Tetrazoles are a class of synthetic organic heterocyclic compound, consisting of a 5-member ring of four nitrogen atoms and one carbon atom. The name tetrazole also refers to the parent compound with formula CH2N4, of which three isomers can be formulated.
Three isomers of the parent tetrazole exist, differing in the position of the double bonds: 1H-, 2H-, and 5H-tetrazole. The 1H- and 2H- isomers are tautomers, with the equilibrium lying on the side of 1H-tetrazole in the solid phase.[3][4][5] In the gas phase, 2H-tetrazole dominates.[4][6][7] These isomers can be regarded as aromatic, with 6 π-electrons, while the 5H-isomer is nonaromatic.
Tautomerization of the 1H-tetrazole (left) and 2H-tetrazole (middle) aromatic isomers in comparison with the nonaromatic 5H-tetrazole (right)
Phosphorus analogs do not have the same electronic nature, with 1H-tetraphosphole having a more pyramidal geometry of the phosphorus at position 1. Instead, it is the anionic tetraphospholides that are aromatic.[8]
There are several pharmaceutical agents which are tetrazoles, including several cephalosporin-class antibiotics. Tetrazoles can act as bioisosteres for carboxylate groups because they have similar pKa and are deprotonated at physiological pH. Angiotensin II receptor blockers — such as losartan and candesartan, often are tetrazoles.
A well-known tetrazole is dimethyl thiazolyl diphenyl tetrazolium bromide (MTT). This tetrazole is used in the MTT assay to quantify the respiratory activity of live cells culture, although it generally kills the cells in the process. Some tetrazoles can also be used in DNA assays.[12] Studies suggest VT-1161 and VT-1129 are a potential potent antifungal drugs as they disturbs fungal enzymatic function but not human enzymes.[13][14]
Other tetrazoles are used for their explosive or combustive properties, such as tetrazole itself and 5-aminotetrazole, which are sometimes used as a component of gas generatorsinautomobileairbags. Tetrazole based energetic materials produce high-temperature, non-toxic reaction products such as water and nitrogen gas,[17] and have a high burn rate and relative stability,[18] all of which are desirable properties. The delocalization energy in tetrazole is 209 kJ/mol.
1H-Tetrazole and 5-(benzylthio)-1H-tetrazole (BTT) are widely used as acidic activators of the coupling reaction in oligonucleotide synthesis.[19]
^Mihina, Joseph S.; Herbst, Robert M. (1950). "The Reaction of Nitriles with Hydrazoic Acid: Synthesis of Monosubstituted Tetrazoles". J. Org. Chem.15 (5): 1082–1092. doi:10.1021/jo01151a027.
^Collier, S. J. (2004). "Product Class 24: Tetraphospholes". In Storr, R. C.; Gilchrist, T. L. (eds.). Science of Synthesis. Vol. 13: Category 2, Hetarenes and Related Ring Systems. Thieme. doi:10.1055/sos-SD-013-01194. ISBN978-3-13-112281-0.
^Niko Fischer; Konstantin Karaghiosoff; Thomas M. Klapötke; Jörg Stierstorfer (April 2010). "New Energetic Materials featuring Tetrazoles and Nitramines – Synthesis, Characterization and Properties". Zeitschrift für Anorganische und Allgemeine Chemie. 636 (5): 735–749. doi:10.1002/zaac.200900521.
^Nicholas Piekiel & Michael R. Zachariah (2012). "Decomposition of Aminotetrazole Based Energetic Materials under High Heating Rate Conditions". J. Phys. Chem. A. 116 (6): 1519–1526. Bibcode:2012JPCA..116.1519P. doi:10.1021/jp203957t. PMID22214278.
^Xia Wei (May 6, 2013). "Coupling activators for the oligonucleotide synthesis via phosphoramidite approach". Tetrahedron. 69 (18): 3615–3637. doi:10.1016/j.tet.2013.03.001.
^Huisgen, Rolf; Seidel, Michael; Sauer, Juergen; McFarland, James; Wallbillich, Guenter (June 1959). "Communications: The Formation of Nitrile Imines in the Thermal Breakdown of 2,5-Disubstituted Tetrazoles". The Journal of Organic Chemistry. 24 (6): 892–893. doi:10.1021/jo01088a034.
^Bertrand, Guy; Wentrup, Curt (17 March 1994). "Nitrile Imines: From Matrix Characterization to Stable Compounds". Angewandte Chemie International Edition in English. 33 (5): 527–545. doi:10.1002/anie.199405271.
^Huisgen, Rolf (October 1963). "1,3-Dipolar Cycloadditions. Past and Future". Angewandte Chemie International Edition in English. 2 (10): 565–598. doi:10.1002/anie.196305651.
