Organic Syntheses, CV 7, 126
Submitted by R. D. Bach and J. W. Knight
1.
Checked by K. W. Fowler and G. Büchi.
1. Procedure
Caution! Organic-soluble peroxides may be explosive (Note 4)!
In a
5-L, three-necked, round-bottomed flask fitted with a
mechanical overhead stirrer,
addition funnel, and
thermometer are placed
484 g (4.4 mol) of cis-cyclooctene,
3 L of reagent methanol (Note
1),
330 g (8.04 mol) of acetonitrile, and
77 g (0.77 mol) of potassium bicarbonate (Note
2). To the resulting heterogeneous mixture is added dropwise
522 g (4.6 mol) of 30% hydrogen peroxide with cooling at a rate that maintains the temperature of the reaction at 25–35°C (Note
3). Following the addition of
hydrogen peroxide, the
ice bath is removed and the reaction mixture is allowed to stir at room temperature overnight. The reaction mixture is divided in half, and each portion is diluted with
500 mL of a saturated sodium chloride solution. Each portion is then extracted with four
500-mL portions of methylene chloride (Note
4). The organic phases are combined, dried over
magnesium sulfate, and concentrated at reduced pressure by rotary evaporation. Short-path distillation of the crude product (Note
5) under reduced pressure gives
333–337 g (
60–61%) of
cis-cyclooctene oxide, bp
85–87°C (20 mm), as a white solid, mp
53–56°C (Note
6).
2. Notes
1. Omission of the
methanol resulted in substantially reduced yields.
3. The reaction is exothermic and caution should be exercised to keep the reaction temperature from rising. The time required for complete addition of the
hydrogen peroxide is ca. 2–3 hr. The temperature is maintained at 25–35°C by employing an
ice-water bath. When the
hydrogen peroxide was added too rapidly, the reaction temperature rose until the solvents refluxed.
4. To check for organic-soluble peroxides, add several milliliters of the
methylene chloride solution to a solution containing ca.
1 mg of sodium dichromate, 1 mL of water, and 1 drop of dilute
sulfuric acid. A blue color in the organic layer is a positive test for perchromate ion. The checkers found that the combined organic phases exhibited a positive test and therefore stirred them overnight with a solution of
100 g of sodium metabisulfite in 500 mL of water prior to drying.
5. Heat from an IR lamp or heat gun must be applied to the condenser to keep the product from solidifying. The distillation pot should not be taken to dryness because of the possibility of the presence of organic peroxides.
6. The crude product may be used in many cases without further purification. Sublimation of the distilled
oxirane affords the product as white needles, mp
56–57°C. The checkers obtained a broader melting point of the distillate, but the product was pure by analytical VPC.
3. Discussion
Oxiranes are typically formed by the action of a peracid such as
m-chloroperbenzoic acid8 on an alkene.
9 The present method has the advantage of being useful for both large- and small-scale reactions. The actual epoxidizing agent is generated in situ from the addition of
hydrogen peroxide to a nitrile, forming a
peroxyimidic acid.
10 This procedure is an adaptation of the method of Payne that utilized an intermediate peroxyimidic acid derived from the reaction of
hydrogen peroxide with
acetonitrile11 and
benzonitrile.
12 The alkaline hydrogen peroxide-benzonitrile system has more recently been used with steroids,
13 and in the total synthesis of prostaglandin F
2α.
14 The present method does not require the separation of
benzamide from the product. In addition, the reagents are inexpensive and the method is convenient and safe since it does not require large-scale preparation and handling of an organic peracid. Recently, it has been shown that substitution of
trichloroacetonitrile for
acetonitrile produces an even more reactive reagent.
15
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