Imidazolium Salt Catalyzed para-Selective Halogenation of Electron-Rich Arenes

Abstract

A highly para-selective halogenation of arenes bearing coordinating groups in the presence of a dimidazolium salt as a catalyst is reported. A series of electron-rich p-haloarenes were prepared in good yields and good to excellent selectivities. We also propose a plausible mechanism for the catalytic reaction.

Key words

arenes - regioselectivity - halogenation - amides - ethers - catalysis

• References and Notes

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• 9 Chloroarenes 2a–j; General Procedure A mixture of anilide or ether 1 (0.2 mmol), NCS (0.26 mmol), d-CSA (0.1 mmol), and imidazolium salt 8 (0.01 mmol) in 1,4-dioxane (1 mL) was stirred at r.t. (25 °C) under air for 24 h. When the substrate was completely consumed (GC–MS), the reaction was quenched with sat. aq NaHCO₃ (4 mL), and the mixture was extracted with EtOAc (3 × 4 mL). The organic layer was washed with H₂O (3 × 4 mL), dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica gel). N-(4-Chloro-2-methylphenyl)acetamide (2b) The general procedure gave a 93:7 mixture of products 2b and 2b′ in 98% yield. 2b was isolated as a white solid; yield: 33.4 mg (91%); mp 140–141 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.69 (d, J = 9.2 Hz, 1 H), 7.16 (d, J = 6.3 Hz, 2 H), 6.99 (br s, 1 H), 2.22 (s, 3 H), 2.19 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 168.4, 134.2, 131.1, 130.3, 130.3, 126.7, 124.5, 24.3, 17.7. HRMS (ESI): m/z [M + H]⁺ calcd for C₉H₁₁ ³⁵ClNO: 184.0524; found: 184.0520. N-(3-Bromo-4-chlorophenyl)acetamide (2d) and N-(3-Bromo-2-chlorophenyl)acetamide (2d′) The general procedure gave an 85:15 mixture of the products 2d and 2d′ in 98% yield. 2d: White solid; yield: 41.4 mg (83%); mp 118–119 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.87 (d, J = 2.1 Hz, 1 H), 7.51 (br s, 1 H), 7.38 (dt, J = 15.8, 5.4 Hz, 2 H), 2.18 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 168.4, 137.2, 130.3, 129.5, 124.6, 122.5, 119.7, 24.5. HRMS (ESI): m/z [M + H]⁺ calcd for C₈H₈Br⁷⁹Cl³⁵NO: 247.9472; found: 247.9468. 2d′: White solid; yield: 7.3 mg (15%); mp 118–119 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.62 (s, 1 H), 7.65–7.45 (m, 1 H), 7.22 (d, J = 8.5 Hz, 1 H), 7.17 (dd, J = 8.5, 2.1 Hz, 1 H), 2.25 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 168.4, 137.3, 130.3, 129.5, 124.6, 122.5, 119.7, 24.5. HRMS (ESI): m/z [M + H]⁺ calcd for C₈H₇Br⁷⁹Cl³⁵NO: 247.9472; found: 247.9467.