The Synthetic Routes of 6-Methyl-3-oxo-2,3-dihydropyridazine-4-carboxylic acid

6-Methyl-3-oxo-2,3-dihydropyridazine-4-carboxylic acid is an important intermediate in the production of various pharmaceuticals and agrochemicals.
It is also used as a building block for the synthesis of other chemicals.
The synthetic routes for 6-methyl-3-oxo-2,3-dihydropyridazine-4-carboxylic acid can be broadly classified into two categories: synthesis via oxidation of methyloxirane and synthesis via decarboxylation of 6-methyl-2,3-dihydro-1H-pyridazine-4-carboxylic acid.

Synthesis via oxidation of methyloxirane:
Methyloxirane is an attractive starting material for the synthesis of 6-methyl-3-oxo-2,3-dihydropyridazine-4-carboxylic acid because it is easily accessible and can be prepared in high yield from methyl iodide and hydrogen peroxide.
The synthesis of 6-methyl-3-oxo-2,3-dihydropyridazine-4-carboxylic acid via oxidation of methyloxirane involves several steps, including the oxidation of methyloxirane to form a carbocation intermediate, followed by nucleophilic attack by a carboxylate anion to form the final product.

One of the most commonly used methods for the synthesis of 6-methyl-3-oxo-2,3-dihydropyridazine-4-carboxylic acid via oxidation of methyloxirane involves the use of sodium hydroxide and sodium hypochlorite.
The reaction proceeds in three steps:

1. Oxidation of methyloxirane to form a carbocation intermediate: This step is typically carried out in the presence of an acid catalyst, such as sulfuric acid or phosphoric acid.
   The carbocation intermediate is then stabilized by base, such as sodium hydroxide, which is added to the reaction mixture.
   
2. Nucleophilic attack by a carboxylate anion: The carbocation intermediate is then attacked by a carboxylate anion, such as 6-methyl-2,3-dihydro-1H-pyridazine-4-carboxylate, which is generated in situ by the reaction of phosphorus oxychloride with sodium hydroxide.
   
3. Decarboxylation to form 6-methyl-3-oxo-2,3-dihydropyridazine-4-carboxylic acid: The final step involves the removal of the carboxyl group from the product of step 2 to form 6-methyl-3-oxo-2,3-dihydropyridazine-4-carboxylic acid.
   This step is typically carried out in the presence of an acid catalyst, such as hydrochloric acid or sulfuric acid.
   

Synthesis via decarboxylation of 6-methyl-2,3-dihydro-1H-pyridazine-4-carboxylic acid:
Another route to 6-methyl-3-oxo-2,3-dihydropyridazine-4-carboxylic acid involves the decarboxylation of 6-methyl-2,3-dihydro-1H-pyridazine-4-carboxylic acid.
This intermediate can be prepared from 2,3-dihydro-1H-pyridazine-4-carboxylic acid and methyl iodide in the presence of an acid catalyst, such as sulfuric acid or phosphoric acid.