The hydrolysis of 4-acyloxy-4-substituted-2,5-cyclohexadienones: Limitations of aryloxenium ion chemistry

Article abstract of DOI:10.1021/ja050899q

The title compounds serve as potential precursors to aryloxenium ions, often proposed, but primarily uncharacterized intermediates in phenol oxidations. The uncatalyzed and acid-catalyzed decomposition of 4-acetoxy-4-phenyl-2,5-cyclohexadienone, 2a, generates the quinol, 3a. ¹⁸O-Labeling studies performed in ¹⁶O-H₂O, and monitored by LC/MS and1 ¹³C NMR spectroscopy that can detect ¹⁸O-induced chemical shifts on ¹³C resonances, show that 3a was generated in both the uncatalyzed and acid-catalyzed reactions by C _alkyl-O bond cleavage consistent with formation of an aryloxenium ion. Trapping with N₃- and Br^- confirms that both uncatalyzed and acid-catalyzed decompositions occur by rate-limiting ionization to form the 4-biphenylyloxenium ion, 1a. This ion has a shorter lifetime in H₂O than the corresponding nitrenium ion, 7a (12 ns for 1a, 300 ns for 7a at 30 °C). Similar analyses of the product, 3b, of acid- and base-catalyzed decomposition of 4-acetoxy-4-methyl-2,5-cyclohexadienone, 2b, in ¹⁸O-H₂O show that these reactions are ester hydrolyses that proceed by C_acyl-O bond cleavage processes not involving the p-tolyloxenium ion, 1b. Uncatalyzed decomposition of the more reactive 4-dichloroacetoxy-4-methyl-2,5-cyclohexadienone, 2b′, is also an ester hydrolysis, but 2b′ undergoes a kinetically second-order reaction with N₃^- that generates an oxenium ion-like substitution product by an apparent S_N2′ mechanism. Estimates based on the lifetimes of 1a, 7a, and the p-tolylnitrenium ion, 7b, and the calculated relative stabilities of these ions toward hydration indicate that the aqueous solution lifetime of 1b is ca. 3-5 ps. Simple 4-alkyl substituted aryloxenium ions are apparently not stable enough in aqueous solution to be competitively trapped by nonsolvent nucleophiles.

Full text of DOI:10.1021/ja050899q

Published on Web 05/11/2005
The Hydrolysis of
4-Acyloxy-4-substituted-2,5-cyclohexadienones: Limitations
of Aryloxenium Ion Chemistry
Michael Novak*,† and Stephen A. Glover§
Contribution from the Department of Chemistry and Biochemistry, Miami UniVersity,
Oxford, Ohio 45056, and School of Biological, Biomedical, and Molecular Sciences,
DiVision of Chemistry, UniVersity of New England, Armidale 2351, New South Wales, Australia
Received February 11, 2005; E-mail: novakm@muohio.edu
Abstract: The title compounds serve as potential precursors to aryloxenium ions, often proposed, but
primarily uncharacterized intermediates in phenol oxidations. The uncatalyzed and acid-catalyzed
decomposition of 4-acetoxy-4-phenyl-2,5-cyclohexadienone, 2a, generates the quinol, 3a. 18O-Labeling
studies performed in 18O-H2O, and monitored by LC/MS and 13C NMR spectroscopy that can detect 18O-
induced chemical shifts on 13C resonances, show that 3a was generated in both the uncatalyzed and acid-
catalyzed reactions by Calkyl-O bond cleavage consistent with formation of an aryloxenium ion. Trapping
with N3- and Br- confirms that both uncatalyzed and acid-catalyzed decompositions occur by rate-limiting
ionization to form the 4-biphenylyloxenium ion, 1a. This ion has a shorter lifetime in H2O than the
corresponding nitrenium ion, 7a (12 ns for 1a, 300 ns for 7a at 30 °C). Similar analyses of the product, 3b,
of acid- and base-catalyzed decomposition of 4-acetoxy-4-methyl-2,5-cyclohexadienone, 2b, in 18O-H2O
show that these reactions are ester hydrolyses that proceed by Cacyl-O bond cleavage processes not
involving the p-tolyloxenium ion, 1b. Uncatalyzed decomposition of the more reactive 4-dichloroacetoxy-
4-methyl-2,5-cyclohexadienone, 2b′, is also an ester hydrolysis, but 2b′ undergoes a kinetically second-
-
order reaction with N3 that generates an oxenium ion-like substitution product by an apparent SN2′
mechanism. Estimates based on the lifetimes of 1a, 7a, and the p-tolylnitrenium ion, 7b, and the calculated
relative stabilities of these ions toward hydration indicate that the aqueous solution lifetime of 1b is ca.
3-5 ps. Simple 4-alkyl substituted aryloxenium ions are apparently not stable enough in aqueous solution
to be competitively trapped by nonsolvent nucleophiles.
Introduction
substituted examples, such as 1a and 1b, from literature data.
Some examples of stable, highly delocalized 1, such as 1c and
1d, have been observed or isolated,4 but these stable species
provide little insight into the reactions of transient members of
this class of ions. The mechanistic studies of transient ions that
do exist are not consistent with each other.8-13 There are
discrepancies in the literature concerning the regiochemistry of
reaction of purported examples of 1 generated from different
sources and the possible involvement of triplet ions.2,8,10,12,13
Aryloxenium ions, 1, have often been proposed to explain
the products of the synthetically useful electrochemical and
chemical oxidations of phenols1-5 and the generation of com-
mercially useful polymers, such as poly(2,6-dimethyl-1,4-phenyl-
ene oxide).6,7 Despite this, surprisingly little is known of the
reactivity and selectivity of these species, or even whether they
have actually been generated in the cases in which they have
been invoked.1,3,5 For example, so little is known of substituent
effects in these ions that prior to our investigation it was not
possible to determine the relative stability of aryl- and alkyl-
† Miami University.
§ University of New England.
(1) (a) Swenton, J. S.; Carpenter, K.; Chen, Y.; Kerns, M. L.; Morrow, G. W.
J. Org. Chem. 1993, 58, 3308-3316. (b) Swenton, J. S.; Callinan, A.; Chen,
Y.; Rohde, J. L.; Kerns, M. L.; Morrow, G. L. J. Org. Chem. 1996, 61,
1267-1274.
(2) Rieker, A.; Beisswenger, R.; Regier, K. Tetrahedron 1991, 47, 645-654.
(3) Pelter, A.; Ward, R. S. Tetrahedron 2001, 57, 273-282.
(4) (a) Rieker, A.; Speiser, B.; Straub, H. Dechema-Monographien 1992, 125,
777-782. (b) Dimroth, K.; Umbach, W.; Thomas, H. Chem. Ber. 1967,
100, 132-141.
(5) Rodrigues, J. A. R.; Abramovitch, R. A.; de Sousa, J. D. F.; Leiva, G. C.
J. Org. Chem. 2004, 69, 2920-2928.
(6) (a) Baesjou, P. J.; Driessen, W. L.; Challa, G.; Reedjik, J. J. Am. Chem.
Soc. 1997, 119, 12590-12594. (b) Driessen, W. L.; Baesjou, P. J.; Bol, J.
E.; Kooijman, H.; Spek, A. L.; Reedjik, J. Inorg. Chim. Acta 2001, 324,
16-20.
(7) Kobayashi, S.; Higashimura, H. Prog. Polym. Sci. 2003, 28, 1015-1048.
9
8090
J. AM. CHEM. SOC. 2005, 127, 8090-8097
10.1021/ja050899q CCC: $30.25 © 2005 American Chemical Society

Hydrolysis of 4-Acyloxy-4-substituted-2,5-cyclohexadienones
A R T I C L E S
In our recent Communication, we showed that the uncatalyzed
decomposition of 2a in aqueous solution that predominates under
neutral to mildly acidic conditions does generate a short-lived
- 13
cation, identified as 1a, that can be trapped by N3
.
Acid-
catalyzed decomposition of 2a also occurs, but it was not known
if this reaction generates 1a by Calkyl-O cleavage or if it is an
acid-catalyzed ester hydrolysis that occurs with Cacyl-O bond
cleavage. Although it was clear that the uncatalyzed decomposi-
tion of 2b was much slower than that of 2a, it was not
determined whether 1b is formed from that uncatalyzed
decomposition because acid- and base-catalyzed reactions
dominated the aqueous solution chemistry of 2b. The more
reactive dichloroacetic acid ester 2b′ exhibits a predominant
uncatalyzed decomposition under mildly acidic conditions that
makes it possible to evaluate whether 1b is generated from
substrates of this type under any of the observed kinetic terms.
In this paper, we report the results of hydrolysis of 2a, 2b, and
2b′ in 18O-H2O and nucleophilic trapping experiments on 2a
and 2b′ that demonstrate how these compounds decompose
under acid- and base-catalyzed conditions, as well as under
uncatalyzed conditions. The results of ab initio (HF/6-31G*//
6-31G*) and DFT (pBP/DN*//HF/6-31G*) calculations that help
to rationalize the experimental results are also reported. These
results place some limits on the aqueous solution stability of
aryloxenium ions.
Figure 1. Log kobs versus pH for 2a, 2b, and 2b′. Data were fit to eq 1 by
least-squares procedures.
Results
Kinetics of decomposition of 2a and 2b′ at 30 °C and 2b at
80 °C were measured in 5 vol % CH3CN-H2O at µ ) 0.5
(NaClO4) in HClO4 solutions (pH < 3.0), or in HCO2H/
NaHCO2, AcOH/AcONa, and Na2HPO4/NaH2PO4 buffers by
monitoring changes in UV absorbance as a function of time.
All data fit a standard first-order rate equation well. Decomposi-
tion rate constants, kobs, were independent of buffer concentration
in the range 0.02-0.25 M, except for the common ion rate
depression previously reported for 2a,13 but were dependent on
pH. The value of kobs for 2a in acetate buffers was extrapolated
to zero buffer concentration. Figure 1 shows the pH dependence
of kobs for all three compounds. The rate data were fit to the
rate law of eq 1, although only one compound (2b) exhibited
all three terms of the rate law in the pH range examined (1.0-
8.0). Individual rate constants for all three compounds are
reported in Table 1.
Figure 2. Decomposition of 2b at pH 1.0 and 80 °C monitored by HPLC.
Data for 3b and 4b were fit to a consecutive first-order rate equation.
Table 1. Rate Constants for the Decomposition of 2a and 2b′ at
30 °C and 2b at 80 °C from Least-Squares Fits to Equation 1
1
1
1
ester
k
o (s-
)
k
H (M-1 s-
)
k )
OH (M-1 s-
2a
2b
2b′
(2.50 ( 0.05) × 10-5
(5.4 ( 0.5) × 10-7
(2.66 ( 0.08) × 10-5
(1.45 ( 0.08) × 10-3
(3.8 ( 0.2) × 10-3
104 ( 6
5790 ( 260
most important for 2b, it accounts for <80% of kobs. Previously,
-
we showed by common ion rate depression and N3 trapping
that the process governed by ko for 2a involves formation of
the cation 1a, but the mechanisms of the processes governed
by kH and kOH for all compounds, as well as ko for 2b or 2b′,
were not examined.13
kobs ) ko + kH[H+] + kOH[OH-]
(1)
HPLC examination of the reactions at pH 1.0, 4.6, and 7.0
showed that for all cases, in the absence of any nucleophile
other than H2O, the only products observed were the corre-
sponding quinols 3a or 3b. The HPLC data showed that 2a,b
and 2b′ disappeared and 3a,b were generated in a first-order
manner with rate constants equivalent, within experimental error,
to kobs measured by UV methods. In one case (2b at pH 1.0
and 80 °C), the HPLC data (Figure 2) showed slow subsequent
rearrangement of 3b into 4b that was identified by comparison
of the isolated compound to an authentic sample. The overall
process was governed by two rate constants (k1 and k2 of Figure
2). The larger rate constant, k1, was equivalent, within experi-
mental error, to kobs measured by UV methods for 2b at the
same pH. The smaller rate constant, k2, was equivalent to the
rate constant obtained for the rearrangement of authentic 3b at
the same pH. The dienone-phenol rearrangement of 3b into
The uncatalyzed term, ko, dominates over much of the pH
range examined for both 2a and 2b′, but it is only a minor
contributor to kobs for 2b. Even at the pH (4.8) at which ko is
(8) (a) Abramovitch, R. A.; Inbasekaran, M.; Kato, S. J. Am. Chem. Soc. 1973,
95, 5428-5430. (b) Abramovitch, R. A.; Alvernhe, G.; Inbasekaran, M.
N. Tetrahedron Lett. 1977, 1113-1116. (c) Abramovitch, R. A.; Inbaseka-
ran, M. N. J. Chem. Soc., Chem. Commun. 1978, 149-150. (d) Abramo-
vitch, R. A.; Alvernhe, G.; Bartnik, R.; Dassanayake, N. L.; Inbasekaran,
M. N.; Kato, S. J. Am. Chem. Soc. 1981, 103, 4558-4565.
(9) Li, Y.; Abramovitch, R. A.; Houk, K. N. J. Org. Chem. 1989, 54, 2911-
2914.
(10) (a) Endo, Y.; Shudo, K.; Okamoto, T. J. Am. Chem. Soc. 1977, 99, 7721-
7723. (b) Shudo, K.; Orihara, Y.; Ohta, T.; Okamoto, T. J. Am. Chem.
Soc. 1981, 103, 943-944. (c) Endo, Y.; Shudo, K.; Okamoto, T. J. Am.
Chem. Soc. 1982, 104, 6393-6397.
(11) Uto, K.; Miyazawa, E.; Ito, K.; Sakamoto, T.; Kikugawa, Y. Heterocycles
1998, 48, 2593-2600.
(12) Hegarty, A. F.; Keogh, J. P J. Chem. Soc., Perkin Trans. 2 2001, 758-
762.
(13) Novak, M.; Glover, S. A. J. Am. Chem. Soc. 2004, 126, 7748-7749.
9
J. AM. CHEM. SOC. VOL. 127, NO. 22, 2005 8091

A R T I C L E S
Scheme 1
Novak and Glover
Figure 3. Portions of the 13C NMR spectrum of 3a generated by
decomposition of 2a in 25 atom % 18O-H2O at pH 1.0. The upper region
contains the carbonyl-C resonance; the lower region contains the hydroxyl-C
resonance.
ionization conditions for 3a were found to be negative ion ESI,
so peaks at m/e 185 ((M - 1)-), 187 ((M + 1)-), and 189 ((M
+ 3)-) were analyzed. Results of triplicate injections for each
experiment are shown in Scheme 1. The control experiments
show that 18O is incorporated into the carbonyl-O of 3a at pH
1.0, but not at pH 7.5. The observed (187/185)% for 3a
incubated in unlabeled H2O at pH 7.5 is 1.10 ( 0.02, which is
equivalent, within experimental error, to (187/185)% observed
for 3a incubated in the 18O-H2O at pH 7.5.
4b in concentrated HClO4 solution (Ho < -2.2) has been
reported previously.14 At pH 1.0 and 30 °C, rearrangement of
3a and 3b was sufficiently slow that it was not noticeable during
the course of our experiments.
MS analysis of 3a obtained from the hydrolysis of 2a in 18O-
H2O shows that 18O has been incorporated into the hydroxyl-O
at pH 7.5, and into both hydroxyl-O and carbonyl-O at pH 1.0.
The latter conclusion is supported not only by the large value
of (187/185)% observed at pH 1.0 but also by the unusually
large value of (189/185)% measured at this pH. This value is
only (0.40 ( 0.04)% in the corresponding control experiment.
Both conclusions were confirmed by 13C NMR results from
hydrolysis of 2a in 25 atom % 18O-H2O. The product 3a was
extracted into CH2Cl2 after 10 half-lives of the reaction, and
13C NMR spectra were measured at 125.8 MHz in CD2Cl2. In
the pH 1.0 experiment, upfield satellites were observed for both
the carbonyl-C (42 ppb upfield, 37% of the integrated intensity
of the main peak at 185.510 ppm) and the hydroxyl-C (21 ppb
upfield, 34% of the integrated intensity of the main peak at
70.926 ppm) (Figure 3). In pH 7.5 phosphate buffer, an upfield
satellite was observed for the hydroxyl-C (21 ppb upfield, 35%
of the intensity of the main peak). A small peak, ca. 5% of the
intensity of the main peak, was observed 42 ppb upfield of the
carbonyl-C with long-term signal averaging. Due to its small
magnitude, this peak cannot be unequivocally identified as an
18O satellite, but it does place an upper limit on the amount of
exchange occurring into the carbonyl position at neutral pH.
Such a small amount of 18O incorporation would not have been
noted in the MS experiment that was run at smaller atom %
18O and for only one half-life of the hydrolysis reaction. No
Mass spectral analysis of the 18O content of 3a,b generated
during the hydrolysis of the esters 2a, 2b, and 2b′ in 18O-H2O
can show whether the quinols are generated by processes
involving Calkyl-O or Cacyl-O bond cleavage in the esters.
Analysis is complicated by 18O exchange into the carbonyl-O
of 3a,b, but the two labeling sites can be distinguished by the
18O-induced upfield chemical shift on the 13C NMR signal of
carbon bonded to the 18O.15,16
The results of the LC/MS analysis of 3a obtained from the
hydrolysis of 2a in 10 atom % 18O-H2O in pH 1.0 HClO4 and
pH 7.5 0.02 M phosphate buffer at 30 °C for one half-life of
the hydrolysis reaction of 2a (5060 s at pH 1.0, 29 400 s at pH
7.5) and of 3a incubated in the same solutions for the same
length of time as controls are summarized in Scheme 1. Paired
control and experimental runs at the same pH were performed
with the same aqueous solutions on consecutive days. The best
(14) Vitullo, V. P.; Logue, E. A. J. Org. Chem. 1973, 38, 2265-2267.
(15) Rayat, S.; Majumdar, P.; Tipton, P.; Glaser, R. J. Am. Chem. Soc. 2004,
126, 9960-9969.
(16) (a) Jameson, C. J. J. Chem. Phys. 1977, 66, 4983-4988. (b) Jiang, C.;
Suhadolnik, R. J.; Baker, D. C. Nucleosides Nucleotides 1988, 7, 271-
294.
9
8092 J. AM. CHEM. SOC. VOL. 127, NO. 22, 2005

Hydrolysis of 4-Acyloxy-4-substituted-2,5-cyclohexadienones
A R T I C L E S
Scheme 2
Figure 4. Trapping out of 3a by Br- to generate 5a during the
decomposition of 2a at pH 1.0. The ratio kBr/ks was calculated from a least-
squares fit of the data to the “azide clock” formulas.18
18O-related satellites were observed in any other 13C resonances
of 3a at either pH, and no satellites were observed in control
experiments in which 3a was generated from 2b in H2O with
normal isotopic abundance.
The 18O data for the reaction run in pH 7.5 phosphate buffer
support our previous conclusion, based on common ion rate
depression and N3- trapping, that 2a decomposes via Calkyl-O
bond cleavage into 1a under conditions in which ko is the
dominant rate term.13 The 18O data indicate that at pH 1.0, where
kH[H+] accounts for 85% of kobs, Calkyl-O bond cleavage also
occurs. The 18O results are consistent with generation of 1a by
the acid-catalyzed pathway, but they cannot rule out some other
process that leads to Calkyl-O bond cleavage without generation
of 1a.
Trapping of the cation by N3- cannot be done at pH 1.0, but
other potential nucleophiles, such as Br-, are not protonated
under these conditions. We found that Br- does trap out 3a to
form the substitution product 5a, identified by comparison to
an authentic sample (Figure 4).17 At high [Br-], the yield of 3a
asymptotes to 0%, indicating that Cacyl-O bond cleavage does
not compete significantly with the dominant Calkyl-O bond
cleavage process. Trapping occurs without rate acceleration: kobs
at pH 1.00 in 0.5 M ClO4- is (1.81 ( 0.07) × 10-4 s-1, and at
pH 1.00 in 0.5 M Br-, conditions in which ca. 95% of 3a has
been trapped out, kobs is (1.38 ( 0.05) × 10-4 s-1. This indicates
that the trapping occurs on an intermediate generated after the
rate-limiting step of the reaction. Application of the “azide-
clock” formulas18 to the data of Figure 4 provides a value of
the ratio of the second-order rate constant for trapping of the
intermediate by Br- and the pseudo-first-order rate constant for
the corresponding control experiment were performed in 25
atom % 18O-H2O. In all cases, reactions were run for one half-
life of the hydrolysis reaction of 2b or 2b′ (2300 s at pH 1.0,
22 200 s at pH 4.6, and 25 000 s at pH 7.5) with experimental
runs and the corresponding controls performed with the same
aqueous solutions on consecutive days. Ionization conditions
used for 3b were positive ion ESI, so peaks at m/e 125 ((M +
1)+) and 127 ((M + 3)+) were monitored. Results of triplicate
injections for each experiment are reported in Scheme 2. At 80
°C at both pH 1.0 and 7.5, the carbonyl-O of 3b undergoes
apparently complete exchange with 18O-H2O, but no significant
exchange occurs at 30 °C at pH 4.6. The observed value of
(127/125)% for 3b incubated in unlabeled H2O at pH 4.6 is
(0.40 ( 0.10)%. The experimental data at pH 4.6 and 7.5 are
indistinguishable from the data for the corresponding controls
at the 95% confidence level, but the experimental result for (127/
125)% at pH 1.0 is different from the control at the 95%
confidence level, but not at the 99% confidence level. If the
result from the control experiment represents complete exchange
of 18O into the carbonyl-O, the small excess incorporation in
the hydrolysis experiment indicates that Calkyl-O bond cleavage
trapping by the aqueous solvent, kBr/ks, of (46 ( 5) M-1
.
Trapping by Br- at pH 7.5 occurs without rate acceleration of
the hydrolysis of 2a to yield the same product, 5a, with the
same trapping efficiency, indicating that the same intermediate,
1a, is generated and trapped by Br- at both pH.
Results of 18O-labeling experiments performed on 2b at 80
°C at pH 1.0 in HClO4 solution and at pH 7.5 in 0.02 M
phosphate buffer, and on 2b′ at 30 °C at pH 4.6 in 0.02 M
acetate buffer, are summarized in Scheme 2. The experiments
on 2b and the corresponding control experiments on 3b were
performed in 10 atom % 18O-H2O. The experiment on 2b′ and
(17) Gutsche, C. D.; No, K. H. J. Org. Chem. 1982, 47, 2708-2712.
(18) Richard, J. P.; Jencks, W. P. J. Am. Chem. Soc. 1982, 104, 4689-4691;
1982, 104, 4691-4692; 1984, 106, 1383-1396.
9
J. AM. CHEM. SOC. VOL. 127, NO. 22, 2005 8093

A R T I C L E S
Novak and Glover
may occur to the extent of 8 ( 5% of the overall reaction under
acidic conditions. The predominant, if not exclusive, mode of
reaction under all three pH conditions is Cacyl-O bond cleavage.
This is particularly true for 2b′ at pH 4.6, where ko is the
dominant kinetic term since these data were collected in 25 atom
%
18O-H2O. This would have made it possible to detect as
little as 3% Calkyl-O bond cleavage ((127/125)% ca. 1.0%
greater than the control). A (127/125)% of ca. 1.9% compared
to the control of 0.9% would have been a statistically significant
difference at the 95% confidence level within the observed
reproducibility of these experiments.
13C NMR experiments confirmed that at pH 7.5 the carbo-
nyl-C of 3b generated from decomposition of 2b in 10 atom %
18O-H2O showed an 18O-induced satellite. The satellite was
observed in CDCl3 at 49 ppb upfield from the main carbonyl-C
resonance at 185.323 ppm. The satellite had an integrated
intensity 9% of that of the main peak. No other resonances of
3b generated in this manner exhibited observable upfield
satellites. The NMR experiment was not attempted at pH 4.6
because of the lack of significant labeling observed by MS. The
NMR analysis at pH 1.0 is complicated by the dienone-phenol
rearrangement of 3b. It is possible to stop the reaction at a point
where this rearrangement has not become extensive, but >90%
of 2b has reacted. For an experiment run in 25 atom % 18O-
H2O, a prominent 18O satellite of the carbonyl-C resonance is
observed, but no 18O satellite can be detected for the hydroxyl-C
after 24 h of signal averaging. If its chemical shift difference is
similar to that observed for the hydroxyl-C of 3a (ca. 20 ppb),
it would have been possible to detect a signal about 2-3% of
the magnitude of the main hydroxyl-C peak of 3b. This
establishes an upper limit of ca. 6-9% reaction by Calkyl-O
bond cleavage at pH 1.0.
Figure 5. (A) Yield of 6b as a function of [N3-] during the decomposition
of 2b′ at pH 4.6. (B) Rate constants for decomposition of 2b′ as a function
of [N3-] at pH 4.6.
at the HF/6-31G* level, and these were used to compute energies
at the density functional level (pBP/DN*//HF/6-31G*).21 A full
frequency analysis at the pBP/DN* level was used to obtain
zero-point energies, enthalpies, and entropies. Optimized ge-
ometries are provided in the Supporting Information. Compari-
sons of the geometries, vibrational frequencies, and other
properties of the oxenium species and the corresponding
nitrenium and carbenium ions will be presented elsewhere.22
Here, we are primarily concerned with the stabilities of the
oxenium and nitrenium species 1 and 7 relative to each other
and to their hydration products 3 and 8. The energetics of the
isodesmic eqs 2 and 3 were calculated at three levels of theory:
(1) HF/6-31G*, (2) pBP/DN*//HF/6-31G* with ZPE corrections,
and (3) pBP/DN*//HF/6-31G* with ZPE corrections and
thermodynamic corrections at 298.15 °C.
Although 2b′ appears to react entirely by an ester hydrolysis
pathway under conditions in which ko is the dominant rate term,
it is possible to generate an oxenium-like substitution product
from this ester. At pH 4.6 in the presence of N3-, the product
6b is generated in an [N3-]-dependent manner (Figure 5A). This
product is formed in a kinetically second-order process (Figure
5B), so it is clearly not generated from trapping an oxenium
ion generated in a rate-limiting step. The yield of the substitution
product correlates well with the observed kinetics; the ratio kaz/ko
derived from the kinetics and the product yield data are in good
agreement with each other. An analogous product, 6a, was ob-
-
tained from N3 trapping experiments on 2a, but in this case,
the reaction was kinetically first-order and the product was deriv-
ed from 1a generated during rate-limiting decomposition of 2a.13
Calculations have been carried out on 1a, 1b, and the
unsubstituted phenyloxenium ion 1e, on the corresponding
quinols 3a, 3b, and 3e, as well as on the corresponding nitrenium
species 7a, 7b, and 7e, and iminoquinols 8a, 8b, and 8e. The
iminoquinols are known to be the initial major or exclusive
hydration products of the nitrenium ions, and 3a is the only
product of hydration of 1a.13,19,20 Geometries were optimized
9
8094 J. AM. CHEM. SOC. VOL. 127, NO. 22, 2005

Hydrolysis of 4-Acyloxy-4-substituted-2,5-cyclohexadienones
A R T I C L E S
Table 2. Energetics of Isodesmic Reactions of Equations 2 and 3
Scheme 3
at HF and DFT Levels
first cmpd
in eq
∆
E (kcal/mol)
∆
E (kcal/mol)
∆E (kcal/mol)
pBP/DN*, ZPE, thermo
eq
HF/6-31G*
pBP/DN*, ZPE
2
2
2
3
3
3
3
1a
1b
1e
1a
1b
7a
7b
-12.2
-18.9
-21.3
25.9
10.6
16.7
-12.3
-19.2
-19.8
28.2
9.5
20.8
-11.0
-18.4
-19.3
29.0
10.3
20.6
8.2
9.0
9.4
Comparisons of the reaction energies in Table 2 show that,
in general, inclusion of electron correlation, ZPE corrections,
and thermodynamic quantities make little difference to the
results. The isodesmic reaction of eq 2 compares the stabilities
of the oxenium ions with the corresponding nitrenium ions
relative to the respective hydration products. All oxenium ions
are less stable than the corresponding nitrenium species, but
the 4-phenyl substituent of 1a stabilizes it to the reaction of eq
2 by ca. 7 kcal/mol relative to the 4-methyl substituted 1b and
ca. 8 kcal/mol relative to the unsubstituted 1e. The calculated
results for 1a and 7a are in accord with the experimentally
estimated lifetimes of the two ions in aqueous solution at 30
°C (12 ns for 1a and 300 ns for 7a).13,23 The p-tolyloxenium
ion, 1b, is calculated to be ca. 19 kcal/mol less stable to
hydration than 7b, which has a lifetime of only ca. 0.8 ns at 20
°C.20 The isodesmic reactions of eq 3 compare the hydration
stabilities of the substituted oxenium ions 1a and 1b to the
unsubstituted ion 1e and the similar hydration stabilities of 7a
and 7b relative to the unsubstituted nitrenium ion 7e. The
energetics of this reaction were previously calculated at the HF/
6-31G*//HF/3-21G* level for a series of nitrenium ions includ-
ing 7a and 7b. The ∆E calculated at that level for 7a (19.3
kcal/mol) and 7b (8.1 kcal/mol) are comparable to the values
shown in Table 2.24 The results show that the 4-phenyl
substituent stabilizes 7a relative to the 4-methyl substituted 7b
by ca. 11 kcal/mol. The effect of the 4-phenyl substituent on
the stabilization of 1a relative to 1b is significantly larger at
ca. 19 kcal/mol.
Table 3. Rate Constant Ratios and Estimated Rate Constants for
Reaction of Nucleophiles with 1a at 30 °C
1
1
nucleophile
k
Nu/ks (M-
)
k )
Nu (M-1 s-
-
N3
77 ( 5a
46 ( 5
6.5 × 109 b
3.9 × 109
2.8 × 108
Br-
OAc-
H2O
3.3 ( 0.2a
(8.4 × 107 s-1
)
c
a From ref 13. b Assumed diffusion limit based on observed kaz for 7a;
see ref 13. c This is ks, the pseudo-first-order rate constant for reaction with
solvent.
Discussion
The 18O-labeling results and nucleophilic trapping experi-
ments performed under neutral and acidic conditions for 2a and
the common ion rate depression observed for this compound
are readily interpreted in terms of the mechanism of Scheme 3.
Both of the processes governed by ko and kH generate the same
reactive intermediate, identified as the oxenium ion 1a. The
regiochemistry of reaction with 1a differs for the nucleophiles
examined (Br-, N3-, OAc-, H2O) and is not completely
understood at this time. The regiochemistry of reaction with
H2O was also previously observed for similarly substituted
nitrenium ions.19,20 An analogous product may initially be
formed with other nucleophiles, but these products would be
expected to decompose rapidly by loss of the leaving group.20
The common ion rate depression observed for 2a in acetate
buffers requires that OAc- reacts at the same position as H2O.
It has been noted previously that π-donor substituents
considerably stabilize nitrenium ions compared to the corre-
sponding carbenium ions.19,20,23-25 These calculations indicate
that aryloxenium ions are even more sensitive to π-donor
stabilization than are nitrenium ions. This is consistent with
greater localization of the positive charge at the 4-position of
the ring of the oxenium ion caused by the more electronegative
oxygen.13,25
-
The unusual product 9a (18% of the isolated N3 adducts of
2a) is thought to arise because of the significant amount of
charge delocalization that occurs into the distal ring of 1a that
is calculated to be coplanar with the proximal ring.13 Analogous
products were not observed from reaction with H2O or Br-.
Samples of both of these products analogous to 9a are available,
so it is possible on the basis of HPLC data to set upper limits
of 1 and 2%, respectively, for the yields of 4,4′-dihydroxybi-
phenyl and 4′-bromo-4-hydroxybiphenyl under conditions in
which the yields of 3a or 5a, respectively, are maximized.
The rate constant ratios, kNu/ks, obtained from nucleophilic
trapping experiments and common ion rate depression measure-
ments on 1a are gathered in Table 3. Rate constants, kaz, for
(19) Novak, M.; Kahley, M. J.; Eiger, E.; Helmick, J. S.; Peters, H. E. J. Am.
Chem. Soc. 1993, 115, 9453-9460.
(20) (a) Novak, M.; Kahley, M. J.; Lin, J.; Kennedy, S. A.; Swanegan, L. A. J.
Am. Chem. Soc. 1994, 116, 11626-11627. (b) Novak, M.; Kahley, M. J.;
Lin, J.; Kennedy, S. A.; James, T. G. J. Org. Chem. 1995, 60, 8294-
8304.
(21) (a) Becke, A. D. Phys. ReV. A 1988, 38, 3098-3100. (b) Perdew, J. P.
Phys. ReV. B 1986, 33, 8822-8824.
(22) Glover, S. A.; Novak, M. Can. J. Chem. Submitted.
(23) McClelland, R. A.; Davidse, P. A.; Hadzialic, G. J. Am. Chem. Soc. 1995,
117, 4173-4174.
(24) Novak, M.; Lin, J. J. Org. Chem. 1999, 64, 6032-6040.
(25) (a) Robbins, R. J.; Laman, D. M.; Falvey, D. E. J. Am. Chem. Soc. 1996,
118, 8127-8135. (b) Srivastava, S.; Ruane, P. H.; Toscano, J. P.; Sullivan,
M. B.; Cramer, C. J.; Chiapperino, D.; Reed, E. C.; Falvey, D. E. J. Am.
Chem. Soc. 2000, 122, 8271-8278.
reaction of nitrenium ions with N3 with kaz/ks as large as 105
-
M-1 are diffusion limited, so it is likely that kaz for 1a is also
diffusion limited.23,26 The estimated value for kaz in Table 3 is
9
J. AM. CHEM. SOC. VOL. 127, NO. 22, 2005 8095

A R T I C L E S
Scheme 4
Novak and Glover
mechanisms do not occur,27 and energetic conditions that must
be met for a concerted transition state involving multiple bond-
making/bond-breaking events are stringent.28 Nevertheless, if
the intermediate is too short-lived to exist as an intermediate
(lifetime <10-13 s), the concerted mechanism is enforced.29 This
may be the case for 10b. Isolation experiments for 6b at high
[N3-] show that the yield of 3b becomes vanishingly small.
The results indicate that ks′ is at least 50-fold smaller than kp
for 10b. If ks′ is of the same magnitude as the estimated ks for
1b, it is ca. (2-3) × 1011 s-1, and kp is at least 1013 s-1. This,
in turn, suggests that 10b is not an intermediate at all, but a
transition state. The error limits on the estimated value of ks′
are large, probably an order of magnitude or more, so we cannot
preclude the possibility that 10b is an intermediate with a very
short lifetime. An upper limit of the lifetime of 10b and similar
species of ca. 10-10 to 10-11 s is enforced by the rate of
diffusional separation of ion pair intermediates in aqueous
solution, so kp must be at least ca. 1011 s-1 if the reaction does
occur through this species.30
the observed value of kaz for 7a at 20 °C corrected to 30 °C.13
All other rate constants in Table 3 are estimated based on the
observed rate constant ratios and on the assumption that kaz is
diffusion limited for 1a. The rate constant for reaction with Br-,
kBr, is also large, but about a factor of 2 below the diffusion
limit. The estimated lifetime of 1a at 30 °C in aqueous solution,
1/ks, is 12 ns. This is considerably shorter than the lifetime of
7a of 300 ns extrapolated to 30 °C from data obtained at 20
°C.13,23 The lifetimes are in accord with the relative stabilities
of 1a and 7a toward hydration calculated from the isodesmic
reaction of eq 2 (Table 2).
Conclusion
An aryloxenium ion stabilized by a π-donor substituent at
the 4-position appears to be stable enough in an aqueous
environment to be readily generated and to have sufficient life-
time to react with some selectivity with nonsolvent nucleophiles.
A σ-donor, such as a 4-methyl substituent, is far less effective
at stabilizing the ion; 1b cannot be generated under conditions
in which 1a is readily formed, and the calculations indicate that
even if this species could be formed in a nucleophilic solvent,
such as H2O or MeOH, it would be far too reactive with the
solvent to be effectively trapped by nonsolvent nucleophiles.
An apparent oxenium ion nucleophilic substitution product can
be generated from a precursor to the 4-methyl ion, but this
product is generated by a kinetically second-order process that
has the characteristics of an SN2′ reaction. We will continue to
delineate substituent effects on the stability/reactivity of these
ions and will make efforts to generate sufficiently stable
examples by laser flash photolysis methods.
Unlike 2a, 2b and 2b′ decompose predominately by ester
hydrolysis pathways involving Cacyl-O bond cleavage under
all pH conditions examined. The calculations suggest that this
may be due to the instability of 1b in an aqueous environment.
Since the oxenium ion pathway is energetically unfavorable for
2b and 2b′, these esters react predominately by an alternative
pathway that does not involve 1b. The calculated stability toward
hydration of 1b provides a way to estimate the lifetime of 1b,
provided that log ks correlates with these calculated stabilities.
There is evidence that this is the case for nitrenium ions.24 Log
ks for a series of 18 nitrenium ions with widely varying structure
correlates with ∆E of eq 3 (all relative to 7e) calculated at the
HF6-31G*//3-21G level with slope -0.19 ( 0.02 (r2 ) 0.89).24
If a similar correlation holds for the oxenium ions, the calculated
value of 1/ks for 1b based on the lifetime of 1a and the calculated
values for the hydration stabilities of 1a and 1b relative to 1e
(eq 3) is 3 ps. An estimate based on the isodesmic reactions of
eq 2 and the lifetimes of 1a, 7a, and 7b provides a similar value
for the lifetime of 1b of 5 ps. Simple 4-alkyl substituted
aryloxenium ions are unlikely to be generated in aqueous
solution as trappable intermediates in diffusional equilibrium
with nonsolvent nucleophiles. Although 1b is apparently not
formed to a significant extent from 2b or 2b′ in H2O in the
absence of other nucleophiles, 2b′ can be induced to undergo
bimolecular substitution reactions that generate oxenium-like
Experimental Section
Synthesis: The syntheses of 2a,b and 3a,b were described previ-
ously.13 A sample of 2-bromo-4-phenylphenol (5a) was obtained from
a previously published procedure.17 Methylhydroquinone (4b), 4′-
bromo-4-hydroxybiphenyl, and 4,4′-dihydroxybiphenyl were com-
mercially available.
4-Dichloroacetoxy-4-methyl-2,5-cyclohexadienone (2b′): A 0.54
g sample of p-cresol (5 mmol) was dissolved in 40 mL of dichloroacetic
acid, and the resulting solution was stirred vigorously as 1.77 g (5.5
mmol) of phenyliodonium diacetate (PIDA) in 40 mL of dichloroacetic
acid was added in a dropwise fashion over a period of ca. 8 h. After
completion of addition, the solution was diluted with 150 mL of CH2-
Cl2 and washed with saturated aqueous NaHCO3 (3 × 50 mL), followed
by brine (1 × 50 mL). The CH2Cl2 solution was dried over anhydrous
Na2SO4, filtered, and evaporated to dryness under vacuum. The crude
(26) (a) Davidse, P. A.; Kahley, M. J.; McClelland, R. A.; Novak, M. J. Am.
Chem. Soc. 1994, 116, 4513-4514. (b) Bose, R.; Ahmad, A. R.; Dicks, A.
P.; Novak, M.; Kayser, K. J.; McClelland, R. A. J. Chem. Soc., Perkin
Trans. 2 1999, 1591-1599. (c) Ren, D.; McClelland, R. A. Can. J. Chem.
1998, 76, 78-84. (d) McClelland, R. A.; Gadosy, T. A.; Ren, D. Can. J.
Chem. 1998, 76, 1327-1337.
(27) Bordwell, F. G. Acc. Chem. Res. 1970, 3, 281-290.
(28) Guthrie, J. P. J. Am. Chem. Soc. 1996, 118, 12878-12885.
(29) Jencks, W. P. Acc. Chem. Res. 1980, 13, 161-169.
(30) (a) Richard, J. P.; Jencks, W. P. J. Am Chem. Soc. 1984, 106, 1373-1383.
(b) Toteva, M. M.; Richard, J. P. J. Am. Chem. Soc. 1996, 118, 11434-
11445.
-
products. Since N3 clearly accelerates the decomposition of
2b′, the reaction of 2b′ with N3- must occur by a preassociation
process. Two mechanisms are possible: a fully concerted SN2′
process, or a stepwise process involving N3 trapping of an
intermediate ion sandwich, 10b, that is generated by N3 -assisted
-
-
ionization (Scheme 4). It has been argued that concerted SN2′
9
8096 J. AM. CHEM. SOC. VOL. 127, NO. 22, 2005

Hydrolysis of 4-Acyloxy-4-substituted-2,5-cyclohexadienones
A R T I C L E S
product was triturated with hot hexanes (4 × 5 mL). After evaporation
of the hexanes, the residue was subjected to chromatography on a
chromatatron (2 mm silica gel, 75/25 hexanes/EtOAc) to yield 150-
200 mg (13-17%) of a yellowish waxy solid that was sufficiently pure
for most purposes. A cleaner sample could be obtained by recrystal-
lization from hexanes or by vacuum sublimation (-5 °C coldfinger,
40 °C bath): mp 69-71 °C; IR 3022, 1749, 1665, 1629, 1272, 1050
solution incubated at 30 °C for 15 min prior to injection. The resulting
solution was incubated at 30 °C for one half-life (5060 s at pH 1.0,
29 400 s at pH 7.5), cooled in an ice water bath, and analyzed by LC/
MS using triplicate injections. LC conditions: 2 mm × 50 mm C-18
column, 30/70 CH3CN/H2O, 0.2 mL/min, 10 µL injection, retention
time for 3a ca. 2.8 min. MS conditions: negative ion-ESI scanned from
m/e 183-191 in profile mode.
1
cm-1; H NMR (300 MHz, CDCl3) δ 1.70 (3H, s), 5.92 (1H, s), 6.33
Similarly, 2 µL of a 0.15 M solution of 3b or a 0.30 M solution of
(2H, d(AB), J ) 10.2 Hz), 6.92 (2H, d(AB), J ) 10.2 Hz); 13C NMR
(125.8 MHz, CDCl3) δ 25.8, 64.1, 77.2, 129.3, 146.4, 162.7, 184.3;
LC/MS (ESI positive) m/e 235 (100%) (35Cl2M + H)+, 237 (70%) (35-
Cl37ClM + H)+, 239 (10%) (37Cl2M + H)+; high-resolution MS (ES,
positive), C9H835Cl2O3Na (M + Na) requires m/e 256.9748, found
256.9752, C9H835Cl37ClO3Na requires m/e 258.9718, found 258.9717.
2-Azido-4-methylphenol (6b): A 70 mg (0.30 mmol) sample of
2b′ was dissolved in 1 mL of CH3CN and added in 200 µL portions at
20 min intervals to 100 mL of a 0.5 M NaN3, 0.25 M HClO4 buffer
(1/1 NaN3/HN3, pH 4.6) in 5 vol % CH3CN-H2O incubated at 30 °C.
The reaction mixture was extracted (4 × 50 mL) with CH2Cl2 after
the disappearance of 2b′ was confirmed by HPLC (ca. 3 h after the
last addition). After drying over Na2SO4, the CH2Cl2 extract was
evaporated to dryness under vacuum, and the residue was subjected to
vacuum sublimation (-15 °C coldfinger, 30 °C bath) to provide 23
mg (51%) of the off-white azide adduct: mp 42.5-44 °C; IR (thin
2b in CH3CN was injected into 200 µL of the aqueous 10 atom % 18
O
solution preincubated at 80 °C. The solution was incubated at 80 °C
for one half-life (2300 s at pH 1.0, 25 000 s at pH 7.5), cooled to room
temperature, and analyzed by LC/MS using triplicate injections. LC
conditions: 2 mm × 50 mm C-18 column, 17/83 MeOH/H2O, 0.2 mL/
min, 10 µL injection, retention time for 3b ca. 2.4 min. MS condi-
tions: positive ion-ESI scanned from m/e 123-130 in profile mode.
A 2 µL solution of a 0.04 M solution of 3b or a 0.08 M solution of
2b′ in CH3CN was injected into 200 µL of a 25 atom % pH 4.6 acetate
buffer preincubated at 30 °C. After one half-life (22 200 s), the reaction
mixture was cooled in an ice-water bath and analyzed by LC/MS using
triplicate injections. LC conditions: 4.6 mm × 250 mm C-18 column,
60/40 H2O/MeOH (0.1% HOAc), 1 mL/min, 20 µL injection, retention
time for 3b ca. 4.2 min. MS conditions: positive ion-ESI.
For 13C NMR analysis, 2 mL of 10 or 25 atom % 18O-H2O pH 1.0
and 7.5 solutions were prepared. For 2b, 200 µL of a 0.25 M solution
of the ester in CH3CN was injected into the aqueous solution
preincubated at 80 °C. For 2a, the 0.25 M 200 µL stock solution of
the ester was injected in 20 µL increments at one half-life intervals
into the aqueous solution preincubated at 30 °C. The reaction mixtures
were monitored by HPLC, and at appropriate reaction times, the
mixtures were cooled in an ice-water bath; the acidic solutions were
neutralized with Na2HPO4, and the solutions were extracted with CH2-
Cl2 (4 × 2 mL). The extracts were dried over Na2SO4 and evaporated
to dryness under vacuum. The residue was dissolved in 750 µL of CD2-
Cl2 or CDCl3. The resulting solutions were analyzed by 13C NMR at
125.8 MHz. Acquisition and processing parameters were standard,
except that the line broadening parameter was set at 0.25 Hz. Data
acquisition was continued until 18O satellites clearly emerged. Control
experiments were run in normal isotopic abundance aqueous solutions.
Calculations: Calculations were performed with MAC Spartan Pro
Version 1 and Spartan Version 5.31 Geometries were optimized at the
HF/6-31G* level, and frequency analyses were performed to verify that
the geometries corresponded to true stationary points. These geometries
were used to obtain energies at the perturbative Becke-Perdew density
functional level pBP/DN*//HF/6-31G*.21 A full frequency analysis at
the pBP/DN* level was used to obtain zero-point energies, and
enthalpies and entropies at 298.15 °C.
1
film) 3415, 2120, 1600, 1510, 1305 cm-1; H NMR (500 MHz, CD2-
Cl2) δ 2.33 (3H, s), 5.22 (1H, s), 6.82 (1H, d, J ) 8.2 Hz), 6.89 (1H,
dd, J ) 1.3, 8.2 Hz), 6.95 (1H, d, J ) 1.2 Hz); 13C NMR (125.8 MHz,
CD2Cl2) δ 20.3, 115.5, 118.8, 125.5, 126.5, 130.9, 145.1; LC/MS (ESI,
negative) m/e 148 (M - H)- (weak), (ESI positive) m/e 122 (M-N2
+ H)+; high-resolution MS (ES, positive) C7H7N3ONa (M + Na)
requires m/e 172.0487, found 172.0484.
Kinetics and Product Studies: Reactions were performed in 5 vol
% CH3CN-H2O, µ ) 0.5 (NaClO4) at 30 °C for 2a and 2b′, and at 80
°C for 2b. The pH was maintained with HClO4 solutions (pH < 3.0),
or with HCO2H/NaHCO2, AcOH/AcONa, and Na2HPO4/NaH2PO4
buffers. All pH values were measured at ambient (24-26 °C)
temperature and are uncorrected. Detailed procedures utilized for the
kinetics studies of 2a and 2b have been published.13 For 2b′, reactions
were initiated by injection of 15 µL of a ca. 0.02 M CH3CN solution
of 2b′ into 3 mL of the reaction solution incubated at 30 °C for 15-20
min prior to initiation. Kinetics were monitored by changes in UV
absorption at 220, 236, 240, and 250 nm. Absorbance changes were
fit to a standard first-order rate equation. Product studies were performed
in pH 1.0, 4.6, and 7.0 solutions by HPLC analysis of the kinetics
solutions after 7-10 half-lives of the hydrolysis reactions. At these
pH values, reactions were also monitored as a function of time by
HPLC. HPLC conditions include the following: 20 µL injections,
Novapak 8 mm × 100 mm C-18 radial compression column with 4 µ
particle size, 60/40 CH3CN/H2O eluent, 0.5 mL/min flow rate, UV
detection at 240 nm, or a 4.7 mm × 250 mm C-18 column, 60/40
MeOH/H2O or 50/50 MeOH/H2O eluent, 1.0 mL/min flow rate, UV
detection at 240 nm. Product yield data for 3a, 5a, and 6b as a function
of [Br-] or [N3-] were fit to eqs 4 and 5, where [Nu] ) [Br-] or [N3-].18
Acknowledgment. M.N. thanks Miami University for a
sabbatical leave, and The University of New England for
providing facilities at which much of this work was ac-
complished. 13C NMR data were collected on a 500 MHz
spectrometer provided by a Hayes Investment Fund grant to
MU from the Ohio Board of Regents, and the LC/MS used for
18O analysis was provided by an LIEF grant to UNE from the
Australian Research Council.
3a% ) max% (1/(1 + kNu[Nu]/ks))
(4)
Supporting Information Available: Rate constants for the
decomposition of 2b′ and selected rate constants for the
decomposition of 2a in the presence and absence of Br-, HF/
6-31G* geometries of the ions 1 and 7, and the hydration
products 3 and 8, 1H and 13C NMR spectra of 2b′ and 6b, and
COSY NMR spectrum of 6b (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
5a% or 6b% ) max% ((kNu[Nu]/ks)/(1 + kNu[Nu]/ks)) (5)
The parameter max% is a least-squares adjustable parameter. In all
of the fits reported here, it is 97-102%
18O-Labeling Studies: Solutions (pH 1.0 HClO4, pH 4.6 0.02 M
OAc-/HOAc, pH 7.5 0.02 M HPO4-2/H2PO4-) were identical to those
used for kinetics, except that they were made to nominally contain 10
or 25 atom % 18O-H2O. This was accomplished by appropriate dilution
of commercially available 10 and 95 atom % 18O-H2O.
JA050899Q
A 2 µL injection of a 0.05 M solution of 3a or a 0.10 M solution of
(31) Wavefunction, Inc.; 18401 Van Karman Ave., Suite 370, Irvine, CA, 92612
U.S.A.
2a in CH3CN was made into 200 µL of an aqueous 10 atom % 18O
9
J. AM. CHEM. SOC. VOL. 127, NO. 22, 2005 8097