Org. Synth. 1974, 54, 37
DOI: 10.15227/orgsyn.054.0037
Submitted by R. B. Woodward1, I. J. Pachter2, and M. L. Scheinbaum3.
Checked by J. G. Green and S. Masamune.
1. Procedure
Caution! Benzene has been identified as a carcinogen; OSHA has issued emergency standards on its use. All procedures involving benzene should be carried out in a well-ventilated hood, and glove protection is required.
A 300-ml., one-necked flask equipped with a reflux condenser, the top of which is attached to a nitrogen inlet tube, is charged with 3.85 g. (0.0338 mole) of 2-hydroxymethylenecyclohexanone (Note 1), 10 g. (0.025 mole) of ethylene dithiotosylate (Note 2), and 10 g. of potassium acetate in 150 ml. of methanol. The mixture is refluxed under nitrogen for 3 hours with stirring, the solvent is removed from the reaction mixture on a rotary evaporator, and the residue is extracted with three 50-ml. portions of diethyl ether. The combined ethereal extracts are washed with cold, aqueous 2 N sodium hydroxide (Note 3) until the aqueous layer is basic to litmus, then with 50 ml. of saturated aqueous sodium chloride. The ethereal layer is dried over anhydrous magnesium sulfate, filtered, and concentrated on a rotary evaporator. The oily residue is diluted with 1 ml. of benzene and 3 ml. of cyclohexane and transferred to a chromatographic column (14 × 2 cm.) prepared with 50 g. of alumina (Note 4) and a 3:1 mixture of cyclohexane and benzene. With this solvent system the desired product moves with the solvent front, and the first 100 ml. of eluent contains 85% of the total product. Further elution with approximately 100 ml. of the same solvent mixture removes the rest of the material before a second component begins to come off. Evaporation of the solvent from the combined 200 ml. of eluent leaves an oily residue which crystallizes on standing, yielding 2.76–3.04 g. (57–64%) of crude 2,2-(ethylenedithio)cyclohexanone. Recrystallization from approximately 50 ml. of pentane affords 2.1–2.6 g. (45–55%) of needles, m.p. 56–57° (Note 5).
2. Notes
1. 2-Hydroxymethylenecyclohexanone was prepared by both the submitters and checkers by a procedure similar to, but slightly modified from, that described in Org. Synth., Coll. Vol. 4, 536 (1963). To a cooled (ice bath), stirred suspension of 10.2 g. (0.189 mole) of commercial sodium methoxide in 75 ml. of anhydrous benzene under nitrogen was added dropwise, but rapidly (ca. 2 minutes), a mixture of 9.8 g. (0.10 mole) of distilled cyclohexanone and 14.8 g. (0.200 mole) of distilled ethyl formate. After addition, the reaction was allowed to warm to room temperature and left overnight. Ice water (100 ml.) was added to the resulting suspension. The aqueous layer was separated, and the benzene layer was washed three times with 50 ml. of cold, aqueous 0.1 N sodium hydroxide. The aqueous layers were combined, and the product was isolated according to the procedure referenced above. This modified version provided slightly higher yields of the product than that recorded in Org. Synth., and the ease of handling sodium methoxide, compared with sodium metal, is advantageous.
2. Ethylene dithiotosylate, m.p. 73–73.5°, as described in Org. Synth., Coll. Vol. 6, 1016 (1988), is employed.
3. Treatment with alkali removes the various acidic by-products and their salts (acetate, sulfinate, and formate) and also serves to hydrolyze and remove unreacted starting materials.
4. The checkers used "Aluminum Oxide" purchased from J. T. Baker Chemical Company.
5. The 1H NMR spectrum of the product (CDCl3): δ 1.83 (m, 4H), 2.42 (m, 2H), 2.73 (m, 2H), 3.30 (s, 4H).
3. Discussion
The procedure for the preparation of a dithiolane from a hydroxymethylene derivative of a ketone and ethylene dithiotosylate (ethane-1,2-dithiol di-p-toluenesulfonate) can be varied to produce dithianes, when the latter reagent is replaced with trimethylene dithiotosylate.4,5 Dithiotosylates also react with enamine derivatives, producing dithiaspiro compounds.5,6

References and Notes
  1. 1965 Nobel Laureate in Chemistry; deceased July 8, 1979; formerly at the Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138.
  2. Present address: Bristol Laboratories, Division of Bristol-Myers Company, Syracuse, New York 13201.
  3. Present address: Sterling-Winthrop Research Institute, Rensselaer, New York 12144.
  4. R. B. Woodward, I. J. Pachter, and M. L. Scheinbaum, Org. Synth., Coll. Vol. 6, 1016 (1988).
  5. R. B. Woodward, I. J. Pachter, and M. L. Scheinbaum, J. Org. Chem., 36, 1137 (1971).
  6. R. B. Woodward, I. J. Pachter, and M. L. Scheinbaum, Org. Synth., Coll. Vol. 6, 1014 (1988).

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

Benzene (71-43-2)

methanol (67-56-1)

diethyl ether (60-29-7)

sodium hydroxide (1310-73-2)

Cyclohexanone (108-94-1)

sodium chloride (7647-14-5)

nitrogen (7727-37-9)

cyclohexane (110-82-7)

sodium methoxide (124-41-4)

sodium (13966-32-0)

ethyl formate (109-94-4)

Pentane (109-66-0)

magnesium sulfate (7487-88-9)

potassium acetate (127-08-2)

aluminum oxide (1344-28-1)

2-Hydroxymethylenecyclohexanone (823-45-0)

1,4-Dithiaspiro[4,5]decan-6-one (27694-08-2)

ethylene dithiotosylate

trimethylene dithiotosylate (3866-79-3)

ethane-1,2-dithiol di-p-toluenesulfonate