Synthesis of Hydroxy Aryl Ketones via a Novel Low Temperature Variant of the Fries Rearrangement

The aim of the current study was to examine the protection of phenol with various acyl chloride derivatives and anhydride derivatives at different temperatures in the presence of different simpler catalytic agents to produce corresponding ester in good yield after workup. All prepared esters were isolated and identified by their physical properties and spectrophotometrically methods such as FT IR, ۱H-NMR, and ۱۳C-NMR. Rearrangement of phenolic esters was done by Fries rearrangement with ۵ equivalents of anhydrous Lewis acid, aluminum chloride in nitromethane, at low temperature. Aluminum chloride pre-dissolved in nitromethane occurred smoothly, enabling the desired regioselective para–isomer in moderate to good yield. All the products of the rearrangement were isolated and established by detecting their physicochemical properties and by analyzing their FT-IR, ۱H-NMR, and ۱۳C-NMR spectroscopy. In vitro four compounds, phenyl benzoate (۳), phenyl ۴-methoxy benzoate (۴), ۴-hydroxybenzophenone (۴a), and (۴-hydroxyphenyl)۴-methoxyphenyl)methanone (۴b) were evaluated for  inhibition extracting DNA from HepG۲ and MEF cells at IC۵۰ for ۲۴ hours. The results showed that ۴-hydroxybenzophenoneand ۴-hydroxyphenyl)(۴-methoxyphenyl)methanone were induced apoptosis by mitochondrial Intrinsic pathway after ۲۴ hours of exposure.

Keywords:

Acylation , Chemo selective , C- acylation , Fries rearrangement