No abstract

While the gauche effect in 1,2‐difluoroethane is widely known as being due to hyperconjugative interactions between σCH electron‐donating orbitals and σ*CF electron‐accepting orbitals, the corresponding 1,2‐dichloro, 1,2‐dibromo, and 1,2‐diiodo derivatives are preferentially in the anti conformation. 2‐Halofluoroethanes (F‐CH2‐CH2‐X) combine a small halogen (fluorine) and a vicinal low‐lying energy antibonding orbital (σ*CX) that activates a stabilizing antiperiplanar σCH → σ*CX electron delocalization, which can induce the gauche effect. On the other hand, σCX orbitals are good electron donors to σ*CF, that would favor an “anti effect”, in addition to traditional interpretations based on steric and electrostatic repulsion. Therefore, a balance of steric, dipolar and hyperconjugative effects drive the conformational equilibrium of these compounds – hyperconjugation was found to explain the gauche effect in some cases, whilst Lewis‐type interactions determine the anti preference in others. The gauche effect takes place in a polar solvent, but not for 1‐fluoro‐2‐iodoethane. According to NMR three‐bond spin‐spin coupling constants, the gauche population increases when fluorine is replaced by a hydroxyl group (except for 2‐fluoroethanol relative to 1,2‐difluoroethane), but this is not primarily due to intramolecular hydrogen bond.

One-bond spin–spin coupling constant (SSCC) data may be useful in providing information on the stereochemistry and intramolecular interactions in molecules.

2-Haloketones are building blocks that combine physical, chemical and biological features of materials and bioactive compounds, while organic fluorine plays a fundamental role in the design of performance organic molecules. Since these features are dependent on the three-dimensional chemical structure of a molecule, simple structural modifications can affect its conformational stability and, consequently, the corresponding physicochemical/biological property of interest. In this work, structural changes in 2-fluorocyclohexanone were theoretically studied with the aim at finding intramolecular interactions that induce the conformational equilibrium towards the axial or equatorial conformer. The interactions evaluated were hydrogen bonding, hyperconjugation, electrostatic and steric effects. While the gauche effect, originated from hyperconjugative interactions, does not appear to cause some preferences for the axial conformation of organofluorine heterocycles, more classical effects indeed rule the conformational equilibrium of the compounds. Spectroscopic parameters (NMR chemical shifts and coupling constants), which can be useful to determine the stereochemistry and the interactions operating in the series of 2-fluorocyclohexanone derivatives, were also calculated.

A series of aryloxyacetic acid derivatives have demonstrated promising herbicidal performance by inhibition of the hydroxyphenylpyruvate deoxygenase (HPPD) enzyme. We hereby applied quantitative structure−activity relationship (QSAR) and docking strategies to model and chemically understand the bioactivities of these compounds and subsequently propose unprecedented analogues aiming at improving the herbicidal and environmental properties. Bulky halogens at the 2-, 3-, 4-, and 6positions of an aromatic ring, CF 3 in 4-position, and the 2-NO 2 group in a phenyl ring appear to favor the HPPD inhibition. At the same time, Me and OMe substituents contribute to decreasing the pK i values. Accordingly, a few compounds were proposed and the candidate with 2,4,6-triBr substituents demonstrated an estimated pK i similar to those of the best library compounds. This finding was corroborated by the docking scores of the ligand−enzyme interactions. In addition, the high calculated lipophilicity of some proposed agrochemicals suggests that they should have low soil mobility and, therefore, are not prone to easily leach out and reach groundwater, despite causing other ecological issues.