Formaldehyde → 4-Bromo-2-hydroxybenzaldehyde

Temperature

80 °C

A solution of 3-bromophenol (100.00 g, 0.576 mol) in a mixture of 600 mL of toluene/acetonitile (2:1) was added MgCl2 (110.6 g, 3.68 mol), paraformaldehyde (40.00 g) and the mixture was maintained at 80° C. for 1.5 h while the by-product was distilled off. A second portion of paraformaldenhyde (40.00 g) was added and the mixture was stirred for 2.5 h at 80° C., and the third portion of paraformaldenhyde (30.6 g) was added and stirred for 2 h at 80° C. The reaction was quenched with cool 2.5 N hydrochloride acid, and the mixture was stirred at room temperature for 1 h to afford a biphasic solution. The aqueous phase was extracted with EtOAc. And the combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to afford 4-bromo-2-hydroxybenzaldehyde. 1H-NMR (400 MHz, CDCl3) 11.10 (s, 1H), 9.86 (s, 1H), 7.40˜7.43 (d, J=8.4 Hz, 1H), 7.15˜7.20 (m, 2H).

1. distillationwas distilled off
2. additionA second portion of paraformaldenhyde (40.00 g) was added
3. additionthe third portion of paraformaldenhyde (30.6 g) was added
4. stirringstirred for 2 h at 80° C
5. customThe reaction was quenched
6. temperaturewith cool 2.5 N hydrochloride acid
7. stirringthe mixture was stirred at room temperature for 1 h
8. customto afford a biphasic solution
9. extractionThe aqueous phase was extracted with EtOAc
10. washAnd the combined organic extracts were washed with brine
11. dry with materialdried over anhydrous sodium sulfate
12. concentrationconcentrated
13. customThe residue was purified by silica gel column chromatography

ORD record

ord-415850b16e1b40d38230b0fb11bb71f0

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09056859B2