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

Confirmação é feita para os doadores de American química sociedade petróleo fundo de investigação do suporte parcial desta pesquisa. Estamos gratos à Fundação Nacional de ciência (-0619275 e-0963165) para renovação e instrumentação subsídios que apoiou esta pesquisa.

1. padrão protocolo para a separação de aldeídos aromáticos de uma mistura. Exemplo: Separação de benzila butirato de uma mistura 1:1 com Anisaldeído.
<ol><li>Dissolver 175 μL de Anisaldeído e 250 μL de butirato de benzila em 5 mL de metanol e transferir a solução para um funil de separação. Cuidado: Bissulfito de sódio pode gerar gás dióxido de enxofre, assim, o presente protocolo deve ser efectuado com ventilação adequada, como em uma coifa.</li>
	<li>Adicionar 1 mL de bissulfito de sódio aquosa saturada e agitar vigorosamente por cerca de 30 s.</li>
	<li>Adicionar 25 mL de água desionizada e 25 mL de acetato de etila/hexanos de 10% e agitar vigorosamente.</li>
	<li>Separe as camadas. Seque a camada orgânica com sulfato de magnésio anidro. Filtre a solução para remover o sulfato de magnésio e concentre-se no vácuo usando um evaporador rotativo.</li>
</ol>2. separação de aldeídos alifáticos e cetonas de uma mistura. Exemplo: Separação de benzila butirato de uma mistura 1:1 com Benzylacetone.
<ol><li>Dissolver 213 μL de benzylacetone e 250 μL de butirato de benzila em 10 mL de dimetilformamida e transferir a solução para um funil de separação. Cuidado: Bissulfito de sódio pode gerar gás dióxido de enxofre, assim, o presente protocolo deve ser efectuado com ventilação adequada, como em uma coifa.</li>
	<li>Adicionar 25 mL de bissulfito de sódio aquosa saturada e agitar vigorosamente por cerca de 30 s.</li>
	<li>Adicionar 25 mL de água desionizada e 25 mL de acetato de etila/hexanos de 10% e agitar vigorosamente.</li>
	<li>Separe as camadas. Retornar a fase aquosa para o funil de separação, adicionar 25 mL de acetato de etila/hexanos de 10% e agitar vigorosamente. Escorra a camada aquosa, deixando a camada orgânica no funil de separação. Adicione a anterior camada orgânica para o funil de separação.</li>
	<li>Lave as camadas orgânicas combinadas três vezes com água desionizada (10 mL para cada lavagem). Seque a camada orgânica com sulfato de magnésio anidro. Filtre a solução para remover o sulfato de magnésio e concentre-se no vácuo usando um evaporador rotativo.</li>
</ol>3. separação de aldeídos de uma mistura contendo um alqueno. Exemplo: Separação de benzila butirato de uma mistura 1:1 com citronelal.
<ol><li>Dissolver 255 μL de citronelal e 250 μL de butirato de benzila em 10 mL de dimetilformamida e transferir a solução para um funil de separação. Cuidado: Bissulfito de sódio pode gerar gás dióxido de enxofre, assim, o presente protocolo deve ser efectuado com ventilação adequada, como em uma coifa.</li>
	<li>Adicionar 25 mL de bissulfito de sódio aquosa saturada e agitar vigorosamente por cerca de 30 s.</li>
	<li>Adicionar 25 mL de água desionizada e 25 mL de hexanos e agitar vigorosamente.</li>
	<li>Separe as camadas. Retornar a fase aquosa para o funil de separação, adicionar hexanos 25 mL e agitar vigorosamente. Escorra a camada aquosa, deixando a camada orgânica no funil de separação. Adicione a anterior camada orgânica para o funil de separação.</li>
	<li>Lave as camadas orgânicas combinadas três vezes com água desionizada (10 mL para cada lavagem). Seque a camada orgânica com sulfato de magnésio anidro. Filtre a solução para remover o sulfato de magnésio e concentre-se no vácuo usando um evaporador rotativo.</li>
</ol>4. re-isolamento de aldeídos a partir de uma mistura. Exemplo: Separação de Piperonal de uma mistura 1:1 com butirato de benzila.
<ol><li>Dissolver 217 mg de piperonal e 250 μL de butirato de benzila em 5 mL de metanol e transferir a solução para um funil de separação. Cuidado: Bissulfito de sódio pode gerar gás dióxido de enxofre, assim, o presente protocolo deve ser efectuado com ventilação adequada, como em uma coifa.</li>
	<li>Adicionar 1 mL de bissulfito de sódio aquosa saturada e agitar vigorosamente por cerca de 30 s.</li>
	<li>Adicionar 25 mL de água desionizada e 25 mL de acetato de etila/hexanos de 10% e agitar vigorosamente.</li>
	<li>Separe as camadas. Retorna a camada aquosa para o funil de separação.<ol>
<li>Opcional: Lavar a camada aquosa, uma vez com 25 mL de 10% de acetato de etilo/hexanos, para remover a pequena quantidade de butirato de benzila restantes.</li>
	</ol>
</li>
	<li>Adicionar 25 mL de acetato de etilo e adicione hidróxido de sódio 50% até uma faixa de pH indica que o pH é 12. Agite vigorosamente. Cuidado: Evolução de gás tem sido observada durante esta etapa e pode causar o acúmulo de pressão. Certifique-se de ventilar adequadamente o funil de separação. Ampliação deste procedimento fará com que evolução de gás mais pronunciada. Tenha cuidado.</li>
	<li>Separe as camadas. Retornar a fase aquosa para o funil de separação e adicionar 25 mL de acetato de etila. Agite vigorosamente.</li>
	<li>Separe as camadas. Combine a camada orgânica com a camada orgânica da etapa anterior. Seque a camada orgânica combinada com sulfato de magnésio anidro. Filtre a solução para remover o sulfato de magnésio e concentre-se no vácuo usando um evaporador rotativo.</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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Tentativas iniciais para usar a reação de bissulfito como um método para remover aldeídos usando uma extração em duas fases típica levaram a níveis muito baixos de remoção. Formulamos a hipótese que a reação não foi rápida o suficiente para ocorrer durante o tempo muito limitado que as duas camadas estavam em contato. Para aumentar o contato entre os reagentes, desenvolvemos um protocolo de extração de dois estágios, em que um solvente miscível com água é usado inicialmente para permitir suficiente d...

A separação dos componentes de misturas de um outro é essencial para a preparação de materiais puros. O método descrito neste documento permite a fácil separação dos aldeídos e desimpedido estericamente cíclico e metil cetonas de outras moléculas orgânicas1. A técnica baseia-se a reatividade de bissulfito com o grupo carbonila para criar uma carga aduto que podem ser separados em uma camada aquosa, enquanto outros componentes separam em uma camada orgânica imiscível. A chave para alcançar a reatividade entre bissulfito e a carbonila é a utilização de um solvente miscível, o que permite que a reação ocorra antes a separação em fases separadas. Sem a adição da separação mínima solvente miscível é obtida, presumivelmente devido ao mau contacto entre o bissulfito hidrofílico e os produtos orgânicos hidrofóbicos.
A vantagem deste método de separação para a purificação é a facilidade do protocolo. Extração líquido-líquido é uma operação simples para executar e pode ser realizado em grande escala. Técnicas de purificação alternativos, tais como cromatografia de coluna, são muito mais caro, demorado e desafiador para executar em grande escala e requerem suficiente diferenciação dos componentes em termos de polaridade. Purificação por recristalização ou destilação requer suficiente diferenciação entre a solubilidade ou pontos de ebulição dos componentes da mistura, respectivamente. Como a extração de bissulfito depende da diferença de reatividade do grupo carbonila de aldeídos e cetonas, compostos com pontos de ebulição, solubilidade similar ou polaridades podem ser efetivamente separados. Outros métodos de separação química existem para a separação selectiva de aldeídos e cetonas de misturas, por exemplo, a formação seletiva de oximas2, acetais cíclicos3ou formação de4 mercaptal. Esses métodos requerem uma etapa adicional para separar as espécies formadas da mistura, porque o produto não é solúvel em água e, portanto, não pode ser separado por um protocolo de extração simples. Oxidação de aldeído para formar os ácidos carboxílicos removíveis é outro relatou a técnica5, mas a etapa de oxidação necessária é menos chemoselective do que as condições de bissulfito suave aqui descritos e requer o uso de gás oxigênio e um catalisador de cobalto.
Este método é aplicável para a separação de aldeídos (Figura 1) e desimpedido estericamente cíclicas e metil cetonas (Figura 2) de moléculas que não contêm estes grupos funcionais. Cetonas particularmente reativas, tais como α-ceto ésteres também são removidas usando este processo. Alcanos, alcenos, dienos, alquinos, ésteres, amidas, ácidos carboxílicos, haletos de alquila, álcoois, fenóis, nitrilos, cloretos de benzila, epóxidos, anilinas, acetais, e ligeiramente prejudicada, α, β-insaturados, ou arila cetonas são todos ́ nas condições e pode ser separado do aldeído ou componente reativa cetona da mistura (figuras 2 e 3). Etílico cetonas ou cetonas cíclicas α-substituídos, por exemplo, são suficientemente prejudicadas e, portanto, são separáveis de aldeídos e cetonas mais reativas. Ao usar alcenos, hexano é recomendado como o solvente imiscível para evitar a decomposição indesejada devido ao dióxido de enxofre presente na solução de bissulfito. A grupo funcional de compatibilidade do protocolo de extração de bissulfito é extremamente ampla e, portanto, é aplicável a um vastíssimo leque de separações, se o contaminante de carbonila ser separado da mistura é um aldeído ou uma progressista metil ou cetona cíclica. Menos reativas cetonas não reagem com bissulfito nestas condições e, portanto, não são removidas.

<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

A purificação de compostos orgânicos é um componente essencial das operações de rotina sintéticos. A capacidade de remover contaminantes em uma fase aquosa, gerando uma estrutura carregada fornece uma oportunidade para usar extração como uma técnica de purificação simples. Combinando o uso de um solvente orgânico miscível com bissulfito de sódio saturada, aldeídos e cetonas reativas pode ser transformado com sucesso em cobrado bissulfito adutos que pode então ser separada de outros componentes orgânicos de uma mistura pelo introdução de uma camada orgânica imiscível. Aqui, descrevemos um protocolo simples para a remoção dos aldeídos, incluindo aldeídos Neopentil impedida estericamente e algumas cetonas, de misturas químicas. Cetonas podem ser separadas, se eles são desimpedidos estericamente cíclica ou metil cetonas. Para aldeídos alifáticos e cetonas, dimetilformamida é usada como solvente miscível para melhorar as taxas de remoção. A reação de adição de bissulfito pode ser revertida por Basificação da camada aquosa, permitindo o re-isolamento do componente reactive do carbonyl de uma mistura.

Procedimento 1 para remoção de aldeído é usado para aldeídos aromáticos. Procedimento 2, no qual dimetilformamida é usada como solvente miscível, deve ser usado para cetonas e aldeídos alifáticos. Procedimento 2 também deve ser usado em misturas que não são totalmente solúvel em metanol. O material obtido a partir de cada um dos protocolos é analisada para pureza usando 1análise de integração H NMR e taxa de r...

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

Separação de aldeídos e cetonas reativas de misturas usando um protocolo de extração de bissulfito

Aqui, apresentamos um protocolo para remover aldeídos e cetonas reativas de misturas por um protocolo de extração líquido-líquido diretamente com bissulfito de sódio saturada em um solvente miscível. Este protocolo combinado é rápida e fácil de executar. O aldeído ou cetona pode ser re-isolada, a Basificação da camada aquosa.

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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33.9K visualizações.  Trinity College. Aqui, apresentamos um protocolo para remover aldeídos e cetonas reativas de misturas por um protocolo de extração líquido-líquido diretamente com bissulfito de sódio saturada em um solvente miscível. Este protocolo combinado é rápida e fácil de executar. O aldeído ou cetona pode ser re-isolada, a Basificação da camada aquosa.

Vídeo: 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.

Síntese de ésteres através de uma esterificação Steglich mais verde em acetonitrila

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

Química

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.

Preparação de bisaziridinas contíguas para reações regiosseletivas de abertura de anéis

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 redutores

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.

Álcoois de Compostos Carbonílicos: Redução

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 orgânica

Unidade 1

Álcoois e Fenóis

TERMOS E CONCEITOS CHAVE

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.

Preparação de Aldeídos e Cetonas a partir de Álcoois, Alquenos e alquinos

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

Aldeídos e Cetonas

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.

Preparação de Aldeídos e Cetonas a partir de Nitrilas e 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.

Preparação de Aldeídos e Cetonas a partir de Derivados de Ácidos Carboxílicos

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

Reações de Aldeídos e Cetonas: Oxidação 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 via Acoplamento Redutor de Ésteres: Visão Geral da Condensação de Aciloína

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

Radicais

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

Alquilação de Enolatos de β-Cetoéster: Síntese de Éster Acetoacético

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 ...