| 摘要註: |
苯並咪唑類化合物合成反應的相關探討已有許多研究,但這些研究都著重於以離線方式探討產物的選擇性。本研究則利用文氏管電噴灑游離質譜法(Venturi electrospray ionization mass spectrometry, VESI-MS)進行線上即時分析,觀測鄰苯二胺(o-phenyldiamine,o-PD)與苯甲醛(benzaldehyde,BA)合成苯並咪唑(benzimidazole)時,不同合成條件下主要成分的生成變化趨勢;探討的反應條件包含改變溶劑、鄰苯二胺和苯甲醛上的取代基、酸的催化等條件。以甲醇為溶劑,在60分鐘的觀察時間內顯示中間產物快速生成後逐漸減少,伴隨著單取代產物的增加,雙取代產物的變化趨勢則不明顯。改以乙醇和水做為溶劑時,各種成分的變化趨勢也隨之改變,但中間產物於水中的變化量則顯示無太大的改變。當將BA上4號碳位置的-H以不同取代基置換時,屬於拉電子取代基的-CN和-Cl會抑制合成反應的進行,而-CN基的抑制效應強於-Cl基。相反的,推電子基-CH3則可以加速反應的進行。若將o-PD上4號碳位置的-H以-CH3取代,則也會減慢反應速率。o-PD與CH3-BA反應時,將4號碳上-CH3改置於3號碳上,也會造成中間產物生成速率的變化。添加酸於o-PD與CN-BA反應液中可以明顯的增加反應速率,三氟醋酸(TFA)加速反應速率的效果勝於醋酸,但是TFA會與CN-BA進行副反應。本研究成功展示VESI-MS可以做為線上即時偵測苯並咪唑合成時各成分的即時變化,結果證明溶劑、取代基、酸都會影響反應速率,本研究所觀察的化合物生成變化是依據質譜圖中特定離子的強度變化,並不代表該化合物的實際產率,因此無法將實驗結果與已知合成條件對產物選擇性的影響做直接的比較。 Benzimidazole compound synthesis reactions have been many studies, however, these studies have focused on offline in order to explore the selective product. In this study, the use of Venturi Electrospray Ionization Mass Spectrometry ( VESI-MS) for online real-time analysis, change trend generate major component observation o-phenylenediamine and benzaldehyde under different synthesis conditions benzimidazole, discussion reaction conditions included changing the solvent, the substituents o-phenylenediamine and benzaldehyde on acid catalysis conditions. Methanol as solvent, displayed within 60 minutes of the observation time is gradually reduced after the intermediate product quickly generate, along with the mono-substituted product is increased, di-substituted product will not change significantly. When changed to ethanol and water as a solvent, change trend of the various components will be different, but the intermediate change in water no too much. When the BA of number 4 carbon positions at different substituents replacement, -CN and -Cl electron-withdrawing substituents can inhibit the synthesis reaction, and the inhibitory effect -CN group is stronger than the -Cl group. Instead, electron-donating substituents -CH3 can accelerate the reaction. If o-PD of -H on the 4th carbon position replace with -CH3, it will slow down the rate of reaction. When o-PD and CH3-BA reaction, the carbon on the 4th replace on the 3rd -CH3 change on carbon, can also cause changes in the rate of formation of the intermediate product. Adding an acid to o-PD and CN-BA reaction solution can significantly increase the rate of reaction, trifluoroacetic acid (TFA) to accelerate the reaction rate is better than the effect of acetic acid, but TFA and CN-BA will be side effects. This study successfully demonstrated VESI-MS can be used as real-time changes in the components of online instant detection of benzimidazole synthesis, results show that solvent, substituent, acid will affect the reaction rate. A compound of changes observed in this study was based on intensity change in a particular ion mass spectrum, it does not represent the actual yield of the compound, and therefore can not directly affect the results of the comparison with the known synthetic conditions on the product selectivity to do |