Real-time, On-line Monitoring Of Paal–knorr Reactions Using Mass Spectrometry

Pyrroles and their derivatives are very important heterocyclic compounds having different biological activities, which are widely used in medicine, food, pesticide, daily chemicals, paper, photosensitive materials, polymer materials and so on. Many methods for the synthesis of substituted pyrroles have been described in the literature, but the Paal-Knorr reaction remains one of the most attractive methods for the synthesis of pyrroles. The EESI-MS in situ monitoring can capture the molecular ion peak of reactants, intermediates and products in the process of organic reactions to implement the research of reaction mechanism. In this paper, the catalytic mechanism of the different Catalyst were investigated by using the extractive electrospray ionization mass spectrometry, And then we find new catalyst through the research of catalytic mechanism.This paper mainly consists of five parts:The first part: Literature review. The review covers the latest results on real-time, on-line monitoring of organic chemical reactions using mass spectrometry.The second part: Real-time, on-line monitoring of acetic-acid-catalyzed Paal-Knorr reaction process using extractive electrospray ionization mass spectrometry was studied in this section. Primarily the experimental device was put up, then the reaction conditions were optimized. The changing of reactants, intermediates, and products with time were described and analyzed respectively due to getting the reaction mechanism. The change of the reaction products with time were studied under the conditions of acetic acid as the catalyst, and realizing the organic reaction process regulation, creating the method of organic mechanism and controlling the process of organic reaction using EESI-MS.The third part: The mechanism of TCCA-catalyzed synthesis of pyrroles and its derivatives under solvent-free condition or solvent-acetonitrile condition was studied in this part. The changing of molecular ion peak about reactants, intermediates, and products with time were captured, CID described and analyzed respectively due to getting the TCCA-catalyzed reaction mechanism.The fourth part: The contrast of catalytic process and its mechanism with Organic acid and inorganic acid catalyst was studied in this section. The changing of reactants, intermediates, and products with time were described and analyze, respectively due to getting the reaction mechanism. The change of the reaction products with time were studied under the conditions of acetic acid, amino sulfonic acid, Zr OCl₂?8H₂O, TCCA as the catalyst, and realizing the organic reaction process regulation under different conditions, creating the method of organic mechanism and controlling the process of organic reaction using EESI-MS.The fifth part: L-cysteine-catalyzed synthesis of pyrroles and its derivatives under solvent-free condition. A novel methodology for the synthesis of pyrroles and its derivatives by the reaction of primary amine and 2, 5-hexanedione under solvent-free condition has been developed, and the influences of the reaction media, amino acids, temperature, and the structure of substrate were investigated. L-cysteine showed excellent catalytic activity for a series of substrates and lead to the formation of 11 pyrroles and its derivatives in 65%-97% yields.In this paper, the catalytic mechanism of the catalysts such as amino acids, TCCA and so on was investigated by using the extractive electrospray ionization mass spectrometry for Paal-Knorr, and then find the new green L-cysteine amino acid catalyst. The changing full presented of reactants, intermediates, and products with time were described and analyzed respectively due to getting the reaction mechanism and then guiding the organic synthesis, and it is beneficial for promoting the development of mechanism research and the methodology in organic synthesis.