METHOD FOR OBTAINING 2-ALKYL-SUBSTITUTED SEMICARBAZIDES Russian patent published in 2018 - IPC C07C281/06 

FIELD: chemistry.

SUBSTANCE: invention relates to the field of organic chemistry, namely a process for the preparation of 2-alkyl-substituted semicarbazides of formula (I) or their hydrochlorides of formula (II), wherein R = alkyl or substituted alkyl. Method consists in indirect alkylation of unsubstituted semicarbazide at the nitrogen atom N2 and includes steps a) to e). In step a), the reaction of semicarbazide hydrochloride with acetone is carried out in the presence of sodium acetate in water to obtain the acetone semicarbazone, which precipitates during the reaction and is isolated by the filtration operation. In step b) the acetone semicarbazone is deprotonated by the action of an equivalent amount of sodium hydride with stirring in dry acetonitrile for 1 hour at room temperature. In step c), the resulting sodium salt of semicarbazone acetone without isolation and in the same solvent, acetonitrile, is alkylated at the nitrogen atom N2 by suitable alkylating reagents, wherein: (i) an equivalent amount of dimethyl sulphate is used to introduce a methyl group and the reaction is carried out for 17 hours at room temperature; (ii) for the introduction of other alkyl groups, in addition to the methyl group, a 5–10-fold molar excess of the corresponding alkyl bromide is used, and the reaction is carried out by boiling in acetonitrile for 9 hours; (iii) an equivalent amount of the corresponding bromide is used to introduce the substituted alkyl group and the reaction is carried out by boiling in acetonitrile for 9 hours. In step d), the resulting 2-alkyl-substituted semicarbazones without intermediate isolation and purification are subjected to acid hydrolysis, for which the reaction mass after the alkylation filtered from the precipitation of salts, the solvent is removed in vacuo at a bath temperature of up to 40 °C, 17–36 % hydrochloric acid is added to the residue in an amount of 5–10 equivalents of HCl per 1 equivalent of semicarbazone and the resulting solutions are immediately evaporated in vacuo at a bath temperature of up to 60 °C. Solid residues, that are the hydrochlorides of the 2-alkyl substituted semicarbazides of formula (II), are triturated with isopropyl alcohol, the precipitates are filtered off and dried. In step e), the hydrochlorides of the 2-alkyl-substituted semicarbazides of the formula (II) are treated to form the 2-alkyl-substituted semicarbazides of the formula (I), obtained in the previous step, with a small excess of sodium carbonate in water, followed by extraction of the product with ethyl acetate, distilling off the solvent from the combined extract, trituration of the residue with petroleum ether until crystallization.

EFFECT: proposed method is universal, simple and allows, under mild conditions, to obtain the desired products in high yield.

1 cl, 6 ex