Electrophilic aromatic hydrogen exchange

Electrophilic aromatic hydrogen exchange reactions fall into two classes, namely those reactions catalysed by acid and those reactions catalysed by base. Of these the former are by far the most common and have been subjected to the most extensive and intensive kinetic studies. 

Kinetic studies of substituent effects in electrophilic aromatic hydrogen exchange... 

A class of reactions in which the variation of with ApK has been extensively investigated is electrophilic aromatic substitution, in which the rate-determining step is proton loss from a phenonium-ion intermediate. This includes diazo-coupling [56], nitrosation [63] and aromatic hydrogen exchange [47,51,64,65]. Aromatic hydrogen... 

The advantages of the hydrogen exchange as a model electrophilic aromatic substitution are now well recognised and have been emphasised504, 522, 523, so that a very considerable body of data is now to be found in the literature. In order to simplify presentation of this, the data are considered under headings of the acid medium employed for the studies. 

In Volume 13 reactions of aromatic compounds, excluding homolytic processes due to attack of atoms and radicals (treated in a later volume), are covered. The first chapter on electrophilic substitution (nitration, sulphonation, halogenation, hydrogen exchange, etc.) constitutes the bulk of the text, and in the other two chapters nucleophilic substitution and rearrangement reactions are considered. 

The rate of hydrogen exchange with a base depends, as we know, on the proton mobility of the hydrogen atoms in aromatic CH bonds, which is very dependent on the inductive shift of cr-electrons in the carbon skeleton of the aromatic ring. In hydrogen exchange with an acid (just as in other electrophilic substitution reactions in compounds... 

In this review we have gathered the important work on quantitative and mechanistic aspects of electrophilic aromatic reactivity of heterocycles. We have concentrated in particular on acid-catalyzed hydrogen exchange, nitration, and gas-phase elimination, these being the major efforts of our own research groups. However all other electrophilic substitution reactions are covered for completeness. 

Hydrogen exchange can occur under either acid- or base-catalyzed conditions. Both can be considered electrophilic aromatic substitutions, the latter involving attack of the electrophile upon an aromatic anion, zwitterion, or ylide. The former reaction is aided by electron supply, the latter by electron withdrawal (particularly by -/ effects) as the ratedetermining step is the initial proton loss. Steric hindrance, negligible in virtually all cases under acid-catalyzed conditions, appears to be of slightly greater importance under base-catalyzed conditions. 

Replacement of hydrogen in an aromatic ring by lithium is an electrophilic substitution, entry of lithium taking place in the second and fast step of the reaction the reaction mechanism parallels that for base-catalyzed hydrogen exchange. Since the most acidic hydrogen is replaced,... 

The electrophilic aromatic substitution reaction may be advantageously modeled by isotopic exchange reactions. Shatenshtein and his co-workers77-79 studied hydrogen exchange catalyzed by acids and bases in nonaqueous solution, and their studies throw considerable light on both electrophilic substitution and protophilic (base-induced) replacement of hydrogen in the system (see Section V, A). 

In a proton transfer to an aromatic carbon atom, a so-called sigma complex is formed in which the configuration of the valence electrons of the carbon has been changed from sp2 to sp3. In the next step, the other electrophilic atom or group bonded to the same carbon may be split off. This leads to an electrophilic aromatic substitution. Examples are aromatic hydrogen isotope exchange, aromatic decarboxylation, deboro-nation, and deiodination (see Sect. 9 Chap. 2, and Vol. 13, Chap. 1). 

Data on hydrogen exchange have been of particular interest for comparison with theoretical predictions of aromatic reactivity. Because the electrophile is well defined and small, calculation of the stability of various competing intermediates by... 

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