DOI QR코드

DOI QR Code

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

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.

References

  1. (a) Vlahov, R.; Parushev, St.; Vlahov, J. Pure & Appl. Chem. 1990, 62, 1303. https://doi.org/10.1351/pac199062071303
  2. (b) Sweeney, A. W.; Blackburn, C. R. B.; Rieckmann, K. H. Am. J. Trop. Med. Hyg. 2004, 71, 187.
  3. (c) Mohana, K. N.; Mallesha, L.; Gurudatt, D. M. International Journal of Drug Design and Discovery 2011, 2, 584.
  4. (a) Piplani, P.; Rania, A.; Sandhir, R.; Kulkarni, S. K. J. Young Pharm. 2009, 1, 341. https://doi.org/10.4103/0975-1483.59325
  5. (b) Piplani, P.; Rania, A.; Saihgal, R.; Sharma, M. Arzneimittelforschung 2011, 61, 373. https://doi.org/10.1055/s-0031-1296213
  6. (a) Wu, Q.; Jiao, X.; Wang, L.; Xiao, Q.; Liu, X.; Xie, P. Tetrahedron Lett. 2010, 51, 4806. https://doi.org/10.1016/j.tetlet.2010.06.022
  7. (b) Lan, T.; Yuan, X. X.; Yu, J. H.; Jia, C.; Wang, Y. S.; Zhang, H. J.; Maa, Z. F.; Ye, W. D. Chin. Chem. Lett. 2011, 22, 253. https://doi.org/10.1016/j.cclet.2010.10.005
  8. (c) Rajapakse, A.; Linder, C.; Morrison, R. D.; Sarkar, U.; Leigh, N. D.; Barnes, C. L.; Daniels, J. S.; Gates, K. S. Chem. Res. Toxicol. 2013, 26, 555. https://doi.org/10.1021/tx300483z
  9. 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. Bioorg. Med. Chem. Lett. 2003, 11, 2163. https://doi.org/10.1016/S0968-0896(03)00120-2
  10. 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. Bioorg. Med. Chem. Lett. 2006, 16, 6067. https://doi.org/10.1016/j.bmcl.2006.08.102
  11. Nutaitis, C. F.; Smith, Kimberly. Org. Prep. Proced. Int. 2007, 39, 611. https://doi.org/10.1080/00304940709458646
  12. Cukalovic, A.; Stevens, C. V. Green Chem. 2010, 12, 1201. https://doi.org/10.1039/c002340j
  13. Anderson, K. W.; Tundel, R. E.; Ikawa, T.; Altman, R. A.; Buchawald, S. L. Angew. Chem. Int. Ed. 2006, 45, 6523. https://doi.org/10.1002/anie.200601612
  14. Ogata, T.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 13848. https://doi.org/10.1021/ja805810p
  15. Ueda, S.; Su, M.; Buchwald, S. L. Angew. Chem. Int. Ed. 2011, 50, 8944. https://doi.org/10.1002/anie.201103882
  16. (a) Cho, S.-D.; Park, Y.-D.; Kim, J.-J.; Lee, S.-G.; Ma, C.; Song, S.-Y.; Joo, W.-H.; Flack, J. R.; Shiro, M.; Shin, D.-S.; Yoon, Y.-J. J. Org. Chem. 2003, 68, 7918. https://doi.org/10.1021/jo034593i
  17. (b) Zuo, H.; Kam, K.-H.; Kwon, H.-J.; Meng, L.-J.; Ahn, C.; Won, T.-J.; Kim, T.-H.; Raji Reddy, Ch.; Chandrasekhar, S.; Shin, D.-S. Bull. Korean Chem. Soc. 2008, 29, 1379. https://doi.org/10.5012/bkcs.2008.29.7.1379
  18. (c) Zuo, H.; Meng, L.; Ghate, M.; Hwang, K.-H.; Cho, K. Y.; Chandrasekhar, S.; Raji Reddy, C.; Shin, D.-S. Tetrahedron Lett. 2008, 49, 3827. https://doi.org/10.1016/j.tetlet.2008.03.120
  19. (d) Yang, H.; Li, Z.-B.; Shin, D.-S.; Wang, L.-Y.; Zhou, J.-Z.; Qiao, H.-B.; Tian, X.; Ma, X.-Y.; Zuo, H. Syn. Lett. 2010, 3, 483.
  20. (e) Meng, L.-J.; Zuo, H.; Vijaykumar, B. V. D.; Gautam, D.; Kiwan, J.; Yoon, Y.-J.; Shin, D.-S. Bull. Korean. Chem. Soc. 2013, 34, 585. https://doi.org/10.5012/bkcs.2013.34.2.585
  21. (f) Xie, Y.-S.; Vijaykumar, B. V. D.; Jang, K.; Shin, H.-H.; Zuo, H.; Shin, D.-S. Tetrahedron Lett. 2013, 54, 5151. https://doi.org/10.1016/j.tetlet.2013.06.022
  22. Peet, N. P.; Weidner, J. J. US6034241(A), March 7, 2000.
  23. Wang, D.-P.; Ding, K. Chem Commun. 2009, 1891.

Cited by

  1. -arylated coumarin/pyran derivatives vol.42, pp.14, 2018, https://doi.org/10.1039/C8NJ02109K
  2. ChemInform Abstract: Smiles Rearrangement Based Practical One‐Pot Synthesis of N‐Alkyl/Aryl‐6‐aminoquinolines from 6‐Hydroxylquinoline. vol.45, pp.18, 2014, https://doi.org/10.1002/chin.201418157
  3. Brønsted Acid Catalyzed Functionalization of Aromatic Alcohols through Nucleophilic Substitution of Hydroxyl Group vol.81, pp.6, 2016, https://doi.org/10.1021/acs.joc.5b02849