2-Hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone

2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone is an aromatic ketone.

Taking a 25 ml Schlenk reaction tube, adding N - bromo succimide (NBS) 18 mg (0.1mmol) as catalyst, 4' - (2 - hydroxy ethoxy group) -2 - methylpropiophenone 105 mg (0.5mmol), dimethyl sulfoxide (DMSO) 1 ml as the oxidizing agent, carbonylating and solvent, for 100 °C stirring for 24 hours. After the reaction by adding ethyl acetate 15 ml, salt water 3 ml, ethyl acetate 3 times, the combined organic phase, column chromatography separation to obtain 2 - hydroxy -4 ' - (2 - hydroxy ethoxy group) -2 - methylpropiophenone pure product 103 mg, yield 92percent.44.1 g (0.5 mol) of 4-(2-hydroxyethoxy)isobutyrophenone, 300 mL of dichloroethane and 283.3 g (2.5 mol) of 30percent hydrogen peroxide solution were uniformly mixed and placed in a microwave reactor (power of 500 W). , Stir vigorously, and control the reaction temperature at about 30 °C reaction, using TLC or GC to monitor the reaction, the reaction is complete, the microwave radiation, the reaction system was slowly added sodium bisulfite aqueous solution (containing 146g of sodium bisulfite), The reaction was extirpated for 2 h, allowed to stand, separated, and the organic phase was washed with water. The solvent was recovered by decompression at atmospheric pressure, and the residue was recrystallized from methanol.The white solid 2-hydroxy-1-(4-(2-hydroxyethoxy)phenyl)-2-methyl-1-propanone 79.6 g was obtained, HPLC content was 99.1percent, yield 71.0percent.In the clean 3LFour reaction bottles, add water 400 g, Stir intoSodium hydroxide400 g (10 mol), After the sodium hydroxide is completely dissolved, That is, the mass fraction of 50percent sodium hydroxide solution, Control reaction temperature 30 , Slowly drop A: 408 g(1.63 mol) / carbon tetrachloride: 276 g (1.63 mol) / DMAC: 61 g, Control reaction temperature 30 reverseShould be 24h, The reaction ends with thickThe pH of the reaction solution was adjusted to neutral by hydrochloric acid, followed by the addition of 1.4 LofMethyl acetate, Stir for 10 minutes, Filter the by-product of sodium chloride in the feed, Filtrate static stratification, The lower aqueous phase is further added to 1LOf methyl acetate extraction once, After combining the organic phase, Atmospheric pressure recovery of methyl acetate to recover the application, When the amount of methyl acetate is relatively small, To vacuum concentration, Control temperature of 70 , Vacuum 0.08Mpa, After concentrating for half an hour, the mass of the residue is twice as high as that of the residual solution1, 2-dichloroethane, Stirring down to 0 crystallization, And the temperature is maintained for 2 h, Filtered crude product A wet weight 395 g, drying 315 g, The content is greater than 97percent and the molar yield is about 85percent.(3) crude C is refinedAdd 630 g of dichloroethane in a clean 1 L three-necked reaction flask, add the crude C315 g to the mixture, and then raise the temperature to 55 ° C, After the crude product was completely dissolved, 31.5 g of activated char was added, stirred for 1 hour with stirring, then filtered and washed with 50 g of dichloroethaneFilter cake, and finally combined filtrate and lotion into a clean 1L three mouth reaction flask, stirring down to 5 crystallization, filtration finishedDry weight 280 g, content greater than 99percent.(2) Weigh 6.76g of the above intermediate, 9.96g of 2959 photoinitiator, 100ml of dimethylformamide (DMF) and methanesulfonic acid, Under stirring and under the protection of nitrogen, the temperature was raised to 105 C to start the reaction.The reaction time is 4h.Add 80ml of dichloromethane to dissolve the product, Wash twice with 50ml saturated saline, Wash twice with 50ml of deionized water, The dried organic phase was further purified by column chromatography.The developing solvent is a mixed solvent of petroleum ether and ethyl acetate.The ratio is v (petroleum ether): v (ethyl acetate) = 2: 1, Dried to give yellow powder 10.85g, The yield was 70.87%Put 23.8 g (0.1 mol) of 2-hydroxy-1- (2-methyl-4- (2-hydroxyethoxy) phenyl) -2-methylpropane-1-one in a 250 ml three-necked flask, 150 ml of dichloromethane and 10.1 g (0.1 mol) of triethylamine were added.After stirring well, 18 g (0.1 mol) of 3- (4-methylphenyl) acryloyl chloride was added, and the reaction was stirred at room temperature for 3 h. Then, 10.1 g (0.1 mol) of triethylamine was added to the reaction flask, After stirring well, 19.6 g (0.1 mol) of 3- (4-methoxyphenyl) acryloyl chloride was added to the reaction flask, and the temperature was raised to 35 C., and the reaction was performed for 4 hours.The filtrate was washed with dilute hydrochloric acid (5%), saturated aqueous sodium bicarbonate solution and distilled water in this order, and then dried over anhydrous sodium sulfate overnight, then filtered, and the organic phase was distilled off under reduced pressure.Obtained light yellow crystals, a total of 30g (54.2g), yield 70%, This product was confirmed to be the title compound by 1H-NMR spectrum.Put 22.4g (0.1mol) of 2-hydroxy-1- (4- (2-hydroxyethoxy) phenyl) -2-methylpropane-1-one in a 250ml three-necked bottle, 100 ml of dichloromethane and 10.1 g (0.1 mol) of triethylamine were added.After mixing well, 21.2 g (0.1 mol) of 3- (4- (methylthio) phenyl) acryloyl chloride was added, and the reaction was stirred at room temperature for 3 h.Then, the reaction solution was filtered, and the filtrate was sequentially washed with dilute hydrochloric acid (5%), saturated aqueous sodium hydrogen carbonate solution and distilled water, and then dried overnight with anhydrous sodium sulfate, and then filtered. The organic phase was distilled off under reduced pressure.Light yellow crystals were obtained, a total of 30 g, yield 75%, This product was confirmed to be the title compound by 1H-NMR spectrum.Put 22.4g (0.1mol) of 2-hydroxy-1- (4- (2-hydroxyethoxy) phenyl) -2-methylpropane-1-one in a 250ml three-necked bottle, 100 ml of dichloromethane and 2.4 g (0.1 mol) of sodium hydride were added.After stirring well, 33.2 g (0.2 mol) of cinnamoyl chloride was added, and the reaction was stirred at room temperature for 3 h.Then, the reaction solution was filtered, and the filtrate was sequentially washed with dilute hydrochloric acid (5%), saturated aqueous sodium hydrogen carbonate solution and distilled water, and then dried overnight with anhydrous sodium sulfate, and then filtered. The organic phase was distilled off under reduced pressure.Obtained pale yellow crystals, a total of 40 g, yield 83%, This product was confirmed to be the title compound by 1H-NMR spectrum.2-hydroxy-1- (4- (2-hydroxyethoxy) phenyl) -2-Dimethylpropanone(Darocur 2959)(33.69g, 0.15mol), maleic anhydride (9.81g, 0.1mol), Catalyst anhydrous AlCl3 (10.67, 0.08 mol) and 100 ml of toluene solution were added to a 250 ml three-necked flask equipped with a mechanical stirring and constant pressure dropping funnel, and stirred at 90 C for 60 min.After the reaction, the solid impurities were removed by filtration, and the water phase was removed by washing with water and liquid separation three times.The toluene was removed by rotary evaporation, and finally the solvent and water were removed by vacuum drying.Intermediate A was obtained; Intermediate A and 2, 3-dimercaptosuccinic acid (18.2 g, 0.1 mol) dissolved in 60 ml of acetonitrile were then added to a 250 ml four-necked flask equipped with a mechanical stirring and constant pressure dropping funnel Under nitrogen, stir at 40 C, monitor the progress of the reaction by TLC, remove the solvent by suspension distillation, It is further purified by gel column separation, and the pure product 1 is finally obtained.The structure was identified by nuclear magnetic resonance spectroscopy.Dissolve 12 g of 80-100 mesh magnesium powder in 100 ml of DMF solvent.Stirring to -20 C under nitrogen atmosphere, 9.8 g of cyclohexanone and 23.46 g4-Hydroxyethyltrichloromethylbenzene is dissolved in 40 ml of DMF solvent.Slowly dripping into the system of the first step, Maintain system temperature below -20 ~ -10 C for 2 hours, Naturally warmed to room temperature, filtered, washed with water, extracted with petroleum etherAdd 30% NaOH 20g aqueous solution and tetrabutylammonium bromide 0.2g, Control the reaction temperature to 50 C for two hours, wash, Desolvation and recrystallization gave the product 17.5 g, purity 98.5%, yield 78%.The compound 2, 2?-[carbonothioylbis(thio)]bis[2- methylpropanoic acid] was prepared according to Chakraborty et al., Macromolecules, 47(13), 4186-4198 (2014). 1.23 g (4.36 mmol) 2, 2?-[carbonothioylbis(thio)]bis [2-methylpropanoic acid] and 3.93 g (15 mmol) triphenyl phosphine were dissolved in 25 ml THF. The mixture was stirred for 30 minutes at room temperature. 3.48 g (15.5 mmol) IrgacureTM 2959 in 25 ml THF was added and the mixture was cooled to 0 C. 6.53 g (15 mmol) of solution of 40 w % diethylazodicarboxylate in toluene was added while the temperature was kept below 10 C. The mixture wasallowed to heat to room temperature and the reaction was allowed to continue for 16 hours at room temperature. The solvent was removed under reduced pressure and INIRAFT-4 was purified by preparative column chromatography on a GraceResolveTM column, using a gradient elution from methylene chloride to methylene chloride/ethyl acetate 50/50. 0.65 g of INI-RAFT-4 was isolated (TLC analysis on LiChrospherTM RP-18WF254 supplied by MERCK, eluent methanol/1M NaC1:R10.21). The molecular mass was confirmed using the TLC-MS methodology described above.0.72 g (3.2 mmol) IrgacureTM 2959 and 0.89 g (3.2 mmol) 4-cyano-4-[(phenylthioxomethyl)thio]pentanoic acid were dissolved in 10 ml methylene chloride. The mixture was cooled to 0 C. and 1.32 g (6.4 mmol) dicyclohexyl carbodiimide and 0.08 g (0.64 mmol) 4-dimethylamino- pyridine in 5 ml methylene chloride were added. The reaction was allowed to continue for 16 hours at room temperature. The precipitated dicyclohexyl ureum was removed by filtration. The methylene chloride fraction was washed twice with 25 ml iN hydrochloric acid and once with 25 ml water. The organic fraction was dried over Mg504 and the solvent was evaporated under reduced pressure. INI-RAFT-9 was purified with preparative colunm chromatography on a ChromabondTM flash MN column supplied by MACHEREY-NAGEL GmbH. 0.25 g of INIRAFT-9 was isolated (TLC analysis on Silica gel 60F254, supplied by MERCK, eluent methylene chloride/ethyl acetate 90/10 R10.44). The molecular mass was confirmed using the TLC-MS methodology described above.

Molecular Weight:224.25
XLogP3:0.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:5
Exact Mass:224.10485899
Monoisotopic Mass:224.10485899
Topological Polar Surface Area:66.8
Heavy Atom Count:16
Complexity:229
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes