A molecular electron density theory study of the Grignard reagent‐mediated regioselective direct synthesis of 1,5‐disubstituted‐1,2,3‐triazoles

Abstract

AbstractThe [3 + 2] cycloaddition (32CA) reaction of phenyl azide4with ethynylbenzene5in presence of ethyl magnesium bromide (EtMgBr) has been studied within the Molecular Electron Density Theory with the aim to rationalise the high‐yielding direct regioselective synthesis of 1,5‐disubstituted‐1,2,3‐triazoles. Topological analysis of the electron localisation function (ELF) of phenyl azide4indicates that it has azwitterionicstructure participating inzw‐type32CA reactions. Computed activation parameters along the two feasible reaction paths for this 32CA reaction makes the rationalisation of the experimental outcomes possible. Grignard reagent‐mediated processes have a polar character and complete regioselectivity, which is in line with the fast, clean, and high yielding reaction experimentally observed. The reaction follows aone‐stepmechanism involving a high asynchronous transition state structure. Topological analysis of the ELF and calculated quantum theory of atoms‐in‐molecule parameters indicate that formation of new C–N single bonds does not begin exactly at the corresponding transition state structure.