Synthesis, crystal structure and computational analysis of 2,7-bis(4-chlorophenyl)-3,3-dimethyl-1,4-diazepan-5-one

Abstract

In the title compound, C19H20Cl2N2O, the seven-membered 1,4-diazepane ring adopts a chair conformation while the 4-chlorophenyl substituents adopt equatorial orientations. The chlorophenyl ring at position 7 is disordered over two positions [site occupancies 0.480 (16):0.520 (16)]. The dihedral angle between the two benzene rings is 63.0 (4)°. The methyl groups at position 3 have an axial and an equatorial orientation. The compound exists as a dimer exhibiting intermolecular N—H...O hydrogen bonding with R22(8) graph-set motifs. The crystal structure is further stabilized by C—H...O hydrogen bonds together with two C—Cl...π (ring) interactions. The geometry was optimized by DFT using the B3LYP/6–31 G(d,p) level basis set. In addition, the HOMO and LUMO energies, chemical reactivity parameters and molecular electrostatic potential were calculated at the same level of theory. Hirshfeld surface analysis indicated that the most important contributions to the crystal packing are from H...H (45.6%), Cl...H/H...Cl (23.8%), H...C/C...H (12.6%), H...O/O...H (8.7%) and C...Cl/Cl...C (7.1%) interactions. Analysis of the interaction energies showed that the dispersion energy is greater than the electrostatic energy. A crystal void volume of 237.16 Å3 is observed. A molecular docking study with the human oestrogen receptor 3ERT protein revealed good docking with a score of −8.9 kcal mol−1.

Keywords

• synthesis
• x-ray crystal structure
• c—h...o and n—h...o hydrogen bonds
• c—cl...π (ring) interactions
• 1,4-diazepane derivative
• chair conformation
• dft
• hirshfeld surface analysis
• 3ert protein
• molecular docking