Chemical reactivity of 3-substituted-6,8-dimethylchromones towards 1H-benzimidazol-2-ylacetonitrile and 5-amino-2,4-dihydro-3H-pyrazol-3-one: Spectroscopic, theoretical and in silico ADME studies

Abstract

The reactivity of 1H-benzimidazol-2-ylacetonitrile and 5-amino-2,4-dihydro-3H-pyrazol-3-one, as nucleophilic reagents, was examined towards some 3-substituted-6,8-dimethylchromones 2a-d. A diversity of novel pyrido[1,2-a]benzimidazoles, chromeno[2,3-b]pyridines, pyrazolo[3,4-b]pyridines and chromenopyrazolopyridines was efficiently synthesized through different chemical transformations; depending on the functional group present at C-3 position of the chromone moiety. With B3LYP/6–311 G(d,p) basis set in the ground state, density functional theory (DFT) is used to determine the molecular geometry of synthesized compounds. The reactivity of the current compounds was studied by global reactivity descriptors at the same level of theory. In order to forecast the reactive locations on the starting substrates 2a-d for nucleophilic and electrophilic attacks, Fukui functions (local reactivity descriptors) were computed at the same level of theory. On the other hand, molecular electrostatic potential (MEP) surface maps were used to identify the nucleophilic and electrophilic sites. Moreover, 1H and 13C NMR chemical shift values in the ground state was calculated using the Gauge-Including Atomic Orbital (GIAO) technique, and the predicted values were compared with the experimental results. To interpret the nonlinear optical (NLO) property of the synthesized compounds, the dipole moment, polarizability, and first hyperpolarizability values have been measured (in the range β = 0.38 × 1030 - 3.28 × 10−30 esu). First hyperpolarizabilities of the investigated compounds indicate promising candidates for nonlinear optical applications. Also, using web-based platforms, in silico ADME calculations were performed.