Hydrogen exchange, base-catalyzed

Reactivities, relative to benzene, in gas-phase protonation of five-membered heterocycles by 3HeT+ are pyrrole, 30 N-methylpyrrole, 6 furan, 0.7 and thiophene, 0.5 (84JA37). The low substrate selectivities are consistent with the anticipated high reactivity of the unsolvated electrophile. Demands for conjugative electron release by the heteroatom will be small, thus accounting for the low reactivity of furan and thiophene (see Section 5). 

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Ring hydrogen atoms can be abstracted from the a-carbon atoms of azolium ions b strong bases, as demonstrated in base-catalyzed hydrogen exchange (Section 4.02.1.7.2... 

Base-catalyzed hydrogen exchange has been summarized for five-membered rings (74AHC(l6)l). In many reactions of this type the protonated azole is attacked by hydroxide... 

Base-catalyzed hydrogen exchange occurs at the 3- and 5-positions of 1,2-dimethyl-pyrazolium salts. 2-Unsubstituted 1,3-dithiolylium salts are easily deprotonated by nucleophilic attack of hydrogen. The intermediate carbene easily undergoes dimerization. Hydrogen exchange can also occur (Scheme 23) (80AHC(27)15l). 

Similar behavior was found for carbanions generated by base-catalyzed hydrogen exchange (Reaction 12-1) ... 

The most reactive position for base-catalyzed hydrogen exchange of the 1-oxide derivatives of quinoline and isoquinoline is the position adjacent to the heteroatom and nearest the fused benzene ring. Thus for isoquinoline 1-oxide the positionalreactivity is given by 1 > >3 > > 4,... 

Base-catalyzed hydrogen exchange in pyridazine (74) occurs in NaOD-DgO and MeONa-MeOD, ° the positional reactivity being 4(5) > 3(6) in both cases. Once more the decreased reactivity of a center ortho to a nitrogen atom relative to a more removed center is evident like pyridine, pyridazine does not have the regular geometry of benzene. 

Related to the pyridine studies are the results of base-catalyzed hydrogen exchange in cyclobutabenzene derivatives, which suggest that cyclobutyl annelation increases both the kinetic and thermodynamic acidity at the a-position. The most significant study is the thermodynamic deprotonation/carboxylation reaction of cyclobutabenzene with amyl sodium/COj, in which only the a-carboxy isomer is formed (Figure 6). This is consistent with the value for the a-proton being several p units lower than that for the P-proton in cyclobutabenzene (38). 

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

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

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