This work was supported by the UOIT start-up fund. We thank Mr. Matthew Baxter (UOIT) for his assistance in the laboratory.

1. Síntese de Ynone <ol><li> Usando uma balança analítica, pesam 0,15 mmol de potássio desejado sal alkynyltrifluoroborate (1,5 equivalentes) e adicionar a um frasco limpo equipado com uma barra magnética. </li><li> Utilizando uma seringa de êmbolo de vidro equipada com uma agulha, adicionar 0,5 ml de DCM anidro para o frasco para se obter uma solução 0,3 M de trifluoroborato. NOTA: Uma vez que esta é uma nova metodologia, as reações têm sido realizadas para prova de conceito. De modo a reduzir o desperdício de terem sido realizados a uma escala pequena. A reacção pode ser dimensionado para produzir maiores rendimentos, conforme necessário. </li><li> Usando uma seringa de vidro, adicionar 0,15 mmol de 1,0 M de solução de tricloreto de boro (1,5 equivalentes, 150? L) gota a gota, ao vaso da reacção à temperatura ambiente (20 ° C) com agitação. Recoloque a tampa. Segurar ou prender o recipiente de reacção tapado de modo a que a solução de reacção é abaixo da linha de água no sonicador. Sonicar a solução durante 30 segundos a 20 ° C e a uma frequência of 40 kHz. </li><li> Agita-se a solução de reacção à temperatura ambiente (20 ° C) durante um adicional de 20 minutos. Dependendo da natureza do material de partida alkynyltrifluoroborate, observar uma mudança de cor. A mudança de cor do branco ao bege ou marrom escuro, vermelho ou roxo é comum. </li><li> Adicionar 0,1 mmol do cloreto de acilo desejado (1,0 equivalente) para o frasco à temperatura ambiente (20 ° C) com agitação. Alternativamente, transferir o conteúdo do vaso da reacção para um balão carregado com uma barra de agitação magnética e 0,1 mmol de cloreto de acilo. Recoloque a tampa. Agita-se a solução de reacção à temperatura ambiente (20 ° C) durante 30 min. NOTA: De um modo geral, uma mudança de uma cor muito escura é uma indicação de que a reacção está a ter lugar. </li><li> Usando uma cromatografia em camada fina (TLC) 34 monitorar o progresso da reacção por comparação com padrão de cloreto de acilo apropriado. NOTA: Dependendo da natureza dos materiais de partida, a reacção pode não ficar completa. A umcloreto cyl material de partida foi observada como um local de funcionamento mais elevada do que o produto final de todos os ynones preparados até à data usando este método. <ol><li> Prepare o padrão de cloreto de acilo por diluição de cerca de 10 mg do material de partida cloreto de acilo com 1 ml de acetato de etilo em um pequeno frasco. </li><li> Usando um spotter TLC, manchar a solução de reacção e o padrão na linha de partida da placa de TLC. Um co-mancha com tanto a solução de reacção e padrão podem ser úteis para determinar se existe ainda materiais presentes na solução da reacção de partida. </li><li> Determinar uma fase móvel adequada TLC por tentativa e erro. Para a preparação do produto 1a, uma fase móvel consistindo de 01:30 acetato de etilo: hexanos resulta em valores de Rf de cerca de 0,5 e 0,8 para o produto ynone e cloreto de benzoílo material de partida, respectivamente. </li><li> Visualize a placa TLC desenvolvido sob a luz UV. Use um lápis para marcar todos os pontos visíveis. </li></ol></li></ol> 2. O processamento aquoso <ol><li> Extingue-se a reacção por adição de 1 mL de água fria (cerca de 5 ° C) para o vaso de reacção. Usando uma pipeta de Pasteur, transferir a solução para um funil de separação limpa. Diluir o conteúdo do funil de decantação com 10 ml de água fria e extrai-se o produto uma vez em 15 ml de acetato de etilo. </li><li> Rejeitar a camada aquosa inferior e lava-se a camada orgânica uma vez adicional com 10 ml de água e uma vez com 10 ml de salmoura. Recolher a camada orgânica para um balão de Erlenmeyer limpo e seco com sulfato de magnésio. Filtrar a solução para um balão de fundo redondo limpo usando filtração por gravidade. </li></ol> 3. Purificação de Ynone <ol><li> Usando cromatografia de camada fina, determinar uma fase móvel adequada para purificação através de cromatografia do produto. Um factor de retenção (Rf) de cerca de 0,5 é geralmente suficiente para separar o produto a partir de qualquer partida remanescenteing produtos materiais e laterais. NOTA: No caso de uma separação deficiente, um sistema solvente menos polar pode ser utilizado de tal modo que o produto tem um valor Rf inferior. Dependendo da polaridade dos materiais de partida, uma mistura de hexanos: acetato de etilo no intervalo de 30: 1 a 5: 1 é geralmente adequado. </li><li> Prepara-se uma coluna contendo sílica gel húmida com a fase móvel adequada. Adicione uma camada de areia para a parte superior da coluna, a fim de evitar sílica perturbador após a adição do produto e eluente. </li><li> Evapora-se a solução de processamento utilizando um evaporador rotativo com a temperatura do banho a 40 ° C e a rotação definido para 120 rpm. Dissolve-se o conteúdo do balão em um 2 ml de fase móvel e carregar cuidadosamente a solução uniformemente sobre a coluna. Assegure-se que a sílica está molhado, mas a linha de solvente não exceda a altura da sílica. Permitir que algum solvente de eluição tais que o produto está na sílica. Adicionar uma pequena quantidade de fase móvel e repita. </li><li> Encha o column com a fase móvel determinado no passo 3.1; no caso do produto 1a, a 30: 1 hexanos: acetato de etila é apropriado. Recolher as fracções em tubos de ensaio, utilizando cromatografia flash, para acelerar o processo de purificação. Basta conectar um adaptador com tubulação para uma saída de ar. Ajustar a pressão do ar de tal modo que o eluente flui através da coluna a uma velocidade adequada. </li><li> Detectar cada uma das fracções da coluna numa placa de TLC. Opcionalmente, detectar o padrão de cloreto de acilo, tal como uma referência. Desenvolver o TLC com a fase móvel considerada adequada na etapa 1.8. Marque todos os pontos visíveis sob luz UV, lembrando que o produto é esperado para ter um R f mais baixa do que o padrão de cloreto de acila. </li><li> Recolha todas as frações contendo manchas visíveis em um balão de fundo redondo grande. Se mais de um local com um Rf inferior ao do material de partida está presente, recolher em frascos separados. Evapora-se o solvente usando um evaporador rotativo e secar o material recolhido under alto vácuo durante duas horas. </li><li> Se necessário, efectuar uma lavagem com pentano sobre uma pequena coluna de modo a purificar ainda mais um produto ynone preparado a partir de um material de má electrões de partida cloreto de acilo. Numa pequena escala, este pode ser realizado utilizando uma pipeta de Pasteur, como a coluna. <ol><li> Dissolve-se o produto numa quantidade mínima de clorofórmio, DCM, ou éter dietílico e de carga numa coluna de sílica húmido com pentano. Comprimentos Elute 1-2 coluna de pentano através da coluna e recolher em um copo de resíduos. </li><li> Eluir o produto ynone puro a partir da coluna usando pentano éter dietílico ou acetato de etilo. Recolhe eluente num balão separado, evapora-se, e colocar sob alto vácuo durante um mínimo de duas horas. Obter aproximadamente 10 mg de produto para caracterização por espectroscopia de RMN. </li></ol></li></ol> 4. Caracterização de Ynone <ol><li> Caracterizar e avaliar a pureza do produto final, utilizando 1 H e 13 C RMN espectroscopia. 34Tipicamente, o desvio químico de carbono do carbonilo aparece perto de 177 ppm no espectro de 13 C RMN. Os dois átomos de carbono SP do grupo funcional ynone são representados por picos característicos próximos 87 e 93 ppm. </li><li> Use espectroscopia de infravermelhos 34 para identificar o pico carbonilo característica do produto ynone. Electron deslocalização da ligação tripla adjacente normalmente faz com que o pico de carbonilo a aparecer entre 1.600 e 1.650 centímetros -1, dependendo das características do composto electrónicos. </li><li> Determinar a massa molecular do produto e ainda validar a identidade utilizando espectrometria de massa de alta resolução. 34 </li></ol>

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W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+student's+lab+companion:+laboratory+techniques+for+organic+chemistry:+standard+scale+and+microscale.">The student's lab companion: laboratory techniques for organic chemistry: standard scale and microscale.</a> Pearson College Div. , (2008).</li><li>Molander, G. A., Cavalcanti, L. N., Canturk, B., Pan, P. -. S., Kennedy, L. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficient+Hydrolysis+of+Organotrifluoroborates+via+Silica+Gel+and+Water.">Efficient Hydrolysis of Organotrifluoroborates via Silica Gel and Water.</a> 74, 7364-7369 (2009).</li><li>Molander, G. A., Ellis, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Organotrifluoroborates:+protected+boronic+acids+that+expand+the+versatility+of+the+Suzuki+coupling+reaction.">Organotrifluoroborates: protected boronic acids that expand the versatility of the Suzuki coupling reaction.</a> Acc. Chem. Res. 40, 275-286 (2007).</li><li>Calloway, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Friedel-Crafts+Syntheses.">The Friedel-Crafts Syntheses.</a> Chem. Rev. 17, 327-392 (1935).</li><li>Gore, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Friedel-Crafts+acylation+reaction+and+its+application+to+polycyclic+aromatic+hydrocarbons.">The Friedel-Crafts acylation reaction and its application to polycyclic aromatic hydrocarbons.</a> Chem. Rev. 55, 229-281 (1955).</li><li>Groves, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Friedel&#8211;Crafts+acylation+of+alkenes.">The Friedel&#8211;Crafts acylation of alkenes.</a> Chem. Soc. Rev. 1, 73-97 (1972).</li><li>Kim, B. J., Matteson, D. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conversion+of+alkyltrifluoroborates+into+alkyldichloroboranes+with+tetrachlorosilane+in+coordinating+solvents.">Conversion of alkyltrifluoroborates into alkyldichloroboranes with tetrachlorosilane in coordinating solvents.</a> Angew. Chem. 116, 3118-3120 (2004).</li><li>Thompson, L., Doraiswamy, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sonochemistry:+science+and+engineering.">Sonochemistry: science and engineering.</a> Ind. Eng. Chem. Res. 38, 1215-1249 (1999).</li></ol>

The authors declare that they have no competing financial interests.

A Tabela 1 ilustra os passos tomados para optimizar as condições para a reacção de fenilacetileno trifluoroborato com cloreto de benzoílo para formar o produto ynone correspondente. Inicialmente, catalisadores conhecidos para converter organotrifluoroborates para organodifluoroboranes foram testados. Infelizmente gel de sílica, 35 tetracloreto de silício, 36 e 31,32 de trifluoreto de boro não promover a formação do ynone desejado (Tabela 1, entradas 1-3). O uso de clorados catalisadores ácidos de Lewis provou ser mais bem sucedido. Um baixo rendimento do ynone 1a desejado foi obtido na presença de um catalisador de ferro (III), cloreto de (Tabela 1, entrada 4). Em seguida, alumínio (III), cloreto foi investigada como um resultado da sua capacidade bem estabelecido para promover a formação de iões oxocarbenium em acilações de Friedel-Crafts. 37-39 O produto desejado foi obtido com um rendimento de 62%, quando uma lata de alumínio (III), cloreto de catalisador foi employed. Optimização adicional revelou que o ar e a humidade tem pouco efeito sobre o rendimento da reacção (Tabela 1, entradas 5-7). Como resultado, as reacções subsequentes foram realizadas em material de vidro não seca na presença de ar. As tentativas para optimizar o solvente revelou que diclorometano (DCM) é particularmente bem adequado para a reacção (Tabela 1, entradas 8-12). Inconsistências nos resultados de reacções catalisadas por alumínio (III), cloreto de solicitado a exploração de catalisadores alternativos. Comercialmente disponível de alumínio (III) de hexahidrato de cloreto era completamente inactivo sob as condições de reacção (Tabela 1, entrada 13). Este é um bom indicador de que a formação de hidrato de alumínio (III), cloreto de inibe a reacção. Tricloreto de boro foi encontrado para produzir rendimentos similares com melhor consistência (Tabela 1, entrada 14). Após a interacção do potássio alkynyltrifluoroborate com tricloreto de boro, uma espécie organodichloroborane mais reactivos é formado. 40 Este passo inicial é crítica para a reacção com o cloreto de acilo e formação do ynone para prosseguir. Desde organotrifluoroborate sais não são solúveis em DCM, a reacção ocorre como uma mistura heterogénea. Depois da adição de tricloreto de boro, a solução é sonicada a fim de facilitar a formação das espécies reactivas dichloroborane aumentando a área de superfície do sal trifluoroborato disponível para reagir. Aplicação de ondas de ultra-sons à mistura de reacção provoca efeitos mecânicos, através da geração de bolhas de cavitação. Durante a sonicação, colapso de bolhas de cavitação nos resultados do fluido em áreas localizadas de altas temperaturas e pressões. 41 As ondas de choque são produzidas que criar turbulência microscópica resultando num aumento da energia cinética dos sais de trifluoroborato sólidos. O aumento da energia do sistema, durante sonificação promotes fragmentação do sal trifluoroborato resultante aumento da área de superfície disponível para interagir com tricloreto de boro. A sonicação da mistura de reacção antes da adição do material de partida cloreto de acilo garante uma formação eficiente das espécies reactivas alkynyldichloroborane sem a necessidade de condições de extracção ou mais tempos de reacção mais longos. A Figura 2 ilustra os resultados obtidos quando fenilacetileno trifluoroborato foi feito reagir com uma variedade de cloretos de acilo sob as condições de reacção optimizadas. Neutral aromático (1B, 1C) e alifáticos (1-J-l) cloretos de acila fornecer os ynones correspondentes em rendimentos sinteticamente úteis. Esses cloretos de ácido que comportam grupos doadores de electrões (1D-g) proporcionar excelentes rendimentos, enquanto os grupos electrões resultar em rendimentos relativamente modestos (1h, 1i, 1M). Interestingly, quando o grupo de remoção de electrões está localizado na posição orto (1i, 59%), um aumento do rendimento significativo é observado em comparação com o parágrafo análogo substituído de cloreto de acilo (1 h, 30%). A interacção estérica do substituinte na posição orto podem forçar o grupo funcional carbonilo para fora do plano, compensando assim o carácter de remoção de electrões do anel aromático. Vale a pena notar que o cloreto de 4-bromobutirilo reagiram para produzir o produto desejado 1m em 39% de rendimento. Para nosso conhecimento, esta é a primeira protocolo para a síntese de ynones para tolerar um grupo funcional brometo de alquilo. Ocasionalmente, quando o material de partida cloreto de acilo é neutro ou deficiente em electrões, impurezas alifáticos aparece na RMN de protões. Isto pode necessitar de uma lavagem com pentano de modo a purificar ainda mais o produto. Embora possível, não é económico para realizar a lavagem com pentano durante a primeira fase de purificação sesde pentano é caro em comparação com hexano. Completando a purificação secundária separadamente numa escala mais pequena, tal como uma coluna de uma pipeta de Pasteur reduz significativamente a quantidade de pentano necessária. A Figura 3 ilustra o efeito da identidade do sal alkynyltrifluoroborate sobre o rendimento da reacção. Em geral, os derivados do fenilacetileno trifluoroborato rolamento sal substituintes doadores de electrões no anel aromático reagir com cloretos de acilo aromáticos e alifáticos para produzir os ynones desejados com bons a excelentes rendimentos (2a-c, 3a-c). Sais alkynyltrifluoroborate alifáticos provaram ser substratos menos reactivos. Modestos rendimentos foram obtidos quando hexynyl- e sais cyclopentylethynyltrifluoroborate foram feitos reagir com derivados ricos em electrões de cloreto de benzoílo (4a, 5a). Em conclusão, um novo método para a preparação of ynones de cloretos de acilo e sais de potássio alkynyltrifluoroborate tem sido desenvolvido. Os rendimentos obtidos para a síntese de ynones por este método gama de modesta a excelente, dependendo da natureza do cloreto de acilo e trifluoroborato materiais de partida. Em geral esses materiais de partida que ostentam elétrons substituintes doadores de sofrer a reação mais facilmente do que matérias-primas que possuem grupos funcionais neutros e electrões. O valor desta abordagem reside na simplicidade e grupo funcional tolerância operacional do método. Este, reacção de um só recipiente simples procede rapidamente a temperatura ambiente na presença de tricloreto de boro sem exclusão de ar e humidade. Este método conveniente pode ser empregue na preparação de ynones em excelentes rendimentos modestos a partir de uma variedade de cloretos de acilo e sais alkynyltrifluoroborate.

The intention of this video is to demonstrate a straightforward approach for the preparation of compounds containing an ynone functional group from convenient starting materials. Ynones are valuable building blocks in organic chemistry that have been shown to have biomedical and material significance. Ynones are precursors to valuable organic functional groups including pyrimidines,1,2 quinolones,3 furans,4 pyrazoles,5,6 flavones,7 oximes,8 and chiral propargylic alcohols.9-11 A more convenient method for the preparation of ynones has been sought as a result of the drawbacks of traditional methods including poor functional group tolerance and tedious synthetic routes.
The reaction of metal12,13 and metalloid14 acetylides with acyl chlorides is one common route for the preparation of ynones. Alternatively, the synthesis of ynones from acyl chloride can be achieved via two-step procedures using Weinreb amides and organolithium or Grignard reagents.15 Another prevalent approach includes the addition of organolithium or Grignard reagents to an aldehyde, which is followed by the oxidation of a secondary alcohol to the corresponding ketone.16-19 Poor functional group tolerance of metal acetylides and the need to purify synthetic intermediates after each step are main deficiencies of the aforementioned methods. Transition-metal-catalyzed carbonylative couplings have recently emerged as an alternative approach for the preparation of ynones.20-22 Unfortunately, in addition to cost and toxicity associated with transition metals, metal-catalyzed carbonylative reactions often require elevated CO pressures and suffer from the presence of an undesired Sonogashira coupling byproduct. Given their utility in organic synthesis as well as the drawbacks associated with traditional synthetic methods, the development of a more straightforward method for the preparation of ynones is appealing.
Potassium organotrifluoroborate salts have recently emerged as versatile reagents in organic synthesis. Advantages including ease of preparation,23 inherent stability, low toxicity, and good functional group tolerance have made organotrifluoroborate salts attractive synthetic reagents.24-27 Organotrifluoroborate salts have been used primarily as a bench-stable equivalent of boronic acids for palladium-catalyzed Suzuki-Miyaura coupling.26 Recently, following a seminal work by Matteson and co-workers,28 Bode, Molander and others have highlighted the utility of organotrifluoroborates as reagents in non-metal catalyzed reactions.29-33 The field of transition-metal-free reactions of trifluoroborates is still in its infancy stage. Given the great potential for use of organotrifluoroborate salts in non-metal catalyzed organic synthesis, we sought to develop a novel method for the preparation of ynones from acyl chlorides and alkynyltrifluoroborate salts.

<table><tbody><tr><td>Sonicator</td><td>VGT</td><td>1860QT</td><td>Ultrasonic cleaner. Similar sonication devices may be used.</td></tr><tr><td>Dichloromethane</td><td>Sigma</td><td>270997</td><td>Anhydrous</td></tr><tr><td>Boron trichloride solution&amp;nbsp;</td><td>Sigma</td><td>178934</td><td>1 M solution in DCM</td></tr><tr><td>Acyl chloride</td><td>Sigma</td><td>Various</td><td>Acyl chlorides from other suppliers such as Alfa Aesar may be used. Caution: refer to MSDS for safety information.</td></tr><tr><td>Potassium alkynyltrifluoroborate salt</td><td>N/A</td><td>N/A</td><td>Synthesized&lt;sup&gt;23 &lt;/sup&gt;from terminal alkyne</td></tr><tr><td>Ethyl acetate</td><td>ACP</td><td>E-2000</td><td>ACS grade</td></tr><tr><td>Hexanes</td><td>ACP</td><td>H-3500</td><td>ACS grade</td></tr><tr><td>Pentane</td><td>Sigma</td><td>236705</td><td>Anhydrous</td></tr><tr><td>Magnesium sulfate</td><td>Sigma</td><td>M7506</td><td></td></tr><tr><td>Filter paper</td><td>Whatman</td><td>1093 126</td><td>Student grade. This speceific variety is not necessary.</td></tr><tr><td>Silica Gel 60</td><td>EMD</td><td>1.11567.9026</td><td>Particle size 0.040-0.063</td></tr></tbody></table>

metal-free synthesis of ynones from acyl chlorides and potassium alkynyltrifluoroborate salts

Ynones are a valuable functional group and building block in organic synthesis. Ynones serve as a precursor to many important organic functional groups and scaffolds. Traditional methods for the preparation of ynones are associated with drawbacks including harsh conditions, multiple purification steps, and the presence of unwanted byproducts. An alternative method for the straightforward preparation of ynones from acyl chlorides and potassium alkynyltrifluoroborate salts is described herein. The adoption of organotrifluoroborate salts as an alternative to organometallic reagents for the formation of new carbon-carbon bonds has a number of advantages. Potassium organotrifluoroborate salts are shelf stable, have good functional group tolerance, low toxicity, and a wide variety are straightforward to prepare. The title reaction proceeds rapidly at ambient temperature in the presence of a Lewis acid without the exclusion of air and moisture. Fair to excellent yields may be obtained via reaction of various aryl and alkyl acid chlorides with alkynyltrifluoroborate salts in the presence of boron trichloride.

Os esforços iniciais centraram-se em torno da preparação de ynone 1a de fenilacetileno trifluoroborato S1 e cloreto de benzoílo (Figura 1). A Tabela 1 ilustra os passos de optimização realizada, incluindo o rastreio de vários ácidos de Lewis, solventes, assim como o exame do efeito da água sobre o reaccional . Em seguida, o escopo da reacção foi explorado através da apresentação de fenilacetileno trifluoroborato para as condições optimizadas na presença de uma variedade de cloretos de acilo (Figura 2). Modesta a excelentes rendimentos podem ser obtidos, dependendo da natureza do substrato de cloreto de acilo. O âmbito de aplicação da reacção foi ainda avaliada através da preparação de vários exemplos adicionais de sais alkynyltrifluoroborate. A Figura 3 ilustra exemplos seleccionados de outros sais alkynyltrifluoroborate que podem ser empregues na preparação de ynones sob as condições desenvolvidas. Derivados de fenylacetylene electrões rolamento trifluoroborato substituintes doadores proporcionou os correspondentes produtos ynone em bons a excelentes rendimentos, enquanto derivados alifáticos de sais alkynyltrifluoroborate provou ser proporcionando rendimentos modestos ligeiramente menos reactivos. <img alt="Figura 1" src="/files/ftp_upload/52401/52401fig1highres.jpg" /> Figura 1: Preparação de Ynone 1a de fenilacetileno trifluoroborato S1 e cloreto de benzoílo Esquema que ilustra as condições para a preparação de ynone 1a incluindo a formação de dichloroborane intermediário reactivo.. <img alt="Figura 2" src="/files/ftp_upload/52401/52401fig2highres.jpg" /> Figura 2:. Representativas 1 H RMN espectro de ynone 1a Os desvios químicos e as integrações relativas dos protões característicos são rotulados. Figura 3:. Representativas 13 C, Espectro de RMN de ynone 1a desvios químicos dos carbonos característicos são rotulados. <img alt="Figura 4" src="/files/ftp_upload/52401/52401fig4highres.jpg" /> Figura 4:. HRMS espectro representativas de ynone 1a obtido através de ionização química à pressão atmosférica O valor m / z medido do [M + H] + ião é relatado. <img alt="Figura 5" src="/files/ftp_upload/52401/52401fig5highres.jpg" /> Figura 5: Reacções de sal phenylacetylenetrifluoroborate S1 com cloretos de ácido Estruturas e rendimentos para os produtos produzidos pela variação da identidade.do material de partida cloreto de acilo são ilustrados. As reacções foram corridas com 1 equivalente de cloreto de acilo, 1,5 equiv S1 phenylacetylenetrifluoroborate de potássio, e 1,5 equiv tricloreto de boro. <img alt="Figura 6" src="/files/ftp_upload/52401/52401fig6highres.jpg" /> Figura 6:. Reacções de vários alkynyltrifluoroborates com cloretos de acilo estruturas e os rendimentos para os produtos produzidos pela variação da identidade do material de partida alkynyltrifluoroborate são ilustrados. As reações foram executados com 1 equiv de cloreto de acila, 2,5 equiv sal de potássio organotrifluoroborate e 2,5 equiv tricloreto de boro. <table border="0" cellpadding="0" cellspacing="0"><tbody><tr><td> Entrada </td><td> Ácido de Lewis </td><td> Ácido de Lewis (equiv) </td><td> Condições </td><td> Rendimento (%) </td></tr><tr><td> 1 b &lt;/ Sup&gt; </td><td> SiO2 </td><td> 16,5 </td><td> CH 2 Cl 2 </td><td> 0 </td></tr><tr><td> 2 </td><td> SiCl4 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> traço </td></tr><tr><td> 3 </td><td> BF3 · OEt2 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> traço </td></tr><tr><td> 4 b </td><td> FeCl3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 24 </td></tr><tr><td> 5 c </td><td> AlCl3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 62 </td></tr><tr><td> 6 d </td><td> AlCl3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 66 </td></tr><tr><td> 7 e </td><td> AlCl3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 60 </td></tr><tr><td> 8 </td><td> AlCl3 </sub&gt; </td><td> 1 </td><td> THF </td><td> traço </td></tr><tr><td> 9 </td><td> AlCl3 </td><td> 1 </td><td> tolueno </td><td> traço </td></tr><tr><td> 10 </td><td> AlCl3 </td><td> 2 </td><td> ClCH 2 CH 2 Cl </td><td> 33 </td></tr><tr><td> 11 </td><td> AlCl3 </td><td> 1 </td><td> DMSO </td><td> traço </td></tr><tr><td> 12 </td><td> AlCl3 </td><td> 2 </td><td> acetonitrila </td><td> traço </td></tr><tr><td> 13 </td><td> AlCl 3 .6H 2 O </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 0 </td></tr><tr><td> 14 b </td><td> BCl3 </td><td> 1,5 </td><td> CH 2 Cl 2 </td><td> 67 </td></tr><tr><td> 15 </td><td> BBr3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 20 </td></tr></tbody></table><strong&gt; Tabela 1:. Optimização de condições para a preparação de um ynone 1a Rendimento do produto 1a mediante variação das condições de reacção e do catalisador de ácido de Lewis. As reacções foram corridas um cloreto de benzoilo com 1 equiv e 1 equiv phenylacetylenetrifluoroborate potássio S1. B 1,5 equiv S1. C condições anidras. D A reacção foi realizada em material de vidro não-seco sob ar. E condições anidras + 1 ml de água.

Watch this Scientific Journal Video about Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts at JoVE.com

Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts

The goal of this manuscript is to demonstrate a straightforward method for the preparation of ynones from acyl chloride and potassium alkynyltrifluoroborate salt starting materials. The one-pot reaction proceeds rapidly in the presence of boron trichloride without exclusion of air and moisture.

Síntese livre de metais de Ynones da Acil cloretos de potássio e sais Alkynyltrifluoroborate

Ynones are a valuable functional group and building block in organic synthesis. Ynones serve as a precursor to many important organic functional groups ...

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11.1K visualizações.  University of Ontario Institute of Technology. The goal of this manuscript is to demonstrate a straightforward method for the preparation of ynones from acyl chloride and potassium alkynyltrifluoroborate salt starting materials. The one-pot reaction proceeds rapidly in the presence of boron trichloride without exclusion of air and moisture.

Vídeo: Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts

Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent reactions with azides to form cyanocarbene intermediates. The synthesis of hypervalent iodonium alkynyl triflates can be facile, but difficulties stem from their isolation and reactivity. In particular, the necessity to use filtration under inert atmosphere at -45 &deg;C for some HIATs requires special care and equipment. Once isolated, the compounds can be stored and used in reactions with azides to form cyanocarbene intermediates. 
The evidence for cyanocarbene generation is shown by visible extrusion of dinitrogen as well as the characterization of products that occur from O-H insertion, sulfoxide complexation, and cyclopropanation. A side reaction of the cyanocarbene formation is the generation of a vinylidene-carbene and the conditions to control this process are discussed. There is also potential to form a hypervalent iodonium alkenyl triflate and the means of isolation and control of its generation are provided. The O-H insertion reaction involves using a HIAT, sodium azide or tetrabutylammonium azide, and methanol as solvent/substrate. The sulfoxide complexation reaction uses a HIAT, sodium azide or tetrabutylammonium azide, and dimethyl sulfoxide as solvent. The cyclopropanations can be performed with or without the use of solvent. The azide source must be tetrabutylammonium azide and the substrate shown is styrene.

Herein is described the synthesis, isolation, and reactions of hypervalent iodonium alkynyl triflates (HIATs) with azides to generate cyanocarbenes. The procedures will involve air-sensitive and cryogen techniques, including cold filtration under an inert atmosphere. Handling and safety of the synthesized compounds will also be discussed.

Síntese de hipervalente iodónio Alquinilo triflatos de Aplicação de Geração Cyanocarbenes

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent ...

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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 ...

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. ...

Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes

The selective activation of one carbon-fluorine bond in polyfluorinated aromatic molecules or in trifluoromethyl-containing substrates offers the possibility of accessing unique fluorine-containing molecules, which are difficult to obtain by other synthetic pathways. Among various metals, which can undergo C-F activation, lanthanides (Ln) are good candidates as they form strong Ln-F bonds. Lanthanide metals are strong reducing agents with a redox potential Ln3+/Ln&#160;of approximately -2.3 V, which is comparable to the value of the Mg2+/Mg&#160;redox couple. In addition, lanthanide metals display a promising functional group tolerance and their reactivity can vary along the lanthanide series, making them suitable reagents for fine-tuning reaction conditions in organic and organometallic transformations. However, due to their oxophilicity, lanthanides react readily with oxygen and water and therefore require special conditions for storage, handling, preparation, and activation. These factors have limited a more widespread use in organic synthesis. We herein present how dysprosium metal - and by analogy all lanthanide metals - can be freshly prepared under anhydrous conditions using glovebox and Schlenk techniques. The freshly filed metal, in combination with aluminum chloride, initiates the selective C-F activation in trifluoromethylated benzofulvenes. The resulting reaction intermediates react with nitroalkenes to obtain a new family of difluoroalkenes.

This protocol describes the preparation of elemental lanthanides under inert atmosphere and their application in a selective C-F activation process involving trifluoromethylated benzofulvenes.

Aplicação de lantanídeos elementares na ativação seletiva de Benzofulvenes de Trifluoromethylated, fornecendo acesso a vários Difluoroalkenes C-F

The selective activation of one carbon-fluorine bond in polyfluorinated aromatic molecules or in trifluoromethyl-containing substrates offers the ...

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and 1-methyl-4-(1,2,2-triiodovinyl)benzene as representative examples for the practical chemoselective preparation of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes from the chemoselective iodination of terminal alkynes mediated by hypervalent-iodine reagents. The chemoselectivity was confirmed by using p-tolylethyne as a model substrate to screen a variety of iodine sources and/or the hypervalent-iodine reagents. A combination of tetrabutylammonium iodide (TBAI) and (diacetoxyiodo)benzene (PIDA) selectively generates 1-iodoalkynes, while a combination of KI and PIDA generates 1,2-diiodoalkenes. A one-pot synthesis based on both TBAI-PIDA and KI-PIDA yields the corresponding 1,1,2-triiodoalkenes. These protocols were subsequently applied to the synthesis of synthetically important aromatic and aliphatic 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes, which were obtained in good yield with excellent chemoselectivity.

Herein, detailed protocols for the oxidative iodination of terminal alkynes using hypervalent-iodine reagents are presented, which chemoselectively afford 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes.

Preparação Quimiosseletiva de 1-iodoalquinos, 1,2-diiodoalqueenos e 1,1,2-triiodoalqueenos Baseada na Iodação Oxidativa de Alquinos Terminais

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and ...

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals

Protocols for the isolation of the commonly employed cyclic (alkyl)(amino) carbene (CAAC) and N-heterocyclic carbene (NHC) are reported. Furthermore, the synthesis of their mixed CAAC&#8211;NHC &#8220;Wanzlick&#8221; dimer and the synthesis of the related stable organic &#8220;olefin&#8221; radical are presented. The main goal of this manuscript is to give a detailed and general protocol for the synthetic chemist of any skill level on how to prepare free heterocyclic carbenes by deprotonation using filter cannulas. Due to the air-sensitivity of the synthesized compounds, all experiments are performed under inert atmosphere using either Schlenk technique or a dinitrogen filled glovebox. Controlling Wanzlick&#8217;s equilibrium (i.e., the dimerization of free carbenes), is a crucial requirement for the application of free carbenes in coordination chemistry or organic synthesis. Thus, we elaborate on the specific electronic and steric requirements favoring the formation of dimers, heterodimers, or monomers. We will show how proton catalysis allows for the formation of dimers, and how the electronic structure of carbenes and their dimers affects the reactivity with either moisture or air. The structural identity of the reported compounds is discussed based on their NMR spectra.

We present protocols for the isolation of stable heterocyclic carbenes. The synthesis of a cyclic (alkyl)(amino) carbene (CAAC) and an N-heterocyclic carbene (NHC) is demonstrated using filter cannulas and Schlenk technique. We furthermore present the synthesis of the related oxygen-sensitive, electron-rich mixed &#8220;Wanzlick dimer&#8221; and the reduced stable organic radical.

Isolando carbenos livre, misto de dímeros e radicais orgânicos

Protocols for the isolation of the commonly employed cyclic (alkyl)(amino) carbene (CAAC) and N-heterocyclic carbene (NHC) are reported. Furthermore, the ...

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the preparation of all-carbon quaternary centers. Though conjugate additions of organometallic reagents are typically performed utilizing highly reactive organolithium or Grignard reagents, organozinc reagents have garnered attention for their enhanced chemoselectivity and mild reactivity. Despite numerous recent advances with more reactive diorganozinc and mixed diorganozinc reagents, the generation of all-carbon quaternary centers via the conjugate addition of functionalized monoorganozinc reagents remains a challenge. This protocol details a convenient and mild &#8220;one-pot&#8221; preparation and copper mediated conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to afford a broad scope of all-carbon quaternary centers in generally excellent yield and diastereoselectivity. Key to the development of this technology is the utilization of DMA as a reaction solvent with TMSCl as a Lewis acid. Notable advantages to this methodology include the operational simplicity of the organozinc reagent preparation afforded by the utilization of DMA as a solvent, as well as an efficient conjugate addition mediated by various Cu(I) and Cu(II) salts. Moreover, an intermediate silyl enol ether can be isolated utilizing a modified workup procedure. The substrate scope is limited to cyclic unsaturated ketones, and the conjugate addition is impeded by stabilized (e.g., allyl, enolate, homoenolate) and sterically encumbered (e.g., neopentyl, o-aryl) monoorganozinc reagents. Conjugate additions to five- and seven-membered rings were effective, albeit in lower yields compared with six-membered ring substrates.

A simple and practical protocol for the efficient conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to furnish all-carbon quaternary centers was developed.

Síntese eficiente de todos os centros quaternários de carbono através da adição conjugada de brometos Monoorganozinc funcionalizados

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the ...

Acidity of 1-Alkynes

<h4></h4>
The acidic strength of hydrocarbons follows the order: Alkynes &#62; Alkenes &#62; Alkanes. The strength of an acid is commonly expressed in units of pKa &#8212; the lower the pKa, the stronger the acid. Among the hydrocarbons, terminal alkynes have lower pKa values and are, therefore, more acidic. For example, the pKa values for ethane, ethene, and acetylene are 51, 44, and 25, respectively, as shown here.
<table style="margin-left: auto; margin-right: auto;">
	<tbody style="border: 1px solid black;">
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure1left" src="/files/ftp_upload/11833/11833_PT_Figure_1_left.svg" style="text-align: center; height: 75px;" /> 
			Ethane 
			(pKa&#160;= 51)</td>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure1middle" src="/files/ftp_upload/11833/11833_PT_Figure_1_Middle.svg" style="text-align: center; height: 50px;" /> 
			 
			Ethene 
			(pKa&#160;= 44)</td>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;">
			
			<img alt="Figure1right" src="/files/ftp_upload/11833/11833_PT_Figure_1_Right.svg" style="text-align: center; height: 20px;" /> 
			 
			&#160;
			Ethyne 
			(pKa&#160;= 25)
			</td>
		</tr>
	</tbody>
</table>
With a pKa difference of 26 units, acetylene is 1026 times more acidic than ethane. Similarly, a difference of 19 pKa units makes it 1019 times stronger than ethene.
<h4>Hybridization effect</h4>
The pronounced increase in the acidity of terminal alkynes relative to the other hydrocarbons can be explained by considering the stability of the corresponding carbanions formed by deprotonation. Note that, in the nomenclature of organic compounds, the suffix &#34;-ide&#34; indicates that the molecule is a negatively charged ion.
<table style="margin-left: auto; margin-right: auto;">
	<tbody style="border: 1px solid black;">
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure2top" src="/files/ftp_upload/11833/11833_PT_Figure_2_top.svg" style="text-align: center; height: 80px;" /> 
			ethanide&#160;(an alkyl anion) 
			sp3&#160;lone pair, 25% &#8220;s&#8221; character</td>
		</tr>
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure2middle" src="/files/ftp_upload/11833/11833_PT_Figure_2_middle.svg" style="text-align: center; height: 60px;" /> 
			ethenide&#160;(a vinylic anion) 
			sp2&#160;lone pair, 33% &#8220;s&#8221; character</td>
		</tr>
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure2bottom" src="/files/ftp_upload/11833/11833_PT_Figure_2_bottom.svg" style="text-align: center; height: 40px;" /> 
			acetylide&#160;(an acetylenic anion) 
			sp&#160;lone pair, 50% &#8220;s&#8221; character</td>
		</tr>
	</tbody>
</table>
The stability of the carbanion depends on the nature of the hybridized orbital occupied by the lone pair of electrons. As shown above, in ethane&#160;the lone pair resides in an sp3 orbital, while in ethene&#160;it occupies the sp2 orbital and an sp orbital in the case of acetylene. The sp3, sp2, and sp orbitals have 25%, 33%, and 50% &#34;s&#34; character, respectively. Since &#34;s&#34; orbitals are closer to the positively charged nucleus, a hybrid orbital with a higher &#34;s&#34; character will effectively stabilize the negative charge. Thus, the acetylide ions will be the most stable and readily formed in the presence of a suitable base.
<h4>Choosing a suitable base</h4>
In general, for a base to deprotonate an acid, the pKa of the base&#39;s conjugate acid must be at least 10 pKa units greater than that of the acid.
<img alt="Figure3" src="/files/ftp_upload/11833/11833_Figure_3v2.svg" style="text-align: center; height: 80px;" />
Terminal alkynes have a pKa of 25. Therefore, an appropriate base would be one where the conjugate acid has a pKa that is at least 35. Recall that for an acid-base reaction, the equilibrium favors the formation of weaker acids and bases from stronger acids and bases.
stronger acids + stronger bases <img alt="arrow" src="/files/ftp_upload/11833/arrow.png" style="text-align: center; height: 13px;" />weaker acids + weaker bases
With sodium amide as the base, terminal alkynes form sodium acetylide and ammonia as the conjugate acid. Since the pKa of ammonia is greater than 25, the equilibrium favors the formation of sodium acetylide, making sodium amide a strong enough base for the deprotonation reaction.
<img alt="Figure4" src="/files/ftp_upload/11833/11833_Figure_4.svg" style="text-align: center; height: 100px;" />
Apart from sodium amide, sodium hydride, butyllithium, and lithium diisopropylamide (LDA) are other commonly used bases to form acetylide ions.
<table style="margin-left: auto; margin-right: auto;">
	<tbody style="border: 1px solid black;">
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;">
			<img alt="Figure5left" src="/files/ftp_upload/11833/11833_PT_Figure_5_left.svg" style="height: 25px;" />
			Sodium hydride
			</td>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure5middle" src="/files/ftp_upload/11833/11833_PT_Figure_5_middle.svg" style="text-align: center; height: 60px;" /> 
			Butyllithium (n-BuLi)</td>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure5right" src="/files/ftp_upload/11833/11833_PT_Figure_5_right.svg" style="text-align: center; height: 60px;" /> 
			Lithium diisopropylamide (LDA)</td>
		</tr>
	</tbody>
</table>
In the presence of sodium hydroxide as the base, terminal alkynes form sodium acetylide and water as the conjugate acid. However, since the pKa of water is less than 25, the equilibrium favors the reactants. Therefore, sodium hydroxide is not a suitable base to form acetylide ions.
<img alt="Figure6" src="/files/ftp_upload/11833/11833_Figure_6.svg" style="text-align: center; height: 110px;" />
<h4>Synthesis of organometallic reagents </h4>
The relative acidity of terminal alkynes finds application in the synthesis of organometallic compounds when treated with Grignard or organolithium reagents. These are examples of transmetalation reactions involving the transfer of a metal atom from one carbon to another, thereby forming new metal&#8211;carbon bonds. However, they can also be interpreted as acid&#8211;base reactions that favor the formation of weaker acids and bases.
<img alt="Figure7top" src="/files/ftp_upload/11833/11833_Figure_7v3.svg" style="text-align: center; height: 225px;" />
<div></div>

Acidity of Terminal Alkynes: Formation of Acetylide Anions

Acidez de 1-Alquinos


The acidic strength of hydrocarbons follows the order: Alkynes &#62; Alkenes &#62; Alkanes. The strength of an acid is commonly expressed in units of pKa ...

Química orgânica

Unidade 1

Alquinos

TERMOS E CONCEITOS CHAVE

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="Figure1" src="/files/ftp_upload/11834/11834_PT_Figure_1.svg" style="text-align: center; height: 50px;" />
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="Figure2" src="/files/ftp_upload/11834/11834_PT_Figure_2.svg" style="text-align: center; height: 50px;" />
2. The second step is a nucleophilic substitution reaction in which the acetylide ion reacts with the alkyl halide to form a new C&#8211;C bond.
<img alt="Figure3" src="/files/ftp_upload/11834/11834_PT_Figure_3.svg" style="text-align: center; height: 50px;" />
<h4>Reaction Mechanism &#8212;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="Figure4" src="/files/ftp_upload/11834/11834_PT_Figure_4.svg" style="text-align: center; height: 250px;" />
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="Figure5" src="/files/ftp_upload/11834/11834_PT_Figure_5.svg" style="text-align: center; height: 50px;" />

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 ...

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="Figure1" src="/files/ftp_upload/11835/11835_PT_Figure_1.svg" style="text-align: center; height: 200px;" />
<h4>Reaction Mechanism &#8211; 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="Figure2" src="/files/ftp_upload/11835/11835_PT_Figure_2.svg" style="text-align: center; height: 90px;" />
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="Figure3" src="/files/ftp_upload/11835/11835_PT_Figure_3.svg" style="text-align: center; height: 90px;" />
Geminal dihalides
Likewise, geminal dihalides, when treated with two equivalents of a sodium amide, undergo double dehydrohalogenation to give alkynes.
<img alt="Figure4" src="/files/ftp_upload/11835/11835_PT_Figure_4.svg" style="text-align: center; height: 90px;" />
<img alt="Figure5" src="/files/ftp_upload/11835/11835_PT_Figure_5.svg" style="text-align: center; height: 90px;" />
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="Figure6" src="/files/ftp_upload/11835/11835_PT_Figure_6.svg" style="text-align: center; height: 70px;" />
Protonation of the acetylide ions with water or an aqueous acid completes the reaction.
<img alt="Figure7" src="/files/ftp_upload/11835/11835_PT_Figure_7.svg" style="text-align: center; height: 50px;" />
<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 &#8211; a vicinal dihalide, which upon double dehydrohalogenation yields 1-propyne.
<img alt="Figure8" src="/files/ftp_upload/11835/11835_PT_Figure_8.svg" style="text-align: center; height: 60px;" />
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 &#8211; a geminal dihalide, which undergoes double dehydrohalogenation to give 1-propyne.
<img alt="Figure9" src="/files/ftp_upload/11835/11835_PT_Figure_9.svg" style="text-align: center; height: 80px;" />

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 ...