Manipulation of N,O-nucleophilicity: efficient formation of 4-N-substituted 2,4-dihydro-3H-1,2,4-triazolin-3-ones

Xianhai Huang; Anandan Palani; Dong Xiao; Robert Aslanian; Neng-Yang Shih

doi:10.1021/ol0478638

Manipulation of N,O-nucleophilicity: efficient formation of 4-N-substituted 2,4-dihydro-3H-1,2,4-triazolin-3-ones

Org Lett. 2004 Dec 9;6(25):4795-8. doi: 10.1021/ol0478638.

Authors

Xianhai Huang¹, Anandan Palani, Dong Xiao, Robert Aslanian, Neng-Yang Shih

Affiliation

¹ Department of Medicinal Chemistry, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA. [email protected]

PMID: 15575688
DOI: 10.1021/ol0478638

Abstract

A new efficient two-step synthesis of 2,4-dihydro-3H-1,2,4-triazolin-3-ones (triazolinones) from readily available amines is reported. Our novel conditions using hexamethyl disilazane, bromotrimethylsilane, and a catalytic amount of ammonium sulfate smoothly cyclize 1-formyl and 1-acetyl semicarbazides to the target triazolinones. This transformation features simultaneous manipulation of N- and O-nucleophilicity as well as differentiation of the nucleophilicity of a urea and an acyl carbonyl.