Integrated One-Flow Synthesis of Heterocyclic Thioquinazolinones through Serial Microreactions with Two Organolithium Intermediates
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SCOPUS
- Title
- Integrated One-Flow Synthesis of Heterocyclic Thioquinazolinones through Serial Microreactions with Two Organolithium Intermediates
- Authors
- Kim, H; Lee, HJ; Kim, DP
- Date Issued
- 2015-02-02
- Publisher
- ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
- Abstract
- The synthesis of pharmaceutical compounds via short-lived intermediates in a microreactor is attractive, because of the fast flow and high throughput. Additionally, intermediates can be utilized sequentially to efficiently build up a library in a short time. Here we present an integrated microfluidic synthesis of biologically active thioquinazolinone libraries. Generation of o-lithiophenyl isothiocyanate and subsequent reaction with aryl isocyanate is optimized by controlling the residence time in the microreactor to 16ms at room temperature. Various S-benzylic thioquinazolinone derivatives are synthesized within 10s in high yields (75-98%) at room temperature. These three-step reactions involve two organolithium intermediates, an isothiocyanate-functionalized aryllithium intermediate, and a subsequent lithium thiolate intermediate. We also demonstrate the gram-scale synthesis of a multifunctionalized thioquinazolinone in the microfluidic device with a high yield (91%) and productivity (1.25g in 5min).
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/27209
- DOI
- 10.1002/ANIE.201410062
- ISSN
- 1433-7851
- Article Type
- Article
- Citation
- ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, vol. 54, no. 6, page. 1877 - 1880, 2015-02-02
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