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5-Formyl-2,4-dimethoxy-pyrimidine is an important intermediate in the synthesis of various pharmaceuticals, agrochemicals, and dyestuffs.
Its synthesis has been achieved by various chemical methods, but the most popular and widely used methods are the ones that have been developed in the chemical industry.
Synthetic Route 1: via Chlorination
The first synthetic route for 5-formyl-2,4-dimethoxy-pyrimidine involves its chlorination.
To synthesize 5-formyl-2,4-dimethoxy-pyrimidine via chlorination, 2,4-dimethoxy-pyrimidine is treated with chloroform and a sufficient amount of a chlorinating agent such as chlorine gas or hydrogen chloride.
The reaction is exothermic, and it is carried out under careful control to avoid excessive heating.
The reaction mixture is then treated with water, and the precipitated solid is collected by filtration and dried.
The product is then purified by recrystallization or chromatography to obtain pure 5-formyl-2,4-dimethoxy-pyrimidine.
Synthetic Route 2: via Reduction
Another synthetic route for 5-formyl-2,4-dimethoxy-pyrimidine is via reduction of the corresponding nitro compound.
To synthesize 5-formyl-2,4-dimethoxy-pyrimidine via reduction, 2,4-dimethoxy-5-nitro-pyrimidine is treated with a reducing agent such as lithium aluminum hydride (LAH) or hydrogen in the presence of a catalyst such as iodine or pyridine.
The reducing agent is added to the nitro compound in small portions while the reaction mixture is being stirred.
The reaction is exothermic, and it is carried out under careful control to avoid excessive heating.
The reaction mixture is then treated with water, and the precipitated solid is collected by filtration and dried.
The product is then purified by recrystallization or chromatography to obtain pure 5-formyl-2,4-dimethoxy-pyrimidine.
Synthetic Route 3: via Hydrolysis
5-Formyl-2,4-dimethoxy-pyrimidine can also be synthesized via hydrolysis of the corresponding nitrile.
To synthesize 5-formyl-2,4-dimethoxy-pyrimidine via hydrolysis, 2,4-dimethoxy-5-nitrile is treated with a strong base such as sodium hydroxide or potassium hydroxide.
The base is added to the nitrile in small portions while the reaction mixture is being stirred.
The reaction mixture is then treated with water, and the precipitated solid is collected by filtration and dried.
The product is then purified by recrystallization or chromatography to obtain pure 5-formyl-2,4-dimethoxy-pyrimidine.
Advantages of Synthetic Routes
The three synthetic routes outlined above for the synthesis of 5-formyl-2,4-dimethoxy-pyrimidine are widely used in the chemical industry and have several advantages over other methods.
The chlorination route is economical and easy to operate, as it uses readily available reagents and is well established in the industry.
The reduction route is more selective and mild than other reducing methods, and it produces less hazardous waste.
The hydrolysis route is also mild and can be used to prepare nitriles that are difficult to handle or unstable.
Conclusion
5-Formyl-2,4-dimethoxy-pyrimidine is an important intermediate in