Hydrogen exchange solvent effect

Extensive studies on hydrogen exchange in aqueous sulfuric acid on 1 -methylpyrazole,252 isoxazole,328 and isothiazole328 and their methylated derivatives252,328 have been reported, but calculated partial rate factors derived from treatment of the form of Eq. (12) do not tally with those observed. This emphasizes the contribution from interactions between donor and acceptor groups or solvent effects which also lead to breakdown in the interpretation of nitration results.83... 

B. Effect of Complex Formation between the Substrate and the Solvent on the Hydrogen Exchange Rate... 

VIII. The Kinetic Isotope Effect in the Hydrogen Exchange in Protophilic Solvents and in Metallation... 

A similar effect is also observed in the hydrogen exchange for this reaction, the a /3 ratio is strongly dependent on the nature of the solvent and the acidity of the medium also (Table X). 

The mechanism of heteroaromatic hydrogen exchange can therefore be determined for a wide variety of substrates in the manner described in the previous sections in particular, the nature of the species undergoing reaction may be elucidated. The next stage is to compare rates, and this can be done provided all the kinetic data can be extrapolated to the same standard conditions of acidity and temperature. These relative rates will, however, as in the case of electrophilic substitution of all heterocycles in solution (especially ir-deficient heterocycles in protic solvents), be subject to the modifying effect of hydrogen bonding, correction for which has so far been applied in only a relatively few cases. 

A related solvent effect was found for the proton exchange between acetic acid and methanol in tetrahydrofuran by Bureiko et al [88] and by Gerritzen et al. [9]. Hydrogen bonding to the solvent prevents the formation of the cyclic complexes in which the proton exchange takes place. Unfortunately, these complexes could not be seen directly. The rate constants were measured as a function of concentra-... 

Figure 14.1. Hydrogen exchange mechanisms (a) Amide exchange at neutrai pH invoives base cataiyzed proton abstraction and acid cataiyzed transfer of deuterium from solvent. Measurable isotope effects on the amide hydrogen and a lack of a solvent isotope effect indicate that proton abstraction is rate limiting [1]. (b) Schematic diagram of the two-state model for hydrogen exchange in native proteins and kinetic prediction. The rate of...

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