2-氨基烟酸的合成

2-氨基烟酸(2-aminonicotinic acid),化学名2-氨基吡啶-3-羧酸,作为中间体在药物合成中有着广泛的应用[1-5].如Alexandros等[5]以2-氨基烟酸为原料合成抗菌、抗炎药物萘啶酮.因此,开发其简便、高效、操作安全的合成工艺,具有极其重要的意义.

Synthesis of 2-aminonicotinic acid

2-Aminonicotinic acid is an important synthetic intermediate of many drugs.A novel four-step synthesis method for preparing 2-aminonicotinic acid from quinoline is developed.The overall yield of 2-aminonicotinic acid is up to 29% based on quinoline.The oxidation of quinoline gives 2,3-pyridine dicarboxylic acid, and after intramolecular dehydration mediated by acetic anhydride, 2,3-pyridine dicarboxylic anhydride is obtained.Then, this anhydride is subjected to ammonolysis followed by Hofmann degradation reaction to introduce C(2）amino group,completing the synthesis of target molecule 2-aminonicotinic acid.NaClO₃-H₂SO₄-CuSO₄ is prominently superior to KMnO₄ as oxidant to quinoline, so that the yield is improved to 65.2%.The conditions of anhydride ammonolysis and Hofmann degradation were also optimized.The developed synthetic technologies are suitable for large-scale preparation, and the highlights include low cost and availability of starting material, safe operation, simple separation and purification, and high purity of final product.The target product with 98% HPLC purity is characterized by 1H NMR and IR.