Formic Acid → 2-(4-Fluoro-3-methylphenyl)-4,4,6,6-tetramethylcyclohex-1-enecarboxaldehyde

Participants

Reaction Steps

To a mixture of 20 kg of 1-fluoro-2-methyl-4-(3,3,5,5-tetramethyl-1-cyclohexen-1-yl)benzene, 72 kg of 96% formic acid and 3.6 kg of 1,3,5-trioxane, 96 g of 70% benzoyl peroxide catalyst was added and the bath was heated to reflux for about 3 hours. The mixture was then cooled to room temperature and 48 kg of heptane was added with stirring. The phases were allowed to separate and the bottom layer was discarded. The top layer was washed with water, then 48 kg of methanol and 7.2 kg of 50% aqueous sodium hydroxide were added. The mixture was stirred for about 10 minutes, washed with water and dried with 10 kg of anhydrous sodium sulfate. The sodium sulfate was filtered off and the filter cake was washed with 10 kg of heptane. To the combined filtrates, 96 kg of dimethyl sulfoxide and 28 kg of triethylamine were added. Sulfur trioxide/pyridine complex (36 kg) was then charged portionwise at 30°-35° C. The batch was agitated for 15 minutes and the reaction was quenched with 96 kg of iced water. The phases were allowed to separate and the bottom layer was discarded. The top layer was washed with dilute hydrochloric acid and with brine. Methanol (48 kg) and 50% sodium hydroxide (4.8 kg) were added and the batch was stirred at 21°-25° C. for one hour. Ice (0.6 kg) was added and the mixture was stirred for 15 minutes. The phases were allowed to separate and the bottom layer was discarded. The top solution was washed with brine and concentrated in vacuo to remove the volatiles. The residue was dissolved in 22 kg of isopropanol and 2.8 kg of water. The mixture was then cooled to about -10° C., seeded and stirred for 16 hours. The crystallized product was filtered off, washed with cold aqueous isopropanol and dried to constant weight. Yield: 8.5 kg of 2-(4-fluoro-3-methylphenyl)- 4,4,6,6-tetramethylcyclohex-1-enecarboxaldehyde; m.p. 50.5°-51.5° C.

Provenance & Evidence