Solvolytic reactivity of pyridinium ions

Article abstract of DOI:10.1002/poc.3412

The leaving group abilities of pyridine, 4-methylpyridine, and 4-chloropyridine in S_N1 solvolytic reactions have been determined by analyzing the rate constants of X,Y-substituted benzhydrylpyridinium salts obtained in various solvents. By applying the linear free energy relationship equation, log k = s_f (E_f + N_f), the nucleofuge specific parameters of 4-substituted pyridine have been extracted. Because of solvation in the reactant ground state, the reactivity (nucleofugality, N_f) of a given pyridine decreases as the polarity of the solvent increases. High slope parameters (s_f > 1) may be due to the spread of the energy levels of the benzhydrylium ion/pyridine pair intermediates in comparison to benzhydrylium ion/chloride pairs (s_f ≈ 1). Because of slow heterolysis step of pyridinium salts in various solvents, some are stable under normal conditions.

Full text of DOI:10.1002/poc.3412

Research Article
Received: 04 October 2014,
Revised: 24 November 2014,
Accepted: 27 November 2014,
Published online in Wiley Online Library: 23 February 2015
(wileyonlinelibrary.com) DOI: 10.1002/poc.3412
Solvolytic reactivity of pyridinium ions
Sandra Jurića and Olga Kronjaa*
The leaving group abilities of pyridine, 4-methylpyridine, and 4-chloropyridine in SN1 solvolytic reactions have been deter-
mined by analyzing the rate constants of X,Y-substituted benzhydrylpyridinium salts obtained in various solvents. By apply-
ing the linear free energy relationship equation, log k = sf (Ef + Nf), the nucleofuge specific parameters of 4-substituted
pyridine have been extracted. Because of solvation in the reactant ground state, the reactivity (nucleofugality, Nf) of a given
pyridine decreases as the polarity of the solvent increases. High slope parameters (sf > 1) may be due to the spread of the
energy levels of the benzhydrylium ion/pyridine pair intermediates in comparison to benzhydrylium ion/chloride pairs
(sf ≈ 1). Because of slow heterolysis step of pyridinium salts in various solvents, some are stable under normal conditions.
Copyright © 2015 John Wiley & Sons, Ltd.
Keywords: intrinsic barriers; kinetics; nucleofugality; pyridinium ions; solvolysis
nucleofugality/electrofugality scales have been developed using
neutral substrates that generate negatively charged leaving
INTRODUCTION
Pyridinium ions have an important role as organic catalysts and
also as substrates for investigation of the reaction mecha-
nisms.[1–3] Compounds containing a pyridinium moiety have
found use as cationic surfactants,[4] which are employed in vari-
ous areas ranging from biological to industrial applications (e.g.,
cosmetics, pharmaceuticals, gene delivery, and polymerization).
Quaternary pyridinium salts are also useful as acylating agents,[5]
phase transfer catalysts,[6] dyes,[7] and biocides with a wide range
of antimicrobial activity.[8] High toxicity of pyridinium com-
pounds for microorganisms is complemented by their low toxic-
ity for man and other mammalian species causing their use as
disinfecting or sanitizing agents. Accessibility of easy and quick
prediction of their reactivity with solvents is very important as
well as recognition of the structural features that determine it.
Mayr et al. have investigated the nucleophilicities of the series
of substituted pyridines kinetically, by combining them with
substituted benzhydrylium ions.[9] In order to obtain a complete
profile of solvolytic behavior of pyridines, we set out to investi-
gate the heterolytic bond breaking of pyridinium ions and for-
mation of the free pyridine derivative and benzhydrylium ion
in the rate-determining step of SN1 solvolysis. It is the reversible
combination reaction investigated by Mayr (Scheme 1), in which
the pyridine derivative acts as an uncharged leaving group.
The reactivity of the leaving group is well defined with its
nucleofugality according to the special linear free energy rela-
tionship in which the contribution of the electrofuge and the
nucleofuge on the overall rate is separated and the absolute
rate of the SN1 reaction can be estimated applying the following
Eqn :(1)[10,11]
groups, investigation of the benzhydrylsulfonium ions revealed
that the same approach can be used with charged substrates
in which neutral nucleofuges are generated.[12,13]
RESULTS AND DISCUSSION
The X,Y-substituted benzhydryl-4-chloropyridinium 2a–5a, pyri-
dinium 1b–4b, and 4,4′-dimethoxybenzhydryl-4-methyl-
pyridinium 1c perchlorates (syntheses shown in the
Experimental) were subjected to solvolysis in the series of
aqueous and alcoholic solvents. The solvolysis rates were
followed by titration of the liberated pyridinium perchlorates
with solution of sodium hydroxide in appropriate solvent.
Since the second step (Scheme 1), the combination reaction
between the generated benzhydrylium ion and the solvent is
very fast (for all cases k2 > 105 Mꢀ1 sꢀ1);[14] formation of
pyridinium perchlorate corresponds to the heterolysis rate con-
stant (k). Activation parameters were calculated from rate con-
stants determined at least at three different temperatures. The
measured and the extrapolated rate constants (25 °C) and the
activation parameters are presented in Table 1 (k measured
at different temperatures is given in Table S1 of the
Supporting information).
The logarithms of the first-order rate constants at 25 °C for sol-
volysis of benzhydryl-4-chloropyridinium ions 2a–5a and
benzhydrylpyridinium ions 1b–4b in the given solvents were
plotted against Ef. Electrofugality parameters of X,Y-substituted
benzhydrylium ions are taken from Streidl et al. [11] The plots ob-
tained for benzhydrylpyridinium ions 1b–4b are presented in
Fig. 1 (other plots for benzhydryl-4-chloropyridinium ions 2a–
log kð25 °CÞ ¼ sf ðEf þ Nf Þ
(1)
in which k is the first-order ionization rate constant, sf is the
nucleofuge-specific slope parameter, Nf is the nucleofugality,
and Ef is the electrofugality parameter. Ef is an independent var-
iable determined only with substituents on the benzhydryl sys-
tem, whereas the nucleofuges are characterized with two
parameters, Nf and sf, which are defined for the specific combi-
nation of a leaving group and a solvent. Although the
* Correspondence to: Olga Kronja, University of Zagreb, Faculty of Pharmacy
and Biochemistry Ante Kovačića 1, Zagreb 10000, Croatia.
E-mail: okronja@pharma.hr
a S. Jurić, O. Kronja
Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovačića 1,
Zagreb 10000, Croatia
J. Phys. Org. Chem. 2015, 28 314–319
Copyright © 2015 John Wiley & Sons, Ltd.

SOLVOLYTIC REACTIVITY OF PYRIDINIUM IONS
that the nucleofugality of 4-chloropyridine in
water is ꢀ2.95. Similarly, taking the
electrofugality for 4,4′-bis(methylamino)
benzhydrylium ion (Ef = 4.84)[11] and aver-
age sf = 1.18, by applying Eqn (1) we ob-
tained that the nucleofugality of pyridine in
water is ꢀ4.00.
The solvolysis rates of pyridinium ions
slightly decrease as the polarity of the sol-
vent increases, similarly as it has repeatedly
been shown for charged substrates, such as
dimethylsulfonium[17,18] and thiophenium
salts.[19] In more polar solvents, pyridinium
ions are more stabilized by solvation in the
reactant ground state than in the corre-
Scheme 1. Solvolysis of X,Y-substituted benzhydrylpyridinium perchlorates
5a, see in Fig. S1 of the Supporting information). The nucleofuge-
specific parameters (Nf and sf) for pyridine and 4-chloropyridine
have been extracted from the correlation lines (R2 > 0.99;
Table 2). Essentially invariant sf for pyridine and 4-chloropyridine
in aqueous alcohol mixtures enabled determination of the
nucleofugalities of 4-methylpyridine from a single rate constant
taking the average sf value (1.21 for MeOH, 1.16 for 80% aq.
MeOH, 1.23 for EtOH, and 1.12 for 80% aq. EtOH).
The values of sf determined for pyridinium ions are all in the
range of the sf values obtained with numerous substrates that
solvolyze via SN1 route.[11] The fundamentals of the reaction con-
stant sf and the Hammett–Brown ρ+ parameter are principally the
same (ρ+ ≈ ꢀ4.4sf),[15] so they can be related to typical ρ+ values
for solvolysis of monosubstituted benzhydryl derivatives that fol-
low SN1 pathway (ρ+ = ꢀ4.06 in 2-propanol and ρ+ = ꢀ4.05 in eth-
anol).[16] The high values of the reaction constants (sf > 1) are the
most important parameters that indicate development of the
positive charge on the benzhydryl moiety in the transition state
(TS), verifying the formation of the intermediate benzhydrylium
ion in a rate-determining step (Scheme 1) and at the same time
ruling out the concerted mechanism.
sponding TS, because in the latter the charge is delocalized, be-
cause of its partial transfer from pyridine to the benzhydryl
moiety. The net effect is an increase of the activation barrier.
The exception is solvolysis of charged adamantyl derivatives (e.
g., sulfonium ions) in which the heterolysis rate increases very
slightly as the polarity of the solvent increases because of spe-
cific solvation caused with the cage structure.[20]
The two major features that give rise to the overall entropy of
activation (ΔS‡) are the gain of translational and vibrational free-
dom because of the elongated C–N bond and the diminished
solvation due to positive charge delocalization in the TS. As
shown in Table 1, the most reactive derivative of benzhydryl-4-
chloropyridinium ion (2a) has lower entropies of activation
(ΔS‡) than other benzhydrylpyridinium ions. To examine the
charge distribution and thus compare the importance of solva-
tion in the reactant ground state of 2a with other
benzhydrylpyridinium ions, we fully optimized the geometry of
benzhydryl-4-chloropyridinium ion and benzhydrylpyridinium
ion at IEFPCM-M06-2X/6-311 + G(2d,p) level in a dielectric contin-
uum representing water as solvent and calculated the group
charges (natural bond orbital NBO; data of quantum chemical calcula-
tions with appropriate references shown in the Experimental and the
Supporting information). It turned out that substituent on the pyridine
has no influence on the charge distribution and that the charge is
equally distributed between the pyridine (+0.66) and benzhydryl
(+0.34) moiety in both substrates (Table S2 of the Supporting informa-
tion). The result is in accord with Mayr’s results obtained in the gas
phase,[9] showing that 65–70% of the positive charge is located
on the pyridine moiety and that charge distribution is almost in-
variant on the substituents on the benzhydryl group or on pyridine
moiety.
Mayr has presented rate constants and the corresponding equi-
librium coefficients for combination reactions of 4-chloropyridine
with 4,4′-bis(morpholino)benzhydrylium ion and pyridine with
4,4′-bis(methylamino)benzhydrylium ion in water.[9] We calculated
the corresponding rates of the heterolysis reactions (k) using the fol-
lowing equation: Keq = kꢀ1/k (Scheme 1). Then, by applying Eqn (1)
and taking an average sf value (1.18) and the Ef parameter for 4,4′-
bis(morpholino)benzhydrylium ion (Ef = 3.03),[11] we determined
Assuming that the stabilization by solvation in the reactant
ground state of 4-chloropyridinium ions is similar to that of the
other pyridinium ions, because of the similar charge distribution,
the considerable lower entropies of activation for 2a come from
earlier TSs of the heterolysis step. It seems that, because of earlier
TS of more reactive 4-chloropyridinium ions, the transfer of the
positive charge to the carbon atom is considerably less advanced
than in the TS of other pyridinium ions and the charge distribution
in the TS is similar to that in the reactant ground state; hence, the
demand for solvation is still high. On the other hand, in less-
reactive substrates, the charge transfer in the TS of the heterolysis
process is more advanced, and the positive charge is more distrib-
uted, so the demand for solvation is diminished, giving rise to ΔS‡.
For comparison, calculations at the same level of theory have
been performed with benzhydryldimethylsulfonium ions. The re-
sults revealed that, unlike in pyridines, the positive charge is
Figure 1. Plots of solvolysis rate constants log k (25 °C) versus the
electrofugality parameters Ef[11] of X,Y-substituted benzhydrylpyridinium
perchlorates. Binary solvents are given as v/v at 25 °C: A, acetone; E, eth-
anol; M, methanol; and W, water
J. Phys. Org. Chem. 2015, 28 314–319
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/poc

S. JURIĆ AND O. KRONJA
Table 1. Solvolysis rate constants and activation parameters of some X,Y-substituted benzhydrylpyridinium perchlorates in vari-
ous solvents at 25 °C
Solventa
100M
Substrate
k/sꢀ1b
ΔH‡/kJmolꢀ1c
ΔS‡/JKꢀ1molꢀ1c
2a
3a
4a
5a
1b
2b
3b
4b
1c
2a
3a
4a
1b
2b
3b
4b
1c
2a
3a
4a
5a
1b
2b
3b
4b
1c
2a
3a
4a
1b
2b
3b
4b
1c
5.71 × 10ꢀ3d
(1.56 0.04) × 10ꢀ3
(1.83 0.10) × 10ꢀ4
3.48 × 10ꢀ6d
88.9 1.6
10.2 5.8
124.3 3.4
109.0 1.6
67.8 10.7
69.5 5.7
2.11 × 10ꢀ3d
(2.35 0.03) × 10ꢀ4
(4.54 0.04) × 10ꢀ5
7.59 × 10ꢀ6d
113.4 0.1
89.6 0.5
37.4 0.4
7.8 1.8
(1.97 0.04) × 10ꢀ4
3.10 × 10ꢀ3d
80M20W
(9.35 0.04) × 10ꢀ4
(1.33 0.10) × 10ꢀ4
(1.53 0.06) × 10ꢀ3
(1.67 0.03) × 10ꢀ4
3.91 × 10ꢀ5d
113.2 3.3
119.6 2.4
50.5 10.4
55.0 7.7
5.23 × 10ꢀ6d
(1.48 0.02) × 10ꢀ4
4.55 × 10ꢀ3d
100E
88.9 0.2
8.9 0.2
(1.26 0.13) × 10ꢀ3
(1.48 0.03) × 10ꢀ4
2.64 × 10ꢀ6d
118.9 0.6
47.0 1.9
(1.85 0.02) × 10ꢀ3
(2.41 0.12) × 10ꢀ4
4.34 × 10ꢀ5d
110.9 3.4
117.5 1.5
44.4 10.7
49.1 4.9
5.99 × 10ꢀ6d
(1.99 0.03) × 10ꢀ4
2.87 × 10ꢀ3d
80E20W
88.1 4.2
18.1 14.9
(8.89 0.04) × 10ꢀ4
(1.21 0.10) × 10ꢀ4
(1.07 0.03) × 10ꢀ3
(1.33 0.04) × 10ꢀ4
3.11 × 10ꢀ5d
107.7 2.5
110.8 2.9
30.0 8.9
26.1 8.9
5.49 × 10ꢀ6d
(1.24 0.07) × 10ꢀ4
(6.93 0.04) × 10ꢀ4
(8.77 0.11) × 10ꢀ5
2.19 × 10ꢀ5d
90A10W
80A20W
1b
2b
3b
4b
1c
1b
2b
3b
4b
1c
114.7 2.5
114.3 2.6
49.1 8.0
34.7 8.4
3.83 × 10ꢀ6d
(7.24 0.03) × 10ꢀ5
(4.67 0.07) × 10ꢀ4
(7.11 0.04) × 10ꢀ5
1.87 × 10ꢀ5d
110.1 2.7
116.4 1.6
34.0 8.4
40.6 5.1
3.32 × 10ꢀ6d
(4.73 0.01) × 10ꢀ5
aBinary solvents are given as v/v at 25 °C: A, acetone; E, ethanol; M, methanol; and W, water.
bAverage rate constants from at least three runs performed at 25 °C. Errors are standard deviations.
cErrors shown are standard errors.
dExtrapolated from data at different temperatures by using the Eyring equation.
almost completely (about 97%) located on the sulfur. These re-
sults would imply increase of the demand for solvation in the re-
actant ground state and thus increase of ΔS‡. Indeed, the
entropies of activation of benzhydryldimethylsulfonium ions are
in average for about 40 Jmolꢀ1 Kꢀ1 more favorable than those
for benzhydrylpyridinium ions (ΔS‡ for dimethylsulfonium ions
is between 77 and 98 Jmolꢀ1 Kꢀ1 in aqueous alcohols).[12] In the
reactant ground state, the demand for solvation is more impor-
tant for sulfonium than for pyridinium ions, because in the latter
the charge in the reactant ground state is already somewhat
delocalized. Therefore, because of less-pronounced gain of the
degrees of freedom in the TS of pyridinium ions than sulfonium
slats, the entropy of activation is lower, contributing that
pyridinium ions solvolyze over higher barrier.
wileyonlinelibrary.com/journal/poc
Copyright © 2015 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2015, 28 314–319

SOLVOLYTIC REACTIVITY OF PYRIDINIUM IONS
We plotted the Nf values for 4-substituted pyridines a–c
against the Hammett’s σp constants and obtained good correla-
tion in aqueous and alcoholic solvents (R2 > 0.99; Fig. S2 of the
Supporting information). Although this correlation has to be con-
sidered with caution because only three data points are avail-
able, it undoubtedly shows that the substituents on pyridine
influence on the stability of the TS via inductive and resonance
effects. As expected, positive slope of the correlation lines
(ρ ≈ 5) has been obtained, revealing that electron-withdrawing
substituents increase the rate of heterolysis step.
As mentioned previously, the value of sf may indicate more
or less positive charge on the reaction center in the TS, that is,
earlier or later TS. The slopes of all log k versus Ef correlation
lines obtained here are well above unity (Table 2), which
might indicate late carbocation-like TS. To rationalize this ob-
servation, it is advantageous to compare the nucleofuge-
specific parameters of pyridine (Nf = ꢀ2.71 in 80% aq. ethanol)
with more reactive nucleofuge, for example, chloride (Nf = 3.24
in 80% aq. ethanol).[10]
Figure 2. Illustration of the relative energy profiles of some X,Y-
substituted pyridinium ions and chloride in 80% aq. ethanol. Estimated
energies are given in kJmolꢀ1
Mayr showed that the combination reactions between chlo-
ride ion and less stabilized benzhydrylium ions (Ef < ꢀ3.5) are
diffusion-controlled processes that proceed without a bar-
rier.[14] On the other hand, the intrinsic barriers for combina-
tion of various pyridines with benzhydrylium ions in
dichloromethane, which are almost independent of the nature
benzhydrylpyridinium ions has been calculated from the reported
kꢀ1 and Keq for 4,4′-(N,N-dimethylamino)benzhydrylpyridinium ion
in water,[9] by applying Marcus equation: ΔG‡ = ΔG0‡ + 0.5 ΔrG°
+ [(ΔrG°)2/16ΔG0‡]. The barrier obtained (ΔG‡0 = 46 kJ molꢀ1) has
been approximated for those in 80% aq. ethanol. The Gibbs free
energies of activation (ΔG‡) in 80% aq. ethanol for pyridinium salts
and chlorides (at 25 °C) have been calculated from the solvolysis
rate constants presented here or from the solvolysis rate constants
taken from Denegri et al.[10a] or from those obtained by applying
Eqn (1). Finally, taking those ΔG‡0 and ΔG‡s, the Gibbs free energies
(ΔrG0) for heterolysis step of pyridinium ions in 80% aq. ethanol have
been calculated by applying the aforementioned Marcus equation.
Indeed, the energy levels of the benzhydrylium ion/pyridine pairs
are more spread than those of benzhydrylium ion/chloride pairs;
hence, with increasing Ef the trend of increasing solvolysis rates of
pyridinium ions is more pronounced than the trend of the corre-
sponding chlorides, resulting in steeper log k versus Ef correlation
lines (sf > 1). Even though that the actual intrinsic barriers somewhat
differ from that used in calculation because of the different solvent
used (e.g., it is 53 kJ molꢀ1 in dichloromethane), it should be empha-
sized that the energy profiles would have the same pattern regard-
less of the height of the actual ΔG‡0, that is, the energy levels of
benzhydrylium ion/chloride pairs would be closer. Although the
of the carbocation, are between 50 and 60 kJmolꢀ1 [9]
Having
.
in mind the observation that the height of these intrinsic bar-
riers is mainly determined with the structure of the pyridine
derivative and not with the structure of the carbocation
(electrofuge), according to microscopic reversibility rule, the re-
actions examined here should proceed over intrinsic barrier of
similar height although less reactive benzhydrylium ions are
generated. Therefore, the TSs of less reactive pyridinium ions
that solvolyze over higher barriers are for sure less
carbocation-like than those of the corresponding chlorides.
This is in discrepancy with the much higher slope parameters
for pyridine (average sf = 1.18) in comparison to chloride (aver-
age sf = 0.98).[10] One may speculate that high reaction con-
stant sf is due to the expansion of the range of relative
Lewis acidities of the benzhydrylium cations if the chloride
counterion is replaced with the pyridinium ion.
This premise is illustrated in Fig. 2, showing the estimated
energy profiles of the heterolysis step of some benzhyd-
rylpyridinium ions and benzhydryl chlorides in 80% aq. ethanol.
The intrinsic barrier (ΔG‡0) for heterolysis of X,Y-substituted
Table 2. Nucleofugality parameters Nf and sf for 4-chloropyridine, pyridine, and 4-methylpyridine in various solvents at 25 °C
Solventa
4-ClPy
Py
4-MePy
b
b
b
b
c
Nf
sf
Nf
sf
Nf
100M
80M20W
100E
80E20W
90A10W
80A20W
ꢀ0.95 0.03
ꢀ1.34 0.02
ꢀ1.02 0.16
ꢀ1.37 0.10
—
1.24 0.01
1.14 0.01
1.25 0.06
1.14 0.05
—
ꢀ2.28 0.17
ꢀ2.39 0.09
ꢀ2.24 0.19
ꢀ2.71 0.14
ꢀ2.93 0.06
ꢀ3.22 0.15
1.18 0.06
1.18 0.03
1.21 0.07
1.10 0.04
1.09 0.01
1.03 0.04
ꢀ3.06
ꢀ3.30
ꢀ3.01
ꢀ3.48
ꢀ3.80
ꢀ4.20
—
—
aBinary solvents are given as v/v: A, acetone; E, ethanol; M, methanol; and W, water.
bErrors shown are standard errors.
cCalculated from the rate of 1c (X = Y = 4-OMe) and the average sf value in a given solvent using Eqn (1).
J. Phys. Org. Chem. 2015, 28 314–319
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/poc

S. JURIĆ AND O. KRONJA
assumption about expanding the range Lewis acidity is yet to be
proven experimentally, it could be stated that conclusion about
the quantity of the positive charge on the reaction center or about
earlier or later TS based on the value of the reaction constants sf
(or ρ+) could only be drawn if structurally closely related compounds
are considered, which solvolyze over similar intrinsic barrier.
General procedure for preparation of X,Y-substituted benzhydr-
ylpyridinium perchlorates
Pyridine (30.00 mmol) and the appropriate benzhydryl chloride
(9.00 mmol) were added to 50 mL of dichloromethane and stirred for
30 min at ambient temperature.
A solution of silver perchlorate
(9.00 mmol) in dichloromethane was then added dropwise, and the mix-
ture was stirred overnight. The solid silver chloride was removed by filtra-
tion. Removal of solvent on rotary evaporator yielded oil, which was
diluted with ether. Filtration and washing with small portions of ether
and petroleum (1:1) led to 43–68% of the desired products. The perchlorates
are potentially dangerous species, and they should be handled with caution.
Finally, it is worth to compare the leaving group ability of pyr-
idine derivatives with those of other nucleofuges (Fig. 3). Pyridine
and its derivatives investigated here are relatively poor leaving
groups, similarly as for example, formate, acetate, benzoate, and
nitrobenzoates. Thus, in 80% aq. ethanol the nucleofugality pa-
rameters for 4-nitrobenzoate (Nf = ꢀ2.78) and pyridine
(Nf = ꢀ2.72) are virtually the same, as are the nucleofugalities
of 3,5-dinitrobenzoate (Nf = ꢀ1.43) and 4-chloropyiridine
(Nf = ꢀ1.37). Pyridinium ions are less reactive than the corre-
sponding chlorides (Nf = 3.24 in 80% aq. ethanol) for about five
orders of magnitude and less reactive than tosylates for about
10 orders of magnitude (Nf = 7.45 in 80% aq. ethanol). Because
of their low reactivity, numerous pyridinium, 4-chloropyridinium,
or 4-methylpyridinium salts are stable in aqueous solvents. Thus,
for example, the half-life of 1-adamantyl-4-chloropyridinium ion
(Ef ≈ ꢀ11) in 80% ethanol is more than 50 000 years and that of
tert-butylpyridinium ion (Ef ≈ ꢀ8) is more than 1000 years. While
1-(2-phenyl-2-adamantyl)-4-methylpyridinium salt (Ef ≈ ꢀ4.2) is a
stable compound in aqueous acetone (t1/2 ≈ 67 years in 90% aq.
acetone), the half-life of for example, 1-(2-phenyl-2-adamantyl)-
4-chloropyridinium salts in pure methanol at 25 °C is 1 day; hence,
it should be handled carefully in alcoholic solvents.
4-Methoxy-4′-phenoxybenzhydryl-4-chloropyridinium perchlorate
(2a)
Mp 111.4–111.7 °C, proton nuclear magnetic resonance (1H NMR) (300 MHz,
CDCl3): δ = 3.79 (s, 3H, ArOCH3), 6.83–7.43 (m, 14H, ArH + Ar-OC6H5 + Ar2CH),
7.99–8.00 (d, 2H, Py+H), 8.86–8.91 (d, 2H, Py+H). Carbon nuclear magnetic
resonance (13C NMR) (75 MHz, CDCl3): δ = 55.5 (ArOCH3), 79.4 (Ar2CH),
114.1, 115.7, 118.8, 119.5, 120.2, 124.7, 128.2, 130.4, 131.4, 132.6, 143.7 (Ar),
154.4, 159.4, 161.2 (Py+C). High-resolution mass spectrometry (HRMS)
(MALDI TOF/TOF 4800): calcd. for C25H22ClNO2 404.1417; found 404.1435.
4-Methoxy-4′-methylbenzhydryl-4-chloropyridinium
(3a)
perchlorate
Mp 104.5–104.8 °C, 1H NMR (300 MHz, CDCl3): δ = 2.33 (s, 3H, ArCH3), 3.78
(s, 3H, ArOCH3), 6.93–7.38 (m, 9H, ArH + Ar2CH), 7.80–8.02 (d, 1H, Py+H),
8.67–8.69 (d, 2H, Py+H). 13C NMR (75 MHz, CDCl3): δ = 21.5 (ArCH3), 55.8
(ArOCH3), 76.7 (Ar2CH), 115.5, 126.9, 130.5, 130.7, 131.7, 132.7, 136.4,
140.4 (Ar), 144.3, 146.7, 161.1 (Py+C). HRMS (MALDI TOF/TOF 4800): calcd.
for C20H19ClNO 324.1155; found 324.1170.
EXPERIMENTAL
4-Methoxybenzhydryl-4-chloropyridinium perchlorate (4a)
Substrate preparation
Mp 101.3–102.8 °C, 1H NMR (300 MHz, CDCl3): δ = 3.78 (s, 3H, ArOCH3),
6.81–6.86 (d, 2H, ArH), 7.20–7.27 (m, 8H, ArH + Ar2CH), 7.78–7.82 (d, 2H,
Py+H), 8.76–8.80 (d, 2H, Py+H). 13C NMR (75 MHz, CDCl3): δ = 55.6
(ArOCH3), 79.8 (Ar2CH), 114.1, 126.8, 127.5, 127.6, 130.0, 131.0, 132.6,
134.6 (Ar), 142.8, 143.1, 159.3 (Py+C). Collection of HRMS data was not
possible for this compound, because of its limited stability.
4,4′-Dimethylbenzhydrol, 4-methoxybenzhydrol, and 4,4′-dimethoxybe-
nzhydrol were prepared by reduction of the commercially available
substituted benzophenones with sodium borohydride in methanol. 4-
Methoxy-4′-methylbenzhydrol and 4-methoxy-4′-phenoxylbenzhydrol
were prepared by the procedure given in Denegri and Kronja.[21]
4,4′-Dimethylbenzhydryl-4-chloropyridinium perchlorate (5a)
Mp 110.2–110.4 °C, 1H NMR (300 MHz, CDCl3): δ = 2.32 (s, 6H, ArCH3),
7.10–7.28 (m, 9H, ArH + Ar2CH), 7.91–7.93 (d, 2H, Py+H), 8.84–8.86 (d,
2H, Py+H). 13C NMR (75 MHz, CDCl3): δ = 21.5 (ArCH3), 55, 77.8 (Ar2CH),
127.5, 127.9, 129.3, 129.5 (Ar), 137.2, 139.9, 142.8 (Py+C). HRMS (MALDI
TOF/TOF 4800): calcd. for C20H19ClN 308.1206; found 308.1220.
4,4′-Dimethoxybenzhydrylpyridinium perchlorate (1b)
Mp 101.3–101.7 °C, 1H NMR (300 MHz, CDCl3): δ = 3.77 (s, 6H, ArOCH3),
6.91–6.94 (d, 4H, ArH), 7.16–7.19 (d, 4H, ArH), 7.44 (s, 1H, Ar2CH),
8.04–8.51 (t, 2H, Py+H), 8.73–8.75 (d, 1H, Py+H), 8.81–8.85 (d, 2H,
Py+H). 13C NMR (75 MHz, CDCl3): δ = 55.8 (ArOCH3), 77.8 (Ar2CH),
115.4, 127.3, 128.8, 130.7 (Ar), 144.2, 146.6, 161.0 (Py+C). HRMS (MALDI
TOF/TOF 4800): calcd. for C20H20NO2 306.1494; found 306.1487.
4-Methoxy-4′-phenoxybenzhydrylpyridinium perchlorate (2b)
Mp 93.2–93.9 °C, 1H NMR (300 MHz, CDCl3): δ = 3.79 (s, 3H, ArOCH3),
6.49–7.35 (m, 14H, ArH + Ar-OC6H5 + Ar2CH), 8.12–8.34 (t, 2H, Py+H),
8.49–8.52 (d, 1H, Py+H), 8.84–8.86 (d, 2H, Py+H). 13C NMR (75 MHz, CDCl3):
δ = 55.8 (ArOCH3), 79.4 (Ar2CH), 114.1, 115.4, 119.3, 120.1, 124.7, 127.2,
129.0, 130.1, 141.5, 144.5, 146.7 (Ar), 156.1, 159.2, 161.0 (Py+C). HRMS
(MALDI TOF/TOF 4800): calcd. for C25H22NO2 368.1650; found 368.1643.
Figure 3. Comparison of the nucleofugalities of pyridines in 80% aq.
ethanol with some selected leaving groups
wileyonlinelibrary.com/journal/poc
Copyright © 2015 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2015, 28 314–319

SOLVOLYTIC REACTIVITY OF PYRIDINIUM IONS
[3] a) A. R. Katritzky, M. L. Lopez-Rodrigues, J. Marquet, J. Chem. Soc.
Perkin Trans. 2, 1984, 349–354. b) A. R. Katritzky, B. Brycki, J. Am.
Chem. Soc. 1986, 108, 7295–7299. c) A. R. Katritzky, C. H. Watson,
Z. Dega-Szafran, J. R. Eyler, J. Am. Chem. Soc. 1990, 112, 2471–2478.
[4] P. Madaan, V. K. Tyagi, J. Oleo Sci. 2008, 57, 197–215.
[5] J. Pernak, J. Rogoza, ARKIVOC 2000, 889–904.
4-Methoxy-4′-methylbenzhydrylpyridinium perchlorate (3b)
Mp 90.1–92.7 °C, 1H NMR (300 MHz, CDCl3): δ = 2.34 (s, 3H, ArCH3), 3.79 (s,
3H, ArOCH3), 6.91–7.47 (m, 9H, ArH + Ar2CH), 8.02–8.08 (t, 2H, Py+H),
8.50–8.55 (d, 1H, Py+H), 8.72–8.76 (d, 2H, Py+H). 13C NMR (75 MHz, CDCl3):
δ = 21.5 (ArCH3), 55.8 (ArOCH3), 76.7 (Ar2CH), 115.5, 126.9, 130.5, 130.7,
131.7, 132.7, 136.4, 140.4 (Ar), 144.3, 146.7, 161.1 (Py+C). HRMS (MALDI
TOF/TOF 4800): calcd. for C20H20NO 290.1544; found 290.1558.
[6] E. V. Dehmalow, S. S. Dehmalow, Phase Transfer Catalysis, 3rd Ed.,
VCH, Weinheim, New York, Basel, Cambridge, Tokyo, 1993.
[7] W. Śliwa, N-Substituted Salts of Pyridine and Related Compounds, Syn-
thesis, Properties,Applications, Academic press, Czestochowa, Poland,
1996.
4-Methoxybenzhydrylpyridinium perchlorate (4b)
[8] T. Maeda, Y. Manabe, M. Yamamoto, M. Yoshida, K. Okazaki, H.
Nagamune, H. Kourai, Chem. Pharm. Bull. 1999, 47, 1020–1023.
[9] F. Brotzel, B. Kempf, T. Singer, H. Zipse, H. Mayr, Chem. Eur. J. 2007,
13, 336–345.
[10] a) B. Denegri, A. Streiter, S. Jurić, A. R. Ofial, O. Kronja, H. Mayr, H.
Chem. Eur. J. 2006, 12, 1648–1656. b) Correction: B. Denegri, A.
Streiter, S. Jurić, A. R. Ofial, O. Kronja, H. Mayr, Chem. Eur. J. 2006,
12, 5415–5415. c) B. Denegri, A. R. Ofial, S. Jurić, A. Streiter, O. Kronja,
H. Mayr, Chem. Eur. J. 2006, 12, 1657–1666.
Mp 89.8–91.3 °C, 1H NMR (300 MHz, CDCl3): δ = 3.80 (s, 3H, ArOCH3),
6.92–6.94 (d, 2H, ArH), 7.18–7.40 (m, 8H, ArH + Ar2CH), 8.03–8.06 (t, 2H,
Py+H), 8.49–8.52 (d, 1H, Py+H), 8.72–8.74 (d, 2H, Py+H). 13C NMR
(75 MHz, CDCl3): δ = 55.8 (ArOCH3), 77.4 (Ar2CH), 115.5, 125.9, 126.5,
128.7, 130.0, 131.3, 135.8 (Ar), 144.4, 146.7, 161.2 (Py+C). HRMS (MALDI
TOF/TOF 4800): calcd. for C19H18NO 276.1380; found 276.1393.
[11] N. Streidl, B. Denegri, O. Kronja, H. Mayr, Acc. Chem. Res. 2010, 43,
4,4′-Dimethoxybenzhydryl-4-methylpyridinium perchlorate (1c)
1537–1549.
Mp 104.8–106.3 °C, 1H NMR (300 MHz, CDCl3): δ = 2.60–2.75 (d, 3H,
Py+CH3), 3.89 (s, 6H, ArOCH3), 7.00–7.03 (d, 4H, ArH), 7.25–7.28 (d, 4H,
ArH), 7.43 (s, 1H, Ar2CH), 7.90–7.92 (d, 2H, Py+H), 8.64–8.68 (d, 2H,
Py+H). 13C NMR (75 MHz, CDCl3): δ = 22.6 (Py+CH3), 55.8 (ArOCH3), 76.9
(Ar2CH), 115.4, 127.3, 129.1, 130.6 (Ar), 143.8, 160.0, 161.0 (Py+C). HRMS
(MALDI TOF/TOF 4800): calcd. for C21H22NO2 320.1650; found 320.1646.
[12] S. Jurić, B. Denegri, O. Kronja, J. Org. Chem. 2010, 75, 3851–3854.
[13] S. Jurić, B. Denegri, O. Kronja, J. Phys. Org. Chem. 2012, 25, 147–152.
[14] S. Minegishi, R. Loss, S. Kobayashi, H. Mayr, J. Am. Chem. Soc. 2005,
127, 2641–2649.
[15] M. Matić, S. Jurić, B. Denegri, O. Kronja, Int. J. Mol. Sci. 2012, 13,
2012–2024.
[16] D. B. Ledlie, W. Barber, F. Switzer, Tetrahedron Lett. 1977, 18,
607–610.
[17] D. N. Kevill, N. H. J. Ismail, M. J. D’Souza, J. Org. Chem. 1994, 59,
Kinetic measurements
6303–6312.
Solvolysis rate constants of compounds were measured titrimetrically by
means of a TIM 856 titration manager (Radiometer Analytical SAS Villeur-
banne Cedex, Lyon, France), using a Red Rod combined pH electrode.
Typically, 20–50 mg of the substrate was dissolved in 0.10–0.20 mL of di-
chloromethane and inject into the appropriate solvent that was
thermostated at the required temperature ( 0.01 °C). The liberated
pyridinium perchlorates were continuously titrated at pH = 7.00 by using
a 0.008-M solution of NaOH in the appropriate solvent. Individual rate
constants were obtained by the least-squares fitting of data to the first-
order kinetic equation for three to four half-lives. The rate constants were
averaged from at least three measurements.
[18] D. N. Kevill, S. W. Anderson, N. H. J. Ismail, J. Org. Chem. 1996, 61,
7256–7262.
[19] D. N. Kevill, S. W. Anderson, J. Org. Chem. 1991, 56, 1845–1850.
[20] D. N. Kevill, S. W. Anderson, J. Am. Chem. Soc. 1986, 108, 1579–1585.
[21] B. Denegri, O. Kronja, J. Org. Chem. 2007, 72, 8427–8433.
[22] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb,
J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A.
Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F.
Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara,
K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y.
Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Jr. Montgomery, J. E.
Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin,
V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A.
Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega,
J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo,
J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin,
R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma,
V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S.
Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J.
Cioslowski, D. J. Fox, Gaussian 09 (Revision A.02), Gaussian Inc.,
Wallingford, CT, 2009.
Quantum chemical calculations
Geometries of the most stable conformations of the sulfonium and
pyridinium ions were fully optimized at the M06-2X/6-311 + G(2d,p)
level of theory with Gaussian 09 program suite.[22] Using the same
level of theory, stationary points were verified as minima (no imaginary
frequencies) by frequency calculations, and natural bond orbital
charges were calculated. Influences of solvation effects are included
by employing the IEFPCM solvation model in all calculations.[23]
[23] a) J. Tomasi, B. Mennucci, E. Cancès, J. Mol. Struct. (Theochem) 1999,
464, 211–226. b) J. Tomasi, B. Mennucci, R. Cammi, Chem. Rev. 2005,
105, 2999–3093.
Acknowledgements
SUPPORTING INFORMATION
The authors gratefully acknowledge the financial support of
this research from the Croatian Science Foundation (under
the project number 1021). Computations were performed on
the Isabella cluster at Computing Centre SRCE of the University
of Zagreb (isabella.srce.hr), and we thank B. Denegri for com-
puter time used for this work.
Additional supporting information may be found in the online
version of this article at the publisher’s website.
Solvolytic activation parameters, additional solvolysis rate
constants at various temperatures, correlation of solvolysis rate
constants log k (25 °C) vs the electrofugality parameters Ef of X,
Y-substituted benzhydryl-4-chloropyridinium perchlorates, cor-
relation of Nf with σp for solvolysis of 4-X-substituted pyridines,
data of quantum chemical calculations and 1H and 13C NMR
spectra of X,Y-substituted benzhydrylpyridinium salts.
REFERENCES
[1] E. F. V. Scriven, Chem. Soc. Rev. 1983, 12, 129–161.
[2] G. C. Fu, Acc. Chem. Res. 2000, 33, 412–420.
J. Phys. Org. Chem. 2015, 28 314–319
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/poc

Copyright of Journal of Physical Organic Chemistry is the property of John Wiley & Sons,
Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv
without the copyright holder's express written permission. However, users may print,
download, or email articles for individual use.