G. A. Suárez-Ortiz et al. / Tetrahedron Letters 52 (2011) 1641–1643
1643
1
1
1
1
1
1
1
1
1
1
0. Pellon, R.; Docampo, M.; Kunakbaeva, Z.; Gomez, V.; Velez-Castro, H. Synth.
Commun. 2006, 36, 481.
1. Rosas, N.; Cabrera, A.; Sharma, P.; Arias, J. L.; García, J. L.; Arzoumanian, H. J.
Mol. Catal. A 2000, 156, 103.
2. Rosas, N.; Sharma, P.; Arellano, I.; Pérez, D.; Cabrera, A. Organometallics 2005,
2
4, 4893.
3. Arzoumanian, H.; Jean, M.; Nuel, D.; Cabrera, A.; García, J. L.; Rosas, N.
Organometallics 1995, 14, 5438.
4. Arzoumanian, H.; Jean, M.; Nuel, D.; García, J. L.; Rosas, N. Organometallics
1997, 16, 2726.
5. Rosas, N.; Sharma, P.; Cabrera, A.; Pénieres, G.; García, J. L.; Maldonado, L. A.
Heterocycles 2003, 60, 2631.
6. Rosas, N.; Sharma, P.; Álvarez, C.; Cabrera, A.; Ramírez, R.; Delgado, A.;
Arzoumanian, H. J. Chem. Soc., Perkin. Trans. 1 2001, 2341.
7. Rosas, N.; Sharma, P.; Álvarez, C.; Cabrera, A.; Ramírez, R.; Gutiérrez, Y.;
Méndez, M.; Toscano, R. A.; Maldonado, L. A. Tetrahedron. Lett. 2003, 44, 8019.
8. Rosas, N.; Salmon, M.; Sharma, P.; Álvarez, C.; Ramírez, R.; García, J. L.;
Arzoumanian, H. J .Chem. Soc., Perkin Trans. 1 2000, 1493.
9. Synthesis of benzo[b][1,8]naphthyridin-5(10H)-one (3).A typical experiment was
performed as follows. A 2M NaOH solution (10 mL) was degassed and saturated
with CO under atmospheric pressure for 30 min. To the solution was then added
Figure 1. Molecular structure of 2-ethylbenzo[b][1,8]naphthyridin-5(10H)-one
3b).
(
2 2
0.04 mmol of Ni(CN) 4H O, the mixture was kept at room temperature
overnight with stirring and slow bubbling of CO (2–3 mL/min) until a pale
yellow solution was obtained. Addition of 0.25 mmol of KCN resulted in a color
change to orange. To this resulting catalytic system, the corresponding
peak was observed for all the compounds, followed by a peak with
+
Silyl-a-ketoalkynes (1 mmol) and the 2-amino-4(1H)quinolinone compounds
a loss of the carbonyl group (M ÀCO). Vibrations corresponding to
À1
were added (1 mmol). The evolution of the reaction was followed by TLC. At
the end of the reaction, ether was used to extract the product. The product
was concentrated and purified by column chromatography over silica gel
using hexane–ethyl acetate (1:1) as the eluent to obtain pure
benzo[b][1,8]naphthyridin-(10H)-5-one. The compound 3b was recrystallized
from methanol:pentane mixture.
the C@O group between 1596–1620 cm and vibrations corre-
À1
sponding to the N–H amine group between 3208–3269 cm were
observed in the FT–IR spectra.
In all these compounds, proton signals were individually
assigned based on the JHH coupling constant values. All assigna-
tions were corroborated by COSY and HETCOR experiments.
X-ray crystal structure of 3b has been determined as shown in
Figure 1. The molecule is chiral. The compound show N–HÁ Á ÁC@O
intermolecular interactions in the unit cell forming a chain
2
-ethylbenzo[b][1,8]naphthyridin-5(10H)-one (3a) Yellow solid; yield 70%; mp:
À1
279–281 °C; FT-IR (vmax cm ): 3208 (N–H), 3137 (C–H Ar), 2998 (CH
3
), 2923
+
(
CH ), 1606 (C=O), 1437 (C–N), 1268 (C=N Ar); MS(EI) m/z 210[M] ;
3
+ 1
1
82[MÀCO] ; H NMR (300 MHz, DMSO-d
6 3
, d ppm) 2.48 (s, 3H, -CH ), 7.17 (d,
J = 8.10 Hz, 1H, CH-Ar), 7.24 (td, J = 7.08 Hz, 1H, CH-Ar), 7.59 (d, J = 8.19 Hz, 1H,
CH-Ar), 7.7 (td J = 6.96 Hz, 1H, CH-Ar), 8.16 (dd, J = 8.04 Hz 1H, CH-Ar), 8.4 (d,
J = 8.07 Hz, 1H,), 12.18 (s, 1H, N–H); 13C NMR (75 MHz, DMSO-d , d ppm) 24.57,
2
0
6
structure.
1
2
13.0, 117.6, 117.9, 120.9, 121.6, 125.8, 133.7, 135.7, 140.8, 150.6, 164.2, 177.1.
-ethylbenzo[b][1,8]naphthyridin-5(10H)-one (3b) Yellow solid; yield 75%; mp:
233–235 °C; FT-IR (vmax cm-1): 3209 (vN–H), 3135 (C–H Ar), 2936 (CH
), 2866
In conclusion, the methodology shows an easy way to carry out
heterocyclization reactions to obtain benzo[b][1,8]naphthyridin-5-
ones derivatives, in a single step under very mild conditions in
water. This work presents, the employment of a nickel catalyst in
aqueous medium having significant advantages such as the absence
of organic solvents, fast reaction and elimination of tiresome exper-
imental methodologies. The work is in process to generalize the
transformation of aminoquinolinones to benzo[b][1,8]naphthyri-
din-5-ones using this catalytic system.
3
+
(
[
3
CH ), 1620 (C-O), 1438 (C–N), 1276 (C–N Ar); MS(EI) m/z 224 [M] ; 192
+ 1
MÀCO] ; H NMR (300 MHz DMSO-d
6
, d ppm) 1.3 (t, J = 7.56 Hz,3H), 2.88 (q,
J = 7.53 Hz 2H), 7.22 (d, J = 8.10 Hz, 1H), 7.26 (td, J = 6.87 Hz, 1H), 7.63 (d,
J = 7.83 Hz, 1H), 7.7 (td J = 6.87 Hz, 1H), 8.18 (dd, J = 8.1 Hz 1H, CH-Ar), 8.47 (d,
J = 8.1 Hz, 1H), 12.22 (s, 1H, N–H); 13C NMR (DMSO-d
, d ppm) 13.8, 39.5, 113.9,
17.5, 118.3, 121.4, 122.2, 126.4, 134.4, 136.5, 141.4, 151.2, 169.4, 177.7.
6
1
2
-propylbenzo[b][1,8]naphthyridin-5(10H)-one (3c) Yellow solid; yield 75%; mp:
À1
214–216 °C; FT-IR (vmax cm ): 3212 (N–H), 3131 (C–H Ar), 2959 (CH ), 2930
(CH
1
1
3
+
3
), 1607 (C=O), 1432 (C–N), 1260 (
m
C=N Ar); MS (EI) m/z 238 [M] ;
, d ppm) 0.9 (t, J = 7.20 Hz,3H, -CH ),
), 2.8 (t, J = 7.8 Hz, 2H), 7.18 (d, J = 8.10 Hz, 1H), 7.24 (td,
+
1
81[MÀCO] ; H NMR (300 MHz DMSO-d
6
3
.7 (m, 2H, -CH
2
Acknowledgment
J = 6.9 Hz, 1H), 7.61 (dd, J = 9.3 Hz, 1H), 7.7 (td, J = 6.9 Hz, 1H), 8.17 (dd,
J = 8.1 Hz 1H), 8.4 (d, J = 8.1 Hz, 1H), 12.17 (s, 1H, N–H); 13C NMR (75 MHz,
DMSO-d
6
, d ppm) 13.7, 22.0, 39.8, 113.3, 117.4, 117.6, 120.8, 121.6, 125.8, 133.7,
Authors are grateful to DGAPA (IN-204507) for financing the
work.
135.7, 140.8, 150.6, 167.6, 177.13.
2
-phenylbenzo[b][1,8]naphthyridin-5(10H)-one (3d) Yellow solid; yield 80%; mp:
À1
286–288 °C; FT-IR (vmax cm ): 3244 (N–H), 3149 (C–H Ar), 1596 (C=O), 1430
+
+ 1
(
C–N), 1385 (C=N Ar); MS (EI) m/z 272 [M] ; 243 [MÀCO] ; H NMR (300 MHz
DMSO-d , d ppm) 7.26 (td, J = 6.9 Hz, 1H), 7.5-7-6 (m, 3H), 7.67 (dd, J = 8.4 Hz,
H), 7.72 (td, J = 6.9Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 8.19–7.24 (m, 1H), 8.6 (d,
References and notes
6
1
1
.
Tabart, M.; Picaut, G.; Lavergne, M.; Wentzler, S.; Malleron, J.; Dutka-Malen, S.;
Berthaud, N. Bioorg. Med. Chem. Lett. 2003, 13, 1329.
13
J = 8.4 Hz, 1H), 12.25 (s, 1H, N–H); C NMR (75 MHz DMSO-d
6
, d ppm), 114.1,
14.7, 117.7, 121.0, 121.7, 125.9, 127.4 (2C), 128.9 (2C), 130.4, 133.9, 136.8,
37.6, 141.1, 150.8, 160.4, 177.1.
1
1
2
3
.
.
Mitsos, A.; Zografos, A.; Markopoulou, O. J. Org. Chem. 2003, 68, 4567.
Tabart, M.; Picaut, G.; Desconclois, J. F.; Dutka-Malen, S.; Huet, Y.; Berthaud, N.
Bioorg. Med. Chem. Lett. 2001, 11, 919.
2
-p-tolylbenzo[b][1,8]naphthyridin-5(10H)-one (3e) Yellow solid; yield 80%; mp:
À1
338–341 °C; FT-IR (vmax cm ): 3244 (N–H), 3140 (C–H Ar), 2916 CH
3
),1603
4.
5.
6.
Deady, L. W.; Rodemann, T.; Zhuang, L.; Baguley, B. C.; Denny, W. A. J. Med.
Chem. 2003, 46, 1049.
Zhang, S-X.; Bastow, K. F.; Tachibana, Y.; Kuo, S-K.; Hamel, E.; Mauger, A.;
Narayanan, V. L.; Lee, K-H. J. Med. Chem. 1999, 42, 4081.
Ferrarini, P. L.; Betti, L.; Cavallini, T.; Giannaccini, G.; Lucacchini, A.; Manera, C.;
Martinelli, A.; Ortore, G.; Saccomanni, G.; Tuccinardi, T. J. Med. Chem. 2004, 47,
+
+
1
(
(
C=O), 1433 (C–N), 1282 (C–N Ar); MS (EI) m/z 286 [M] ; 257[M-CHO] ; H NMR
300 MHz, DMSO-d , d ppm) 2.38 (s, 3H), 7.26 (td, J = 6.9 Hz, 1H) 7.35 (d,
6
J = 7.8 Hz, 2H), 7.67 (d, J = 7.5 Hz), 7.72 (td, J = 6.9 Hz, 1H), 7.8 (d, J = 8.4 Hz, 1H),
.12 (d, J = 8.1 Hz 2H), 8.19 (dd, J = 8.1 Hz), 8.58 (d, J = 8.4 Hz), 12.08 (s, 1H, N–
8
13
H); C NMR (75 MHz, DMSO-d
6
, d ppm) 20.8, 113.8, 114.3, 117.7, 121.0, 121.6,
25.8, 127.3 (2C), 129.5 (2C), 133.8, 134.8, 136.6, 140.2, 141.2, 150.8, 160.3,
77.0.
1
1
3
019.
7.
8.
9.
Chen, Q.; Deady, L. W.; Aguley, B.; Denny, W. J. Med. Chem. 1994, 37, 593.
Ivanov, S. A.; Tugusheva, N. Z.; Granik, V. G. Russ. Chem. Rev. 2005, 74, 915.
Dormer, P. G.; Eng, K.; Farr, R.; Humphrey, G. R.; McWilliams, J. C.; Reidor, P. J.;
Sager, J. W.; Volante, R. P. J. Org. Chem. 2003, 68, 467.
2
0. Supplementary Material Crystallographic data for the structural analysis have
been deposited with the Cambridge Crystallographic Data Centre CCDC No.
791910.