Electrophilic aromatic substitution reactions exchange

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). 

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. 

Probably the best modem method for introduction of OF by electrophilic aromatic substitution is lithiation, reaction with a boronate ester, and oxidation.4 These are the same boron compounds that are used in Suzuki coupling (chapter 18) and are made the same way. In this example, selective mono-lithiation by Br/Li exchange on available tribromoanisole 39 (easily prepared by bromination of anisole or phenol) occurs ortho to the MeO group and reaction of aryl-lithium 39 with trimethyl borate gives the boronic ester 40. Peroxyacids such as peracetic acid are usually used for the final oxidation. 

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 intermediate tricyclic ketones 495 and 496 have been transformed to the methoxy-substituted derivative 97284,285) latter ketone is subject to hydrogen-deuterium exchange only under basic conditions and appears to exist entirely in the keto form despite the ready formation of its anion and successful methylation on oxygen . In agreement with the aromatic nature of 490, the hydrocarbon undergoes electrophilic substitution reactions... 

It is possible to replace the ring hydrogens of many aromatic compounds by exchange with strong acids. When an isotopically labeled acid such as D2S04 is used, this reaction is an easy way to introduce deuterium. The mechanism is analogous to other electrophilic substitutions ... 

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... 

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