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

Shanmugasundaram Akila; Thankakan Vidhyasagar; John Peter Winfred Jebaraj; Aravazhi Amalan Thiruvalluvar; Krishnan Rajeswari

doi:10.1107/S2056989023010162

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

Acta Crystallogr E Crystallogr Commun. 2023 Nov 30;79(Pt 12):1212-1217. doi: 10.1107/S2056989023010162. eCollection 2023 Dec 1.

Authors

Shanmugasundaram Akila¹, Thankakan Vidhyasagar¹, John Peter Winfred Jebaraj², Aravazhi Amalan Thiruvalluvar³, Krishnan Rajeswari^{1

4}

Affiliations

¹ Department of Chemistry, Annamalai University, Annamalai Nagar 608 002, Tamil Nadu, India.
² Department of Chemistry, St. John's College, Palayamkottai 627 002, Tamil Nadu, India.
³ Principal (Retired), Kunthavai Naacchiyaar Government Arts College for Women (Autonomous), Thanjavur 613 007, Tamil Nadu, India.
⁴ PG & Research Department of Chemistry, Government Arts College, Chidambaram 608 102, Tamil Nadu, India.

Abstract

In the title compound, C₁₉H₂₀Cl₂N₂O, the seven-membered 1,4-diazepane ring adopts a chair conformation while the 4-chloro-phenyl substituents adopt equatorial orientations. The chloro-phenyl 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 inter-molecular N-H⋯O hydrogen bonding with R ² ₂(8) graph-set motifs. The crystal structure is further stabilized by C-H⋯O hydrogen bonds together with two C-Cl⋯π (ring) inter-actions. 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 mol-ecular 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%) inter-actions. Analysis of the inter-action energies showed that the dispersion energy is greater than the electrostatic energy. A crystal void volume of 237.16 Å³ is observed. A mol-ecular docking study with the human oestrogen receptor 3ERT protein revealed good docking with a score of -8.9 kcal mol^-1.

Keywords: 1,4-diazepane derivative; 3ERT protein; C—Cl⋯π (ring) interactions; C—H⋯O and N—H⋯O hydrogen bonds; DFT; Hirshfeld surface analysis; X-ray crystal structure; chair conformation; molecular docking; synthesis.