Uses
In the field of medicinal chemistry, 4-bromoindole-3-carbaldehyde can be used to synthesize compounds with specific biological activities, such as building blocks for drug molecules.
Synthesis
In a 500 mL three-necked round-bottomed flask, 120 mL of anhydrous N,N-dimethylformamide (DMF) was added and the temperature of the reaction system was lowered to 0 °C. Under vigorous stirring, 11 mL (0.12 mol) of phosphoryl chloride (POCl3) was slowly added dropwise. After continuing stirring for 5 min, 10 g (0.048 mol, 95% purity) of 4-bromoindole dissolved in 20 g of anhydrous DMF was added slowly dropwise. After the dropwise addition was completed, the ice bath was removed and the reaction was continued for 1 hour. At this point, the reaction mixture transformed into a viscous suspension. Subsequently, 4.7 M potassium hydroxide solution was slowly added dropwise to the reaction suspension (dropwise acceleration was controlled to maintain the reaction temperature between 65-75 °C, and cooled if the temperature was too high). After the reaction has continued for 6 hours, 20 mL of saturated sodium bicarbonate solution is added and stirring is continued for 5 minutes. The reaction mixture was diluted with ethyl acetate, dried and concentrated under reduced pressure to give crude 4-bromoindole-3-carboxaldehyde 12 g. Immediately 2.5 mL of acetone was added and heated to reflux until dissolved. Subsequently, petroleum ether with a boiling range of 60-90 °C was added at a ratio of 11 mL/g of the crude product, and white fine needle-like crystals were immediately precipitated. The mixture was kept at a low temperature of -5°C for 10 minutes. After crystallization was complete, the mixture was filtered through a sand core funnel and washed twice with petroleum ether. If there is still uncrystallized product in the filtrate, the crystallization process can be repeated by evaporating the solvent. After four crystallizations, all the white crystals of 4-bromoindole-3-carboxaldehyde were combined and air-dried to give a final product of 10.3 g in 95% yield.
References
[1] Organic Letters, 2006, vol. 8, # 23, p. 5287 - 5289
[2] Journal of the American Chemical Society, 2009, vol. 131, # 31, p. 10796 - 10797
[3] Organic Letters, 2013, vol. 15, # 21, p. 5448 - 5451
[4] Patent: CN107935905, 2018, A. Location in patent: Paragraph 0029-0031; 0034; 0038
[5] Journal of Organic Chemistry, 2016, vol. 81, # 4, p. 1723 - 1730
