Substitution nucleophilic aromatic radical chain mechanism

Fig. 5.45. Mechanism of the nucleophilic aromatic substitution reaction of Figure 5.44. The radical I2 plays the role of the chain-carrying radical and also the important role of the initiating radical in this chain reaction. The scheme shows how this radical is regenerated. It remains to be added how it is presumably formed initially (1) Ar—N+=N + I- ->...

The Skv I radical chain mechanism lor nucleophilic substitution [I70. as illustrated generally in eqs (2.64a-c), has been absent from our discussions. This mechanism has been shown to occur itt malty displacement reactions of leaving groups front both aromatic and aliphatic substrates. I low ever, in most of the aliphatic eases the substrates have a nitro or nilrophcnyl group (or other effective electron acceptor) in the a-position to the leaving group. The combination of I he nucleophile with the radical from the substrate must also lot m a relatively stable radical-anion in step 2.6lb. which is capable of propagating the chain... 

Besides nucleophilic and electrophilic pathways for aromatic substitutions, there are also radical pathways. With aromatic rings that are easily reduced, this is a common mechanism, because the benzene ring can delocalize the radical anion. The radical chain mechanism is referred to as SrnI, (substitution, radical-nucleophilic, unimolecular). An example is shown in Eq. 10.118. 

There is still another substitution mechanism to consider, although it is much less common. It is called SrnI (substitution, radical, nucleophilic, unimolecular) and involves a radical chain mechanism, unlike the SET mechanism just described. We have seen a radical chain substitution mechanism in Chapter 10 when we considered radical aromatic substitution (Section 10.22). 

In the context of the direct mechanism, several perplexing features concerning nuclear and side-chain substitution of aromatic compounds have been highlighted [124-126], and in the search for explanations attempts have been made to estimate, by thermo-chemically based calculations, free energies of activation for reactions between radical cations and nucleophiles. Long-standing puzzles in this area include the dependence of the ratio of side chain/nuclear substituted products on the nucleophile for alkylbenzenes, side-chain acetoxylation predominates in acetic acid (AcOH) unless AcO is present, when nuclear substitution becomes important. 

There has been a major review of substitution by the radical-chain 5rn1 mechanism. It has been shown that reaction by the SrnI pathway of the enolate anions of 2- and 3-acetyl-l-methylpyrrole may yield a-substituted acetylpyrroles. The dichotomy of reactions of halonitrobenzenes with nucleophiles has been nicely summarized major pathways include reduction via radical pathways and. SnAt substitution of halogen. EPR spectroscopy has been used to detect radical species produced in the reactions of some aromatic nitro compounds with nucleophiles however, whether these species are on the substitution pathway is questionable. The reaction of some 4-substimted N,N-dimethylanilines with secondary anilines occurs on activation by thallium triacetate to yield diphenylamine derivatives radical cation intermediates are proposed. ... 

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. 

Nuclear and side chain substitution in aromatics or substitution of a -hydrogen in alkylamines is — in most cases — best rationalized by postulating radical cations as intermediates. For anodic nuclear substitution of aromatics, especially for acyloxylation, cyanation or bromination a ECnECb3 -mechanism is assumed 37,4 9,50,226,227). jc-oxidation of the aromatic to the radical cation 28, which reacts with a nucleophile Nu, e.g., acetate, cyanide, alkoxide, followed by a second electron transfer and deprotonation (Eq. (98) ) ... 

Generation of substituted aryl radical cations in the presence of nucleophiles can lead to products of side-chain substitution (processes such as anodic benzylic substitution of toluenes, which are dealt with in a separate chapter) or to products of addition to the aromatic ring itself. Nuclear addition products in /j /m-substituted systems have been proposed to form in essentially one of two ways, depending on substitution pattern and reaction conditions. Radical cations formed by electrochemical reaction (E) may be trapped by chemical reaction (C) with a nucleophile (or its anion). Repeating this sequence leads to nuclear addition products (LXV), formed by what is referred to as the ECEC mechanism [Eq. (31)] [74]. An analogous pattern may be inferred for or / (9-substituted systems. 

The mechanism composed of Eqs. (2), (3), (5), and (7) is observed typically for nuclear substitution in aromatic compounds, whereas side-chain substitutions, for instance, typically proceed according to Eqs. (2), (4), (6), and (8). (For a more thorough discussion of the reactions between radical cations and nucleophiles, the reader is referred to the rich literature on this subject [1,2].) Essentially the same mechanistic pattern is found in oxidative substitution driven by high valent inorganic ions [3-6]. 

For unactivated aromatic and heteroaromatic substrates, where a polar substitution is not favorable, nucleophilic substitution is feasible through processes that involve electron transfer (ET) steps. In these reactions, an aromatic compound bearing an adequate leaving group is substituted at the ipso position by a nucleophile in a unimolecular radical nucleophilic substitution mechanism (or S,y.jl), which is a chain process that involves radicals and radical anions as intermediates. 

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