Synthesis
General procedure for the synthesis of 4-methyl-2-nitrobenzoic acid from 2,5-dimethylnitrobenzene: 1,4-dimethyl-2-nitrobenzene (907 mg, 6 mmol, 1.0 eq.) and sodium hydroxide (1.8 g, 45.0 mmol, 7.5 eq.) were added to a 100 mL autoclave with 10 mL of 80% (v/v) aqueous ethanol (8 mL of ethanol mixed with 2 mL of water). After oxygenation three times, oxygen was passed to a pressure of 1.8 MPa. The reaction was carried out in an oil bath at a controlled temperature of 65 °C for 24 h. After the reaction was completed, the reaction was diluted with methanol. After completion of the reaction, the reaction mixture was diluted with methanol and the pH was adjusted to 2-3. The solvent was removed by distillation under reduced pressure. Ethyl acetate was added for extraction and the organic phase was dried and filtered. The product was separated by column chromatography and 129 mg (0.85 mmol) of unreacted 1,4-dimethyl-2-nitrobenzene was recovered, giving 86% conversion of 1,4-dimethyl-2-nitrobenzene. The target product 4-methyl-2-nitrobenzoic acid 811 mg (4.48 mmol) was obtained in 75% yield.
References
[1] Patent: CN106995374, 2017, A. Location in patent: Paragraph 0031; 0032; 0033; 0034; 0035; 0036; 0037-0042
[2] Journal of Organic Chemistry, 2018, vol. 83, # 15, p. 8092 - 8103
