Name: real-time monitoring of reactions performed using continuous-flow processing: the preparation of 3-acetylcoumarin as an example
Uploaded: 2015-11-18T13:00:00.000+00:00
Duration: 9 min 56 s
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. 반응 모니터링에 적합한 신호를 찾기 <ol><li> 모든 출발 물질 및 제품에 대한 라만 스펙트럼을 얻습니다. </li><li> 스펙트럼 오버레이 및 제품에 고유 한 강렬한 밴드를 식별합니다. </li><li> 반응의 진행을 모니터하기 위해 라만 밴드를 사용한다. 1,608cm에서 밴드는 -1이 경우 선정되었다. </li></ol> 2. 플로우 셀을 설정 <ol><li> 적절한 흐름 세포를 얻습니다. 6.5 mm의 폭, 20mm의 높이 및 5mm (그림 2A)의 경로 길이 : 여기에 다음과 같은 치수 하나를 사용하십시오. </li><li> 외광이없는 환경을 제공하는 용기의 플로우 셀을 배치했다. </li><li> (이 경우 1mm ID PFA 튜브에서) 플로우 셀의 입구 및 출구에 배관을 연결한다. </li></ol> 3. 플로우 셀과 라만 분광계를 인터페이싱 <ol><li> C에 배치 될 수있는가요 성 광학 어셈블리와 적합한 라만 분광을 얻기플로우 셀에 근접을 잃는다. </li><li> 흐름 셀 어셈블리 (그림 2B)를 포함하는 상자에 적절한 크기의 구멍을 통해 광학 어셈블리를 놓습니다. </li><li> 는 흐름 세포에 닿을 때까지 광학 어셈블리를 밀어 후 1 ~ 2 mm의 간격을두고 다시 그것을 잡아 당깁니다. </li><li> 100 % 아세톤 흐름 셀을 채 웁니다. </li><li> 라만 분광기를 켜고 연속 스캔 모드에서 스펙트럼을 취득. </li><li> 부드럽게시 도광판을 분획을 이동시킴으로써 레이저 초점. 신호가 가장 큰 강도로하고 피크가 샤프하고 잘 정의 될 때까지 광 파이프를 이동하십시오. </li></ol><img alt="그림 2" src="/files/ftp_upload/52393/52393fig2.jpg" /> 그림 2. (A) 휴대 및 사용 (B) 라만 인터페이스 흐름. <a href="https://www.jove.com/files/ftp_upload/52393/52393fig2large.jpg" target="_blank">더 큰 VE를 보려면 여기를 클릭하십시오</a>이 그림의 rsion. 4. 시약 및 용매 솔루션을 준비 <ol><li> 50 ㎖ 용량 플라스크에 (6.106 50 밀리몰를 들어, 1 당량) 및 에틸 아세토 아세테이트 (6.507 g, 50 밀리몰, 1 당량) 살리 실을 추가합니다. </li><li> 50 ㎖의 전체 부피에 에틸 아세테이트를 추가 한 다음 내용물을 완전히 혼합한다. </li><li> 자기 교반 막대를 함유하는 20 mL 유리 바이알에 스톡 용액 10 ㎖ 분취 량을 전송. 이 유리 병 &quot;시약을.&quot;레이블 </li><li> 100 ㎖ 병 위의 에틸 아세테이트 90 mL에. &quot;용매&quot;이 병 레이블. 100 ㎖ 병 장소 아세톤 90 mL 중에. 이 병 &quot;용매 절편을&quot;레이블. </li></ol> 5. 흐름 장치를 준비 <ol><li> &quot;P1&quot;및 &quot;P2&quot;를 유동 장치는 적어도 두 개의 펌프가 있는지 확인하고 레이블을 붙입니다. 각 펌프에 대한 용매와 시약 입구 라인을 확인합니다. 두에 &quot;수집&quot;및 &quot;폐기물&quot;라인에서 출구 라인을 놓고 전ndividual 100 ㎖ 병은 각각 &quot;제품&quot;및 &quot;폐기물&quot;로 표시된. </li><li> 반응기로서, 가열 될 수있는 10 ㎖ 용량 PFA 코일을 사용한다. </li><li> PFA 반응기 코일의 입구에 튜브 종료 (P1)를 연결합니다. </li><li> 반응기 코일 후 3 포트 폴리 에테르 에테르 케톤 (PEEK) - 티 혼합기를 설치한다. </li><li> , 티 - 믹서 반응기 코일 출구 튜브에서 180 ° 튜브 종료 (P2)를 연결합니다. 티 - 믹서의 제 3 포트에 튜브의 조각을 연결합니다. 이 관의 타단에 배압 조절기를 배치했다. </li><li> 플로우 셀의 입력에 배압 조절기의 출력으로부터 라인을 연결한다. &quot;폐기물 / 수집&quot;스위치에 흐름 전지의 출력에서​​ 회선을 연결합니다. </li><li> 프라임 P1과 P2뿐만 아니라 용매 (P1)의 시약 라인 모두를위한 용매 라인. 시약 병에 용매 병에서 P1의 시약 라인을 이동합니다. </li><li> P1을 사용하여, 반응기를 에틸 아세테이트 합격2ml의 코일에 / 분이를 때까지 충전된다. 2 분 / 2 ml의 유속으로 P2를 통해 분 아세톤 합격. </li><li> 1 ml / 분에게 모두 P1 및 P2에 대한 용매 유량을 조정합니다. 7 bar의 압력을 배압 조절기를 설정한다. 원하는 온도까지 반응기 코일 온도를 설정한다. </li><li> 그림 3의 회로도와 같이 장비가 구성되어 두 번 확인합니다. </li><li> 시스템은 일정 온도 및 압력에 도달하면, 누출을 확인하고, 반응을 실행. </li></ol><img alt="그림 3" src="/files/ftp_upload/52393/52393fig3.jpg" /> 그림 반응 모니터링 실험에 사용되는 장비 구성 3. 도식. <a href="https://www.jove.com/files/ftp_upload/52393/52393fig3large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> 6. 반응을 모니터링 <ol><li> 탁에틸 아세테이트 / 아세톤 용매 계의 EA 백그라운드 스캔이 플로우 셀을 통과있다. 이것은 자동으로 모든 후속 검사에서 차감됩니다. </li><li> 스캔마다 15 초 걸릴 분광계 구성 (이 경우 라만 분광기는 10 초 적분 시간에 박스 카 = 3을 설정하고, 1 = 평균 하였다). </li><li> &quot;시약&quot;라는 레이블이 붙은 유리 병에 한 번에 (0.05 ㎖, 0.05 밀리몰, 0.1 당량) 피 페리 딘을 주입한다. </li><li> 철저히에서, 스위치 (P1)을 혼합 한 후 &quot;시약.&quot;할 수있는 출구 스트림 &quot;용매&quot;설정 &quot;을 수집합니다.&quot; </li><li> 모든 재료가 완전히 위로 &quot;시약&quot;에서, 스위치 (P1) &quot;용매를.&quot;로드 될 때 또 다른 30 ​​분 동안 원자로 코일을 통해 용매 흐르는 계속합니다. 이 시간이 경과되면, 난방을 끄십시오. </li><li> 원자로 코일 온도가 50 ° C 이하로 냉각되면 전원을 켜고은 P1과 P2 오프 펌프. </li></ol> 7. 데이터 분석 <ol&gt; <li> 1,608cm -1 대에서 스프레드 시트 플롯 라만 강도 라만 분광기 데이터를 내보낼 시간. </li><li> 조건을 최적화하기 위해, 반복적 인 방식으로 유량 및 반응기 온도의 숫자에서 반응을 수행한다. </li><li> 1,608cm -1 대에서 라만 강도의 오버레이 플롯 시간. 주 : 높은 라만 강도가 높은 제품 변환과 상관. </li></ol> 8. 최적화 된 조건을 사용하여 반응을 실행 <ol><li> 스크리닝 다양한 조건 (가변 유량 / 반응기 온도)을 갖는, 높은 변환 생성물을 수득하기 위해 최적화 된 조건을 이용하여 반응을 실행. </li></ol> 9. 제품을 분리 <ol><li> 제품 플라스크의 내용물을 얼음 100 ㎖ 및 2 M 염산 20 ㎖를 넣은 비커에 넣고, 그것을 붓는다. </li><li> 비이커에 에틸 아세테이트 (2 mL) 및 전사 최소량 상품 플라스크를 씻어. </li><li> 얼음 혼합물을 교반모든 얼음이 완전히 녹아 때까지. </li><li> 허쉬 깔때기, 사이드 암 플라스크, 고무 칼라 고무 진공 튜브의 길이와 여과 시스템을 설정합니다. </li><li> 진공 하에서 생성 된 침전물을 필터링 냉 디 에틸 에테르 (10 ㎖)로 세정하고 가열 램프 (2-3 시간) 또는 건식 O / N 진공하에 건조 할 수있다. </li><li> 용매로서 사용을 CDCl3 1 H 핵 자기 공명 (NMR) 분광법에 의한 생성물의 신원을 확인한다. 다음 500 MHz의 NMR 분광계를 들어, 3 acetylcoumarin의 1H NMR 데이터는 : δ = 2.73 (S, 3 H) 7.31-7.40 (m, 2 H) 7.65 (DDD, J = 7.53, 4.37, 2.60 Hz의 , 2 H) 8.51 (S, 1H) PPM, 13 C NMR 데이터 : δ = 30.84 (CH 3) 117.00 (CH) 118.56 (C) 124.86 (CH) 125.27 (CH) 130.51 (CH) 134.68 (C) 147.74 (CH) 155.64 (C) 159.52 (C) 195.77 (C) PPM. </li></ol>

<ol>
	<li>Wiles, C., Watts, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Micro Reaction Technology in Organic Synthesis. , (2011).</li><li>van den Broek, S. A. M. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continuous+Flow+Production+of+Thermally+Unstable+Intermediates+in+a+Microreactor+with+Inline+IR-Analysis:+Controlled+Vilsmeier&#8211;Haack+Formylation+of+Electron-Rich+Arenes.">Continuous Flow Production of Thermally Unstable Intermediates in a Microreactor with Inline IR-Analysis: Controlled Vilsmeier&#8211;Haack Formylation of Electron-Rich Arenes.</a> Org. Process Res. Dev. 16 (5), 934-938 (2012).</li><li>Baxendale, I. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+integration+of+flow+reactors+into+synthetic+organic+chemistry.">The integration of flow reactors into synthetic organic chemistry.</a> J. Chem. Technol. Biotechnol. 88 (4), 519-552 (2013).</li><li>Malet-Sanz, L., Susanne, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continuous+Flow+Synthesis.">Continuous Flow Synthesis.</a> A Pharma Perspective J. Med. Chem. 55 (9), 4062-4098 (2012).</li><li>Hartwig, J., Metternich, J. B., Nikzad, N., Kirschning, A., Ley, S. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continuous+flow+chemistry:+a+discovery+tool+for+new+chemical+reactivity+patterns.">Continuous flow chemistry: a discovery tool for new chemical reactivity patterns.</a> Org. Biomol. Chem. 12 (22), 3611-3615 (2014).</li><li>De Beer, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Near+infrared+and+Raman+spectroscopy+for+the+in-process+monitoring+of+pharmaceutical+production+processes.">Near infrared and Raman spectroscopy for the in-process monitoring of pharmaceutical production processes.</a> Int. J. Pharm. 417, 32-47 (2001).</li><li>McMullen, J. P., Jensen, K. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Integrated+microreactors+for+reaction+automation:+New+approaches+to+reaction+development.">Integrated microreactors for reaction automation: New approaches to reaction development.</a> Annu. Rev. Anal. Chem. 3, 19-42 (2010).</li><li>Moore, J. S., Jensen, K. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automated+multitrajectory+method+for+reaction+optimization+in+a+microfluidic+system+using+online+IR+analysis.">Automated multitrajectory method for reaction optimization in a microfluidic system using online IR analysis.</a> Org. Process Res. Dev. 16 (8), 1409-1415 (2012).</li><li>Carter, C. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ReactIR+Flow+Cell:+A+New+Analytical+Tool+for+Continuous+Flow+Chemical+Processing.">ReactIR Flow Cell: A New Analytical Tool for Continuous Flow Chemical Processing.</a> Org. Process Res. Dev. 14 (2), 393-404 (2010).</li><li>Ferstl, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inline+Analysis+in+Microreaction+Technology:+A+Suitable+Tool+for+Process+Screening+and+Optimization.">Inline Analysis in Microreaction Technology: A Suitable Tool for Process Screening and Optimization.</a> Chem. Eng. Technol. 30 (3), 370-378 (2007).</li><li>Benito-Lopez, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optical+fiber-based+on-line+UV/Vis+spectroscopic+monitoring+of+chemical+reaction+kinetics+under+high+pressure+in+a+capillary+microreactor.">Optical fiber-based on-line UV/Vis spectroscopic monitoring of chemical reaction kinetics under high pressure in a capillary microreactor.</a> Chem. Commun. (22), 2857-2859 (2005).</li><li>Gökay, O., Albert, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=From+single+to+multiple+microcoil+flow+probe+NMR+and+related+capillary+techniques:+a+review.">From single to multiple microcoil flow probe NMR and related capillary techniques: a review.</a> Anal. Bioanal. Chem. 402 (2), 647-669 (2012).</li><li>Jones, C. J., Larive, C. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Could+smaller+really+be+better?+Current+and+future+trends+in+high-resolution+microcoil+NMR+spectroscopy.">Could smaller really be better? Current and future trends in high-resolution microcoil NMR spectroscopy.</a> Anal. Bioanal. Chem. 402 (1), 61-68 (2012).</li><li>Mozharov, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+Method+for+Kinetic+Studies+in+Microreactors+Using+Flow+Manipulation+and+Noninvasive+Raman+Spectrometry.">Improved Method for Kinetic Studies in Microreactors Using Flow Manipulation and Noninvasive Raman Spectrometry.</a> J. Am. Chem. Soc. 133 (10), 3601-3608 (2011).</li><li>Chaplain, G., Haswell, S. J., Fletcher, P. D. I., Kelly, S. M., Mansfield, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+and+evaluation+of+a+Raman+flow+cell+for+monitoring+continuous+flow+reactions.">Development and evaluation of a Raman flow cell for monitoring continuous flow reactions.</a> Aust. J. Chem. 66 (2), 208-212 (2013).</li><li>Browne, D. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continuous+flow+reaction+monitoring+using+an+on-line+miniature+mass+spectrometer.">Continuous flow reaction monitoring using an on-line miniature mass spectrometer.</a> Rapid Comm. Mass. Spectrosc. 26 (17), (1999).</li><li>Koster, S., Verpoorte, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+decade+of+microfluidic+analysis+coupled+with+electrospray+mass+spectrometry:+An+overview.">A decade of microfluidic analysis coupled with electrospray mass spectrometry: An overview.</a> Lab Chip. 7 (11), 1394-1412 (2007).</li><li>Leadbeater, N. E., Schmink, J. R., Hamlin, T. A., de la Hoz, A., Loupy, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tools+for+Monitoring+Reactions+Performed+Using+Microwave+Heating.">Tools for Monitoring Reactions Performed Using Microwave Heating.</a> Microwaves in Organic Synthesis. 1, 327-376 (2012).</li><li>Leadbeater, N. E., Schmink, 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=Use+of+Raman+spectroscopy+as+a+tool+for+in+situ.+monitoring+of+microwave-promoted+reactions.">Use of Raman spectroscopy as a tool for in situ. monitoring of microwave-promoted reactions.</a> Nature Protoc. 3 (1), 1-7 (2008).</li><li>Schmink, J. R., Holcomb, J. L., Leadbeater, N. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Use+of+Raman+spectroscopy+as+an+In+Situ.+Tool+to+Obtain+Kinetic+Data+for+Organic+Transformations.">Use of Raman spectroscopy as an In Situ. Tool to Obtain Kinetic Data for Organic Transformations.</a> Chem. Eur. J. 14 (32), 9943-9950 (2008).</li><li>Hamlin, T. A., Leadbeater, N. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Raman+spectroscopy+as+a+tool+for+monitoring+mesoscale+continuous-flow+organic+synthesis:+Equipment+interface+and+assessment+in+four+medicinally-relevant+reactions.">Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions.</a> Beilstein J. Org. Chem. 9, 1843-1852 (2013).</li><li>Kelly, C. B., Lee, C., Leadbeater, N. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+approach+for+continuous-flow+processing+of+reactions+that+involve+the+in+situ.+formation+of+organic+products.">An approach for continuous-flow processing of reactions that involve the in situ. formation of organic products.</a> Tetrahedron Lett. 52 (2), 263-265 (2011).</li><li>Wren, S. N., Donaldson, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glancing-angle+Raman+spectroscopic+probe+for+reaction+kinetics+at+water+surfaces.">Glancing-angle Raman spectroscopic probe for reaction kinetics at water surfaces.</a> Phys. Chem. Chem. Phys. 12, 2648-2654 (2010).</li><li>Leadbeater, N. E., Smith, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Real-Time+Monitoring+of+Microwave-Promoted+Suzuki+Coupling+Reactions+Using+in+Situ.+Raman+Spectroscopy.">Real-Time Monitoring of Microwave-Promoted Suzuki Coupling Reactions Using in Situ. Raman Spectroscopy.</a> Org. Lett. 8 (20), 4589-4591 (2006).</li></ol>

The authors have nothing to disclose.

라만 분광기는 유동 장치와 인터페이스 할 수있는 용이성 반응 모니터링에 유용한이 인라인 기술한다. 반응 변수의 수는 사용자가 빠른 오프라인 방법을 사용할 때보다 최적의 반응 조건에 도달 할 수 있도록 신속하게 탐색 할 수있다. 또한 본원에 설명 된 기술의 애플리케이션은 적합한 대역이 발견 될 수있다 가정하면, 부 생성물의 형성을 모니터링 할 수있다. 조건은 또한 불순물의 양이 낮은 ...

연속 흐름 처리를 사용함으로써, 화학자들은 안전하게 효과적으로 용이성 1,2-로 화학 반응을 수행 할 수있는 범위에 있음을 발견하고있다. 그 결과, 흐름 화학 장비는 교육 기관에서 산업 설정에 모두 반응뿐만 아니라 연구소를 실행하기위한 필수적인 도구가되고있다. 합성 화학 변환의 다양한 유동 반응기는 3,4-에서 수행되었다. 선택의 경우, 일괄 적으로 동작하지 않는 반응은 연속 흐름 조건 하에서 5 순조롭게 진행하는 것으로 나타났다. 반응 최적화 및 품질 제어 모두, 인라인 반응물 흐름 프로세싱 모니터링 혼입은 상당한 이점을 제공한다. 인라인 모니터링 실제 샘플 조건에 실시간 응답에 연속 분석을 제공한다. 이 빠르며, 유사한 오프라인 기술보다 어떤 경우에는,보다 신뢰성. 인 - 라인 분석 기법의 수는 F와 인터페이스 된낮은 원자로 7. 예를 들면 적외선 등이 8,9, UV-NMR 가시 12,13, 14,15 라만 분광법 및 질량 분석법 16,17, 10,11. 우리의 연구 그룹은 과학적 마이크로파 (18)와 라만 분광기 인터페이싱있다. 이 사용의 반응 범위는 모두 19 질적 및 양적 20 관점에서 모니터링 하였다. 이러한 성공을 바탕으로, 우리는 최근 지속적인 흐름 단위 중 하나로 우리 라만 분광 인터페이스와 키 의약 관련 유기 변형 다수의 인라인 반응 모니터링을 채용 하였다. (21)가 모니터링 할 수 있었다 각 경우에 반응과 같은 일 예시에서, 검량선을 이용하여, 우리는 라만 분광 데이터로부터 제품 전환을 결정할 수있다. 여기에서 우리는 장치를 설치하고 반응을 모니터하는 데 사용하는 방법을 설명한다. 우리는 3-AC의 피 페리 딘 촉매 합성을 사용etylcoumarin (1) 여기에 모델 반응으로 에틸 아세토 아세테이트 (그림 1)과 살리 실에서. <img alt="그림 1" src="/files/ftp_upload/52393/52393fig1.jpg" /> 그림 1. 자료 (1). 3 acetylcoumarin을 얻었다 살리 실 알데히드와 에틸 아세토 아세테이트 사이의 축합 반응을 촉매 <a href="https://www.jove.com/files/ftp_upload/52393/52393fig1large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a>

<table><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, &gt;99.7%</td></tr><tr><td>Acetone</td><td>Sigma-Aldrich</td><td>650501</td><td>CHROMASOLV, for HPLC, &gt;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

인라인 모니터링을 이용하여, 간단하고 신속하게 연속 흐름 처리를 수행하여 반응을 최적화하는 것이 가능하다. 그것은이 기술을 이용하여 시간에 걸쳐 일관된 제품 품질을 보장​​하는 것도 가능하다. 우리는 여기에 라만 분광기로 시판 흐름 장치를 인터페이스하는 방법을 보여줍니다. 라만 플로우 셀은 대기압에서 작동 될 수 있음을 의미 배압 조절기 뒤에 배치된다. 또한, 상기 생성물 스트림은 플로우 셀에 들어가기 전에 튜빙의 길이를 통과한다는 사실 재료 RT에 있다는 것을 의미한다. 이는 라만 신호 강도는 온도에 의존하기 때문에 스펙트럼 등온 조건 하에서 획득하는 것이 중요하다. 장치를 조립하는 데, 우리는 다음의 화학 반응을 모니터링하는 방법을 보여, 살리 실 알데히드, 에틸 아세토 아세테이트로부터 3 acetylcoumarin 피 페리 딘의 합성 촉매는 예로서 사용된다. 흐름 속도를 반응물 범위에서 수행 될 수있다D 온도, 인 시츄 모니터링 도구는 간단하고 용이하게 조건을 최적화하기 위해 사용된다.

3 acetylcoumarin의 연속 흐름 준비가 인라인 모니터링을위한 대표적인 반응으로 선택되었다. 용매로서 아세트산 에틸을 사용할 때 일괄 적으로, 반응이 충분히 진행한다. 그러나, 제품 (1)을 실온에서 완전히 용해되지. 배압 조절기의 전위 막힘을 방지뿐만 아니라, 신호 포착을 교란 할 플로우 셀에 고체 입자를 갖는 위험을 완화하기 위해, 우리는 우리가 다른 반응 (22)에 대해 이?...

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

실시간 모니터링은 연속 흐름 처리를 수행하여 빠른 반응의 최적화를 허용한다. 여기 -3- acetylcoumarin의 제조는 예로서 사용된다. 반응을 최적화하는데 필요한 단계는 다음과 같이 인 시츄 라만 모니터링을 수행하기위한 장치가 설명된다.

연속 흐름 처리를 사용하여 수행 반응의 실시간 모니터링 : 예를 들어 3 Acetylcoumarin의 제조

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 ...

real-time-monitoring-reactions-performed-using-continuous-flow

Research

JoVE Journal

Chemistry

9.7K 조회수.  University of Connecticut.  실시간 모니터링은 연속 흐름 처리를 수행하여 빠른 반응의 최적화를 허용한다. 여기 -3- acetylcoumarin의 제조는 예로서 사용된다. 반응을 최적화하는데 필요한 단계는 다음과 같이 인 시츄 라만 모니터링을 수행하기위한 장치가 설명된다. 

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

Microfluidic On-chip Capture-cycloaddition Reaction to Reversibly Immobilize Small Molecules or Multi-component Structures for Biosensor Applications

Methods for rapid surface immobilization of bioactive small molecules with control over orientation and immobilization density are highly desirable for biosensor and microarray applications. In this Study, we use a highly efficient covalent bioorthogonal [4+2] cycloaddition reaction between trans-cyclooctene (TCO) and 1,2,4,5-tetrazine (Tz) to enable the microfluidic immobilization of TCO/Tz-derivatized molecules. We monitor the process in real-time under continuous flow conditions using surface plasmon resonance (SPR). To enable reversible immobilization and extend the experimental range of the sensor surface, we combine a non-covalent antigen-antibody capture component with the cycloaddition reaction. By alternately presenting TCO or Tz moieties to the sensor surface, multiple capture-cycloaddition processes are now possible on one sensor surface for on-chip assembly and interaction studies of a variety of multi-component structures. We illustrate this method with two different immobilization experiments on a biosensor chip; a small molecule, AP1497 that binds FK506-binding protein 12 (FKBP12); and the same small molecule as part of an immobilized and in situ-functionalized nanoparticle.

We present a method for rapid, reversible immobilization of small molecules and functionalized nanoparticle assemblies for Surface Plasmon Resonance (SPR) studies, using sequential on-chip bioorthogonal cycloaddition chemistry and antibody-antigen capture.

역으로 작은 분자 또는 바이오 센서 애플리케이션을위한 다중 구성 요소 구조를 무력화하는 미세 유체 온칩 캡처 - 고리 화 반응

Methods  for rapid surface immobilization of bioactive small molecules with control over  orientation and immobilization density are highly desirable for ...

연구

화학

Monitoring the Reductive and Oxidative Half-Reactions of a Flavin-Dependent Monooxygenase using Stopped-Flow Spectrophotometry

Aspergillus fumigatus siderophore A (SidA) is an FAD-containing monooxygenase that catalyzes the hydroxylation of ornithine in the biosynthesis of hydroxamate siderophores that are essential for virulence (e.g. ferricrocin or N',N",N'''-triacetylfusarinine C)1. The reaction catalyzed by SidA can be divided into reductive and oxidative half-reactions (Scheme 1). In the reductive half-reaction, the oxidized FAD bound to Af SidA, is reduced by NADPH2,3. In the oxidative half-reaction, the reduced cofactor reacts with molecular oxygen to form a C4a-hydroperoxyflavin intermediate, which transfers an oxygen atom to ornithine. Here, we describe a procedure to measure the rates and detect the different spectral forms of SidA using a stopped-flow instrument installed in an anaerobic glove box. In the stopped-flow instrument, small volumes of reactants are rapidly mixed, and after the flow is stopped by the stop syringe (Figure 1), the spectral changes of the solution placed in the observation cell are recorded over time. In the first part of the experiment, we show how we can use the stopped-flow instrument in single mode, where the anaerobic reduction of the flavin in Af SidA by NADPH is directly measured. We then use double mixing settings where Af SidA is first anaerobically reduced by NADPH for a designated period of time in an aging loop, and then reacted with molecular oxygen in the observation cell (Figure 1). In order to perform this experiment, anaerobic buffers are necessary because when only the reductive half-reaction is monitored, any oxygen in the solutions will react with the reduced flavin cofactor and form a C4a-hydroperoxyflavin intermediate that will ultimately decay back into the oxidized flavin. This would not allow the user to accurately measure rates of reduction since there would be complete turnover of the enzyme. When the oxidative half-reaction is being studied the enzyme must be reduced in the absence of oxygen so that just the steps between reduction and oxidation are observed. One of the buffers used in this experiment is oxygen saturated so that we can study the oxidative half-reaction at higher concentrations of oxygen. These are often the procedures carried out when studying either the reductive or oxidative half-reactions with flavin-containing monooxygenases. The time scale of the pre-steady-state experiments performed with the stopped-flow is milliseconds to seconds, which allow the determination of intrinsic rate constants and the detection and identification of intermediates in the reaction4. The procedures described here can be applied to other flavin-dependent monooxygenases.5,6

We describe the use of a stopped-flow instrument to investigate both the reductive and oxidative half-reactions of Aspergillus fumigatus siderophore A (SidA), a flavin-dependent monooxygenase. We then show the spectra corresponding to the species in the reaction of SidA and we calculate the rate constants for their formation.

중단 - 흐름 분광 광도법을 사용하여 플라빈 종속 Monooxygenase의 Reductive 및 산화 반쪽 반응을 모니터링

Aspergillus fumigatus siderophore A (SidA) is an FAD-containing monooxygenase that catalyzes the hydroxylation of ornithine in the biosynthesis of ...

생체공학

Millifluidics for Chemical Synthesis and Time-resolved Mechanistic Studies

Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the first, synthesis of ultra-small copper nanoclusters is described. The second example provides their utility for investigating time resolved kinetics of chemical reactions by analyzing gold nanoparticle formation using in situ X-ray absorption spectroscopy. The final example demonstrates continuous flow catalysis of reactions inside millifluidic channel coated with nanostructured catalyst.

Millifluidic devices are utilized for controlled synthesis of nanomaterials, time-resolved analysis of reaction mechanisms and continuous flow catalysis.

화학 합성 및 시간 - 해결 기계론의 연구 Millifluidics

Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the ...

Temperature-programmed Deoxygenation of Acetic Acid on Molybdenum Carbide Catalysts

Temperature programmed reaction (TPRxn) is a simple yet powerful tool for screening solid catalyst performance at a variety of conditions. A TPRxn system includes a reactor, furnace, gas and vapor sources, flow control, instrumentation to quantify reaction products (e.g., gas chromatograph), and instrumentation to monitor the reaction in real time (e.g., mass spectrometer). Here, we apply the TPRxn methodology to study molybdenum carbide catalysts for the deoxygenation of acetic acid, an important reaction among many in the upgrading/stabilization of biomass pyrolysis vapors. TPRxn is used to evaluate catalyst activity and selectivity and to test hypothetical reaction pathways (e.g., decarbonylation, ketonization, and hydrogenation). The results of the TPRxn study of acetic acid deoxygenation show that molybdenum carbide is an active catalyst for this reaction at temperatures above ca. 300 &#176;C and that the reaction favors deoxygenation (i.e., C-O bond-breaking) products at temperatures below ca. 400 &#176;C and decarbonylation (i.e., C-C bond-breaking) products at temperatures above ca. 400 &#176;C.

Presented here is a protocol for the operation of a micro-scale temperature-programmed reactor for evaluating the catalytic performance of molybdenum carbide during acetic acid deoxygenation.

몰리브덴 초경 촉매에 초산의 온도 프로그램 탈산 소화

Temperature programmed reaction (TPRxn) is a simple yet powerful tool for screening solid catalyst performance at a variety of conditions. A TPRxn system ...

Optimization of the Ugi Reaction Using Parallel Synthesis and Automated Liquid Handling

The optimization of a Ugi reaction involving the mixing of furfurylamine, benzaldehyde, boc-glycine and t-butylisocyanide is described. Triplicate runs of 48 parallel experiments are reported, varying concentration, solvent and the excess of some of the reagents. The isolation of the product was achieved by a simple filtration and wash procedure. The highest yield obtained was 66% from 0.4 M methanol with 1.2 eq. of imine. This is significantly above the 49% yield obtained from the initial reaction under equimolar concentration at 0.4 M in methanol. Methanol solutions with reagent concentrations of 0.4M or 0.2M gave superior yields while all solvent systems at 0.07M performed poorly. At 0.2M, methanol and ethanol/methanol (60/40) mixtures were statistically equally good while THF/methanol (60/40) was poor and acetonitrile/methanol (60/40) was intermediate. Good reproducibility of the precipitate yields was obtained in these replicate experiments, allowing for subtle interaction effects to be positively identified.

The Ugi reaction has proved to be a convenient way to quickly create diverse libraries of compounds. It involves the reaction of an amine, an aldehyde, a carboxylic acid and an isonitrile typically in methanol at room temperature. In this video, we utilize a 48-slot Mettler-Toledo MiniBlock equipped with filtration tubes and a Mettler-Toledo MiniMapper automated liquid handler was used to deliver the reagents and solvent. The parameters of interest were the concentration, the solvent composition and the excess of some of the reagents.

병렬 합성 및 자동 액체 처리를 사용하여 Ugi 반응의 최적화

The optimization of a Ugi reaction involving the mixing of furfurylamine, benzaldehyde, boc-glycine and t-butylisocyanide is described.  Triplicate runs ...

생물학

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

Continuous flow technology has been identified as instrumental for its environmental and economic advantages leveraging superior mixing, heat transfer and cost savings through the &#34;scaling out&#34; strategy as opposed to the traditional &#34;scaling up&#34;. Herein, we report the reaction of diphenyldiazomethane with p-nitrobenzoic acid in both batch and flow modes. To effectively transfer the reaction from batch to flow mode, it is essential to first conduct the reaction in batch. As a consequence, the reaction of diphenyldiazomethane was first studied in batch as a function of temperature, reaction time, and concentration to obtain kinetic information and process parameters. The glass flow reactor set-up is described and combines two types of reaction modules with &#34;mixing&#34; and &#34;linear&#34; microstructures. Finally, the reaction of diphenyldiazomethane with p-nitrobenzoic acid was successfully conducted in the flow reactor, with up to 95% conversion of the diphenyldiazomethane in 11 min. This proof of concept reaction aims to provide insight for scientists to consider flow technology&#39;s competitiveness, sustainability, and versatility in their research.

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

Flow chemistry carries environmental and economic advantages by leveraging superior mixing, heat transfer and cost benefits. Herein, we provide a blueprint to transfer chemical processes from batch to flow mode. The reaction of diphenyldiazomethane (DDM) with p-nitrobenzoic acid, conducted in batch and flow, was chosen for proof of concept.

P-Nitrobenzoic 산 Diphenyldiazomethane의 연속 흐름 화학: 반응

Continuous flow technology has been identified as instrumental for its environmental and economic advantages leveraging superior mixing, heat transfer and ...

Biosynthesis of a Flavonol from a Flavanone by Establishing a One-pot Bienzymatic Cascade

Flavonols are a major subclass of flavonoids with a variety of biological and pharmacological activities. Here, we provide a method for the in vitro enzymatic synthesis of a flavonol. In this method, Atf3h and Atfls1, two key genes in the biosynthetic pathway of the flavonols, are cloned and overexpressed in Escherichia coli. The recombinant enzymes are purified via an affinity column and then a bienzymatic cascade is established in a specific synthetic buffer. Two flavonols are synthesized in this system as examples and determined by TLC and HPLC/LC/MS analyses. The method displays obvious advantages in the derivation of flavonols over other approaches. It is time- and labor-saving and highly cost-effective. The reaction is easy to be accurately controlled and thus scaled up for mass production. The target product can be purified easily due to the simple components in the system. However, this system is usually restricted to the production of a flavonol from a flavanone.

The derivation of a flavonol is crucial for its application in healthcare and the food industry. Here, we provide a detailed protocol for the biosynthesis of a flavonol from a flavanone and discuss the crucial steps and its advantages over other approaches.

플라바놀에서 플라보놀의 생합성은 원팟 비엔자이매틱 캐스케이드를 확립하여

Flavonols are a major subclass of flavonoids with a variety of biological and pharmacological activities. Here, we provide a method for the in vitro ...

생화학

Utilization of Stop-flow Micro-tubing Reactors for the Development of Organic Transformations

A new reaction screening technology for organic synthesis was recently demonstrated by combining elements from both continuous micro-flow and conventional batch reactors, coined stop-flow micro-tubing (SFMT) reactors. In SFMT, chemical reactions that require high pressure can be screened in parallel through a safer and convenient way. Cross-contamination, which is a common problem in reaction screening for continuous flow reactors, is avoided in SFMT. Moreover, the commercially available light-permeable micro-tubing can be incorporated into SFMT, serving as an excellent choice for light-mediated reactions due to a more effective uniform light exposure, compared to batch reactors. Overall, the SFMT reactor system is similar to continuous flow reactors and more superior than batch reactors for reactions that incorporate gas reagents and/or require light-illumination, which enables a simple but highly efficient reaction screening system. Furthermore, any successfully developed reaction in the SFMT reactor system can be conveniently translated to continuous-flow synthesis for large scale production.

A protocol for organic reaction screening using stop-flow micro-tubing (SFMT) reactors employing gaseous reactants and/or visible-light mediated reactions is presented.

유기 변환의 개발에 대 한 중지 흐름 마이크로 튜브 원자로의 활용

A new reaction screening technology for organic synthesis was recently demonstrated by combining elements from both continuous micro-flow and conventional ...

A Modular Microfluidic Technology for Systematic Studies of Colloidal Semiconductor Nanocrystals

Colloidal semiconductor nanocrystals, known as quantum dots (QDs), are a rapidly growing class of materials in commercial electronics, such as light emitting diodes (LEDs) and photovoltaics (PVs). Among this material group, inorganic/organic perovskites have demonstrated significant improvement and potential towards high-efficiency, low-cost PV fabrication due to their high charge carrier mobilities and lifetimes. Despite the opportunities for perovskite QDs in large-scale PV and LED applications, the lack of fundamental and comprehensive understanding of their growth pathways has inhibited their adaptation within continuous nanomanufacturing strategies. Traditional flask-based screening approaches are generally expensive, labor-intensive, and imprecise for effectively characterizing the broad parameter space and synthesis variety relevant to colloidal QD reactions. In this work, a fully autonomous microfluidic platform is developed to systematically study the large parameter space associated with the colloidal synthesis of nanocrystals in a continuous flow format. Through the application of a novel translating three-port flow cell and modular reactor extension units, the system may rapidly collect fluorescence and absorption spectra across reactor lengths ranging 3 - 196 cm. The adjustable reactor length not only decouples the residence time from the velocity-dependent mass transfer, it also substantially improves the sampling rates and chemical consumption due to the characterization of 40 unique spectra within a single equilibrated system. Sample rates may reach up to 30,000 unique spectra per day, and the conditions cover 4 orders of magnitude in residence times ranging 100 ms - 17 min. Further applications of this system would substantially improve the rate and precision of the material discovery and screening in future studies. Detailed within this report are the system materials and assembly protocols with a general description of the automated sampling software and offline data processing.

Detailed herein are the operation and assembly protocols of a modular microfluidic screening platform for the systematic characterization of colloidal semiconductor nanocrystal syntheses. Through fully adjustable system arrangements, highly efficient spectra collection may be carried out across 4 orders of magnitude reaction time scales within a mass transfer-controlled sampling space.

콜 로이드 반도체 나노의 체계적인 연구를 위한 모듈형 미세 기술

Colloidal semiconductor nanocrystals, known as quantum dots (QDs), are a rapidly growing class of materials in commercial electronics, such as light ...

공학

A Continuous-flow Photocatalytic Reactor for the Precisely Controlled Deposition of Metallic Nanoparticles

In this work, a novel photocatalytic reactor for the pulsed and controlled excitation of the photocatalyst and the precise deposition of metallic nanoparticles is developed. Guidelines for the replication of the reactor and its operation are provided in detail. Three different composite systems (Pt/graphene, Pt/TiO2, and Au/TiO2) with monodisperse and uniformly distributed particles are produced by this reactor, and the photodeposition mechanism, as well as the synthesis optimization strategy, are discussed. The synthesis methods and their technical aspects are described comprehensively. The role of the ultraviolet (UV) dose (in each excitation pulse) on the photodeposition process is investigated and the optimum values for each composite system are provided.

For a continuous and scalable synthesis of noble-metal-based nanocomposites, a novel photocatalytic reactor is developed and its structure, operation principles, and product quality optimization strategies are described.