Ionizing power of aprotic solvents

Article abstract of DOI:10.1002/ejoc.201001700

Rate constants for the heterolysis reactions (S_N1) of a series of chloro-diarylmethanes in aprotic solvents (dimethyl sulfoxide (DMSO), acetonitrile, carboxamides, etc.) have been determined conductometrically in the presence of amines or triphenylphosphane, which trap the intermediate ion-pairs and suppress ion recombination. The operation of S_N2 mechanisms can be excluded because the observed first-order rate constants become almost independent of the nature of the nucleophilic additive when a certain concentration of nucleophile is exceeded. The heterolysis rate constants are used to calculate nucleofugality parameters N_f and s_f for chloride in aprotic solvents according to the linear free-energy relationship lgak (25 °C) = s_f(N_f + E_f). Ionizing powers Y_BnCl of these solvents were calculated according to the Winstein-Grunwald equation. Because the heterolysis rate constants in aprotic solvents correlate only poorly with dielectric constants or empirical solvent parameters such as Gutmann's acceptor numbers or E_T^N values, the most common solvent polarity parameters do not reliably predict ionization rates in aprotic solvents. The kinetics of the heterolyses of chloro-diarylmethanes in aprotic solvents have been studied conductometrically by suppressing ion recombination with amine additives. In this way it became possible to determine the ionizing power of aprotic solvents and compare them to those of protic solvents. Copyright

Full text of DOI:10.1002/ejoc.201001700

FULL PAPER
DOI: 10.1002/ejoc.201001700
Ionizing Power of Aprotic Solvents
[a]
[a]
Nicolas Streidl and Herbert Mayr*
Dedicated to Professor Masatomo Nojima on the occasion of his 70th birthday
Keywords: Kinetics / Reaction mechanisms / Solvent effects / Linear free energy relationships / Ion pairs / Heterolysis
reactions
Rate constants for the heterolysis reactions (S
chloro-diarylmethanes in aprotic solvents (dimethyl sulfoxide
DMSO), acetonitrile, carboxamides, etc.) have been deter-
N
1) of a series of
calculate nucleofugality parameters N
aprotic solvents according to the linear free-energy relation-
ship lgk (25 °C) = s (N + E ). Ionizing powers YBnCl of these
f f
and s for chloride in
(
f
f
f
mined conductometrically in the presence of amines or tri-
phenylphosphane, which trap the intermediate ion-pairs and
solvents were calculated according to the Winstein–Grun-
wald equation. Because the heterolysis rate constants in
suppress ion recombination. The operation of S
N
2 mecha- aprotic solvents correlate only poorly with dielectric con-
stants or empirical solvent parameters such as Gutmann’s ac-
nisms can be excluded because the observed first-order rate
constants become almost independent of the nature of the
nucleophilic additive when a certain concentration of nucleo-
phile is exceeded. The heterolysis rate constants are used to
N
ceptor numbers or E
T
values, the most common solvent po-
larity parameters do not reliably predict ionization rates in
aprotic solvents.
Introduction
ionizing power were later introduced for a more reliable pre-
diction of the solvolysis rate constants for structurally re-
In 1948, Winstein and Grunwald reported that the rates
[3a,10–14]
lated compounds.
However, most of these scales
of the S 1 solvolyses of neutral RX substrates in different
N
were restricted to protic solvents such as alcohols, water, or
mixtures of protic and aprotic solvents, where the interme-
diate carbocations may irreversibly be trapped, so that the
course of the reactions can be followed by monitoring the
formation of the acid HX. Only a few aprotic solvents have
solvents (Scheme 1) can be described by the linear free-en-
ergy relationship [Equation (1)][
1]
lg(k/k
0
) = mY
(1)
[
13]
so far been investigated. SN1 reactivities of tert-butyl ha-
lides and adamantyl derivatives have been studied in mod-
erately basic solvents, such as dimethylformamide and acet-
amide, which become alkylated by the intermediate, highly
where the solvent ionizing power Y (Y = 0 for 80% aqueous
ethanol) is defined as the ratio of the solvolysis rates of tert-
butyl chloride (m = 1) in a given solvent (k) and in 80%
aqueous ethanol (k ) at 25 °C.
0
[
15]
reactive carbenium ions.
The ionization rates of ada-
mantyl arenesulfonates have been investigated in acetoni-
trile solutions by titrimetric determination of the consump-
tion of added azide ions; under these conditions the inter-
mediate adamantyl cations are either trapped directly by
azide ions or are intercepted by the solvent to give N-ada-
N
Scheme 1. Simplified scheme for S 1 solvolysis.
Initially assumed to be applicable to all types of S 1 sol- mantyl-nitrilium ions, which undergo 1,3-dipolar cycload-
N
volyses, it was soon realized that deviations from Equa- ditions with the azide ions.[16a] By following the rate of de-
tion (1) were due to variable degrees of solvation of the de- velopment of toluenesulfonic acid from p-methoxyneophyl
veloping carbocations, particularly of alkyl and aryl toluenesulfonate, Winstein and co-workers were able to
[
2–9]
groups.
As a consequence, numerous Y scales of solvent compare the ionizing power of protic and aprotic sol-
[
16b]
vents.
[
a] Department Chemie, Ludwig-Maximilians-Universität
Heterolysis rate constants in aprotic solvents have also
been determined by the so-called “verdazyl method” intro-
München,
Butenandtstrasse 5-13 (Haus F), 81377 München, Germany
Fax: +49-89-2180-77717
[17]
duced by Dvorko and co-workers, in which triphenylver-
E-mail: Herbert.Mayr@cup.uni-muenchen.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001700.
dazyl radicals react with solvent-separated ion-pairs. The
reaction rates are usually monitored spectrophotometrically
2498
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Ionizing Power of Aprotic Solvents
by following the decrease in the absorbance of the radical. Table 2. Products of the reactions of 1 with piperidine or PPh
We now report a more direct and general method to deter-
3
in
different solvents at 20 °C.
mine the ionizing power of aprotic solvents.
Recently, we have shown that amines and phosphanes
can suppress common ion return in S 1 solvolysis reactions
N
of chloro-diarylmethanes in protic solvents (acetone/water
and acetonitrile/water mixtures) without reacting by the
[
18]
SN2 mechanism.
Because the intermediate carbocations
are trapped quantitatively by formation of benzhydryl-
ammonium ions, the ionization rate constants could be de- Solvent
termined conductometrically by using conventional and
Sub-
strate
Nucleo-
phile
Crude products [%][a]
Yield [%][b]
3
CH CN
1c
piperidine
piperidine
piperidine
piperidine
piperidine
piperidine
piperidine
100 (2c)
100 (2f)
97 (2c), 3 (3c)
68 (2f), 32 (3f)
76 (2c), 9 (3c), 15 (4c)
100 (2c)
80 (2c)
85 (2f)
72 (2c)
stopped-flow techniques. This methodology has now been
similarly employed to determine the ionization rates of the
chloro-diarylmethanes 1a–f (Table 1) in aprotic solvents.
These rate constants will be used to include aprotic solvents
into the previously established scales of solvent ionizing
power and to calculate the nucleofugality parameters Nf
1
f
DMSO
1c
1f
1c
1c
1c
1c
58 (2f), 28 (3f)
60 (2c)
DMA
DMF
acetone
80 (2c)
84 (2c)
95 (5c)
100 (2c)
CHCl
3
PPh
3
–
and s of chloride ions in aprotic solvents according to the
f
linear free-energy relationship [Equation (2)][19,20]
[a] By GC-MS analysis after aqueous workup. [b] Isolated products
after recrystallization or column chromatography.
lgk(25 °C) = s
f
(N
f
+ E
f
)
(2)
Kinetics
–
1
where the heterolysis rate constants k (s ) are expressed as
a function of the solvent-independent electrofuge-specific
As previously shown for the reactions of other halo-di-
[
18,21]
parameter E and the nucleofuge-specific parameters s and arylmethanes in protic solvents and DMSO,
it is pos-
f
f
N , which refer to combinations of leaving groups and sol- sible to follow the course of the reactions by conductivity
f
vents.
measurements because ionic products are formed from co-
valent starting materials. Because the observed conductivi-
ties are directly proportional to the concentrations of the
products, we were able to obtain rate constants kobs by fit-
ting the time-dependent conductivities G to the monoex-
ponential function (3)
Table 1. Chloro-diarylmethanes 1a–f and electrofugality param-
eters E
[
20]
+
+
f
of the corresponding benzhydrylium ions 1a –f .
G = Gmax (1 – e–k(obs)t) + const.
(3)
A typical example for such experiments is illustrated in
Figure 1 for the reaction of chloro-(2,3-dihydro-5-benzo-
furanyl)-(4-methoxyphenyl)methane (1b) with variable con-
centrations of piperidine in acetonitrile.
Results
Product Analysis
Figure 1. Plot of the observed rate constants kobs vs. c(piperidine)
for the reaction of chloro-(2,3-dihydro-5-benzofuranyl)-(4-meth-
oxyphenyl)methane (1b) with piperidine in acetonitrile at 25 °C.
In the absence of additives, solutions of the chloro-di-
arylmethanes 1a–f were stable in all solvents used for this
study [CH CN, dimethyl sulfoxide (DMSO), dimethylacet-
3
amide (DMA), dimethylformamide (DMF), N-methylpyr-
As mentioned above, 1b is stable in pure acetonitrile in
rolidin-2-one (NMP), propylene carbonate (PC), CHCl3, the absence of piperidine, and there is no observable change
CH Cl , and acetone]. When piperidine or triphenylphos- of conductivity. In the presence of a low concentration of
2
2
phane was added, the formation of 2–5 was observed by piperidine [c(piperidine) = 0.03 m] a change in conductivity
NMR or GC-MS analysis after aqueous workup (Table 2). is observed, the time dependence of which can be fitted to
Eur. J. Org. Chem. 2011, 2498–2506
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N. Streidl, H. Mayr
FULL PAPER
–
1
Equation (3) to yield a rate constant kobs = 13.3 s . As de- to the influence of the solvent and the substituents X and
picted in Figure 1, the observed rate constants increase with Y on the magnitude of kmax. Therefore, kmax values ob-
increasing piperidine concentrations. A maximum rate con- tained with different trapping reagents are jointly listed as
–
1
stant of kobs,max = 17.0 s is finally observed at c(piperid- k1 in Table 3. Whereas piperidine was the preferred trapping
ine) = 0.50 m, and at higher piperidine concentrations the agent in most solvents, it reacts with dichloromethane, chlo-
[
22]
rate constants decrease slightly.
roform,
and propylene carbonate, and therefore cannot
The observation that the rate constants kobs increase with be employed in these solvents. For that reason, piperidine
increasing piperidine concentrations, until a plateau is was replaced by PPh in CH Cl and CHCl , and by pyr-
3
2
2
3
reached at a certain concentration of piperidine, indicates idine in propylene carbonate, in which PPh is poorly solu-
3
the operation of an S 1 mechanism (Scheme 2). If the reac- ble.
N
tions proceeded by S 2 mechanisms, kobs would increase
N
linearly with the piperidine concentrations. A detailed dis-
cussion will be given below.
1
Table 3. Conductometrically measured rate constants (k , 25 °C)
of the reactions of the chloro-diarylmethanes 1a–f with different
trapping reagents.
Solvent[a]
CH
CN[b]
Substrate
Electrofugality E
–1
f
1
k [s ]
1
1
3
1a
1.07
0.61
0.00
–0.86
–1.32
–2.09
1.07
0.61
0.00
–0.86
–1.32
–2.09
1.07
0.61
0.00
–0.86
–1.32
1.07
0.61
0.00
–0.86
–1.32
1.07
0.61
0.00
–0.86
–1.32
1.07
0.61
0.00
–0.86
–1.32
1.07
0.61
0.00
–0.86
1.07
0.61
9.51ϫ10
1.70ϫ10
2.40
1.47ϫ10
3.77ϫ10
3.60ϫ10
8.85ϫ10
1.57ϫ10
2.46
1.89ϫ10
5.03ϫ10
6.78ϫ10
2.35
1
b
1
c
Scheme 2. Heterolyses of chloro-diarylmethanes in the presence of
piperidine.
–1
–2
1
d
1
e
–
3
1
f
DMSO[b]
1a
1b
1
The situation described in Figure 1, i.e., increase of kobs
with increasing piperidine concentration until a plateau is
reached, has been observed for numerous reactions of
chloro-diarylmethanes 1a–f with piperidine in different
aprotic solvents (see the Supporting Information). When
pyridine was used to trap the intermediate carbocations, a
somewhat lower plateau was observed (for 1c in acetonitrile
kmax,piperidine/kmax,pyridine = 1.6, see Figure 2).
1
1
c
–
1
1
d
–2
–3
1
e
1
f
DMA[b]
DMF[b]
NMP[b]
PC[c]
1a
–
–
1
2
1
b
4.81ϫ10
7.86ϫ10
6.66ϫ10
1.37ϫ10
1
c
–3
1
d
–
3
1
e
1
1a
1.44ϫ10
1
b
2.55
–
1
2
3
1
c
3.69ϫ10
2.73ϫ10
6.02ϫ10
1.45
2.94ϫ10
5.32ϫ10
4.16ϫ10
1.04ϫ10
4.63ϫ10
8.47
1.22
1.05ϫ10
2.47ϫ10
–
–
1
d
1
e
1a
–
–
–
–
1
2
3
3
1
b
1
c
1
d
1
e
1
1a
1b
1
c
–
1
2
1d
–
Figure 2. Plot of the observed rate constants kobs vs. c(amine) for
the reactions of chloro-bis(4-methoxyphenyl)methane (1c) with pi-
peridine (circles) and pyridine (diamonds) in pure acetonitrile.
1e
1a
1b
CHCl [
d]
1.54ϫ10
1
3
3.17
–
1
2
1c
4.98ϫ10
5.82ϫ10
4.84
–
Plateaus of similar, but not identical heights had also
been observed when different amines or triphenylphos-
phane were used to trap benzhydrylium ions, which were
reversibly generated from chloro-diarylmethanes in aqueous
acetone or acetonitrile.[18] The small differences in the pla-
teaus obtained with different nucleophiles can again be ex-
plained by the fact that diffusion-limited trapping reactions
will partially occur at the ion-pair stage. In the case of pi-
peridine, its weak hydrogen-bond donating abilities may
also contribute.
1d
1a
CH
2 2
Cl [
d]
1
b
1.02
–
1
1
c
0.00
1.72ϫ10
1.54ϫ10
4.00ϫ10
1.40
2.71ϫ10
3.49ϫ10
3.31ϫ10
6.12ϫ10
–2
–3
1d
–0.86
–1.32
1.07
0.61
0.00
–0.86
–1.32
1e
1a
Acetone[b]
–
–
1
2
1
b
1
c
–3
–4
1d
1
e
[
a] For acronyms see Table 4. [b] Piperidine as trapping reagent. [c]
The dependence of the heights of these plateaus on the
Pyridine as trapping reagent. [d] Triphenylphosphane as trapping
nature of the trapping nucleophiles is negligible compared reagent.
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Ionizing Power of Aprotic Solvents
Figure 3 shows that the heterolysis rate constants of 2-
In the absence of nucleophiles, the chloro-diarylmethanes
chloro-2-phenylpropane (cumyl chloride) in aprotic sol- 1a–f are stable in all solvents listed in Table 3, indicating
vents, which were determined by Dvorko’s verdazyl tech- that the covalent chloro-diarylmethanes 1 are favored in the
[
17]
+
–
nique,
correlate roughly (slope of 1.11) with those of dynamic ionization equilibria 1i1 Cl . In the presence of
chloro-bis(4-methoxyphenyl)methane (1c), which were de- low concentrations of the trapping reagents, ion recombina-
termined by the “amine method” described in this work.
tion is accompanied by the reactions of the ions or ion-
pairs with triphenylphosphane or piperidine, yielding benz-
hydrylphosphonium salts or 1-benzhydryl-piperidines 2,
respectively. When the concentrations of the trapping rea-
gents are increased, the observed rate constants increase
due to the fact that ion recombination (k ) becomes in-
–1
creasingly suppressed. At a certain concentration, indepen-
dence of the rate constant kobs,max of the nucleophile con-
centration is observed, indicating that ion recombination is
completely suppressed and that the ionization of 1 has be-
come rate-determining. Under these conditions, the ob-
served rate constants kobs,max correspond to the ionization
rate constants k defined in Scheme 1 and Scheme 3. The
1
slight decrease of reactivity at high concentrations of
amines can be explained by a change of solvent polarity.
The situation is different in DMSO solution because this
solvent is a stronger O-nucleophile than water and ordinary
1
Figure 3. Correlation of the heterolysis rate constants lgk of 2-
chloro-2-phenylpropane (by verdazyl method[ ) with those of
chloro-bis(4-methoxyphenyl)methane (1c) in various aprotic sol-
vents.
17]
[
21]
alcohols. When 1 is dissolved in pure DMSO, a reversible
+
–
ionization leads to 1 Cl , which is reversibly attacked by
DMSO to form 1-DMSO (Scheme 4). As conductivity does
not change, one can conclude that in these equilibria the
covalent chloro-diarylmethanes 1 are the dominating spe-
cies. In contrast, the corresponding bromo-diarylmethanes
have been observed to react with DMSO also in the absence
Discussion
Reaction Mechanism
The reactions of the chloro-diarylmethanes 1a–f with pi-
peridine or triphenylphosphane in acetonitrile, DMF, acet-
one, CHCl , or CH Cl give rise to the formation of 1-
3
2
2
benzhydrylpiperidines 2 or benzhydryl phosphonium salts
Scheme 3). As pointed out above, the non-linearity of the
(
plots of kobs vs. the concentration of the trapping reagents,
and the plateaus in these plots (Figures 1, 2 and the Sup-
porting Information) suggest that the reactions proceed
through the S 1 mechanism; after ionization of 1, the inter-
N
mediate carbocation is rapidly trapped by either piperidine
or triphenylphosphane.
Scheme 3. Heterolyses of chloro-diarylmethanes in the presence of
piperidine or triphenylphosphane.
Scheme 4. Heterolyses of chloro-diarylmethanes in DMSO in the
presence of piperidine.
Eur. J. Org. Chem. 2011, 2498–2506
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N. Streidl, H. Mayr
FULL PAPER
of amine.[21] When piperidine is present, two reaction path- 4c. Hydrolysis during aqueous workup of the concomi-
ways are possible: The left path shown in Scheme 4 is iden- tantly generated amidinium ion 7 (Scheme 5) might regen-
tical to that shown in Scheme 3, where the intermediate erate the starting materials.
carbocation is trapped by piperidine to form 1-benzhydryl-
piperidines 2. Alternatively (right path in Scheme 4) an oxy-
sulfonium ion 1-DMSO is formed, which yields a sulfur
ylide by deprotonation at a methyl group. Eventually, a pro-
ton shift and cleavage of the O–S bond yields the benzo-
phenones 3 (Kornblum oxidation).[
23]
The question can be asked: Why does one obtain a much
higher percentage of benzophenone with 1f than with 1c in
DMSO/piperidine (Table 2)? As previously shown,[ Equa-
24]
Scheme 5. Possible hydride transfer during the heterolysis reaction
of 1c in DMA in the presence of piperidine.
tion (4) can be used to calculate the rate constants of the
reactions of carbocations with a large variety of nucleo-
philes, including amines,[ halide ions, and solvents.
25]
[26]
[27]
lgk = s
N
(E + N)
(4)
Hammett Correlation
–
1 –1
In Equation (4) k is a second-order (m s ) or first-order
–
1
+
(
s , for reactions with solvents) rate constant, s and N are
From the plots of lgk (i.e., kobs,max) vs. Σσ , the Ham-
1
N
empirical, nucleophile-specific parameters (sN has pre- mett reaction constants of ρ ≈ –4 can be derived for the
viously been called s), and E is an empirical electrophilicity heterolysis reactions of the chloro-diarylmethanes 1a–f in
parameter.
From the electrophilicity parameters for the benzhy- DMF, and DMA in Figure 4 (for Hammett correlations of
various aprotic solvents, as exemplified for acetonitrile,
[
24]
+
+
drylium ions 1c (E = 0.00) and 1f (E = 2.11) and the the other solvents in this study see the Supporting Infor-
nucleophile-specific parameters for piperidine in DMSO (N mation).
[
28]
9
–1 –1
=
17.19, sN = 0.71) one can calculate k Ͼ 5ϫ10 m s
for the reactions of both benzhydrylium ions with piperi-
+
+
dine, i.e., trapping of 1c and 1f is diffusion limited. As-
9
–1 –1
suming a second-order rate constant of k = 5ϫ10 m s
2
for the diffusion-limited reaction of a carbocation with a
neutral nucleophile, multiplication with c(piperidine) =
0
2
.5 m yields pseudo-first-order rate constants of k
.5ϫ10 s for the reactions of 1c and 1f with piperidine.
=
obs
9
–1
+
+
This value is significantly larger than the first-order rate
8
–1
constant (k = 2.30ϫ10 s ) calculated by using Equation
1
[
21]
(
4) for the reaction of DMSO (N = 11.3, s = 0.74) with
c (E = 0.00). In line with this calculation, the main prod-
1 N
+
1
uct of the reaction of 1c with piperidine in DMSO is the 1-
benzhydryl-piperidine 2c, and only traces (GC-MS: 3%) of
the benzophenone 3c can be detected.
From the reactivity parameters for DMSO (N = 11.3,
1
+
[24]
–1
sN = 0.74) and 1f (E = 2.11)
one can calculate a first-
1
Figure 4. Plots of lgk (= lgkobs,max) of the heterolysis reactions
9
order rate constant of 8ϫ10 s , which is in the same order of benzhydryl chlorides 1a–1f in different solvents vs. Hammett’s
of magnitude as the pseudo-first-order rate constant for the
diffusion-limited reaction of 1f with piperidine (c = 0.5 m).
substituent constants Σσ+ (σ from ref. ).
+
[29]
+
The formation of comparable quantities of 2f and 3f
The excellent linear correlations and the magnitude of
(Table 2) can thus be explained.
the reaction constants ρ suggest transition states in which
When 1c was dissolved in DMA or NMP in the presence the positive charge of the carbocations is fully developed.
of piperidine, dimethoxybenzophenone (3c) and bis(4-meth- The Hammett plots thus support the conclusion from the
oxyphenyl)methane (4c) were formed as minor products, in kinetic data that kobs,max corresponds to the ionization step
addition to formation of 2c as the major product (GC-MS: of an S 1 reaction and not to an S 2-type attack of the
N
N
Ն75% yield). At present, it is not clear how 3c and 4c are amine at the chloro-diarylmethanes. These results are in line
formed under these conditions. A conceivable mechanism with previous findings for the reactions of bromo-diaryl-
may involve attack of the solvent and piperidine at the di- methanes with amines in DMSO, showing that only the
+
methoxybenzhydrylium ion (1c ) with formation of 6. Hy- first-order rate constants k (S 1 reaction) and not the sec-
1
N
dride abstraction from 6 by a second dimethoxybenz- ond-order rate constants k (S 2 reaction) correlate with
2
N
+
+ [21]
hydrylium ion (1c ) may then lead to formation of 3c and the substituent constants σ .
2502
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Ionizing Power of Aprotic Solvents
Nucleofugality of Chloride in Different Solvents
the diffusion limit in acetonitrile and, therefore, proceed
without activation energy. Because the other solvents used
in this study are of similar or lower polarity than acetoni-
In previous work,[19,20] we have demonstrated that Equa-
tion (2) can be used to calculate the heterolysis rate con-
–
trile, the combinations of these carbocations with Cl will
stants k of benzhydryl derivatives in various solvents. Plots
1
also proceed without barriers in these solvents. From the
principle of microscopic reversibility, one can now derive
that there is no energy maximum between reactants and
of lgk (i.e., the maximum observed first-order rate con-
1
stants kobs,max) vs. the electrofugality parameters E of the
benzhydrylium ions (see Table 1) are linear, as exemplified
in Figure 5 for the heterolyses of the chloro-diarylmethanes
f
+
–
ionic intermediates in the ionization process (1 Ǟ 1 + Cl )
in these solvents, i.e., the activation free energies of the ion-
1
a–f in DMSO, CH Cl , and acetone. Analogous corre-
2 2
ization (heterolysis) step (k ) equal the differences between
1
lations have been observed in acetonitrile, DMA, DMF,
+
–
the free energies of the ions 1 + Cl and their precursors
NMP, PC, and CHCl (see the Supporting Information).
3
1.
From these correlations, one can extract the nucleofugality
The same line of reasoning can now be used for the ion-
ization of chloro-diarylmethanes 1a–f in protic solvents. Di-
parameters N of chloride in these solvents as the negative
f
intercepts on the abscissa (E axis) and the s parameters as
f
f
rect measurements of the rates of the reactions of these
the slopes (Table 4).
–
carbocations with Cl in protic solvents have shown that
these reactions are not diffusion-limited, i.e., there is a bar-
[
26]
rier for ion combination.
As a consequence, the carbo-
cationic character is not yet fully developed in the transition
state of the ionizations of these chloro-diarylmethanes in
protic solvents, which results in smaller values of sf.
Furthermore, the different magnitudes of s may also be due
f
to the fact that the differences in the Gibbs free energies
+
–
between covalent precursors 1 and ion-pairs 1 Cl are
somewhat attenuated in more polar solvents such as
alcohols and water.
With the newly determined nucleofugality parameters Nf
and s (Table 4) it now becomes possible to directly compare
f
the leaving group ability of chloride in protic and aprotic
solvents (Figure 6).
1
Figure 5. Plots of the first-order rate constants lgk (kobs,max) of
the heterolyses of chloro-diarylmethanes 1a–f in different solvents
in the presence of trapping reagents against the electrofugality pa-
rameters E .
f
f f
Table 4. Nucleofugality parameters N and s of chloride in dif-
ferent solvents.
Solvent
N
f
s
f
DMSO (dimethyl sulfoxide)
0.35
0.30
0.10
–0.18
–0.28
–0.57
–0.82
–0.98
–1.00
1.30
1.39
1.35
1.25
1.39
1.28
1.33
1.31
1.38
CH
PC (propylene carbonate)
CHCl
DMF (dimethylformamide)
CH Cl
3
CN
3
2
2
DMA (diemthylacetamide)
NMP (N-methylpyrrolidin-2-one)
Acetone
As shown in Table 4, the s parameters of chloride in the
f
aprotic solvents are substantially higher (1.25 Յ s Յ 1.39)
f
than the corresponding s parameters in protic solvents
f
[20]
(
usually 0.85 Յ s Յ 1.11). How can these differences be
f
explained?
Substitution of the nucleophilicity parameters N and s of
chloride in acetonitrile (N = 17.20, sN = 0.60)[ and the
electrophilicity parameters E of the benzhydrylium ions
26]
+
+
[24]
Figure 6. Comparison of the nucleofugality parameters N (s pa-
f
f
1
a –f (–1.36 Ͻ E Ͻ 2.11)
into Equation (4) yields the
rameter in parentheses) of chloride in various protic and aprotic
9
–1 –1
second-order rate constants k Ͼ 3ϫ10 m s for the reac-
[20]
solvents (data from this work and ref. ). Mixtures of solvents are
–
tions of these benzhydrylium ions with Cl , i.e., all ion re-
given (v/v); A = acetone, AN = acetonitrile, E = ethanol, TFE =
combinations are diffusion-limited or at least very close to 2,2,2-trifluoroethanol, W = water.
Eur. J. Org. Chem. 2011, 2498–2506
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2503

N. Streidl, H. Mayr
FULL PAPER
As mentioned above, the s parameters of chloride in
As the stopped-flow conductivity technique is only appli-
f
aprotic solvents are exceptionally high. Thus, for a precise cable to solvent mixtures where a solution of the substrate
comparison with other nucleofuges with smaller s param- in an inert aprotic solvent is mixed with the protic solvent,
f
eters, s should not be neglected. However, the N param- it was not possible to determine k experimentally for all
f
f
1
eters given in Figure 6 show the qualitative trend of the heterolysis reactions of 1a–f plotted in Figure 7. The reli-
leaving group ability (S 1 reactivity) of chloride in aprotic ability of Equation (2) for predicting benzhydryl solvolysis
N
and protic solvents. The nucleofugality of chloride in the rate constants (see Figure 5) allowed us, however, to sup-
aprotic solvents studied in this work is in the range –1 Ͻ plement missing experimental rate constants in Figure 7 by
[
20]
N Ͻ 0.5. DMSO, the aprotic solvent with the highest ioniz- calculated values (N , s , and E from ref. ), which are
f
f
f
f
ing power of this series, is about 1.5 orders of magnitude identified by open symbols.
less ionizing than ethanol. The leaving group ability of chlo- Substitution of the heterolysis rate constants k of the
ride decreases by more than 6.5 orders of magnitude from chloro-diarylmethanes 1a–f in aprotic solvents (Table 3)
,2,2-trifluoroethanol (TFE) to acetone, which fall at the into the correlation equations in Figure 7 allows the solvent
extremes of this scale. Thus, whereas the half-life of chloro- ionizing powers YBnCl to be calculated for aprotic solvents,
4-methoxyphenyl)-phenylmethane (1f) in acetone in the which are listed in Table 5 (see also the correlation on
presence of a trapping agent is about 3.5 h, it is less than page 5 of the Supporting Information). As the correlations
1
2
(
[
20]
1
ms in TFE.
of the solvolysis rate constants of the chloro-diarylmeth-
anes 1a–f in protic solvents with other Y scales, such as
YOTs, are of lower quality, we have not attempted to deter-
mine YOTs for aprotic solvents from the rate constants in
Table 3. It should be noted, however, that previously pub-
Determination of the Solvent Ionizing Power Y for Aprotic
Solvents
In the Winstein–Grunwald[1] relationship [Equation (1)],
the solvent ionizing power is expressed by the empirical pa-
lished YOTs values for CH CN, DMF and DMA (–3.21,
3
[13]
–4.14, and –4.99, respectively)
show the same ordering;
[
1–14]
rameter Y.
As most readers will be familiar with the Y
the YOTs values for these solvents are approximately 0.5
units less negative than the YBnCl values determined in this
work (Table 5).
The ionizing powers YBnCl of different aprotic solvents
in this study differ by almost 2.5 units, ranging from the
least ionizing solvent, acetone (YBnCl = –5.96), to best ioniz-
ing solvent, DMSO (YBnCl = –3.52). Although aprotic sol-
vents generally have a smaller ionizing power than protic
solvents, Figure 8 shows that protic solvents such as 2-pro-
scale, the information given by the N scale in Figure 6 was
f
converted into Winstein–Grunwald Y values.
In line with previous reports,[
30]
the heterolysis rates
(
lgk ) of the chloro-diarylmethanes 1a–f correlate well with
1
the solvent ionizing power Y derived from secondary benzyl
derivatives such as the YBnCl scale (Figure 7).[10]
Figure 7. Plot of the first-order rate constants lgk
1
for the solvo-
lyses of 1a–f in different solvents [filled symbols: experimental val-
Figure 8. YBnCl scale for protic and aprotic solvents [this work and
[
20]
[10b]
ues from ref. ; open symbols: calculated by using Equation (2)]
against the solvent ionizing power YBnCl [mixtures of solvents are
given (v/v); A = acetone, E = ethanol, M = methanol, W = water].
from ref.
; mixtures of solvents are given (v/v); A = acetone,
E = ethanol, M = methanol, TFE = 2,2,2-trifluoroethanol, W =
water].
Table 5. Calculated solvent ionizing power YBnCl for aprotic solvents.
Solvent
DMSO
1f
1e
1d
1c
1b
1a
Average YBnCl[a]
–3.65
–3.97
–3.67
–3.82
–4.05
–3.78
–3.92
–4.12
–4.46
–4.89
–5.23
–5.72
–5.99
–6.12
–3.40
–3.42
–3.80
–4.30
–4.47
–4.90
–5.34
–5.56
–5.80
–3.43
–3.39
–3.82
–4.43
–4.56
–5.13
–5.60
–5.90
–5.95
–3.19
–3.14
–3.61
–4.34
–4.38
–5.10
–5.57
–5.89
–5.91
–3.52 (Ϯ0.22)
–3.61 (Ϯ0.34)
–3.88 (Ϯ0.21)
–4.38 (Ϯ0.07)
–4.62 (Ϯ0.22)
–5.07 (Ϯ0.13)
–5.56 (Ϯ0.14)
–5.81 (Ϯ0.17)
–5.96 (Ϯ0.12)
3
CH CN
PC
CHCl
DMF
3
–4.79
–5.01
–5.58
–5.72
–6.00
2 2
CH Cl
DMA
NMP
Acetone
[a] Standard deviations in parentheses.
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Eur. J. Org. Chem. 2011, 2498–2506

Ionizing Power of Aprotic Solvents
panol or 90% aqueous acetone are only one unit higher on this macroscopic quantity is often a poor measure of sol-
the YBnCl scale than DMSO and acetonitrile.
ute–solvent interactions at the microscopic level. Whereas
methanol and NMP have almost the same relative permit-
tivities (ε = 32.7 and 32.2, respectively), 1c is ionized about
r
Comparison with Other Solvent Polarity Scales
four orders of magnitude faster in methanol than in NMP.
2
Figure 9 (b, c) shows better correlations (R ≈ 0.87) be-
It is well-recognized that there is no universal solvent po-
[
31]
tween the ionization rates of 1c with Gutmann’s acceptor
larity scale, and, even worse, the term “polarity” itself is
[
33,35]
[
32]
numbers AN
and the empirical solvent parameters
“rather ill-defined” as noted in the IUPAC Gold Book.
N [33,34,36]
ET
sidered, the correlations with AN and ET break down (R2
0.47 and 0.32, respectively) as shown on page 4 of the
.
However, when only aprotic solvents are con-
Figure 9 compares the suitability of different solvent po-
N
larity parameters for predicting the S 1 rates of a typical
N
=
chloro-diarylmethane (e.g., 1c).
Supporting Information. Thus, none of the common sol-
vent polarity parameters are suitable for predicting the rela-
tive ionizing powers of aprotic solvents. Therefore, the
method introduced in this work is recommended for a sys-
tematic investigation of ionization rates in aprotic solvents.
Experimental Section
General: Anhydrous solvents for the kinetic experiments were pur-
chased (Ͻ50 ppm H O) and used without further purification.
2
Kinetic Experiments: The heterolysis rates of the chloro-diarylmeth-
anes 1a–f (Table 1) were monitored by following the increase of the
conductivity of the reaction mixtures using a conventional con-
ductometer (Tacussel CD 810, Pt electrode: WTW LTA 1/NS). The
solvent (20 mL) containing a defined amount of trapping reagent
(
piperidine, pyridine or triphenylphosphane) was thermostatted (Ϯ
0
1
.1 °C) at 25.0 °C for 5 min prior to adding the substrate. Typically,
0 to 80 mg of substrate was dissolved in 100 μL of the correspond-
ing solvents, then injected into the solution of the trapping agent,
and the conductance (G) was recorded at given time intervals. For
–
2
the study of reactions with half lives of 10 s Ͻ τ1/2 Ͻ 10 s, a
stopped-flow conductometer (Hi-Tech Scientific SF-61DX2, Pt
–
1
electrodes, cell volume 21 μL, cell constant 4.24 cm , minimum
dead time 2.2 ms) was used. The temperature was kept constant at
25 °C in all experiments using a circulating water bath.
Typical Procedure for the Determination of the Reaction Products:
The chloro-diarylmethanes (0.40 mmol) and piperidine (2.13 g,
2
5.0 mmol) or triphenylphosphane (6.56 g, 25.0 mmol) were dis-
solved in the corresponding solvent (50 mL) and stirred for at least
half-lives. Water (50 mL) was added, and the mixture was ex-
tracted with diethyl ether (2ϫ30 mL) and dichloromethane
5
(
(
2ϫ30 mL), then the organic layer was washed with water
2ϫ30 mL) and brine (30 mL). The solvent was dried (MgSO
4
)
and evaporated under reduced pressure and the crude residue was
either crystallized or purified by column chromatography to yield
the products described in Table 2.
Supporting Information (see footnote on the first page of this arti-
cle): Preparative procedures, details of the kinetic experiments, cor-
relations of lgk vs. E and Hammett correlations for the heterolyses
f
of chloro-diarylmethanes are available.
1
Figure 9. Plots of the first-order rate constants lgk for the solvo-
lyses of 1c in different solvents against (a) the relative permittivities
N
[33]
Acknowledgments
ε
r
, (b) acceptor number AN, and (c) E
T
(constants from ref.
,
N
[34]
additional E
T
values for acetone/water mixtures from ref. ).
We thank Johannes Ammer for helpful discussions, Dr. Armin R.
Ofial for help during preparation of the manuscript and the Deut-
Among the well-known solvent polarity scales, the corre-
lation is worst with the relative permittivities (dielectric con- sche Forschungsgemeinschaft (DFG) (Ma 673/20-3) for financial
[
33]
stants) ε (Figure 9a), in line with previous reports
that support.
r
Eur. J. Org. Chem. 2011, 2498–2506
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2505

N. Streidl, H. Mayr
FULL PAPER
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Eur. J. Org. Chem. 2011, 2498–2506