Drugs in the tetrazole series. (Review)

Data on drugs of the tetrazole series published over the last decade are reviewed. The use of tetrazoles as isosteric substituents of various functional groups is examined. Dedicated to outstanding scientist Prof. E. Lukevics on his 70th birthday. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 3–13, January, 2007.     

Tetrazoles: L. Microwave-activated alkylation of 5-aryltetrazoles and 1-substituted tetrazole-5-thiones with 1,3-dibromo-2,2-bis(bromomethyl)propane

Alkylation of 5-aryltetrazoles and 1-substituted tetrazole-5-thiones with 1,3-dibromo-2,2-bis(bromomethyl)propane in dimethylformamide in the presence of sodium hydroxide leads to the formation of tetrakis(5-aryltetrazol-2-ylmethyl)methanes and tetrakis(1-R-tetrazol-5-ylsulfanylmethyl)methanes, respectively. Microwave activation considerably shortens the reaction time and increases the yield.     

Tetrazoles: LI. Synthesis of 5-substituted tetrazoles under microwave activation

Reaction of nitriles with sodium azide in the presence of ZnCl₂ under microwave activation (MWA) leads to the formation of 5-tetrazoles in high yields; therewith the process is 2–3 times shorter than the inactivated reaction.     

A simple method for the preparation of 5-alkylsulfinyl-1-aryltetrazoles

A simple method is suggested for the preparation of 5-alkylsulfinyl-1-aryltetrazoles via oxidation of 5-alkylsulfanyltetrazoles with 34% peracetic acid in high yields under mild conditions.     

Synthesis of Unsymmetrical Sulfides Derived from Tetrazole-5-thiols

A series of unsymmetrical sulfides derived from 1-substituted tetrazole-5-thiols was prepared by fusion of the corresponding 1-R-tetrazole-5-thiol sodium salt with 1-R'-5-halotetrazole. The structure was confirmed by ¹H NMR and ¹³C NMR spectra. The target compounds were prepared in 50-80% yields.     

1-Substituted 5-Alkyl(aryl)sulfanyltetrazoles and Their Derivatives

The review analyzes published data on the synthesis, chemical properties, and application of 1-substituted 5-alkyl(aryl)sulfanyltetrazoles. Specific attention is given to reactions of metalated 1-alkyl(aryl)-5-alkylsulfonyltetrazoles with electrophilic reagents as a general and highly stereoselective method for the preparation of functionally substituted olefins.     

Tetrazoles: XLVI. Alkylation of 5-Substituted Tetrazoles with Methyl Chloromethyl Ether and α-Methylstyrene

Alkylation of 5-aryl(hetaryl)tetrazoles with methyl chloromethyl ether under conditions of phase-transfer catalysis leads to formation of isomeric 1- and 2-methoxymethyltetrazoles at a ratio of ~1 : 2. The reaction of 5-substituted tetrazoles with -methylstyrene in the presence of trichloroacetic acid gives the corresponding 2-(,-dimethylbenzyl)tetrazoles in high yield and with high regioselectivity.