Decarboxylation of some 2-substituted pyridinecarboxylic acids

Abstract

Previous investigations have dealt with the decarboxylation of 2-pyridinecarboxylic acids in various solvents.1-6We believed that 3-and 4-pyridinecarboxylic acids would not decarboxylate in 3-nitrotoluene at measureable rates since the rates of decarboxylation of these acids (266°, k = 6.0 X 10-6 sec-1, and 288°, k = 6.0 X 10-6 sec-1, respectively) in pyrene are so small.7 We felt that by placing electron-withdrawing and -attracting groups at the 2 position we might be able to lower the temperature at which decarboxylation takes place.

Investigations into an Intramolecular Proton Transfer and Solvent Dependent Acid‐Base Equilibria in 2,6‐Pyridine Diacetic Acid

“…Decarboxylation of pyridine acids in 3‐nitrotoluene, occurred above 423 K. . Another interesting case is the β‐keto acids, which decarboxylates spontaneously at lower temperatures in aqueous solution through a unimolecular pathway . For example, the monoanion of oxalacetic acid, decarboxylates spontaneously in nonpolar solvents at 303 K, while oxalo‐2‐propionic acid can decarboxylate at 305 ± 1 K with a metal or pyridoxamine catalyst …”

A convenient synthesis of [2,6‐14C]‐2‐chloroisonicotinic acid

“…A literature survey revealed no short syntheses useful for preparing material labeled with 14 C in the pyridine ring, and the more easily accessible 14 C-carboxyl-labeled material was not acceptable. Most literature preparations of 2-chloroisonicotinic acid have involved the conversion of isonicotinic acid or a derivative thereof to its N-oxide, followed by introduction of chlorine at the 2-position using POCl 3 or PCl 5 radiolabeled material, since [2][3][4][5][6][7][8][9][10][11][12][13][14] C]-isonicotinic acid can be prepared from 14 C-potassium cyanide via [2-14 C]picoline. 2 However, in our hands, the preparation of 14 C-labeled isonicotinic acid by this route has proved difficult and time-consuming.…”