Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Tetrazole: Difference between pages

|Watchedfields = changed

|verifiedrevid = 470605243

|Name = 1''H''-Tetrazole

|ImageFileL1 = Tetrazole-2D-numbering.svg

|ImageFileR1 = Tetrazole3d.png

|Section1 = {{Chembox Identifiers

|InChI = 1/CH2N4/c1-2-4-5-3-1/h1H,(H,2,3,4,5)

|InChIKey = KJUGUADJHNHALS-UHFFFAOYAI

|InChI1 = 1S/CH2N4/c1-2-4-5-3-1/h1H,(H,2,3,4,5)

|InChIKey1 = KJUGUADJHNHALS-UHFFFAOYSA-N

|CASNo = 288-94-8

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = D34J7PAT68

|PubChem = 67519

|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

|ChemSpiderID = 60842

|ChEBI_Ref = {{ebicite|correct|EBI}}

|ChEBI = 33193

|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

|StdInChIKey = KJUGUADJHNHALS-UHFFFAOYSA-N

|SMILES = [nH]1nnnc1

|StdInChI_Ref = {{stdinchicite|correct|chemspider}}

|StdInChI =1S/CH2N4/c1-2-4-5-3-1/h1H,(H,2,3,4,5)

|Section2 = {{Chembox Properties

|Formula =CH₂N₄

|MolarMass = 70.05 g/mol

|Density = 1.477 g/mL

|MeltingPtC = 157 to 158

|MeltingPt_ref = <ref>{{cite journal | doi = 10.1021/jo01151a027 | title =The Reaction of Nitriles with Hydrazoic Acid: Synthesis of Monosubstituted Tetrazoles | last1 = Mihina | first1 = Joseph S. | last2 = Herbst | first2 = Robert M. | journal = [[J. Org. Chem.]] | year = 1950 | volume = 15 | issue = 5 | pages = 1082–1092}}</ref>

|BoilingPtC = 220 +/- 23

|pKa = 4.90<ref>{{cite journal | author1 = Satchell, Jacqueline F. | author2 = Smith, Brian J. | title = Calculation of aqueous dissociation constants of 1,2,4-triazole and tetrazole: A comparison of solvation models | journal = [[Phys. Chem. Chem. Phys.]] | year = 2002 | volume = 4 | issue = 18 | pages = 4314–4318 | doi = 10.1039/b203118c | bibcode = 2002PCCP....4.4314S}}</ref>

}}

}}

'''Tetrazoles''' are a class of [[chemical synthesis|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.

== Structure and bonding ==

Three isomers of the parent tetrazole exist, differing in the position of the double bonds: 1''H''-, 2''H''-, and 5''H''-tetrazole. The 1''H''- and 2''H''- isomers are [[tautomer]]s, with the equilibrium lying on the side of 1''H''-tetrazole in the solid phase.<ref>{{Cite journal|last1=Goddard|first1=R.|last2=Heinemann|first2=O.|last3=Krüger|first3=C.|date=1997-05-15|title=α-1H-1,2,3,4-Tetrazole|url=http://scripts.iucr.org/cgi-bin/paper?S0108270197000772|journal=Acta Crystallographica Section C|language=en|volume=53|issue=5|pages=590–592|doi=10.1107/S0108270197000772|bibcode=1997AcCrC..53..590G |issn=0108-2701}}</ref><ref name="Kiselev">{{Cite journal|last1=Kiselev|first1=Vitaly G.|last2=Cheblakov|first2=Pavel B.|last3=Gritsan|first3=Nina P.|date=2011-03-10|title=Tautomerism and Thermal Decomposition of Tetrazole: High-Level ab Initio Study|url=https://doi.org/10.1021/jp112374t|journal=The Journal of Physical Chemistry A|volume=115|issue=9|pages=1743–1753|doi=10.1021/jp112374t|pmid=21322546|bibcode=2011JPCA..115.1743K|issn=1089-5639}}</ref><ref>Razynska, A.; Tempczyk, A.; Malinski, E.; Szafranek, J.; Grzonka, Z.; Hermann, P.: in [[J. Chem. Soc.]] Perkin Trans. 2 1983, 379.</ref> In the gas phase, 2''H''-tetrazole dominates.<ref name="Kiselev"/><ref>{{Cite journal|last1=Wong|first1=Ming Wah|last2=Leung-Toung|first2=Regis|last3=Wentrup|first3=Curt|date=1993-03-01|title=Tautomeric equilibrium and hydrogen shifts of tetrazole in the gas phase and in solution|url=https://doi.org/10.1021/ja00059a048|journal=Journal of the American Chemical Society|volume=115|issue=6|pages=2465–2472|doi=10.1021/ja00059a048|issn=0002-7863}}</ref><ref>{{Cite journal|last1=Rażyńska|first1=Anna|last2=Tempczyk|first2=Anna|last3=Maliński|first3=Edmund|last4=Szafranek|first4=Janusz|last5=Grzonka|first5=Zbigniew|last6=Hermann|first6=Peter|date=1983-01-01|title=Application of mass spectrometry to the study of prototropic equilibria in 5-substituted tetrazoles in the gas phase; experimental evidence and theoretical considerations|url=https://pubs.rsc.org/en/content/articlelanding/1983/p2/p29830000379|journal=Journal of the Chemical Society, Perkin Transactions 2|language=en|issue=3|pages=379–383|doi=10.1039/P29830000379|issn=1364-5471}}</ref> These isomers can be regarded as [[aromatic]], with 6 π-electrons, while the 5''H''-isomer is nonaromatic.

[[File:Tetrazole_Tautomerism_V.png|thumb|center|400px|Tautomerization of the 1''H''-tetrazole (left) and 2''H''-tetrazole (middle) aromatic isomers in comparison with the nonaromatic 5''H''-tetrazole (right)]]

Phosphorus analogs do not have the same electronic nature, with 1''H''-tetraphosphole having a more [[pyramidal]] geometry of the phosphorus at position 1. Instead, it is the [[anion]]ic tetraphospholides that are aromatic.<ref>{{cite encyclopedia |title= Science of Synthesis |volume= 13: Category 2, Hetarenes and Related Ring Systems |chapter= Product Class 24: Tetraphospholes |first= S. J. |last= Collier |editor1-first= R. C. |editor1-last= Storr |editor2-first= T. L. |editor2-last= Gilchrist |publisher= Thieme |year= 2004 |doi= 10.1055/sos-SD-013-01194 |isbn= 978-3-13-112281-0 }}</ref>

==Synthesis==

1''H''-Tetrazole was first prepared by the reaction of anhydrous [[hydrazoic acid]] and [[hydrogen cyanide]] under pressure. Treatment of organic [[nitriles]] with [[sodium azide]] in the presence of [[iodine]] or silica-supported [[sodium bisulfate]] as a heterogeneous [[catalyst]] enables an advantageous synthesis of 5-substituted 1''H''-tetrazoles. Another method is the deamination of [[5-aminotetrazole]], which can be commercially obtained or prepared in turn from [[aminoguanidine]].<ref>{{Cite journal|last1=Henry|first1=Ronald A.|last2=Finnegan|first2=William G.|date=1954-01-01|title=An Improved Procedure for the Deamination of 5-Aminotetrazole|url=https://doi.org/10.1021/ja01630a086|journal=Journal of the American Chemical Society|volume=76|issue=1|pages=290–291|doi=10.1021/ja01630a086|issn=0002-7863}}</ref><ref>{{Cite journal|last1=Kurzer|first1=F.|last2=Godfrey|first2=L. E. A.|date=1963|title=Syntheses of Heterocyclic Compounds from Aminoguanidine|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.196304591|journal=Angewandte Chemie International Edition in English|language=en|volume=2|issue=8|pages=459–476|doi=10.1002/anie.196304591|issn=1521-3773}}</ref>

:[[File:Tetrazole_synthesis_02.svg|900px]]

2-Aryl-''2H''-tetrazoles are synthesized by a [3+2] [[cycloaddition]] reaction between an aryl [[Diazonium compound|diazonium]] and [[trimethylsilyldiazomethane]].<ref>{{Cite journal|last1=Patouret|first1=Remi|last2=Kamenecka|first2=Theodore M.|date=2016-04-06|title=Synthesis of 2-aryl-2H-tetrazoles via a regioselective [3+2] cycloaddition reaction|journal=Tetrahedron Letters|volume=57|issue=14|pages=1597–1599|doi=10.1016/j.tetlet.2016.02.102|pmc=4810784|pmid=27041776}}</ref>

==Uses ==

There are several pharmaceutical agents which are tetrazoles, including several [[cephalosporin]]-class antibiotics. Tetrazoles can act as [[bioisostere]]s for [[Carboxylic acid|carboxylate group]]s 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 [[cell respiration|respiratory activity]] of live cells [[cell culture|culture]], although it generally kills the cells in the process. Some tetrazoles can also be used in DNA assays.<ref>{{cite journal | journal = Nucleic Acids Res | date = Feb 11, 1989 | volume = 17 | issue = 3 | pages = 853–864 | title = Studies on the role of tetrazole in the activation of phosphoramidites |author1=S Berner |author2=K Mühlegger |author3=H Seliger |name-list-style=amp | pmc = 331708 | doi=10.1093/nar/17.3.853 | pmid=2922273}}</ref> Studies suggest VT-1161 and VT-1129 are a potential potent antifungal drugs as they disturbs fungal enzymatic function but not human enzymes.<ref>{{cite journal |last1=Warrilow |first1=A. G. S. |last2=Hull |first2=C. M. |authorlink2=Christina M. Hull|last3=Parker |first3=J. E. |last4=Garvey |first4=E. P. |last5=Hoekstra |first5=W. J. |last6=Moore |first6=W. R. |last7=Schotzinger |first7=R. J. |last8=Kelly |first8=D. E. |last9=Kelly |first9=S. L. |title=The Clinical Candidate VT-1161 Is a Highly Potent Inhibitor of Candida albicans CYP51 but Fails To Bind the Human Enzyme |journal=Antimicrobial Agents and Chemotherapy |date=December 2014 |volume=58 |issue=12 |pages=7121–7127 |doi=10.1128/AAC.03707-14|pmc=4249504 |pmid=25224009}}</ref><ref>{{cite journal |last1=Lockhart |first1=Shawn R. |last2=Fothergill |first2=Annette W. |last3=Iqbal |first3=Naureen |last4=Bolden |first4=Carol B. |last5=Grossman |first5=Nina T. |last6=Garvey |first6=Edward P. |last7=Brand |first7=Stephen R. |last8=Hoekstra |first8=William J. |last9=Schotzinger |first9=Robert J. |last10=Ottinger |first10=Elizabeth |last11=Patterson |first11=Thomas F. |last12=Wiederhold |first12=Nathan P. |title=The Investigational Fungal Cyp51 Inhibitor VT-1129 Demonstrates Potent Activity against Cryptococcus neoformans and Cryptococcus gattii |journal=Antimicrobial Agents and Chemotherapy |date=April 2016 |volume=60 |issue=4 |pages=2528–2531 |doi=10.1128/AAC.02770-15|pmc=4808209 |pmid=26787697}}</ref>

Some tetrazole [[derivative (chemistry)|derivatives]] with high energy have been investigated as high performance [[explosives]] as a replacement for [[TNT]] and also for use in high performance [[solid rocket propellant]] formulations.<ref>{{cite web | url = http://www.rsc.org/chemistryworld/News/2008/October/02100801.asp | title = Greener explosives show promise | date = 2 October 2008 | publisher = Chemistry World}}</ref><ref>{{cite journal | title = New Energetic Materials featuring Tetrazoles and Nitramines – Synthesis, Characterization and Properties | author1 = Niko Fischer|author2=Konstantin Karaghiosoff|author3=[[Thomas M. Klapötke]]|author4=Jörg Stierstorfer | journal = Zeitschrift für Anorganische und Allgemeine Chemie | volume = 636 | issue =5 | pages = 735–749 | date = April 2010 |doi = 10.1002/zaac.200900521| doi-access = }}</ref> These include the [[azidotetrazolate]] salts of nitrogen bases.

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 generator]]s in [[automobile]] [[airbags]]. Tetrazole based energetic materials produce high-temperature, non-toxic reaction products such as water and nitrogen gas,<ref>{{cite book | chapter = Energetic Tetrazole N-oxides | author = Tore Brinck, Thomas M. Klapötke and Jörg Stierstorfer | title = Energetic Tetrazole N -oxides| doi = 10.1002/9781118676448.ch06 | journal=Green Energetic Materials | pages=133–178| year = 2014 | isbn = 9781118676448 }}</ref> and have a high burn rate and relative stability,<ref>{{cite journal | title = Decomposition of Aminotetrazole Based Energetic Materials under High Heating Rate Conditions |author1=Nicholas Piekiel |author2=Michael R. Zachariah |name-list-style=amp | journal = J. Phys. Chem. A | date = 2012 | volume = 116 | issue = 6 | pages = 1519–1526 | doi = 10.1021/jp203957t|pmid=22214278 |bibcode=2012JPCA..116.1519P}}</ref> all of which are desirable properties. The delocalization energy in tetrazole is 209&nbsp;kJ/mol.

1''H''-Tetrazole and 5-(benzylthio)-1''H''-tetrazole (BTT) are widely used as acidic activators of the coupling reaction in [[oligonucleotide synthesis]].<ref>{{cite journal | title = Coupling activators for the oligonucleotide synthesis via phosphoramidite approach | author = Xia Wei | journal = Tetrahedron | volume = 69 | issue = 18 | pages = 3615–3637 | date = May 6, 2013 |doi = 10.1016/j.tet.2013.03.001 }}</ref>

2-Tetrazoles can undergo controlled [[thermal decomposition]] to form highly reactive [[nitrilimine]]s.<ref>{{cite journal |last1=Huisgen |first1=Rolf |last2=Seidel |first2=Michael |last3=Sauer |first3=Juergen |last4=McFarland |first4=James |last5=Wallbillich |first5=Guenter |title=Communications: The Formation of Nitrile Imines in the Thermal Breakdown of 2,5-Disubstituted Tetrazoles |journal=The Journal of Organic Chemistry |date=June 1959 |volume=24 |issue=6 |pages=892–893 |doi=10.1021/jo01088a034}}</ref><ref>{{cite journal |last1=Bertrand |first1=Guy |last2=Wentrup |first2=Curt |title=Nitrile Imines: From Matrix Characterization to Stable Compounds |journal=Angewandte Chemie International Edition in English |date=17 March 1994 |volume=33 |issue=5 |pages=527–545 |doi=10.1002/anie.199405271}}</ref> These can in turn undergo a variety of [[1,3-dipolar cycloaddition]] reactions.<ref>{{cite journal |last1=Huisgen |first1=Rolf |title=1,3-Dipolar Cycloadditions. Past and Future |journal=Angewandte Chemie International Edition in English |date=October 1963 |volume=2 |issue=10 |pages=565–598 |doi=10.1002/anie.196305651}}</ref>

[[Image:Nitrilimine origin.png|400px|center|Scheme 2. Nitrilimine formation]]

==Related heterocycles==

* [[Triazole]]s, analogs with three nitrogen atoms

* [[Pentazole]], the analog with five nitrogen atoms (strictly speaking, an inorganic homocycle, not a heterocycle)

* [[Oxatetrazole]]

* [[Thiatetrazole]]

==References==

{{reflist}}

[[Category:Tetrazoles| ]]

[[Category:Simple aromatic rings]]