ThePellizzari reaction was discovered in 1911 by Guido Pellizzari, and is theorganic reaction of anamide and ahydrazide to form a1,2,4-triazole.[1]
The product is similar to that of theEinhorn-Brunner reaction, but the mechanism itself is notregioselective.
The mechanism begins by thenitrogen in the hydrazide attacking thecarbonyl carbon on the amide to form compound3. The negatively charged oxygen then abstracts two hydrogens from neighboring nitrogens in order for a molecule of water to be released to form compound5. The nitrogen then performs an intramolecular attack on the carbonyl group to form the five-membered ring of compound6. After another proton migration from the nitrogens to the oxygen, another water molecule is released to form the 1,2,4-triazole8.[2]
The synthesis of the 1,2,4-triazole has a wide range of biological functions.[citation needed] 1,2,4-triazoles haveantibacterial,antifungal,antidepressant andhypoglycemic properties. 3-benzylsulfanyl derivates of the triazole also show slight to moderate antimycobacterial activity, but are considered moderately toxic.[3]
The Pellizzari reaction is limited in the number of substituents that can be on the ring, so other methods have been developed to incorporate three elements of diversity. Liquid-phase synthesis of 3-alkylamino-4,5-disubstituted-1,2,4-triazoles by PEG support has given moderate yields with excellent purity.[4] In practice, the Pellizzari reaction requires high temperatures, long reaction times, and has an overall low yield. However, adding microwave irradiation shortens the reaction time and increases its yield.[5]