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Clear out junk files and repair common Windows errorsFree Scan →Fix the driver behind crashes, sound loss and screen glitchesFind Drivers →A flow-chemistry method reported by the University of Amsterdam uses cesium fluoride—not a PFAS reagent as the fluorine source—to make compounds with a trifluoromethyl group attached through nitrogen, sulfur, or oxygen. The “PFAS-free” description applies to that reagent choice: it does not mean every product is outside every PFAS definition, or that the resulting drugs, pesticides, or process have been shown to be environmentally safe.
What the synthesis method does
The University of Amsterdam’s Van ’t Hoff Institute for Molecular Sciences reported the method on 29 August 2024. It is a flow-chemistry strategy for making N–CF3, S–CF3, and O–CF3 compounds: the trifluoromethyl group is connected to a molecule through nitrogen, sulfur, or oxygen.
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The work was published as Mauro Spennacchio, Miguel Bernús, Jelena Stanić, Daniele Mazzarella, Marco Colella, James J. Douglas, Omar Boutureira, and Timothy Noël, “A unified flow strategy for the preparation and use of trifluoromethyl-heteroatom anions,” Science 385(6712), 991–996, DOI 10.1126/science.adq2954.
How the flow setup works
- Generate reactive intermediates: Suitable sulfur-, oxygen-, or nitrogen-containing precursors pass through a packed-bed reactor containing cesium fluoride. The setup generates reactive N–, S–, or O–CF3 anions.
- React them with a substrate: A downstream module brings those intermediates into reaction with suitable substrates, producing the targeted heteroatom-linked trifluoromethyl compounds.
The University of Amsterdam account attributes the method’s efficiency to the salt’s surface area and improved mixing. It also says that keeping the reactive intermediates contained within the microfluidic system improves safety. These are reported advantages of the described setup, not a head-to-head demonstration that it outperforms every alternative.
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What “PFAS-free” means here—and what it does not
In this report, “PFAS-free” describes the choice to avoid PFAS reagents as the fluorine source in the synthesis. Cesium fluoride is the fluorine source named for the method. The claim is not that the products contain no fluorine, that every reagent or part of every possible implementation is PFAS-free, or that the products cannot meet a PFAS definition.
The distinction matters because “PFAS” is defined in more than one way. A broad structural definition can include some molecules with a single fully fluorinated carbon, while a narrower regulatory definition may exclude them. The University of Amsterdam account specifically cautions that some of the resulting heteroatom–CF3 compounds may be considered part of the PFAS family under broad definitions.
| Definition or framework | Structural point relevant to this method | What that means for an N–, S–, or O–CF3 product |
|---|---|---|
| OECD definition described in a 2021 paper | Includes substances containing at least one fully fluorinated methyl or methylene carbon. | A CF3 group may meet this structural criterion; classification depends on the molecule and the definition being applied. |
| US EPA definition discussed on its page updated 26 November 2025 | Uses specified molecular structures and excludes molecules with only a single fluorinated carbon. | A product with only one fluorinated carbon may be excluded under this definition, even if a broader structural definition would treat it differently. |
These frameworks are not interchangeable: the OECD account describes a broad structural definition, while the EPA page presents a US regulatory framing. Neither classification alone establishes a product’s hazard or environmental fate. The EPA says pesticide reviews are chemical-specific and consider hazard and exposure, including persistence, bioaccumulation, and toxicity.
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The institutional account reports satisfactory yields in many cases, but it does not give one overall yield figure for the route. It establishes a reported flow architecture, use of cesium fluoride, and N-, S-, and O-linked trifluoromethylation; it does not provide a systematic comparison against batch chemistry or other fluorination methods.
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The project involved academic and industry researchers in Italy, Spain, and the UK, including scientists from AstraZeneca. That collaboration does not establish commercial deployment or routine manufacturing adoption. Nor does the account provide a full life-cycle assessment, a quantified environmental benefit, or evidence of commercial-scale production.
Independent reader supportYour contribution helps us test, update, and keep practical guides available for everyone.Why the distinction matters for drugs and pesticides
The method is relevant to the preparation of fluorinated pharmaceutical and agrochemical compounds, but the report should not be read as evidence that a particular approved medicine or pesticide was made with this route. A synthesis method addresses how certain molecular structures can be prepared; it does not by itself establish efficacy, regulatory approval, safety, persistence, or environmental impact for any finished product.
For pesticide regulation in the United States, the EPA describes chemical-specific reviews that consider both hazard and exposure. Whether a molecule falls within a particular PFAS definition is a separate question from how that chemical performs in such an assessment.
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