Radical-nucleophilic aromatic substitution initiation step

Almost quantitative radical nucleophilic aromatic substitution reactions were reported by Corsico and Rossi from the reaction of nucleophile trimethylstannyl ions with mono-, di- and trichloro-substituted aromatic substrates in Hquid ammonia.The chain process shown in Scheme 9 requires an initiation step, and it can be either Hght induced or be a spontaneous electron transfer from the nucleophile to the aromatic substrate. 

Equation 2.1). Three propagation steps then follow, including dissociation of the radical anion to an aryl radical and X- (Equation 2.2). In contrast, the corresponding alternative SN1 reaction would lead to the much less stable aryl cation (the empty p-orbital is part of the a-framework, and so cannot be stabilised by the n -electrons). The aryl radical then reacts rapidly with another nucleophile (Y in general or NH2- in this case) to give another radical anion (Equation 2.3) then electron transfer from one radical anion to another reactant molecule (Equation 2.4) initiates another chain. The overall consequence of the three propagation steps is nucleophilic aromatic substitution (Equation 2.5). 

In the S l mechanism of aromatic substitution the initiating step is the formation of a radical anion. In order to distinguish the process from the route described above (SR+N1) in which a radical cation plays a crucial role, the symbol S l has been used17. Creation of the radical anion can occur by several procedures. The reaction can be electrochemically initiated, a solvated electron in a solution of alkali metal in liquid ammonia may be involved or a radical anion may be used as the source of electrons. The most common source of electrons is, however, the nucleophile itself involved in the substitution reaction. In many cases the electron transfer from nucleophile to substrate is light-catalysed and the process is then sometimes referred to as S l Ar. Although the nucleofugic group in S l... 

Photonucleophilic substitution of fluoro- and chloro-anisoles has been the subject of three reports within the year. Cornelisse and co-workers have studied the photocyanation and photohydrolysis of 4-fluoro- and chloro-anisoles by laser spectroscopy and report that the initial step of the reaction involves formation of a triplet state transient complex composed of a ground state and an excited state aromatic molecule. Only in the presence of water does the complex yield radical ions and it is this process which determines the product quantum yield. The radical cation then reacts with the nucleophile to give a neutral radical which yields the substituted arene in a single step. Liu and Weiss report on anomalous effects during photonucleophilic aromatic substitution of 2- and 4-fluoroanisoles and also on the photo-... 

Photonucleophilic aromatic substitution reactions of phenyl selenide and telluride with haloarenes have also been proven to involve the S jlAr mechanism, with the formation of anion radical intermediates. Another photonucleophihc substitution, cyanomethylation, proves the presence of radical cations in the reaction mechanism. Liu and Weiss have reported that hydroxy and cyano substitution competes with photo substitution of fluorinated anisoles in aqueous solutions, where cation and anion radical intermediates have been shown to be the key factors for the nucleophilic substitution type. Rossi et al. have proposed the S j lAr mechanism for photonucleophihc substitution of carbanions and naphthox-ides to halo anisoles and l-iodonaphthalene. > An anion radical intermediate photonucleophilic substitution mechanism has been shown for the reactions of triphenyl(methyl)stannyl anion with halo arenes in liquid ammonia. Trimethylstannyl anion has been found to be more reactive than triphenylstannyl anion in the photostimulated electron- transfer initiation step. 

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. 

The reaction, a versatile synthetic tool, is initiated by generation of a radical anion. The designation Sr I indicates that the reaction is a nucleophilic substitution proceeding through a radical intermediate and that the rate-limiting step is unimolecular decay of the radical anion intermediate formed from the substrate (see a review by Bunnett, J. F. Acc. Chem. Res. 1978, 11, 413-420). Sr I reactions occur with both aliphatic and aromatic compounds. 

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