2-Chloro-4-bromopyridine

Chemical Properties

Off-white Cryst

Uses

It is used in the synthesis of quaterpyridine nemertelline.

Synthesis

Step a: Synthesis of 2-chloro-4-bromopyridine To 8.9 g (69.2 mmol) of 2-chloro-4-aminopyridine was added 81.5 mL of 48% aqueous hydrobromic acid at 0 °C. Subsequently, 33.4 g (208.75 mmol) of bromine monomer was slowly added over 10 min. The reaction mixture was cooled to -10°C and 10.65 g (154 mmol) of sodium nitrite dissolved in 20 mL of water was added dropwise over 30 min. After the dropwise addition was completed, stirring was continued at -10°C for 10 minutes and then brought to room temperature and stirred for 1.5 hours. Upon completion of the reaction, the mixture was cooled to 5°C and saturated aqueous sodium sulfite solution was added until the reaction solution was colorless. The reaction solution was adjusted to alkaline with 35% sodium hydroxide aqueous solution. The basic aqueous phase was extracted twice with diethyl ether, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated. The yellow oil obtained (13 g) was purified by silica gel column chromatography (eluent: ethyl acetate/heptane=1/9). The product was a light-colored oily substance in 52% yield. 1H NMR (CDCl3): δ 8.25 (d, 1H, J = 5Hz), 7.55 (s, 1H), 7.4 (d, 1H, J = 5Hz).

References

[1] Journal of Organic Chemistry, 2006, vol. 71, # 22, p. 8602 - 8609
[2] Synlett, 2016, vol. 27, # 1, p. 67 - 69
[3] Patent: US2006/89364, 2006, A1. Location in patent: Page/Page column 22
[4] Roczniki Chemii, 1955, vol. 29, p. 1019,1025
[5] Chem.Abstr., 1956, p. 12045