The growing intention in chemistry to lean towards a greener path raises questions about the real need to purify a product for its characterization since the number of purifications steps can generate a large volume of residues. The idea of minimizing these residues in chemical processes has stimulated scientists in developing methodologies for characterizing individual molecules present in a mixture. Nuclear Magnetic Resonance (NMR) spectroscopy is a paramount tool in the structural assignment, especially in fluorine-containing molecules due to 19F nuclei characteristics, its importance in medicinal chemistry, its interactions (such as hydrogen bonding), and the effects of these interactions in molecular properties. An epoxide ring-opening can be used to introduce fluorine atom vicinal to a hydroxyl group, leading to an intramolecular hydrogen bonding responsible for dictating the conformational preference in such compounds. The present study investigates the fluorination of epoxide rings (Scheme 1) and determines the structure of formed products without any physical purification of the crude reaction mixture. To this end, selective NMR experiments based on the FESTA approach and DFT calculations were applied.
The 13C{1H} NMR spectra of the mixture provided information suggesting that the 1,4-products are preferably formed and supporting the proposal of the addition of two fluorine atoms in the molecule. The 19F spectra showed two mains signals that correspond to the 1,3 and 1,4 products. COSY 1H-19F allowed the differentiation between 1H signals coupled with the corresponding 19F atoms. Thus, by selecting the coupled 1H and 19F, it was possible to generate a 1D 1H spectrum for the pure 1,3 product, allowing the measurement of coupling constants used in the structural assignment. For the 1,4 products, the signals are more complicated to assign, and further studies are being carried out to confirm the proposed structure. DFT calculations are also used to support the assignments, and conformational preferences for the cited compounds are under investigation. These results suggest that the structure assignment of fluorinated compounds present as a mixture can be made even for unknown compounds, without any physical purification, avoiding the production of waste (e.g., Solvent).