Triazole

Isomerism

There are four triazole isomers, which are conventionally divided into two pairs of tautomers. In the 1,2,3-triazoles, the three nitrogen atoms are adjacent; in the 1,2,4-triazoles, an interstitial carbon separates out one nitrogen atom. Each category has two tautomers that differ by which nitrogen has a hydrogen bonded to it.

Preparation

There are several methods to prepare triazoles.

1,2,3-Triazoles

Main article: 1,2,3-Triazole

1,2,3-Triazoles, also known as vicinal triazoles, are usually prepared following (3+2) cycloaddition protocols. A common technique for unsubstituted triazoles is the Huisgen azide-alkyne 1,3-dipolar cycloaddition: a azide and an alkyne react at high temperature to form a ring. However, the Huisgen strategy produces a mixture of isomers (typically 1,4- and 1,5-disubstituted) when used to produce substituted triazoles. [[File:Huisgen-azide-alkyne-cycloaddition.png|frameless|center|upright=2|Thermal addition gives a mixture of 1,4 and 1,5 isomers]]

In order to selectively prepare a desired isomer, metal catalysts are employed. In the copper-catalysed azide-alkyne cycloaddition (CuAAC), copper(I) salts select for the formation of 1,4-disubstituted 1,2,3-triazoles. One such catalyst is CuBr(PPh3)3, which is relatively stable towards oxidation even at elevated temperatures and can produce triazoles with a broad range of substituents either in solvent or under neat reaction conditions. [[File:CuAAC-triazole-synthesis.png|frameless|center|upright=2|1,4 isomer from a CuI catalyst]]

Conversely, ruthenium catalysts (RuAAC) select for 1,5-disubstituted 1,2,3-triazoles. [[File:RuAAC-triazole-synthesis.png|frameless|center|upright=2|1,5 isomer from a Ru catalyst]]

1,2,4-Triazoles

Main article: 1,2,4-Triazole

Most techniques for producing 1,2,4-triazoles use the free energy of water, either by dehydrating a mixture of amides and hydrazides (the Pellizzari reaction) or imides and alkyl hydrazines (the Einhorn-Brunner reaction). Of those two, only the Einhorn-Brunner reaction is regioselective. Recent research has focused on grinding and microwave irradiation as greener substitutes.

Applications

Triazoles are compounds with a vast spectrum of applications, varying from materials (polymers), agricultural chemicals, pharmaceuticals, photoactive chemicals and dyes.

Benzotriazole is used in chemical photography as a restrainer and fog suppressant.

Cyclohexylethyltriazol was briefly used as an alternative to Cardiazol (Metrazol) in convulsive shock therapy treatment of mental illnesses during the 1940s.

Importance in agriculture

Many triazoles have antifungal effects: the triazole antifungal drugs include fluconazole, isavuconazole, itraconazole, voriconazole, pramiconazole, ravuconazole, and posaconazole and triazole plant-protection fungicides include epoxiconazole, , myclobutanil, propiconazole, prothioconazole, metconazole, cyproconazole, tebuconazole, flusilazole and paclobutrazol.

Due to spreading resistance of plant pathogens towards fungicides of the strobilurin class, control of fungi such as Septoria tritici or Gibberella zeae relies heavily on triazoles. Food, like store bought potatoes, contain retardants such as triazole or tetcyclacis.

In addition, paclobutrazol, uniconazole, , and triadimefon are used as plant growth retardants. Brassinazole inhibits brassinosteroid biosynthesis.

Importance in chemical synthesis

The azide alkyne Huisgen cycloaddition

Related heterocycles

• Imidazole, an analog with two nonadjacent nitrogen atoms
• Pyrazole, an analog with two adjacent nitrogen atoms
• Tetrazole, an analog with four nitrogen atoms
• Triazolium salts, substituted analogues that can be used as NHC precursors

References

References

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