Reaction mechanisms aromatic/heteroaromatic compounds

Nucleophilic aromatic substitution of hydrogen in heteroaromatic compounds, reactivity and reaction mechanisms 94MI2. 

Using Saveanfs terminology, such a process is called redox catalysis in its proper meaning, while Shono formed the expression homomediatory system . This type of mechanism was already schematically presented in the case of an oxidation in Eqs. (2) to (4). To this category of redox catalysts belong, for example, the radical anions and cations of aromatic and heteroaromatic compounds and some reactions of triaryl amine radical cations. 

The most widespread and convenient method for the preparation of nitrobenzazoles is the reaction of nitration. Electrophilic substitution of azoles is a complex reaction in which the experimental conditions can modify the product orientation. The ability of azoles to electrophilic substitution is determined by the activity of reagents, the basicity of substrates, and the acidity of medium. This caused some uncertainty in interpreting the results and complicated comparison of the reactivity of various azoles among them. The situation has changed after Katritzky and Johnson [7] had reported the criteria allowing, with a sufficient degree of reliance, the establishment in what form (base or conjugative acid) the compound reacts. The information on the mechanism of nitration of azoles is basically borrowed from the extensive literature on the nitration of aromatic and heteroaromatic compounds [8] therefore, it does not make sense to discuss this point in the review. 

On the other hand, the direct arylation of carbanionic species generated from substrates having relatively acidic hydrogens such as active methylene compounds and ketones can occur (mechanism B) [5,6]. Aryl halides are also capable of coupling directly with appropriately functionalized aromatic substrates and five-membered heteroaromatic compounds as formal carbon nucleophiles via cleavage of their unactivated C-H bonds [5,7-9]. The Fujiwra-Moritani reaction, which is the arylation of alkenes with arenes, is also useful for preparing arylalkenes without employing any halides (mechanism D) [10,11]. 

Arenes, especially electron-rich ones, and five-membered-ring heteroaromatic compounds have been found to react with alkynes in the presence of Pd(II) or Pt(II) species in acidic solvents to give the corresponding hydroaryl-ation products (Eqs. 68 and 69) [155-158]. The mechanism proposed for the reaction involves aromatic palladation to form ArPd(II) species, as in the Fujiwara-Moritani reaction [10], insertion of an alkyne,and protonolysis of the... 

Regio-chemical control and outcome are important aspects in terms of using the reaction. Aromatic azine s amination is subjected to variables such as the compound s class, substituents, substitution pattern, reaction condition and consequently the reaction mechanism. All variables are used for predicting and explaining the regio-chemical outcome for the reaction. Although it is outside the scope of this summary to provide examples from every heteroaromatic azine used synthetically, below is a sample of some representative examples. 

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. 

Both acid and base catalysis have been used extensively to catalyze exchange in aromatic, and to a lesser extent, heterocyclic molecules. In acid exchange, the most widely used catalysts are sulfuric acid,122,129, 131 phosphoric acid,132 trifluoroacetic acid5133 perchloric acid,134 aluminum chloride,135 and the phosphoric acid-boron trifluoride complex.132 These reactions constitute the simplest electrophilic substitution. The mechanism for such substitution in benzenoid compounds is now comparatively well understood 122 however, the problem of heteroaromatic electrophilic substitution is still being clarified and has led to renewed interest in acid-catalyzed exchange in heterocyclic compounds.122... 

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