Il finanziamento per questo progetto dal Petroleum Fund American Chemical Society Research (52488-DNI1) e la University of North Carolina a Greensboro si ringrazia. Ringraziamo anche il Dott. Terry Nilo (UNCG) per noi prestato la vetreria appropriata per questi esperimenti. È anche riconosciuto di consulenza e montaggio video di Aaron Glancy.

1. Sintesi di Phenyl HIAT <ol><li> Attrezzare un Pallone da 100 ml a fondo rotondo secco con un agitatore magnetico e hanno il matraccio sotto atmosfera di argon. Fissare il pallone a un supporto e posizionarlo in un bagno cryogen di acetonitrile e anidride carbonica solida pellet. Nota: Il cryogen dovrebbe essere di circa -45 ° C. </li><li> Aggiungere 10 ml di diclorometano anidro al pallone freddo e che il solvente raggiunga la temperatura del criogeno. Nota: Lo spazio di testa eccesso nel pallone è importante per l&#39;aggiunta di etere dietilico successivamente forzare precipitazione. </li><li> Pesare 0,35 g (1 equiv.) Di cyanophenyliodonium triflato e rapidamente trasferirlo al pallone freddo. Nota: I solidi devono essere abbastanza insolubile a questa temperatura. </li><li> Tarare la massa di una siringa vuota e quindi utilizzarlo pesare 0,37 g (1 equiv.) Di phenylethynyltributyltin. </li><li> Iniettare il phenylethynyltributyltin nella soluzione fredda. Nota: La dissoluzione dei solidi è un&#39;indicazione cheil HIAT è stato formato. Il tempo approssimativo di scioglimento è di 30 min. </li><li> Aggiungere dietil etere ed esano per forzare precipitazione del prodotto. Nota: Se un precipitato non si forma, si evapora il solvente a pressione ridotta e aggiungere una miscela di dietil etere ed esano per forzare precipitazione del HIAT. </li><li> Dotare una beuta da vuoto con un imbuto Büchner e versare la soluzione sul imbuto per filtrazione. </li><li> Raccogliere i solidi e memorizzare fredda in un contenitore opaco. </li></ol> 2. Sintesi di n-pentile HIAT <ol><li> Attrezzare un secco 250 ml a tre colli pallone a fondo con un agitatore magnetico e hanno il matraccio sotto atmosfera di argon. Fissare il pallone a un supporto e posizionarlo in un bagno cryogen di acetonitrile e anidride carbonica solida pellet. Nota: Il cryogen dovrebbe essere di circa -45 ° C. </li><li> Assemblare un apparato di filtrazione Schlenk sul pallone in modo che la filtrazione può essere eseguita rapidamente e ad una tem freddotemperatura. Grasso e serrare insieme ogni articolazione dell&#39;apparato. Nota: Il sistema di filtrazione può essere costruito in vari modi, ma è importante che il sistema ha la capacità di spingere con gas inerte e tirare con un vuoto attraverso un filtro di vetro. </li><li> Aggiungere 10 ml di diclorometano anidro al pallone freddo e che il solvente raggiunga la temperatura del criogeno. Nota: Lo spazio di testa eccesso nel pallone è importante per l&#39;aggiunta di esano poi a forzare precipitazione. </li><li> Pesare 0,35 g (1 equiv.) Di cyanophenyliodonium triflato e rapidamente trasferirlo al pallone freddo. Nota: I solidi devono essere abbastanza insolubile a questa temperatura. </li><li> Tarare la massa di una siringa vuota e quindi utilizzarlo pesare 0,44 g (1 equiv.) Di tributilstagno heptyne. </li><li> Iniettare la heptyne tributilstagno nella soluzione fredda. Nota: La dissoluzione dei solidi è un&#39;indicazione che il HIAT è stato formato. Il tempo approssimativo di scioglimento è di 30 min. </li><li> Iniettare 75 ml di hexane nello spazio di testa supplementare del pallone per formare un precipitato. </li><li> Introdurre il pallone di raccolta sotto vuoto. </li><li> Sganciare l&#39;apparecchio dal supporto e inclinarlo accuratamente di versare la soluzione sul filtro di vetro. Aprire il vuoto pallone di raccolta per estrarre il liquido attraverso. Nota: Non lasciare che il vuoto per aspirare aria nel recipiente. </li><li> Smontare l&#39;apparecchio e raschiare i solidi fuori il filtro una volta che la filtrazione è completo. Una volta che il solido viene rimosso dal filtrato è meno aria e temperatura sensibile e può essere maneggiato all&#39;aria aperta. </li><li> Raccogliere i solidi e memorizzare fredda in un contenitore opaco. </li></ol> 3. OH Inserimento di Cyanocarbenes Realizzato da Fenil HIAT <ol><li> Attrezzare un 50 ml pallone a fondo rotondo secco con un agitatore magnetico e hanno il matraccio sotto atmosfera di argon. Fissare il pallone ad un piatto mescolare e iniettare 20 ml di metanolo secco al pallone. </li><li> Pesare 0,300 g (1 equiv.) Del già SYNTHESIzed Fenil HIAT e rapidamente aggiungerlo al pallone. </li><li> Aggiungere 0,047 g (1 equiv.) Di sodio azide al pallone. Nota: La soluzione si scurisce nel tempo e azoto viene generato dalla formazione cyanocarbene. </li><li> Sia la reazione continua finché si verifica la formazione di bolle. Il tempo approssimativo per il completamento è di 20 min. </li><li> Esporre la soluzione di aria e si evapora il solvente sotto pressione ridotta. </li><li> Aggiungere diclorometano al liquido residuo e procedere all&#39;estrazione acquosa per rimuovere il triflato di sodio. Raccogliere le fasi organiche di diclorometano e secca con solfato di sodio anidro. </li><li> Decantare la soluzione e far evaporare con pressione ridotta. </li><li> Eseguire cromatografia su colonna per purificare il prodotto cyanocarbene. </li></ol> 4. Ciclopropanazione Cyanocarbene Reazione Uso Fenil HIAT <ol><li> Pesare 0,125 g (1 equiv.) Di tetrabutilammonio azide in un cassetto portaoggetti e collocarlo in un luogo asciutto da 10 ml a fondo rotondo pallone equipped con un agitatore magnetico. </li><li> Chiudere la 10 ml pallone contenente la azide tetrabutilammonio, rimuoverlo dal cassetto portaoggetti e posizionarlo su un piatto mescolare sotto gas argon utilizzando una linea Schlenk. </li><li> Aggiungere 1,0 ml di stirene al pallone e lasciare il pallone a mescolare. Nota: L&#39;azide non deve sciogliersi. </li><li> Aggiungere rapidamente 0,200 g (1 equiv.) Fenile HIAT a questo slurry e posizionare il setto indietro sul pallone che è collegato ad una linea Schlenk. Nota: La soluzione deve immediatamente scurire e generare azoto dalla formazione cyanocarbene. </li><li> Lasciare la reazione di continuare finché si verifica la formazione di bolle. Il tempo approssimativo per il completamento è di un minuto. </li><li> Dopo le bolle sono fermi, esporre la soluzione di aria ed eseguire cromatografia su colonna per purificare il prodotto. </li></ol>

<ol>
	<li>Hyatt, I. F. D., Meza-Avi&#241;a, M. E., Croatt, M. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alkynes+&amp;+Azides:+Not+Just+for+Click+Reactions.">Alkynes &amp; Azides: Not Just for Click Reactions.</a> Synlett. 23 (20), 2869-2874 (2012).</li><li>Meza-Avi&#241;a, M. E., Patel, M. K., Lee, C. B., Dietz, T. J., Croatt, M. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+Formation+of+1,5-Substituted+Sulfonyl+Triazoles+Using+Acetylides+and+Sulfonyl+Azides.">Selective Formation of 1,5-Substituted Sulfonyl Triazoles Using Acetylides and Sulfonyl Azides.</a> Organic Letters. 13 (12), 2984-2987 (2011).</li><li>Hyatt, I. F. D., Croatt, M. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reactions+of+Hypervalent+Iodonium+Alkynyl+Triflates+with+Azides:+Generation+of+Cyanocarbenes.">Reactions of Hypervalent Iodonium Alkynyl Triflates with Azides: Generation of Cyanocarbenes.</a> Angewandte Chemie International Edition. 51 (30), 7511-7514 (2012).</li><li>Banert, K., Hagedorn, M., Wutke, J., Ecorchard, P., Schaarschmidt, D., Lang, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Elusive+ethynyl+azides:+trapping+by+1,3-dipolar+cycloaddition+and+decomposition+to+cyanocarbenes.">Elusive ethynyl azides: trapping by 1,3-dipolar cycloaddition and decomposition to cyanocarbenes.</a> Chemical Communications. 46 (23), 4058-4060 (2010).</li><li>Koumbis, A., Kyzas, C., Savva, A., Varvolis, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Formation+of+New+Alkynyl(phenyl)iodonium+Salts+and+Their+Use+in+the+Synthesis+of+Phenylsulfonyl+Indenes+and+Acetylenes.">Formation of New Alkynyl(phenyl)iodonium Salts and Their Use in the Synthesis of Phenylsulfonyl Indenes and Acetylenes.</a> Molecules. 10 (10), 1340-1350 (2005).</li><li>Banert, K., Arnold, R., Hagedorn, M., Thoss, P., Auer, A. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=1-Azido-1-Alkynes:+Synthesis+and+Spectroscopic+Characterization+of+Azidoacetylene.">1-Azido-1-Alkynes: Synthesis and Spectroscopic Characterization of Azidoacetylene.</a> Angewandte Chemie International Edition. 51 (30), 7515-7518 (2012).</li><li>Zhdankin, V. V., Stang, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chemistry+of+Polyvalent+Iodine.">Chemistry of Polyvalent Iodine.</a> Chemical Reviews. 108 (12), 5299-5358 (2008).</li><li>Br&#228;se, S., Banert, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Organic Azides - Syntheses and Applications. , (1002).</li><li>Stang, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alkynyl-+and+Alkenyl(phenyl)iodonium+Compounds.">Alkynyl- and Alkenyl(phenyl)iodonium Compounds.</a> Angewandte Chemie International Edition. 31 (3), 274-285 (2003).</li><li>Hembre, R. T., Scott, C. P., Norton, J. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conversion+of+olefins+to+ditriflates+by+&#956;-oxobis[(trifluoromethanesulfonato)(phenyl)iodine.">Conversion of olefins to ditriflates by &#956;-oxobis[(trifluoromethanesulfonato)(phenyl)iodine.</a> Journal of Organic Chemistry. 52 (16), 3650-3654 (1987).</li><li>Stang, P. J., Surber, B. W., Chen, Z., Roberts, K. A., Anderson, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acetylenic+Esters.+Preparation+and+Mechanism+of+Formation+of+Alkynyl+Tosylates+and+Mesylates+via+Tricoordinate+Iodonium+Species.">Acetylenic Esters. Preparation and Mechanism of Formation of Alkynyl Tosylates and Mesylates via Tricoordinate Iodonium Species.</a> Journal of the American Chemical Society. 109 (1), 228-235 (1987).</li><li>Zhdankin, V. V., Crittell, C. M., Stang, P. J., Zefirov, N. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+general+approach+to+unsymmetrical+tricoordinate+iodinanes:+Single+step+preparation+of+mixed+iodosobenzene+sulfonates+Phl(X)OSO2R,+via+reaction+of+iodosobenzene+with+Me3SiX.">A general approach to unsymmetrical tricoordinate iodinanes: Single step preparation of mixed iodosobenzene sulfonates Phl(X)OSO2R, via reaction of iodosobenzene with Me3SiX.</a> Tetrahedron Letters. 31 (34), 4821-4824 (1990).</li><li>Lee, H., Jung, Y., Yoon, Y., Kim, B. G., Kim, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Angularly+Fused+Triquinanes+from+Linear+Substrates+through+Trimethylenemethane+Diyl+[2+++3]+Cycloaddition+Reaction.">Angularly Fused Triquinanes from Linear Substrates through Trimethylenemethane Diyl [2 + 3] Cycloaddition Reaction.</a> Organic Letters. 12 (11), 2672-2674 (2010).</li><li>Beauchard, A., Phillips, V. A., Lloyd, M. D., Threadgill, M. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+2-(4-carboxybutenyl)-+and+2-(4-carboxybutynyl)-cyclopentene-1-carboxamides.">Synthesis of 2-(4-carboxybutenyl)- and 2-(4-carboxybutynyl)-cyclopentene-1-carboxamides.</a> Tetrahedron. 65 (39), 8176-8184 (2009).</li><li>Kitamura, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+Alternative+Synthesis+of+Alkynyl(phenyl)iodonium+Triflates+Using+(Diacetoxyiodo)benzene+and+Alkynylsilanes.">An Alternative Synthesis of Alkynyl(phenyl)iodonium Triflates Using (Diacetoxyiodo)benzene and Alkynylsilanes.</a> Synthesis. 10, 1416 (1998).</li><li>Bouma, M. J., Olofsson, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=General+One-Pot+Synthesis+of+Alkynyliodonium+Salts+and+Alkynyl+Benziodoxolones+from+Aryl+Iodides.">General One-Pot Synthesis of Alkynyliodonium Salts and Alkynyl Benziodoxolones from Aryl Iodides.</a> Chemistry A European Journal. 18, 14242 (2012).</li><li>Williamson, B. L., Stang, P. J., Preparation Arif, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+Structure,+and+Diels-Alder+Cycloaddition+Chemistry+of+&#946;-Functionalized+Alkynyl(phenyl)iodonium+Salts.">Molecular Structure, and Diels-Alder Cycloaddition Chemistry of &#946;-Functionalized Alkynyl(phenyl)iodonium Salts.</a> Journal of the American Chemical Society. 115 (7), 2590-2597 (1993).</li></ol>

Gli autori dichiarano di non avere interessi finanziari in competizione.

Hypervalent iodonio alchinile triflati, o HIATs, si formano e possono essere fatti reagire con fonti di azide per formare cyanocarbenes. E &#39;molto importante che siano adottate tutte le precauzioni necessarie, poiché molti dei reagenti e intermedi mostrati in questo video sono potenzialmente esplosiva e altamente tossico. Nonostante l&#39;elevato livello di reattività può essere pericoloso se mal preparata, è mostrato in questo video che la reattività intrinseca dei composti può essere sfruttata catturando le c...

La continua evoluzione della chimica organica perno sulla progettazione e sviluppo di nuove reazioni. In particolare, la scoperta di nuove reazioni che consentono vie sintetiche inimmaginabili bear significato ultimo. A tal fine, il gruppo desiderato per convertire due atomi di carbonio di un alchino e un azoto di una azide in un cyanocarbene. 1 Questa trasformazione precedentemente sconosciuto consentirebbe un significativo aumento della complessità molecolare poiché il cyanocarbene reattiva sarebbe rapidamente reagire ulteriormente. Lo sforzo iniziale era di utilizzare un alchino nucleofila ed elettrofila azide, ma triazoli stati efficacemente formata in questo caso invece di cyanocarbenes. 2 Usando un approccio umpolung, il secondo metodo utilizza un azide e alchino nucleofila elettrofila e prodotti risultanti da reazioni cyanocarbene sono fortunatamente formata in questo caso. 3 Ci sono molte fonti di azide nucleofila, tuttavia, alchini elettrofili sonomolto meno comune. Il gruppo di Klaus Banert precedentemente segnalato il proof-of-concept per questa reazione utilizzando un alchinile-cloruro, 4 ma il nostro gruppo e il gruppo Banert indipendentemente e contemporaneamente ha stabilito che hypervalent iodonio alchinilico triflati (HIATs) sono elettrofili molto meglio per i motivi di stabilità e reattività. 3,6 Noi qui descrivono la sintesi, l&#39;isolamento e la reazione di questi HIATs con azidi di formare e reagire in situ come cyanocarbenes. Diversi precauzioni di sicurezza devono essere considerati prima di procedere con questi esperimenti. Alcuni triflati alchinilici hypervalent iodonio sono instabili e si decompongono, a volte violentemente, quando esposto all&#39;aria e alla luce. 7 Per formare il cyanocarbene intermedio, la procedura richiede l&#39;utilizzo di fonti azide. Azidi sono esplosivi e altamente tossico. 8 corretto equipaggiamento di protezione personale devono essere indossati quando si maneggia questi materiali, in particolare organostannici,e tutti manipolazione dei reagenti dovrebbe avvenire nelle cappe adeguatamente ventilati. Il cyanocarbene è un potente e instabile intermedio reattivo. Fare attenzione ad eseguire esperimenti inizialmente su piccole scale in modo che l&#39;evoluzione azoto è controllabile e mai eseguire queste reazioni in sistemi chiusi. Se si desidera scale-up della reazione, si consiglia fortemente l&#39;uso di uno schermo di sicurezza. La sintesi di molti HIATs essere stata precedentemente pubblicata compreso l&#39;uso di reagente di Zefirov 9,10, e il reagente di Koser, 9,11 tuttavia, questo video userà il cyanophenyliodonium triflato reagente 9,12 (Figura 1). Cyanophenyliodonium triflato è stato sintetizzato sulla base di una preparazione letteratura precedentemente riportato visualizzato. 13 Il reagente reagisce con trialchil-stagno alchini modificati 14 per formare il prodotto desiderato. Dopo il HIAT è sintetizzato e isolato può essere fatto reagire con azide per formareun reattivo cyanocarbene intermedio (Figura 2). Ci sono molti altri metodi che possono essere utilizzati per sintetizzare i alchini iodonio come l&#39;utilizzo di silani alchinile 15 e alchinile esteri boronici 16 ma il metodo nel video è stato scelto perché, nella nostra esperienza, è meglio che l&#39;efficienza e la resa. Il nostro meccanismo proposto 3,5 (Figura 3) per questa reazione con l&#39;aggiunta di una fonte azide alla β-carbonio del alchino, formando così una iodo-ylide che si decompone a iodobenzene e un vinilidene-carbene. Il vinilidene-carbene può quindi subire un 1,2-riarrangiamento attraverso la migrazione di una R-gruppo o azide di permettersi un alchinilico-azide. Il alchinile-azide poi estrude diazoto per formare un cyanocarbene che può reagire con un substrato. Va notato che non ci può essere la formazione di un hypervalent iodonio alchenile triflato specie, a seconda delle condizioni. Il sottoprodotto èfavorita a temperature più basse in solventi protici cui la protonazione del iodo-ylide è più veloce del riarrangiamento al azide alchinile. Un altro possibile prodotto che si verifica durante reazioni di inserzione OH è un vinil etere dove il vinilidene-carbene è intrappolato prima della ridisposizione alla può verificarsi alchinile-azide. La propensione a formare questa vinil etere è determinato dal gruppo R. Uno dei principali vantaggi di questa reazione è che dopo la carbene reagisce, il gruppo nitrile risultante è una comoda maniglia per ulteriore funzionalizzazione. Molti sintoni possono essere immaginate con questo metodo e diversi prodotti possono essere formati con gli stessi substrati. Controllare la miscela di prodotto con la temperatura, la concentrazione e il gruppo R del alchino è necessario. 3 Con una corretta comprensione di come si comportano cyanocarbenes, il metodo mostra uno strumento efficace per aggiungere rapidamente complessità chimica per formare una molecola bersaglio. Esempi di come il cyanocarbene reagisce includono inserimento OH in cui l&#39;atomo di ossigeno nucleofilo dell&#39;alcool attacca il carbene e poi si verifica trasferimento di protoni, dimetilsolfossido complessazione, dove il carbene combina con l&#39;atomo di zolfo, e dove il ciclopropanazione carbene reagisce con un alchene.

<table border="1">
<tbody>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Reagent</td>
 </tr>
 <tr>
 <td>Phenyl acetylene</td>
 <td>Acros</td>
 <td>AC152461000</td>
 <td></td>
 </tr>
 <tr>
 <td>Tri-n-butyltin chloride</td>
 <td>Acros</td>
 <td>139351000</td>
 <td></td>
 </tr>
 <tr>
 <td>Lithium bis(trimethysilyl)amide</td>
 <td>Acros</td>
 <td>347701000</td>
 <td></td>
 </tr>
 <tr>
 <td>Iodobenzene diacetate</td>
 <td>Acros</td>
 <td>176560250</td>
 <td></td>
 </tr>
 <tr>
 <td>Trimethylsilyl cyanide</td>
 <td>Aldrich</td>
 <td>212849</td>
 <td>Extremely toxic. Handle this chemical only in an adequately ventilated hood with extreme caution.</td>
 </tr>
 <tr>
 <td>Trimethylsilyl triflate</td>
 <td>Alfa Aesar</td>
 <td>A12535</td>
 <td></td>
 </tr>
 <tr>
 <td>Sodium Azide</td>
 <td>Sigma-Aldrich</td>
 <td>S8032</td>
 <td>Shock sensitive.</td>
 </tr>
 <tr>
 <td>Tetrabutylammonium azide</td>
 <td>Aldrich</td>
 <td>651664</td>
 <td>If possible, store and handle in a glovebox due to this compound's hygroscopic nature.</td>
 </tr>
 <tr>
 <td>1-Heptyne</td>
 <td>Acros</td>
 <td>223460250</td>
 <td></td>
 </tr>
 <tr>
 <td>Styrene</td>
 <td>Aldrich</td>
 <td>240869</td>
 <td></td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>[header]</td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Material</td>
 </tr>
 <tr>
 <td>Rotary Evaporator (Hei-VAP)</td>
 <td>Heidolph</td>
 <td>517-61000-01-0</td>
 <td></td>
 </tr>
 <tr>
 <td>Glovebox</td>
 <td>MBRAUN</td>
 <td>UL-018</td>
 <td></td>
 </tr>
 </tbody>
</table>

synthesis of hypervalent iodonium alkynyl triflates for the application of generating cyanocarbenes

Le procedure descritte in questo articolo riguardano la sintesi e l&#39;isolamento di hypervalent iodonio alchinilici triflati (HIATs) e loro successive reazioni con azidi per formare intermedi cyanocarbene. La sintesi di hypervalent iodonio triflati alchinilici può essere facile, ma le difficoltà derivano dal loro isolamento e reattività. In particolare, la necessità di utilizzare filtrazione sotto atmosfera inerte a -45 ° C per alcuni HIATs richiede particolare cura e attrezzature. Una volta isolati, i composti possono essere memorizzati e utilizzati in reazioni con azidi per formare intermedi cyanocarbene. L&#39;evidenza di generazione cyanocarbene è indicato per estrusione visibile di diazoto e la caratterizzazione dei prodotti che si verificano dall&#39;inserzione, OH, complessazione solfossido e ciclopropanazione. Una reazione secondaria di formazione cyanocarbene è la generazione di un vinilidene-carbene e le condizioni per controllare questo processo sono discussi. C&#39;èanche potenziale di formare un alchenile triflato hypervalent iodonio e mezzi di isolamento e di controllo della sua generazione sono forniti. La reazione di inserimento OH comporta l&#39;uso di un HIAT, sodio azide o tetrabutilammonio azide, e metanolo come solvente / substrato. La reazione solfossido complessazione utilizza un HIAT, sodio azide o tetrabutilammonio azide, e dimetilsolfossido come solvente. Le cyclopropanations possono essere effettuate con o senza l&#39;uso di solventi. La fonte azide deve essere azide tetrabutilammonio e il substrato indicato è lo stirene.

La Figura 1 illustra la sintesi di un HIAT utilizzando cyanophenyliodonium alchinile triflato. Il HIAT può quindi essere utilizzato per generare cyanocarbenes che saranno sottoposti OH inserimento di ciclopropanazione. La reazione inserimento OH con Phenyl HIAT produce 2-metossi-2-phenylacetonitrile fino a una resa del 75%. La reazione ciclopropanazione con Phenyl HIAT produce 1,2-diphenylcyclopropanecarbonitrile fino a una resa del 61%. Anche se non mostrato nel video, dimetilsolfossido complessazione...

Watch this Scientific Journal Video about Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes at JoVE.com

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

Qui viene descritta la sintesi, l&#39;isolamento, e le reazioni di hypervalent iodonio alchinilici triflati (HIATs) con azidi per generare cyanocarbenes. Le procedure comporteranno tecniche aria sensibili e criogeno, incluse filtraggio a freddo sotto atmosfera inerte. Saranno inoltre discussi manipolazione e la sicurezza dei composti sintetizzati.

Sintesi di hypervalent iodonio Alchinile triflati per l&#39;applicazione di Generazione Cyanocarbenes

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

synthesis-hypervalent-iodonium-alkynyl-triflates-for-application

Research

JoVE Journal

Chemistry

10.8K Views.  University of North Carolina at Greensboro.  Qui viene descritta la sintesi, l'isolamento, e le reazioni di hypervalent iodonio alchinilici triflati (HIATs) con azidi per generare cyanocarbenes. Le procedure comporteranno tecniche aria sensibili e criogeno, incluse filtraggio a freddo sotto atmosfera inerte. Saranno inoltre discussi manipolazione e la sicurezza dei composti sintetizzati. 

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

Synthesis, Cellular Delivery and In vivo Application of Dendrimer-based pH Sensors

The development of fluorescent indicators represented a revolution for life sciences. Genetically encoded and synthetic fluorophores with sensing abilities allowed the visualization of biologically relevant species with high spatial and temporal resolution. Synthetic dyes are of particular interest thanks to their high tunability and the wide range of measureable analytes. However, these molecules suffer several limitations related to small molecule behavior (poor solubility, difficulties in targeting, often no ratiometric imaging allowed). In this work we introduce the development of dendrimer-based sensors and present a procedure for pH measurement in vitro, in living cells and in vivo. We choose dendrimers as ideal platform for our sensors for their many desirable properties (monodispersity, tunable properties, multivalency) that made them a widely used scaffold for several biomedical devices. The conjugation of fluorescent pH indicators to the dendrimer scaffold led to an enhancement of their sensing performances. In particular dendrimers exhibit reduced cell leakage, improved intracellular targeting and allow ratiometric measurements. These novel sensors were successfully employed to measure pH in living HeLa cells and in vivo in mouse brain.

Synthesis, Cellular Delivery and In vivo Application of Dendrimer-based pH Sensors

Fluorescence sensors are powerful tools in life science. Here we describe a methodology to synthesize and use dendrimer-based fluorescent sensors to measure pH in living cells and in vivo. The dendritic scaffold enhances the properties of conjugated fluorescent dyes leading to improved sensing properties.

Sintesi, Consegna Cellulare e<em&gt; In vivo</em&gt; Applicazione di sensori di pH basati Dendrimero

The development of  fluorescent indicators represented a revolution for life sciences. Genetically  encoded and synthetic fluorophores with sensing ...

Ricerca

Chimica

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

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

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

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

Protocollo per la sintesi di<em&gt; Ortho</em&gt; Derivati ​​all&#39;anilina -trifluoromethoxylated

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

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 come catalizzatore eterogeneo per la sintesi di vanillina

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

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.

Sintesi di proteine ​​bioconiugati<em&gt; via</em&gt; Chimica cisteina-maleimmide

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.

Sintesi facile di micelle vermiforme dalla luce visibile mediata polimerizzazione in dispersione Utilizzando Photoredox Catalyst

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

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.

Sintesi e analisi di spettrometria di massa di Oligo-peptoids

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

Synthesis of Substrate-Bound Au Nanowires Via an Active Surface Growth Mechanism

Advancing synthetic capabilities is important for the development of nanoscience and nanotechnology. The synthesis of nanowires has always been a challenge, as it requires asymmetric growth of symmetric crystals. Here, we report a distinctive synthesis of substrate-bound Au nanowires. This template-free synthesis employs thiolated ligands and substrate adsorption to achieve the continuous asymmetric deposition of Au in solution at ambient conditions. The thiolated ligand prevented the Au deposition on the exposed surface of the seeds, so the Au deposition only occurs at the interface between the Au seeds and the substrate. The side of the newly deposited Au nanowires is immediately covered with the thiolated ligand, while the bottom facing the substrate remains ligand-free and active for the next round of Au deposition. We further demonstrate that this Au nanowire growth can be induced on various substrates, and different thiolated ligands can be used to regulate the surface chemistry of the nanowires. The diameter of the nanowires can also be controlled with mixed ligands, in which another &#34;bad&#34; ligand could turn on the lateral growth. With the understanding of the mechanism, Au nanowire-based nanostructures can be designed and synthesized.

We report a solution-based method to synthesize substrate-bound Au nanowires. By tuning the molecular ligands used during the synthesis, the Au nanowires can be grown from various substrates with different surface properties. Au nanowire-based nanostructures can also be synthesized by adjusting the reaction parameters.

Sintesi di nanofili Au associato a substrato tramite un meccanismo di crescita superficiale attiva

Advancing synthetic capabilities is important for the development of nanoscience and nanotechnology. The synthesis of nanowires has always been a ...

Synthesis of Soft Polysiloxane-urea Elastomers for Intraocular Lens Application

This study discusses a synthesis route for soft polysiloxane-based urea (PSU) elastomers for their applications as accommodating intraocular lenses (a-IOLs). Aminopropyl-terminated polydimethylsiloxanes (PDMS) were previously prepared via the ring-chain equilibration of the cyclic siloxane octamethylcyclotetrasiloxane (D4) and 1,3-bis(3-aminopropyl)-tetramethyldisiloxane (APTMDS). Phenyl groups were introduced into the siloxane backbone via the copolymerization of D4 and 2,4,6,8-tetramethyl-2,4,6,8-tetraphenyl-cyclotetrasiloxane (D4Me,Ph). These polydimethyl-methyl-phenyl-siloxane-block copolymers were synthesized for increasing the refractive indices of polysiloxanes. For applications as an a-IOL, the refractive index of the polysiloxanes must be equivalent to that of a young human eye lens. The polysiloxane molecular weight is controlled by the ratio of the cyclic siloxane to the endblocker APTMDS. The transparency of the PSU elastomers is examined by the transmittance measurement of films between 200 and 750 nm, using a UV-Vis spectrophotometer. Transmittance values at 750 nm (upper end of the visible spectrum) are plotted against the PDMS molecular weight, and &#62; 90% of the transmittance is observed until a molecular weight of 18,000 g&#183;mol&#8722;1. Mechanical properties of the PSU elastomers are investigated using stress-strain tests on die-cut dog-bone-shaped specimens. For evaluating mechanical stability, mechanical hysteresis is measured by repeatedly stretching (10x) the specimens to 5% and 100% elongation. Hysteresis considerably decreases with the increase in the PDMS molecular weight. In vitro cytotoxicity of some selected PSU elastomers is evaluated using an MTS cell viability assay. The methods described herein permit the synthesis of a soft, transparent, and noncytotoxic PSU elastomer with a refractive index approximately equal to that of a young human eye lens.

This study describes synthetic routes for aminopropyl-terminated polydimethylsiloxanes and polydimethyl-methyl-phenyl-siloxane-block copolymers and for soft polysiloxane-based urea (PSU) elastomers. It presents the application of PSUs as accommodating an intraocular lens. An evaluation method for in vitro cytotoxicity is also described.

Sintesi degli elastomeri molli polisilossano-urea per applicazione di lente intraoculare

This study discusses a synthesis route for soft polysiloxane-based urea (PSU) elastomers for their applications as accommodating intraocular lenses ...

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates

Maleimide-bearing bifunctional probes have been employed for decades for the site-selective modification of thiols in biomolecules, especially antibodies. Yet maleimide-based conjugates display limited stability in vivo because the succinimidyl thioether linkage can undergo a retro-Michael reaction. This, of course, can lead to the release of the radioactive payload or its exchange with thiol-bearing biomolecules in circulation. Both of these processes can produce elevated activity concentrations in healthy organs as well as decreased activity concentrations in target tissues, resulting in reduced imaging contrast and lower therapeutic ratios. In 2018, we reported the creation of a modular, stable, and easily accessible phenyloxadiazolyl methyl sulfone reagent &#8212; dubbed &#8216;PODS&#8217; &#8212; as a platform for thiol-based bioconjugations. We have clearly demonstrated that PODS-based site-selective bioconjugations reproducibly and robustly create homogenous, well-defined, highly immunoreactive, and highly stable radioimmunoconjugates. Furthermore, preclinical experiments in murine models of colorectal cancer have shown that these site-selectively labeled radioimmunoconjugates exhibit far superior in vivo performance compared to radiolabeled antibodies synthesized via maleimide-based conjugations. In this protocol, we will describe the four-step synthesis of PODS, the creation of a bifunctional PODS-bearing variant of the ubiquitous chelator DOTA (PODS-DOTA), and the conjugation of PODS-DOTA to the HER2-targeting antibody trastuzumab.

In this protocol, we will describe the synthesis of PODS, a phenyoxadiazolyl methyl sulfone-based reagent for the site-selective attachment of cargos to the thiols of biomolecules, particularly antibodies. In addition, we will describe the synthesis and characterization of a PODS-bearing bifunctional chelator and its conjugation to a model antibody.

Sintesi e Bioconjugation di tiolo-reattive reagenti per la creazione del sito-selettivamente per volta efattori

Maleimide-bearing bifunctional probes have been employed for decades for the site-selective modification of thiols in biomolecules, especially antibodies. ...

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

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

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

Sintesi efficiente dei centri quaternari All-Carbon tramite l'aggiunta di coniugato di Monoorganozinc di bromide funzionalizzati

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