Trifluoromethyl: An Amphiphilic Noncovalent Bonding Partner

Abstract

The traditional picture of bonded fluorine as strongly δ-suggests that it can only interact with electrophilic centers [1] and does not form halogen bonds,[2] however this view does not take polarization into account. In trifluoromethyl groups negative hyperconjugation (anomeric polarizability) results in two of the fluorine atoms becoming more polarizable and thus more able to form σ-holes.[3] The unique combination of the anomeric effect and the group-polarization process associated with it in trifluoromethyl groups allows the most negative molecular electrostatic potential (MEP) on the surface in contact with a nucleophile to become zero, so that the area of positive MEP on the backside of the carbon atom becomes dominant. The unusual group polarizability therefore results in the trifluoromethyl groups exhibiting amphiphilic behavior, i.e. acting not only as nucleophiles (as expected) but also as electrophiles and thus as halogen bond donors. A survey of experimental crystal structures obtained from the Cambridge Structural Database (CSD) and the Protein Databank (PDB) as well as MP2/aug-cc-pVDZ calculations on model systems demonstrate these interactions. In particular, a survey of structures in the CSD containing the trifluorotoluene moiety shows that the trifluoromethyl group forms more, and stronger, interactions with neighboring species than the F in fluorobenzene moieties, which does not experience anomeric polarization.

Nature of halogen‐centered intermolecular interactions in crystal growth and design: Fluorine‐centered interactions in dimers in crystalline hexafluoropropylene as a prototype

“…EDA based on the DFT‐based SAPT was performed at the zeroth level (called SAPT0) using PSI4 . Previous results by Esterhuysen et al show that as long as the MP2/aug‐cc‐pVDZ optimized geometries are reasonable, the CBS‐extrapolated DFT–SAPT interaction energies should be close to the state‐of‐the‐art CCSD(T)/CBS results. The SAPT tool is commonly used to provide insight into energetic contributions to the binding energy of a binary complex.…”

Intramolecular interactions in sterically crowded hydrocarbon molecules

“…Namely, the stability of the system not only strongly enhances mainly by increasing dispersion interactions with an increase of the sizes of the substituent groups but also by significant charge‐penetration electrostatic interactions. As the total noncovalent interactions in the systems studied are characterized by a delicate balance between attractive and repulsive forces, in the future it seems worthwhile to investigate the influence of other substituent groups to enhance the steric crowding, for example, using triflouromethyl groups as an alternative dispersion energy donor …”

B–H⋯π: a nonclassical hydrogen bond or dispersion contact?

“…In such a case, carboranes would qualify to the definition of an ''amphiphilic noncovalent bonding partner.'' 15 Additionally, one could envisage a situation in which the strong electronwithdrawing substituents (such as fluorines or cyano groups) on the phenyl ring create a p-hole (positive region), which would then interact with the B-H hydridic hydrogens. 16 We scrutinize here all these options for the interpretation of B-HÁ Á Áp contacts as weak H-bond by means of the advanced QM computational techniques first on the model systems and then on the Ir-dithiolene-phosphine complexes studied by Cremer et al…”

“…2B) with the polarization of the CF 3 group in the trifluoro-toluene (TFT)Á Á Ábenzene complex, whose geometry was adopted from ref. 15. We first analyzed the shift in the electron density of the studied molecules upon the complex formation, i.e.…”

“…Although the induction term was considerably smaller than the dispersion and electrostatic terms in the DFT-SAPT analysis, it should not be underestimated. In order to test whether the closo-1,2-C 2 B 10 H 12 molecule may be an ''amphiphilic nonbonding partner'', as has recently been shown for trifluorotoluene (TFT), 15 we compared the polarization of the B(9)-H bond in the closo-1,2-C 2 B 10 H 12 Á Á Ábenzene complex in B(9)-H geometry (Fig. 2B) with the polarization of the CF 3 group in the trifluoro-toluene (TFT)Á Á Ábenzene complex, whose geometry was adopted from ref.…”