5
Piperidine-catalyzed aldol condensation of aldehyde 3c with acetone 4 mediated by silica gela
a 4-Chlorobenzaldehyde (3c) (2.0 mmol), acetone (4) (12.0 mmol), piperidine (0.4 mmol), silica gel 60 (63-200 μm, spherical, Nacalai, 12.0 g), 120 °C, 24 h.
b + (Silica gel was added), - (silica gel was not added).
c + (Reflux condenser was equipped), - (reflux condenser was not equipped).
d Calculated from the recovery of 3c.
e Isolated yields.
f 80 °C
g Complex mixture was obtained.
h Polymeric material was obtained.
In conclusion, silica gel-mediated self-aldol condensation of aldehydes was carried out in the presence of a catalytic amount of
piperidine. The substrates with low boiling points could be employed even without a reflux condenser which requires continuous
cooling by water. Volatilization would be suppressed because the reactions progressed inside the pore of silica gel. In addition,
hydrogen bonding between surface hydroxy groups of silica gel and carbonyl groups of aldehydes or acetone would play an important
role. The reactions can be carried out with preventing the discharge of toxic organic solvents and highly volatile material. Silica gel-
mediated reactions also make it possible to carry out the heating above their boiling points of substrates. We believe that our approach
can be adapted to other reactions using highly volatile substrates if appropriate porous material such as alumina and activated carbon
was chosen.
Table 6
Recycle experiments for the reactions mediated by silica gel
Yields (%)a
Entry
1st
86
86
82
73
2nd
83
87
82
70
3rd
66
91
84
70
4th
18
89
80
72
5th
0
1b
2c
3d
4e
89
81
70
a Isolated yields.
b Aldehyde 1a (2.0 mmol), piperidine (0.2 mmol), silica gel 60 (63-200 μm, spherical, Nacalai, 2.0 g), 80 °C, 2 h. Silica gel was washed with Et2O (10 mL).
c Aldehyde 1a (2.0 mmol), piperidine (0.2 mmol), silica gel 60 (63-200 μm, spherical, Nacalai, 2.0 g), 80 °C, 2 h. Silica gel was washed with Et2O (10 mL)
followed by acetone (10 mL).
d Aldehyde 1f (2.0 mmol), piperidine (0.2 mmol), silica gel 60 (63-200 μm, spherical, Nacalai, 2.0 g), 80 °C, 1 h. Silica gel was washed with Et2O (10 mL)
followed by acetone (10 mL). Reflux condenser was not equipped.
e Aldehyde 3c (2.0 mmol), acetone 4 (12.0 mmol), piperidine (0.4 mmol), silica gel 60 (63-200 μm, spherical, Nacalai, 12.0 g), 120 °C, 24 h. Silica gel was
washed with Et2O (60 mL) followed by acetone (60 mL).
Yields (%)e
Acknowledgments
Entry
Silica gelb Condenserc Conv. (%)d
5c
0
6c
73
70
66
0
7c
0
We thank Center for Coordination of Research Facilities,
Institute for Research Promotion, Niigata University for NMR
measurements. We thank the Research Promotion Grant (NDU
Grants N-19009) from Nippon Dental University.
1
+
+
-
+
-
100
100
100
62
2
0
0
3f,g
4f,h
+
-
0
0
Supplementary data
-
0
0
Supplementary data associated with this article can be found, in
the online version.
References
[1] G. Bosica, R. Abdilla, Molecules 21 (2016) 815.
[2] B. Hatano, S. Toyota, F. Toda, Green Chem. 3 (2001) 140-142.
[3] A. Loupy, A. Petit, M. Ramdani, C. Yvanaeff, M. Majdoub, B. Labiad, D. Villemin, Can. J. Chem. 71 (1993) 90-95.
[4] D. M. Pore, U. V. Desai, T. S. Thopate, P. P. Wadgaonkar, Arkivoc 12 (2006) 75-80.
[5] M. Saikia, D. Kakati, M. S. Joseph, J. C. Sarma, Lett. Org. Chem. 6 (2009) 654-658.
[6] A. Sakakura, Y. Koshikari, K. Ishihara, Tetrahedron Lett. 49 (2008) 5017-5020.
[7] K. Tanaka, F. Toda, Chem. Rev. 100 (2000) 1025-1074.
[8] F. Toda, T. Suzuki, S. Higa, J. Chem. Soc., Perkin Trans. 1 (1998) 3521-3522.
[9] K. Yoshizawa, S. Toyota, F. Toda, Tetrahedron Lett. 42 (2001) 7983-7985.
[10] A. Bladé-Font, Tetrahedron Lett. 21 (1980) 2443-2446.
[11] Y. Z. Jin, N. Yasuda, H. Furuno, J. Inanaga, Tetrahedron Lett. 44 (2003) 8765-8768.
[12] Y. Z. Jin, N. Yasuda, J. Inanaga, Green Chem. 4 (2002) 498-500.
[13] S. Minakata, D. Kano, Y. Oderaotoshi, M. Komatsu, Angew. Chem. Int. Ed. 43 (2004) 79-81.
[14] M. D. G. Nascimento, S. P. Zanotto, M. Scremin, M. C. Rezende, Synth. Commun. 26 (1996) 2715-2721.
[15] S. Onitsuka, Y. Z. Jin, A. C. Shaikh, H. Furuno, J. Inanaga, Molecules 17 (2012) 11469-11483.