alpha-(3,4-Dimethoxyphenyl)-acetoacetonitrile
A solution of sodium ethylate was prepared from 389 g (17 moles) of sodium and 4530 cc. of absolute ethanol. To this hot solution was added a solution of 1000g (5.65 moles) of 3,4-dimethoxyphenylacetonitrile in 1710 g (19.4 moles) of dry ethyl acetate. After refluxing for 4 hours the mixture, containing a light precipitate, was allowed to stand at room temperature overnight. The white crystalline mass was filtered off after cooling in ice for 2 hours. Washing with ethyl acetate and then ether gave 1403g of the sodium salt, mp 296-300°C dec. Solution of the salt in 5400 ml of water, cooling to 10°C and acidifying with 1420 ml of glacial acetic acid gave a nearly solid mass. The product was collected and washed with water; weight 1244g (97.7%), mp 77.5-78°C. Recrystallization from methanol gave analytically pure material, mp 98-100°C.
3,4-Dimethoxyphenylacetone
Crude nitrile from above (1212 g) was added over one hour to a stirred and cooled (0-5°C) solution of 3008 ml of concentrated sulfuric acid in 727 ml of water. The brown solution resulting on heating to 80°C for 10 minutes was cooled to 0°C and diluted (stirring) with 10.75 L of cold water. During heating on the steam-bath for 3 hours, an oily layer separated. After cooling, ether extraction, washing of the extract with dilute bicarbonate solution, and drying, the ether extract was concentrated to give 610.8g (56.5%) of orange oil which was purified by vacuum distillation; weight 549.3g (51%), bp 142°C/2.6mmHg (bp 118°C/0.4mmHg).
alpha-(3-Methoxyphenyl)-acetoacetonitrile
Treatment of 3-methoxyphenylacetonitrile essentially as described above for 3,4-dimethoxyphenylacetorlitrile was followed by addition of petroleum ether to precipitate 275g of the sodium salt of alpha-(3-methoxyphenyl)-acetoacetonitrile, mp 280-290°C (dec). After acidification with acetic acid the yield was 206g (83.6%), mp 83-85°C. Two recrystallizations from methanol gave analytically pure material, mp 90-91°C.
3-Methoxyphenylacetone
The crude nitrile was hydrolyzed as described for 3,4-dimethoxyphenylacetonitrile but at 90-95°C. The yield of ketone was rather poor (46.5%), and considerable unreacted nitrile was recovered. After redistillation the ketone was analytically pure, bp 95-97°C/0.7 mmHg.
Ref: JACS 77, 700 (1955)