Synthesis, structure and properties of 2(6)-hidroxy-6(2)-oxo-N(1), 4-disubtituted-1,2(1,6)-dihydropyridine-3-carbonitriles and their azo derivates

Abstract

In this work, a simple and convenient synthesis of tautomeric (6 or 2)-hydroxy-4-methyl-(2 or 6)-oxo-1-(substituted phenyl)-(1,2 or 1,6)-dihydro- pyridine-3-carbonitriles from ethyl acetoacetate and 2-cyano-N-(substituted phenyl)-ethanamides using microwave assisted chemistry is presented. The structure of the obtained product was confirmed by the use of FTIR, NMR, UV and MS techniques. Presence of tautomeric forms, 6-hydroxy-4-methyl-2-oxo-1-(substituted phenyl)-1,2-dihydropyridine-3-carbonitriles and 2-hydroxy-4-methyl -6-oxo-1-(substituted phenyl)-1,6-dihydropyridine-3-carbonitriles, and state of equilibrium in DMSO-d6 of the obtained product was studied by 1H and 13C NMR spectroscopy, as well as B3LYP/6-311++G(d,p) and GIAO/WP04/aug-cc-pVDZ theoretical calculations. Tautomeric equilibria of title compounds were quantitatively analyzed by UV/Vis spectroscopy and theoretical approaches. Kamlet-Taft and Catalán correlation analysis were done. The LFER correlation results showed significant influence of the solvent effects on the transmission mode of substituent effects. In order to calculate optimal geometries of investigated compounds, a conformation with minimum energies were determined using semi-empirical PM6 method, as well as B3LYP (DFT) hybride method with 6-311G(d,p) basis set. The state of the tautomeric equilibria of 6(2)-hydroxy-4-methyl-2(6)-oxo-1-(substituted phenyl)-1,2(1,6)-dihydropyridine-3-carbonitriles were evaluated from UV/Vis and NMR spectral data. Quantum chemical calculations of geometries and electronic energies were performed by density functional theory (B3LYP). The experimental data were interpreted with the aid of time-dependent density functional (TD-DFT) method. Electron charge density was obtained by the use of Quantum Theory of Atoms in Molecules, i.e. Bader's analysis. Linear solvation energy relationships (LSER) rationalized solvent influence on tautomeric equilibrium. Linear free energy relationships (LFERs) was applied to the substituent-induced NMR chemical shifts (SCS) with σ using SSP (single substituent parameter), inductive (σI) and resonance (σR) parameters using DSP (dual substituent parameter), as well as the Yukawa–Tsuno model. Theoretical calculations and obtained correlations gave insight into the influence molecular conformation on the transmission of substituent effects, as well as on different solvent‒solute interactions on state of tautomeris equilibria.

Sinteza proizvoda tautomerne smeše 2(6)-hidroksi-4-metil-6(2)-okso-1-(supstituisanih fenil)-1,2(1,6)-dihidropiridina-3-karbonitrila (serija 1), izvršena je polazeći iz etil-acetoacetata i 2-cijano-N-(supstituisanih fenil)-etanamida primenom konvencionalne i mikrotalasne metode...