Microwave-Assisted Demethylation
of Methyl Aryl Ethers Using an Ionic Liquid

Jiyeon Park; Junghyun Chae

doi:10.1055/s-0030-1258087

LETTER

Microwave-Assisted Demethylation of Methyl Aryl Ethers Using an Ionic Liquid

Jiyeon Park, Junghyun Chae*
Department of Chemistry and Institute of Basic Sciences, Sungshin Women’s University, Seoul 136-742, Korea
Fax: +82(2)9202058; e-Mail: jchae@sungshin.ac.kr;

Abstract

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Abstract

An efficient demethylation of methyl aryl ethers using an ionic liquid, 1-n-butyl-3-methylimidazolium bromide ([bmim][Br]) has been developed. Methyl aryl ethers are successfully cleaved by the halide anion of [bmim][Br], without aid of any other activating agents. In this reaction, microwave irradiation was found to be crucial for the effective conversion. The newly developed protocol is a very attractive green chemical process as it utilizes minimal amount of cleaving reagents and does not require additional activating agents or solvents. Under the conditions described herein, a broad range of methyl aryl ethers were converted to the corresponding phenolic compounds in moderate to excellent yields in a short time.

Key words

demethylation - methyl aryl ether - ionic liquid - microwave irradiation

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References

References and Notes

<A NAME="RU02910ST-1A">1a</A> Wuts PGM. Greene TW. Greene’s Protective Groups in Organic Synthesis 4th ed.: Wiley; New York: 2006.

<A NAME="RU02910ST-1B">1b</A> Kocienski PJ. Protecting Groups 3rd ed.: Thieme; Stuttgart: 2005.

<A NAME="RU02910ST-2A">2a</A> McOmie JFW. West DE. Org. Synth., Collect. Vol. V Wiley; New York: 1973. p.412

<A NAME="RU02910ST-2B">2b</A> Parker KA. Petraitis JJ. Tetrahedron Lett. 1981, 22: 397

<A NAME="RU02910ST-2C">2c</A> Li T. Wu YL. J. Am. Chem. Soc. 1981, 103: 7007

<A NAME="RU02910ST-2D">2d</A> Kawasaki I. Matsuda K. Kaneko T. Bull. Chem. Soc. Jpn. 1971, 44: 1986

<A NAME="RU02910ST-2E">2e</A> Jung ME. Lyster MA. J. Org. Chem. 1977, 42: 376l

<A NAME="RU02910ST-3A">3a</A> Kende AS. Rizzi JP. Tetrahedron Lett. 1981, 22: 1779

<A NAME="RU02910ST-3B">3b</A> Bernard AM. Ghiani MR. Piras PP. Rivoldini A. Synthesis 1989, 287

<A NAME="RU02910ST-3C">3c</A> McCarthy JR. Moore JL. Crege RJ. Tetrahedron Lett. 1978, 183

<A NAME="RU02910ST-3D">3d</A> Gates M. Tschudi G. J. Am. Chem. Soc. 1956, 78: 1380

<A NAME="RU02910ST-4A">4a</A> Node M. Nishide K. Fuji K. Fujita E. J. Org. Chem. 1980, 45: 4275

<A NAME="RU02910ST-4B">4b</A> Inaba T. Umezawa I. Yuasa M. Inoue T. Mihashi S. Itokawa H. Ogura K. J. Org. Chem. 1987, 52: 2957

For reviews on ionic liquids, see:

<A NAME="RU02910ST-5A">5a</A> Zhao H. Malhotra SV. Aldrichimica Acta 2002, 35: 75

<A NAME="RU02910ST-5B">5b</A> Welton T. Chem. Rev. 1999, 99: 2071

<A NAME="RU02910ST-5C">5c</A> Sheldon R. Chem. Commun. 2001, 2399

<A NAME="RU02910ST-5D">5d</A> Wasserscheid P. Keim W. Angew. Chem. Int. Ed. 2000, 39: 3772

<A NAME="RU02910ST-5E">5e</A> Jain N. Kumar A. Chauhan S. Chauhan MS. Tetrahedron 2005, 61: 1015

<A NAME="RU02910ST-5F">5f</A> Chowdhury S. Mohan RS. Scott JL. Tetrahedron 2007, 63: 2363

<A NAME="RU02910ST-6A">6a</A> Wheeler C. West KN. Liotta CL. Eckert CA. Chem. Commun. 2001, 887

<A NAME="RU02910ST-6B">6b</A> Judeh ZMA. Shen HY. Chi BC. Feng LC. Selvasothi S. Tetrahedron Lett. 2002, 43: 9381

<A NAME="RU02910ST-6C">6c</A> Lourenco NMT. Alfonso CMA. Tetrahedron Lett. 2003, 59: 789

<A NAME="RU02910ST-6D">6d</A> Chiappe C. Pieraccini D. Saullo P. J. Org. Chem. 2003, 68: 6710

<A NAME="RU02910ST-6E">6e</A> Crowhurst L. Lancaster NL. Arlandis JMP. Welton T. J. Am. Chem. Soc. 2004, 126: 11549

<A NAME="RU02910ST-6F">6f</A> Lancaster NL. Chem. Res. 2005, 413

<A NAME="RU02910ST-6G">6g</A> Landini D. Maia A. Tetrahedron Lett. 2005, 46: 3961

<A NAME="RU02910ST-6H">6h</A> For a recent review on nucleophilic substitution reaction in ionic liquids, see: Jorapur YR. Chi DY. Bull. Korean Chem. Soc. 2009, 27: 345

<A NAME="RU02910ST-7">7</A> Driver G. Johnson KE. Green Chem. 2003, 5: 163

<A NAME="RU02910ST-8A">8a</A> Kemperman GJ. Roeters TA. Hilberink PW. Eur. J. Org. Chem. 2003, 1681

<A NAME="RU02910ST-8B">8b</A> Liu T. Hu Y. Synth. Commun. 2004, 34: 3209

<A NAME="RU02910ST-9">9</A> Boovanahalli SK. Kim DW. Chi DY. J. Org. Chem. 2004, 69: 3340

<A NAME="RU02910ST-10">10</A> Cheng L. Aw C. Ong SS. Lu X. Bull. Chem. Soc. Jpn. 2007, 80: 2008

<A NAME="RU02910ST-11">11</A> Chae J. Arch. Pharm. Res. 2008, 31: 305

<A NAME="RU02910ST-12">12</A> Kappe CO. Angew. Chem. Int. Ed. 2004, 43: 6250

<A NAME="RU02910ST-13A">13a</A> Brauman JI. Olmstead WN. Lieder CA. J. Am. Chem. Soc. 1974, 96: 4030

<A NAME="RU02910ST-13B">13b</A> Olmstead WN. Brauman JI. J. Am. Chem. Soc. 1977, 99: 4219

<A NAME="RU02910ST-13C">13c</A> Tanaka K. Mackay GI. Payzant JD. Bohme DK. Can. J. Chem. 1976, 54: 1643

<A NAME="RU02910ST-14A">14a</A> Lancaster NL. Welton T. Young GB. J. Chem. Soc., Perkin Trans. 2 2001, 2267

<A NAME="RU02910ST-14B">14b</A> Lancaster NL. Salter PA. Welton T. Young GB. J. Org. Chem. 2002, 67: 8855

<A NAME="RU02910ST-15">15</A> Anne G. Glenn AG. Jones PB. Tetrahedron Lett. 2004, 45: 6967

All the reagents were purchased from Aldrich or TCI. Column chromatography was performed on Silica gel 60 (230-400 mesh, Merck) and TLC was performed on silica gel 60 F₂₅₄ glass plate (Merck). Microwave reactions were conducted on a CEM Discover® S-class instrument. ^¹H NMR (500 MHz) and ^¹³C NMR (125MHz) spectra were recorded on a Varian 500 NMR spectrometer with chemical shifts reported in ppm relative to residual solvent peaks or to TMS as the internal standard. Yields refer to isolated yields of compounds greater than 95% pure as determined by ^¹H NMR and GC analyses. All compounds were characterized by ^¹H NMR and ^¹³C NMR. Gas chromatography analyses were performed on a Hewlett Packard 6890 instrument with HP-1 capillary column and mass spectra were recorded by HP 5973 MSD with EI as the ionization method.
Representative Procedure: To a microwave tube were added methyl aryl ether (2.0 mmol) and 1-n-butyl-3-methylimidazolium bromide (1.32 g, 6.0 mmol). The reaction tube was flushed with argon and then was irradiated at 20 W for 40 min while cooled by air flow (power control mode). After cooling to r.t., the reaction mixture was acidified with 1 N HCl solution and extracted with EtOAc
(3 × 20 mL). The combined organic layer was washed with H₂O, brine, dried over MgSO₄ and the solvent was evaporated under vacuum. Purification of the crude product by column chromatography (EtOAc in n-hexane) afforded the desired product.
1-Naphthol (Table [4] , entry 1): pale pink solid (265 mg, 92%). ^¹H NMR (500 MHz, CDCl₃): δ = 8.15-8.20 (m, 1 H), 7.79-7.82 (m, 1 H), 7.46-7.51 (m, 2 H), 7.44 (d, J = 8.0 Hz, 1 H), 7.30 (t, J = 8.0 Hz, 1 H), 6.80 (d, J = 8.0 Hz, 1 H), 5.34 (s, 1 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 151.6, 135.0, 127.9, 126.7, 126.1, 125.5, 124.6, 121.8, 120.9, 108.9. MS (EI): m/z = 144 [M⁺].
2-Naphthol (Table [4] , entry 2): pale pink solid (256 mg, 89%). ^¹H NMR (500 MHz, CDCl₃): δ = 7.74-7.77 (m, 2 H), 7.67 (d, J = 8.5 Hz, 1 H), 7.43 (t, J = 7.5 Hz, 1 H), 7.32 (t,
J = 7.4 Hz, 1 H), 7.14 (d, J = 2.5 Hz, 1 H), 7.10 (dd, J = 2.5, 8.5 Hz, 1 H), 5.10 (s, 1 H). ^¹³C NMR (125 MHz, CDCl₃):
δ = 153.6, 134.8, 130.1, 129.2, 128.0, 126.8, 126.6, 123.9, 118.0, 109.7. MS (EI): m/z = 144 [M⁺].
4-Phenylphenol (Table [4] , entry 3): white solid (333 mg, 98%). ^¹H NMR (500 MHz, CDCl₃): δ = 7.53-7.55 (m, 2 H), 7.46-7.49 (m, 2 H), 7.40-7.43 (m, 2 H), 7.29-7.32 (m, 1 H), 6.89-6.92 (m, 2 H), 5.10 (s, 1 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 155.3, 141.0, 134.2, 129.0, 128.7, 127.0, 126.9, 115.9. MS (EI): m/z = 170 [M⁺].
4-Hydroxyphenylphenylmethanone (Table [4] , entry 4): white solid (376 mg, 95%). ^¹H NMR (500 MHz, CDCl₃):
δ = 7.78 (d, J = 9.0 Hz, 2 H), 7.76 (d, J = 7.0 Hz, 2 H), 7.64 (s, 1 H), 7.58 (t, J = 7.5 Hz, 1 H), 7.48 (t, J = 8.0 Hz, 2 H), 6.95 (td, J = 2.0, 9.0 Hz, 2 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 197.3, 161.2, 138.2, 133.5, 132.5, 130.2, 129.7, 128.6, 115.7. MS (EI): m/z = 198 [M⁺].
2′-Hydroxyacetophenone (Table [4] , entry 5): pale yellow oil (231 mg, 85%). ^¹H NMR (500 MHz, CDCl₃): δ = 12.27 (s, 1 H), 7.74 (ddd, J = 1.5, 2.5, 7.9 Hz, 1 H), 7.46-7.50 (m, 1 H), 6.98 (ddd, J = 1.5, 2.5, 8.3 Hz, 1 H), 6.89-6.93 (m, 1 H), 2.64 (s, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 204.8, 162.6, 136.7, 131.0, 120.0, 119.2, 118.7, 26.9. MS (EI): m/z = 136 [M⁺].
3′-Hydroxyacetophenone (Table [4] , entry 6): yellow solid (250 mg, 92%). ^¹H NMR (500 MHz, CDCl₃): δ = 7.54 (t, J = 2.5 Hz, 1 H), 7.51 (td, J = 1.0, 7.5 Hz, 1 H), 7.34 (t, J = 7.5 Hz, 1 H), 7.11 (ddd, J = 1.0, 2.5, 8.0 Hz, 1 H), 6.05 (br s, 1 H), 2.61 (s, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 200.0, 156.7, 138.5, 130.2, 121.3, 121.1, 114.9, 27.1. MS (EI): m/z = 136 [M⁺].
4′-Hydroxyacetophenone (Table [4] , entry 7): white solid (267 mg, 98%). ^¹H NMR (500 MHz, CDCl₃): δ = 7.91 (d, J = 8.5 Hz, 2 H), 6.91 (d, J = 8.5 Hz, 2 H), 6.66 (br s, 1 H), 2.59 (s, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 198.9, 161.7, 131.5, 129.8, 115.8, 26.6. MS (EI): m/z = 136 [M⁺].
Estrone (Table [4] , entry 8): white solid (286 mg, 53%). ^¹H NMR (500 MHz, CDCl₃): δ = 7.16 (d, J = 8.5 Hz, 1 H), 6.65 (dd, J = 2.0, 9.0 Hz, 1 H), 6.59 (d, J = 2.0 Hz, 1 H), 4.74 (s, 1 H), 2.87 (dd, J = 3.5, 10.0 Hz, 2 H), 2.46 (q, J = 9.0 Hz, 1 H), 2.38 (t, J = 10.0 Hz, 1 H), 2.24 (m, 1 H), 1.91-2.21 (m, 4 H), 1.27-1.68 (m, 4 H), 1.25 (t, J = 7.0 Hz, 2 H), 0.91 (s, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 221.5, 153.7, 138.3, 132.3, 126.8, 115.5, 113.1, 50.6, 48.3, 44.2, 38.6, 36.2, 31.8, 29.7, 26.7, 26.2, 21.8, 14.1. MS (EI): m/z = 270 [M⁺].
4-Cyanophenol (Table [4] , entry 9): white solid (217 mg, 91%). ^¹H NMR (500 MHz, CDCl₃): δ = 7.56 (d, J = 9.0 Hz, 2 H), 6.92 (d, J = 9.0 Hz, 2 H), 6.31 (br s, 1 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 160.6, 134.6, 119.6, 116.8, 103.0. MS (EI): m/z = 119 [M⁺].
α,α,α-Trifluoro- m -cresol (Table [4] , entry 10): yellow oil (305 mg, 94%). ^¹H NMR (500 MHz, CDCl₃): δ = 7.37 (t,
J = 8.0 Hz, 1 H), 7.23 (d, J = 8.0 Hz, 1 H), 7.11 (s, 1 H), 7.03 (dd, J = 2.5, 8.0 Hz, 1 H), 5.39 (br s, 1 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 155.7, 132.3 (q, J = 32.0 Hz), 130.6, 124.0 (q, J = 270 Hz), 119.1 (d, J = 1.4 Hz), 118.0 (d, J = 4.1 Hz), 112.6 (d, J = 4.3 Hz). MS (EI): m/z = 162 [M⁺].
3-Bromophenol (Table [4] , entry 11): yellow solid (320 mg, 93%). ^¹H NMR (500 MHz, CDCl₃): δ = 7.10 (t, J = 8.0 Hz, 1 H), 7.05-7.08 (m, 1 H), 7.02 (t, J = 2.0 Hz, 1 H), 6.76-6.78 (m, 1 H), 5.24 (s, 1 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 156.6, 131.1, 124.2, 123.0, 119.1, 114.5. MS (EI): m/z = 172 [M⁺].

4-Isopropylphenol (Table [4] , entry 12): pale yellow solid (267 mg, 98%). ^¹H NMR (500 MHz, CDCl₃): δ = 7.12 (d,
J = 9.0 Hz, 2 H), 6.79 (d, J = 9.0 Hz, 2 H), 5.15 (br s, 1 H), 2.83-2.91 (m, 1 H), 1.24 (d, J = 7.0 Hz, 6 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 153.7, 141.5, 127.7, 115.3, 33.5, 24.5. MS (EI): m/z = 136 [M⁺].
2,6-Diisopropylphenol (Table [4] , entry 13): yellow oil (335 mg, 94%). ^¹H NMR (500 MHz, CDCl₃): δ = 7.10 (d, J = 7.5 Hz, 2 H), 6.94 (t, J = 7.5 Hz, 1 H), 4.84 (s, 1 H), 3.10-3.30 (m, J = 7.0 Hz, 2 H), 1.30 (d, J = 7.0 Hz, 12 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 150.2, 133.8, 123.7, 120.9, 27.4, 23.0. MS (EI): m/z = 178 [M⁺].
4-Hydroxybenzaldehyde (Table [4] , entry 14): yellow solid (102 mg, 42%). ^¹H NMR (500 MHz, CDCl₃): δ = 9.87 (s, 1 H), 7.82 (d, J = 9.0 Hz, 2 H), 6.97 (d, J = 9.0 Hz, 2 H), 6.22 (br s, 1 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 191.5, 162.0, 132.8, 130.0, 116.3. MS (EI): m/z = 121 [M⁺].
Ethyl 4-Hydroxybenzoate (Table [4] , entry 15): white solid (83 mg, 25%). ^¹H NMR (500 MHz, CDCl₃): δ = 7.96 (d, J = 7.2 Hz, 2 H), 6.88 (d, J = 7.8 Hz, 2 H), 6.51 (br s, 1 H), 4.36 (q, J = 7.0 Hz, 2 H), 1.39 (t, J = 7.0 Hz, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 167.2, 160.5, 132.2, 122.8, 115.5, 61.2, 14.6. MS (EI): m/z = 166 [M⁺].
2-Methoxyphenol (Table [4] , entry 16): colorless oil (87 mg, 35%). ^¹H NMR (500 MHz, CDCl₃): δ = 6.91-6.95 (m, 1 H), 6.82-6.90 (m, 3 H), 5.64 (s, 1 H), 3.88 (s, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 146.8, 145.9, 121.7, 120.4, 114.8, 110.9, 56.1. MS (EI): m/z = 124 [M⁺].