1-(2-HYDROXY-ETHYL)-PYRROLE-2,5-DIONE

A 0.19 mol (4Og) sample of the HEMI-A from above was mixed with 227g of xylene and 0.005g methyl hydroquinone (MEHQ), an antioxidant. After heating under reflux and nitrogen sparging for 3 hours 15 minutes at 130The synthesis of 1-(2-Hydroxyethyl)-1H-pyrrole-2, 5-dione (5) was carried out following methods reported in a previous publication [43]. In a 50mL round-bottom flask adapted with a flux condenser and magnetic stirring, the intermediate 4 (2.30g, 10.99mmol) was combined with toluene (30mL). The reaction was refluxed for 7h. The resulting mixture was immediately filtered, and the product crystallised from toluene in 81percent yield (1.25g, 8.87mmol). Maleic anhydride 0.6mmol weighed into three neck round bottom flask, dissolve with 5ml of acetone, 0.66mmol ethanolamine with 5ml of acetone was dissolved by constant pressure funnel was slowly added dropwise three-necked flask, with magnetic stirring. After the reaction at room temperature for 1h , the acetone solvent was removed by rotary evaporation, use 5ml of toluene as a solvent, 0.012g of anhydrous sodium acetate were added to the reaction system, 0.2ml of triethylamine, 0.018 g of hydroquinone, 115 deg.] C was slowly warmed to reflux for 2.5h, tracing the reaction by thin layer chromatography on silica plates.After the reaction was cooled to room temperature, the solvent was removed by rotary evaporation, to obtain a concentrate, the concentrate was subjected to silica gel column chromatography (eluent: VMaleic anhydride 0.6mmol weighed into three neck round bottom flask, dissolve with 5ml of acetone, 0.66mmol ethanolamine with 5ml of acetone was dissolved by constant pressure funnel was slowly added dropwise three-necked flask, with magnetic stirring. After the reaction at room temperature for 1h , the acetone solvent was removed by rotary evaporation, use 5ml of toluene as a solvent, 0.012g of anhydrous sodium acetate were added to the reaction system, 0.2ml of triethylamine, 0.018 g of hydroquinone, 115 deg.] C was slowly warmed to reflux for 2.5h, tracing the reaction by thin layer chromatography on silica plates.After the reaction was cooled to room temperature, the solvent was removed by rotary evaporation, to obtain a concentrate, the concentrate was subjected to silica gel column chromatography (eluent: VPetroleum ether: VEthyl acetate= 12: 1), and collecting the target fluid, the rotation solvent in vacuo to give the desired product.Yield 30percent.Under an atmosphere of argon, compound 5 (98.0 mg, 98.0 mol) was dissolved in drytetrahydrofuran (6 mL) and dry triethylamine (68 L, 490 mol). The mixture was stirred at room temperature for 30 min and then cooled to 0 C. Consecutively, N(2-hydroxyethyl)maleimide (13.8 mg, 98.0 mol), 2-chloromethylpyridinium iodide (CMPI, 33.2 mg, 130 mol) and 4-dimethylaminopyridine(5.50 mg, 45.0 mol) were given into the reaction which thereupon was allowed to warm to roomtemperature and stirred overnight. After 18 h, the reaction was quenched with aqueous HCl (0.36 M, 20 mL), the phases were separated, the aqueous layer was extracted with dichloromethane (2 10 mL) and the combined organic layers were concentrated under reduced pressure. According toMALDI-(+)-MS (Figure S1), this crude product mixture was composed of Finland trityl substrate, theone-fold and the two-fold 2-hydroxyethylmaleimide ester products. The crude product was coatedonto silica gel (w/w = 1/3), packed into a cartridge which was mounted on a reversed phase column(Buechi FlasPure EcoFlex C18, 20 g, Buechi, Essen, Germany) and eluted with an acetonitrile gradient(10-100%) in deionized water (Figure S2). The product was isolated (Figures S3-S5) as a brown solidin a yield of 21% (22.7 mg, 20.2 mol). Figure S6 shows UV/Vis and cw EPR spectra of the isolatedcompound 9 in buer solutions. Figure S7 displays cw EPR spectra of compound 9 dissolved in organicsolvents and revealing a A(1H) hyperfine coupling constant of 0.28 MHz and a giso-value of 2.0035.

Molecular Weight:141.12
XLogP3:-0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:141.042593085
Monoisotopic Mass:141.042593085
Topological Polar Surface Area:57.6
Heavy Atom Count:10
Complexity:179
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes