Continuous flow reaction monitoring using an on-line miniature mass spectrometer
Continuous flow reaction monitoring using an on-line miniature mass spectrometer
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DOI：
10.1002/rcm.6312
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发表时间：
2012-09-15
影响因子：
2
通讯作者：
Ley, Steven V.
中科院分区：
文献类型：
--
作者：
Browne, Duncan L.;Wright, Steven;Ley, Steven V.
原理：最近开发的微型电喷雾电离质谱仪已与制备流化学系统耦合，以监测反应中间体和竞争反应路径，筛选起始材料，并优化反应条件。虽然质谱仪非常适合应用，但很少以这种方式使用，因为传统仪器太笨重，无法方便地与流动化学平台耦合。方法采用六端口开关阀，配以5 μ L回路，对离开反应器线圈的流体进行周期性取样。样品环含量对应的质谱约为10？S激活阀门后。始终保持高流体压力，以确保气态产物保持在溶液中。作为该装置如何使用的一个说明性例子，研究了苯的生成及其随后与呋喃的反应。以亚硝酸盐叔丁基为原料，对苯甲酸进行重氮化反应制备了苯。结果出乎意料的是，在较低的线圈温度和较短的停留时间下，质谱联用仪检测到爆炸性重氮中间体。生产Diels-Alder产品的最佳反应器温度和停留时间为50℃和35℃。分别为最小值。有一些相互竞争的反应途径导致吖啶酮和其他一些副产物的形成。结论：在线质谱法可以快速调整流动条件，以确保安全操作和最佳生成所需产品。通过液相色谱/质谱（LC/MS）对流动样品进行离线分析，验证了该方法的有效性。版权所有：John Wiley & Sons， Ltd
RATIONALE A recently developed miniature electrospray ionisation mass spectrometer has been coupled to a preparative flow chemistry system in order to monitor reactive intermediates and competing reaction paths, screen starting materials, and optimise reaction conditions. Although ideally suited to the application, mass spectrometers have rarely been used in this way, as traditional instruments are too bulky to be conveniently coupled to flow chemistry platforms. METHODS A six-port switching valve fitted with a 5 mu L loop was used to periodically sample the flow stream leaving the reactor coil. Mass spectra corresponding to the sample loop contents were observed approximately 10?s after activating the valve. High fluidic pressure was maintained throughout to ensure that gaseous products remained in solution. As an illustrative example of how this apparatus can be employed, the generation of benzyne and its subsequent reaction with furan were investigated. Benzyne was prepared via diazotisation of anthranilic acid using tert-butyl nitrite. RESULTS Unexpectedly, the explosive diazotised intermediate was detected by the mass spectrometer at low coil temperatures or short residence times. The optimum reactor temperature and residence time for production of the desired Diels-Alder product are 50 degrees C and 35?min, respectively. There are competing reaction pathways leading to the formation of acridone and several other by-products. CONCLUSIONS On-line mass spectrometry allowed the flow conditions to be quickly tuned for safe operation and optimal generation of the desired product. The validity of this approach was corroborated by off-line liquid chromatography/mass spectrometry (LC/MS) analysis of flow samples. Copyright (C) 2012 John Wiley & Sons, Ltd.