3-chlorosulfonyl-4-methyl-benzoic acid Chemical Properties

Melting point:

173 °C(Solv: chloroform (67-66-3))

Boiling point:

420.0±38.0 °C(Predicted)

Density 

1.514±0.06 g/cm3(Predicted)

storage temp. 

Inert atmosphere,Room Temperature

pka

3.17±0.10(Predicted)

Appearance

White to off-white Solid

3-chlorosulfonyl-4-methyl-benzoic acid Usage And Synthesis

Synthesis

The general procedure for the synthesis of 3-(chlorosulfonyl)-4-methylbenzoic acid from p-methylbenzoic acid was as follows: p-methylbenzoic acid (500 mg, 3.67 mmol) was added to chlorosulfonic acid (1.5 mL, 23 mmol) in batches at 0 °C. After the addition was completed, the reaction was maintained for 10 min, followed by warming the reaction mixture to 100 °C and maintaining it for 2 h. The reaction was carried out at 0 °C for 2 h. The reaction mixture was then heated up to 100 °C. At the end of the reaction, the reaction solution was slowly added dropwise onto ice and left to stand until the ice completely melted. Subsequently, the precipitated product was collected by filtration, washed with water and dried to afford 3-(chlorosulfonyl)-4-methylbenzoic acid (746 mg, 87% yield) as a light brown solid. The product was characterized by 1H NMR (400 MHz, d6-DMSO): δ 8.32 (d, J = 1.9 Hz, 1H), 7.76 (dd, J = 7.8, 1.9 Hz, 1H), 7.25 (d, J = 7.8 Hz, 1H), 5.55 (br s, 1H), 2.58 (s, 3H).LC-MS (APCI-) analysis showed : m/z 233 ([M-H]+, 35Cl, 100%), 235 ([M-H]+, 37Cl, 40%). Further, the above obtained sulfonyl chloride (82 mg, 0.35 mmol) was separated by column chromatography with sodium bicarbonate (30 mg, 0.18 mmol) in a mixed solvent of dichloromethane and methanol (initial ratio of 98:2, gradually adjusted to 19:1, and finally to 9:1) to give a yellow solid target product 6h (42 mg, 60% yield).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 5, p. 1725 - 1729
[2] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 1, p. 58 - 68
[3] Patent: WO2004/18414, 2004, A2. Location in patent: Page 132
[4] Journal of Medicinal Chemistry, 2013, vol. 56, # 15, p. 6146 - 6155
[5] ChemMedChem, 2016, vol. 11, # 8, p. 893 - 899

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