Name: separation of aldehydes and reactive ketones from mixtures using a bisulfite extraction protocol
Uploaded: 2018-04-02T15:00:00.000+00:00
Duration: 9 min 8 s
Description: Watch this Scientific Journal Video about Separation of Aldehydes and Reactive Ketones from Mixtures Using a Bisulfite Extraction Protocol at JoVE.com

对美国化学学会石油研究基金的捐助者的承认是对这项研究的部分支持。我们感谢国家科学基金会 (CHE-0619275 和 CHE-0963165) 的革新和仪器赠款, 支持这项研究。

1. 从混合物中分离芳香醛的标准协议。例子: 从1:1 混合物与茴香醛分离丁酸苄酯。
<ol><li>将 175 ul 的茴香醛和 250 ul 的丁酸苄酯溶解在5毫升甲醇中, 并将溶液转移到部位漏斗上。 注意: 亚硫酸氢钠可以产生二氧化硫气体, 因此该协议应进行适当的通风, 如通风罩。</li>
	<li>加入1毫升饱和水亚硫酸氢钠, 并大力摇动大约三十年代。</li>
	<li>加入25毫升去离子水和25毫升10% 乙酸乙酯/hexanes, 并大力摇动。</li>
	<li>分隔图层。用无水硫酸镁干燥有机层。过滤解决方案, 以去除硫酸镁和集中在真空使用旋转蒸发器。</li>
</ol>2. 从混合物中分离脂肪醛和酮。例子: 从1:1 混合物与 Benzylacetone 分离丁酸苄酯。
<ol><li>在10毫升的甲基酰胺中溶解 213 ul 的 benzylacetone 和 250 ul 的丁酸苄酯, 并将溶液转移到部位漏斗上。 注意: 亚硫酸氢钠可以产生二氧化硫气体, 因此该协议应进行适当的通风, 如通风罩。</li>
	<li>加入25毫升饱和水亚硫酸氢钠, 并大力摇动大约三十年代。</li>
	<li>加入25毫升去离子水和25毫升10% 乙酸乙酯/hexanes, 并大力摇动。</li>
	<li>分隔图层。将水层返回部位漏斗, 加入25毫升10% 乙基醋酸盐/hexanes, 并大力摇动。排出水层, 将有机层留在部位漏斗中。将以前的有机层添加回部位漏斗。</li>
	<li>用去离子水洗三次组合的有机层 (每洗涤10毫升)。用无水硫酸镁干燥有机层。过滤解决方案, 以去除硫酸镁和集中在真空使用旋转蒸发器。</li>
</ol>3. 从含有烯烃的混合物中分离醛。例子: 从1:1 混合物与香茅醛物分离丁酸苄酯。
<ol><li>在10毫升的甲基酰胺中溶解 255 ul 的香茅醛物和 250 ul 的丁酸苄酯, 并将溶液转移到部位漏斗上。 注意: 亚硫酸氢钠可以产生二氧化硫气体, 因此该协议应进行适当的通风, 如通风罩。</li>
	<li>加入25毫升饱和水亚硫酸氢钠, 并大力摇动大约三十年代。</li>
	<li>加入25毫升去离子水和25毫升的 hexanes, 并大力摇动。</li>
	<li>分隔图层。将水层返回部位漏斗, 加入25毫升 hexanes, 用力摇动。排出水层, 将有机层留在部位漏斗中。将以前的有机层添加回部位漏斗。</li>
	<li>用去离子水洗三次组合的有机层 (每洗涤10毫升)。用无水硫酸镁干燥有机层。过滤解决方案, 以去除硫酸镁和集中在真空使用旋转蒸发器。</li>
</ol>4. 从混合物中重新分离醛类。例子: 从1:1 混合物中分离胡椒与丁酸苄酯。
<ol><li>在5毫升甲醇中溶解217毫克的胡椒和 250 ul 的丁酸苄酯, 并将溶液转移到部位漏斗上。 注意: 亚硫酸氢钠可以产生二氧化硫气体, 因此, 该协议应进行适当的通风, 如在油烟机。</li>
	<li>加入1毫升饱和水亚硫酸氢钠, 并大力摇动大约三十年代。</li>
	<li>加入25毫升去离子水和25毫升10% 乙酸乙酯/hexanes, 并大力摇动。</li>
	<li>分隔图层。将水层回流回部位漏斗。<ol>
<li>可选: 用25毫升10% 乙酸乙酯/hexanes 洗涤水层, 除去少量残留的丁酸苄酯。</li>
	</ol>
</li>
	<li>加入25毫升醋酸乙酯, 然后加入50% 氢氧化钠, 直到 ph 条指示 ph 值为12。用力摇动。 注意: 在这一步骤中已经观察到气体的演化, 并可能导致压力积聚。一定要正确地排出部位漏斗。扩大这一过程将使气体演化更加明显。请小心。</li>
	<li>分隔图层。将水层返回部位漏斗, 加入25毫升醋酸乙酯。用力摇动。</li>
	<li>分隔图层。从上一步将有机层与有机层结合起来。用无水硫酸镁将有机复合层干燥。过滤解决方案, 以去除硫酸镁和集中在真空使用旋转蒸发器。</li>
</ol>

<ol>
	<li>Boucher, M. M., Furigay, M. H., Quach, P. K., Brindle, C. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liquid-Liquid+Extraction+Protocol+for+the+Removal+of+Aldehydes+and+Highly+Reactive+Ketones+from+Mixtures.">Liquid-Liquid Extraction Protocol for the Removal of Aldehydes and Highly Reactive Ketones from Mixtures.</a> Org. Process Res. Dev. 21 (9), 1394-1403 (2017).</li><li>Lauer, G. G., Pratt, R. S., Wilson, W. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Separation+of+Aldehydes+and+Ketones.">Separation of Aldehydes and Ketones.</a> , (1951).</li><li>Hsu, W. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Separation of Aldehydes from Ketones via Acid-Catalyzed Cyclotrimerization of the Aldehyde. , 4701561 (1987).</li><li>Schreiber, R. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Process+for+Separating+Aldehydes+and+Ketones.">Process for Separating Aldehydes and Ketones.</a> , (1942).</li><li>Bludworth, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Separation+of+Aldehyde-Ketone+Mixtures.">Separation of Aldehyde-Ketone Mixtures.</a> , (1944).</li><li>Masilamani, D., Manahan, E. H., Vitrone, J., Rogic, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Organic+Reactions+of+Sulfur+Dioxide.+Reactions+with+Nucleophilic+Double+Bonds+Leading+to+the+Isomerization,+Aromatization,+Selective+Hydrogen-Deuterium+Exchange,+and+Electron-Transfer+Proceses.">Organic Reactions of Sulfur Dioxide. Reactions with Nucleophilic Double Bonds Leading to the Isomerization, Aromatization, Selective Hydrogen-Deuterium Exchange, and Electron-Transfer Proceses.</a> J. Org. Chem. 48 (25), 4918-4931 (1983).</li><li>Masilamani, D., Rogic, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Organic+Reactions+of+Sulfur+Dioxide.+4.+A+Facile+Regiospecific+Hydrogen-Deuterium+Exchange+in+Olefins.+Consequence+of+the+Intermediacy+of+Allylic+Sulfinic+Acids+in+the+Ene+Reaction+of+Sulfur+Dioxide+with+Double+Bonds.">Organic Reactions of Sulfur Dioxide. 4. A Facile Regiospecific Hydrogen-Deuterium Exchange in Olefins. Consequence of the Intermediacy of Allylic Sulfinic Acids in the Ene Reaction of Sulfur Dioxide with Double Bonds.</a> J. Am. Chem. Soc. 100 (14), 4634-4635 (1978).</li><li>Makitra, R. G., Kal'muk, S. D., Bryk, D. V., Polyuzhin, I. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Factors+Controlling+Sulfur+Dioxide+Solubilities+in+Organic+Solvents.">Factors Controlling Sulfur Dioxide Solubilities in Organic Solvents.</a> Russ. J. Inorg. Chem. 55 (8), 1322-1329 (2010).</li><li>van Dam, M. H. H., Lamine, A. S., Roizard, D., Lochon, P., Roizard, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+Sulfur+Dioxide+Removal+Using+Organic+Solvents.">Selective Sulfur Dioxide Removal Using Organic Solvents.</a> Ind. Eng. Chem. Res. 36 (11), 4628-4637 (1997).</li><li>Li, H., Jiao, X., Chen, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Solubility+of+Sulphur+Dioxide+in+Polar+Organic+Solvents.">Solubility of Sulphur Dioxide in Polar Organic Solvents.</a> Phys. Chem. Liq. 52 (2), 349-353 (2014).</li><li>Trost, B. M., Brindle, C. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Direct+Catalytic+Asymmetric+Aldol+Reaction.">The Direct Catalytic Asymmetric Aldol Reaction.</a> Chem. Soc. Rev. 39 (5), 1600 (2010).</li></ol>

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最初尝试使用亚硫酸氢反应作为一种方法来去除醛使用典型的两相萃取, 导致极低的去除水平。我们假设, 反应是不够快, 在非常有限的时间内发生的两层接触。为了增加反应物之间的接触, 我们开发了一个两阶段萃取协议, 在这种条件下, 首先使用水混溶溶剂, 使反应物在引入不溶溶剂之前有足够的混合。引入不相容的溶剂, 然后允许分离的带电亚硫酸氢合物从带电有机成分。该协议的关键步骤是使...

混合物组分的分离对制备纯材料是必不可少的。本文介绍的方法允许从其他有机分子中简便地分离醛和 sterically 不受阻碍的循环和甲基酮1。该技术依赖亚硫酸氢与羰基基团的反应性, 创建一个可分离成水层的带电加合物, 而其他组分则分离成不相容的有机层。在亚硫酸氢和羰基之间实现反应性的关键是使用一种混溶溶剂, 这使得在分离之前的反应发生在不同的阶段。如果没有加入混溶溶剂的最小分离, 大概是由于亲水性亚硫酸氢和疏水性有机物之间的接触差。
这种分离方法的优点是能方便地进行纯化。液-液萃取是一种简单的操作, 可以大规模地进行。替代纯化技术, 如柱层析, 是昂贵得多, 耗时, 并具有挑战性的大规模执行, 需要充分的差异, 在极性方面的成分。通过再结晶或蒸馏提纯, 需要对混合物组分的溶解度或沸点进行充分的分异。由于亚硫酸氢提取依赖于醛和酮羰基基团反应性的差异, 具有相似溶解度、沸点或极性的化合物可以有效地分离。其他化学分离方法存在选择性地分离醛和酮从混合物, 例如, 选择性形成肟2, 循环缩醛产物3, 或缩4 形成。这些方法需要额外的步骤来分离形成的物种与混合物, 因为产品不是水溶性的, 因此不能用简单的萃取协议分离。醛氧化形成可移动羧酸是另一种报告的技术5, 但所需的氧化步骤是低于 chemoselective 的温和亚硫酸氢条件, 并要求使用氧气气体和钴催化剂。
此方法适用于不包含这些功能组的分子的分离醛 (图 1) 和 sterically 不受阻碍的循环和甲基酮 (图 2)。特别是反应性酮, 如α-酮酯也被删除使用这个过程。烷烃, 烯烃, 二烯烃, 炔烃, 酯, 酰胺, 羧酸, 烷基卤化物, 醇, 酚, 腈, 苄基氯化物, 环氧化合物, 苯胺, 缩醛产物, 和稍受阻, α, β不饱和, 或芳酮都不活跃在条件下并且可以与混合物中的醛或反应性酮组分 (图2和图形 3) 分开。例如, 乙基酮或α取代的循环酮受到了充分的阻碍, 因此可从醛类和更多反应性酮中分离出来。当使用烯烃时, 将己烷推荐为不溶溶剂, 以防止亚硫酸氢溶液中的二氧化硫造成不必要的分解。亚硫酸氢萃取协议的官能团相容性非常广泛, 因此适用于极宽范围的分离, 如果要从混合物中分离的羰基污染物要么是醛或不受阻碍甲基或循环酮。没有反应的酮在这些情况下不会与亚硫酸氢反应, 因此不被去除。

<table><tbody><tr><td>sodium bisulfite</td><td>Fisher</td><td>AC419440010&amp;nbsp;</td><td>1 kg</td></tr><tr><td>benzyl butyrate</td><td>Fisher</td><td>AAB2424130&amp;nbsp;</td><td>250 g</td></tr><tr><td>anisaldehyde</td><td>Fisher</td><td>AC104801000&amp;nbsp;</td><td>100 mL</td></tr><tr><td>magnesium sulfate</td><td>Fisher</td><td>M65-500&amp;nbsp;</td><td>500 g</td></tr><tr><td>ethyl acetate</td><td>Fisher</td><td>E195-4&amp;nbsp;</td><td>4 L</td></tr><tr><td>hexanes</td><td>Fisher</td><td>H292-4&amp;nbsp;</td><td>4 L</td></tr><tr><td>methanol&amp;nbsp;</td><td>Fisher</td><td>A456-1&amp;nbsp;</td><td>1 L</td></tr><tr><td>dimethylformamide</td><td>Fisher</td><td>D119-1&amp;nbsp;</td><td>1 L</td></tr><tr><td>citronellal</td><td>Fisher</td><td>AAL15753AE&amp;nbsp;</td><td>100 mL</td></tr><tr><td>benzylacetone&amp;nbsp;</td><td>Fisher</td><td>AC105832500&amp;nbsp;</td><td>250 mL</td></tr><tr><td>deionized water</td><td>Fisher</td><td>BP28194&amp;nbsp;</td><td>4 L</td></tr><tr><td>piperonal&amp;nbsp;</td><td>Sigma-Aldrich</td><td>P49104-25G</td><td>25 G</td></tr><tr><td>sodium hydroxide</td><td>Fisher</td><td>S318-1&amp;nbsp;</td><td>1 kg</td></tr><tr><td>separatory funnel with cap</td><td>Fisher</td><td>10-437-5B&amp;nbsp;</td><td>125 mL</td></tr><tr><td>ring stand</td><td>Fisher</td><td>03-422-215</td><td>3 aluminum rods</td></tr><tr><td>ring clamp</td><td>Fisher</td><td>12-000-104&amp;nbsp;</td><td>5 cm</td></tr><tr><td>cork ring</td><td>Fisher</td><td>07-835AA&amp;nbsp;</td><td>8 cm outer dimension</td></tr><tr><td>round bottom flask</td><td>Fisher</td><td>31-501-107&amp;nbsp;</td><td>100 mL</td></tr><tr><td>rotary evaporator with accessories</td><td>Fisher</td><td>05-000-461&amp;nbsp;</td><td>cold trap bondenser</td></tr><tr><td>bump trap 14/20 joint</td><td>Fisher</td><td>CG132201</td><td>14/20 joint</td></tr><tr><td>funnel</td><td>Fisher</td><td>05-555-6&amp;nbsp;</td><td>organic solvent compatible</td></tr><tr><td>cotton</td><td>Fisher</td><td>22-456-881</td><td>non-sterile</td></tr><tr><td>glass pipets</td><td>Fisher</td><td>13-678-20A&amp;nbsp;</td><td>borosilicate 5.75&quot;</td></tr><tr><td>two 250 microliter syringes</td><td>Fisher</td><td>14-813-69&amp;nbsp;</td><td></td></tr><tr><td>4 erlenmeyer flasks</td><td>Fisher</td><td>10-040D&amp;nbsp;</td><td>125 mL</td></tr><tr><td>fume hood&amp;nbsp;</td><td>Fisher</td><td>13-118-370&amp;nbsp;</td><td></td></tr><tr><td>nitrile gloves</td><td>Fisher</td><td>19-149-863B&amp;nbsp;</td><td>medium</td></tr><tr><td>safety goggles</td><td>Fisher</td><td>17-377-403&amp;nbsp;</td><td></td></tr><tr><td>spatula</td><td>Fisher</td><td>14-357Q</td><td></td></tr><tr><td>balance</td><td>Fisher</td><td>01-912-403&amp;nbsp;</td><td>120 g capacity</td></tr></tbody></table>

separation of aldehydes and reactive ketones from mixtures using a bisulfite extraction protocol

有机化合物的提纯是常规合成作业的重要组成部分。通过生成带电结构将污染物移到水层中的能力提供了利用萃取作为一种简单的净化技术的机会。通过将混溶有机溶剂与饱和亚硫酸氢钠结合使用, 可以成功地将醛类和反应性酮转化为带电的亚硫酸氢加合物, 然后将其与混合物的其他有机成分分离。介绍一种不相容的有机层。在这里, 我们描述了一个简单的协议, 以去除醛, 包括 sterically 受阻的新戊二醛和一些酮, 从化学混合物。酮可以分离, 如果他们是 sterically 不受阻碍的循环或甲基酮。对于脂肪族醛类和酮类, 甲基酰胺被用作混溶溶剂, 以提高去除率。亚硫酸氢的加入反应可以通过碱化的水层来逆转, 从而使混合物的反应羰基组分重新分离。

用于醛去除的过程1用于芳香醛。过程2, 其中甲基酰胺用作混溶溶剂, 应用于脂肪族醛和酮。过程2还应用于不完全溶于甲醇的混合物。利用1H 核磁共振积分分析和质量恢复率分析了从每种协议获得的材料的纯度。典型的纯度和恢复大于 95% (图 1)。成功的分离取决于醛或酮组件 (图 4和...

Watch this Scientific Journal Video about Separation of Aldehydes and Reactive Ketones from Mixtures Using a Bisulfite Extraction Protocol at JoVE.com

Separation of Aldehydes and Reactive Ketones from Mixtures Using a Bisulfite Extraction Protocol

用亚硫酸氢萃取协议分离混合物中的醛和反应性酮

在这里, 我们提出了一个协议, 从混合物中去除醛和反应酮的液体-液体萃取协议直接与饱和亚硫酸氢钠在混溶溶剂。这个组合协议是快速和轻便的执行。醛或酮可以通过水层的碱化重新分离。

The purification of organic compounds is an essential component of routine synthetic operations. The ability to remove contaminants into an aqueous layer ...

separation-aldehydes-reactive-ketones-from-mixtures-using-bisulfite

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Introduction: Matter and Measurement

SCIENTISTS IN ACTION

33.8K 次观看.  Trinity College. 在这里, 我们提出了一个协议, 从混合物中去除醛和反应酮的液体-液体萃取协议直接与饱和亚硫酸氢钠在混溶溶剂。这个组合协议是快速和轻便的执行。醛或酮可以通过水层的碱化重新分离。

视频: Separation of Aldehydes and Reactive Ketones from Mixtures Using a Bisulfite Extraction Protocol

Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile

The Steglich esterification is a widely-used reaction for the synthesis of esters from carboxylic acids and alcohols. While efficient and mild, the reaction is commonly performed using chlorinated or amide solvent systems, which are hazardous to human health and the environment. Our methodology utilizes acetonitrile as a greener and less hazardous solvent system. This protocol exhibits rates and yields that are comparable to traditional solvent systems and employs an extraction and wash sequence that eliminates the need for the purification of the ester product via column chromatography. This general method can be used to couple a variety of carboxylic acids with 1&#176; and 2&#176; aliphatic alcohols, benzylic and allylic alcohols, and phenols to obtain pure esters in high yields. The goal of the protocol detailed here is to provide a greener alternative to a common esterification reaction, which could serve useful for ester synthesis in both academic and industrial applications.

A modified Steglich esterification reaction was used to synthesize a small library of ester derivatives with primary and secondary alcohols. The methodology uses a non-halogenated and greener solvent, acetonitrile, and enables product isolation in high yields without the need for chromatographic purification.

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 ...

科研

化学

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions

Aziridines, a class of reactive organic molecules containing a three-membered ring, are important synthons for the synthesis of a large variety of functionalized nitrogen-containing target compounds through the regiocontrolled ring-opening of C-substituted aziridines. Despite the tremendous progress in aziridine synthesis over the past decade, accessing contiguous bisaziridines efficiently remains difficult. Therefore, we were interested in synthesizing contiguous bisaziridines bearing an electronically diverse set of N-substituents beyond the single aziridine backbone for regioselective ring-opening reactions with diverse nucleophiles. In this study, chiral contiguous bisaziridines were prepared by organocatalytic asymmetric aziridination of chiral (E)-3-((S)-1-((R)-1-phenylethyl)aziridin-2-yl)acrylaldehyde with N-Ts-O-tosyl or N-Boc-O-tosyl hydroxylamine as the nitrogen source in the presence of (2S)-[diphenyl(trimethylsilyloxy)methyl]pyrrolidine as a chiral organocatalyst. Also demonstrated here are representative examples of regioselective ring-opening reactions of contiguous bisaziridines with a variety of nucleophiles such as sulfur, nitrogen, carbon, and oxygen, and the application of contiguous bisaziridines to the synthesis of multi-substituted chiral pyrrolidines by Pd-catalyzed hydrogenation.

Contiguous bisaziridines containing non-activated and activated aziridines were synthesized by asymmetric organocatalytic aziridinations and then subjected to chemoselective ring-opening reactions under acidic or basic conditions. The non-activated aziridine ring opens with less reactive nucleophiles under acidic conditions, whereas the activated aziridine ring opens with more reactive nucleophiles under basic conditions.

用于区域选择性开环反应的连续双氮丙啶的制备

Aziridines, a class of reactive organic molecules containing a three-membered ring, are important synthons for the synthesis of a large variety of ...

Reducing Agents

Source: Vy M. Dong and Daniel Kim, Department of Chemistry, University of California, Irvine, CA
Controlling the reactivity and selectivity during the synthesis of a molecule is very important criteria for chemists. This has led to the development of many reagents that allow chemists to pick and choose reagents suitable for a given task. Quite often, a balance between reactivity and selectivity needs to be achieved. This experiment will use IR spectroscopy to monitor the reaction and to understand the reactivity of carbonyl compounds as well as the reactivity of hydride-reducing reagents.

Reduction of Carbonyl Compounds

还原剂

Source: Vy M. Dong and Daniel Kim, Department of Chemistry, University of California, Irvine, CA
Controlling the reactivity and selectivity during the ...

教育

JoVE Science Education

有机化学 (2)

Alcohols from Carbonyl Compounds: Reduction

Reduction is a simple strategy to convert a carbonyl group to a hydroxyl group. The three major pathways to reduce carbonyls to alcohols are catalytic hydrogenation, hydride reduction, and borane reduction.
Catalytic hydrogenation is similar to the reduction of an alkene or alkyne by adding H2 across the pi bond in the presence of transition metal catalysts like Raney Ni, Pd&#8211;C, Pt, or Ru. Aldehydes and ketones can be reduced by this method, often under mild to moderate heat (25&#8211;100&#176;C) and pressure (1&#8211;5 atm H2), to yield 1&#176; and 2&#176; alcohols, respectively.
<img alt="Figure1" src="/files/ftp_upload/11925/11925_PT_Figure_1.svg" style="text-align: center; height: 90px;" />
Figure 1. Catalytic hydrogenation can be suitable for industrial applications when harsh conditions are not required, but unsaturated carbon&#8211;carbon bonds are also reduced.
Hydride reduction can be achieved by hydride transfer reagents, like sodium borohydride (NaBH4) and lithium aluminum hydride (LiAlH4, or LAH), as nucleophilic attack by a free hydride ion, <img alt="Figure2" src="/files/ftp_upload/11925/11925_PT_Figure_2.svg" style="height: 18px;" />, is almost unknown for NaH salts due to its high charge density, making it a strong base. The hydrogen atoms of LAH and NaBH4, being covalently bonded to boron and aluminum atoms, have partial negative charges, thereby enhancing their nucleophilicity at the cost of basicity. The first step of nucleophilic addition leads to the formation of alkoxide ions. The byproduct alkoxyborohydride or alkoxyaluminate reduces three more carbonyl molecules, successively transferring all their hydrogen atoms. Since hydride is a poor leaving group, the hydride transfer steps are irreversible, and therefore the reaction proceeds to completion. Lastly, the reaction mixture is worked up with solvent (i.e., water or alcohol in the case of NaBH4 and dilute acid in the case of LAH).
<img alt="Figure3" src="/files/ftp_upload/11925/11925_PT_Figure_3.svg" style="text-align: center; height:55px;" />
Figure 2. Aldehydes and symmetrical esters produce one 1&#176; alcohol product. Unsymmetrical esters produce a mixture of 1&#176; alcohols.
LAH, NaBH4, and their derivatives are highly useful in the reduction of aldehydes and ketones. LAH, a powerful reducing agent, can also reduce carbonyl compounds like acids, esters, acyl chlorides, and amides. LAH reacts violently with water and other protic solvents, liberating hydrogen gas and forming metal hydroxides/alkoxides. Hence, LAH reductions are typically carried out in aprotic solvents like anhydrous diethyl ether and THF.
<img alt="Figure4" src="/files/ftp_upload/11925/11925_PT_Figure_4.svg" style="text-align: center; height: 45px;" />
Figure 3. An alcoholic solution of lithium borohydride is a non-hazardous alternative to LAH in selectively reducing esters over acids.
On the other hand, NaBH4 is of a milder nature and generally reduces only in protic solvents like ethanol or methanol. Therefore, NaBH4 can be used to reduce aldehydes and ketones in the presence of functional groups like alkyl halides, esters, alkyl tosylates, and nitro groups. Diisobutylaluminum hydride (DIBAL-H) can also convert carbonyls to alcohols at room temperature by two successive additions of hydride ions. However, when reacted with esters at low temperatures, this reaction can be stopped at the aldehyde stage by adding only one equivalent of hydride ion.
Borane reduction uses a borane (BH3) solution in diethyl ether, THF, or Me2S to selectively reduce electron-rich carbonyl groups like carboxylic acids in the presence of other reducible functional groups such as esters and even ketones.
<img alt="Figure5" src="/files/ftp_upload/11925/11925_PT_Figure_5.svg" style="text-align: center; height: 65px;" />
Figure 4. The formation of a reactive triacylborate intermediate with a more electrophilic carbonyl group than the starting ester molecule drives the reduction reaction forward.
For living organisms, reduced coenzyme NADH or its phosphoester NADPH is equivalent to laboratory hydride reagents in enzyme catalysis of similar biological reductions.

羰基化合物中的醇类:还原

Reduction is a simple strategy to convert a carbonyl group to a hydroxyl group. The three major pathways to reduce carbonyls to alcohols are catalytic ...

有机化学

Unit 1

醇类和酚类

关键术语与概念

Preparation of Aldehydes and Ketones from Alcohols, Alkenes, and Alkynes

Aldehydes and ketones are prepared from alcohols, alkenes, and alkynes via different reaction pathways. Alcohols are the most commonly used substrates for synthesizing aldehydes and ketones. The conversion of alcohol to aldehyde, which involves the oxidation process, depends on the class of the alcohol used and the strength of the oxidizing agent. For instance, primary alcohol will form an aldehyde when treated with a weak oxidizing agent; however, it gets over-oxidized to a carboxylic acid in the presence of a strong oxidizing agent. Hence, a mild oxidant like pyridinium chlorochromate is used to convert primary alcohols to aldehydes.
Similarly, Swern and Dess&#8211;Martin oxidations, which employ weaker oxidizing agents, convert primary alcohols to aldehydes. The strength of the oxidizing agent is irrelevant when converting secondary alcohol to a ketone. Both mild and strong oxidants give ketones from secondary alcohols.
Unsaturated hydrocarbons like alkenes undergo an ozonolysis reaction to give aldehydes and ketones. The product formed depends on the substitution present across the double bond in an alkene. A monosubstituted alkene forms formaldehyde and another aldehyde molecule. However, disubstitution gives rise to two cases. A 1,1-disubstituted alkene upon ozonolysis forms a mixture of formaldehyde and ketone, while a 1,2-disubstituted alkene yields a mixture of aldehydes. Both aldehydes and ketones are formed when trisubstituted alkenes undergo ozonolysis, while tetrasubstituted alkenes form ketones exclusively.
Alkynes&#160;also form aldehydes and ketones under hydroboration-oxidation and acid-catalyzed hydration reaction conditions. The hydroboration-oxidation reaction favors anti-Markovnikov&#8217;s addition. Hence terminal alkynes form aldehydes, and internal alkynes&#160;yield ketones. On the other hand, the acid-catalyzed hydration reaction follows Markonikov&#8217;s addition, and thus both terminal and internal alkynes generate&#160;ketones.

从醇、烯烃和炔烃制备醛和酮

Aldehydes and ketones are prepared from alcohols, alkenes, and alkynes via different reaction pathways. Alcohols are the most commonly used substrates for ...

Aldehydes and Ketones

Preparation of Aldehydes and Ketones from Nitriles and Carboxylic Acids

Although it is possible to reduce a carboxylic acid to an aldehyde, strong reducing agents, like lithium aluminum hydride (LAH), prohibit a controlled reduction, instead causing the generated aldehyde to instantly over-reduce to a primary alcohol.
Reducing carboxylic acid derivatives like acyl chlorides (RCOCl), esters (RCO2R&prime;), and nitriles (RCN) using milder aluminum hydride agents like lithium tri-tert-butoxyaluminum hydride [LiAlH(O-t-Bu)3] and diisobutylaluminum hydride [DIBAL-H] allows the easy conversion of the derivative to the corresponding aldehyde. This is because alkylaluminum hydrides are less reactive than LAH, as the former is more sterically hindered.
According to recent studies, a reductant like diphenylsilane in combination with an air-stable Ni precatalyst and dimethyl dicarbonate as an activator converts most of the carboxylic acid to the aldehyde without causing any over-reduction.
In other studies, a hydrosilane through visible light photoredox catalysis efficiently reduces carboxylic acids to aldehydes.
Ketones, unlike aldehydes, can be directly prepared from carboxylic acids using organolithium reagents. The acid rapidly reacts with two equivalents of an organolithium reagent to form a dianion. This dianion gets protonated to form the corresponding hydrate, which loses a water molecule to give a ketone.
Both aldehydes and ketones can be prepared from nitriles using suitable reducing agents. Aldehydes are formed by the partial reduction of nitriles in the presence of DIBAL-H. The nitrile first forms an aluminum complex, which later, on hydrolysis, yields the corresponding aldehyde. Nitriles can be reduced to ketones via imine intermediates using Grignard or organolithium reagents.

从腈和羧酸制备醛和酮

Although it is possible to reduce a carboxylic acid to an aldehyde, strong reducing agents, like lithium aluminum hydride (LAH), prohibit a controlled ...

Preparation of Aldehydes and Ketones from Carboxylic Acid Derivatives

Aldehydes are more reactive than carboxylic acids and hence, can get over-reduced to alcohol in the presence of strong reducing agents. Therefore, carboxylic acids are&#160;inefficient in preparing aldehydes using LAH.
Carboxylic acid derivatives like acid chlorides and esters are more easily reducible than the corresponding acids. The derivatives reduce in the presence of mild reducing agents to give aldehydes. Aldehydes can also be prepared by Rosenmund reduction, that is, the reduction of acid chloride via hydrogenation over a poisoned catalyst. Catalytic poisoning inhibits the over-reduction of aldehydes. A Grignard reagent reduces an acid chloride to tertiary alcohol via a ketone intermediate. The reaction can be stopped at the ketone stage using a milder reducing agent like the Gilman reagent (R2CuLi). Aryl ketones can be prepared by Friedel&#8211;Crafts acylation&#160;in which acid chloride is treated with benzene and AlCl3.
Another carboxylic acid derivative, an ester, can be reduced to an aldehyde using DIBAL-H at dry ice temperature to give an aldehyde. Ketones cannot be prepared directly from esters because ketones are more reactive than esters and tend to over-reduce to tertiary alcohol.

从羧酸衍生物制备醛和酮

Aldehydes are more reactive than carboxylic acids and hence, can get over-reduced to alcohol in the presence of strong reducing agents. Therefore, ...

Reactions of Aldehydes and Ketones: Baeyer&ndash;Villiger Oxidation

Baeyer&#8211;Villiger oxidation converts aldehydes to carboxylic acids and ketones to esters. The reaction uses peroxy acids or peracids and is often catalyzed by acid. The reaction is named after its pioneers, Adolf von Baeyer and Victor Villiger. The reaction is achieved by a wide range of peracids such as m-chloroperoxybenzoic acid (mCPBA), perbenzoic acid (C6H5COOOH), peracetic acid (CH3COOOH), hydrogen peroxide (H2O2), and tert-butyl hydroperoxide (t-BuOOH).
The carbonyl center is activated by protonating the carbonyl oxygen. The peracid then adds across the C=O bond to give a tetrahedral intermediate called the Criegee intermediate. During the concerted intramolecular rearrangement that follows, the carbonyl group is restored, a group migrates from carbon to oxygen, and the weak peroxide bond cleaves to give an acid (if the substrate is an aldehyde) or an ester (if the substrate is a ketone).
<img alt="Figure1" src="/files/ftp_upload/12341/12341_PT_Figure_1.svg" style="text-align: center; height: 275px;" />
The migratory aptitude of different groups follows the order of &#8211;H &#62; &#8211;CR3 &#62; &#8211;CHR2 &approx; &#8211;Ph &#62; &#8211;CRH2 &#62; &#8211;&NoBreak;CH3. This makes Baeyer&#8211;Villiger oxidation regioselective. Also, the reaction retains the stereochemistry at the migrating center for asymmetrical substrates. Reactions involving cyclic ketones produce lactones.

Reactions of Aldehydes and Ketones: Baeyer&amp;#8211;Villiger Oxidation

醛和酮的反应:Baeyer-Villiger 氧化

Baeyer&#8211;Villiger oxidation converts aldehydes to carboxylic acids and ketones to esters. The reaction uses peroxy acids or peracids and is often ...

&alpha;-Hydroxy Ketones via Reductive Coupling of Esters: Acyloin Condensation Overview

The pinacol and McMurry reactions involve the reductive coupling of ketones or aldehydes. Similarly, the bimolecular reductive coupling of two ester molecules in the presence of sodium metal in an aprotic solvent yields an &#945;-hydroxy ketone product. The &#945;-hydroxy ketone is also called acyloin, so the reaction is referred to as &#8216;acyloin condensation.&#8217;
<img alt="Figure1" src="/files/ftp_upload/12908/12908_PT_Figure_1.svg" style="text-align: center; height: 65px;" />
In the acyloin condensation reaction, esters are converted to ketyls, which undergo radical dimerization to form an unstable tetrahedral intermediate. Further, this intermediate collapses to give a 1,2-diketone intermediate. The 1,2-diketones are comparatively more reactive than ketones towards electrophiles and reducing agents because of lower &#960;* energy. Consequently, two electrons sequentially transfer to the 1,2-diketone to form an enediolate. Lastly, the enediolate intermediate is quenched with acid to yield an &#945;-hydroxy ketone with a good yield.
Often some by-products are obtained alongside the major product because of the reactivity of nucleophilic enediolate. To overcome the side reactions and improve the yield of an acyloin, trimethylsilyl chloride is used to silylate the enediolate. This results in a bis-silyl ether, further hydrolyzed with aqueous acid to give &#945;-hydroxy ketones.

&amp;#945;-Hydroxy Ketones via Reductive Coupling of Esters: Acyloin Condensation Overview

通过酯的还原偶联得到 α-羟基酮:Acyloin 缩合概述

The pinacol and McMurry reactions involve the reductive coupling of ketones or aldehydes. Similarly, the bimolecular reductive coupling of two ester ...

Radical Chemistry

Alkylation of &beta;-Ketoester Enolates: Acetoacetic Ester Synthesis

Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and &beta;-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the &beta;-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C&#8211;C bond. The hydrolysis of the intermediate, followed by acidification, results in an alkylated &beta;-keto acid. Under high-temperature conditions, the &beta;-keto acid undergoes decarboxylation to form a ketone. However, if the alkylation is repeated before hydrolysis and decarboxylation steps, a disubstituted ketone is obtained.

Alkylation of &amp;#946;-Ketoester Enolates: Acetoacetic Ester Synthesis

β-酮酯烯醇化物的烷基化反应:乙酰乙酸酯合成

Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and &beta;-keto esters. The reaction occurs in the presence of an alkoxide ...