The Synthetic Routes of ISOQUINOLINE-5-CARBOXYLIC ACID

The synthesis of ISOQUINOLINE-5-CARBOXYLIC ACID, a valuable intermediate in the pharmaceutical and agrochemical industries, has been the subject of extensive research over the past few decades.
There are various methods for its synthesis, each with its own advantages and disadvantages.
In this article, we will discuss some of the most commonly used synthetic routes for ISOQUINOLINE-5-CARBOXYLIC ACID.

1. The classical approach to synthesizing ISOQUINOLINE-5-CARBOXYLIC ACID involves the condensation of 2-methylquinoline-5-sulfonic acid with chloroacetic acid followed by reduction of the resulting 5-chloro-2-methylquinolin-4-one with lithium aluminum hydride.
   However, this method involves several steps, requires the handling of hazardous reagents, and is not very efficient.
   
2. Another route involves the reaction of para-toluenesulfonic acid with N-methyl-D-glucamine, followed by treatment with hydrochloric acid and sodium nitrite.
   This method has the advantage of using less hazardous reagents, but it is still relatively complex and suffers from low yield.
   
3. A recent method for the synthesis of ISOQUINOLINE-5-CARBOXYLIC ACID uses a tandem reaction involving the reaction of para-fluoroacetophenone with azide, followed by conversion of the resulting azide into 5-azido-2-methylquinoline using hydraziine.
   Finally, the azide is reduced to the carboxylic acid using lithium aluminum hydride.
   This method involves fewer steps than the classical approach and is more efficient, with a higher yield.
   
4. Another efficientsynthetic route for ISOQUINOLINE-5-CARBOXYLIC ACID employs the use of a redox catalyst such as iron powder or cobalt chloride to catalyze the reaction of 2-methylquinoline-5-sulfonic acid with chloroacetic acid.
   This method offers good yield and is relatively simple and safe to perform.
   
5. A newer route for the synthesis of ISOQUINOLINE-5-CARBOXYLIC ACID involves the use of a microwave-assisted reaction.
   In this method, 2-methylquinoline-5-sulfonic acid and chloroacetic acid are reacted in the presence of a polar solvent such as acetonitrile or DMF using microwave irradiation.
   This method offers several advantages, including high yield, short reaction time, and easy work-up.
   

In conclusion, there are various methods for the synthesis of ISOQUINOLINE-5-CARBOXYLIC ACID, each with its own advantages and disadvantages.
The choice of method depends on factors such as the availability and cost of reagents, the scale of synthesis, and the desired yield.
As more research is conducted in this area, it is likely that new and more efficient methods will be developed for the synthesis of this important intermediate.