隨著質譜儀(Mass Spectrometer)的進步，提供快速的偵測速度，分析物的準確分子量以及利用二次質譜(MS/MS)可提供分析物的結構鑑定。因此快速的偵測速度，不僅可以即時偵測到化學反應中反應物以及產物的訊號，也可偵測存在時間極短的中間體的形成。但是要即時監測液相中化學反應，不僅要偵測時間快速的質譜儀，也需要有合適的游離源系統。而本研究主要是利用離子噴灑游離源(ion spray ionization source)，在空氣中進行液珠合成反應的探討。在實驗中，主要是利用氣動式霧化(pneumatic nebulizer)裝置，其霧化效果主要是利用高速氣流通過液體表面，利用空氣摩擦以達到撕裂液體表面而產生中性液珠。本實驗中主要是利用兩管氣動式霧化裝置，以特定的角度進行中性液珠的噴灑，帶有不同分析物的液珠，會在氣相中再次進行液珠融合，此時融合液珠中的反應物A以及反應物B，在短短的幾百微秒中進行化學反應。而進行完化學反應的液珠，會再經由氣體的帶動，傳送到質譜入口附近，此時再利用質譜入口流出的乾燥氣流(dry gas)去溶劑化的動作，此時質譜內部所施加-4.5kV再利用場游離的方式，將產生誘導電噴灑機構，形成分析物離子，再送入至質譜中進行分析物離子的偵測。 在本實驗中，已經對於數項實驗參數進行討論，其中包含有霧化器的噴灑角度(15度- 90度)、霧化氣流速(3 psi- 15 psi)、樣品流速(100 μL/hr-500 μL/hr)、質譜內部乾燥氣體的流速(3 L/min- 12 L/min)以及溫度(50 oC-300 oC)，以達到最佳化的反應性以游離效果。最後在最佳化的實驗參數下進行氣相液珠合成反應，其反應物A中主要是利用苯環上接有不同官能基(-OH、NO2)之苯胺(aniline)，來達到以不同的官能基來改變反應物A在反應速率的變化，再分別與苯甲醛(benzaldehyde)以及醋酸酐(acetic anhydride)進行加成脫去反應，進行氣相液珠合成反應的探討。此外所有所測試的化學反應中，皆有再利用液相反應加以驗證。再經由觀察質譜圖，比較化學反應在液珠合成中和在液相中是否有所不同。

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 μL/hr. - 500 μL/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.

論文審定書 ....................................................................................................................... I
謝誌……………………………………………………………………………………...II
論文摘要 .........................................................................................................................III
英文摘要……………………………………………………………………………….IV
目錄 ............................................................................................................................... VI
圖目錄 ............................................................................................................................ IX
壹、緒論 ...........................................................................................................................1
一、 前言: ..................................................................................................................... 1
二、 電噴灑游離法及其衍生技術 .............................................................................. 4
1.電噴灑游離法(Electrospray Ionization, ESI) ............................................................. 4
2.電噴灑游離法衍生技術 (大氣壓力游離源) ............................................................ 7
2.1 離子噴灑法(Ion Spray, IS)................................................................. 7
2.2 氣相層析法連接電噴灑游離法(Gas Chromatography- Electrospray
Ionization, GC-ESI ) ................................................................................. 7
2.3 融合微滴電噴灑游離(Fused-Droplets Electrospray Ionization,
FD-ESI) .................................................................................................... 8
2.4 脫附電噴灑游離法(Desorption Electrospray Ionization, DESI) ...... 9
2.5 電噴灑輔助雷射脫附游離法(Electrospray-assisted Laser
Desorption Ionization, ELDI) ................................................................. 10
2.6 探針式電噴灑游離法(Probe Electrospray Ionization, PESI)........... 11
2.7 萃取式電噴灑游離法(Extractive Electrospray Ionization, EESI) .. 12
三、化學反應監測方法的介紹 ................................................................................ 14
1.非連續性監測(Off-line Monitoring ): ....................................................................... 15
1.1 Desorption/Ionization on Silicon(DIOS) .......................................... 15
1.2 Direct Analysis in Real Time (DART) ............................................. 16
2.連續性監測(Continuous On-line Monitoring): ........................................................ 18
2.1 電噴灑游離法(Electrospray Ionization) .......................................... 18
2.2 萃取式電噴灑游離法(Extractive Electrospray Ionization, EESI) .. 19
三、 論文目標 ............................................................................................................ 21
貳、實驗 .........................................................................................................................22
一、儀器裝置 ............................................................................................................ 22
1.質譜儀.. .................................................................. ……………………………..……..22
2.質譜入口不鏽鋼管 ....................................................................................................... 22
3.微量注射幫浦 ............................................................................................................... 22
4.微量注射筒 .................................................................................................................... 22
6.玻璃裝置 ........................................................................................................................ 22
7.壓克力板 ........................................................................................................................ 23
8.自組裝化學反應反應裝置 .......................................................................................... 23
9.高電壓電源供應器 ....................................................................................................... 23
10.離子噴灑游離源 ......................................................................................................... 23
二、化學藥品與分析樣品 ........................................................................................ 24
三、 藥品配置、實驗參數及實驗步驟 .................................................................... 26
1.藥品配置 ........................................................................................................................ 26
2.實驗參數 ........................................................................................................................ 26
2.1 液滴反應 .......................................................................................... 26
2.2 液相反應 .......................................................................................... 26
3.實驗步驟: ....................................................................................................................... 28
3.1 液滴反應 .......................................................................................... 28
3.2 液相反應 .......................................................................................... 29
參、結果與討論 .............................................................................................................30
(一) 脫水反應 (Dehydration reaction) ...................................................................... 39
反應機制: ................................................................................................................... 39
(二) 親核性醯基化取代反應(Nucleophilic Acylation Substitution Reaction)......... 45
反應機制: ................................................................................................................... 45
(三) 環氧化反應(Epoxidation Reaction) ................................................................... 55
(四) 裝置設計 ............................................................................................................ 58
肆、結論 .........................................................................................................................63
五、參考文獻 .................................................................................................................64
陸、 附錄 .......................................................................................................................69

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