Biocatalytic Generation of o-Quinone Imines in the Synthesis of 1,4-Benzoxazines and Its Comparative Green Chemistry Metrics
Document Type
Article
Publication Date
2-1-2024
Abstract
1,4-Benzoxazines are important motifs in many pharmaceuticals and can be formed by a reaction sequence involving the oxidation of o-aminophenols to their corresponding quinone imine followed by an in situ inverse electron demand Diels-Alder (IEDDA) cycloaddition with a suitable dienophile. Reported herein is the development of a reaction sequence that employs horseradish peroxidase to catalyze the oxidation of the aminophenols prior to the IEDDA as a more sustainable alternative to the use of conventional stoichiometric oxidants. The synthesis of 10 example benzoxazines is demonstrated in this ``one-pot, two-step'' procedure with yields between 42% and 92%. The green chemistry metrics, including the E-factor and generalized reaction mass efficiency, for this biocatalytic reaction were compared against the conventional chemical approach. It was found that the reported biocatalytic route was approximately twice as green by these measures.
Keywords
peroxidase, horseradish peroxidase, Diels-Alderreaction, inverse electron demand Diels-Alder, E-factor, reaction mass efficiency, tandem reaction
Divisions
CHEMISTRY,advanced
Funders
The British Council in India (172701477); (EP/K011685/1); (EP/P510889/1); (EP/J50032X/1),UK Research & Innovation (UKRI) Engineering & Physical Sciences Research Council (EPSRC) (BB/M011208/1),UK Research & Innovation (UKRI) Biotechnology and Biological Sciences Research Council (BBSRC)
Publication Title
ACS Sustainable Chemistry & Engineering
Volume
12
Issue
7
Publisher
American Chemical Society
Publisher Location
1155 16TH ST, NW, WASHINGTON, DC 20036 USA