Preparation of 4-aminopyridine-3-carboxylic acid_industrial additives

Preparation background and overview of 4-aminopyridine-3-carboxylic acid

4-Aminopyridine-3-carboxylic acid (4-Aminopyridine-3-carboxylic acid) is widely used as an intermediate in drug synthesis. For example, 4-aminopyridine-3-carboxylic acid is used as raw material to synthesize the antibacterial and anti-inflammatory drug nalidinone. Therefore, it is of extremely important significance to develop a simple, efficient and safe synthesis process. The current synthesis route is to use 3-nitrilepyridine or 3-phthalaminepyridine or nicotinic acid as raw materials, activate the pyridine ring through nitrogen oxidation, chlorine at the 4-position of the pyridine ring, and finally obtain 4-aminopyridine-3 through hydroxylamination. -carboxylic acid. The method of synthesizing 4-aminopyridine-3-carboxylic acid using pyridine N-oxide as an intermediate has the disadvantages of expensive raw materials, difficult chlorination operations, and low yield. Taking nicotinic acid as an example, the total yield of synthesis is only 2.5% calcium carbonate. Therefore, there is an urgent need to develop a synthetic process with cheap and easily available raw materials, safe operation, and suitable for large-scale preparation, which can simplify product separation and purification and increase product yield.

4-Aminopyridine-3-carboxylic acid

Preparation and application of 4-aminopyridine-3-carboxylic acid

4-Aminopyridine-3-carboxylic acid is a nitrogen heterocyclic nitrogen coordination chelating agent. The nitrogen atom on the pyridine ring has a strong coordination function and can form stable complexes with metal ions. It is suitable for It is used to selectively separate and recover heavy metal ions in solutions, and has wide application value in analytical chemistry, environmental protection, hydrometallurgy, etc.

Preparation of 4-aminopyridine-3-carboxylic acid

Step 1. Add the catalyst S-SnO/MWCNTs, 3,4-pyridinedicarboxylic acid, and acetic anhydride into the reaction bottle, heat and react for 4 hours, then concentrate under reduced pressure, and dry the residue to obtain yellow mixed powder A;

Step 2. Add the above yellow mixed powder A and ammonia water with a concentration of 28% into a round-bottomed flask with a condensation device, heat to 50°C and stir for 3 hours; neodymium carbonate

Step 3. After the reaction is completed, cool down, adjust the pH with hydrochloric acid, if solid precipitates, filter, wash the filter cake with distilled water until the filtrate is colorless, and dry in vacuum to obtain 4-amidopyridine-3-carboxylic acid;

Step 4. Add 5mol·L sodium hydroxide solution to the flask, add bromine dropwise at 5℃, stir for 0.5h, add 4-amidopyridine-3-carboxylic acid, raise the temperature to 85℃ and react for 2h;

Step 5. After the reaction is completed, part of the solvent is concentrated under reduced pressure, cooled, adjusted to pH=7 with hydrochloric acid, filtered with suction, dried the filter cake, and recrystallized with distilled water to obtain 4-aminopyridine-3-carboxylic acid as a light yellow solid.