Active Intermediates-involved Gas-phase Ionic Reactions In Atmospheric Pressure Ionization Mass Spectrometry

Atmospheric pressure ionization mass spectrometry(API-MS)is one of the most important tools in qualitative and quantitative analysis of organic compounds and gas-phase ion chemistry research.As one of the most fundamental scientific area,the study of gas-phase ion chemistry not only lays a theoretical foundation for the application of mass spectrometry in analytical chemistry,but also provides convincing technical support for studying organic reactive intermediates and exploring reaction mechanisms.In this dissertation,with the assistance of targeted substrate selection and design,the research efforts were put in two perspectives,namely unusual gas-phase reactions in ion source and unimolecular fragmentation reactions in tandem mass spectrometry,in which we focus on several reactive intermediate-involved gas phase ionic reactions.The specific content mainly includes the following four parts:1.Phenylnitrenium ion-involved gas phase amination reaction of aromatic hydrocarbons under atmospheric chemical ionizationTaking toluene as a model compound,the gas phase amination reaction of aromatics under corona discharge with the N2 as the nitrogen source was investigated.During the atmospheric chemical ionization mass spectrometric analysis of toluene,unusual product ions,[M+16]+ and[M+14]+ were observed.Taking the high resolution mass spectrometric data and tandem mass spectrometric information into account,[M+16]+was confirmed to be protonated p-toluidine and[M+14]+ was confirmed to be p-methylphenylnitrenium.According to the experimental results of isotopic labelling and substituent effect,the mechanism was proposed as follows:firstly,N2 was activated by corona discharge and electrophilically attacked toluene,yielding the key intermediate,p-methylphenylnitrenium;secondly,the intermediate underwent double-hydrogen transfer reaction with the environmental protonic molecules to give rise to the final product ion,protonated p-toluidine.The proposed mechanism was verified by theoretical calculation,ion-molecule reaction and etc.2.Gas-phase Williamson ether synthesis-like reaction under atmospheric chemical ionizationTaking trifluorotoluene and methanol as model compounds,the gas phase Williamson-like reactions between benzyl halides and alcohol/phenols under corona discharge were investigated.During the atmospheric chemical ionization mass spectrometric analysis of trifluorotoluene-methanol solution,reactions in which fluorine(s)was(were)mono-or di-substituted by the methoxyl group(s)were observed,yielding PhC+F(OCH3)or PhC+(OCH3)2 respectively.According to the experimental results of isotopic labelling and substrates altering,a Williamson reaction-like mechanism was proposed:firstly,the reaction was triggered by the fluorine dissociation under corona discharge,generating a key intermediate,benzyl cation;secondly,the methanol oxygen nucleophilically attacked carbocation center,accompanied by the neutral loss of HF,yielding mono-or di-substituted product ions.The proposed mechanism was further verified by theoretical calculation.The results of substrate expansion experiments indicated that this in-source reaction has potential application in distinguishing primary alcohol and ortho-diphenol hydroxyl-like structures.3.Benzyl cation-involved electrophilic substitution reaction in the fragmentation of protonated N-benzylbenzaldimine analoguesTaking N-benzyl-1-p-methoxybenzimide and N-benzyl-l-m-methoxybenzimide as model compounds,the electrophilic substitution reaction of benzyl cation in the fragmentation of their protonated molecules was investigated.During the tandem mass spectrometric analysis of these two protonated compounds,it was found that both of them could generate a key intermediate,benzyl cation,which would act as an electrophile to undergo intra-complex electrophilic substitution reaction mediated by ion-neutral complex.Specifically,in the fragmentation of protonated N-benzyl-1-p-methoxybenzimide,benzyl cation electrophilically attacked the para-position,causing stepwise neutral losses of HCN and benzene,yielding product ion,p-methoxylbenzyl cation;in the fragmentation of protonated N-benzyl-1-m-methoxybenzimide,benzyl cation electrophilically attacked the ortho-or para-position,causing a cyclodeamination reaction to generate a tricyclic product.The mechanism was further verified by the theoretical calculation,substituent effect and etc.4.Benzyl anion-involved nucleophilic substitution reaction in the fragmentation of deprotonated N-(phenylsulfonyl)-benzeneacetamidesTaking N-(phenylsulfonyl)-benzeneacetamide as a model compound,the nucleophilic substitution reaction of benzyl anion during the unimolecular dissociation process was investigated.Under collision-induced dissociation,deprotonated N-(phenylsulfonyl)-benzeneacetamide underwent a charge-induced hetero-cleavage of the CH2-CO bond,resulting in an ion-neutral complex([C6H5CH2-/C6H5SO2NCO]).Subsequently,benzyl anion nucleophilically attacked ortho-position benzenesulfonyl isocyanate,accompanied by the elimination of HNCO,yielding a final product ion,2-benzylbenzene sulfinate ion.The proposed mechanism was further verified by the theoretical calculation,breakdown curve,substituent effect and etc.In addition,the ionization principles of API,collision-induced dissociation and theoretical calculation were briefly introduced.The researches on unusual in-source reaction,ion-neutral complex-mediated unimolecular fragmentation reaction and gas-phase reactive intermediate preparation were mainly reviewed.