Intrinsic Nucleophilicity of Solvated Nucleophiles
A R T I C L E S
induced dipole interactions, and/or intramolecular hydrogen
3
1,32
bonding.
This makes the set of the alkoxides a good model
system for studying the effect of intramolecular microsolvation
3
3
on nucleophilicity. The exothermicities of the corresponding
-1
SN2 reactions span over a ∼30 kcal mol range, which makes
obvious the nonlinear relationship between the exothermicity
and the barrier height predicted by Marcus theory. Despite the
great difference in the overall exothermicities, the measured
intrinsic barrier heights for the alkoxides with various polar
-
1
group substitutions are essentially the same, ∼3.8 kcal mol
.
Figure 1. ∆Eint and ∆Eact in Marcus theory for a single-barrier potential
energy surface.
Therefore, we conclude that polar group substitution does not
significantly affect intrinsic nucleophilicity. On the other hand,
hydrogen bonding does lower intrinsic nucleophilicity. For
alkoxides, a single hydrogen bond increases the intrinsic barrier
height by ∼3 kcal mol . Other factors, such as conjugation
and steric hindrance, also lower intrinsic nucleophilicity to
different extents.
-
1
a large amount, typically ∼20 kcal mol for single solvent
molecule solvation. A great portion of the thermodynamic
driving force is lost, and the reactivity significantly lowered.
However, it is not clear how the intrinsic nucleophilicity is
affected by microsolvation. To understand this, the contribution
from exothermicity must first be excluded.
-1
Experimental Section
Marcus theory predicts a simple relationship between the
observed activation energy, ∆Eact, and the overall exo/endot-
Materials. All reagents used in this study were commercially
available except for 1,3-cyclohexanediols and 1,4-cyclohexanediols,
which were purchased as mixtures of cis and trans isomers. Pure
samples were obtained by separating the mixtures through previ-
1
6,17
hermicity of the reaction, ∆Erxn.
∆Eact consists of two
components; one is the intrinsic component and the other arises
solely from the thermodynamic driving force. The intrinsic
activation energy, ∆Eint, is defined as the barrier height in
absence of a thermodynamic bias, Figure 1. Therefore, ∆Eact
and ∆Eint are equal only in thermoneutral reactions. For
nonthermoneutral reactions, ∆Eint can be related to ∆Eact by eq
3
2
ously reported procedures.
Ab Initio Calculations. MP2 (second-order Møller-Plesset
34
35,36
theory) and DFT (density functional theory)
calculations were
performed. Geometries were optimized at the B3LYP/6-31+G*
level of theory. Single-point MP2 energies were calculated on the
DFT geometries at the 6-311+(2d,p) basis set. These calculations
were used for energetic and structural analysis as well as for input
parameters for RRKM (Rice, Ramsperger, Kassel, Marcus) modeling.
Reaction Rates. All reaction rates were measured in the gas
phase using an IonSpec OMEGA Fourier transform ion cyclotron
resonance spectrometer (FT-ICR). The magnetic field strength was
0.6 T. The temperature of the 2 in. cubic stainless steel cell was
1
.
2
∆
Erxn (∆Erxn
)
∆
Eact ) ∆Eint
+
+
(1)
2
16∆Eint
Although Marcus theory was originally designed for electron-
transfer reactions, the underlying kinetic-thermodynamic re-
3
3
estimated to be 350 K. Background pressures ranged from 0.5 to
-
9
1
6-19
4
.0 × 10 Torr, and operating pressures ranged from 0.3 to 5.0
lationship goes far beyond,
applied to a variety of organic reactions,
cleophilic substitution reactions in the gas phase.
and it has been successfully
-6
2
0-24
× 10 Torr. A Granville Phillips 330 ion gauge was used to obtain
including nu-
6
,25-30
pressure readings, which were calibrated against an MKS Baratron
Using
1
70 capacitance manometer (315BH-1 sensor). Absolute pressure
Marcus theory, we can analyze how solvent molecules affect
intrinsic nucleophilicity without the complications from reaction
exothermicity. In this work, we report the gas-phase SN2
reactivities of a set of selected alkoxides toward methyl chloride.
These alkoxides were substituted with a variety of functional
groups, including polar groups and hydrogen-bond donors. The
functional group substitution can introduce ion-dipole, ion-
33
measurements were estimated to have an error of (20%.
The rate constants for the S 2 reactions of various alkoxides
N
with methyl chloride are reported in Table 1. Primary ions, fluoride
or tert-butoxide, were generated from nitrogen trifluoride and di-
tert-butyl peroxide, respectively. Other alkoxides were produced
via proton transfer reactions between the primary ions and corre-
sponding alcohols. Buffer gases were added to ensure that the ions
were completely thermalized. The reaction rates measured by
monitoring disappearance of the alkoxides as well as appearance
of chloride. No pressure dependence on buffer was observed in
the reaction rates of most alkoxides except fluoride or tert-butoxide.
The rates for the two ions were slightly slower under very low
(
(
(
(
16) Marcus, R. A. Annu. ReV. Phys. Chem. 1964, 15, 155–196.
17) Marcus, R. A. J. Am. Chem. Soc. 1969, 91, 7224–7225.
18) Murdoch, J. R. J. Am. Chem. Soc. 1972, 94, 4410–4418.
19) Magnoli, D. E.; Murdoch, J. R. J. Am. Chem. Soc. 1981, 103, 7465–
-
7
7
469.
20) Richard, J. P.; Amyes, T. L.; Williams, K. B. Pure Appl. Chem. 1998,
0, 2007–2014.
21) Richard, J. P.; Williams, K. B.; Amyes, T. L. J. Am. Chem. Soc. 1999,
buffer pressures (<3 × 10
Torr). The reactivities become
(
(
-6
pressure-independent under relatively high pressures (3 × 10
Torr) or after waiting a few hundred milliseconds. The reported
values for these ions were measured in the pressure-independent
region.
7
1
21, 8403–8404.
(
(
22) Guthrie, J. P. J. Am. Chem. Soc. 2000, 122, 5529–5538.
23) Alabugin, I. V.; Manoharan, M.; Breiner, B.; Lewis, F. D. J. Am. Chem.
Soc. 2003, 125, 9329–9342.
Accurate measurements of slow reaction rates require extra
attention to exclude artifacts introduced from trace amounts of
(
(
(
24) Richard, J. P.; Williams, K. B. J. Am. Chem. Soc. 2007, 129, 6952–
6
961.
25) Wolfe, S.; Mitchell, D. J.; Schlegel, H. B. J. Am. Chem. Soc. 1981,
03, 7694–7696.
26) Pellerite, M. J.; Brauman, J. I. J. Am. Chem. Soc. 1983, 105, 2672–
(31) Crowder, C. A.; Bartmess, J. E. J. Am. Soc. Mass Spectrom. 1993, 4,
723–726.
1
(32) Chen, X.; Walthall, D.; Brauman, J. J. Am. Chem. Soc. 2004, 126,
12614–12620.
2
680.
(
(
(
27) Dodd, J. A.; Brauman, J. I. J. Phys. Chem. 1986, 90, 3559–3562.
28) Uggerud, E. J. Chem. Soc., Perkin Trans. 2 1999, 7, 1459.
29) Hoz, S.; Basch, H.; Wolk, J. L.; Hoz, T.; Rozental, E. J. Am. Chem.
Soc. 1999, 121, 7724–7725.
(33) Craig, S. L.; Brauman, J. I. J. Am. Chem. Soc. 1999, 121, 6690–6699.
(34) Curtiss, L. A.; Raghavachari, K.; Trucks, G. W.; Pople, J. A. J. Chem.
Phys. 1991, 7221.
(35) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37, 785.
(36) Becke, A. D. J. Chem. Phys. 1993, 98, 1372.
(
30) Uggerud, E. Chem.sEur. J. 2006, 12, 1127–1136.
J. AM. CHEM. SOC. 9 VOL. 130, NO. 45, 2008 15039