LETTER
Ionic Liquid Promoted Synthesis of b-Enamino Ketones
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Table 2 Recycle Use of Ionic Liquid in b-Enamino Ketone Synthesis
Entry
1,3-Diketone
Amine
Product
Time (h)
Yield (%)
Recycle 1
Recycle 2
Recycle 3
1
2
3
1a
1i
2a
2i
3a
3i
3
88
85
87
84
82
85
84
82
85
3.4
3.6
1j
2j
3j
(9) Bozell, J. J.; Hegedus, L. S. J. Org. Chem. 1981, 46, 2561.
(10) Murahashi, S. I.; Tsumiyama, T.; Mitsue, Y. Chem. Lett.
1984, 1419.
(11) (a) Stefani, H. A.; Costa, I. M.; de Silva, D. O. Synthesis
2000, 1526. (b) Arcadi, A.; Bianchi, G.; Di Giuseppe, S.;
Marinelli, F. Green Chem. 2003, 5, 64. (c) Gao, Y.; Zhang,
Q.; Xu, J. Synth. Commun. 2004, 34, 909.
(12) (a) Welton, T. Chem. Rev. 1999, 99, 207. (b)Wasserscheid,
P.; Keim, W. Angew. Chem. Int. Ed. 2000, 39, 3772.
(c) Scheldon, R. Chem. Commun. 2001, 2399. (d) Zhao, D.;
Wu, M.; Kou, Y.; Min, E. Catal. Today 2002, 1, 2654.
(e) Gordon, C. M. Appl. Catal. A 2002, 222, 101.
(f) Oupont, J.; Souza, R. F. D.; Suarez, P. A. Z. Chem. Rev.
2002, 102, 3667.
(13) (a) Yao, Q. Org. Lett. 2002, 4, 2197. (b) Itoh, T.; Akasaki,
E.; Nishimura, Y. Chem. Lett. 2002, 2, 154. (c) Yeung, K.
S.; Farkas, M. E.; Qui, Z.; Yung, Z. Tetrahedron Lett. 2002,
43, 5793. (d) Jarikote, D. V.; Siddiqui, S. A.; Rajagopal, R.;
Lahoti, R. J.; Daniel, T.; Srinivasan, K. V. Tetrahedron Lett.
2003, 9, 1835. (e) Panchgalle, S. P.; Kalkote, U. R.;
Niphadkar, P. S.; Joshi, P. N.; Chavan, S. P.; Chaphekar, G.
M. Green Chem. 2004, 6, 308.
it is evident that both aliphatic as well as substituted
aromatic amines participate well in the reaction. The
protocol is also applicable for the synthesis of b-enamino
ester (entry m).
Similarly, the reaction of dimedone 1a with aniline 2a was
also carried out using 1,3-dibutyl imidazolium bromide
[bbim]Br ionic liquid for comparison. The resulting b-
enamino ketone 3a forms with same yield. The ionic liq-
uid used in b-enamino ketones synthesis was recovered
and reused with identical results. Thus, the recyclibility
was conformed as listed in Table 2.
In summary, we have demonstrated an efficient and mild
protocol for the condensation of 1,3-dicarbonyl com-
pounds and different amines (aliphatic and aromatic) to b-
enamino ketones at room temperature in ionic liquid with-
out adding any catalyst. The procedure is simple and can
be used as an alternative to the existing producers.
(14) (a) Deshmukh, R. R.; Rajagopal, R.; Srinivasan, K. V.
Chem. Commun. 2001, 1544. (b) Ohara, H.; Kiyokane, H.;
Itoh, T. Tetrahedron Lett. 2002, 43, 3041. (c) Revell, J. D.;
Gansen, A. Org. Lett. 2002, 4, 3071. (d) Vallin, K. S. A.;
Emilsson, P.; Larhed, M.; Hallberg, A. J. Org. Chem. 2002,
67, 6243.
(15) (a) Walton, T. Chem. Rev. 1999, 99, 2071. (b) Walden, P.
Bull Acad. Imper. Sci. (St. Petersburg) 1914, 1800.
(c) Sugden, S.; Wilkins, H. J. Chem. Soc. 1929, 1291.
(16) General Experimental Procedure for the Synthesis of
b-Enamino Ketones:
References and Notes
(1) Caprathe, B. W.; Jaen, J. C.; Wise, L. D.; Heffner, T. G.;
Pudsley, T. A.; Melther, L. T.; Parvez, M. J. Med. Chem.
1991, 34, 3726.
(2) Gatta, F.; Del Giudice, M. R.; Pomponi, M.; Marta, M.
Heterocycles 1992, 34, 991.
(3) Bell, I. M.; Erb, J. M.; Freidinger, R. M.; Gallicchio, R. A.;
Hobbs, D. W.; Hominck, C. F.; Kuo, M. S.; Lis, E. V.;
Mathse, D. J.; Michelson, S. R.; Pawluczk, J. M.; Pettibone,
D. J.; Reiss, D. R.; Michelson, S. R.; Pawluczyk, J. M.;
Pettibone, D. J.; Reiss, D. R.; Vickers, S.; Williams, P. D.;
Woyden, C. J. J. Med. Chem. 1998, 41, 2146.
(4) Scott, K. R.; Edafiogho, I. O.; Richardson, E. C.; Farrar, V.
A.; Moore, J. A.; Tietz, E. I.; Hinko, C. N.; Chang, H.; El-
Assadi, A.; Nicholson, J. M. J. Med. Chem. 1993, 36, 1947.
(5) Dondoni, A.; Perrone, D. Synthesis 1993, 1162.
(6) Azzaro, M.; Geribaldi, S.; Videan, B. Synthesis 1981, 880.
(7) (a) Texier-Boullet, F.; Kelin, B.; Hamelin, J. Synthesis 1986,
409. (b) Baribanbte, M. E. F.; Braibabte, H. S.; Missio, L.;
Andricoputo, A. Synthesis 1994, 898.
A mixture of 1,3-diketones 1 (2 mmol) and amine 2 (2
mmol) in ionic liquid [EtNH3]NO3 (4 mmol) was stirred at
r.t. The progress of the reaction was monitored by TLC.
After completion of reaction, the reaction mixture was
diluted with EtOAc and extracted with H2O and brine. The
organic layer was dried over MgSO4, filtered and the solvent
was removed under reduced pressure. The products obtained
were purified using column chromatography on SiO2 and
identified by comparing with authentic samples by TLC, 1H
NMR and IR spectra.
(8) Alberola, A.; Andres, C.; Gonzales Ortega, A.; Pedrosa, R.;
Vicente, M. An. Quim. Ser. C. 1987, 83, 55.
Synlett 2006, No. 6, 933–935 © Thieme Stuttgart · New York