2-Chloro-4-methylbenzaldehyde

Synthesis

6627-51-6

68-12-2

50817-80-6

GENERAL STEPS: 165 mL (413 mmol) of a hexane solution of 2.5 M n-butyllithium (nBuLi) was slowly added dropwise to 82.2 g (400 mmol) of 4-bromo-3-chlorotoluene dissolved in 400 mL of tetrahydrofuran (THF) over a period of 1 h. The reaction system was required to be cooled to -88 °C. At this temperature, the reaction mixture was stirred continuously for 30 min. Subsequently, 44.0 g (602 mmol) of N,N-dimethylformamide (DMF) was added dropwise over 10 minutes by vigorous stirring. The reaction mixture was stirred overnight at room temperature. After that, 100 mL of water and 400 mL of 3 N hydrochloric acid (HCl) were added to the reaction mixture at 0 °C. The organic layer was separated and the aqueous layer was extracted with dichloromethane (2 x 125 mL). The organic extracts were combined, dried with potassium carbonate (K2CO3), and filtered through a short silica gel 60 (40-63 μm) layer. The silica gel layer was washed with 50 mL of dichloromethane. The organic eluates were combined and evaporated to dryness to give a light orange liquid. The liquid was distilled under vacuum and the fractions with boiling points of 99-102 °C/11 mmHg were collected to give 58.0 g (94% yield) of 2-chloro-4-methylbenzaldehyde as a colorless liquid, which crystallized after standing overnight.

References