Uses
5-Bromo-2-iodobenzaldehyde is a useful synthetic intermediate. It is used to prepare aza-fused polycyclic quinolines via copper-catalyzed cascade intermolecular condensation. It is also used in the synthesis of oxoindenopyrroles via copper-catalyzed tandem cycloaddition and coupling of iodoarylynones with isocyanides.
Synthesis
General procedure for the synthesis of 5-bromo-2-iodobenzaldehyde from (5-bromo-2-iodophenyl)methanol: Oxalyl chloride (1.99 mL, 23.04 mmol, 1.6 eq.) was dissolved in dichloromethane (DCM, 25 mL) under drying conditions and cooled to -70°C. In another vessel, DMSO (2.44 mL, 34.5 mmol, 2.4 eq.) was dissolved in DCM (25 mL) and similarly cooled to -65°C to -70°C. The DMSO solution was slowly added to the oxalyl chloride solution under nitrogen protection, keeping the temperature at -70 °C and stirring for 10 min. Subsequently, a solution of (5-bromo-2-iodophenyl)methanol (4.55 g, 14.4 mmol, 1.0 eq.) in DCM (100 mL) was added and the reaction mixture was continued to be stirred at -65 °C for 15 min. Next, triethylamine (10 mL, 72 mmol, 5.0 eq.) was added and the reaction mixture was gradually warmed to -10 °C and stirred at this temperature for 1 hour. Upon completion of the reaction, the reaction was quenched by the addition of water (40 mL) and the mixture was gradually warmed to room temperature. The organic layer was separated and concentrated by evaporation to give 5-bromo-2-iodobenzaldehyde (4.2 g, 93% yield) as a white solid. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 7.45 (d, J = 7.6 Hz, 1H), 7.81 (d, J = 11.6 Hz, 1H), 7.98 (d, J = 1.6 Hz, 1H), 9.97 (s, 1H).
References
[1] Organic Letters, 2008, vol. 10, # 14, p. 3001 - 3004
[2] Tetrahedron, 2011, vol. 67, # 1, p. 125 - 143
[3] Organic Letters, 2016, vol. 18, # 9, p. 2126 - 2129
[4] Patent: WO2018/15879, 2018, A1. Location in patent: Page/Page column 81-82
[5] Patent: US2004/92521, 2004, A1. Location in patent: Page/Page column 19-20; 46
