The use of biocatalysis
for classically synthetic transformations
has seen an increase in recent years, driven by the sustainability
credentials bio-based approaches can offer the chemical industry.
Despite this, the biocatalytic reduction of aromatic nitro compounds
using nitroreductase biocatalysts has not received significant attention
in the context of synthetic chemistry. Herein, a nitroreductase (NR-55)
is demonstrated to complete aromatic nitro reduction in a continuous
packed-bed reactor for the first time. Immobilization on an amino-functionalized
resin with a glucose dehydrogenase (GDH-101) permits extended reuse
of the immobilized system, all operating at room temperature and pressure
in aqueous buffer. By transferring into flow, a continuous extraction
module is incorporated, allowing the reaction and workup to be continuously
undertaken in a single operation. This is extended to showcase a closed-loop
aqueous phase, permitting reuse of the contained cofactors, with a
productivity of >10 gproductgNR-55–1and milligram isolated yields >50% for the
product
anilines. This facile method removes the need for high-pressure hydrogen
gas and precious-metal catalysts and proceeds with high chemoselectivity
in the presence of hydrogenation-labile halides. Application of this
continuous biocatalytic methodology to panels of aryl nitro compounds
could offer a sustainable approach to its energy and resource-intensive
precious-metal-catalyzed counterpart.