Aromatic substitution hydrogen exchange

Table 10.8. Partial Rate Factors for Hydrogen Exchange in Some Substituted Aromatic Compounds...

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. 

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... 

Reactivity of Electron Donor-Acceptor Complexes. Part. 6. Hydrogen Exchange of Aromatic Cyano-Substituted Compounds. Trans. Faraday Soc. 63, 997 (1967). 

Alkylcarbonium ions, spectroscopic observation in strong acid solutions, 4, 305 Ammonia, liquid, isotope exchange reactions of organic compounds in, 1, 156 Aromatic substitution, a quantitative treatment of directive effects in, 1, 35 Aromatic substitution reactions, hydrogen isotope effects in, 2, 163 Aromatic systems, planar and non-planar, 1, 203... 

Indications of the occurrence of cycloaddition were first obtained from reactions of specifically deuterated allyl anions with tetrafluoroethylene. Assuming that no hydrogen/deuterium exchange occurs in the collision complex as shown for the allyl anions themselves (Dawson el al., 1979a), the results obtained (Nibbering, 1979) may be interpreted as indicating that 65% of the allyl anions react by a linear addition (51), 20% by a [2 + 2] atom cycloaddition (52) and 15% by a [2 + 3] atom cycloaddition. (53). It should be noted here that the precise mechanistic details of the losses of HF molecules from the collision complexes in eqns (51)—(53) are not known. However, in view of the nucleophilic aromatic substitution discussed in the previous section, it is quite likely that they occur in a stepwise fashion in which complexes solvated by fluoride anions play a role. 

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). 

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