Error in Predicted Acidic pKa for Nicotinic Acid

The predicted pKa values for nicotinic acid do not match those given in the literature. Any ideas?





acid pKa - Marvin 3.77, literature 4.75





Compare this to the result for p-aminobenzoic acid





acid pKa - Marvin 4.77, literature 4.8

Dear Carl,





Ring nitrogen pKa of nicotinic acid given here:


Proc.Nat.Acad.Sci.


Vol. 70, No. 2, pp. 564-568, February 1973





Nicotinic acid pKa (ring nitrogen) = 4.90








I think the pKa of the COOH group of nicotinic acid is about 3.0;





Jozsi

Marvin Predicts Ring N pKa of 3. pKa of carboxy acid predicted 3.77





I found a reference for pKa = 4.75 (DEAN,JA (1985)), Which atom is ionized is not stated.





ring N has that large an effect on carboxy pKa? or carboxy has large effect on ring N pKa?








Benzoic acid has carboxy pKa of 4.2

Another reference confirms carboxy pKa of 4.8 for nicotinic acid.





What is causing Marvin to calculate 3.8?

Dear Carl,

Quote:

ring N has that large an effect on carboxyl pKa? or carboxyl has large effect on ring N pKa?

Both ionizable groups have effect on each other. Macro pKa of the aromatic 'N' and the carboxyl groups are related through 4 micro ionization steps.





The protonated ring 'N' has strong effect on the 'COOH' group,


and the deprotonated 'COO-'group has strong effect on the aromatic ring 'N'; "strong effect" to be understand relatively to the uncharged nicotinic acid.





The aromatic 'N' has a tendency to withdraw electrons from the aromatic ring; therefore, pKa of the 'COOH' should be decrease relatively to the benzoic acid pKa.

Quote:

What is causing Marvin to calculate 3.8?

One of the micro ionization constants was predicted purely. I fixed this problem recently.





I think our reference is correct:





pKa of the aromatic ring 'N' =4.9;





pKa of the ‘COOH’ group is ca. 3.0








Jozsi