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 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

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

9.6K 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

Rapid High-throughput Species Identification of Botanical Material Using Direct Analysis in Real Time High Resolution Mass Spectrometry

We demonstrate that direct analysis in real time-high resolution mass spectrometry can be used to produce mass spectral profiles of botanical material, and that these chemical fingerprints can be used for plant species identification. The mass spectral data can be acquired rapidly and in a high throughput manner without the need for sample extraction, derivatization or pH adjustment steps. The use of this technique bypasses challenges presented by more conventional techniques including lengthy chromatography analysis times and resource intensive methods. The high throughput capabilities of the direct analysis in real time-high resolution mass spectrometry protocol, coupled with multivariate statistical analysis processing of the data, provide not only class characterization of plants, but also yield species and varietal information. Here, the technique is demonstrated with two psychoactive plant products, Mitragyna speciosa (Kratom) and Datura (Jimsonweed), which were subjected to direct analysis in real time-high resolution mass spectrometry followed by statistical analysis processing of the mass spectral data. The application of these tools in tandem enabled the plant materials to be rapidly identified at the level of variety and species.

A method for species identification of botanical material by direct analysis in real time-high resolution mass spectrometry and multivariate statistical analysis is presented.

실시간 고해상도 질량 분석에 직접 분석을 사용하여 식물 소재의 신속한 높은 처리량 종 확인

We demonstrate that direct analysis in real time-high resolution mass spectrometry can be used to produce mass spectral profiles of botanical material, ...

연구

화학

Capillary Electrophoresis to Monitor Peptide Grafting onto Chitosan Films in Real Time

Free-solution capillary electrophoresis (CE) separates analytes, generally charged compounds in solution through the application of an electric field. Compared to other analytical separation techniques, such as chromatography, CE is cheap, robust and effectively requires no sample preparation (for a number of complex natural matrices or polymeric samples). CE is fast and can be used to follow the evolution of mixtures in real time (e.g., chemical reaction kinetics), as the signals observed for the separated compounds are directly proportional to their quantity in solution.
Here, the efficiency of CE is demonstrated for monitoring the covalent grafting of peptides onto chitosan films for subsequent biomedical applications. Chitosan&#39;s antimicrobial and biocompatible properties make it an attractive material for biomedical applications such as cell growth substrates. Covalently grafting the peptide RGDS (arginine - glycine - aspartic acid - serine) onto the surface of chitosan films aims at improving cell attachment. Historically, chromatography and amino acid analysis have been used to provide a direct measurement of the amount of grafted peptide. However, the fast separation and absence of sample preparation provided by CE enables equally accurate yet real-time monitoring of the peptide grafting process. CE is able to separate and quantify the different components of the reaction mixture: the (non-grafted) peptide and the chemical coupling agents. In this way the use of CE results in improved films for downstream applications.
The chitosan films were characterized through solid-state NMR (nuclear magnetic resonance) spectroscopy. This technique is more time-consuming and cannot be applied in real time, but yields a direct measurement of the peptide and thus validates the CE technique.

Free solution capillary electrophoresis is a fast, cheap and robust analytical method that enables the quantitative monitoring of chemical reactions in real time. Its utility for rapid, convenient and precise analysis is demonstrated here through analysis of covalent peptide grafting onto chitosan films for improved cell adhesion.

모세관 전기 영동은 실시간으로 키토산 필름에 펩타이드 접목을 모니터링하는

Free-solution capillary electrophoresis (CE) separates analytes, generally charged compounds in solution through the application of an electric field. ...

A Protocol for Safe Lithiation Reactions Using Organolithium Reagents

Organolithium reagents are powerful tools in the synthetic chemist&#39;s toolbox. However, the extreme pyrophoric nature of the most reactive reagents warrants proper technique, thorough training, and proper personal protective equipment. To aid in the training of researchers using organolithium reagents, a thorough, step-by-step protocol for the safe and effective use of tert-butyllithium on an inert gas line or within a glovebox is described. As a model reaction, preparation of lithium tert-butyl amide by the reaction of tert-butyl amine with one equivalent of tert-butyl lithium is presented.

The safe and proper use of organolithium reagents is described.

유기 리튬 시약을 사용하여 안전 리튬 화의 반응을위한 프로토콜

Organolithium reagents are powerful tools in the synthetic chemist&#39;s toolbox. However, the extreme pyrophoric nature of the most reactive reagents ...

Monitoring the Effects of Illumination on the Structure of Conjugated Polymer Gels Using Neutron Scattering

We demonstrate a protocol to effectively monitor the gelation process of a high concentration solution of conjugated polymer both in the presence and absence of white light exposure. By instituting a controlled temperature ramp, the gelation of these materials can be precisely monitored as they proceed through this structural evolution, which effectively mirrors the conditions experienced during the solution deposition phase of organic electronic device fabrication. Using small angle neutron scattering (SANS) and ultra-small angle neutron scattering (USANS) along with appropriate fitting protocols we quantify the evolution of select structural parameters throughout this process. Thorough analysis indicates that continued light exposure throughout the gelation process significantly alters the structure of the ultimately formed gel. Specifically, the aggregation process of poly(3-hexylthiophene-2,5-diyl) (P3HT) nano-scale aggregates is negatively affected by the presence of illumination, ultimately resulting in the retardation of growth in conjugated polymer microstructures and the formation of smaller scale macro-aggregate clusters.

A protocol for the analysis of gels formed from the optoelectronic conjugated polymer poly(3-hexylthiophene-2,5-diyl) (P3HT) using small and ultra-small angle neutron scattering in both the presence and absence of illumination is presented.

중성자 산란을 사용 하 여 활용 된 중합체 젤의 구조에 조명 효과 모니터링

We demonstrate a protocol to effectively monitor the gelation process of a high concentration solution of conjugated polymer both in the presence and ...

Measurements of Long-range Electronic Correlations During Femtosecond Diffraction Experiments Performed on Nanocrystals of Buckminsterfullerene

The precise details of the interaction of intense X-ray pulses with matter are a topic of intense interest to researchers attempting to interpret the results of femtosecond X-ray free electron laser (XFEL) experiments. An increasing number of experimental observations have shown that although nuclear motion can be negligible, given a short enough incident pulse duration, electronic motion cannot be ignored. The current and widely accepted models assume that although electrons undergo dynamics driven by interaction with the pulse, their motion could largely be considered &#39;random&#39;. This would then allow the supposedly incoherent contribution from the electronic motion to be treated as a continuous background signal and thus ignored. The original aim of our experiment was to precisely measure the change in intensity of individual Bragg peaks, due to X-ray induced electronic damage in a model system, crystalline C60. Contrary to this expectation, we observed that at the highest X-ray intensities, the electron dynamics in C60 were in fact highly correlated, and over sufficiently long distances that the positions of the Bragg reflections are significantly altered. This paper describes in detail the methods and protocols used for these experiments, which were conducted both at the Linac Coherent Light Source (LCLS) and the Australian Synchrotron (AS) as well as the crystallographic approaches used to analyse the data.

We describe an experiment designed to probe the electronic damage induced in nanocrystals of Buckminsterfullerene (C60) by intense, femtosecond pulses of X-rays. The experiment found that, surprisingly, rather than being stochastic, the X-ray induced electron dynamics in C60 are highly correlated, extending over hundreds of unit cells within the crystals1.

펨 회절 실험 Buckminsterfullerene의 나노에 수행 하는 동안 장거리 전자 상관 관계의 측정

The precise details of the interaction of intense X-ray pulses with matter are a topic of intense interest to researchers attempting to interpret the ...

Real-time Breath Analysis by Using Secondary Nanoelectrospray Ionization Coupled to High Resolution Mass Spectrometry

Exhaled volatile organic compounds (VOCs) have aroused considerable interest, since they can serve as biomarkers for disease diagnosis and environmental exposure in a non-invasive manner. In this work, we present a protocol to characterize the exhaled VOCs in real time by using secondary nanoelectrospray ionization coupled to high resolution mass spectrometry (Sec-nanoESI-HRMS). The homemade Sec-nanoESI source was readily set up based on a commercial nanoESI source. Hundreds of peaks were observed in the background-subtracted mass spectra of exhaled breath, and the mass accuracy values are -4.0-13.5 ppm and -20.3-1.3 ppm in the positive and negative ion detection modes, respectively. The peaks were assigned with accurate elemental composition according to the accurate mass and isotopic pattern. Less than 30 s is used for one exhalation measurement, and it takes approximately 7 min for six replicated measurements.

A protocol for characterizing chemical composition of exhaled breath in real time by using secondary nanoelectrospray ionization coupled to high resolution mass spectrometry is demonstrated.

고 분해능 질량 분석을 결합 하는 보조 Nanoelectrospray 이온화를 사용 하 여 실시간 호흡 분석

Exhaled volatile organic compounds (VOCs) have aroused considerable interest, since they can serve as biomarkers for disease diagnosis and environmental ...

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 ...

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.

금속 나노 입자의 정확 하 게 제어 증 착에 대 한 연속 흐름 촉매 반응 기

In this work, a novel photocatalytic reactor for the pulsed and controlled excitation of the photocatalyst and the precise deposition of metallic ...

Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941

Positron emission tomography (PET) is an essential molecular imaging technique providing insights into pathways and using specific targeted radioligands for in vivo investigations. Within this protocol, a robust and reliable remote-controlled radiosynthesis of [11C]SNAP-7941, an antagonist to the melanin-concentrating hormone receptor 1, is described. The radiosynthesis starts with cyclotron produced [11C]CO2 that is subsequently further reacted via a gas-phase transition to [11C]CH3OTf. Then, this reactive intermediate is introduced to the precursor solution and forms the respective radiotracer. Chemical as well as the radiochemical purity are determined by means of RP-HPLC, routinely implemented in the radiopharmaceutical quality control process. Additionally, the molar activity is calculated as it is a necessity for the following real-time kinetic investigations. Furthermore, [11C]SNAP-7941 is applied to MDCKII-WT and MDCKII-hMDR1 cells for evaluating the impact of P-glycoprotein (P-gp) expression on cell accumulation. For this reason, the P-gp expressing cell line (MDCKII-hMDR1) is either used without or with blocking prior to experiments by means of the P-gp substrate (&#177;)-verapamil and the results are compared to the ones observed for the wildtype cells. The overall experimental approach demonstrates the importance of a precise time-management that is essential for every preclinical and clinical study using PET tracers radiolabelled with short-lived nuclides, such as carbon-11 (half-life: 20 min).

Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941

Here, we represent a protocol for the fully automated radiolabelling of [11C]SNAP-7941 and the analysis of the real-time kinetics of this PET-tracer on P-gp expressing and non-expressing cells.

[11C]SNAP-7941의 자동 합성및 실시간 역학 평가의 기술적 측면

Positron emission tomography (PET) is an essential molecular imaging technique providing insights into pathways and using specific targeted radioligands ...

Optimization of Radiochemical Reactions using Droplet Arrays

Current automated radiosynthesizers are designed to produce large clinical batches of radiopharmaceuticals. They are not well suited for reaction optimization or novel radiopharmaceutical development since each data point involves significant reagent consumption, and contamination of the apparatus requires time for radioactive decay before the next use. To address these limitations, a platform for performing arrays of miniature droplet-based reactions in parallel, each confined within a surface-tension trap on a patterned polytetrafluoroethylene-coated silicon "chip", was developed. These chips enable rapid and convenient studies of reaction parameters including reagent concentrations, reaction solvent, reaction temperature and time. This platform permits the completion of hundreds of reactions in a few days with minimal reagent consumption, instead of taking months using a conventional radiosynthesizer.

This method describes the use of a novel high-throughput methodology, based on droplet chemical reactions, for the rapid and economical optimization of radiopharmaceuticals using nanomole amounts of reagents.