Regioselective [3 + 2] cycloaddition synthesis and theoretical calculations of new chromene-pyrazole hybrids: A DFT-based Parr Function, Fukui Function, local reactivity indexes, and MEP analysis

Abstract

The [3 + 2] cycloaddition synthesis of new series of chromene-pyrazole hybrids was the focus of this research. New chromene-based enaminones were synthesized and used as reactive ethylene derivatives in this study. The respective nitrilimines, or three-atom-components (TACs), were prepared in situ by the action of triethylamine on the appropriate hydrazonyl chlorides. The desired reaction was carried out in benzene for 3 h, yielding the target hybrids in 81–93% yields. The structure of the regioisomeric products was confirmed as 4-aroylpyrazoles rather than 5-aroyl analogues using both 1D and 2D NMR techniques. To better understand the regioselectivity observed in this [3 + 2] cycloaddition reaction, DFT calculations were performed at the B3LYP/6–31+G(d,p) computational level. The increased stability of 4-aroylpyrazoles and the possibility that they are the regioisomeric products are supported by the above calculations. Local reactivity indexes, NBO, and MEP mapping were used at the same calculation level to shed more light on the regioselectivity in the desired reaction by pinpointing the preferred regions for electrophilic and nucleophilic attack. We looked at two possible interactions between TACs and ethylene derivatives. All of the results suggest that the interaction that results in the formation of the regioisomeric 4-aroyl product is superior to the other.