New strategies toward the preparation and use of unstable nitroso species
Kassin, Victor-Emmanuel
Promoteur(s) : Monbaliu, Jean-Christophe
Date de soutenance : 27-jui-2017 • URL permanente : http://hdl.handle.net/2268.2/2493
Détails
Titre : | New strategies toward the preparation and use of unstable nitroso species |
Auteur : | Kassin, Victor-Emmanuel |
Date de soutenance : | 27-jui-2017 |
Promoteur(s) : | Monbaliu, Jean-Christophe |
Membre(s) du jury : | Damblon, Christian
Detrembleur, Christophe Lemaire, Christian |
Langue : | Anglais |
Nombre de pages : | 83 |
Mots-clés : | [en] Nitroso [en] α-chloro-nitroso [en] Hetero Diels-Alder [en] Electrophilic amination [en] Continuous-Flow processes |
Discipline(s) : | Physique, chimie, mathématiques & sciences de la terre > Chimie |
Centre(s) de recherche : | Center for Integrated Technology and Organic Synthesis |
Public cible : | Chercheurs Professionnels du domaine Etudiants |
Institution(s) : | Université de Liège, Liège, Belgique |
Diplôme : | Master en sciences chimiques, à finalité approfondie |
Faculté : | Mémoires de la Faculté des Sciences |
Résumé
[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.
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