Checked by Thomas G. Marron, Lance A. Pfeifer, and William R. Roush.
1. Procedure
A.
Dimethyldioxirane (See
f.htmigure 1). A
2-L, three-necked, round-bottomed flask containing a mixture of water (80 mL),
acetone (50 mL, 0.68 mol), and
sodium bicarbonate (96 g), is equipped with a
magnetic stirring bar and a
pressure equalizing addition funnel containing water (60 mL) and
acetone (60 mL, 0.82 mol) (Note
1). A solid addition flask containing
Oxone (180 g, 0.29 mol) is attached to the reaction vessel via a rubber tube (Note
2). An
air condenser (20 cm length) loosely packed with glass wool is attached to the reaction vessel. The outlet of the air condenser is connected to a
75 × 350-mm Dewar condenser filled with dry ice-acetone that is connected to a receiving flask (100 mL) cooled in a
dry ice-acetone bath. The receiving flask is also connected in series to a second dry ice-acetone cold trap, a
trap containing a potassium iodide solution, and a
drying tube. A
gas inlet tube is connected to the reaction flask and a stream of
nitrogen gas is bubbled through the reaction mixture (Note
3). The
Oxone is added in portions (10–15 g) while the acetone-water mixture is simultaneously added dropwise (Note
4). The reaction mixture is stirred vigorously throughout the addition of reagents (ca. 30 min). A yellow solution of
dimethyldioxirane in
acetone collects in the receiving flask. Vigorous stirring is continued for an additional 15 min while a slight vacuum (ca.
30 mm, water aspirator) is applied to the cold trap (Note
5). The yellow dioxirane solution (
62–76 mL, (Note
6)) is dried over
sodium sulfate (Na2SO4), filtered and stored in the freezer (−25°C) over Na
2SO
4. The dioxirane content of the solution is assayed using
phenyl methyl sulfide and the GLC method ((Note
7) and (Note
8)). Generally concentrations in the range of 0.07–0.09 M are obtained.
Figure 1
B.
trans-Stilbene oxide. To a magnetically stirred solution of
trans-stilbene (0.724 g, 4.02 mmol) (Note
9) in
5 mL of acetone is added a solution of
0.062 M dimethyldioxirane in
acetone (66 mL, 4.09 mmol) at room temperature. The progress of the reaction is followed by GLC (Note
10), which analysis indicates that
trans-stilbene is converted to the oxide in 6 hr (Note
11). Removal of solvent on a
rotary evaporator gives a white crystalline solid. The solid is dissolved in
dichloromethane (CH2Cl2) (30 mL) and dried with anhydrous Na
2SO
4. The drying agent is filtered off and washed with CH
2Cl
2. The solvent is removed on a rotary evaporator. Remaining solvent is removed under reduced pressure to give an analytically pure sample of the oxide (
0.788 g,
100% yield). Recrystallization from
aqueous ethanol gives white plates/prisms, mp
69–70°C ((Note
12), (Note
13)).
2. Notes
1. A
mechanical stirrer may also be used.
2. The submitters used
Oxone supplied by DuPont, whereas the checkers used
Oxone purchased from Aldrich Chemical Company, Inc.
3. The submitters recommended that a stream of
helium be passed through the reaction system during the course of the experiment. The checkers substituted
nitrogen for
helium with no decrease in yield . In addition, on several occasions the checkers did not use a gas purge and there was no decrease in yield. Therefore, use of a gas purge is viewed as optional, not mandatory. It is noted that other investigators have reported
dimethyldioxirane preparations that do not require use of a gas purge.
2
4. The procedure followed was generally that contained in the original publication.
3 See an alternative procedure, by Adam.
2
5. The submitters recommended that the distillation be performed at ca. 30 mm. By using this procedure the checkers obtained an average of
67 mL (range: 62–76 mL) of dioxirane solution with an average concentration of 0.077 M (range: 0.068–0.087 M) over 10 repetitions of the procedure. When the distillation was performed at 80 mm for up to 90 min, greater volumes of
dimethyldioxirane solution were obtained (
84–89 mL), but with a corresponding decrease in the reagent concentration (0.053–0.066 M).
7. Determination of
dimethyldioxirane concentration by the GLC method is as follows: A standard solution of
thioanisole (phenyl methyl sulfide) is prepared. The solution is usually 0.2 M in
acetone, but other concentrations may be used. It is important to keep the sulfide in excess so that oxidation by the dioxirane will produce largely or exclusively the sulfoxide and not the sulfone.
A standard solution of an internal standard
(dodecane or hexadecane) is also prepared in
acetone. This solution should be at the same concentration as that of the sulfide.
To determine the dioxirane concentration 1 mL each of the dioxirane, sulfide, and internal standard solutions are combined in a vial. The GLC analysis is then carried out using the following: Column: DB 210; temp 1 = 60°C, time 1 = 5 min, rate 1 = 20°/min; temp 2 = 200°C, time 2 = 5 min. The analysis is conducted on 1 μL of solution. The analysis is made quantitative by determining the response factors of the sulfide and internal standard in the usual manner. The
dimethyldioxirane concentration is determined by measuring the sulfide concentration before and after adding the dioxirane. Under these conditions the following retention times are observed:
dodecane, 7.15 min; sulfide, 8.2 min; sulfoxide, 12.9 min.
8. Generally concentrations in the range of 0.07–0.09 M are obtained. The submitters reported a concentration range of 0.05–0.10 M.
9.
trans-Stilbene was purchased from Eastman Organic Chemical Co. The purity of the sample was 99%. Sample purity was also checked by GLC and GC-MS. The GC-MS analysis suggests that the sample contains
bibenzyl (<1%) as an impurity.
10. Gas chromatographic conditions are as follows: Column DB-210 (30 m × 0.318 mm × 0.5 μm, fused silica capillary column), column temp 1 = 100°C, time 1 = 5 min, rate = 20°/min; temp 2 = 200°C, time 2 = 7 min, injector temp 250°C, detector temp 250°C, inlet P, 24 psi, retention times:
trans-stilbene 11.4 min,
trans-stilbene oxide 11.9 min.
11. In 2 hr, 96% conversion had occurred.
13.
trans-Stilbene oxide has the following properties:
1H NMR (300 MHz, CDCl
3) δ: 3.86 (s, 2 H, 2 × -CH-), 7.26–7.45 (m, 10 H, 2 × C
6H
5-);
13C NMR (75 MHz, CDCl
3) δ: 62.81 (-CH-); 125.4 (C-4, Ar), 128.19 (C-3,5, Ar), 128.44 (C-2,6, Ar), 136.99 (C-1, ipso C of phenyl); IR (CHCl
3) cm
−1: 3076, 3036, 2989, 1603, 1497, 1457, 870, 698; high resolution mass spectrum, Calcd. for C
14H
12O, 196.0888. Found 196.0896. Anal. Calcd. for C
14H
12O: C, 85.68; H, 6.16. Found: C, 85.76; H, 6.05.
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
For most epoxidations
dimethyldioxirane (DMD) is the reagent of choice. The reaction is usually carried out at room temperature or below and in neutral solution. The reaction is stereospecific, proceeds rapidly, and generally in essentially quantitative yield. The procedure is remarkably convenient. In many cases removal of the solvent gives the pure product. The reaction is applicable to a variety of unsaturated systems (Table). The data given in the Table also compare yields with the commonly used epoxidation reagent m-chloroperbenzoic acid (MCPBA). In almost every case use of DMD gave a higher yield than did MCPBA. In many cases the difference is dramatic (see entries 1 and 2, for example). The use of MCPBA frequently leads to opening of sensitive epoxides under the acidic conditions of the reaction. This problem is conveniently avoided when using DMD. In a growing number of cases DMD has successfully given an epoxide when other methods fail. A particularly pleasing example
4 of this is the preparation of the 8,9-epoxide of the mycotoxin, aflatoxin B
1.
Linear free energy relationship studies
10,11 have demonstrated that DMD is an electrophilic reagent. This property is demonstrated in the Table where substrates with electron-withdrawing substituents require longer reaction times (compare entries 1 and 2 with 4, for example). This is particularly noticeable in entry 8 where the substrate contains a strong electron-withdrawing substituent. The previously reported
10 faster rates for DMD epoxidation of cis-alkenes compared to their trans stereoisomers is seen in the longer reaction times required for the trans isomers (compare entries 1 and 2, and 3 and 4). This difference in rates is taken as support for a spiro transition state
10 for epoxidation. A number of reviews
12,13,14,15,16 of the chemistry of DMD, including its use as an epoxidizing reagent, have been published.
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