Endo-Peroxides

This group is prepared by the reaction of the anion of 9-hydroxyanthracene and the tosylate of an alcohol. Since the formation of this group requires an S 2 displacement on the alcohol to be protected, it is best suited for primaiy alcohols. It is cleaved by a novel singlet oxygen reaction followed by reduction of the endo-peroxide with hydrogen and Raney nickel. 

The thiophene endoperoxides ate considerably more labile than the furan endo-peroxides 26), but diimide is sufficiently reactive even at —30 to —50 °C to trap them in the form of thiaozonides 13. 

In the case of chemiluminescence occurring on treatment of di-benzanthrone with hypochlorite, as mentioned above, an endo peroxide might well be a key intermediate formed from 4 and singlet oxygen. The emitting species, however, is trichloro-dibenzanthrone, not 4 itself 70h... 

From all anthracene endo peroxides investigated so far (71> 1>, p. 132) the compound 7 (1.4-dimethoxy-9.10-diphenylanthracene 1.4-endoperox-ide) was found to exhibit the most efficient chemiluminescence 72> on... 

Dufraisse has shown that the oxygen liberation from acene endo-peroxides is quite often accompanied by chemiluminescence, the spectrum of which is usually similar to the fluorescence of the corresponding hydrocarbon,271-273 although this point seems to require confirmation.274 According to Bowen,275 the most likely processes involved are... 

Another interesting question is whether excited singlet states of oxygen are released during the photochemical decomposition of the Co-0-0-Co5+ chromophore. We explored this question by decomposing 2-p in the presence of 1,3-cyclohexadiene which is known to react with excited singlet states of 02 to give the endo peroxide.82 Some endo peroxide may have been formed, and other peroxidic products were formed, but the nature of this reaction is not yet clear. 

It has recently been shown that 1,2-dihydropyridines react with singlet oxygen to give endo-peroxides (75CPB2567, 80TL839, 81H(16)973). These compounds react with nucleophiles... 

In some cases, the structures of oxygenation products have been crucial for assigning the structures of unusual radical cations. Eor example, the endo-peroxides (83 and 85) support the structures assigned to radical cations (24 and 84 ) derived from l,l-diaryl-2-methylenecyclopropane (23) and 2,5-diaryl-l,5-hexadiene, respectively.Time-resolved spectroscopic data suggest that 83 is generated by coupling of triplet biradical (24 ) with (triplet) molecular oxygen. 

In this section, we will present examples of the concerted ET reduction of the 0—0 bond in a number of simple alkyl peroxides (RO-OR) and endo-peroxides. These systems provide the first clear examples of the parabolic activation/driving force relationships. The necessary background is provided in the section below. The data provided by the peroxide systems also allow us to introduce important new insights into concerted dissociative processes, particularly the importance of steric and nonadiabatic effects. Finally, data for perbenzoates, another peroxide system related to the early studies, provide evidence for the transition between the concerted and stepwise dissociative mechanisms. 

Nirofuran compounds are also effective anti-parasitic drugs. Nifurtimox, for example, is used to treat Chagas disease (caused by Trypansoma cruzi) but has side effects. In exploring the use of alternatives to nifurtimox, Olea-Azar et al. have examined radical formation from two analogues. Radical anions were observed upon electrolytic reduction of the compounds and a nitroxide, believed to be the glutathionyl radical-adduct, was detected upon electrolysis in the presence of DMPO and GSH. Radical adducts were also detected upon incubation of one of the analogues with microsomes from T. Cruzi.m A novel endo-peroxide reductase has been isolated from T. Cruzi. Whereas the flavoenzyme was found to reduce quinones to their semiquinones, nifurtimox underwent a direct, two-electron reduction, without the formation of radicals.129... 

Figure 16.5 Second-order rate constants [multiplied by (1 - aia) for phenols] for reactions of several compounds with 02 (left scale) as a function of pH. The abbreviations in parentheses indicate the reaction type ef = endo-peroxide formation (Eq. 16-14) er = ene reaction et = electron transfer so = sulfur oxidation. The scale on the right indicates the half-lives of the compounds in the epilimnion of Greifensee on a clear summer day (data from Scully and Hoigne, 1987).

With endo-peroxides obtained similarly in the presence of tetraphenylporphyrin from 2-methoxy-3-carbomethoxy-5-arylfurans 202, when the aryl group is electron donating (para-anisyl, p-An), the product 206 is derived from a dioxirane 205 formed by the isomerization of the intermediate carbonyl oxide (Scheme 68). With methanol a hydroperoxide 207 is obtained as in the previous case <1994JCS(P1)147>. 

An interesting 2-oxetanyl hydroperoxide 209 was obtained by Methylene Blue photosensitized oxidation as the main product from a furanic endo-peroxide 208 (Scheme 70) <2001JOC4732>. 

In 2004, a report appeared that 9,10-dimethylanthracene-9,10-endoperoxide (48) arose from an electron-transfer photooxidation of 9,10-dimethylanthracene (38) with the use of the sensitizer Acr+-Mes in 02-saturated CH3CN at 0 °C [32]. Subsequent coupling of the anthracene radical cation and the superoxide ion generated endo-peroxide 48. Endoperoxide 48 was detected during the initial stage of the photooxidation, but was not isolated over time, the reaction yielded 10-hydroxanthrone, anthraquinone, and H202. 

Funk, C. D., and Powell, W. S. 1983. Metabolism of linoleic acid by prostaglandin endo-peroxide synthase from adult and fetal blood vessels. Biochim. Biophys. Acta, 754, 57-71. 

Quite surprisingly, in addition to forseeable products, photo-oxidation of 2,5-dimethyl122 and 2,5-dimethyl-3,4-diethyl-pyrrole123 afforded lactams like (19) with R4 = CH2OCH3, the formation of which is not easily rationalized. It was assumed that all these products can be derived from an endo-peroxide (20). 

Qinghao (Sweet Wormwood) is the dried aerial parts of the herb Artemisia annua L. (Asteraceae family), which has been used in China for centuries to treat fever and malaria. Artemisinin (Nl) (Qing Hao Su) (128), the active principle, directly kills Plasmodium falciparum (malaria parasites) with little toxicity to animals and humans. Thus, it is a clinically effective, safe, and rapid antimalarial agent (129, 130). The novel endo-peroxide link is essential for the antimalarial activity. 

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