Org. Synth. 1951, 31, 56
DOI: 10.15227/orgsyn.031.0056
[Hydrocinnamic acid, α-acetyl-2,3-dimethoxy-, ethyl ester]
Submitted by E. C. Horning, J. Koo, M. S. Fish, and G. N. Walker1.
Checked by T. L. Cairns and Charles W. Todd.
1. Procedure
A. Ethyl α-acetyl-β-(2,3-dimethoxyphenyl)acrylate. In a 1-l. round-bottomed flask fitted with a water-benzene separator2 and a reflux condenser are placed 183 g. (1.1 moles) of 2,3-dimethoxybenzaldehyde (Note 1) and 130 g. (1.0 mole) of ethyl acetoacetate. The water-benzene separator is filled with benzene, an additional 70 ml. of benzene is added to the mixture, and the 2,3-dimethoxybenzaldehyde is brought into solution by warming. Piperidine (4 ml.) and glacial acetic acid (12 ml.) are added, and the mixture is heated under reflux for 2–3 hours (Note 2). The mixture is cooled, poured into a separatory funnel with 800 ml. of ether, and washed successively with 200-ml. portions of 5% hydrochloric acid, 5% sodium bicarbonate solution, and 5% acetic acid, and twice with water. The extract is dried over anhydrous magnesium sulfate (about 250 g.). After filtration, the ether and benzene are distilled under atmospheric pressure, and the residue is distilled under reduced pressure. The yield of viscous, yellow oil collected at 186–190°/2 mm. (Note 3) is 180–199 g. (64–72%), nD25 1.5507–1.5508.
B. Ethyl α-acetyl-β-(2,3-dimethoxyphenyl)propionate. The product obtained in Part A is divided into two approximately equal portions, and to each are added 125 ml. of ethyl acetate and 5 g. of 5% palladium-on-carbon catalyst (Note 4). Each solution is shaken with hydrogen at pressures between 20 and 40 lb. in a low-pressure apparatus. About 45 minutes is usually needed for complete reduction. The two solutions are then combined, and the catalyst is removed by filtration and washed with 20 ml. of ethyl acetate. The ethyl acetate is distilled at atmospheric pressure, and distillation of the residue under reduced pressure yields 158–176 g. (56–63% over-all) of a colorless product collected at 175–177°/3 mm., nD25 1.5042–1.5044 (Note 3) and (Note 5).
2. Notes
1. A practical grade of 2,3-dimethoxybenzaldehyde, although discolored, is satisfactory. It is best handled and weighed as a liquid. This is done by warming the container on a steam bath for several minutes.
2. The time of reflux is determined by the rate at which water separates from the reaction mixture. In general, the theoretical amount of water (18 ml.) is collected in the water separator after about 1 hour, but additional refluxing usually results in the separation of another 4–5 ml. Anhydrous materials are not necessary for the reaction.
3. Using a 6-in. Vigreux column with a wide side arm, the checkers observed a boiling point of 166–168°/3 mm. for ethyl α-acetyl-β-(2,3-dimethoxyphenyl)propionate and 176–179°/2 mm. for the acrylate.
4. These quantities are convenient for hydrogenation in a Parr low-pressure apparatus; if a larger apparatus is available, it is unnecessary to divide the material. The palladium-on-carbon catalyst is prepared by Hartung's method,3 using sufficient Norit to give a 5% catalyst. A few chips of Dry Ice should be placed in the bottle before the catalyst is added to provide an inert atmosphere. The checkers used a catalyst obtained from Baker and Company, Inc., 113 Astor Street, Newark, New Jersey.
5. The same procedure may be used with other aromatic aldehydes. The acrylate ester prepared from veratraldehyde is a crystalline compound melting at 82.5–84.5°. It may be purified by distillation under reduced pressure, b.p. 190–196°/0.8 mm. The yield is 53–63%. The hydrogenated product is obtained as a colorless oil, b.p. 180–183°/1.0 mm., in 38–44% over-all yield.
3. Discussion
Substituted α-benzylacetoacetic esters have usually been prepared by the general method of Leuchs,4 in which ethyl acetoacetate is alkylated in ethanol solution with benzyl chloride and sodium ethoxide. The present method is based upon Cope's5 procedure for the condensation of carbonyl compounds with ethyl acetoacetate, followed by catalytic reduction of the condensation product.
This preparation is referenced from:

References and Notes
  1. University of Pennsylvania, Philadelphia, Pennsylvania.
  2. Org. Syntheses Coll. Vol. 3, 382 (1955).
  3. Org. Syntheses Coll. Vol. 3, 685 (1955), Method D.
  4. Leuchs, Ber., 44, 1510 (1911).
  5. Cope and Hofmann, J. Am. Chem. Soc., 63, 3456 (1941).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)


α-benzylacetoacetic esters

ethanol (64-17-5)

hydrochloric acid (7647-01-0)

acetic acid (64-19-7)

Benzene (71-43-2)

ethyl acetate (141-78-6)

ether (60-29-7)

hydrogen (1333-74-0)

sodium bicarbonate (144-55-8)

Norit (7782-42-5)

piperidine (110-89-4)

sodium ethoxide (141-52-6)

benzyl chloride (100-44-7)

Ethyl acetoacetate (141-97-9)

magnesium sulfate (7487-88-9)

Veratraldehyde (120-14-9)


2,3-dimethoxybenzaldehyde (86-51-1)

Hydrocinnamic acid, α-acetyl-2,3-dimethoxy-, ethyl ester,
Ethyl α-acetyl-β-(2,3-dimethoxyphenyl)propionate (53608-80-3)

Ethyl α-acetyl-β-(2,3-dimethoxyphenyl)acrylate (19411-81-5)