A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Page
GO
GO
?
^
Top
Org. Synth. 1951, 31, 1
DOI: 10.15227/orgsyn.031.0001
α-ACETYL-δ-CHLORO-γ-VALEROLACTONE
[Valeric acid, 2-acetyl-5-chloro-4-hydroxy-, γ-lactone]
Submitted by G. D. Zuidema, E. van Tamelen, and G. Van Zyl1.
Checked by William S. Johnson and Herbert I. Hadler.
1. Procedure
A 1-l. three-necked round-bottomed flask is equipped with a sealed stirrer, a thermometer, a dropping funnel, and an efficient condenser, the upper end of which is protected with a calcium chloride drying tube. In this flask 23 g. (1 g. atom) of lustrous sodium (Note 1) is dissolved in 400 ml. of absolute ethanol (Note 2). The sodium is cut into about 25 pieces, and the entire amount is added at one time. It may be necessary to cool the flask in a cold-water bath if the reaction becomes violent. When all the sodium has dissolved, the solution is cooled to 50° and 130 g. (127 ml., 1 mole) of ethyl acetoacetate (Note 3) is added dropwise while the temperature is maintained between 45° and 50°. The resulting solution is cooled to about 35°, and 92.5 g. (78.4 ml., 1 mole) of epichlorohydrin (Note 4) is added dropwise with stirring over a period of 20 minutes. The temperature is then raised to 45° and is kept at 45–50° for 18 hours. The clear red-orange solution is cooled to 15°, and chilled glacial acetic acid (60–65 ml.) is added with stirring until the solution is just acid to litmus; a mush of sodium acetate crystals precipitates. The dropping funnel is replaced by a capillary tube, and the condenser is set for distillation. About three-fourths of the ethanol is removed under reduced pressure while air is bubbled into the mixture through the capillary tube (Note 5). Care is taken that the internal temperature does not exceed 100°.
The mushy residue is shaken with 250–300 ml. of water until the sodium acetate dissolves. The oily layer of lactone is separated, and the aqueous phase is extracted with two 100-ml. portions of ether. The combined oil and ether extracts are washed with 150 ml. of water and dried overnight over anhydrous sodium sulfate. The ether is removed under reduced pressure, and the product is distilled from a modified Claisen flask. The fraction boiling at 160–170°/11 mm. is collected; refractionation yields 107–114 g. (61–64%) of product boiling at 164–168°/11 mm. or 151–156°/8 mm.; n25D 1.4815–1.4830 (Note 6) and (Note 7).
2. Notes
1. The sodium must be present in an equivalent amount for best results. When 0.2 g. atom of sodium was used, the yield was only 10%.
2. It is necessary to maintain strictly anhydrous conditions in this reaction. The apparatus should be carefully predried and the absolute ethanol freshly prepared either by the diethyl phthalate method2 or by the magnesium ethoxide method.3
3. Eastman Kodak Company white label quality ethyl acetoacetate (b.p. 78–79°/11 mm.) was used.
4. Epichlorohydrin may be prepared from glycerol-α,γ-dichlorohydrin.4 It is also commercially available.
5. Unless this precaution is taken, there is considerable bumping due to the presence of the solid sodium acetate in the mixture.
6. The product may become slightly colored upon standing.
7. This reaction is typical of those between the following epoxides and ethyl acetoacetate:

Epoxide

Boiling Point of Product

% Yield of Product


Butadiene monoxide

148–151°/32 mm.

54

Propylene oxide

138–141°/26 mm.

49

Styrene oxide

164–167°/3 mm.

60

Ethyl glycidyl ether

160–163°/14–15 mm.

46

Phenyl glycidyl ether

195–197°/1 mm.

77


3. Discussion
α-Acetyl-δ-chloro-γ-valerolactone has been prepared only by the condensation of epichlorohydrin with ethyl acetoacetate. The preparation described is based on the method of Traube and Lehman.5

References and Notes
  1. Hope College, Holland, Michigan.
  2. Manske, J. Am. Chem. Soc., 53, 1106 (1931), footnote 9.
  3. Lund and Bjerrum, Ber., 64, 210 (1931). Fieser, Experiments in Organic Chemistry, 3rd ed., p. 286, D. C. Heath and Company, Boston, Massachusetts, 1955.
  4. Org. Syntheses Coll. Vol. 1, 233 (1941).
  5. Traube and Lehman, Ber., 34, 1980 (1901).

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

glycerol-α,γ-dichlorohydrin

ethanol (64-17-5)

acetic acid (64-19-7)

ether (60-29-7)

sodium acetate (127-09-3)

Epichlorohydrin (106-89-8)

sodium sulfate (7757-82-6)

propylene oxide (75-56-9)

sodium (13966-32-0)

Ethyl acetoacetate (141-97-9)

Styrene oxide (96-09-3)

α-Acetyl-δ-chloro-γ-valerolactone,
Valeric acid, 2-acetyl-5-chloro-4-hydroxy-, γ-lactone (3154-75-4)

Butadiene monoxide (930-22-3)

Ethyl glycidyl ether (4016-11-9)

Phenyl glycidyl ether (122-60-1)