Uses
2-Bromo-5-fluorobenzaldehyde is used as a precursor for the synthesis of 5-fluoro-3-substituted benzoxaboroles, which is used in material science as molecular receptors, building block in crystal engineering, as steroid conjugates for molecular imprinting , dyes and biosensors of alpha hydroxyl carboxylic acids. It is also used in the synthesis of 5-arylindazolo[3,2-b]quinazolin-7(5H)-one by reacting with 2-amino-N'-arylbenzohydrazide in the presence of Copper(I) bromide by the Ullmann-type reaction.
Synthesis
General procedure for the synthesis of 2-bromo-5-fluorobenzaldehyde from 2-bromo-5-fluorobenzyl alcohol: to a solution of 2-bromo-5-fluorobenzyl alcohol (0.852 g, 4.156 mmol) in dichloromethane (15 mL) was added manganese dioxide (4.254 g, 85%, 41.56 mmol). The reaction mixture was stirred at room temperature for 48 h. The solid was subsequently separated by filtration and washed with dichloromethane. The filtrate was concentrated to give 777 mg of 2-bromo-5-fluorobenzaldehyde (92% yield). Subsequently, the newly prepared 2-bromo-5-fluorobenzaldehyde (0.777 g, 3.828 mmol) was dissolved in anhydrous tetrahydrofuran (10 mL) and the solution was cooled to 0 °C. At low temperature, trifluoromethyltrimethylsilane (1.13 mL, 7.656 mmol) and tetrabutylammonium fluoride (0.020 g, 0.076 mmol) were added sequentially. After that, the reaction mixture was slowly warmed up to room temperature and stirring was continued at that temperature for 5 hours. After completion of the reaction, the reaction mixture was diluted with ethyl acetate, washed sequentially with water and brine and dried with magnesium sulfate. The solvent was removed under reduced pressure to afford 1.1 g (90% purity) of the crude product of 2-bromo-5-fluorophenyl-2,2,2-trifluoroethanol, which could be used in subsequent steps without further purification.
References
[1] New Journal of Chemistry, 2017, vol. 41, # 22, p. 13377 - 13381
[2] Patent: US2008/153852, 2008, A1. Location in patent: Page/Page column 23
[3] RSC Advances, 2014, vol. 4, # 25, p. 12834 - 12839
[4] Tetrahedron, 2015, vol. 71, # 38, p. 6744 - 6748
[5] Patent: CN104817441, 2017, B. Location in patent: Paragraph 0050-00053
