Org. Synth. 1965, 45, 22
DOI: 10.15227/orgsyn.045.0022
γ-CROTONOLACTONE
[Δα,β-Butenolide]
Submitted by Charles C. Price and Joseph M. Judge
1.
Checked by Richard F. Atkinson and E. J. Corey.
1. Procedure
Caution! Contact with α-bromo-γ-butyrolactone can cause severe eye and skin irritation. This preparation should be carried out in a good hood, and the operator should wear protective goggles and rubber gloves.
A. α-Bromo-γ-butyrolactone. In a 1-l., three-necked, round-bottomed flask equipped with a dropping funnel, sealed stirrer, and an efficient reflux condenser (Note 1) are placed 100 g. (1.16 moles) of redistilled γ-butyrolactone and 13.4 g. (0.43 g. atom) of red phosphorus. Over a half-hour interval, 195 g. (66.5 ml., 1.22 moles) of bromine is added, the mixture being stirred moderately and cooled by an ice bath.
This mixture is heated to 70° and an additional 195 g. (66.5 ml., 1.22 moles) of bromine added over a half-hour interval. After the bromine addition, the temperature is raised to 80° and the mixture held at that temperature for 3 hours. Air is blown into the cooled reaction until the excess bromine and hydrogen bromide are removed (Note 1). This process usually requires one hour (Note 2).
The aerated reaction mixture is heated to 80° and 25 ml. of water is added cautiously, with stirring. A vigorous reaction ensues, and upon cessation of the reaction an additional 300 ml. of water is added.
The reaction mixture of two layers and some solid residue is heated under reflux for 4 hours. Upon cooling, two layers again appear. The product is extracted with two portions of ether (200 ml. each), and the extracts are dried over magnesium sulfate (Note 3). Care should be taken since the α-bromolactone is a vesicant.
The dried crude material is distilled, b.p. 125–127° (13 mm.), n25D 1.5030, yield 105 g. (55%).
B.
Δα,β-Butenolide. In a
500-ml. three-necked flask fitted with a
mechanical stirrer, a reflux condenser, and a
250-ml. dropping funnel containing a solution of
61 g. (84.5 ml., 0.6 mole) of triethylamine in
70 ml. of dry diethyl ether, a solution of
83 g. (0.5 mole) of α-bromo-γ-butyrolactone and
200 ml. of dry diethyl ether is heated to reflux, with stirring. The amine solution is added, slowly, during 5 hours and the stirring under reflux continued for an additional 24 hours. The brown precipitate (40 g.) is removed by filtration. Most of the solvent is removed from the filtrate by evaporation, and the additional precipitate (8 g.) is removed. This precipitate is predominantly
triethylamine hydrobromide. The liquid residue is distilled under reduced pressure and the
Δα,β-butenolide is collected at
107–109° (24 mm.); yield
25 g. (
60%,
33% overall), m.p.
5°2,3,4 (Note 4).
2. Notes
1.
A
trap to catch the resulting
bromine-hydrogen bromide vapors is desirable.
2.
Plieninger
5 reports that the product at this stage is
α,γ-dibromobutyryl bromide.
3.
Extraction with
ether is necessary to separate the
bromolactone efficiently.
4.
The infrared spectrum of
γ-crotonolactone shows two bands in the carbonyl region at 5.60 and 5.71 μ in
carbon tetrachloride (5%) [shifted to 5.61 and 5.71 μ. in
chloroform (5%)] and carbon-carbon stretching absorption at 6.23 μ. The nuclear magnetic resonance spectrum shows olefinic peaks centered at 2.15τ (pair of triplets) and 3.85τ (pair of triplets), each due to one proton, and a two-proton triplet centered at 5.03τ (in CCl
4).
In the ultraviolet, γ-crotonolactone shows end absorption at 205 mμ (ε ca. 11,000) and no maximum at higher wavelength.
Oxidation of this product by
potassium permanganate affords
2,3-dihydroxy-4-butyrolactone.
2
3. Discussion
The original preparation of
γ-crotonolactone by Lespieau involved a five-step sequence from
epichlorohydrin and
sodium cyanide.
2 A recent detailed study of this procedure reported an overall yield of
25% for the lactone.
3 Glattfeld
4 used a shorter route from
glycerol chlorohydrin and
sodium cyanide; hydrolysis and distillation of the intermediate dihydroxy acid yielded
γ-crotonolactone in
23% yield and
β-hydroxy-γ-butyrolactone in
28% yield.
4 The formation of
γ-crotonolactone in
15% yield has also been reported from pyrolysis of
2,5-diacetoxy-2,5-dihydrofuran at 480–500°.
6 The lactone has been prepared in
37% overall yield from
propynol by carboxylation and hydrogenation.
7The formation of
α-bromo-γ-butyrolactone has been reported in
70% yield by uncatalyzed reaction of
bromine at 160–170°,
8 as well as by the catalyzed procedure used here.
34. Merits of the Preparation
γ-Crotonolactone is the simplest example of the butenolide ring system, which occurs in many natural products. In view of the availability of butyrolactone, the present procedure represents the most convenient method of synthesis of the unsaturated lactone.
The dehydrohalogenation by a tertiary amine illustrates the utility of such amines for dehydrohalogenations which produce a double bond normally activated for attack by many bases.
9
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
bromolactone
Δα,β-Butenolide
α-bromolactone
bromine-hydrogen bromide
glycerol chlorohydrin
ether,
diethyl ether (60-29-7)
chloroform (67-66-3)
Epichlorohydrin (106-89-8)
potassium permanganate (7722-64-7)
sodium cyanide (143-33-9)
hydrogen bromide (10035-10-6)
bromine (7726-95-6)
PHOSPHORUS (7723-14-0)
carbon tetrachloride (56-23-5)
γ-butyrolactone,
Butyrolactone (96-48-0)
magnesium sulfate (7487-88-9)
triethylamine (121-44-8)
γ-Crotonolactone (497-23-4)
α-Bromo-γ-butyrolactone (5061-21-2)
triethylamine hydrobromide (636-70-4)
α,γ-dibromobutyryl bromide
2,3-dihydroxy-4-butyrolactone (15667-21-7)
β-hydroxy-γ-butyrolactone (7331-52-4)
2,5-diacetoxy-2,5-dihydrofuran
propynol
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