Fused pyrimidine derivatives R 0515 Novel Alkylations of Cyclic Thioureas by α-Halocarboxylic Acids and Their Esters. Part 4. Alkylation of 1-Methyltetrahydropyrimidine-2(1H)-thione. -Alkylation of the cyclic thiourea (I) with α-chloroor bromoacetic acids or esters affords chloro or bromo salts of type (III). The chloro salts are readily hydrolyzed to the open-chain ammonium salt of type (IV) whereas the bromo salts are considerably more stable towards hydrolysis. -(KUSHAKOVA, P. M.; BASAN, Y. V.; YULISOVA, A. I.; LIFONTOVA, V. V.; RAMSH, S. M.; GARABADGIU, A. V.; BELOBRZECKAJA COSTA, L. N.; Chem. Heterocycl.

A detailed study of the different reaction pathways for the alkylation of 2-imidazolidinethione (I) with α-halocarboxylic acids (II) is given. -(KUSHAKOVA, P. M.; RAMSH, S. M.; GARABADGIU, A. V.; Chem. Heterocycl. Compd. (N. Y.) 42 (2006) 2, 221-226; State Technol. Inst., St. Petersburg State Tech. Univ., St. Petersburg 198013, Russia; Eng.) -H. Haber 45-130

CO 3 solution occurs in two steps: in the first step, cleavage of the tetrahydrotriazine ring occurs; and in the second step, opening of the perhydrooxazine ring occurs.

The detailed scheme of reactions, occurring on interacting ethylene thiourea with chloroacetic acid and its esters, has been supplemented with a series of new reactions. The whole spectrum of products formed on interaction of ethylene thiourea with 2-bromobutyric acid has been obtained.Keywords: ethylene thiourea (2-imidazolidinethione), interaction with 2-bromobutyric acid, interaction with chloroacetic acid and its esters.The alkylation products of cyclic thioureas with α-halocarboxylic acids and their esters are of interest as substances with possible biological activity due to affinity towards NO synthase [1] and GABA receptors [2]. Although the considered reactions of individual representatives of this series of compounds have been studied in some detail, their synthetic possibilities are far from being exhausted. In addition there has been no systematic consideration of the character of the conversions as a function of the size of the heterocycle of cyclic thioureas. The present work is the first step on the route of such consideration and suggests a continuation to examples of six-and seven-membered cyclic thioureas.Alkylation of the five-membered cyclic thiourea, ethylene thiourea (2-imidazolidinethione, 1), with α-halocarboxylic acids and their esters has been studied in [3][4][5][6][7][8][9][10], most thoroughly in [3]. We have added to the data obtained in these studies, pertaining to chloroacetic acid and its esters, with a series of new reactions, and also have obtained all the possible products formed on interacting ethylene thiourea (1) with 2-bromobutyric acid, an alkylating agent not used previously.None of the mentioned studies reported the preparation of [(4,5-dihydro-2-imidazolyl)thio]acetic acid hydrochloride (2a) in one step, directly by the interaction of compound 1 with chloroacetic acid. Only a two-step procedure for obtaining this compound was proposed. First the corresponding free base, the zwitter-ion [(4,5-dihydroimidazol-3-ium-2-yl)thio]acetate (3a) (pathway a), was obtained by the action of chloroacetic acid on compound 1 in the presence of sodium acetate in boiling ethanol. Compound 3a was then converted into the desired hydrochloride 2a (pathway b) [3]. Attempts to alkylate compound 1 with chloroacetic acid under the "usual" conditions, i.e. in boiling ethanol or water, gave not the expected amino acid hydrochloride 2a but the hydrochloride of 3-(2-aminoethyl)-2,4-thiazolidinedione (4a) (pathway c) [3]. We succeeded in developing a one-step method of obtaining compound 2a by the interaction of compound 1 with chloroacetic acid in anhydrous acetone at room temperature (pathway d).

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