Uses
3,5-Difluoro-4-hydroxybenzaldehyde is used in the preparation of (Z)-2,6- difluoro-((2-methyl-5-oxooxazol-4(5H)-ylidene)methyl)phenylacetate.
Synthesis
The compound was prepared based on the method described by Lawrence et al [29] with the following modification: 2,6-difluorophenol (0.300 g, 2.3 mmol) was dissolved in hexamethylenetetramine (urotropine, 0.323 g, 2.3 mmol) in trifluoroacetic acid (3.5 mL, 45.7 mmol) under argon gas protection and the reaction was carried out at reflux for 15 hours. After completion of the reaction, the mixture was concentrated, mixed with 15 mL of ice water and stirred for 30 min. Subsequently, the aqueous phase was alkalized with Na2CO3 and extracted with dichloromethane. The aqueous phase was further acidified with 1 mol/L HCl, followed by four extractions with dichloromethane. The organic phases were combined, dried with anhydrous MgSO4 and concentrated under reduced pressure. The final 3,5-difluoro-4-hydroxybenzaldehyde was obtained as a milky white solid (0.212 g, 58% yield) with a melting point of 116-118 °C.
References
[1] Journal of Fluorine Chemistry, 2003, vol. 123, # 1, p. 101 - 108
[2] Journal of Molecular Liquids, 2018, vol. 264, p. 327 - 336
[3] South African Journal of Chemistry, 1997, vol. 50, # 1, p. 40 - 47
[4] Chemical Communications, 2011, vol. 47, # 22, p. 6449 - 6451
[5] Journal of Medicinal Chemistry, 1989, vol. 32, # 2, p. 450 - 455
