The Synthetic Routes of 3,6-Difluoro-2-pyridinecarbonitrile

3,6-Difluoro-2-pyridinecarbonitrile is an important intermediate in the synthesis of various pharmaceuticals, agrochemicals, and chemicals.
The demand for this compound has been increasing in recent years, and as a result, various synthetic routes have been developed to meet this demand.
In this article, we will discuss some of the synthetic routes that are commonly used to prepare 3,6-difluoro-2-pyridinecarbonitrile.

1. Direct Nitration of 2-Pyridinecarbonitrile
   The direct nitration of 2-pyridinecarbonitrile with nitric acid and sulfuric acid has been reported as a synthetic route to 3,6-difluoro-2-pyridinecarbonitrile.
   The reaction mixture is stirred at room temperature for several hours, and the resulting product is then purified by recrystallization.
   This method is relatively simple and cost-effective, but it can be dangerous due to the high risk of explosion associated with nitric acid.
   
2. Halogenation with N-Bromosuccinimide
   3,6-Difluoro-2-pyridinecarbonitrile can also be prepared by halogenating 2-pyridinecarbonitrile with N-bromosuccinimide (NBS) in the presence of a solvent such as dichloromethane.
   The reaction mixture is stirred at room temperature for several hours, and the resulting product is then purified by recrystallization.
   This method is generally more efficient and less dangerous than direct nitration, and it does not produce as much waste.
   
3. Reduction of Nitro Compound with Hydrazine
   3,6-Difluoro-2-pyridinecarbonitrile can also be synthesized by reducing a nitro compound with hydrazine.
   The nitro compound is first prepared by nitrating 2-pyridinecarbonitrile with nitric acid and sulfuric acid, and then the resulting nitro compound is reduced with hydrazine.
   This method is generally safer and more efficient than direct nitration, and it produces less waste.
   
4. From 2-Picoline
   2-Picoline can be converted into 3,6-difluoro-2-pyridinecarbonitrile through a sequence of reactions.
   The conversion of 2-picoline into 3,6-difluoro-2-pyridinecarbonitrile can be accomplished through various routes, including nitration, halogenation, and sulfonation.
   This synthetic route is generally more efficient and less costly than direct nitration, and it produces less waste.
   

In conclusion, there are several synthetic routes to 3,6-difluoro-2-pyridinecarbonitrile, including direct nitration, halogenation with N-bromosuccinimide, reduction of nitro compound with hydrazine, and conversion of 2-picoline.
Each of these routes has its advantages and disadvantages, and the choice of route depends on various factors, including the desired yield, cost, and safety.
Nonetheless, it is important to note that all these routes require careful handling of chemicals and should be carried out in well-ventilated areas with appropriate safety measures in place.