Name: continuous flow chemistry: reaction of diphenyldiazomethane with p-nitrobenzoic acid
Uploaded: 2017-11-15T15:00:00.000+00:00
Duration: 7 min 6 s
Description: Watch this Scientific Journal Video about Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid at JoVE.com

我们要感谢康宁玻璃流反应器的礼物。

健康警告和试剂规格 
二苯甲酮腙: 可能引起消化道发炎。该物质的毒理学性质尚未得到充分研究。可能引起呼吸道刺激。该物质的毒理学性质尚未得到充分研究。可能引起皮肤刺激和眼部刺激 18 . 
 活性氧化锰 (MnO 2 ): (健康 MSDS 等级为 2) 在皮肤接触, 眼睛接触, 摄入和吸入的情况下有危险 19 。
 二元磷酸钾 (2) PO 4 ): (健康 MSDS 评级为 2) 在皮肤接触, 眼睛接触, 摄入和吸入的情况下危险的 20 。
 二氯甲烷: (健康 MSDS 额定值为 2, 火等级为 1) 非常危险的情况下, 眼睛接触 (刺激性), 摄入, 吸入。皮肤接触时有危险 (刺激性, permeator)。眼睛发炎的特点是发红, 浇水, 发痒 21 . 
 1. Diphenyldiazomethane 的合成: <ol> <li> 在开始综合之前, 请确保所列的所有必需材料以及必要的试剂, 以确保能够进行适当的合成. </li>
	<li> 添加10克 (72 当量) 无水的, 2 PO 4 和31克活化二氧化锰, MnO 2 (3.5 当量) 到250毫升3颈圆底烧瓶 (1), 和磁力搅拌器. </li>
	<li> 将20克苯甲酮腙添加到单独的100毫升2颈圆底烧瓶 (2), 磁力搅拌器, 室温下贮存. </li>
	<li> 添加67毫升的二氯甲烷 (DCM), 并装备两个烧瓶 (1 和 2) 与塞子, 温度计, 和热电偶. </li>
	<li> 将两个烧瓶与惰性气体一起清除15分钟后, 将冰浴应用于 2 PO 4 和 MnO 2 解决方案 (烧瓶 1)。确保解决方案的温度在0和 #176 时保持不变; C 至少 30 min. </li>
	<li> 在30分钟的恒温读数后, 将二苯甲酮腙 (烧瓶 2) 转到包含 "2" PO 4 和 MnO 2 (烧瓶 1) 的烧瓶中。进行24小时的反应, 以达到完成. </li>
</ol> 2。纯化: <ol> <li> 在24小时后, 在反应混合物中加入120毫升戊烷 (深红色紫色溶液). </li>
	<li> 通过中性硅胶 (50-200 和 #181; m) 快速过滤解决方案。重要的是, 该产品的接触时间与二氧化硅做 不 超过5分钟, 是酸敏感的;在更长的接触时间 22 下会发生严重的分解. 
	<ol> <li> 在真空过滤系统或油烟罩真空系统上安装中孔烧结玻璃漏斗进行过滤. </li>
	</ol> </li> <li> 在真空 中将滤液和旋转蒸发器的溶剂移除。由此产生的原油产品是一种 deep-purple 的石油. 
	<ol> <li> 在烧瓶周围用铝箔包住, 以避免光线脱离。是光敏感的. </li>
	</ol> </li> <li> 在用铝箔盖好烧瓶后, 在冷冻库中储存纯净的气体, 密封, 并在惰性气体的气氛下. </li>
	<li> 显示器进行结晶, 通常需要 2-3 天。从冰箱取出烧瓶, 使其达到室温。一个进一步纯化步是必要的。在烧瓶中加入200的乙醇, 过滤然后用旋转蒸发器除去剩余的溶剂。此时, 剩余的大部分杂质应该被去除. 
	<ol> <li> 通过紫外光谱分析产生的深红色紫色晶体。实验测定的摩尔吸收率是 (和 #949;) 94.8, 与文献值匹配. 
		警告: 下面是相关的健康警告和试剂的规格, 以正确和安全地处理执行的反应协议的管理。在处理这些物质时, 要确保在任何时候都有适当的 PPE 和通风罩下的工作环境. 
		 : 长期或重复暴露可能会导致某些敏感个体的过敏反应 23 . 
		 p -硝基苯甲酸: (MSDS 的健康等级为 2) 确保试剂远离热量。远离火源。空集装箱造成火灾风险;将残留物蒸发在通风罩下。研磨所有含有材料的设备。如果摄入, 立即寻求医疗建议, 并显示容器或标签。避免与皮肤和眼睛接触 24 . 
		乙醇, 200 证明: (MSDS 健康等级为 2, 健康等级为 3) 在皮肤接触, 眼睛接触和吸入的情况下危险。乙醇能迅速吸收空气中的水分, 并能与氧化剂 25 强烈反应. 
		甲苯: (MSDS 健康等级为 2, 健康等级为 3) 在皮肤接触 (刺激性), 眼睛接触 (刺激性), 摄入和吸入的情况下危险。皮肤接触时有轻微危险 (permeator)。高度易燃的 26 . 
		 o -二甲苯: (MSDS 的健康等级为 2, 健康等级为 3) 发育致畸作用的可能性, 对雄性生殖系统的发育毒性, 以及摄入肾脏、肝脏、上呼吸道、皮肤、眼睛和中央的毒性神经系统。远离皮肤接触 (刺激性, permeator), 眼睛接触 (刺激性), 或 #160; 摄入和 #160; 吸入 27 . </li>
	</ol> </li> </ol> 3。为连续流准备解决方案: <ol> <li> 用乙醇冲洗100毫升的容积烧瓶. </li>
	<li> 将6个 dram 小瓶放在分析天平上, 并将1942克的内存添加到 dram 瓶中。将无水乙醇 (5 毫升) 添加到小瓶中, 在2到3的增量中, 直到所有的方法都进入解决方案。用吸管将溶液从 6 dram 小瓶转移到清洁的100毫升容积烧瓶中. 
	<ol> <li> 小心地添加乙醇, 直到半月板的最小点与容量烧瓶中的线对齐. </li>
		<li> 加入1毫升的甲苯, 内部标准, 进入烧瓶。容积烧瓶现在可以封顶和储存, 直到两个解决方案和 p 硝基苯甲酸溶液都准备好连续流动反应. </li>
	</ol> </li> </ol> 4。 p 硝基苯甲酸 0.1 M 库存溶液的制备: <ol> <li> 用无水乙醇多次冲洗250毫升容积烧瓶. </li>
	<li> 在分析天平上包装一个 6 dram 小瓶。在 dram 瓶中加入4.1780 克的 p 硝基苯甲酸。加入酸后, 将无水乙醇 (5 毫升) 添加到2至3的小瓶中, 直到所有的 p 硝基苯甲酸进入溶液. 
	<ol> <li> 用吸管将溶液从 6 dram 小瓶转移到清洁的250毫升容积烧瓶中. </li>
		<li> 小心地添加乙醇直到半月板的最小点与容积烧瓶的线对齐. </li>
		<li> 添加1毫升 o -二甲苯, 内部标准, 进入 fl问.容积烧瓶现在可以根据需要进行封顶和储存. </li>
	</ol> </li> </ol> 5。连续流反应器的制备: <ol> <li> 检查传感器是否连接到门户 A 中的 ISCOs 的泵控制器, 以及每个出口管末端的空收集烧杯, 以收集反应解决方案、废料和溶剂. 
	<ol> <li> 设置并检查分类 1 ( p -硝基苯甲酸) 和分类 2 (数据), 如 图 9 所示. </li>
		<li> 设置每个分类泵与自己的控制器, 以独立控制试剂流。这样就可以根据需要独立调整流量. </li>
	</ol> </li> <li> 在单独的烧杯中, 添加400毫升的乙醇。这将被用来冲洗反应堆. 
	<ol> <li> 逆时针旋转入口阀, 直到阀门完全打开 (分别表示为阀 A 和 B)。压力机和 #34; 泵控制器上的恒流和 #34; 然后, #34; A 和 #34;, 表示传感器与分类连接的入口。此操作会提示用户输入所需的流率. </li>
		<li> 输入 #34 的流量; 70 和 #34;, 按下 #34; 输入和 #34;。当准备, 命中和 #34; 填充和 #34; 要与系统通信以70毫升/分钟的速度绘制解决方案. </li>
		<li> 开始通过入口管绘制乙醇溶剂。请注意, 如果流速是在绘制溶剂, ISCOs 的流速应改为-70.000 毫升/分钟。烧瓶中的溶剂水平将开始下降. 
		#8203; 注意: 如果溶剂的体积与控制器上显示的体积不符, 这是完全正常的。空气也会部分地被纳入到系统中. </li>
	</ol> </li> <li> 当分类1和分类2都已完全填满, 并且控制器通过读取和 #34 指示此项时; 已停止和 #34; #34; 停住; 关闭阀门 A 和 B 完全关闭, 完全顺时针转动阀. </li>
	<li> 打开阀门, 其操作方式类似于进气阀, 即通向反应堆的阀门, 通过逆时针旋转。出口阀通过过滤器, 通过 one-way 阀, 并从那里过去的压力释放阀和进入流反应器. </li>
	<li> 此时, 更改流率。在单个运行中建议的最大总流量不应超过30毫升/分钟. 
	<ol> <li> 分别清除每个分类, 以30毫升/分钟的流速运行每一个. </li>
	</ol> </li> <li> 按下和 #34; A 和 #34; 在当前设置为通过系统运行乙醇的分类上。通过输入所需的流量和 #34 来改变流速; 30 和 #34; #34; 进入 #34;, 最后, #34; 奔跑和 #34;。这与系统通信以30毫升/分钟的速率运行. 
	#8203; 注意: 当流动均衡, 溶剂开始流经系统。
	<ol> <li> 监视反应器中的泄漏或堵塞, 并在整个反应器中流动有溶剂。一旦两个 ISCOs 都被清理 2-3 次, 系统现在已经准备好运行这个实验. </li>
	</ol> </li> </ol> 6。设置. 01 M 分类2泵: <ol> <li> 将入口进给100毫升容积烧瓶中。打开进气阀 B (在 图 9 中为 2). </li>
	<li> 将分类设置为70毫升/分钟的流速. 开始绘制解决方案, 直到所有的它被拿起到注射器通过打击和 #34; 灌装和 #34;. </li>
	<li> 注意, 分类中的溶液体积和烧瓶中溶液的原始体积可能稍有不同。空气也被拉进了分类泵. 
	<ol> <li> 如果有剩余的分类, 则在解决方案的摄取量达到最大容量后, 按下 #34; 运行和 #34; 从入口向外推进与烧瓶一起绘制的空气。一旦开始推开, 打击和 #34; 停止和 #34; 然后, #34; 填充和 #34; 开始重新灌装分类. </li>
		<li> 继续重复这些步骤, 直到所有的占用都已占了 (这将被应用到 p 硝基苯甲酸以及). </li>
		<li> 流量约1毫升从泵。分类2泵已准备好运行。溶剂水平是在线的, 并准备开始流经连续流反应器. </li>
	</ol> </li> <li> 关闭入口阀 B, 将髋部阀门顺时针旋转, 直到它不能进一步转动, 然后打开向连续流反应器注入的出口阀, 将阀门逆时针旋转, 直到完全打开。将1毫升的试管和甲苯溶液转化为紫外-可见光分析. </li>
	<li> 将流率设置为1.42 毫升/分钟。不要攻击和 #34; 运行和 #34; 直到 p 硝基苯甲酸分类1已由同一协议设置为3.58 毫升/分钟的流速, 并准备串联运行. </li>
</ol> 7。设置. 1 M p 硝基苯甲酸分类1泵: <ol> <li> 打开分类1泵的入口阀 A, 在进料管的末端有250毫升的 p-硝基苯甲酸的容积烧瓶. 
	<li> 一旦进料管完全浸入容积式烧瓶中, 则将分类设置为70毫升/分钟的流量。再次, 检查控制器上的流量是否在命中和 #34 时读取70.00 毫升/分钟; 重新填充和 #34;. </li>
	<li> 开始绘制解决方案, 直到所有的问题都被注入到注射器中, 然后使用上面列出的相同技术将所有解决方案放入系统中. </li>
	<li> 按顺时针方向关闭入口阀, 直到完全闭合。打开向连续流反应器注入的出口阀门, 将阀门逆时针旋转直到完全打开. </li>
	<li> 将流率设置为3.58 毫升/分钟。总的流量, 包括1.42 毫升/分钟的计算将是5.00 毫升/分钟, 在一个总停留时间在反应器内大约11分钟, 与 10:1 p 硝基苯甲酸的比率. </li>
</ol> 8。用10:1 摩尔当量的 p -硝基苯甲酸和流量来传导反应: <ol> <li> 一旦每个泵都准备好试剂和 #39; s 溶液, 阀门适当地调整, 并且正确的流速被输入了, 命中#34; 在两个水泵上运行和 #34;one-way 阀压力平衡后, 试剂和 #39 的解决方案将开始流入反应堆模块. 
	<ol> <li> 监视流。在模块 1, p -硝基苯甲酸和 #39 的进料进入模块 2, 混合发生在模块3。居住时间大约是11分钟. </li>
		<li> 监视颜色更改 (指示反应进度)。模块2的颜色, 在混合之前, 是强的粉红色。颜色强度降低, 它变得暗淡粉红色在模块3和苍白粉红色的模块4。模块尔后是无色的. </li>
	</ol> </li> </ol> 9。清洗连续流反应器: <ol> <li> 一旦两个运行的管理和 p 硝基苯甲酸完成, 填补一个烧杯与400毫升乙醇。这将用于清洁反应堆和分类泵. </li>
	<li> 逆时针旋转入口阀, 直到阀门完全打开. </li>
	<li> 将流率设置为 70, 按和 #34; 输入和 #34; #34; 填充和 #34; 通过进气管开始绘制乙醇溶剂 (注意, 如果流速是在吸入溶剂, ISCOs 的流速应为70毫升/分). </li>
	<li> 一旦填充了 ISCOs, ISCOs 将自动停止, 控制器将读取和 #34; 汽缸满 #34; #34; 停止 #34;。在这一点上, 关闭阀门完全关闭, 旋转阀顺时针, 直到髋部阀门不能进一步转向. </li>
	<li> 打开与进口阀门相似的出口阀门, 将其逆时针旋转。出口阀通过过滤器, 通过 one-way 阀, 并从那里流过压力释放阀和进入流动反应器. </li>
	<li> 调整流量不超过30毫升/分钟. </li>
	<li> 按 #34; #34; 在当前设置为通过系统运行乙醇的分类上。通过输入所需的流量和 #34 来更改流速; 10 和 #34; 命中和 #34; 输入和 #34;, 然后命中和 #34; 运行和 #34;检查系统, 看有没有泄漏或堵塞, 并有溶剂流经整个系统. 
	注: 一旦两个 ISCOs 已被清洗2次与乙醇, 一旦与公正的空气遵循上述步骤, 系统现在已经准备好运行, 为未来的实验. </li>
</ol>

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本议定书中的任何作者都没有任何相互竞争的金融利益或利益冲突。

最近, 在化学 (29%) 和工程学 (25%) 的研究领域中, 平均每年大约有1500份关于这个主题的出版物引起了流动化学的关注。许多成功的流程都是在流程中进行的。在许多情况动化学被证明表现出优异的性能 , 以批处理很多应用 , 如准备药学活性成分30,31, 自然产品32, 以及专业, 高价值的化学品, 如高性能的聚合物33,<s...

绿色化学与工程正在为工业的未来方向创造文化变革1,2,3,4。通过 "扩展" 策略, 而不是传统的 "向上扩展"5 , 连续流技术已被确定为利用优异的混合、传热和成本节约的环境和经济优势的工具。,6,7,8,9,10。
虽然制药行业等高价值产品的行业长期青睐批量加工, 但由于经济竞争和商业生产效益的不断增加, 流动技术的优势已变得十分诱人11. 例如, 当扩展批处理过程时, 必须建立和操作先导刻度单位, 以确定精确的热传导和传质机制。这是几乎不可持续的并且从产品的适销对路的专利生活极大地减去。相比之下, 连续流程处理允许扩展的优势, 消除了与生产规模相关的先导工厂阶段和工程-一项重大的财务激励。除了经济影响之外, 连续的技术还能使原子能和能源效率的过程。例如, 增强的混合改善了双相系统的传质, 从而提高了产量、催化剂回收策略和随后的回收计划。此外, 准确地管理反应温度的能力导致反应动力学的精确控制和产品分布12。强化过程控制、产品质量 (产品选择性) 和重现性都对环境和财务观点都有影响力。
流动反应器是可利用的商业与各种各样的大小和设计。此外, 可以很容易地实现对反应器的定制以满足工艺需要。在此, 我们报告在玻璃连续流反应器中进行的实验 (图 1)。由玻璃制成的微结构 (161 毫米 x 131 mm x 8 mm) 的组装与多种化学品和溶剂相兼容, 并且在广泛的温度范围内 (-25–200° c) 和压力 (高达 18 bar) 具有耐腐蚀性。设计了 multi-injection、高性能混合、弹性停留时间、精确传热的显微组织及其布置。所有的显微组织都装有两个射流层 (-25–200° c, 高达 3 bar), 用于在反应层的两侧进行热交换。传热速率与传热面面积成正比, 与体积成反比。因此, 这些微结构促进了最佳的表面积比以改善传热。有两种类型的微结构 (即模块): "混合" 模块和 "线性" 模块 (图 2)。心形 "混合" 模块的设计, 以诱导湍流和最大的混合。相反, 线性模块提供额外的居留时间。
作为概念的证明, 我们选择了羧酸 diphenyldiazomethane 的描述反应13,14,15,16,17。反应方案显示在图 3中。质子从羧酸到 diphenyldiazomethane 的初始转移是缓慢的, 是速率决定的步骤。第二步是快速, 产生反应产物和氮。初步研究了有机羧酸的相对酸度 (质子和质子) 的反应。反应是第一顺序在 diphenyldiazomethane 和一阶在羧酸。
实验中, 这种反应是在大量过量的羧酸 (10 摩尔当量) 的存在下进行的。因此, 这一比率是伪的第一个订单就 diphenyldiazomethane。通过将实验所得的伪一阶速率常数除以羧酸的初始浓度, 即可得到二阶速率常数。初步研究了 diphenyldiazomethane 与苯甲酸 (pKa = 4.2) 的反应。在间歇期, 反应似乎相对缓慢, 在96分钟内达到约90% 的转换。由于反应速率与羧酸的酸度成正比, 我们选择作为反应伙伴的酸性羧酸、 p硝基苯甲酸 (pKa = 3.4) 来缩短反应时间。因此, 在间歇和流中对 diphenyldiazomethane 在无水乙醇中的反应进行了研究 ( 图 4)。下一节将详细介绍结果。
当反应在乙醇中进行时, 可以形成三产品: (i) benzhydryl-4-nitrobenzoate, 这是由p硝基苯甲酸与甲烷氮中间体的反应产生的;(二) 从溶剂、乙醇和甲烷氮反应得到的 benzhydryl 乙醚;和 (iii) 氮。产品分布没有研究, 因为它在文献中有很好的记载;相反, 我们关注的是批量反应的技术转移到连续流13,14,15。实验 diphenyldiazomethane 的消失被监测。反应进行生动的颜色变化, 可以直观地观察到紫外-可见光谱。这是由于 diphenyldiazomethane 是一种强烈的紫色化合物, 而所有其他的反应产物都是无色的。因此, 这种反应可以在定性的基础上进行目视监测, 并定量地遵循紫外光谱 (即 525 nm 的二苯基甲烷吸收消失)。本文首先报告了 diphenyldiazomethane 和p硝基苯甲酸在间歇性乙醇中的反应, 作为时间的函数。然后将反应成功地转移到玻璃流反应器中进行。利用紫外光谱 (分批和流态) 监测 diphenyldiazomethane 的消失, 确定了反应的进展。

<table><tbody><tr><td>Thermometer</td><td>HB-USA/ Enviro-safe</td><td></td><td>Any other instrument scientific company provider works</td></tr><tr><td>Benzophenone hydrazone</td><td>Sigma-Aldrich</td><td></td><td>Store at 2-8 &amp;deg;C, 96% purity</td></tr><tr><td>Activated MnO&lt;span class=&quot;font6&quot;&gt;&lt;sub&gt;2&lt;/sub&gt;&lt;/span&gt;</td><td>Fluka</td><td></td><td>&amp;ge; 90% purity, harmful if inhaled or swallowed. Refer to MSDS for more safety precautions</td></tr><tr><td>Dibasic KH&lt;sub&gt;2&lt;/sub&gt;PO&lt;sub&gt;4&lt;/sub&gt;</td><td>Sigma-Aldrich</td><td></td><td>Serious eye damage, respiratory irritant. Refer to MSDS for more safety precautions</td></tr><tr><td>Dichloromethane (DCM)</td><td>Alfa Aesar</td><td></td><td>&amp;ge; 99.7% purity, argon packed</td></tr><tr><td>Rotovap</td><td>B&amp;uuml;chi</td><td></td><td>accessory parts include Welch self-cleaning dry vacuum model 2027, and Neuberger KNP dry ice trap&amp;nbsp;</td></tr><tr><td>Bump trap</td><td>Chemglass</td><td></td><td>Any other instrument scientific company provider works&amp;nbsp;</td></tr><tr><td>Neutral Silica Gel (50-200 mM)</td><td>Acros Organic/ Sorbent Technology</td><td></td><td>Respiratory irritant if inhaled, refer to MSDS for more safety precautions</td></tr><tr><td>Inert Argon Gas</td><td>Airgas</td><td></td><td>Always ensure proper regulator is in place before using</td></tr><tr><td>Medium Porosity Sintered Funnel Glass Filter</td><td>Sigma-Aldrich</td><td></td><td>Any other instrument scientific company provider works</td></tr><tr><td>Aluminum Foil</td><td>Reynolds Wrap</td><td></td><td>Any other company works. Used to prevent photolytic damage towards DDM</td></tr><tr><td>Para-NO&lt;sub&gt;2&lt;/sub&gt; benzoic acid</td><td>Sigma-Aldrich</td><td></td><td>Skin contact irritant, eye irritant, respiratory irritant. Refer to MSDS for more safety precautions</td></tr><tr><td>Pure ethyl alcohol (200 proof)</td><td>Sigma-Aldrich</td><td></td><td>&amp;ge; 99.5% purity, anhydrous. Highly flammable</td></tr><tr><td>Toluene</td><td>Sigma-Aldrich</td><td></td><td>&amp;ge; 99.8% purity, anhydrous. Skin permeator, flammable</td></tr><tr><td>Ortho-xylene</td><td>Sigma-Aldrich</td><td></td><td>99% purity, anhydrous. Toxic to organs and CNS. Adhere to specifications dictated within MSDS</td></tr><tr><td>Diphenyl diazo methane</td><td>Produced in-house</td><td></td><td>Respiratory irritant, refer to MSDS for more safety precautions</td></tr><tr><td>Corning reactor</td><td>Corning Proprietary</td><td></td><td>Manufactured in 2009. model number MR 09-083-1A</td></tr><tr><td>Stop watch</td><td>Traceable Calibration Control Company</td><td></td><td>Any other company that provides monitoring with laboratory grade accredidation works</td></tr><tr><td>Analytical balance</td><td>Denver Instruments</td><td></td><td>Model M-2201, or any analytical balance that has sub-milligram capabilities</td></tr><tr><td>Dram vials</td><td>VWR</td><td></td><td>2 dram, 4 dram, and 6 dram vials&amp;nbsp;</td></tr><tr><td>Micropipettes</td><td>Eppendorf</td><td></td><td>2-20 &amp;mu;L and 100-1000 &amp;mu;L micropipettes work</td></tr><tr><td>Glass pipettes</td><td>VWR</td><td></td><td>Any other instrument scientific company provider works</td></tr><tr><td>GC-MS</td><td>Shimadzu GC</td><td></td><td>Software associated: GC Real Time Analysis</td></tr><tr><td>GC vials</td><td>VWR</td><td></td><td>Any other providing company works</td></tr><tr><td>Beakers</td><td>Pyrex</td><td></td><td>500 mL beakers&amp;nbsp;</td></tr><tr><td>Syringe pumps</td><td>Sigma Aldrich</td><td></td><td>Teledyne Isco Model 500D</td></tr><tr><td>Relief valve</td><td>Swagelok</td><td></td><td>Spring loaded relieve valve&amp;nbsp;</td></tr><tr><td>One-way valves</td><td>Nupro&amp;nbsp;</td><td></td><td>10 psi grade</td></tr><tr><td>Two-way straight valves</td><td>HiP</td><td></td><td>15,000 psi grade</td></tr></tbody></table>

continuous flow chemistry: reaction of diphenyldiazomethane with p-nitrobenzoic acid

连续流技术被确定为它的环境和经济优势的工具, 利用优越的混合, 传热和成本节约通过 "扩展" 战略, 而不是传统的 "扩大"。在此, 我们报告的反应 diphenyldiazomethane 与p硝基苯甲酸在批和流模式。为了有效地将反应从批处理转移到流模式, 必须在批处理过程中首先进行反应。因此, diphenyldiazomethane 的反应首先作为温度、反应时间和浓度的函数来研究, 以获得动力学信息和工艺参数。描述了玻璃流反应器的结构, 并将两类反应模块结合为 "混合" 和 "线性" 显微组织。最后, 在流动反应器中成功地进行了 diphenyldiazomethane 与p硝基苯甲酸的反应, 在11分钟内, diphenyldiazomethane 的转化率高达95%。这一概念反应的证明旨在为科学家们提供洞察力, 以考虑流动技术的竞争力、可持续性和在其研究中的通用性。

间歇反应 Diphenyldiazomethane 根据文献28,29编写。该化合物由石油醚结晶而成: 乙酸乙酯 (100:2) 和紫晶固体, 用 H1核磁共振、熔点和 MS 进行了分析。分析结果与文献资料的结构和报道的价值是一致的。
diphenyldiazomethane (1.0 毫米) 与苯甲酸 (10 毫米) 在无水乙醇中的反?...

Watch this Scientific Journal Video about Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid at JoVE.com

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

流动化学通过利用优异的混合、传热和成本效益来实现环境和经济优势。在此, 我们提供了一个蓝图, 从分批转移到流程模式的化学过程。采用间歇和流动的方法对 diphenyldiazomethane 的反应进行了研究, 选择了以批和流为依据的p硝基苯甲酸。

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 ...

continuous-flow-chemistry-reaction-diphenyldiazomethane-with-p

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

Unit 1

Carboxylic Acids

Chemical Kinetics

SCIENTISTS IN ACTION

11.4K 次观看.  Georgia Institute of Technology. 流动化学通过利用优异的混合、传热和成本效益来实现环境和经济优势。在此, 我们提供了一个蓝图, 从分批转移到流程模式的化学过程。采用间歇和流动的方法对 diphenyldiazomethane 的反应进行了研究, 选择了以批和流为依据的p硝基苯甲酸。

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

Ethylene Polymerizations Using Parallel Pressure Reactors and a Kinetic Analysis of Chain Transfer Polymerization

We demonstrate a method for high-throughput catalyst screening using a parallel pressure reactor starting from the initial synthesis of a nickel &#945;-diimine ethylene polymerization catalyst. Initial polymerizations with the catalyst lead to optimized reaction conditions, including catalyst concentration, ethylene pressure and reaction time. Using gas-uptake data for these reactions, a procedure to calculate the initial rate of propagation (kp) is presented. Using the optimized conditions, the ability of the nickel &#945;-diimine polymerization catalyst to undergo chain transfer with diethylzinc (ZnEt2) during ethylene polymerization was investigated. A procedure to assess the ability of the catalyst to undergo chain transfer (from molecular weight and 13C NMR data), calculate the degree of chain transfer, and calculate chain transfer rates (ke) is presented.

A protocol for the high-throughput analysis of polymerization catalyst, chain transfer polymerizations, polyethylene characterization, and reaction kinetic analysis is presented.

乙烯聚合中使用并联电抗器的压力和链转移聚合的动力学分析

We demonstrate a method for high-throughput catalyst screening using a parallel pressure reactor starting from the initial synthesis of a nickel ...

科研

化学

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from benzimidazolium salts. Detailed and generalized protocols are also presented for testing the catalytic activity of such complexes in arylation and Suzuki-Miyaura cross-coupling reactions. Representative results are shown for the catalytic activity of the four complexes in arylation and Suzuki-Miyaura type reactions. For each of the reactions investigated, at least one of the four complexes successfully catalyzed the reaction, qualifying them as promising candidates for catalysis of many carbon-carbon bond-forming reactions. The protocols presented are general enough to be adapted for the synthesis, purification and catalytic activity testing of new palladium N-heterocyclic carbene complexes.

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from benzimidazolium salts. The complexes were tested for catalytic activity in arylation and Suzuki-Miyaura reactions. For each reaction investigated, at least one of the four complexes successfully catalyzed the reaction.

钯<em&gt;ñ</em&gt; - 杂环碳烯配合物:苯并咪唑盐的合成和碳 - 碳键合反应中的催化活性

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from ...

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 ...

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the aziridine ring. The utility of bicyclic aziridinium ions, specifically 1-azoniabicyclo[3.1.0]hexane and 1-azoniabicyclo[4.1.0]heptane tosylate highlighted in the aziridine ring openings by the nucleophile with the release of the ring strain to yield the corresponding ring-expanded azaheterocycles such as pyrrolidine, piperidine and azepane with diverse substituents on the ring in regio- and stereospecific manner. Herein, we report a simple and convenient method for the preparation of the stable 1-azabicyclo[4.1.0]heptane tosylate followed by selective ring opening via a nucleophilic attack either at the bridge or at the bridgehead carbon to yield piperidine and azepane rings, respectively. This synthetic strategy allowed us to prepare biologically active natural products containing piperidine and azepane motif including sedamine, allosedamine, fagomine and balanol in highly efficient manner.

Bicyclic aziridinium ions such as 1-azoniabicyclo[4.1.0]heptane tosylate were generated from 2-[4-tolenesulfonyloxybutyl]aziridine, which was utilized for the preparation of substituted piperidines and azepanes via regio- and stereospecific ring-expansion with various nucleophiles. This highly efficient protocol allowed us to prepare diverse azaheterocycles including natural products such as fagomine, febrifugine analogue and balanol.

稳定笼 Aziridinium 离子的制备及其开环 Azaheterocycles 的合成

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the ...

[(DPEPhos)(bcp)Cu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst

Our group recently reported the use of [(DPEPhos)(bcp)Cu]PF6 as a general copper-based photoredox catalyst which proved efficient to promote the activation of a broad variety of organic halides, including unactivated ones. These can then participate in various radical transformations such as reduction and cyclization reactions, as well as in the direct arylation of several (hetero)arenes. These transformations provide a straightforward access to a range of small molecules of interest in synthetic chemistry, as well as to biologically active natural products. Altogether, [(DPEPhos)(bcp)Cu]PF6 acts as a convenient photoredox catalyst which appears to be an attractive, cheap and complementary alternative to the state-of-the-art iridium- and ruthenium-based photoredox catalysts. Here, we report a detailed protocol for the synthesis of [(DPEPhos)(bcp)Cu]PF6, as well as NMR and spectroscopic characterizations, and we illustrate its use in synthetic chemistry for the direct arylation of (hetero)arenes and radical cyclization of organic halides. In particular, the direct arylation of N-methylpyrrole with 4-iodobenzonitrile to afford&#160;4-(1-methyl-1H-pyrrol-2-yl)benzonitrile and the radical cyclization of N-benzoyl-N-[(2-iodoquinolin-3-yl)methyl]cyanamide to afford natural product luotonin A are detailed. The scope and limitations of this copper-based photoredox catalyst are also briefly discussed.

[DPEPhosbcpCu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst

Detailed and general protocols are presented for the synthesis of [(DPEPhos)(bcp)Cu]PF6, a general copper-based photoredox catalyst, and for its use in synthetic chemistry for the direct arylation of C-H bonds in (hetero)arenes and radical cyclization of organic halides.

[(Dpepphos) (bcp) Cu]PF6: 一种通用的、广泛适用的铜基光氧催化剂

Our group recently reported the use of [(DPEPhos)(bcp)Cu]PF6 as a general copper-based photoredox catalyst which proved efficient to promote the ...

A Scalable Balz-Schiemann Reaction Protocol in a Continuous Flow Reactor

The demand for aromatic fluorides is steadily increasing in the pharmaceutical and fine chemical industries. The Balz-Schiemann reaction is a straightforward strategy for preparing aryl fluorides from aryl amines, via the preparation and conversion of diazonium tetrafluoroborate intermediates. However, significant safety risks exist in handling the aryl diazonium salts when scaling up. In order to minimize the hazard, we present a continuous flow protocol that has been successfully performed at a kilogram scale that eliminates the isolation of aryl diazonium salts while facilitating efficient fluorination. The diazotization process was performed at 10 &#176;C with a residence time of 10 min, followed by a fluorination process at 60 &#176;C with a residence time of 5.4 s with about 70% yield. The reaction time has been dramatically reduced by introducing this multi-step continuous flow system.

A detailed scalable continuous flow protocol is presented to synthesize an aryl fluoride from an aryl amine through the Balz-Schiemann reaction.

连续流反应器中的可扩展巴尔茨-席曼反应方案

The demand for aromatic fluorides is steadily increasing in the pharmaceutical and fine chemical industries. The Balz-Schiemann reaction is a ...

Molecular Orbital (MO) Theory

Source: Tamara M. Powers, Department of Chemistry, Texas A&#38;M University
This protocol serves as a guide in the synthesis of two metal complexes featuring the ligand 1,1&#39;-bis(diphenylphosphino)ferrocene (dppf): M(dppf)Cl2, where M = Ni or Pd. While both of these transition metal complexes are 4-coordinate, they exhibit different geometries at the metal center. Using molecular orbital (MO) theory in conjunction with 1H NMR and Evans method, we will determine the geometry of these two compounds.

Molecular Orbital MO Theory: Predicting Geometry of Transition Metal Complexes

分子轨道 (MO) 理论

Source: Tamara M. Powers, Department of Chemistry, Texas A&#38;M University
This protocol serves as a guide in the synthesis of two metal complexes ...

教育

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无机化学

Carboxylic Acids to Methylesters: Alkylation using Diazomethane

Carboxylic acids react with diazomethane in an ether solvent&#160;via alkylation at the carboxylate oxygen atom&#160;to give&#160;methyl esters of the corresponding acid with excellent yields.
<img alt="Figure1" src="/files/ftp_upload/12349/12349_PT_Figure_1.svg" style="text-align: center; height: 60px;" />
Diazomethane is a yellow gas having a boiling point of &#8722;23 &#176;C. It is conveniently prepared by the action of a base on N-methyl-N-nitrosourea or N-methyl-N-nitrosotoluenesulphonamide.
The esterification mechanism involves the protonation of diazomethane by the carboxylic acid to yield a carboxylate salt and methyldiazonium cation. The methyldiazonium cation is highly unstable due to the presence of N&#8801;N, which&#160;functions as an excellent leaving group.
<img alt="Figure2" src="/files/ftp_upload/12349/12349_PT_Figure_2.svg" style="text-align: center; height: 72px;" />
In the final alkylation step,&#160;an SN2 attack on the methyldiazonium ion by the carboxylate anion&#160;produces a methyl ester, along with the elimination of N2 gas.
<img alt="Figure3" src="/files/ftp_upload/12349/12349_PT_Figure_3.svg" style="text-align: center; height: 70px;" />
However, diazomethane&#160;is a potentially explosive gas and requires precautions during its handling and storage. It undergoes spontaneous detonation upon contact with rough or scratched surfaces. Therefore, flame-polished glassware and a blast shield are often recommended in reactions involving diazomethane. Moreover, diazomethane is highly toxic as well as&#160;carcinogenic.
Diazomethane decomposes in the presence of heat or light to generate carbenes and eliminate nitrogen.
<img alt="Figure4" src="/files/ftp_upload/12349/12349_PT_Figure_4.svg" style="text-align: center; height: 52px;" />

羧酸制甲酯:使用重氮甲烷进行烷基化

Carboxylic acids react with diazomethane in an ether solvent&#160;via alkylation at the carboxylate oxygen atom&#160;to give&#160;methyl esters of the ...

有机化学

关键术语与概念

Hydrolysis of Chlorobenzene to Phenol: Dow Process

Simple aryl halides do not react with nucleophiles under normal conditions. However, the reaction can proceed under drastic conditions involving high temperatures and high pressure&#160;to give the substituted products. For example,&#160;chlorobenzene is converted to&#160;phenol using&#160;aqueous sodium hydroxide at 350 &#176;C&#160;under high pressure by the Dow process. The reaction follows an elimination-addition mechanism involving a benzyne intermediate. Here, the chloride ion is eliminated to generate the benzyne intermediate. The benzyne intermediate then reacts with the base, followed by&#160;an acid workup that&#160;generates phenol as the final product.

氯苯水解制苯酚:陶氏工艺

Simple aryl halides do not react with nucleophiles under normal conditions. However, the reaction can proceed under drastic conditions involving high ...

Reactions of Aromatic Compounds

Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions

Arenediazonium substitution reactions occur when the diazonium group is substituted by various functional groups such as halides, hydroxyl, nitrile, etc. For instance, arenediazonium salts react with copper(I) salts of chloride, bromide, or cyanide to form corresponding aryl chlorides, bromides, and nitriles. These reactions are named Sandmeyer reactions. Although the mechanism of this reaction is complicated, as illustrated in Figure 1, they are believed to progress via an aryl copper intermediate.
<img alt="Figure1" src="/files/ftp_upload/12539/12539-PT_Figure_1.svg" style="text-align: center; height: 275px;" />
Figure 1. The formation of aryl halides and nitriles via the Sandmeyer reaction
The hydrolysis of aryl nitriles into carboxylic acids is very facile. In this context, the Sandmeyer reaction plays a crucial role in converting aryl amines to substituted benzonitrile, as shown in Figure 2.
<img alt="Figure2" src="/files/ftp_upload/12539/12539-PT_Figure_2.svg" style="text-align: center; height: 85px;" />
Figure 2. The conversion of aryl amines to substituted benzonitrile.
Sandmeyer reactions are not used to prepare aryl fluorides and aryl iodides. For aryl fluorides, the arenediazonium salts react with fluoroboric acid to give diazonium fluoroborate in the form of a precipitated salt. As depicted in Figure 3, these residues are isolated, dried, and heated until they decompose to form the corresponding aryl fluorides. Such reactions are named Schiemann reactions. Similarly, arenediazonium salts react with potassium iodide to form aryl iodides.
<img alt="Figure3" src="/files/ftp_upload/12539/12539-PT_Figure_3.svg" style="text-align: center; height: 90px;" />
Figure 3. The formation of aryl fluoride via the Schiemann reaction.

用卤素和氰化物取代重氮基团:Sandmeyer 和 Schiemann 反应

Arenediazonium substitution reactions occur when the diazonium group is substituted by various functional groups such as halides, hydroxyl, nitrile, etc. ...