Org. Synth. 1968, 48, 126
DOI: 10.15227/orgsyn.048.0126
2,2,4-TRIMETHYL-3-OXOVALERYL CHLORIDE
[Valeryl chloride, 2,2,4-trimethyl-3-oxo-]
Submitted by Edward U. Elam, P. Glenn Gott, and Robert H. Hasek
1.
Checked by V. Boekelheide and G. Singer.
1. Procedure
Caution! The starting material in this preparation, 3-hydroxy-2,2,4-trimethyl-3-pentenoic acid β-lactone, is a mild but deceptively persistent lachrymator.
A mixture of
5 g. of anhydrous zinc chloride (Note 1) and
280 g. (2.00 moles) of 3-hydroxy-2,2,4-trimethyl-3-pentenoic acid β-lactone2 is placed in a
500-ml. three-necked flask equipped with a
sealed stirrer (Note 2), a
coarse fritted-glass gas-dispersion thimble, a
thermometer immersed in the liquid, and an
air-cooled reflux condenser (Note 3). The outlet of the condenser is connected to a bubble counter filled with concentrated
sulfuric acid; this in turn is vented to the atmosphere through a water scrubber. The flask is immersed in an
ice bath, and stirring is started. When the temperature of the mixture is about 10°, anhydrous
hydrogen chloride is introduced through the gas-dispersion tube at such a rate that a slow stream of bubbles escapes through the
bubble counter. Gas absorption is slow at first, but after a few minutes the
zinc chloride dissolves and the rate of gas absorption increases sharply. The temperature rises rapidly to 50–70° at the same time
(Note 4). After about 10 minutes the temperature falls and the rate of gas absorption decreases. The ice bath is revmoed, and the addition of
hydrogen chloride is continued for 30 minutes.
The reaction mixture is distilled rapidly under reduced pressure through a short Vigreux column (Note 5). The yield of crude product, b.p. 50–80° (5–10 mm.), n20D 1.4410–1.4416, is 310–330 g. (88–93%). This material is sufficiently pure for most purposes (Note 6). Fractionation through a 1 × 36-in. column packed with 8 × 8-mm. glass helices gives, after removal of a small amount of forerun, pure 2,2,4-trimethyl-3-oxovaleryl chloride, b.p. 86° (23 mm.), n20D 1.4418.
2. Notes
1.
Reagent grade anhydrous zinc chloride from a freshly opened bottle may be used without special drying.
2.
A
glass or Teflon stirrer should be used.
3.
An
air-cooled condenser long enough to
trap escaping spray is sufficient since the mixture is never hot enough to reflux.
4.
Overheating of the mixture at this point or during the subsequent distillation causes decomposition of the crude acid chloride with formation of tarry by-products. This decomposition in the presence of
zinc chloride is fairly rapid at temperatures above 100°.
5.
Since
hydrogen chloride is evolved in the early stages of this distillation, no effort is made to control the pressure. The
vacuum pump is protected from the
hydrogen chloride by insertion of a
1.5 × 15-in. glass tube packed with
sodium hydroxide pellets in the vacuum line. The purpose of this distillation is to remove dissolved
hydrogen chloride and the
zinc chloride catalyst; it should be completed as rapidly as possible, under the best vacuum attainable, with no attempt at fractionation. The distillate may be fractionally distilled for further purification if desired.
2,2,4-Trimethyl-3-oxovaleryl chloride is stable at its normal boiling point,
190° (730 mm.), after the
zinc chloride has been removed. Contact of the acid chloride with metals should be avoided.
6.
The
chlorine content of the crude product varied from 19.9% to 20.1% in successive experiments; saponification analysis indicated a purity above 97%.
3. Discussion
The procedure described is related to that for preparing
acetoacetyl chloride from
diketene and
hydrogen chloride.
34. Merits of the Preparation
Unlike acetoacetyl chloride, which decomposes at temperatures above −20°, 2,2,4-trimethyl-3-oxovaleryl chloride is stable at elevated temperatures. It may find use as an intermediate; for example, it can be used in the preparation of acid chlorides by an exchange reaction which is forced to completion by decarboxylation of the by-product, β-keto acid:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
sulfuric acid (7664-93-9)
hydrogen chloride (7647-01-0)
sodium hydroxide (1310-73-2)
diketene (674-82-8)
chlorine (7782-50-5)
zinc chloride (7646-85-7)
acetoacetyl chloride
3-hydroxy-2,2,4-trimethyl-3-pentenoic acid β-lactone (3173-79-3)
2,2,4-Trimethyl-3-oxovaleryl chloride,
Valeryl chloride, 2,2,4-trimethyl-3-oxo- (10472-34-1)
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