Theoretical Study of Copper Acetonitrile Effects on Parr Functions Indices and Regioselectivity Using Density Functional Theory (DFT)

Copper-catalyzed azide–alkyne cycloaddition (CuAAC) is a straightforward way for making covalent connections between building blocks containing various functional groups. It is widely used in organic synthesis, medicinal chemistry, polymer chemistry, and bioconjugation applications. Using copper acetonitrile as catalyst for click reactions (CuAAC) lead to a non-concerted reaction, and affect Parr functions indices to determine the polar sites, therefore predict the favorable regioisomer (1,4-regioisomer) and explain the contradiction obtained to the experimental results. The huge difference of activation barriers between catalyzed and uncatalyzed reaction indicate that is a selective reaction.