Pyridine Improves Aluminum Triiodide Induced Selective Cleavage of Alkyl o-Hydroxyphenyl Ethers: A Practical and Efficient Procedure for the Preparation of Hydroxychavicol by Demethyl­ation of Eugenol

Abstract

Demethylation of eugenol with aluminum triiodide is complicated by an unexpected hydrogenation side reaction. The hydrogenation proceeds through a cascade deprotonation, hydroiodination, and hydrogen–halogen exchange process, and can be prevented by suppressing the hydroiodination in advance. A practical demethylation procedure is thus developed that delivers hydryoxychavicol in essentially quantitative yield by using pyridine as an additive. The method is selective towards cleaving alkyl o-hydroxyphenyl ethers and is compatible with a variety of functional groups.

Key words

eugenol - demethylation - hydroxychavicol - hydroiodination - hydrogen–halogen exchange - alkyl o-hydroxyphenyl ether - aluminum triidodide–pyridine

• References and Notes

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• 34 General Procedure To a solution of AlI₃ (36.6 mmol, 1.1 equiv) in MeCN (100 mL) was added dropwise a solution of pyridine (12.2 g, 154.2 mmol, 4.6 equiv) and eugenol (5.4 g, 33.0 mmol). The mixture was stirred at 80 °C for 18 h. After cooling to room temperature, the mixture was quenched with aq HCl (2 mol/L, 50 mL), and was extracted with EtOAc (4 × 50 mL). The combined organic phases were washed with brine and dried by MgSO₄. After evaporation of solvents by a rotary evaporator, the residue was purified through flash column chromatography to afford 5 as a white solid (4.9 g, 99%). R_f = 0.46 (PE–EtOAc = 3:1, v/v). ¹H NMR (400 MHz, CDCl₃): δ = 6.80 (d, J = 8.0 Hz, 1 H), 6.72 (d, J = 2.0 Hz, 1 H), 6.63 (dd, J ₁ = 8.0 Hz, J ₂ = 2.0 Hz, 1 H), 6.10 (br s, 2 H), 5.92 (ddt, J ₁ = 17.2 Hz, J ₂ = 10.4 Hz, J ₂ = 6.8 Hz, 1 H), 5.05 (dq, J ₁ = 16.8 Hz, J ₂ = 1.6 Hz, 1 H), 5.03 (dq, J ₁ = 10.0 Hz, J ₂ = 1.6 Hz, 1 H), 3.26 (d, J = 6.4 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 143.35, 141.54, 137.65, 133.60, 121.33, 116.09, 115.80, 115.71, 39.50.
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