RU2461545C1 - Method of producing 2-methylpyrimidine-4,6-(3h,5h)-dione - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method of producing 2-methylpyrimidine-4,6-(3H,5H)-dione by reacting acetamidine hydrochloride with malonic ester in a methyl alcohol medium in the presence of sodium methylate, followed by evaporation of the solution, dissolution of the residue in water and acidification. The starting compound used is acetonitrile, which is successively treated with gaseous hydrogen chloride, ammonia solution in an organic solvent and malonic ester without separating acetamidine hydrochloride.

EFFECT: method enables to obtain a product with high output using an acetonitrile compound as the starting compound instead of unstable crystalline acetamidine hydrochloride.

3 cl

Description

The invention relates to a method for producing heterocyclic compounds of the pyrimidine series, namely, 2-methylpyrimidine-4,6- (3H, 5H) -dione, which is used to obtain a powerful low-sensitivity explosive - 1,1-diamino-2,2-dinitroethylene (DADNE, FOX 7), and may also find application for the synthesis of biologically active substances.

A known method of producing 2-methylpyrimidine-4,6- (3H, 5H) -dione with a yield of 43% [J. Am. Chem. Soc. 62, 606-607, 1940] by the interaction of 1.8 mol of acetamidine hydrochloride with 1.2 mol of malonic ether in a solution of 3.5 g of sodium metal in 150 ml of absolute alcohol for three days, followed by neutralization with concentrated hydrochloric acid and removal of sodium chloride by washing water.

The disadvantages of the method are:

- the use of inaccessible, highly toxic in handling and hydrolytically unstable acetamidine hydrochloride in crystalline form;

- the duration of the process;

- low yield of the target product;

- the use of concentrated hydrochloric acid with high correlating activity.

Known is an improved method for producing 2-methylpyrimidine-4,6- (3H, 5H) -dione, providing a 97% yield [Z. Chylen, S. Cudzilo, J. Bladen, and S. Pietzyk, Optimization of 1,1- diamino-2,2-dinitroethelene synthesis. New Trends in Research of Energetic Materials, Pardubice, Czech Republic, 212-216, 2005], by sequential interaction of 2.5 moles of sodium methylate in 1300 ml of methanol and 1 mole of acetamidine hydrochloride with one mole of malonic ether at room temperature, followed by heating to 50 ° C and boiling the reaction mixture under reflux with stirring for 2 hours and holding for 24 hours at room temperature, followed by neutralization of the reaction mixture with concentrated hydrochloric acid to pH 6, filtering the insoluble product and washing with water minutes to remove sodium chloride.

The above method was adopted by us as the closest analogue.

The disadvantages of the analogue are:

- the use of inaccessible, highly toxic in circulation and hydrolytically unstable acetamidine hydrochloride in crystalline form;

- the use of concentrated hydrochloric acid to neutralize the reaction mass, which has a high correlating activity.

In addition, verification of this method showed that this forms a difficult to filter fine crystalline precipitate of the target product.

The technical task of the invention is to develop a method for producing 2-methylpyrimidin-4,6- (3H, 5H) -dione, devoid of the above disadvantages.

The technical result is achieved by using acetonitrile as the starting compound, which is successively treated with gaseous hydrogen chloride in a dichloroethane-methanol medium, a methanol solution of ammonia, then it is separated from the precipitated ammonium chloride by filtration, the solvents are distilled off (methanol with dichloroethane), diluted with methanol and formed in during the reaction, acetamidine hydrochloride without isolation is treated with malonic ether in the presence of sodium methylate at boiling, methanol is distilled off, the precipitate is dissolved digested in water and acidified with glacial acetic acid at a temperature of 50-55 ° C. The precipitate formed is filtered off, washed on the filter with water and alcohol.

Distinctive features of the invention are:

- the use of acetonitrile as the starting compound, followed by its conversion into a methanol solution of acetamidine hydrochloride, instead of the unstable crystalline acetamidine;

- the use of acetic acid to neutralize a solution of the product in water instead of hydrochloric acid;

- neutralization of the solution of the product in water at elevated temperatures to improve the filterability of the product.

The method for producing 2-methylpyrimidin-4,6- (3H, 5H) -dione is illustrated by the following example.

41.0 g (1.0 mol) of acetonitrile, 35.2 g (1.1 mol) of methanol and 46 g of dichloroethane are charged into a reaction flask equipped with a mechanical stirrer with a shutter, a thermometer and a capillary for dosing hydrogen chloride under a liquid layer. At a temperature of minus 5 ° to plus 5 ° C and stirring, under the liquid layer, gaseous hydrogen chloride is passed to absorb about 40.0 g (~ 1.1 mol) and the temperature of the reaction mixture is gradually increased to 20 ± 2 ° C. Maintained at this temperature for 20 hours and get a suspension of acetiminoether in dichloroethane, which is dosed to a saturated solution of ammonia in methanol (180 ml), maintaining the temperature of the reaction mass at about 20 ° C and the pH of the reaction mass is greater than or equal to 8. Then the reaction mass is heated to a boil, kept at a boil for 15 ÷ 30 min and filtered from ammonium chloride.

At the end of filtration, about 75 ml of a mixture of solvents (dichloroethane and methanol) is distilled off from the resulting solution, pure methanol is added until the precipitate is completely dissolved at room temperature, and about 490 ml of a solution containing about 88 g of acetamidine hydrochloride are obtained.

170 g of a methanol solution of sodium methylate containing 46 g (0.85 mol) of sodium methylate are placed in a flask, a methanol solution of acetamidine hydrochloride (130 ml) containing 24 g, obtained by the above procedure, is poured into it at a temperature of 20 ÷ 25 ° C and stirring (0.25 mol) of the product. Then add 48 g (0.30 mol) of malonic ester. The reaction mass is boiled for 4 hours, methanol is distilled off under vacuum, the residue is dissolved in 150 ml of water, the solution is heated to 50-55 ° C and acidified with glacial acetic acid (80-120 ml) to acidic, the mass is allowed to cool slowly to room temperature , the precipitate is filtered off, washed on the filter with water, alcohol and dried. Obtain 27.93 g (88.7% of theory) of 2-methylpyrimidin-4,6- (3H, 5H) -dione with a purity of more than 95%.

Claims (3)

1. The method of obtaining 2-methylpyrimidine-4,6- (3H, 5H) -dione by the interaction of acetamidine hydrochloride with malonic ether in the presence of methyl alcohol in the presence of sodium methylate, followed by evaporation of the solution, dissolving the precipitate in water and acidifying, characterized in that as the starting compound uses acetonitrile, which is successively treated with hydrogen chloride gas, a solution of ammonia in an organic solvent and without isolation of acetamidine hydrochloride with malonic ether. 2. The method according to claim 1, characterized in that a monohydric alcohol, for example methyl alcohol, is used as a solvent for ammonia. 3. The method according to claim 1, characterized in that an organic acid, for example glacial acetic, is used to acidify the salt solution of the obtained 2-methylpyrimidin-4,6- (3H, 5H) -dione.