Synthesis of 5-aryloxymethyl-2-bromo-5,6-dihydrothiazolo-[3,2-b]-1,2,4-triazoles

Abstract

Derivatives of thiazolo[3,2-b]-1,2,4-triazole exhibit versatile kinds of biological activity, in particular, antiphlogistic [1], antibacterial [2], anticonvulsant [3], anticancer [4], and are promising objects for the search for new biologically active substances. However the information on the procedures of the synthesis of 5-substituted 5,6-dihydro thiazolo[3,2-b]-1,2,4-triazoles is limited to the description of the preparation of 5-substituted 5,6-dihydro thiazolo[3,2-b]-1,2,4-triazol-6-ones and 5-arylidenethiazolo[3,2-b]-1,2,4-triazol-6-ones [3–5]. We showed formerly that in the synthesis of 5-substituted 5,6-dihydro thiazolo[3,2-b]-1,2,4-triazoles iit is possible to utilize the reactions of 3,5-dibromo1,2,4-triazole with monofunctional thiiranes [6] or with 3,5-dibromo-1-(thiiran-2-ylmethyl)-1,2,4-triazole (I) with amines [7, 8]. In extension of these studies we examined the reactions of 3,5-dibromo-1-(thiiran-2-ylmethyl)1,2,4-triazole (I) with phenols. Reactions of 3,5-dibromo-1-(thiiran-2-ylmethyl)1,2,4-triazole (I) with 1.2–3-fold molar excess of potassium phenolates formed in situ in the reaction mixture was carried out at boiling in ethanol or butanol. Similar to the reaction with amines, thiirane (I) under the action of the phenolates opened at the side of the less substituted carbon atom in keeping with Krasusky rule [9] affording 5-aryloxymethyl-2-bromo-5,6-dihydrothiazolo [3,2-b]1,2,4-triazoles IIа–IId. The composition and structure of obtained compounds IIа–IId were confi rmed by the elemental analysis, IR, 1Н and 13С NMR spectra. The presence in the 1Н NMR spectra of compounds IIb, IId in C6D6 of the characteristic signals of the protons of NCH2 group in the form of two doublets of doublets in the range 3.3–3.4 and 3.6–3.9 ppm and of a multiplet of the proton of SСН group in the range 3.3–3.6 ppm confi rms the formation of the fused system of dihydrothiazolo[3,2-b]-1,2,4-triazole [7, 8]. In the 1Н NMR spectra of compounds IIa, IIc in CDCl3 the proton signals of the dihydrothiazole ring are shifted downfi eld by 1 ppm, therewith the signals of the protons