"Carbocation watching" in solvolysis reactions

Article abstract of DOI:10.1002/anie.200800354

(Figure Presented) The missing link between conventional S_N1 reactions and the chemistry of stable carbocations has been found. When water is added to the colorless solution of the covalent compound Ar₂CH-OAc (Ar = morpholinophenyl)

Full text of DOI:10.1002/anie.200800354

Communications
DOI: 10.1002/anie.200800354
Carbocations
“Carbocation Watching” in Solvolysis Reactions**
Heike F. Schaller and Herbert Mayr*
Dedicated to Professor R. W. Hoffmann on the occasion of his 75th birthday
The mechanisms of SN1 reactions were one of the most
intensively studied topics in organic chemistry during the
middle of the 20th century.[1] These reactions typically
proceed with slow formation of the carbocations followed
by fast subsequent reactions with the solvent (Scheme 1).
Scheme 1. A typical solvolysis reaction.
Detailed mechanistic studies by Winstein et al.[2] showed that
intermediate carbocations can recombine with the leaving
group at the ion-pair or free-ion stage before being trapped by
the solvent. Since methods for studying fast reaction kinetics
Scheme 2. Solvolysis reaction of 4,4’-bis(morpholino)benzhydryl car-
were not available at that time, most information on the
relative rates of ionization, ion recombination, and reaction of
the intermediate carbocation with the solvent was derived
indirectly from measurement of the overall solvolysis rates.
Recently we have shown that the ionization rates of
covalent benzhydryl esters can be observed photometrically if
the resulting carbocations are highly stabilized and do not
undergo subsequent reactions with the solvent.[3] We have
also reported that the trifluoroethanolysis of chlorobis(p-
methoxyphenyl)methane proceeds with instantaneous forma-
tion of the carbocation, and its subsequent combination with
trifluoroethanol could be followed photometrically with a
stopped-flow instrument.[4] Based on these results it was
predicted that it should be possible to design systems where
both the ionization and the following reaction can be
measured. We have now realized such systems and report
on the first solvolysis reactions in which the formation of
carbocations and their subsequent disappearance in aqueous
acetone and acetonitrile can be measured directly and fitted
by the kinetic model depicted in Scheme 2.
boxylates in aqueous acetone or acetonitrile.
the solution rapidly turned blue, then faded again within a
couple of minutes. A video demonstrating such “carbocation
watching” is provided in the Supporting Information (see also
Experimental Section).
Photometric monitoring of this process showed that the
maximum of the carbocation concentration was reached after
7 s in 80% aqueous acetonitrile. From the absorbance one
could derive that at this point, the concentration of the
carbocation corresponded to approximately 3% of the initial
substrate concentration. The fact that the blue color appears
much faster than it disappears indicates that the small
maximum concentration of the carbocation must result from
the fast recombination of the carbocations with the acetate
anions. Owing to the involvement of several rate and
equilibrium constants (partial dissociation of acetic acid) we
were not able to find a kinetic model that fits the resulting plot
of the carbocation concentration versus time (see Figure S6 in
the Supporting Information). However, the corresponding
reaction in the presence of diisopropyl-methylamine
((iPr)2NMe), which shows a similar absorbance–time corre-
lation (Figure 1), could be fitted to the kinetic model shown in
Scheme 1. The resulting rate constants and the Gepasi[5] fit of
the carbocation concentration are shown in Figure 1.
When water was added to the colorless solution of 4,4’-
bis(morpholino)benzhydryl acetate (1-OAc) in acetonitrile,
[*] Dipl.-Chem. H. F. Schaller, Prof. Dr. H. Mayr
Department Chemie und Biochemie
Ludwig-Maximilians-Universität München
Butenandtstrasse 5–13, Haus F, 81377 München (Germany)
Fax: (+49)89-2180-77717
When the solvolysis reaction of 1-OAc was followed
conductimetrically under the same conditions, a continuous
increase of the ion concentration (see Figure S4 in the
Supporting Information) was observed. We assumed a direct
proportionality between conductivity and the concentration
of [(iPr)2NHMe]+OAcꢀ, and fitted this curve by Gepasi to
obtain values of kꢀ1 = 1.09 ” 10ꢀ3 Lmolꢀ1 sꢀ1 and kSolv = 2.01 ”
E-mail: Herbert.Mayr@cup.uni-muenchen.de
Homepage: http://www.cup.uni-muenchen.de/oc/mayr
[**] We thank Dr. A. A. Tishkov, Dr. A. R. Ofial, and M. Breugst for helpful
discussions, and the Deutsche Forschungsgemeinschaft (Ma 673/
20-3) and the Fonds der Chemischen Industrie for financial support.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Scheme 3. Trapping of the intermediate benzhydrylium ions by DMAP.
Figure 1. Formation and consumption of the blue 1+ ion (monitored
photometrically at 612 nm) during the solvolysis of 1-OAc
(1.09 mmolLꢀ1) in 80% aqueous acetonitrile in the presence of
(iPr)2NMe (5.24 mmolLꢀ1) at 258C.
10ꢀ1 sꢀ1, which are almost identical to those derived photo-
metrically. In contrast, the value for the ionization constant
(k1 = 2.13 ” 10ꢀ2 sꢀ1) is 25% larger than that derived from the
absorbance of the intermediate carbocation (see Figure 1).[6]
The value of kSolv derived from Figure 1 and the conducti-
metrical curve is similar to that previously reported for the
hydrolysis of 1+BF4ꢀ in 80% aqueous acetonitrile (0.251 sꢀ1 at
208C).[7]
The high degree of reversibility of the ionization step
(mass law effect, common-ion rate depression) implies that
the increase of conductivity does not follow an exponential
function (see Figure S3 in the Supporting Information).
However, when the solvolysis of 1-OAc (0.62 mmolLꢀ1) was
performed in the presence of 4-(dimethylamino)pyridine
(DMAP, 5.02 mmolLꢀ1) or quinuclidine (5.24 mmolLꢀ1),
the solution did not turn blue, and a monoexponential
increase of conductivity was observed (see Figures S1 and
S2 in the Supporting Information) owing to quantitative
trapping of the intermediate carbocations by these amines
(Scheme 3).[8]
Figure 2. Formation and consumption of the blue 1+ ion (monitored
photometrically at 612 nm) during the solvolysis of 1-PNB
(1.04”10ꢀ5 molLꢀ1) in 80% aqueous acetone in the presence of
different amounts of nBu4N+PNBꢀ at 258C.
The maxima of the curves correspond to stationary points,
where Equations (1) or (2) hold.
The resulting first-order rate constants, k1 = 2.04 ” 10ꢀ2 sꢀ1
(in the presence of DMAP) and 2.01 ” 10ꢀ2 sꢀ1 (in the
presence of quinuclidine), were the same (within the exper-
imental error) as those derived from experiments in which the
intermediate carbocations were visible (Figure 1 and Fig-
ure S4 in the Supporting Information).
d½1þŠ
¼ k1 ½1-PNBŠꢀkꢀ1 ½1þŠ½PNBꢀŠꢀkSolv ½1þŠ ¼ 0
ð1Þ
ð2Þ
dt
½1þŠ
k1
¼
½1-PNBŠ kꢀ1 ½PNBꢀŠ þ kSolv
In the presence of extra tetrabutylammonium acetate, the
ionization equilibrium lies far to the side of the covalent
benzhydryl acetates; therefore, we were not able to study the
solvolysis of 1-OAc photometrically at constant acetate anion
concentrations. However, the ionization equilibria of the
corresponding p-nitrobenzoates lie more towards the side of
the ions, and it was possible to study their solvolyses at almost
constant concentrations of p-nitrobenzoate anions (PNBꢀ).
Figure 2 shows that the maximum concentration of the
intermediate carbocation, which is reached after 0.7 to 1.0 s,
decreases with increasing concentrations of nBu4N+PNBꢀ.
In accordance with Equation (2), the maxima of the
concentrations of the carbocations decrease as the concen-
trations of the carboxylate anions increase. At a concentra-
tion of 9.20 ” 10ꢀ5 molLꢀ1 of nBu4N+PNBꢀ, the observed
carbocation absorbance corresponds to a concentration of 1+
that is approximately 12% of the initial concentration of 1-
PNB. Figure 2 shows that the curves corresponding to higher
carbocation concentrations decline faster, resulting in a
crossing of the plots at 10 s. This observation reflects the
common-ion effect: At high carboxylate anion concentra-
tions, the overall hydrolysis reactions proceed more slowly,
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Communications
and small equilibrium concentrations of carbocations are
preserved for an extended period of time.
tion constant k1 by a factor of 7 while kꢀ1 and kSolv remain
almost constant. In accordance with this finding we had
previously reported that the nucleophilicities of 80% and
90% aqueous acetone (kSolv) are almost identical.[9]
“Carbocation watching” was also possible during the
solvolysis of the benzhydrylium p-nitrobenzoate 2-PNB in
80% and 60% aqueous acetone. Since replacement of the
morpholino groups by the N-methylanilino groups acceler-
ates ionization (k1) more than it affects ion recombination
(kꢀ1) (cf. Figures 2–4), larger equilibrium concentrations of
The individual curves in Figure 2, except that for the
lowest concentration of nBu4N+PNBꢀ, can be fitted satisfac-
torily by the kinetic model of Scheme 1. From all curves in
Figure 2 Gepasi arrives at the same value of kSolv = (1.49 ꢁ
0.4) sꢀ1, which is 1.5 times larger than that reported for the
hydrolysis of 4,4’-bis(morpholino)benzhydrylium tetrafluor-
oborate in the same solvent at 208C.[7] The other rate
constants depend slightly on the ionic strengths of the
solutions (see the Supporting Information). Thus the ion-
combination constant kꢀ1 decreases from (5800 ꢁ 50) mꢀ1 sꢀ1
at [PNBꢀ]0 = 0.37 mmolLꢀ1 to (2980 ꢁ 50) mꢀ1 sꢀ1 at
[PNBꢀ]0 = 0.76 mmolLꢀ1. The unexpected finding that the
ionization rate constant k1 is also calculated to decrease from
0.257 sꢀ1 (for [PNBꢀ]0 = 0.37 mmolLꢀ1) to 0.161 sꢀ1 (for
[PNBꢀ]0 = 0.76 mmolLꢀ1) may be explained by the fact that
ion pairing, which is more important in the more concentrated
salt solutions, is not considered in our kinetic model, which
generally assumes [PNBꢀ]0 = [nBu4N+PNBꢀ]0.
When the solvolyses of 1-PNB were studied in 60%
aqueous acetone at variable p-nitrobenzoate anion concen-
trations, similar absorbance–time correlations were observed,
but the concentration maxima of the intermediate carboca-
tions were higher (corresponding to 27–32% ionization) and
less affected by the carboxylate anion concentration
(Figure 3). As expected, the ionization equilibria lie more
towards the side of the ions in the more polar solvent.
Figure 4. Rate constants for the solvolysis of the 2-PNB
(9.48”10ꢀ4 molLꢀ1) in 80% and 60% aqueous acetone in the pres-
ence of 3.67”10ꢀ4 molLꢀ1 nBu4N+PNBꢀ.
benzhydrylium ions are produced when 2-PNB is solvolyzed
under the same conditions as 1-PNB. As a consequence of the
higher concentration of the intermediate carbocations, the
agreement of the individual rate constants k1, kꢀ1, and kSolv
obtained at different carboxylate anion concentrations is
much better than in the case of 1 (see the Supporting
Information).
SN2C+ reactions, postulated more than 50 years ago by
Ingold et al.,[10] have thus been established as the missing link
between conventional SN1 reactions, where carbocations
appear as short-lived intermediates, and the domain of
stable carbocations, where subsequent reactions of carboca-
tions do not occur.[11,3] Our philicity[12] and fugality[13] scales
can be employed to identify the range where the change of
mechanism occurs.
Experimental Section
Demonstration experiment: A colorless solution was obtained by
dissolving 4,4’-bis(morpholino)benzhydryl acetate (1-OAc, ꢂ 10 mg)
in acetone (8 mL) at room temperature. When 8 mL of water was
added, the solution turned blue (4,4’-bis(morpholino)benzhydrylium
ion 1+) and subsequently faded within about 80 s (formation of the
colorless benzhydrol). A video of this experiment is provided in the
Supporting Information.
Figure 3. Formation and consumption of the blue 1+ ion (monitored
photometrically at 612 nm) during the solvolysis of 1-PNB
(1.04”10ꢀ5 molLꢀ1) in 60% aqueous acetone in the presence of
different amounts of nBu4N+PNBꢀ at 258C.
The same values for k1 and kSolv are derived from the
different curves, and kꢀ1 is calculated to decrease by 27%
when [PNBꢀ] increases from 0.37 mmolLꢀ1 to 0.76 mmolLꢀ1
(see the Supporting Information). In line with expectation,
the variation of ion strength is less important in the more
polar solvent.
Received: January 23, 2008
Keywords: kinetics · nucleophilic aliphatic substitution ·
.
reactive intermediates · SN2C+ mechanism · solvolysis
Comparison of the rate constants in 80% aqueous acetone
(Figure 2) and 60% aqueous acetone (Figure 3) shows that
the doubling of the water concentration increases the ioniza-
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[6] In the initial phase of the reaction, the conductivity is partially
due to the presence of the benzhydrylium ions. Since the
maximum of the benzhydryliums ions is only 3% of the initial
concentration of benzhydryl acetate, we have neglected the fact
that the specific conductivity of benzhydrylium ions differs from
that of trialkylammonium ions.
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