Nine 3-substituted (I-IX) and one 2-substituted (XI) bicyclo[2,2,2]octane-1-carboxylic acids were prepared as model compounds for verification of the electrostatic theory of substituent effects. On the one hand they are regular-shaped and suitable for calculations, on the other hand they allow to evaluate the role of the angle θ of the substituent dipole. The apparent pK values in 50% ethanol and 80% methyl cellosolve were correlated with σI constants (ρI 1.18 and 1.42, respectively) and compared with theoretical predictions based on the spherical and ellipsoidal cavity models. The agreement is very good with the new Ehrenson model but still satisfactory with some others not matching exactly the actual molecule shape. The substituent effects are resonably correlated with the substituent dipoles and with the geometrical parameters but exceptions are notable. Comparison with the previous results implies that the theory reproduces fairly the substituent effects in carboxylic acids of a given molecular size and not too unsymmetrical shape; the cavity model is, however, sufficiently flexible to compensate partly even for some non-electrostatic effects neglected by the basic theory.
Reaction of 2,3-dihydro-1,3-6H-oxazine-2,6-dione (I) with amines in aqueous medium leads predominantly to N-substituted amides of (Z)-3-carboxylamino-2-propenoic acid. Isomeric 3-(N'-alkylureido)-2-propenoic acids are formed as by-products in the reaction of compound I with ammonia or methylamine; tert-butylamine affords ureido derivative as the sole reaction product. Secondary amines react with compound I substantially more rapidly than primary amines. In both cases the branching on the α-carbon decreases the reactivity distinctly while the branching on the β-carbon does not have a significant effect on the rate of aminolysis. The results of kinetic measurements of the reaction of compound I with amino acids are discussed n connection with the possible interaction of compound I with enzymes.
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