Nitroarene reactions, electron-transfer

A completely different behavior was reported for the photochemical interaction between halogenonitrothiophenes and arylalkenes. When 5-iodo-2-nitrothiophene (121) was irradiated in the presence of styrene, the formation of a mixture of nitrones 149 and 150 was observed. The same behavior was observed by using nitroarenes, such as nitrothiophene or nitrobenzene (94JPP(A)(79)67). The reaction can be explained on the basis of a work published in 1955 where an electron transfer mechanism was proposed. The radical thus formed can give the product of addition of the nitro group to the double bond that, then, can be converted into the product (55JOC1086). 

Nitroarenes, on the other hand, are strong electron acceptors and easily undergo one-electron reduction (12, 13). Thus, nitrobenzene, to cite one example, has been customarily used as an effective quencher in chain reactions involving radical anion intermediates, such as in SRN1 reactions (3). Under different conditions, nitroarene radical anions are reactive species. In particular, Zinin (14) reported that treatment of nitroarenes with hot alkaline alcoholic solutions results in products of reduction, mainly the azoxy derivative (equation 2). These complex multistep processes involve nitroarene radical anion intermediates and are quite effectively inhibited by oxygen (10, 15, 16). In 1964, Russell et al. (17) wrote that apparently much of the chemistry of aromatic nitro, nitroso and azo compounds in basic solution involves electron-transfer processes . 

Nitroarenes can react with reducing radicals in two general pathways, radical-addition or outer-sphere electron-transfer, although electron transfer can proceed via adducts in an inner-sphere addition/elimination reaction [98]. Prototypical behaviour was established from electron paramagnetic resonance (epr) experiments [99], which showed that hydroxymethyl radicals reduced nitrobenzene via an intermediate adduct, relatively stable in acid but which underwent base-catalyzed heterolysis ... 

There are several parallels in the reduction chemistry of nitroarenes and aromatic N-oxides, such as similar kinetics of electron transfer reactions of the radical-anions and the effects of prototropic equilibria on radical lifetimes in aqueous solution [16]. The benzotriazine di-N-oxide, tirapazamine (Figure 1,16) is currently in Phase III clinical trial as a hypoxic cell cytotoxin in conjunction with cisplatin [132]. The mechanism of its action appears to involve the one-electron reduction product [133] cleaving DNA [134], probably also sensitizing the damage by a radical-addition step [135-138]. 

We observed two different effects. One effect is that the chloride anion substantially increases the rate of interconversion of Ru3(CO)i2 and Ru(CO)s, which would otherwise be slow even at high temperature. Thus the presence of chloride in the reaction mixture enables more rapid formation of the active Ru(CO)s moiety under the reaction conditions. The importance of a slow conversion of Ru3(CO)i2 into Ru(CO)5 and its acceleration by chloride goes well beyond the current mechanistic study, because it might be relevant to many of the catalytic reactions in which the trinuclear cluster is used as a precatalyst. A second effect is to be found in the acceleration of the initial activation of the nitroarene. We could observe this effect on the reactivity of both Ru3(CO)i2 and Ru(CO)5. The effect is derived from the formation of a chloride adduct, which for Ru3(CO)i2 is [Ru3(CO)n(Cl)] but is not isolable for Ru(CO)5. This adduct is more easily oxidizable than the starting neutral compounds. As the initial activation of the nitroarene is always an electron transfer from the metal to the nitro group, this increase in oxidizability renders the reaction much easier. Several experiments were done to assess which of the two effects of chloride identified is that responsible for the acceleration of the catalytic reaction. It turned out that only the first effect is kinetically relevant to the acceleration of the... 

When analyzing plausible mechanisms of the VNS reactions of nitroarenes with a-chlorocarbanions, one should clarify a few key questions how to proceed the addition and subsequent conversion of adducts and how other substituents may affect both of these steps - rate and orientation of the addition, rate of the elimination, etc. It is well known that nitroarenes are active electron acceptors, whereas carbanions are good electron donors thus, these reactants can enter a single-electron transfer (SET) to form anion radicals of nitroarenes and radicals from carbanions [21, 22]. Further coupling of these electrophilic radicals with nucleophilic anion-radical species could give adducts. This SET pathway, alternative to the direct addition, is often favored by authors and the concept is sometimes abused, see [23] and rebuttal [24]. Nevertheless, numerous observations contradict participation of the SET mechanism in the VNS reactions ... 

A second effect is to be found in the acceleration of the initial activation of the nitroarene. We could observe this effect on the reactivity of both Ru3(CO)i2 and Ru(CO)s. We have previously mentioned that Han and others could not evidence any accelerating effect of chloride in the reaction between Ru3(CO)i2 and nitrobenzene [157]. However, from several studies, partly conducted by us yide infra), it has become now clear that the initial aetivation of nitroarenes from transition metal complexes always proceeds through an intermediate electron transfer from the complex to the nitro compound. Thus, any modification of Ru3(CO)i2 which increases its oxidability, specifically the introduction of the anionic ligand chloride, should increase its reactivity towards nitroarenes. However, the reaction between Ru3(CO)i2 and unsubstituted nitrobenzene requires a relatively high temperature even in the presence of chloride and at temperatures over 50°C and under a nitrogen atmosphere the initially formed [Ru3(CO)u(Cl)] is rapidly converted to a less reactive tetranuclear cluster, [Ru4(CO)i3(p-Cl)] [179]. 

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