Electrophilic Substitution Reactions on Metalated Aromatic Compounds

3 Electrophilic Substitution Reactions on Metalated Aromatic Compounds 

1 Electrophilic Substitution Reactions of o/7/io-Lithiated Benzene and Naphthalene Derivatives 

DMG and thus enables oriho-lithiation via a transition state analogous to C and the formation of a lithiated aromatic structure A. 

Any reaction Ar—H +. vec-BuLi — Ar—Li +. sec-BuH possesses a considerable driving force. In an DMG-controlled ortho-lithiation it is even greater than it would be normally. This is due to the stabilization of the orfho-lithiated aromatic compound A because of the intramolecular complexation of the Li atom by the donor oxygen of the neighboring DMG and, at least in some cases, to inductive stabilization provided by the DMG. The exclusive occurrence of orfho-lithiation is thus a consequence not only of the precoordination of sec-BuLi by the DMG but also of product development control. 

Aryllithium Compounds That Are Accessible from Aryl Halides 

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Electrophilic Substitution Reactions on Metallated Aromatic Compounds... 

After some comments on what was named the medium polarity effect and the medium dielectric constant the authors came to the following conclusions such nucleophilic addition reactions of diphenylmagnesium compounds with ketones and metallation reactions of 1-alkynes have some common features. Apparently, they can both be considered as a special case of aromatic electrophilic substitution, differing from (what the authors named) the classical examples of this reaction, in that the latter one has a more pronounced reagent-like transition state. 

Heterocyclic aromatic compounds such as pyrrole are readily metallated with Grignard reagents. The resulting compounds have N"Mg bonds and are, therefore, not organometallic compounds, but on reaction with electrophiles give 2-substituted pyrroles [14] (eq (4)). The reaction of chloroform or bromoform with PrMgCl at -78 °C in THF-HMPA (4 1) is mild and convenient method for the generation of an unstable carbenoid in the solution [15] (eq (5)). 

Successively, Friedel and Crafts studied the generality and the limitations of the new synthetic method. They found that the reaction could be successfully applied to a large number of aromatic compounds, as well as alkyl and acyl chlorides or anhydrides in the presence of chlorides of certain metals such as aluminum, zinc, and iron. A mechanistic hypothesis was postulated on the basis of the possible existence of an intermediate compound 3 formed between benzene and aluminum chloride (Scheme 1.2). This intermediate would react with the electrophilic reagent, giving the substitution product and restoring the catalyst. 

Aromatic compounds (eqs 16 and 17) are acylated by PhCOCI in the presence of a Lewis acid such as AICI3, TiCU, BF3, SnCU, ZnClz, or FeClz, or of a strong acid such as polyphos-phoric acid or CF3SO3H. Metallic A1 or Fe and iodine (in situ formation of a Lewis acid) can also act as a catalyst. Various solvents that have been used to perform this reaction are CSz, CH2CI2, 1,2-dichloroethane, nitrobenzene, and nitromethane. PhCOCI is less reactive than aliphatic carboxylic acid chlorides (with benzene in nitromethane the relative reaction rates are Ph-COCl MeCOCl = 6 100). As for all electrophilic substitutions, the rate and the regioselectivity of the acylation closely depend on the nature and on the position of the substituents on the aromatic system (eqs 16 and 18 ). The nature of the solvent can also exert a strong influence. ... 

Besides the applications of the electrophilicity index mentioned in the review article [40], following recent applications and developments have been observed, including relationship between basicity and nucleophilicity [64], 3D-quantitative structure activity analysis [65], Quantitative Structure-Toxicity Relationship (QSTR) [66], redox potential [67,68], Woodward-Hoffmann rules [69], Michael-type reactions [70], Sn2 reactions [71], multiphilic descriptions [72], etc. Molecular systems include silylenes [73], heterocyclohexanones [74], pyrido-di-indoles [65], bipyridine [75], aromatic and heterocyclic sulfonamides [76], substituted nitrenes and phosphi-nidenes [77], first-row transition metal ions [67], triruthenium ring core structures [78], benzhydryl derivatives [79], multivalent superatoms [80], nitrobenzodifuroxan [70], dialkylpyridinium ions [81], dioxins [82], arsenosugars and thioarsenicals [83], dynamic properties of clusters and nanostructures [84], porphyrin compounds [85-87], and so on. 

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