Name: facile preparation of (2z,4e)-dienamides by the olefination of electron-deficient alkenes with allyl acetate
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Cuidado: consulte todas as folhas relevantes de dados de segurança de material (MSDS) antes de usar. Todas as reações de acoplamento cruzado devem ser realizadas em frascos sob atmosfera de argônio selada (1 atm). 1. Preparação de butadienos pela olefinação de acrilamidas com acetato de alilo <ol><li> Secar um frasco parafuso-tampão (8 mL) com uma barra de agitação magnética compatível em um forno a 120 ° C por mais de 2 h. Arreme o frasco quente à temperatura ambiente soprando com gás inerte antes de usar. </li><li> Use um balanço analítico e pesa 3,7 mg (~ 3% molar, ~ 0,005 mmol) de [Ru ( p- cimeno) Cl 2 ] 2 (pó marrom) e 13,7 mg (20% molar, 0,04 mmol) de AgSbF6 (branco Sólido) no frasco de reação acima. NOTA: uma vez que esta é uma nova metodologia, as reações de acoplamento cruzado foram realizadas em pequena escala para prova de conceito para reduzir a formação de resíduos. AgSbF 6 é usado como um aditivo que pode abstratar o cloreto para gerar umComplexo de rutênio catiônico para a ativação da ligação CH eletrofílica 13 . Outros sais de prata, como Ag 2 CO 3 , também foram testados, mas nenhum produto foi detectado. O peso do catalisador ([Ru ( p- cimeno) Cl 2 ] 2 ) não é muito preciso e está na faixa de 3,4-3,9 mg. </li><li> Adicionar 1 mL de 1,2-dicloroetano seco ao frasco de reação. NOTA: A quantidade de solvente é flexível - 1 mL de 1,2-dicloroetano é apenas o suficiente para atender ao requisito mínimo de volume para a reação de acoplamento cruzado. No entanto, um pouco mais (~ 0,1 mL) de solvente também é permitido para uma reação desta escala. O 1,2-dicloroetano foi seco sobre um peneiro molecular de 3-ieve antes da sua utilização. </li><li> Use um balanço analítico e adicione acrilamida (0,2 mmol, 1,0 equiv, sólido ou óleo) ao frasco de reação acima. </li><li> Use uma micro-seringa para adicionar 43 μL (0,4 mmol, 2,0 equiv) de acetato de alilo (um líquido incolor) ao frasco de reação acima. <br/&gt; NOTA: Aqui, é necessária uma quantidade excessiva de acetato de alilo para inibir o homo-acoplamento da acrilamida e garantir que a acrilamida seja totalmente convertida. O rendimento do produto diminui se for adicionado menos acetato de alilo (1,5 equiv). A adição de mais acetato de alilo (3,0 equiv) não pode melhorar ainda mais o rendimento. Na prática, não há homo-acoplamento observado de acetato de alilo, e o acetato de alilo residual pode ser recuperado. </li><li> Sopre suavemente no frasco de reação com gás argônio e cubra o frasco com uma tampa de rosca compatível o mais rápido possível. NOTA: O frasco deve ser coberto com uma tampa roscada o mais rápido possível porque uma atmosfera inerte é crucial para a reação de acoplamento cruzado. É melhor executar o protocolo acima em uma luva. </li><li> Agitar a mistura reaccional à temperatura ambiente durante mais 5 min. </li><li> Aqueça o frasco de reacção a 110 ° C num banho de óleo com agitação durante 16-18 h. NOTA: Geralmente, uma mudança de cor para vermelho escuro é uma indQue a reação está ocorrendo. </li><li> Após o resfriamento do frasco para baixo, use misturas de acetato de etilo: éter de petróleo (2: 1 ou 1: 3) como solvente para desenvolver as placas de cromatografia em camada fina (TLC) para monitorar o progresso da reação comparando a mistura com um padrão de acrilamida . NOTA: Dependendo da natureza dos materiais de partida, a reação pode não ser concluída. Os valores Rf típicos dos produtos e dos materiais de partida estão na faixa de 0,3 a 0,7. O material de partida de acrilamida foi observado como um ponto de funcionamento inferior do que o produto de butadieno. </li><li> Dissolver o produto em bruto em um mínimo de DCM e carregá-lo sobre uma coluna de sílica molhada com éter de petróleo. Separar o produto de acoplamento cruzado por cromatografia em coluna utilizando uma mistura de acetato de etilo: éter de petróleo (1: 100 a 1: 4) como eluente. <ol><li> Recolher o eluente em um balão separado, evaporar o solvente em um evaporador rotativo, umD colocá-lo sob alto vácuo por um mínimo de 2 h. </li><li> Obtenha aproximadamente 20-50 mg de produto para caracterização por espectroscopia de RMN. NOTA: A mistura reaccional deve ser aplicada à cromatografia em coluna para purificação directamente após a conclusão da reacção. </li></ol></li></ol> 2. Caracterização de Dienamides <ol><li> . Caracterizar e avaliar a pureza do produto final utilizando espectroscopia RMN 1 H e 13C 14 . Tipicamente, o deslocamento químico do carbono carbonílico aparece perto de 170 ppm no espectro de RMN 13C. Os três protões de sp 2 do grupo funcional de butadieno são representados por picos característicos próximos de 6.0 e 5.6 ppm. </li><li> Use a espectroscopia de infravermelho 14 para identificar o carbono característico de carbonil e CC de ligação dupla do produto de dieno. </li><li> Determine a massa molecular do produto e valide ainda mais a identidade usando alto-Espectrometria de massa de resolução (HRMS) 14 . </li><li> Determine o ponto de fusão dos produtos sólidos 14 . </li></ol>

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Agradecemos a Fundação Nacional de Ciências Naturais da China (NSFC) (Números 21502037, 21373073 e 21672048), a Fundação de Ciências Naturais da Província de Zhejiang (N ° LY15B020008), o PCSIRT (No. IRT 1231) e Hangzhou Universidade Normal para apoio financeiro. A GZ reconhece um prêmio Qianjiang Scholar da província de Zhejiang, na China.

[Ru ( p -cymene) Cl 2 ] 2 é um catalisador baseado em Ru barato, facilmente acessível, a prova de ar e altamente ativo com excelente tolerância ao grupo funcional que opera eficientemente em condições de reação suave para dar produtos de butadieno de acoplamento CH / CH. O sal de prata AgSbF6 foi utilizado como um aditivo que pode abstrair o cloreto de [Ru ( p- cimeno) Cl 2 ] 2 para gerar um complexo de ruténio catiónico para a seguinte activação d...

Os butadienos estão ocorrendo amplamente e são comumente encontrados em muitos produtos naturais, drogas e moléculas bioativas 1 . Os químicos fizeram intensos esforços para desenvolver uma metodologia sintética eficiente, seletiva e prática para a síntese de 1,3-butadienos 2 , 3 . Recentemente, desenvolveu-se acoplamentos cruzados diretos entre dois alcenos através da ativação de ligação de vinilo CH duplo, representando uma estratégia eficiente para a síntese de butadienos, com alta economia atômica e gradual. Entre eles, o acoplamento cruzado catalisado por paládio de dois alquenos atraiu muita atenção, proporcionando butadienos configurados ( E, E ) através de espécies de alcenil-Pd 4 , 5 . Por exemplo, o grupo de Liu desenvolveu uma síntese de butadieno catalisada por Pd pelo acoplamento cruzado direto de alcenos e acetato de alilo ( Figura 1 </Forte&gt; e Equação 3 ) 4 . Enquanto isso, o acoplamento cruzado direcionado do grupo funcional entre alcenos forneceu butadienos com excelente ( Z, E ) -estereoselectividade devido ao evento de ciclometalação CH olefínica, representando um método complementar 6 . Até à data, alguns grupos direcionadores, como enolates, amidas, ésteres e fosfatos, foram introduzidos com sucesso no acoplamento cruzado entre os alcenos, fornecendo uma série de 1,3-butadienos valiosos e funcionalizados. No entanto, a reação de acoplamento cruzado direcionado não foi desenvolvida, pois ainda existem grupos direcionados limitados em uso prático. Em particular, geralmente é necessária uma quantidade estequiométrica de oxidante para manter o ciclo catalítico, o que produz uma grande quantidade de resíduos orgânicos e inorgânicos. Existem exemplos muito limitados usando alquenos ricos em elétrons como o parceiro de acoplamento. O acetato de alil e seus derivados foram profundamenteNvestigados em transformações orgânicas como poderosos reagentes de alilação e olefinação, incluindo acoplamento cruzado catalisado, alilação de Friedel-Crafts de arenos ricos em elétrons e ativação catalítica de ar de arenos deficiente em elétrons ( Figura 1 e Equação 1 ) 7 . Mais recentemente, o grupo Loh desenvolveu uma alilação de CH catalisada por ródio (III) de alcenos deficiente em elétrons com acetatos de alilo, criando 1,4-dienos ( Figura 1 e Equação 2 ) 8 . Enquanto isso, o grupo de Kanai relatou uma alilação de CH direta desidratante com álcoois alílicos usando um catalisador de Co (III) 9 . Curiosamente, Snaddon e colegas de trabalho revelaram um novo método cooperativo baseado em catálise para o α- linear direto de ésteres acíclicos 10 . Muito recentemente, o grupo de Ackermann relatou vários exemplos de alilação novos usinG catalisadores baratos Fe, Co e Mn 11 . Esses relatórios fizeram avanços nas reações de alilação e olefinação, mas a migração de dupla ligação e baixa regioselectividade são geralmente inevitáveis ​​e não são facilmente controladas. Assim, o desenvolvimento de padrões de reação mais eficientes e seletivos de acetatos de alilo para a construção de moléculas valiosas é ainda altamente desejável. Com o nosso interesse na nova síntese de 1,3-butadieno através de olefinação de CH, assumimos que o acetato de alilo poderia ser introduzido na alilação dirigida de alcenos com deficiência de elétrons, primeiro fornecendo 1,4-dieno. Em seguida, o 1,3-butadieno mais termodinamicamente estável pode ser formado após a isomerização migratória da ligação dupla CC 7 , formando o produto dieno que não pode ser obtido por acoplamento cruzado usando alcenos ricos em elétrons, como propeno, como parceiro de acoplamento 6 . Aqui, relatamos uma olefinatio de ligação CH olefínica catalisada por Ru (III), de baixo custoN de acrilamidas com acetatos de alilo na ausência de qualquer oxidante, o que abre uma nova rota sintética para a criação de ( Z, E ) -butadienos ( Figura 1 e Equação 4 ) 13 .

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

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

O acoplamento cruzado direto entre dois alcenos através da ativação de ligação de vinil CH representa uma estratégia eficiente para a síntese de butadienos com alta economia atômica e gradual. No entanto, esta reação de acoplamento cruzado direcionada à funcionalidade não foi desenvolvida, pois ainda existem grupos limitados de direção em uso prático. Em particular, geralmente é necessária uma quantidade estequiométrica de oxidante, produzindo uma grande quantidade de resíduos. Devido ao nosso interesse na nova síntese de 1,3-butadieno, descrevemos a olefinação catalisada por rutênio de alquenos deficiente em elétrons usando acetato de alilo e sem oxidante externo. A reacção de 2-fenil acrilamida e acetato de alilo foi escolhida como uma reacção modelo, e o produto dieno desejado foi obtido com 80% de rendimento isolado com boa estereoselectividade ( Z, E / Z, Z = 88:12) em condições ideais: [ Ru ( p- cimeno) Cl2] 2 (3% molar) e AgSbF6 (20% molar) em DCE a 110 ºC fOu 16 h. Com as condições catalíticas otimizadas na mão, foram investigadas acrilamidas representativas de α e / ou β , e todas reagiram suavemente, independentemente de grupos alifáticos ou aromáticos. Além disso, as acrilamidas N- substituídas diferentemente provaram ser bons substratos. Além disso, examinamos a reatividade de diferentes derivados alílicos, sugerindo que a quelação de acetato de oxigênio para o metal é crucial para o processo catalítico. Experimentos rotulados com deutério também foram conduzidos para investigar o mecanismo de reação. Foram observadas apenas trocas de H / D seletivas Z sobre acrilamida, indicando um evento reversível de ciclometalação. Além disso, observou-se um efeito de isótopo cinético (KIE) de 3,2 no estudo isotópico intermolecular, sugerindo que o passo de metalurgia CH olefínico está provavelmente envolvido no passo determinante da velocidade.

Nossos esforços foram focados na preparação de 1,3-butadieno a partir de acrilamida e acetato de alilo. A Tabela 1 ilustra a otimização de condições, incluindo o rastreio de vários aditivos e solventes, utilizando o [Ru ( p- cieno) Cl2] 2 como catalisador. Após a triagem de uma série de solventes representativos, ficamos satisfeitos ao descobrir que o rendimento do produto melhoro...

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

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

A olefinação catalisada por rutênio de alcenos deficiente em elétrons com acetato de alilo é aqui descrita. Ao usar aminocarbonilo como grupo direcionador, este protocolo externo livre de oxidantes tem alta eficiência e boa estereo- e regioselectividade, abrindo uma nova rota sintética para esqueletos ( Z , E ) -butadieno.

Preparação Fácil de (2Z,4E)-Dienamidas pela Olefinação de Alquenos Elétron-deficientes com Acetato de Alila

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

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

Dienes, Conjugated Pi Systems, and Pericyclic Reactions

Alkene Structure and Reactivity

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7.3K visualizações.  Hangzhou Normal University.  A olefinação catalisada por rutênio de alcenos deficiente em elétrons com acetato de alilo é aqui descrita. Ao usar aminocarbonilo como grupo direcionador, este protocolo externo livre de oxidantes tem alta eficiência e boa estereo- e regioselectividade, abrindo uma nova rota sintética para esqueletos ( Z , E ) -butadieno. 

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

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 &#176;C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

Protocolo para a Síntese de Derivados de Anilina Orto-trifluorometoxilados

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

Química

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

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

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

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

Preparação de N-(2-alcoxivinil)sulfonamidas a partir de N-tosil-1,2,3-triazóis e Conversão Subsequente para Fitalanos e Fenetilaminas Substituídas

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

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

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

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

Um Protocolo em Duas Etapas para Funcionalização de Umpolung de Cetonas via Espécies de Enolonium

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

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

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

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

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

Uma síntese direta, regioseletiva e atom-econômica de 3-Aroyl-N-hidroxi-5-nitroindoles por Cycloaddition de 4-Nitronitrosobenze com Alkynones

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

Preparation of Alkynes: Alkylation Reaction

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

Preparação de Alquinos: Reação de Alquilação

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

Química orgânica

Unidade 1

Alquinos

TERMOS E CONCEITOS CHAVE

Preparation of Alkynes: Dehydrohalogenation

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

Preparação de Alquinos: Desidrohalogenação

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

Preparation of Epoxides

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

Preparation of Epoxides via Alkene Oxidation

Preparação de Epóxidos

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

Éters, Epóxidos e Sulfetos

Carboxylic Acids to Methylesters: Alkylation using Diazomethane

Carboxylic acids react with diazomethane in an ether solvent via alkylation at the carboxylate oxygen atom to give methyl esters of the corresponding acid with excellent yields.
<img alt="Esterification reaction: carboxylic acid with diazomethane formula, chemical process diagram." src="/files/ftp_upload/12349/12349_PT_Figure_1.svg" style="text-align: center; height: 60px;" data-altupdatedat="1747908711000" data-alt="Figure1">
Diazomethane is a yellow gas having a boiling point of −23 °C. It is conveniently prepared by the action of a base on N-methyl-N-nitrosourea or N-methyl-N-nitrosotoluenesulphonamide.
The esterification mechanism involves the protonation of diazomethane by the carboxylic acid to yield a carboxylate salt and methyldiazonium cation. The methyldiazonium cation is highly unstable due to the presence of N≡N, which functions as an excellent leaving group.
<img alt="Chemical reaction, Curtius rearrangement equations, molecular transformation diagram." src="/files/ftp_upload/12349/12349_PT_Figure_2.svg" style="text-align: center; height: 72px;" data-altupdatedat="1747908711000" data-alt="Figure2">
In the final alkylation step, an SN2 attack on the methyldiazonium ion by the carboxylate anion produces a methyl ester, along with the elimination of N2 gas.
<img alt="SN2 reaction mechanism diagram; nucleophile attack on carbonyl, forming new bond, expelling N2." src="/files/ftp_upload/12349/12349_PT_Figure_3.svg" style="text-align: center; height: 70px;" data-altupdatedat="1747908711000" data-alt="Figure3">
However, diazomethane is a potentially explosive gas and requires precautions during its handling and storage. It undergoes spontaneous detonation upon contact with rough or scratched surfaces. Therefore, flame-polished glassware and a blast shield are often recommended in reactions involving diazomethane. Moreover, diazomethane is highly toxic as well as carcinogenic.
Diazomethane decomposes in the presence of heat or light to generate carbenes and eliminate nitrogen.
<img alt="Chemical reaction diagram; azide decomposition to form methylene and nitrogen under heat or light." src="/files/ftp_upload/12349/12349_PT_Figure_4.svg" style="text-align: center; height: 52px;" data-altupdatedat="1747908711000" data-alt="Figure4">

Ácidos Carboxílicos a Ésteres Metílicos: Alquilação Usando Diazometano

Carboxylic acids react with diazomethane in an ether solvent&#160;via alkylation at the carboxylate oxygen atom&#160;to give&#160;methyl esters of the ...

Ácidos Carboxílicos

Amines to Alkenes: Hofmann Elimination

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

Aminas a Alquenos: Eliminação de Hofmann

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

Aminas

&alpha;-Alkylation of Ketones via Enolate Ions

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