4-Bromo-2-nitrobenzaldehyde

Uses

4-Bromo-2-nitrobenzaldehyde is used along with in the synthesis of Tyrian Purple as a teaching material, from o-Nitrotoluene via 4-Bromo-2-nitrotoluene and 4-Bromo-2-nitrobenzylidene diacetate;Also, it is used as a starting material in the synthesis of heterocyclyl as HDAC3 inhibitors.

Synthesis Reference(s)

The Journal of Organic Chemistry, 72, p. 5867, 2007 DOI: 10.1021/jo070477u

Synthesis

Step A: Concentrated sulfuric acid (324 mL) was added slowly and dropwise to a solution of 4-bromo-1-methyl-2-nitrobenzene (300 g, 1.38 mol) in acetic anhydride (2400 mL) at 0 °C. Subsequently, a solution of chromium trioxide (384 g, 3.84 mol) dissolved in acetic anhydride (2160 mL) was added, keeping the internal temperature of the reaction system below 10 °C during the process. The reaction mixture was stirred for 1 hour and then slowly poured into an ice-water mixture. The solid product was collected by filtration and washed with plenty of water until the washings were colorless. The resulting solid was suspended in 1800 mL of a 2% aqueous sodium carbonate solution, stirred thoroughly and then filtered again, washed with water and finally dried under reduced pressure. [000195] The diacetate product obtained above was suspended in a mixed solution comprising 1360 mL of concentrated hydrochloric acid, 1250 mL of water and 480 mL of ethanol and refluxed for 45 minutes. After the reaction was completed, it was cooled to room temperature, the solid product was collected by filtration and washed with water. The final 4-bromo-2-nitrobenzaldehyde (147 g, 45% overall yield in two steps) was obtained as a brown solid, which could be used in the subsequent reaction without further purification.

References

[1] Patent: WO2012/97177, 2012, A2. Location in patent: Page/Page column 57-58
[2] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 7, p. 2462 - 2467
[3] Organic Preparations and Procedures International, 2006, vol. 38, # 3, p. 325 - 331
[4] Synthetic Communications, 2001, vol. 31, # 23, p. 3721 - 3727
[5] Heterocycles, 1994, vol. 39, # 2, p. 767 - 778