The Synthetic Routes of ethyl6-chloro-3-hydroxypyridazine-4-carboxylate

Ethyl 6-chloro-3-hydroxypyridazine-4-carboxylate is an organic compound that is commonly used as an intermediate in the synthesis of various chemicals, pharmaceuticals, and agrochemicals.
The compound is a yellow or light brown solid that is soluble in various organic solvents.
It is commonly synthesized using several different methods, each of which has its own advantages and disadvantages.

One of the most commonly used synthetic routes for ethyl 6-chloro-3-hydroxypyridazine-4-carboxylate is the route that involves the reaction of 6-chloro-3-hydroxypyridazine-4-carboxaldehyde with a Grignard reagent.
This route involves the following steps:

1. Preparation of 6-chloro-3-hydroxypyridazine-4-carboxaldehyde: This compound is synthesized by treating 3-hydroxypyridazine-4-sulfonic acid with a chlorinating agent, such as chloroform or carbon tetrachloride.
   
2. Preparation of the Grignard reagent: A Grignard reagent, such as magnesium metal or a derivative of magnesium metal, is prepared by treating magnesium with a halogen, such as iodine or bromine.
   
3. Reaction of the Grignard reagent with 6-chloro-3-hydroxypyridazine-4-carboxaldehyde: The Grignard reagent is added to a solution of 6-chloro-3-hydroxypyridazine-4-carboxaldehyde in a suitable solvent, such as ether or a polar solvent like acetonitrile.
   The reaction is typically carried out at room temperature and is accompanied by the evolution of hydrogen chloride gas.
   
4. Hydrolysis of the intermediateethyl 6-chloro-3-hydroxypyridazine-4-carboxylate: The intermediate is treated with water to hydrolyze the carboxylate group and produce ethyl 6-chloro-3-hydroxypyridazine-4-carboxylate.
   

Another commonly used synthetic route for ethyl 6-chloro-3-hydroxypyridazine-4-carboxylate is the route that involves the reaction of 3-chloro-5,6-dihydro-2H-pyridazine-2-carboxylic acid with a suitable derivative of ethyl benzene.
This route involves the following steps:

1. Preparation of 3-chloro-5,6-dihydro-2H-pyridazine-2-carboxylic acid: This compound is synthesized by treating 2H-pyridazine-2-sulfonic acid with a chlorinating agent, such as chloroform or carbon tetrachloride.
   
2. Preparation of the ethyl benzene derivative: A suitable derivative of ethyl benzene, such as ethyl chloride or ethyl bromide, is prepared by treating ethyl benzene with a halogen in the presence of a Lewis acid catalyst, such as aluminum chloride.
   
3. Reaction of the ethyl benzene derivative with 3-chloro-5,6-dihydro-2H-pyridazine-2-carboxylic acid: The ethyl benzene derivative is added to a solution of 3-chloro-5,6-dihydro-2H-pyridazine-2-carboxylic acid in a suitable solvent, such as acetonitrile or an ether.
   The reaction is typically carried out at an elevated temperature,