July 2011
Using Morita–Baylis–Hillman Acetates of 2-Azidobenzaldehydes for the
Synthesis of 2-Alkoxy-3-Cyanomethylquinolines and Alkyl Quinoline-3-Carboxylates
971
7.09–7.13 (m, 1H, aromatic), 7.43–7.59 (m, 9H, aromatic),
7.69–7.76 (m, 6H, aromatic), 8.95 (s, 1H, CH); 13C-NMR
(deuteriochloform) d 52.2, 72.9, 117.4, 118.0, 128.1, 128.4,
128.6, 128.8, 128.9, 129.8, 130.9, 131.1, 131.9, 132.0, 132.4,
132.5, 149.3, 151.8, 167.3; 31P-NMR [deuteriochloform/
(PhO)3PO] d 20.94. ms: m/z (%) 277 (100), 199 (45). Anal.
Calcd. for C29H25N2O4P: C, 70.15; H, 5.08; N, 5.64. Found:
C, 69.91; H, 4.79; N, 5.43.
123.2, 126.8, 127.4, 129.1, 129.4, 131.7, 138.6, 149.8, 150.0,
165.3 [13].
Butyl quinoline-3-carboxylate (10e). Reaction time: 20 h;
yield: 40%; yellow oil; IR (neat) 1720 cmꢂ1 1H-NMR (deu-
;
teriochloform) d 1.02 (t, J ¼ 7.4 Hz, 3H, CH3), 1.47–1.59 (m,
2H, CH2), 1.78–1.88 (m, 2H, CH2), 4.43 (t, J ¼ 6.6 Hz, 2H,
CH2), 7.61–7.66 (m, 1H, aromatic), 7.82–7.87 (m, 1H, aro-
matic), 7.96 (d, J ¼ 8.0 Hz, 1H, aromatic), 8.18 (d, J ¼ 8.5
Hz, 1H, aromatic), 8.85 (d, J ¼ 2.2 Hz, 1H, aromatic), 9.46
(d, J ¼ 2.2 Hz, 1H, aromatic); 13C-NMR (deuteriochloform) d
13.8, 19.2, 30.7, 65.4, 122.3, 126.8, 127.4, 129.1, 129.4, 131.8,
138.7, 149.8, 150.1, 165.4; ms: m/z (%) 229 (8) [Mþ], 228
(13), 173 (100), 155 (47), 128 (32). Anal. Calcd. for
C14H15NO2: C, 73.34; H, 6.59; N, 6.11. Found: C, 73.21; H,
6.38; N, 6.03.
Methyl quinoline-3-carboxylate (10a). Iminophosphorane
7a (0.98 g, 2 mmole) in 5 mL of anhydrous toluene was
stirred at reflux temperature for 22 h. The mixture was concen-
trated under reduced pressure, and the residue was chromato-
graphed on silica gel and was eluted with hexane and ethyl
acetate (2:1) providing 0.20 g (54%) of 10a as a white solid
and 0.35 g (63%) of triphenylphosphine oxide in the order of
elution: mp 76–77ꢁC (hexane–EtOAc); IR (potassium bromide)
1
1723 cmꢂ1; H-NMR (deuteriochloform) d 4.02 (s, 3H, CH3),
Acknowledgment. This work was supported in part by the Brain
Korea 21 program, Republic of Korea.
7.60–7.65 (m, 1H, aromatic), 7.81–7.87 (m, 1H, aromatic), 7.93
(d, J ¼ 8.0 Hz, 1H, aromatic), 8.17 (d, J ¼ 8.5 Hz, 1H, aro-
matic), 8.85 (d, J ¼ 1.7 Hz, 1H, aromatic), 9.45 (d, J ¼ 2.2 Hz,
1H, aromatic); 13C-NMR (deuteriochloform) d 52.5, 122.9,
126.7, 127.4, 129.1, 129.4, 131.8, 138.7, 149.7, 149.9, 165.8;
ms: m/z (%) 187 (52) [Mþ], 156 (80), 128 (100) [5,12].
General procedure for one-pot synthesis of alkyl quino-
line-3-carboxylates 10. A mixture of 2-nitromethylazide 6 (4
mmole) and Ph3P (1.15 g, 4.4 mmole) in 10 mL of toluene
was stirred at reflux temperature for 8–50 h. The mixture was
cooled to room temperature and concentrated under reduced
pressure. The resulting mixture was chromatographed on silica
gel and was eluted with hexane and ethyl acetate (2:1) to pro-
duce pure quinoline 10.
Methyl quinoline-3-carboxylate (10a). Reaction time: 22 h;
yield: 48%; white solid: mp 76–77ꢁC (hexane–EtOAc). The
spectral data were the same as previously described.
Methyl 6-chloroquinoline-3-carboxylate (10b). Reaction
time: 27 h; yield: 49%; white solid: mp 169–170ꢁC (hexane–
;
EtOAc); IR (potassium bromide) 1723 cmꢂ1 1H-NMR (deu-
REFERENCES AND NOTES
[1] For reviews of the Morita–Baylis–Hillman reaction, see: (a)
Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44, 4653; (b) Basa-
vaiah, D.; Rao, P. D.; Hyma, R. S. Tetrahedron 1996, 52, 8001; (c) Ciga-
nek, E. Org React 1997, 51, 201; (d) Langer, P. Angew Chem Int Ed
2000, 39, 3049; (e) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem
Rev 2003, 103, 811; (f) Kataoka, T.; Kinoshita, H. Eur J Org Chem
2005, 45; (g) Basavaiah, D.; Rao, K. V.; Reddy, R. J Chem Soc Rev
2007, 36, 1581; (h) Singh, V.; Batra, S. Tetrahedron 2008, 64, 4511; (i)
Declerck, V.; Martinez, J.; Lamaty, F. Chem Rev 2009, 109, 1; (j) Ma,
G.-N.; Jiang, J.-J.; Shi, M.; Wei, Y. Chem Commun 2009, 5496.
[2] Michael, J. P. Nat Prod Rep 1997, 14, 605.
[3] (a) McAteer, C. H.; Balasubramanian, M.; Murugan, R. In
Comprehensive Heterocyclic Chemistry III; Katritzky, A. R., Ramsden,
C. A., Scriven, E. F. V., Taylor, R. J. K., Eds.; Pergamon Press:
Oxford, 2008; Vol. 7, pp 309–336; (b) Gray, N. M.; Dappen, M. S.;
Cheng, B. K.; Cordi, A. A.; Biesterfeldt, J. P.; Hood, W. F.; Monahan,
J. B. J Med Chem 1991, 34, 1283; (c) Baston, E.; Palusczak, A.; Hart-
mann, R. W. Eur J Med Chem 2000, 35, 931; (d) Hazeldine, S. T.;
Polin, L.; Kushner. J.; White, K.; Corbett, T. H.; Biehl, J.; Horwitz, J.
P. Bioorg Med Chem 2005, 13, 1069; (e) Upadhayaya, R. S.; Vanda-
vasi, J. K.; Vasireddy, N. R.; Sharma, V.; Dixit, S. S.; Chattopad-
hyaya, J. Bioorg Med Chem 2009, 17, 2830.
teriochloform) d 4.03 (s, 3H, CH3), 7.76 (dd, J ¼ 9.0 and 2.2
Hz, 1H, aromatic), 7.91 (d, J ¼ 2.2 Hz, 1H, aromatic), 8.10
(d, J ¼ 9.0 Hz, 1H, aromatic), 8.75 (d, J ¼ 1.7 Hz, 1H, aro-
matic), 9.43 (d, J ¼ 1.9 Hz, 1H, aromatic),13C-NMR (deuterio-
chloform) d 52.6, 123.7, 127.4, 127.5, 131.0, 132.7, 133.3,
137.7, 148.1, 150.1, 165.4 [5,12(a)].
[4] For a recent review of the synthesis of substituted quinolines
and quinoline-annulated ring systems, see: (a) Madapa, S.; Tusi, Z.;
Batra, S. Curr Org Chem 2008, 12, 1116, and references cited therein;
For other examples, see: (b) Keller, P. A. In Comprehensive Heterocy-
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Taylor, R. J. K., Eds.; Pergamon Press: Oxford, 2008; Vol. 7, pp
217–308; (c) Qiang, L. G.; Baine, N. H. J Org Chem 1988, 53, 4218;
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Org Biomol Chem 2006, 4, 3960; (o) Basavaiah, D.; Reddy, R. J.; Rao,
Methyl 6-methoxyquinoline-3-carboxylate (10c). Reaction
time: 8 h; yield: 41%; light yellow solid: mp 119–120ꢁC (hex-
ane–EtOAc); IR (potassium bromide) 1710 cmꢂ1 1H-NMR
;
(deuteriochloform) d 3.95 (s, 3H, CH3), 4.01 (s, 3H, CH3),
7.15 (d, J ¼ 2.8 Hz, 1H, aromatic), 7.47 (dd, J ¼ 9.3 and 2.8
Hz, 1H, aromatic), 8.04 (d, J ¼ 9.3 Hz, 1H, aromatic), 8.72
(d, J ¼ 1.7 Hz, 1H, aromatic), 9.29 (d, J ¼ 2.2 Hz, 1H, aro-
matic); 13C-NMR (deuteriochloform) d 52.4, 55.6, 105.9,
123.1, 124.7, 127.9, 130.7, 137.3, 146.0, 147.5, 158.2, 166.0
[5].
Ethyl quinoline-3-carboxylate (10d). Reaction time: 12 h;
yield: 42%; white solid: mp 63–65ꢁC (hexane–EtOAc); IR (po-
tassium bromide) 1713 cmꢂ1 1H-NMR (deuteriochloform) d
;
1.47 (t, J ¼ 7.2 Hz, 3H, CH3), 4.49 (q, J ¼ 7.2 Hz, 2H, CH2),
7.60–7.65 (m, 1H, aromatic), 7.81–7.87 (m, 1H, aromatic),
7.94 (d, J ¼ 8.3 Hz, 1H, aromatic), 8.17 (d, J ¼ 8.3 Hz, 1H,
aromatic), 8.85 (d, J ¼ 1.9 Hz, 1H, aromatic), 9.46 (d, J ¼ 2.2
Hz, 1H, aromatic); 13C-NMR (deuteriochloform) d 14.3, 61.5,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet