Name: real-time monitoring of reactions performed using continuous-flow processing: the preparation of 3-acetylcoumarin as an example
Uploaded: 2015-11-18T13:00:00
Description: Watch this Scientific Journal Video about Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example at JoVE.com

Financial support provided by National Science Foundation (CAREER award CHE-0847262. We thank Vapourtec Ltd and Enwave Optronics for equipment support, and Daniel Daleb of the University of Connecticut for his assistance in construction of the flow cell apparatus.

1. Find Egnede Signaler for reaktion Overvågning <ol><li> Opnå Raman spektre for alle udgangsmaterialer og produktet. </li><li> Overlay spektre og identificere en intenst bånd der er unik for produktet. </li><li> Brug denne Raman band til at overvåge forløbet af reaktionen. Et bånd ved 1.608 cm-1 blev udvalgt i dette tilfælde. </li></ol> 2. Opsæt Flow Cell <ol><li> Opnåelse af en passende flow-celle. Her bruger en med følgende dimensioner: bredde på 6,5 mm, højde på 20...

<ol>
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Den lethed, hvor Raman spektrometer kan være forbundet med luftmængdeenheden gør denne inline teknik værdifulde til omsætning overvågning. En række reaktionsbetingelser variabler kan probes i en fremskyndet måde, så brugeren kan nå frem til optimerede reaktionsbetingelser hurtigere end ved brug offline metoder. Anvendelse af teknikkerne beskrevet heri, også er muligt at overvåge dannelsen af ​​biprodukter, under forudsætning af en passende bånd kan findes. Betingelser kan screenes og udvælges, som gø...

Ved at bruge kontinuerlig flow behandling, er kemikere konstateringen af, at de kan udføre en række kemiske reaktioner sikkert, effektivt og med lethed 1,2. Som følge heraf er flow kemi udstyr blive en integreret værktøj til at køre reaktioner både i industrielle indstillinger samt forskningslaboratorier i akademiske institutioner. En lang række syntetiske kemi transformationer er blevet udført i flow reaktorer 3,4. I udvalgte tilfælde har reaktioner, der ikke fungerer i batch vist sig at forløbe glat under kontinuerlig strømning 5. For både reaktionen optimering og kvalitetskontrol, inkorporering af in-line reaktionen overvågning med flow forarbejdning giver betydelige fordele. In-line overvågning giver kontinuerlig analyse med real-time reaktion på faktiske prøve forhold. Det er hurtigere og, i nogle tilfælde, mere pålidelig end sammenlignelige off-line teknikker. En række in-line analyseteknikker er blevet sammenkoblet med flave reaktorer 7. Eksempler omfatter infrarød 8,9, UV-synlige 10,11, NMR 12,13, Raman spektroskopi 14,15, og massespektrometri 16,17. Vores forskergruppe har grænseflader en Raman spektrometer med en videnskabelig mikrobølgeenhed 18. Ved hjælp af denne, har en række reaktioner blevet overvåget fra både et kvalitativt 19 og kvantitativ 20 synspunkt. Med udgangspunkt i denne succes, har vi for nylig grænseflader vores Raman spektrometer med en af vores kontinuerlig gennemstrømning enheder og ansat den til in-line reaktion overvågning af en række centrale medicinsk relevante organiske transformationer. 21 I hvert tilfælde var det muligt at overvåge reaktioner og også i et eksempel ved hjælp af en kalibreringskurve, kunne vi bestemme produktets konvertering fra Raman spektrale data. I Her beskriver vi, hvordan du opsætter apparatet og bruge det til at overvåge reaktioner. Vi bruger piperidin-katalyserede syntese af 3-acetylcoumarin (1) fra salicylaldehyd med ethylacetoacetat (figur 1) som model reaktionen her. <img alt="Figur 1" src="/files/ftp_upload/52393/52393fig1.jpg" /> Figur 1. Base katalyseret kondensationsreaktion mellem salicylaldehyd og ethylacetoacetat at give 3 acetylcoumarin (1). <a href="https://www.jove.com/files/ftp_upload/52393/52393fig1large.jpg" target="_blank">Klik her for at se en større version af dette tal.</a>

<table border="0">
	<tbody>
		<tr>
			<td>Salicylaldehyde</td>
			<td>Sigma-Aldrich</td>
			<td>S356</td>
			<td>Reagent Grade, 98%</td>
		</tr>
		<tr>
			<td>Ethyl acetoacetate</td>
			<td>Acros Organics</td>
			<td>117970010</td>
			<td>99%</td>
		</tr>
		<tr>
			<td>Piperidine</td>
			<td>Sigma-Aldrich</td>
			<td>104094</td>
			<td>Reagent Plus, 99%</td>
		</tr>
		<tr>
			<td>Hydrochloric acid</td>
			<td>Sigma-Aldrich</td>
			<td>320331</td>
			<td>ACS Reagent, 37%</td>
		</tr>
		<tr>
			<td>Ethyl acetate</td>
			<td>Sigma-Aldrich</td>
			<td>34858</td>
			<td>CHROMASOLV, for HPLC, &#62;99.7%</td>
		</tr>
		<tr>
			<td>Acetone</td>
			<td>Sigma-Aldrich</td>
			<td>650501</td>
			<td>CHROMASOLV, for HPLC, &#62;99.9%</td>
		</tr>
		<tr>
			<td>Flow cell</td>
			<td>Starna Cells</td>
			<td></td>
			<td>583.65.65-Q-5/Z20</td>
		</tr>
		<tr>
			<td>Flow unit</td>
			<td>Vapourtec</td>
			<td></td>
			<td>E-series system</td>
		</tr>
		<tr>
			<td>Raman spectrometer</td>
			<td>Enwave Optronics Inc</td>
			<td></td>
			<td>Model EZRaman-L</td>
		</tr>
	</tbody>
</table>

real-time monitoring of reactions performed using continuous-flow processing: the preparation of 3-acetylcoumarin as an example

Ved at bruge inline overvågning, er det muligt at optimere reaktioner udført med kontinuerlig strømning forarbejdning i en enkel og hurtig måde. Det er også muligt at sikre en ensartet produktkvalitet over tid ved hjælp af denne teknik. Vi viser her hvordan interface en kommercielt tilgængelig flow enhed med en Raman-spektrometer. Raman flow Cellen anbringes efter modtryksregulator, hvilket betyder, at den kan betjenes ved atmosfærisk tryk. Desuden kan den omstændighed, at strømmen af ​​produkt passerer gennem en slangelængde før indtastning strømningscellen betyder, at materialet er ved stuetemperatur. Det er vigtigt, at spektrene er erhvervet under isotermiske betingelser, da Raman signalintensitet er temperaturafhængig. Efter at have samlet apparatet, så viser vi, hvordan at overvåge en kemisk reaktion, idet piperidin-katalyserede syntese af 3-acetylcoumarin fra salicylaldehyd og ethylacetoacetat brugt som et eksempel. Reaktionen kan udføres over et område af strømningshastigheder end temperaturer, in-situ overvågning værktøj, der bruges til at optimere betingelserne enkelt og nemt.

Fremstillingen af ​​3-acetylcoumarin med kontinuerlig strømning blev valgt som en repræsentativ reaktion til in-line overvågning. I batch, forløber reaktionen godt, når anvendelse af ethylacetat som opløsningsmiddel. Men produktet (1) ikke er fuldstændig opløseligt ved stuetemperatur. For at forhindre potentiel tilstopning af modtryksregulator, samt mindske risikoen for at faste partikler i strømmen celle, som ville forstyrre signal erhvervelse, brugte vi en teknik, som vi udviklet tidliger...

Watch this Scientific Journal Video about Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example at JoVE.com

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

Tidstro overvågning muliggør hurtig optimering af reaktioner udført med kontinuerlig strømning behandling. Her fremstilling af 3-acetylcoumarin anvendes som et eksempel. Apparatet til at udføre in-situ Raman overvågning beskrives, ligesom de trin, der kræves for at optimere reaktionen.

Real-time overvågning af reaktioner udført Brug af kontinuerlig flow Behandler: fremstilling af 3-acetylcoumarin som et eksempel

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

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