Green, Mild, and Efficient Friedel–Crafts Benzylation of Scarcely Reactive Arenes and Heteroarenes under On‐Water Conditions

Abstract

Metal‐free Friedel–Crafts benzylation (FCB) of scarcely reactive arenes and heteroarenes was performed under on‐water conditions by an environmentally sustainable procedure. The catalytic strategy exploits the hydrophobicity of the resorcinarene macrocycle 1 a. The proposed mechanism is based on the activation of benzyl chloride by H‐bonding interactions with catalyst 1 a. In fact, under on‐water conditions the hydrophobic amplification of the strength of the H‐bonding interactions between the OH groups of the resorcinarene catalyst and the chlorine atom of benzyl chloride leads to polarization of the C−Cl bond, which consequently promotes electrophilic attack of the π nucleophile. Thus, many arenes and heteroarenes were efficiently benzylated under mild on‐water conditions by using resorcinarene 1 a as catalyst. The FCB of benzene is industrially relevant for the synthesis of diphenylmethane, and hence the on‐water procedure was extended to the gram‐scale synthesis of diphenylmethane, starting from benzene and benzyl chloride in the presence of resorcinarene catalyst 1 a.

Light on the sustainable preparation of aryl-cored dibromides

“…Using the peroxide-bromide conditions developed for p-xylene, 4a was obtained with a 42% yield. In this case, two chromatographic separations in sequence were necessary to remove most of the core brominated byproducts, that were still detected in small amounts through 1 H NMR (see the image in the Supporting Information File 1).…”

“…Solvents and reagents were commercial grade and used as received. 1 H NMR spectra were acquired with a Bruker Avance 400 spectrometer (Billerica, MA, USA). The lighting was achieved by means of a standard household white LED bulb (OSRAM 6.5 W, 2700 K, 806 lm).…”

“…Benzyl and aryl halides, collectively referred to as 'aryl-cored halides', have found extensive applications across various fields, including synthesis [ 1 ], photonics [ 2 ], and diagnostics [ 3 ]. Their popularity stems from their structural rigidity, potential conjugation with the remaining structure, and the capability to form additional π–π-stacking interactions.…”

“…1 H NMR (400 MHz, 298 K, CDCl 3 ) δ 7.35 (s, 3H), 4.45 (s, 6H) ppm.1,3,5-Tribromo-2,4,6-trimethylbenzene (4b): The general procedure was adapted considering the three ring positions to be halogenated (3.5 equiv of NaBr were used instead of 2.33 equiv). The raw product appears as pale-yellow solid, yield: 89%.…”

Hydrogen-bonding and acid cooperative catalysis for benzylation of arenes with benzyl alcohols over ionic liquids

“…Diarylmethanes are important architectures that are widely present in compounds with biological and physiological activities, 1,2 in supramolecules and functional materials. 3 Some approaches have been reported for their synthesis, 4,5 among which benzylation of arenes with benzyl alcohols is an eco-friendly way. 6 To date, various catalysts including Brønsted acids ( e.g.…”