[98-98-6] · C6H5NO2 · (MW 123)
(reagent used as a partner in the Mitsunobu reaction. The resulting esters can be hydrolyzed under mild conditions using Cu(OAc)2 in methanol. Used as a substrate in the Hammick reaction)
Physical Data: crystalline solid, mp 139-142 °C.
Solubility: soluble in water and alcoholic solvents. Partially soluble in polar organic solvents such as THF, ethyl acetate, chloroform, and dichloromethane. Not soluble in hexanes.
Form Supplied in: crystalline solid.
Purification: crystallized from water or benzene.1
Handling, Storage, and Precautions: no special instructions for storage and handling are mentioned in the literature. Use in a fume hood.
Picolinic acid has been used as a partner in the Mitsunobu reaction2,3 and offers the advantage that the resulting picolinate ester can be cleaved under very mild conditions. Recent advances in understanding the mechanism of the Mitsunobu reaction have led to the use of acids that are more acidic than benzoic acid as partners, and p-nitrobenzoic acid has emerged as the reagent of choice, especially for less reactive systems.4 Cleavage of the resulting p-nitrobenzoate ester is most commonly accomplished by alkaline hydrolysis, and for base-sensitive substrates this can be problematic. Picolinic acid exhibits comparable, and at times superior, reactivity to p-nitrobenzoic acid in the Mitsunobu reaction, and the resulting p-nitrobenzoate esters can be cleaved with copper acetate in methanol. Notable examples of the use of picolinic acid in the Mitsunobu reaction include the hindered alcohols 1 and 2, which proceed in 80 and 94% yields, respectively (eqs
Notable examples of the methanolysis of picolinate esters include substrates 4 and 5, which can be cleaved in 79% and 95% yields, respectively, using copper acetate in methanol (eqs
Picolinic acid has been used as a substrate in the Hammick reaction.7 The Hammick reaction consists of heating a 2-pyridyl, quinolyl or isoquinolyl carboxylic acid in the presence of an aldehyde. Decarboxylation of the heterocycle occurs and produces a nucleophilic species, which undergoes addition to the aldehyde and competitive protonation. The reaction was originally run in neat aldehyde. However, subsequent studies showed that p-cymene is an effective solvent and that near-stiochiometric quantities of aldehyde can be employed (eqs
A modification of the Hammick reaction has been reported that provides significantly higher yields.10 In this reaction, the trimethylsilyl ester is used in place of the free acid. This procedure minimizes protonation of the nucleophilic intermediate, and funnels the reaction pathway to the addition product (
University of Colorado, Boulder, CO, USA