Reconhecemos fundos start-up generosos da Universidade Estadual de Nova York em Stony Brook, em apoio deste trabalho. Agradecemos também TOSOH F-Tech, Inc. para fornecer-nos TMSCF 3 reagente para a síntese de Togni reagente II.

1. Precursor Preparação: Síntese do 4- (N -hydroxyacetamido) benzoato de metilo (1a) <ol><li> Redução de 4-nitrobenzoato de metilo. <ol><li> Adicionar 5,00 g de 4-nitrobenzoato de metilo (27,6 mmol, 1,00 equiv), 159 mg de ródio a 5% sobre carvão (Rh / C, Rh 0,300 mol%), e uma barra de agitação magnética, a uma seco em forno de 250 mL de dois pescoço balão de fundo redondo (seca a 150 ° C durante 18 h). NOTA: Os reagentes podem ser pesadas sob atmosfera ambiente. No entanto, a reacção tem de ser levada a cabo sob atmosfera de azoto. </li><li> Conectar um gargalo do balão a um azoto / distribuidor de vácuo e a tampa da outra pescoço com um septo. Executar três ciclos de vácuo-de recarga (por exemplo, bombear o ar para fora do frasco e substituindo o vácuo resultante com azoto gasoso) para substituir o ar no balão com azoto gasoso. </li><li> Adicionar 138 ml de tetra-hidrofurano anidro (THF, 0,200 M) ao balão de reacção utilizando seringa estanque ao ar. Esfrie e agitar as mixt reaçãoure, a 0 ° C durante 15 min. </li><li> Adicionar 1,47 ml de mono-hidrato de hidrazina (1,52 g, 30,4 mmol, 1,20 equiv) gota a gota à mistura de reacção a 0 ° C usando uma seringa estanque ao ar. Monitorizar a reacção utilizando uma cromatografia em camada fina (TLC). Use hexanos: acetato de etilo (EtOAc) (4: 1 v / v, Rf = 0,23) como um eluente, para desenvolver a TLC. </li><li> Quando metil-4-nitrobenzoato de metilo é completamente consumida, filtrar a mistura reaccional através de uma almofada curta de terra de diatomáceas (por exemplo, Celite, 5 g) em 60 ml frit funil de Buchner utilizando filtração sob vácuo. Lavar o filtro com EtOAc (20 ml x 3 vezes). Concentra-se o filtrado in vácuo utilizando um evaporador rotativo para se obter o benzoato de metilo em bruto 4- (N -hydroxyamino), que é utilizado directamente sem purificação adicional. </li></ol></li><li> Protecção de acetilo de metil 4- (N -hydroxyamino) benzoato <ol><li> Adicionar 2,55 g de bicarbonato de sódio (NaHCO3, 30,4 mmol, 1,20 equiv), todo o petróleo bruto4- (N -hydroxyamino) benzoato de metilo obtido a partir do passo anterior, e uma barra de agitação, num balão de 500 ml de fundo redondo de duas tubuladuras seco no forno. </li><li> Uma tampa de gargalo com um septo e ligar outro pescoço de um tubo de distribuição de azoto / vácuo. Executar três ciclos de vácuo-recarga para substituir o ar no balão com azoto gasoso. </li><li> Adicionar 138 ml de éter dietílico anidro (Et2O, 0,200 M) ao balão reaccional usando uma seringa estanque ao ar. Fresco e agita-se a mistura de reacção a 0 ° C durante 15 min. </li><li> Prepara-se uma solução de cloreto de acetilo (2,17 ml, 2,39 g, 30,4 mmol, 1,20 equiv) em Et 2 O anidro (138 mL, 0,220 M). Adicionar a solução à mistura de reacção a 0 ° C, utilizando uma bomba de seringa a uma taxa de 10,0 ml / hr. </li><li> No final da adição, filtrar a mistura reaccional através de uma almofada curta de terra de diatomáceas (por exemplo, Celite, 5 g) em 60 ml frit funil de Buchner utilizando filtração sob vácuo. Lavar o filtro com EtOAc (20 ml x 3 vezes). Concentra-se afiltrado in vácuo utilizando um evaporador rotativo. </li><li> Purifica-se o produto em bruto com cromatografia flash em coluna 35 eluindo com hexanos: EtOAc (4: 1 a 1: 1 (v / v)), (Rf = 0,13, hexanos: EtOAc (4: 1 (v / v)) para se obter 5,31 g de metil 4- (N -hydroxyacetamido) benzoato de metilo como um sólido (25,4 mmol, rendimento de 92%) amarelo claro. </li></ol></li></ol> 2. Síntese do 4- (N - (trifluorometoxi) acetamido) benzoato de metilo (2a) <ol><li> Adicionar 2,00 g de 4- (N -hydroxyacetamido) benzoato de metilo (1a) (9,56 mmol, 1,00 equiv), 311 mg de Cs 2 CO 3 (0,956 mmol, 10,0% em mol), 3,63 g de reagente Togni II (11,5 mmol, 1,20 equiv), e uma barra de agitação magnética, num balão de 250 ml de fundo redondo, seco no forno no interior de uma caixa de luvas (atmosfera de azoto). NOTA: Este reacção também pode ser realizada utilizando técnicas de Schlenk fora da caixa de luvas. Cuidado: Pure reagente Togni II é impacto e atrito sensível, chama abertas, faíscas e / ou moagem deve ser evitado. Ferramentas macias e polidos devem ser usadas para manipulações. Além disso, a mistura reaccional deve ser agitada por trás de uma protecção de segurança 36. </li><li> Adicionar 95,6 ml de clorofórmio seco e desgaseificado (CHCl 3, 0,100 M) ao balão de reacção. </li><li> Tapar o frasco com septo e agita-se a mistura de reacção a 23 ° C sob atmosfera de N2, dentro ou fora da caixa de luvas durante 16 horas. </li><li> Filtra-se a mistura de reacção através de um funil de filtro para remover qualquer resíduo sólido. Concentra-se o filtrado in vácuo utilizando um evaporador rotativo. </li><li> Purifica-se o produto impuro por cromatografia em coluna flash, eluindo com hexanos: diclorometano (CH 2 Cl 2) (7: 3 a 0: 1 (v / v)), (Rf = 0,44 (CH 2 Cl 2) para dar 2,51 g de 4- (N - (trifluorometoxi) acetamido) benzoato de metilo (9,05 mmol, 95% de rendimento). NOTA: Togni reagente II é acordo preparadoção aos procedimentos da literatura 37 e armazenadas no congelador a -35 luvas ° C para manter a sua qualidade durante um longo período de tempo. Esta reação é oxigênio sensível. Apesar de todos os reagentes podem ser pesados ​​sob atmosfera ambiente, à TA, a remoção de todo o oxigénio do balão de reacção é crítica. Seco e desgaseificado CHCl3 é preparado por destilação do que a partir de CaH2 sob atmosfera de azoto, seguido de realizar um de três ciclos de congelamento do processo de bombagem-descongelamento. </li></ol> 3. Síntese de 4-acetamido-3- (trifluorometoxi) benzoato de metilo através OCF3 -migration (3a) <ol><li> Adicionar 2,51 g de metil-4- (N - (trifluorometoxi) acetamido) benzoato de metilo (9,05 mmol, 1,0 equiv), uma barra de agitação magnética, e 9,05 ml de meno 2 (1,00 M) em um vaso de pressão de 50 ml. Tapar o recipiente com uma tampa de rosca. </li><li> Agita-se a mistura de reacção a 120 ° C, por trás da blindagem de segurança, durante 20 horas. Cuidado: nitrometano Impureé explosiva, de modo que a mistura reaccional deve ser agitada por trás da blindagem de segurança. </li><li> Arrefece-se a mistura de reacção até à temperatura ambiente. </li><li> Transferir a mistura reaccional para um balão de fundo redondo de 100 ml. </li><li> Concentra-se a mistura de reacção in vácuo utilizando um evaporador rotativo. </li><li> Purifica-se o produto impuro por cromatografia em coluna flash, eluindo com hexanos: EtOAc (9: 1 a 7: 3 (v / v)), (Rf = 0,51 hexanos: EtOAc (4: 1 (v / v)) para se obter 2,13 g de metil (trifluorometoxi) benzoato de metilo-3- acetamido-4 (7,69 mmol, 85%). NOTA: Esta reacção pode ser levada a cabo sob atmosfera ambiente. Atmosfera de azoto não é necessária. Um balão de fundo redondo equipado com um condensador de água pode ser usado como um aparelho de reacção alternativa. </li></ol> 4. Caracterização de Novos Produtos <ol><li> Caracterizar todos os novos compostos por 1 H, 13 C RMN e espectroscopia de espectroscopia de massa de alta resolução e utilizar espectroscopia de RMN de 19Fpara caracterizar compostos que contêm átomos de flúor 34. </li></ol>

<ol>
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Dev. 17, 318-319 (2013).</li><li>Matousek, V., Pietrasiak, E., Schwenk, R., Togni, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=One-pot+synthesis+of+hypervalent+iodine+reagents+for+electrophilic+trifluoromethylation.">One-pot synthesis of hypervalent iodine reagents for electrophilic trifluoromethylation.</a> J. Org. Chem. 78, 6763-6768 (2013).</li></ol>

The authors declare no competing financial interests.

Devido à falta de um procedimento geral e user-friendly para a síntese de arenes trifluoromethoxylated, muitos compostos aromáticos OCF 3 -containing são extremamente caros. 34 Nossa estratégia desloca uma tolerância grupo funcional ampla e oferece um fácil acesso a várias arenes trifluoromethoxylated. Estes compostos podem servir como valiosos blocos de construção para a descoberta e desenvolvimento de novos produtos farmacêuticos, agrotóxicos e materiais. ...

O trifluorometoxilo (OCF 3) grupo fez um impacto profundo na pesquisa vida e ciência dos materiais, desde a primeira síntese de éter trifluorometil em 1935. 2 Devido à sua combinação única de alta eletronegatividade (χ = 3,7) 3 e excelente lipofilicidade (Π x = 1,04), o grupo 4 trifluorometoxilo encontrou amplas aplicações na medicina, agricultura e indústria de materiais. 5-10 No entanto, a introdução fácil do grupo OCF 3 em moléculas orgânicas, especialmente compostos aromáticos, continua sendo um grande desafio na química sintética. Ao longo das últimas décadas, os esforços para enfrentar este desafio levou ao desenvolvimento de um punhado de transformações para a síntese de arenes trifluoromethoxylated 5-7,9-11 Estas incluem: (i) troca de cloro / flúor sobre precursores trichlorinated;. 1,12 -17 (ii) deoxyfluorination de fluoroformates; 18 </sup&gt; (iii) fluorodesulfurization oxidativo; 19-21 (iv) trifluoromethylation electrofílico de álcoois; 22-25 (v) trifluoromethoxylation nucleofílica; 26-30, (VI) transição trifluoromethoxylation mediada por metais de boratos e estananos de arilo; e 31 (vii ) trifluoromethoxylation radical. 32,33 No entanto, muitas dessas abordagens sofrem de um ou outro substrato pobre âmbito ou requer o uso de reagentes altamente tóxicos e / ou termicamente lábeis. Portanto, devido à falta de um método geral e de fácil utilização para sintetizar compostos -containing OCF3, o potencial do grupo OCF 3 não foi totalmente explorada em química. Como parte do nosso interesse em reacções trifluoromethoxylation, 34 descrevemos aqui um protocolo de dois passos (isto é, -trifluoromethylation O radical e induzida termicamente OCF 3 -migration) para a síntese de 4-acetamido-3- (trifluorometoxi) benzoato de (3a) a partir de 4- (N -hydroxyacetamido) benzoato de metilo (1a). A estratégia é fácil de operar e aplicável para a síntese de uma ampla gama de derivados de anilina orto -trifluoromethoxylated.

<table border="0" cellpadding="0" cellspacing="0" width="573">
	<tbody>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">5% Rhodium on carbon</td>
			<td style="width:71px;">Aspira Scientific</td>
			<td style="width:119px;">300835</td>
			<td style="width:167px;">5% wt% dry loading</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">hydrazine monohydrate</td>
			<td style="width:71px;">Sigma-Alderich</td>
			<td style="width:119px;">13696HMV</td>
			<td style="width:167px;">Reagent grade, 98%</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Acetyl chloride</td>
			<td style="width:71px;">Alfa Aesar</td>
			<td style="width:119px;">10176887</td>
			<td style="width:167px;">98%</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Sodium bicarbonate</td>
			<td style="width:71px;">Fisher Scientific</td>
			<td style="width:119px;">134826</td>
			<td style="width:167px;">Chemical pure</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Cesium carbonate</td>
			<td style="width:71px;">Alfa Aesar</td>
			<td style="width:119px;">12887</td>
			<td style="width:167px;">99.9%, metals basis</td>
		</tr>
		<tr height="148">
			<td height="148" style="height:148px;width:216px;">Togni Reagent II</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Prepared according to the literature procedure (ref 37). Caution: Pure Togni reagent II is impact and friction sensitive, treat it with great care (see ref. 36).</td>
		</tr>
		<tr height="64">
			<td height="64" style="height:64px;width:216px;">Tetrahydrofuran</td>
			<td style="width:71px;">BDH</td>
			<td style="width:119px;">BDH1149-4LG</td>
			<td style="width:167px;">Distilled from deep purple sodium benzophenone ketyl.</td>
		</tr>
		<tr height="64">
			<td height="64" style="height:64px;width:216px;">Diethyl Ether</td>
			<td style="width:71px;">Fisher Scientific</td>
			<td style="width:119px;">148221</td>
			<td style="width:167px;">Distilled from deep purple sodium benzophenone ketyl.</td>
		</tr>
		<tr height="47">
			<td height="47" style="height:47px;width:216px;">Chloroform</td>
			<td style="width:71px;">Fisher Scientific</td>
			<td style="width:119px;">141739</td>
			<td style="width:167px;">Dried over CaH2 and distilled</td>
		</tr>
		<tr height="47">
			<td height="47" style="height:47px;width:216px;">nitro methane</td>
			<td style="width:71px;">Alfa Aesar</td>
			<td style="width:119px;">J03z053</td>
			<td style="width:167px;">Dried over CaSO4 and distilled</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Silica gel</td>
			<td style="width:71px;">SILICYCLE</td>
			<td style="width:119px;">60514</td>
			<td style="width:167px;">40-63 &#181;m (230-400 mesh)</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">Cilite</td>
			<td style="width:71px;">EMD</td>
			<td style="width:119px;">2012040674</td>
			<td style="width:167px;">Not acid washed</td>
		</tr>
	</tbody>
</table>

protocol for the synthesis of ortho-trifluoromethoxylated aniline derivatives

Moléculas que carregam trifluorometoxilo grupo (OCF 3) muitas vezes apresentam propriedades farmacológicas e biológicas desejado. No entanto, síntese fácil de compostos aromáticos trifluoromethoxylated continua a ser um desafio formidável em síntese orgânica. As abordagens convencionais muitas vezes sofrem de âmbito substrato pobre, ou requerem o uso de altamente tóxico, alça de difícil, e / ou reagentes termicamente instáveis. Relata-se um protocolo de fácil utilização para a síntese de 4-acetamido-3- (trifluorometoxi) benzoato de metilo, utilizando 1-trifluorometil-1,2-benziodoxol-3 (1H) -ona (Togni reagente II). Tratar metil 4- (N -hydroxyacetamido) benzoato de metilo (1a) com Togni reagente II na presença de uma quantidade catalítica de carbonato de césio (Cs 2 CO 3) em clorofórmio a temperatura ambiente proporcionou 4- (N - (trifluorometoxi) acetamido) benzoato (2a). Este intermediário foi em seguida convertido para o produto final, metil 4-acetamido-3- (trifluoromethoxy) benzoato de (3a) em nitrometano, a 120 ° C. Este procedimento é geral e pode ser aplicado para a síntese de uma ampla gama de derivados de anilina orto -trifluoromethoxylated, que poderia servir como blocos de construção sintéticos úteis para a descoberta e desenvolvimento de novos fármacos, agroquímicos e materiais funcionais.

Dissolveu-se 4- (N -hydroxyacetamido) benzoato de metilo (1a) foi sintetizado em 92% de rendimento isolado através de um procedimento em duas etapas (ou seja, a redução de 4-nitrobenzoato de metilo com hidrazina, utilizando 5% de Rh / C como catalisador, para formar 4- ( N -hydroxyamino) benzoato de metilo, seguido de protecção acetilo da hidroxilamina resultante). O- Trifluoromethylation de 1a com Togni reagente ...

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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Protocolo para a Síntese de Derivados de Anilina Orto-trifluorometoxilados

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.

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

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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

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9.8K visualizações.  State University of New York at Stony Brook. 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.

Vídeo: Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

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 ...

Química

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order to streamline synthesis by saving steps, time and material compared to conventional methods that require the introduction and removal of activating or directing groups. Therefore, the functionalization of C-H bonds is also attractive for green chemistry. Under oxidative conditions, two C-H bonds or one C-H and one heteroatom-H bond can be transformed to C-C and C-heteroatom bonds, respectively. Often these oxidative coupling reactions require synthetic oxidants, expensive catalysts or high temperatures. Here, we describe a two-step procedure to functionalize indole derivatives, more specifically tetrahydrocarbazoles, by C-H amination using only elemental oxygen as oxidant. The reaction uses the principle of C-H functionalization via Intermediate PeroxideS (CHIPS). In the first step, a hydroperoxide is generated oxidatively using visible light, a photosensitizer and elemental oxygen. In the second step, the N-nucleophile, an aniline, is introduced by Br&#248;nsted-acid catalyzed activation of the hydroperoxide leaving group. The products of the first and second step often precipitate and can be conveniently filtered off. The synthesis of a biologically active compound is shown.

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS

A two-step procedure for the synthesis of pharmaceutically active indole-derivatives by C-H functionalization with anilines is described, using photo- and Br&#248;nsted acid catalysis.

Síntese de Antiviral tetrahidrocarbazole Derivativos por fotoquímica e catalisada por ácido CH funcionalização via Peróxidos intermediários (CHIPS)

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order ...

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important structural element found in many complex natural products and pharmaceuticals. Owing to the continual discovery of new guanidine-containing natural products and designed small molecules, rapid and efficient guanidinylation methods are of keen interest to synthetic and medicinal organic chemists. Because the nucleophilicity and basicity of guanidines can affect subsequent chemical transformations, traditional, indirect guanidinylation is typically pursued. Indirect methods commonly employ multiple protection steps involving a latent amine precursor, such as an azide, phthalimide, or carbamate. By circumventing these circuitous methods and employing a direct guanidinylation reaction early in the synthetic sequence, it was possible to forge the linear terminal guanidine containing backbone of clavatadine A to realize a short and streamlined synthesis of this potent factor XIa inhibitor. In practice, guanidine hydrochloride is elaborated with a carefully constructed protecting array that is optimized to survive the synthetic steps to come. In the preparation of clavatadine A, direct guanidinylation of a commercially available diamine eliminated two unnecessary steps from its synthesis. Coupled with the wide variety of known guanidine protecting groups, direct guanidinylation evinces a succinct and efficient practicality inherent to methods that find a home in a synthetic chemist&#39;s toolbox.

Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol.

Um direto, Early Stage Guanidinylation Protocolo para a Síntese de complexos contendo aminoguanidina Produtos Naturais

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important ...

HKUST-1 as a Heterogeneous Catalyst for the Synthesis of Vanillin

Vanillin (4-hydoxy-3-methoxybenzaldehyde) is the main component of the extract of vanilla bean. The natural vanilla scent is a mixture of approximately 200 different odorant compounds in addition to vanillin. The natural extraction of vanillin (from the orchid Vanilla planifolia, Vanilla tahitiensis and Vanilla pompon) represents only 1% of the worldwide production and since this process is expensive and very long, the rest of the production of vanillin is synthesized. Many biotechnological approaches can be used for the synthesis of vanillin from lignin, phenolic stilbenes, isoeugenol, eugenol, guaicol, etc., with the disadvantage of harming the environment since these processes use strong oxidizing agents and toxic solvents. Thus, eco-friendly alternatives on the production of vanillin are very desirable and thus, under current investigation. Porous coordination polymers (PCPs) are a new class of highly crystalline materials that recently have been used for catalysis. HKUST-1 (Cu3(BTC)2(H2O)3, BTC = 1,3,5-benzene-tricarboxylate) is a very well known PCP which has been extensively studied as a heterogeneous catalyst. Here, we report a synthetic strategy for the production of vanillin by the oxidation of trans-ferulic acid using HKUST-1 as a catalyst.

The conversion of trans-ferulic acid to vanillin was achieved by heterogeneous catalysis. HKUST-1 was employed in this synthesis and the essential step in the catalytic process was the generation of unsaturated metal sites. Thus, when the catalyst was activated under vacuum, full vanillin conversion (yield of 95%) was obtained.

HKUST-1 como um catalisador heterogéneo para a Síntese de vanilina

Vanillin (4-hydoxy-3-methoxybenzaldehyde) is the main component of the extract of vanilla bean. The natural vanilla scent is a mixture of approximately ...

A Protocol for the Production of Gliadin-cyanoacrylate Nanoparticles for Hydrophilic Coating

This article presents a protocol for the production of protein-based nanoparticles that changes the hydrophobic surface to hydrophilic by a simple spray coating. These nanoparticles are produced by the polymerization reaction of alkyl cyanoacrylate on the surface of cereal protein (gliadin) molecules. Alkyl cyanoacrylate is a monomer that instantly polymerizes at RT when it is applied to the surface of materials. Its polymerization reaction is initiated by the trace amounts of weakly basic or nucleophilic species on the surface, including moisture. Once polymerized, the polymerized alkyl cyanoacrylates show a strong affinity with the object materials because nitrile groups are in the backbone of poly (alkyl cyanoacrylate). Proteins also work as initiator for this polymerization because they contain amine groups that can initiate the polymerization of cyanoacrylate. If aggregated protein is used as an initiator, protein aggregate is surrounded by the hydrophobic poly(alkyl cyanoacrylate) chains after the polymerization reaction of alkyl cyanoacrylate. By controlling the experimental condition, particles in the nanometer range are produced. The produced nanoparticles readily adsorb to the surface of most materials including glass, metals, plastics, wood, leather, and fabrics. When the surface of a material is sprayed with the produced nanoparticle suspension and rinsed with water, the micellar structure of nanoparticle changes its conformation, and the hydrophilic proteins are exposed to the air. As a result, the nanoparticle-coated surface changes to hydrophilic.

This article presents a protocol for the production of protein-based nanoparticles that changes the hydrophobic surface to hydrophilic. The produced nanoparticle is an assembly of gliadin-cyanoacrylate diblock copolymers. Spray coating with the produced nanoparticle changes the surface of target material to a hydrophilic surface.

Um protocolo para a produção de nanopartículas Gliadina-cianoacrilato para hidrofílico Coating

This article presents a protocol for the production of protein-based nanoparticles that changes the hydrophobic surface to hydrophilic by a simple spray ...

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the development of antibody drug conjugates (ADCs) and nanomedicine, fluorescent microscopy and systems chemistry. For many of these applications, specificity of the bioconjugation method used is of prime concern. The Michael addition of maleimides with cysteine(s) on the target proteins is highly selective and proceeds rapidly under mild conditions, making it one of the most popular methods for protein bioconjugation.
We demonstrate here the modification of the only surface-accessible cysteine residue on yeast cytochrome c with a ruthenium(II) bisterpyridine maleimide. The protein bioconjugation is verified by gel electrophoresis and purified by aqueous-based fast protein liquid chromatography in 27% yield of isolated protein material. Structural characterization with MALDI-TOF MS and UV-Vis is then used to verify that the bioconjugation is successful. The protocol shown here is easily applicable to other cysteine - maleimide coupling of proteins to other proteins, dyes, drugs or polymers.

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

This protocol details the important steps required for the bioconjugation of a cysteine containing protein to a maleimide, including reagent purification, reaction conditions, bioconjugate purification and bioconjugate characterization.

Síntese de Bioconjugados de proteínas<em&gt; via</em&gt; Química cisteína-maleimida

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the ...

Facile Synthesis of Worm-like Micelles by Visible Light Mediated Dispersion Polymerization Using Photoredox Catalyst

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins with the synthesis of a hydrophilic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) homopolymer using reversible addition-fragmentation chain-transfer (RAFT) polymerization. Under mild visible light irradiation (&#955; = 460 nm, 0.7 mW/cm2), this macro-chain transfer agent (macro-CTA) in the presence of a ruthenium based photoredox catalyst, Ru(bpy)3Cl2 can be chain extended with a second monomer to form a well-defined block copolymer in a process known as Photoinduced Electron Transfer RAFT (PET-RAFT). When PET-RAFT is used to chain extend POEGMA with benzyl methacrylate (BzMA) in ethanol (EtOH), polymeric nanoparticles with different morphologies are formed in situ according to a polymerization-induced self-assembly (PISA) mechanism. Self-assembly into nanoparticles presenting POEGMA chains at the corona and poly(benzyl methacrylate) (PBzMA) chains in the core occurs in situ due to the growing insolubility of the PBzMA block in ethanol. Interestingly, the formation of highly pure worm-like micelles can be readily monitored by observing the onset of a highly viscous gel in situ due to nanoparticle entanglements occurring during the polymerization. This process thereby allows for a more reproducible synthesis of worm-like micelles simply by monitoring the solution viscosity during the course of the polymerization. In addition, the light stimulus can be intermittently applied in an ON/OFF manner demonstrating temporal control over the nanoparticle morphology.

This article describes a process for producing polymeric self-assembled nanoparticles using visible light mediated dispersion polymerization. Using low energy visible light to control the polymerization allows for the reproducible formation of self-assembled worm-like micelles at high solids content.

Síntese Facile de micelas Worm-like por luz visível Mediated Dispersão Polimerização Usando Photoredox Catalisador

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins ...

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

Solid-phase synthesis has been used to obtain canonical and modified polymers of nucleic acids, specifically of DNA or RNA, which has made it a popular methodology for applications in various fields and for different research purposes. The procedure described herein focuses on the synthesis, purification, and characterization of dodecamers of RNA 5&#39;-[CUA CGG AAU CAU]-3&#39; containing zero, one, or two modifications located at the C2&#39;-O-position. The probes are based on 2-thiophenylmethyl groups, incorporated into RNA nucleotides via standard organic synthesis and introduced into the corresponding oligonucleotides via their respective phosphoramidites. This report makes use of phosphoramidite chemistry via the four canonical nucleobases (Uridine (U), Cytosine (C), Guanosine (G), Adenosine (A)), as well as 2-thiophenylmethyl functionalized nucleotides modified at the 2&#39;-O-position; however, the methodology is amenable for a large variety of modifications that have been developed over the years. The oligonucleotides were synthesized on a controlled-pore glass (CPG) support followed by cleavage from the resin and deprotection under standard conditions, i.e., a mixture of ammonia and methylamine (AMA) followed by hydrogen fluoride/triethylamine/N-methylpyrrolidinone. The corresponding oligonucleotides were purified via polyacrylamide electrophoresis (20% denaturing) followed by elution, desalting, and isolation via reversed-phase chromatography (Sep-pak, C18-column). Quantification and structural parameters were assessed via ultraviolet-visible (UV-vis) and circular dichroism (CD) photometric analysis, respectively. This report aims to serve as a resource and guide for beginner and expert researchers interested in embarking in this field. It is expected to serve as a work-in-progress as new technologies and methodologies are developed. The description of the methodologies and techniques within this document correspond to a DNA/RNA synthesizer (refurbished and purchased in 2013) that uses phosphoramidite chemistry.

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

This article provides a detailed procedure on the solid-phase synthesis, purification, and characterization of dodecamers of RNA modified at the C2&#39;-O-position. UV-vis and circular dichroism photometric analyses are used to quantify and characterize structural aspects, i.e., single-strands or double-strands.

Protocolo para síntese de fase sólida de oligómeros de ARN contendo um 2&#39;-<em&gt; O</em&gt; -tiofenilmetilo Modificação e Caracterização através do Dicroísmo Circular

Solid-phase synthesis has been used to obtain canonical and modified polymers of nucleic acids, specifically of DNA or RNA, which has made it a popular ...

Synthesis and Mass Spectrometry Analysis of Oligo-peptoids

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have been thought of as a type of molecular information storage. Mass spectrometry analysis has been considered the method of choice for sequencing peptoids. Peptoids can be synthesized via solid phase chemistry using a repeating two-step reaction cycle. Here we present a method to manually synthesize oligo-peptoids and to analyze the sequence of the peptoids using tandem mass spectrometry (MS/MS) techniques. The sample peptoid is a nonamer consisting of alternating N-(2-methyloxyethyl)glycine (Nme) and N-(2-phenylethyl)glycine (Npe), as well as an N-(2-aminoethyl)glycine (Nae) at the N-terminus. The sequence formula of the peptoid is Ac-Nae-(Npe-Nme)4-NH2, where Ac is the acetyl group. The synthesis takes place in a commercially available solid-phase reaction vessel. The rink amide resin is used as the solid support to yield the peptoid with an amide group at the C-terminus. The resulting peptoid product is subjected to sequence analysis using a triple-quadrupole mass spectrometer coupled to an electrospray ionization source. The MS/MS measurement produces a spectrum of fragment ions resulting from the dissociation of charged peptoid. The fragment ions are sorted out based on the values of their mass-to-charge ratio (m/z). The m/z values of the fragment ions are compared against the nominal masses of theoretically predicted fragment ions, according to the scheme of peptoid fragmentation. The analysis generates a fragmentation pattern of the charged peptoid. The fragmentation pattern is correlated to the monomer sequence of the neutral peptoid. In this regard, MS analysis reads out the sequence information of the peptoids.

A protocol is described for the manual synthesis of oligo-peptoids followed by sequence analysis by mass spectrometry.

Síntese e análise de espectrometria de massa de Oligo-peptoids

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have ...

The MPLEx Protocol for Multi-omic Analyses of Soil Samples

Mass spectrometry (MS)-based integrated metaproteomic, metabolomic, and lipidomic (multi-omic) studies are transforming our ability to understand and characterize microbial communities in environmental and biological systems. These measurements are even enabling enhanced analyses of complex soil microbial communities, which are the most complex microbial systems known to date. Multi-omic analyses, however, do have sample preparation challenges, since separate extractions are typically needed for each omic study, thereby greatly amplifying the preparation time and amount of sample required. To address this limitation, a 3-in-1 method for the simultaneous extraction of metabolites, proteins, and lipids (MPLEx) from the same soil sample was created by adapting a solvent-based approach. This MPLEx protocol has proven to be both simple and robust for many sample types, even when utilized for limited quantities of complex soil samples. The MPLEx method also greatly enabled the rapid multi-omic measurements needed to gain a better understanding of the members of each microbial community, while evaluating the changes taking place upon biological and environmental perturbations.

A protocol is presented for simultaneously extracting metabolites, proteins, and lipids from a single soil sample, allowing reduced sample preparation times and enabling multi-omic mass spectrometry analyses of samples with limited quantities.

O protocolo de mplexas para Multi-omic análises de amostras de solo

Mass spectrometry (MS)-based integrated metaproteomic, metabolomic, and lipidomic (multi-omic) studies are transforming our ability to understand and ...