Name: facile preparation of (2z,4e)-dienamides by the olefination of electron-deficient alkenes with allyl acetate
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注意:使用前请咨询所有相关材料安全数据表（MSDS）。所有交叉偶联反应应在密封氩气氛（1大气压）下在小瓶中进行。 丙烯酰胺与乙酸烯丙酯的合成制备丁二烯<ol><li>在120℃的烘箱中用兼容的磁力搅拌棒将螺旋盖小瓶（8mL）干燥2小时以上。使用前，将惰性气体吹入冷热瓶至室温。 </li><li>使用分析天平，称量3.7mg（〜3mol％，〜0.005mmol）[Ru（ p-色胺）Cl 2 ] 2 （棕色粉末）和13.7mg（20mol％，0.04mmol）AgSbF 6 （白色固体）加入到上述反应小瓶中。 注意:由于这是一种新的方法，所以交叉耦合反应已经进行了小规模的验证，以减少废物形成。 AgSbF 6用作可以提取氯化物以产生a的添加剂用于亲电CH键活化的阳离子钌络合物13 。还测试了其它银盐，例如Ag 2 CO 3 ，但没有检测到产物。催化剂（[Ru（ 对 -异氰酸酯）Cl 2 ] 2 ）的重量不是很准确，在3.4-3.9mg的范围内。 </li><li>向反应瓶中加入1 mL干燥的1,2-二氯乙烷。 注意:溶剂的量是柔性的 - 1mL的1,2-二氯乙烷刚好足以满足交叉偶联反应的体积的最小要求。但是，对于该刻度尺的反应，还可以使用更多（〜0.1mL）的溶剂。 1,2-二氯乙烷在使用前在3-分子筛上干燥。 </li><li>使用分析天平，并向上述反应小瓶中加入丙烯酰胺（0.2mmol，1.0当量;固体或油）。 </li><li>使用微量注射器向上述反应小瓶中加入43μL（0.4mmol，2.0当量）乙酸烯丙酯（无色液体）。 <br/&gt;注意:在这里，需要过量的乙酸烯丙酯来抑制丙烯酰胺的均相偶联，并确保丙烯酰胺完全转化。如果加入较少的乙酸烯丙酯（1.5当量），则产物产率降低。加入更多的乙酸烯丙酯（3.0当量）不能进一步提高产率。实际上，没有观察到乙酸烯丙酯的均相偶联，可以回收残余的乙酸烯丙酯。 </li><li>用氩气轻轻吹入反应瓶，并尽快用兼容的螺帽盖住小瓶。 注意:由于惰性气氛对于交叉耦合反应至关重要，瓶子应尽快用螺帽盖住。最好在手套箱中执行上述协议。 </li><li>将反应混合物在室温下再搅拌5分钟。 </li><li>将反应瓶在油浴中加热至110℃，同时搅拌16-18小时。 注意:通常，颜色变为深红色是ind反应正在发生。 </li><li>冷却小瓶后，使用乙酸乙酯:石油醚（2:1或1:3）混合物作为溶剂，开发薄层色谱（TLC）板，通过将混合物与丙烯酰胺标准物进行比较来监测反应进程。 注意:根据起始材料的性质，反应可能无法完成。产品和原料的典型R f值在0.3-0.7的范围内。已经观察到丙烯酰胺原料比丁二烯产物低的流动点。 </li><li> 将粗产物溶解在最少的DCM中，并将其装载到用石油醚润湿的硅胶柱上。 通过柱色谱法使用乙酸乙酯:石油醚（1:100至1:4）的混合物作为洗脱剂分离交叉​​偶联产物。 <ol><li>在单独的烧瓶中收集洗脱液，在旋转蒸发器上蒸发溶剂，d将其置于高真空下至少2小时。 </li><li>通过NMR光谱法获得约20-50mg的产物进行表征。 注意:反应完成后，反应混合物应直接用于柱层析纯化。 </li></ol></li></ol>二烯酰胺的表征<ol><li>使用1 H和13 C NMR光谱鉴定和评估最终产物的纯度14 。通常，羰基碳的化学位移在13 C NMR谱上出现在170ppm附近。丁二烯官能团的三个sp 2质子由6.0和5.6ppm附近的特征峰表示。 </li><li>使用红外光谱14鉴定二烯产物的特征羰基和CC双键峰。 </li><li>确定产品的分子质量，并进一步验证身份，分辨率质谱（HRMS） 14 。 </li><li>确定固体产品的熔点14 。 </li></ol>

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我们感谢中国国家自然科学基金（NSFC）（编号21502037,21373073和21672048），浙江省自然科学基金（ZJNSF）（No.LY15B020008），PCSIRT（IRT 1231）和杭州师范大学资助。 GZ承认中国浙江省钱江奖学金。

[Ru（ p-异氰酸酯）Cl 2 ] 2是一种便宜，易于使用的空气稳定且高活性的Ru基催化剂，具有优异的官能团耐受性，可在温和的反应条件下有效运行，得到CH / CH偶联丁二烯产物。使用银盐AgSbF 6作为可以抽出[Ru（ p-色胺）Cl 2 ] 2的氯化物以产生用于以下CH键活化的阳离子钌络合物的添加剂。然而，只有α取代和α，β-二取代的丙烯酰胺适...

Butadienes广泛存在，常见于许多天然产物，药物和生物活性分子1 。化学家已经作出了巨大的努力，开发出一种有效的，有选择性的，实用的合成1,3-二丁二烯合成方法2,3 。最近，开发了通过双乙烯基CH键活化的两种烯烃之间的直接交联，代表了具有高原子和逐步经济性的丁二烯的合成的有效策略。其中，钯催化的两种烯烃的交叉偶联引起了很大的关注， 通过烯基 - Pd物种4,5提供（ E，E ） - 配位丁二烯。例如，Liu的研究小组通过烯烃和乙酸烯丙酯的直接交叉偶联来开发Pd催化的丁二烯合成（ 图1 </strong&gt;和等式3 ） 4 。同时，由于烯烃CH环金属化事件，烯烃之间的官能团导向交叉偶联提供了具有优异（ Z，E ） - 立体选择性的丁二烯，代表了互补方法6 。迄今为止，一些指导小组，如烯醇化酶，酰胺，酯和磷酸酯已被成功地引入烯烃之间的交叉耦合，提供了一系列有价值和功能化的1,3-丁二烯。然而，有针对性的交叉偶联反应尚未得到发展，因为在实际应用中仍然有限的导向基团。特别地，通常需要化学计量的氧化剂以维持催化循环，这产生大量的有机和无机废物。使用富电子烯烃作为偶合配体的实例非常有限。 醋酸烯丙酯及其衍生物已经深入我在有机转化中被研究为强力的烯丙基化和烯化试剂，包括催化交叉偶联，富含电子的芳烃的Friedel-Crafts烯丙基化和电子缺乏的芳烃的催化CH活化（ 图1和方程1 ） 7 。最近，Loh集团开发了电子缺乏烯烃与乙酸烯丙酯的铑（III）催化CH烯丙基化，形成1,4-二烯（ 图1和方程2 ） 8 。同时，Kanai组通过使用Co（III）催化剂9报道了与烯丙醇的脱水直接CH烯丙基化。有趣的是，Snaddon及其同事们公开了一种新型的基于非催化剂的非对称α-烯丙基酯10的合作催化方法。最近，Ackermann集团报道了几个新的相关例子g便宜的Fe，Co和Mn催化剂11 。这些报告在烯丙基化和烯化反应中取得突破，但双键迁移和区域选择性差，通常是不可避免的，不易控制。因此，开发更有效和选择性的乙酸烯丙酯的反应模式来构建有价值的分子仍然是非常需要的。由于我们对通过 CH烯化的新型1,3-丁二烯合成的兴趣，我们假设可以将乙酸烯丙酯引入到电子缺陷烯烃的定向烯丙基化中，首先递送1,4-二烯。然后，在CC双键7的迁移异构化之后可以形成更多的热力学稳定的1,3-丁二烯，形成不能通过使用富电子的烯烃例如丙烯的交联而获得的二烯产物作为偶联配体6 。在这里，我们报告了廉价的Ru（III）催化的烯烃CH键烯烃n的丙烯酰胺与烯丙基乙酸酯在没有任何氧化剂的情况下，这为开创（ Z，E ） - 丁二烯（ 图1和方程4 ） 13创造了新的合成途径。

<table><tbody><tr><td>Allyl Acetate</td><td>TCI</td><td>A0020</td><td>&gt;98.0%(GC), 25 mL package</td></tr><tr><td>Dichloro(p-cymene)ruthenium(II) dimer</td><td>TCI</td><td>D2751</td><td>&gt;95.0%(T), 5 g package</td></tr><tr><td>Silver hexafluoroantimonate</td><td>TCI</td><td>S0463</td><td>&gt;97.0%(T),&amp;nbsp; 5 g package</td></tr><tr><td>1,2-Dichloroethane</td><td>TCI</td><td>D0364</td><td>&gt;99.5%(GC), 500 g package</td></tr><tr><td>Rotavapor</td><td>EYELA</td><td>N-1200A</td><td>Use to dry solvent</td></tr><tr><td>Silica gel</td><td>Merck</td><td>107734</td><td>Silica gel 60 (0.063-0.2 mm), for column chromatoraphy</td></tr></tbody></table>

facile preparation of (2z,4e)-dienamides by the olefination of electron-deficient alkenes with allyl acetate

通过乙烯基CH键活化，两种烯烃之间的直接交叉耦合代表了合成具有高原子和经济经济性的丁二烯的有效策略。然而，这种功能导向的交叉偶联反应还没有被开发出来，因为在实际应用中仍然有限的导向基团。特别地，通常需要化学计量的氧化剂，产生大量的废物。由于我们对新型1,3-丁二烯合成的兴趣，我们描述了使用乙酸烯丙酯和没有外部氧化剂的电子缺陷烯烃的钌催化烯化反应。选择2-苯基丙烯酰胺和乙酸烯丙酯的反应作为模型反应，在最佳条件下，以80％的分离收率获得所需的二烯产物，具有良好的立体选择性（ Z，E / Z，Z = 88:12）:[ Ru（ p-色胺）Cl 2 ] 2 （3mol％）和AgSbF 6 （20mol％）在DCE中在110℃或16小时。通过优化的催化条件，研究了代表性的α - 和/或β-取代的丙烯酰胺，并且所有反应都是平滑的，而不管脂族或芳族基团。此外，不同的N-取代的丙烯酰胺已被证明是良好的底物。此外，我们检查了不同烯丙基衍生物的反应性，表明醋酸氧化物对金属的螯合对催化过程至关重要。还进行氘标记实验以研究反应机理。仅观察到丙烯酰胺上的Z选择性H / D交换，表明可逆的环金属化事件。此外，在分子间同位素研究中观察到3.2的动力学同位素效应（KIE），表明烯烃CH金属化步骤可能参与速率确定步骤。

我们的努力集中在从丙烯酰胺和乙酸烯丙酯制备1,3-丁二烯。 表1说明了使用[Ru（β-异氰酸酯）Cl 2 ] 2作为催化剂的条件优化，包括各种添加剂和溶剂的筛选。在筛选出一系列有代表性的溶剂后，我们很高兴地发现，产物产率显着提高到80％，选择性好（ Z，E / Z，Z = 88:12）。通过NOESY NMR...

Watch this Scientific Journal Video about Facile Preparation of 2Z,4E-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate at JoVE.com

Facile Preparation of 2Z,4E-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate

这里描述了电子缺乏烯烃与乙酸烯丙酯的钌催化烯化反应。通过使用氨基羰基作为引导基团，该外部无氧化剂方案具有高效率和良好的立体选择性和开放的新的合成途径（ Z ， E ） - 丁二烯骨架。

（2<em&gt;ž</em&gt;，4<em&gt;电子</em&gt;） - 通过电子缺陷烯烃与烯丙基乙酸酯的烯化反应制备二烯酰胺

Direct cross-coupling between two alkenes via vinylic C-H bond activation represents an efficient strategy for the synthesis of butadienes with high ...

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Unit 1

Facile Preparation of (2Z,4E)-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate

Dienes, Conjugated Pi Systems, and Pericyclic Reactions

Alkene Structure and Reactivity

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7.3K 次观看.  Hangzhou Normal University. 这里描述了电子缺乏烯烃与乙酸烯丙酯的钌催化烯化反应。通过使用氨基羰基作为引导基团，该外部无氧化剂方案具有高效率和良好的立体选择性和开放的新的合成途径（ Z ， E ） - 丁二烯骨架。 

视频: Facile Preparation of 2Z,4E-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides, which react under a variety of conditions to afford useful N- and O-containing compounds. Acid-catalyzed addition of alcohols or thiols to N-(2-alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and thioketals, respectively. Selective reduction of the vinyl group in N-(2-alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the corresponding phthalan in good yield, whereas reduction with sodium bis(2-methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue. Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically versatile, but often hydrolytically unstable, this protocol emphasizes key techniques in preparing, handling, and reacting these pivotal substrates in several useful transformations.

Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Representative experimental procedures for the synthesis of N-(2-alkoxyvinyl)sulfonamides and subsequent conversion to phthalan and phenethylamine derivatives are presented in detail.

准备n-(2-alkoxyvinyl) 磺胺从n-tosyl-1,2,3-triazoles 和随后转换为取代 Phthalans 和 Phenethylamines

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile ...

科研

化学

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. Recently, we have developed a two-step strategy for ketone enolate umpolung that has enabled the development of methods for chlorination, azidation, and amination using azoles. In addition, we have developed C-C bond&#8211;forming arylation and allylation reactions. At the heart of these methods is the preparation of the intermediate and highly reactive enolonium species prior to addition of a reactive nucleophile. This strategy is thus reminiscent of the preparation and use of metal enolates in classical synthetic chemistry. This strategy allows the use of nucleophiles that would otherwise be incompatible with the strongly oxidizing hypervalent iodine reagents. In this paper we present a detailed protocol for chlorination, azidation, N-heteroarylation, arylation, and allylation. The products include motifs prevalent in medicinally active products. This article will greatly assist others in using these methods.

A two step one-pot protocol for the umpolung of ketone enolates to enolonium species and addition of a nucleophile to the &#945;-position is described. Nucleophiles include chloride, azide, azoles, allyl-silanes, and aromatic compounds.

Enolonium 种极性转换酮功能化的两步协议

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. ...

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

We introduced a regioselective and atom-economical procedure for the synthesis of 3-substituted indoles by annulation of nitrosoarenes with ethynyl ketones. The reactions were carried out achieving indoles without any catalyst and with excellent regioselectivity. No traces of 2-aroylindole products were detected. Working with 4-nitronitrosobenzene as starting material, the 3-aroyl-N-hydroxy-5-nitroindole products precipitated from the reaction mixtures and were isolated by filtration without any further purification technique. Differently from the corresponding N-hydroxy-3-aryl indoles that, spontaneously in solution, give dehydrodimerization products, the N-hydroxy-3-aroyl indoles are stable and no dimerization compounds were observed.

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

3-Aroyl-N-hydroxy-5-nitroindoles were synthesized by cycloaddition of 4-nitronitrosobenzene with a conjugated terminal alkynone in a one-step thermal procedure. Preparation of the nitrosoarene and of the alkynones were adequately reported and respectively through oxidation procedures on the corresponding aniline and on the alkynol.

A 直接、再生和原子经济合成3-Aroyl-N-羟基-5-硝基胺基，通过环加4-硝基苯与烷基诺

We introduced a regioselective and atom-economical procedure for the synthesis of 3-substituted indoles by annulation of nitrosoarenes with ethynyl ...

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

Nitrogen-containing heterocycle aziridines are synthetically very valuable for the preparation of azacyclic and acyclic molecules. However, it is very difficult and laborious to make aziridines in optically pure forms on a large scale to apply asymmetric synthesis of aza compounds. Fortunately, we successfully achieved both enantiomers (2R)- and (2S)-aziridine-2-carboxylates with the electron-donating &#945;-methylbenzyl group at the ring nitrogen as non-activated aziridines. These starting aziridines have two distinct functional groups-highly reactive three-membered ring and versatile carboxylate. They are applicable in ring-opening or ring-transformation with aziridine and in functional group transformation to others from carboxylate. Both of these enantiomers were utilized in the preparation of biologically important amino acyclic and/or aza-heterocyclic compounds in an asymmetric manner. Specifically, this report describes the first expedient asymmetric synthesis of both enantiomers of 5, 6-dihydrouracil-type marine natural products biemamide B and D as potential TGF-&#946; inhibitors. This synthesis consisted of regio- and the stereoselective ring-opening reaction of aziridine-2-carboxylate and subsequent formation of 4-aminoteterahydropyrimidine-2,4-dione. One more example in this protocol dealt a highly stereoselective Mukaiyama reaction of aziridine-2-carboxylate and silyl enol ether, following intramolecular aziridine ring-opening to provide easy and facile access to (-)-epiallo-isomuscarine.

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

In this study, we prepare both enantiomers of aziridine-2-carboxylate, which are used in the asymmetric synthesis of alkaloids, including biemamide B and D, and (-)-epiallo-isomuscarine.

对映草非活化氮丙啶的制备及比咪咪唑B、D和 表皮异毒羯碱的合成

Nitrogen-containing heterocycle aziridines are synthetically very valuable for the preparation of azacyclic and acyclic molecules. However, it is very ...

Preparation of Alkynes: Alkylation Reaction

<h4>Introduction</h4>
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
<img alt="Alkyne alkylation reaction using NaNH2 and ethyl bromide, chemical equation diagram." src="/files/ftp_upload/11834/11834_PT_Figure_1.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure1">
The reaction takes place in two steps:
1. The first step is the deprotonation of the terminal alkyne by the strong base forming an acetylide ion.
<img alt="Alkyne ionization reaction equation NaNH2, diagram shows acetylene converting to acetylide ion." src="/files/ftp_upload/11834/11834_PT_Figure_2.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure2">
2. The second step is a nucleophilic substitution reaction in which the acetylide ion reacts with the alkyl halide to form a new C–C bond.
<img alt="Organic reaction mechanism, Na+ and Br- ion exchange, illustrates chemical synthesis process." src="/files/ftp_upload/11834/11834_PT_Figure_3.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure3">
<h4>Reaction Mechanism —SN2 pathway </h4>
Acetylide ions are strong bases and can also function as good nucleophiles. The substitution reaction follows an SN2 pathway where the nucleophilic acetylide ion attacks the electrophilic carbon of the primary alkyl halide from the backside.
<img alt="Nucleophilic substitution reaction mechanism diagram with alkynes, NaBr formation, chemical process." src="/files/ftp_upload/11834/11834_PT_Figure_4.svg" style="text-align: center; height: 250px;" data-altupdatedat="1747908711000" data-alt="Figure4">
Since this is a concerted process, the nucleophilic attack and the departure of the leaving group takes place simultaneously to form the product with an inverted stereochemistry at the reaction center.
The reaction works best with unhindered alkyl halides like methyl halide and other primary halides. With secondary and tertiary alkyl halides, acetylide ions act as strong bases, in which case E2 elimination is the preferred pathway.
<h4>Application in organic synthesis </h4>
Alkylation of simple terminal alkynes is a useful method to extend the length of the carbon chain. Acetylene, a terminal alkyne, can be converted to a higher internal alkyne by repeated alkylation as shown below:
<img alt="Alkyne chain elongation via NaNH₂, CH₃Br; reaction equation diagram for organic synthesis." src="/files/ftp_upload/11834/11834_PT_Figure_5.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure5">

炔烃的制备:烷基化反应

Introduction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for ...

教育

有机化学

炔烃

关键术语与概念

Preparation of Alkynes: Dehydrohalogenation

<h4>Introduction</h4>
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
<img alt="Chemical reaction diagram, alkyne synthesis, 2NaNH2/NH3, hydrogen elimination, organic chemistry." src="/files/ftp_upload/11835/11835_PT_Figure_1.svg" style="text-align: center; height: 200px;" data-altupdatedat="1747908711000" data-alt="Figure1">
<h4>Reaction Mechanism – E2 pathway</h4>
Vicinal dihalides
In the first elimination step, the strong base abstracts the proton from the dihalide that is oriented anti to the leaving group. Since E2 reactions follow a concerted pathway, the abstraction of a proton and departure of the halide leaving group occur simultaneously to form a haloalkene.
<img alt="Birch reduction mechanism diagram, showing electron flow in organic compound reaction." src="/files/ftp_upload/11835/11835_PT_Figure_2.svg" style="text-align: center; height: 90px;" data-altupdatedat="1747908711000" data-alt="Figure2">
In the second elimination reaction, another equivalent of the strong base reacts with the haloalkene in a similar fashion to give the desired alkyne.
<img alt="Elimination reaction mechanism diagram, E2 mechanism, showing alkene formation from alkyl halide." src="/files/ftp_upload/11835/11835_PT_Figure_3.svg" style="text-align: center; height: 90px;" data-altupdatedat="1747908711000" data-alt="Figure3">
Geminal dihalides
Likewise, geminal dihalides, when treated with two equivalents of a sodium amide, undergo double dehydrohalogenation to give alkynes.
<img alt="Alkyne formation reaction; sodium amide abstracting proton; chemical equation diagram; synthesis method." src="/files/ftp_upload/11835/11835_PT_Figure_4.svg" style="text-align: center; height: 90px;" data-altupdatedat="1747908711000" data-alt="Figure4">
<img alt="Chemical reaction mechanism, arrow-pushing diagram, alkyne formation using sodium amide." src="/files/ftp_upload/11835/11835_PT_Figure_5.svg" style="text-align: center; height: 90px;" data-altupdatedat="1747908711000" data-alt="Figure5">
Terminal dihalides 
Dehydrohalogenation of terminal dihalides yields terminal alkynes as the final product. In the presence of a strong base like sodium amide, terminal alkynes get converted to acetylide ions. In such cases, a third equivalent of the base is required to complete the dehydrohalogenation of the remaining haloalkene.
<img alt="Hofmann elimination reaction; chemical equations diagram; synthesis process using NaNH2; alkyne formation." src="/files/ftp_upload/11835/11835_PT_Figure_6.svg" style="text-align: center; height: 70px;" data-altupdatedat="1747908711000" data-alt="Figure6">
Protonation of the acetylide ions with water or an aqueous acid completes the reaction.
<img alt="Organic reaction mechanism with sodium acetylide, water; diagram illustrating nucleophilic attack." src="/files/ftp_upload/11835/11835_PT_Figure_7.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure7">
<h4>Application in Organic Synthesis</h4>
Dehydrohalogenation of vicinal dihalides is a useful intermediate step in the conversion of alkenes to alkynes. For example, chlorination of 1-propene gives 1,2-dichloropropane – a vicinal dihalide, which upon double dehydrohalogenation yields 1-propyne.
<img alt="Alkene to alkyne conversion diagram; chemical reaction mechanism, dichlorination, dehydrohalogenation." src="/files/ftp_upload/11835/11835_PT_Figure_8.svg" style="text-align: center; height: 60px;" data-altupdatedat="1747908711000" data-alt="Figure8">
Similarly, alkynes can also be synthesized from ketones via dehydrohalogenation of geminal dihalides. For example, treatment of acetone with phosphorous pentachloride yields 2,2-dichloropropane – a geminal dihalide, which undergoes double dehydrohalogenation to give 1-propyne.
<img alt="Organic synthesis mechanism; ketone to alkyne via substitution and elimination; chemical reaction diagram." src="/files/ftp_upload/11835/11835_PT_Figure_9.svg" style="text-align: center; height: 80px;" data-altupdatedat="1747908711000" data-alt="Figure9">

炔烃的制备:脱卤化氢

Introduction
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ...

Preparation of Epoxides

<h4>Overview</h4>
Epoxides result from&#160;alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
<h4>Epoxidation with Peroxy Acids</h4>
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon&#8211;carbon double bond to an epoxide using the oxidizing agent&#160;meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O&#8211;O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to alkenes occurs with ease, thereby following syn addition. Hence, the epoxides are produced with the retention of the alkene configuration.
<h4>Epoxidation via Air Oxidation</h4>
Although peroxy-mediated epoxidation is the most common method for alkene oxidation, ethylene oxide is synthesized at the industrial scale via air oxidation by treating a mixture of ethylene and air in the presence of a silver catalyst.
<h4>Cyclization of Halohydrins</h4>
Cyclization of halohydrins of alkenes in the presence of a base also yields epoxides, and the reaction follows the SN2 substitution mechanism. Hence, the nucleophile&#8212;the oxygen anion&#8212;and the leaving group&#8212;the chloride ion&#8212;must orient anti to each other in the transition state to make the halohydrins cyclization feasible.
<img alt="Figure1" src="/files/ftp_upload/12094/12094Figure 1.svg" style="text-align: center; height: 260x;" />
In noncyclic halohydrins, this anti-relationship is achieved by an internal rotation. For instance, in 1-chloro-2-methyl-2-propanol, shown in Figure 1, the hydroxyl and the chloro group are not oriented anti to each other. To achieve the anti-relationship, the carbon-bearing chloro group undergoes an internal rotation, thereby making the nucleophile attack&#8212;from the backside of the C&#8211;X bond&#8212;and the ejection of the leaving group feasible. Thus, the epoxides formed via halohydrin cyclization also retain the alkene configuration.
Similarly, the cyclic halohydrins must undergo conformational changes to achieve the anti-relationship. For example, the halohydrin of cyclohexane, shown in Figure 2, undergoes a conformational change from diequatorial to diaxial to successfully form&#160;an epoxide.
<img alt="Figure2" src="/files/ftp_upload/12094/12094Figure 2.svg" style="text-align: center; height: 120px;" />

Preparation of Epoxides via Alkene Oxidation

环氧化物的制备

Overview
Epoxides result from&#160;alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin ...

醚类、环氧化物、硫化物

Carboxylic Acids to Methylesters: Alkylation using Diazomethane

Carboxylic acids react with diazomethane in an ether solvent via alkylation at the carboxylate oxygen atom to give methyl esters of the corresponding acid with excellent yields.
<img alt="Esterification reaction: carboxylic acid with diazomethane formula, chemical process diagram." src="/files/ftp_upload/12349/12349_PT_Figure_1.svg" style="text-align: center; height: 60px;" data-altupdatedat="1747908711000" data-alt="Figure1">
Diazomethane is a yellow gas having a boiling point of −23 °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≡N, which functions as an excellent leaving group.
<img alt="Chemical reaction, Curtius rearrangement equations, molecular transformation diagram." src="/files/ftp_upload/12349/12349_PT_Figure_2.svg" style="text-align: center; height: 72px;" data-altupdatedat="1747908711000" data-alt="Figure2">
In the final alkylation step, an SN2 attack on the methyldiazonium ion by the carboxylate anion produces a methyl ester, along with the elimination of N2 gas.
<img alt="SN2 reaction mechanism diagram; nucleophile attack on carbonyl, forming new bond, expelling N2." src="/files/ftp_upload/12349/12349_PT_Figure_3.svg" style="text-align: center; height: 70px;" data-altupdatedat="1747908711000" data-alt="Figure3">
However, diazomethane 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 carcinogenic.
Diazomethane decomposes in the presence of heat or light to generate carbenes and eliminate nitrogen.
<img alt="Chemical reaction diagram; azide decomposition to form methylene and nitrogen under heat or light." src="/files/ftp_upload/12349/12349_PT_Figure_4.svg" style="text-align: center; height: 52px;" data-altupdatedat="1747908711000" data-alt="Figure4">

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 ...

Carboxylic Acids

Amines to Alkenes: Hofmann Elimination

Alkenes can be obtained from amines via an E2 elimination. The amine is first converted into a good leaving group, such as a quaternary ammonium salt. This is accomplished by treating the amine with an excess of alkyl halide, which results in a halide salt. Next, the halide salt is transformed into a hydroxide salt that functions as a base to enable elimination.
Under thermal conditions, the hydroxide can abstract a proton from the &#946; carbon; this generates an alkene with the simultaneous release of a neutral amine molecule. This elimination process is called the Hofmann elimination. For the elimination to occur, the &#946; proton and tertiary amine group must be positioned opposite or anti-periplanar to each other. This reaction yields the less substituted alkene as the major product, also known as the Hofmann product.

胺到烯烃:Hofmann 消元法

Alkenes can be obtained from amines via an E2 elimination. The amine is first converted into a good leaving group, such as a quaternary ammonium salt. ...

Amines

&alpha;-Alkylation of Ketones via Enolate Ions

Ketones with &#945; protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by resonance, and its hybrid structure exhibits negative charges on the carbonyl oxygen and the &#945; carbon. This ambident nucleophile can attack an electrophile via two possible sites: the carbonyl oxygen, known as O-attack, or the &#945;&nbsp;carbon, known as C-attack. The nucleophilic attack via the carbanionic site is preferred. This is due to the strong interaction of the positive counterpart of the base with the anionic oxygen, which restricts the approaching electrophile, making the reaction less favorable. Also, the product obtained through C-attack is more stable than that obtained through O-attack, as the stronger C=O &#960; bond is retained in the former, whereas a weaker C=C &#960; bond is preserved in the latter.
A subsequent reaction of the enolate with electrophiles such as alkyl halides produces an &#945;-alkylated ketone via the SN2 pathway. The &#945;-alkylation of ketones is achieved with the halides of primary alkyl, benzyl, and allylic groups. With secondary and tertiary alkyl halides, elimination predominates over substitution.

（2

摘要

探索更多视频

此视频中的章节

准备n-(2-alkoxyvinyl) 磺胺从n-tosyl-1,2,3-triazoles 和随后转换为取代 Phthalans 和 Phenethylamines

Enolonium 种极性转换酮功能化的两步协议

A 直接、再生和原子经济合成3-Aroyl-N-羟基-5-硝基胺基，通过环加4-硝基苯与烷基诺

对映草非活化氮丙啶的制备及比咪咪唑B、D和表皮异毒羯碱的合成

炔烃的制备:烷基化反应

炔烃的制备:脱卤化氢

环氧化物的制备

羧酸制甲酯:使用重氮甲烷进行烷基化

胺到烯烃:Hofmann 消元法

酮的α-烷基化通过烯醇化离子

（2

摘要

探索更多视频

此视频中的章节

准备n-(2-alkoxyvinyl) 磺胺从n-tosyl-1,2,3-triazoles 和随后转换为取代 Phthalans 和 Phenethylamines

Enolonium 种极性转换酮功能化的两步协议

A 直接、再生和原子经济合成3-Aroyl-N-羟基-5-硝基胺基，通过环加4-硝基苯与烷基诺

对映草非活化氮丙啶的制备及比咪咪唑B、D和 表皮异毒羯碱的合成

炔烃的制备:烷基化反应

炔烃的制备:脱卤化氢

环氧化物的制备

羧酸制甲酯:使用重氮甲烷进行烷基化

胺到烯烃:Hofmann 消元法

酮的α-烷基化通过烯醇化离子

对映草非活化氮丙啶的制备及比咪咪唑B、D和表皮异毒羯碱的合成