4-(Methylsulfonyl)phenylacetic acid

yellow to beige-brown crystalline powder

The synthesis was carried out as described in Scheme 2. Step a. A mixture of 4-(methylsulfonyl)acetophenone (5.5 g, 27.8 mmol), morpholine (2.5 mL), and sulfur (0.89 g, 27.8 mmol) was refluxed for 10 h, and poured into ice. The precipitated solid was filtered, and washed with cold ethyl acetate. The solid was added to 10percent sodium hydroxide (55 mL), heated to 84° C. for 12 h, and the alkaline solution was acidified with 12 N HCl. The resulting solid was filtered, dried, and recrystallized from hexane-ethyl acetate (1:1) to give 4-methylsulfonylphenylacetic acid (white solid, 4.2 g, 52percent overall yield). Step b. 2-Bromoacetophenone (1.02 g, 5.12 mmol), dissolved in acetonitrile, was added to Et3N (1.74 mL), followed by 4-methylsulfonylphenylacetic acid (1 g, 4.67 mmol). After 1.5 h at room temperature, 1, 8-diazabicyclo[5, 4, 0]undec-7-ene (1.67 mL) was added. The reaction mixture was stirred for another 1 h, and then treated with 1 N HCl (35 mL). The product was extracted with ethyl acetate, dried over sodium sulfate, and recrystallized from ethyl acetate-hexane (1:1) to give 46b (880 mg, 60percent overall yield). 1H NMR (CDCl3) δ 3.08 (s, 3H), 5.24 (s, 2H), 7.18-7.30 (m, 5H), 7.66 (dd, J=1.9, 6.7 Hz, 2H), 7.96 (dd, J=1.9, 6.7 Hz, 2H); HRMS calc'd for M+ 314.0605, found 314.0632. Anal. (C17H14O4S)C, H.General procedure: Scheme I(c) In a 500 mL dry three-necked bottle, 50.0 g of 4-methanesulfonyl phenylacetaldehyde was added, 200 mL of water was added, and sodium carbonate was added.30g, add 0.5g of sodium tungstate under stirring, 70 mL of 30percent hydrogen peroxide solution was slowly added dropwise, and the reaction solution gradually became clear as the reaction proceeded.TLC test, after the end of the reaction, filtration, the filtrate was slowly added 10percent hydrochloric acid, adjust the pH to 2-3, filtered, This gave crude 4-methanesulfonylphenylacetic acid.The above 4-methylsulfonylphenyl acetic acid was dissolved in 1percent sodium hydroxide, and saturated sodium thiosulfate solution was added in 10 mL.After extracting 50 mL of ethyl acetate twice, 200 mL of ethyl acetate was added to the aqueous layer, and 10percent hydrochloric acid was added to adjust the pH to 2-3.The ethyl acetate layer was separated. The aqueous layer was extracted once with 200 mL of ethyl acetate.Combine the ethyl acetate layers, heat to reflux, add 200 mL of n-heptane, slowly cool to 0-5 °C, The mixture was stirred at this temperature for 1 hour, filtered and vacuum dried to give 54.2 g of 4-methanesulfonylphenylacetic acid. Yield: 84.0percent.

Molecular Weight:214.24
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:214.02997997
Monoisotopic Mass:214.02997997
Topological Polar Surface Area:79.8
Heavy Atom Count:14
Complexity:293
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes