Phorochuiiiirrrr nnd Phorohiologr. zyxwvutsrqponmlk Vol. 28. zyxwvutsrqpo pp. 71 I- 719. zyxwvutsrqp 0 Pergamon Press Ltd zyxwvutsrqponmlk . 197X. Printed in Great Britain zyxwvutsrqp 0031-8655/78/1101-071 I zy S02.00/0 CHEMICAL REACTIONS OF SUPEROXIDE ANION RADICAL IN APROTIC SOLVENTS ARYEH A. FRIMER and IONEL ROSENTHAL Department of Chemistry, Bar llan University, Ramat Gan. Israel, and Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot, Israel zyx (Received 31 March 1978; accepted 6 April 1978) Abstract-While superoxide anion radical does not normally react with olefins, it does react with activated double bonds. Thus zyxwvut '0; oxidatively cleaves certain a&unsaturated ketones such as chalcones and tetracyclone and electron poor olefins such as 1.1-dicyano and 1.1-dinitro olcfins. Similarly '0; can react with substituted nitrobenzenes to yield the corresponding nitrophenols. EPR and oxygen labeling (KO:') experiments confirm an electron transfer mechanism. In spite of its biological importance, until 1975 only a few studies had been carried out on the organic chemistry of superoxide ion in aprotic media (Schmidt and Bipp, 1960; Le Berre and Berguer, 1965, 1966; Dietz et a/. 1970; Merrit and Sawyer, 1970; Poupko and Rosenthal, 1973). Such studies would seem to be of great importance since most of the bio- logical research had been carried out in aqueous media in which it is likely that not only zyxwvuts .O; but its conjugate acid, HO;, and hydroxyl radical, HO., are the reactive species (Fridovich, 1976). The superoxide salts can conveniently serve as a well-defined source of .O;. In addition, the complex- ation of KO, with crown ethers (Valentine and Curtis, 1974) bypasses the solubility restrictions of those salts in aprotic media such as dimethylsulfoxide, benzene or acetonitrile. Once the solubility hurdle had been overcome, the use of the KO,-crown ether reagent was sharply pro- moted. This reagent-complex has allowed for a more in depth study of the nature of .O; reactions. In short, four basic modes of attack have been observed for .O;. (1) Nucleophilic substitution. This category includes the aliphatic substitution (SN2) of halides, sulfonates and other leaving groups (Le Berre and Berguer, 1965, 1966; Dietz et a/., 1970; Merrit and Sawyer, 1970; San Fillipo et al., 1975; Johnson and Nidy, 1975; corey er a/., 1975a, b; Rosenthal and Frimer, 1975; Divisek and Kastening. 1975; Gibian and Ungerman, 1976; Danen and Warner, 1977; Merrit and Johnson, 1977) to produce peroxides, hydroperoxides, alcohols or aldehydes depending on reaction conditions and workup. Similarly, the cleavage of esters and acyl chlorides to produce acids (Le Berre and Berguer, 1965, 1966; Dietz er al., 1970; San Fillipo et al., 1976b; Magno and Bontempelli, 1976) or diacylperox- ides (Johnson, 1976) seems to proceed by a nucleo- philic substitution mechanism as well. Interestingly, nucleophilic substitution of an inorganic anion has also been reported (Hill et al.. 1974). (2) Elimination. .O; can react in a fashion similar to HO - producing olefins from the corresponding halides (Le Berre and Berguer, 1965, 1966; Dietz et al.. 1970; San Fillipo et a/., 1975; Corey et a/., 1975b) and diphenylacetylene from dibromostilbene (Frimer, unpublished results). (3) Hydrogen abstraction. The reaction of superox- ide anion radical with sources of abstractable hydro- gens has been observed in the case of hydroperoxides (Le Berre and Berguer. 1965, 1966; Peters and Foote, 1976), ketones (Corey et al., 1975b) and benzylic sys- tems (Tezuka et al., 1975; Morooka et al., 1976; Sagae et a/., 1977). The oxidative cleavage of a-hydroxy and a-halo carbonyl compounds (San Fillipo et a/., 1976a) tocopherol-like compounds (Matsumoto and Matsuo, 1977) as well as the oxidation of hydrazines, hydra- zones and related compounds (Chern and San Fillipo, 1977) most likely proceed via an initial hydrogen abstraction. (4) Electron transjier. The oxidation of benzyli- denefluorene (Dietz et a/., 1970) catechols (Morooka and Foote, 1976: Lee-Ruff et al., 1976) N-methyl- acridone (Rosenthal and Bercovici, 1973) quinones (Poupko and Rosenthal, 1973) hydroperoxides (Peters and Foote, 1976) N-methyl benzo-pyridinium fluosul- fonates and benzo-pyridine N-oxides (Picot et al., 1977) all presumably proceed via an electron transfer from '0; to substrate. The homogeneous electron transfer reaction between superoxide and ferricenium ions has been reported to produce ferrocene and '02 (Mayeda and Bard, 1973). The co-ordination of free superoxide ion with metallo-organics (Ellis et a/., 1973; Valentine and Curtis, 1975; Valentine and Quinn, 1976; Valentine et a/., 1977) can also be explained by a charge transfer mechanism. Finally the dismutation of .O; belongs to this gen- eral reaction type. The supposed self-reaction of '0; in aprotic solvents to generate '02 (Khan. 1970) could not be experimentally supported (Poupko and Rosenthal, 1973; Nilsson and Kearns, 1974) and the 71 1