Atetrazole is asynthetic organicheterocyclic compound, consisting of a 5-member ring of fournitrogen atoms and onecarbon atom. The name tetrazole also refers to the parent compound - a whitish crystalline powder with the formula CH2N4, of which three isomers exist.
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 aretautomers, 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 asaromatic, 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 morepyramidal geometry of the phosphorus at position 1. Instead, it is theanionic tetraphospholides that are aromatic.[8]
Stronglyinductively electron-withdrawing functional groups attached to a tetrazole may stabilize a tautomeric ring-opening equilibrium with an azidoimine form.[9]
There are several pharmaceutical agents which are tetrazoles, including severalcephalosporin-class antibiotics. Tetrazoles can act asbioisosteres forcarboxylate groups because they have similar pKa and are deprotonated at physiological pH.Angiotensin II receptor blockers — such aslosartan andcandesartan, often are tetrazoles.A well-known tetrazole is dimethyl thiazolyl diphenyl tetrazolium bromide (MTT). This tetrazole is used in theMTT assay to quantify therespiratory activity of live cellsculture, although it generally kills the cells in the process. Some tetrazoles can also be used in DNA assays.[14] Studies suggest VT-1161 and VT-1129 are a potential potent antifungal drugs as they disturbs fungal enzymatic function but not human enzymes.[15][16]
Other tetrazoles are used for their explosive or combustive properties, such as tetrazole itself and5-aminotetrazole, which are sometimes used as a component ofgas generators inautomobileairbags. Tetrazole based energetic materials produce high-temperature, non-toxic reaction products such as water and nitrogen gas,[19] and have a high burn rate and relative stability,[20] 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 inoligonucleotide synthesis.[21]
^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.
^Burke, Luke A. (25 April 1983). "Possible cause for 5-trichloromethyltetrazole explosion" (letter to the editor),Chemical & Engineering News. p. 2.doi:10.1021/cen-v061n017.p002;but see Beck, Wolfgang and Geisenberger, Josef (5 Mar 1984). "5-Trichloromethyltetrazole",Ibid. p. 39.doi:10.1021/cen-v062n010.p002, which indicates that the trichloromethyl derivative does not exhibit such an equilibrium.
^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.
