Picolinic acids, substituent effects

For coupling with 2-naphthol-6,8-disulphonic-l-isotope effects (kK/kD) varied with the substituent in the benzenediazonium ion as follows 4-C1 (6.55) 3-C1 (5.48) 4-N02 (4.78), i.e. the reactivity of the ion was increased so that i correspondingly decreased. Base catalysis was observed127, 129, and there was a free energy relationship between this catalytic effect and the basicity of pyridine, 3- and 4-picoline. However, for 2-picoline and 2,6-lutidine, the catalysis was 3 times and 10 times less than expected from their basicities showing that, in this particular proton transfer, steric hindrance is important. 

The situation is simplified if the substituent is at a para position to the reaction site since in this case there are no conditions for realizing the indirect resonance effect. The substituent and the reaction site cannot be simultaneously directly conjugated with the nitrogen heteroatom of the azine ring and, as a rule, the reactivity parameters correlate well with the Hammett ffp values. Examples include (1) the ionization constants of 5-substituted picolinic (57) and 6-substituted nicotinic acids (59) (59NKZ1293) (2) the rates of alkaline hydrolysis of 5-substituted methyl picolinates (58) (70JCS(B) 1063) ... 

Polar effects, arising from inductive and resonance influences of substituents, are considered to affect A H but not A S, Examples of this are the picolines and toluic acids. 

---