Group contribution methods shortcomings

One shortcoming of the benzoic acid system is the extent of coupling between the car-bo l group and certain lone-pair donors. Insertion of a methylene group between the core (benzene ring) and the functional group (COOH moiety) leads to phenylacetic acids and the establishment of scale from the ionization of X-phenylacetic acids. A flexible method of dealing with the variability of the resonance contribution to the overall electronic demand of a reaction is embodied in the Yukawa-Tsuno equation (86). It includes nor-nial d enhanced resonance contributions to an LFER. 

The acidities of substituted pyridines have been studied by a number of groups using several different methods. In 1951 Gero and Markham [371] found a linear relationship between the pK s of methyl pyridines and the number of methyl substituents. Abboud et al. [372] analyzed the gas-phase and aqueous acidities of a large number of substituted pyridines in terms of polarizability, field, and resonance contributions from the substituents. Chen and MacKerell [353] used AMI and MP2 calculations to examine substituent effects on pyridine pKj,s, concluding that the greatest shortcomings in the calculations stemmed from limitations of the solvent model. 

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