Hydrogen exchange, acid-catalyzed

Proton-deuterium exchange in pyrazolium salts has been reported by Begtrup to take place at positions 3 and 5 92ACS1096 . Older references were reported in 90AHC(47)139 . 

Considerable work has also been done with activated derivatives of the diazines. 4-Aminopyridazine and pyridazin-4-one undergo exchange in the form of their free bases at position 5. Comparisons of (95) with (102) and (103) show the considerable effect of a para-N, while that of the meta-N is much less. 

In the quinolinium cation, there is little difference in reactivity between position 3 and all the positions of the benzene ring (105). 

Pyrimidin-2-one exchanges its 5-hydrogen much faster than pyridin-2-one. However, this is due to the existence of a small proportion of the covalent hydrate (106) which undergoes rapid exchange. 

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Acid-catalyzed hydrogen exchange Halogenation Acylation and alkylation Mercuration Diazo coupling Nitrosation... 

Acid-catalyzed hydrogen exchange is used as a measure of the comparative reactivity of different aromatic rings (see Table 5). These reactions take place on the neutral molecules or, at high acidities, on the cations. At the preferred positions the neutral isoxazole, isothiazole and pyrazole rings are all considerably more reactive than benzene. Although the 4-position of isothiazole is somewhat less reactive than the 4-position in thiophene, a similar situation does not exist with isoxazole-furan ring systems. 

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. 

Scheme 2.1. The A-SE2 mechanism for acid-catalyzed hydrogen exchange.

General equations for the kinetics of acid-catalyzed hydrogen exchange of bases have been derived [68JCS(B)1484]. 

Acid-catalyzed hydrogen exchange has important advantages as a quantitative measure of heteroaromatic reativity. 

Relative Rates of 2-Substitution of Thiophenes RC4HjS in Acid-Catalyzed Hydrogen Exchange... 

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