A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1941, 21, 4
DOI: 10.15227/orgsyn.021.0004
Submitted by Jonathan W. Williams and John A. Krynitsky.
Checked by Nathan L. Drake and Joseph Lann.
1. Procedure
In a 500-ml. round-bottomed three-necked flask fitted with a reflux condenser, a dropping funnel, and a mercury-sealed stirrer (Note 1) is placed a solution of 46 g. (0.5 mole) of dry aniline in 125 ml. of pure dry benzene. Stirring is started, and a solution of 42 g. (0.5 mole) of ketene dimer (p. 508) in 75 ml. of pure dry benzene is added dropwise over a period of 30 minutes. The reaction mixture is then heated under reflux on the steam bath for 1 hour. After the major portion of the benzene has been removed by distillation from the steam bath, the remainder is removed under reduced pressure. The residue is dissolved in 500 ml. of hot 50% aqueous ethanol from which the acetoacetanilide separates on cooling. The mixture is cooled to 0° before filtration. A second crop of crystals can be obtained by adding 250 ml. of water to the mother liquor and cooling again (Note 2). The total yield of product, m.p. 82–83.5°, is 65 g. (74%). Further purification by recrystallization from 300 ml. of 50% ethanol yields 55 g. of a product that melts at 84–85°.
2. Notes
1. A seal of rubber tubing lubricated by glycerol is satisfactory.
2. If the second mother liquor is evaporated to about half of its original volume, a small third crop of very impure crystals may be obtained.
3. Discussion
Acetoacetanilide has been prepared by the reaction of aniline with ethyl acetoacetate1,2,3,4,5 or acetoacetyl chloride,6 and by the reaction of ketene dimer with aniline.7,8

References and Notes
  1. Knorr, Ann., 236, 69 (1886).
  2. Roos, Ber., 21, 624 (1888).
  3. Knorr and Reuter, Ber., 27, 1169 (1894).
  4. Mizuno, J. Pharm. Soc. Japan, 69, 126 (1949).
  5. U. S. pat. 2,416,738 [C. A., 41, 3485 (1947)].
  6. Hurd and Kelso, J. Am. Chem. Soc., 62, 1548 (1940).
  7. Chick and Wilsmore, J. Chem. Soc., 1908, 946.
  8. Boese, Ind. Eng. Chem., 32, 16 (1940).

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

Ketene dimer

ethanol (64-17-5)

Benzene (71-43-2)

aniline (62-53-3)

glycerol (56-81-5)

Ethyl acetoacetate (141-97-9)

Acetoacetanilide (102-01-2)

acetoacetyl chloride