Dynamics for reaction of an ion pair in aqueous solution: reactivity of carboxylate anions in bimolecular carbocation-nucleophile addition and unimolecular ion pair collapse.

Article abstract of DOI:10.1021/ol015706s

[reaction: see text]. The sum of the rate constants for solvolysis and 18O-scrambling of 4-MeC6H4(13)CH(Me)18OC(O)C6F5 in 50/50 (v/v) trifluoroethanol/water, k(solv) + k(iso) = 1.22 x 10(-5) s(-1), is larger than k(solv) = 1.06 x 10(-5) s(-1) for solvolys

Full text of DOI:10.1021/ol015706s

ORGANIC
LETTERS
2001
Vol. 3, No. 8
1237-1240
Dynamics for Reaction of an Ion Pair in
Aqueous Solution: Reactivity of
Carboxylate Anions in Bimolecular
Carbocation−Nucleophile Addition and
Unimolecular Ion Pair Collapse
,#
Yutaka Tsuji,‡ Tetsuo Mori,‡ John P. Richard,* Tina L. Amyes,#
Mizue Fujio,¶ and Yuho Tsuno¶
Department of Biochemistry and Applied Chemistry, Kurume National
College of Technology, Komorinomachi, Kurume 830-8555, Japan,
Department of Chemistry, UniVersity at Buffalo, SUNY,
Buffalo, New York 14260, and Institute for Fundamental Research of Organic
Chemistry, Kyushu UniVersity, Hakozaki, Fukuoka 812-8581, Japan
jrichard@chem.buffalo.edu
Received February 13, 2001
ABSTRACT
The sum of the rate constants for solvolysis and 18O-scrambling of 4-MeC H 13CH(Me)18OC(O)C F5 in 50/50 (v/v) trifluoroethanol/water, ksolv
+
6
4
6
k
iso ) 1.22 × 10-5 s-1, is larger than ksolv ) 1.06 × 10-5 s-1 for solvolysis of the unlabeled ester. This shows that the ion pair intermediate
undergoes significant internal return. The data give k-1 ) 7 × 109 s-1 for internal return by unimolecular collapse of the ion pair, which is
significantly larger than kNu ) 5 × 108 M-1 s-1 for bimolecular nucleophilic addition of carboxylate anions to 4-MeC H CH(Me)+.
6
4
Although the experimental protocols for detection of the
reactions of carbocation-anion ion pairs are well developed,1
there is substantial unrealized potential for the utilization of
these methods in the estimation of absolute rate constants
for the very fast reactions of ion pairs.2,3
We report here an examination of 18O-scrambling that
accompanies solvolysis of the 18O-labeled ester 4-MeC6H4
-
13
CH(Me)18OC(O)C6F5 (1-18OC(O)C6F5, Scheme 1) and a
determination of the relative rates of reaction of the ion pair
intermediate to form the 18O-scrambeled isomerization
product 1-OC(18O)C6F5 (k-1′) and the solvent adducts (ks′
+ k-d, Scheme 1). The results of these experiments allow
for an estimate of the absolute rate constant k-1 ≈ k-1′ for
unimolecular carbocation-anion collapse (Scheme 1) and a
comparison of the reactivity of carboxylate anions toward
‡ Kurume National College of Technology.
# University at Buffalo, SUNY.
¶ Kyushu University.
(1) (a) Harris, J. M. Prog. Phys. Org. Chem. 1974, 11, 89-173. (b) Raber,
D. J.; Harris, J. M.; Schleyer, P. v. R. In Ions and Ion Pairs in Organic
Reactions; Szwarc, M., Ed.; John Wiley & Sons: New York, 1974; Vol. 2.
(c) Allen, A. D.; Fujio, M.; Tee, O. S.; Tidwell, T. T.; Tsuji, Y.; Tsuno,
Y.; Yatsugi, K.-I. J. Am. Chem. Soc. 1995, 117, 8974-8981. (d) Tsuji, Y.;
Yatsugi, K.; Fujio, M.; Tsuno, Y. Tetrahedron Lett. 1995, 36, 1461-1464.
(e) Tsuji, Y.; Kim, S. H.; Saeki, Y.; Yatsugi, K.-i.; Fujio, M.; Tsuno, Y.
Tetrahedron Lett. 1995, 36, 1465-1468. (f) Goering, H. L.; Briody, R. G.;
Sandrock, G. J. Am. Chem. Soc. 1970, 92, 7401-7407.
(2) (a) Richard, J. P.; Rothenberg, M. E.; Jencks, W. P. J. Am. Chem.
Soc. 1984, 106, 1361-1372. (b) Richard, J. P.; Jencks, W. P. J. Am. Chem.
Soc. 1984, 106, 1373-1383. (c) Richard, J. P. J. Org. Chem. 1992, 57,
625-629.
(3) Richard, J. P.; Tsuji, Y. J. Am. Chem. Soc. 2000, 122, 3963-3964.
10.1021/ol015706s CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/27/2001

esters.1c-e The ratio of the integrated areas of the two peaks
for the benzylic carbons was 1.21:1, which shows that the
18O enrichment of the bridging ester oxygen was 45%.
The reaction of the mixture of 1-OC(O)C6F5 (55%) and
1-18OC(O)C6F5 (45%) in 50/50 (v/v) TFE/H2O (TFE )
trifluoroethanol) (80 mol % water) at 25 °C (I ) 0.50,
NaClO4) was monitored by quantitative 13C NMR spectros-
copy.9 A low substrate concentration (0.3 mM) was used
because of its low solubility in this predominantly aqueous
solvent.10 This solvent allows for an examination of the
reactions of the carbocation-anion ion pair intermediate
under conditions where it is particularly unstable and
undergoes very fast diffusional separation to give the free
ions.2b
Scheme 1
Table 1 gives the decreases with time in the normalized
areas, Anor, of the 13C NMR signals due to the benzylic carbon
the 1-(4-methylphenyl)ethyl carbocation 1+ in unimolecular
and bimolecular reactions.
1-(4-Methylphenyl)ethyl pentafluorobenzoate labeled with
carbon-13 at the benzylic carbon and oxygen-18 at the
bridging benzoate oxygen was prepared by the following
sequence of reactions: (1) Reaction of 4-MeC6H4MgBr with
Table 1. Normalized Areas of the 13C NMR Signals Due to
the Benzylic Carbon during Reaction of an Isotopic Mixture of
1-OC(O)C6F5 and 1-18OC(O)C6F5 in 50/50 (v/v)
13CO2 to give 4-MeC6H413CO2H;4 addition of MeLi by
Trifluoroethanol/Water at 25 °C (I ) 0.50, NaClO4)
13
adaptation of a published procedure to give 4-MeC6H4
-
Anor
COMe;5,6 reduction with sodium borohydride to give
4-MeC6H413CH(Me)OH. (2) Perchloric acid-catalyzed ex-
change of the hydroxyl group of the alcohol in H218O to give
a mixture of 4-MeC6H413CH(Me)18OH and 4-MeC6H413CH-
(Me)OH.7 (3) Esterification of this isotopic mixture of
alcohols with pentafluorobenzoyl chloride.8
1-OC(O)C6F 5 1-OC(18O)C6F 5 1-18OC(O)C6F 5
a
time (s) (Anor
)
T
75.520 ppm
75.514 ppm
75.481 ppm
0
1.00
0.55b
0.23c,d
0.088c,d
0.45b
0.17f
0.055f
81 000 0.42
172 800 0.16
0.026c,e
0.010c,e
The 13C NMR spectrum of the final ester product showed
peaks at 75.520 and 75.481 ppm due to the carbon-13-
enriched benzylic carbons of 1-OC(O)C6F5 and 1-18OC(O)-
C6F5, respectively.9 The 18O perturbation of the chemical
shift of the benzylic carbon, 0.039 ppm upfield, is similar
to that observed in earlier work for related sulfonate
a Normalized sum of the 13C NMR peak areas due to the benzylic carbon
of all isotopic forms of the ester, calculated as (Anor
)
) e-kt, where k )
T
ksolv ) 1.06 × 10-5 s-1 for solvolysis of the unlabeled ester determined by
HPLC analysis. b Calculated from the overall 45% 18O enrichment of the
starting ester (16O:18O ) 1.21:1) determined by 13C NMR (see text). c The
13C NMR signals for the benzylic carbons of 1-OC(O)C6F5 and
1-OC(18O)C6F5, both of which contain 16O at the bridging position, are
partly resolved (see text). d Calculated from (Anor
) ) 0.55 at zero time
o
using the relationship Anor ) (Anor)oe-kt, where k ) ksolv ) 1.06 × 10-5 s-1
for solvolysis of the unlabeled ester determined by HPLC analysis.
(4) 4-Methylphenylmagnesium bromide was prepared by reaction of 2.5
g of magnesium with 17 g (99 mmol) of 4-bromotoluene in 200 mL of
ether. This solution was stirred overnight at room temperature in the presence
of 1 L of 13CO2 (99% enrichment, Aldrich). The reaction was quenched
with 10% HCl (200 mL), the product was extracted into ether, and the
ethereal layer was washed with saturated brine. The acid was extracted
into 10% NaOH which was then carefully neutralized with concentrated
HCl. The product was collected by filtration, dried in vacuo, and used
without further purification (58% yield).
e Calculated as the difference between (Anor
)
T and the sum of the values of
A
nor for the other two isotopic forms of the ester. f Calculated from (Anor
)
T
and the experimental ratio of the integrated areas of the combined signals
due to the two esters containing 16O at the bridging position and the signal
due to the ester containing 18O at the bridging position.
(5) Rubottom, G. M.; Kim, C.-W. J. Org. Chem. 1983, 48, 1550-1552.
(6) 4-MeC6H413CO2H (7.9 g, 58 mmol) was dissolved in 400 mL of dry
tetrahydrofuran at 0 °C, and 200 mL of a 1.4 M solution (0.28 mol) of
methyllithium in pentane (Kantoh) was added. The mixture was stirred at
0 °C for 2 h. The reaction was quenched by the addition of trimethyl-
chlorosilane (116 g, 1.1 mol), and stirring was continued for 2 h. Then
10% HCl (200 mL) was added, and the product was extracted into ether
and purified by chromatography on silica gel to give 4-MeC6H413COMe
(64% yield).
of the starting esters 1-OC(O)C6F5 (75.520 ppm) and
1-18OC(O)C6F5 (75.481 ppm) and the 18O-scrambeled isomer-
ization product 1-OC(18O)C6F5 (75.514 ppm) (Scheme 1).
The latter signal is partly resolved from the signal for 1-OC-
(O)C6F5. The solvolysis of unlabeled 1-OC(O)C6F5 under
the same reaction conditions has been shown to proceed by
a stepwise mechanism through the 1-(4-methyphenyl)ethyl
(7) 4-MeC6H413CH(Me)OH (1 g) was suspended in 1 g of H218O (98%
enrichment, Shoko Ltd.), and 0.10 mL aqueous 1 M HClO4 was added.
The mixture was stirred at room temperature for 1 week. The alcohol was
extracted into ether, and the ethereal solution was washed with saturated
brine, dried over MgSO4, and evaporated to give the oxygen-18 enriched
alcohol which was esterified without further purification.
(9) Proton-decoupled 13C NMR spectra were recorded on a JNM-A500
FT NMR spectrometer operating at 126 MHz. Spectra used to determine
the oxygen-18 enrichment at the bridging and nonbridging positions of the
ester were acquired using a sweep width of 250 Hz, 8192 data points (0.03
Hz/pt), and an 8 s relaxation delay.
(10) The ester substrate (20 mg) was dissolved in 1 mL of acetonitrile,
and this solution was added to 200 mL of 50/50 (v/v) TFE/H2O (I ) 0.50,
NaClO4) to give a final substrate concentration of 0.3 mM. At specified
reaction times of 22.5 or 48 h, the remaining substrate and reaction products
were extracted into 400 mL of ether, the ethereal extract was washed with
water, dried over MgSO4, and evaporated. The resulting residue was
dissolved in CDCl3 and analyzed by 13C NMR.
(8) Oxygen-18 enriched 4-MeC6H413CH(Me)OH (0.34 g, 2.5 mmol) was
reacted with 1.7 molar equiv of pentafluorobenzoyl chloride with stirring
at 0 °C for 0.5 h followed by 1 h at room temperature. The reaction was
quenched with ice-cold NaHCO3 (30 mL). Recrystallization from ether/
hexane gave the ester (52% yield): mp 62-63 °C (lit. mp 63-64 °C).2a
The carbon-13 enrichment of the ester (99%) was determined by comparison
of the integrated 1H NMR (500 MHz) peak areas of the quartets due to the
methine protons attached to carbon-12 and to carbon-13 (JCH ) 150 Hz).
1238
Org. Lett., Vol. 3, No. 8, 2001

carbocation intermediate 1+ which has a significant lifetime
in 50/50 (v/v) TFE/H2O and undergoes solvent addition with
ks ) 6 × 109 s-1.2 Any isomerization of this substrate by
intramolecular 18O-scrambling should also proceed through
this moderately stabilized carbocation, because there is no
significant driving force for a concerted reaction that avoids
its formation.11
The data in Table 1 are governed by two first-order rate
constants. (1) Values of (Anor)T, which is the normalized sum
of the 13C NMR peak areas due to the benzylic carbon of all
isotopic forms of the ester, were calculated from ksolv ) 1.06
× 10-5 s-1 for solvolyses of both the 16O- and 18O-labeled
forms of substrate that were determined by following the
disappearance of the unlabeled substrate under the same
(S)C6F5, kr ) k-r ) 1011 s-1, is significantly faster than
nucleophilic addition of solvent to and diffusional separation
of the ion pair, kr > (ks′ + k-d) ) 2.2 × 1010 s-1.3 Therefore,
the observation that the isomerization of 1-18OC(O)C6F5 is
slower than its solvolysis requires that reaction of the ion
pair to form 1-OSolv be faster than unimolecular collapse
of the ion pair, (ks′ + k-d) > k-1′ (Scheme 1). This shows
that isomerization of 1-18OC(O)C6F5 to give 1-OC(18O)-
C6F5 takes place by reorganization of the first-formed ion
pair intermediate (kr) followed by rate-limiting ion pair
collapse (k-1′).
Equations 1-3 give the relationships between the experi-
mental rate constants ksolv and kiso and the microscopic rate
constants for the individual steps in Scheme 1. These rate
reaction conditions by HPLC. (2) A larger value of kobsd
)
laws were derived by making the assumptions that k-1 )
(ksolv + kiso) ) 1.22 × 10-5 s-1 for the disappearance of
1-18OC(O)C6F5 to give both the solvolysis products 1-OSolv
and the isomerization product 1-OC(18O)C6F5. This rate
constant was determined from the changes in Anor for 1-18OC-
(O)C6F5 with time. The difference in these rate constants,
(kobsd - ksolv), gives kiso ) 1.6 × 10-6 s-1, the rate constant
for isomerization of 1-18OC(O)C6F5 to give 1-OC(18O)-
C6F5.12
k-l′ for unimolecular collapse of the two equivalent ion pairs
and that the degenerate reorganization of the ion pair that
exchanges the two equivalent benzoate oxygens (kr ) k-r)
is much faster than the other reactions of the ion pair, so
that kr . (ks′ + k-d), k-1′. Under these conditions both the
steady-state concentrations and the rates of internal return
of the two ion pairs to give the neutral esters will be equal.
The fraction of 1-18OC(O)C6F5 that undergoes isomer-
ization to give 1-OC(18O)C6F5, kiso/kobsd ) 0.13, is much
smaller than the observed 73% isomerization of the corre-
sponding thionobenzoate ester 1-OC(S)C6F5 to give the
thiolbenzoate ester 1-SC(O)C6F5 under the same reaction
conditions.3 This reflects the greater nucleophilic reactivity
of sulfur at an ion pair containing the thiobenzoate anion
than of oxygen at an ion pair containing the pentafluoro-
benzoate anion.13
Scheme 1 shows a minimal mechanism for the observed
solvolysis and isomerization reactions of 1-18OC(O)C6F5 in
50/50 (v/v) TFE/H2O. Values of ks′ ) 6 × 109 s-1 for the
direct nucleophilic addition of solvent to, and k-d ) 1.6 ×
1010 s-1 for the irreversible diffusional separation of, 1-(4-
methylphenyl)ethyl carbocation-anion ion pairs have been
reported in earlier work.2b Both of these reactions result,
eventually, in formation of the solvent adducts 1-OSolv
(Scheme 1). We have shown in previous work that reorga-
nization of the ion pair intermediate of the reaction of 1-OC-
k1(ks′ + k-d)
ks′ + k-d + k-1
ksolv
)
(1)
k1k-1′
kiso
)
(2)
(3)
(4)
2(ks′ + k-d + k-1)
kiso
k-1′
)
ksolv
2(ks′ + k-d)
enck-1′
k-d + k-1′
k
kNu
)
A value of k-1′ ) 7 × 109 s-1 for unimolecular ion pair
collapse can be calculated from the ratio of experimental
rate constants kiso/ksolv ) 0.15 using eq 3 with ks′ ) 6 × 109
s-1 and k-d ) 1.6 × 1010 s-1.2b The magnitude of this rate
constant for internal ion pair return provides the vital
“missing link” in the analyses of the reactions of ion pairs
1+‚-O2CR reported in earlier work.2b
The value of k-1′ ) 7 × 109 s-1 for unimolecular ion pair
collapse of 1+‚-O2CC6F5 is substantially larger than the pKa-
independent values of kNu ) 5 × 108 M-1 s-1 for bimolecular
addition of a series of alkyl carboxylate anions to 1+ in 50/
50 (v/v) TFE/H2O (Scheme 2 and eq 4).2b The difference in
(11) Jencks, W. P. Acc. Chem. Res. 1980, 13, 161-169. Jencks, W. P.
Chem. Soc. ReV. 1981, 10, 345-375. Dewar, M. J. S. J. Am. Chem. Soc.
1984, 106, 209-219.
(12) (a) Our analysis makes the assumption that formation of the
rearranged ester 1-OC(18O)C6F5 represents the irreversible formation of a
reaction product. This is reasonable because the very small replenishment
of 1-18OC(O)C6F5 by a second 18O-scrambling of the small amount of
1-OC(18O)C6F5 that is formed will not lead to a significant deviation from
first-order kinetics or to a significant decrease in the rate constant for the
disappearance of 1-18OC(O)C6F5. For example, after 1 halftime, less than
(0.5)(0.13)(0.13)/0.5 ) 1.7% of the remaining 1-18OC(O)C6F5 can be
attributed to the occurrence of consecutive 18O-scrambling. (b) Competing
solvolysis and oxygen-18 equilibration was observed in an earlier study of
the reactions of oxygen-18 labeled 1-(4-methoxyphenyl)ethyl and 1-phe-
nylethyl 4-nitrobenzoates in 70% and 90% aqueous acetone.1f These data
provide a qualitative description of the partitioning of the ion pair
intermediates of these reactions but not the absolute rate constant for ion
pair return reported here.
Scheme 2
(13) The reaction of thiobenzoate anion with the 1-(4-thiomethylphenyl)-
ethyl carbocation in 50/50 (v/v) TFE/H2O to form the thiol ester is diffusion-
limited3 and is ca. 80-fold faster than addition of the more basic acetate
ion to the same carbocation.2b
Org. Lett., Vol. 3, No. 8, 2001
1239

this observed second-order rate constant for reaction of
carboxylate anions in bulk solvent and the first-order rate
constant for collapse of the carbocation-carboxylate anion
ion pair provides direct evidence that the reactivity of free
carboxylate anions is “suppressed” by aqueous solvation. A
value of kenc ) 1.5 × 109 M-1 s-1 for formation of an ion
pair encounter complex between carboxylate anions and the
carbocation 1+ can be calculated using eq 4 derived for
Scheme 2, with k-1′ ) 7 × 109 s-1 determined here and k-d
) 1.6 × 1010 s-1.2b This is significantly smaller than the
values of kaz ) (5-7) × 109 M-1 s-1 determined for the
diffusion-limited reactions of azide ion with unstable car-
bocations.14 It is consistent with the earlier conclusion that
the formation of encounter complexes between 1+ and
carboxylate anions is slower than a simple diffusional
encounter as a result of a requirement for desolvation of the
carboxylate anion.2b
Acknowledgment. We acknowledge the National Insti-
tutes of Health (Grant GM 39754) for its generous support
of this work.
OL015706S
(14) McClelland, R. A.; Kanagasabapathy, V. M.; Banait, N. S.; Steenken,
S. J. Am. Chem. Soc. 1991, 113, 1009-1014.
1240
Org. Lett., Vol. 3, No. 8, 2001