Peroxyacetimidic Acid

(R = Me)

[64415-45-8]  · C2H5NO2  · Peroxyacetimidic Acid  · (MW 75.08) (R = Ph)

[20996-66-1]  · C7H7NO2  · Peroxybenzimidic Acid  · (MW 137.15)

(oxygen atom transfer that is useful for the epoxidation of alkenes)

Preparative Methods: these reagents are generated in situ by the reaction of 30% aqueous H2O2 with either Acetonitrile or benzonitrile at room temperature.

Alkene Epoxidation.

Although Hydrogen Peroxide is readily available and relatively inexpensive, it is not a very reactive oxidant. For example, H2O2 will not effect the epoxidation of a nonconjugated carbon-carbon double bond. Heterolytic cleavage of the O-O bond in H2O2 has a relatively high activation barrier since the hydroxy anion is a poor leaving group. Alkene epoxidation1 is typically achieved by its reaction with a peroxy acid (1) such as Peracetic Acid or m-Chloroperbenzoic Acid (m-CPBA).2

When the -OOH functional group is placed in conjugation with a carbonyl group, a carboxylate anion is the leaving group upon heterolylic cleavage of the O-O bond. Trifluoroperacetic Acid (CF3CO3H) is a highly reactive epoxidizing reagent since electron-withdrawing groups stabilize the departing carboxylate anion.

The O-O bond in H2O2 can also be activated by its conjugative interaction with an imine functionality. One of the earliest and most useful adaptations of this type of O-O bond activation was accomplished by Payne.3 The peroxyimidic acid derived from the alkaline hydrogen peroxide/benzonitrile system has been used with steroids4a and in the total synthesis of prostaglandin F2a.4b Hydrogen peroxide reacts with nitriles under controlled pH conditions (~pH 8) to generate a peroxyimidic acid (eq 1). Although peroxyimidic acids (2) have not been isolated, they react rapidly with a variety of reducing agents.

Acetonitrile, benzonitrile, and Trichloroacetonitrile3,5a have been used as coreactants to produce peroxyimidic acids that are highly effective oxidants for the epoxidation of alkenes. This oxidation reaction has the advantage of being useful for both large- and small-scale reactions. For example, the epoxidation of (Z)-cyclooctene has been carried out with acetonitrile and H2O2 (eq 2) on a 4.4 mol scale to afford (Z)-cyclooctene oxide in 60-61% isolated yield.5b

The epoxidation procedure is usually carried out in methanol solvent using KHCO3 as a buffer. The reaction does not proceed well when sodium bicarbonate is employed and omission of a protic solvent such as methanol results in substantially reduced yields. The rate limiting step appears to be the nucleophilic attack of the alkene on the O-O bond.6 Formation of the epoxide is an exothermic reaction and caution should be exercised to keep the temperature of the reaction mixture from rising.

Wiberg7 has investigated the mechanism of the addition of H2O2 to a nitrile in the pH range 7-8. At higher pH values the mechanism can change and nucleophilic attack by the anion of (2) on H2O2 can result in the formation of dioxygen and the corresponding amide.8 Radical pathways for the decomposition of (2) have also been proposed.9 The epoxidation of aliphatic alkenes with peroxybenzimidic acid (2; R = Ph) has been shown to be less selective and have greater steric requirements than a peroxy acid.10 Differences in the stereoselectivity of diepoxide formation between peroxy acids and peroxyimidic acids have also been noted.11

Related Reagents.

O-Ethylperoxycarbonic Acid.

1. (a) Sharpless, K. B.; Verhoeven, T. R. Aldrichim. Acta 1979, 12, 63. (b) Finn, M. G.; Sharpless, K. B. Asymmetric Synth. 1986, 5, 247. (c) Plesnicar, B. In The Chemistry of Peroxides; Patai, S., Ed.; Wiley: New York, 1983; p 521. (d) Cremer, D. In The Chemistry of Peroxides; Patai, S., Ed.; Wiley: New York. 1983; p 1.
2. Swern, D. OR 1953, 7, 378. Harrison, I. T.; Harrison, S. Compendium of Organic Synthetic Methods; Wiley: New York, 1971; Vol. 1, pp 325-326. Harrison, I. T.; Harrison, S. Compendium of Organic Synthetic Methods; Wiley: New York, 1974; Vol. 2, pp 134-135.
3. (a) Payne, G. B.; Deming, P. H.; Williams, P. H. JOC 1961, 26, 659. (b) Payne, G. B. T 1962, 18, 763.
4. (a) Ballantine, J. D.; Sykes, P. J. JCS(C) 1970, 731. (b) Woodward, R. B.; Gosteli, J.; Ernst, I.; Friary, R. J.; Nestler, G.; Raman, H.; Sitrin, R.; Suter, Ch.; Whitsell, J. K. JACS 1973, 95, 6853.
5. (a) Arias, L. A.; Adkins, S.; Nagel, C. J.; Bach, R. D. JOC 1983, 48, 888. (b) Bach, R. D.; Knight, J. W. OS 1981, 60, 63; OSC 1990, 7, 126.
6. Sawaki, Y.; Ogata, Y. BCJ 1981, 54, 793.
7. Wiberg, K. B.; JACS 1953, 75, 3961; 1955, 77, 2519.
8. McIsaac, J. E., Jr.; Ball, R. E.; Behrman, E. J. JOC 1971, 36, 3048.
9. Gibian, M. J.; Ungermann, T. JACS 1979, 101, 1291.
10. Causa, A. G.; Chen, H. Y.; Tark, S. Y.; Harwood, H. J. JOC 1973, 38, 1385.
11. Carlson, R. G.; Behn, N. S.; Cowles, C. JOC 1971, 36, 3832.

Robert D. Bach

Wayne State University, Detroit, MI, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.