The Synthetic Routes of 4-Hydroxy-7-methoxy-3-quinolinecarboxylic acid

4-Hydroxy-7-methoxy-3-quinolinecarboxylic acid, also known as HML-213, is a synthetic compound commonly used in the pharmaceutical and agrochemical industries.
It is a white to off-white solid that is soluble in water and has a molecular formula of C14H12N2O3.

There are several synthetic routes to 4-hydroxy-7-methoxy-3-quinolinecarboxylic acid, each with its own advantages and disadvantages.
The choice of synthetic route depends on factors such as the availability of starting materials, the desired yield and purity of the final product, and the cost of the process.

One of the most common synthetic routes to HML-213 is through the Schmidt reaction.
This involves the condensation of 7-methoxy-3-quinolinecarboxylic acid with formaldehyde and sodium hydroxide in the presence of a solvent such as dimethylformamide (DMF).
The reaction proceeds through an intermediate aldol condensation product, which is then reduced with lithium aluminum hydride (LAH) to produce 4-hydroxy-7-methoxy-3-quinolinecarboxylic acid.

Another synthetic route to HML-213 is through the Grignard reaction.
This involves the synthesis of a Grignard reagent, which is then treated with a base such as sodium hydroxide to form the quinolinecarboxylic acid.
The Grignard reagent is typically prepared by the reaction of magnesium metal with a halogenated alkane, such as bromobutane.

A third synthetic route to HML-213 is through the Orellana-Williams reaction.
This involves the condensation of 3-chloro-7-methoxyquinoline with dimethyl acetaldehyde in the presence of a base such as sodium hydroxide.
The reaction product is then reduced with lithium aluminum hydride to produce the final product.

Each of these synthetic routes has its own advantages and disadvantages.
The Schmidt reaction, for example, involves the use of hazardous reagents such as sodium hydroxide and LAH, and requires careful handling to avoid injury or harm to the environment.
The Grignard reaction, on the other hand, can be more user-friendly and does not require the use of hazardous reagents.
However, it does require the synthesis of a Grignard reagent, which can be time-consuming and costly.

The Orellana-Williams reaction, meanwhile, involves the use of methylene chloride, which is a volatile organic solvent and can present environmental and safety concerns.
Additionally, the reaction requires the use of lithium aluminum hydride, which is a hazardous reagent.

Overall, the choice of synthetic route to HML-213 will depend on a variety of factors, including the availability of starting materials, the desired yield and purity of the final product, and the cost and safety of the process.