The Synthetic Routes of 6-Chloro-5-hydroxy-nicotinic acid methyl ester

6-Chloro-5-hydroxy-nicotinic acid methyl ester is an important intermediate in the synthesis of several pharmaceuticals and agrochemicals.
Its synthesis has been extensively researched in the chemical industry, and several synthetic routes have been developed to produce this compound.
In this article, we will discuss some of the most commonly used synthetic routes for the production of 6-chloro-5-hydroxy-nicotinic acid methyl ester.

Route 1: via Hydrolysis of N-Methyl-5-chloro-2-(methylthio)benzamide

One of the most common synthetic routes for the production of 6-chloro-5-hydroxy-nicotinic acid methyl ester involves the hydrolysis of N-methyl-5-chloro-2-(methylthio)benzamide.
The reaction begins by treating 2-methylthio-5-chloro-N-methylbenzamide with a strong base such as sodium hydroxide in the presence of water.
The resulting compound is then treated with a mineral acid such as hydrochloric acid to produce 6-chloro-5-hydroxy-nicotinic acid methyl ester.

Route 2: via Reduction of N-Methyl-5-chloro-2-(methylthio)benzamide with Hydrogen in the Presence of Catalysts

Another common synthetic route for the production of 6-chloro-5-hydroxy-nicotinic acid methyl ester involves the reduction of N-methyl-5-chloro-2-(methylthio)benzamide with hydrogen in the presence of catalysts such as palladium on barium oxide.
The reaction is typically carried out under high pressure and temperature conditions to ensure maximum conversion.

Route 3: via Decarboxylation of N-Methyl-5-chloro-2-(methylthio)benzeneacetamide

A third synthetic route for the production of 6-chloro-5-hydroxy-nicotinic acid methyl ester involves the decarboxylation of N-methyl-5-chloro-2-(methylthio)benzeneacetamide.
The reaction is typically carried out by heating the compound in the presence of a weak acid such as acetic acid.
The resulting compound is then treated with a mineral acid such as hydrochloric acid to produce 6-chloro-5-hydroxy-nicotinic acid methyl ester.

Route 4: via Nitration of Methyl-5-chloro-2-(methylthio)benzamide

Another route for the production of 6-chloro-5-hydroxy-nicotinic acid methyl ester involves the nitration of methyl-5-chloro-2-(methylthio)benzamide.
The reaction is typically carried out by treating the compound with nitric acid under conditions suitable for the formation of the desired nitrate ester.
The resulting nitrate ester can then be converted to 6-chloro-5-hydroxy-nicotinic acid methyl ester by treating it with a mineral acid such as hydrochloric acid.

Route 5: via Halogenation of Methyl-5-chloro-2-(methylthio)benzamide

Another synthetic route for the production of 6-chloro-5-hydroxy-nicotinic acid methyl ester involves the halogenation of methyl-5-chloro-2-(methylthio)benzamide.
The reaction is typically carried out by treating the compound with a halogenating agent such as chloroform in the presence of a Lewis acid catalyst such as aluminum chloride.
The resulting comp