Uses
2-Fluoro-6-(trifluoromethyl)benzaldehyde may be employed for the synthesis of diaryl ether, 2-(3,5-dimethoxyphenoxy)-6-(trifluoromethyl)- benzonitrile and substituted benzo[
b]thiophene-2-carboxylates.
General Description
2-Fluoro-6-(trifluoromethyl)benzaldehyde participates in the synthesis of 2-amino-5-trifluoromethylquinazoline.
Synthesis
In a 5L three-necked round-bottomed flask, 3-fluorobenzotrifluoride (492.0 g, 3.0 mol), N,N,N',N'-tetramethylethylenediamine (TMEDA, 383.2 g, 3.3 mol), diisopropylamine (DIPA, 21.3 g, 0.16 mol), and anhydrous tetrahydrofuran (THF, 1.5 L) were added and the reaction system was cooled to -70 to - 78 °C. A solution of n-butyllithium (n-BuLi, 211.5 g, 3.3 mol) was slowly added dropwise at -70 to -78 °C. The reaction was maintained at this temperature for 2 to 3 hours. Subsequently, N,N-dimethylformamide (DMF, 328.7 g, 4.5 mol) was slowly added and the reaction was continued at this temperature for 1-2 hours. After completion of the reaction, it was slowly warmed up to room temperature, the reaction was quenched with saturated ammonium chloride (NH4Cl) solution (500 ml) and extracted with ethyl acetate (500 ml x 3). The organic layers were combined and concentrated to dryness to give 510.1 g of the solid product 2-fluoro-6-trifluoromethylbenzaldehyde in 88.7% yield.
References
[1] Patent: CN107935863, 2018, A. Location in patent: Paragraph 0040-0043; 0053-0054; 0060-0061
[2] Tetrahedron Letters, 1992, vol. 33, # 49, p. 7499 - 7502
[3] Tetrahedron Letters, 2013, vol. 54, # 45, p. 6053 - 6056
