2-Methyl-4-(2-methylbenzamido)benzoic acid

Chemical Properties

off-white to white powder

Uses

2-Methyl-4-(2-methylbenzamido)benzoic acid is a synthetic drug that has oxidizing properties. It is used as an intermediate in the synthesis of medicines, and can also be used as an intermediate in the synthesis of dyes and pesticides. The structure of this molecule consists of two methyl groups on a benzene ring with two aminobenzoic acid molecules attached to it. This molecule has hydrogen bonds with both aminobenzoic acid groups, one of which has an alkyl group attached to it. 2-Methyl-4-(2-methylbenzamido)benzoic acid crystallizes in the monoclinic system and its molecular weight is 256.24 g/mol.

Synthesis

79-37-8

317374-08-6

General procedure for the synthesis of 2-methyl-4-(2-methylbenzoylamino)benzoic acid from oxalyl chloride: 3-(2-methylbenzoylamino)toluene (50.0 g, 0.222 mol) was dissolved in dichloromethane (50 mL) under nitrogen protection, and cooled to 3 °C. Aluminum chloride (88.8 g, 0.666 mol) was added slowly, about 10 min after addition. Maintaining the temperature at 3-7 °C, oxalyl chloride (25.2 mL, 0.289 mol) was added dropwise. The reaction mixture was stirred at 2-7 °C for 5 hours until the feedstock was completely consumed. Upon completion of the reaction, it was diluted with dichloromethane (100 mL) and the reaction was quenched by the addition of ice water. Dichloromethane was removed by distillation and the resulting aqueous suspension was refluxed for 30 minutes and cooled to room temperature. Crystals were collected by filtration and dried at 60 °C to give the crude product (58.33 g). The crude product (29.17 g) was dissolved in 2.5 mol/L aqueous sodium hydroxide solution (400 mL) and toluene (100 mL), filtered to remove insoluble matter and partitioned. The aqueous layer was washed with toluene (100 mL x 2) and neutralized with 6 mol/L hydrochloric acid (300 mL). The precipitated crystals were collected by filtration, dried at 60 °C and recrystallized from methanol (540 mL) to afford the target product 2-methyl-4-(2-methylbenzoylamino)benzoic acid (19.67 g, yield 65.8%, HPLC purity 99.4%). The structure of the product was confirmed by 1H NMR (300 MHz, DMSO-d6): δ=2.39 (3H, s), 2.53 (3H, s), 7.31 (br.t, J=7.1Hz), 7.32 (1H, d, J=7.2Hz), 7.41 (1H, br.t, J=7.2Hz), 7.47 (1H, d, J=7.2Hz ), 7.68 (br.d, J=8.2Hz), 7.69 (1H, s), 7.86 (1H, d, J=8.2Hz), 10.50 (1H, s), 12.6 (1H, br.s). The melting point was determined as 231.3-232.6 ℃, white powder.HPLC analysis conditions: the detector was ultraviolet absorber (wavelength 254 nm), the column was YMC-Pack ODS-A A-312, the mobile phase was 3 mmol/L sodium dodecyl sulfate solution/acetonitrile/phosphoric acid solution (600:400:1), the column temperature was about 25 ℃.

structure and hydrogen bonding

References

[1] Patent: WO2007/26971, 2007, A2. Location in patent: Page/Page column 38-39