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. Funzionalizzazione di 2,15-Dimethylhexahelicene <ol><li> Dibromination di 2,15-dimethylhexahelicene <ol><li> Pesare 0,356 g (1,0 mmol) di 2,15-dimethylhexahelicene, 0,374 g (2,1 mmoli) di -bromosuccinimide appena ricristallizzato N (NBS) e 24 mg (0,07 mmoli) di perossido di benzoile (BPO) (70% in peso con il 30% di acqua come stabilizzatore). Mettere tutti i solidi in un pallone da 100 ml Schlenk con ancoretta magnetica. Mettere in atmosfera di azoto da tre cicli di evacuazione gas seguita da riempimento con gas inerte nella linea Schlenk. </li><li> Aggiungere 21 ml di tetracloruro di carbonio (CCL 4). Degassare la soluzione dallo stesso evacuazione / processo di riempimento (fase 1.1.1) sotto vigorosa agitazione e con attenzione per evitare perdita massiccia di solvente. </li><li> Calore a riflusso (77 ° C) la miscela con un bagno di olio per 4 ore. Controllare la reazione mediante risonanza magnetica 1 H-nucleare (NMR). Doppietti tra 3,7 ppm e 4,0 ppm shoULD appaiono. Essi indicano la presenza di -CH diastereotopici 2 - gruppi (Figura 1). </li><li> Una volta terminato, raffreddare la miscela a temperatura ambiente e rimuovere il solvente sotto vuoto. Impostare una trappola piena di azoto liquido per evitare la contaminazione della pompa. </li><li> Riprendere il grezzo in 30 ml di diclorometano (DCM), trasferire in un pallone a fondo rotondo e mescolare con 4 g di gel di silice (tipicamente aggiungere 5 volte il peso grezzo). Concentrare la miscela in un evaporatore rotante. </li><li> Nel frattempo, riempire una colonna (lunghezza circa 20 cm ed uno spessore di 4,5 cm) con SiO 2 gel miscelato in precedenza con esano / acetato di etile (95: 5) come fase mobile. Aggiungere la miscela al superiore della colonna e quindi aggiungere uno strato di sabbia (2 cm). </li><li> Versare con cautela nella nuova fase mobile e eseguire la cromatografia attraverso la raccolta di frazioni in provette (in genere 20 ml per provetta e 4 ml vicino l&#39;eluizione del prodotto atteso). Controllare frazioni di cromatografia su strato sottile(TLC) con la stessa fase mobile (esano / acetato di etile 95: 5) e l&#39;immagine sotto luce UV. Il prodotto atteso (4b) dovrebbe eluire con un fattore di ritenzione (Rf) di 0,35 come olio giallo dopo aver combinato tutti frazioni voluto e rimuovendo il solvente in evaporatore rotante. 334 mg dovrebbero essere ottenuti (resa 65%). NOTA: Tutte le tecniche Schlenk, l&#39;uso di un bagno d&#39;olio per riscaldamento e di colonna impostazioni cromatografiche saranno ampiamente utilizzati nella maggior parte dei protocolli, così da ora in poi, non verrà descritta in dettaglio e solo poche osservazioni, quando necessario, essere dato. </li></ol></li></ol><img alt="Figura 1" src="/files/ftp_upload/53954/53954fig1.jpg" /> . Figura 1 1 H-NMR (500 MHz, CDCl 3) di 2,15 -dimethylhelicene (in alto) e una aliquota scattata dopo 2 ore nuovi segnali, corrispondenti a -CH 2 -.., sono raffigurati in un cerchio rosso (in basso) <a href="https://www.jove.com/files/ftp_upload/53954/53954fig1large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> <ol start="2"><li> Sintesi di 2,15-bis (azidomethyl) hexahelicene <ol><li> Pesare 0,103 g (0,2 mmol) di 2,15-bis (bromometil) hexahelicene e 0,390 g (6 mmoli) di sodio azide. Posizionare entrambi i solidi in un matraccio da 50 ml dotato di Schlenk barra magnetica e posto sotto atmosfera di azoto. </li><li> Mescolare 8,6 ml di tetraidrofurano (THF) con 5,2 ml di acqua (H 2 O) e versare la miscela di solventi nel pallone Schlenk. Degassare la soluzione. </li><li> Calore a riflusso (65 ° C) per 3 ore. Controllare la reazione 1 H-NMR. -CH 2 - segnali dovrebbero trasferire al 3,75 ppm (Figura 2). </li><li> In seguito, cool giù la miscela a temperatura ambiente e rimuovere THF sotto vuoto. Diluire con 50 ml di H 2 O. </li><li> Trasferire la miscela in un imbuto separatore ed estrarre tre volte con 40 ml di DCM. Unire tutte le fasi organiche e lavare con puro H 2 O (50 ml). </li><li> Purificare il grezzo mediante cromatografia su colonna su gel di silice usando esano / acetato di etile (85:15) come fase mobile per dare un olio giallo a Rf = 0,38 corrispondente a 2,15-bis (azomethyl) hexahelicene (5b). 70 mg dovrebbe essere ottenuto (resa 80%). </li></ol></li></ol><img alt="figura 2" src="/files/ftp_upload/53954/53954fig2.jpg" /> Figura 2: 1 H-NMR (500 MHz, CDCl 3) 4 b (in alto) e un&#39;aliquota presa dopo 3 ore(in basso). Notare i cambiamenti nella regione alifatici. <a href="https://www.jove.com/files/ftp_upload/53954/53954fig2large.jpg" target="_blank">Cliccate qui per vedere una versione più grande di questa figura.</a> 2. Funzionalizzazione di corannulene <ol><li> Monobromination di corannulene <ol><li> Pesare 0,125 g (0,5 mmoli) di corannulene, 89 mg (0,5 mmol) di appena ricristallizzato NBS e 17 mg di oro (III) cloruro idrato. </li><li> Mettere tutti i composti in un flaconcino da 10 ml appositamente progettati per le reazioni a microonde dotati di una barra magnetica e poi messo in atmosfera di azoto, con l&#39;aiuto di un pallone a 2 colli. </li><li> Aggiungere 7 ml di 1,2-dicloroetano (DCE) e degassare la soluzione. </li><li> Sonicare la miscela per 2 minuti per disperdere particelle di sale d&#39;oro. </li><li> Il calore all&#39;interno del reattore a microonde a 100 ° C per 2 ore. </li><li> Al termine, trasferire il grezzo in un pallone a fondo rotondo e rimuovere il solvente dal rotarevaporazione y. </li><li> Purificare il grezzo mediante cromatografia su colonna su SiO 2 gel usando esano come fase mobile. NOTA: Bromocorannulene (4a) è ottenuto come solido giallo a Rf = 0.38. 99 mg dovrebbe essere ottenuto (resa 60%). Corannulene non reagito (3a) può essere recuperato e conservato per ulteriori usi. Sembra a Rf = 0,29. </li></ol></li><li> Sonogashira Accoppiamento di Bomocorannulene e Ethynyltrimethylsilane <ol><li> Pesare 49 mg (0,15 mmol) di bromocorannulene, 11 mg (0,015 mmol) di [PdCl 2 (dppf)] 49,50 (dppf essere 1,1-&#39;bis (diphenylphsphino) ferrocene, 3 mg (0,015 mmol) di cui. 51 </li><li> Mettere tutti i solidi in un matraccio da 50 ml Schlenk assieme con una barra magnetica e posto sotto atmosfera di azoto. </li><li> Aggiungere 5,0 ml di trietilammina (Net 3) e degassare la miscela. </li><li> Infine, aggiungere 104 ml (0,75 mmol) di ethynyltrimethylsilane. </li><li> Sonicare la miscela per 2 minuti perdisperdere le particelle di sale di metallo. </li><li> Riscaldare a 85 ° C per 24 ore con sonicazione periodica per evitare la deposizione di sali metallici. NOTA: Il colore della miscela acceso al nero presto, indicando la presenza di palladio (0). </li><li> Raffreddare a temperatura ambiente ed evaporare NEt 3 sotto vuoto. </li><li> Riprendere in 20 ml di DCM e purificare mediante cromatografia in colonna su gel di silice eluendo con esano per dare un solido giallo a Rf = 0,28 corrispondente a 5a. 41 mg dovrebbe essere ottenuto (resa 78%). NOTA: Se il grezzo viene filtrato attraverso un tampone di Celite in DCM, un campione puro ragionevole potrebbe essere ottenuto, comunque derivati ​​fosfinici non vengono rimossi completamente. </li></ol></li><li> Preparazione di Ethynylcorannulene da TMS deprotezione <ol><li> Pesare 35 mg (0,10 mmoli) di 5a e 7,3 mg (0,125 mmoli) di fluoruro di potassio anidro. </li><li> Mettere tutti i solidi in un matraccio da 50 ml Schlenk attrezzato con una barra di magneticad Mettere in atmosfera di azoto. </li><li> Mescolare 4 ml di THF e 4 ml di metanolo (MeOH) e versare il composto nel pallone Schlenk. Degas a fondo. </li><li> Lasciar reagire a temperatura ambiente, Mantenere il matraccio lontano dalla luce coprendolo con una pellicola opaca. Controllare la reazione 1 H-NMR, cercando in 3,48 ppm. Un segnale corrispondente -CCH deve emergere (Figura 3). NOTA: Anche se questo composto ha una alkyne terminale che è reattivo e si decompone facilmente, abbiamo riscontrato problemi durante il lavoro fino descritto di seguito. È stata effettuata sotto la luce naturale. </li><li> Una volta terminato, rimuovere THF sotto vuoto e diluire con 10 ml di acqua, trasferire tutto in un imbuto separatore. </li><li> Estrarre con DCM (3 x 15 ml), combinare tutte le fasi organiche in un pallone a fondo rotondo e concentrato in un evaporatore rotante a temperatura ambiente per ottenere finalmente un solido giallo corrispondente 6a. 27 mg dovrebbe essere ottenuto (resa quantitativa). </li></ol></li></ol><img alt="Figura 3" src="/files/ftp_upload/53954/53954fig3.jpg" /> Figura 3:.. 1 H-NMR (500 MHz, CDCl 3) di 5 A (in alto) e 6 bis (basso) singoletto -CCH è raffigurato in un cerchio rosso <a href="https://www.jove.com/files/ftp_upload/53954/53954fig3large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> 3. Montaggio finale da Click Chimica <ol><li> Pesare 15,3 mg (0,035 mmoli) di 5b, 20,0 mg (0,073 mmoli) di 6a, 1,4 mg (0,007 mmoli) di sale sodico dell&#39;acido ascorbico, 1,7 mg (0,007 mmoli) di CuSO 4 · 5H 2 O. </li><li> Mettere tutti i solidi in un matraccio da 50 ml dotato di Schlenk ambar agnetica e messo in atmosfera di azoto. </li><li> Mescolare 3 ml di H 2 O e 12 ml di THF e versare il composto nel pallone Schlenk. Degassare bene la soluzione. </li><li> Riscaldare a 65 ° C per 3 giorni con un condensatore collegato alla sommità del pallone e controllare periodicamente la reazione per controllare la temperatura, agitazione e volume di solvente. Controllare la reazione 1 H-NMR. Il segnale a 3.48 ppm dovrebbe scomparire e essere spostato a 7.27 ppm indicante il consumo di etinil corannulene e l&#39;esistenza del gruppo triazolo (Figura 4). </li><li> Al termine, rimuovere THF sotto vuoto e diluire con 20 ml di acqua, trasferendo la miscela in un imbuto separatore. </li><li> Estrarre con DCM (3 x 20 ml), combinare tutte le fasi organiche in un pallone a fondo rotondo e concentrato in un evaporatore rotante. </li><li> Purificare il grezzo mediante cromatografia su colonna su gel di SiO 2 eluendo con esano / acetato di etile (1: 1) per dare un solido giallo pallido a Rf = 0,59corrispondente al 7. 27 mg dovrebbe essere ottenuto (resa 75%). </li></ol><img alt="Figura 4" src="/files/ftp_upload/53954/53954fig4.jpg" /> Figura 4: 1 H-NMR (500 MHz, CDCl 3) di 5 B (in alto), 6 bis (al centro) e una aliquota prelevata dopo 2 giorni (in basso) Si noti la scomparsa del segnale di -CCH nel greggio.. <a href="https://www.jove.com/files/ftp_upload/53954/53954fig4large.jpg" target="_blank">Si prega clicca qui per vedere una versione più grande di questa figura.</a>

The authors have nothing to disclose.

Composto finale 7 è stato preparato dopo 6 passi da precursori poliaromatici non planari 3 A e 3 B da moderata a molto buone rese in ogni reazione. La limitazione principale osservata in questo percorso è stata la bromurazione di composti poliaromatici non planari. Tuttavia, nel caso del composto 4 bis, una quantità importante di corannulene libero può essere recuperato per altri usi. La sintesi di ...

Grazie alla loro particolare geometria, corannulene e helicenes sono molecole che possono adottare una struttura lontano dalla planarità e dar luogo a proprietà interessanti. 1-15 Negli ultimi anni, la ricerca dei recettori molecolari per nanotubi di carbonio e fullereni è una zona molto attiva 16-19 a causa, principalmente, alle loro potenziali applicazioni come materiali per le celle organiche solari, transistor, sensori e altri dispositivi. 20-28 l&#39;ottima complementarietà di forma tra il corannulene e un fullerene hanno attirato l&#39;attenzione di numerosi ricercatori, con l&#39;obiettivo di progettare recettori molecolari in grado di stabilire un&#39;associazione supramolecolare da parte delle forze di dispersione. 29-39 La chimica dei composti poliaromatici non planari suddetti è simile a quella descritta per le molecole totalmente planari, ma a volte è difficile trovare condizioni adatte per raggiungere le selettività e le rese desiderati. 40 </sup&gt; In questo lavoro presentiamo la sintesi di una molecola (7) avente tre unità poliaromatici in pochi passi con buone rese applicando tecniche semplici e tipiche presenti in ogni laboratorio di ricerca. La molecola è di grande importanza perché può adottare una conformazione tenaglia per stabilire buone interazioni con C 60 37 in soluzione; e può aprire una linea di ricerca come potenziale recettore per maggiori fullereni chirali grazie al linker eliceni, che è una molecola chirale a causa dell&#39;esistenza di un asse stereogenico. 41-45 Tuttavia, solo eliceni racemico saranno utilizzati in questo lavoro. A questo punto, l&#39;unica limitazione per sintetizzare questi recettori è la preparazione di helicenes e corannulenes, dal momento che non sono disponibili in commercio. Ma, secondo i nuovi metodi pubblicati altrove 46-48 possono essere ottenuti in quantità adatte in un breve periodo di tempo ragionevole.

<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) può essere preparato secondo i metodi attuali 46-48 in modo semplice con ottime rese (Figura 5). Entrambi condividono una molecola comune, 2,7-dimetilnaftalene, come materiale di partenza, dando luogo a una divergente alla sintesi convergente della molecola finale. <img alt="F...

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

Qui, vi presentiamo un protocollo per sintetizzare un complesso composto organico composto da tre unità poliaromatici non planari, montato facilmente con rendimenti ragionevoli.

Preparazione di un Hexahelicene corannulene-funzionalizzati da rame (I) -catalyzed Acetilene-azide cicloaddizione di unità non planare policiclici aromatici

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 Views.  Universidad de Valladolid.  Qui, vi presentiamo un protocollo per sintetizzare un complesso composto organico composto da tre unità poliaromatici non planari, montato facilmente con rendimenti ragionevoli. 

Video: 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.

Preparazione ed uso di samario diioduro (SMI<sub&gt; 2</sub&gt;) Nella sintesi organica: il ruolo meccanicistico di HMPA e Ni (II) sali nella reazione Samario Barbier

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

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Chimica

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 preparazione delle pareti cellulari batteriche per l'analisi compositia mediante cromatografia liquida ad alte prestazioni

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.

Monitoraggio in tempo reale delle reazioni eseguita utilizzando la lavorazione a flusso continuo: La preparazione di 3-Acetylcoumarin come un esempio

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.

Preparazione e caratterizzazione di individuale e Multi-droga Loaded Fisicamente intrappolate polimerici Micelle

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.

Preparazione facile di Internamente auto-assemblato Lipid particelle stabilizzati da nanotubi di carbonio

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.

Preparazione di macroporosi Epitassiali Films quarzo su silicio da Solution Chemical Deposition

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.

Anionico polimerizzazione di un copolimero Amphiphilic per la preparazione di copolimero a blocchi micelle stabilizzata da π-¸ Interazioni Stacking

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.

Preparazione e reattività di un Triphosphenium Bromuro di sale: una fonte conveniente e stabile di fosforo (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.

Preparazione e valutazione di<sup&gt; 99m</sup&gt; Tc marcato tridentate chelati di pre-targeting Utilizzando Bioorthogonal Chimica

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.

Accesso prezioso Ligand Supporti per metalli di transizione: una versione modificata, Intermedio Scala Preparazione di 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 ...

Preparazione di un Hexahelicene corannulene-funzionalizzati da rame (I) -catalyzed Acetilene-azide cicloaddizione di unità non planare policiclici aromatici

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Preparazione ed uso di samario diioduro (SMI