Denegri and Kronja
JOCArticle
TABLE 3. Values of mOTs Parameters from the Grunwald-Winstein Correlations for Solvolysis of X,Y-Substituted Benzhydryl Heptafluorobutyrates
and Trifluoroacetates
b,c
mOTs
HFB
TFA
solventa
2
3
4
5
6
3
4
5
6
M-W
E-W
A-W
0.65 (2)
0.52 (2)
0.73 (0)
0.64 (1)
0.59 (2)
0.73 (1)
0.64 (2)
0.55 (0)
0.61 (5)
0.64 (2)
0.52 (0)
0.58 (2)
b
0.65 (1)
0.62 (1)
0.64 (6)
0.66 (1)
0.62 (0)
0.68 (5)
0.64 (4)
0.62 (0)
0.66 (2)
0.53 (2)
0.52 (4)
0.57 (1)
0.58 (3)
aBinary solvents are A = acetone, E = ethanol, W = water. Obtained from log k vs. YOTs plots. The uncertainties of the last reported figure
c
(standard error) are shown in parentheses.
the sensitivity toward the solvents is almost independent of
the benzhydryl structure. The decrease of mOTs as the
electrofugality of the substrate increases was taken as an
indication of diminished solvation due to charge delocaliza-
tion in the nucleofuge. Therefore, almost invariant mOTs
values indicate that delocalization in the carboxylate moiety
does not diminish the importance of solvation very much in
HFBs, which is in agreement with the above drawn conclu-
sions based on practically invariant sf values for HFB. On the
basis of the trends of mOTs values and on the above sf, the
same can be concluded for TFAs.
Somewhat higher reactivity of HFBs than TFAs in solvo-
lysis may come from back strain due to the size of HFB, and/
or also from different charge distribution in the TS. It has
FIGURE 3. Optimized PCM-B3LYP/6-311þG(2d,p) geometries
been shown that relief of back strain leads to an early
transition state with little charge separation, and therefore
of the most stable conformers of benzhydryl heptafluorobutyrate
and heptafluorobutanoate anion with selected bond lengths
(angstroms).
an unusually small F value.10,11 Even though sf values
obtained are almost equal, indicating that the relief of the
back strain is probably not a very important parameter that
determines the relative reactivities of HFBs and TFAs, it
cannot be ruled out that the size of the fluorinated alkyl
group does at least partially influence the relative reactivities.
Solvolytic reactivity is also in accordance with experimental
findings that heptafluorobutyric acid is slightly more acidic
than trifluoroacetic acid (ΔpK ≈ 0.1),15 i.e., that the less basic
HFB anion is a better leaving group.
Quantum Chemical Calculations. To identify the structural
features that are responsible for slightly different nucleofug-
alities of TFA and HFB, we carried out quantum chemical
calculations using the Gaussian 03 program suite.16 Geome-
tries of 3-TFA and 3-HFB, and those of the corresponding
anions (trifluoroacetate and heptafluorobutyrate anions,
respectively), were fully optimized at B3LYP/6-31G(d,p)
levels. For benzhydryl heptafluorobutyrate 14 energy
minimum structures were located on the PES, while two
structures were located for benzhydryl trifluoroacetate (all
presented in the Supporting Information). For the most
stable conformers, the geometries were optimized and the
frequencies were calclated at the B3LYP/6-311þG(2d,p)
level. NBO charges in the gas phase and in ethanol were
calculated at the B3LYP/6-311þG(2d,p) level (for complete
data see the Supporting Information). The most stable
optimized B3LYP/6-311þG(2d,p) structures of benzhydryl
heptafluorobutyrate and the HFB anion are presented in
Figure 3, along with some parameters.
By using the polarizable continuum model (PCM), the
geometries of the most stable conformers of 3-TFA and 3-
HFB and the corresponding anions, and the benzhydrylium
ion in ethanol were optimized at the PCM-B3LYP/6-311þG
(2d,p) level.
The affinity of the benzhydrylium cation toward a given
leaving group, presented with the following process (LG=
TFA and HFB)
Ph2CHþþLG- f Ph2CH-LG
(15) Moroi, Y.; Yano, H.; Yonemitsu, T. Bull. Chem. Soc. Jpn. 2001, 74,
667–672.
is calculated according to eq 2, taking the calculated energies
for the most stable conformers:
(16) (a) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant,
J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi,
M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.;
Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.;
Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma,
K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.;
Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford,
S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi,
I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara,
A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.;
Gonzalez, C.; and Pople, J. A. Gaussian 03, Revision D.02; Gaussian, Inc.,
Wallingford, CT, 2004
ΔEaff ¼ EcalcdðPh2CH-LGÞ -½EcalcdðPh2CHþÞ
þEcalcdðLG-Þꢁ
ð2Þ
The affinities (ΔEaff) are presented in Table 4, along with
NBO charge distributions between the carboxylate moiety
and the fluorinated alkyl group (R).
Both theoretical results and the charge distribution and
affinities of the benzhydrylium ion toward the leaving groups
are consistent with experimental findings that HFBs are
somewhat more reactive in SN1 reactions. Interestingly, the
5932 J. Org. Chem. Vol. 74, No. 16, 2009
Denegri, Bernard
