Reactions of aromatic and heteroaromatic nitriles with sodium azide in the presence of zinc oxide under the conditions of microwave activation provide 5-aryl(hetaryl)tetrazoles in high yields.
SHORT COMMUNICATIONSDespite considerable interest in 2,5-disubstituted tetrazoles as potential substrates for the synthesis of biologically active substances, methods for their preparation have been developed to insufficient extent. Arylation of tetrazole and 5-substituted tetrazoles is one of the least studied reactions of these compounds. On the other hand, it may underlie a promising procedure for the preparation of difficultly accessible 2-substituted tetrazoles. Known methods for arylation of 5-substituted tetrazoles [1, 2] lead to formation of mixtures of isomeric 1,5-and 2,5-disubstituted derivatives. However, in some cases such reactions are characterized by high selectivity. For example, the arylation of 5-substituted tetrazolates [3-6] with diaryliodonium salts in the presence of different catalysts gives only 2,5-disubstituted tetrazoles. The arylation of 5-aryltetrazoles with 2,4-dinitrofluorobenzene also occurs at the 2-position of the tetrazole ring with high selectivity [7].In continuation of our studies on the synthesis of functionally substituted tetrazoles under conditions of microwave activation [8,9], we examined arylation of 5-aryl(alkyl)tetrazoles with 4-nitrofluorobenzene in DMF in the presence of sodium hydroxide under microwave irradiation. We previously showed [2] that the arylation of 5-methylsulfanyltetrazole with 4-nitrofluorobenzene in DMF in the presence of sodium hydroxide yields a mixture of 1,5-and 2,5-disubstituted isomers. However, no arylation of 5-alkyl-or 5-aryltetrazoles occurred under analogous conditions despite microwave activation or conventional heating. Obviously, the reason is low nucleophilicity of tetrazolate ion and competing reaction of 4-nitrofluorobenzene with DMF.We presumed that arylation of 5-alkyl(aryl)tetrazoles could be accomplished in another polar solvent, dimethyl sulfoxide. In fact, the arylation of 5-aryltetrazoles with 4-nitrofluorobenzene in DMSO in the presence of sodium hydroxide under microwave activation or without it (on heating) gave only the corresponding 2,5-diaryltetrazoles. Our results showed that microwave irradiation increases the yield of the arylation products by a factor of 1.5 to 3. Below are given the yields of 2,5-diaryltetrazoles IIId-IIIg obtained in microwave-assisted reaction and under conventional heating, respectively, %: IIId, 55, 40; IIIe, 77, 40; IIIf, 67, 40; IIIg, 60, 21. High yields of the arylation products under microwave activation made it possible to simplify the isolation procedure and avoid additional purification. Thus microwave-assisted arylation of 5-aryltetrazoles with 4-nitrofluorobenzene in DMSO in the presence of sodium hydroxide may be regarded as one of the simplest and effective procedures for the synthesis of 2,5-diaryltetrazoles.The arylation of 5-methyl-, 5-benzyl-, and 5-(4-chlorobenzyl)tetrazoles in all cases afforded mixtures of isomeric 1-and 2-aryl-5-alkyltetrazoles. The ratio of isomeric tetrazoles IIa : IIIa was 2 : 3, and the R = Me (a), PhCH 2 (b), 4-ClC 6 H 4 CH 2
SHORT COMMUNICATIONSTetrazole ring is stable toward oxidants [1,2], and its decomposition by the action of oxidants is a very rare case [3]. Reactions of mono-and disubstituted tetrazoles with oxidants usually involve only the substituents whose transformations depend on their nature and position in the heteroring. Therefore, oxidation of mono-and disubstituted tetrazoles may be regarded as a simple and efficient method for their functionalization, as well as for the preparation of monosubstituted tetrazoles.In continuation of our studies on the chemical properties of tetrazoles we examined oxidation of some 1-substituted tetrazole-5-thiones under microwave (MW) activation. Among various oxidants used previously for the oxidation of 1-substitued tetrazole-5-thiones [4-6], we selected hydrogen peroxide as the most convenient in handling and ecologically safe. As shown in [6], treatment of 1-aryltetrazole-5-thiones with 12% hydrogen peroxide in ethanol at 60°C (reaction time 10 min) leads to the formation of the corresponding bis-tetrazolyl disulfides in good yields. We found that oxidation of 1-substituted tetrazole-5-thiones with hydrogen peroxide under microwave activation gives 1-substituted tetrazoles. The reaction direction strongly depended on the concentration of hydrogen peroxide and reaction medium. Microwaveassisted oxidation of 1-phenyltetrazole-5-thione with 3.5% hydrogen peroxide gave 92% of bis(1-phenyl-1H-tetrazol-5-yl) disulfide. When the concentration of hydrogen peroxide was raised to 17.5% and acetic acid was used as solvent, the product was 1-phenyl-1H-tetrazole (Ic, yield 91%). Analogous relations were observed for the other examined tetrazole-5-thiones.Thus hydrogen peroxide under conditions of microwave activation is much more efficient than other oxidants, such as chromic [4] or nitric acid [7], that are usually used for oxidative desulfurization of 1-substituted tetrazole-5-thiones. 1-Ethyl-1H-tetrazole (Ia). 1-Ethyl-4,5-dihydro-1H-tetrazole-5-thione, 0.5 g (3.8 mmol), was dissolved in 10 ml of chloroform, 5 ml of 17.5% hydrogen peroxide and 0.5 ml of glacial acetic acid were added under stirring, and the mixture was stirred for 45 min at 50°C under microwave activation (20 W). The mixture was cooled to 20°C, 15 ml of cold water was added, and the organic layer was separated. The aqueous phase was neutralized to pH 7 with 25% aqueous ammonia and extracted with chloroform (2 × 10 ml). The extracts were combined, dried over magnesium sulfate, and evaporated under reduced pressure. Yield 85%, colorless oily substance [8]. IR spectrum, ν, cm -1 : 3436,
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