One-Pot Synthesis of 3,4,5-Trisubstituted 1,2,4-Triazoles via the Addition of Hydrazides to Activated Secondary Amides

Abstract

A general approach has been developed for the one-pot synthesis of 3,4,5-trisubstituted 1,2,4-triazoles from secondary amides and hydrazides via triflic anhydride activation followed by microwave-induced cyclodehydration. In addition, the 1,2,4-triazole moiety is shown to be a useful directing group for Ru-catalyzed C-H arylation. Access to 1,2,4-triazolophenanthridine can be achieved from the reaction products using a Pd-catalyzed intramolecular C-H functionalization reaction.

Amide activation: an emerging tool for chemoselective synthesis

“…102 In 2015, the group of Charette reported the use of hydrazides for the formation of 1,2,4-triazoles (175) and 3-aminoindazoles (176) from activated secondary and tertiary amides, respectively. 103,104 In analogy to the previously mentioned pyridine and isoquinoline syntheses, Movassaghi et al employed nitriles for the formation of pyrimidines (180) (Scheme 25b). 105,106 The addition of pyridine, known to form stable adducts with activated amides, has been utilised for the elegant synthesis of natural products (Scheme 26).…”

Synthesis, structure and properties of N-R-amides and hydrazides of 2-[4-R-5-(theophylline-7ʹ-yl)-1,2,4-triazole-3-ylthio]acetic acid

“…The derivatives of 1,2,4-triazole-3-thiol and theophylline are a very promising class of chemical compounds for the synthesis of biologically active compounds based on them, due to the wide spectrum of biological activity of these heterocycles' derivatives [2][3][4][5][6][7]10]. Objective reasons for the search for a number of 1,2,4-triazol-3-thiol and theophylline derivatives are the high synthetic and pharmacological potential of these synthones [2,5,7,10]. Our attention was drawn to previously unexplored amides and 2-[4-R-5-(theophylline-7'-yl)-1,2,4-triazole-3-ylthio]acetic acid.…”

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

“…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.…”