This work was funded by the Spanish Ministerio de Econom&#236;a y Competitividad (CTQ 2013-41067-P). H.B. acknowledge with thanks a MEC-FPI grant.

1. A funcionalização de 2,15-Dimethylhexahelicene <ol><li> Dibromination de 2,15-dimethylhexahelicene <ol><li> Pesar 0,356 g (1,0 mmol) de 2,15-dimethylhexahelicene, 0,374 g (2,1 mmol) de bromo-succinimida recristalizado recém-N (NBS) e 24 mg (0,07 mmol) de peróxido de benzoilo (BPO) (70% em peso com 30% de água como estabilizador). Coloque todos os sólidos num balão de Schlenk de 100 mL com uma barra de agitação magnética. Coloque sob atmosfera de azoto por três ciclos de evacuação de gás seguido de preenchimento de gás inerte na linha de Schlenk. </li><li> Adicionar 21 ml de tetracloreto de carbono (CCI4). Desgaseificar a solução por o mesmo evacuação / reenchimento processo (passo 1.1.1) com agitação vigorosa e cuidadosamente a fim de evitar a perda de massa de solvente. </li><li> Aquece-se ao refluxo (77 ° C) a mistura com um banho de óleo durante 4 horas. Verifique a reacção por ressonância magnética nuclear de 1H (RMN). Doublets entre 3,7 ppm e 4,0 ppm shoaparecem uld. Eles indicam a presença de diastereotópico -CH 2 - grupos (Figura 1). </li><li> Uma vez terminado, a mistura arrefecer até à temperatura ambiente e remover o solvente sob vácuo. Criar uma armadilha preenchido com nitrogênio líquido para evitar a contaminação da bomba. </li><li> Redissolve-se o produto bruto em 30 ml de diclorometano (DCM), transferir para um balão de fundo redondo e misturar com 4 g de gel de sílica (tipicamente adicionar 5 vezes o peso bruto). Concentra-se a mistura num evaporador rotativo. </li><li> Neste meio tempo, encher uma coluna (comprimento cerca de 20 cm e uma espessura de 4,5 cm) com SiO2 gel misturado previamente com hexano / acetato de etilo (95: 5) como fase móvel. Adicionar a mistura ao topo da coluna e, em seguida, adicionar uma camada de areia (2 cm). </li><li> Com cuidado, despeje na nova fase móvel e realizar a cromatografia através da recolha de fracções em tubos de ensaio (normalmente 20 ml por tubo e 4 ml perto da eluição produto esperado). Verificar fracções por cromatografia em camada fina(TLC) com a mesma fase móvel (hexano / acetato de etilo 95: 5) e uma imagem com luz UV. O produto pretendido (4b) deve eluir com um factor de retenção (Rf) de 0,35, como um óleo amarelo após a combinação de todas as fracções e queria remover-se o solvente no evaporador rotativo. 334 mg devem ser obtidos (rendimento de 65%). NOTA: Todas as técnicas de Schlenk, o uso de um banho de óleo para as configurações de cromatografia de aquecimento e colunas serão amplamente utilizados na maioria dos protocolos, por isso a partir de agora, eles não serão cobertos em detalhes e apenas alguns comentários, quando necessário, seja dado. </li></ol></li></ol><img alt="figura 1" src="/files/ftp_upload/53954/53954fig1.jpg" /> . Figura 1 1 H-RMN Os espectros (500 MHz, CDCl 3) de 2,15 -dimethylhelicene (parte superior) e uma alíquota tomada após 2 horas Novos sinais, correspondente a -CH 2 -.., são retratados em um círculo vermelho (inferior) <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53954/53954fig1large.jpg" target="_blank">Por favor clique aqui para ver uma versão maior desta figura.</a> <ol start="2"><li> Síntese de 2,15-bis (azidometil) hexahelicene <ol><li> Pesar 0,103 g (0,2 mmol) de 2,15-bis (bromometil) hexahelicene e 0,390 g (6 mmol) de azida de sódio. Coloque ambos os sólidos em um frasco de 50 ml Schlenk equipado com barra magnética e colocado sob atmosfera de azoto. </li><li> Misturar 8,6 ml de tetra-hidrofurano (THF) com 5,2 ml de água (H2O) e verter a mistura de solventes para o balão de Schlenk. Desgaseificar a solução. </li><li> Aquece-se ao refluxo (65 ° C) durante 3 h. Verifique a reacção por 1H-RMN. -CH 2 - sinais deve mudar para 3,75 ppm (Figura 2). </li><li> Depois, cool para baixo a mistura até à temperatura ambiente e remover o THF sob vácuo. Dilui-se com 50 ml de H 2 O. </li><li> Transferir a mistura para uma ampola de decantação e extrai-se três vezes com 40 ml de DCM. Combinar todas as fases orgânicas e lava-se com puro H2O (50 ml). </li><li> Purifica-se o produto em bruto por cromatografia em coluna sobre gel de sílica usando hexano / acetato de etilo (85:15) como fase móvel para dar um óleo amarelo, a Rf = 0,38 correspondente a 2,15-bis (azomethyl) hexahelicene (5b). 70 mg deve ser obtidos (rendimento de 80%). </li></ol></li></ol><img alt="Figura 2" src="/files/ftp_upload/53954/53954fig2.jpg" /> Figura 2: 1 H-RMN Os espectros (500 MHz, CDCl3) de 4 b (em cima) e uma alíquota tomada depois de 3 h(parte inferior). Observe as mudanças na região alifático. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53954/53954fig2large.jpg" target="_blank">Por favor clique aqui para ver uma versão maior desta figura.</a> 2. A funcionalização da Corannulene <ol><li> Monobromination de Corannulene <ol><li> Pesar 0,125 g (0,5 mmol) de corannulene, 89 mg (0,5 mmol) de NBS recentemente recristalizado e 17 mg de ouro (III) hidrato de cloreto. </li><li> Coloque todos os compostos em um frasco de 10 ml especialmente concebidos para reacções de microondas equipado com uma barra magnética e, em seguida, colocado em atmosfera de azoto, com a ajuda de um balão de fundo redondo com duas tubuladuras. </li><li> Adicionar 7 ml de 1,2-dicloroetano (DCE) e desgaseificar a solução. </li><li> Sonicar a mistura durante 2 minutos para dispersar as partículas de sal de ouro. </li><li> O calor no interior do reactor de micro-ondas a 100 ° C durante 2 h. </li><li> Quando terminou, transferir o produto em bruto para um balão de fundo redondo e remover o solvente por rotarY evaporação. </li><li> Purifica-se o produto em bruto por cromatografia em coluna sobre gel de SiO2, utilizando hexano como fase móvel. NOTA: Bromocorannulene (4a) é obtido na forma de um sólido de cor amarela, a Rf = 0,38. 99 mg deve ser obtidos (rendimento de 60%). Corannulene que não reagiu (3a) pode ser recuperado e armazenado para outras utilizações. Ele aparece a um Rf = 0,29. </li></ol></li><li> Acoplamento de Sonogashira de Bomocorannulene e etiniltrimetilsilano <ol><li> Pesar 49 mg (0,15 mmol) de bromocorannulene, 11 mg (0,015 mmol) de [PdCl2 (dppf)] 49,50 (dppf sendo 1,1-&#39;bis (diphenylphsphino) ferroceno, 3 mg (0,015 mmol) de Cul. 51 </li><li> Coloque todos os sólidos num num frasco Schlenk de 50 ml junto com uma barra magnética e colocar sob atmosfera de azoto. </li><li> Adicionar 5,0 ml de trietilamina (NEt3) e desgaseificar a mistura. </li><li> Finalmente, adicionar 104 ul (0,75 mmol) de etiniltrimetilsilano. </li><li> Sonicar a mistura durante 2 min adispersar partículas de sal de metal. </li><li> Aquece-se a 85 ° C durante 24 h com ultra-sons periódica para evitar a deposição de sais metálicos. NOTA: A mistura tornou-se de cor para preto em breve, indicando a presença de paládio (0). </li><li> Arrefecer até à temperatura ambiente e evapora-se NEt 3 em vácuo. </li><li> Redissolve-se em 20 ml de DCM e purifica-se por cromatografia em coluna sobre gel de sílica eluindo com hexano para dar um sólido de cor amarela, a Rf = 0,28 correspondente a 5a. 41 mg deve ser obtidos (rendimento de 78%). NOTA: Se o produto em bruto é filtrado através de uma almofada de Celite em DCM, pode ser obtida uma amostra pura razoável, contudo derivados de fosfina não são removidos totalmente. </li></ol></li><li> Preparação de Ethynylcorannulene por desprotecção TMS <ol><li> Pesar 35 mg (0,10 mmol) de 5-A e 7,3 mg (0,125 mmol) de fluoreto de potássio anidro. </li><li> Coloque todos os sólidos num balão de Schlenk de 50 ml equipado com uma barra magnética de umd colocado sob atmosfera de azoto. </li><li> Mistura-se 4 ml de THF e 4 ml de metanol (MeOH) e derramar a mistura para dentro do balão de Schlenk. Degas completamente. </li><li> Deixar reagir à temperatura ambiente, mantem o balão ao abrigo da luz, cobrindo-o com uma película opaca. Verifique a reacção por 1H-RMN, olhando para 3,48 ppm. Um sinal correspondente a -CCH deve surgir (Figura 3). NOTA: Embora este composto tem uma alcino terminal que é reativo e decompõe facilmente, não encontramos problemas durante o trabalho de descrito abaixo. Foi realizado sob luz natural. </li><li> Uma vez terminado, remover o THF sob vácuo e dilui-se com 10 ml de água, transferindo tudo para um funil de separação. </li><li> Extrai-se com DCM (3 x 15 mL), combinam todas as fases orgânicas, num balão de fundo redondo e concentra-se num evaporador rotativo à temperatura ambiente para finalmente obter um sólido amarelo correspondente a 6a. 27 mg deve ser obtidos (rendimento quantitativo). </li></ol></li></ol><img alt="Figura 3" src="/files/ftp_upload/53954/53954fig3.jpg" /> Figura 3:.. 1 H-NMR espectro (500 MHz, CDCl3) de 5-A (superior) e 6-A (baixo) singlet -CCH é retratado em um círculo vermelho <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53954/53954fig3large.jpg" target="_blank">Por favor clique aqui para ver uma versão maior desta figura.</a> 3. Montagem Final por Click Química <ol><li> Pesar 15,3 mg (0,035 mmol) de 5-B, 20,0 mg (0,073 mmol) de 6a, 1,4 mg (0,007 mmol) de sal de sódio de ácido ascórbico, 1,7 mg (0,007 mmol) de CuSO 4 5H 2 O. · </li><li> Coloque todos os sólidos num balão de Schlenk de 50 ml equipado com AMbar agnetic e colocado sob atmosfera de azoto. </li><li> Misturar 3 ml de H2O e 12 ml de THF e derramar a mistura para dentro do balão de Schlenk. Desgaseificar a solução completamente. </li><li> Aquece-se a 65 ° C durante 3 dias, com um condensador ligado ao topo do frasco e verificar periodicamente a reacção para controlar a temperatura, agitação e o volume de solvente. Verifique a reacção por 1H-RMN. O sinal a 3,48 ppm deve desaparecer e ser desviado para 7,27 ppm indicando o consumo de corannulene etinilo e a existência da unidade triazole (Figura 4). </li><li> Quando terminado, remover o THF sob vácuo e dilui-se com 20 ml de água, transferindo a mistura para um funil de separação. </li><li> Extrai-se com DCM (3 x 20 mL), combinam todas as fases orgânicas, num balão de fundo redondo e concentra-se num evaporador rotativo. </li><li> Purifica-se o produto em bruto por cromatografia em coluna sobre gel de SiO 2 eluindo-se com hexano / acetato de etilo (1: 1) para dar um sólido amarelo pálido, a Rf = 0,59correspondente a 7. 27 mg deve ser obtidos (rendimento de 75%). </li></ol><img alt="Figura 4" src="/files/ftp_upload/53954/53954fig4.jpg" /> Figura 4: 1 H-RMN Os espectros (500 MHz, CDCl3) de 5 b (parte superior), 6 um (meio) e uma alíquota tomada depois de 2 dias (inferior) Nota o desaparecimento do sinal a -CCH em bruto.. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53954/53954fig4large.jpg" target="_blank">Por favor clique aqui para ver uma versão maior desta figura.</a>

The authors have nothing to disclose.

O composto final 7 foi preparado após 6 passos a partir de precursores poliaromáticos não planares e um 3 3 b com moderada a muito bons rendimentos de cada reacção. A principal limitação observada nesta via foi a bromação de ambos os compostos poliaromáticos não planas. No entanto, no caso de um composto 4, uma quantidade importante de corannulene livre pode ser recuperada para outras utiliza...

Devido à sua geometria especial, corannulene e helicenes são moléculas que podem adoptar uma estrutura longe de planaridade e dão origem a propriedades interessantes. 1-15 Nos últimos anos, a pesquisa de receptores moleculares de nanotubos de carbono e fulerenos é uma área muito activa 16-19, devido, principalmente, às suas potenciais aplicações como materiais para células solares orgânicas, transistores, sensores e outros dispositivos. 20-28 a excelente complementaridade em forma entre corannulene e um fulereno têm atraído a atenção de vários pesquisadores, com o objetivo de projetar receptores moleculares capazes de estabelecer associação supramolecular pelas forças de dispersão. 29-39 A química dos compostos poliaromáticos não planares acima mencionados é semelhante ao descrito para moléculas totalmente planas, mas às vezes é difícil encontrar condições adequadas para a realização selectividades e os rendimentos desejados. 40 </sup&gt; Neste trabalho apresentamos a síntese de uma molécula (7) que tem três unidades poliaromáticos em poucos passos com bons rendimentos através da aplicação de técnicas simples e típicos encontrados em cada laboratório de pesquisa. A molécula é de grande importância porque pode adotar uma conformação tipo tenaz para estabelecer boas interações com C 60 37 em solução; e que pode abrir uma linha de pesquisa como um receptor potencial para maiores fulerenos quirais graças ao ligante helicene, que é uma molécula quiral, devido à existência de um eixo estereogénico. 41-45 No entanto, apenas helicene racémica será usado neste trabalho. Neste ponto, a única limitação para sintetizar estes receptores é a preparação de helicenes corannulenes e, uma vez que não estão disponíveis comercialmente. Mas, de acordo com novos métodos publicados em outras posições 46-48 que pode ser obtido em quantidades adequadas num curto período de tempo razoável.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>2,15-Dimethylhexahelicene</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Prepared according to reference 5b,c in the main text.</td>
		</tr>
		<tr>
			<td>Corannulene</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Prepared according to reference 5a in the main text.</td>
		</tr>
		<tr>
			<td>N-Bromosuccinimide (NBS)</td>
			<td>Sigma Aldrich</td>
			<td>B8.125-5</td>
			<td>ReagentPlus&#174;, 99%. Recrystallized from hot water.</td>
		</tr>
		<tr>
			<td>Benzoyl peroxide (BPO)</td>
			<td>Sigma Aldrich</td>
			<td>B-2030</td>
			<td>~70% (titration). 30% water as stabilizer.</td>
		</tr>
		<tr>
			<td>Sodium azide</td>
			<td>Sigma Aldrich</td>
			<td>S2002</td>
			<td>ReagentPlus&#174;, &#8805;99.5%.</td>
		</tr>
		<tr>
			<td>Gold (III) chloride Hydrate</td>
			<td>Sigma Aldrich</td>
			<td>50778</td>
			<td>puriss. p.a., ACS reagent, &#8805;49% Au basis.</td>
		</tr>
		<tr>
			<td>Ethynyltrimethylsilane</td>
			<td>Sigma Aldrich</td>
			<td>218170</td>
			<td>98%.</td>
		</tr>
		<tr>
			<td>[PdCl2(dppf)]</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Prepared according to reference 6 in the main text.</td>
		</tr>
		<tr>
			<td>CuI</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Prepared according to reference 7 in the main text.</td>
		</tr>
		<tr>
			<td>KF</td>
			<td>Sigma Aldrich</td>
			<td>307599</td>
			<td>99%, spray-dried.</td>
		</tr>
		<tr>
			<td>(+)-Sodium L-ascorbate</td>
			<td>Fluka</td>
			<td>11140</td>
			<td>BioXtra, &#8805;99.0% (NT).</td>
		</tr>
		<tr>
			<td>Copper(II) Sulphate 5-hydrate</td>
			<td>Panreac</td>
			<td>131270</td>
			<td>for analysis.</td>
		</tr>
		<tr>
			<td>Carbon tetrachloride (CCl4)</td>
			<td>Fluka</td>
			<td>87030</td>
			<td>for IR spectroscopy, &#8805;99.9%.</td>
		</tr>
		<tr>
			<td>Dichloromethane (DCM)</td>
			<td>Fisher Scientific</td>
			<td>D/1852/25</td>
			<td>Analytical reagent grade. Distilled prior to use.</td>
		</tr>
		<tr>
			<td>Hexane</td>
			<td>Fisher Scientific</td>
			<td>H/0355/25</td>
			<td>Analytical reagent grade. Distilled prior to use.</td>
		</tr>
		<tr>
			<td>Ethyl acetate</td>
			<td>Scharlau</td>
			<td>AC0145025S</td>
			<td>Reagent grade. Distilled prior to use.</td>
		</tr>
		<tr>
			<td>Tetrahydrofuran (THF)</td>
			<td>Fisher Scientific</td>
			<td>T/0701/25</td>
			<td>Analytical reagent grade. Distilled prior to use.</td>
		</tr>
		<tr>
			<td>1,2-Dichloroethane (DCE)</td>
			<td>Sigma Aldrich</td>
			<td>D6,156-3</td>
			<td>ReagentPlus&#174;, 99%.</td>
		</tr>
		<tr>
			<td>Methanol (MeOH)</td>
			<td>VWR</td>
			<td>20847.36</td>
			<td>AnalaR NORMAPUR.</td>
		</tr>
		<tr>
			<td>Triethyl amine (NEt3)</td>
			<td>Sigma Aldrich</td>
			<td>T0886</td>
			<td>&#8805;99%.</td>
		</tr>
		<tr>
			<td>Silica gel</td>
			<td>Acros</td>
			<td>360050010</td>
			<td>Particle size 40-60mm.</td>
		</tr>
		<tr>
			<td>Sand - low iron</td>
			<td>Fisher Scientific</td>
			<td>S/0360/63</td>
			<td>General purpose grade.</td>
		</tr>
		<tr>
			<td>TLC Silica gel 60 F254</td>
			<td>Merck</td>
			<td>1.05554.0001</td>
			<td></td>
		</tr>
		<tr>
			<td>Monowave 300 (Microwave reactor)</td>
			<td>Anton Para</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Sonicator</td>
			<td>Grupo Selecta</td>
			<td>3000513</td>
			<td>6 Litres.</td>
		</tr>
	</tbody>
</table>

preparation of a corannulene-functionalized hexahelicene by copper(i)-catalyzed alkyne-azide cycloaddition of nonplanar polyaromatic units

The main purpose of this video is to show 6 reaction steps of a convergent synthesis and prepare a complex molecule containing up to three nonplanar polyaromatic units, which are two corannulene moieties and a racemic hexahelicene linking them. The compound described in this work is a good host for fullerenes. Several common organic reactions, such as free-radical reactions, C-C coupling or click chemistry, are employed demonstrating the versatility of functionalization that this compound can accept. All of these reactions work for planar aromatic molecules. With subtle modifications, it is possible to achieve similar results for nonplanar polyaromatic compounds.

Corannulene (3-A) e 2,15-dimethylhexahelicene (3 b) pode ser preparado seguindo os métodos actuais 46-48 de uma forma simples com muito bons rendimentos (Figura 5). Ambos compartilham uma molécula comum, 2,7-dimetilnaftaleno, como o material de partida, dando origem a um divergente de síntese convergente da molécula final. <...

Watch this Scientific Journal Video about Preparation of a Corannulene-functionalized Hexahelicene by CopperI-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units at JoVE.com

Preparation of a Corannulene-functionalized Hexahelicene by CopperI-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

Aqui, apresentamos um protocolo para sintetizar um composto orgânico complexo composto de três unidades poliaromáticos não planas, montadas facilmente com rendimentos razoáveis.

Preparação de um Hexahelicene Corannulene-funcionalizado por cobre (I) catalisada por cicloadição alcino azida de unidades não planar aromáticos policíclicos

The main purpose of this video is to show 6 reaction steps of a convergent synthesis and prepare a complex molecule containing up to three nonplanar ...

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Preparation of a Corannulene-functionalized Hexahelicene by Copper(I)-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

Aromatic Compounds

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11.4K visualizações.  Universidad de Valladolid.  Aqui, apresentamos um protocolo para sintetizar um composto orgânico complexo composto de três unidades poliaromáticos não planas, montadas facilmente com rendimentos razoáveis. 

Vídeo: Preparation of a Corannulene-functionalized Hexahelicene by CopperI-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

Preparation and Use of Samarium Diiodide (SmI2) in Organic Synthesis: The Mechanistic Role of HMPA and Ni(II) Salts in the Samarium Barbier Reaction

Although initially considered an esoteric reagent, SmI2 has become a common tool for synthetic organic chemists. SmI2 is generated through the addition of molecular iodine to samarium metal in THF.1,2-3 It is a mild and selective single electron reductant and its versatility is a result of its ability to initiate a wide range of reductions including C-C bond-forming and cascade or sequential reactions. SmI2 can reduce a variety of functional groups including sulfoxides and sulfones, phosphine oxides, epoxides, alkyl and aryl halides, carbonyls, and conjugated double bonds.2-12 One of the fascinating features of SmI-2-mediated reactions is the ability to manipulate the outcome of reactions through the selective use of cosolvents or additives. In most instances, additives are essential in controlling the rate of reduction and the chemo- or stereoselectivity of reactions.13-14 Additives commonly utilized to fine tune the reactivity of SmI2 can be classified into three major groups: (1) Lewis bases (HMPA, other electron-donor ligands, chelating ethers, etc.), (2) proton sources (alcohols, water etc.), and (3) inorganic additives (Ni(acac)2, FeCl3, etc).3
Understanding the mechanism of SmI2 reactions and the role of the additives enables utilization of the full potential of the reagent in organic synthesis. The Sm-Barbier reaction is chosen to illustrate the synthetic importance and mechanistic role of two common additives: HMPA and Ni(II) in this reaction. The Sm-Barbier reaction is similar to the traditional Grignard reaction with the only difference being that the alkyl halide, carbonyl, and Sm reductant are mixed simultaneously in one pot.1,15 Examples of Sm-mediated Barbier reactions with a range of coupling partners have been reported,1,3,7,10,12 and have been utilized in key steps of the synthesis of large natural products.16,17 Previous studies on the effect of additives on SmI2 reactions have shown that HMPA enhances the reduction potential of SmI2 by coordinating to the samarium metal center, producing a more powerful,13-14,18 sterically encumbered reductant19-21 and in some cases playing an integral role in post electron-transfer steps facilitating subsequent bond-forming events.22 In the Sm-Barbier reaction, HMPA has been shown to additionally activate the alkyl halide by forming a complex in a pre-equilibrium step.23
Ni(II) salts are a catalytic additive used frequently in Sm-mediated transformations.24-27 Though critical for success, the mechanistic role of Ni(II) was not known in these reactions. Recently it has been shown that SmI2 reduces Ni(II) to Ni(0), and the reaction is then carried out through organometallic Ni(0) chemistry.28
These mechanistic studies highlight that although the same Barbier product is obtained, the use of different additives in the SmI2 reaction drastically alters the mechanistic pathway of the reaction. The protocol for running these SmI2-initiated reactions is described.

Preparation and Use of Samarium Diiodide SmI2 in Organic Synthesis: The Mechanistic Role of HMPA and NiII Salts in the Samarium Barbier Reaction

A straightforward procedure for the preparation of samarium diiodide (SmI2) in THF is described. The role of two main additives namely hexamethylphosphoramide (HMPA) and Ni(acac)2 in Sm mediated reactions is demonstrated in the Sm-Barbier reaction.

Preparação e Uso de Samário diiodeto (SMI<sub&gt; 2</sub&gt;) Em Organic Synthesis: The Role mecanístico de HMPA e (II) de Ni Sais na Reacção Barbier Samário

Although initially considered an esoteric reagent, SmI2 has become a common tool for synthetic organic chemists. SmI2 is generated through the addition of ...

Química

Isolation and Preparation of Bacterial Cell Walls for Compositional Analysis by Ultra Performance Liquid Chromatography

The bacterial cell wall is critical for the determination of cell shape during growth and division, and maintains the mechanical integrity of cells in the face of turgor pressures several atmospheres in magnitude. Across the diverse shapes and sizes of the bacterial kingdom, the cell wall is composed of peptidoglycan, a macromolecular network of sugar strands crosslinked by short peptides. Peptidoglycan&#8217;s central importance to bacterial physiology underlies its use as an antibiotic target and has motivated genetic, structural, and cell biological studies of how it is robustly assembled during growth and division. Nonetheless, extensive investigations are still required to fully characterize the key enzymatic activities in peptidoglycan synthesis and the chemical composition of bacterial cell walls. High Performance Liquid Chromatography (HPLC) is a powerful analytical method for quantifying differences in the chemical composition of the walls of bacteria grown under a variety of environmental and genetic conditions, but its throughput is often limited. Here, we present a straightforward procedure for the isolation and preparation of bacterial cell walls for biological analyses of peptidoglycan via HPLC and Ultra Performance Liquid Chromatography (UPLC), an extension of HPLC that utilizes pumps to deliver ultra-high pressures of up to 15,000 psi, compared with 6,000 psi for HPLC. In combination with the preparation of bacterial cell walls presented here, the low-volume sample injectors, detectors with high sampling rates, smaller sample volumes, and shorter run times of UPLC will enable high resolution and throughput for novel discoveries of peptidoglycan composition and fundamental bacterial cell biology in most biological laboratories with access to an ultracentrifuge and UPLC.

The bacterial cell wall is composed of peptidoglycan, a macromolecular network of sugar strands crosslinked by peptides. Ultra Performance Liquid Chromatography provides high resolution and throughput for novel discoveries of peptidoglycan composition. We present a procedure for the isolation of cell walls (sacculi) and their subsequent preparation for analysis via UPLC.

Isolamento e Preparação de Paredes Celulares Bacterianas para Análise Composicional por Cromatografia Líquida de Ultra Desempenho

The bacterial cell wall is critical for the determination of cell shape during growth and division, and maintains the mechanical integrity of cells in the ...

Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example

By using inline monitoring, it is possible to optimize reactions performed using continuous-flow processing in a simple and rapid way. It is also possible to ensure consistent product quality over time using this technique. We here show how to interface a commercially available flow unit with a Raman spectrometer. The Raman flow cell is placed after the back-pressure regulator, meaning that it can be operated at atmospheric pressure. In addition, the fact that the product stream passes through a length of tubing before entering the flow cell means that the material is at RT. It is important that the spectra are acquired under isothermal conditions since Raman signal intensity is temperature dependent. Having assembled the apparatus, we then show how to monitor a chemical reaction, the piperidine-catalyzed synthesis of 3-acetylcoumarin from salicylaldehyde and ethyl acetoacetate being used as an example. The reaction can be performed over a range of flow rates and temperatures, the in-situ monitoring tool being used to optimize conditions simply and easily.

Real-time monitoring allows for fast optimization of reactions performed using continuous-flow processing. Here the preparation of 3-acetylcoumarin is used as an example. The apparatus for performing in-situ Raman monitoring is described, as are the steps required to optimize the reaction.

Monitoramento em tempo real de Reações realizada utilizando processamento de fluxo contínuo: A Preparação de 3-Acetylcoumarin como Exemplo

By using inline monitoring, it is possible to optimize reactions performed using continuous-flow processing in a simple and rapid way. It is also possible ...

Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles

Amphiphilic block copolymers like polyethyleneglycol-block-polylactic acid (PEG-b-PLA) can self-assemble into micelles above their critical micellar concentration forming hydrophobic cores surrounded by hydrophilic shells in aqueous environments. The core of these micelles can be utilized to load hydrophobic, poorly water soluble drugs like docetaxel (DTX) and everolimus (EVR). Systematic characterization of the micelle structure and drug loading capabilities are important before in vitro and in vivo studies can be conducted. The goal of the protocol described herein is to provide the necessary characterization steps to achieve standardized micellar products. DTX and EVR have intrinsic solubilities of 1.9 and 9.6 &#181;g/ml respectively Preparation of these micelles can be achieved through solvent casting which increases the aqueous solubility of DTX and EVR to 1.86 and 1.85 mg/ml, respectively. Drug stability in micelles evaluated at room temperature over 48 hr indicates that 97% or more of the drugs are retained in solution. Micelle size was assessed using dynamic light scattering and indicated that the size of these micelles was below 50 nm and depended on the molecular weight of the polymer. Drug release from the micelles was assessed using dialysis under sink conditions at pH 7.4 at 37 oC over 48 hr. Curve fitting results indicate that drug release is driven by a first order process indicating that it is diffusion driven.

The goal of this protocol is to describe the preparation and characterization of physically entrapped, poorly water soluble drugs in micellar drug delivery systems composed of amphiphilic block copolymers.

Preparação e caracterização de Individual e Multi-carregadas com droga Fisicamente Entrapped poliméricos Micelles

Amphiphilic block copolymers like polyethyleneglycol-block-polylactic acid (PEG-b-PLA) can self-assemble into micelles above their critical micellar ...

Facile Preparation of Internally Self-assembled Lipid Particles Stabilized by Carbon Nanotubes

We present a facile method to prepare nanostructured lipid particles stabilized by carbon nanotubes (CNTs). Single-walled (pristine) and multi-walled (functionalized) CNTs are used as stabilizers to produce Pickering type oil-in-water (O/W) emulsions. Lipids namely, Dimodan U and Phytantriol are used as emulsifiers, which in excess water self-assemble into the bicontinuous cubic Pn3m phase. This highly viscous phase is fragmented into smaller particles using a probe ultrasonicator in presence of conventional surfactant stabilizers or CNTs as done here. Initially, the CNTs (powder form) are dispersed in water followed by further ultrasonication with the molten lipid to form the final emulsion. During this process the CNTs get coated with lipid molecules, which in turn are presumed to surround the lipid droplets to form a particulate emulsion that is stable for months. The average size of CNT-stabilized nanostructured lipid particles is in the submicron range, which compares well with the particles stabilized using conventional surfactants. Small angle X-ray scattering data confirms the retention of the original Pn3m cubic phase in the CNT-stabilized lipid dispersions as compared to the pure lipid phase (bulk state). Blue shift and lowering of the intensities in characteristic G and G&#39; bands of CNTs observed in Raman spectroscopy characterize the interaction between CNT surface and lipid molecules. These results suggest that the interactions between the CNTs and lipids are responsible for their mutual stabilization in aqueous solutions. As the concentrations of CNTs employed for stabilization are very low and lipid molecules are able to functionalize the CNTs, the toxicity of CNTs is expected to be insignificant while their biocompatibility is greatly enhanced. Hence the present approach finds a great potential in various biomedical applications, for instance, for developing hybrid nanocarrier systems for the delivery of multiple functional molecules as in combination therapy or polytherapy.

We report on a smart application of carbon nanotubes for kinetic stabilization of lipid particles that contain self-assembled nanostructures in their cores. The preparation of lipid particles requires rather low concentrations of carbon nanotubes permitting their use in biomedical applications such as drug delivery.

Preparação Facile da Internamente auto-montados Lipid partículas estabilizada por nanotubos de carbono

We present a facile method to prepare nanostructured lipid particles stabilized by carbon nanotubes (CNTs). Single-walled (pristine) and multi-walled ...

Preparation of Macroporous Epitaxial Quartz Films on Silicon by Chemical Solution Deposition

This work describes the detailed protocol for preparing piezoelectric macroporous epitaxial quartz films on silicon(100) substrates. This is a three-step process based on the preparation of a sol in a one-pot synthesis which is followed by the deposition of a gel film on Si(100) substrates by evaporation induced self-assembly using the dip-coating technique and ends with a thermal treatment of the material to induce the gel crystallization and the growth of the quartz film. The formation of a silica gel is based on the reaction of a tetraethyl orthosilicate and water, catalyzed by HCl, in ethanol. However, the solution contains two additional components that are essential for preparing mesoporous epitaxial quartz films from these silica gels dip-coated on Si. Alkaline earth ions, like Sr2+ act as glass melting agents that facilitate the crystallization of silica and in combination with cetyl trimethylammonium bromide (CTAB) amphiphilic template form a phase separation responsible of the macroporosity of the films. The good matching between the quartz and silicon cell parameters is also essential in the stabilization of quartz over other SiO2 polymorphs and is at the origin of the epitaxial growth.

A protocol is presented for the preparation of piezoelectric macroporous epitaxial films of quartz on silicon by solution chemistry using dip-coating and thermal treatments in air.

Preparação de macroporosas Epitaxial quartzo Filmes sobre Silicon Chemical Solution Deposition por

This work describes the detailed protocol for preparing piezoelectric macroporous epitaxial quartz films on silicon(100) substrates. This is a three-step ...

Anionic Polymerization of an Amphiphilic Copolymer for Preparation of Block Copolymer Micelles Stabilized by &#960;-&#960; Stacking Interactions

In this study, an amphiphilic copolymer that includes a core-forming block with phenyl groups was synthesized by living anionic polymerization of phenyl glycidyl ether (PheGE) on methoxy-polyethylene glycol (mPEG-b-PPheGE). Characterization of the copolymer revealed a narrow molecular distribution (PDI &#60; 1.03) and confirmed the degree of polymerization of mPEG122-b-(PheGE)15. The critical micelle concentration of the copolymer was evaluated using an established fluorescence method with the aggregation behavior evaluated by dynamic light scattering and transmission electronic microscopy. The potential of the copolymer for use in drug delivery applications was evaluated in a preliminary manner including in vitro biocompatibility, loading and release of the hydrophobic anti-cancer drug doxorubicin (DOX). A stable micelle formulation of DOX was prepared with drug loading levels up to 14% (wt%), drug loading efficiencies &#62; 60% (w/w) and sustained release of drug over 4 days under physiologically relevant conditions (acidic and neutral pH, presence of albumin). The high drug loading level and sustained release is attributed to stabilizing &#960;-&#960; interactions between DOX and the core-forming block of the micelles.

The key steps of living anionic polymerization of phenyl glycidyl ether (PheGE) on methoxy-polyethylene glycol (mPEG-b-PPheGE) are described. The resulting block copolymer micelles (BCMs) were loaded with doxorubicin 14% (wt%) and sustained release of drug over 4 days under physiologically relevant conditions was obtained.

Aniônico polimerização de um copolímero anfifílicas para Preparação de copolímero em bloco As micelas estabilizada por interacções de empilhamento π-¸

In this study, an amphiphilic copolymer that includes a core-forming block with phenyl groups was synthesized by living anionic polymerization of phenyl ...

Preparation and Reactivity of a Triphosphenium Bromide Salt: A Convenient and Stable Source of Phosphorus(I)

We present herein the optimized synthesis of a triphosphenium bromide salt. Apart from being a versatile metathesis reagent, this unusually stable low-valent-phosphorus-containing compound acts as a useful P+ transfer agent. Unlike traditional methods employed to access low-coordinate phosphorus species which usually require pyrophoric phosphorus-containing precursors (white phosphorus, Tris(trimethylsilyl)phosphine, etc.), or harsh reducing agents (alkali metals, potassium graphite, etc.), the current approach does not involve pyrophoric or explosive reagents and can be done on large scales (&#62;20 g) in excellent yields by undergraduates with basic air-free synthetic training. The bromide counter ion is readily exchanged with other anions such as tetraphenyl borate (described herein) using typical salt metathesis reagents to obtain materials with desired properties and reactivities. The versatility of this P+ transfer approach is exemplified by the reactions of these triphosphenium precursors with an N-heterocyclic carbene and an anionic bisphosphine, each of which readily displace the neutral bisphosphine to give an NHC-stabilized phosphorus(I) cation and a phosphorus(I) containing zwitterion, respectively.

Preparation and Reactivity of a Triphosphenium Bromide Salt: A Convenient and Stable Source of PhosphorusI

The synthesis of a triphosphenium bromide salt is described and its use as a P+ transfer agent is outlined by reactions with an N-heterocyclic carbene and an anionic bisphosphine, yielding an NHC-stabilized P(I) cation and a P(I) containing zwitterion, respectively.

Preparação e Reatividade de uma Triphosphenium Brometo Sal: Uma fonte adequada e estável de fósforo (I)

We present herein the optimized synthesis of a triphosphenium bromide salt. Apart from being a versatile metathesis reagent, this unusually stable ...

Preparation and Evaluation of 99mTc-labeled Tridentate Chelates for Pre-targeting Using Bioorthogonal Chemistry

Pre-targeting combined with bioorthogonal chemistry is emerging as an effective way to create new radiopharmaceuticals. Of the methods available, the inverse electron demand Diels-Alder (IEDDA) cycloaddition between a radiolabeled tetrazines and trans-cyclooctene (TCO) linked to a biomolecule has proven to be a highly effective bioorthogonal approach to imaging specific biological targets. Despite the fact that technetium-99m remains the most widely used isotope in diagnostic nuclear medicine, there is a scarcity of methods for preparing 99mTc-labeled tetrazines. Herein we report the preparation of a family of tridentate-chelate-tetrazine derivatives and their Tc(I) complexes. These hitherto unknown compounds were radiolabeled with 99mTc using a microwave-assisted method in 31% to 83% radiochemical yield. The products are stable in saline and PBS and react rapidly with TCO derivatives in vitro. Their in vivo pre-targeting abilities were demonstrated using a TCO-bisphosphonate (TCO-BP) derivative that localizes to regions of active bone metabolism or injury. In murine studies, the 99mTc-tetrazines showed high activity concentrations in knees and shoulder joints, which was not observed when experiments were performed in the absence of TCO-BP. The overall uptake in non-target organs and pharmacokinetics varied greatly depending on the nature of the linker and polarity of the chelate.

Preparation and Evaluation of 99mTc-labeled Tridentate Chelates for Pre-targeting Using Bioorthogonal Chemistry

Here, we describe a protocol for radiolabeling and in vivo testing of tridentate 99mTc(I) chelate-tetrazine derivatives for pre-targeting and bioorthogonal chemistry.

Preparação e Avaliação de<sup&gt; 99m</sup&gt; Tc-rotulados tridentadas Quelatos de Pré-alvo Usando Bioorthogonal Química

Pre-targeting combined with bioorthogonal chemistry is emerging as an effective way to create new radiopharmaceuticals. Of the methods available, the ...

Accessing Valuable Ligand Supports for Transition Metals: A Modified, Intermediate Scale Preparation of 1,2,3,4,5-Pentamethylcyclopentadiene

A reliable, intermediate scale preparation of 1,2,3,4,5-pentamethylcyclopentadiene (Cp*H) is presented, based on modifications of existing protocols that derive from initial 2-bromo-2-butene lithiation followed by acid mediated dienol cyclization. The revised synthesis and purification of the ligand avoids the use of mechanical stirring while still permitting access to significant quantities (39 g) of Cp*H in good yield (58%). The procedure offers other additional benefits, including a more controlled quench of excess lithium during the production of the intermediate heptadienols and a simplified isolation of Cp*H of sufficient purity for metallation with transition metals. The ligand was subsequently used to synthesize [Cp*MCl2]2 complexes of both iridium and ruthenium to demonstrate the utility of the Cp*H prepared and purified by our method. The procedure outlined herein affords substantial quantities of a ubiquitous ancillary ligand support used in organometallic chemistry while minimizing the need for specialized laboratory equipment, thus providing a simpler and more accessible entry point into the chemistry of 1,2,3,4,5-pentamethylcyclopentadiene.

Reliable, intermediate scale preparation of 1,2,3,4,5-pentamethylcyclopentadiene (Cp*H) is presented. The revised protocol for the synthesis and purification of the ligand minimizes the need for specialized laboratory equipment while simplifying reaction workups and product purification. Use of Cp*H in the synthesis of [Cp*MCl2]2 complexes (M = Ru, Ir) is also described.

Acesso a Suportes de Ligantes Valiosos para Metais de Transição: Preparação Modificada em Escala Intermediária de 1

A reliable, intermediate scale preparation of 1,2,3,4,5-pentamethylcyclopentadiene (Cp*H) is presented, based on modifications of existing protocols that ...