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, 2333 (1994).Hydration rate constants and equilibrium constants have been obtained for 9-acridinecarboxaldehyde in aqueous solution Under acidic conditions where the acridine is protonated, signals for the hydrate and free aldehyde forms can be observed as separate species in the IH NMR spectrum. Integration provides the hydration equilibrium constant Kh4 = [hydrate]l[aldehyde] = 2.5 Using an apparent acidity constant obtained from a spectroscopic tltration curve, the rate-pH profile was fitted to prov~de the hydrat~on constant for the equilibration of the neutral acridines, KH = 0.07. This analysis also provides the acidity constants for the two acridinium ions, the aldehyde with pK = 3.78 and the hydrate with pK = 5.36. A comparison with the 4-pyridinecarboxaldehdye system reveals that the Kh+: Kh ratios for the acridine and pyridine are the same within experimental error, but that the acridine and acridinium aldehydes are 20-fold less hydrated than their pyridine analogs. A comparison with benzaldehydes reveals that, in their reactivities, the two heterocyclic aldehydes behave In a similar manner. Thus, for example, plots of log kH for the acid-catalyzed dehydration and hydrations versus log Kh for the equilibrium hydration show single correlation lines including the polnts for the benzaldehydes and heterocyclic aldehydes (but not the aliphatic aldehydes). Cette analyse fournit aussi les constantes d'aciditi des deux ions acridinium; pour l'aldthyde, le pK = 3,78 alors que, pour l'hydrate, le pK = 5,36. Une comparaison avec le systkme pyridine-4-carboxaldChyde rCvkle que les rapports Kt,+ : Kl, pour l'acridine et la pyridine sont essentiellement les memes, aux erreurs expCrimentales prks, mais que les aldChydes de I'acridine et de l'acridinium sont 20 fois moins hydrates que leurs analogues de la strie pyridinique. Une comparaison avec les benzaldthydes rCvkle que, pour leurs rCactivitCs, les deux aldChydes hitCrocycliques se comportent de manikres similaires. Ainsi, par exemple, les courbes des log kH de la deshydratation ou des hydratations acidocatalysdes en fonction du log Kh pour l'tquilibre d'hydratation prCsentent des droites de corrClation unique comportant les points des benzaldehydes et des aldChydes hCtCrocycliques (mais pas des aldChydes aliphatiques).[Traduit par la rCdaction]The anticonvulsant drug carbamazepine (5H-dibenzrb, f 1-azepine-5-carboxamide) is associated with a significant incidence of idiosyncratic reactions including agranulocytosis. It has been found that many of the drugs that are associated with agranulocytosis are metabolized to reactive species by activated neutrophils (1). The major neutrophil enzyme involved in such oxidations is myeloperoxidase. This enzyme has, as its usual substrate, chloride, which undergoes a two-electron oxidation producing either hypochlorite or an activated chlorine bound to the enzyme that mimics hypochlorite in its behavior.Carbamazepine is indeed oxidized by neutrophils, resulting in covalent binding of radiolabelled drug to the neutrophil (2). T...

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The acid-base catalysed decomposition of hydrates and hemiacetals of carbonyl compounds are classical examples of reactions where (slow) proton transfer is coupled with heavy atom reorganization, i.e., C—O bond breaking and solvent reorganization. We have studied the influence of m- and p-substitution in the carbonyl electrophile on the kinetics of the acid and base catalysis of the decomposition of methyl hemiacetals of benzaldehyde. The experimental data are well described by three-dimensional More O'Ferrall - Jencks energy contour diagrams according to principles developed by Jencks (the BEMA HAPOTHLE). Thus, for acid catalysis, a Cordes cross-interaction coefficient pxy' = δρ/δpKa = 0.15 indicates the coupled nature of the rate-limiting step in a class e mechanism, similar to conclusions reached from systematic substitution in the nucleophile. Our more extensive set of data for base catalysis permits a more rigorous analysis according to the BEMA HAPOTHLE. The data are consistent with a class n mechanism as also suggested earlier on the basis of substitution in the nucleophile. A slight upward curvature observed in the Hammett plots for the various catalysts is described by the direct correlation parameter py = -δρ/δσ = -0.11. This second derivative demonstrates the concerted nature of the C—O bond cleavage and O-H formation in the transition state, which changes with changing substituent. A class n mechanism for base catalysis is also supported by the observation of a Cordes cross-interaction parameter pxy = -δρ/δpKa = -δβ/δσ = 0.03, which describes the experimentally observed decrease in Hammett ρ with increasing pKa of the catalyst. This change may be rationalized by the movement of a saddle point on a diagonal reaction coordinate in the energy contour diagram, as a resultant of shifts parallel and perpendicular to the coordinate, when the energy along one side of the diagram is changed. It is concluded that observed rate changes as a result of substitution in the electrophile are consistent with and present further confirmation of earlier suggested mechanisms of hemiacetal decomposition reactions.Key words: methyl hemiacetals of benzaldehydes, acid-base catalysed breakdown, Hammett plots, More O'Ferrall - Jencks diagrams.

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