Chemical Properties
Class white powder
Uses
2,6-Dibromobenzoic Acid is a reactant used in the synthesis of a novel inhibitor of amyloid secretion.
Synthesis
The general procedure for the synthesis of 2,6-dibromobenzoic acid from carbon dioxide and m-dibromobenzene was carried out as follows: the synthesis was carried out with reference to the literature method (Varcoe, J.R. et al., Chem. Mater. 2007, 19, 2686-2693). The procedure was as follows: anhydrous tetrahydrofuran (THF, 400 mL) was added to a two-necked round-bottomed flask under argon protection and cooled to 0 °C in an ice-water bath. Subsequently, n-butyllithium (2.5 M hexane solution, 117 mL) was added, followed by the slow addition of diisopropylamine (45 mL) at 0 °C to produce lithium diisopropylammonium (LDA). The reaction mixture was stirred for 45 min and then transferred to a dry ice/acetone bath to cool to -78 °C. At this temperature, 1,3-dibromobenzene (50.0 g, 0.212 mol) was added dropwise for a controlled period of 5 minutes and stirring was continued for 1 hour. Next, dry ice was sealed in a glass container and connected to the reaction mixture via a syringe. After bubbling gaseous CO2 into the reaction mixture for 45 min, dry ice was added. The reaction mixture was allowed to slowly warm up to room temperature. Aqueous sodium hydroxide solution (0.5 M) and ethyl acetate (400 mL) were added until all solids were dissolved. The aqueous layer was washed with ethyl acetate and acidified with concentrated hydrochloric acid to pH ≈ 1. The precipitate was dissolved in fresh ethyl acetate, washed with brine, dried over MgSO4, filtered and the solvent was evaporated under vacuum at 40°C. The solvent was then dried over MgSO4 and filtered. The resulting oil was cooled to room temperature and allowed to crystallize. The solid was boiled in hexane (2 L) for 1 hour and then cooled to room temperature. The solid was collected, washed with hexane and dried under vacuum at 80 °C to give 2,6-dibromobenzoic acid (39.3 g, 66% yield) as an off-white powder.1H NMR (500 MHz, DMSO-d6) δ 7.70 (d, J = 8.1 Hz, 2H), 7.29 (t, J = 8.1 Hz, 1H). 13C NMR (125 MHz, DMSO-d6) δ 166.87, 138.67, 131.87, 131.65.
References
[1] European Journal of Organic Chemistry, 2003, # 23, p. 4625 - 4629
[2] Organic Letters, 2009, vol. 11, # 5, p. 1051 - 1054
[3] Angewandte Chemie - International Edition, 2016, vol. 55, # 15, p. 4818 - 4821
[4] Angew. Chem., 2016, vol. 128, # 15, p. 4898 - 4902,5
[5] Patent: WO2017/117678, 2017, A1. Location in patent: Page/Page column 29; 34; 35
