Dichloromethane → 5-Bromo-2-methylbenzaldehyde

Temperature

5 °C

To a suspension of 344 g (2.58 mol, 1.5 eq.) of AlCl3 in 1100 cm3 of dichloromethane 206.8 g (1.72 mol) of 2-methylbenzaldehyde was added dropwise by vigorous stirring for 15 min at 5° C. The resulting mixture was stirred for 15 min at 5° C., and then 88.9 ml (276 g, 1.73 mol) of bromine was added for 1 h at this temperature. The final mixture was additionally stirred for 6 h at room temperature and then poured on 2 kg of ice. The organic layer was separated, the aqueous layer was extracted with 2×200 ml of dichloromethane. The combined organic extract was washed by aqueous NaHCO3, dried over Na2SO4, and then evaporated to dryness to yield reddish liquid. This crude product was distilled in vacuum, b.p. 100-120° C./5 mM Hg. The obtained colorless liquid (which completely crystallizes at 5° C.) was dissolved in 900 ml of n-hexane. Crystals precipitated from this solution for 3 days at 5° C. were collected and dried in vacuum. On the evidence of NMR spectroscopy this mixture consists of 5-bromo-2-methylbenzaldehyde and 3-bromo-2-methylbenzaldehyde in ratio equal ca. 3 to 1. This mixture was recrystallized from 500 ml of hot n-hexane. White crystals precipitated at 5° C. were collected, washed by 150 ml of cold (+5° C.) n-hexane, and dried in vacuum (˜60° C./20 mM Hg) to give colorless liquid which crystallizes at room temperature. Yield 80.9 g (24%) of 5-bromo-2-methylbenzaldehyde including ca. 2% of 3-bromo-2-methylbenzaldehyde.

1. additionwas added dropwise
2. stirringThe resulting mixture was stirred for 15 min at 5° C.
3. customThe organic layer was separated
4. extractionthe aqueous layer was extracted with 2×200 ml of dichloromethane
5. extractionThe combined organic extract
6. washwas washed by aqueous NaHCO3
7. dry with materialdried over Na2SO4
8. customevaporated to dryness
9. customto yield reddish liquid
10. distillationThis crude product was distilled in vacuum, b.p. 100-120° C./5 mM Hg
11. customThe obtained colorless liquid (which completely crystallizes at 5° C.)
12. dissolutionwas dissolved in 900 ml of n-hexane
13. customCrystals precipitated from this solution for 3 days at 5° C.
14. customwere collected
15. customdried in vacuum
16. customThis mixture was recrystallized from 500 ml of hot n-hexane
17. customWhite crystals precipitated at 5° C.
18. customwere collected
19. washwashed by 150 ml of cold (+5° C.) n-hexane
20. customdried in vacuum (˜60° C./20 mM Hg)
21. customto give colorless liquid which
22. customcrystallizes at room temperature

ORD record

ord-c613540ff34742ab82e08019f03ade99

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09187583B2