The Synthetic Routes of 2,3-Diamino-5-trifluoromethylpyridine

2,3-Diamino-5-trifluoromethylpyridine, also known as DMF-Pyridine, is a key intermediate in the synthesis of several important pharmaceuticals, agrochemicals, and dyes.
This article will discuss some of the most common synthetic routes to DMF-Pyridine, which have been reported in the chemical literature over the years.

Route 1: Via 2-Chloro-3-nitroaniline and N-Boc-D-alanine

This route involves the synthesis of 2-chloro-3-nitroaniline from chloramine-T and aniline, followed by its condensation with N-Boc-D-alanine.
The resulting mixture of amides is then hydrolyzed using a basic catalyst, such as NaOH or KOH, to form the desired DMF-Pyridine.

Route 2: Via 2,5-Diamino-4-chloropyridine

This route involves the synthesis of 2,5-diamino-4-chloropyridine from 2-chloro-4-iodopyridine, which is treated with ammonia and hydrochloric acid to form the desired amine.
The amine is then reduced using a reducing agent, such as lithium aluminum hydride (LiAlH4), to form the DMF-Pyridine.

Route 3: Via 2-Chloro-3-nitroaniline and Pyridine-2-carboxaldehyde

This route involves the synthesis of 2-chloro-3-nitroaniline from chloramine-T and aniline, followed by its condensation with pyridine-2-carboxaldehyde.
The resulting mixture of amides is then hydrolyzed using a basic catalyst, such as NaOH or KOH, to form the desired DMF-Pyridine.

Route 4: Via Pyruvic Acid and 3-Fluorophenyl Acetate

This route involves the synthesis of pyruvic acid from either oxalic acid or benzene carboxylic acid, followed by its esterification with 3-fluorophenyl acetate.
The resulting ester is then treated with sodium hydroxide to form the desired DMF-Pyridine.

Route 5: Via N-(2-Chloro-3-nitrophenyl)acetamide

This route involves the synthesis of N-(2-chloro-3-nitrophenyl)acetamide from 2-chloro-3-nitroaniline and acetyl chloride, followed by its reduction using lithium aluminum hydride to form the desired DMF-Pyridine.

Overall, the synthesis of DMF-Pyridine involves several steps and requires the use of various reagents, such as chloramine-T, aniline, ammonia, hydrochloric acid, lithium aluminum hydride, oxalic acid, benzene carboxylic acid, 3-fluorophenyl acetate, and acetyl chloride.
The selection of a specific synthetic route depends on the availability and cost of the reagents, as well as the desired yield and purity of the product.