Substitution, electrophilic hydrogen exchange

Hydrogen exchange, in thiazole, especially deuteration, has been quantitatively investigated (379,380), but the mechanism of the reaction carried out at acidic or neutral pH corresponds to a protonation-deprotonation process (380), different from electrophilic substitution and is discussed in section I.3.E. 

Electrophilic Attack. A variety of boranes, heteroboranes, and metaHaboranes undergo electrophilic substitution. SusceptibiUty of boranes to electrophilic attack is often detected by deuteron—proton exchange experiments. Eor example, electrophilic hydrogen—deuterium exchange of occurs at the l-,2-,3-, and 4-positions when exposed to DCl in the presence of AlCl (81). The trend to increasing positive sites in is... 

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. 

Hydrogen as the Leaving Group in Simple Substitution Reactions A. Hydrogen as the Electrophile 11-1 Hydrogen Exchange Deuterio-de-hydrogenation or deuteriation... 

Two excellent reviews <71AHC(13)235, 72IJS(C)(7)6l) have dealt with quantitative aspects of electrophilic substitution on thiophenes. Electrophilic substitution in the thiophene ring appears to proceed in most cases by a mechanism similar to that for the homocyclic benzene substrates. The first step involves the formation of a cr-complex, which is rate determining in most reactions in a few cases the decomposition of this intermediate may be rate determining. Evidence for the similarity of mechanism in the thiophene and benzene series stems from detailed kinetic studies. Thus in protodetritiation of thiophene derivatives in aqueous sulfuric and perchloric acids, a linear correlation between log k and —Ho has been established the slopes are very close to those reported for hydrogen exchanges in benzene derivatives. Likewise, the kinetic profile of the reaction of thiophene derivatives with bromine in acetic acid in the dark is the same as for bromination of benzene derivatives. The activation enthalpies and entropies for bromination of thiophene and mesitylene are very similar. 

For alkyl substituents, electrophilic substitution (chlorination, bromination, acetylation, trifluoroacetylation, formylation, hydrogen exchange) of 2-alkylthiophenes happens mainly... 

For the purpose of comparing the rates of nitration of different substrates, standard conditions have been defined as T = 25 °C, H0 = -6.6 (75% H2S04 at 25 °C). The procedure for the determination of standard rates from the experimentally measured rates has been evolved <75JCS(P2)1600>. The standard rates of individual substrates towards hydrogen exchange and nitration have been compared. This shows clearly that there is no unique scale of reactivity valid for electrophilic substitution reactions (75JCS(P2)1624). 

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... 

Hydrogen exchange reactions of heteroaromatics64 69, 65 carried out in strongly alkaline media, such as potassium amide/liquid ammonia, alcoholic solutions of alkoxides, or solutions of potassium <-butoxide in dimethyl sulfoxide, proceed through an entirely different mechanism (sometimes called protophilic ) involving a carbanion-type intermediate66, 67 they are not electrophilic substitutions as such and will not be treated in this review. 

Until a few years ago, no quantitative comparison of overall reactivities in electrophilic substitution of the fundamental five-membered rings was available. Only the reactivity of thiophene relative to benzene had been measured quantitatively in several electrophilic substitutions bromination,72 chlorination,72 nitration,121 hydrogen exchange,57 protodesilylation,174 and mercura-tion.121... 

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