SU469241A3 - Method for producing quaternary ammonium compounds - Google Patents

Description

This invention relates to a method for the synthesis of new compounds - quaternary ammonium compounds of general formula I

-R

with a quaternary nitrogen atom, while if R is methyl, then the compound of general formula III cannot be methyl iodide.

The proposed method also provides for the preparation of salts of compounds of the general formula I, for example, hydrohalides.

Thus, in its implementation H- (2-alkyl-4-amino-5-pyrimidylmethyl) -N, N is dialkylamine; N (2-alkyl-4-amino-5-pyrimidylmethyl) -pyrrolidine or M- (2-alkyl-4-amino-5-pyrimidylmethyl) -N-alkylaniline is reacted with 2-alkyl-4-amino-5 pyrimidylmethyl halide.

Compounds in which R2 instead of an amino group means a hydrogen atom, a halogen atom, or an alkoxy group can also be used as the starting material.

The reaction can be carried out in the presence or absence of solvents. Solvents can serve organic and inorganic; aliphatic or aromatic hydrocarbons, such as various gasoline fractions — benzene or its homologs; alcohols, for example methanol, ethanol, propanol; aldehydes, ketones, for example acetone or methyl ethyl ketope; ethers, for example diethyl ether, diisopropyl ether; tetrahydrofuran, dioxane; acids, for example acetic acid, propionic acid; esters, such as ethyl acetate, butyl acetate, or other acid derivatives, such as dimethyl formamide.

In other embodiments of the process, an excess of one of the reaction components is used as a solvent. The reaction temperature depends on the reactivity of the starting materials corresponding to the general formulas P and III. If X denotes a strongly reactive group, the reaction proceeds even at 10-25 ° C. In case the reactivity of the X group is less, or the R, R and R groups decrease the reactivity of the tertiary amine, the reaction mixture is heated to 50-150 ° C. The quaternary ammonium compounds obtained according to the proposed method are isolated by filtration and, if necessary, purified by crystallization.

The resulting products, in the form of raw products or in a purified state, can be converted into any salts, by dissolving the product in an excess amount of the corresponding acid and using a solvent in which the prepared salt is completely insoluble or slightly insoluble.

For this purpose, for example, dioxane, acetone or tetrahydrofuran can be used. For the preparation of iodides, an aqueous solution of potassium iodine is added to the aqueous solution of the product. In the resulting product, the molypus anion can be exchanged for another halide anion or sulfate, for nitrate, phosphate or organic anion. These compounds can also be converted to the corresponding salts.

Example 1: 3, ,8 g L- (2-tropyl-4-amino-5-pyrimidylmethyl), 1-dimethyl amine is dissolved in 17 ml of acetone, after which 1.24 ml of methyl iodide is added. After 10 minutes, the temperature of the reaction mixture was raised to. The reaction mixture was left to stand overnight, after which the precipitated crystals were filtered and washed with acetone. 5.13 g of N- (2-propyl-4-amino-5-pyrimidylmethyl) -N, N, N, N - trimethylammonium iodide, are obtained melting at 161-162 ° C. After acidification of its solution in anhydrous m ethanol with concentrated hydrogen iodide, a salt of iodide hydroiodide is obtained; m.p. 213-215C.

Example 2. 3.5 mg of K- (2-propyl-4-amino-5-pyrimidylmethyl-N, N-dimethylamine) is dissolved in 120 ml of acetone, after which 4.56 g of methyl bromide acetone solution is added. The solution contains 17.4 g Methyl bromide. After a few minutes, the temperature of the reaction mixture was raised to 40 ° C and the crystalline product began to precipitate. The reaction mixture was left to stand overnight, the precipitated product was filtered and washed with acetone to give 47.5 g of 1CH- -5-cyrimidylmethyl) -1, K, trimethylammonium bromide; mp 244-245 C. The product is dissolved in anhydrous ethanol. it follows acidification 48% bro.lshstovodorodnoy acid obtained melting at 225-228 C bromidgndrobromid.

Example 3. 38.8 g of 1M- (2-propyl-4-amino-5-nitrimidylmethyl) -N, N-dimethylamine is dissolved in 194 ml of acetone, which contains 10.1 g of methyl chloride. The reaction mixture was left to stand in a sealed refractory tube at 25 ° C for 65 hours and slowly heated for 4 hours in a water bath at 50 ° C. After cooling, the refractory tube is opened, the precipitated crystals are filtered and tromped with acetone. 29.45 g of K- (2-propyl-4-amino-5-pyrimidylmethyl) -N, N, N-trimethyl ammonium chloride are obtained; m.p. 199-201 ° C. By evaporation of the mother liquor, 15.58 g of N (2-propyl-4-amino-5-pyrimidylmethyl) -N, N-dimethylamine are obtained again. The product was dissolved in anhydrous ethanol, acidified with a solution of hydrochloric acid in ethanol, and the chloride-hydrochloride salt was separated. The salt decomposes at 208.

Example 4. 1.5 g of N- (2-propyl-4-amino-5-nitrimidylmethyl) -N, N-dimethylamine is dissolved in 7 ml of acetone and 0.71 ml of dimethyl sulfate is added. The temperature of the reaction mixture is constantly raised to 48-50 ° C. The reaction mixture was allowed to stand overnight. On the next day, the separated crystals are filtered and washed with acetone. The melting point of the resulting H- (2-propyl-4-amino-5-pyrimidylmethyl) -N, N, N-trimethylammonium methyl sulfate is 158-. The product indicated in Example 3 was converted into the chloride hydrochloride salt; m.p. 208-21 TOS. Example 5, 11 g of M- (2-propyl-4-amino-5-pyrimidylmethyl) -11 yrrong1 was dissolved in 75 ml of acetone and 12.5 g of an acetone solution of methyl bromide was added. The reaction mixture in a sealed refractory tube is left 5 to stand overnight at room temperature. The separated oily phase crystallizes. The resulting M- (2-propyl-4-amino-5-pyrimidylmethyl) -M-methylpyrrolidium bromide plasites at 129-133 ° C. The product is transferred to the bromide hydrobromide salt as described in Example 2; m.p. 216-218 ° C. Example 6. 9.6 g of N- (2-propyl-4-amino-5-pyrimidylmethyl) -pyrrolidine are dissolved in 15 16.2 ml of acetone and 2.2 g of methyl chloride are introduced into the solution. The reaction mixture was left to stand overnight in a sealed tube. The melting point of the preparate H- (2-propyl-4-alMino-5-pyrimidyl) is 20 N-methylpyrrolidinium 128-13 ° C. The product is converted to the chloride hydrochloride salt by the method indicated in Example 3; m.p. 195-196 0. Example 7. 2.56 g of M- (2-propyl-4-amino-5-25 pyrimidylmethyl) -N-methylaniline is dissolved in 30 ml of acetone. After the addition of 1.2 ml of benzyl chloride, the reaction mixture is left to stand overnight in a sealed tube. The precipitated white crystals are filtered and washed with acetone. Melting point of the obtained N- (2-propyl-4-ami110-5-11Irimidylmethyl) -N-methyl-N - benzyl aniline chloride 170-172 ° C. Example 8. 1 g of 2-propyl-4-amino-6-bromo-35 methyl pyrimidine dihydrobromide and 1.48 g of N (2-propyl-4-amino-5-pyrimidylmethyl) - N, N-dimethyl amide are dissolved in 100 ml of dimethylformamide at room temperature. temperature After a hundred or two hours, crystals fall out. 40 After filtering off, the crystals are washed with benzene. The melting point of the obtained M, M-bis- (2-propyl-4-amino-5-pyrimidylmethyl) -Y, M-dimethylammonium bromide is 183-184 ° C. After recrystallization from anhydrous ethanol-45 anol, the product melts at 184-185 ° C. Example 9. 0.5 g of N- (2-propyl-4-amino-5-pyrimidylmethyl) -N, N, N-trimethylammonium iodide is dissolved in 4 ml of concentrated hydrochloric acid. After the addition of 600 ml of acetone, crystals precipitate and are filtered off. The melting point of the chloride salt obtained is 208-211 ° C. Example 10. 2 g of M- (2-propyl-4-amino-5-55 pyridylmethyl) -M, L, L — trimethylammonium bromide is dissolved in 15 ml of concentrated hydrochloric acid. After the addition of 600 ml of acetone, crystals precipitate and are filtered off. The melting point of the obtained chloro-60-hydrochloride salt 208-21 HS, Example I. 2.5 g of M- (2-propyl-4-amino-5-pyrimidylmethyl) - N, N, N - trimethylammonium bromide hydrobromide are dissolved in 5 ml of water. After adding a solution of 2.5 g of potassium iodide 65 to 2.5 ml of water, crystals precipitate and are filtered off. The resulting iodide-hydroiodide salt melts at 213-215 ° C. Example 12. 2.13 g of N- (2-propyl-4-chloro-5-pyrimidylmethyl) -M, N-dimethylamine in 8 ml of acetone is reacted with 0.95 g of methyl bromide at room temperature. The reaction mixture is left to stand for 24 hours. The precipitated crystals are filtered and washed with acetone. N- (2-propyl-4-chloro-5-pyrimidylacetyl) -Y, K, K-trimethylammonium bromide is obtained. Example 13. 1.66 g of N- (2-methyl-4-amino-5-pyri. Imidylmethyl) -K, N-methylamine is reacted with 0.95 g of methyl bromide in 8 ml of acetone at room temperature. The reaction mixture is left to stand for 16 hours. The precipitated crystals are filtered and washed with acetone. N- (2-methyl-4-amino-5-pyrimidylmethyl) -N, N. N-trimethyl ammonium bromide is obtained. Example 14. 1 g of M- (2-prOPtsl-4-amino-5-pyrimidylmethyl) - N, N - N-trimethylammonium bro. The imidhydrobromide is heated with 2.1 g of N- (2-propyl-4-amino-5-pyrimidylmethyl) - M, - dtsmetylamino at a temperature of 135-IO C for 4 hours. After cooling, 5 ml of acetone is added to the reaction mixture. The precipitated crystals are filtered, washed with anhydrous acetone and recrystallized, washed. The melting point of the obtained N, N-bis- (2-propyl-4-a. Amino-5-iirimidylmethyl) -N, N-dimethylammonium bromide is 184-185 ° C. P e d. M with m and 3 about b | et e and. A method for producing quaternary A. moptsev compounds of the general formula I ,, .-- J in where R is alkyl; R2 is hydrogen, halogen, hydroxy, alkoxy or amido; R RS R is aryl, aralkyl, heteroaralkyl or alkyl, and in the latter case, two alkyl together with the nitrogen atom can form a hetero ring; Y is an organic or inorganic acid residue or hydroxyl group, or their salts, characterized in that the compound of the formula Formula P 7 where RR, Rs is aryl, aralkyl, heteroaralkpl, or alklpl, while in the latter case two alkyl groups can to form a hetero ring with a nitrogen atom, is reacted with a compound of the formula P1 Ke-X, where R is alkyl, aralkyl or hetero: Cl, and R 5 and / or R means primer IV R SI, 8 where R and R have the above values , and an X-electrophilic group, such as a halogen atom, followed by isolation of the Vågå product freedom form or as salts in a known manner.