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

Jiyeon Park; Junghyun Chae

doi:10.1055/s-0030-1258087

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml

Share / Bookmark

Facebook X Linkedin Weibo

Download PDF

Synlett 2010(11): 1651-1656
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;

Further Information

Publication History

Received 19 April 2010
Publication Date:
11 June 2010 (online)

Abstract
Full Text
References

Permissions and Reprints All articles of this category

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

References and Notes

1a Wuts PGM. Greene TW. Greene’s Protective Groups in Organic Synthesis 4th ed.: Wiley; New York: 2006.

Google Scholar
1b Kocienski PJ. Protecting Groups 3rd ed.: Thieme; Stuttgart: 2005.

Google Scholar
2a McOmie JFW. West DE. Org. Synth., Collect. Vol. V Wiley; New York: 1973. p.412

Google Scholar
2b Parker KA. Petraitis JJ. Tetrahedron Lett. 1981, 22: 397

Google Scholar
2c Li T. Wu YL. J. Am. Chem. Soc. 1981, 103: 7007

Google Scholar
2d Kawasaki I. Matsuda K. Kaneko T. Bull. Chem. Soc. Jpn. 1971, 44: 1986

Google Scholar
2e Jung ME. Lyster MA. J. Org. Chem. 1977, 42: 376l

Google Scholar
3a Kende AS. Rizzi JP. Tetrahedron Lett. 1981, 22: 1779

Google Scholar
3b Bernard AM. Ghiani MR. Piras PP. Rivoldini A. Synthesis 1989, 287

Google Scholar
3c McCarthy JR. Moore JL. Crege RJ. Tetrahedron Lett. 1978, 183

Google Scholar
3d Gates M. Tschudi G. J. Am. Chem. Soc. 1956, 78: 1380

Google Scholar
4a Node M. Nishide K. Fuji K. Fujita E. J. Org. Chem. 1980, 45: 4275

Google Scholar
4b Inaba T. Umezawa I. Yuasa M. Inoue T. Mihashi S. Itokawa H. Ogura K. J. Org. Chem. 1987, 52: 2957

Google Scholar
For reviews on ionic liquids, see:
5a Zhao H. Malhotra SV. Aldrichimica Acta 2002, 35: 75

Google Scholar
5b Welton T. Chem. Rev. 1999, 99: 2071

Google Scholar
5c Sheldon R. Chem. Commun. 2001, 2399

Google Scholar
5d Wasserscheid P. Keim W. Angew. Chem. Int. Ed. 2000, 39: 3772

Google Scholar
5e Jain N. Kumar A. Chauhan S. Chauhan MS. Tetrahedron 2005, 61: 1015

Google Scholar
5f Chowdhury S. Mohan RS. Scott JL. Tetrahedron 2007, 63: 2363

Google Scholar
6a Wheeler C. West KN. Liotta CL. Eckert CA. Chem. Commun. 2001, 887

Google Scholar
6b Judeh ZMA. Shen HY. Chi BC. Feng LC. Selvasothi S. Tetrahedron Lett. 2002, 43: 9381

Google Scholar
6c Lourenco NMT. Alfonso CMA. Tetrahedron Lett. 2003, 59: 789

Google Scholar
6d Chiappe C. Pieraccini D. Saullo P. J. Org. Chem. 2003, 68: 6710

Google Scholar
6e Crowhurst L. Lancaster NL. Arlandis JMP. Welton T. J. Am. Chem. Soc. 2004, 126: 11549

Google Scholar
6f Lancaster NL. Chem. Res. 2005, 413

Google Scholar
6g Landini D. Maia A. Tetrahedron Lett. 2005, 46: 3961

Google Scholar
6h For a recent review on nucleophilic substitution reaction in ionic liquids, see: Jorapur YR. Chi DY. Bull. Korean Chem. Soc. 2009, 27: 345

Google Scholar
7 Driver G. Johnson KE. Green Chem. 2003, 5: 163

Crossref Google Scholar
8a Kemperman GJ. Roeters TA. Hilberink PW. Eur. J. Org. Chem. 2003, 1681

Google Scholar
8b Liu T. Hu Y. Synth. Commun. 2004, 34: 3209

Google Scholar
9 Boovanahalli SK. Kim DW. Chi DY. J. Org. Chem. 2004, 69: 3340

Crossref Google Scholar
10 Cheng L. Aw C. Ong SS. Lu X. Bull. Chem. Soc. Jpn. 2007, 80: 2008

Crossref Google Scholar
11 Chae J. Arch. Pharm. Res. 2008, 31: 305

Crossref Google Scholar
12 Kappe CO. Angew. Chem. Int. Ed. 2004, 43: 6250

Crossref PubMed Google Scholar
13a Brauman JI. Olmstead WN. Lieder CA. J. Am. Chem. Soc. 1974, 96: 4030

Google Scholar
13b Olmstead WN. Brauman JI. J. Am. Chem. Soc. 1977, 99: 4219

Google Scholar
13c Tanaka K. Mackay GI. Payzant JD. Bohme DK. Can. J. Chem. 1976, 54: 1643

Google Scholar
14a Lancaster NL. Welton T. Young GB. J. Chem. Soc., Perkin Trans. 2 2001, 2267

Google Scholar
14b Lancaster NL. Salter PA. Welton T. Young GB. J. Org. Chem. 2002, 67: 8855

Google Scholar
15 Anne G. Glenn AG. Jones PB. Tetrahedron Lett. 2004, 45: 6967

Crossref Google Scholar

16

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⁺].