Name: real-time monitoring of reactions performed using continuous-flow processing: the preparation of 3-acetylcoumarin as an example
Uploaded: 2015-11-18T13:00:00.000+00:00
Duration: 9 min 56 s
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。 </li><li>将流动池的容器中，提供了一个自由的环境光的环境中。 </li><li>连接管道到流动池的入口和出口（在此情况下1毫米的ID的PFA管）。 </li></ol> 3.接口拉曼光谱仪的流动池<ol><li>获得合适的拉曼光谱仪与柔性光学组件，其可以放置在C失去接近流通池。 </li><li>通过在含有流动池装置（图2B）的框合适尺寸的孔放置光学组件。 </li><li>光学组件滑动，直到它触及流动池，然后将它拉回来留下〜2毫米的间隙。 </li><li>填用100％丙酮流动池。 </li><li>打开拉曼光谱仪，并获得谱在连续扫描模式。 </li><li>通过一次轻轻移动所述光管的一部分聚焦激光。保持移动光管，直到信号处于其最大的强度和峰尖锐且明显。 </li></ol><img alt="图2" src="/files/ftp_upload/52393/52393fig2.jpg" /> 图2.（A）流动池，并用（B）拉曼接口。 <a href="https://www.jove.com/files/ftp_upload/52393/52393fig2large.jpg" target="_blank">请点击此处查看大图已经</a>rsion这个数字。 4.准备试剂和溶剂溶液<ol><li>添加水杨醛（六点一〇六克，50毫摩尔，1当量）和乙酰乙酸乙酯（6.507克，50毫摩尔，1当量）到50ml容量瓶中。 </li><li>加入乙酸乙酯至50毫升的总体积，然后彻底混合内容。 </li><li>转移10ml的等分试样原液含有磁性搅拌棒的20ml玻璃小瓶中。标签此瓶"试剂"。 </li><li>在100毫升的瓶代替90毫升乙酸乙酯。标签这瓶"溶剂"。在100毫升一瓶的地方90毫升丙酮。标签这瓶"溶剂拦截"。 </li></ol> 5.准备流动设备的<ol><li>确保该流动单元具有至少两个泵和标签他们"P1"和"P2"。确定每个泵溶剂和试剂入口线。将在"收"和"废物"生产线出口线路分成两个我，ndividual100毫升瓶标有"产品"和"浪费"分别。 </li><li>作为反应器，用10毫升容量PFA线圈能够被加热的。 </li><li>管排出P1连接到PFA反应器盘管的入口。 </li><li>电感线圈后，安装一个三端口聚醚醚酮（PEEK）发球混合器。 </li><li>管排出的P2连接到T型混合器，从反应器中线圈的出口管道180°。一管件连接到三通混频器的第三端口。在此管的另一端放置一个背压调节器。 </li><li>从回压调节到流通池的输入输出端连接的线。从流动池的输出线连接到"废/收集"开关。 </li><li>素的溶剂线为P1和P2以及为P1中的试剂线用溶剂。从溶剂瓶的试剂瓶移动试剂线P1上。 </li><li>利用P1，通过反应器通过乙酸乙酯线圈在2毫升/分钟，直到它被充满。至P2通过丙酮以2ml /分的流速分钟2分钟。 </li><li>调节溶剂的流速为P1和P2，以1毫升/分钟。设置回压调节到7巴的压力下。设置在反应器线圈温度到所需的温度。 </li><li>仔细检查设备被配置为图 3所示的原理图。 </li><li>一旦系统达到恒定的温度和压力，检查是否漏水，然后运行反应。 </li></ol><img alt="图3" src="/files/ftp_upload/52393/52393fig3.jpg" /> 图3.原理用于反应监测实验设备的配置。 <a href="https://www.jove.com/files/ftp_upload/52393/52393fig3large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 6.监控反应<ol><li>德的乙酸乙酯/丙酮溶剂体系EA后台扫描因为它通过流动池。这将从所有后续的扫描自动扣除。 </li><li>配置分光计采取扫描每15秒（在此情况下，拉曼光谱仪被设定为10秒的积分时间，棚车= 3，平均值= 1）。 </li><li>注射哌啶（0.05毫升，0.05毫摩尔，0.1当量）一次全部进入标有"试剂"的玻璃小瓶。 </li><li>从后充分混合，开关P1"溶剂"到"试剂"将退出流"收集"。 </li><li>当所有材料完全加载从"试剂"，切换P1回"溶剂"。继续通过电感线圈另外30分钟流淌的溶剂。一旦超过这个时间，关掉暖气。 </li><li>转泵P1和P2时关闭反应器线圈温度已冷却至低于50℃。 </li></ol> 7.分析数据<ol&gt; <li>在拉曼光谱仪的数据导出到电子表格和情节拉曼强度1608厘米-1主场迎战时间。 </li><li>为了优化的条件下，进行跨越多个流速和反应器温度的以迭代的方式进行反应。 </li><li>叠加图拉曼强度的1608厘米-1主场迎战时间。 注:更高的拉曼强度与较高的产品转化。 </li></ol> 8.运行反应使用优化的条件<ol><li>有筛选各种条件（不同的流速/反应器温度），运行使用优化的条件下，得到最高的产品转化的反应。 </li></ol> 9.隔离产品<ol><li>取产物烧瓶的内容，并将其倒入含有100毫升冰水和20毫升的2M的HCl的烧杯中。 </li><li>冲洗产物烧瓶用乙酸乙酯（2ml）中，并转移到烧杯最小量。 </li><li>搅拌冰冷混合物直到所有的冰完全融化。 </li><li>设置一个过滤系统，具有赫希漏斗，侧臂烧瓶中，橡胶圈和橡胶真空管的长度。 </li><li>过滤所得沉淀在真空下，冲洗用冷乙醚（10ml）中，并允许它在热灯下（2-3小时）或干燥O / N在真空下干燥。 </li><li>确认产品的通过 1 H核磁共振（NMR）波谱使用为 CDCl 3溶剂的身份。为500MHz的NMR波谱仪，是3-乙酰基香豆素的1 H NMR数据如下:δ= 2.73（S，3H）7.31 - 7.40（米，2H）7.65（DDD，J = 7.53，4.37，2.60 Hz的，2H）8.51（S，1H）ppm的，13 C NMR数据;δ= 30.84（CH 3）117.00（CH）118.56（C）的124.86（CH）125.27（CH）130.51（CH）134.68（C）的147.74 （CH），155.64（C）159.52（C）195.77（C）PPM。 </li></ol>

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The authors have nothing to disclose.

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，校正曲线可以通过记录产品的已知浓度的样品的拉曼光谱得到。用这种方法，有可能的拉曼强度的单位转换为在标准条件浓度的单位。 关键ST在协议中EPS包括反应器管的正确组装和拉曼单元的接口。据表示的配置进行泄漏使用水或丙酮进行反应之前，进行测试。此外，聚焦拉曼激光通过正确定位石英光管是必需的协议的成功。信号强度差是一个标志，或者激光没有适当地聚焦或存在于反应混合物中的一些颗粒物。 此处所描述的装置已被成功地用于监视其他三个反应，轴承产品α，β不饱和羰基部分，即Knovenagel和克莱森-施密特缩合所有涉及的形成，和一个比吉内利反应20。拉曼光谱仪作为补充工具其他原位监控探头。例如，它可以在情况下，IR光谱并不能证明令人满意，如当使用该反应在水性介质中进行，或放置在与反应混合物的物理接触质谱探头时，不希望的24,25。限制拉曼光谱的应用包括一个事实，即反应混合物必须是完全均匀的，以避免信号散射。另外，由于拉曼事件的概率比较低，样品必须相对集中在为了获得良好的信号 - 噪声比。根据我们的经验，这需要在浓度达到或超过0.25米工作

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><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, &gt;99.7%</td></tr><tr><td>Acetone</td><td>Sigma-Aldrich</td><td>650501</td><td>CHROMASOLV, for HPLC, &gt;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节器畅通无阻。 以确定一个合适的拉曼信号并监控我们预测的1的拉曼光谱，并使用计算机程序高斯09（图4A中的两种原料（水杨醛和乙酰乙酸乙酯）的</strong&gt;的信息，B和C）23。应当指出的是，起始原料和产物的实验得出的拉曼光谱也可使用，如果不能够获得高斯09.三种光谱的重叠（图4D）中指出，在1具有强拉曼活性拉伸在1 608名-1和1563厘米-1模式，原料表现出在此区域最小拉曼活性。其结果是，我们选择在1 608名-1来监视该信号。 为起点，将反应在25℃和1毫升/分钟的试剂流量和拉曼强度在1 608名-1记录（图5）。与获得尽可能高的转换的目标，我们接下来进行在较高温度下进行反应。操作以1ml / min的流速，第一提高反应温度到65℃，然后130℃下<html>导致截至1608厘米-1证明拉曼强度稳步上升，同时增加产品的转换。在一个反应器中线圈温度为130℃，1.0至0.5 ml的降低的流率/分钟未显著增加拉曼强度在1 608名-1。在手优化的条件下，我们进行反应一次，分离产物以72％的产率。 <img alt="图4" src="/files/ftp_upload/52393/52393fig4.jpg" /> 图4.拉曼光谱（A）3 -乙酰基香豆素，（B）水杨醛，（CC）乙酰乙酸乙酯，及（D）三个光谱的叠加。 <a href="https://www.jove.com/files/ftp_upload/52393/52393fig4large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 93fig5.jpg"/&gt; 图5，监测转化为在一系列反应条件下3乙酰基香豆素。 <a href="https://www.jove.com/files/ftp_upload/52393/52393fig5large.jpg" target="_blank">请点击此处查看该图的放大版本。</a>

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 ...

real-time-monitoring-reactions-performed-using-continuous-flow

Nanyang Technological University

Research

JoVE Journal

Chemistry

9.7K 次观看.  University of Connecticut. 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。 

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

Microfluidic On-chip Capture-cycloaddition Reaction to Reversibly Immobilize Small Molecules or Multi-component Structures for Biosensor Applications

Methods for rapid surface immobilization of bioactive small molecules with control over orientation and immobilization density are highly desirable for biosensor and microarray applications. In this Study, we use a highly efficient covalent bioorthogonal [4+2] cycloaddition reaction between trans-cyclooctene (TCO) and 1,2,4,5-tetrazine (Tz) to enable the microfluidic immobilization of TCO/Tz-derivatized molecules. We monitor the process in real-time under continuous flow conditions using surface plasmon resonance (SPR). To enable reversible immobilization and extend the experimental range of the sensor surface, we combine a non-covalent antigen-antibody capture component with the cycloaddition reaction. By alternately presenting TCO or Tz moieties to the sensor surface, multiple capture-cycloaddition processes are now possible on one sensor surface for on-chip assembly and interaction studies of a variety of multi-component structures. We illustrate this method with two different immobilization experiments on a biosensor chip; a small molecule, AP1497 that binds FK506-binding protein 12 (FKBP12); and the same small molecule as part of an immobilized and in situ-functionalized nanoparticle.

We present a method for rapid, reversible immobilization of small molecules and functionalized nanoparticle assemblies for Surface Plasmon Resonance (SPR) studies, using sequential on-chip bioorthogonal cycloaddition chemistry and antibody-antigen capture.

微流控芯片上捕获环加成反应可逆地固定小分子或多组分结构的生物传感器应用

Methods  for rapid surface immobilization of bioactive small molecules with control over  orientation and immobilization density are highly desirable for ...

科研

化学

Monitoring the Reductive and Oxidative Half-Reactions of a Flavin-Dependent Monooxygenase using Stopped-Flow Spectrophotometry

Aspergillus fumigatus siderophore A (SidA) is an FAD-containing monooxygenase that catalyzes the hydroxylation of ornithine in the biosynthesis of hydroxamate siderophores that are essential for virulence (e.g. ferricrocin or N',N",N'''-triacetylfusarinine C)1. The reaction catalyzed by SidA can be divided into reductive and oxidative half-reactions (Scheme 1). In the reductive half-reaction, the oxidized FAD bound to Af SidA, is reduced by NADPH2,3. In the oxidative half-reaction, the reduced cofactor reacts with molecular oxygen to form a C4a-hydroperoxyflavin intermediate, which transfers an oxygen atom to ornithine. Here, we describe a procedure to measure the rates and detect the different spectral forms of SidA using a stopped-flow instrument installed in an anaerobic glove box. In the stopped-flow instrument, small volumes of reactants are rapidly mixed, and after the flow is stopped by the stop syringe (Figure 1), the spectral changes of the solution placed in the observation cell are recorded over time. In the first part of the experiment, we show how we can use the stopped-flow instrument in single mode, where the anaerobic reduction of the flavin in Af SidA by NADPH is directly measured. We then use double mixing settings where Af SidA is first anaerobically reduced by NADPH for a designated period of time in an aging loop, and then reacted with molecular oxygen in the observation cell (Figure 1). In order to perform this experiment, anaerobic buffers are necessary because when only the reductive half-reaction is monitored, any oxygen in the solutions will react with the reduced flavin cofactor and form a C4a-hydroperoxyflavin intermediate that will ultimately decay back into the oxidized flavin. This would not allow the user to accurately measure rates of reduction since there would be complete turnover of the enzyme. When the oxidative half-reaction is being studied the enzyme must be reduced in the absence of oxygen so that just the steps between reduction and oxidation are observed. One of the buffers used in this experiment is oxygen saturated so that we can study the oxidative half-reaction at higher concentrations of oxygen. These are often the procedures carried out when studying either the reductive or oxidative half-reactions with flavin-containing monooxygenases. The time scale of the pre-steady-state experiments performed with the stopped-flow is milliseconds to seconds, which allow the determination of intrinsic rate constants and the detection and identification of intermediates in the reaction4. The procedures described here can be applied to other flavin-dependent monooxygenases.5,6

We describe the use of a stopped-flow instrument to investigate both the reductive and oxidative half-reactions of Aspergillus fumigatus siderophore A (SidA), a flavin-dependent monooxygenase. We then show the spectra corresponding to the species in the reaction of SidA and we calculate the rate constants for their formation.

监视依赖黄素单加氧酶和氧化还原半反应，用停流分光光度法

Aspergillus fumigatus siderophore A (SidA) is an FAD-containing monooxygenase that catalyzes the hydroxylation of ornithine in the biosynthesis of ...

生物工程

Millifluidics for Chemical Synthesis and Time-resolved Mechanistic Studies

Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the first, synthesis of ultra-small copper nanoclusters is described. The second example provides their utility for investigating time resolved kinetics of chemical reactions by analyzing gold nanoparticle formation using in situ X-ray absorption spectroscopy. The final example demonstrates continuous flow catalysis of reactions inside millifluidic channel coated with nanostructured catalyst.

Millifluidic devices are utilized for controlled synthesis of nanomaterials, time-resolved analysis of reaction mechanisms and continuous flow catalysis.

Millifluidics的化学合成和时间分辨机理研究

Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the ...

Temperature-programmed Deoxygenation of Acetic Acid on Molybdenum Carbide Catalysts

Temperature programmed reaction (TPRxn) is a simple yet powerful tool for screening solid catalyst performance at a variety of conditions. A TPRxn system includes a reactor, furnace, gas and vapor sources, flow control, instrumentation to quantify reaction products (e.g., gas chromatograph), and instrumentation to monitor the reaction in real time (e.g., mass spectrometer). Here, we apply the TPRxn methodology to study molybdenum carbide catalysts for the deoxygenation of acetic acid, an important reaction among many in the upgrading/stabilization of biomass pyrolysis vapors. TPRxn is used to evaluate catalyst activity and selectivity and to test hypothetical reaction pathways (e.g., decarbonylation, ketonization, and hydrogenation). The results of the TPRxn study of acetic acid deoxygenation show that molybdenum carbide is an active catalyst for this reaction at temperatures above ca. 300 &#176;C and that the reaction favors deoxygenation (i.e., C-O bond-breaking) products at temperatures below ca. 400 &#176;C and decarbonylation (i.e., C-C bond-breaking) products at temperatures above ca. 400 &#176;C.

Presented here is a protocol for the operation of a micro-scale temperature-programmed reactor for evaluating the catalytic performance of molybdenum carbide during acetic acid deoxygenation.

对碳化钼催化合成乙酸的程序升温脱氧

Temperature programmed reaction (TPRxn) is a simple yet powerful tool for screening solid catalyst performance at a variety of conditions. A TPRxn system ...

Optimization of the Ugi Reaction Using Parallel Synthesis and Automated Liquid Handling

The optimization of a Ugi reaction involving the mixing of furfurylamine, benzaldehyde, boc-glycine and t-butylisocyanide is described. Triplicate runs of 48 parallel experiments are reported, varying concentration, solvent and the excess of some of the reagents. The isolation of the product was achieved by a simple filtration and wash procedure. The highest yield obtained was 66% from 0.4 M methanol with 1.2 eq. of imine. This is significantly above the 49% yield obtained from the initial reaction under equimolar concentration at 0.4 M in methanol. Methanol solutions with reagent concentrations of 0.4M or 0.2M gave superior yields while all solvent systems at 0.07M performed poorly. At 0.2M, methanol and ethanol/methanol (60/40) mixtures were statistically equally good while THF/methanol (60/40) was poor and acetonitrile/methanol (60/40) was intermediate. Good reproducibility of the precipitate yields was obtained in these replicate experiments, allowing for subtle interaction effects to be positively identified.

The Ugi reaction has proved to be a convenient way to quickly create diverse libraries of compounds. It involves the reaction of an amine, an aldehyde, a carboxylic acid and an isonitrile typically in methanol at room temperature. In this video, we utilize a 48-slot Mettler-Toledo MiniBlock equipped with filtration tubes and a Mettler-Toledo MiniMapper automated liquid handler was used to deliver the reagents and solvent. The parameters of interest were the concentration, the solvent composition and the excess of some of the reagents.

卯木反应的优化使用平行合成和自动化液体处理

The optimization of a Ugi reaction involving the mixing of furfurylamine, benzaldehyde, boc-glycine and t-butylisocyanide is described.  Triplicate runs ...

生物学

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

Continuous flow technology has been identified as instrumental for its environmental and economic advantages leveraging superior mixing, heat transfer and cost savings through the &#34;scaling out&#34; strategy as opposed to the traditional &#34;scaling up&#34;. Herein, we report the reaction of diphenyldiazomethane with p-nitrobenzoic acid in both batch and flow modes. To effectively transfer the reaction from batch to flow mode, it is essential to first conduct the reaction in batch. As a consequence, the reaction of diphenyldiazomethane was first studied in batch as a function of temperature, reaction time, and concentration to obtain kinetic information and process parameters. The glass flow reactor set-up is described and combines two types of reaction modules with &#34;mixing&#34; and &#34;linear&#34; microstructures. Finally, the reaction of diphenyldiazomethane with p-nitrobenzoic acid was successfully conducted in the flow reactor, with up to 95% conversion of the diphenyldiazomethane in 11 min. This proof of concept reaction aims to provide insight for scientists to consider flow technology&#39;s competitiveness, sustainability, and versatility in their research.

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

Flow chemistry carries environmental and economic advantages by leveraging superior mixing, heat transfer and cost benefits. Herein, we provide a blueprint to transfer chemical processes from batch to flow mode. The reaction of diphenyldiazomethane (DDM) with p-nitrobenzoic acid, conducted in batch and flow, was chosen for proof of concept.

连续流动化学: Diphenyldiazomethane 与p硝基苯甲酸的反应

Continuous flow technology has been identified as instrumental for its environmental and economic advantages leveraging superior mixing, heat transfer and ...

Biosynthesis of a Flavonol from a Flavanone by Establishing a One-pot Bienzymatic Cascade

Flavonols are a major subclass of flavonoids with a variety of biological and pharmacological activities. Here, we provide a method for the in vitro enzymatic synthesis of a flavonol. In this method, Atf3h and Atfls1, two key genes in the biosynthetic pathway of the flavonols, are cloned and overexpressed in Escherichia coli. The recombinant enzymes are purified via an affinity column and then a bienzymatic cascade is established in a specific synthetic buffer. Two flavonols are synthesized in this system as examples and determined by TLC and HPLC/LC/MS analyses. The method displays obvious advantages in the derivation of flavonols over other approaches. It is time- and labor-saving and highly cost-effective. The reaction is easy to be accurately controlled and thus scaled up for mass production. The target product can be purified easily due to the simple components in the system. However, this system is usually restricted to the production of a flavonol from a flavanone.

The derivation of a flavonol is crucial for its application in healthcare and the food industry. Here, we provide a detailed protocol for the biosynthesis of a flavonol from a flavanone and discuss the crucial steps and its advantages over other approaches.

通过建立单罐双酶级联,从弗拉瓦内生物合成一种黄酮

Flavonols are a major subclass of flavonoids with a variety of biological and pharmacological activities. Here, we provide a method for the in vitro ...

生物化学

Utilization of Stop-flow Micro-tubing Reactors for the Development of Organic Transformations

A new reaction screening technology for organic synthesis was recently demonstrated by combining elements from both continuous micro-flow and conventional batch reactors, coined stop-flow micro-tubing (SFMT) reactors. In SFMT, chemical reactions that require high pressure can be screened in parallel through a safer and convenient way. Cross-contamination, which is a common problem in reaction screening for continuous flow reactors, is avoided in SFMT. Moreover, the commercially available light-permeable micro-tubing can be incorporated into SFMT, serving as an excellent choice for light-mediated reactions due to a more effective uniform light exposure, compared to batch reactors. Overall, the SFMT reactor system is similar to continuous flow reactors and more superior than batch reactors for reactions that incorporate gas reagents and/or require light-illumination, which enables a simple but highly efficient reaction screening system. Furthermore, any successfully developed reaction in the SFMT reactor system can be conveniently translated to continuous-flow synthesis for large scale production.

A protocol for organic reaction screening using stop-flow micro-tubing (SFMT) reactors employing gaseous reactants and/or visible-light mediated reactions is presented.

停止流动微管反应器在有机转化发展中的应用

A new reaction screening technology for organic synthesis was recently demonstrated by combining elements from both continuous micro-flow and conventional ...

A Modular Microfluidic Technology for Systematic Studies of Colloidal Semiconductor Nanocrystals

Colloidal semiconductor nanocrystals, known as quantum dots (QDs), are a rapidly growing class of materials in commercial electronics, such as light emitting diodes (LEDs) and photovoltaics (PVs). Among this material group, inorganic/organic perovskites have demonstrated significant improvement and potential towards high-efficiency, low-cost PV fabrication due to their high charge carrier mobilities and lifetimes. Despite the opportunities for perovskite QDs in large-scale PV and LED applications, the lack of fundamental and comprehensive understanding of their growth pathways has inhibited their adaptation within continuous nanomanufacturing strategies. Traditional flask-based screening approaches are generally expensive, labor-intensive, and imprecise for effectively characterizing the broad parameter space and synthesis variety relevant to colloidal QD reactions. In this work, a fully autonomous microfluidic platform is developed to systematically study the large parameter space associated with the colloidal synthesis of nanocrystals in a continuous flow format. Through the application of a novel translating three-port flow cell and modular reactor extension units, the system may rapidly collect fluorescence and absorption spectra across reactor lengths ranging 3 - 196 cm. The adjustable reactor length not only decouples the residence time from the velocity-dependent mass transfer, it also substantially improves the sampling rates and chemical consumption due to the characterization of 40 unique spectra within a single equilibrated system. Sample rates may reach up to 30,000 unique spectra per day, and the conditions cover 4 orders of magnitude in residence times ranging 100 ms - 17 min. Further applications of this system would substantially improve the rate and precision of the material discovery and screening in future studies. Detailed within this report are the system materials and assembly protocols with a general description of the automated sampling software and offline data processing.

Detailed herein are the operation and assembly protocols of a modular microfluidic screening platform for the systematic characterization of colloidal semiconductor nanocrystal syntheses. Through fully adjustable system arrangements, highly efficient spectra collection may be carried out across 4 orders of magnitude reaction time scales within a mass transfer-controlled sampling space.

胶体半导体纳米晶系统研究的模块化微流控技术

Colloidal semiconductor nanocrystals, known as quantum dots (QDs), are a rapidly growing class of materials in commercial electronics, such as light ...

工程学

A Continuous-flow Photocatalytic Reactor for the Precisely Controlled Deposition of Metallic Nanoparticles

In this work, a novel photocatalytic reactor for the pulsed and controlled excitation of the photocatalyst and the precise deposition of metallic nanoparticles is developed. Guidelines for the replication of the reactor and its operation are provided in detail. Three different composite systems (Pt/graphene, Pt/TiO2, and Au/TiO2) with monodisperse and uniformly distributed particles are produced by this reactor, and the photodeposition mechanism, as well as the synthesis optimization strategy, are discussed. The synthesis methods and their technical aspects are described comprehensively. The role of the ultraviolet (UV) dose (in each excitation pulse) on the photodeposition process is investigated and the optimum values for each composite system are provided.

For a continuous and scalable synthesis of noble-metal-based nanocomposites, a novel photocatalytic reactor is developed and its structure, operation principles, and product quality optimization strategies are described.

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

摘要

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