Potassium Superoxide1

KO2

[12030-88-5]  · KO2  · Potassium Superoxide  · (MW 71.10)

(reactive species is the superoxide anion, O2-; solubility of KO2 in aprotic organic solvents is facilitated by crown ethers2,3 or other phase-transfer catalysts;4 O2- reacts with most organic substrates either as an anion or as an electron-transfer (reducing) agent; reacts as a nucleophilic anion toward alkyl halides, sulfonates, and carbonyl groups; other net displacement reactions such as with halocarbons may be initiated by electron transfer; reacts as a basic anion toward substrates bearing acidic protons; used in situ with a variety of activated halogens to form peroxy anions useful for further oxygen transfer, e.g. epoxidations1)

Physical Data: mp 500 °C.5

Solubility: slightly sol DMSO; crown ethers are useful for bringing KO2 into organic solvents such as DMSO,2 DMF, MeCN, THF, benzene;3 reacts rapidly with H2O and protic solvents.

Form Supplied in: small chunks of light yellow powdery solid.

Handling, Storage, and Precautions: chunks of solid may be handled briefly in the atmosphere; prolonged exposure to the atmosphere results in reaction with H2O; storage should be under dry conditions such as a desiccator; reaction with H2O produces O2, H2O2, and OH-.

Dialkyl Peroxide Synthesis.

Primary and secondary alkyl bromides9 and alkyl sulfonates react with KO2 in aprotic organic solvents (except DMSO, see below), giving acyclic (eq 1)3,10 and cyclic (eq 2)11 dialkyl peroxides. The reactions are greatly facilitated by the addition of crown ethers or other phase-transfer catalysts to the reaction medium. The reaction at secondary carbon atoms proceeds with >95% inversion of configuration3,12 and is accompanied by formation of significant amounts of alkene due to elimination reactions. Because of the mechanism by which the dialkyl peroxides are generated, this method is best suited for synthesis of symmetrical dialkyl peroxides.

Alcohol Inversion.

When the reaction between alkyl bromides or alkyl sulfonates and KO2 is performed in DMSO, the major product is an alcohol12 as a consequence of oxygen transfer from the intermediate peroxy anion to the DMSO (eq 1).13 Such displacements of tosylate (eq 3)14 or mesylate (eqs 4 and 5)15,16 by KO2 in DMSO have been used for inversion of the configuration of secondary alcohols and this method is of comparable efficiency to the modified18 Mitsunobu sequence17 used for the same purpose.

Ester Cleavage.

Carboxylic acid esters are cleaved by O2-, giving the corresponding carboxylic acid and alcohol.19 Several studies of the mechanism of this process have been reported.20 Qualitatively, displacement of halide or sulfonate ester occurs in preference to ester hydrolysis (see eq 2). The use of KO2 for ester cleavage generally offers no advantage over conventional ester saponification methods.

Diacyl Peroxide Synthesis.

Acid chlorides react with O2- to give diacyl peroxides,21 which in turn are susceptible to further reaction with O2-.22 Acyl peroxy anions are formed as intermediates in the reactions with acid chlorides and diacyl peroxides as well as in the reaction of O2- with anhydrides as detected by epoxidation of alkenes.22 Applications of this approach to oxygen-transfer chemistry is discussed further below. Eq 6 summarizes the primary events but is an incomplete account of all the reactions occurring between O2- and these substrates. Amides, aldehydes, and nitriles are unreactive with KO2 under most conditions.

Oxygen Transfer via Peroxy Anions.

A number of reagents react with superoxide to form transient peroxy anions which oxidize electrophilic functional groups such as alkenes, sulfides, sulfoxides, etc. Among the reagents forming peroxy anions useful in such oxidations are aryl sulfonyl halides23 (especially 2-nitrobenzenesulfonyl chloride24), acid chlorides,22,25 halocarbons such as carbon tetrachloride,26 dialkyl chlorophosphates27 and alkyl dichlorophosphates,28 carbon dioxide,29 N-(-)-menthoxycarbonyl-4-tolylsulfonimidoyl chloride,30 and phosgene.31 Representative examples of oxidations by these systems include the epoxidation of limonene (eq 7),24 the oxidation of sulfides to sulfoxides (eq 8),32 selective oxidation of sulfoxides to sulfones in the presence of alkenes (eq 9),33 oxidation of benzylic methylenes to ketones (eq 10),34 and cleavage of tosylhydrazones to ketones or aldehydes (eq 11).35

These approaches to oxygen transfer have not been tested beyond the original reports. Comparisons with other established oxygen-transfer reagents such as the peracids (e.g. m-Chloroperbenzoic Acid) and the dioxiranes (e.g. Dimethyldioxirane) still must be explored.

Electron-Transfer Chemistry.

Certain reactions of O2- whose net result appears to be that of either a nucleophilic addition or displacement reaction, instead may be the result of an electron transfer followed by capture of oxygen, giving the peroxy radical. Oxygen labeling experiments are necessary to distinguish between the two mechanisms.

Nucleophilic Displacement of Aromatic Halides.

Aromatic halides substituted with electron-withdrawing groups undergo nucleophilic displacement by KO236 (eq 12)37 as well as by electrochemically generated O2-.38 Yields of phenols are generally good to excellent in these reactions.

Reactions with Electron-Deficient Alkenes.

cis-2,2,6,6-Tetramethylhept-4-en-3-one, a molecule designed as a probe for electron transfer, is isomerized to the trans-enone by KO2, consistent with electron transfer from reagent to the enone.39 Cyclohexenone is epoxidized (30% yield) by electrochemically generated superoxide anion,10 but is converted to a trimeric ketone structure with KO2.40 Other cyclohexenones react with KO2 only when acidic protons are present in the molecule, and then are transformed into mixtures of oxidized products.40 The cyclohexenone system of cholest-4-en-3-one reacts with KO2 to give a mixture of at least five oxidation products.41 Chalcones react with KO2 in a series of steps initiated by electron transfer to yield aryl carboxylic acids (52-72%) (eq 13).42 A series of alkenes highly substituted with electron-withdrawing groups (e.g. 1,2-diphenyl-1-nitroethylene) react with KO2 yielding products of oxidation, e.g. benzoic acid (85%) (eq 14).43 The conversions by KO2 of tetraarylcyclopentadienones to 2-hydroxy-2,4,5-triarylfuran-3-ones44 or to furan-3-ones, 3,4,5,6-triarylpyran-2-ones, and carboxylic acids45 are initiated by electron transfer.

Reactions with Anilines.

Aniline, various substituted anilines, and a-naphthylamine do not react with KO2 suspended in THF at 80 °C,46 but several anilines are converted into azobenzenes by KO2 in benzene containing a crown ether47,48 or in DMSO.49 Both o- and p- but not m-phenylenediamines are converted into azobenzenes by KO2 suspended in THF or pyridine as shown in eq 15. Both o- and p-aminophenol likewise are transformed into azobenzenes46 (Caution: two laboratories have reported violent explosions of mixtures containing o-aminophenol and KO2 in either THF or toluene50). 2-Mercaptoaniline with KO2 gives 2,2-dithiobisaniline in 85% yield,46 the result of coupling of the thiol rather than of the amine substituent.

Reaction with Thiols.

Under mild conditions (suspension of KO2 in toluene), thiophenols and aliphatic thiols are converted into disulfides by KO2 (eq 16).51 Under more vigorous reaction conditions (elevated temperature51 or KO2/crown ether in pyridine52) these thiols are converted into sulfonic acids. Certain thiols (e.g. 2-mercaptophenol) are transformed into sulfonic acids even under the mild reaction conditions. Ethane-1,2-dithiol and propane-1,3-dithiol are converted under mild conditions into the cyclic disulfides 1,2,5,6-tetrathiocan and 1,2,6,7-tetrathiothiecan (eq 17), respectively, while butane-1,4-dithiol forms 1,2-dithian by reaction with KO2.51

Reactions with Phenols, including Catechols and Tocopherols.

Monophenolic compounds do not generally undergo any net change with KO2. Naphthalene diols react with KO2 suspended in a toluene-pyridine mixture under an inert atmosphere to form mono- or dihydroxynaphthoquinones in good yields (eq 18).53

Catechols are first oxidized to o-quinones upon treatment with KO2 followed by further oxidation to a variety of products.54,55 Catechol itself is converted to cis,cis-muconic acid in very low yields accompanied by much polymeric byproduct. 9,10-Dihydroxyphenanthrene is converted to diphenic acid in good yield (90%). 3,5-Di-t-butylcatechol is converted to a mixture of oxidized products. The tocopherol model compound 2,2,5,7,8-pentamethylchroman-6-ol is converted by KO2 suspended in THF into 6-hydroxy-2,2,6,7,8-pentamethylchroman-5(6H)-one (20%)56 but, with a solution of KO2 in AcCN, a low yield (12%) of a diepoxide together with as many as six other compounds are isolated.57 The analogous diepoxide together with a complex mixture was isolated from the reaction of tocopherol with KO2.57

Miscellaneous Transformations.

Practical syntheses of ethyl glyoxylate (72%) and diethyl oxomalonate (83%, via diethyl cyanomalonate) from ethyl cyanoacetate with electrochemically generated superoxide have been reported, as shown in eq 19.58

Aromatic nuclei to which quinones, cyclic alcohols, or cyclic ketones are fused are converted (52-88%) into the aromatic dicarboxylic acids upon reaction with a large excess of KO2/crown ether in DMF (eq 20).59

Tetramethyl- and tetraethylammonium ozonide, whose uses as reagents in organic chemistry are unexplored, have been prepared from the reaction of tetraalkylammonium superoxide and an alkali metal ozonide in liquid ammonia.60 The question of whether the oxygen released following transfer of an electron from superoxide to a substrate is singlet oxygen is discussed in Frimer's excellent review.1a Potassium superoxide was considered to have the molecular formula K2O4 until quantum mechanics predicted the structure of O2- and experimental confirmation of the radical anion nature of the molecule was performed.61

Related Reagents.

Electrochemically generated O2- (for which a tetraalkylammonium cation usually serves as the counter ion);6 tetramethylammonium superoxide (Me4NO2);7 NaO2; radiolysis of O2 in water is used to generate transient O2- in aqueous media.8


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Roy A. Johnson

The Upjohn Company, Kalamazoo, MI, USA



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