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7. For instance see: (a) Sondhi, S. M.; Rani, R.; Roy, P.; Agrawal, S. K.; Saxena, A. K.
Bioorg. Med. Chem. Lett. 2009, 19, 1534–1538; (b) Yunes, J. A.; Cardoso, A. A.;
Yunes, R. A.; Correa, R.; de Campos-Buzzi, F.; Cechinel, F. V. Z. Naturforsch. 2008,
63c, 675–680; (c) Stewart, S. G.; Polomska, M. E.; Lim, R. W. Tetrahedron Lett.
2007, 48, 2241–2244.
8. (a) Kafi, K.; Betting, D. J.; Yamada, R. E.; Bacica, M.; Steward, K. K.; Timmerman,
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8092; (b) Chandrasekhar, S.; Padmaja, M. B.; Raza, A. Synlett 1999, 1597–1599.
10. General procedure for microwave-assisted synthesis of phthalimides (1): DMF
(20 ml) solution of phthalic anhydride (1.5 g; 0.01 mol) and corresponding
amine (0.01) were refluxed with magnetic stirring under microwave
conditions as outlined in Table 1. The reaction mixture was poured onto
crushed ice (ꢀ200 g) and the formed white precipitate was separated by
filtration, washed with water, and dried under reduced pressure. If necessary
further purification was performed by column chromatography. General
procedure for conventional synthesis of phthalimides in conventional method
(1): To a suspension of phthalic anhydride (1 g; 6.8 mmol) and corresponding
amine (0.85 mmol) in toluene (20 ml) triethylamine (1 ml) was added. The
resulting reaction mixture was refluxed. After refluxing for time outlined in
Table 1 the reaction mixture was concentrated to ꢀ1/4 cooled and the formed
crystalline product was separated by filtration. If necessary column
purification was performed.
maleic anhydride followed by the ring closure in acetic anhydride
with a catalytic amount of acetic acid. Isolated yields of the malei-
mides range around 50%.16 In our microwave-assisted preparation
approach we also applied the two-step synthesis (Method B Table
4). In the first step, tetrahydrofuran (THF) solutions of the corre-
sponding amine and maleic anhydride were mixed at room
temperature. The reaction was completed after a few minutes.
The formed precipitate was mixed with acetic anhydride and a
catalytic amount of sodium acetate and then microwaved at
450 W. The reaction conditions and isolated yields are presented
in Table 4.
In conclusion, we have explored the effects of microwave irradi-
ation on the preparation of cyclic imides. Given the possibility to
control the power of microwave radiation, it was possible to use
microwave irradiation for the preparation of cyclic imides that re-
quire microwave radiation in the range of a few minutes to a few
hours. This approach is superior to conventional synthetic ap-
proach in both isolated yield of the product and required reaction
time (see Tables 1–3 for comparisons).
Acknowledgment
11. (a) Borah, N. H.; Boruah, R. C.; Sandhu, J. S. J. Chem. Res. 1998, 272–273; (b)
Pengo, P.; Pantos, G. D.; Otto, S.; Sanders, J. K. M. J. Org. Chem. 2006, 71, 7063–
7066.
We thank the National Science Foundation for financial support
(CHE-0611902) for this work.
12. (a) Chapman, J. M., Jr.; Cocolas, G. H.; Hall, I. H. J. Med. Chem. 1979, 22, 1399–
1402; (b) Perry, C. J.; Parveen, Z. J. Chem. Soc., Perkin Trans. II 2001, 512–521.
13. Khadilkar, B. M.; Madyar, V. R. Indian J. Chem. 2002, 41B, 1083–1085.
14. General procedure for the synthesis of 1,8-naphthalimides using a microwave (2
and 3): Pyridine or DMF (100 ml) solution of an anhydride (5 mmol) and
corresponding amine were refluxed under microwave heating (Table 2). After
cooling to room temperature, the reaction mixture was poured over ice. The
formed white solid was separated by filtration. If necessary, the product was
further purified by dissolving in dichloromethane, washing dichloromethane
with water, and 10% hydrochloric acid. General procedure for conventional
synthesis of 1,8-naphthalimides (2a, 2b and 3): A suspension of anhydride
(5 mmol) and corresponding amine in pyridine (20 ml) or DMF (20 ml) was
refluxed for several hours (Table 2). The reaction mixture was concentrated to
about 1/4 and poured over ice. The formed crystalline product was separated
by filtration.
15. General method for microwave-assisted synthesis of succinimides (4): DMF
(20 ml) solution of succinic anhydride (2 g; 0.02 mol) and corresponding
amine (0.015 mol) were refluxed in microwave reactor (magnetron power of
300 W) for 30 min. Into cooled reaction mixtures acetic anhydride (0.06 mol)
was added and the reaction mixture was refluxed in microwave reactor for an
additional 30 min. This was followed by the addition of water (5 ml) and
microwave refluxed for 20 min. The reaction mixture was diluted with
dichloromethane (100 ml), washed with saturated water solution of sodium
bicarbonate (3 Â 50 ml), water (3 Â 50 ml), and dried over anhydrous sodium
sulfate. After the solvent was evaporated, the crude product was purified by
column chromatography with ethyl acetate–hexane (5:1) as an eluent. General
method for conventional synthesis of succinimides (4). DMF (20 ml) solution of
succinic anhydride (0.02 mol) and corresponding amine (0.015 mmol) was
stirred at 50 °C for 30 min. Into this solution, acetic anhydride (5 ml) was
added and the resulting reaction mixtures were refluxed under microwave for
a few hours as specified in Table 3. After the refluxing reaction mixture was
diluted with ice water (100 ml), it was stirred for 30 min and the product was
isolated by dichloromethane extraction followed by column chromatography.
16. Kalgutkar, A.; Crews, B. C.; Marnett, L. J. J. Med. Chem. 1996, 39, 1692–1703.
17. General procedure for the synthesis of maleimides 5: Tetrahydrofuran (20 ml)
solution of maleic anhydride (0.01 mol) and tetrahydrofuran solution (20 ml)
of corresponding amine (1.1 equiv) were mixed together and stirred at room
temperature for 15 min. The solvent was decanted from white precipitate, and
acetic anhydride (21 ml) and sodium acetate (1 g) were added to the solid
material. The reaction mixture was heated with microwave magnetron power
of 450 for 30 min. The reaction mixture was washed with ether (3 Â 50 ml).
After ether evaporation, the product was purified by column chromatography
with 5% ethyl acetate in dichloromethane as an eluent.
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