Suppression of common-ion return by amines: A method to measure rates of fast SN1 reactions

Article abstract of DOI:10.1021/jo901410b

(Chemical Equation Presented) Rate constants for solvolyses of benzhydryl chlorides, which take place on the 10 ms to minute time scale, have been determined in aqueous acetone and acetonitrile by conductometry, using conventional conductometers as well as stopped-flow techniques. Secondary and tertiary amines were used to suppress ion recombination (common-ion return) thus giving access to the ionization rate constants k₁. The observed common-ion rate depressions can be rationalized by the correlation equation for electrophile-nucleophile combinations, log k(20 °C) = s(E + N), where electrophiles (here: carbocations) are characterized by the parameter Eand nucleophiles (here: chloride anions and solvents) are characterized by N and s. 2009 American Chemical Society.

Full text of DOI:10.1021/jo901410b

pubs.acs.org/joc
Suppression of Common-Ion Return by Amines: A Method to Measure
Rates of Fast SN1 Reactions
Nicolas Streidl, Anna Antipova, and Herbert Mayr*
€
Department Chemie und Biochemie der Ludwig-Maximilians-Universitat Munchen,
€
Butenandtstrasse 5-13 (Haus F), 81377 Mu€nchen, Germany
herbert.mayr@cup.uni-muenchen.de
Received July 3, 2009
Rate constants for solvolyses of benzhydryl chlorides, which take place on the 10 ms to minute time
scale, have been determined in aqueous acetone and acetonitrile by conductometry, using conven-
tional conductometers as well as stopped-flow techniques. Secondary and tertiary amines were used
to suppress ion recombination (common-ion return) thus giving access to the ionization rate
constants k1. The observed common-ion rate depressions can be rationalized by the correlation
equation for electrophile-nucleophile combinations, log k(20 °C) = s(E þ N), where electrophiles
(here: carbocations) are characterized by the parameter E and nucleophiles (here: chloride anions and
solvents) are characterized by N and s.
Introduction
the reactions of the carbocations Rþ with the leaving groups
X- and the solvents HOSolv.3-5 Many of these reactions
have been found to be diffusionally limited and to proceed
without activation energy. In these cases, the principle of
microscopic reversibility requires that there is also no barrier
for the forward reaction (RX f Rþ þ X-), i.e., the activation
free energy of the ionization step (k1) equals the difference
between the free energy of the ion pair (RþX-) and its
precursor (R-X) (Figure 1A).
Rates of SN1 reactions have been the major source of
information on the stabilities of carbocations.1 If the carbo-
cation Rþ is a short-lived, high-energy intermediate, the
transition state of the ionization process (k1) can be approxi-
mated by the structure and energy of the carbocation. This
hypothesis, previously based on Hammond’s postulate,2 has
been examined by the determination of the rate constants of
Figure 1D illustrates the other extreme, i.e., the heterolytic
cleavage of a substrate that yields a persistent carbocation.
In this case, the kinetics of the heterolysis reaction have
been measured directly by monitoring the concentration of
the colored carbocations.6 In line with noncarbocation-like
transition states, in such reactions the correlation between
the rates of heterolysis and the “stabilities” of the carbo-
cations (derived from the ionization equilibria) is rather
poor. The same is true for SN2Cþ reactions, where carbo-
cations are formed as long-lived, directly observable inter-
mediates, before they undergo subsequent reactions with the
solvent (Figure 1C).7
(1) (a) Streitwieser, A., Jr. Solvolytic Displacement Reactions; McGraw-
Hill: New York, 1962. (b) Carbonium Ions; Olah, G. A., Schleyer, P. v. R., Eds.;
Interscience: New York, 1968-1976; Vols. 1-5. (c) Vogel, P. Carbocation
Chemistry; Elsevier: Amsterdam, 1985. (d) Advances in Carbocation Chem-
istry; Creary, X., Ed.; JAI Press: Greenwich, CT, 1989; Vol. 1. (e) Advances in
Carbocation Chemistry; Coxon, J. M., Ed.; JAI Press: Greenwich, CT, 1995; Vol.
2. (f) Katritzky, A. R. Chem. Soc. Rev. 1990, 19, 83–105. (g) McClelland, R. A. In
Reactive Intermediate Chemistry; Moss, R. A., Platz, M. S., Jones, M., Jr., Eds.;
Wiley-Interscience: Hoboken, NJ, 2004; Chapter 1.
(2) Hammond, G. S. J. Am. Chem. Soc. 1955, 77, 334–338.
(3) (a) Richard, J. P. In Advances in Carbocation Chemistry; Creary, X., Ed.;
JAI Press: Greenwich, CT, 1989; Vol. 1, pp 121-169. (b) Amyes, T. L.; Toteva, M.
M.; Richard, J. P. In Reactive Intermediate Chemistry; Moss, R. A., Platz, M. S.,
Jones, M., Jr., Eds.; Wiley-Interscience: Hoboken, NJ, 2004; pp 41-69.
(c) Richard, J. P.; Amyes, T. L.; Toteva, M. M.; Tsuji, Y. Adv. Phys. Org. Chem.
2004, 39, 1–26.
(4) (a) McClelland, R. A. Tetrahedron 1996, 52, 6823–6858. (b) Cozens, F.
L.; Kanagasabapathy, V. M.; McClelland, R. A.; Steenken, S. Can. J. Chem.
1999, 77, 2069–2082. (c) Pezacki, J. P.; Shukla, D.; Lusztyk, J.; Warkentin, J.
J. Am. Chem. Soc. 1999, 121, 6589–6598. (d) Hallett-Tapley, G.; Cozens, F.
L.; Schepp, N. P. J. Phys. Org. Chem. 2009, 22, 343–348.
In the course of our efforts to develop a comprehensive
scheme of heterolysis reactions ranging from classical
SN1 mechanisms on one end (Figure 1A) over the SN2Cþ
(5) (a) Minegishi, S.; Kobayashi, S.; Mayr, H. J. Am. Chem. Soc. 2004,
126, 5174–5181. (b) Minegishi, S.; Loos, R.; Kobayashi, S.; Mayr, H. J. Am.
Chem. Soc. 2005, 127, 2641–2649. (c) Mayr, H.; Ofial, A. R. Pure Appl. Chem.
2009, 81, 667–683.
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2008, 130, 3012–3022.
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7328 J. Org. Chem. 2009, 74, 7328–7334
Published on Web 09/08/2009
DOI: 10.1021/jo901410b
r
2009 American Chemical Society

Streidl et al.
JOCArticle
FIGURE 1. Qualitative free energy profiles for different types of solvolysis reactions.
mechanisms7,8,9a (Figure 1C) to cases where persistent car-
bocations are generated which do not undergo subsequent
reactions with the solvent (Figure 1D),6 we have now
investigated SN1 reactions, which proceed via carbocations
of intermediate reactivity (Figure 1B). These are typically
fast reaction sequences, where the first step is reversible
because the intermediate carbocation reacts faster with the
leaving group than with the solvent. As the overall solvolysis
rate constants of such reactions are retarded by the so-called
common-ion return,10,11 the rate of the ionization step (k1)
can only be measured directly when the recombination of
the carbocation Rþ with the leaving group X- is suppressed.
In this article, we will demonstrate that this can efficiently be
achieved by the addition of amines. Because under these
conditions ionic products are generated from covalent sub-
strates, the rates of the reactions can be followed by con-
ductometry. When common-ion return is suppressed in the
usual way by azide ions,10a the total number of ions remains
constant during the reactions, and conductometry is not
applicable. In this article we will demonstrate that conducto-
metric studies of solvolysis reactions in the presence of
amines are an efficient method to systematically study
ionization rates of substrates which solvolyze in the milli-
second to minute time scale for which only very few kinetic
data are available in the literature.1
TABLE 1. Benzhydryl Chlorides 1a-j and Electrophilicity Parameters
E of the Corresponding Benzhydrylium Ions 1aþ-jþ
aFrom ref 12. bUnpublished.
(8) (a) Gelles, E.; Hughes, E. D.; Ingold, C. K. J. Chem. Soc. 1954, 2918–
2929. (b) Ingold, C. K. Structure and Mechanism in Organic Chemistry, 2nd
ed.; Cornell University Press: Ithaca, NY, 1969.
Results
(9) (a) Denegri, B.; Minegishi, S.; Kronja, O.; Mayr, H. Angew. Chem.
Solvolyses of the benzhydryl chlorides 1a-j (Table 1) in
aqueous acetone or aqueous acetonitrile give rise to the
formation of benzhydrols and equimolar amounts of HCl.
By portionwise addition of a rapidly solvolyzing benzhydryl
chloride (1g) and determination of the conductivity after
completion of the solvolysis (a few seconds after each
addition), the calibration curve of Figure 2 was obtained,
which showed that the conductivity is directly proportional
to the amount of solvolyzed benzhydryl chloride.
When the solvolyses were carried out in the presence of
amines, benzhydrols and/or benzhydrylammonium salts are
formed (Scheme 1). Calibration experiments as depicted in
Figure 2 are reported in Figures S1 and S2 of the Supporting
2004, 116, 2353–2356. Angew. Chem., Int. Ed. 2004, 43, 2302-2305.
ꢀ
(b) Denegri, B.; Streiter, A.; Juric, S.; Ofial, A. R.; Kronja, O.; Mayr, H.
Chem.;Eur. J. 2006, 12, 1648–1656. Chem.;Eur. J. 2006, 12, 5415.
(10) For reviews on common-ion rate depression, see: (a) Raber, D. J.;
Harris, J. M.; Schleyer, P. v. R. In Ions and Ion Pairs in Organic Reactions;
Szwarc, M., Ed.; Wiley: New York, 1974; Vol. 2. (b) Stang, P. J.; Rappoport, Z.;
Hanack, M.; Subramanian, L. R. Vinyl Cations; Academic Press: New York,
1979; Chapter 6, pp 337-338. (c) Rappoport, Z. In Reactive Intermediates;
Abramovitch, R. A., Ed.; Plenum Press: New York, 1983; Vol. 3, pp 583-594.
(d) Kitamura, T.; Taniguchi, H.; Tsuno, Y. In Dicoordinated Carbocations;
Rappoport, Z., Stang, P. J., Eds.; Wiley: Chichester, UK, 1997; pp 321-376.
(11) For other recent work on ion-pair reactivities, see: (a) Peters, K. S.
Acc. Chem. Res. 2007, 40, 1–7. (b) Peters, K. S. Chem. Rev. 2007, 107, 859–
873. (c) Moss, R. A. Acc. Chem. Res. 1999, 32, 969–974. (d) Moss, R. A.
J. Phys. Org. Chem. 2009, 22, 265–273. (e) Moss, R. A.; Fu, X.; Sauers, R. R.
J. Phys. Org. Chem. 2007, 20, 1–10. (f) Hao, W.; Parker, V. D. J. Org. Chem.
2008, 73, 48–55. (g) Tsuji, Y.; Richard, J. P. Chem. Rec. 2005, 5, 94–106.
(h) Huang, X.; Bennet, A. J. Can. J. Chem. 2004, 82, 1336–1340. (i) Koo, I. S.;
An, S. K.; Yang, K.; Lee, I.; Bentley, T. W. J. Phys. Org. Chem. 2002, 15, 758–
764. (j) Tsuji, Y.; Richard, J. P. J. Am. Chem. Soc. 2006, 128, 17139–17145.
(k) Jia, Z. S.; Ottosson, H.; Zeng, X.; Thibblin, A. J. Org. Chem. 2002, 67,
182–187. (l) Tsuji, Y.; Mori, T.; Toteva, M. M.; Richard, J. P. J. Phys. Org.
Chem. 2003, 16, 484–490.
(12) (a) Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker,
B.; Kempf, B.; Loos, R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. J. Am.
Chem. Soc. 2001, 123, 9500–9512. (b) Mayr, H.; Kempf, B.; Ofial, A: R. Acc.
Chem. Res. 2003, 36, 66–77.
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When quoted in the tables, these concentration-dependent
“rate constants” are displayed in italics, whereas in the
figures they are represented by open symbols.
Figure 3d shows that the rate of the reaction increased
significantly upon addition of small concentrations of piper-
idine, but decreased slightly as the piperidine concentration
exceeds 0.24 M. Because ionization of the C-Cl bond
requires solvation of the incipient chloride ion by hydrogen
bonding, one might explain the decrease of reactivity at high
amine concentrations by a solvent effect: The water mole-
cules which are needed for chloride solvation are no longer
fully available because they are already engaged in hydrogen
bonding with the amine. An alternative explanation would
be the change of the dielectric constant of the solvent when
higher concentrations of amine are present.
A similar behavior was observed when the solvolysis
of 4,40-dimethoxybenzhydryl chloride 1h was carried out
in the presence of variable concentrations of triethylamine,
4-dimethylaminopyridine (DMAP), 1,4-diazabicyclo[2.2.2]-
octane (DABCO), and pyridine as depicted in Figure 4,
where the slight reactivity decrease at higher amine concen-
trations, which is shown in the Supporting Information, has
been cut off for the sake of clarity. Addition of the sterically
shielded 2,6-lutidine (= 2,6-dimethylpyridine), which is a
stronger Brønsted base than pyridine, does not affect the
kinetics of the solvolysis reactions. This observation indi-
cates that the amine effect is due to nucleophilic attack of the
amine at the benzhydrylium system and not due to Brønsted
base catalysis.
FIGURE 2. Plot of conductivity Grel versus concentration of the
solvolyzed substrate 4-methoxy-40-phenoxybenzhydryl chloride 1g
without additives in 80% acetone (80A20W).
SCHEME 1. Solvolyses of Benzhydryl Chlorides in the Presence
of Tertiary Amines in Aqueous Solvents
In accord with this interpretation, the solvolysis of 4,40-
dimethoxybenzhydryl chloride 1h in 90% acetone (90A10W)
in the presence of 0.25 M piperidine leads to the exclusive
formation of the benzhydrylpiperidine 3 (Scheme 2). The
benzhydrylammonium ions 2 obtained from 1h and tertiary
amines were not stable under the reaction conditions and
hydrolyzed to give the corresponding benzhydrol 4. How-
ever, because the ammonium chlorides 2 and HNR3þCl-
cannot be expected to have identical equivalent conductiv-
ities, the observation of monoexponential rate laws at high
amine concentrations indicates that the hydrolyses of the
intermediate ammonium ions 2 occur after the complete
consumption of 1h.
The observation that the solvolysis rate constants kobs
reach plateaus when the amine concentrations exceed
a certain value (Figures 3d and 4) excludes the operation
of SN2 mechanisms. It indicates that the acceleration of
the gross reactions by amines is due to the suppression
of common-ion return, i.e., suppression of the reversibility
of the first step of Scheme 2.
This interpretation is in line with the reactivities of
4-methoxybenzhydryl chloride (1e) studied under different
conditions in 60% acetone (60A40W). The solvolysis of a
1 mM solution of 1e follows first-order kinetics with a rate
constant of 18.4 s-1 (at c(DMAP) = 0 mol L-1) (Figure 5).
Because of the low concentration of the substrate, recombi-
nation of the intermediate carbenium ion 1eþ with Cl- (c <
1 mM) does not efficiently compete with the trapping by water.
In an 8 mM solution of 1e, the growing concentration of
Cl- during the reaction is responsible for the gradual retar-
dation of the overall reaction as the common-ion return
increases during the reaction. The “best fit” to the exponen-
tial function yields a value of kobs that is approximately 25%
Information, which show that also under these conditions
the concentration of the ions is directly proportional to the
measured conductivity.
A typical example for the determination of the ionization
rate constants is illustrated in Figure 3 for the solvolysis
of 4,40-dimethoxybenzhydryl chloride 1h in 90% acetone
(90A10W).
When 1h (0.018 M) was dissolved in 90% acetone without
any additives, 90% conversion was reached after 5 s, and
the plot of conductivity versus time deviated noticeably from
the monoexponential function (eq 1), which is shown by the
dashed line in Figure 3a.
G ¼ Gmax½1 -expð -k1tÞꢀþconstant
ð1Þ
When the reaction was followed in a solution containing
0.04 M piperidine, 90% conversion was already achieved
after 0.2 s, and the experimental line got closer to the dashed
exponential function (Figure 3b). Accordance between the
experimental graph and the exponential function was found
when 0.24 M piperidine was present, and 90% of conversion
was now achieved after 0.1 s (Figure 3c).
Because the rate laws to describe the kinetics in panels
a and b of Figure 3 are rather complex (concentrations of
Cl- vary during the reactions) we did not attempt to describe
these traces in detail. We rather extracted “first-order rate
constants” kobs from best fits of these graphs to the expo-
nential function (eq 1). Though these values of kobs are not
well-defined, they give useful information on the half-
lives of the substrates under the given reaction conditions.
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FIGURE 3. (a-c) Plots of conductivity versus time for the solvolysis of 4,40-dimethoxybenzhydryl chloride 1h (0.018 M) in 90% acetone
(90A10W) at 25 °C in the presence of c(piperidine) = 0 (a), 0.04 (b), and 0.24 mol L-1 (c); (d) plot of the observed rate constants kobs versus
c(piperidine) (open symbols represent kinetics that are not of first-order).
constants of the concentrated solutions of 1e than on the
more dilute solutions.
According to Figure 6, the “best-fit rate constant” kobs for
the solvolysis of 4-methoxy-40-methylbenzhydryl chloride
1f (18 mM) in 90A10W in the absence of amine is reduced
by a factor of 2.5 when common-ion return was enhanced by
the addition of 18 mM Bu4NþCl-. This rate reduction
can be compensated by adding amine; in the presence
of high chloride ion concentrations, more DMAP is needed
to suppress ion recombinations.
The situation described in Figures 3d and 4, i.e., increase
of kobs with increasing concentrations of nucleophilic
amines until a plateau or shallow maximum is reached, has
FIGURE 4. Observed rate constants of the solvolysis of 4,40-
dimethoxybenzhydryl chloride 1h in 90% acetone (90A10W) in
been observed for numerous solvolysis reactions in aqueous
the presence of variable concentrations of amines (open symbols
acetone and aqueous acetonitrile (see the Supporting Infor-
represent kinetics that are not of first-order).
mation). Tables 2 and 3 list the maximum values of kobs
smaller than that of the 1 mM solution in the absence of an
amine. The kinetics of the solvolysis reaction of an even more
concentrated solution of 1e ([1e]0 = 18 mM, [DMAP] = 0)
showed a stronger deviation from the exponential function
and a further significant decrease of kobs due to increasing
common-ion return.
In line with the preceding mechanistic analysis, Figure 5
shows that higher amine concentrations are needed to sup-
press common-ion return in the more concentrated substrate
solutions. Remarkably, the first-order rate constants ob-
tained at different substrate concentrations are almost iden-
tical (kobs([1e]) = 18.6 (1 mM), 17.7 (8 mM), and 17.2 s-1
(18 mM)) in the presence of 0.19 M DMAP. As expected, the
amine additives have a bigger effect on the observed rate
obtained with different amine additives. Because the maxi-
mum values of kobs are reached at different amine concentra-
tions, these rate constants do not refer to exactly the same
reaction conditions because the nature of the solvent is
slightly altered by the amines (up to 10 vol %). This is only
a minute effect, however, compared with the large effects
caused by the variation of the substituents in the substrates or
variations of the water concentration in the solvents.
More severe are the uncertainties of some of the kobs values
in Tables 2 and 3, which have been obtained in the absence of
amines. If they are printed in italics, they include a significant
amount of common-ion return and thus are specific for the
selected concentration of the substrate (here: 0.018 M). As
described above, these kobs values reflect a “best fit” to the
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SCHEME 2. Heterolysis of 4,40-Dimethoxybenzhydryl Chloride 1h in Aqueous Solutions of Secondary and Tertiary Amines
Discussion
Qualitatively, the message from Tables 2 and 3 is clear:
The effect of the amine additives increases as the solvolysis
rate constants increase, i.e., as one moves from left to right in
Tables 2 and 3. While the solvolyses of the methyl-substi-
tuted benzhydryl chlorides 1c and 1d (0.018 M) in 90%
acetone (90A10W) are only accelerated by a factor of 1.2
to 1.4 by added DMAP (cf. entries 1 and 4 in Table 2), the
amine effect increases gradually when moving from left
to right and reaches a factor of 65 for benzhydryl chloride
1j, which ionizes 6.5 orders of magnitude faster than 1c
(compare entries 1 and 4 in Table 2).
FIGURE 5. Solvolysis of 4-methoxybenzhydryl chloride (1e) in
60A40W at 25 °C at different substrate concentrations in the
presence of DMAP (open symbols represent kinetics that are not
of first-order, see text).
The increasing importance of common-ion return with
decreasing reactivity of the carbocations has previously been
considered as a consequence of the reactivity-selectivity
principle, which claims that selectivity increases with decreas-
ing reactivity. With the fall of the reactivity-selectivity prin-
ciple17 a more sophisticated explanation becomes necessary.
In previous work,18 we have shown that eq 2 can be used to
calculate the rate constants of the reactions of carbocations
with a large variety of nucleophiles, including amines,19
halide ions,5b and solvents.5a
log k ¼ sðEþNÞ
ð2Þ
FIGURE 6. Solvolysis of 4-methoxy-40-methylbenzhydryl chloride
(1f, 0.018 M) in 90A10W at 25 °C in the presence of Bu4NCl (open
symbols represent kinetics that are not of first-order).
where k is the second-order (M-1 s-1) or first-order (s-1, for
reactions with solvents) rate constant (20 °C), s and N are the
empirical, nucleophile-specific parameters, and E is the
empirical electrophilicity parameter.
We will now employ eq 2 for rationalizing the effects
reported in Tables 2 and 3.
exponential function and thus give useful information about
the gross reactivity at a certain substrate concentration, but
are not real “constants”.
This trapping method also works with other strong nuc-
leophiles like PPh3 as can be seen in entry 10 of Table 2.
(17) Mayr, H.; Ofial, A. R. Angew. Chem. 2006, 118, 1876–1886. Angew.
Chem., Int. Ed. 2006, 45, 1844-1854 and references cited therein.
(18) (a) Mayr, H.; Ofial, A. R. Pure Appl. Chem. 2005, 77, 1807–1821.
(b) Mayr, H.; Ofial, A. R. J. Phys. Org. Chem. 2008, 21, 584–595.
(19) (a) Minegishi, S.; Mayr, H. J. Am. Chem. Soc. 2003, 125, 286–295.
(b) Phan, T. B.; Breugst, M.; Mayr, H. Angew. Chem. 2006, 118, 3954–3959.
Angew. Chem., Int. Ed. 2006, 45, 3869-3874. (c) Brotzel, F.; Chu, Y. C.;
Mayr, H. J. Org. Chem. 2007, 72, 3679–3688. (d) Brotzel, F.; Kempf, B.;
Singer, T.; Zipse, H.; Mayr, H. Chem.;Eur. J. 2007, 13, 336–345.
(13) Berliner, E.; Malter, M. Q. J. Org. Chem. 1968, 33, 2595–2596.
(14) Verbit, L.; Berliner, E. J. Am. Chem. Soc. 1964, 86, 3307–3312.
(15) Liu, K.-T.; Lin, Y.-S.; Tsao, M.-L. J. Phys. Org. Chem. 1998, 11,
223–229.
(16) Bateman, L. C.; Church, M. G.; Hughes, E. D.; Ingold, C. K.; Taher,
N. A. J. Chem. Soc. 1940, 979–1011.
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TABLE 2. Maximum First-Order Rate Constants (kobs,max, s-1) for the Solvolysis Reactions of the Benzhydryl Chlorides 1c-j (0.018 M) in the Presence
of Amines in Aqueous Acetone at 25 °C
amine
1c
1d
1e
1f
1g
1h
1i
1j
90% acetone/10% water, v/v (90A10W)
1
2
3
4
5
6
7
8
9
10
without aminea
piperidine
NEt3
DMAP
DABCO
1.1 ꢁ 10-4b
1.4 ꢁ 10-3c
1.6 ꢁ 10-2
7.8 ꢁ 10-2
1.7 ꢁ 10-1
2.64
1.68
2.09
2.38
3.9 ꢁ 10-1
2.50 ꢁ 101
1.36 ꢁ 101
1.45 ꢁ 101
1.74 ꢁ 101
1.59 ꢁ 101
8.4 ꢁ 10-1
5.4 ꢁ 10-1
1.21 ꢁ 101
2.11 ꢁ 101
2.2
1.01 ꢁ 102
1.04 ꢁ 102
6.2
6.30 ꢁ 10-1
3.95 ꢁ 10-1
5.40 ꢁ 10-1
5.81 ꢁ 10-1
6.13 ꢁ 10-1
4.43 ꢁ 10-2
7.53 ꢁ 10-2d
8.87 ꢁ 10-2
7.89 ꢁ 10-2
2.89 ꢁ 102
4.00 ꢁ 102
4.57 ꢁ 102
1.33 ꢁ 10-4
1.89 ꢁ 10-3
pyridine
2.29
2,6-lutidinea
2-chloropyridinea
Proton Spongeg
PPh3
1.9 ꢁ 10-2
2.2
80% acetone/20% water, v/v (80A20W)
3.3 ꢁ 10-1
11
12
13
14
15
16
17
without aminea
piperidine
NEt3
DMAP
DABCO
1.1 ꢁ 10-3e
1.62 ꢁ 10-3
2.3 ꢁ 10-2f
1.7
5.56
3.9
1.58 ꢁ 101
1.5 ꢁ 101
8.59 ꢁ 10-1
1.57 ꢁ 102
9.58 ꢁ 101
1.37 ꢁ 102
1.60 ꢁ 102
1.56 ꢁ 102
2.80 ꢁ 10-2
9.46 ꢁ 10-1
8.25 ꢁ 10-1
9.16 ꢁ 10-1
3.2 ꢁ 10-1
5.77
5.67
6.06
1.73 ꢁ 101
1.76 ꢁ 101
1.75 ꢁ 101
pyridine
2-chloropyridinea
60% acetone/40% water, v/v (60A40W)
3.8 ꢁ 101
18
19
20
without aminea
DMAP
DABCO
9.2
1.71 ꢁ 101
6.3 ꢁ 101
8.40 ꢁ 101
1.74 ꢁ 102
1.47 ꢁ 101
aItalics: not first-order. Solvolysis rate constants k1 = 1.11 ꢁ 10-4 (from ref 9b), 1.12 ꢁ 10-4 (from ref 13), and 1.15 ꢁ 10-4 s-1 (from ref 14).
b
cSolvolysis rate constants k1 = 1.83 ꢁ 10-3 (from ref 9b) and 1.43 ꢁ 10-3 s-1 (from ref 13). Measured at the stopped-flow conductometer; at the
conventional conductometer kobs,max = 7.23 ꢁ 10-4 s-1. eSolvolysis rate constants k1 = 1.76 ꢁ 10-3 (from ref 9b), 1.64 ꢁ 10-3 (from ref 15), and 1.60 ꢁ
10-3 s-1 (from ref 16). fSolvolysis rate constant k1 = 2.79 ꢁ 10-2 s-1 (from ref 9b). gN,N,N0,N0-Tetramethylnaphthalene-1,8-diamine.
d
TABLE 3. Maximum First-Order Rate Constants (kobs,max, s-1) for the Solvolyses of the Benzhydryl Chlorides 1a-h (6.1 ꢁ 10-3 M) in the Presence of
Amines in Aqueous Acetonitrile at 25 °C
amine
1a
1b
1c
1d
1e
1g
1h
90% acetonitrile/10% water, v/v (90AN10W)
2.50 ꢁ 10-3
4.36 ꢁ 10-2
80% acetonitrile/20% water, v/v (80AN20W)
1
2
3
without aminea
DABCO
piperidine
8.14 ꢁ 10-5
4.2 ꢁ 10-2
4.7 ꢁ 10-1
1.53
1.43
6.0
3.32 ꢁ 101
1.8 ꢁ 101
2.49 ꢁ 102
2.38 ꢁ 102
4.42 ꢁ 10-2
3.30 ꢁ 101
4
5
6
without aminea
DABCO
piperidine
1.09 ꢁ 10-4
1.14 ꢁ 10-3
8.03 ꢁ 10-4
2.28 ꢁ 10-2
3.41 ꢁ 10-1
3.8
7.70
7.76
4.0 ꢁ 101
1.20 ꢁ 102
1.12 ꢁ 102
3.45 ꢁ 10-1
60% acetonitrile/40% water, v/v (60AN40W)
8.29 ꢁ 10-3
7
8
9
without aminea
DABCO
piperidine
1.97 ꢁ 10-1
2.6
2.76
2.63
2.8 ꢁ 101
4.08 ꢁ 101
3.56 ꢁ 101
aItalics: kobs,max was obtained from the “best fit” and does not reflect the real first-order rate constants (see text).
Figure 7 compares the pseudo-first-order rate constants
parameters E of the benzhydrylium ions 1a-j (Table 1) into
eq 2 yields the second-order rate constants, which are multi-
plied by the concentrations of Cl- (6.1 mM)20 to give the
pseudo-first-order rate constants drawn in Figure 7. From
the known nucleophilicity parameters N and s of secondary
and tertiary amines in various solvents19 one can derive that
in 0.1 M solutions of amines in aqueous acetonitrile, most
amines react faster than water and chloride as illustrated for
the reaction of DABCO with benzhydrylium ions in Figure 7.
Only highly reactive carbocations, where the diffusion limit
is close, will react faster with water that is present in higher
concentration.
(calculated by eq 2) for the reactions of benzhydrylium ions
with solvents, chloride ions (6.1 ꢁ 10-3 M),20 and DABCO
(0.1 M). The correlation line for the solvent was calculated by
eq 2 from the published reactivity parameters N = 5.02 and
s = 0.89 for 80% acetonitrile/20% water5a and the electro-
philicity parameters E of the benzhydrylium ions 1a-j
(Table 1). Substitution of the published nucleophile-specific
parameters N =13.30 and s =0.60 for the chloride ion in
80% acetonitrile5b (80AN20W) and the electrophilicity
(20) This concentration corresponds to the final concentration of Cl- at
the end of the solvolysis reactions shown in Table 3, i.e. the maximum
concentration of Cl- during the measurement.
We can now use the graph shown in Figure 7 to rationalize
the observed rate effects. In agreement with the previously
J. Org. Chem. Vol. 74, No. 19, 2009 7333

Streidl et al.
JOCArticle
diffusion and not by activation, it is not surprising that the
heights of the plateaus do not correlate with the previously
reported order of nucleophilicities of amines.19
Conclusion
Nucleophilic secondary and tertiary amines have been
found to suppress common-ion return in the SN1 reactions
of rapidly ionizing benzhydryl chlorides without giving rise
to SN2 reactions. By employing amines as nonionic trapping
agents for carbocations instead of the commonly used azide
ions it has become possible to follow the kinetics by con-
ductometry and thus measure fast ionization processes on
the millisecond time scale, i.e., rates of formation of highly
stabilized carbocations, for which only a few kinetic data
have so far been available. In this way, it has become possible
to close the gap between SN1 reactions without common-ion
return and carbocation-like transition states (Figure 1A) and
SN2Cþ reactions (Figure 1, C), where carbocations accumu-
late before they are trapped by the solvents or other nucleo-
philes.
FIGURE 7. Rate constants (log kobs) for the reactions of benzhy-
drylium ions with 80% acetonitrile/20% water, chloride ion (6.1
mM),20 and DABCO (0.1 M) plotted against the electrophilicity E
of the benzhydrylium ions.
published small mass-law constants for the dimethyl-sub-
stituted benzhydryl chloride 1d (R = k-1/ksolv = 74 M-1
)
Experimental Section
and monomethyl-substituted benzhydryl chloride 1c (R = 32
M
General. Solvolysis rates of the benzhydryl chlorides 1a-j
(Table 1) were monitored by following the increase of the
conductivity of the reaction mixtures, using a conductometer
with a Pt electrode. For the study of solvolysis reactions with
half-lives of 10-2 s < τ1/2 < 10 s, a standard stopped-flow
conductometer was used in single-mixing mode.
Dry acetone and acetonitrile for the kinetic experiments were
purchased (<50 ppm of H2O) and used without further pur-
ification. Mixtures of solvents are given as (v/v) and the solvents
are abbreviated: A = acetone, AN = acetonitrile, W = water.
For example, the solvent mixture 80A20W refers to a mixture of
acetone and water in a ratio of 80/20 (v/v).
Kinetic Experiments. For the study of slow reactions, solvent
mixtures (20 mL) were thermostated ((0.1 °C) at 25.0 °C for
5 min prior to adding the substrate. Typically, 10 to 80 mg of
substrate was dissolved in 100 μL of acetone or acetonitrile, then
injected into the solvent, and the conductance (G) was recorded
at given time intervals. When the stopped-flow equipment was
used, the benzhydryl chlorides were dissolved in pure acetone or
acetonitrile and mixed in the conductivity cell with aqueous
acetone or acetonitrile to give solutions of the desired compo-
sition.
To examine the consistency of the results determined with the
two instruments, the kinetics of the solvolysis of 4-methoxy-
benzhydryl chloride 1e in 90% acetone (90A10W) was studied at
the conventional conductometer as well as at the stopped-flow
instrument. Figure S3 (Supporting Information) shows that the
results obtained with both instruments agreed within experi-
mental error.
-1) in 80% acetone (80A20W),16 ion recombination does
not play an important role in the hydrolyses of these two
compounds in aqueous acetonitrile when dilute solutions
(i.e., small [Cl-]) are considered (for 1dþ and 1cþ, the green
solvent graph is above the red Cl- graph in Figure 7). As a
result, the solvolysis rates of these compounds are almost
unaffected by the addition of amines (Tables 2 and 3). When
methoxy-substituted benzhydrylium ions with E e 2.1 are
considered, the solvent graph drops below the chloride graph
in Figure 7, suggesting that common-ion return becomes
important in aqueous acetonitrile, in agreement with the
deviation of the solvolysis kinetics from the first-order rate
law. Because Figure 7 shows that in this range the amine
graph is far above the graphs for the solvent and for Cl-, one
can explain why moderate amine concentrations are already
sufficient to suppress the common-ion return and thus lead
to an increase of the solvolysis rates. As discussed earlier,5b
the different slopes of the chloride and solvent correlations
account for the decreasing amount of ion return as one
moves from left to right in Figure 7. The decreasing magni-
tude of the amine effect as one moves from left to right in
Figure 7 can be explained analogously.
The preceding discussion suggests that the rate accelera-
tion by added amines is due to suppression of the common-
ion return. One might, therefore, expect the same plateau for
all reactive amines in Figure 4. This is not the case, and
Tables 2 and 3 show that the maximal first-order rate
constants for the various benzhydryl systems in the presence
of different amines differ up to a factor of 2. Most notable,
the relative heights of the plateaus do not reflect the relative
amine nucleophilicities. Thus, pyridine leads generally to
slightly higher limiting rates than DMAP despite of its lower
nucleophilicity19d (see also Figure 4). These modest differ-
ences may be due to the fact that the amines intercept contact
ion pairs as well as free ions. As the rates of most of these
combinations of carbocations with amines are controlled by
Acknowledgment. Dedicated to Professor Shinjiro
Kobayashi on the occasion of his 70th birthday. We thank
Dr. A. R. Ofial for help during preparation of this manuscript
and the Deutsche Forschungsgemeinschaft (Ma 673/20-3) and
the Fonds der Chemischen Industrie for financial support.
Supporting Information Available: Details of the kinetic
experiments and calibration of the conductometers. This material
is available free of charge via the Internet at http://pubs.acs.org.
7334 J. Org. Chem. Vol. 74, No. 19, 2009