Uses
2,2-Difluorocyclopropanecarboxylic acid derivative (i.e. 2,2-difluorocyclopropanecarbonyl chloride) is used in Friedel-Crafts reactions with various arenes to prepare aryl 2,2-difluorocyclopropyl ketones.
Synthesis
The general procedure for the synthesis of 2,2-difluorocyclopropanecarboxylic acid from butyl 2,2-difluorocyclopropanecarboxylate was as follows: butyl 2,2-difluorocyclopropanecarboxylate (65.0 g, 330 mmol) was dissolved in anhydrous aqueous NaOH solution (750 mL of H2O, 52.5 g of NaOH), and the reaction was carried out at reflux for about 14 h, during which a light yellow solution was formed. Upon completion of the reaction, the reaction solution was cooled to room temperature and subsequently concentrated under vacuum to about 250 mL. the residue was adjusted to pH 3-4 with concentrated aqueous hydrochloric acid (about 70 mL) in an ice bath (0-5 °C). the resulting solution was extracted with ethyl acetate (2 x 500 mL), and the organic layers were combined and dried over anhydrous sodium sulfate. Finally, the dried organic layer was concentrated under high vacuum to afford 2,2-difluorocyclopropanecarboxylic acid (30 g, 75% yield) as a yellow oil, which gradually solidified to a light yellow solid after standing. The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 10.78 (s, 1H), 2.41-2.47 (m, 1H), 2.05-2.08 (m, 1H), 1.80-1.83 (m, 1H).
References
[1] Journal of Fluorine Chemistry, 2005, vol. 126, # 3, p. 339 - 343
[2] Advanced Synthesis and Catalysis, 2018, vol. 360, # 21, p. 4104 - 4114
[3] Patent: WO2016/97918, 2016, A1. Location in patent: Page/Page column 96-97
[4] Journal of Organic Chemistry, 2011, vol. 76, # 9, p. 3450 - 3456
