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

Se hace reconocimiento a los donantes de americano químico sociedad investigación fondo petrolero para soporte parcial de esta investigación. Agradecemos a la National Science Foundation (-0619275 y-0963165) becas de renovación y la instrumentación que apoyaron esta investigación.

1. estándar protocolo para la separación de aldehídos aromáticos de una mezcla. Ejemplo: Separación de butirato de bencilo de una mezcla 1:1 con Anisaldehyde.
<ol><li>Disolver 175 μL de anisaldehyde y 250 μL de butirato de bencilo en 5 mL de metanol y transferir la solución a un matraz de filtración. PRECAUCIÓN: Bisulfito de sodio puede generar gas de dióxido de sulfuro, así este protocolo debe realizarse con ventilación adecuada, como en una campana de humos.</li>
	<li>Añadir 1 mL de bisulfito de sodio acuoso saturado y agitar vigorosamente durante aproximadamente 30 s.</li>
	<li>Añadir 25 mL de agua desionizada y 25 mL de 10% de acetato de etilo/hexanes y agite vigorosamente.</li>
	<li>Separar las capas. Secar la capa orgánica con sulfato de magnesio anhidro. Filtrar la solución para eliminar el sulfato de magnesio y concentrarse en vacío usando un evaporador rotatorio.</li>
</ol>2. separación de alifáticos aldehinos y cetonas de una mezcla. Ejemplo: Separación de butirato de bencilo de una mezcla 1:1 con Benzylacetone.
<ol><li>Disolver 213 μL de benzylacetone y 250 μL de butirato de bencilo en 10 mL de dimetilformamida y transferir la solución a un matraz de filtración. PRECAUCIÓN: Bisulfito de sodio puede generar gas de dióxido de sulfuro, así este protocolo debe realizarse con ventilación adecuada, como en una campana de humos.</li>
	<li>Añadir 25 mL de bisulfito de sodio acuoso saturado y agitar vigorosamente durante aproximadamente 30 s.</li>
	<li>Añadir 25 mL de agua desionizada y 25 mL de 10% de acetato de etilo/hexanes y agite vigorosamente.</li>
	<li>Separar las capas. Volver a la capa acuosa al embudo de separatory, añadir 25 mL de 10% de acetato de etilo/hexanes y agite vigorosamente. La capa acuosa, dejando la capa orgánica en el embudo de desagüe. Añadir la capa orgánica anterior hacia el embudo.</li>
	<li>Lavar las capas orgánicas combinadas tres veces con agua desionizada (10 mL en cada lavado). Secar la capa orgánica con sulfato de magnesio anhidro. Filtrar la solución para eliminar el sulfato de magnesio y concentrarse en vacío usando un evaporador rotatorio.</li>
</ol>3. separación de aldehídos de una mezcla que contiene un Alkene. Ejemplo: Separación de butirato de bencilo de una mezcla 1:1 con Citronelal.
<ol><li>Disolver 255 μL de Citronelal y 250 μL de butirato de bencilo en 10 mL de dimetilformamida y transferir la solución a un matraz de filtración. PRECAUCIÓN: Bisulfito de sodio puede generar gas de dióxido de sulfuro, así este protocolo debe realizarse con ventilación adecuada, como en una campana de humos.</li>
	<li>Añadir 25 mL de bisulfito de sodio acuoso saturado y agitar vigorosamente durante aproximadamente 30 s.</li>
	<li>Añadir 25 mL de agua desionizada y 25 mL de hexanes y agite vigorosamente.</li>
	<li>Separar las capas. Retomar la capa acuosa del embudo de separatory, añadir hexanes 25 mL y agitar enérgicamente. La capa acuosa, dejando la capa orgánica en el embudo de desagüe. Añadir la capa orgánica anterior hacia el embudo.</li>
	<li>Lavar las capas orgánicas combinadas tres veces con agua desionizada (10 mL en cada lavado). Secar la capa orgánica con sulfato de magnesio anhidro. Filtrar la solución para eliminar el sulfato de magnesio y concentrarse en vacío usando un evaporador rotatorio.</li>
</ol>4. re-aislamiento de aldehídos de una mezcla. Ejemplo: Separación de Piperonal de una mezcla 1:1 con butirato de bencilo.
<ol><li>Disolver 217 mg de piperonal y 250 μL de butirato de bencilo en 5 mL de metanol y transferir la solución a un matraz de filtración. PRECAUCIÓN: Bisulfito de sodio puede generar gas de dióxido de azufre, por lo tanto, este protocolo debe realizarse con ventilación adecuada, como en una campana de humos.</li>
	<li>Añadir 1 mL de bisulfito de sodio acuoso saturado y agitar vigorosamente durante aproximadamente 30 s.</li>
	<li>Añadir 25 mL de agua desionizada y 25 mL de 10% de acetato de etilo/hexanes y agite vigorosamente.</li>
	<li>Separar las capas. Nuevamente la capa acuosa del embudo.<ol>
<li>Opcional: Lavado acuoso capa una vez con 25 mL de acetato de etilo/hexanes del 10% para eliminar la pequeña cantidad de butirato de bencilo restantes.</li>
	</ol>
</li>
	<li>Añadir 25 mL de acetato de etilo y agregar luego 50% hidróxido de sodio hasta una tira de pH indica que el pH es 12. Agite vigorosamente. PRECAUCIÓN: Evolución de Gas se ha observado durante este paso y puede causar la acumulación de la presión. Asegúrese de ventilar adecuadamente el embudo. Ampliar este procedimiento hará que la evolución de gas más pronunciado. Tenga cuidado.</li>
	<li>Separar las capas. Devolver la capa acuosa para el matraz y añadir 25 mL de acetato de etilo. Agite vigorosamente.</li>
	<li>Separar las capas. Combinar la capa orgánica con la capa orgánica del paso anterior. Secar la capa orgánica combinada con sulfato de magnesio anhidro. Filtrar la solución para eliminar el sulfato de magnesio y concentrarse en vacío usando un evaporador rotatorio.</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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Inicial intenta utilizar la reacción del bisulfito como un método para eliminar aldehídos mediante una extracción de 2 fases típica llevada a niveles muy bajos de retiro. La hipótesis de que la reacción no fue lo suficientemente rápida como para ocurrir durante el tiempo muy limitado que las dos capas en contacto. Para aumentar el contacto entre los reactantes, hemos desarrollado un protocolo de extracción de dos fases en el que un disolvente miscible con agua se utiliza inicialmente para permitir suficiente mez...

La separación de componentes de mezclas entre ellas es esencial para la preparación de los materiales puros. El método descrito en este documento permite la fácil separación de aldehinos y sterically unhindered cíclico y metil cetonas de otras moléculas orgánicas1. La técnica se basa en la reactividad de bisulfito con el grupo carbonilo para crear un aducto que se puede separar en una capa acuosa, mientras que otros componentes de separan en una capa orgánica inmiscible. La clave para alcanzar la reactividad entre el bisulfito y el carbonilo es el uso de un solvente miscible, que permite la reacción que tendrá lugar antes de la separación en fases separadas. Sin la adición de la separación mínima solvente miscible es obtenida, presumiblemente debido al mal contacto entre el bisulfito hidrofílico y los compuestos orgánicos hidrofóbicos.
La ventaja de este método de separación para la purificación es la facilidad del protocolo. Extracción líquido-líquido es una operación sencilla de realizar y puede llevarse a cabo en gran escala. Técnicas de purificación alternativos, tales como cromatografía en columna, son mucho más costosos, desperdiciadores de tiempo y difíciles de realizar en gran escala y requieren suficiente diferenciación de los componentes en términos de polaridad. La purificación por recristalización o destilación requiere suficiente diferenciación entre la solubilidad y puntos de ebullición de los componentes de la mezcla, respectivamente. Porque extracción de bisulfito se basa en la diferencia en la reactividad del grupo carbonilo de aldehídos y cetonas, compuestos con similar solubilidad, puntos de ebullición o polaridades pueden separar con eficacia. Otros métodos de separación químicos existen para la separación selectiva de aldehídos y cetonas de mezclas, por ejemplo, la formación selectiva de oximas2, Acetales cíclicos3o mercaptal4 formación. Estos métodos requieren un paso adicional para separar las especies formadas de la mezcla, porque el producto no es soluble en agua y por lo tanto no se puede separar por un protocolo de extracción simple. Oxidación del aldehído para formar ácidos carboxílicos extraíbles es otro había comunicado técnica5, pero el paso de oxidación requiere menos estereoselectiva que las condiciones de bisulfito leve descrita en este documento y requiere el uso de gas de oxígeno y un catalizador de cobalto.
Este método es aplicable a la separación de aldehidos (figura 1) y unhindered sterically cíclicas y metil cetonas (figura 2) de las moléculas que no contienen estos grupos funcionales. Particularmente reactivas cetonas, como la α-ceto ésteres también se quitan usando este proceso. Alcanos, alquenos, dienos, alquinos, ésteres, amidas, ácidos carboxílicos, halides alkyl, alcoholes, fenoles, nitrilos, cloruros de bencil, epóxidos, anilinas, acetales, y ligeramente obstaculizado, α, β-insaturado, o aril cetonas son todos no reacciona en las condiciones y se puede separar del aldehino o cetona reactivo componente de la mezcla (figuras 2 y figura 3). Cetonas Ethyl o cetonas cíclicas α-sustituido, por ejemplo, son suficientemente obstaculizadas y por lo tanto son separables de aldehídos y cetonas más reactivas. Al usar los alkenes, hexano se recomienda como el solvente inmiscible para evitar descomposición no deseada debido al dióxido de azufre presente en la solución de bisulfito. La compatibilidad de grupo funcional del Protocolo de extracción de bisulfito es extremadamente amplia y por lo tanto es aplicable a una gama muy amplia de las separaciones, si el contaminante de carbonilo que se separará de la mezcla es un aldehído o una sin obstáculos metilo o cetona cíclica. Menos reactivas cetonas no reaccionan con bisulfito bajo estas condiciones y por lo tanto no se quitan.

<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

La purificación de compuestos orgánicos es un componente esencial de las operaciones sintéticas de rutina. La capacidad para eliminar los contaminantes en una capa acuosa generando una estructura cargada proporciona la oportunidad de utilizar extracción como una técnica de purificación simple. Combinando el uso de un disolvente orgánico miscible con bisulfito de sodio saturado, aldehídos y cetonas reactivas puede con éxito transformarse cargado bisulfito de aductos que puede entonces ser separados de otros componentes orgánicos de una mezcla por la introducción de una capa orgánica inmiscible. Aquí, describimos un protocolo simple para la remoción de aldehídos, incluyendo aldehídos Neopentilglicol sterically obstaculizado y algunas cetonas, de mezclas químicas. Las cetonas pueden ser separadas si ellos son sterically unhindered cíclica o metil cetonas. Para alifáticos aldehinos y cetonas, dimetilformamida se utiliza como solvente miscible para mejorar las tasas de extracción. Puede invertirse la reacción de adición de bisulfito por basification de la capa acuosa, lo que permite el nuevo aislamiento del componente carbonilo reactivo de una mezcla.

Procedimiento 1 para el retiro del aldehino se utiliza para aldehídos aromáticos. Procedimiento 2, en el cual dimetilformamida se utiliza como disolvente miscible, puede usarse para cetonas y Aldehídos alifáticos. Procedimiento 2 también puede usarse para mezclas que no son totalmente solubles en metanol. El material obtenido de cada uno de los protocolos se analiza para pureza utilizando 1análisis de integración H NMR y...

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

Separación de aldehidos y cetonas reactivas de mezclas mediante un protocolo de extracción de bisulfito

Aquí, presentamos un protocolo para eliminar aldehídos y cetonas reactivas de mezclas mediante un protocolo de extracción líquido-líquido directamente con bisulfito de sodio saturado en un solvente miscible. Este protocolo combinado es rápido y fácil de realizar. El aldehído o cetona puede aislarse nuevamente por basification de la capa acuosa.

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

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33.8K vistas.  Trinity College. Aquí, presentamos un protocolo para eliminar aldehídos y cetonas reactivas de mezclas mediante un protocolo de extracción líquido-líquido directamente con bisulfito de sodio saturado en un solvente miscible. Este protocolo combinado es rápido y fácil de realizar. El aldehído o cetona puede aislarse nuevamente por basification de la capa acuosa.

Video: 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.

Síntesis de ésteres mediante una esterificación Steglich más verde en acetonitrilo

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

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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.

Preparación de bisaziridinas contiguas para reacciones regioselectivas de apertura de anillo

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

Agentes de reducción

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

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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.

Alcoholes a partir de compuestos carbonilo: Reducción

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 ...

Química Orgánica

Unidad 1

Alcoholes y fenoles

TÉRMINOS Y CONCEPTOS CLAVES

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.

Preparación de aldehídos y cetonas a partir de alcoholes, alquenos y alquinos

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.

Preparación de aldehídos y cetonas a partir de nitrilos y ácidos carboxílicos

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.

Preparación de aldehídos y cetonas a partir de derivados del ácido carboxílico

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

Reacciones de aldehídos y cetonas: oxidación de Baeyer-Villiger

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

α-hidroxicetonas mediante acoplamiento reductor de ésteres: descripción general de la condensación de aciloína

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

Alquilación de enolatos de β-cetóster: síntesis de ésteres acetoacéticos

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 ...