The University of Amsterdam’s chemists have devised a new method for incorporating a trifluoromethyl group into molecules attached to a sulphur, nitrogen, or oxygen atom. This innovative process, detailed in a recent publication in Science, allows for the production of pharmaceutical and agrochemical compounds without the use of PFAS reagents, making it a more environmentally sustainable synthesis route. Led by Prof. Timothy Noël at the Van ‘t Hoff Institute for Molecular Sciences, this research was conducted in collaboration with researchers from Italy, Spain, and the UK, representing both academia and industry.
Employing the principles of flow chemistry, where reactions occur in closed systems of small tubes, the researchers were able to conduct safe and controlled chemistry with greater versatility and flexibility compared to traditional methods using chemical glassware. The introduction of a trifluoromethyl group in pharmaceutical and agrochemical compounds has several benefits, including enhanced hydrophobicity and increased metabolic stability, leading to improved efficacy and potentially lower required dosages. This new synthesis protocol eliminates the need for custom fluorinated reagents that often contain PFAS compounds, aligning with the push for more environmentally friendly synthesis methods in the field.
The integration of a microfluidic flow module for generating reactive N-, S-, and O-CF3 anions, along with a downstream reaction module, offers a streamlined platform for the derivatization of molecules with these fluorinated motifs. By utilizing a packed bed flow reactor containing caesium fluoride salt, the researchers were able to fluorinate appropriate substrates efficiently with high yields. The improved mixing of organic intermediates in the system, along with the containment of all formed intermediates within the microfluidic system, also enhances safety measures, making this approach a promising avenue for pharmaceutical and agrochemical synthesis.
The combination of the anion generator module and the downstream reactor provides a versatile system for producing pharmaceutical and agrochemical active ingredients with N-, S-, and O-CF3 motifs. This innovative approach has the potential to impact the development of new drugs by enhancing their properties and improving safety and sustainability in their production processes. The researchers were able to successfully couple various anions with a range of substrates, resulting in multiple fluorinated products with applications in pharmaceutical and agrochemical syntheses, with promising yields and operational parameters conducive to implementation in both academic and industrial settings.
