O-Benzyl Trichloroacetimidates Having Electron-Withdrawing Substituents in Acid-Catalyzed Diarylmethane Synthesis

Abstract

Reaction of O-benzyl trichloroacetimidates having ­electron-withdrawing substituents with arenes in the presence of catalytic amounts of TMSOTf gave the corresponding diarylmethanes in good to excellent yields.

Key words

O-benzyl trichloroacetimidates - arenes - diarylmethanes - catalysis

References and Notes

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25

All compounds gave satisfactory analytical data. Described below are representative procedures and spectral data for compound 2c, 5c, 6c, and 7c.
General Procedure for the Preparation of Trichloroacetimidates.
To a stirred solution of 4-hydroxymethylbenzonitrile (1c, 2.67 g, 20 mmol) in dry CH₂Cl₂ (20 mL) and trichloroaceto-nitrile (20 mL, 200 mmol) was added DBU (0.03 mL, 0.2 mmol) at r.t. under nitrogen and stirred for 3 h. The reaction mixture was concentrated under reduced pressure and the crude residue was purified by column chromatography (toluene-PE = 1:8, +0.5% Et₃N) to give 2c as a white powder (5.02 g, 90%). ¹H NMR (250 MHz, CDCl₃): δ = 8.47 (br, 1 H, NH), 7.68 (d, 2 H, J = 8.0 Hz), 7.54 (d, 2 H, J = 8.0 Hz), 5.39 (s, 2 H, CH₂). Anal. Calcd for C₁₀H₇Cl₃N₂O (275.96): C, 43.28; H, 2.54; N, 10.09. Found: C, 43.24; H, 2.75; N, 10.20.
General Procedure for the Alkylation Reactions.
To a solution of trichloroacetimidate 2c (1.40 g, 5 mmol) in dry CH₂Cl₂ (20 mL) was added the corresponding acceptors (method A: 5 mmol of 1,3-dimethoxybenzene; method B: 2 mmol of 1,3-dimethoxybenzene; method C: 5 mL of benzene). The mixture was stirred under the protection of N₂ and then TMSOTf (180 mL, 0.5 mmol) was added. After completion of the reaction (TLC), the mixture was neutralized with Et₃N, concentrated in vacuo, and the residue was purified by flash chromatography.
Compound 5c: yield 0.96 g, 76%. ¹H NMR (250 MHz, CDCl₃): δ = 7.52 (d, 2 H, J = 8.3 Hz), 7.26 (d, 2 H, J = 8.3 Hz), 6.98 (d, 1 H, J = 8.3 Hz), 6.45-6.41 (m, 2 H), 3.93 (s, 2 H, CH₂), 3.80 (s, 3 H, OCH₃), 3.76 (s, 3H, OCH₃). ¹³C NMR (62.5 MHz, CDCl₃): δ = 159.95, 158.20, 147.41, 131.99, 130.69, 129.37, 104.20, 98.74, 96.08, 55.30, 35.70. Anal. Calcd for C₁₆H₁₅NO₂ (253.11): C, 75.87; H, 5.97; N, 5.53. Found: C, 75.62; H, 5.75; N, 5.50.
Compound 6c: yield 0.73 g, 79%. ¹H NMR (250 MHz, CDCl₃): δ = 7.53 (d, 4 H, J = 8.4 Hz), 7.26 (d, 4 H, J = 8.4 Hz), 6.83 (s, 1 H), 6.46 (s, 1 H), 3.91 (s, 4 H, 2 × CH₂), 3.79 (s, 6 H, 2 × OCH₃). ¹³C NMR (62.5 MHz, CDCl₃): δ = 157.20, 147.29, 132.09, 132.03, 129.28, 119.59, 109.55, 96.10, 95.49, 55.57, 35.66. Anal. Calcd for C₁₆H₁₅NO₂ (368.15): C, 78.24; H, 5.47; N, 7.60. Found: C, 78.25; H, 5.73; N, 7.60.
Compound 7c: yield 0.72 g, 75%. ¹H NMR (250 MHz, CDCl₃): δ = 7.50 (d, 2 H, J = 8.4 Hz), 7.36-7.16 (m, 7 H), 4.06 (s, 2 H); practically identical to the published data. [22]