A Theoretical Study of the Relationship between the Electrophilicity ω Index and Hammett Constant σp in [3+2] Cycloaddition Reactions of Aryl Azide/Alkyne Derivatives.

Hicham Ben El Ayouchia,Miguel Julve,Hafid Anane,Salah-Eddine Stiriba,Luis Domingo,Moulay El Idrissi Moubtassim

doi:10.3390/molecules21111434

Abstract

The relationship between the electrophilicity ω index and the Hammett constant σp has been studied for the [2+3] cycloaddition reactions of a series of para-substituted phenyl azides towards para-substituted phenyl alkynes. The electrophilicity ω index—a reactivity density functional theory (DFT) descriptor evaluated at the ground state of the molecules—shows a good linear relationship with the Hammett substituent constants σp. The theoretical scale of reactivity correctly explains the electrophilic activation/deactivation effects promoted by electron-withdrawing and electron-releasing substituents in both azide and alkyne components.

Highlights

IntroductionThe [3+2] cycloaddition (32CA) reaction between azides, acting as the three-atom-component (TAC) and carbon–carbon triple bonds is a classical organic reaction initially established by Huisgen, in which five-membered 1,2,3-triazolic compounds are prepared as a mixture of 1,4 and 1,5-regioisomers
The [3+2] cycloaddition (32CA) reaction between azides, acting as the three-atom-component (TAC) and carbon–carbon triple bonds is a classical organic reaction initially established by Huisgen, in which five-membered 1,2,3-triazolic compounds are prepared as a mixture of 1,4 and 1,5-regioisomers.Since triazoles have played central roles in coordination chemistry as nitrogen-containing heterocyclic ligands, in bioconjugation issues, and in peptide-based drug design by mimicking peptide and disulfide bonds, leading to secondary structural components of peptides [1,2,3]
It can be seen that compounds with electron-withdrawing (EW) substituents occupy the top of the scale, while compounds with electron-releasing (ER)

Summary

Introduction

The [3+2] cycloaddition (32CA) reaction between azides, acting as the three-atom-component (TAC) and carbon–carbon triple bonds is a classical organic reaction initially established by Huisgen, in which five-membered 1,2,3-triazolic compounds are prepared as a mixture of 1,4 and 1,5-regioisomers. Unlike 1,3-dienes participating in Diels–Alder reactions [8], the electronic structure of TACs participating in 32CA reactions strongly depends on the type and hybridization of the atoms present in the TAC. Depending on their electronic structure, TACs have recently been classified as pseudodiradical, carbenoid, and zwitterionic TACs (see Scheme 2) [9,10]. TACs such as nitrone or azides have the electronic structure of a 1,3-dipole as Huisgen. TACs such as nitrone or azides have the electronic structure of a 1,3-dipole as Huisgen proposed [6]

Mechanism

Results and Discussion

Theoretical

PlotThe of the global ω regression electrophilicity againstfor thethe

Computational Details

Conclusions