Computational Study for Preparation of Benzoimidazo[1,2-a]pyrimidines from Reaction of Benzaldehyde, Indanedione and 1H-benzo[d]imidazol-2- amine.

Abstract

Background: Benzoimidazo[1,2-a]pyrimidines are important compounds that have many useful effects in the body. They can help fight cancer, fungal infections, inflammation, and viruses. They can also help with various other health conditions. They can act as antineoplastic, antitubercular, parasitical activity, benzodiazepine receptor agonists, calcium channel blockers, potent P38 MAP kinase inhibitors, TIE-2 and/or VEGFR2 inhibitory activities, protein kinase inhibitors, and T cell activation. There are different methods to make the benzoimidazo[1,2- a]pyrimidines. Some of them dealth with the one-pot threecomponent condensation reactions of β- dicarbonyl compounds, aldehyde and 1H-benzo[d]imidazol-2-amine in the presence of catalyst. Although the synthesis of this group of compounds has been done before, and the products have been identified from the spectroscopic point of view, the kinetics and reaction mechanism have not been investigated. The strength of these calculations is that evaluation of the activation energy of various steps suggests possible mechanisms, probable mechanisms, and valuable synthetic intermediates.

Methods: In this report, seven possible mechanisms for synthesizing the benzoimidazo[1,2- a]pyrimidines have been investigated using density functional theory (DFT) at the B3LYP/6- 311G** level of theory. Each synthetic route involves condensation of the benzaldehyde, indanedione and 1H-benzo[d]imidazol-2-amine molecules to yield the proposed product. The calculations showed that the suggested method has six steps; its initiation step includes the Knoevenagel reaction between indanedione and aldehyde, and the rate determining state is dehydration in the fifth step.

Result: Six potential pathways for the reaction will occur. Then, we focused on the best pathway and studied it in detail. The ways that three chemicals-indanedione (R1), benzaldehyde (R2), and 1H-benzo[d]imidazol-2-amine (R3) react with each other were studied using ab-initio program by ChemBio3D, Gauss View, and Gaussian 09. The Density Functional Theory (DFT) using the B3LYP basis set was used to improve the arrangement of molecules involved in the three-part creation of a specific compound called 12-phenyl-5H-benzo[4,5]imidazo[1,2-a]indeno[1,2- d]pyrimidin-13(12H)-one (P).

Conclusion: During the study of the six mechanisms, the proposed pathway 2 is the best mechanism for this reaction because its rate-determining step has the lowest activation energy value. This route consists of 6 steps, the fifth step of which is related to the conversion of IM4 to IM5 (relative ΔE: 109.80 Kj/mol), during which a dehydration reaction is performed, and this step occurs by passing through transition state TS5 (Total Energy (Hart./particles: -1194.747403).