The Desymmetrisation of Resorcinol: The Synthesis of Resorcinol Monoalkyl Ethers

Abstract

The desymmetrisation of resorcinol to give 3-alkoxyresorcinol derivatives can be achieved in excellent yields either from resorcinol monobenzoate and alcohols using Mitsunobu reactions followed by hydrolysis using a strong base or by using 3-iodophenylbenzyl ether as a resorcinol monobenzyl ether equivalent in reactions with alcohols catalysed by copper(I)-9,10-phenanthroline followed by ammonium formate-palladium catalysed hydrogenolysis.

Key words

caesium carbonate - copper(I) iodide - hydrolyses - Mitsunobu reactions - 9,10-phenanthroline

References

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16

Boxhall, J. Y.; Page, P. C. B.; Elsegood, M. R. J.; Chan, Y.; Heaney, H.; Holmes, K. E.; McGrath, M. J. Synlett 2003, following letter.

18

MS: m/z found M⁺ 256.10991; C₁₆H₁₆O₃ requires 256.10995. IR: ν_max = 3069, 2976, 2932, 1735, 1606, 1589, 1485, 1465, 1451, cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.40 (d, 6 H, J = 6.4 Hz), 4.59 (sept., 1 H, J = 6.4 Hz), 6.88 (m, 3 H), 7.35 (m, 1 H), 7.54 (m, 2 H), 7.66 (m, 1 H), 8.28 (m, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 24.23 (Me), 72.29 (CH), 111.67 (CH), 115.71 (CH), 115.89 (CH), 130.86 (2 × Me), 131.83 (C), 132.16 (CH), 132.39 (2 × CH), 135.87 (CH), 154.24 (C), 161.17 (C), and 167.26 (C=O) ppm.

19

MS: m/z found M⁺ 152.08346; C₉H₁₂O₂ requires 152.08346. IR: ν_max = 3385, 2976, 2932, 1595, 1490 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.32 (d, 6 H, J = 6.0 Hz), 4.51 (sept., 1 H, J = 6.0 Hz), 6.40 (m, 2 H), 6.47 (m, 1 H), 7.11 (m, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 22.43 (2 × Me), 70.36 (CH), 103.71 (CH), 107.95 (CH), 108.69 (CH), 130.48 (CH), 157.15 (C), and 159.66 (C) ppm.

20

Mp 118 ºC. MS (FAB): m/z (%) = 202 (100) [M + H⁺] found 202.0868, C₁₂H₁₂NO₂ requires 202.0868. Found: C, 71.61; H, 5.47; N, 6.88%. C₁₂H₁₁NO₂ requires C, 71.63; H, 5.51; N, 6.96%. IR (KBr): ν_max = 3058 (br), 2731, 2611, 1617, 1600, 1572, 1439, 1380, 1300, 1243, 1179, 1157, 1061, 749 cm^-1. ¹H NMR (400 MHz, d ₆-acetone): δ = 5.14 (s, 2 H), 6.46 (ddd, 1 H, J = 1.0, 2.2, 8.0 Hz), 6.50-6.52 (m, 2 H), 7.07-7.12 (m, 1 H), 7.28-7.32 (m, 1 H), 7.52, (br d, 1 H, J = 9.2 Hz), 7.81 (ddd, 1 H, J = 1.8, 7.7, 7.7 Hz), 8.45 (br s, 1 H,), and 8.57 (ddd, 1 H, J = 1.0, 1.7, 4.8 Hz) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 71.3 (CH₂), 103.1 (CH), 106.8, (CH), 109.1 (CH), 122.1 (CH), 123.5 (CH), 130.8 (CH), 137.5 (CH), 150.0 (CH), 158.4 (C), 159.6 (C), and 160.8 (C) ppm.