,
Beilstein Arch. 2026, 202621. https://doi.org/10.3762/bxiv.2026.21.v1
Published 02 Jul 2026
We report a practical and efficient method for the synthesis of trichloromethyl ketones from the corresponding methyl ketones via a two-step sequence involving trifluoroacetylation followed by selective chlorination. The key chlorination step proceeds under mild, weakly acidic conditions using sodium hypochlorite pentahydrate, thus avoiding the use of hazardous chlorine gas or strong base. A wide range of aromatic and aliphatic methyl ketones was successfully converted into the corresponding trichloromethyl ketones in high yields. Mechanistic studies suggest that the reaction involves the formation of a 2,2-dichloro-1,3-diketone intermediate and subsequent cleavage of the trifluoroacetyl group. In contrast to previously reported base-mediated halogenation methods, the present protocol exhibits a high regioselectivity and operational simplicity under acidic conditions. This method provides a convenient alternative for the synthesis of trichloromethyl ketones from readily available substrates and is expected to be broadly applicable in organic synthesis and medicinal chemistry.
Keywords: trichloromethyl ketones; methyl ketones; sodium hypochlorite pentahydrate; b-diketones; chlorination
| Format: PDF | Size: 5.9 MB | Download |
When a peer-reviewed version of this preprint is available, this information will be updated in the information box above. If no peer-reviewed version is available, please cite this preprint using the following information:
Sakai, A.; Tanaka, T.; Hosokawa, T.; Kawai, T.; Tsutsui, H.; Kimura, Y.; Takizawa, S.; Kirihara, M. Beilstein Arch. 2026, 202621. doi:10.3762/bxiv.2026.21.v1
Citation data can be downloaded as file using the "Download" button or used for copy/paste from the text window below.
Citation data in RIS format can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and
Zotero.
© 2026 Sakai et al.; licensee Beilstein-Institut.
This is an open access work licensed under the terms of the Beilstein-Institut Open Access License Agreement (https://www.beilstein-archives.org/xiv/terms), which is identical to the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0). The reuse of material under this license requires that the author(s), source and license are credited. Third-party material in this work could be subject to other licenses (typically indicated in the credit line), and in this case, users are required to obtain permission from the license holder to reuse the material.
