A Multicomponent Electrosynthesis of 1,5-Disubstituted and 1-Aryl 1,2,4-Triazoles

Abstract

A novel electrochemical route has been developed for the synthesis of 1,5-disubstituted and 1-aryl 1,2,4-triazoles from aryl hydrazines, paraformaldehyde, NHOAc, and alcohols. In this multicomponent reaction system, alcohols act as solvents as well as reactants and NHOAc is used as the nitrogen source. With the assistance of reactive iodide radical or I and NH electrogenerated in situ, this process could effectively avoid the use of strong oxidants and transition-metal catalysts and be smoothly carried out at room temperature to give a wide array of 1,2,4-triazole derivatives in good to high yields. Preliminary studies reveal that the reaction mechanism involves a radical process.

Multicomponent reactions and photo/electrochemistry join forces: atom economy meets energy efficiency

“…207 The electrocatalytic synthesis of 1,5-disubstituted and 1-aryl-1,2,4-triazoles was also accomplished by Yang and Yuan. 208 The authors employed aryl hydrazines, paraformaldehyde, NH 4 OAc, and alcohols as starting materials in a multicomponent approach in an undivided cell and without the need of strong exogeneous oxidants or transition metal catalysts. The key steps of this transformation are the anodic oxidation of TBAI (n-Bu 4 NI) to iodine radical or molecular iodine, and the concomitant reduction of NH 4 + at the cathode, thus generating the required NH 3 .…”

Electrifying Sustainability on Transition Metal‐Free Modes: An Eco‐Friendly Approach for the Formation of C−N Bonds

“…Yang and Yuan [35] proved the combination of iodide mediator with electrocatalysis to be successful in promoting the conversion of phenyl hydrazines, paraformaldehyde, and alcohol through a multi‐synthetic route for the synthesis of triazoles using ammonium acetate (NH 4 OAc) as a nitrogen source (Scheme 24). As compared to the traditional approaches, this hybrid electro‐synthetic approach allows the reaction to be conducted at room temperature.…”

Design and synthesis of coumarin-triazole hybrids: biocompatible anti-diabetic agents, in silico molecular docking and ADME screening

“…Structure proofs of the synthesized compounds 5b, 5d, 5e, and 8 (a-e) obtained by 1 H NMR, 13 aromatic region in their respective spectra. The compounds 8 (a-e) show singlets at δ 5.61-5.92 ppm for -NH 2 ; at δ 8.38-8.40 ppm for C 4 -H; and at δ 13.40-13.62 ppm for -SH protons.…”

“…Five-membered heterocycles, specifically, 1,2,4-triazoles plays a pivotal role in medicinal chemistry for their versatile applications. 1,2,4-Triazoles were synthesized by; a cycloaddition of nitriles and amidines in the presence MCM-41/copper(I) complex as heterogeneous catalyst [12], iodine catalyzed multicomponent reaction of aryl hydrazines, paraformaldehyde, NH 4 OAc, and alcohols under electrochemical conditions [13], regio-selective synthesis involving Ag(I) catalyzed reaction of ethyl cyanoacetate with aryldiazoniumtetrafluoroborate in water at 0 C [14], Iodine catalyzed environmentally benign C-N bond formation from isothiocyanates in water at room temperature [15], palladium and copper catalyzed arylation of styrene [16], triflic anhydride activated microwave-induced one-pot synthesis involving secondary amides and hydrazides [17], and by the reaction of hydrazides with isothiocyanate under optimized reaction conditions [18] 1,2,4-Triazoles were reported to show DHFR inhibitor [19], and antimicrobial [20] activities.…”