Formation and stability of the 4-methoxyphenonium ion in aqueous solution

Article abstract of DOI:10.1021/jo202118s

The reaction of 2-methoxyphenylethyl tosylate (MeO-1-Ts) is first-order in [N₃^-]. A carbon-13 NMR analysis of the products of the reactions of MeO-1-[α-¹³C]Ts shows the formation of MeO-1-[β-¹³C]OH and MeO-1-[β-¹³C]N₃ from the trapping of a symmetrical 4-methoxyphenonium ion reaction intermediate 2⁺. An analysis of the rate and product data provides a value of k_az/k_s = 83 M^{- 1} for partitioning of 2 ⁺ between addition of azide ion and solvent. These data set a limit for the lifetime of 2⁺ in aqueous solution.

Full text of DOI:10.1021/jo202118s

Brief Communication
pubs.acs.org/joc
Formation and Stability of the 4-Methoxyphenonium Ion in Aqueous
Solution
Yutaka Tsuji,† Daisuke Hara,† Rui Hagimoto,† and John P. Richard*,‡
†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, United States
S
* Supporting Information
ABSTRACT: The reaction of 2-methoxyphenylethyl tosylate
−
(MeO-1-Ts) is first-order in [N3 ]. A carbon-13 NMR
analysis of the products of the reactions of MeO-1-
[α-13C]Ts shows the formation of MeO-1-[β-13C]OH and
MeO-1-[β-13C]N3 from the trapping of a symmetrical 4-
methoxyphenonium ion reaction intermediate 2+. An analysis
of the rate and product data provides a value of kaz/ks = 83
M−1 for partitioning of 2+ between addition of azide ion and
solvent. These data set a limit for the lifetime of 2+ in aqueous
solution.
he barriers for addition of the solvent water to many
increases in kAcOH. For example, acetolysis of MeO-1-Ts at 115
°C is 34 times faster than acetolysis of the parent 2-phenylethyl
tosylate H-1-Ts.11 This elegant study shows that acetolysis of
MeO-1-Ts proceeds with intramolecular displacement of the
tosylate ion leaving group to form the bridging 4-methox-
yphenonium ion (2+, Scheme 2). The symmetrical cation 2+
1
Tsimple carbocations are known. There is good evidence
that secondary alkyl carbocations are too unstable to exist in
water for the time of a bond vibration2,3 and that solvent
reorganization with a rate constant kr ≈ 1011 s−1 is the rate rate-
limiting step for addition of water to simple tertiary
carbocations (ks ≈ 3 × 1012 s−1, Scheme 1).4 Electron-donating
Scheme 1
Scheme 2
has also been observed by proton NMR in strongly acidic
solution.12
α-substituents such as methoxy5 and 4-methoxyphenyl6,7
(Scheme 1) are required to give carbocations with lifetimes
long enough to permit diffusion-controlled bimolecular
trapping by added nucleophiles. This leaves bridging
phenonium ions, which were at one time the subject of intense
interest in studies to characterize internal [anchimeric]
nucleophilic assistance to solvolysis.8 The chemical community
continues to study the generation and reaction of these
electrophiles;9,10 however, there has been no work to determine
their lifetimes in aqueous solution.
We prepared MeO-1-[α-13C]Ts and determined a value of
k
solv = 1.95 × 10−6 s−1 for solvolysis in 50/50 (v/v) TFE/H2O
(I = 0.5, NaClO4) at 25 °C. A value of (kNu)obs = 3.6 (±0.1) ×
10−6 M−1 s−1 under the same conditions was determined as the
−
slope of a linear plot (not shown) of kobs against [N3 ]. Table 1
reports (1) the yields of the products of reactions of azide ion
and solvent with MeO-1-[α-13C]Ts in 50/50 (v/v) TFE/H2O
(I = 0.5, NaClO4) and at 25 °C that were determined by HPLC
analyses and (2) the relative yields of MeO-1-OH and MeO-1-
N3 labeled with carbon-13 in the α- and β-positions (Scheme
The first-order rate constant kAcOH for acetolysis of ring-
substituted 2-phenylethyl tosylates (X-1-Ts) is insensitive to
changes in electron-withdrawing substituents −X at the
aromatic ring (Hammett substituent constant ρX ≥ −0.19),
Received: October 14, 2011
Published: October 27, 2011
but electron-donating substituents (ρ + < −0.19) cause large
X
© 2011 American Chemical Society
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The Journal of Organic Chemistry
Brief Communication
Table 1. Yields of the Products of the Reaction of MeO-1-[α-13C]Ts in 50/50 (v/v) TFE/H2O (I = 0.5, NaClO4) and at 25 °C in
the Absence and Presence of Azide Anion
a
T
b
c
T
d
e
e
[N3−]/M
(fROSol
)
([α-13C])/([β-13C])
(f RN3
)
([α-13C] )/([β-13C])
MeO-1-[α-13C]N3
MeO-1-[β-13C]N3
0
1.00
0.53
0.27
0.99
1.01
1.05
1.19
1.40
1.61
0.00
0.01
0.03
0.10
0.20
0.30
0.47 (0.47)
0.73 (0.73)
0.91 (0.91)
0.95 (0.955)
0.97 (0.97)
1.06
1.12
1.42
1.86
2.33
0.24
0.39
0.53
0.62
0.68
0.23
0.34
0.38
0.33
0.29
0.094
0.046
0.030
a
The total yield of MeO-1-OH and MeO-1-OTFE. An average product ratio [MeO-1-OH]/[MeO-1-OTFE] = 16.9 ± 0.3 was determined for the
b
reactions at [N3 ] = 0.0, 0.01, and 0.03 M. The ratio of the yields of MeO-1-[α-13C]OH and MeO-1-[β-13C]OH determined by carbon 13
−
c
analyses. The fractional yield of MeO-1-N3. The values in parentheses are the theoretical yields calculated using eq 3 and the partition rate constant
d
ratios determined from the fit of the data in Figure 1 to eq 3 (see text). The ratio of the yields of MeO-1-[α-13C]N3 and MeO-1-[β-13C]N3
e
determined by carbon-13 NMR analyses. The fractional yield of products calculated from (f RN3)T and the ratio of [α-13C] and [β-13C] labeled
MeO-1-N3.
Scheme 3
3), which were determined by carbon-13 NMR analyses. There
was only a low yield of the trifluoroethyl ether MeO-1-OTFE
(Table 1, footnote a).
The total yield of MeO-1-N3 is very much greater than
expected if these products were formed exclusively by a
bimolecular nucleophilic displacement reaction with (kNu)obs
/
ksolv = 1.9 M−1. For example, only a 2% yield of MeO-1-N3 is
predicted for the bimolecular substitution reaction of 0.01 M
azide ion, but the observed yield is 47% (Table 1). The
additional MeO-1-N3 forms by trapping of 2+ (kaz, Scheme 3).
Similar yields of MeO-1-[α-13C]N3 and MeO-1-[β-13C]N3
from trapping of 2+ are observed for the reaction of MeO-1-
[α-13C]Ts in the presence of 0.01 M NaN3 (Table 1). The
increase in the excess of the α- compared to the β-labeled
−
product for reactions at the higher [N3 ] is due to bimolecular
−
Figure 1. Effect of increasing [N3 ] on the observed rate constant
substitution of N3 at MeO-1-[α-13C]Ts. Essentially identical
−
ratio (kaz/ks)obs calculated from the yields of the products of
nucleophilic addition of azide anion and solvent to MeO-[α-13C]-1-
Ts (eq 1) in 50/50 (v/v) TFE/H2O (I = 0.5, NaClO4) and at 25 °C.
yields of the α- and β- carbon-13 labeled alcohol form as
products of solvolysis of MeO-1-[α-13C]Ts ([N3 ] = 0 M), but
−
an excess of the α-carbon-13 alcohol is observed for reactions at
high [N3 ]. This is consistent with azide ion catalysis of
(Table 1). A linear increase in (kaz/ks)obs (M−1) with increasing
[N3 ] was observed in a previous study of the reactions of 4-
methoxybenzyl derivatives, which proceed by competing azide
ion bimolecular substitution and trapping of the 4-methox-
ybenzyl carbocation intermediate.6 By comparison, the down-
ward break in the correlation shown in Figure 1 is consistent
with the formation of additional MeO-1-[α-13C]OSolv from
−
−
addition of water (kB, Scheme 3) to either the sulfonyl group or
to the [α-13C]-carbon of MeO-1-[α-13C]Ts.
−
Figure 1 shows the effect of increasing [N3 ] on the azide ion
selectivity (kaz/ks)obs (eq 1) for the reaction of MeO-1-
[α-13C]Ts, where fRN3 and f ROSolv are the fractional yields of
MeO-1-N3 and (MeO-1-OH + MeO-1-OTFE), respectively
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The Journal of Organic Chemistry
Brief Communication
azide anion catalysis of the direct addition of water to substrate
[kB (M−1 s−1), Scheme 3]. The solid line shows the theoretical
fit of data from Figure 1 to eq 2 derived for Scheme 3 (the
the transition state for nucleophile addition, that results in a
weakening in the bonding to the reacting nucleophile.20
A
similar shift in transition state structure has been proposed to
rationalize the smaller selectivity of methyl perchlorate
compared to methyl iodide toward reaction with nucleophilic
anions.19
derivation is given as Supporting Information) using [(kNu
kB)/ksolv] = (3.64 × 10−6 M−1 s−1)/(1.95 × 10−6 s−1) = 1.9 M−1
determined above and values of kaz/ks = 83 M−1 and kB/kNu
+
=
0.016 for the variable parameters obtained from the nonlinear
least-squares fit of these data. There is good agreement between
EXPERIMENTAL SECTION
■
the total observed yields of MeO-1-N3 (f RN3
)
and the
T
Potassium [13C]-cyanide (99% enriched) was purchased from a
commercial supplier. All other organic and inorganic chemicals were
reagent grade from commercial sources and were used without further
purification. 2-(4-Methoxyphenyl)[1-13C]ethanol [MeO-1-
[α-13C]OH] was synthesized according to a published procedure.21
Carbon-13 NMR Analyses. Proton-decoupled 13C NMR spectra
were recorded at 100.4 MHz. Chemical shifts were measured in ppm,
relative to a value of δ = 77.0 ppm for CDCl3. A pulse angle of 45° was
employed to obtain spectra centered at 55.0 ppm, which spanned
7042.25 Hz and contained 65000K data points (0.107 Hz/pt). Several
delay times between FT pulses, ranging from 8 to 70 s, were examined.
Identical ratios of the peak areas for carbon-1 and carbon-2 of 2-(4-
methoxyphenyl)ethyl derivatives were observed at 35 and 70 s delay
times, and the longer relaxation time of 70 s was used for these spectra.
Generally >1000 FT transients were averaged before the final spectra
were determined.
theoretical yields calculated from eq 3 using the above three
rate constant ratios.
(1)
Kinetic and Product Studies. The progress of the reactions of
MeO-1-[α-13C]Ts in 50/50 (v/v) TFE/H2O (I = 0.5, NaClO4) and at
−
25 °C in the absence or in the presence of N3 was monitored by
HPLC analyses as described in previous work.6,18 The reactions were
initiated by making a 100-fold dilution of 2-(4-methoxyphenyl)ethyl
tosylate dissolved in acetonitrile into 20 mL of 50/50 (v/v) TFE/H2O
(I = 0.5 (NaClO4). The final substrate concentration was 2 mM for
reactions in the presence of 0, 0.1, 0.2, and 0.3 M azide anion and 0.3
mM for reactions in the presence of 0.01 and 0.03 M azide anion. At
specified times, aliquots of 100 μL were applied directly onto an
HPLC column for analysis. The reactant and products were separated
by gradient elution using a mixed MeOH/H2O solvent.22 The peaks
for the substrate and product were monitored at 276 nm, which is λmax
for 2-(4-methoxyphenyl)ethyl alcohol and 2-(4-methoxyphenyl)ethyl
azide. A value of εROTs/εR‑Nu = 1.17 for the ratio of extinction
coefficients of MeO-1-Ts and MeO-1-OH at 276 nm was determined
by comparing the HPLC peak areas at 276 nm of known
concentrations of MeO-1-Ts and MeO-1-OH. The sum of the peak
areas from HPLC analyses at 276 nm for MeO-1-OH and MeO-1-N3
The azide ion selectivity of kaz/ks = 83 M−1 requires that the
lifetime of 2+ in water is sufficiently long to allow for its
diffusion through the nucleophilic solvent and selection for
reaction with strongly nucleophilic azide anion.13,14 The upper
limit for kaz is kd ≈ 5 × 109 M−1 s−1 for a diffusion-controlled
reaction of 2+.15 Combining this and kaz/ks = 83 M−1 gives an
upper limit of ks ≤ 6 × 107 s−1 for addition of solvent. We
expect that ks for addition of solvent to 2+ is smaller than 2 ×
108 s−1 observed for the 4-methoxybenzyl carbocation because
ks = 3.4 × 10−3 s−1 for addition of solvent to the neutral
spiro[2,5]octa-1,4-diene-3-one16 is 1000-fold smaller than ks =
3.3 s−1 for addition of solvent to the unsubsituted p-quinone
methide 4,17 while O-methylation of 4 causes a 108-fold
increase in electrophile reactivity.18 We suggest that the rate
constants for addition of nucleophiles to 2+ lie closer to ks = 105
s−1 and kaz = 107 M−1 s−1 for the addition of azide ion and
solvent, that are estimated from kaz/ks = 83 M−1, and assuming
that O-methylation causes similar ∼108-fold increases in ks for
addition of solvent to 3 and 4.
−
remained constant as [N3 ] was increased from 0.00 [100% yield of
MeO-1-OSolv] to 0.30 M [97% yield of MeO-1-N3]. This shows that
these products have the same extinction coefficient at λmax = 276 nm.
The decrease in the HPLC peak area (AROTs) for the reactant MeO-
1-Ts was monitored for ca. 2-reaction halftimes, and first-order
reaction rate constants were determined as the slopes of semi-
logarithmic plots of reaction progress f S (eq 1) against time, where
ΣARNu is the sum of the peak areas for the products MeO-1-OH
(AROH) MeO-1-OCH2CF3 (AROTFE), and MeO-1-N3 (ARN3). The
ratio of the yields of the products of the reactions of MeO-1-Ts in 50/
50 (v/v) TFE/H2O at I = 0.5 (NaClO4) was determined directly from
the ratio of the HPLC peak areas for the products using eq 5 because
MeO-1-OSolv and MeO-1-N3 have the same extinction coefficient at
λmax = 276 nm (see above).
The value of log(kaz/ks) = 1.9 for the reaction of 2+ is smaller
than the Swain−Scott nucleophilicity parameter of n = 3.9
determined for the reaction of azide anion with methyl
bromide.19 This decrease in selectivity for nucleophile addition
to the more reactive electrophile might reflect the different
diffusion-limited (kd = kaz = 5 × 109 M−1 s−1) and activation-
limited rate constants for addition of azide ion and solvent to
2+, if ks = 6 × 107 s−1 for addition of solvent to 2+. However, we
suggest that this decrease in selectivity with increasing
electrophile reactivity is due to a change in the structure of
(4)
(5)
At ca. 2 half-times for the reaction of MeO-1-[α-13C]Ts the
remaining substrate and the products were extracted into either ether
or toluene. The organic layer was washed with water, dried over
MgSO4, and then removed using a rotary evaporator. The resulting
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The Journal of Organic Chemistry
Brief Communication
sample was dissolved in 0.6 mL of CDCl3 for 13C NMR analysis. The
relative yields of products labeled with carbon-13 in the α- and β-
position were determined by integration of the following product
peaks: MeO-1-[α-13C]OH at 63.83 ppm; MeO-1-[β-13C]OH at 38.24
ppm; MeO-1-[α-13C]OCH2CF3 at 73.87 ppm; MeO-1-[β-13C]-
OCH2CF3 at 35.23 ppm; MeO-1-[α-13C]N3 at 52.69 ppm; MeO-1-
[β-13C]N3 at 34.19 ppm.
ASSOCIATED CONTENT
* Supporting Information
■
S
Derivation of the relationship between the observed product
selectivity (kaz/ks)obs and the rate constants from Scheme 3.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: jrichard@buffalo.edu.
■
ACKNOWLEDGMENTS
We acknowledge the National Institutes of Health (Grant No.
GM39754) for generous support of this work.
■
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