Catalyst- and solvent-free synthesis of 2-fluoro-N-(3-methylsulfanyl-1H-1,2,4-triazol-5-yl)benzamide through a microwave-assisted Fries rearrangement: X-ray structural and theoretical studies

Abstract

An efficient approach for the regioselective synthesis of (5-amino-3-methylsulfanyl-1H-1,2,4-triazol-1-yl)(2-fluorophenyl)methanone, C10H9FN4OS, (3), from the N-acylation of 3-amino-5-methylsulfanyl-1H-1,2,4-triazole, (1), with 2-fluorobenzoyl chloride has been developed. Heterocyclic amide (3) was used successfully as a strategic intermediate for the preparation of 2-fluoro-N-(3-methylsulfanyl-1H-1,2,4-triazol-5-yl)benzamide, C10H9FN4OS, (4), through a microwave-assisted Fries rearrangement under catalyst- and solvent-free conditions. Theoretical studies of the prototropy process of (1) and the Fries rearrangement of (3) to provide (4), involving the formation of an intimate ion pair as the key step, were carried out by density functional theory (DFT) calculations. The crystallographic analysis of the intermolecular interactions and the energy frameworks based on the effects of the different molecular conformations of (3) and (4) are described.

2-Oxo-2H-chromen-7-yl 4-chlorobenzoate

“…In connection with the ongoing development of efficient and simple protocols for the acylation of heterocyclic compounds of biological interest [23,24], we describe an expeditious approach to synthesize 2-oxo-2H-chromen-7-yl 4-chlorobenzoate 3 through an O-acylation reaction between equimolar amounts of 7-hydroxy-2H-chromen-2-one 1 and 4-chlorobenzoyl chloride 2 in dichloromethane, using a slight excess of triethylamine with vigorous stirring at 20 • C for 1 h under normal atmospheric conditions (Scheme 1). After the specified reaction time, the solvent was removed under vacuum using a rotary evaporator.…”

3-(tert-Butyl)-N-(4-methoxybenzyl)-1-methyl-1H-pyrazol-5-amine

“…In connection with the ongoing development of novel protocols for the construction of C-N bonds [20][21][22], and our current studies on the synthetic utility of N-(5-pyrazolyl)imine derivatives for the preparation of N-heterocycles of biological interest [23][24][25], we reported a one-pot two-step synthesis of 3-(tert-butyl)-N-(4-methoxybenzyl)-1-methyl-1H-pyrazol-5-amine 3 through a solvent-free condensation reaction between equimolar amounts of 3-(tert-butyl)-1-methyl-1H-pyrazol-5-amine 1 and p-methoxybenzaldehyde 2 to form the N-(5-pyrazolyl)imine 4, followed by reduction with sodium borohydride in methanol at ambient temperature, as depicted in Scheme 1. After performing a liquid-liquid extraction and removing the excess of solvent under reduced pressure, the resulting crude product was purified by flash chromatography on silica gel using a mixture of DCM/MeOH (30:1, v/v) as eluent to give the N-heterocyclic amine 3 in 88% yield.…”

The Riveting Chemistry of Poly‐aza‐heterocycles Employing Microwave Technique: A Decade Review

“…To delight, up to 84 % of amide on exocyclic nitrogen ( 21 , Fries rearrangement) was obtained (Scheme 8). Notably, the Fries rearrangement under conventional reflux in THF or toluene for 6 h only 30 % of product was observed [14] …”