The Synthetic Routes of 2-(Trifluoromethyl)isonicotinic acid

2-(Trifluoromethyl)isonicotinic acid is an important organic compound that is widely used in various chemical reactions and synthesis methods.
This article aims to provide an overview of the synthetic routes of 2-(Trifluoromethyl)isonicotinic acid.

Method 1: via 2-(Trifluoromethyl)benzaldehyde

The first synthetic route to 2-(Trifluoromethyl)isonicotinic acid is via 2-(Trifluoromethyl)benzaldehyde.
The synthesis of 2-(Trifluoromethyl)benzaldehyde involves the reaction of 2,3-dimethyl-2-oxo-1,3-oxazolidin-3-one with 3-fluoro-2-butanonitrile in the presence of a Lewis acid catalyst such as zinc chloride.
The reaction involves the nucleophilic substitution of the nitrile group in 3-fluoro-2-butanonitrile with the carbonyl group in the oxazolidinone.
The resulting 2-(Trifluoromethyl)benzaldehyde is then converted to 2-(Trifluoromethyl)isonicotinic acid via a condensation reaction with 2-methyl-2-butenoic acid.

Method 2: via 2-(Trifluoromethyl)-4,4,5,5-tetramethylimidazoline-1,3-diium

Another synthetic route to 2-(Trifluoromethyl)isonicotinic acid is via 2-(Trifluoromethyl)-4,4,5,5-tetramethylimidazoline-1,3-diium.
The synthesis of 2-(Trifluoromethyl)-4,4,5,5-tetramethylimidazoline-1,3-diium involves the reaction of 2,3-dimethyl-2-oxo-1,3-oxazolidin-3-one with 4,4,5,5-tetramethylimidazoline-1,3-diium in the presence of a Lewis acid catalyst such as zinc chloride.
The reaction involves the nucleophilic substitution of the imidazoline group in 4,4,5,5-tetramethylimidazoline-1,3-diium with the carbonyl group in the oxazolidinone.
The resulting 2-(Trifluoromethyl)-4,4,5,5-tetramethylimidazoline-1,3-diium is then converted to 2-(Trifluoromethyl)isonicotinic acid via a condensation reaction with 2-methyl-2-butenoic acid.

Method 3: via 2-(Bromomethyl)isonicotinic acid

A third synthetic route to 2-(Trifluoromethyl)isonicotinic acid is via 2-(Bromomethyl)isonicotinic acid.
The synthesis of 2-(Bromomethyl)isonicotinic acid involves the reaction of 2-methyl-2-butenoic acid with 2-bromomethyl-4,4,5,5-tetramethylimidazoline-1,3-diium in the presence of a Lewis acid catalyst such as zinc chloride.
The reaction involves the nucleophilic substitution of the imidazoline group in 2-bromomethyl-4,4,5,5-tetramethylimidazoline-1,3-diium with the carbonyl group in 2-methyl-2-