The Synthetic Routes of 5-AMINO-3-(TRIFLUOROMETHYL)PICOLINONITRILE

The synthesis of 5-amino-3-(trifluoromethyl)picolinonitrile, commonly referred to as TRFN, is an important chemical in the pharmaceutical and agrochemical industries.
TRFN has a wide range of applications, including as a herbicide, a wood preservative, and an intermediate in the production of pharmaceuticals.

There are several synthetic routes for TRFN, each with its own advantages and disadvantages.
The choice of route depends on the scale of production, the availability of starting materials, and the desired purity of the final product.

One of the most commonly used synthetic routes for TRFN is the P2P (Phenyl-2-propanone) route.
This route involves the nucleophilic substitution of the phenyl group of P2P with various nucleophiles, such as amines, thiols, and alcohols, to produce TRFN.
This route is relatively simple and can be scaled up to industrial levels, making it a popular choice for the production of TRFN.

Another synthetic route for TRFN is the N-Boc (N-tert-butoxycarbonyl) route.
This route involves the protection of the amino group of TRFN with a Boc group, followed by the reaction with various electrophiles, such as halides, sulfonates, and isocyanates, to introduce the trifluoromethyl group.
This route is relatively mild and can be used for the synthesis of substituted TRFNs, making it a popular choice in the pharmaceutical industry.

A third synthetic route for TRFN is the nitrile oxide route.
This route involves the reaction of 3-nitro-4-phenyl-5-propionoxy-picolinonitrile with sodium hydroxide to form TRFN.
This route is relatively simple and can be used to synthesize TRFN in high yields, making it a popular choice for large-scale production.

In recent years, there has been an increasing interest in the use of green chemistry in the synthesis of TRFN.
Green chemistry is an approach to chemistry that seeks to reduce or eliminate the use and generation of hazardous substances.
One of the most promising green synthetic routes for TRFN is the one using a transition metal catalyst.
This route involves the reaction of 3-aminopropionitrile and fluoride source in the presence of a transition metal catalyst to form TRFN.
This route is considered as green chemistry approach since it does not use any toxic reagents, and the transition metal catalyst can be recycled and reused.

In conclusion, there are several synthetic routes for TRFN, each with its own advantages and disadvantages.
The choice of route depends on the scale of production, the availability of starting materials, and the desired purity of the final product.
Phenyl-2-propanone, N-Boc, nitrile oxide and green chemistry approach are some of the commonly used methods for the synthesis of TRFN.
With the increasing interest in green chemistry, it is likely that more research will be done in the coming years to develop new, more sustainable synthetic routes for TRFN.