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

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 tri-ethylamine in acetonitrile, heating as fast as possible (AFAP mode) to 60 degrees C, hold time 5 min, and 600 rpm stirring speed in the Monowave 50 reactor based on conventional heating principles. The struc-ture 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 scan-ning calorimetry (DSC), single-crystal and powder X-ray diffraction. X-Ray diffraction analyses show that compound 3 crystallizes in the Monoclinic, P 2 1 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 C -H middotmiddotmiddotO hydrogen bonds. However, Hirsh-feld surfaces demonstrated that C -H middotmiddotmiddotCl interactions are of great importance. Additionally, electrostatic potentials suggest the formation of Sigma-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%. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

In this study, the 2-oxo-2H-chromen-7-yl 4-chlorobenzoate (compound 3) was synthesized with high yield using an O-acylation reaction. The structure of compound 3 was fully characterized, and its crystal structure was determined to be monoclinic. The packing of compound 3 in the crystal structure was mainly controlled by C-H···O hydrogen bonds, but C-H···Cl interactions were also important. Compound 3 showed low activity against several cancer cell lines. These findings are significant for crystal engineering and non-linear optics.