4-Maleimidophenol

General synthetic procedure: To a stirring solution of maleic anhydride (29.42 g, 30 mmol) in dry toluene (300 mL) was added dropwise a solution of aniline (27.4 mL, 30 mmol) in dry toluene (10 mL) at room temperature. The mixture was vigorously stirred for 3 h, and the formed precipitate was separated by filtration. The cake was washed with toluene and dried under reduced pressure to give N-phenylmaleamic acid, as a yellow solid, 95% yield. N-phenylmaleamic acid (4.176 g, 21.8 mmol) thus obtained was added to a flask charged with ionic liquid I (2.302 g, 7.28 mmol) and propyl acetate (66 mL), and the mixture was heated to reflux, and the formed water during the reaction was removed by using a Dean-Stark trap. After maintaining the refluxing for 3 h under intensive stirring, the mixture was cooled to room temperature. The upper layer containing propyl acetate and product were separated by decanting, and the lower layer was extracted by propyl acetate (50 mL × 3). The organic layers were combined, followed by evaporation under vacuum to give N-phenylmaleimide as a pale-yellow crystal solid. Yield, 83%. 1H NMR (300 MHz, CDCl3) delta 7.47 (t, 2H), 7.33-7.39 (t, 3H), 6.85 (s, 2H).To the reaction mixture, a previously formed solution containing 70 ml of dimethylformamide, 11.4 g (0.0803 moles) of phosphorus pentoxide and 5 g (0.049 moles) of sulfuric acid, was added dropwise with the use of a dropping funnel. Thereafter, the reaction was continued at 70 C. for 2 hours. After cooling to room temperature, the resulting reaction mixture was poured into 400 ml of ice water to precipitate N-(p-hydroxyphenyl) maleimide in the form of crystals. The crystals were separated by filtration, washed with water and then dried to obtain 31.3 g (0.165 moles) of N-(p-hydroxyphenyl) maleimide (yield 82.5%).Example 3 4-hydroxyphenylmaleimide To a solution under dry N2 of 54.56 grams para aminophenol (0.5 mole) at 25 percent solids in DMF, add a solution of 49.03 grams maleic anhydride (0.5 mole) at 50 percent solids in DMF at a rate sufficient to keep the temperature below 70 C. Stir solution 15 minutes. Add 122.51 grams acetic anhydride (1 mole+20% molar excess) and 9.84 grams sodium acetate (0.1 mole+20% molar excess). Heating the resulting mixture to 50 C. and maintain for 1.5 hours. At this point, the whole mass yields a yellow precipitate. Filter the cool precipitate, wash well with water, dry in vacuum oven at 40 C. overnight. The product achieved has a melting point of 158-162 C.General procedure: Compounds 8a-g and 10a-e were prepared as follows: isopropyl alcohol (20 mL) was added to a mixture of indole (4) (1.172 g, 10 mmol, 1 eq), 1-tetralone (5) (1.33 mL, 10 mmol, 1 eq), N-phenylmaleimide (7) (1.732 g, 10 mmol, 1 eq) and p-toluenesulfonic acid (0.380 g, 2 mmol, 0.2 eq). 9a-g were prepared similarly: isopropyl alcohol (20 mL) was added to a mixture of indole (4) (1.172 g, 10 mmol, 1 eq), 4-chromanone (6) (1.482 g, 10 mmol, 1 eq), N-phenylmaleimide (7) (1.732 g, 10 mmol, 1 eq) and p-TsOH (0.380 g, 2 mmol, 0.2 eq). The reaction mixture was heated at reflux for three days under a nitrogen atmosphere, and in the absence of light. Upon completion, a solid reaction mixture was cooled down and filtered with IPA (15 mL) and water (5 mL). The crude material was triturated with IPA (20 mL) three times in the absence of light to give a solid. If further purification was necessary, recrystallization with a mixture of dichloromethane and pentane was performed. In the case of 6 derivatives (9a-g) solubility was found to be very poor, and thus recrystallization was performed with a mixture of tetrahydrofuran and pentane. Using this procedure 8a-g, 9a-g, and 10a-e were synthesized.General procedure: Compounds 8a-g and 10a-e were prepared as follows: isopropyl alcohol (20 mL) was added to a mixture of indole (4) (1.172 g, 10 mmol, 1 eq), 1-tetralone (5) (1.33 mL, 10 mmol, 1 eq), N-phenylmaleimide (7) (1.732 g, 10 mmol, 1 eq) and p-toluenesulfonic acid (0.380 g, 2 mmol, 0.2 eq). 9a-g were prepared similarly: isopropyl alcohol (20 mL) was added to a mixture of indole (4) (1.172 g, 10 mmol, 1 eq), 4-chromanone (6) (1.482 g, 10 mmol, 1 eq), N-phenylmaleimide (7) (1.732 g, 10 mmol, 1 eq) and p-TsOH (0.380 g, 2 mmol, 0.2 eq). The reaction mixture was heated at reflux for three days under a nitrogen atmosphere, and in the absence of light. Upon completion, a solid reaction mixture was cooled down and filtered with IPA (15 mL) and water (5 mL). The crude material was triturated with IPA (20 mL) three times in the absence of light to give a solid. If further purification was necessary, recrystallization with a mixture of dichloromethane and pentane was performed. In the case of 6 derivatives (9a-g) solubility was found to be very poor, and thus recrystallization was performed with a mixture of tetrahydrofuran and pentane. Using this procedure 8a-g, 9a-g, and 10a-e were synthesized.

Molecular Weight:189.17
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:189.042593085
Monoisotopic Mass:189.042593085
Topological Polar Surface Area:57.6
Heavy Atom Count:14
Complexity:272
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes