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Smiles Rearrangement Based Practical One-pot Synthesis of N-Alkyl/aryl-6-aminoquinolines from 6-Hydroxylquinoline
Smiles Rearrangement Based Practical One-pot Synthesis of N-Alkyl/aryl-6-aminoquinolines from 6-Hydroxylquinoline
Bulletin of the Korean Chemical Society. 2013. Dec, 34(12): 3881-3884
Copyright © 2013, Korea Chemical Society
  • Received : July 03, 2013
  • Accepted : September 20, 2013
  • Published : December 20, 2013
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About the Authors
Yong-Sheng Xie
College of Chemical and Environmental Engineering, Chongqing Three Gorges University, Chongqing 404100, China
B. V. D. Vijaykumar
Department of Chemistry and Physics, Changwon National University, Changwon 641-773, Korea
Kiwan Jang
Department of Chemistry and Physics, Changwon National University, Changwon 641-773, Korea
Kyung-Min Choi
Department of Chemistry and Physics, Changwon National University, Changwon 641-773, Korea
Hua Zuo
College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China
Yong-Jin Yoon
Department of Chemistry, Gyeongsang National University, Chinju 660-701, Korea
Dong-Soo Shin
Department of Chemistry and Physics, Changwon National University, Changwon 641-773, Korea

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Experimental
General. 1 H and 13 C NMR spectra were recorded on Bruker Advance 400 FT spectrometer (400 MHz for 1 H and 100 MHz for 13 C, respectively) in CDCl 3 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 Cs 2 CO 3 /K 2 CO 3 (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; 1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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; 1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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; 1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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; 1 H NMR (400 MHz, CDCl 3 ) 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). 13 C NMR (100 MHz, CDCl 3 ) 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; 1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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; 1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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; 1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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; 1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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; 1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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; 1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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.
Acknowledgements
This research is financially supported by Changwon National University, South Korea in 2011-2012.
References
Grassmann S. , Apelt J. , Sippl W. , Ligneau X. , Pertz H. H. , Zhao Y. H. , Arrang J.-M. , Ganellin C. R. , Schwartz J.-C. , Schunack W. , Stark H. 2003 Bioorg. Med. Chem. Lett. 11 2163 -    DOI : 10.1016/S0968-0896(03)00120-2
Hu Y. , Gavrin L. K. , Janz K. , Kaila N. , Li H.-Q. , Thomason J. R. , Cuozzo J. W. , Hall J. P. , Hsu S. , Nicherson-Nutter C. , Telliez J.-B. , Lin L.-L. , Tam S. 2006 Bioorg. Med. Chem. Lett. 16 6067 -    DOI : 10.1016/j.bmcl.2006.08.102
Nutaitis C. F. , Smith Kimberly 2007 Org. Prep. Proced. Int. 39 611 -    DOI : 10.1080/00304940709458646
Cukalovic A. , Stevens C. V. 2010 Green Chem. 12 1201 -    DOI : 10.1039/c002340j
Anderson K. W. , Tundel R. E. , Ikawa T. , Altman R. A. , Buchawald S. L. 2006 Angew. Chem. Int. Ed. 45 6523 -    DOI : 10.1002/anie.200601612
Ogata T. , Hartwig J. F. 2008 J. Am. Chem. Soc. 130 13848 -    DOI : 10.1021/ja805810p
Ueda S. , Su M. , Buchwald S. L. 2011 Angew. Chem. Int. Ed. 50 8944 -    DOI : 10.1002/anie.201103882
Peet N. P. , Weidner J. J. 2000 US6034241(A)
Wang D.-P. , Ding K. 2009 Chem Commun. 1891 -