Study on synthesis of 4-Aminonicotinic acid

IR > 石油化工学院

	Study on synthesis of 4-Aminonicotinic acid
	Su, Ce; He, Jun-Hua
	2010-10-01
发表期刊	Gao Xiao Hua Xue Gong Cheng Xue Bao/Journal of Chemical Engineering of Chinese Universities
ISSN	10039015
卷号	24 期号:5 页码:907-910
摘要	4-Aminonicotinic acid is one of the key synthetic intermediates of therapeutic drugs for cardiovascular and cerebrovascular diseases. Here, a novel four-step synthesizing route of 4-aminonicotinic acid starting from isoquinoline was proposed, and its overall yield of 4-aminonicotinic acid can be up to 30% (based on isoquinoline). During the preparation, the oxidation of isoquinoline gives 3, 4-pyridine dicarboxylic acid, and after its intramolecular dehydration by acetic anhydride, the 3, 4-pyridine dicarboxylic anhydride is formed. Then this anhydride is subjected to ammonolysis followed by Hofmann rearrangement reaction to introduce the C(4) amino group into the resulted nicotinic acid, and which leads to form the target product 4-aminonicotinic acid. The target product possessing 98% HPLC purity was characterized by 1H-NMR and IR. Based on comparative experiments, it was found that, as oxidant used in the isoquinoline oxidation process, HNO3-H2SO4 is prominently superior to KMnO4; and using HNO3-H2SO4, the yield can be improved up to 61%. The reaction conditions for anhydride ammonolysis and Hofmann rearrangement were optimized. The proposed synthetic technologies are suitable for large scale production, and their highlights include low cost and easy availability of starting material, safe operation, simple separation and purification, needless of chromatography operation and high purity of final product.
关键词	Manganese compounds Potash Purification Synthesis (chemical) Cerebrovascular disease Comparative experiments Hofmann rearrangementne Intramolecular dehydration Isoquinolines Large scale productions Separation and purification Synthetic intermediates
收录类别	EI
语种	中文
出版者	Zhejiang University
EI入藏号	20104813436381
EI主题词	Chromatography
EI分类号	802.2 Chemical Reactions - 804.2 Inorganic Compounds
来源库	Compendex
分类代码	802.2 Chemical Reactions - 804.2 Inorganic Compounds
文献类型	期刊论文
条目标识符	https://ir.lut.edu.cn/handle/2XXMBERH/111133
专题	石油化工学院
作者单位	School of Petrochemical Engineering, Lanzhou University of Technology, Lanzhou 730050, China
第一作者单位	兰州理工大学
第一作者的第一单位	兰州理工大学
推荐引用方式 GB/T 7714	Su, Ce,He, Jun-Hua. Study on synthesis of 4-Aminonicotinic acid[J]. Gao Xiao Hua Xue Gong Cheng Xue Bao/Journal of Chemical Engineering of Chinese Universities,2010,24(5):907-910.
APA	Su, Ce,&He, Jun-Hua.(2010).Study on synthesis of 4-Aminonicotinic acid.Gao Xiao Hua Xue Gong Cheng Xue Bao/Journal of Chemical Engineering of Chinese Universities,24(5),907-910.
MLA	Su, Ce,et al."Study on synthesis of 4-Aminonicotinic acid".Gao Xiao Hua Xue Gong Cheng Xue Bao/Journal of Chemical Engineering of Chinese Universities 24.5(2010):907-910.