Investigating The Reaction Mechanisms Of Oxidation Deoximation, Synthesis Of Isoquinolinone And Isoindolinone By Esi-MS~N And DFT Theory

The study on the reaction mechanism would provide a theoretical basis for the reaction. In order to control the reaction rate and improve the reaction yield, it is necessary to understand the process of reaction. The scientists have committed to investigating the reaction mechanism by mass spectrometry.Probing into the reactive intermediates in chemical reactions could afford a direct and accurate evidence for tracking the process of reaction and deducing the reaction mechanisms. In this thesis, the synthesis of isoquinolinone reaction, the oxidation deoximation reaction and the synthesis of isoindolinone reaction were explored by electrospray ionization tandem mass spectrometry (ESI-MSn). We successfully captured the reactive intermediates of the three reactions. Combined with high resolution mass spectrum (HRMS) and NMR, the structures of intermediates were educed. Furthermore, their possible reaction mechanisms were proposed. 1. A method based high performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-QTOFMS/MS) was successfully developed for studying the mechanism of the strong base-promoted synthesis of isoquinolinone. The structure of intermediate was proposed using ESI-MS/MS. Furthermore, theoretical calculations were carried out to confirm the reaction mechanism by density functional theory (DFT) method at B3LYP/6-31G (d) level of theory in the Gaussian03program.2. A method based ESI-MS was successfully developed to study the reaction mechanism of FeCl3/TEMPO-catalyzed oxidation deoximation. HRMS was taken to educe the elements of the intermediates and identify the structures of the intermediates. Furthermore, theoretical calculations were carried out to validate the reaction mechanism by density functional theory (DFT) method at B3LYP/6-31++G(d,p) level of theory in the Gaussian03program.3. A method based high performance liquid chromatography coupled to electrospray ionization time-of-flight mass spectrometry (HPLC-ESI-TOFMS) was successfully developed for study the reaction mechanism of the Pd2(dba)3·CHCl3/xantphos-catalyzed synthesis of isoindolinone by monitoring the process of the reaction and capturing the reactive intermediates. Furthermore, the key intermediate was papared by chromatography on silica gel and the structure was identified by NMR. In addition, the experimental results indicate that this reaction was a controllable step-by-step reaction.