Synthesis
At room temperature, 8.5 mL of N-methylformanilide (0.068 mol) was mixed with 6.3 mL of trichlorophosphorus (0.068 mol) and stirred for 40 minutes. Subsequently, 17.8 g of 2,5-dimethoxytoluene (0.117 mol) was added. The reaction mixture was heated to 50 °C and maintained for 6 hours. Upon completion of the reaction, it was cooled to 20 °C and hydrolyzed with 100 mL of 10% aqueous sodium acetate, followed by extraction with ether twice, combining the organic phases and concentrating. The residue was dissolved in aqueous sodium hydroxide and again extracted twice with ether. The aqueous phase was adjusted to pH=12 with base, and a white crystalline product 2,5-dimethoxy-4-toluylaldehyde was precipitated with a melting point of 83 °C and a yield of 67%.
References
[1] Journal of Organic Chemistry, 2012, vol. 77, # 18, p. 8231 - 8243
[2] Patent: US2004/43995, 2004, A1. Location in patent: Page 12
[3] Journal of Medicinal Chemistry, 1976, vol. 19, # 12, p. 1400 - 1404
[4] Patent: US2009/29976, 2009, A1. Location in patent: Page/Page column 22
[5] Patent: US2004/19091, 2004, A1. Location in patent: Page/Page column 6
