Novel Alkylations of Cyclic Thioureas by α‐Halocarboxylic Acids and Their Esters. Part 4. Alkylation of 1‐Methyltetrahydropyrimidine‐2(1H)‐thione.

Abstract

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.

Novel alkylations of cyclic thioureas by α-halocarboxylic acids and their esters. 4. Alkylation of 1-methyltetrahydropyrimidine-2(1H)-thione

“…the substrate 1 alkylation thanks to the greater rate constant for the alkylation with the bromo derivatives when compared with chloro derivatives and also the subsequent stage of cyclization of the intermediate compounds 2e,f,h thanks to their greater concentration as a result of higher rate of build up and greater solubility when compared with the intermediate compounds 2a-d. Also contributing is the greater time they exist in solutions of the first thanks to their higher solubility and longer time for cyclization in the solution state. Our data for the alkylation of homologous cyclic thioureas [1,5,6] also supports the greater solubility of the bromides than the analogous chlorides. In those cases where the intermediate hydrobromides 2e and 2g still fall out of the reaction mixture (see below) they form well defined crystals and not "oil up" the precipitate formed from the reaction mixture thanks to their relatively high concentration in solution.…”

“…In fact, the mass spectrum showed a "molecular ion" peak corresponding to the cation with m/z 171. The 1 H NMR spectrum in DMSO-d 6 also corresponded to structure 3a and strongly recalled that of the desmethyl analog [5] with the exception of a small shift to lower field of the signal for the two H-2 protons (4.39 instead of 4.15 ppm) and this might be explained by the greater positive charge on the sulphur atom in the mesomeric cation 3a when compared with its desmethyl analog. The initial formation of oily materials can be explained by the comparable rates of the alkylation and cyclization stages and the low solubility in acetone of the products of these stages (the hypothetical monocyclic intermediate compounds 2a-d and the final bicycle 3a which simultaneously fall out of the reaction mixture).…”

“…As a result of alkylation with ethylbromo or ethylchloroacetate under "mild" conditions (room temperature in anhydrous acetone) it was possible to prepare "open" S-carbethoxymethyl propylenethiourea hydrohalide derivatives [5]. It was expected that the presence of an N-methyl substituent in the 1-methyltetrahydropyrimidine-2(1H)-thione molecule (1) would hinder the cyclization of the isothiouronium salts 2a-h which were formed when alkylating with α-halocarboxylic acids and their esters.…”

“…A paradoxical trend in the extent of the hydrolysis decreasing with the content of the water in the alcoholic solution comes to a complete stop in water. A possible explanation of this phenomenon is given.Keywords: 1-methyltetrahydropyrimidine-2(1H)-thione (N-methylpropylenethiourea), alkylation with chloro and bromoacetic acids and their esters.The reaction of tetrahydropyrimidine-2(1H)-thione (propylenethiourea) with α-halocarboxylic acids gives only the bicyclic thiazolo[3,2-a]pyrimidine hydrohalide structures [2][3][4][5]. As a result of alkylation with ethylbromo or ethylchloroacetate under "mild" conditions (room temperature in anhydrous acetone) it was possible to prepare "open" S-carbethoxymethyl propylenethiourea hydrohalide derivatives [5].…”

“…The reaction of tetrahydropyrimidine-2(1H)-thione (propylenethiourea) with α-halocarboxylic acids gives only the bicyclic thiazolo[3,2-a]pyrimidine hydrohalide structures [2][3][4][5]. As a result of alkylation with ethylbromo or ethylchloroacetate under "mild" conditions (room temperature in anhydrous acetone) it was possible to prepare "open" S-carbethoxymethyl propylenethiourea hydrohalide derivatives [5].…”