1,2,4-Triazole

1,2,4-Triazole is one of a pair of isomeric chemical compounds with molecular formula CHN, called triazoles, which have a five-membered ring of two carbon atoms and three nitrogen atoms. 1,2,4-Triazole and its derivatives find use in a wide variety of applications.

Structure and properties

1,2,4-Triazole is a planar molecule. The C-N and N-N distances fall into a narrow range 136 - 132 picometers, consistent with the aromaticity. Although two tautomers can be envisioned, only one exists practically speaking.
1,2,4-Triazole is amphoteric, being susceptible to both N-protonation and deprotonation in aqueous solution. The pK_a of 1,2,4-triazolium is 2.45. The pK_a of the neutral molecule is 10.26.

Synthesis and occurrence

1,2,4-Triazoles can be prepared using the Einhorn–Brunner reaction or the Pellizzari reaction. Unsubstituted 1,2,4-triazole can be prepared from thiosemicarbazide by acylation with formic acid followed by cyclization of 1-formyl-3-thiosemicarbazide into 1,2,4-triazole-3-thiol; oxidation of the thiol by nitric acid or hydrogen peroxide yields 1,2,4-triazole.
1,2,4-Triazoles are featured in many kinds of drugs. Notable triazoles include the antifungal drugs fluconazole and itraconazole and the plant growth regulator paclobutrazol. Triazolate is a common bridging ligand in coordination chemistry.
The 3,5dihydroxy derivative, known as urazole, sees extensive industrial use as a blowing agent.