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Y. Dai et al. / Chinese Chemical Letters 21 (2010) 31–34
produced the corresponding b-amino ketones in excellent yields. However, the ortho-substituted anilines generally
gave very low yield, even trace of the products. This could be attributed to the steric hindrance caused by ortho group
on the approaching electrophilic reagents (as was also claimed by Li and Wang [5c,h]). The effect of substitution
related to benzaldehydes was also briefly studied. It was observed that the strong electron-withdrawing groups
decrease the yield of products, whereas weak electron-donating groups increase it. This can be explained from the
stability of intermediate ‘‘[ArNHCHArR2]+’’: When R2 owns strong electron-withdrawing capacity, the carbon cation
is not easy to form due to its instability; but if R2 owns strong electron-donating capacity, the reaction activity to
participate in the next step reaction is weak due to the high stability of the intermediate.
2. Conclusion
In conclusion, three-component Mannich-type reaction of anilines and benzaldehydes with acetophenone was
efficiently catalyzed by CeCl3Á7H2O in ethanol. The noteworthy features of the reported protocol include: (a) simple
procedure; (b) air-stable and water-tolerant catalyst; (c) cheap and non-toxic solvent; (d) the reuse of the catalytic
system. Furthermore, this protocol is adaptive for synthesis of a diverse set of b-amino ketones.
Acknowledgment
We are grateful for the financial support from Nanjing University of Science and Technology.
References
[1] F. Fringuelli, F. Pizzo, L. Vaccaro, J. Org. Chem. 66 (2001) 4719.
[2] X.S. Fan, Y.Z. Li, Y.M. Zhang, Chin. J. Org. Chem. 25 (2005) 1029.
[3] (a) M. Arend, B. Westermann, N. Risch, Angew. Chem. Int. Ed. 37 (1998) 1044;
(b) S. Kobayashi, H. Ishitani, Chem. Rev. 99 (1999) 1069;
(c) M.M.B. Marques, Angew. Chem. Int. Ed. 45 (2006) 348.
[4] (a) A.T. Khan, T. Parvin, L.H. Choudhury, J. Org. Chem. 73 (2008) 8398;
(b) R. Muller, H. Goesmann, H. Waldmann, Angew. Chem. Int. Ed. 38 (1999) 184;
(c) W. Notz, F. Tanaka, S.I. Watanabe, J. Org. Chem. 68 (2003) 9624;
(d) M. Suginome, L. Uehlin, M. Murakami, J. Am. Chem. Soc. 126 (2004) 13196.
[5] (a) M.A. Bigdeli, F. Nemati, G.H. Mahdavinia, Tetrahedron Lett. 48 (2007) 6801;
(b) L. Yi, H. Lei, J. Zou, Synthesis 9 (1991) 717;
(c) Z. Li, X. Ma, J. Liu, J. Mol. Catal. A: Chem. 272 (2007) 132;
(d) T. Akiyama, J. Takaya, H. Kagoshima, Adv. Synth. Catal. 344 (2002) 338;
(e) W.G. Shou, Y.Y. Yang, Y.G. Wang, Tetrahedron Lett. 47 (2006) 1845;
(f) T.P. Loh, S.L. Chen, Org. Lett. 4 (2002) 3647;
(g) L. Ming, J. Han, J. Sheng, Chin. J. Org. Chem. 25 (2005) 591.
[6] General procedure: CeCl3Á7H2O (0.1 mmol) was added to a mixture of anilines (2.3 mmol), benzaldehydes (2.0 mmol) and acetophenone
(2.3 mmol) in ethanol (3 mL). The mixture was stirred at room temperature for a certain time (Table 4) and monitored by TLC, then the contents
of the flask had solidified. The reaction mixture was cooled in refrigerator for one night. The solid was filtered off and the cake was washed with
H2O. Finally, the crude products were purified by crystallization from ethanol affording 3a–3s. The catalyst-containing ethanol was reused in
subsequent runs without further purification. The structures of all the products were unambiguously established on the comparison of their
1
1
melting points, MS, IR, and H NMR spectra data with those of authentic samples. Selective data: 3a: m.p. 169–171 8C; H NMR (CDCl3,
500 MHz): d 3.42 (d, 2H, J = 4.8 Hz), 4.95 (t, 1H, J = 6.1 Hz), 6.52 (s, 2H), 6.65 (s, 1H), 7.05 (s, 2H), 7.24 (s, 2H), 7.31 (s, 2H), 7.42 (s, 4H), 7.55
(s, 1H), 7.88 (d, 2H, J = 4.8 Hz). IR (KBr, nmax): 3200, 1681, 1612, 1511, 1300, 759, 510 cmÀ1. MS (EI) m/z 301 (M+).