Iron-Catalyzed Benzylation Reaction of Arenes with Benzyl Thiocyanates

Abstract

A novel, regioselective protocol for the synthesis of diphenylmethane derivatives has been developed by using iron-­catalyzed Friedel-Crafts reaction of arenes with benzyl thiocyanates. In the presence of FeBr₃, a variety of benzyl thiocyanates underwent the reaction with arenes to selectively afford the corresponding diarylmethane derivatives in moderate to high yields.

iron - benzylation - Friedel-Crafts reaction - benzyl thiocyanate - diarylmethane

References and Notes

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10

Typical Procedure: A mixture of benzyl thiocyanate (1a; 0.4 mmol), substrate (2a; 20 equiv), and FeBr₃ (23.4 mg, 20 mol%) was stirred in a Schlenk tube at 80 ˚C (oil bath temperature) until complete consumption of starting material was observed (reaction monitored by TLC and GC-MS analyses). The mixture was filtered through a crude column, washed with ethyl acetate, and evaporated under vacuum. The residue was purified by flash column chroma-tography (hexane/ethyl acetate) to afford the product 3.
Benzyl-1,4-dimethylbenzene (3): Yellow oil; ^¹H NMR (500 MHz, CDCl₃): δ = 7.25 (t, J = 7.5 Hz, 2 H), 7.19-7.15 (m, 1 H), 7.11 (d, J = 7.5 Hz, 2 H), 7.04 (d, J = 7.6 Hz, 1 H), 6.95 (d, J = 7.7 Hz, 1 H), 6.92 (s, 1 H), 3.94 (s, 2 H), 2.28 (s, 3 H), 2.18 (s, 3 H); ^¹³C NMR (125 MHz, CDCl₃): δ = 140.5, 138.7, 135.3, 133.4, 130.8, 130.2, 128.7, 128.3, 127.1, 125.8, 39.4, 21.0, 19.2; MS (EI, 70 eV): m/z (%) = 196 (90) [M]⁺, 181 (100), 118 (43).
Typical Procedure: A mixture of benzyl thiocyanate (1a; 0.4 mmol), 1,3,5-trimethoxybenzene (2i; 10 equiv), FeBr₃ (23.4 mg, 20 mol%) and DCE (3 mL) was stirred in a Schlenk tube at 80 ˚C (oil bath temperature) until complete consumption of starting material was observed (reaction monitored by TLC and GC-MS analyses). The mixture was filtered through a crude column, washed with ethyl acetate, and evaporated under vacuum. The residue was purified by flash column chromatography (hexane/ethyl acetate) to afford the product 21. 1,3,5-Trimethoxy-2-thiocyanatobenzene (21): Yellow soild; mp 159.3-160.5 ˚C; ^¹H NMR (500 MHz, CDCl₃): δ = 6.15 (s, 2 H), 3.92 (s, 6 H), 3.84 (s, 3 H); ^¹³C NMR (125 MHz, CDCl₃): δ = 164.2, 161.3, 111.8, 91.3, 89.7, 56.3, 55.6; LRMS (EI, 70 eV): m/z (%) = 225 (100) [M]⁺, 179 (34).