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Synthesis of tetrazoles

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Treatment of organic nitriles with NaN3 in the presence of iodine or silica-supported sodium hydrogen sulfate as a heterogeneous catalyst enables an advantageous synthesis of 5-substituted 1H-tetrazoles.
B. Das, C. R. Reddy, D. N. Kumar, M. Krishnaiah, R. Narender, Synlett, 2010, 391-394.


An efficient microwave-accelerated method allows the conversion of inactive nitriles into 5-substituted 1H-tetrazoles in DMF.
H. Yoneyama, Y. Usami, S. Komeda, S. Harusawa, Synthesis, 2013, 45, 1051-1059.


5-Substituted tetrazoles were prepared in very good yields and short reaction times by treatment of nitriles with sodium azide and triethylammonium chloride in nitrobenzene in a microwave reactor. Even sterically hindered tetrazoles, as well as those deactivated by electron-donating groups, can be prepared.
J. Roh, T. V. Artamonova, K. Vávrová, G. I. Koldobskii, A. Hrabálek, Synthesis, 2009, 2175-2178.


Thiocyanates and nitriles are converted efficiently into the corresponding 5-substituted 1H-tetrazoles in the presence of zinc(II) chloride and sodium azide in isopropanol, n-propanol, or n-butanol. The procedure offers mild reaction conditions, short reaction times, and very good yields for a wide range of substrates.
S. Vorona, T. Artamonova, Y. Zevatskii, L. Myznikov, Synthesis, 2014, 46, 781-786.


Activation of the nitrile substrate by the Brřnsted or Lewis acid catalyst is responsible for rate enhancement in azide-nitrile cycloaddition. Lewis acids such as Zn or Al salts perform in a similar manner, activating the nitrile moiety and leading to an open-chain intermediate that subsequently cyclizes to produce the tetrazole nucleus. The desired tetrazole structures were obtained in high yields within 3-10 min employing controlled microwave heating.
D. Cantillo, B. Gutmann, C. O. Kappe, J. Am. Chem. Soc., 2011, 133, 4465-4475.


An organocatalyst, 5-azido-1-methyl-3,4-dihydro-2H-pyrrolium azide, generated in situ from N-methyl-2-pyrrolidone (NMP), sodium azide, and trimethylsilyl chloride, enables the formation of tetrazoles by cycloaddition of sodium azide with organic nitriles under neutral conditions and microwave heating. The organocatalyst accelerates the azide-nitrile coupling by activating the nitrile substrate.
D. Cantillo, B. Gutmann, C. O. Kappe, J. Am. Chem. Soc., 2011, 133, 4465-4475.


An easy and efficient one-pot, three-component reaction of aldehydes, hydroxylamine, and [bmim]N3 enables the synthesis of 5-substituted 1H-tetrazole derivatives.
M. M. Heravi, A. Fazeli, H. A. Oskooie, Y. S. Beheshtiha, H. Valizadeh, Synlett, 2012, 23, 2927-2930.


5-substituted 1H-tetrazole derivatives can be prepared in good to excellent yields from various oximes and sodium azide by using indium(III) chloride as a Lewis acid catalyst. The method has significant advantages, such as an inexpensive catalyst, low catalyst loading, mild reaction conditions, and a convenient experimental procedure.
S. D. Guggilapu, S. K. Prajapti, A. Nagarsenkar, K. K. Gupta, B. N. Babu, Synlett, 2016, 27, 1241-1244.


A series of 1-substituted 1H-1,2,3,4-tetrazole compounds have been synthesized in good yields from amines, triethyl orthoformate, and sodium azide through the catalyzed reaction with Yb(OTf)3.
W.-K. Su, Z. Hong, W.-G. Shan, X.-X. Zhang, Eur. J. Org. Chem., 2006, 2723-2726.


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.


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.


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.


Cascade reactions starting from isocyanides allow a straightforward synthesis of five-membered ring heterocycles. Addition of sodium azide on isocyanide dibromides followed by electrocyclization and a Suzuki coupling affords tetrazoles scaffolds, whereas addition of tetrazoles on isocyanide dibromides followed by Huisgen rearrangement and a Suzuki coupling gives triazoles scaffolds.
L. El Kaim, L. Grimaud, P. Patil, Org. Lett., 2011, 13, 1261-1263.


A general method for the synthesis of 1,5-disubstituted tetrazoles from imidoylbenzotriazoles involves mild reaction conditions and short reaction times.
A. R. Katritzky, C. Cai, N. K. Meher, Synthesis, 2007, 1204-1208.


The reaction of cyanogen azide and primary amines generates imidoyl azides as intermediates in acetonitrile/water. After cyclization, these intermediates gave 1-substituted aminotetrazoles in good yield.
Y.-H. Joo, J. M. Shreeve, Org. Lett., 2008, 10, 4665-4667.


A versatile and highly efficient Zn(OTf)2-catalyzed one-pot reaction of alkenes, NBS, nitriles, and TMSN3 gives various 1,5-disubstituted tetrazoles containing an additional α-bromo functionality of the N1-alkyl substituent.
S. Hajra, D. Sinha, M. Bhowmick, J. Org. Chem., 2007, 72, 1852-1855.


The use of N-Boc-protected hydrazine in the Ugi tetrazole reaction provides a library of highly substituted 5-(hydrazinomethyl)-1-methyl-1H-tetrazoles in good yield.
P. Patil, J. Zhang, K. Kurpiewska, J. Kalinowska-Tłuścik, A. Dömling, Synthesis, 2016, 48, 1122-1130.