[en] An intensified and scalable continuous flow process is presented for the hydroxylation of enolizable tertiary ketones. The procedure relies on molecular oxygen, metal-free conditions and a low toxicity solvent (DMSO). The reaction is optimized on the microfluidic scale with a model ketone substrate (isobutyrophenone) and next extended to a small library of structurally diverse enolizable ketones. High conversion and selectivity are achieved under extremely short residence time. A DFT computational study provides insights on the mechanism and selectivity on various substrates. The scalability of the hydroxylation step is next assessed in a commercial pilot scale continuous flow SiC reactor, hence providing up to 12.5 kg per day of industrially relevant α-ketols with applications ranging from Type I radical photoinitiators to intermediates for the preparation of active pharmaceutical ingredients.
Research Center/Unit :
MolSys - Molecular Systems - ULiège [BE]
Disciplines :
Chemistry
Author, co-author :
Kassin, Victor-Emmanuel ; Université de Liège - ULiège > Département de chimie (sciences) > CITOS
Toupy, Thomas ; Université de Liège - ULiège > Département de chimie (sciences) > CITOS
Petit, Guillaume ; Université de Liège - ULiège > Département de chimie (sciences) > Synthèse organique appliquée
Bianchi, Pauline ; Université de Liège - ULiège > Master en sc. chimiques, à fin.
Salvadeo, Elena
Monbaliu, Jean-Christophe ; Université de Liège - ULiège > Département de chimie (sciences) > Synthèse organique appliquée
Language :
English
Title :
Metal-free hydroxylation of tertiary ketones under intensified and scalable continuous flow conditions
Publication date :
2020
Journal title :
Journal of Flow Chemistry
ISSN :
2062-249X
eISSN :
2063-0212
Publisher :
Akademiai Kiado, Hungary
Volume :
10
Pages :
167-179
Peer reviewed :
Peer Reviewed verified by ORBi
Tags :
CÉCI : Consortium des Équipements de Calcul Intensif
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]