Milda M. Burbuliene

Synthesis of 1-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)acetyl-4-alkyl(aryl)thios emicarbazides and their heterocyclisation to 1,2,4-triazoles and 1,3,4-thiadiazoles

5-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)methyl-1,3,4-oxadiazole-2-thione reacts with amines to give 1-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)acetyl-4-alkyl(aryl)thiosemicarbazides, which on treatment with base or acid undergo cyclisation to 4-alkyl-1,2,4-triazole-2-thiones or 4-amino-1,3,4-thiadiazoles, respectively.

Reactions of 5-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-1,3,4-oxadiazole-2-thione with Electrophiles

Summary. Treatment of 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-1,3,4-oxadiazole-2-thione with haloalkanes yielded oxadiazole S-alkyl derivatives, whereas its reaction with formaldehyde and amines resulted in formation of oxadiazole N(3)-aminomethyl derivatives. The alkylation of 2-alkylsulfanyl-5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-1,3,4-oxadiazoles with methyl bromoacetate proceeded at the N(1)-position of pyrimidine to give 2-alkylsulfanyl-5-(1-methoxycarbonylmethyl-6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-1,3,4-oxadiazoles, whereas aminomethylation, bromination, or nitration took place at position 5 of pyrimidine ring and afforded the corresponding 5-pyrimidine substituted derivatives.

Synthesis of novel derivatives of 5-(4,6-dimethyl-2-pyrimidinylsulfanyl)methyl-1,2,4-triazole-3-thione

Alkylation of 5-(4,6-dimethyl-2-pyrimidinylsulfanyl)methyl-1,2,4-triazole-3-thione (2) with various alkyl halides, 4-chlorophenacyl bromide, chloroacetic acid, and α-chloroacetanilide afforded S-substituted 1,2,4-triazoles (3–11). 3-Carboxymethylsulfanyl-5-(4,6-dimethyl-2-pyrimidinylsulfanyl)methyl-1,2,4-triazole (9), in the presence of acetic anhydride, was cyclized to 6-(4,6-dimethyl-2-pyrimidinylsulfanyl)methylthiazolo[3,2-b][1,2,4]triazol-3(2H)-one (12). The later condensed with aromatic aldehydes to give 6-(4,6-dimethyl-2-pyrimidinylsulfanyl)methyl-6-[(1-aryl)methylidene]thiazolo[3,2-b][1,2,4]triazol-3(2H)-ones (13, 14) and under treatment with aniline underwent ring-disclosure reaction to yield 3-(phenylcarbamoyl)methylsulfanyl-5-(4,6-dimethyl-2-pyrimidinylsulfanyl)methyl-1,2,4-triazole (11).

Synthesis of new pyrimidinylthio-substituted 1,3,4-oxa(thia)diazoles and 1,2,4-triazoles

Novel 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazole-3-thiones bearing the pyrimidinylthio- moiety were synthesized by cyclization of a substituted-thiosemicarbazide precursor under different conditions. The thiosemicarbazide intermediates were easily accessed from reaction of biologically active 2-(4,6-dimethylpyrimidin-2-ylthio)acetohydrazide and 2-(2-dimethylamino-6-methyl pyrimidin-4-ylthio)acetohydrazide with cyclohexyl or phenyl isothiocyanate. The compounds are characterized by 1H, 13C NMR, IR spectroscopy and analytical data.