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Synlett 2008(10): 1449-1454  
DOI: 10.1055/s-2008-1078423
LETTER
© Georg Thieme Verlag Stuttgart · New York

Friedel-Crafts Alkylation of Nitrogen Heterocycles Using [Bmim][OTf] as a Catalyst and Reaction Medium

M. Lakshmi Kantam*a, Rajashree Chakravartia, B. Sreedhara, Suresh Bhargavab
a Inorganic & Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax: +91(40) 27160921; e-Mail: mlakshmi@iict.res.in;
b School of Applied Sciences, RMIT University, Melbourne, Australia
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Publication History

Received 19 March 2008
Publication Date:
19 May 2008 (online)

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Friedel-Crafts Alkylation of Nitrogen Heterocycles Using [Bmim][OTf] as a Catalyst and Reaction MediumSynlett 2008; 2008(12): 1917-1917
DOI: 10.1055/s-2008-1078588

Abstract

Friedel-Crafts alkylation of nitrogen heterocycles, such as indoles and pyrroles, can be carried out in ionic liquids under mild conditions to afford the corresponding alkylated product in moderate to good yields

Keywords

nitrogen heterocycle - ring opening - indole - pyrrole - ionic liquids - epoxide

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General Procedure for the Friedel-Crafts Alkylation of N-Heterocycles Using [Bmim][OTf] To a stirred solution of indole (1.2 mmol, 142 mg) in ionic liquid (1.2 mmol, 0.5mL), styrene oxide (1.0 mmol, 120 mg) was added under nitrogen atmosphere and stirred for 1.5 h at r.t. After completion of the reaction, as monitored by TLC, the crude product was extracted with Et2O (3 × 10 mL). The combined ether extracts were concentrated in vacuo and the resulting product was purified by column chromatography on silica gel (100-200 mesh) with EtOAc-n-hexane (1:4) as eluent to afford pure 2-(3-indolyl)-2-phenylethanol (Table 2, entry 1); yield 85%. 1H NMR (200 MHz, CDCl3): δ = 1.61 (br, 1 H), 4.18-4.23 (m, 2 H), 4.50 (t, J = 6.7 Hz, 1 H), 7.03-7.48 (m, 10 H), 8.11 (br, 1 H). MS (EI): m/z = 237 (25), 206 (100), 178 (30), 128 (15), 102 (10), 77 (15), 63 (5), 51 (11). Other known products were identified by comparison with the data in the literature, see ref. 7 and 10. The ionic liquid was dried under vacuum and preserved for the next run.

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Spectroscopic and analytical data of new compounds.
2-(3-Indolyl)-2-(4-flourophenyl)ethanol (Table 3, Entry 2)
Yield 82%. 1H NMR (300 MHz, CDCl3): δ = 1.81 (1 H, br), 4.06-4.26 (2 H, m), 4.44 (1 H, t, J = 6.7 Hz), 6.90-7.37 (9 H, m), 8.05 (1 H, br). 13C NMR (75 MHz, CDCl3): δ = 44.83, 66.36, 111.28, 115.23, 115.53, 115.84, 119.30, 119.63, 121.90, 122.42, 126.84, 129.69 (2), 136.53, 137.43, 163.33. MS (EI): m/z (rel. intensity) = 255 (13), 224 (100), 222 (14), 196 (10), 177 (7), 77 (12), 63 (13), 41 (14). IR (neat): 3578, 3419, 3069, 2885, 1623, 1556, 1501, 1462, 1412, 1351, 1250, 1106, 1070, 1017, 754 cm-1. Anal. Calcd for C16H14FNO: C, 70.72; H, 5.19; N, 5.15. Found: C, 70.76; H, 5.24; N, 5.11.
2-(3-Indolyl)-2-(naphthyl)ethanol (Table 3, Entry 4)
Yield 78%. 1H NMR (300 MHz, CDCl3): δ = 1.62 (1 H, br), 4.17-4.25 (2 H, m), 4.46 (1 H, t, J = 6.7 Hz), 7.00-7.47 (12 H, m), 8.10 (1 H, br). 13C NMR (75 MHz, CDCl3): δ = 44.96, 66.41, 111.09, 115.36, 119.53, 119.84, 121.86, 122.18, 126.68, 126.82, 126.91, 128.22, 128.53, 129.14, 129.60, 136.61, 137.03, 141.73. MS (EI): m/z (rel. intensity) = 287 (16), 283 (19), 218 (7), 185 (9), 171 (10), 155 (12), 144 (13). IR (neat): 3546, 3409, 3106, 2980, 1614, 1535, 1308, 1061, 1445, 1306, 1077, 1029,752 cm-1. Anal. Calcd for C20H17NO: C, 83.59; H, 5.96; N, 4.87. Found: C, 83.62; H, 5.98; N, 4.80.
2-(2-Pyrrolyl)-2-(4-fluorophenyl)ethanol (Table 4, Entry 2) Yield 80%. 1H NMR (300 MHz, CDCl3): δ = 1.52 (1 H, br), 3.92-4.05 (2 H, m), 4.07-4.10 (1 H, m), 5.91-5.93 (1 H, m), 6.10 (1 H, dd, J = 6.0, 3.0 Hz), 6.70 (1 H, m), 7.18 (2 H, d, J = 8.8 Hz), 7.34 (2 H, d, J = 8.8 Hz), 8.16 (1 H, br). 13C NMR (75 MHz, CDCl3): δ = 57.11, 67.78, 105.92, 108.20, 115.38, 117.41, 118.51, 129.66, 129.75, 129.83, 136.42, 161.76. MS (EI): m/z (rel. intensity) = 205 (15), 174 (100), 154 (5), 146 (17), 127 (14), 91 (27), 78 (18), 51 (16). IR (neat): 3356, 3005, 1706, 1495, 1409, 1095, 1062, 1011, 831, 758 cm-1. Anal. Calcd for C12H12FNO: C, 70.23; H, 5.89; N, 6.82. Found: C, 70.26; H, 5.91; N, 6.79.
2-(2-Pyrrolyl)-2-(4-chlorophenyl)ethanol (Table 4, Entry 3) Yield 80%. 1H NMR (300 MHz, CDCl3): δ = 1.52 (1 H, br), 3.90-4.04 (2 H, m), 4.05-4.12 (1 H, m), 5.91-5.94 (1 H, m), 6.08 (1 H, dd, J = 6.0, 3.0 Hz), 6.64 (1 H, m), 7.25 (2 H, d, J = 8.8 Hz), 7.29 (2 H, d, J = 8.8 Hz), 8.13 (1 H, br). 13C NMR (75 MHz, CDCl3): δ = 56.28, 67.14, 107.0, 109.05, 115.16, 119.08, 130.62, 133.17, 133.24, 156.02. MS (EI): m/z (rel. intensity) = 221 (13), 190 (100), 154 (36), 141 (10), 127 (19), 97 (7), 73 (28), 57 (22), 43 (36). IR (neat): 3346, 2925, 1692, 1490, 1406, 1090, 1058, 1015, 826, 761 cm-1. Anal. Calcd for C12H12ClNO: C, 65.02; H, 5.46; N, 6.32. Found: C, 65.06; H, 5.49; N, 6.29.
2-(2-Pyrrolyl)-2-(4-naphthyl)ethanol (Table 4, Entry 4) Yield 78%. 1H NMR (300 MHz, CDCl3): δ = 1.52 (1 H, br), 4.15 (1 H, dd, J = 5.7, 10.6 Hz), 4.25 (1 H, dd, J = 6.6, 10.6 Hz), 4.36 (1 H, t, J = 7.5 Hz), 6.0 (1 H, dd, J = 6.0, 3.0 Hz), 6.18 (1 H, m), 6.71 (1 H, m), 7.34-7.82 (7 H, m), 8.38 (1 H, br). 13C NMR (75 MHz, CDCl3): δ = 47.16, 66.39, 105.95, 107.03, 117.36, 125.36, 125.82, 125.91, 126.26, 126.40, 127.57, 127.74, 128.56, 132.63, 137.84. MS (EI): m/z (rel. intensity) = 238 (75), 235 (28), 220 (28), 219 (15), 218 (9), 91 (27), 199 (6), 171 (12), 153 (11), 141 (19). IR (neat): 3498, 3349, 3040, 2995, 2925, 1692, 1490, 1241, 1090, 1058, 1015, 826, 711 cm-1. Anal. Calcd for C16H15NO: C, 80.98; H, 6.37; N, 5.90. Found: C, 80.95; H, 6.35; N, 5.92.