PDF herunterladen
Synlett 2013; 24(17): 2305-2309
DOI: 10.1055/s-0033-1338975
letter
© Georg Thieme Verlag Stuttgart · New York

Ascorbic Acid Based Ionic Liquids: Recyclable and Efficient Catalytic Systems for the Huisgen Cycloaddition

Shinichi Koguchi*
Department of Chemistry, School of Science, Tokai University, 4-1-1 Kitakaname, Hiratsuka, Kanagawa 259-1292, Japan   Fax: +81(463)502094   eMail: koguchi@tokai-u.jp
,
Kaori Nakamura
Department of Chemistry, School of Science, Tokai University, 4-1-1 Kitakaname, Hiratsuka, Kanagawa 259-1292, Japan   Fax: +81(463)502094   eMail: koguchi@tokai-u.jp
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 07. August 2013

Accepted after revision: 02. September 2013

Publikationsdatum:
27. September 2013 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik


Abstract

A new method for the Huisgen cycloaddition using an ascorbic acid based ionic liquid and a copper catalyst in an ionic liquid, under microwave irradiation, is described. The reaction times are short and a simple procedure for separation of the products is established. Good conversions are obtained and the ionic liquid based catalytic system can be recycled.

Key words

ionic liquids - microwave irradiation - supported catalysis - heterocycles - oxidation
 

  • References and Notes

  • 3 Cao H, McNamess L, Alper H. J. Org. Chem. 2008; 73: 3530
    CrossrefSuche in Google Scholar
    • 5a Genin MJ, Allwine DA, Anderson DJ, Barbachyn MR, Emmert DE, Garmon SA, Graber DR, Grega KC, Hester JB, Hutchinson DK, Morris J, Reischer RJ, Ford CW, Zurenko GE, Hamel JC, Schaadt RD, Stapert D, Yagi BH. J. Med. Chem. 2000; 43: 953
      CrossrefSuche in Google Scholar
    • 5b Holla BS, Mahalinga M, Karthikeyan MS, Poojary B, Akberali PM, Kumari NS. Eur. J. Med. Chem. 2005; 40: 1173
      CrossrefSuche in Google Scholar
  • 7 Alvarez R, Velazquez S, San-Felix A, Aquaro S, De Clercq E, Perno C.-F, Karlsson A, Balzarini J, Camarasa MJ. J. Med. Chem. 1994; 37: 4194
    Suche in Google Scholar
  • 8 Al-Masoudim NA, Al-Soud YA. Tetrahedron Lett. 2002; 43: 4021
    CrossrefSuche in Google Scholar
  • 12 Dinda E, Si S, Kotal A, Mandal T. Chem. Eur. J. 2008; 14: 5528
    CrossrefSuche in Google Scholar
  • 13 Zhijun D, Jiangna G, Lihua Q, Yinxia Z, Lin X, Feng Y. Polym. Chem. 2012; 3: 2439
    Suche in Google Scholar
  • 14 All reagents and chemicals (reagent grade) were obtained from commercial suppliers, and were used as received. TLC was performed using Merck silica gel 60 F254 aluminum sheets. Column chromatography was performed using Kanto Chemical silica gel 60. Melting points were determined using a Yamoto MP-21 melting point apparatus. 1H (500 MHz) and 13C (125 MHz) NMR spectra were recorded in CDCl3 on a Bruker Avance DRX 500 spectrometer. Chemical shifts (δ) are expressed in ppm and are referenced to the residual peak of the solvent or TMS as an internal standard; coupling constants (J) are quoted in Hz. Mass analyses were performed using a JEOL AccuTOF LC-plus JMS-T100LP spectrometer. MALDI-MS (TOF) spectra were recorded on a Voyager DE-STR instrument; α-cyano-4-hydroxycinnamic acid was used as the matrix. Microwave irradiation was performed using a Shikoku Instrumentation CO., Inc. μReacter EX.
  • 15 1-Ethyl-3-methyl-1H-imidazol-3-ium hydrogencarbonate (1a) Yield: 825 mg (4.79 mmol, 96%); yellow liquid. 1H NMR (500 MHz, CDCl3): δ = 1.38 (t, J = 7.5 Hz, 3 H), 2.50 (s, 3 H), 4.19 (q, J = 7.5 Hz, 2 H), 7.70 (s, 1 H), 7.79 (s, 1 H), 9.13 (s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 15.6, 36.2, 44.6, 122.3, 123.9, 136.6. MALDI-MS (TOF): m/z [M]+ calcd for C6H11N2: 111.0; found: 111.0. 1-Butyl-3-methyl-1H-imidazol-3-ium hydrogencarbonate (1b) Yield: 971 mg (4.85 mmol, 97%); yellow liquid. 1H NMR (500 MHz, CDCl3): δ = 0.89 (t, J = 7.5 Hz, 3 H), 1.24 (m, 2 H), 1.75 (m, 2 H), 2.51 (s, 3 H), 4.16 (t, J = 7.5 Hz, 2 H), 7.70 (s, 1 H), 7.77 (s, 1 H), 9.13 (s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 13.7, 19.2, 31.9, 36.3, 48.8, 122.7, 123.9, 136.9. HRMS (APCI): m/z [M + H]+ calcd for C8H15N2: 139.1235; found: 139.1241.
  • 16 Ascorbic Acid Based Ionic Liquids 2a,b; General Procedure A solution of 1,3-disubstituted imidazolium hydrogencarbonate 1a,b (20 mmol) in MeOH (8 mL) was added to l-ascorbic acid (20 mmol). The resulting mixture was stirred at r.t. for 24 h and then evaporated. 3-Ethyl-1-methyl-1H-imidazol-3-ium ascorbate (2a) Yield: 5060.0 mg (17.2 mmol, 88%); orange liquid. 1H NMR (500 MHz, CDCl3): δ = 0.42–1.39 (m, 3 H), 2.50 (s, 3 H), 3.47–3.48 (m, 3 H), 3.48–3.80 (m, 1 H), 4.18–4.21 (m, 2 H), 7.70 (s, 1 H), 7.79 (s, 1 H), 9.17 (s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 15.6, 36.1, 44.6, 63.5, 77.1, 115.9, 122.4, 123.9, 136.8, 167.5, 172.8, 176.2. MALDI-MS (TOF): m/z [M]+ calcd for C6H11N2: 111.0; found: 110.9. 3-Butyl-1-methyl-1H-imidazol-3-ium ascorbate (2b) Yield: 6179.2 mg (19.2 mmol, 98%); orange liquid. 1H NMR (500 MHz, CDCl3): δ = 0.95–0.98 (m, 3 H), 1.34–1.41 (m, 2 H), 1.84–1.90 (m, 2 H), 3.16–3.20 (m, 3 H), 3.76 (s, 3 H), 3.80–3.85 (m, 1 H), 4.15–4.17 (m, 2 H), 7.25 (s, 1 H), 7.27 (s, 1 H), 10.64 (s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 13.7, 19.2, 31.8, 36.1, 48.9, 63.7, 76.9, 115.8, 122.7, 124.0, 137.2, 163.2, 167.6, 176.5. HRMS (ACPI): m/z [M]+ calcd for C8H15N2: 139.1235; found: 139.1253.
  • 17 1,4-Disubstituted 1,2,3-Triazoles 3a–h; General Procedure A solution of azide (2.0 mmol), acetylene (3.0 mmol), CuSO4 (0.3 mmol) and 3-butyl-1-methyl-1H-imidazol-3-ium ascorbate (2b) (0.5 mmol) in [bmim]BF4 (2 mL) and H2O (1 mL) was stirred for 1 min at 80 °C under microwave irradiation. After the reaction was complete, the mixture was extracted with Et2O and the organic phase evaporated. The product was isolated by silica gel column chromatography. 1-Benzyl-4-phenyl-1H-1,2,3-triazole (3a) Yield: 451 mg (1.90 mmol, 96%); white solid; mp 122–124 °C. 1H NMR (500 MHz, CDCl3): δ = 5.59 (s, 2 H), 7.26–7.42 (m, 8 H), 7.66 (s, 1 H), 7.80 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 54.3, 119.5, 125.7 (2 C), 128.1 (2 C), 128.2, 128.6, 128.8 (2 C), 129.2 (2 C), 130.6, 134.7, 148.3. HRMS (APCI): m/z [M + H]+ calcd for C15H14N3: 236.11877; found: 236.11002. 1-(4-Methylbenzyl)-4-phenyl-1H-1,2,3-triazole (3b) Yield: 481 mg (1.93 mmol, 97%); white solid; mp 108–111 °C. 1H NMR (500 MHz, CDCl3): δ = 2.36 (s, 3 H), 5.54 (s, 2 H), 7.19–7.23 (m, 4 H), 7.30–7.32 (m, 1 H), 7.39–7.41 (m, 2 H), 7.63 (s, 1 H), 7.78–7.80 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 21.2, 54.0, 119.4, 125.7, 128.1 (2 C), 128.8 (2 C), 129.8 (2 C), 130.6 (2 C), 131.7 (2 C), 138.7, 148.2. HRMS (APCI): m/z [M + H]+ calcd for C16H16N3: 250.13442; found: 250.12573. 1-(4-Methoxybenzyl)-4-phenyl-1H-1,2,3-triazole (3c) Yield: 464 mg (1.75 mmol, 87%); white solid; mp 135 °C. 1H NMR (500 MHz, CDCl3): δ = 3.82 (s, 3 H), 5.52 (s, 2 H), 6.92 (d, J = 9 Hz, 2 H), 7.28–7.33 (m, 2 H), 7.38–7.40 (m, 3 H), 7.62 (s, 1 H), 7.79 (d, J = 9 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 53.8, 55.4, 114.2, 114.5 (2 C), 119.3, 120.0, 125.7, 126.7, 128.1, 128.8, 129.7 (2 C), 130.6 (2 C), 159.9. HRMS (APCI): m/z [M + H]+ calcd for C16H16N3O: 266.12934; found: 266.12823. 4-Phenyl-1-(3-phenylpropyl)-1H-1,2,3-triazole (3d) Yield: 420 mg (1.59 mmol, 80%); white solid; mp 82–83 °C. 1H NMR (500 MHz, CDCl3): δ = 2.31 (q, J = 7.5 Hz, 2 H), 2.70 (t, J = 7.5 Hz, 2 H), 4.41 (t, J = 7.5 Hz, 2 H), 7.19–7.35 (m, 6 H), 7.41–7.46 (m, 2 H), 7.72 (s, 1 H), 7.80–7.83 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 30.4, 32.5, 50.6, 119.5, 125.7, 126.4, 126.1, 126.5, 128.49 (2 C), 128.5, 128.6, 128.7, 128.9, 130.7, 140.2, 147.8. HRMS (APCI): m/z [M + H]+ calcd for C17H18N3: 264.15007; found: 264.14639. 1-Benzyl-4-cyclopropyl-1H-1,2,3-triazole (3e) Yield: 353 mg (1.77 mmol, 89%); white solid; mp 58–59 °C. 1H NMR (500 MHz, CDCl3): δ = 0.80–0.83 (m, 2 H), 0.90–0.94 (m, 2 H), 1.89–1.94 (m, 1 H), 5.47 (s, 2 H), 7.13 (s, 1 H), 7.24–7.26 (m, 2 H), 7.33–7.38 (m, 3 H). 13C NMR (125 MHz, CDCl3): δ = 6.7, 7.7, 54.0, 119.6, 128.0, 128.2 (2 C), 128.6 (2 C), 129.0, 135.0, 150.7. HRMS (APCI): m/z [M + H]+ calcd for C12H14N3: 200.11877; found: 200.11366. 1-Benzyl-4-[4-(tert-butyl)phenyl]-1H-1,2,3-triazole (3f) Yield: 638 mg (2.19 mmol, quant.); white solid; mp 112–114 °C. 1H NMR (500 MHz, CDCl3): δ = 1.33 (s, 9 H), 5.58 (s, 2 H), 7.27–7.42 (m, 7 H), 7.63 (s, 1 H), 7.70–7.75 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 31.3, 34.7, 54.2, 119.3, 125.3, 125.4, 125.7, 127.7, 128.0, 128.7 (2 C), 129.1, 131.9, 132.2, 134.8, 148.2, 151.3. HRMS (APCI): m/z [M + H]+ calcd for C19H22N3: 292.18137; found: 292.17627. 1-Benzyl-4-(3-phenylpropyl)-1H-1,2,3-triazole (3g) Yield: 550 mg (1.99 mmol, 99%); white solid; mp 64–65 °C. 1H NMR (500 MHz, CDCl3): δ = 1.95–2.01 (m, 2 H), 2.66 (t, J = 7.75 Hz, 2 H), 2.72 (t, J = 7.75 Hz, 2 H), 5.49 (s, 2 H), 7.15–7.18 (m, 5 H), 7.24–7.27 (m, 2 H), 7.33–7.39 (m, 4 H). 13C NMR (125 MHz, CDCl3): δ = 25.3, 31.1, 35.4, 54.0, 120.8, 125.8, 125.9, 127.9, 128.35, 128.39, 128.4 (2 C), 128.5, 128.6, 129.1, 135.0, 141.9, 148.4. HRMS (APCI): m/z [M + H]+ calcd for C18H20N3: 278.16572; found: 278.16215. 1-Benzyl-4-butyl-1H-1,2,3-triazole (3h) Yield: 319 mg (1.48 mmol, 74%); white solid; mp 60–62 °C. 1H NMR (500 MHz, CDCl3): δ = 0.91 (t, J = 7.25 Hz, 3 H), 1.33–1.40 (m, 2 H), 1.59–1.70 (m, 2 H), 2.69 (t, J = 7.75, 2 H), 5.49 (s, 2 H), 7.17 (s, 1 H), 7.24–7.26 (m, 2 H), 7.33–7.39 (m, 3 H). 13C NMR (125 MHz, CDCl3): δ = 13.8, 22.3, 25.4, 31.5, 53.9, 127.9, 128.2, 128.3, 128.6 (2 C), 128.8, 129.0, 135.1. HRMS (APCI): m/z [M + H]+ calcd for C13H18N3: 216.15007; found: 216.14352.