反应详情

4-Chloro-3-methylanisole (15.4 g., 0.10 mole) was taken into 200 ml. of methylene chloride and cooled to 0° C. Titanium tetrachloride (37.9 g., 0.2 mole) and then 1,1-dichloromethyl methyl ether (13.8 g., 0.12 mole) were added, each over a 2 minute period. The reaction mixture was stirred at room temperature for 1 hour, poured over 500 ml. of ice and water and the organic layer separated. The aqueous layer was extracted with two portions of fresh methylene chloride and these extracts combined with the original organic layer. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated dryness (15.2 g., 82%), containing two thirds 5-chloro-2-methoxy-4-methylbenzaldehyde [Rf 0.35 (1:1 chloroform:hexane] and one third of the desired isomeric product [Rf 0.28 (1:1 chloroform:hexane]. These two compounds were separated by chromatography on 1 kg. of silica gel, eluting with 1:1 methylene chloride:hexane, collecting 15 ml. fractions and monitoring by tlc. Fractions 115-140 were combined and evaporated to dryness to yield the undesired Rf 0.35 isomer (860 mg., m.p. 86°-88° C.). Fractions 240-310 were combined to yield the desired 3-chloro-6-methoxy-2-methylbenzaldehyde [1.61 g.; m.p. 95°-97° C., pnmr/CDCl3 /delta 2.4 (s, 3H), 3.9 (s, 3H), 6.8 (s, 1H), 7.7 (s, 1H), 10.4 (s, 1H); Rf 0.28 (1:1 methylene chloride:hexane)].

1. additionpoured over 500 ml
2. customof ice and water and the organic layer separated
3. extractionThe aqueous layer was extracted with two portions of fresh methylene chloride
4. washThe combined organic layers were washed with brine
5. dry with materialdried over anhydrous magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated dryness (15.2 g., 82%)
8. additioncontaining two thirds 5-chloro-2-methoxy-4-methylbenzaldehyde [Rf 0.35 (1:1 chloroform
9. customThese two compounds were separated by chromatography on 1 kg
10. washof silica gel, eluting with 1:1 methylene chloride
11. customhexane, collecting 15 ml
12. customevaporated to dryness
13. customto yield the undesired Rf 0.35 isomer (860 mg., m.p. 86°-88° C.)