Hydrogen exchange heterocycles

Kinetic studies of base-catalysed hydrogen exchange of heterocyclic compounds have been carried out. Paudler and Helmick515 measured second-order rate coefficients for deuteration of derivatives of imidazo[l,2-a]pyridine(XXXIII), imidazo[l,2-a]pyrimidine(XXXIV), and 1,2,4-triazolo[1,5-a]pyrimidine(XXXV)... 

There are three methods that are widely used to follow the rates of isotopic hydrogen exchange in heterocyclic compounds. First, infrared spectroscopy enables the replacement of a hydrogen atom by a deuterium atom within a molecule to be detected. When an —H bond becomes an X—D bond there is a reduction in the stretching frequency... 

For a review of base-catalyzed hydrogen exchange on heterocycles, see Elvidge Jones O Brien Evans Sheppard Adv. Helerocycl. Chem. 1974, 16, 1-31. 

Transition metals also catalyze isotopic exchange reactions. Platinum is the most active catalyst for most heterocycles. The mechanism may involve metallation, addition, o--addition and ir-complex formation. a-Hydrogen exchange in pyridine is favored over 3- and 7-positions, particularly by a cobalt catalyst whereas platinum is much less selective. In isoquinoline both the 1- and 3-position protons are exchanged at almost the same rates with very little exchange at any other position. In 3-substituted pyridines exchange is preferred at the 6-position, the more so as the size of the 3-substituent increases (73AHC(15)140). 

Base-Catalyzed Hydrogen Exchange J. A. Elvidge et al., Adv. Heterocycl. Chem., 1974, 16, 1-32. 

In alcohol, the substance reacts as a base with respect to the nitrogen atom and as an acid with respect to the CH3-group. The proton acceptor in the hydrogen exchange is apparently the nitrogen atom of another molecule of the heterocycle. In ethoxide solution, the C2H50 ion acts as the proton acceptor. 

Homolytic substitution of heteroaromatic compounds, 16, 123 Hydantoins, chemistry of, 38, 177 Hydrogen cyanide derivatives, synthesis of heterocycles from, 41, 1 Hydrogen exchange base-catalyzed, 16, 1 one-step (labeling) methods, 15, 137 Hydrogenated porphyrin derivatives hydroporphyrins, 43, 73 Hydroxamic acids, cyclic, 10, 199 1 -Hydroxyindoles, 1 -hydroxytryptophans, and 1-hydroxytryptamines,... 

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. 

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. 

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