Organic Syntheses, CV 9, 585
Submitted by Karl R. Dahnke and Leo A. Paquette
1.
Checked by M. Amornmarn, A. Focella, and David L. Coffen.
1. Procedure
A.
2-Chloromethyl-1,3-dithiolane. A
500-mL, three-necked, round-bottomed flask equipped with a
dropping funnel and
magnetic stirrer is charged with
59.5 mL (0.71 mol) of 1,2-ethanedithiol (Note
1) and
50 mL of concd hydrochloric acid. This mixture is cooled to 0°C and
89 mL (0.78 mol) of chloroacetaldehyde dimethyl acetal (Note
2) is added via the dropping funnel over 2 hr (Note
3). After an additional 30 min, the
ice bath is removed and the reaction mixture is stirred for 3 hr at room temperature. The resulting two-phase mixture is partitioned between
dichloromethane (100 mL) and water (100 mL). The organic phase is separated and the aqueous phase is extracted with
dichloromethane (100 mL). The combined organic layers are washed with water (100 mL), saturated
sodium bicarbonate solution (100 mL), and
brine (100 mL), then dried over
magnesium sulfate. After removal of the solvent under reduced pressure, the viscous, colored residue (111 g) is subjected to bulb-to-bulb distillation using
500-mL and 250-mL collector bulbs and a
500-mL flask to hold the crude product. The
oven temperature is initially 20°C and is gradually increased to 120°C. Pressure is maintained at 0.25 mm. Initially
only the bulb remote from the oven is cooled, using an
acetone/dry ice bath. Solvent and volatile impurities are collected in this bulb. The product is then condensed in the bulb nearest the oven by placing a dry ice/acetone bath under this bulb after the higher boiling material begins to distill. The clear colorless oil thus obtained consists of fairly pure
2-chloromethyl-1,3-dithiolane (
59.3–65.0 g,
54–59%) (Note
4), (Note
5) and (Note
6).
B.
2-Methylene-1,3-dithiolane. A
1-L, three-necked, round-bottomed flask equipped with a pressure-equalizing dropping funnel,
thermometer, magnetic stirrer, and
nitrogen inlet is charged with
33.0 g (0.213 mol) of 2-chloromethyl-1,3-dithiolane and
diethyl ether (400 mL) (Note
7). After the flask is flushed with
nitrogen, the solution is cooled to 0°C.
Methyllithium-lithium bromide complex in
diethyl ether (156 mL of 1.5 M solution, 0.235 mol) (Note
8) is transferred into the dropping funnel via
cannula and added dropwise over 2 hr. After an additional 30 min, the ice bath is removed and the mixture is allowed to warm gradually to room temperature. After 2 hr at room temperature when
methane evolution has ceased, the mixture is recooled to 0°C and quenched by dropwise addition of
50 mL of saturated ammonium chloride solution followed by sufficient water to just dissolve the salts. The organic layer is separated, washed with water (3 × 100 mL), saturated
sodium bicarbonate solution (100 mL), and
brine (100 mL), then dried over
magnesium sulfate. The solvent is removed under reduced pressure and the residue is distilled through a
short-path distillation apparatus (34–40°C at 1.0 mm) (Note
9) to give
20.6–21.6 g (
82–86%) of
2-methylene-1,3-dithiolane as a light yellow oil (Note
10).
2. Notes
1.
1,2-Ethanedithiol was purchased from the Aldrich Chemical Company, Inc., and used without further purification.
3. The addition was performed sufficiently slowly to maintain a temperature of 5–10°C.
4. During the thioketalization and distillation, thermal extrusion of HCl and isomerization to
2,3-dihydro-1,4-dithiin is observed
2 and the product of Step A typically contains ca. 10% of this impurity.
5. Storage of this material in a freezer is recommended.
6. Spectral characteristics are as follows: IR (CHCl
3) cm
−1: 3000, 2910, 1430, 1260;
1H NMR (300 MHz, CDCl
3) δ: 3.22 (s, 4 H), 3.61 (d, 2 H, J = 7.2), 4.63 (t, 1 H, J = 7.2);
13C NMR (CDCl
3) δ: 38.36, 49.64, 54.23. Peaks arising from the 1,4-dithiin impurity appear at 3.18 and 6.08 ppm in the
1H NMR.
7.
Ether was distilled from
sodium-benzophenone ketyl before use.
9. The receiver was cooled to −78°C and a small amount of
triethylamine was added to the cold solution to stabilize the product against acid-catalyzed polymerization. As an added precaution, all glassware was base-washed prior to use.
10. Spectral characteristics are as follows: IR (CHCl
3) cm
−1: 3000, 2930, 1675, 1575, 1525, 1425, 1285;
1H NMR (300 MHz, CDCl
3) δ: 3.37 (s, 4 H), 5.13 (s, 2 H);
13C NMR (75 MHz, CDCl
3) δ: 38.47, 99.60, 144.50. Peaks attributable to the 1,4-dithiin impurity carried through from Step A also appear in the
1H NMR spectrum.
Waste Disposal Information
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
The process requires vast amounts of solvent, proceeds in low yield, and is plagued by the need to isolate and handle a potentially explosive intermediate.
Herein is described a much simpler dehydrohalogenation alternative that had been earlier applied successfully to the preparation of ketene acetals
6,7 and 2-alkylidene-1,3-dithianes.
8 This route appears not to have been examined for preparing the title compound because of an early report that
2-lithio-1,3-dithiolanes undergo ready fragmentative elimination to form
ethylene and
dithiocarbonate unlike their stable
1,3-dithiane homologues.
8 In point of fact, the loss of chloride ion from lithiated
2-chloromethyl-1,3-dithiolane is the kinetically-favored elimination reaction. Use of the present two-step procedure makes possible the safe, direct acquisition of
2-methylene-1,3-dithiolane in unlimited quantities.
One of the uses of this reactive intermediate is illustrated on
page 396.
9
This preparation is referenced from:
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
brine
sodium-benzophenone ketyl
2-lithio-1,3-dithiolanes
hydrochloric acid (7647-01-0)
ether,
diethyl ether (60-29-7)
ammonium chloride (12125-02-9)
acetonitrile (75-05-8)
sodium bicarbonate (144-55-8)
nitrogen (7727-37-9)
methane (7782-42-5)
ethylene (9002-88-4)
dichloromethane (75-09-2)
magnesium sulfate (7487-88-9)
triethylamine (121-44-8)
1,2-ethanedithiol (540-63-6)
1,3-Dithiane (505-23-7)
diisopropylethylamine (7087-68-5)
Methyllithium-lithium bromide
2-Methylene-1,3-dithiolane,
1,3-Dithiolane, 2-methylene- (26728-22-3)
2-Chloromethyl-1,3-dithiolane (86147-22-0)
chloroacetaldehyde dimethyl acetal (97-97-2)
2,3-dihydro-1,4-dithiin
2-methyl-1,3-dithiolan-2-yl perchlorate
dithiocarbonate
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved