3
3. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 16, 4467.
4. Negishi, E.; King, A. O.; Okukado, N. J. Org. Chem. 1977, 42,
1821.
and C-C coupled 1-[4'-acetyl(1,1'-biphenyl)-4-yl]ethanone (Table
3, entry 2). 2-Nitroacetophenone gave mainly 2-
aminoacetophenone and a small amount of the desired product
(6%) and 4-methylquinoline (Table 3, entry 3). In the reaction of
3-nitroacetophenone no isolable product was obtained.
5. Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1978, 100, 3636.
6. Okude, Y.; Hirano, S.; Hiyama, T.; Nozaki, H. J. Am. Chem. Soc.
1977, 99, 3179.
Aldehydes did not give the corresponding chain-elongated
products. In the reaction of 2-nitrobenzaldehyde the dimer of 2-
aminobenzaldehyde was obtained as the major product, along
with quinoline (Table 4, entry 1). From the reaction of 3-
nitrobenzaldehyde only the addition product of 3-
aminobenzaldehyde and acetaldehyde could be identified (Table
4, entry 2). 4-Nitrobenzaldehyde gave an undefiniable product
mixture.
7. Johansson Seechurn, C. C. C.; Kitching, M. O.; Colacot, T. J.;
Snieckus, W. Angew. Chem. Int. Ed. 2012, 51, 5062.
8. Yin, L.; Liebscher, J. Chem. Rev. 2007, 107, 133.
9. Pagliaro, M.; Pandarus, V.; Ciriminna, R.; Beland, F.; Demma
Cara, P. ChemCatChem. 2012, 4, 432.
10. Lamblin, M.; Nassar-Hardy, L.; Hierso, J.-C.; Fouquet, E.; Felpin,
F.-X. Adv. Synth. Catal. 2010, 352, 33.
11. Cwik, A.; Hell, Z.; Figueras, F. Adv. Synth. Catal. 2006, 348, 523.
12. Cwik, A.; Hell, Z.; Figueras, F. Tetrahedron Lett. 2006, 47, 3023.
13. Cwik, A.; Hell, Z.; Figueras, F. Org. Biomol. Chem. 2005, 3,
4307.
Table 4. Reaction of different nitrobenzaldehydes with ethanol.a
Productb
14. Haber, F. Z. Elektrochem. 1898, 22, 506.
15. Blaser, H. U. Science 2006, 313, 312.
16. Pitre, S. V.; Vankar, P. S.; Vankar, Y. D. Tetrahedron 1996, 52,
12291.
Entry Aldehyde
NO2
O
1
N
OHC
N
N
17. Liu, C.; Wang, J.; Meng, L.; Deng, Y.; Li, Y.; Lei, A. Angew.
Chem. Int. Ed. 2011, 50, 5144.
O
18. Navarro, O.; Marion, N.; Oonishi, Y.; Kelly, R. A.; Nolan, S. P. J.
Org. Chem. 2006, 71, 685.
19. Navarro, O.; Kaur, H.; Mahjoor, P.; Nolan, S. P. J. Org. Chem.
2004, 69, 3173.
82%
18%
NO2
OH
2
O
20. Chen, J.; Zhang, Y.; Yang, L.; Zhang, X.; Liu, J.; Li, L.; Zhang,
H. Tetrahedron 2007, 63, 4266.
OHC
40%
NH2
21. Reduction and chain elongation:
A
mixture of 4-
nitroacetophenone (0.83 g, 5 mmol), NaOH (0.6 g), Pd/MgLaO
(0.2 g) and the appropriate alcohol (10 ml) were stirred at 120 °C
(bath temperature) for 24 hours. The mixture was filtered, the
solid washed with MeOH and the filtrate concentrated in vacuum.
The residue was dissolved in Et2O and H2O. Dilute HCl (25%)
was added until pH 1. The two phases were separated and the
aqueous phase basified to pH 8 by adding NaHCO3. The aqueous
phase was extracted with Et2O (2 × 50 mL). The organic phase
was dried over Na2SO4 and concentrated in vacuum. The products
were purified by column chromatography (Kieselgel,
hexane:acetone, 4:1). All products exhibited satisfactory spectral
data (1H NMR, mass spectra).22
NO2
3
c
-
CHO
a5 mmol aldehyde, 0.2 g catalyst, 0.6 g NaOH, 10 ml ethanol, 24 h, reflux
bRelative yield based on GC-MS analysis of the product
cNo identifiable product was obtained
The formation of the quinoline derivatives can be explained
by the reaction of the intermediate amino-carbonyl compound
with acetaldehyde, to give an aldehyde which undergoes
intramolecular cyclization (Scheme 4). This mechanism is
supported by the product obtained in the reaction of 3-
nitrobenzaldehyde (Table 4, entry 2).
22. Selected spectroscopic data: 1-(4-aminophenyl)butan-1-one (5a):
1H NMR (CDCl3, 300 MHz): 0,9 (t, J=7.6 Hz, 3H), 1,66 (m, 2H),
2,76 (t, J=7.6 Hz, 2H), 3,91 (br s, 2H), 6,56 (d, J=8.6 Hz, 2H),
7,73 (d, J=8.6 Hz, 2H); MS m/z(%):163 (M+, 15), 135 (80%), 120
(100%), 92 (27%), 65 (22%); 1-(4-Aminophenyl)hexan-1-one
(5d): 1H NMR (CDCl3, 300 MHz): 0.88 (t, J=7.6 Hz , 3H), 1.33
(m, 2H), 1.69 (m, 2H), 2.83 (s, 2H), 4.02 (br s, 2H), 6.62 (d, J=8.6
Hz, 2H), 7.79 (d, J=8.6 Hz, 2H); MS m/z (%):191 (M+, 2), 148 (3),
135 (80), 120 (100), 92 (25), 65 (22); 1-(4-Aminophenyl)-2-
propylpentan-1-one (6): 1H NMR (CDCl3, 300 MHz, crude
product): 0.92 (t, J=7.5 Hz, 6H), 1.38 (m, 4H), 1.85 (m, 4H), 3.52
(m, 1H), 4,05 (br s, 2H), 6.64 (d, J=8.6 Hz, 2H), 7.75 (d, J=8.6
Hz, 2H); 13C NMR (CDCl3, 300 MHz): 14.9, 22.8, 26.7, 36.1,
128.8, 133.1, 138.2, 150.6, 201.4; MS m/z (%): 219 (M+, 1), 148
(9), 135 (100), 120 (85), 92 (22), 65 (18).
O
O
OH
R
CH3CHO
R
R
O
NO2
NH2
NH2
R
N
HO
R
-H2O
-H2O
N
Scheme 4. Proposed mechanism for the formation of quinoline
derivatives.
Taking into account that the quinoline derivatives were
obtained in only small amounts, their formation does not
contradict the mechanism depicted in Scheme 2.
In conclusion, we have described an interesting heterogeneous
catalytic method for the chain elongation of 4-nitroacetophenone
with simultaneous reduction of the nitro group. The carbonyl
group remained intact under the reported reaction conditions.
References and notes
1. Heck, R. F.; Nolley, J. P. J. Org. Chem. 1972, 37, 2320.
2. Miyaura, N.; Suzuki, A. Chem. Commun. 1979, 866.