A Simple Regioselective Demethylation of p‐Aryl Methyl Ethers Using Aluminum Chloride‐Dichloromethane System

Abstract

Several aryl methyl ethers of phenolic esters and diaryl ketones have been selectively demethylated to their corresponding 4‐hydroxy derivatives by using aluminium chloride‐dichloromethane system at room temperature in good yields (53–85%).

Keywords:

• Aryl methyl ethers
• regioselectivity
• aluminium chloride

Acknowledgment

The authors are grateful to the Director, CIMAP for providing facilities and encouragement for this work. The financial assistance from the Department of Science and Technology (DST), Govt. of India is duly acknowledged.

Notes

¹Selected data for 5a: ¹H NMR (300 MHz CDCl₃, TMS): 3.49 (s 3H C‐17, OCH₃), 3.79 (s, 6H, 3′ & 5′, OCH₃), 3.81 (s, 3H, C‐11, OCH₃), 3.92 (s, 3H, 4′, OCH₃). ¹³C NMR (75.46 MHz, CDCl₃): 16.8 (C‐6), 24.2 (C‐14), 29.7 (C‐19), 32.3 (C‐15), 34.0 (C‐20), 49.0 (C‐21), 51.2 (C‐5), 51.6 (C‐16), 51.7 (OCH₃ at C‐11), 53.7 (C‐3), 56.2 (3′ & 5′, OCH₃), 60.80 (4′, OCH₃), 77.8 (C‐18), 78.0 (C‐17), 95.3 (C‐12), 107.0 (C‐2′ & 6′), 108.0 (C‐7), 108.9 (C‐10), 118.9 (C‐9), 122.2 (C‐8), 125.3 (C‐1′), 130.5 (C‐2), 136.4 (C‐13), 143.0 (C‐4′), 152.9 (C‐3′ & 5′), 156.2 (C‐11), 165.4 (ester carbonyl at C‐18), 172.7 (ester carbonyl at C‐16); Electrospray Mass: 609 [M]⁺. Selected data for 5b: m.p.: oil. Yield: 68% ¹H NMR (300 MHz, CDCl₃, TMS): 3.52 (s, 3H, C‐17, OCH₃), 3.84 (s, 9H, C‐11, 3′ & 5′, OCH₃), ¹³C NMR (75.46 MHz, CDCl₃): 51.87 (C‐17), 57.7 (3′ & 5′, OCH₃), 60.7 (C‐11), 77.4 (C‐18), 79.6 (C‐17), 106.9 (C‐2′ & 6′), 124.9 (C‐1′), 138.4 (C‐4′), 153.9 (C‐3′ & 5′), 155.8 (C‐11), 171.6 (ester carbonyl at C‐16), 165.3 (ester carbonyl at C‐18). Electrospray Mass: 595 [M]⁺; Selected data for 6a: m.p.; 138–40°C; ¹H NMR (300 MHz, CDCl₃, TMS): 3.70 (s, 6H, 3′ & 5′, OCH₃), 3.93 (s, 3H, 4′, OCH₃), 6.90–7.93 (m, 8H, aromatic protons), 10.84 (s, 1H, phenolic OH); ¹³C NMR (75.46 MHz, CDCl₃): 56.63 (3′ & 5′ OCH₃), 61.02 (4′, OCH₃), 108.57–160.47 (aromatic carbons), 198.73 (ketone); Electrospray Mass: 360.9 [M + Na]⁺, 338.9 [M + H]⁺; Analysis: C₂₀H₁₈O₅, Calcd: C, 71.01%; H, 5.32%. Obsd: C, 71.48%; H, 4.92%. Selected data for 6b: Yield 69 mg (72%). m.p.: 116–18°C. ¹H NMR (300 MHz, CDCl₃, TMS): 3.75 (s, 6H, 3′ & 5′, OCH₃), 6.96–7.94 (m, 8H, aromatic protons), 5.99 (s, 1H, phenolic OH), 10.92 (s, 1H, phenolic OH); ¹³C NMR (75.46 MHz, CDCl₃): 56.33 (3′ & 5′, OCH₃), 107.47–159.79 (aromatic carbons), 198.29 (ketone); Analysis: C₁₉H₁₆O₅, Calcd: C, 67.28%; H, 4.94%. Obsd: C, 66.84%; H, 4.69%. Selected data for 7a: m.p.: 132–35°C; ¹H NMR (300 MHz, CDCl₃, TMS): 3.74 (s, 6H, 3′ & 5′, OCH₃), 3.92 (s, 3H, 4′, OCH₃), 4.77 (s, 2H, OCH₂), 7.16–7.97 (m, 8H, aromatic); ¹³C NMR (75.46 MHz, CDCl₃): 56.73 (3′ & 5′, OCH₃), 60.86 (4′, OCH₃), 67.17 (OCH₂), 108.85–153.60 (aromatic carbons), 170.39 (‐COOH), 196.11 (ketone); Electrospray Mass: 419 [M + Na]⁺, 397 [M + H]⁺; Analysis: C₂₂H₂₀O₇, Calcd: C, 66.67%; H, 5.05%. Obsd: C, 67.18%; H, 5.39%. Selected data for 7b: Yield: 53%. m.p.: 109–110°C. ¹H NMR (300 MHz, CDCl₃, TMS): 3.80 (s, 6H, 3′ & 5′, OCH₃), (s, 2H, OCH₂), 7.18–7.72 (m, 8H, aromatic protons); ¹³C NMR (75.46 MHz, CDCl₃): 56.62 (3′ & 5′‐OCH₃), 67.24 (OCH₂), 109.1–154.42 (aromatic carbons), 170.68 (‐COOH), 196.62 (ketone); Analysis: C₂₁H₁₈O₇, Calcd: C, 65.97%; H, 4.71%. Obsd: C, 66.43%; H, 4.29%.