Study On Gas Phase Behavior Of Three Classes Of Heterocyclic Compounds In Electrospray Mass Spectrometry

Nitrogen-containing heterocycles are privileged structural units that are frequently found in natural products and pharmaceuticals.Accordingly,given the intriguing structures and diverse pharmaceutical properties,nitrogen heterocyclic compounds have attracted considerable interest from the chemists.Electrospray mass spectrometry is not only an important tool for structural characterization and identification of organic compounds,but also an important experimental method for studying the gas-phase reaction mechanism.Thus in this thesis,the gas-phase fragmentation behaviors of three types N-containing condensed heterocyclic compounds were investigated by ESI-MSⁿin combination with quantum calculation,and the fragmentation pathways were proposed.The main research contents are including these three parts:Firstly,2,4-substituted thieno[3,2-d]pyrimidines,with different L-amino acid methyl ester substituent on 4-C and methyl or methylthio substituent on 2-C,showed a complex and analytically valuable fragmentation behavior under positive ion electrospray ionization collision-induced dissociation??+?-ESI-CID?mass spectrometry.Protonated 2,4-substituted thieno[3,2-d]pyrimidines firstly lose a neutral fragment C₂H₄O₂?MS²?and the ion[M+H-60]⁺thus formed,then dissociates by losing of extended series of neutral molecule fragmentation from amino acid methyl ester substituent,in competition with the expulsion of CS or CH₃SH and other direct bond scissions.Moreover,losing of NH₃,CHN and CH₂NH from the precursor ions of[M+H-60]⁺were proposed to occur via rearrangements.The formation of diagnostic product ions and the series neutral eliminations provided information about the properties of substituents,assisting their characterization via MS/MS,high-resolution mass spectrometry and density functional theory?DFT?calculations.The proposed fragmentation patterns of these compounds give an insight into the understanding of gas-phase reactions in mass spectrometric studies of thieno[3,2-d]pyrimidine derivatives.Secondly,the complete fragmentation mechanisms of Imidazo[1,2-a]pyridine derivatives have been investigated under ESI and tandem mass spectrometry and identified by high-resolution mass spectrometry experiments.Studies have showed that tthere are three fragmentation pathways for the protonated ions[M+H]+of Imidazo[1,2-a]pyridine derivatives after collision induced dissociation:fragment ions with stable structure formed by loss of substituted benzene radical and phenoxyradical,and secondary fragments obtained by loss of neutral molecule CO through proton migration in the ring.Moreover,it is found that the effect of the substituents on the fragmentation process is not obvious.Finally,a series of benzo[4,5]imidazo[1,2-a]pyrimidin derivatives have been synthesised in order to broadening the scopes of our studing objects.Then the combination of HPLC-Triple quadrupole mass spectrometry and MSⁿhas been used to isolate and identify the positional isomers which are obstained in synthesis process.The results showed that the positional isomers have the same characteristic fragmentation pathways;moreover,the effectof the substituents on the fragmentation process is obvious.The benzo[4,5]imidazo[1,2-a]pyrimidin derivatives composed by para-substituted?-bromophenylethanone with 5-substituted2-aminobenzimidazole,revealedobviouslyeliminationsof cyclohexa-1,3-dien-5-ynecarbaldehyde and CO molecules in the initial fragentations.On the other hand,the benzo[4,5]imidazo[1,2-a]pyrimidin derivatives composed by meta-substituted?-bromophenylethanone with 5-substituted 2-aminobenzimidazole showed relatively complex fragment pattern.