Mild acid promoted bromination with H2O2/NaBr at room temperature inspired by flavin-dependent halogenase (FDH)
- 1Tongji medical college
- 2Huazhong University of Science and Technology
Abstract
Bromination is an important and frequently used organic transformation. Many elegant and reliable bromination methods have been well established; however, limitations still exist, thus calling for more sustainable approaches with broader substrate scope, better selectivity, milder condition and lower cost. In this manuscript, an effective bromination method has been established utilizing low-toxic and cost-friendly carboxylic acid/NaBr/H2O2, including bromination of (hetero)arenes, decarboxylative bromination of (hetero)aryl/vinyl carboxylic acid, ipsohydroxylation-bromination of (hetero)aryl boronic acids/esters, hydroxybromination of alkyne/alkene, and 𝛼-bromination of ketone. Broad substrate scope, good functional group tolerance, operation-friendly procedure, moderate to excellent yields, and late-stage bromination of small molecule natural products and drugs have been achieved. The carboxylic acid was hypothesized to play dual roles as providing H-bond, proton donor and acceptor in this reaction. Compared many previously reported bromination methods, this method shows evidently better sustainability, and can serve as a useful synthetic tool for related research.
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BibTeX
@misc{chen2026mild,
title = {{Mild acid promoted bromination with H2O2/NaBr at room temperature inspired by flavin-dependent halogenase (FDH)}},
author = {Zhilong Chen},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010583/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010583/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Mild acid promoted bromination with H2O2/NaBr at room temperature inspired by flavin-dependent halogenase (FDH)
AU - Zhilong Chen
PY - 2026
DA - 2026/10/16
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010583/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010583/v1
AB - Bromination is an important and frequently used organic transformation. Many elegant and reliable bromination methods have been well established; however, limitations still exist, thus calling for more sustainable approaches with broader substrate scope, better selectivity, milder condition and lower cost. In this manuscript, an effective bromination method has been established utilizing low-toxic and cost-friendly carboxylic acid/NaBr/H2O2, including bromination of (hetero)arenes, decarboxylative bromination of (hetero)aryl/vinyl carboxylic acid, ipsohydroxylation-bromination of (hetero)aryl boronic acids/esters, hydroxybromination of alkyne/alkene, and 𝛼-bromination of ketone. Broad substrate scope, good functional group tolerance, operation-friendly procedure, moderate to excellent yields, and late-stage bromination of small molecule natural products and drugs have been achieved. The carboxylic acid was hypothesized to play dual roles as providing H-bond, proton donor and acceptor in this reaction. Compared many previously reported bromination methods, this method shows evidently better sustainability, and can serve as a useful synthetic tool for related research.
ER -