Organic Syntheses, CV 5, 303
Submitted by Ronald A. Daignault and E. L. Eliel
1.
Checked by J. R. Edman and B. C. McKusick.
1. Procedure
A.
1,4-Dioxaspiro[4.5]decane. A
1-l. round-bottomed flask is charged with
118 g. (1.20 moles) of cyclohexanone,
82 g. (1.32 moles) of 1,2-ethanediol,
250 ml. of reagent grade benzene, and
0.05 g. of p-toluenesulfonic acid monohydrate. The flask is attached to a
water separator2 under a
reflux condenser fitted with a drying tube. A heating mantle is placed under the flask, and the reaction mixture is refluxed until close to the theoretical amount of water (21.6 ml.) has collected in the
trap; this requires about 6 hours. The reaction mixture is cooled to room temperature, extracted successively with
200 ml. of 10% sodium hydroxide solution and five 100-ml. portions of water, dried over anhydrous
potassium carbonate, and distilled through a
20-cm. Vigreux column.
1,4-Dioxaspiro[4.5]decane is obtained as a colorless liquid, b.p.
65–67° (13 mm.), weight
128–145 g. (
75–85%),
n25D 1.4565–1.4575.
B.
2-Cyclohexyloxyethanol. A well-dried,
3-l. three-necked, round-bottomed flask is equipped with a
stirrer, a
pressure-equalizing dropping funnel, and a condenser to whose top is attached a
calcium chloride drying tube. The flask is charged with
242 g. (1.81 moles) of anhydrous aluminum chloride powder and is immersed in an
ice-salt bath. Anhydrous
ether (25–50 ml.) is added dropwise through the dropping funnel, stirring is begun as soon as possible, and an additional
450–475 ml. of ether is added rapidly
(total volume of ether added: 500 ml.). The mixture is stirred for approximately 30 minutes and becomes a light gray solution. During this period a mixture of
16.7 g. (0.44 mole) of lithium aluminum hydride and
500 ml. of anhydrous ether is vigorously stirred in a 1-l. round-bottomed flask under a
nitrogen atmosphere (Note
1). The resulting suspension is added to the ethereal
aluminum chloride solution through the dropping funnel. The resulting mixture, a gray slurry, is stirred for at least 30 minutes.
A solution of
125 g. (0.88 mole) of 1,4-dioxaspiro[4.5]decane in 200 ml. of anhydrous ether is added at a rate to cause gentle refluxing. The ice-salt bath is replaced by a
steam bath, and the reaction mixture is refluxed for 3 hours. The calcium chloride drying tube is removed, and the steam bath is replaced by an
ice bath. The excess hydride is carefully destroyed by adding water dropwise until
hydrogen is no longer evolved; about 12 ml. of water is needed. This is followed by the more rapid addition of
1 l. of 10% sulfuric acid and then 400 ml. of water. This combination dissolves all the inorganic salts formed and results in the formation of two clear layers. The
ether layer is separated in a
3-l. separatory funnel, and the aqueous layer is extracted with three
200-ml. portions of ether. The combined ethereal extracts are washed successively with
200 ml. of saturated sodium bicarbonate solution and
200 ml. of saturated brine. The ethereal solution is dried overnight over anhydrous
potassium carbonate, filtered through a
fluted filter paper, and concentrated by distillation on a steam bath. The residue, a pale yellow liquid weighing about
130 g., is distilled through a 20-cm. Vigreux column under reduced pressure.
2-Cyclohexyloxyethanol is obtained as a colorless liquid, b.p.
96–98° (13 mm.), weight
105–119 g. (
83–94%),
n25D 1.4600–1.4610.
2. Notes
1. Most of the
lithium aluminum hydride is in solution, but some is in suspension. When the humidity is below 35%,
lithium aluminum hydride can be weighed in air; otherwise the weighing should be done in a dry box. Although some workers pulverize
lithium aluminum hydride before dissolving or suspending it in a liquid,
the checkers recommend that this not be done because it has led to several explosions in their laboratory. The present procedure gives a fine suspension that generally passes through the
stopcock of the dropping funnel without plugging it. A wooden stick or
copper wire should be in readiness to clear the stopcock if it plugs up.
3. Discussion
The present method of preparing
2-cyclohexyloxyethanol has been described before,
5 but on a smaller scale. Other β-hydroxy ethers
5 and β-hydroxy thio ethers
6 can be prepared by the same method. Hydrogenolysis of the C-O bond in acetals has also been reported
7 with
diisobutylaluminum hydride; for example,
2-cyclohexyloxyethanol was obtained in
91% yield in this manner.
4. Merits of the Preparation
The method described is more convenient than earlier methods of preparing
2-cyclohexyloxyethanol. It may be adapted to the preparation of other β-hydroxyethyl and γ-hydroxypropyl ethers
5 and the corresponding thio ethers.
6,10 Although ketals are resistant to reduction by
lithium aluminum hydride alone, the presence of a Lewis acid facilitates C-O cleavage, presumably via an oxocarbonium ion,
11 as the procedure demonstrates.
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