基于电喷雾-离子淌度质谱技术检测铃木-宫浦的反应中间体  

Detection of Reaction Intermediates in Suzuki-Miyaura by Electrospray Ionization Ion Mobility Mass Spectrometry

作　　者：李哲 邱朝辉 王伟民 徐福兴 丁传凡 LI Zhe;QIU Chao-hui;WANG Wei-min;XU Fu-xing;DING Chuan-fan(School of Materials Science and Chemical Engineering,Ningbo University,Ningbo 315211,China;Zhejiang Provincial Key Laboratory of Advanced Mass Spectrometry Technology and Molecular Detection,Institute of Mass Spectrometry Technology and Application,Ningbo 315211,China)

机构地区：[1]宁波大学材料科学与化学工程学院,浙江宁波315211 [2]质谱技术与应用研究院,浙江省先进质谱技术与分子检测重点实验室,浙江宁波315211

出　　处：《质谱学报》2024年第1期165-173,I0006,共10页Journal of Chinese Mass Spectrometry Society

基　　金：科技部重大科学仪器设备开发(2020YFF01014601);国家自然科学青年基金(22104067)。

摘　　要：本研究主要以铃木-宫浦反应(Suzuki-Miyaura)中的C—C偶联反应为研究对象,使用四(三苯基膦)钯作为催化剂,将3-溴吡啶、3-溴喹啉、3-溴-5-苯基吡啶分别与苯硼酸、2-甲基苯硼酸、3,5-二甲基苯硼酸在甲苯溶剂环境中进行“一锅法反应”。反应过程中定时取样,采用电喷雾-捕集离子淌度飞行时间质谱(ESI-TIMS-TOF MS)对Suzuki-Miyaura偶联反应的氧化加成过程与转移金属化过程后生成的中间体进行检测。研究表明:1)在氧化加成过程中,由于苯硼酸并未参与中间体的形成,所以在含有不同苯硼酸参与的反应中检测到的中间体质荷比相同,然而转移金属化过程后,由于参与偶联反应的2种物质不同,检测到的中间体不同;2)检测到的中间体同位素峰与预测图谱一致;3)使用捕集离子滴度飞行时间(TIMS-TOF)对检测到的基团进行离子迁移率检测以区分同分异构体,同时对检测到的中间体进行MS/MS分析,研究碎裂基团,利用TIMS-TOF得到的质荷比、离子迁移率、MS/MS等数据研究有机反应机理,可为金属Pd催化的反应机制研究提供参考。Mass spectrometry is one of the most extensive scientific analysis techniques,which plays an important role in analysis and research of biology,pharmaceutical,chemical industry,new materials and so on.At present,the research method of organic reaction mechanism is mainly through the detection of hypothetical organic reaction intermediates,combined with density functional calculation.Therefore,it is of great significance for mass spectrometer with high sensitivity to analyze and detect the intermediates in organic reactions.In this study,C—C coupling reaction in Suzuki-Miyaura reaction was studied.3-Bromopyridine,3-bromoquinoline and 3-bromo-5-phenylpyridine were used to react with phenylboronic acid,2-methylphenylboric acid and 3,5-dimethylphenylboric acid,respectively,and Pd(PPh 3)4 was used as catalyst to carry out one-pot reaction in toluene solvent.During the reaction,the samples were taken at regular intervals,and the intermediates generated after the oxidative addition and transmetalation processes in the Suzuki-Miyaura coupling reaction were detected using electrospray ionization-ion mobility time-of-flight mass spectrometry(ESI-TIMS-TOF MS).The results showed that:1)For the intermediates formed in the oxidative addition process,arylboric acids are not involved in the formation of arylboric acids,the mass-charge ratios observed in the reactions with different arylboric acids are the same.While,the intermediates formed after transfer metallization are different with the two substances involved in the coupling reaction.2)The isotopic peaks of the detected intermediates are consistent with the predicted spectra.3)The ion mobility of the detected groups can be detected by TIMS-TOF to distinguish the isomers,and the fragmented small groups can be observed by MS/MS analysis of the detected intermediates.The data of mass-charge ratio,ion mobility and MS/MS obtained by TIMS-TOF are helpful to study organic reaction mechanism,and also can provide a reference for the reaction mechanism catalyzed by metal Pd.

关 键 词：捕集离子淌度飞行时间质谱(TIMS-TOF MS) 反应中间体 离子迁移率 铃木-宫浦反应(Suzuki-Miyaura) 

分 类 号：O657.63[理学—分析化学]