethyl)-aminomethane that possesses antacide activity with systemic effect and can be used, in particular, for correction of acid-alkaline equilibrium. Method involves reduction reaction of nitro-group with hydrogen in tri-(hydroxymethyl)-nitromethane (nitrotris) used as a solution in an organic solvent (methanol, ethanol, acetonitrile) at temperature 5-20°C in the presence of palladium catalyst applied on carbon in the concentration of palladium from 1 to 5% of the parent substance mass, and under pressure 1-2 kgf/cm². The end product is isolated by separation of solution from catalyst by filtration followed by evaporation of solution under vacuum at temperature 50°C, not above, cooling and filtration. Method provides enhancing the technological effectiveness of the process, in particular, due to reducing temperature and pressure values.

EFFECT: improved preparing method.

2 cl, 1 ex

Description

The invention relates to organic chemistry. Specifically, to a method for producing 2-amino-2- (hydroxymethyl) propanediol-1,3 (trisamine) of the formula:

Trisamine is a systemic antacid with a buffering effect. Trisamine refers to drugs for the correction of acid-base conditions. Trisamine is obtained by reducing the nitro group of 2-nitro-2- (hydroxymethyl) propanediol-1,3 (nitrotris) with a mixture of zinc and hydrochloric acid (Piloty O., Ruff O., Ber. - 1897. - V.30. - P. 2062). Also described is a method for reducing the nitro group of nitrotris using metallic sodium in absolute ethanol (Demyanov M., ZhRFKHO. - 1903. - T.35. - P.23). Most widely used in industry was the method of hydrogen nitrotris reduction using skeletal nickel (Raney nickel) (G. A. Gareev, L. G. Svirskaya, Chemistry of nitromethane. - Novosibirsk: Science, Siberian Publishing Company RAS. - 1995. - P.186 )

The method is as follows.

1.75 kg of freshly prepared Raney nickel as a suspension in absolute ethanol are charged into the hydrogenation apparatus. At a temperature of 40 ° C, hydrogen is passed through while maintaining a pressure of 5-7 kgf / cm ² for 30 minutes. Then, at a temperature of 48 ° C, the dosage of the nitrotris solution obtained in the condensation step is started, maintaining the temperature in the range of 50-55 ° C and the hydrogen pressure of 5-7 kgf / cm ² . After dosing, the nitrotris can withstand a mass of 1 hour under the same conditions. The spent catalyst is filtered off on a suction filter and water is removed from the mother liquor in a vacuum evaporator at a temperature not exceeding 60 ° C and a vacuum not lower than 0.6 kgf / cm ² until spontaneous crystallization of the product in the selected sample begins. A saturated aqueous solution of trisamine is treated with ethanol and the suspension is maintained at a temperature of 10-15 ° C for 12 hours. The crystalline trisamine is filtered off on a suction filter, washed with absolute ethanol and dried in a vacuum oven. Purification of trisamine is carried out by recrystallization from absolute ethyl alcohol in the presence of activated carbon at the rate of 5.65 kg of ethanol and 0.04-0.06 kg of coal per 1 kg of trisamine. The resulting mixture is boiled for 30 minutes, filtered through a filter, and the filtrate is kept in the crystallizer for 12-14 hours at 10-15 ° C. Crystalline trisamine is filtered off on a suction filter and washed with ethyl alcohol until the color disappears. The purified product is dried in a vacuum oven at a temperature of 50-65 ° C and a vacuum below 0.5 kgf / cm ² .

Further recrystallization from demineralized water in the ratio of trisamine: water equal to 1: 0.84, (heating temperature 80-90 ° C, crystallization at 5 ° C) provides trisamine corresponding to TU 6-09-4292-76, Tm = 169 -172 ° C, the content of the basic substance is 99.8%.

The yield of the target product by this method is not specified by the authors. The disadvantages of the prototype method are:

- the use of absolute ethyl alcohol;

- increased 5-7 kgf / cm ² hydrogen pressure;

- the danger of working with Raney nickel;

- the need for additional purification of the target product.

The disadvantages inherent in this method make the process time-consuming and dangerous from the point of view of production safety.

The present invention is based on the technical task of developing a method for producing trisamine, which would be distinguished by manufacturability, availability of raw materials, would make it possible to obtain a final product with a high yield and satisfying the requirements of TU 6-09-4292-76 without additional purification.

To achieve the technical result, trisamine is obtained by reacting nitrotris with hydrogen in an organic solvent (methanol, ethanol, acetonitrile) in the presence of a catalyst, which is used as a palladium catalyst supported on coal at a palladium concentration of 1-5% by weight of the starting material. Nitrotris is used as a solution in an organic solvent (methanol, ethanol, acetonitrile), the hydrogenation process is carried out for 6-8 hours at a temperature of 5-20 ° C and a pressure of 1-2 kgf / cm ² , the end of the process is controlled at the end of hydrogen consumption. The target product is isolated by filtering the solution from the catalyst and evaporating into 2/3 of the volume under vacuum at a temperature not exceeding 50 ° C. Upon completion of distillation of the excess solvent, the reaction mass is cooled to a temperature of 10-15 ° C, the precipitated trisamine is filtered.

The invention consists in the following:

Nitrotris is dissolved in an organic solvent (methanol, ethanol, acetonitrile) and the catalyst is charged. After purging the reaction vessel with an inert gas, preferably nitrogen, hydrogen is supplied at a pressure of 1-2 kgf / cm ² and room temperature. The end of the reaction is controlled by the flow of hydrogen. Then the catalyst is filtered off, the solution is evaporated at a temperature not exceeding 50 ° C, cooled to a temperature of 10-15 ° C and trisamine is filtered off. The yield is 85%, mp = 169-172 ° C, the content of the basic substance is not lower than 99.5%. Unlike the prototype, absolute ethanol is not used in the hydrogenation step. The process does not require elevated temperatures and pressures, which reduces the complexity and danger of the process.

The product is of high quality, does not require additional many hours of cleaning.

When the palladium content is below 1% by weight of the starting nitrotris, the yield of the target product decreases and the duration of the hydrogenation process significantly increases. When the palladium content is above 5% by weight of the target product, the cost of the target product significantly increases.

Lowering the temperature below 5 ° C during hydrogenation leads to an increase in the duration of the process, increasing the temperature above 20 ° C leads to a decrease in the yield and quality of the resulting trisamine.

The invention is illustrated by the following specific embodiment.

In a flask equipped with a stirrer, load 150 ml of 96% ethanol and dissolve at room temperature 10 g of nitrotris with Tm. 168 ° C, after which 8 g of catalyst are loaded (granular carbon coated with 4% by weight palladium). The reaction mass is purged with nitrogen, after which hydrogen is supplied at a pressure of 1 kgf / cm ² . The dosage is carried out for 6-8 hours, then the hydrogen supply is turned on, the reaction mass is purged with nitrogen and the catalyst is filtered off. The resulting solution of trisamine in ethanol is evaporated to 2/3 of the volume under vacuum and cooled to a temperature of no higher than 10-15 ° C for 4-5 hours and filtered. The filtered trisamine is dried under vacuum at a temperature not exceeding 50 ° C.

The yield of 6.81 g, which is 85% per nitrotris. Mp 169-172 ° C, the content of the basic substance is 99.5%.

The same results are obtained when methanol and acetonitrile are used as an organic solvent.

Thus, the developed method for producing trisamine allows you to:

- organize the industrial production of trisamine on the basis of more affordable raw materials and standard technological equipment;

- to have high quality and high yield of the target product without a stage of additional purification.

The method may find application in the chemical, pharmaceutical industry for the production of amino alcohols.

Claims (1)

A method of producing trisamine by reacting nitrotris with hydrogen in the presence of a catalyst in an organic solvent (methanol, ethanol, acetonitrile) with the allocation of the target product, including filtering the solution from the catalyst, evaporation under vacuum, cooling and filtering, characterized in that the nitrotris is used as a solution in an organic solvent (methanol, ethanol, acetonitrile), a palladium catalyst supported on coal is used as a catalyst at a palladium concentration of 1-5% of m ssy starting material and the process is conducted at a temperature of 5-20 ° C and pressure of 1-2 kgf / cm ^2, wherein the evaporation is carried out at a temperature not higher than 50 ° C.