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Org. Synth. 1938, 18, 33
DOI: 10.15227/orgsyn.018.0033
ETHYL BENZOYLACETATE
[Acetic acid, benzoyl-, ethyl ester]
Submitted by R. L. Shriner, A. G. Schmidt, and L. J. Roll.
Checked by C. R. Noller and I. Bergsteinsson.
1. Procedure
(A) Preparation of Ethyl Benzoylacetoacetate.—In a 5-l. three-necked flask, fitted with a liquid-sealed mechanical stirrer and a reflux condenser, are placed 3.4 l. of dry benzene (Note 1), 195 g. (1.5 moles) of ethyl acetoacetate (Org. Syn. Coll. Vol. I, 1941, 235), and 34.5 g. (1.5 gram atoms) of clean sodium. The mixture is heated on a steam cone with stirring and allowed to reflux gently for twenty-four hours. After the suspension of the sodioacetoacetic ester has been cooled slightly, 263 g. (218 cc., 1.9 moles) of benzoyl chloride is added over a period of three hours. The mixture is refluxed with stirring for an additional eight hours. It is then cooled to room temperature, and 375 g. of cracked ice is added. After thorough shaking, the benzene layer, which contains the ethyl benzoylacetoacetate, is separated, washed with 75 cc. of 5 per cent sodium bicarbonate solution, dried with sodium sulfate, and the benzene distilled (Note 2). The residue is distilled in vacuo from a 500-cc. Claisen flask with a 50-cm. fractionating side arm. After a small fore-run of benzoyl chloride, the fraction boiling at 142–148°/6 mm., or 177–181°/20 mm., is collected. The yield is 223–263 g. (63–75 per cent of the theoretical amount).
(B) Hydrolysis of Ethyl Benzoylacetoacetate.—Thirty-two grams (0.6 mole) of ammonium chloride is dissolved in 150 cc. (8.3 moles) of water in a 500-cc. Erlenmeyer flask, and 10 cc. (0.15 mole) of ammonia (sp. gr. 0.9) is added. The solution is warmed to 42°, 58.5 g. (0.25 mole) of ethyl benzoylacetoacetate at 20° is added quickly, and the mixture is shaken (Note 3). The flask is placed in a water bath at 42° for exactly ten minutes and then cooled rapidly by placing it in an ice bath. The solution is extracted twice with 100-cc. portions of ether, and the ether solution is dried with anhydrous magnesium sulfate. The ether is distilled, and the residue distilled in vacuo; the yield is 37.0–37.5 g. (77–78 per cent of the theoretical amount) of ethyl benzoylacetate boiling at 132–137°/4 mm., or 165–169°/20 mm.
2. Notes
1. The benzene was dried by distillation, the first portion of the distillate being discarded.
2. It is essential that these steps in the isolation be carried through as rapidly as possible.
3. Larger amounts gave lower yields. The exact procedure must be followed as to time, temperature, and amounts of reagents, and the procedure must be completed without interruption.
3. Discussion
Ethyl benzoylacetate has been prepared by the condensation (by means of sodium ethoxide) of ethyl acetate with ethyl benzoate,1 acetophenone with ethyl carbonate,2 and acetophenone with ethyl oxalate, with subsequent heating;3 by treatment of ethyl phenylpropiolate4 or α-bromocinnamic acid5 with concentrated sulfuric acid, and of ethyl diazoacetate with benzaldehyde;6 by the condensation of benzene with the monoethyl ester of malonyl monoacid chloride and aluminum chloride,7 of benzoyl chloride with the product of the reaction of magnesium and ethyl chloroacetate in ether;8 by the action of alcohol on benzoylacetimino ethyl ether hydrochloride;9 and by the hydrolysis of ethyl benzoylacetoacetate.10

References and Notes
  1. Claisen and Lowman, Ber. 20, 651 (1887).
  2. Claisen, ibid. 20, 655 (1887).
  3. Wislicenus, ibid. 28, 811 (1895).
  4. Baeyer, ibid. 15, 2705 (1882).
  5. Michael and Browne, ibid. 19, 1392 (1886).
  6. Buchner and Curtius, ibid. 18, 2371 (1885).
  7. Marguery, Bull. soc. chim. (3) 33, 549 (1905).
  8. Meyer and Tögel, Ann. 347, 76 (1906).
  9. Haller, Bull. soc. chim. (2) 48, 23 (1887).
  10. Claisen, Ann. 291, 71 (1896); Shriner and Schmidt, J. Am. Chem. Soc. 51, 3636 (1929).

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

sodioacetoacetic ester

monoethyl ester of malonyl monoacid chloride

sulfuric acid (7664-93-9)

ammonia (7664-41-7)

Benzene (71-43-2)

ethyl acetate (141-78-6)

ether (60-29-7)

ammonium chloride (12125-02-9)

sodium bicarbonate (144-55-8)

magnesium (7439-95-4)

sodium sulfate (7757-82-6)

benzaldehyde (100-52-7)

Acetophenone (98-86-2)

benzoyl chloride (98-88-4)

aluminum chloride (3495-54-3)

sodium (13966-32-0)

sodium ethoxide (141-52-6)

Ethyl chloroacetate (105-39-5)

ethyl benzoate (93-89-0)

Ethyl acetoacetate (141-97-9)

Ethyl oxalate

magnesium sulfate (7487-88-9)

Ethyl benzoylacetate,
Acetic acid, benzoyl-, ethyl ester (94-02-0)

Ethyl benzoylacetoacetate (569-37-9)

ethyl carbonate

ethyl phenylpropiolate (2216-94-6)

α-bromocinnamic acid

ethyl diazoacetate (623-73-4)

benzoylacetimino ethyl ether hydrochloride