Toward a Physical Interpretation of Substituent Effects: The Case of Fluorine and Trifluoromethyl Groups

Abstract

The application of ab initio and DFT computational methods at six different levels of theory (MP2/cc-pVDZ, MP2/aug-cc-pVTZ, B3LYP/cc-pVDZ, B3LYP/aug-cc-pVTZ, M06/cc-pVDZ, and M06/aug-cc-pVTZ) to meta- and para-substituted fluoro- and trifluoromethylbenzene derivatives and to 1-fluoro- and 1-trifluoromethyl-2-substituted trans-ethenes allowed the study of changes in the electronic and geometric properties of F- and CF3-substituted systems under the impact of other substituents (BeH, BF2, BH2, Br, CFO, CHO, Cl, CN, F, Li, NH2, NMe2, NO, NO2, OH, H, CF3, and CH3). Various parameters of these systems have been investigated, including homodesmotic reactions in terms of the substituent effect stabilization energy (SESE), the π and σ electron donor-acceptor indexes (pEDA and sEDA, respectively), the charge on the substituent active region (cSAR, known earlier as qSAR), and bond lengths, which have been regressed against Hammett constants, resulting mostly in an accurate correspondence except in the case of p-fluorobenzene derivatives. Moreover, changes in the characteristics of the ability of the substituent to attract or donate electrons under the impact of the kind of moiety to which the substituent is attached have been considered as the indirect substituent effect and investigated by means of the cSAR model. Regressions of cSAR(X) versus cSAR(Y) for any systems X and Y allow final results to be obtained on the same scale of magnitude.

How OH and O– groups affect electronic structure of meta-substituted and para-substituted phenols and phenolates

“…Moreover, the cSAR approach can be applied to both, the varying substituents, [as cSAR(X)], as well as to the reaction site (or a fixed functional group in the series X-R-Y), [cSAR(Y)], and allows to estimate the regression line cSAR(Y) vs. cSAR(X). The slope of this regression describes the strength of interactions between X and Y [9,10]. It was also shown that changes in geometry of the components of the functional group Y correlate well with cSAR(Y) [12] and hence correlate also with cSAR(X) that was documented for aniline [10], nitrobenzene [13], and benzoic acid [14] substituted derivatives.…”

“…By definition, cSAR(X) is a sum of atomic charges at all atoms of the substituent and the ipso carbon atom [7]. This descriptor correlates well with substituent constants [7][8][9][10]. It is important to stress that the cSAR(X) approach realized by the use of different atomic charge schemes leads to the results which are, as a rule, mutually well correlated [11].…”

“…This approach allows to determine, in an energetic scale, the nature of the interaction between substituents in disubstituted systems. It was documented that the SESE characteristic correlates well with classical substituent constants [9,10]. SESE is a descriptor of substituent electron donating/attracting properties and takes into account all interactions in the X-R-Y system.…”

Towards physical interpretation of substituent effects: the case of N- and C3-substituted pyrrole derivatives

“…cSAR(X) is a sum of atomic charges of X and of the ipso atom (carbon or nitrogen in our case) to which the substituent is attached. It was shown that cSAR(X) values correlate well [15,[19][20][21][22] with the Hammett substituent constants [13]. Moreover, it was documented that cSAR of a functional group (NO and NMe 2 ) in para-substitute d d e r i v a t i v e s o f n i t r o s o b e n z e n e a n d N , Ndimethylaminebenzene nicely describes changes in the geometry in these groups [23].…”

“…The other face of intramolecular interactions described as substituent effects is named reverse substituent effect. This means that electron-donating/electronattracting properties of X depend on the kind of R-Y part of the molecule [15][16][17]. A great number of various substituent constants (see a complete collection of them in [13]) are just a result of this kind of interactions.…”