736
Z.-G. Le, Z.-C. Chen, Y. Hu and Q.-G. Zheng
Vol. 42
Table 1
The Reaction of Phthalic Anhydride with Amine in Ionic Liquid [Bmim][PF ] [a]
6
Entry
Amine (RNH )
M.p.(°C)
Lit. mp(°C)
Yield (%)
2
1
2
3
4
5
6
7
8
9
C H NH
2
207.9-208.9
196.8-197.9
204.6-205.2
269.8-271.4
173.7-173.9
243.0-243.9
115.9-116.0
194.7-195.6
177.4-178.1
31.8-32.5
206-208 [6]
192-194 [6]
203-204 [6]
264-266 [6]
173-174 [6]
242-243.5 [10]
114-115 [9a]
194-197 [2a]
175-177 [11]
32 [9a]
98 (97 [b])
97 (98 [b])
6
5
p-ClC H NH
6
5
2
p-CH C H NH
95
98
96
90
3
6
5
2
p-NO C H NH
2
6
5
2
m-HOC H NH
6
5
2
4,5-dimethoxyaniline
C H CH NH
96 (94 [b])
6
5
2
2
NH CH COOH
94
91
95
94
2
2
L-phenylalanine
n-C H NH
10
11
4
9
2
NH CH CH OH
126.1-126.7
126 [12]
2
2
2
[a] All reactions were run with phthalic anhydride (2 mmol), amine (2 mmol) in ionic liquid [Bmim][PF ] (2 mL) at
6
130 °C for 5 min; [b] In ionic liquid [Bmim][BF ]
4
Table 2
General Procedure for the N-Alkylation of Heterocyclic
Compounds.
Recycling of [Bmim][PF ] in N-Benzyl Phthalimide [a]
6
Phthalic anhydride (2 mmol) and the corresponding amine (2
Entry
Cycle
Yield (%)
mmol) were added to the ionic liquids [Bmim][PF ] or
6
[Bmim][BF ] (2 mL) as appropriate, the mixture was stirred at
4
1
2
3
1
2
3
96
97
95
130 °C for 5 min and cooled to room temperature. The solid was
collected by filtration and washed with AcOEt to give the corre-
sponding pure N-alkyl or N-arylphthalimide. In some case, the
product was further purified by recrystallization from a mixture
of EtOH-AcOEt. After collecting the product by filtration, the
remaining viscous ionic liquid was further washed with a mixture
of ether-ethyl acetate (1:1) and dried at 80 °C under reduced pres-
sure and reused in subsequent runs.
[a] All reactions were run with phthalic anhydride (2 mmol), benzy-
lamine (2 mmol) in ionic liquid [Bmim][PF ] (2 mL) at 130 °C for 5 min.
6
In conclusion, we have demonstrated that the reaction
of phthalic anhydride with amine can be performed
rapidly in the ionic liquids [Bmim][PF ] or [Bmim][BF ]
6
4
REFERENCES AND NOTES
at 130 °C to give the corresponding imide derivatives in
excellent yields. The ionic liquid plays the dual role of
solvent and promoter. The substrates show significant
increase in reactivity thus improving the yield substan-
tially. The present method has many obvious advantages
compared to that of classical methods reported in litera-
ture, including its high efficiency, operational simplicity,
environmentally benign character and its ability to be
recycled. Further studies to expand this methodology for
the preparation of other cyclic imide derivatives is now
under way in our laboratory.
[1a] J. M. Chapman, P. J. Vorstad, G. H. Cocolas and I. H. Hall, J.
Med. Chem., 26, 237 (1983); [b] M. K. Hargreaves, J. G. Pritchard and h.
R. Dave, Chem. Rev., 70, 439 (1970); [c] Y. Shibata, K. Sasaki, Y.
Hashimoto and S. Iwasaki, Chem. Pharm. Bull., 44, 156 (1996); [d] H.
Miyachi, A. Azuma, A. Ogasawara, E. Uchimura, N. Watanabe, Y.
Kobayashi, F. Kato, M. Kato and Y. Hashimoto, J. Med. Chem., 40, 2858
(1997).
[2a] T. Vidal, A. Petit, A. Loupy, and R. N. Gedye, Tetrahedron,
56, 5473 (2000); [b] L. M. Lima, P. Castro, A. L. Machado, C. A. M.
Fraga, C. Lugnier, V. L. G. Moreas and E. Barreiro, J. Bioorg. Med.
Chem. 10, 3067 (2002).
[3] R. Jayakumar, R. Balaji and S. Nanjundan, Eur. Polym. J., 36,
1659 (2000).
[4a] P. Y. Reddy, S. Kondo, T. Toru and Y. Ueno, J. Org. Chem.,
62, 2652 (1997); [b] A. Kamal, E. Laxman, N. Laxman, N. V. Rao,
Tetrahedron Lett., 39, 8733 (1998).
EXPERIMENTAL
[5a] B. M. Barchin, A. M. Cuadro and A. B. Julio, Synlett, 343
(2002); [b] S. Chandrasekhar, N. B. Padmaja and A. Raza, Synlett, 1597
(1999).
[6] M. Y. Zhou, Y. Q. Li and X. M. Xu, Synth. Commun., 33, 3777
(2003) and references therein.
[7a] Welten, T. Chem. Rev., 99, 2071 (1999); [b] P. Wassercheid
and W. Keim, Angew. Chem. Int. Ed., 39, 3772 (2000); [c] R. Sheldon,
Chem. Commun., 2399 (2001); [d] C. M. Gordon, Appl. Catal., A, 101
(2001); [e] H. Olivier-Bourbigou and I. Magna, J. Mol. Catal., A, 419
Melting points were determined on digital melting point appa-
ratus and were not corrected. Infrared spectra were recorded on a
VECTOR22 (Bruker) infrared spectrometer, nuclear magnetic
resonance spectra were recorded on AVANCE DMX 400
(Bruker) spectrometer. The ionic liquids [bmim][BF ] and
4
[bmim][PF ] were synthesized according to reported procedures
6
[13]. All other materials are commercially available and were
used without further purification.