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

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

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• 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.