Name: synthesis of esters via a greener steglich esterification in acetonitrile
Uploaded: 2018-10-30T15:00:00
Description: Watch this Scientific Journal Video about Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile at JoVE.com

这项研究得到了锡耶纳学院和本科生研究和创意活动中心的支持。我们感谢托马斯休斯博士和克里斯托 Kolonko 博士的帮助对话, Allycia 女士为早期阶段的工作, 这一方法, 和锡耶纳学院斯图尔特的先进仪器仪表和技术 (圣) 仪器资源中心。

注意: 在本程序使用化学品之前, 请查阅安全数据表 (SDSs)。使用适当的个人防护设备 (PPE), 包括飞溅护目镜、实验室大衣、丁腈橡胶或丁基手套, 因为许多试剂和溶剂都是腐蚀性或易燃的。在烟雾罩中进行所有反应。不需要干燥的玻璃器皿或使用氮气气氛的协议。
1. 初级醇的氢化物偶联反应
<ol><li>在一个50毫升圆底烧瓶, 结合(E)-肉桂酸 (151 毫克, 1.02 毫摩尔, 1.2 等效), DMA...

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本文介绍的方法是通过使用更环保的溶剂系统和减少对柱层析8、9的需求, 将与传统 Steglich 酯化相关的溶剂的危害降至最低。可以通过使用乙腈代替干氯化溶剂或 DMF22来实现可比的反应屈服率和速率。
几个关键步骤可实现产品的高效纯化, 而无需进行色谱分析。反应后, 乙腈首先通过旋转蒸发去除。溶剂的去除是必...

酯类化合物广泛用于香精化合物、药品、化妆品和材料等应用领域。通常, 使用氢化物偶联试剂用于促进酯的形成从羧酸和酒精1。例如, 在 Steglich 酯化中, 碳 (DCC) 在存在 4-dimethylaminopyridine (DMAP) 时与羧酸反应, 形成活性酸衍生物, 通常在氯化溶剂体系中或二甲基甲酰胺 (DMF)2,3,4。激活后的酸衍生物, 然后经历一个亲核酰取代与酒精形成酯产品, 通常通过色谱纯化。Steglich 酯化可实现大型、复杂羧酸和醇的温和耦合, 包括空间位阻阻碍的二次和第三醇2、5、6。这项工作的目标是修改标准的 Steglich 酯化协议, 为这种常见的酯化反应提供更绿色的合成选项。
新合成方法设计的一个重要方面是力求尽量减少有害物质的使用和形成。十二绿色化学7原则可用于为创建更安全的合成提供指导。其中一些措施包括防止废物产生 (原则 1) 和使用更安全的溶剂 (原则 5)。特别是, 在制药制造8中, 溶剂占材料非水质量的80-90%。因此, 修改协议以使用更少的危险溶剂会对有机反应的绿色产生很大的影响。
Steglich 酯化反应常使用无水氯化溶剂体系或 DMF;然而, 这些溶剂是对环境和人类健康的关注。二氯甲烷 (CH2Cl2) 和氯仿 (氯仿3) 是可能的人类致癌物, 并且 DMF 具有生殖毒性问题9。此外, CH2Cl2是消耗臭氧的10。因此, Steglich 酯化的低危险溶剂将是非常有用的。虽然尚无极性非质子溶剂的绿色替代品, 但推荐使用乙腈作为绿色替代 CH2Cl2、氯仿3和 DMF9。乙腈是目前生产丙烯腈生产的副产品;然而, 从生物量上的一个绿色合成乙腈的学术规模已报告11, 并正在调查从废物流的重复使用和回收的潜在选择12。乙腈在固相肽合成中作为氢化物偶联反应的一种更环保的溶剂替代剂, 可形成酰胺链13。使用乙腈作为溶剂系统的 Steglich 酯化已经证明了14,15,16,17,18,19, 20,21;然而, 这些方法并没有侧重于溶剂的绿色方面, 也采用柱层析法进一步纯化。
减少对柱层析的需要作为纯化步骤, 也可最大限度地减少有害溶剂浪费8。除了使用不太危险的反应溶剂, 该方法还能在不需要色谱的情况下分离出高纯度的产品。传统上使用的碳 (DCC) 耦合试剂被取代 1-乙基 3-(3-丙基) 氢化物盐酸盐 (EDC)。该试剂的碱性胺官能团可使反应副产品和任何残留试剂通过酸性和基本洗涤步骤去除。
本文提供的协议可与各种酸性和酒精合作伙伴一起使用 (图 1)。它被用来合成一个小库肉桂酯衍生物使用初级, 二次, 苄基, 和烯丙醇和酚22。此外, 乙腈中酯化反应的速率与氯化和 DMF 溶剂体系中的相媲美, 在反应22之前无需干燥或蒸馏乙腈。从第三醇合成的酯类尚未分离, 这是目前的方法的局限性与传统的 Steglich 酯化在氯化溶剂23。此外, 其他酸不稳定基团可能会受到酸性洗涤步骤的影响, 可能需要柱层析来纯化乙腈后去除。尽管存在这些局限性, 该反应是一种简便而通用的方法, 用于在高产量中使用多种醇和羧酸组分合成酯。使用更环保的溶剂系统和高纯度而不需要色谱步骤, 使本协议成为传统 Steglich 酯化的诱人替代品。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/58803/58803fig1.jpg"> 图1。一般反应方案.反应的一般方案包括羧酸和酒精的耦合, 这是使用氢化物耦合试剂 (1-乙基-3-(3-丙基) 氢化物盐酸盐, 或 EDC) 和 4-dimethylaminopyridine (DMAP) 乙腈。为了证明反应的广度, 酯的形成使用各种酸 (1-5) 与主要 (6) 或次要 (7) 酒精。<a href="https://www.jove.com/files/ftp_upload/58803/58803fig1large.jpg" target="_blank">请点击这里查看这个数字的更大版本.</a>

<table>
	<tbody>
		<tr>
			<td>trans -cinnamic acid</td>
			<td>Acros Organics</td>
			<td>158571000</td>
			<td></td>
		</tr>
		<tr>
			<td>butyric acid</td>
			<td>Sigma-Aldrich</td>
			<td>B103500</td>
			<td>Caution: corrosive</td>
		</tr>
		<tr>
			<td>hexanoic acid</td>
			<td>Sigma-Aldrich</td>
			<td>153745-100G</td>
			<td>Caution: corrosive</td>
		</tr>
		<tr>
			<td>decanoic acid</td>
			<td>Sigma-Aldrich</td>
			<td>21409-5G</td>
			<td>Caution: corrosive</td>
		</tr>
		<tr>
			<td>phenylacetic acid</td>
			<td>Sigma-Aldrich</td>
			<td>P16621-5G</td>
			<td></td>
		</tr>
		<tr>
			<td>3-methoxybenzyl alcohol</td>
			<td>Sigma-Aldrich</td>
			<td>M11006-25G</td>
			<td></td>
		</tr>
		<tr>
			<td>diphenylmethanol</td>
			<td>Acros Organics</td>
			<td>105391000</td>
			<td>Benzhydrol</td>
		</tr>
		<tr>
			<td>chloroform-d</td>
			<td>Acros Organics</td>
			<td>166260250</td>
			<td>99.8% with 1% v/v tetramethylsilane, Caution: toxic</td>
		</tr>
		<tr>
			<td>hexane</td>
			<td>BDH Chemicals</td>
			<td>BDH1129-4LP</td>
			<td>Caution: flammable</td>
		</tr>
		<tr>
			<td>ethyl acetate</td>
			<td>Sigma-Aldrich</td>
			<td>650528</td>
			<td>Caution: flammable</td>
		</tr>
		<tr>
			<td>diethyl ether</td>
			<td>Fisher Scientific</td>
			<td>E138-500</td>
			<td>Caution: flammable</td>
		</tr>
		<tr>
			<td>acetonitrile</td>
			<td>Fisher Scientific</td>
			<td>A21-1</td>
			<td>ACS Certified, &#62;99.5%, Caution: flammable</td>
		</tr>
		<tr>
			<td>4-dimethylaminopyridine</td>
			<td>Acros Organics</td>
			<td>148270250</td>
			<td>Caution: toxic</td>
		</tr>
		<tr>
			<td>magnesium sulfate</td>
			<td>Fisher Scientific</td>
			<td>M65-3</td>
			<td></td>
		</tr>
		<tr>
			<td>hydrochloric acid, 1 M</td>
			<td>Fisher Scientific</td>
			<td>S848-4</td>
			<td>Caution: corrosive</td>
		</tr>
		<tr>
			<td>sodium chloride</td>
			<td>BDH Chemicals</td>
			<td>BDH8014</td>
			<td></td>
		</tr>
		<tr>
			<td>sodium bicarbonate</td>
			<td>Fisher Scientific</td>
			<td>S25533B</td>
			<td></td>
		</tr>
		<tr>
			<td>1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride</td>
			<td>Chem-Impex</td>
			<td>00050</td>
			<td>Caution: skin and eye irritant</td>
		</tr>
		<tr>
			<td>thin layer chromatography plates</td>
			<td>EMD Millipore</td>
			<td>1055540001</td>
			<td>aluminum backed sheets</td>
		</tr>
		<tr>
			<td>Note: All commercially available reagents and solvents were used as received without further purification.</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

synthesis of esters via a greener steglich esterification in acetonitrile

Steglich 酯化是一种广泛使用的反应, 用于合成羧酸和醇类酯。虽然效率和温和, 反应通常使用氯化或酰胺溶剂系统, 这是危险的人类健康和环境。我们的方法采用乙腈作为绿色和低危险的溶剂体系。该协议展示了与传统溶剂系统相媲美的速率和产量, 并采用了萃取和洗涤序列, 无需通过柱层析纯化酯类产品。这种通用方法可用于将各种羧酸与1°和2°脂肪醇、苄基和烯丙基醇、酚类结合, 以获得高产量的纯酯。这里详细介绍的协议的目标是提供一个更绿色的替代通用酯化反应, 这可能有助于酯合成在学术和工业应用。

在乙腈改性 Steglich 酯化反应后进行酸碱萃取检查后, 3-氧苄肉桂 (8) 获得了淡黄色油 (205 毫克, 90% 屈服), 不需要柱层析。1图 2给出了 H 和13C 核磁共振谱, 以确认结构并表示纯度。
化合物9-17是使用类似的协议 (图 3) 合成的, 产量为...

Watch this Scientific Journal Video about Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile at JoVE.com

Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile

采用改良的 Steglich 酯化反应, 合成了一个小的酯类衍生物与初级和二醇。该方法使用非卤化和更环保的溶剂, 乙腈, 并使产品在高产量的隔离, 而无需色谱纯化。

乙腈绿色 Steglich 酯化合成酯的研究

The Steglich esterification is a widely-used reaction for the synthesis of esters from carboxylic acids and alcohols. While efficient and mild, the ...

这项实验的总体目标是为常见的酯化反应提供更环保的方法，这种反应对学术和工业应用中的雌激素合成非常有用。我们的方法可用于高效和温和的合成酯类物质，通过将碳氧酸与初级或二次醇或酚类结合。该技术的主要优点是，它消除了有害氯化或内含反应溶剂的使用，并在不牺牲反应速率或产品纯度的情况下，最大限度地减少了纯化期间的溶剂浪费。演示这个程序将是安德鲁卢特珍和麦肯齐奎克，本科研究员从我的实验室。首先，将跨辛纳酸、DMAP 和 EDC 组合在 50 毫升的圆底烧瓶中。在混合物中加入15毫升乙酰酸酯和98微升的3-甲基苯酶醇，以及磁搅拌棒。将烧瓶夹在40摄氏度的水浴中，搅拌反应。使用乙酸乙酯和六烷监测TLC的反应。一旦反应完成，使用旋转蒸发器在减压下去除乙酮，以获得粗固体。在残留物上，加入20毫升的二乙醚和一个盐酸摩尔。旋转烧瓶，将残留物溶解到溶剂层中。接下来，将溶液倒入分离漏斗中。用五毫升二乙醚冲洗蒸发的烧瓶，并将冲洗加入分离漏斗。轻轻摇动分离漏斗，将产品提取到乙醚层中，定期通风。允许层分离，然后将其从漏斗底部排入 Erlenmeyer 烧瓶中，将其排出水层。对分离漏斗中剩余的有机层，加入20毫升一摩尔盐酸，轻轻摇动分离烧瓶，定期通风。允许层分离，然后通过将水层从漏斗底部排入 Erlenmeyer 烧瓶中将其排出来去除水层。使用饱和碳酸氢钠和饱和氯化钠重复洗涤程序。完成洗涤步骤后，将有机层从分离漏斗转移到干净的 Erlenmeyer 烧瓶中。用硫酸镁擦干层。然后重力通过滤纸将溶液过滤成屏蔽蒸发瓶。之后，使用旋转蒸发器在减压下去除二乙醚溶剂。通过质子和碳 NMR 光谱法分析脱化氯仿中的产品样品，以及质谱法分析产品样品。在50毫升的圆底烧瓶中，结合跨辛纳酸、DMAP和EDC。在混合物中加入15毫升乙酮酸酯和157毫克二苯甲醇，以及磁搅拌棒。夹紧烧瓶，在室温下搅拌反应24小时。将空气冷凝器插入烧瓶颈部，以最大限度地减少溶剂蒸发。反应完成后，按照前面所述的提取工作和洗涤程序进行。在 50 毫升的圆底烧瓶中，结合十二酸、DMAP 和 EDC。在混合物中加入15毫升乙酰三酯和157毫克二苯丙胺醇，以及磁搅拌棒。夹紧烧瓶，在室温下搅拌反应24小时。将空气冷凝器插入烧瓶颈部，以最大限度地减少溶剂蒸发。反应完成后，按照前面所述的提取工作和洗涤程序进行。使用经过改良的Steglich酯化反应，3-甲基苯酶辛纳马在90%的屈服率下得到，无需柱色谱，如质子和碳 NMR 光谱学 所证实。使用类似协议合成的化合物9至17，通过NPYR光谱和高分辨率质谱分析，所有化合物的纯度为77至90%，通过NNR分析，发现其纯度与3-甲基苯酶辛纳马。对初级醇的规程进行了细微的修改，以获得最佳产量和纯度，化合物为12至17。二次酒精反应运行更长的时间，使反应去完成。在十二酸反应中，对于酯化合物12和17，使用1.2等量的碳氧酸，相当于一种和二次醇的酒精，产生含有十二酸杂质的酯。杂质问题通过使用一比一的十分酸与酒精的比例得到解决，反应时间稍长。这些条件产生了纯酯产品，表明质子 NMR 光谱中杂质信号损失为百万分之2.35。与任何有机合成方法一样，应参考化学品的安全数据表，并在执行本程序时使用适当的个人防护设备和设施。

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Education

JoVE Core

JoVE Journal

Organic Chemistry

Chemistry

Unit 1

Carboxylic Acid Derivatives

SCIENTISTS IN ACTION

Preparation and Use of Samarium Diiodide (SmI2) in Organic Synthesis: The Mechanistic Role of HMPA and Ni(II) Salts in the Samarium Barbier Reaction

Preparation and Use of Samarium Diiodide SmI2 in Organic Synthesis: The Mechanistic Role of HMPA and NiII Salts in the Samarium Barbier Reaction

二碘化钐的制备和使用（SMI<sub&gt; 2</sub&gt;）在有机合成中：HMPA和镍（II）盐的钐巴尔比耶反应的机理作用

Although initially considered an esoteric reagent, SmI2 has become a common tool for synthetic organic chemists. SmI2 is generated through the addition of ...

科研

化学

Synthesis and Exfoliation of Discotic Zirconium Phosphates to Obtain Colloidal Liquid Crystals

合成与盘状磷酸盐锆剥落获取胶体液晶

Due to their abundance in natural clay and potential applications in advanced materials, discotic nanoparticles are of interest to scientists and ...

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

蛋白质生物缀合物的合成<em&gt;通过</em&gt;半胱氨酸马来酰亚胺化学

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the ...

The Synthesis of [Sn10(Si(SiMe3)3)4]2- Using a Metastable Sn(I) Halide Solution Synthesized via a Co-condensation Technique

The Synthesis of [Sn10SiSiMe334]2- Using a Metastable SnI Halide Solution Synthesized via a Co-condensation Technique

的合成[锡<sub&gt; 10</sub&gt;（SI（SIME<sub&gt; 3</sub&gt;）<sub&gt; 3</sub&gt;）<sub&gt; 4</sub&gt;]<sup&gt; 2</sup<sup&gt; -</sup&gt;使用亚稳锡（I）卤溶液通过共缩聚合成技术

The number of well-characterized metalloid tin clusters, synthesized by applying the disproportionation of a metastable Sn(I) halide in the presence of a ...

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

用于固相合成含有2&#39;-<em&gt; 0</em通过圆二色性修饰和表征

Solid-phase synthesis has been used to obtain canonical and modified polymers of nucleic acids, specifically of DNA or RNA, which has made it a popular ...

One-pot Microwave-assisted Conversion of Anomeric Nitrate-esters to Trichloroacetimidates

硝酸酯 Anomeric Trichloroacetimidates 的单锅微波辅助转化

The goal of the following procedure is to provide a demonstration of the one-pot conversion of a 2-azido-1-nitrate-ester to a trichloroacetimidate ...

Synthesis of Substrate-Bound Au Nanowires Via an Active Surface Growth Mechanism

通过活性表面生长机制合成基片束缚金纳米线

Advancing synthetic capabilities is important for the development of nanoscience and nanotechnology. The synthesis of nanowires has always been a ...

A Rapid Synthesis Method for Au, Pd, and Pt Aerogels Via Direct Solution-Based Reduction

直接溶液还原法快速合成金、钯、铂气凝胶的研究

Here, a method to synthesize gold, palladium, and platinum aerogels via a rapid, direct solution-based reduction is presented. The combination of various ...

Solid-phase Synthesis of [4.4] Spirocyclic Oximes

[4.4] 刺环氧基的固相合成

A convenient synthetic route for spirocyclic heterocycles is well sought after due to the molecule&#39;s potential use in biological systems. By means of ...

Synthesis of Monodisperse Cylindrical Nanoparticles via Crystallization-driven Self-assembly of Biodegradable Block Copolymers

通过结晶驱动生物降解块共聚物的自组装合成单分散圆柱状纳米粒子

The production of monodisperse cylindrical micelles is a significant challenge in polymer chemistry. Most cylindrical constructs formed from diblock ...