New strategies toward the preparation and use of unstable nitroso species
Kassin, Victor-Emmanuel
Promotor(s) : Monbaliu, Jean-Christophe
Date of defense : 27-Jun-2017 • Permalink : http://hdl.handle.net/2268.2/2493
Details
Title : | New strategies toward the preparation and use of unstable nitroso species |
Author : | Kassin, Victor-Emmanuel |
Date of defense : | 27-Jun-2017 |
Advisor(s) : | Monbaliu, Jean-Christophe |
Committee's member(s) : | Damblon, Christian
Detrembleur, Christophe Lemaire, Christian |
Language : | English |
Number of pages : | 83 |
Keywords : | [en] Nitroso [en] α-chloro-nitroso [en] Hetero Diels-Alder [en] Electrophilic amination [en] Continuous-Flow processes |
Discipline(s) : | Physical, chemical, mathematical & earth Sciences > Chemistry |
Research unit : | Center for Integrated Technology and Organic Synthesis |
Target public : | Researchers Professionals of domain Student |
Institution(s) : | Université de Liège, Liège, Belgique |
Degree: | Master en sciences chimiques, à finalité approfondie |
Faculty: | Master thesis of the Faculté des Sciences |
Abstract
[en] Nitroso species and their wide variety are known for decades and are involved in numerous applications such as hetero Diels-Alder reactions or electrophilic aminations on α-ketones. However, they intrinsic poor stability, toxicity and their relative hazardous profile tuned down their potential use at an industrial-scale. In a conventional batch reactor, these reactions are relatively long (20-45 min) and the conversions associated are uncomplete.
In this work, safe and efficient continuous-flow procedures for the preparation of α-chloro-nitroso species from aqueous sodium hypochlorite and oximes were developed. The conditions were first developed in a microfluidic setup, and next transposed to an industrial mesofluidic flow reactor. The lab-scale continuous-flow setup developed in this project affords complete conversion within minutes for different kinds of starting oximes (aliphatic and alicyclic, including chiral substrates). The process is very safe, and in-line IR analysis complements the control over the process conditions. The setup is amenable to the generation of libraries of α-chloro-nitroso and sustains productivities of up to 6 mL min-1, delivering ready-to-use α-chloro-nitroso species.
The scope of the method was next assessed with a concrete application of α-chloro-nitroso species toward the synthesis of pharmacological active norephedrine. The optimized strategy toward norephedrine from propiophenone involved four steps with an overall isolated yield of 53%. Besides, several α-chloro-nitroso classes (aliphatic, alicyclic and chiral) were tested. In the last part of this work, we assessed the full development of a continuous-flow process toward norephedrine from a propiophenone derivative. Encouraging preliminary data was obtained.
File(s)
Document(s)
Description:
Size: 3.7 MB
Format: Adobe PDF
Cite this master thesis
The University of Liège does not guarantee the scientific quality of these students' works or the accuracy of all the information they contain.