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Smiles Rearrangement Based Practical One-pot Synthesis of N-Alkyl/aryl-6-aminoquinolines from 6-Hydroxylquinoline

  • Xie, Yong-Sheng (Department of Chemistry and Physics, Changwon National University) ;
  • Vijaykumar, B.V.D. (Department of Chemistry and Physics, Changwon National University) ;
  • Jang, Kiwan (Department of Chemistry and Physics, Changwon National University) ;
  • Choi, Kyung-Min (Department of Chemistry and Physics, Changwon National University) ;
  • Zuo, Hua (College of Pharmaceutical Sciences, Southwest University) ;
  • Yoon, Yong-Jin (Department of Chemistry, Gyeongsang National University) ;
  • Shin, Dong-Soo (Department of Chemistry and Physics, Changwon National University)
  • Received : 2013.07.03
  • Accepted : 2013.09.20
  • Published : 2013.12.20
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Abstract

Keywords

Experimental

General. 1H and 13C NMR spectra were recorded on Bruker Advance 400 FT spectrometer (400 MHz for 1H and 100 MHz for 13C, respectively) in CDCl3 with chemical shift values reported in δ units (ppm) relative to an internal standard (TMS). IR spectra were recorded on a FT-IR-6300 (JASCO, Japan). Gas chromatography-mass spectrometric (GC-MS) analyses were carried out with a Hewlett-Packard 6890 & 5973 system (AGILENT, USA). Melting points were determined on a digital SMP10 capillary melting point apparatus (SRUAT, UK). Silical gel (70-230 mesh) was used for flash column chromatography. All chemicals were used as delivered from Sigma-Aldrich.

General Procedure for the Synthesis of Compound 5. To a solution of 6-hydroxylquinoline 1 (1.0 mmol, 1.0 eq.) and N-alkyl/aryl 2-chloroacetamides 2 (1.2 mmol, 1.2 eq.) in DMF (8 mL) was added Cs2CO3/K2CO3 (2.5 mmol, 2.5 eq.) as indicated in Table 2. The mixture was stirred at 90 °C for 1 h followed at 150 °C for 2 h. Then, the mixture was cooled to room temperature and the solvent was removed under reduced pressure. The residue was adsorbed onto silica gel and purified by flash column chromatography to give the product 5.

N-Benzylquinolin-6-amine (5a)9: Off-white solid, mp 125-126 °C; 1H NMR (400 MHz, CDCl3) δ 8.61 (d, J = 4.0 Hz, 1H), 7.89 (d, J = 8.8 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.34-7.43 (m, 4H), 7.30 (t, J = 7.2 Hz, 1H), 7.23 (dd, J = 8.0, 4.0 Hz, 1H), 7.12 (dd, J = 2.8, 8.8 Hz, 1H), 6.71 (d, J = 2.8 Hz, 1H), 4.47 (s, br, 1H), 4.42 (d, J = 4.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 146.27, 146.07, 143.44, 138.80, 133.81, 130.39, 130.14, 128.76, 127.53, 127.45, 121.34, 121.26, 103.44, 48.33; MS (EI) m/z: 235 (M+), 234 (M+), 233, 91 (100).

N-(Pyridin-2-ylmethyl)quinolin-6-amine (5b): Brown semisolid; 1H NMR (400 MHz, CDCl3) δ 8.58-8.63 (m, 2H), 7.89 (d, J = 9.0 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.65 (dt, J = 7.6, 1.8 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1 H), 7.17-7.25 (m, 3 H), 6.69 (d, J = 2.6 Hz, 1H), 5.25 (s, br, 1H), 4.54 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 157.70, 149.33, 146.28, 145.89, 143.49, 136.69, 133.82, 130.42, 130.17, 122.30, 121.66, 121.53, 121.34, 103.57, 49.16; MS (EI) m/z: 236 (M+), 235 (M+), 234, 158, 157(100).

N-((Tetrahydrofuran-2-yl)methyl)quinolin-6-amine (5c): Light-brown oil; 1H NMR (400 MHz, CDCl3) δ 8.60 (dd, J = 4.4, 1.6 Hz, 1H), 7.89 (d, J = 8.3, 1.6 Hz, 1H), 7.86 (d, J = 9.2 Hz, 1H), 7.23 (dd, J = 8.3, 4.4 Hz, 1H), 7.11 (dd, J = 9.2, 2.6 Hz, 1H), 6.70 (d, J = 2.6 Hz, 1H), 4.43 (s, 1H), 4.13-4.21 (m, 1H), 3.87-3.94 (m, 1H), 3.76-3.83 (m, 1H), 3.30-3.38 (m, 1H), 3.13-3.21 (m, 1H), 2.01-2.10 (m, 1H), 1.86-1.99 (m, 2H), 1.62-1.72 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 146.46, 146.14, 143.44, 133.70, 130.29, 130.18, 121.57, 121.31, 103.27, 68.13, 48.19, 29.23, 25.83, 14.20; MS (EI) m/z: 229 (M+), 228 (M+), 158, 157 (100).

N-Cyclohexylquinolin-6-amine (5d): Light-green solid, mp 77-79 °C; 1H NMR (400 MHz, CDCl3) δ 8.58 (dd, J = 4.2, 1.6 Hz, 1H), 7.89 (d, J = 8.3 Hz, 1H), 7.85 (d, J = 9.0 Hz, 1H), 7.24 (dd, J = 8.3, 4.2 Hz, 1H), 7.05 (dd, J = 9.0, 2.6 Hz, 1H), 6.68 (d, J = 2.6 Hz, 1H), 3.88 (s, br, 1H), 3.34-3.44 (m, 1H), 2.08-2.18 (m, 2H), 1.75-1.85 (m, 2H), 1.65-1.74 (m, 1H), 1.36-1.50 (m, 2H), 1.15-1.33 (m, 3H). 13C NMR (100 MHz, CDCl3) δ 145.81, 145.39, 143.00, 133.69, 130.35, 130.32, 121.67, 121.31, 103.32, 51.84, 33.28, 25.97, 25.00; MS (EI) m/z: 227 (M+), 226 (M+), 184, 183 (100), 170, 169.

N-(3,4-Dimethoxyphenethyl)quinolin-6-amine (5e): Off-white solid, mp 96-98 °C; 1H NMR (400 MHz, CDCl3) δ 8.61 (dd, J = 4.2, 1.6 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 9.1 Hz, 1H), 7.26 (dd, J = 8.3, 4.2 Hz, 1H), 7.05 (dd, J = 9.1, 2.6 Hz, 1H), 6.84 (d, J = 8.1 Hz, 1H), 6.79 (dd, J = 8.1, 1.9 Hz, 1H), 6.75 (d, J = 1.9 Hz, 1H), 6.73 (d, J = 2.6 Hz, 1H), 4.02 (s, br, 1H), 3.88 (s, 3H), 3.86 (s, 3H), 3.49 (m, 2H), 2.94 (t, J = 6.9 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 149.35, 148.03, 146.24, 146.02, 143.42, 133.74, 131.66, 130.41, 130.22, 121.44, 121.40, 120.81, 112.37, 111.83, 103.40, 56.07, 56.00, 45.11, 34.84; MS (EI) m/z: 309 (M+), 308 (M+), 158, 157 (100).

N-(4-Methoxyphenyl)quinolin-6-amine (5f): Light-yellow solid, mp 126-128 °C; 1H NMR (400 MHz, CDCl3) δ 8.66 (dd, J = 4.2, 1.6 Hz, 1H), 7.95 (d, J = 9.0 Hz, 1H), 7.88 (d, J = 8.3 Hz, 1H), 7.31 (dd, J = 9.0, 2.6 Hz, 1H), 7.27 (dd, J = 8.4, 4.2 Hz, 1H), 7.16-7.22 (m, 2H), 7.10 (d, J = 2.6 Hz, 1H), 6.90-6.96 (m, 2H), 5.79 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 156.20, 147.02, 144.03, 143.84, 134.93, 134.09, 130.56, 129.86, 123.46, 122.09, 121.44, 114.96, 107.06, 55.63; MS (EI) m/z: 251 (M+), 250 (M+, 100), 236, 235.

N-Phenylquinolin-6-amine (5g): Light-yellow solid, mp 177-179 °C; 1H NMR (400 MHz, CDCl3) δ 8.71 (dd, J = 1.5, 4.2 Hz, 1H), 7.99 (d, J = 9.0 Hz, 1H), 7.94 (d, J = 8.2 Hz, 1H), 7.42 (dd, J = 2.6, 9.0 Hz, 1H), 7.32-7.37 (m, 3H), 7.30 (dd, J = 4.2, 8.3 Hz, 1H), 7.20 (d, J = 7.6 Hz, 2H), 7.04 (t, J = 7.3 Hz, 1H), 6.02 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 147.66, 144.53, 142.32, 141.87, 134.37, 130.72, 129.68, 129.57, 123.13, 122.34, 121.52, 119.30, 109.67; MS (EI) m/z 221 (M+), 220 (M+, 100), 219.

N-(4-Chlorophenyl)quinolin-6-amine (5h): Light-yellow solid, mp 189-191 °C; 1H NMR (400 MHz, CDCl3) δ 8.73 (dd, J = 4.2, 1.6 Hz, 1H), 8.00 (d, J = 9.0 Hz, 1H), 7.95 (d, J =7.5 Hz, 1H), 7.40 (dd, J = 9.0, 2.6 Hz, 1H), 7.25-7.35 (m, 4H), 7.13 (m, 2H), 6.00 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 147.92, 144.62, 141.40, 141.02, 134.46, 130.86, 129.59, 129.57, 127.05, 123.12, 121.63, 120.32, 110.18; MS (EI) m/z: 256 (M+), 255 (M+), 254 (M+, 100), 253, 219, 218.

N-Allylquinolin-6-amine (5i)13: Light-yellow solid, mp 59-60 °C; 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 3.2 Hz, 1H), 7.72-7.84 (m, 2H), 7.17 (dd, J = 8.4, 4.4 Hz, 1H), 6.98 (dd, J = 9.2, 2.4 Hz, 1H), 6.55 (d, J = 2.4 Hz, 1H), 5.86-6.06 (m, 1H), 5.31 (dd, J = 17.2, 1.2 Hz, 1H), 5.18 (dd, J = 10.1, 1.2 Hz, 1H), 4.19 (s, br, 1H), 3.85 (d, J = 3.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 145.76, 145.64, 143.44, 134.71, 133.34, 130.50, 129.95, 121.06, 121.04, 116.64, 103.22, 46.44; MS (EI) m/z 185 (M+), 184 (M+, 100), 183.

N-Hexylquinolin-6-amine (5j): Light-yellow solid, mp 65-66 °C; 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 3.2 Hz, 1H), 7.77-7.85 (m, 2H), 7.19 (dd, J = 8.0, 4.0 Hz, 1H), 7.02 (dd, J = 9.2, 2.4 Hz, 1H), 6.60 (d, J = 2.4 Hz, 1H), 5.86-6.06 (m, 1H), 5.31 (dd, J = 17.2, 1.2 Hz, 1H), 5.18 (dd, J = 10.1, 1.2 Hz, 1H), 4.11 (s, br, 1H), 1.54-1.74 (m, 2H), 1.20-1.52 (m, 6H), 0.79-0.90 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 146.19, 145.34, 143.23, 133.20, 130.26, 130.11, 121.16, 120.99, 102.37, 43.82, 31.64, 29.27, 26.92, 22.06, 14.07; MS (EI) m/z 229 (M+), 228 (M+), 158 (100), 157.

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