2-CHLORO-3-HYDROXY-4-METHOXYBENZALDEHYDE

Uses

Reactant for:

• BODIPY fluorescent sensors

Synthesis

621-59-0

37687-57-3

Step 1 Synthesis of 2-chloro-3-hydroxy-4-methoxybenzaldehyde: 41.2 g (0.271 mol) of isovanillin was dissolved in 160 mL of 90% acetic acid under heating conditions. 29.41 g of tert-butyl hypochlorite (t-BuOCl) was added slowly and dropwise to the above solution at 35°C to 40°C. The reaction mixture was stirred at room temperature. The reaction mixture was stirred at room temperature for 3 hours, followed by the addition of 200 mL of ether. The mixture was allowed to stand overnight and the precipitated crystals were separated by filtration and washed with ether. The crude product (42.0 g) was purified by recrystallization from acetonitrile to give 35 g of 2-chloro-3-hydroxy-4-methoxybenzaldehyde in 69% yield. The melting point of the product was 203-205 °C. NMR hydrogen spectrum (90 MHz, DMSO-d6) δ: 3.94 (3H, s, OCH3), 7.10 (1H, d, Ar-H), 7.42 (1H, d, Ar-H), 9.84 (1H, s, CHO), 10.16 (1H, s, OH).

References

[1] Journal of Medicinal Chemistry, 1986, vol. 29, # 11, p. 2315 - 2325
[2] Organic Process Research and Development, 2001, vol. 5, # 1, p. 45 - 49
[3] Synlett, 2014, vol. 25, # 20, p. 2891 - 2894
[4] Journal of Organic Chemistry, 2012, vol. 77, # 2, p. 977 - 984
[5] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 6, p. 1805 - 1814