Name: real-time monitoring of reactions performed using continuous-flow processing: the preparation of 3-acetylcoumarin as an example
Uploaded: 2015-11-18T13:00:00
Description: Watch this Scientific Journal Video about Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example at JoVE.com

Financial support provided by National Science Foundation (CAREER award CHE-0847262. We thank Vapourtec Ltd and Enwave Optronics for equipment support, and Daniel Daleb of the University of Connecticut for his assistance in construction of the flow cell apparatus.

1.查找反应监测合适信号。 <ol><li>获得的拉曼光谱对所有的起始原料和产物。 </li><li>叠加光谱并确定一个强烈频带是唯一的产物。 </li><li>使用该拉曼频带以监测反应的进度。在1608厘米的带-1在这种情况下被选中。 </li></ol> 2.设置流动池<ol><li>获得合适的流动池。这里使用一个具有以下尺寸：宽度为6.5毫米，20毫米的高度，并且为5毫米（图2A）的路径长度。...

<ol>
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在该拉曼光谱仪可以与流动单元被接口易于使这一直列技术反应监测有价值。一些反应变量可以探测在加速方式，允许用户在优化的反应条件下使用脱机方法时，速度比到达。本文所述也技术应用允许监视的副产物的形成的，假设一个合适的带都可以找到。条件可筛选和选择，这使得既为最高的转换产物，并​​还杂质的最低量。反应的定量监测也是可能的。由于拉曼信号强度与浓度成正比，校?...

通过采用连续流动加工，化学家们发现他们可以执行一系列的化学反应，安全，高效，轻松，1,2。其结果是，流动化学设备正在成为在学术机构同时运行在工业设置的反应以及研究实验室的整工具。各种各样的合成化学转化已进行了在流反应器3,4。在选择的情况下，反应不以间歇工作已显示出平滑连续流动条件下5继续。对于这两种反应优化和质量控制，串联反应监测与流处理的掺入提供显著优点。在在线监​​测提供连续的分析与实时响应，以实际样品条件。这是更快的，并且在一些情况下，比同类的离线技术更可靠。若干的在线分析技术已接口和f低电抗器7。实施例包括红外8,9，紫外可见10,11，12,13核磁共振，拉曼光谱14,15，和质谱16,17。 我们的研究小组接口拉曼光谱仪用科学的微波单元18。使用此，一系列的反应已经从监测都有了质19和定量的20立场。在此基础上的成功，我们最近接口我们的拉曼光谱仪与我们的连续流单元中的一个，并采用它用于线反应的一个数字键医药相关的有机转化的监视。21在每种情况下，有可能监视反应以及在一个实例中，由校准曲线的装置，我们可以判断从拉曼光谱数据产品转化。在这里，我们介绍如何设置设备，并用它来监视反应。我们使用的哌啶催化的合成的3 - 交流etylcoumarin（1）从水杨醛与乙酰乙酸乙酯（图1）作为此处的模型反应。 <img alt="图1" src="/files/ftp_upload/52393/52393fig1.jpg" /> 图1.碱催化水杨醛与乙酰乙酸乙酯的缩合反应，得到3-乙酰基香豆素（1）。 <a href="https://www.jove.com/files/ftp_upload/52393/52393fig1large.jpg" target="_blank">请点击此处查看该图的放大版本。</a>

<table border="0">
	<tbody>
		<tr>
			<td>Salicylaldehyde</td>
			<td>Sigma-Aldrich</td>
			<td>S356</td>
			<td>Reagent Grade, 98%</td>
		</tr>
		<tr>
			<td>Ethyl acetoacetate</td>
			<td>Acros Organics</td>
			<td>117970010</td>
			<td>99%</td>
		</tr>
		<tr>
			<td>Piperidine</td>
			<td>Sigma-Aldrich</td>
			<td>104094</td>
			<td>Reagent Plus, 99%</td>
		</tr>
		<tr>
			<td>Hydrochloric acid</td>
			<td>Sigma-Aldrich</td>
			<td>320331</td>
			<td>ACS Reagent, 37%</td>
		</tr>
		<tr>
			<td>Ethyl acetate</td>
			<td>Sigma-Aldrich</td>
			<td>34858</td>
			<td>CHROMASOLV, for HPLC, &#62;99.7%</td>
		</tr>
		<tr>
			<td>Acetone</td>
			<td>Sigma-Aldrich</td>
			<td>650501</td>
			<td>CHROMASOLV, for HPLC, &#62;99.9%</td>
		</tr>
		<tr>
			<td>Flow cell</td>
			<td>Starna Cells</td>
			<td></td>
			<td>583.65.65-Q-5/Z20</td>
		</tr>
		<tr>
			<td>Flow unit</td>
			<td>Vapourtec</td>
			<td></td>
			<td>E-series system</td>
		</tr>
		<tr>
			<td>Raman spectrometer</td>
			<td>Enwave Optronics Inc</td>
			<td></td>
			<td>Model EZRaman-L</td>
		</tr>
	</tbody>
</table>

real-time monitoring of reactions performed using continuous-flow processing: the preparation of 3-acetylcoumarin as an example

通过使用内嵌的监测，可以优化以简单和快速的方式使用连续流动处理进行的反应。另外，也可以确保在一段时间一致的产品质量使用这种技术。我们在这里显示了如何用拉曼光谱仪接口的市售流动单元。拉曼流动池被放置在回压调节器后，这意味着它可以在大气压力下操作。此外，该产品流通过管道进入流动池之前的长度的事实意味着该材料是在室温下。重要的是，该光谱等温条件下获得的，因为拉曼信号强度取决于温度。具有组装的装置中，我们然后显示如何监视一个化学反应中，哌啶催化的合成将3-乙酰基香豆素从水杨醛和乙酰乙酸乙酯被用作一个例子。该反应可以在一定范围的流率的执行Ð的温度下， 在现场监测工具被用于简单而容易地优化条件。

连续流动制备3-乙酰基香豆素被选定为在在线监测一个代表反应。在分批，反应进行很好，使用乙酸乙酯作为溶剂时。然而，产物（1）是不完全溶解在RT。为了防止回压调节器的潜在的堵塞，以及减轻在流动池这会扰乱信号采集具有固体颗粒的风险，我们使用了我们先前开发针对此等反应22技术。我们将反应线圈用丙酮后截获产品流以溶解产物，并允许它穿过流动池和背压调?...

Watch this Scientific Journal Video about Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example at JoVE.com

Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example

实时监控允许使用连续流动处理进行的反应的快速优化。这里的3-乙酰基香豆素，制剂被用作示例。用于进行原位拉曼监测装置进行说明，因为都是以优化反应所需的步骤。

反应执行使用连续流处理的实时监控：3  - 乙酰基香豆素的制备为例

By using inline monitoring, it is possible to optimize reactions performed using continuous-flow processing in a simple and rapid way. It is also possible ...

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