Uses
2-Hydroxy-3,6-dimethylbenzaldehyde
Synthesis
To a solution of 2,5-dimethylphenol (7.0 g, 57.3 mmol) in acetonitrile (250 mL) was sequentially added triethylamine (30.1 mL, 0.212 mol) and magnesium chloride (8.17 g, 86 mmol). The reaction mixture was stirred at room temperature for 15 minutes before adding paraformaldehyde (11.5 g, 0.38 mol). Subsequently, the mixture was heated to 80 °C and kept for 20 hours. After completion of the reaction, acetonitrile was removed by distillation under reduced pressure. A 10% hydrochloric acid solution was added to the residue and stirred for 30 min at room temperature. The mixture was extracted with dichloromethane (2 x 40 mL), the organic layers were combined and dried over anhydrous sodium sulfate. The organic phase was concentrated under reduced pressure and the resulting crude product was purified by fast column chromatography on silica gel (eluent: dichloromethane) to afford the target product 3,6-dimethyl-2-hydroxybenzaldehyde (27a) (3.56 g, 23.7 mmol, 42% yield). The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 2.21 (s, 3H), 2.57 (s, 3H), 6.62 (d, J = 8.0 Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H), 10.30 (s, 1H), 12.18 (s, 1H).
References
[1] Journal of Organometallic Chemistry, 2005, vol. 690, # 23, p. 5125 - 5144
[2] Journal of the Chemical Society, Perkin Transactions 2, 2001, # 9, p. 1573 - 1584
[3] Patent: WO2012/140243, 2012, A1. Location in patent: Page/Page column 137-138
[4] Journal of Organic Chemistry, 2013, vol. 78, # 14, p. 6890 - 6910
[5] Patent: US2016/152543, 2016, A1. Location in patent: Paragraph 1197; 1198; 1199
