Alkylation of tetrazoles

Alkylation of tetrazoles as the anions gives mixtures of 1- and 2-alkyl isomers. In general, electron-donating substituents in the 5-position slightly favor alkylation of the 1-position and electron-withdrawing 5-substituents slightly favor the 2-position. 

In general, tetrazolium salts are prepared by (a) oxidation of formazans and (b) alkylation of tetrazoles. Therefore, synthetic methods for formazans and tetrazoles are discussed first, followed by some direct and miscellaneous methods. 

Preparative methods and chemical properties of tetrazole-5-thiones (tetrazole-5-thiols) have been summarized in a review <2004RJ0447>. The most significant results in this field were obtained in the last decade while studying the alkylation of tetrazole-5-ylthiones (tetrazole-5-ylthiols), and the oxidation of 1-substituted 5-alkylsulfatetrazoles to the corresponding sulfinyl and sulfonyl derivatives. Special attention should be paid to the Kocienski-modified Julia olefination based on the application of 5-alkylsulfonyltetrazoles to the activation of chemical reactions. 

As previously mentioned (cf. Sections 6.07.4.2.2 and 6.07.5.3), 2-( 1 -methylvinyl)tetrazoles 201 have been obtained by regioselective alkylation of tetrazole 2 and 5R-tetrazoles 24 with l-halopropan-2-ols and 3-bromopropene followed by dehydrohalogenation of the intermediate products 266 (Scheme 30) <1997MC41>. Similarly, dehydrobromina-tion of 2-bromoethyl-5-nitrotetrazole 457 afforded in good yield 2-vinyl-5-nitrotetrazole 458 (Equation 89) <1997RJO 771>. 

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