5-Nitroisoxazoles in S_NAr reactions: access to polysubstituted isoxazole derivatives

Abstract

An efficient protocol for straightforward functionalization of isoxazole ring via the reactions of aromatic nucleophilic substitution of nitro group with various nucleophiles has been elaborated. The method is featured with...

Synthesis and Biological Evaluation of Substituted 3‐Isoxazolethioethers as Antileishmanial and Antibacterial Agents

“…The mechanism for the reaction is analogous to the one presented by Averina et al [22] . It is anticipated that the formation of a new C−S bond and the C−NO 2 bond breaking occurs in a concomitant fashion (see Scheme 1 in SI).…”

“…The scalability of the reaction was tested by reacting 1 ac and 1 ae with thiol 2 c and it was observed that though the solid products 3 acc and 3 aec separated from the reaction mixture, the yields were marginally lower. The mechanism for the reaction is analogous to the one presented by Averina et al [22] It is anticipated that the formation of a new CÀ S bond and the CÀ NO 2 bond breaking occurs in a concomitant fashion (see Scheme 1 in SI).…”

“…Thus, the optimized condition that gave the best yield of 3 acc was via treating 3-nitroisoxazole 1 ac with 2 c in the presence of 50 mol % of DBU in MeCN at room temperature for 5 min followed by filtration of solid product. Perhaps, the expedited reaction in the presence of DBU could be attributed to stronger basicity of DBU than DIPEA that was used by Averina et al [22] Moreover, the remarkable ease of isolating the solid product under the optimized conditions within 5 min. invoked us to use this method herein.…”

“…[18][19][20][21] During our studies, Averina et al citing our previous findings, disclosed the results of their work on the S N Ar reactions with different nucleophiles including phenols and thiophenols on 5-nitroisoxazoles and 3-nitroisoxazoles in the presence of DIPEA. [22] Independent of their report, to meet our objective of developing broader SAR, we have earlier initiated investigations by performing the reactions of 3-nitroisoxazoles with thiols in inorganic bases followed by organic bases and discovered that in the presence of 0.5 equiv. of DBU, reactions were complete within 5 min to offer the products, which separated as solid in the reaction medium.…”

A Facile Approach to Bis(isoxazoles), Promising Ligands of the AMPA Receptor

“…In particular, the structures containing the phenylene-based linkers and aminoisoxazole moieties were identified among the most promising potential PAMs. Recently, we have elaborated a novel preparative method for the synthesis of 3-EWG-5-nitroisoxazoles, based on the heterocyclization of electrophilic alkenes via treatment with the tetranitromethane-triethylamine (TNM-TEA) complex [36][37][38][39]. Until now, this method has been used to produce polysubstituted isoxazoles containing one heterocyclic fragment in a molecule.…”