Synthesis, anticancer evaluation, thermal and X-ray crystallographic analysis of 2-oxo-2H-chromen-7-yl 4-chlorobenzoate using a conductively heated sealed-vessel reactor

Abstract

We report the synthesis of the 2-oxo-2H-chromen-7-yl 4-chlorobenzoate 3 in 94% yield by an O-acylation reaction of 7‑hydroxy-2H-chromen-2-one 1 and 4-chlorobenzoyl chloride 2 using a slight excess of triethylamine in acetonitrile, heating as fast as possible (AFAP mode) to 60 °C, hold time 5 min, and 600 rpm stirring speed in the Monowave 50 reactor based on conventional heating principles. The structure of the 2-oxo-2H-chromen-7-yl 4-chlorobenzoate 3 was fully characterized by FT–IR, UV–vis, NMR spectroscopy, mass spectrometry (EI-MS), elemental analysis, thermogravimetry (TG), differential scanning calorimetry (DSC), single-crystal and powder X-ray diffraction. X-Ray diffraction analyses show that compound 3 crystallizes in the Monoclinic, P21 space group. Despite the absence of chiral atoms, the structural restrains imposed by the molecular conformation drive these compounds to crystallize in a Sohncke space group. These results are of great importance in crystal engineering and non-linear optics. In the crystal structure, the packing is controlled mainly by CH‧‧‧O hydrogen bonds. However, Hirshfeld surfaces demonstrated that CH‧‧‧Cl interactions are of great importance. Additionally, electrostatic potentials suggest the formation of σ-holes over the Cl atoms, allowing this atom to behave as a Lewis acid-base. The packing is studied in terms of B3LYP/6-31G(d,p) energy frameworks. Finally, compound 3 showed low activity against MCF7 Breast, SNB-19 Central nervous system, and UO-31 Renal cancer cell lines with a growth inhibition percentage (GI%) ranging from 5.98% to 13.33%.