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Synthesis of 2H-tetrazoles


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A series of primary alcohols and aldehydes were treated with iodine in ammonia water under microwave irradiation to give the intermediate nitriles, which without isolation underwent [2 + 3] cycloadditions with dicyandiamide and sodium azide to afford the corresponding triazines and tetrazoles in high yields.
J.-J. Shie, J.-M. Fang, J. Org. Chem., 2007, 72, 3141-3144.

J.-J. Shie, J.-M. Fang, J. Org. Chem., 2007, 72, 3141-3144.

An alkylation reaction of monosubstituted tetrazoles via the diazotization of aliphatic amines enables preferential formation of 2,5-disubstituted tetrazoles. A one-pot 1,3-dipolar cycloaddition/diazotization sequence starting from widely available nitriles is also described.
G. Reynard, H. Lebel, J. Org. Chem., 2021, 86, 12452-12459.

The reaction of aryldiazonium salts with amidines followed by oxidative ring closure with I2/KI under basic conditions provides 2,5-disubstituted tetrazoles in good yields. This one-pot synthesis offers mild reaction conditions, short reaction time and a convenient workup.
M. Ramanathan, Y.-H. Wang, S.-T. Liu, Org. Lett., 2015, 17, 5886-5889.

The use of diaryliodonium salts enables a simple, metal-free regioselective N2-arylation strategy for 5-substituted-1H-tetrazoles to provide 2-aryl-5-substituted-tetrazoles. Diaryliodonium salts with a wide range of both electron-rich and previously challenged electron-deficient aryl groups are applicable. A one-pot system achieves the synthesis of 2,5-diaryl-tetrazoles directly from nitriles.
R. A. Saikia, A. Dutta, B. Sarma, A. J. Takur, J. Org. Chem., 2022, 87, 9782-9796.

A mild and highly regioselective 2-arylation of 5-substituted tetrazoles proceeds with various arylboronic acids in the presence of [Cu(OH)(TMEDA)]2Cl2 to afford 2,5-disubstituted tetrazoles.
T. Onaka, H. Umemoto, Y. Miki, A. Nakamura, T. Maegawa, J. Org. Chem., 2014, 79, 6703-6707.

Various 5-aryl-2-methyltetrazoles and 5-aryl-2-benzyltetrazoles were directly prepared in good yields under transition metal-free and mild conditions by the reaction of aromatic aldehydes with methylhydrazine and benzylhydrazine, followed by treatment with di-tert-butyl azodicarboxylate and [bis(trifluoroacetoxy)iodo]benzene in a mixture of dichloromethane and 2,2,2-trifluoroethanol at room temperature.
T. Imai, R. Harigae, K. Moriyama, H. Togo, J. Org. Chem., 2016, 81, 3975-3980.

[3+2]-Cycloaddition of arenediazonium salts with a wide range of readily available α-diazocarbonyl compounds provides 2-aryl-5-acyl-2H-tetrazoles of high value in medicinal chemistry.
S. Chuprun, D. Dar'in, G. Kantin, M. Krasavin, Synthesis, 2019, 51, 3998-4005.

N-Iodosuccinimide promotes a [3 + 2] annulation reaction of aryldiazonium salts with guanidines for the construction of previously elusive 2-aryl-5-amino-2H-tetrazoles. This transformation takes advantage of readily available starting materials, proceeds under metal-free, mild, and robust conditions, and offers broad functional group compatibility.
Y.-L. Yang, S. Li, F.-G. Zhang, J.-A. Ma, Org. Lett., 2021, 23, 8894-8898.