Name: microwave-assisted preparation of 1-aryl-1h-pyrazole-5-amines
Uploaded: 2019-06-23T14:00:00
Description: Watch this Scientific Journal Video about Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines at JoVE.com

这项研究得到了比尔和琳达·弗罗斯特基金的支持。

注意:请在使用前查看所有相关材料安全数据表 (MSDS)。使用微波反应器时,请遵循所有适当的安全做法,包括审查微波反应器协议和使用个人防护设备(安全眼镜、手套、实验室外套、全长裤子、闭趾鞋)。此过程旨在使用丙烯酸氢化物和 3-氨基克罗酮或 β-氰酮。应根据制造商指定的反应量度使用适当的微波炉小瓶和搅拌棒。
1. 制备反应混合物
注:盐酸4氟苯甲?...

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O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microwave-assisted+synthesis+of+tetrahydro-&#946;-carbolines+and+&#946;-carbolines.">Microwave-assisted synthesis of tetrahydro-&#946;-carbolines and &#946;-carbolines.</a> European Journal of Organic Chemistry. (8), 1653-1665 (2014).</li><li>Everson, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microwave+synthesis+of+1-aryl-1H-pyrazole-5-amines.">Microwave synthesis of 1-aryl-1H-pyrazole-5-amines.</a> Tetrahedron Letters. 60 (1), 72-74 (2019).</li></ol>

通过将β-氰酮或3-氨基克罗尼酮与1M HCl中的丙烯氢化物结合,并在微波反应器中加热至150°C,制备了多种1-aryl-1 H-pyrazole-5胺。几乎所有的化合物在10-15分钟内合成,最慢的基板需要35分钟的加热14。使用水作为溶剂可快速加热溶液,并最大限度地减少危险有机溶剂的使用。
微波反应器中当然可以达到更高的温度和压力,但反应混合物只加热到150°C,以便安全地将...

由于这些小分子的无数应用,能够推动1-aryl-1 H-pyrazole-5胺的流线化合成。它们出现在激酶抑制剂1,抗生素2,杀虫剂3,和许多其他生物活性化合物4,5。这些化合物的合成方案非常丰富,但大多数都涉及复杂的隔离和纯化技术。一种常见的方法包括在酒精或水溶液中反流丙烯和3-氨基克罗诺辛,然后通过色谱和/或再结晶进行随后的纯化 6、7、 8,9,10.少数孤立的报告详细说明了这些化合物使用微波辐射的合成,但所有方法都需要大量的加热时间,与以前报告的其他方法11、12相比,几乎没有任何优势。.
尽管它们用途广泛,但从商业供应商那里可以获得的1-aryl-1 H-pyrazole-5胺数量有限。我们最近成功地利用微波反应器13制备了氮异变周期,并决定研究一种用于pyrazole-5-胺模拟物的相关方法。在本文中,我们详细介绍了在微波辐射下,在微波辐射下,在1M HCl中与3氨基甲苯或β-氰酮反应的丙烯氢化物,制备1-aryl-1 H-pyrazole-5-胺的程序。这个程序的优点包括反应时间短,并能够纳入各种功能组,包括卤化物,硝基,酚类,磺胺和硝基组14。

<table border="0" cellpadding="0" cellspacing="0" style="width:757px;" width="757">
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		<col />
		<col />
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	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:284px;">2-5mL Microwave vial set</td>
			<td style="width:121px;">Chemglass</td>
			<td style="width:185px;">CG-4920-01&#160;</td>
			<td style="width:167px;">Set includes appropriate stir bars and 20mm aluminum seals</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:284px;">Biotage Initiator+ microwave</td>
			<td style="width:121px;">Biotage</td>
			<td style="width:185px;">356007</td>
			<td>Includes crimper and decapper tool.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:284px;">Sonicator</td>
			<td style="width:121px;">Kendal</td>
			<td style="width:185px;">Ultrasonic Cleaner GB-928</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:284px;">Glassware oven</td>
			<td style="width:121px;">Quincy Lab</td>
			<td style="width:185px;">20GC</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:284px;">4-Fluorophenylhydrazine hydrochloride</td>
			<td style="width:121px;">Fisher</td>
			<td style="width:185px;">AC119590100</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:284px;">3-Aminocrotonitrile</td>
			<td style="width:121px;">Fisher</td>
			<td style="width:185px;">AC152451000</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:284px;">CDCl3</td>
			<td style="width:121px;">Cambridge Labs</td>
			<td style="width:185px;">DLM-7-100</td>
			<td>99.8% D</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:284px;">Hydrochloric acid, concentrated</td>
			<td style="width:121px;">Fisher</td>
			<td style="width:185px;">A144SI-212</td>
			<td>Used to prepare 1 M HCl solution</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:284px;">Sodium hydroxide pellets</td>
			<td style="width:121px;">Fisher</td>
			<td style="width:185px;">S318-100</td>
			<td>Used to prepare 10% NaOH solution</td>
		</tr>
	</tbody>
</table>

microwave-assisted preparation of 1-aryl-1h-pyrazole-5-amines

开发了一种用于制备各种1-aryl-1H-pyrazole-5胺的合成工艺。该方法的微波介导特性使其在时间和资源上都有效,并利用水作为溶剂。3-氨基克罗酮酸盐或适当的β-氰酮与丙烯氢化物结合,溶解在1 M HCl中。然后,在微波反应器中,在150°C下加热混合物,通常加热10-15分钟。该产品可以通过10%NaOH对溶液进行bas-beh化,并通过简单的真空过滤隔离所需的化合物,从而轻松获得。在这种反应中使用水作为溶剂,使其在生产中易于和实用,并且该方法很容易用于各种功能组。典型的分离产量范围从70-90%,反应可以在毫克到克尺度上执行,而观察到的产量变化很小或没有变化。这些分子及其衍生物的一些应用包括杀虫剂、抗疟疾和化疗药物等。

在本演示中,对3-氨基甲酸酯和4氟苯甲酸盐酸反应,以产生1-(4-氟芬基)-3-甲基-1 H-pyrazol-5-胺(图1)。图2 a所示的微波小瓶中起始材料的混合物显示了在1M HCl溶剂中组合起始材料所产生的异构悬浮液。建议在搅拌板上预混合溶液几秒钟,以确保搅拌棒可以自由旋转。微波反应发生后,溶液变成同质混合物,如图2 b</st...

Watch this Scientific Journal Video about Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines at JoVE.com

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines

1-Aryl-1H-pyrazole-5-胺由丙烯氢化物制备,与使用微波反应器的1M HCl溶液中的3氨基克罗诺辛或β-氰酮结合制备。大多数反应在10-15分钟内完成,纯产品可以通过真空过滤获得,典型的隔离产量为70-90%。

微波辅助制备1-Aryl-1 H-pyrazole-5胺

A synthetic process for the preparation of a variety of 1-aryl-1H-pyrazole-5-amines was developed. The microwave-mediated nature of this method makes it ...

本程序描述了一种在微波辐射下使用带3-阿米诺酮或α氰酮的丙烯氢化物分离1-Aryl-1H-pyrazole-5-amines的方法。这个程序的主要优点是快速反应时间，因为大多数反应在几分钟内完成。我们的程序还可耐受各种功能组，如卤化物、氮化物、苯酚、磺胺和异质环。为了使反应成功，关键是反应储存得当，微波在加热前要完全密封。首先，获得一个微波邪恶设计的反应体积为2至5毫升，已经干了一夜在玻璃器皿烤箱，并添加一个适当的搅拌棒。在烟气罩中，在微波炉中加入两千万千万万的四氟苯乙基氢胺酸和两毫摩尔的三氨基氯酮。然后，加入五毫升一摩尔盐酸，使起始试剂的浓度0.4摩尔。将卑鄙放在搅拌板上，搅拌异质悬架。如果反应物的溶解性差，且反应混合物不能正确搅拌，则将溶液转移到更大的卑鄙成分中，并添加额外的一个摩尔盐酸。避免超出微波反应器操作手册中指定的推荐溶剂量。现在，使用适当的压接机工具，用微波卑鄙的帽子密封微波卑鄙。将烟罩的邪恶转移到微波反应器中，将微波程序的反应时间调整到10分钟，温度在150摄氏度，吸收到非常高。在加热阶段，注意反应器压力。压力的突然下降可能表示泄漏或容器故障。一旦反应冷却到40摄氏度以下，将恶的不良反应从微波反应器转移到烟罩中。使用适当的贴花工具，拆下盖。在烟熏的嘘声中， 把微波炉夹在支撑板上。加入两毫升10%氢氧化钠搅拌，使产品立即沉淀。将溶液滴放在指示器纸中，以显示 pH 值大于 10。然后，将卑鄙者放在音速器中5至10分钟，以帮助根据需要混合。设置真空过滤装置，将溶液倒入漏斗中。用铲子刮掉卑鄙的东西，把产品从船壁上运出。然后，使用去电化水冲洗任何剩余的产品从微波炉卑鄙和清洗孤立的固体产品。在某些情况下，产品油出碱性溶液。使用二氯甲烷或乙酸乙酯获得液体萃取产品。之后，将原油转移到干燥器中，在一夜之间干燥。在德乌氯仿中获取质子 NMR 光谱，以确认产品特性和纯度。在本次演示中，对盐酸3-氨基氯酮和4氟苯乙二苯酸酯发生反应，产生1，4-氟苯基-3-甲基-1H-丙醇-5-胺。NMR 确认目标 5-氨基苯甲酸酯的合成，其特征单峰在化学转移区域之间为 5.4 至 6.0 ppm，对应于丙子四位置的芳香质子。通过改变反应的规模，用户可以迅速产生毫克到克的产品。还可以通过改变反应物来添加其他功能。我们方法的主要优点是，它允许快速合成1-Aryl-1H-丙类胺。这些是有用的脚手架，已经被纳入许多生物活性分子。在使用腐蚀性解决方案时，请记住遵循标准操作程序。使用微波炉反应器时，请遵守安全准则。

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Unit 1

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines

Aromatic Compounds

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化学

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