Synthesis and Crystal Structures of Four New Dihydropyridine Derivatives

Abstract

Four new Hantzsch 1,4-dihydropyridine derivatives, dimethyl 4-(4-hydroxy-3-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, (I), dimethyl 4-(4-bromophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, (II), dimethyl 4-(3-bromo-4-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, (III), and dimethyl 2-(2,5-dimethoxyphenyl)-4,6-dimethyl-1,2-dihydropyridine-3,5-dicarboxylate, (IV), have been synthesized and examined by X-ray crystallography, B3LYP/6-31 G (d) molecular orbital calculations and Hirshfeld surface and fingerprint plots. (I), C₁₈H₂₀NO₆, is monoclinic with space group P21/n and cell constants a = 9.60810(10) Å, b = 7.41900(10) Å, c = 24.1821(3) Å, = 94.1970(10)°, V = 1719.14(4) ų, and Z = 4. (II), C₁₇H₁₅BrN₂O₆, is orthorhombic with space group P2₁2₁2₁ and cell constants a = 11.8865(5) Å, b = 13.1157(4) Å, c = 21.9515(9) Å, V = 3422.2(2) ų, and Z = 8. (III), C₁₈H₂₀BrNO₅, is orthorhombic with space group Pbca and cell constants a = 8.55470(10) Å, b = 15.5248(2) Å, 27.0657(5) Å, V = 3594.60(9) ų, and Z = 8. (IV), C₁₉H₂₃NO₆, is orthorhombic with space group Pbca and cell constants a = 11.6798(3) Å, b = 13.6319(3) Å, 23.0976(5) Å, V = 3677.55(15) ų, and Z = 8. The first three have the same 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate skeleton with different substituted phenyl ligands attached to the 4-site of the dihydropyridine ring. The fourth derivative (IV) consists of a related 4,6-dimethyl-1,2-dihydropyridine-3,5-dicarboxylate skeleton with 2,5-dimethoxyphenyl and methyl ligands attached to the 2 and 4 sites of the 1,2-dihydropyridine ring. The dihedral angle between the mean planes of the dihydropyridine and benzene rings is 89.6(2)° (I), 86.0(6)° or 87.2(9)° (II), 87.7(6)° (III), and 87.3(8)° (IV), respectively. O–H··· (I), N–H···O (II), N–H···O (IV) hydrogen bonds and weak N–H···O, C–H···O (I), C–H···O (II), N–H···O (III), C–H···O (IV) intermolecular hydrogen bond interactions help stabilize crystal packing in each of their unit cells. A comparison of the angles between mean planes of the benzene rings in the crystals and with the DFT theoretical calculation as well as inclusion of weak intermolecular hydrogen bond interactions has been included for each molecule. Hirshfeld surface analysis for visually analyzing intermolecular interactions in crystal structures employing 3D molecular surface contours and 2D fingerprint plots have also been used to examine molecular shapes. Molecular orbital diagrams provide visual representations of the top level molecular orbital surfaces in each compound.

Graphical Abstract

Synthesis, crystal structures, density functional theory (DFT), Hirshfeld and molecular orbital surface calculations of four new dihydropyridine derivitives.