Online monitoring of chemical reactions by contactless atmospheric pressure ionization mass spectrometry.

Online monitoring of the appearance of the intermediates and products during chemical reactions is helpful to understand reaction mechanisms. Various analytical tools including nuclear magnetic resonance spectroscopy, Raman spectroscopy and mass spectrometry (MS) have been employed for the study. MS is one of the most promising means among analytical tools that can provide information of mass-to-charge ratios for intermediates and products generated from chemical reactions. The main challenge for online monitoring of species generated from chemical reactions by MS is the interface design. The success of online monitoring of chemical reactions using MS relies on real-time recording of the generated species from reactions without sacrificing kinetic information during coupling. In addition, MS can only detect gas-phase ions. Nevertheless, most chemical reactions occur in liquid phase. Thus, generating gas-phase ions from liquid samples is vital for the success of this study. Electrospray ionization (ESI) is one of the most common atmospheric pressure ionization (API) methods that generate gas-phase ions from liquid-reacting species/products in the proximity of a mass spectrometer for online monitoring of chemical reactions. In addition, some recently developed ambient ionization methods such as desorption ESI, extractive ESI, electrospray desorption ionization, fused droplet ESI, low-temperature plasma probe for ambient desorption ionization and ultrasonication-assisted spray ionization [27] also have shown their usefulness in monitoring reactions in real time. High-voltage electric power supply, gas supply, or laser is generally required for these approaches. High-voltage free approaches such as Venturi easy ambient sonic-spray ionization with gas supply only have been used to online monitoring of organic reactions. A comprehensive description about the progress using MS to monitor chemical reactions can refer to the recently published book written by Santos. Some of these techniques may be suitable for monitoring fast reactions that take place during desorption/ionization process. However, our current study is focused on using a recently developed API technique for monitoring the changes of reacting species from an organic reaction requiring a long reaction time to reach the end of the reaction. A continuous-flow API method was recently explored, called contactless API (C-API), which uses a short tapered-capillary tip (~ 1 cm) as the spray emitter for the generation of gas-phase ions from a liquid solution. High-voltage electric power supply, gas supply and laser are not required for the C-API approach. The C-API approach only requires a tapered capillary for the generation of gas-phase ions in the proximity of MS (Fig. 1). The sample solution can flow continuously from the sample inlet