Peracetic Acid1

[79-21-0]  · C2H4O3  · Peracetic Acid  · (MW 76.06)

(electrophilic reagent capable of reacting with many functional groups; delivers oxygen to alkenes, sulfides, selenides, and amines)

Alternate Name: peroxyacetic acid.

Physical Data: mp 0 °C; bp 25 °C/12 mmHg; d 1.038 g cm-3 at 20 °C.

Solubility: sol acetic acid, ethyl acetate, CHCl3, acetone, benzene, CH2Cl2, ethylene dichloride, water.

Form Supplied in: 40% solution in acetic acid (d 1.15 g cm-3) having approximately the following composition by weight: peracetic acid, 40-42%; H2O2, 5%; acetic acid, 40%; H2SO4, 1%; water, 13%; diacetyl peroxide, nil; other organic compounds, nil; stabilizer, 0.05%. A solution of the peracid in ethyl acetate is also available commercially.

Analysis of Reagent Purity: assay using iodometry;2 estimation of diacetyl peroxide.3

Preparative Methods: prepared in the laboratory by reacting Acetic Acid with hydrogen peroxide in the presence of catalytic quantities (1% by weight) of Sulfuric Acid; when 30% H2O2 is used the concentration of the peracid reagent obtained is less than 10%.1a If a stronger solution of the reagent is required, 70-90% H2O2 must be used. Caution: for hazards see Hydrogen Peroxide. Hydrogen Peroxide-Urea (which is commercially available and is safe to handle) has been used as a substitute for anhydrous hydrogen peroxide.3 In the preparation of peracetic acid from acetic anhydride and H2O2, the dangerously explosive diacetyl peroxide may become the major product if the reaction is not carried out properly.1a

Purification: peracetic acid is rarely prepared in pure undiluted form for safety reasons. The commercially available material contains acetic acid, water, H2O2, and H2SO4. After neutralization of the sulfuric acid, this reagent is satisfactory for most reactions. If water is undesirable, an ethyl acetate solution of the reagent may be used. Details for the preparation of the H2O2-free reagent are available.4

Handling, Storage, and Precautions: peracetic acid is an explosive compound but is safe to handle at room temperature in organic solutions containing less than 55%. Use in a fume hood. Since peroxides are potentially explosive, a safety shield should generally be used.5 Peracetic acid can be stored at 0 °C with essentially no loss of active oxygen and at rt with only negligible losses over several weeks.

General Considerations.

Peracetic acid oxidizes simple alkenes, alkenes carrying a variety of functional groups (such as ethers, alcohols, esters, ketones, and amides), some aromatic compounds, furans, sulfides, and amines. It oxidizes b-lactams in the presence of catalysts. Ketones and aldehydes undergo oxygen insertion reaction (Baeyer-Villiger oxidation).

Epoxidation of Alkenes.

Peracetic acid is a comparatively safe reagent for small-scale reactions. In industry, to avoid the hazards involved in handling large quantities of the reagent, it is prepared in situ. Peracetic acid prepared in this fashion is widely used for epoxidation of vegetable oils and fatty acid esters. To the substrate in acetic acid containing catalytic (1% by weight) quantities of H2SO4 maintained around 50 °C is added gradually, with stirring, 50% H2O2 at such a rate that there is no buildup in the concentration of H2O2. The peracid is consumed as it is formed (eq 1). The addition of H2O2 is usually completed in 2 h and then the temperature is raised to and maintained at 60 °C until all the H2O2 is consumed (about 3 h). The reaction mixture is diluted with water, at which point the epoxides (being water-insoluble) separate out. The use of hexane during the reaction minimizes epoxide ring opening. Since the catalyst (H2SO4) is essential for the speedy formation of peracetic acid, in situ methods can be used for preparing only those epoxides which can tolerate the presence of the acid catalyst. Epoxides of fatty acid esters are obtained in good yields if the reaction temperature and time taken for completion of the reaction are properly controlled.

Peracetic acid in ethyl acetate is a better reagent for preparing epoxides from alkenes than the reagent in acetic acid since the large quantities of acetic acid in the latter reagent facilitate epoxide ring opening. However, since the reagent in acetic acid is more readily available, it is normally used for epoxidation; the sulfuric acid present in the commercial sample has to be neutralized by adding sodium acetate before the epoxidation. After epoxidizing the alkene with peracetic acid, the reaction mixture is diluted with water. The unreacted peracid, acetic acid, and traces of hydrogen peroxide are removed in the aqueous layer. The separated epoxide is filtered if it is a solid; when the epoxide is a liquid, the organic layer is separated using a small quantity of solvent, if needed. Another method of workup is to remove unreacted peracid and acetic acid through evaporation under reduced pressure.

Epoxidation of terminal alkenes with organic peracids is sluggish since the double bond is not electron rich (eq 2).6

Adequately substituted acrylic esters furnish epoxides in good yields. Ethyl crotonate has been epoxidized in kg quantities according to eq 3;7 the workup is simple, involving direct fractionation of the reaction mixture. For the preparation of epoxide (1) from ethyl crotonate using Trifluoroperacetic Acid, the yield is 73%.8 The sensitive allylic epoxide (2) has been prepared according to eq 4.9 This procedure has been applied successfully for the preparation of allylic epoxides from 1,3-cyclopentadiene, 1,3-cycloheptadiene, and 1,3-cyclooctadiene.

Epoxidation of the triene (3)2 is regioselective, involving reaction at the tetrasubstituted double bond (eq 5). Epoxidation of (3) using m-Chloroperbenzoic Acid furnishes the monoepoxide in 76% yield.10 Epoxidation of the diene (4) was regio- and stereoselective (eq 6);11 the more substituted double bond was epoxidized from the less hindered side.

Epoxidation of the unsaturated g-lactone (5) furnished stereoselectively the epoxide (6), involving approach of the reagent from the more hindered side of the double bond (eq 7).12 This selectivity is observed only when acetic acid is the solvent. The selectivity was much less when m-CPBA was used.

Moderate stereoselectivity is observed during the epoxidation of sterically unbiased 3,3-diarylcyclopentenes; the major product is formed through approach of the electrophile from the side trans to the better electron donor (eq 8).13

A systematic study of the epoxidation of the acyclic allyl alcohol (7) has been carried out, employing several reagents.14 Epoxidation with peracetic acid generated from urea/H2O2 showed small syn selectivity (eq 9). m-CPBA epoxidation of (7) furnished in 87% yield a 40:60 mixture of the epoxy alcohols (8) and (9).

Epoxidation of Alkenes via Peracids Generated In Situ.

Alkenes have been epoxidized by reacting them with peracids generated in situ. The system consisting of molecular oxygen and aldehydes, particularly isobutyraldehyde and Pivalaldehyde, converts various alkenes to epoxides in high yields when they are reacted at 40 °C for 3-6 h (eq 10).15

Oxidation of Furans.

2,5-Disubstituted furans are oxidatively cleaved by peracids; for example, see eq 11.16 m-CPBA can also be used for this reaction. D3-Butenolides have been synthesized by oxidizing 2-trimethylsilyl furans with peracetic acid; as in eq 12.17

This reaction does not proceed smoothly when there is a hydroxyl group in the furfuryl position; however, the reaction is facile if the furfuryl OH is blocked. The reaction does not take place if electron-withdrawing groups are present on the furan ring. m-CPBA is not a good reagent for this oxidation. An interesting application of this reaction has been published.18

Oxidation of Aromatic Compounds.

Suitably substituted aromatic compounds are oxidized efficiently to the quinones by peracetic acid. The quinone (10) is obtained in 22% yield by oxidizing naphtho[b]cyclobutene.19 Slow addition of 1,5-dihydroxynaphthalene to excess peracetic acid furnished juglone (11) in 46-50% yield.20

Baeyer-Villiger Oxidation.

A systematic study of the Baeyer-Villiger reaction of the bicyclic ketone (12) has been carried out employing different organic peracids.21 Selective formation of lactone (13) was highest when peracetic acid was used (eq 13). Reaction of (12) with m-CPBA furnishes a 55:45 mixture of (13) and (14) in 81% yield.

Position-specific Baeyer-Villiger rearrangement has been observed in the reaction of peracetic acid with some polycyclic ketones.22,23 An ε-lactone, required for the synthesis of erythronolide B, was synthesized in 70% yield through position-specific Baeyer-Villiger rearrangement of a cyclohexanone having substituents on all the ring carbons;24 the ketone was treated with excess 25% peracetic acid in ethyl acetate for 6 days at 55-58 °C. Peracetic acid oxidation of the keto b-lactam (15) furnishes stereoselectively the interesting b-lactam (16) (eq 14);25 the initially formed Baeyer-Villiger reaction product undergoes further reaction. Ketone (15) has also been reacted with m-CPBA in acetic acid but the selectivity is slightly less, forming (16):(17) in 10:1 ratio.

Ruthenium- and Osmium-Catalyzed Oxidations.

a-Ketols have been synthesized by reacting alkenes with peracetic acid in the presence of a Ruthenium(III) Chloride catalyst.26 a-Ketol (19) was synthesized from the alkene (18) chemo- and stereoselectively (eq 15). The two-phase aqueous system is essential for this reaction. Conjugated dienes, allylic azides, and a,b-unsaturated esters have been oxidized with this reagent.

The methylene group adjacent to the nitrogen of b-lactams has been oxidized with peracetic acid in the presence of a ruthenium catalyst (eq 16).27 Peracetic acid is the best oxidant for this reaction. Instead of ruthenium, OsCl3 can be used to catalyze the oxidation.28 The peracetic acid required for the reaction can be generated in situ from acetaldehyde and molecular oxygen (eq 17).29

Other Applications.

Peracetic acid has been used to (a) oxidize primary amines to nitroso compounds,30 (b) oxidize secondary alcohols to ketones in the presence of a CrVI ester catalyst (eq 18)31 or sodium bromide,32 (c) oxidize sulfenamides to sulfonamides (eq 19),33 (d) oxidize iodobenzene to iodosobenzene diacetate34 and iodoxybenzene,35 and (e) oxidize N-heterocycles such as pyridine to N-oxides.36 a,b-Unsaturated aldehydes (and a,b-unsaturated ketones) do not undergo facile epoxidation with peracetic acid since the double bond is not electron rich. However, the acetals of a,b-unsaturated aldehydes can be oxidized readily (eq 20).37 For the epoxidation of a,b-unsaturated aldehydes with H2O2/base see Hydrogen Peroxide.

For industrial applications, peracetic acid is the most widely used organic peracid since it is inexpensive. It is the only commonly used peracid which can be prepared in situ for epoxidation reactions, since the acid catalyst (1% H2SO4; eq 1), which can facilitate epoxide ring opening, is used in low concentrations; the accompanying acetic acid, being a weak acid, is not very efficient in epoxide opening. The in situ method is not hazardous. Although the reagent is available commercially, it is also prepared in the laboratory since its preparation is easy, fairly fast, and no solvent is required for isolation. Epoxidation reactions and subsequent workup can be performed with no solvent, or only small quantities of solvent since the peracid and accompanying acetic acid are both water soluble and volatile. It is not essential that the substrate should dissolve in the reagent (peracetic acid-acetic acid).

Related Reagents.

m-Chloroperbenzoic Acid; Perbenzoic Acid.

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A. Somasekar Rao & H. Rama Mohan

Indian Institute of Chemical Technology, Hyderabad, India

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