Mechanistic Study of 6-Amino-3-Methyl-4-Phenyl-1,4-Dihydropyrano [2,3-c]Pyrazole-5-Carbonitrile Synthesis: A Computational Chemistry Approach.

INTRODUCTION

The main goal of this research is to determine the most proposed mechanism for the synthesis of 6-amino-3-methyl-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5- carbonitrile (P) from benzaldehyde, malononitrile, hydrazine, and ethyl acetoacetate as starting materials, which was investigated based on density functional theory (DFT).

METHODS

In this report, seven possible mechanisms for the synthesis of the 1,4- dihydropyrano[2,3-c]-pyrazole have been investigated using density functional theory (DFT) at the B3LYP/6-311G** level of theory. Each synthetic route involves the condensation of ethyl acetoacetate, hydrazine hydrate, malononitrile, and benzaldehyde molecules to yield the proposed product.

RESULTS

Herein, seven reaction mechanisms were scrutinized for the synthesis of the 6-Amino-3- methyl-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile from benzaldehyde, malononitrile, hydrazine, and ethyl acetoacetate as starting compounds. DFT with the B3LYP basis set was used to optimize the structure of the studied molecules related to the four-component synthesis of 6-amino-3-methyl-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (P). Finally, we investigated the most favorable reaction mechanism and its corresponding steps using computational methods.

DISCUSSION: The computational results in this research are based on transition state kinetic studies, and due to the volume of calculations, experimental or thermodynamic studies were not possible. Nevertheless, a review of the scientific literature indicates that there is strong agreement between these computational findings and the experimental data reported in the literature.

CONCLUSION

In summary, the best proposed mechanism for the synthesis of the 6-amino-3- methyl-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile in ethanol has been investigated using DFT at the B3LYP/6-311G** level. This route involves the Knoevenagel condensation between benzaldehyde and ethyl acetoacetate, followed by dehydration, Michael addition reaction, imination, and intramolecular nucleophilic reaction of the hydrazine, respectively, which corresponds to proposed pathway 6.