Solid Phase Synthesis of 3,4,5-Trisubstituted-1,2,4-Triazoles Derivatives from the Resin-Bound Acylhydrazines

Abstract

An extension of our methodology on solid-phase synthesis of 3,4,5-trisubstituted-1,2,4-triazoles under mild conditions has been developed. Firstly, the resin-bound acylhydrazine is reacted with orthoesters to provide resin-bound 1,3,4oxadiazoles. Secondly, condensation of 1,3,4-oxadiazoles resin with the corresponding arylamines hydrochloride to form the resin-bound triazoles. 3,4,5-Trisubstituted-1,2,4-triazoles derivatives were obtained from resin-bound acylhydrazines in several steps providing 78%-87% overall yields and excellent purity. The advantages of this method include straightforward operation and high yield and purity of the products.

A Review on Methods of Synthesis of 1,2,4-Triazole Derivatives

“…A mixture of compound 105 (5mmol) and phosphorus pentasulfide (5mmol) in dry xylene (50mL) refluxed for 1h, the product 106 obtained. A mixture of compound 106 (5mmol) and thiosemicarbazide (5mmol) and phosphorus oxychloride (5mmol) warmed at 60˚C for 1h and the temperature raised to 90˚C for additional 2h, the contents poured onto crushed ice, cooled to 10˚C, pH adjusted to 8 -10 with NaOH and the resulting solid separated as compound 107 67 .…”