A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1967, 47, 37
DOI: 10.15227/orgsyn.047.0037
[Ethanol, 2-(cyclohexyloxy)-]
Submitted by Ronald A. Daignault and E. L. Eliel1.
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.
Twice the theoretical amount of lithium aluminum hydride is used, but this is necessary for the best yields.
3. Discussion
The method of preparing 1,4-dioxaspiro[4.5]decane is that of Salmi.3 The methods used by Lorette and Howard4 to prepare ketals are convenient for preparing 1,4-dioxaspiro[4.5]decane.
The present method of preparing 2-cyclohexyloxyethanol has been described before,5 but on a smaller scale. Other β-hydroxy ethers5 and β-hydroxy thio ethers6 can be prepared by the same method. Hydrogenolysis of the C-O bond in acetals has also been reported7 with diisobutylaluminum hydride; for example, 2-cyclohexyloxyethanol was obtained in 91% yield in this manner.
2-Cyclohexyloxyethanol has also been prepared by reduction of cyclohexyloxyacetic acid with lithium aluminum hydride8 and by decomposition of cyclohexanone methanesulfonylhydrazone with sodium in ethylene glycol.9
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 ethers5 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.

References and Notes
  1. Department of Chemistry, University of Notre Dame, Notre Dame, Indiana.
  2. S. Natelson and S. Gottfried, Org. Syntheses, Coll. Vol. 3, 381 (1955).
  3. E. J. Salmi, Ber., 71B, 1803 (1938).
  4. N. B. Lorette and W. L. Howard, J. Org. Chem., 25, 521, 525, 1814 (1960); Org. Syntheses, 42, 34 (1962).
  5. E. L. Eliel, V. G. Badding, and M. N. Rerick, J. Am. Chem. Soc., 84, 2371 (1962).
  6. E. L. Eliel, L. A. Pilato, and V. G. Badding, J. Am. Chem., Soc., 84, 2377 (1962).
  7. L. I. Zakharkin and I. M. Khorlina, Izv. Akad. Nauk. SSSR, Otd. Khim. Nauk, 2255 (1959) [C.A., 54, 10837 (1960)].
  8. M. Mousseron, R. Jacquier, M. Mousseron-Canet, and R. Zagdoun, Bull. Soc. Chim. France, [5] 19, 1042 (1952).
  9. J. W. Powell and M. C. Whiting, Tetrahedron, 7, 305 (1959).
  10. M. N. Rerick in R. L. Augustine, "Reduction," Marcel Dekker, Inc., New York, 1968, pp. 46–52.
  11. B. E. Leggetter and R. K. Brown, Can. J. Chem., 41, 2671 (1963).

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


potassium carbonate (584-08-7)

sulfuric acid (7664-93-9)

Benzene (71-43-2)

ether (60-29-7)

hydrogen (1333-74-0)

sodium hydroxide (1310-73-2)

sodium bicarbonate (144-55-8)

Cyclohexanone (108-94-1)

nitrogen (7727-37-9)

copper (7440-50-8)

aluminum chloride,
aluminum chloride powder (3495-54-3)

sodium (13966-32-0)

ethylene glycol,
1,2-ethanediol (107-21-1)

lithium aluminum hydride (16853-85-3)

diisobutylaluminum hydride (1191-15-7)

Ethanol, 2-(cyclohexyloxy)- (1817-88-5)

1,4-Dioxaspiro[4.5]decane (177-10-6)

cyclohexyloxyacetic acid

cyclohexanone methanesulfonylhydrazone

p-toluenesulfonic acid monohydrate (6192-52-5)