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Tetrahedron Letters
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2011, 46, 5283-5292; (b) Candéa, A. L.; Ferreira, M. L.; Pais, K. 260
reactor (the highest power: 150 W; run time: 5 min; hold time: 30
min; temperature: 95 °C). The resulting reaction mixture was con-
centrated in vacuo, and the crude residue was purified by flash
chromatography on silica gel using hexane/EtOAc as eluent.
2-(bromomethyl)quinoline 4a:18 white solid (m.p. 55-56 °C), 1H
NMR (400 MHz, CDCl3) δ = 8.16 (d, J=8.4 Hz, 1H, ArH), 8.07 (d,
J=8.4 Hz, 1H, ArH), 7.80 (dd, J=8.0 Hz, 1.2 Hz, 1H, ArH), 7.74 –
7.70 (m, 1H, ArH), 7.57 – 7.52 (m, 2H, ArH), 4.71 (s, 2H, BrCH2);
13C NMR (100 MHz, CDCl3) δ 156.59, 147.08, 137.29, 129.90,
128.93, 127.36, 127.20, 126.95, 121.03, 34.15.
C.; Cardoso, L. N. F.; Kaiser, C. R.; Henriques, M. G. M. O.; Lou- 261
renço, M. C. S.; Bezerra, F. A. F. M.; Souza, M. V. Bioorg. Med. 262
Chem. Lett. 2009, 19, 6272-6274.
263
6. (a) Sahu, U.; Sidhar, H.; Ghate, P. S; Advirao, G. M.; Raghavan, S. 264
C.; Giri, R. K. PLoS ONE 2013, 8, e66430; (b) Chang, F. S.; Chen, 265
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18, 124-133.
267
7. (a) Gong, L.; Tan, Y. C.; Boice, G.; Abbot, S.; McCaleb, K.; Iyer, 268
P.; Zuo, F. R.; Porto, J. D.; Wong, B.; Jin, S.; Chang, A.; Tran, P.; 269
Hsieh, G.; Niu, L.; Shao, A.; Reuter, D.; Lukacs, C. M.; Kammlott, 270
R. U.; Kuglstatter, A.; Goldstein, D. Bioorg. Med. Chem. Lett. 271
2012, 22, 7381–7387; (b) Larsen, R. D.; Corley, E. G.; King, A. O.;
Carroll, J. D.; Davis, P.; Verhoeven, T. R.; Reider, P. J. J. Org.
Chem. 1996, 61, 3398-3405; (c) Halama, A.; Jirman, J.; Boušková,
O.; Gibala, P.; Jarrah, K. Org. Process Res. Dev. 2010, 14, 425-
431.
18. Zhao, Q.; Liu, S.; Li, Y.; Wang, Q. J. Agric. Food Chem. 2009, 57,
2849-2855.
8. Verhoest, P. R.; Chapin, D. S.; Corman, M.; Fonseca, K.; Harms, J.
F.; Hou, X. J.; Marr, E.S.; Menniti, F. S.; Nelson, F.; O’Connor, R.;
Pandit, J.; Proulx-LaFrance, C.; Schmidt, A. W.; Schmidt, C. J.;
Suiciak, J. A.; Liras, S. J. Med. Chem. 2009, 52, 5188-5196.
9. (a) White, J. D.; Yager, K. M.; Stappenbeck, F. J. Org. Chem.1993,
58, 3466-3468; (b) Jiang, N.; Zhai, X.; Li, T.; Liu, D. F.; Zhang, T.
T.; Wang, B.; Gong, P. Molecules 2012, 17, 5870-5881; (c) Hanao-
ka, K.; Kikuchi, K.; Kobayashi, S.; Nagano, T. J. Am. Chem. Soc.
2007, 129, 13502-13509.
10. (a) Stock, N. S.; Bain, G.; Zunic, J.; Li, Y. W.; Ziff, J.; Roppe, J.;
Santini, A.; Darlington, J.; Prodanovich, P.; King, C. D.; Baccei,
C.; Lee, C.; Rong, H. J.; Chapman, C.; Broadhead, A.; Lorrain, D.;
Correa, L.; Hutchinson, J. H.; Evans, J. F.; Prasit, P. J. Med. Chem.
2011, 54, 8013-8029; (b) Yuan, Z.; Kuang, G. C.; Clark, R. J.; Zhu,
L. Org. Lett. 2012, 14, 2590-2593.
11. Kuchař, M.; Kmoníček, V.; Panajotová, V.; Jandera, A.; Brunová,
B.; Junek, R.; Bucharová, V.; Čejka, J.; Šatinský, D. Collect.
Czechoslov. Chem. Commun. 2004, 69, 2098-2120.
12. (a) Chen, H. F.; Sweet, J. A.; Lam, K. C.; Rheingold, A. L.;
McGrath, D. V. Tetrahedron: Asymmetry 2009, 20, 1672-1682; (b)
Newkome, G. R.; Theriot, K. J.; Gupta, V. K.; Fronczek, F. R.;
Baker, G. R. J. Org. Chem. 1989, 54, 1766-1769.
13. Ho, M. L.; Flynn, A. B.; Ogilvie, W. W. J. Org. Chem. 2007, 72,
977-983.
14. General procedure for chlorination of 2-methylquinolines: 2-
methylquinolines 1 (2 mmol), TBAI (2 mmol), urea (2 mmol), and
1,2-dichloroethane (10 mL) were mixed in a microwave tube. The
reaction mixture was stirred at 110 °C for 30 min under microwave
irradiation using a CEM Discover microwave reactor (the highest
power: 150 W; run time: 5 min; hold time: 30 min; temperature:
110 °C). The resulting reaction mixture was concentrated in vacuo,
and the crude residue was purified by flash chromatography on sili-
ca gel using hexane/EtOAc as eluent.
2-(chloromethyl)quinoline 2a:15 white solid (m.p. 54-55 °C), 1H
NMR (400 MHz, CDCl3) δ = 8.18 (d, J=8.4 Hz, 1H, ArH), 8.06 (d,
J=8.4 Hz, 1H, ArH), 7.81 (d, J=8.4 Hz, 1H, ArH), 7.72 (dt, J=1.2,
8.4 Hz, 1H, ArH), 7.59 (d, J=8.4 Hz, 1H, ArH), 7.54 (t, J=7.6 Hz,
1H, ArH), 4.84 (s, 2H, ClCH2); 13C NMR (100 MHz, CDCl3) δ
156.45, 147.22, 137.04, 129.72, 129.06, 127.35, 127.26, 126.75,
120.24, 47.33.
2-(chloromethyl)-6-methylquinoline 2b:9c white solid (m.p. 107-
108 °C), 1H NMR (400 MHz, CDCl3) δ = 8.07 (d, J=8.8 Hz, 1H,
ArH), 7.93 (d, J=8.4 Hz, 1H, ArH), 7.55 – 7.52 (m, 3H, ArH), 4.81
(s, 2H, ClCH2), 2.52 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ
155.48, 145.75, 136.74, 136.45, 132.06, 128.65, 127.29, 126.25,
12.0.32, 47.43, 21.68; MS (ESI) m/z 192, 194 [M+H]+, HRMS (ESI)
calcd for C11H11ClN [M+H]+191.0575, found 191.0570.
2-(dichloromethyl)quinoline 3a:16 white solid (m.p. 78-79 °C), 1H
NMR (400 MHz, CDCl3) δ = 8.27 (dd, J=8.4 Hz, 1.6, 1H, ArH),
8.05 (d, J=8.4 Hz, 1H, ArH), 7.89 (dd, J=8.4 Hz, 1.2 Hz, 1H, ArH),
7.83 (d, J=8.4 Hz, 1H, ArH), 7.76 – 7.72 (m, 1H, ArH), 7.60 – 7.56
(m, 1H, ArH), 6.86 (s, 1H, ClCH2). 13C NMR (100 MHz, CDCl3) δ
157.32, 146.00, 138.01, 130.15, 129.43, 127.90, 127.62, 127.41,
118.03, 72.19.
15. Li, C.; Wong, W. T. J. Org. Chem. 2003, 68, 2956-2959.
16. Jeromin, G. E.; Orth, W.; Rapp, B.; Weiß, W. Chemische Berichte
1987, 120, 649-651.
17. General procedure for bromination of 2-methylquinolines: 2-
methylquinolines 1 (2 mmol), TBAI (2 mmol), urea (2 mmol), 1,2-
dibromoethane (6 mL), and acetonitrile (6 mL) were mixed in a mi-
crowave tube. The reaction mixture was stirred at 95 °C for 30 min
under microwave irradiation using a CEM Discover microwave