Accompanied with the improvements of instrument, design, mass spectrometer can provide rapid detection speed, accurate molecular weight of the analyte, and analyte structure, which was identified by tandem mass spectrometry (MS / MS). Because of rapid detection speed of mass spectrometer not only can be applied for real-time detection of the signals of the reactants and products in chemical reactions, but also was validated to detect the intermediates, which have existed in a very short time. For real-time monitoring of liquid phase chemical reactions, it not only must has an the rapid detection speed of mass spectrometer, but also have a suitable ionization source, which can assist that neutral analytes in the liquid directly fused into gas phase and be ionized to form analyte ion. In this study, ion spray ionization source was applied to explore the drolpet-synthesis reaction in the gas phase. In the experimental process, pneumatic nebulizer was validated for producing neutral droplets. The atomization effect is mainly caused by validating high-speed air flow through the liquid surface to shatter the liquid solution into population of droplets. In this experiment, two pneumatic atomizer set at a particular angle for spraying neutral droplets; some of neutral droplets with different analytes would fused into larger one in the gas phase. At the same time, reactant A and reactant B in the fused droplet would process chemical reaction in just a few hundred microseconds. End of the chemical reaction, fused droplets was sent near the entrance of MS inlet by the transmission of gas flow, dry air eluted from mass entrance outflow (dry gas) was validated for the desolvation. Based on the field ionization mechanism, induced electrospray ionization was occurred when MS inlet applied with 4.5 kV. Then, analyte ions via induced electrospray ionization were transferred to the inner of MS inlet and detected by mass spectrometer. In this experiment, several experimental parameters have been discussed and optimized including the angle of nebulizer (15 degrees - 90 degrees), the flow rate of nebulizing gas (3 psi -15 psi), the flow rate of sample solution (100 £gL/hr. - 500 £gL/hr), the flow rate of dry gas (3 L/min - 12 L/min) and the temperature of dry gas (50 oC-300 oC) for improvement of the reaction process and ionization efficiency. Finally, the droplet-synthesis reaction was performed under the optimal experimental parameters. The derivatives of aniline as reagent A, consisting a phenyl group attached to the different functional groups including hydroxyl group (-OH), nitric group (NO2), varied the different functional groups to change the reaction rate of reactant A in the chemical reaction. Then, benzaldehyde and acetic anhydride as reagent B was separately reacted with reagent A via droplet synthesis process to perform addition-elimination reaction. Beside, all of the tested chemical reactions through droplet-synthesis device were also re-verified by the liquid phase chemical reaction. Through the observation of mass spectra, The comparison of the differences (i.e. intermediate and product) between droplets synthesis reaction and liquid phase chemical reaction can also be obtained.

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