Hydrogen Peroxide1

HOOH

[7722-84-1]  · H2O2  · Hydrogen Peroxide  · (MW 34.02)

(nucleophilic reagent capable of effecting substitution reactions2 and epoxidation of electron-deficient alkenes;3 weak electrophile whose activity is enhanced in combination with transition metal oxides4 and Lewis acids;5 strong nonpolluting oxidant which can oxidize hydrogen halides6)

Physical Data: 95% H2O2: mp -0.41 °C; bp 150.2 °C; d 1.4425 g cm-3 (at 25 °C). 90% H2O2: mp -11.5 °C; bp 141.3 °C; d 1.3867 g cm-3. 30% H2O2: mp -25.7 °C; bp 106.2 °C; d 1.108 g cm-3.

Solubility: sol ethanol, methanol, 1,4-dioxane, acetonitrile, THF, acetic acid.

Form Supplied in: clear colorless liquid widely available as a 30% aqueous solution and 50% aqueous solution; 70% and 90% H2O2 are not widely available.

Analysis of Reagent Purity: titration with KMnO4 or cerium(IV) sulfate.7

Purification: 95% H2O2 (caution!) can be prepared from 50% solution by distilling off water in a vacuum at rt.8

Handling, Storage, and Precautions: H2O2 having a concentration of 50% or more is very hazardous and can explode violently, particularly in the presence of certain inorganic salts and easily oxidizable organic material. A safety shield should be used when handling this reagent.9 After the reaction is complete, excess H2O2 should be destroyed by treatment with MnO2 or Na2SO3 soln. Before solvent evaporation, ensure absence of peroxides. The use of acetone as solvent should be avoided.10 The reagent should be stored in aluminum drums in a cool place away from oxidizable substances.

Synthesis of Peroxides via Perhydrolysis.

H2O2 and the hydroperoxy anion are excellent nucleophiles which react with alkyl halides and other substrates having good leaving groups to furnish hydroperoxides. The hydroperoxide (2) has been prepared employing 98% H2O2 (eq 1).11 To a stirred mixture of THF (50 mL), Silver(I) Trifluoromethanesulfonate (0.04 mol), and pyridine (0.02 mol) kept at 6 °C under argon and protected from light is gradually added 98% H2O2 (0.32 mol). The chloride (1) (0.02 mol) dissolved in THF (10 mL) is next added dropwise with cooling (6 °C). The reaction mixture is kept at rt for 24 h; the organic layer is separated by gravity filtration, diluted with ether, and washed with saturated aq NaHCO3 at 0 °C. The organic layer is dried. The solvent as well as traces of pyridine and starting material are distilled out at rt under vacuum. The residual material is the hydroperoxide (2) which has been distilled in high vacuum using a bath maintained at 40 °C. The hydroperoxide (3) has been prepared in a similar fashion employing 30% H2O2 (eq 2).12

Tertiary alcohols R1R2R3COH and other alcohols which can readily furnish carbenium ion intermediates are solvolyzed by 90% H2O2 in the presence of acid catalysts to yield hydroperoxides R1R2R3COOH.13 Trimeric hydroperoxides having a nine-membered oxa heterocyclic ring have been prepared from ketones and hydrogen peroxide in the presence of acid catalysts.14

N-Alkyl-N-tosyl hydrazides are oxidized by H2O2 and Na2O2 in THF at rt to the corresponding hydroperoxides; by employing this procedure, cyclohexyl hydroperoxide has been obtained in 92% yield.15

Several gem hydroperoxides have been prepared from acetals (eq 3).16

The prostaglandin PGG2 (5) has been synthesized from the dibromide (4) (eq 4).17

Perhydrolysis of acid anhydrides furnishes the corresponding peroxy acids (for an example, see Trifluoroperacetic Acid). Perhydrolysis of acid chlorides also furnishes peroxy acids.18 When an organic acid is mixed with H2O2 an equilibrium reaction is established, as shown in eq 5.18 Methanesulfonic Acid has been used to accelerate the reaction and also to function as solvent (see preparation of Perbenzoic Acid).

A number of diacyl peroxides have been prepared in 90-95% yield by reacting the acid chloride (for example, phenylacetyl chloride) (1 equiv) with 30% H2O2 (0.55 equiv) in ether in the presence of pyridine (2 equiv) at 0 °C for 2 h.19

Reactions with Amides, Aldehydes, and Ketones.

The oxazolidinone (6) is deacylated regioselectively on treatment with Lithium Hydroperoxide (eq 6).20 For another example, see Evans.21

Aromatic aldehydes can be transformed to phenols by oxidizing with H2O2 in acidic methanol (eq 7).22 Dilute alkaline H2O2 can convert only aldehydes having an hydroxyl in the ortho or para position to the corresponding phenols (Dakin reaction).1b m-CPBA is not useful for the preparation of phenol (8) from (7).22

Alkyl and aryl aldehydes are oxidized to the corresponding carboxylic acids in high yields via oxidation with H2O2 in the presence of Benzeneseleninic Acid as catalyst.23 Cyclobutanones and other strained ketones undergo Baeyer-Villiger oxidation with H2O2. The cyclobutanone (9) has thus been oxidized to the g-lactone (10) (eq 8).24 Baeyer-Villiger oxidation of some cyclobutanones proceeds under very mild conditions (-78 °C).25 Baeyer-Villiger reaction of ketones having isolated double bonds can be carried out with H2O2 without reaction at the double bond; however, when organic peroxy acids are used, the alkene often is oxidized.26

Epoxidation of a,b-Unsaturated Ketones and Acids.

a,b-Unsaturated ketones furnish the corresponding a,b-epoxy ketones in high yields on treatment with H2O2 in the presence of a base.3 In the cyclopentenone (11), approach to the b-face is sterically hindered. Epoxidation of (11) at -40 °C furnishes quantitatively a 94:6 mixture of a- and b-epoxides; the selectivity is less when the reaction is carried out at higher temperatures (eq 9).27 Optically active epoxy ketones (about 99%) have been prepared with high ee by carrying out the epoxidation in the presence of a chiral catalyst such as polymer-supported poly(L-leucine).28

a,b-Unsaturated acids have been epoxidized with 35% H2O2 using a catalyst prepared from 12-tungstophosphoric acid (WPA) and cetylpyridinium chloride (CPC) (pH 6-7, 60-65 °C); by this method, crotonic acid furnishes the a,b-epoxy acid in 90% yield.29

Synthesis of Epoxides, Vicinal Diols, Dichlorides, and Ketones from Alkenes.

Terminal alkenes, as well as di- and trisubstituted alkenes, have been epoxidized at 25 °C using a molybdenum blue-Bis(tri-n-butyltin) Oxide catalyst system (eq 10).30 Epoxides have been prepared with 16% H2O2 using a (diperoxotungsto)phosphate catalyst (12) in a biphasic system.31

Asymmetric epoxidation of 1,2-dihydronaphthalene has been achieved employing a chiral manganese(III) salen complex with an axial N-donor; even 1% H2O2 can be used as oxidant and the highest ee observed was 64%.32

Vicinal diols have been prepared from alkenes by oxidizing with H2O2 in the presence of Re2O7 catalyst, in dioxane at 90 °C for 16 h; the mole ratio of Re2O7:alkene:H2O2 is 1:100:120. The reaction proceeds via epoxidation followed by acid-catalyzed ring opening. Cyclohexene furnishes trans-cyclohexane-1,2-diol in 74% yield.33

Oxidative cleavage of ene-lactams takes place during oxidation with H2O2 in the presence of a selenium catalyst (eq 11).34 The reaction proceeds under neutral and mild conditions. For the preparation of macrocyclic ketoimides, Palladium(II) Acetate is used as the catalyst.34

Alkenes have been chlorinated with concentrated HCl/30% H2O2/CCl4 in the presence of the phase-transfer catalyst Benzyltriethylammonium Chloride. Side reactions take place when gaseous chlorine and sulfuryl chloride react with alkenes; under ionic conditions these side reactions are not favored. The method has also been applied for the bromination of alkenes.6 1-Octene furnishes 1,2-dichlorooctane in 56% yield.

Oxidation of Alcohols and Phenols.

The system H2O2/RuCl3.3H2O/phase-transfer catalyst (didecyldimethylammonium bromide) oxidizes a variety of alcohols selectively; the requirement of ruthenium is very low; ratio of substrate:RuCl3 = 625:1.35 By this method, p-methylbenzyl alcohol was oxidized to p-methylbenzaldehyde in 100% yield.

Vicinal diols are oxidized to a-hydroxy ketones by 35% H2O2 in the presence of peroxotungstophosphate (PCWP; 1.6 mol %) in a biphasic system using CHCl3 as solvent. 1,2-Hexanediol has been oxidized in 93% yield to 1-hydroxy-2-hexanone.36

When 1,4-dihydroxybenzenes are reacted with stoichiometric quantities of iodine, the corresponding p-benzoquinones are formed in poor yields; however, they are oxidized in very good yields to p-quinones by reaction with 60% H2O2 in methanol or aq solution at rt in the presence of catalytic quantities of I2 or HI. 2-Methyl-1,4-dihydroxynaphthalene has been oxidized to 2-methyl-1,4-naphthoquinone in 98% yield.37

Radical Reactions.

Homolytic substitutions of pyrrole, indole, and some pyrrole derivatives have been carried out using electrophilic carbon centered radicals generated in DMSO by Fe2+/H2O2 and ethyl iodoacetate or related iodo compounds; the substrate is taken in large excess (eq 12).38

N-Acylpyrrolidines and -piperidines are oxidized by FeII/hydrogen peroxide in aqueous 95% acetonitrile to the corresponding pyrrolidin-2-ones and piperidin-2-ones;39 N-phenylcarbamoyl-2-phenylpiperidine was oxidized to the corresponding lactam in 61% yield.

Oxidation of Organoboranes.

Oxidative cleavage of the C-B bond with alkaline H2O2 to convert organoboranes to alcohols is a standard step in hydroboration reactions. In some procedures, organoboranes are formed in the presence of 1,4-oxathiane. When a mixture of tri-n-octylborane and 1,4-oxathiane in THF was treated initially with NaOH and subsequently with 30% H2O2, the organoborane was selectively oxidized to furnish in 98% yield a mixture (93:7) of octan-1-ol and octan-2-ol.40

Oxidation of Organosilicon Compounds.

Organosilicon compounds having at least one heteroatom on silicon undergo oxidative cleavage of the Si-C bond when treated with H2O2 (eq 13).41 For additional examples, see Roush42a and Andrey.42b

Oxidation of Amines.

H2O2 in the presence of Na2WO4 has been used to oxidize (a) 2,4,4-trimethyl-2-pentanamine to the corresponding nitroso compound in 52% yield,43 and (b) a primary amine (containing b-lactam and phenolic OH) to the corresponding oxime in 72% yield.44

The secondary amine 2-methylpiperidine (13) has been oxidized to the nitrone (14) with H2O2/Na2WO4 (eq 14);45 the oxidation product also contains about 6-15% of the isomeric 2-methyl-2,3,4,5-tetrahydropyridine N-oxide (Selenium(IV) Oxide is also an effective catalyst for this oxidation).46 1,2,3,4-Tetrahydroquinoline is oxidized to the 1-hydroxy-3,4-dihydroquinolin-2(1H)-one in 84% yield by H2O2/Na2WO4.47 The flavin, FlEt+ClO4- (15) is a good catalyst for the H2O2 oxidation of secondary amines to nitrones.48

The tertiary amine N-methylmorpholine has been oxidized to the N-oxide in 84-89% yield; the reaction is carried out at 75 °C with 30% H2O2 and the reaction time (0.3 mol scale) is about 24 h.49 The trans-N-oxide (16) has been obtained stereoselectively (trans:cis  = 95:5) by reacting the corresponding N-methylpiperidine with 30% H2O2 in acetone at 25 °C.50

Oxidation of Sulfur-Containing Compounds.

Oxidation of di-n-butyl sulfide with H2O2 in the presence of the catalyst FlEt+ClO4- (15) furnished the corresponding sulfoxide in 99% yield.48 Sulfides have been oxidized to the corresponding sulfoxides with H2O2 in CH2Cl2 solution in the presence of the heterocycle (17); di-n-octyl sulfide yields n-octyl sulfoxide in 96% yield, and benzylpenicillin methyl ester is oxidized to the (S)-S-oxide in 90% yield.51

The oxidation of sulfides to sulfones proceeds in good yields when the reaction is catalyzed by tungstic acid; the cyclic sulfide thietane is oxidized to the sulfone (thietane 1,1-dioxide) in 89-94% yield.52

Oxidation of Selenium-Containing Compounds.

Oxidation of the phenyl selenide (18) with H2O2 in THF furnishes the alkene (19) (eq 15);53 the selenoxide initially formed through oxidation of (18) undergoes facile syn elimination (see also Grieco54).

Hydrogen peroxide has a high (47%) active oxygen content and low molecular weight. It is cheap and is widely available. After delivering oxygen, the byproduct formed in H2O2 oxidations is the nonpolluting water. Hence the use of H2O2 in industry is highly favored. This reagent is able to oxidize SeO2, WO3, MoO3, and several other inorganic oxides efficiently to the corresponding inorganic peroxy acids which are the actual oxidizing agents in many reactions described above.4 Use of these oxides in catalytic amounts along with H2O2 as the primary oxidant reduces the cost of production, simplifies workup and minimizes the effluent disposal problem. Phase-transfer-catalyzed (PTC) reactions in a two-phase system are well suited for H2O2 oxidations and are widely used; epoxides are susceptible to ring opening by water and the PTC procedure allows the preparation of epoxides even with 16% aq H2O2 since the epoxide and water are in different phases.31 Handling chlorine and bromine poses many problems, but HCl/H2O2 and HBr/H2O2 systems may be used as substitutes for chlorine and bromine, respectively.6 The solids Sodium Perborate, sodium percarbonate, and Hydrogen Peroxide-Urea, which are prepared from H2O2, have wide applications since they release H2O2 readily.

Reactions with Nitriles.

Treatment of nitriles (20) with NaOH/H2O2 in aqueous ethanol is a standard synthetic procedure for the preparation of amides (21); aromatic nitriles furnish amides in high yields but aliphatic nitriles give amides in moderate yields (50-60%).55 It has been suggested56 that addition of the hydroperoxy anion to the nitrile (20) furnishes the peroxycarboximidic acid (22) which reacts with H2O2 to give the amide (21) and molecular oxygen.

It has been observed57 that in the reaction of nitriles with 30% H2O2 in the presence of 20% NaOH there is a significant increase in the reaction rate when n-tetrabutylammonium hydrogen sulfate (20 mol %) is used as phase-transfer catalyst. The reaction is carried out at 25 °C for 1-2 h employing CH2Cl2; aromatic as well as aliphatic amides are obtained in high yields (e.g. eq 16). This method cannot be used if the nitrile has an electron-withdrawing substituent on the carbon atom a to the cyano group.57

Treating a DMSO solution of a nitrile with an excess of 30% H2O2 in the presence of a catalytic amount of K2CO3 for 1-30 min at 25 °C furnishes the corresponding amide in high yields58 (e.g. eq 17). Under these conditions, esters, amides, and urethanes do not react. a,b-Unsaturated nitriles furnish a,b-epoxy amides.58 For other routes for the synthesis of amides from nitriles, see Cacchi57 and Katritzky.58

Related Reagents.

Hydrogen Peroxide-Ammonium Heptamolybdate; Hydrogen Peroxide-Boron Trifluoride; Hydrogen Peroxide-Iron(II) Sulfate; Hydrogen Peroxide-Tellurium Dioxide; Hydrogen Peroxide-Tungstic Acid; Hydrogen Peroxide-Urea; Iron(III) Acetylacetonate-Hydrogen Peroxide; Perbenzoic Acid; Peroxyacetimidic Acid; Trifluoroperacetic Acid.


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A. Somasekar Rao & H. Rama Mohan

Indian Institute of Chemical Technology, Hyderabad, India



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