Trichloroperoxyacetamidic Acid

[84694-15-1]  · C2H2Cl3NO2  · Trichloroperoxyacetamidic Acid  · (MW 178.40)

(oxygen atom transfer reagent that is useful for the epoxidation of alkenes at a neutral pH8)

Physical Data: not isolated; prepared in situ.

Solubility: sol standard organic solvents such as CH2Cl2.

Preparative Methods: Trichloroacetonitrile (8.5 g, 0.049 mol) and 5-methyl-5-hepten-2-one (3.72 g, 0.029 mol) in 40 mL of methylene chloride were added dropwise to a stirring solution of 5.0 mL of 30% Hydrogen Peroxide (0.44 mol). The H2O2 solution was adjusted to pH 6.8 by the addition of 2.25 g of K2HPO4 prior to addition. The biphasic mixture was magnetically stirred at room temperature while the depletion of alkene was monitored by GLC (6 ft column, 10% UCW on Chromosorb W, 130 °C). After 3 h, 25 mL of pentane was added, and the precipitated trichloroacetamide was removed by filtration through a fritted disk and washed with pentane. More complete removal of the trichloroacetamide may be achieved by chilling the reaction mixture prior to filtration. The filtrates were washed with water (20 mL), cold 3% Na2SO3 solution (25 mL), and brine (25 mL), and then dried (MgSO4). The solvents were removed by aspiration, and the yellow residue was fractionally distilled to afford 3.35 g (80%) of epoxide, bp 42-42.5 °C/20 mmHg).

Handling, Storage, and Precautions: this reagent is generated in situ and is not stable to storage.

Alkene Epoxidation.

Epoxides are typically prepared from alkenes on a laboratory scale by the action of organic peroxides and metal catalysts or by oxidation with a peroxy acid.1,2 The more commonly used commercially available oxidants for the epoxidation of simple alkenes include Peracetic Acid, m-Chloroperbenzoic Acid (m-CPBA), and Monoperoxyphthalic Acid, magnesium salt hexahydrate (MMPP). Trifluoroperacetic Acid is one of the most reactive peroxy acids, but it suffers the disadvantage of having to be prepared in situ by the action of trifluoroacetic anhydride and 90% hydrogen peroxide.3 The resulting solution is highly acidic and can have a deleterious effect upon the yield of epoxide.

Although hydrogen peroxide is not sufficiently electrophilic to directly epoxidize a nonconjugated carbon-carbon double bond, its reactivity may be enhanced by placing the OOH moiety in conjugation with a multiple bond, as exemplified by a peroxy acid (1).4

One of the earliest and most useful adaptations of this concept was accomplished by Payne.5 He successfully activated the O-O bond by the in situ formation of a peroxyimidic acid (2) resulting from the base-catalyzed addition of H2O2 to a nitrile. Both aceto- and benzonitrile were employed as coreactants in the epoxidation of a variety of alkenes in methanol solvent. More recently, Rebek6 and co-workers have developed a number of reactive oxidizing reagents resembling (1) and (2) and related activated hydroperoxides.

The mechanism of alkene epoxidation involves a bimolecular nucleophilic attack of the alkene (HOMO) on the antibonding s* orbital of the O-O bond.7 Consequently, heterolytic cleavage of the peroxide bond is facilitated by electron-withdrawing groups on the multiple bond. A trichloromethyl substituent increases the reactivity of a peroxy acid and a peroxyimidic acid.8 Reaction of 30% aqueous H2O2 with the electron-deficient nitrile trichloroacetonitrile affords a highly efficient oxygen transfer reagent that can compete with m-CPBA on both a cost and reactivity basis (eq 1).

The rate of epoxidation is faster with more highly substituted and strained alkenes. Trichloroperoxyimidic acid (3) is sufficiently reactive to effect epoxidation of the terminal alkene 1-nonene (71%). This reagent will also epoxidize the deactivated double bond of a,b-unsaturated ketones in a highly chemoselective manner without affording products derived from a Baeyer-Villiger oxidation (eq 2).

Another unique feature of the reagent is its ability to epoxidize 1-cyclopenteneacetonitrile without disturbing the nitrile functional group. The oxygen transfer reaction is stereospecific, as evidenced by the formation of only the (Z)-epoxide from (Z)-stilbene, and the (E)-epoxides from (E)-cinnamyl alcohol, (E)-stilbene, and (E)-cyclooctene. The procedure is readily adaptable to the large-scale syntheses of epoxides. For example, 50 g (0.45 mol) of cis-cyclooctene on treatment with 1.5 equiv of CCl3CN and 3 equiv of H2O2 (pH 6.8) afforded 48.0 (84%) of cis-cyclooctene oxide. On a 2 molar scale the yield of epoxide was 76%.

One potential disadvantage of this procedure from an operational perspective is the fact that it operates in a very narrow pH range. An increase in pH favors the formation of (3), but a competing reaction with the anion of H2O2 reduces the concentration of active oxygen (eq 3). The formation of dioxygen is pH dependent. Maintaining the optimal pH is best achieved by the use of a pH meter. The mechanism for the addition of H2O2 to a nitrile has been studied by Wiberg9a in the pH range 7-8 and by McIsaac and his co-workers9b at a pH of 9.75. The rate limiting step for oxygen atom transfer is the nucleophilic attack of (3) on the carbon-carbon double bond.9c

Related Reagents.

O-Ethylperoxycarbonic Acid; Peroxyacetimidic Acid.


1. Sharpless, K. B.; Verhoeven, T. R. Aldrichim. Acta 1979, 12, 63.
2. (a) House, H. O. Modern Synthetic Reactions, 2nd ed.; Benjamin: Menlo Park, CA, 1972; p 292. (b) Swern, D. OR 1953, 7, 378.
3. Lewis, S. N. In Oxidation, Augustine, R. L., Ed.; Dekker: New York, 1969; Vol. 1, p 216.
4. For a recent review see: Rebek, J., Jr. H 1981, 15, 517.
5. (a) Payne, G. B.; Deming, P. H.; Williams, P. H. JOC 1961, 26, 659. (b) Payne, G. B. T 1962, 18, 763.
6. (a) Rebek, J., Jr.; Wolf, S.; Mossman, A. JOC 1978, 43, 180. (b) Rebek, J., Jr.; McCready, R.; Wolf, S.; Mossman, A. JOC 1979, 44, 1485.
7. (a) Bach, R. D.; Willis, C. L.; Lang, T. J. T 1979, 35, 1239. (b) Lang, T. J.; Wolber, G. J.; Bach, R. D. JACS 1981, 103, 3275.
8. Arias, L. A.; Adkins, S.; Nagel, C. J.; Bach, R. D. JOC 1983, 48, 888.
9. (a) Wiberg, K. B. JACS 1953, 75, 3961. Wiberg, K. B. JACS 1955, 77, 2519. (b) McIsaac, J. E., Jr.; Ball, R. E.; Behrman, E. J. JOC 1971, 36, 3048. (c) Sawaki, Y.; Ogata, Y. BCJ 1981, 54, 793.

Robert D. Bach

Wayne State University, Detroit, MI, USA



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