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Selective hydrogenation of nitro compounds to amines by coupled redox reactions over a heterogeneous biocatalyst

Abstract:
Cleaner synthesis of amines remains a key challenge in organic chemistry because of their prevalence in pharmaceuticals, agrochemicals and synthetic building blocks. Here, we report a different paradigm for chemoselective hydrogenation of nitro compounds to amines, under mild, aqueous conditions. The hydrogenase enzyme releases electrons from H2 to a carbon black support which facilitates nitro-group reduction. For 30 nitroarenes we demonstrate full conversion (isolated yields 78 – 96%), with products including pharmaceuticals benzocaine, procainamide and mesalazine, and 4-aminophenol – precursor to paracetamol (acetaminophen). We also showcase gram-scale synthesis of procainamide with 90% isolated yield. We demonstrate potential for extension to aliphatic substrates. The catalyst is highly selective for reduction of the nitro group over other unsaturated bonds, tolerant to a wide range of functional groups, and exhibits excellent stability in reactions lasting up to 72 hours and full reusability over 5 cycles with a total turnover number over 1 million, indicating scope for direct translation to fine chemical manufacturing.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-024-51531-2

Authors


More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Inorganic Chemistry
Role:
Author
ORCID:
0000-0003-0357-6171
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Inorganic Chemistry
Role:
Author
ORCID:
0000-0003-3275-4408
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Inorganic Chemistry
Role:
Author
ORCID:
0000-0002-1590-8674
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Inorganic Chemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Inorganic Chemistry
Role:
Author
ORCID:
0000-0001-5855-651X


More from this funder
Funder identifier:
https://ror.org/0472cxd90
Grant:
819580
More from this funder
Funder identifier:
https://ror.org/0439y7842
Grant:
EP/N013514/1
515587
More from this funder
Funder identifier:
https://ror.org/00cwqg982
Grant:
BB/X002624/1


Publisher:
Springer Nature
Journal:
Nature Communications More from this journal
Volume:
15
Issue:
1
Article number:
7297
Place of publication:
England
Publication date:
2024-08-24
Acceptance date:
2024-08-11
DOI:
EISSN:
2041-1723
Pmid:
39181899


Language:
English
Pubs id:
2024377
Local pid:
pubs:2024377
Deposit date:
2024-09-21

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