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Org. Synth. 1939, 19, 43
DOI: 10.15227/orgsyn.019.0043
ETHYL BENZOYLDIMETHYLACETATE
[Isobutyric acid, α-benzoyl-, ethyl ester]
Submitted by C. R. Hauser and W. B. Renfrow, Jr.
Checked by Lee Irvin Smith and E. C. Ballard.
1. Procedure
To a freshly prepared solution of 0.187 mole of triphenylmethylsodium (p. 607), contained in the flask into which it was transferred after preparation, is added 21.7 g. (25 cc., 0.187 mole) of pure ethyl isobutyrate (Note 1). The mixture is shaken, and, after it has stood at room temperature for ten minutes, a solution of 26 g. (21.5 cc., 0.186 mole) of pure benzoyl chloride in 50 cc. of dry ether is added, with shaking. The mixture becomes warm, and a white precipitate of sodium chloride separates immediately. After standing at room temperature for several hours the mixture is heated on a water bath and ether is distilled until the volume is reduced to 300–400 cc. A solution of 5 cc. of acetic acid in 300 cc. of water is added, and the mixture is shaken in a separatory funnel until two homogeneous layers separate on standing. The aqueous layer is drawn off and discarded; the ethereal layer is shaken with 10 per cent sodium carbonate solution and dried over calcium chloride or Drierite. The solution is filtered from the drying agent and distilled on a water bath until most of the ether is removed. The residue is cooled in a refrigerator, and the triphenylmethane which crystallizes is filtered with suction and washed with several small portions of dry ether. The filtrate, after removal of ether, is distilled under reduced pressure and all material boiling up to 180° at 15 mm. collected. The distillate is redistilled and the fraction boiling up to 160° at 15 mm. is subjected to a final redistillation. There is obtained 20.5–22.5 g. (50–55 per cent of the theoretical amount) of ethyl benzoyldimethylacetate, b.p. 146–148° at 15 mm. or 133–135° at 9 mm (Note 2) and (Note 3).
2. Notes
1. It is essential to use pure reagents. Commercial ethyl isobutyrate may be purified satisfactorily by washing with 10 per cent sodium carbonate solution, drying over Drierite for several days, and fractionating through an effective column; material boiling over a one-degree range (110–111°) is recommended for this preparation. Benzoyl chloride was purified by distillation under reduced pressure, and a fraction collected over less than a two-degree range was used.
2. If the more concentrated solution of triphenylmethylsodium, prepared as described in Note 3, p. 609, is employed, approximately 120 g. of ethyl benzoyldimethylacetate can be prepared in a single experiment.
The bottle containing an ether solution of 0.85 mole of triphenylmethylsodium is immersed to two-thirds of its depth in an ice bath. When the bottle is thoroughly cold, the stopper is removed while a tube delivering a rapid stream of dry nitrogen is held at the mouth of the bottle. The bottle is quickly fitted with a three-holed rubber stopper carrying a mechanical stirrer (with open shaft), a dropping funnel, and a bent tube which extends into the bottle for a distance of 1 cm. below the neck. A slow stream of dry nitrogen passes through the bent tube; the nitrogen supply is also connected to the top of the dropping funnel. One hundred two grams (0.875 mole) of ethyl isobutyrate is added rapidly to the vigorously stirred contents of the bottle. After five minutes, 123 g. (101 cc., 0.875 mole) of benzoyl chloride is added through the dropping funnel at such a rate that the mixture does not reflux too vigorously (the addition takes about five minutes). Stirring is continued for two or three minutes after the addition is complete. The bottle is then removed from the ice bath, stoppered, shaken, and allowed to stand for half an hour. The reaction mixture is transferred to a 2.5-l. separatory funnel and the mercury drained off. The remaining mixture is extracted with 300 cc. of water, any sludge formed being collected separately. The sludge is extracted with a little ether, the extract being added to the ether layer in the funnel. The ether solution is washed with two 100-cc. portions of 10 per cent sodium carbonate solution, and dried by shaking with 50 g. of anhydrous sodium or magnesium sulfate and by standing with 50 g. of Drierite in a stoppered 2-l. Erlenmeyer flask. The solution is filtered into a 2-l. round-bottomed flask and the ether removed by distillation. The residue is transferred to a 1-l. Claisen flask and distilled in vacuum, using a metal or oil bath and collecting all the material boiling below 175° at 15 mm. The distillate is transferred to a 200-cc. round-bottomed flask fitted with a 6-inch Widmer fractionating column and redistilled from a metal bath. The ethyl benzoyldimethylacetate boils at 146–148°/15 mm. and weighs 115–125 g. (61–67 per cent of the theoretical amount based on the quantity of triphenylmethylsodium used). (Charles R. Hauser and Boyd E. Hudson, Jr., private communication.)
3. The submitters report that ethyl isobutyrylisobutyrate (ethyl α,α,γ,γ-tetramethylacetoacetate) may be prepared in a similar manner, using isobutyryl chloride instead of benzoyl chloride. The yield of this ester, b.p. 94.5–95.5°/18 mm., is about 55 per cent of the theoretical amount. Several other examples of the acylation of esters by this procedure are given by Hudson, Jr., and Hauser.1
3. Discussion
Ethyl benzoyldimethylacetate has been prepared by the condensation of ethyl isobutyrate with ethyl benzoate,2 phenyl benzoate, benzoic anhydride, or benzoyl chloride.3 The procedure described above3 is a modification of the method of Scheibler and Stein.4
This preparation is referenced from:

References and Notes
  1. Hudson, Jr., and Hauser, J. Am. Chem. Soc. 63, 3159 (1941).
  2. Renfrow, Jr., and Hauser, ibid. 60, 464 (1938).
  3. Hudson, Jr., Dick, and Hauser, ibid. 60, 1961 (1938).
  4. Scheibler and Stein, J. prakt. Chem. (2) 139, 111 (1934).

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

Drierite

sodium or magnesium sulfate

calcium chloride (10043-52-4)

acetic acid (64-19-7)

ether (60-29-7)

sodium chloride (7647-14-5)

sodium carbonate (497-19-8)

nitrogen (7727-37-9)

mercury (7439-97-6)

benzoyl chloride (98-88-4)

Benzoic anhydride (93-97-0)

ethyl benzoate (93-89-0)

Triphenylmethane (519-73-3)

Ethyl benzoyldimethylacetate (25491-42-3)

Isobutyric acid, α-benzoyl-, ethyl ester

Triphenylmethylsodium (4303-71-3)

ethyl isobutyrate (97-62-1)

Ethyl isobutyrylisobutyrate

isobutyryl chloride (79-30-1)

phenyl benzoate (93-99-2)

ethyl α,α,γ,γ-tetramethylacetoacetate