SYNTHESIS AND PROPERTIES OF 4-AMINO-2-METHYL-PYRIMIDINE-5-IL-METHYL ESTERS OF AROMATIC THIOSULFOACIDS

2019;
: 122-128
1
Lviv Polytechnic National University
2
Lviv Polytechnic National University
3
Lviv Polytechnic National University
4
Lviv Polytechnic National University
5
Lviv Polytechnic National University

Derivatives of pyrimidine are the object of interest to researchers working in the field of medical chemistry. However, despite the rich history of searching for potential biologically active agents among substances containing this heterocyclic fragment, their potential is still unused. There are vitamins, vasodilators, antidiabetic, antibacterial, antimalarial substances among the derivatives of pyrimidine. A special group among the biologically active compounds is sulfurcontaining derivatives of pyrimidine (sulfides, salts of sulfonic acids, sulfonamides, sulfenamides, disulfides). These compounds are characterized as plant growth regulators, herbicides, insecticides and acaricides, fungicides, bactericides, and herbicide antidotes, and others. Some sulfur-containing pyrimidine derivatives are active substances in medical preparations. In addition, pyrimidine derivatives are intermediates for the synthesis of many active phosphororganic insecticides and derivatives of urea and carbamate acid.

Taking into account the wide range of biological effects of esters of thiosulphonic acid and their high reactivity, it is possible to modify the structure of the heterocyclic pyrimidine framework by thiosulfonate fragments and then construct target physiologically active molecules.

The production of esters of thiosulfonic acid with a pyrimidine moiety is complicated by the lack of data on the synthesis of chlorohydrid sulfonic acid of pyrimidine as a key raw material for the synthesis of esters of thiosulfonic acid.

The ways of synthesis of esters of thiosulfoacids with a pyrimidine moiety have been studied. The method for the preparation of esters of thiosulfoacids by chlorosulfurisation of the basic structures with the further preparation of the corresponding salts of pyridine-containing thiosulfonic acids and esters of thiosulfoacids based on them is not suitable for the studied pyrimidines (2-amino-6-methylpyrimidine-4-ol, 5- bromomethyl-2-methylpyrimidine-4-amine).

The result of further study was a new approach to the synthesis of promising nitrogen-containing heterocyclic esters of thiosulfoacid by the heterolitication of salts of aromatic and heterocyclic thiosulfonic acids. The possibility of obtaining of esters of thiosulfoacid with the pyrimidine moiety from the side of thiol sulfur by the alkylation of potassium or sodium salts of aromatic thiosulfonic acid with 5-bromomethyl-2-methylpyrimidine-4-amine in an acetone-aqueous medium at room temperature have been shown. The alkylation lasted 7-10 days, and the yield of the target esters of thiosulfoacids (29-57%) depended on the reactivity of the reagents. For the prevention of adverse reactions (formation of thiosulfonic acids and their decomposition), 5-bromomethyl-2-methylpyrimidin-4-amine was transferred into the corresponding base. The reagent was selected depending on the purity of the final product.

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