INVESTIGATION INTO THE REGIOCHEMISTRY OF SOME PYRAZOLES DERIVED FROM 1, 3-DIPOLAR CYCLOADDITION OF ACRYLONITRILE WITH SOME NITRILIMINES: THEORETICAL AND EXPERIMENTAL STUDIES

Abstract

dipolar cycloaddition between acrylonitrile and two N-(4-substituted)phenyl-C-(4-chlorophenyl)nitrilimines which were generated in situ afforded the new pyrazoles. The regiochemistry and reactivity of these reactions has been investigated on the basis of density functional theory (DFT) -based reactivity indexes and activation energy calculations. The theoretical 13C NMR chemical shifts of the cycloadducts which were obtained by GIAO method were comparable with the observed values. the Diels-Alder (DA) reactions and the 1,3-DCs has grown from a fruitful interplay between theory and experiment 2-4. Two major factors i.e. the steric and electronic effects can influence the regioselectivity of these reactions 2. Although transition state theory remains the most widely used and the most rigorous approach for the study of the mechanism and the regiochemistry of these reactions, the localization of transition states is not always easier. Furthermore, transition state calculations are often very time-consuming when bulky substituents are present in reactive systems. Recently, reactivity descriptors based on the density functional theory (DFT), such as Fukui indexes, local softnesses and local electrophilicity, have been extensively used for the prediction of the regioselectivity. For instance, several treatments of 1,3-DC reactions of nitrilimines with various dipolarophiles can be found in the literature 5-8. In this context, we became interested in the reactivity of acrylonitrile 3 as dipolarophile towards two N-(4-substituted)phenyl-C-(4- chlorophenyl)nitrilimines 2 as dipoles which were generated in situ by base treatment of the corresponding hydrazonoyl chlorides 1 in order to synthesize the new 3-(4-chlorophenyl)-1-(4-nitrophenyl)-4,5-dihydro-1H-pyrazole-4- carbonitrile 4a and 1-(4-bromophenyl)-3-(4-chlorophenyl)-4,5-dihydro-1H- pyrazole-5-carbonitrile 5b (Scheme1). In addition, we found it worthwhile to analyze the regioselectivity of these 1,3-DC reactions by several theoretical approaches, namely, activation energy calculations and DFT-based reactivity indexes. Finally, the gauge-invariant atomic orbital (GIAO) method 9 was used to calculate NMR chemical shifts, to help the experimental cycloadduct determination, because it has shown to yield data comparable to those of the experiment 10.