activation enthalpy follows such a trend, while the trend
overcompensating the effects brought about around the react-
in activation entropy is reversed. Furthermore, the differ-
ing oxygen atom, resulting in the small negative slope value of
eqn. (7). The larger activation enthalpy for the reaction of
methyl iodide with the first series nucleophiles by comparison
to the activation enthalpy for the third series nucleophiles, ca. 5
kJ molϪ1 (see Fig. 3) would be rationalized as the extra enthalpy
that is required for more advanced partial desolvation around
a non-reacting oxygen. Eqns. (7) and (11) cross each other at
ential activation entropy, (∆S‡
Ϫ ∆S‡EtI) increases with
MeI
increasing specific interaction enthalpy of the nucleophile,
AN
∆tHSI
Specific interaction enthalpy, ∆tHSI
MeOH [eqn. (11)].
AN
MeOH, was origin-
ally introduced to characterize the nucleophile–methanol inter-
action, arising mainly from hydrogen-bonding interactions,
with acetonitrile being used as a reference.13 Acetonitrile as a
solvent possesses a definite hydrogen-bond donor acidity i.e. α =
0.19,18 although not as significant as for methanol, α = 0.93.18 In
accord with this, the single ion enthalpy of transfer for halide
ions from acetonitrile to amides, which do not have any
hydrogen-bond donor acidity, i.e., α = 0,18 are all positive.19
These facts suggest that hydrogen-bonding interactions
between acetonitrile and the anion do make a finite contri-
AN
MeOH
the specific interaction enthalpy, ∆tHSI
= Ϫ15.0 kJ
molϪ1. This suggests that in the benzoate ion reaction, the con-
tribution from the partial desolvation around the non-reacting
oxygen atom becomes negligible at this enthalpy.
Because of the large size and large polarizability of the
chlorine atom, a large number of solvent molecules surround-
ing the chlorine atom substituted at the para-position are
supposed to sense the variation of charge accompanying
activation. The extent of solvent expulsion around the chlorine
atom is supposed to be more prominent for a stronger
hydrogen-bond accepting anion and for the methyl iodide reac-
tion. This results in the larger negative slope in eqn. (9).
AN
MeOH
bution to the specific interaction enthalpy, ∆tHSI
.
Recently, partial desolvation around a nucleophilic central
atom accompanying activation has been suggested as the major
factor determining nucleophilic reactivity in acetonitrile.6,7
Analysis of kinetic isotope effects on nucleophilic substitution
reactions suggest that the nucleophile–α-carbon bond distance
is crucial in influencing reaction behavior, including kinetic
isotope effects.20 As the approach of a nucleophile to the reac-
tion center in the alkyl iodide becomes more unfavorable, by
substituting one of the α-hydrogen atoms in methyl iodide by a
methyl group, partial desolvation around the nucleophilic
center is more significant. That is to say, a larger number of
solvent molecules will have to be squeezed out of the solvation
sphere around the nucleophilic center. This led us to expect that
activation enthalpy as well as activation entropy for the ethyl
iodide reaction should become larger by comparison to those
of the methyl iodide reaction, and, as a result, the difference,
Concluding remarks
Partial desolvation accompanying activation proceeds at
various sites in anionic nucleophiles, and every site exerts indi-
vidual effects on the activation parameters. At least two types
of partial desolvation must be taken into account. Firstly,
solvent molecules surrounding the nucleophilic center have to
be squeezed out of the solvation sphere by the approach of the
nucleophile to the electrophile, and the contribution to the
activation parameters for the ethyl iodide reaction exceeds that
for the methyl iodide reaction. Secondly, accompanying the
partial shift of anionic charge from nucleophile to leaving
group, solvent molecules surrounding a non-reacting oxygen
atom in the carboxylate anion will have to be released; the
contribution for the methyl iodide reaction exceeds that for the
ethyl iodide reaction, since the transition state is located later.
The concept of steric effects in a conventional sense has to be
revised, in order to include the fact that partial desolvation
accompanying activation becomes more significant, the more
unfavorable steric crowding is in the transition state. In order
to unravel the molecular mechanistic features operating in
solution, examination of both enthalpic and entropic effects
is necessary, because enthalpy is a relevant thermodynamic
function for probing strong interactions in solution, whilst
entropic effects are more related to weak interactions.
∆S‡
Ϫ ∆S‡EtI, should become more negative as the nucleo-
MeI
phile is more solvated. According to this line of argument, the
empirical correlations, eqns. (10) and (11), would be rational-
ized as the result of partial desolvation of the solvation sphere
around the nucleophilic center for the third series, i.e., nucleo-
philes with a single reaction site. Empirical correlations eqns.
(5) and (11) could be transformed into common units (kJ
molϪ1), with the former being multiplied by 2.3 RT and the
latter by T . The value of the slope reduce to 0.31 for the former
and to 0.23 for the latter. This indicates that ca. 75% (∼0.23/
0.31) of the relative reactivity of methyl iodide to ethyl iodide is
determined by the partial desolvation discussed above.
In the reaction of carboxylate ions, two types of partial
desolvation are taking place. The first is that proceeding around
a reacting oxygen, the same type as the one discussed above,
and the second is that proceeding around non-reacting oxygen
atoms. Characteristic features of methyl iodide reactions which
are compared with those of ethyl iodide reactions, are summar-
ized as follows: the activation enthalpy in acetonitrile, is a little
smaller, by ca. 1.5 kJ molϪ1, the reaction enthalpy in acetonitrile
is less exothermic by ca. 6 kJ molϪ1, and the dissociation energy
is larger by ca. 4 kJ molϪ1.21 Consideration of these results on
the basis of such non-linear energy correlations as the Marcus
equation22 would lead us to conclude that the transition state is
located a little later along the reaction coordinate for the methyl
iodide reaction by comparison to that for the ethyl iodide
reaction. This is supported by the larger negative value of the
Hammett ρ for the methyl iodide reaction [eqn. (12)] by
Experimental
Materials
Tetramethylammonium salts containing the conjugate base
anion of a weak acid were prepared from tetramethylam-
monium hydroxide and the corresponding acid in methanol
according to the procedures described elsewhere.23 Solvents for
recrystallization and the results of elementary analysis are
summarized in Table 5. Other compounds were treated as
described elsewhere.24,25
Product analysis and kinetic measurements
Analysis of reaction products was performed by large scale
experiments under the same reaction condition as the kinetic
measurements, as described elsewhere.10 Reaction rates were
determined by measuring the concentration of iodide ion that
was produced by the reaction, by potentiometric titration using
silver nitrate solution,6,10 at four of the following temperatures:
0.0, 20.0, 30.0, 40.0, 50.0 and 60.0 ЊC. Experimental errors were
estimated from duplicate or triplicate runs to be ca. 2% for rate
constants, 0.8 kJ molϪ1 for ∆H‡ and 2.5 J KϪ1 molϪ1 for ∆S‡.
log kMeI = Ϫ0.592 Ϫ 0.92 Σσi
n = 4, r = 0.99
(12)
comparison to that for the ethyl iodide reaction [eqn. (3)] Ϫ0.92
( 0.02) vs. Ϫ0.78 ( 0.03). (The number in parenthesis gives the
standard error for a respective ρ value.)
The partial desolvation around the non-reacting oxygen is
supposed to proceed further for the methyl iodide reaction,
J. Chem. Soc., Perkin Trans. 2, 2002, 1449–1454
1453