Pyrimidine 1-oxides, hydrogen-exchange

Second-Order Rate Coefficients for Base-Catalyzed Deuterium-Hydrogen Exchange in 5-Substituted Pyrimidine A/-Oxides"... 

In pyridazines, base-catalyzed hydrogendeuterium exchange takes place at positions 4 and 5 more easily than at positions 3 and 6. Pyridazine 1-oxide reacts first at positions 5 and 6 and then at C(3) and C(4). Pyrimidine exchanges most readily at the S-position, next at the 4-position, and least readily at the 2-position. In pyrimidine 1-oxide, the reactivity order is 2>6>4>>5. 1,2,4-Triazines easily undergo base-catalyzed hydrogen exchange at the 2-position. 

A similar difference in reactivity is evident in the N-oxides pyrazine N-oxide is even more reactive than pyrimidine or pyridine N-oxide. Substituents in the 3-position appear to act mainly through their inductive effects (Table 10.3). Log k2 varies linearly with p/Ca, and the carbanion mechanism probably operates (there is, however, doubt about the mode of substitution at C-6 in pyrazine N-oxides) (70JOC3467). All four hydrogens of pyrazine N,AT-dioxide are exchanged in MeOD at 65°C (68MI2). 

Sulfur-containing pyrimidines are frequent intermediates in substitution reactions. Several methods exist for exchange of the thiol group with hydrogen, either by hydrogenolysis, especially by the use of Raney Nickel, or by oxidative desulfurization which involves a sulfinic acid intermediate. Oxidation may also lead to a sulfonic acid. The 2- and 4-/6-thiones are considerably more stable to air oxidation than 5-thiol derivatives. Disulfides are conveniently formed by oxidation with bromine. Oxidation with chlorine at low temperature can be used to prepare sulfonyl chlorides. These reactions have been summarized [Pg.187]

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