Work

A Regioselective Synthesis of 2,4-Disubstituted 2 H -1,2,3-Triazoles by Coupling of N -Tosylhydrazones and Anhydro-Aldose Tosylhydrazones with 4-Substituted 1 H -1,2,3-Triazoles – Scope and Limitations

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide In this paper we present the first investigation of the C–N coupling reaction between N -tosylhydrazones including O -peracylated 2,6-anhydro-aldose tosylhydrazones and 1 H -1,2,3-triazoles under catalyst-free conditions. This transformation is characterized by relatively mild thermal conditions, high regioselectivity in favor of 2,4-disubstituted 2 H -1,2,3-triazoles and broad functional group tolerance as well as applicability in medicinal chemistry due to the absence of transition metal residues. Tosylhydrazones of aldehydes showed better results in terms of yields (20–61%) than those of ketones (13–16%). From the 1,2,3-triazole side the reactions gave very good results in terms of regioselectivity with both electron-withdrawing and electron-donating groups in the 4-position aromatic substituents, while benzotriazoles proved unselective. The extension of the reaction to 2,6-anhydro-aldose tosylhydrazones retained the excellent regioselectivity with high yields, to provide a new synthetic pathway for 2-glycosylmethyl-4-substituted-2 H -1,2,3-triazoles, a novel type of glycomimetics. The carbohydrate derivatives were evaluated as potential galectin-1 antagonists and glycogen phosphorylase enzyme inhibitors. In addition to classical 1 H and 13 C NMR characterizations, advanced 1 H– 15 N multiple-bond correlation NMR experiments were also performed on some glycomimetics to get direct evidence for the regioisomer synthesized.

Source: ACS Omega

DOI: 10.1021/acsomega.5c06151