Choline Chloride Based Deep Eutectic Solvents as a Tuneable Medium for Synthesis of Coumarinyl 1,2,4‐Triazoles: Effect of Solvent Type and Temperature

Abstract

A study of 1,2,4‐triazole synthesis from 2‐((4‐methyl‐2‐oxo‐2H‐chromen‐7‐yl)oxy)acetohydrazide (1) or 2‐(7‐hydroxy‐2‐oxo‐2H‐chromen‐4‐yl)acetohydrazide (2) and various isothiocyanates, in deep eutectic solvents, was performed. In order to find the best conditions for 1,2,4‐triazole formation, a model reaction on 1 and phenylisothiocyanate was performed in 14 different choline chloride based deep eutectic solvents, at two different temperatures (40 °C and 80 °C). Pure 1,2,4‐triazoles were obtained in choline chloride/urea (1:2) and choline chloride/N‐methyl urea (1:3) deep eutectic solvents at 80 °C. Pure thiosemicarbazides were obtained in choline chloride/ethane‐1,2‐diol (1:2), choline chloride/malic acid (1:1), choline chloride/malonic acid (1:1), choline chloride/butane‐1,4‐diol (1:3) and choline chloride/glycerole (1:2) at 40 °C. The ratio of 1,2,4‐triazoles and thiosemicarbazides in reaction mixtures was determined by HPLC and 1H NMR. After the best conditions for 1,2,4‐triazole synthesis were found, some coumarinyl 1,2,4‐triazoles were synthesized from two different coumarinyl hydrazides (1 and 2) and various alkyl and aryl isothiocyanates in one step reaction.