Pellizzari reaction

The Pellizzari reaction was discovered in 1911 by Guido Pellizzari, and is the organic reaction of an amide and a hydrazide to form a 1,2,4-triazole.[1]

The product is similar to that of the Einhorn-Brunner reaction, but the mechanism itself is not regioselective.

An overview of the Pellizzari reaction

Mechanism

The mechanism begins by the nitrogen in the hydrazide attacking the carbonyl carbon on the amide to form compound 3. The negatively charged oxygen then abstracts two hydrogens from neighboring nitrogens in order for a molecule of water to be released to form compound 5. The nitrogen then performs an intramoleculer attack on the carbonyl group to form the five-membered ring of compound 6. After another proton migration from the nitrogens to the oxygen, another water molecule is released to form the 1,2,4-triazole 8.[2]

Pellizzari reaction mechanism

Uses

The synthesis of the 1,2,4-triazole has a wide range of biological functions. 1,2,4-triazoles have antibacterial, antifungal, antidepressant and hypoglycemic properties. 3-benzylsulfanyl derivates of the triazole also show slight to moderate antimycobacterial activity, but are considered moderately toxic. [3]

Problems and variations

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]

  • Einhorn-Brunner reaction
gollark: Which planes need. A lot.
gollark: Except fuel-y stuff is actually energy- and power-dense.
gollark: > One inadequately solved design problem was the need for heavy shielding to protect the crew and those on the ground from acute radiation syndrome; other potential problems included dealing with crashes.[2] ah yes.
gollark: That is not much of an issue. The carbon dioxide production from them is. If we ran out somehow, it would be possible to synthesize more (with energy input, obviously).
gollark: Also, I think there are some nuclear plane concepts? Generally they use the heat from the nuclear stuff directly in some way.

References
  1. Pellizzari, G. Gazz. Chim. Ital. 1911, 41, 20.
  2. Wang, Z (2009). Comprehensive Organic Name Reactions. 2. John Wiley & Sons. pp. 2157–2158. ISBN 9780471704508.
  3. Klimesová, V.; Zahajská, L. (2004). "Synthesis and antimycobacterial activity of 1,2,4-triazole 3-benzylsulfanyl derivatives". Il Farmaco. 4: 279–288.
  4. Zong, Ying-Xiao; Wang, Jun-Ke; Yue, Guo-Ren; Feng, Lei; Song, Zheng-En; Song, Hai; Han, Yu-Qi (2005). "Traceless liquid-phase synthesis of 3-alkylamino-4,5-disubstituted-1,2,4-triazoles on polyethylene glycol (PEG)". Tetrahedron Letters. 46 (31): 5139–5141. doi:10.1016/j.tetlet.2005.05.121.
  5. Lee, Jongbok; Hong, Myengchan; Jung, Yoonchul; Cho, Eun Jin; Rhee, Hakjune (2012). "Synthesis of 1,3,5-trisubstituted-1,2,4-triazoles by microwave-assisted N-acylation of amide derivatives and the consecutive reaction with hydrazine hydrochlorides" (PDF). Tetrahedron. 68: 2045–2051. doi:10.1016/j.tet.2012.01.003. Archived from the original (PDF) on 2016-03-04. Retrieved 2014-05-20.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.