Ion-radical mechanism

Section 3.4 is devoted to organic ion-radical behavior in living organisms. Particularly, the consideration of an ion-radical mechanism of carcinogenesis reflects a point of view, which is new, and, in many respects, promising. 

Scheme 3.8 represents a typical ion-radical mechanism of the so-called vicarious nucleophilic substitution of hydrogen as it was described by the pioneering chemist M kocza (M kocza 1989) in his summarizing review. ESR studies of other heterocyclic systems in conditions of the hydrogen-to-nucleophile vicarious substitution were reported by the research group at the Siberian branch of the Russian Academy of Sciences (Donskaya et al. 2002, Vakul skaya et al. 2005, 2006, Titova et al. 2005). 

Some ion-radical mechanisms are implicated in the DNA damage others can be described as repairing the damage. In normal DNA, bases belonging to the two opposite strands are bound by relatively weak hydrogen bonds. In case of complementary base pairs, several hydrogen bonds are formed they are depicted in Scheme 3.71. 

The yields of the first two products are insensitive to changes in solvent polarities. The yield of the third (the last) product increases with changing the solvent from CD2CI2 to CDjCN and, especially, addition of LiC104 to CD3CN reaction medium. Obviously, the third product is formed on a parallel reaction having ion-radical mechanism (for details, see Painter and Blackstock 1995). The dependence of reaction kinetics on ionic strength can supposedly be an indicator of ion-radical participation in rate control. 

Hence, analyzing the structure of the final products, we can tell whether the reaction has chosen the ion-radical mechanism. To this end, not only the main reaction products but also side or secondary ones should be subjected to analysis. The reaction, however, may yield a single product only. And though the reaction may take the ion-radical pathway, the final product may not differ from the product anticipated from the ordinary reaction. Fortunately, there are also other ways to discern the ion-radical mechanism if the reaction has really chosen it. 

In a similar way, Kim and Bunnett (1970) demonstrated that the substitution of amino group for iodine in iodotrimethylbenzene proceeds via the ion-radical mechanism, in contrast to the bromo and chloro analogs. The reaction of 5- and 6-halo-l,2,4-trimethylbenzenes with potassium amide in liquid ammonia gives rise to 5- and 6-aminoderivatives. This is the cine-substitution reaction (see Scheme 4.12). 

To discern the ion-radical nature of reactions, the so-called intramolecular and intermolecular proton/deuterium isotope effects may be of use. Baciocchi et al. (2005) revealed ion-radical mechanism for A-demethylation of A,A-dimethylanilines, (CH3)2NAr, by phthalimide-A-oxyl radical (Scheme 4.14). In this reaction, ( e/ D)intra values were derived for reactivity of (CD3)(CH3)NAr, whereas ( H/ D)inter was referred for the reactivity of (CD3)2NAr. The values of (A e/ D)intra were found to be always different and higher than These results, although are incompat-... 

EXAMPLES OF COMPLEX APPROACHES TO DISCERNMENT OF ION-RADICAL MECHANISM OF ORGANIC REACTIONS... 

Recent research into the ter Meer reaction (Shugalei and Tselinskii 1994) has demonstrated that it actually chooses the chain ion-radical mechanism. Chain branching is attributed to air oxygen, after transformation into the superoxide ion (O2 see Section 1.7.1). The whole process of substitution in the aqueous-alkaline buffer medium is expressed by a 14-step sequence summed in Scheme 4.36. 

The chain ion-radical mechanism of ter Meer reaction has been supported by a thorough kinetic analysis. The reaction is well-described by a standard equation of chain-radical processes (with square-law chain termination) (Shugalei et al. 1981). This mechanism also explains the nature of side products—aldehydes (see steps 13 and 14) as well as vicinal dinitroethylenes. Scheme 4.37 explains formation of vic-dinitroethylenes. 

The revealed mechanism of ter Meer reaction is well-founded. It helps us to understand the peculiarities of nucleophilic substitution reactions having the chain ion-radical mechanism and involving the interaction of radicals with anions at the chain propagation steps. It also demonstrates how the knowledge of kinetics and mechanism can be used to find new ways of initiating and optimizing the reactions important for technical practice. The ter Meer reaction turns out to be a reaction having one name and mechanism. This differs from, say, aromatic nitration, which has one name bnt different mechanisms. 

In the past two decades, there has been an increasing recognition that ion-radicals play a very important role in many organic reactions. Eventnally, a situation has arisen where, for practically every reaction between a donor and an acceptor, an ion-radical mechanism has to be carefully considered in addition to the classical polar pathway. The very subject of this book directs attention to cases where ion-radical formation is the obvions effect in play. 

Feng et al. (1986) performed quantum-chemical calculations of aromatic nitration. The resnlts they obtained were in good accordance with the IPs of N02 and benzene and its derivatives. The radical-pair recombination mechanism is favored for nitration whenever the IP of an aromatic molecule is much less than that of N02. According to calculations, nitration of toluene and xylene with N02 most probably proceeds according to ion-radical mechanism. Nitration of nitrobenzene and benzene derivatives with electron-acceptor substituents can proceed through the classical polar mechanism only. As for benzene, both mechanisms (ion-radical and polar) are possible. Substituents that raise the IP of an aromatic molecule to a value higher than that of N02 prevent the formation of this radical pair (one-electron transfer appears to be forbidden). This forces the classical mechanism to take place. It shonld be nnderlined that a solvent plays the decisive role in nitration. 

When considering aromatic nitration, it seems reasonable to examine other nitrating agents (besides the nitrating mixture leading to the formation of nitronium ion) and outline the scope of ion-radical mechanism in each case. 

The ion-radical mechanism is characteristic in cases of substrates, which are ready for one-electron oxidation and capable to give stable cation-radicals in appropriate solvents. As the cited examples show, such a mechanism can really be revealed. However, very rapid transformations of aromatic cation-radicals can mask the ion-radical nature of many other reactions and create an illusion of their nonradical character. At the same time, the ion-radical mechanism demands its own approaches for farther optimization of commercially important cases of nitration. This mechanism deserves onr continned attention. 

A large body of literature exists investigating the mechanism of the Sandmayer reaction, and as early as 1942, ion-radical mechanisms were thought to be applicable (Waters 1942). Kochi (1957) furthered this mechanistic interpretation, and the current consensus keeps this opinion (Galli 1988b, Weaver et al. 2001). 

A choice between the conventional (or classical) and ion-radical mechanism is a very important issue. The ion-radical pathway leads to products of the desired structure, makes the conversion conditions milder, or changes the reactivity of the secondary intermediate particles. If ion-radicals form and react in a solvent cage, reaction proceeds rapidly, product... 

The ion-radical mechanism should be checked with respect to every individual reaction. Compounds of even one class may behave differently—some of them react by ion-radical mechanism, whereas others may take quite another pathway. At this point, it is very important to guess why the reaction chooses one or the other mechanism. 

Ion-radical reactions require special methods to stimulate or impede them. The specificity of these methods is determined with particular properties of ion-radicals. Many ion-radical syntheses are highly selective yielding products unattainable by other methods. The aim of this chapter is to analyze the phenomena that determine the ways to optimize ion-radical reactions. This chapter considers factors governing the development of the reactions with proven ion-radical mechanisms. Two groups of optimizing factors will be discussed physical and purely chemical ones. Factors such as solvent change and salt addition are certainly in the borderline between chemical and physical effects. 

According to Ando et al. (2000), the sonolytic acetoxylation of styrene by lead tetraacetate follows the ion-radical mechanism. Lead tetraacetate was not subject to the sonication influence. The ultrasonic effect facilitates electron transfer from styrene (the nonmetallic donor) to lead tetraacetate. 

This process is of interest because the reaction reveals an nnexpected effect of snch additives, which usually hinder anion-radical reactions. According to the anthors, the considered reaction has the ion-radical mechanism (Scheme 5.10). 

Meanwhile, ion-radicals differ from ions and neutral molecules in their lower stability. As a rule, ion-radicals exist at lower temperatures. Therefore, heating is not a typical way to stimulate ion-radical reactions. Such reactions often require a controlled (inert) atmosphere, apparatus with polished walls, and so on. In general, approaches to the stimulation of ion-radical reactions do not seem to be quite regular or usual for organic chemists. Nevertheless, the high activity of ion-radicals permits different kinds of directed influence over the reactions, which follow ion-radical mechanisms. 

The anion-radical mechanism for these syntheses is based on the following facts. The reactions require photo- or electrochemical initiation. Oxygen inhibits the reactions totally, even with photoirradiation. Indoles are formed from o-iodoaniline only the meta isomer does not give rise to indole. Hence, the alternative aryne mechanism (cine-substitution) is not valid. What remains as a question is the validity of the ion-radical mechanism exclusively to the substitution of the acetonyl group for the halogen atom in o-haloareneamine or also for intramolecular condensation. 

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