eprintid: 8008 rev_number: 5 userid: 6 dir: disk0/00/00/80/08 datestamp: 2011-11-10 19:46:21 lastmod: 2016-11-15 13:44:13 status_changed: 2011-11-10 19:46:21 type: thesis_degree metadata_visibility: show contact_email: huf1@pitt.edu item_issues_count: 0 eprint_status: archive creators_name: Fang, Hui creators_email: huf1@pitt.edu creators_id: HUF1 title: Capillary-based Microreactor System Integrated with UHPLC/GC for High Throughput Screening of Catalysts for Organic Reactions ispublished: unpub divisions: sch_as_chemistry full_text_status: public keywords: Capillary; Catalyst screening; Microreactor; Reactions abstract: Catalyst discovery through high throughput screening can greatly take advantage of automated microreactor technology. Quantitative analysis of reaction outcomes is necessary for evaluating catalyst activities and GC and/or LC are common tools. Few microfluidic systems, however, have the capability of automatically screening catalysts in slow reactions with in situ chromatography analysis. Thus, a novel microreactor was developed that integrated sample loading, reaction and online analysis functions in a totally automated format. An autosampler and syringe pump load homogeneous catalysts and reagents. The chemicals are mixed and reacted in a long capillary followed by online analysis, either by GC or UHPLC. The approach of parallel reactions in a flow stream is good for either slow reactions or fast reactions depending on the operation mode. Some palladium and ligand complex catalysts for the Stille reaction were chosen and screened by a stop-flow approach with GC analysis for validation. The screening results were in good accordance with the literature.The first application of this microreactor was to discover peptidic catalysts for the direct aldol reaction. A major difficulty was the poor solubility of peptidic catalysts. This was solved by allowing catalysts to react with one of the aldol substrates to form soluble catalyst adduct, which was then loaded into the microreactor to complete the reaction. This two-step approach was used to screen a diverse set of amino acids and short peptidic catalysts, in which two groups of peptides containing r-Glu and b-Asp residues showed higher activities than other catalysts. The second application was to screen Bronsted or Lewis acid catalysts for an internal cyclization reaction. This reaction can be used to prepare large libraries of amide compounds for drug discovery. A continuous flow approach with online UHPLC analysis was applied to study this relatively fast reaction. The experimental throughput can reach 9 reactions/h. Results showed that strong acids are generally good for conversion and yield. Lanthanide triflate compounds, although having weak acidity, had better conversion and selectivity than other acids. Side reaction analysis by GC-MS and LC-MS indicated that strong and weak Bronsted acids can lead to the formation of different major byproducts. date: 2009-09-30 date_type: completed institution: University of Pittsburgh refereed: TRUE etdcommittee_type: committee_chair etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_name: Weber, Stephen G etdcommittee_name: Day, Billy W etdcommittee_name: Floreancig, Paul E etdcommittee_name: Nelson, Scott G etdcommittee_email: sweber@pitt.edu etdcommittee_email: bday@pitt.edu etdcommittee_email: florean@pitt.edu etdcommittee_email: sgnelson@pitt.edu etdcommittee_id: SWEBER etdcommittee_id: BDAY etdcommittee_id: FLOREAN etdcommittee_id: SGNELSON etd_defense_date: 2009-05-13 etd_approval_date: 2009-09-30 etd_submission_date: 2009-06-04 etd_access_restriction: 5_year etd_patent_pending: FALSE assigned_doi: doi:10.5195/pitt.etd.2011.8008 thesis_type: dissertation degree: PhD committee: Stephen G Weber (sweber@pitt.edu) - Committee Chair committee: Billy W Day (bday@pitt.edu) - Committee Member committee: Paul E Floreancig (florean@pitt.edu) - Committee Member committee: Scott G Nelson (sgnelson@pitt.edu) - Committee Member etdurn: etd-06042009-163807 other_id: http://etd.library.pitt.edu/ETD/available/etd-06042009-163807/ other_id: etd-06042009-163807 citation: Fang, Hui (2009) Capillary-based Microreactor System Integrated with UHPLC/GC for High Throughput Screening of Catalysts for Organic Reactions. Doctoral Dissertation, University of Pittsburgh. (Unpublished) document_url: http://d-scholarship-dev.library.pitt.edu/8008/1/ETDdissertationFANG29JUN09.pdf