New synthesis of 5,6-dihydrothiazolo[3,2-b][1,2,4]triazoles

Abstract

SHORT COMMUNICATIONS Fused 5,[1,2,4]triazole system may be constructed in several ways: (1) by reaction of 1,2,4-triazole-3(5)-thiols with 1,2-dibromoethane [1, 2], (2) by cyclization of 3-allylsulfanyl-1,2,4-triazoles by the action of iodine [3], and (3) by reaction of 3,5-dibromo-1-(thiiran-2-ylmethyl)-1,2,4-triazole with nucleophiles [4]. In the first two methods, isomeric 5,6-dihydrothiazolo[2,3-c][1,2,4]triazoles are formed as by-products [1][2][3].We now propose a new one-step procedure for the synthesis of 5,6-dihydrothiazolo[3,2-b][1,2,4]triazole derivatives by reaction of 3,5-dibromo-1,2,4-triazole with thiiranes. 5,6-Dihydrothiazolo[3,2-b][1,2,4]triazoles IIIa-IIIc were synthesized in 44-67% yield by heating triazole I with an equimolar amount of thiirane IIa-IIc in dimethylformamide in the presence of potassium hydroxide. The structure of compounds IIIa-IIIc was confirmed by elemental analysis and IR and 1 H and 13 C NMR spectroscopy. methods showed no depression of the melting point on mixing, and their IR spectra completely coincided. These data indicated that the thiirane ring is opened according to the Krasuskii rule [5]. 2-Bromo-5,6-dihydrothiazolo[3,2-b][1,2,4]triazole (IIIa).A solution of 2.26 g (10 mmol) of triazole I, 0.56 g (10 mmol) of KOH, and 0.60 g (10 mmol) of thiirane (IIa) in 20 ml of DMF was heated for 5 h at 45-50°C. The mixture was diluted with water to a ratio of 1 : 10 and extracted with ethyl acetate (2 × 50 ml), and the extract was evaporated. Yield 0.98 g (48%), mp 115-117°C (from i-PrOH). 2-Bromo-5-morpholinomethyl-5,6-dihydrothiazolo[3,2-b][1,2,4]triazole (IIIb).A solution of 1.59 g (7 mmol) of triazole I, 0.39 g (7 mmol) of KOH, and 1.10 g (7 mmol) of thiirane IIb in 15 ml of DMF was heated for 2 h under reflux. The mixture was cooled and diluted with water until a solid separated, and the precipitate was filtered off. Yield 1.43 g (67%), mp 163.5-165°C (from i-PrOH). IR spectrum, ν, cm -1 : . Found, %: C 35.34; H 4.35; N 18.24. C 9 H 13 BrN 4 OS. Calculated, %: C 35.42; H 4.29; N 18.36. 2-Bromo-5-methoxymethyl-5,6-dihydrothiazolo-[3,2-b][1,2,4]triazole (IIIc) was synthesized as described above for compound IIIb from 2.26 g (10 mmol) of triazole I and 1.04 g (10 mmol) of thiirane IIc in the presence of 0.56 g (10 mmol) of KOH. The mixture was diluted with water to a ratio of 1 : 10 and extracted with diethyl ether (3 × 40 ml), and the extract was evaporated. Yield 1.09 g (44%), mp 69-70°C