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

1. Sintesi di Ynone <ol><li> Utilizzando una bilancia analitica, pesare 0,15 mmol di potassio desiderato sale alkynyltrifluoroborate (1,5 equivalenti) e aggiungere ad una fiala pulita dotata di ancoretta magnetica. </li><li> Usando una siringa di vetro stantuffo con ago, aggiungere 0,5 ml di DCM anidro alla fiala di permettersi una soluzione 0.3 M di trifluoroborate. NOTA: Dal momento che si tratta di una nuova metodologia, le reazioni sono state eseguite per prova di concetto. Al fine di ridurre i rifiuti che sono stati effettuati su piccola scala. La reazione può essere scalata a produrre rendimenti più grandi come richiesto. </li><li> Usando una siringa di vetro, aggiungere 0,15 mmoli di 1,0 M soluzione di tricloruro di boro (1,5 equivalenti, 150 microlitri) goccia a goccia nel recipiente di reazione a temperatura ambiente (20 ° C) sotto agitazione. Sostituire il tappo. Tenere o bloccare il recipiente di reazione capped tale che la soluzione di reazione è al di sotto della linea di galleggiamento in sonicatore. Sonicare la soluzione per 30 sec a 20 ° C e una frequenza of 40 kHz. </li><li> Mescolare la soluzione di reazione a temperatura ambiente (20 ° C) per un ulteriore 20 min. A seconda della natura del materiale di partenza alkynyltrifluoroborate, osservare un cambiamento di colore. Un cambiamento di colore dal bianco al marrone chiaro o marrone scuro, rosso, o viola è comune. </li><li> Aggiungere 0,1 mmoli di cloruro acilico desiderato (1,0 equivalenti) al flaconcino a temperatura ambiente (20 ° C) sotto agitazione. In alternativa, trasferire il contenuto del recipiente di reazione in un pallone caricato con ancoretta magnetica e 0,1 mmoli di cloruro acilico. Sostituire il tappo. Mescolare la soluzione di reazione a temperatura ambiente (20 ° C) per 30 min. NOTA: Generalmente, una modifica a un colore molto scuro è un&#39;indicazione che la reazione ha luogo. </li><li> Utilizzando una cromatografia su strato sottile (TLC) 34 monitorare l&#39;andamento della reazione confrontando con appropriata norma cloruro acilico. NOTA: A seconda della natura dei materiali di partenza, la reazione non può andare a completamento. L&#39;acyl cloruro di materiale di partenza è stato osservato come un punto di funzionamento più elevata del prodotto finale per tutte le ynones preparati per data utilizzando questo metodo. <ol><li> Preparare lo standard cloruro acilico diluendo circa 10 mg di cloruro acilico materiale di partenza di 1 ml di acetato di etile in una piccola fiala. </li><li> Utilizzando un spotter TLC, individuare la soluzione di reazione e lo standard sulla linea di partenza della piastra TLC. Un co-spot con la soluzione di reazione e standard può essere utile per determinare se vi è ancora materiale di partenza presenti nella soluzione di reazione. </li><li> Determinare un adeguato fase mobile TLC per tentativi ed errori. Per la preparazione del prodotto 1a, una fase mobile consistente 1:30 acetato di etile: esani produce valori R f di circa 0,5 e 0,8 per il prodotto ynone e cloruro di benzoile materiale di partenza, rispettivamente. </li><li> Visualizza la piastra TLC sviluppata sotto la luce UV. Utilizzare una matita per segnare tutti i punti visibili. </li></ol></li></ol> 2. acquosa Workup <ol><li> Quench la reazione aggiungendo 1 ml di acqua fredda (circa 5 ° C) al recipiente di reazione. Usando una pipetta Pasteur, trasferire la soluzione in un imbuto separatore pulita. Diluire ulteriormente il contenuto del imbuto separatore con 10 ml di acqua fredda ed estrarre il prodotto una volta in 15 ml di acetato di etile. </li><li> Eliminare lo strato acquoso inferiore e lavare lo strato una volta in più organica con 10 ml di acqua e una volta con 10 ml di salamoia. Raccogliere la fase organica in una beuta pulita e asciutta con solfato di magnesio. Filtrare la soluzione in un pallone a fondo tondo pulito con filtrazione a gravità. </li></ol> 3. Purificazione di Ynone <ol><li> Usando cromatografia su strato sottile, determinare una fase mobile adatto per la purificazione cromatografia flash del prodotto. Un fattore di ritenzione (R f) di circa 0,5 è generalmente sufficiente per separare il prodotto da qualsiasi dall&#39;inizio rimanenteing materiali e prodotti collaterali. NOTA: Nel caso di separazione poveri, un sistema solvente meno polare può essere utilizzato in modo tale che il prodotto ha un valore f R inferiore. A seconda della polarità dei materiali di partenza, una miscela esano: acetato di etile nell&#39;intervallo di 30: 1 a 5: 1 è generalmente adatto. </li><li> Preparare una colonna contenente silice bagnata con la fase mobile appropriata. Aggiungere uno strato di sabbia alla parte superiore della colonna in modo da non disturbare silice dopo l&#39;aggiunta del prodotto e eluente. </li><li> Evaporare la soluzione workup utilizzando un evaporatore rotante con la temperatura del bagno a 40 ° C e la rotazione impostato a 120 rpm. Sciogliere il contenuto del pallone in un 2 ml di fase mobile e caricare la soluzione con attenzione in modo uniforme sulla colonna. Assicurarsi che la silice è bagnato ma la linea del solvente non superi l&#39;altezza della silice. Ad alcuni solvente per eluire tale che il prodotto è silice. Aggiungere una piccola quantità di fase mobile e ripetere. </li><li> Riempire il colleumn con la fase mobile determinata al punto 3.1; nel caso del prodotto 1a, a 30: 1 esani: miscela acetato di etile è appropriato. Raccogliere le frazioni in provette mediante cromatografia flash per accelerare il processo di purificazione. È sufficiente collegare un adattatore con tubi a una presa d&#39;aria. Regolare la pressione dell&#39;aria in modo tale che l&#39;eluente scorre attraverso la colonna ad una velocità adeguata. </li><li> Spot ciascuna delle frazioni di colonna su una piastra TLC. Facoltativamente, individuare lo standard cloruro acilico come riferimento. Sviluppare il TLC con la fase mobile ritenuto opportuno nella fase 1.8. Segnare eventuali macchie visibili ai raggi UV, notando che il prodotto dovrebbe avere un R f inferiore allo standard acilcloruro. </li><li> Raccogliere tutte le frazioni contenenti macchie visibili in un grande pallone a fondo tondo. Se più di un punto con un R f inferiore al materiale di partenza è presente, raccoglierle in flaconi separati. Si evapora il solvente usando un evaporatore rotante e asciugare il materiale raccolto under alto vuoto per due ore. </li><li> Se necessario, effettuare un lavaggio pentano su una piccola colonna per purificare ulteriormente un prodotto ynone preparato da una scarsa cloruro acilico materiale di partenza di elettroni. Su una scala ridotta, ciò può essere eseguita usando una pipetta Pasteur come colonna. <ol><li> Sciogliere il prodotto in un minimo di cloroformio, DCM, o dietiletere e il carico su una colonna di silice bagnata con pentano. Eluire 1-2 lunghezze di colonna di pentano attraverso la colonna e raccogliere in un becher rifiuti. </li><li> Eluire il prodotto puro ynone dalla colonna pentano utilizzando dietiletere o acetato di etile. Raccogliere eluente in un pallone separato, evaporare, e posto sotto alto vuoto per almeno due ore. Ottenere circa 10 mg di prodotto per la caratterizzazione mediante spettroscopia NMR. </li></ol></li></ol> 4. Caratterizzazione di Ynone <ol><li> Caratterizzare e valutare la purezza del prodotto finale con 1 H e 13 spettroscopia NMR C. 34Tipicamente, il chemical shift del carbonio carbonilico appare vicino 177 ppm nello spettro 13 C NMR. I due carboni SP del gruppo funzionale ynone sono rappresentati dai picchi caratteristici vicino 87 e 93 ppm. </li><li> Utilizzare spettroscopia infrarossa 34 per identificare il picco caratteristico carbonilico del prodotto ynone. Electron delocalizzazione del triplo legame adiacente solito provoca il picco carbonilico appaia tra 1.600 e 1.650 cm-1, a seconda delle caratteristiche elettroniche del composto. </li><li> Determinare la massa molecolare del prodotto e convalidare ulteriormente l&#39;identità utilizzando la spettrometria di massa ad alta risoluzione. 34 </li></ol>

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

The authors declare that they have no competing financial interests.

La tabella 1 illustra le misure adottate per ottimizzare le condizioni per la reazione di fenilacetilene trifluoroborate con cloruro di benzoile per formare il prodotto ynone corrispondente. Inizialmente, catalizzatori noti per convertire organotrifluoroborates a organodifluoroboranes sono stati testati. Purtroppo gel di silice, tetracloruro di silicio 35, 36 e trifluoruro di boro 31,32 non promuove la formazione del ynone desiderato (Tabella 1, voci 1-3). L&#39;uso di clorurati catalizzatori acidi Lewis ha dimostrato di essere più successo. Una bassa resa del ynone 1a desiderato è stato ottenuto in presenza di un ferro (III) cloruro di catalizzatore (Tabella 1, voce 4). Successivamente, alluminio (III) cloruro è stato studiato come risultato della sua capacità consolidata per promuovere la formazione di ioni oxocarbenium in acylations Friedel-Crafts. 37-39 Il prodotto desiderato è stato ottenuto nel 62% di resa ottenuta con un alluminio (III) cloruro catalizzatore era employed. Ulteriore ottimizzazione rivelato che l&#39;aria e l&#39;umidità hanno scarso effetto sulla resa della reazione (Tabella 1, voci 5-7). Di conseguenza, le reazioni successive sono state effettuate in vetro non essiccato in presenza di aria. I tentativi di ottimizzare il solvente rivelato che diclorometano (DCM) è particolarmente adatto per la reazione (Tabella 1, voci 8-12). Le incoerenze nei risultati delle reazioni catalizzate da alluminio (III) cloruro richiesto l&#39;esplorazione di catalizzatori alternativi. Commercialmente alluminio disponibili (III) cloruro esaidrato era completamente inattivo nelle condizioni di reazione (Tabella 1, voce 13). Questo è un buon indicatore che la formazione di alluminio (III) cloruro idrato inibisce la reazione. Boro tricloruro stato trovato per produrre rese simili con maggiore coerenza (Tabella 1, voce 14). Su interazione del alkynyltriflu potassiooroborate con tricloruro di boro, a più reattivi specie organodichloroborane è formata. 40 Questa fase iniziale è fondamentale per la reazione con il cloruro acilico e formazione del ynone procedere. Poiché i sali organotrifluoroborate non sono solubili in DCM, la reazione avviene come miscela eterogenea. Dopo aggiunta di boro tricloruro, la soluzione è per facilitare la formazione delle specie reattive dichloroborane aumentando l&#39;area superficiale del sale trifluoroborate disponibili per reagire sonicato. Applicazione di ultrasuoni alla miscela di reazione provoca effetti meccanici attraverso la generazione di bolle di cavitazione. Durante sonicazione, collasso della cavitazione bolle nei risultati fluido in aree localizzate di alte temperature e pressioni. 41 onde d&#39;urto sono prodotti che creano turbolenze microscopica risultante in un aumento dell&#39;energia cinetica dei sali trifluoroborate solidi. L&#39;aumento di energia del sistema durante sonicazione promoTES frammentazione del sale trifluoroborate conseguente aumento della superficie disponibile per interagire con tricloruro di boro. Sonicazione della miscela di reazione prima dell&#39;aggiunta del materiale di partenza cloruro acilico assicura la formazione efficace delle specie reattive alkynyldichloroborane senza la necessità di ulteriori condizioni di separazione o tempi di reazione più lunghi. La Figura 2 illustra i risultati ottenuti quando fenilacetilene trifluoroborate stato fatto reagire con una varietà di cloruri acilici nelle condizioni di reazione ottimizzate. Neutral aromatico (1b, 1c) e alifatici (1 undecies-l) cloruri acilici fornire i ynones corrispondenti rendimenti sinteticamente utili. Quei cloruri acilici portanti gruppi elettron donatori (1d-g) offrono eccellenti rendimenti mentre i gruppi elettron producono rendimenti relativamente modesti (1h, 1i, 1m). Interestingly, quando il gruppo ritirare elettroni si trova in posizione orto (1i, 59%), un significativo aumento di resa è osservata rispetto al para analoghi sostituiti cloruro acilico (1h, 30%). L&#39;interazione sterico del sostituente in posizione orto- può forzare il gruppo funzionale carbonilico fuori dal piano, compensando così il carattere elettron-attrattore dell&#39;anello aromatico. Vale la pena notare che il cloruro di 4-bromobutirril reagito permettere il 1m prodotto desiderato nel 39% di rendimento. A nostra conoscenza, questo è il primo protocollo per la sintesi di ynones tollerare un gruppo funzionale alchilico bromuro. Occasionalmente, quando il cloruro acilico materiale di partenza è neutro o deficiente di elettroni, impurità alifatici appaiono sul NMR protonica. Ciò può richiedere un lavaggio pentano per purificare ulteriormente il prodotto. Mentre possibile, non è economico per effettuare il lavaggio pentano durante la prima fase di purificazione since pentano è costoso in confronto a esani. Completano la purificazione secondaria separatamente su scala minore, come una colonna pipetta Pasteur riduce significativamente la quantità di pentano necessaria. La figura 3 illustra l&#39;effetto dell&#39;identità del sale alkynyltrifluoroborate sulla resa della reazione. In generale, i derivati ​​di cuscinetti sale sostituenti elettron-donatori il fenilacetilene trifluoroborate sull&#39;anello aromatico reagito con cloruri acilici aromatici e alifatici per produrre i ynones desiderati in buono a rendimenti eccellenti (2a-c, 3a-c). Sali alkynyltrifluoroborate alifatici dimostrato di essere substrati meno reattivi. I rendimenti modesti sono stati ottenuti quando hexynyl- e sali cyclopentylethynyltrifluoroborate stati reagire con derivati ​​ricchi di elettroni di cloruro di benzoile (4a, 5a). In conclusione, un nuovo metodo per la preparazione of è stato sviluppato ynones da cloruri acilici e potassio sali alkynyltrifluoroborate. Le rese ottenute per la sintesi di ynones da questo intervallo metodo dal modesto eccellente a seconda della natura del cloruro acilico e trifluoroborate materiali di partenza. In generale, tali materiali di partenza recanti sostituenti elettron donatori subiscono la reazione più facilmente di materiali di partenza recanti gruppi funzionali neutri e elettron. Il valore di questo approccio risiede nella semplicità e gruppo funzionale tolleranza operativa del metodo. Questo semplice, reazione one-pot procede rapidamente a temperatura ambiente in presenza di boro tricloruro senza esclusione di aria e umidità. Questo metodo conveniente può essere impiegato nella preparazione di ynones in modesto ottime rese da una varietà di cloruri acilici e sali alkynyltrifluoroborate.

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

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

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

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

Gli sforzi iniziali sono concentrati intorno alla preparazione di ynone 1a dal fenilacetilene trifluoroborate S1 e cloruro di benzoile (Figura 1). Tabella 1 illustra i passi di ottimizzazione eseguita compresa proiezione di vari acidi di Lewis, solventi, nonché esame l&#39;effetto dell&#39;acqua sulla reazione . Successivamente, la portata della reazione è stato esplorato presentando fenilacetilene trifluoroborate alle condizioni ottimizzate in presenza di una varietà di cloruri acilici (Figura 2). Modesto rese eccellenti possono essere ottenuti a seconda della natura del substrato cloruro acilico. La portata della reazione è stata ulteriormente valutata attraverso la preparazione di numerosi altri esempi di sali alkynyltrifluoroborate. La figura 3 illustra esempi selezionati di altri sali alkynyltrifluoroborate che possono essere impiegati nella preparazione dei ynones alle condizioni sviluppati. Derivati ​​di phenylacetylene elettrone cuscinetto trifluoroborate donazione sostituenti offerte i prodotti ynone corrispondenti in buona eccellenti rendimenti, mentre i derivati ​​alifatici di sali alkynyltrifluoroborate dimostrato di essere un po &#39;meno reattivi che offrano rendimenti modesti. <img alt="Figura 1" src="/files/ftp_upload/52401/52401fig1highres.jpg" /> Figura 1: Preparazione di Ynone 1a dal fenilacetilene trifluoroborate S1 e benzoil cloruro Scheme illustrando le condizioni per la preparazione di ynone 1a compresa formazione del dichloroborane intermedio reattivo.. <img alt="Figura 2" src="/files/ftp_upload/52401/52401fig2highres.jpg" /> Figura 2:. Rappresentante 1 H NMR del ynone 1a turni chimici e integrazioni relative di protoni caratteristici sono etichettati. Figura 3:. Rappresentante 13 C spettro NMR di ynone 1a cambiamenti chimici di carboni caratteristici sono etichettati. <img alt="Figura 4" src="/files/ftp_upload/52401/52401fig4highres.jpg" /> Figura 4:. Rappresentante spettro HRMS di ynone 1a ottenuta tramite ionizzazione chimica a pressione atmosferica Il valore m / z misurata del [M + H] + ioni viene segnalato. <img alt="Figura 5" src="/files/ftp_upload/52401/52401fig5highres.jpg" /> Figura 5: Reazioni di sale phenylacetylenetrifluoroborate S1 con cloruri acilici Strutture e dei rendimenti per i prodotti fabbricati variando l&#39;identità.del materiale di partenza cloruro acilico sono illustrati. Le reazioni sono state eseguite con 1 equiv di cloruro acilico, 1.5 equiv phenylacetylenetrifluoroborate potassio S1, e 1,5 equiv tricloruro di boro. <img alt="Figura 6" src="/files/ftp_upload/52401/52401fig6highres.jpg" /> Figura 6:. Reazioni di varie alkynyltrifluoroborates con cloruri acilici Strutture e rese dei prodotti ottenuti variando l&#39;identità del materiale di partenza alkynyltrifluoroborate sono illustrati. Le reazioni sono state eseguite con 1 equiv di cloruro acilico, 2,5 di potassio equiv sale organotrifluoroborate e 2,5 equiv tricloruro di boro. <table border="0" cellpadding="0" cellspacing="0"><tbody><tr><td> Ingresso </td><td> Acido di Lewis </td><td> Acido di Lewis (equiv) </td><td> Condizioni </td><td> Dare La Precedenza (%) </td></tr><tr><td> 1 b &lt;/ Sup&gt; </td><td> SiO 2 </td><td> 16.5 </td><td> CH 2 Cl 2 </td><td> 0 </td></tr><tr><td> 2 </td><td> SiCl 4 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> traccia </td></tr><tr><td> 3 </td><td> BF 3 · OEt 2 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> traccia </td></tr><tr><td> 4 b </td><td> FeCl 3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 24 </td></tr><tr><td> 5 c </td><td> AlCl 3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 62 </td></tr><tr><td> 6 d </td><td> AlCl 3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 66 </td></tr><tr><td> 7 e </td><td> AlCl 3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 60 </td></tr><tr><td> 8 </td><td> AlCl 3 </sub&gt; </td><td> 1 </td><td> THF </td><td> traccia </td></tr><tr><td> 9 </td><td> AlCl 3 </td><td> 1 </td><td> toluene </td><td> traccia </td></tr><tr><td> 10 </td><td> AlCl 3 </td><td> 2 </td><td> ClCH 2 CH 2 Cl </td><td> 33 </td></tr><tr><td> 11 </td><td> AlCl 3 </td><td> 1 </td><td> DMSO </td><td> traccia </td></tr><tr><td> 12 </td><td> AlCl 3 </td><td> 2 </td><td> acetonitrile </td><td> traccia </td></tr><tr><td> 13 </td><td> AlCl 3 · 6H 2 O </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 0 </td></tr><tr><td> 14 b </td><td> BCL 3 </td><td> 1.5 </td><td> CH 2 Cl 2 </td><td> 67 </td></tr><tr><td> 15 </td><td> BBr 3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 20 </td></tr></tbody></table><strong&gt; Tabella 1:. Ottimizzazione delle condizioni per la preparazione di ynone 1a un rendimento del prodotto 1a al variare delle condizioni di reazione e di catalizzatore acido di Lewis. A reazioni sono stati eseguiti con 1 equiv cloruro di benzoile e 1 equiv phenylacetylenetrifluoroborate potassio S1. B 1.5 equiv S1. C condizioni anidro. D La reazione è stata fatta in vetreria non essiccato sotto aria. E condizioni anidre + 1 ml di acqua.

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

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

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

Sintesi senza metallo di Ynones da Acyl Cloruri e Potassio Alkynyltrifluoroborate Sali

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

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

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

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

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

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

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 ...

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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

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

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

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

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 ...

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. Recently, we have developed a two-step strategy for ketone enolate umpolung that has enabled the development of methods for chlorination, azidation, and amination using azoles. In addition, we have developed C-C bond&#8211;forming arylation and allylation reactions. At the heart of these methods is the preparation of the intermediate and highly reactive enolonium species prior to addition of a reactive nucleophile. This strategy is thus reminiscent of the preparation and use of metal enolates in classical synthetic chemistry. This strategy allows the use of nucleophiles that would otherwise be incompatible with the strongly oxidizing hypervalent iodine reagents. In this paper we present a detailed protocol for chlorination, azidation, N-heteroarylation, arylation, and allylation. The products include motifs prevalent in medicinally active products. This article will greatly assist others in using these methods.

A two step one-pot protocol for the umpolung of ketone enolates to enolonium species and addition of a nucleophile to the &#945;-position is described. Nucleophiles include chloride, azide, azoles, allyl-silanes, and aromatic compounds.

Un protocollo in due fasi per Umpolung funzionalizzazione di chetoni Via Enolonium le specie

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. ...

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

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

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

Applicazione dei lantanidi elementari nell'attivazione selettiva di C-F di triflurometilate Benzofulvenes fornire accesso ai vari Difluoroalkenes

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

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

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

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

Chemoselective preparazione di 1-Iodoalkynes, 1,2-Diiodoalkenes e 1,1,2-Triiodoalkenes basato sull'iodurazione ossidativo degli alchini terminali

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

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals

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

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

Isolando gratis carbeni, loro misto dimeri e radicali organici

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

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

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

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

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 ...

Acidity of 1-Alkynes

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

Acidity of Terminal Alkynes: Formation of Acetylide Anions

Acidità degli alchini


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

Didattica

Chimica Organica

Unità 1

Alchini

TERMINI E CONCETTI CHIAVE

Preparation of Alkynes: Alkylation Reaction

<h4>Introduction</h4>
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
<img alt="Alkyne alkylation reaction using NaNH2 and ethyl bromide, chemical equation diagram." src="/files/ftp_upload/11834/11834_PT_Figure_1.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure1">
The reaction takes place in two steps:
1. The first step is the deprotonation of the terminal alkyne by the strong base forming an acetylide ion.
<img alt="Alkyne ionization reaction equation NaNH2, diagram shows acetylene converting to acetylide ion." src="/files/ftp_upload/11834/11834_PT_Figure_2.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure2">
2. The second step is a nucleophilic substitution reaction in which the acetylide ion reacts with the alkyl halide to form a new C–C bond.
<img alt="Organic reaction mechanism, Na+ and Br- ion exchange, illustrates chemical synthesis process." src="/files/ftp_upload/11834/11834_PT_Figure_3.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure3">
<h4>Reaction Mechanism —SN2 pathway </h4>
Acetylide ions are strong bases and can also function as good nucleophiles. The substitution reaction follows an SN2 pathway where the nucleophilic acetylide ion attacks the electrophilic carbon of the primary alkyl halide from the backside.
<img alt="Nucleophilic substitution reaction mechanism diagram with alkynes, NaBr formation, chemical process." src="/files/ftp_upload/11834/11834_PT_Figure_4.svg" style="text-align: center; height: 250px;" data-altupdatedat="1747908711000" data-alt="Figure4">
Since this is a concerted process, the nucleophilic attack and the departure of the leaving group takes place simultaneously to form the product with an inverted stereochemistry at the reaction center.
The reaction works best with unhindered alkyl halides like methyl halide and other primary halides. With secondary and tertiary alkyl halides, acetylide ions act as strong bases, in which case E2 elimination is the preferred pathway.
<h4>Application in organic synthesis </h4>
Alkylation of simple terminal alkynes is a useful method to extend the length of the carbon chain. Acetylene, a terminal alkyne, can be converted to a higher internal alkyne by repeated alkylation as shown below:
<img alt="Alkyne chain elongation via NaNH₂, CH₃Br; reaction equation diagram for organic synthesis." src="/files/ftp_upload/11834/11834_PT_Figure_5.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure5">

Preparazione degli alchini: reazione di alchilazione

Introduction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for ...

Preparation of Alkynes: Dehydrohalogenation

<h4>Introduction</h4>
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
<img alt="Chemical reaction diagram, alkyne synthesis, 2NaNH2/NH3, hydrogen elimination, organic chemistry." src="/files/ftp_upload/11835/11835_PT_Figure_1.svg" style="text-align: center; height: 200px;" data-altupdatedat="1747908711000" data-alt="Figure1">
<h4>Reaction Mechanism – E2 pathway</h4>
Vicinal dihalides
In the first elimination step, the strong base abstracts the proton from the dihalide that is oriented anti to the leaving group. Since E2 reactions follow a concerted pathway, the abstraction of a proton and departure of the halide leaving group occur simultaneously to form a haloalkene.
<img alt="Birch reduction mechanism diagram, showing electron flow in organic compound reaction." src="/files/ftp_upload/11835/11835_PT_Figure_2.svg" style="text-align: center; height: 90px;" data-altupdatedat="1747908711000" data-alt="Figure2">
In the second elimination reaction, another equivalent of the strong base reacts with the haloalkene in a similar fashion to give the desired alkyne.
<img alt="Elimination reaction mechanism diagram, E2 mechanism, showing alkene formation from alkyl halide." src="/files/ftp_upload/11835/11835_PT_Figure_3.svg" style="text-align: center; height: 90px;" data-altupdatedat="1747908711000" data-alt="Figure3">
Geminal dihalides
Likewise, geminal dihalides, when treated with two equivalents of a sodium amide, undergo double dehydrohalogenation to give alkynes.
<img alt="Alkyne formation reaction; sodium amide abstracting proton; chemical equation diagram; synthesis method." src="/files/ftp_upload/11835/11835_PT_Figure_4.svg" style="text-align: center; height: 90px;" data-altupdatedat="1747908711000" data-alt="Figure4">
<img alt="Chemical reaction mechanism, arrow-pushing diagram, alkyne formation using sodium amide." src="/files/ftp_upload/11835/11835_PT_Figure_5.svg" style="text-align: center; height: 90px;" data-altupdatedat="1747908711000" data-alt="Figure5">
Terminal dihalides 
Dehydrohalogenation of terminal dihalides yields terminal alkynes as the final product. In the presence of a strong base like sodium amide, terminal alkynes get converted to acetylide ions. In such cases, a third equivalent of the base is required to complete the dehydrohalogenation of the remaining haloalkene.
<img alt="Hofmann elimination reaction; chemical equations diagram; synthesis process using NaNH2; alkyne formation." src="/files/ftp_upload/11835/11835_PT_Figure_6.svg" style="text-align: center; height: 70px;" data-altupdatedat="1747908711000" data-alt="Figure6">
Protonation of the acetylide ions with water or an aqueous acid completes the reaction.
<img alt="Organic reaction mechanism with sodium acetylide, water; diagram illustrating nucleophilic attack." src="/files/ftp_upload/11835/11835_PT_Figure_7.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure7">
<h4>Application in Organic Synthesis</h4>
Dehydrohalogenation of vicinal dihalides is a useful intermediate step in the conversion of alkenes to alkynes. For example, chlorination of 1-propene gives 1,2-dichloropropane – a vicinal dihalide, which upon double dehydrohalogenation yields 1-propyne.
<img alt="Alkene to alkyne conversion diagram; chemical reaction mechanism, dichlorination, dehydrohalogenation." src="/files/ftp_upload/11835/11835_PT_Figure_8.svg" style="text-align: center; height: 60px;" data-altupdatedat="1747908711000" data-alt="Figure8">
Similarly, alkynes can also be synthesized from ketones via dehydrohalogenation of geminal dihalides. For example, treatment of acetone with phosphorous pentachloride yields 2,2-dichloropropane – a geminal dihalide, which undergoes double dehydrohalogenation to give 1-propyne.
<img alt="Organic synthesis mechanism; ketone to alkyne via substitution and elimination; chemical reaction diagram." src="/files/ftp_upload/11835/11835_PT_Figure_9.svg" style="text-align: center; height: 80px;" data-altupdatedat="1747908711000" data-alt="Figure9">

Preparazione degli alchini: deidroalogenazione

Introduction
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ...

Sintesi senza metallo di Ynones da Acyl Cloruri e Potassio Alkynyltrifluoroborate Sali

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Sintesi di hypervalent iodonio Alchinile triflati per l'applicazione di Generazione Cyanocarbenes

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