80% |
With boron trifluoride diethyl ether complex In ethyl acetate at 60℃; for 6h; |
Appendix A.2. General Procedure for the Synthesis of Compounds (3a-3x)
General procedure: A mixture of 117 mg (1 mmol) indole, 97 mg (1 mmol) maleimide andapproximately adrop of BF3OEt2 (0.5 mmol) in 5 mL of ethyl acetate solvent was stirred at 60 °C for 6 h.Completion of reaction was monitor by TLC. After completion, the mixture was cooledto room temperature. In some cases where the product succinimide appeared as a solidfrom the reaction mixture filtered and recrystallized. Otherwise, H2O (20 mL) was addedto the solution and extracted with EtOAc (2 x25 mL). The combined organic layer wasdried over anhydrous Na2SO4 and concentrated by rotary evaporation to afford crudeproduct which was further purified by column chromatography using EtOAc and hexaneas solvent system. |
79.58% |
In glacial acetic acid for 36h; Reflux; |
4.1.4. 3-(1H-Indol-3-yl)pyrrolidine-2,5-dione (1)
A mixture of indole (9.7 g 0.1 mol) and maleimide (11.7 g0.1 mol) in acetic acid (125 ml) was refluxed on stirring for about 36 h. The completion time of reaction was assigned chromatographically (TLC). The reaction mixture was cooled, the solvent was removed under vacuo and the crude product was crystallized from ethanol to give compound (1) |
79.58% |
With glacial acetic acid for 36h; Reflux; |
1.1 3-(1H-indol-3-yl)pyrrolidine-2,5-dione(1) and 1-(4-bromobutyl)-3-(1H-indol-3-yl)pyrrolidine-2,5-dione (2g)
A mixture of indole (9.7 g 0.1 mol) and maleimide (11.7 g 0.1 mol) inacetic acid (125 ml) was refluxed on stirring for about 36 h. The completiontime of reaction was assigned chromatographically (TLC). The reaction mixturewas cooled, the solvent was removed under vacuo and the crude product wascrystallized from ethanol to give compound (1) [1-3] The title compound wasisolated as a light brown powder. Yield: 79.58% 17.12 g, m.p. 190-191 °C (lit. 196-197 °C[4]). 3-(1H-indol-3-yl)pyrrolidine-2,5-dione (1) (2.14 g0.01 mol) and 1,4-dibromobutane (0.05mol) and K2CO3 (0.02 mol) and 100 ml acetone were stirredand refluxed for 4 h. Reaction time was monitored using TLC. After cooling, themixture was filtered, and the filtrate was evaporated to dryness. The cruderesidue was purified by flash chromatography using CH2Cl2/MeOH(98:2 v/v) as an eluent. Proper fractions were identified by TLC, evaporated todryness and crystallized from diethyl ether to afford 2g. |
79.58% |
With glacial acetic acid for 36h; Reflux; |
1. Synthesis of: 1.1 3-(1H-indol-3-yl)pyrrolidine-2,5-dione (1) and 1-(4-bromobutyl)-3-(1H-indol-3-yl)pyrrolidine-2,5-dione (2)
3-(1H-indol-3-yl)pyrrolidine-2,5-dione (1) and 1-(4-bromobutyl)-3-(1H-indol-3-yl)pyrrolidine-2,5-dione (2) A mixture of indole (9.7 g 0.1 mol) and maleimide (11.7 g 0.1 mol) in acetic acid (125.0 mL) was refluxed on stirring for about 36 h. The completion time of reaction was assigned chromatographically (TLC). The reaction mixture was cooled, the solvent was removed under vacuo and the crude product was crystallized from ethanol to give compound (1) [1-3]. The title compound was isolated as a light brown powder. Yield: 79.58% 17.12 g, m.p. 190-191 °C (lit. 196-197 °C [4]). |
78% |
With trimethyl-(2-hydroxyethyl)ammonium chloride; anhydrous zinc chloride at 130℃; Ionic liquid; |
3-(1H-indol-3-yl)pyrrolidine-2,5-dione 1
The choline chloride/ZnCl2 1:2 liquidionic (50 g) was stirred in an oil bath at 130 C. Indole (5 g, 43 mmol) andmaleimide (5.8 g, 60 mmol) were successively added and dissolved. Themixture was stirred at 130 C for 45 min. After cooling, EtOAc and waterwere added and the aqueous phase was saturated with NaCl. After extractionwith EtOAc, the combined organic phases were washed with brine, dried overMgSO4, and evaporated. The crude residue was recrystallized from methanoland the filtrate was further purified by column chromatography (EtOAc/cyclohexane, 1:1) to give 1 (7.1 g, 33 mmol, 78%) as a yellow solid |
74% |
With glacial acetic acid for 36h; Heating; |
|
48% |
With glacial acetic acid for 72h; Heating / reflux; |
|
|
With anhydrous zinc chloride In 1,2-dichloro-ethane Reflux; |
|
|
In glacial acetic acid at 170℃; for 2h; Microwave irradiation; |
|
|
With glacial acetic acid for 48h; Inert atmosphere; Reflux; |
|
|
With boron trifluoride diethyl ether complex In dichloromethane at 40℃; for 4h; |
1.1 Example 1
(1) indole 4.35g (0.037mol), maleimide 3.0g (0.031mol) and boron trifluoride etherate 0.88g (0.0062mol) were added to a 100mL round bottom flask,And added 50 mL of dichloroethane. The mixture was heated to 40 ° C under reflux and stirred for 4 hours. After completion of the reaction, the solvent was evaporated to dryness under reduced pressure to give 3-indane succinimide. |
|
With anhydrous zinc chloride |
|
|
With boron trifluoride diethyl ether complex at 90℃; for 3h; Inert atmosphere; |
|