Chemical Properties
Off-white powder
Uses
2-Chloro-5-(trifluoromethyl)benzoic acid may be used as surrogate standard to investigate the pesticide exposure and home contamination in urine and hand wipe samples collected from farmers.
General Description
2-Chloro-5-(trifluoromethyl)benzoic acid is a carboxylic acid building block.
Synthesis
Under nitrogen protection, n-BuLi (2.5 M hexane solution, 22 mL, 55 mmol) was added dropwise to a stirred solution of 4-chlorobenzotrifluoride (9.177 g, 50.8 mmol) and TMEDA (6.3030 g, 54.2 mmol) in THF (89 mL) over a period of 8 min, keeping the reaction temperature at -78 °C. After 52 min of reaction, the reaction solution was transferred via cannula to a vessel containing dry ice (~200 g) within 20 min. Care was taken to keep the cannula fully lagged to prevent rapid darkening of the anion solution on slight warming. The mixture was slowly warmed to room temperature and the solvent was evaporated (temperature controlled at <30°C) to give an orange to yellow solid. The solid was dissolved in water (70 mL) and the aqueous layer was washed with ether (3 x 30 mL). Subsequently, the aqueous layer was adjusted to pH 1 with acid and extracted with DCM (3 x 30 mL). The organic layers were combined, evaporated to dryness (<30°C), and the residue was dissolved in refluxed hexane, hot-filtered and cooled to 4°C for overnight crystallization. The first sand-colored solids (4.5243 g) were obtained by vacuum filtration. The mother liquor was concentrated to half volume to give a second batch of lemon yellow crystals (2.2998 g). The two batches were dried under vacuum to give 4.5030 g and 2.2093 g, respectively, for a total yield of 6.712 g (59%).LCMS analysis showed a purity of 96.3 Apercent (at 254 nm) for the first batch and 95.1 Apercent for the second batch, [M + H] + 225.0, at an Rt = 5.94 min. No starting material was detected.
References
[1] Tetrahedron Letters, 1996, vol. 37, # 16, p. 2767 - 2770
[2] Patent: EP2468746, 2012, A1. Location in patent: Page/Page column 6
[3] Patent: WO2012/85654, 2012, A1. Location in patent: Page/Page column 6; 7
[4] Patent: WO2013/38259, 2013, A1. Location in patent: Page/Page column 11-12
