Chemistry of 4-alkylaryloxenium ion "precursors": Sound and fury signifying something?

Article abstract of DOI:10.1021/jo701853e

(Chemical Equation Presented) Quinol esters 2b, 2c, and 3b and sulfonamide 4c were investigated as possible precursors to 4-alkylaryloxenium ions, reactive intermediates that have not been previously detected. These compounds exhibit a variety of interesting reactions, but with one possible exception, they do not generate oxenium ions. The 4-isopropyl ester 2b predominantly undergoes ordinary acid- and base-catalyzed ester hydrolysis. The 4-tert-butyl ester 2c decomposes under both acidic and neutral conditions to generate tert-butanol and 1-acetyl-1,4-hydroquinone, 8, apparently by an S_N1 mechanism. This is also a minor decomposition pathway for 2b, but the mechanism in that case is not likely to be S_N1. Decomposition of 2c in the presence of N ₃^- leads to formation of the explosive 2,3,5,6-tetraazido-1,4-benzoquinone, 14, produced by N₃ -induced hydrolysis of 8, followed by a series of oxidations and nucleophilic additions by N₃ . No products suggestive of N₃^--trapping of an oxenium ion were detected. The 4-isopropyl dichloroacetic acid ester 3b reacts with N₃^- to generate the two adducts 2-azido-4-isopropylphenol, 5b, and 3-azido-4-isopropylphenol, 11b. Although 5b is the expected product of N₃^- trapping of the oxenium ion, kinetic analysis shows that it is produced by a kinetically bimolecular reaction of N₃^- with 3b. No oxenium ion is involved. The sulfonamide 4c predominantly undergoes a rearrangement reaction under acidic and neutral conditions, but a minor component of the reaction yields 4-tert-butylcresol, 17, and 2-azido-4-tert-butylphenol, 5c, in the presence of N₃^-. These products may indicate that 4c generates the oxenium ion 1c, but they are generated in very low yields (ca. 10%) so it is not possible to definitively conclude that 1c has been produced. If 1c has been generated, the N₃^--trapping data indicate that it is a very short-lived and reactive species in H₂O. Comparisons with similarly reactive nitrenium ions indicate that the lifetime of 1c is ca. 20-200 ps if it is generated, so it must react by a preassociation process. Density functional theory calculations at the B3LYP/6-31G*//HF/6-31G* level coupled with kinetic correlations also indicate that the aqueous solution lifetimes of 1a-c are in the picosecond range.

Full text of DOI:10.1021/jo701853e

Chemistry of 4-Alkylaryloxenium Ion “Precursors”: Sound and
Fury Signifying Something?
Michael Novak,*,† Aaron M. Brinster,† Jill N. Dickhoff,† Jeremy M. Erb,†
Matthew P. Jones,† Samuel H. Leopold,† Andrew T. Vollman,† Yue-Ting Wang,† and
Stephen A. Glover§
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
noVakm@muohio.edu
ReceiVed August 23, 2007
Quinol esters 2b, 2c, and 3b and sulfonamide 4c were investigated as possible precursors to
4-alkylaryloxenium ions, reactive intermediates that have not been previously detected. These compounds
exhibit a variety of interesting reactions, but with one possible exception, they do not generate oxenium
ions. The 4-isopropyl ester 2b predominantly undergoes ordinary acid- and base-catalyzed ester hydrolysis.
The 4-tert-butyl ester 2c decomposes under both acidic and neutral conditions to generate tert-butanol
and 1-acetyl-1,4-hydroquinone, 8, apparently by an SN1 mechanism. This is also a minor decomposition
pathway for 2b, but the mechanism in that case is not likely to be SN1. Decomposition of 2c in the
-
presence of N3 leads to formation of the explosive 2,3,5,6-tetraazido-1,4-benzoquinone, 14, produced
-
-
by N3 -induced hydrolysis of 8, followed by a series of oxidations and nucleophilic additions by N3 .
-
No products suggestive of N3 -trapping of an oxenium ion were detected. The 4-isopropyl dichloroacetic
-
acid ester 3b reacts with N3 to generate the two adducts 2-azido-4-isopropylphenol, 5b, and 3-azido-
4-isopropylphenol, 11b. Although 5b is the expected product of N3- trapping of the oxenium ion, kinetic
analysis shows that it is produced by a kinetically bimolecular reaction of N3- with 3b. No oxenium ion
is involved. The sulfonamide 4c predominantly undergoes a rearrangement reaction under acidic and
neutral conditions, but a minor component of the reaction yields 4-tert-butylcresol, 17, and 2-azido-4-
-
tert-butylphenol, 5c, in the presence of N3 . These products may indicate that 4c generates the oxenium
ion 1c, but they are generated in very low yields (ca. 10%) so it is not possible to definitively conclude
-
that 1c has been produced. If 1c has been generated, the N3 -trapping data indicate that it is a very
short-lived and reactive species in H2O. Comparisons with similarly reactive nitrenium ions indicate that
the lifetime of 1c is ca. 20-200 ps if it is generated, so it must react by a preassociation process. Density
functional theory calculations at the B3LYP/6-31G*//HF/6-31G* level coupled with kinetic correlations
also indicate that the aqueous solution lifetimes of 1a-c are in the picosecond range.
Introduction
and chemical oxidations of phenols1-5 and the generation of
commercially useful polymers such as poly(2,6-dimethyl-1,4-
phenylene oxide).6,7 Until recently these species have received
little mechanistic attention. Some examples of stable, highly
delocalized 1, such as 1e and 1f, have been observed or
Aryloxenium ions, 1, have often been invoked to explain a
variety of products of the synthetically useful electrochemical
† Miami University.
§ University of New England.
10.1021/jo701853e CCC: $37.00 © 2007 American Chemical Society
Published on Web 11/21/2007
9954
J. Org. Chem. 2007, 72, 9954-9962

Chemistry of 4-Alkylaryloxenium Ion “Precursors”
isolated,4,8 but these stable species provide little insight into the
reactions of transient members of this class of ions. Previous
mechanistic studies of transient ions were not consistent with
each other.9-13 There are discrepancies in the literature concern-
ing the regiochemistry of reaction of purported examples of 1
generated from different sources and the possible involvement
of triplet ions.2,9,11,13
SCHEME 1. Possible Routes to 4-Alkylaryloxenium Ions
Recently we have investigated the possibility of generation
of 1 in aqueous solution from precursors such as 2, 3, and 4
(Scheme 1).14-16 We have found that oxenium ions with
electron-donating 4-aryl substituents such as 1d can be generated
readily from these precursors and their reactions with H2O and
nonsolvent nucleophiles such as N3- and Br- can be character-
ized. The 4-aryl-substituted ions behave as singlets and have
aqueous solution lifetimes that are somewhat shorter than their
nitrenium ion analogues.14-16 Attempts to generate the 4-methyl-
substituted ion 1a from 2a and 3a were unsuccessful.14,15
Although an oxenium-like N3--adduct, 5a, was isolated from
the reaction of 3a with N3-, kinetic analysis showed that this
product is derived directly from 3a without the involvement of
a transient ion.15 Calculations and kinetic extrapolations suggest
that the 4-alkyl-substituted ions may have aqueous solution
lifetimes in the picosecond range, which would make them
impossible to detect by nucleophilic trapping experiments and
would make alternative bimolecular mechanisms for formation
of oxenium-like products competitive.15,17
intrigued by our inability to detect 1a. As a result we have
expanded our study to include the potential precursors 2b, 2c,
3b, 3c, and 4c. We reasoned that the steric bulk of the isopropyl
or tert-butyl groups in 2b, 2c, 3b, and 3c might enhance the
rate of ionization to form 1b or 1c if these are accessible species.
The precursor 4c was chosen because of our success with 4d
and related sulfonamides. The compound 3c was not isolated,
but all of the other compounds were synthesized and purified,
and their aqueous solution chemistry was examined. Although
we discovered a range of interesting reactivities, only one of
these compounds, 4c, exhibits reactions that may be attributable
to a transient oxenium ion.
Since many of the examples of possible aryloxenium ion
reactions in the literature involve alkyl-substituted ions, we were
(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.
Results and Discussion
(3) Pelter, A.; Ward, R. S. Tetrahedron 2001, 57, 273-282.
(4) (a) Rieker, A.; Speiser, B.; Straub, H. DECHEMA Monogr. 1992,
125, 777-782. (b) Dimroth, K.; Umbach, W.; Thomas, H. Chem. Ber. 1967,
100, 132-141.
All compounds were synthesized by procedures that we have
used previously to make 2a, 3a, or 4d.14-16 All of the target
compounds except 3c were isolated and purified by conventional
methods, although 2c was quite sensitive to acid impurities.
Attempts to make 3c by oxidation of 4-tert-butylphenol with
phenyliodonium diacetate in dichloroacetic acid led to an
intractable tar that did not appear to contain the desired product.
The phenol had been consumed, so the oxidation did occur.
The synthesis of 3b was also accompanied by a significant
amount of tarry byproduct, but in that case a sufficient amount
of the desired product was present so that it could be isolated
and purified. Details of synthesis and compound characterization
can be found in the Supporting Information.
The reactions of all compounds were followed in 5 vol %
CH3CN-H2O at µ ) 0.5 (NaClO4) in HClO4 solutions (pH <
3.0), or in HCO2H/NaHCO2, AcOH/AcONa, NaH2PO4/Na2-
HPO4, or TrisH+/Tris buffers at 30 °C (2c, 3b), 50 °C (4c), or
80 °C (2b). Reaction kinetics were monitored as a function of
pH because compounds such as 2d and 4d typically generate
oxenium ions while undergoing pH-independent hydrolysis and,
less commonly, acid-catalyzed hydrolysis.14-16 Pseudo-first-
order rate constants for the decomposition of all compounds
could be obtained by UV spectroscopic methods or by HPLC.
Some compounds, notably 2b and 4c (at pH > 8) exhibited
distinctly non-first-order UV behavior. This was shown by
HPLC to be due to decomposition of initially formed reaction
products. In these cases HPLC was used as the primary tool
for kinetic analysis. Rate constants smaller than ca. 5 × 10-6
s-1 were obtained by initial rates methods.14 Details of kinetic
(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.
(8) (a) Williams, L. L.; Webster, R. D. J. Am. Chem. Soc. 2004, 126,
12441-12450. (b) Lee, S. B.; Lin, C. Y.; Gill, P. M.; Webster, R. D. J.
Org. Chem. 2005, 70, 10466-10473.
(9) (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.;
Inbasekaran, M. N. J. Chem. Soc., Chem. Commun. 1978, 149-150. (d)
Abramovitch, R. A.; Alvernhe, G.; Bartnik, R.; Dassanayake, N. L.;
Inbasekaran, M. N.; Kato, S. J. Am. Chem. Soc. 1981, 103, 4558-4565.
(10) Li, Y.; Abramovitch, R. A.; Houk, K. N. J. Org. Chem. 1989, 54,
2911-2914.
(11) (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.
(12) Uto, K.; Miyazawa, E.; Ito, K.; Sakamoto, T.; Kikugawa, Y.
Heterocycles 1998, 48, 2593-2600.
(13) Hegarty, A. F.; Keogh, J. P. J. Chem. Soc., Perkin Trans. 2 2001,
758-762.
(14) Novak, M.; Glover, S. A. J. Am. Chem. Soc. 2004, 126, 7748-
7749.
(15) Novak, M.; Glover, S. A. J. Am. Chem. Soc. 2005, 127, 8090-
8097.
(16) Novak, M.; Poturalski, M. J.; Johnson, W. L.; Jones, M. P.; Wang,
Y.; Glover, S. A. J. Org. Chem. 2006, 71, 3778-3785.
(17) Glover, S. A.; Novak, M. Can. J. Chem. 2005, 83, 1372-1381.
J. Org. Chem, Vol. 72, No. 26, 2007 9955

Novak et al.
TABLE 1. Derived Rate Parameters for 2a-c, 3a, 3b, and 4ca
temp
compd (°C) (M-1 s-1
103kH
kOH
)
107ko (s-1
)
(M-1 s-1
)
pKa
107k- (s-1
)
2ab
2b
2c
80
80
3.8 ( 0.2
5.4 ( 0.4
5.4 ( 0.5 104 ( 6
48 ( 6
30 100 ( 2
25.8 ( 0.5
3ab
3b
4c
30
30
50
266 ( 8
5790 ( 260
68 ( 11 3920 ( 570
2210 ( 20
8.3 ( 0.1 1250 ( 60
a All kinetic parameters are defined in the text. b Data for 2a and 3a
come from ref 15.
Table 1 for comparison purposes.15 All compounds except 2b
do have a significant pH-independent hydrolysis rate constant,
ko, while 2b and 2c exhibit acid-catalyzed decomposition.
Kinetically, the isopropyl esters 2b and 3b behave similarly
to their methyl analogues 2a and 3a. The rate data for 2b and
3b were fit by nonlinear least-squares methods to eqs 1 and 2,
respectively:
For 2b: kobs ) kH[H+] + kOH[OH-]
For 3b: kobs ) ko + kOH[OH-]
(1)
(2)
FIGURE 1. Log kobs vs pH for 2a (red circles), 2b (blue circles), 3a
(red triangles), and 3b (blue triangles). Data for 2a and 3a were obtained
at 80 °C; data for 2b and 3b were obtained at 30 °C. Data were fit as
described in the text.
These are the same rate equations, with one additional term,
that were used to fit kobs for 2a and 3a.15 The additional
parameter for 2a was a pH-independent rate term (ko) in eq
1.15 Since the kinetics for 2b were not followed in the
intermediate pH region where that term would be important, it
is not possible to determine whether a pH-independent decom-
position also occurs for 2b. It is clear that there is no significant
acceleration of decomposition of 2b or 3b compared to 2a or
3a. Decomposition of 2a and 3a in aqueous solution led to only
the corresponding quinol 6a that subsequently underwent a
dienone-phenol rearrangement into 7a under strongly acidic
conditions (Scheme 2).15 18O-Labeling experiments showed that
6a was formed by cleavage of the acyl C-O bond in both 2a
and 3a, so that both compounds decomposed by ordinary ester
hydrolysis mechanisms without the intermediacy of 1a.15
Similarly, 3b decomposed into 6b at both pH 4.5 and 7.4 at
30 °C. No other products were detected by HPLC. These pH
conditions were chosen because ko dominates at pH 4.5 and
kOH dominates at pH 7.4. At pH 7.4 and 80 °C 2b also
decomposes into 6b, but at the higher temperature 6b apparently
undergoes a base-catalyzed dienone-phenol rearrangement. The
decomposition product of 6b was not isolated. At pH 1.0 and
80 °C, 2b predominantly yields 6b that undergoes decomposition
into the same final product, apparently 7b, observed at pH 7.4.
Under these conditions an additional decomposition product of
2b is detected. Figure 3 shows that 8 is generated at early
reaction times as 2b decomposes. HPLC shows that 8 subse-
quently decomposes into hydroquinone, 9, and under the reaction
conditions 9 is oxidized to benzoquinone, 10. This pathway
accounts for (32 ( 6)% of the decomposition of 2b at pH 1.0.
Although 8 was not isolated, it was identified by HPLC
comparison with an authentic sample of 8. Authentic 8 also
decomposed into 9, with subsequent oxidation to 10 at pH 1.0
at the same rate as 8 detected in the reaction mixture of 2b.
Since the isopropyl esters 2b and 3b yield reaction products
similar to 2a and 3a, and with similar rate constants, it appears
that these compounds also do not generate an oxenium ion.
Confirmation of this conclusion was provided by the results of
N3- trapping experiments with 3b at pH 4.5 (Scheme 3). Figure
FIGURE 2. Log kobs vs pH for 2c (red circles) and 4c (blue triangles).
Data for 2c were obtained at 30 °C; data for 4c were obtained at
50 °C. Data were fit as described in the text.
methodology can be found in the Experimental Section. In all
cases pseudo-first-order rate constants, kobs, could be obtained
for the decomposition of each compound under all conditions
studied. All individual rate constants are reported in the
Supporting Information (Tables S1-S4). The pH dependence
of kobs for all compounds is shown in Figures 1 and 2. Previously
reported data for 2a and 3a are included for comparison
purposes.14,15 The kinetics results, product analyses, and trapping
data for each compound are discussed separately below. The
kinetic parameters derived for each compound from the fit of
log kobs to pH are gathered in Table 1 and discussed below.
Previously reported parameters for 2a and 3a are included in
9956 J. Org. Chem., Vol. 72, No. 26, 2007

Chemistry of 4-Alkylaryloxenium Ion “Precursors”
SCHEME 2. Reaction Products from 2a, 2b, 3a, and 3b
FIGURE 3. Formation and decay of 8 during decomposition of 2b at
pH 1.0 and 80 °C. Concentration vs time data were fit to the first-
order rate equation for 2b and the consecutive first-order rate equation
for 8: kobs ) (4.8 ( 0.1) × 10-4 s-1 for 2b; k1 ) (3.8 ( 0.6) × 10-4
s-1 and k2 ) (9.3 ( 1.7) × 10-4 s-1 for 8.
SCHEME 3. Products of the Reactions of 3a and 3b with
-
N3
FIGURE 4. Plot of kobs vs [N3-] for the decomposition of 3b in 1/1
N3-/HN3 buffers at pH 4.5 and 30 °C. Rate constants were determined
from HPLC data.
-
4 shows that decomposition of 3b in the presence of N3 is
accompanied by a modest rate acceleration. The observed kaz′/
ko is 3.8 ( 0.1 M-1. At 0.25 M N3 the N3 dependent term,
kaz′[N3-], accounts for (49 ( 2)% of the overall rate of
decomposition of 3b. Under these conditions two isomeric azide
products, 5b and 11b, are detected by HPLC as shown in Figure
-
-
1
5. The two isomers were distinguished by H and 13C NMR
chemical shifts and 2D NMR correlations. NOESY correlations
between the aromatic H-3 and H-5 and CH of the isopropyl
1
group in 5b were particularly helpful. Complete H and 13C
NMR assignments for both isomers are provided in the
Supporting Information. NMR assignments for 5b were con-
sistent with analogous assignments previously reported for 5a.15
The only other product of decomposition of 3b is 6b. All three
of these compounds are formed at the same rate at which 3b
decomposes. The combined yield of 5b and 11b is (51 ( 3)%,
FIGURE 5. Formation of 5b, 6b, and 11b from 3b in 0.25 M N3- at
pH 4.5 and 30 °C monitored by HPLC. Data were fit to the first-order
rate equation for all compounds.
-
in excellent agreement with the kinetics result. At 0.125 M N3
-
the yield of the azide products predicted by the kinetics data is
that in that case the only product observed was 5a, and N3
(32 ( 2)%. The observed combined yield of 5b and 11b at
trapping was more efficient with kaz′/ko ) 69 ( 6 M-1 15
. Both
-
0.125 M N3 is (32 ( 3)%. The 5b/11b ratio also remains
3a and 3b mimic aryloxenium ion precursors without actual
generation of an oxenum ion.
constant at both concentrations at (1.8 ( 0.1)/1. It appears that
both azide products are produced by direct reaction of N3- with
3b. There is no evidence for the involvement of 1b. This result
is similar to that found earlier for 5a generated from 3a except
The product 11b appears to be formed by a conjugate addition
at C-3 to the dienone component of 3b. An analogous product
was not observed during N3 trapping of 3a.15 The low
-
J. Org. Chem, Vol. 72, No. 26, 2007 9957

Novak et al.
rate constant of (6.7 ( 0.3) × 10-5 s-1. The initial decomposi-
tion product 8 is detected by HPLC, but it decomposes into a
new product that is generated after a noticeable delay time. This
product is generated from the decomposition of authentic 8,
hydroquinone 9, benzoquinone 10, and 2-azidohydroquinone
1319 under the same conditions. The isolated product was
identified as 2,3,5,6-tetraazidobenzoquinone14, on the basis of
its IR and 13C NMR spectra and by comparison to an authentic
sample.20 Since 14 is reported to be a dangerous explosive,20,21
the compound was not purified, but the crude product is
significantly more pure as isolated than the authentic sample
produced by the reaction of NaN3 with chloranil in EtOH.20
No other N3--containing product was detected.
SCHEME 4. Products of the Decomposition of 2c
The reaction in N3-/HN3 buffers indicates that decomposition
-
of 2c does not occur via an E2 elimination, since N3 is a
stronger base than H2O and would be expected to accelerate
the elimination reaction. No acceleration of decomposition of
2c is observed, although N3- accelerates the decomposition of
8. The lack of N3--containing product other than 14 suggests
that no minor pathway leading to 1c occurs.
Sulfonamides similar to 4c are known to require addition of
TFA or TFSA to decompose in benzene,9,11,12 but 4d undergoes
pH-independent decomposition in aqueous solution in the pH
range 1-7 with no acid catalysis.16 At pH > 7.0 there is a
decrease in the rate of decomposition of 4d associated with
ionization of the substrate.16 The sulfonamide 4c shows the same
behavior (Figure 2). Kinetic data for 4c at 50 °C were fit to eq
4, the same equation previously used to fit the rate data for
4d.16
-
selectivity for reaction with N3 exhibited by 3b may account
for this difference. If both compounds have similar reactivity
for conjugate addition at C-3, the 18-fold greater reactivity of
3a would be due to its greater tendency to react at C-2. Then
the 5a/11a ratio for 3a would be ca. 30/1. This would make
detection of 11a unlikely. It is not clear why 3b is less reactive
-
to N3 than 3a.
Although 2b decomposes at rates that are very similar to 2a,
the decomposition of 2c under acidic conditions is significantly
accelerated (Figure 2). At pH 1.0 and 30 °C, 2c decomposes
26-fold more rapidly than 2a does at the same pH at 80 °C.
Rate data for 2c were fit to eq 3.
For 4c: kobs ) ([H+]/(Ka + [H+]))ko + (Ka/(Ka + [H+]))k- (4)
The apparent pKa of 8.3 ( 0.1 obtained from the kinetic fit
was verified by spectrophotometric titration of 4c. A plot of
initial absorbance of 4c at 205 nm versus pH (Figure S1 in the
Supporting Information) yields a pKa of 8.5 ( 0.2. In eq 4, ko
is the rate constant for spontaneous decomposition of 4c, and
k- is the rate constant for decomposition of its conjugate base,
4c-.
The decomposition of 4c at 50 °C yields three products: the
rearranged sulfonamide 15, 4-tert-butylphenol 16, and 4-tert-
butylcatechol 17 (Scheme 5). At pH e 7.0, 15 is the major
reaction product [(67 ( 11)%], while 16 [(19 ( 2)%], and 17
[(10 ( 4)%] are minor products. At higher pH, 15 is subject to
decomposition so its yield cannot be determined accurately. The
other two products are stable to the reaction conditions. The
yield of the catechol 17 decreases as pH increases. It cannot be
detected at pH > 8.2. The yield of the phenol 16 increases as
pH increases and reaches a yield of (68 ( 4)% at pH 9.2. A
plot of product yields versus pH is provided in Figure S2 in
the Supporting Information. The data indicate that 16 is the
major product of the decomposition of 4c-. This may be
occurring by an R-elimination process (Scheme 5) to yield the
known nitrene 18, but it is unlikely that the significant amount
of 16 detected at acidic pH is produced by such a process.22,23
Decomposition of neutral 4c leads predominantly to the rear-
For 2c: kobs ) kH[H+] + ko
(3)
The uncatalyzed decomposition is also accelerated. The rate
constant for uncatalyzed decomposition of 2c at 30 °C (ko) is
4.8-fold larger than ko observed for 2a at 80 °C. The only
reaction product detected by HPLC in >95% yield from the
decomposition of 2c at pH 2.0 and pH 7.0 is 8, which was
isolated and purified from the reaction mixture at pH 2.0
(Scheme 4). HPLC indicates that 8 is the only observable
reaction product at all pH examined. At 30 °C 8 does not
decompose to an observable extent except at pH 1.0, where it
very slowly undergoes hydrolysis to hydroquinone, 9. The other
product, tert-BuOH, 12, was detected by GC at pH 1.0 ((98 (
4)%) and pH 7.0 ((87 ( 4)%). It appears that 2c undergoes
acid-catalyzed and uncatalyzed C-C bond cleavage to generate
the tert-butyl cation, (or an E2 elimination with solvent H2O as
the base) but does not lose AcO- to generate 1c. The tert-butyl
cation has a very short lifetime in H2O, on the order of 10-12
s, so reaction with solvent would occur on an ion-molecule or
ion pair rather than the free ion.18 The analogous reaction of
2b to form 8 as a minor product is unlikely to proceed through
the isopropyl cation but could proceed by an E2 elimination.
An SN2 reaction is unlikely since 2a does not generate 8.
At pH 4.5 and 50 °C in 1/1 N3-/HN3 buffers, 2c decomposes
without rate acceleration at [N3-] e 0.25 M with an average
(19) Couladouros, E. A.; Plyta, Z. F. Haroutounian S. A. Papageorgiou,
V. P. J. Org. Chem. 1997, 62, 6-10.
(20) Winkelman, E. Tetrahedron 1969, 25, 2427-2454.
(21) Gilligan, W. H.; Kamlet, M. J. Tetrahedron Lett. 1978, 1675-1676.
(22) (a) Lwowski, W.; Maricich, T. J.; Mattingly, T. W., Jr. J. Am. Chem.
Soc. 1963, 85, 1200-1202. (b) Lwowski, W.; Maricich, T. J. J. Am. Chem.
Soc. 1965, 87, 3630-3637.
(18) Toteva, M. M.; Richard, J. P. J. Am. Chem. Soc. 1996, 118, 11434-
11445.
9958 J. Org. Chem., Vol. 72, No. 26, 2007

Chemistry of 4-Alkylaryloxenium Ion “Precursors”
SCHEME 5. Products of the Decomposition of 4c with
Possible Mechanisms
FIGURE 6. Concentration of products vs time during the decomposi-
-
tion of 4c at pH 7.0 and 50 °C in the presence of 0.45 M N3 (open
symbols) and in its absence (solid symbols).
rangement product 15, which may be generated by a concerted
process or by internal return of an ion pair.24,25 We are
investigating the mechanisms of formation of the rearrangement
product and the phenol in more detail in a different reaction
system.26
FIGURE 7. Yield of 5c obtained from the reaction of 4c at pH 7.0
and 50 °C as a function of [N3-]. Data were fit to eq 5.
The catechol 17 could be obtained from attack of H2O on
1c. By analogy to 1d and other 4-aryl-substituted aryloxenium
ions, one would have expected to obtain the quinol, 6c, as the
major product of attack of solvent.14-16 Neither 6c nor its
expected dienone-phenol rearrangement product, tert-butylhy-
droquinone, were detected by HPLC in reaction mixtures of
4c. The steric bulk of the tert-butyl group might alter the
preferred site of attack of H2O. If 1c is formed, it should be
possible to trap it with N3-. Figures 6 and 7 summarize the
results of N3--trapping experiments performed in phosphate
buffer at pH 7.0. In the absence of N3-, all products are formed
in a first-order fashion. Under our HPLC conditions 4c and 16
coelute, but the HPLC peak area for the combined peak
containing both components is fit by a first-order rate equation
as expected. In the presence of 0.45 M N3-, the yields of all
products are altered to some extent and one new product, 5c, is
detected. The overall rate of reaction appears to be unaffected
by the presence of N3- and all products are still produced in a
first-order manner. The percentage yield of 15 decreases from
relative effect on the yield of 17 is the largest. The HPLC peak
for this compound is quite small and is partly obscured by the
-
large N3 peak, but the yield of this compound has decreased
-
from ca. 13% to less than 5% in the presence of N3-. The N3
-
adduct 5c is easy to detect in the presence of N3 because it
has a long retention time. Its yield is ca. 6% in the presence of
-
0.45 M N3
.
Figure 7 shows that the yield of 5c depends on [N3-] in the
concentration range 0-0.45 M. The yield of 5c was fit by eq
5, where S is the observed azide/solvent selectivity and [5c]max
is the maximum yield of 5c at infinite [N3-]. It can be shown
that S g kaz/ks, the ratio of the second-order rate constant for
-
trapping of the free cation by N3 and the pseudo-first-order
rate constant for trapping of the ion by the solvent (Scheme
5).25
-
-
[5c] ) ([5c]max)(S[N3 ])/(1 + S[N3 ])
(5)
-
ca. 54% to 42% in the presence of N3 and the yield of 16
increases by about half that amount, from ca. 17% to 24%. The
The data are adequately fit by eq 5 with S ) 2.1 ( 0.8 M-1
and [5c]max ) (1.1 ( 0.3) × 10-5 M, or (13 ( 3)%. Trapping
by N3- accounts for only a small part of the overall reaction of
4c and is also inefficient for the fraction of the path that is
trapped.
(23) (a) Wasserman, E.; Smolinsky, G.; Yager, W. A. J. Am. Chem. Soc.
1964, 86, 3166-3167. (b) Moriarty, R. M.; Rahman, M.; King, G. J. J.
Am. Chem. Soc. 1966, 88, 842-8433. (c) Abramovitch, R. A.; Knaus, G.
N.; Uma, V. J. Am. Chem. Soc. 1969, 91, 7532-7533.
(24) Oae, S.; Sakurai, T. Tetrahedron 1976, 32, 2289-2294.
(25) Novak, M.; Kahley, M. J.; Lin, J.; Kennedy, S. A.; James, T. G. J.
Org. Chem. 1995, 60, 8294-8304.
For long-lived, highly selective ions S ) kaz/ks, but for
unstable species with short aqueous solution lifetimes (<1 ns)
the majority of the trapping occurs via a preassociation
(26) Y. Wang and M. Novak, work in progress.
J. Org. Chem, Vol. 72, No. 26, 2007 9959

Novak et al.
BPW91/cc-pVDZ.17,28 This is due, at least in part, to limited
configuration interaction caused by the relatively large singlet-
triplet energy gap in these ions.17 This is also true for similarly
substituted aryloxenium ions.17 It appears that the B3LYP/6-
31G*//HF/6-31G* calculations provide useful results, particu-
larly when applied to isodesmic reactions.15-17 We have
previously shown that zero-point energy (ZPE) and thermody-
namic corrections to ∆E largely cancel, so they have not been
included in these calculations.15,17 The results shown in Table
2 suggest that electron correlation effects also largely cancel,
as previously observed.15-17
SCHEME 6. Isodesmic Reaction of 4-Substituted
Aryloxenium Ions
TABLE 2. Calculated Values of ∆E for 1a-e and Extrapolated
kaz/ks for 1a-c
The 4-alkyl-substituted ions 1a-c are clearly significantly
destabilized compared to 1d and 1e, although the isopropyl and
tert-butyl substituents of 1b and 1c apparently provide marginal
stabilization (ca. 5 kcal/mol) for hydration of these two species.
We have previously noted that 4-aryl substituents have a
significant stabilizing effect on aryloxenium ions.15,16 A previ-
ously published correlation of observed log (kaz/ks) at 30 °C
versus ∆E at the B3LYP/6-31G*//HF/6-31G* level for four
4-aryl-substituted aryloxenium ions including 1d and 1e provides
a means to extrapolate kaz/ks for 1a-c.16 The extrapolation
provides the values shown in Table 2. The measured kaz/ks for
the ions used in the correlation are in the range from ca. 102 to
105 M-1, and ∆E at the B3LYP/6-31G*//HF/6-31G* level for
those ions are in the range 29-43 kcal/mol, so the extrapolation
is quite long. Assuming that kaz is diffusion-limited at ca. 6 ×
∆E (kcal/mol)
extrapolated
ion
HF/6-31G*
B3LYP/6-31G*//HF/6-31G*
kaz/ks (M-1
)
1a
1b
1c
1d
1e
10.6
16.0
15.2
30.6
25.9
11.2
16.6
16.0
35.4
30.3
1.8 × 10-3
3.8 × 10-2
2.8 × 10-2
mechanism and S > kaz/ks.18,25,27 For the present case, since the
-
N3 trapping accounts for such a small part of the reaction of
4c, it is not possible to unequivocally state that an oxenium ion
has been trapped. Rate changes that could distinguish between
trapping of an intermediate generated after a rate-limiting step
or direct reaction on 4c are within the error limits of the kinetics
measurements when trapping amounts to <10% of the overall
reaction. If the oxenium ion 1c is trapped, kaz must be diffusion-
limited at ca. 1010 M-1 s-1 at 50 °C for such a reactive species,
and ks is g 0.5 × 1010 s-1. The lifetime (1/ks) of the putative
ion is no more than 0.2 ns if the reaction occurs through a free
ion. In contrast, 1d has an estimated lifetime of ca. 170 ns at
30 °C based on N3- trapping16 The azide/solvent selectivity for
1c is in the range in which a significant amount of the trapping
occurs via preassociation.18,25,27 The lifetime estimate of 0.2 ns
for 1c must be considered an upper limit since it cannot be
established that the trapping actually occurs on the ion, and if
an ion is involved a significant part of the trapping must occur
by preassociation. For nitrenium ions with similar azide/solvent
selectivity, the lifetime of the “free” ion is approximately an
order of magnitude less than calculated from the experimental
azide/solvent selectivity.25 This would suggest that the lifetime
of “free” 1c is no larger than ca. 20 ps. This is similar to the
estimates of 3-5 ps for 1a based on earlier density functional
theory (DFT) calculations and kinetic extrapolations of ions with
known lifetimes.15
109 M-1 s-1 14
, the estimated lifetimes (1/ks) of 1a (0.3 ps), 1b
(6 ps), and 1c (5 ps) are too short by 2-3 orders of magnitude
to be diffusionally trapped by a non-solvent nucleophile.18,25,27
The estimated lifetime of 1a is about 10-fold shorter than we
have previously estimated by two other kinetic extrapola-
tions.15,29 These lifetime estimates have an error limit of at least
an order of magnitude, but they do indicate that simple
4-alkylaryloxenium ions are fleeting and unselective species in
water that will react only with nucleophiles that are present in
the solvation shell in which they are generated.18,25,27 The
calculations also suggest that the reason precursors such as 2a-
c, 3a,b, and 4c do not efficiently generate 4-alkylaryloxenium
ions while 2d, 4d, and similar compounds do generate 4-ary-
laryloxenium ions is due to the significant stabilization provided
to the latter species by the 4-aryl substituent.
Conclusion
The putative oxenium precursors 2b, 2c, 3b, and 4c exhibit
a variety of chemistry, but with one possible exception, they
do not generate an oxenium ion. The 4-isopropyl ester 2b,
similar to its 4-methyl analogue 2a, reacts predominantly by
ordinary ester hydrolysis, while the 4-tert-butyl ester 2c appar-
ently generates the tert-butyl cation by acid-catalyzed and
uncatalyzed pathways. The 4-isopropyl ester with the dichlo-
The isodesmic reaction of Scheme 6 has proven to be a useful
tool for the correlation of experimental and calculated properties
of oxenium ions.15-17 ∆E for the reaction provides the calculated
driving force for hydration of 4-substituted aryloxenium ions
to form the corresponding quinols, 6, relative to the unsubstituted
ion. ∆E values calculated at the HF/6-31G* and B3LYP/6-
31G*//HF/6-31G* levels for ions 1a-e are presented in Table
2. We have previously shown that singlet-triplet energy gaps
and structures of para-substituted arylnitrenium ions calculated
by DFT methods on HF/6-31G* geometries are comparable to
those calculated on the same ions with full DFT optimization
on a correlation-consistent polarized valence double-ú basis set,
-
roacetate leaving group, 3b, generates the oxenium-like N3
trapping product 5b but does so by a kinetically bimolecular
path that does not involve an oxenium ion. The sulfonamide 4c
(28) Sullivan, M. B.; Brown, K.; Cramer, C. J.; Truhlar, D. G. J. Am.
Chem. Soc. 1998, 120, 11778-11783.
(29) A reviewer has suggested that solvation effects might significantly
alter the extrapolations of these kinetic correlations. In a preliminary study
we added the AM1 SM5.4 aqueous solvation energies to the B3LYP/6-
31G*//HF/6-31G* energies of 1 and 6 in Scheme 6. The correlation of the
four original ions was not significantly altered, and the long extrapolation
to 1a-c led to modest changes in the estimated lifetime of these ions: 1.7
ps for 1a, 12.8 ps for 1b, and 3.3 ps for 1c. These lifetime estimates do not
change our original conclusions.
(27) Novak, M.; Rajagopal, S. AdV. Phys. Org. Chem. 2001, 36, 167-
254.
9960 J. Org. Chem., Vol. 72, No. 26, 2007

Chemistry of 4-Alkylaryloxenium Ion “Precursors”
+ H - N2); high-resolution MS (ES, positive) C10H13N3ONa (M
+ Na) calcd 214.0956, found 214.0951.
may generate the oxenium ion 1c via a minor decomposition
pathway, but if the ion is generated, its aqueous solution lifetime
is in the range of 20-200 ps. Many of the cases in which
oxenium ions have been invoked to explain reaction products
have involved alkyl-substituted ions in nucleophilic solvents
such as H2O or MeOH.1-13 In view of our results, alternative
mechanisms should be considered in these cases.
Product 14. A 50 mg sample of 2-azidohydroquinone 1318 (0.33
mmol) was dissolved in 1 mL of dry CH3CN. This solution was
added in 0.1 mL aliquots every 0.5 h to 0.5 L of a 0.5 M 1/1 NaN3/
HN3 buffer containing 5 vol % CH3CN that was incubated at 50
°C in a shaker bath. The mixture was periodically monitored by
HPLC. After 12 h the reaction mixture was refrigerated overnight
and then brought back to room temperature the next day. HPLC
showed the peak for the product continued to increase in intensity
during the day. The sample was refrigerated overnight and brought
back to room temperature during the day for 5 days until HPLC
indicated that the product peak had reached maximum intensity.
The reaction mixture was then neutralized to a pH of 7 with
saturated aqueous NaHCO3 and extracted (3 × 100 mL) with CH2-
Cl2. The combined extracts were dried over Na2SO4, filtered, and
evaporated to dryness on a rotary evaporator to yield 25 mg of a
blue-black solid. TLC on silica gel with CH2Cl2 eluent indicated
one major component, as did HPLC analysis. HPLC analysis
showed that the isolated product had the same retention time as
Experimental Section
Synthesis of compounds 2b, 2c, 3b, and 4c followed procedures
that we have published for related materials.14-16 Details of the
synthesis, purification, and characterization of these materials can
be found in the Supporting Information.
Isolation, Purification, and Characterization of Reaction
Products. Four azide-containing products were isolated from large-
scale decomposition reactions in buffers containing N3-: 5b, 5c,
11b, and 14.
Products 5b and 11b. A 136 mg sample of 3b (0.52 mmol)
was dissolved in 1 mL of dry CH3CN. This solution was added in
0.1 mL aliquots every 3 h to 1 L of a 5 M 1/1 NaN3/HN3 buffer
containing 5 vol % CH3CN that was incubated at 30 °C in a shaker
bath. (Caution: HN3 is nearly saturated under these conditions. The
reaction flask should be kept stoppered in a well-ventilated location,
and inhalation of toxic HN3 should be avoided.) The reaction
mixture was neutralized with solid NaHCO3 to a pH of 6.5 when
HPLC indicated that the reaction was complete (48 h). The aqueous
reaction mixture was extracted with CH2Cl2 (5 × 100 mL). The
combined organic extracts were dried over Na2SO4, filtered, and
evaporated on a rotary evaporator at ambient temperature to yield
95 mg of crude product. This material was applied to a 2 mm silica
gel chromatatron plate and eluted with CH2Cl2. Two azide-
containing materials were isolated: 20 mg of 5b and 12 mg of
11b. 2D NMR data and complete NMR assignments for both
compounds are presented in the Supporting Information.
2-Azido-4-isopropylphenol (5b). mp 43-44 °C; IR 3425, 2960,
-
the material obtained from the reaction mixtures of 2c in N3
solutions.
2,3,5,6-Tetrazido-1,4-benzoquinone (14). Blue-black solid; IR
2105, 1662, 1581, 1327 cm-1 13C NMR (125.8 MHz, CD2Cl2) δ
;
126.7, 176.1. The compound is described in the literature, but IR
and NMR data have not been previously reported.20,21 A sample
prepared from chloranil according to the literature procedure20 has
the same IR and 13C NMR peaks as the compound isolated from
the product study but is significantly less pure. Since the compound
is reported to be highly explosive,20,21 and scratching of 5 mg of
the sample prepared from chloranil on a glass plate led to a spark
and an audible pop, no further attempts to purify either sample
were made.
Reaction products that did not contain azide, 6b, 8, 15, 16, and
17, were isolated from large-scale decomposition reactions. Products
8, 16, and 17 were identified by direct IR and NMR comparison to
authentic samples. Hydroquinone 9, and benzoquinone 10 were not
isolated but were identified by HPLC retention time comparisons
to authentic materials. Isolation, purification, and characterization
of 6b and 15 are described below.
Product 6b. A 50 mg sample of 3b (0.19 mmol) was dissolved
in 1 mL of dry CH3CN. This solution was added in 0.1 mL aliquots
every 15 min to 250 mL of a 0.02 M phosphate buffer, pH 7.45,
containing 5 vol % CH3CN that was incubated at 30 °C in a water
bath. The reaction mixture was incubated for an additional 3 h after
addition of the last aliquot of 3b. The reaction mixture was extracted
(5 × 50 mL) with CH2Cl2. The combined extracts were dried over
Na2SO4, filtered, and evaporated to dryness on the rotary evaporator
to yield 25 mg of an off-white solid that was sufficiently pure for
characterization.
1
2104, 1600, 1510, 1300, 1249, 1195 cm-1; H NMR (500 MHz,
CD2Cl2) δ 1.22 (6H, d, J ) 6.9 Hz), 2.86 (1H, septet, J ) 6.9 Hz),
5.22 (1H, s), 6.82 (1H, d, J ) 8.3 Hz), 6.92 (1H, dd, J ) 1.8, 8.2
Hz), 6.95 (1H, d, J ) 2.1 Hz); 13C NMR (125.8 MHz, CD2Cl2) δ
24.2, 33.9, 116.0, 116.7, 124.3, 125.9, 142.6, 145.7; LC/MS (APCI,
positive) m/e 150 (100%) (M + H - N2); high-resolution MS (ES,
positive) C9H11N3ONa (M + Na) calcd 200.0800, found 200.0800.
3-Azido-4-isopropylphenol (11b). mp 54-55 °C; IR 3333,
1
2963, 2110, 1609, 1591, 1504, 1297, 1218 cm-1; H NMR (500
MHz, CD2Cl2) δ 1.16 (6H, d, J ) 6.9 Hz), 3.11 (1H, septet, J )
6.9 Hz), 4.98 (1H, s), 6.59 (1H, dd, J ) 2.5, 8.4 Hz) 6.63 (1H, d,
J ) 2.4 Hz), 7.10 (1H, d, J ) 8.4 Hz); 13C NMR (125.8 MHz,
CD2Cl2) δ 23.1, 27.7, 105.5, 112.4, 127.9, 132.8, 138.5, 154.9; LC/
MS (APCI, positive) m/e 150 (100%) (M + H - N2); high-
resolution MS (ES, positive) C9H11N3ONa (M + Na) calcd
200.0890, found 200.0794.
4-Hydroxy-4-isopropyl-2,5-cyclohexadienone (6b). mp 70.5-
1
71.5 °C; IR 3337, 2963, 1655, 1615, 971 cm-1; H NMR (300
MHz, CD2Cl2) δ 0.95 (6H, d, J ) 6.9 Hz), 2.06, (1H, septet, J )
6.9 Hz), 2.09 (1H, s), 6.18, (2H, d, J ) 10.2 Hz), 6.80 (2H, d, J )
10.2 Hz); 13C NMR (75.5 MHz, CD2Cl2) δ 17.0, 37.1, 72.6, 129.3,
150.5, 185.9; LC/MS (APCI, positive) m/e 135 (100%) (M + H -
H2O); high-resolution MS (ES, positive) C9H12O2Na (M + Na)
calcd 175.0735, found 175.0733.
Product 15. A 100 mg sample of 4c (0.41 mmol) was dissolved
in 2 mL of dry CH3CN. This solution was added in 0.2 mL aliquots
every 50 min to 500 mL of a 0.02 M phosphate buffer, pH 6.6,
containing 5 vol % CH3CN that was incubated in a water bath at
50 °C. The reaction mixture was incubated overnight after addition
of the last aliquot of 4c. The mixture was extracted (5 × 50 mL)
with CH2Cl2. The combined extracts were dried over Na2SO4,
filtered, and evaporated to dryness on the rotary evaporator. The
residue was applied to a 2 mm silica gel chromatatron plate and
eluted with 90/10 CH2Cl2/EtOAc. The fraction containing 15
Product 5c. A 100 mg sample of 4c (0.5 mmol) was dissolved
in 10 mL of dry CH3CN. This solution was added over 4 h via
syringe pump to 1 L of a 0.02 M phosphate buffer, pH 7.0,
containing 5 vol % CH3CN and 0.45 M NaN3 that was incubated
in a shaker bath at 50 °C. The reaction mixture was extracted (4 ×
100 mL) with CH2Cl2 when HPLC indicated that the reaction was
complete (10 h). The combined extracts were dried over Na2SO4,
filtered, and evaporated at ambient temperature on a rotary
evaporator. The residue was applied to a 2 mm silica gel
chromatatron plate and eluted with 95/5 CH2Cl2/EtOAc. One azide-
containing product was isolated: 4 mg of 5c.
2-Azido-4-tert-butylphenol (5c). Yellow to brown oil; IR 3300,
2963, 2119, 1514 cm-1; 1H NMR (300 MHz, CD2Cl2) δ 1.33 (9H,
s), 5.25 (1H, br s), 6.86 (1H, d, J ) 8.6 Hz) 7.08-7.12 (2H, m);
13C NMR (75.5 MHz, CD2Cl2) δ 31.5, 34.7, 115.6, 115.9, 123.4,
125.5, 145.0, 145.4; LC/MS (APCI, positive) m/e 164 (100%) (M
J. Org. Chem, Vol. 72, No. 26, 2007 9961

Novak et al.
yielded 55 mg of a white solid that was sufficiently pure for
characterization.
at 30 °C, and the reaction was monitored by HPLC. Control
experiments with 2 × 10-2 M 12 were run at the same time. When
2c had disappeared from the reaction mixture according to HPLC,
the reaction and control mixtures were cooled to room temperature,
n-decanol (2 × 10-2 M) was added followed by 0.30 g of NaCl,
and the aqueous mixtures were extracted with 2 mL of CH2Cl2.
The organic extract was removed to a separate conical vial by pipet,
dried over Na2SO4, and kept tightly sealed until GC analysis that
was initiated within 20 min of completion of extraction. Duplicate
injections of each sample were averaged. All data were corrected
to the internal standard, and yields were determined by comparison
of the corrected peak areas for 12 in the experimental and control
run.
N-(5-tert-Butyl-2-hydroxyphenyl)methanesulfonamide (15).
mp 145-147 °C; IR 3382, 3297, 2954, 1615, 1514, 1382, 1303,
1288, 1130, 1124 cm-1; 1H NMR (300 MHz, CD2Cl2) δ 1.29 (9H,
s), 2.98 (3H, s), 6.2 (2H, br s), 6.90 (1H, d, J ) 8.3 Hz) 7.21 (1H,
dd, J ) 2.3, 8.4 Hz), 7.24 (1H, d, J ) 2.1 Hz); 13C NMR (75.5
MHz, CD2Cl2) δ 31.5, 34.5, 38.9, 116.9, 122.9 123.0, 125.7, 145.2,
148.3; LC/MS (ESI, positive) m/e 266 (80%) (M + Na), 165
(100%) (M + H - SO2CH3); LC/MS (ESI, negative) m/e 242
(100%) (M - H); high-resolution MS (ES, positive) C11H17NO3-
SNa (M + Na) calcd 266.0827, found 266.0823.
Kinetics and Product Analyses. All kinetics were run in 5 vol
% CH3CN-H2O at µ ) 0.5 (NaClO4) in HClO4 solutions (pH <
3.0), or in 0.02 M HCO2H/NaHCO2, AcOH/AcONa, NaH2PO4/ Na2-
HPO4, or TrisH+/Tris buffers at 30 °C (2c, 3b), 50 °C (4c), or 80
°C (2b). Reactions were initiated by injection of 15 µL of a 0.01-
0.02 M stock solution of the desired compound in dry CH3CN into
3 mL of the reaction solution that had been incubated at the
appropriate temperature for at least 15 min. UV absorption versus
time data were taken at 244 nm for 2b; at 240, 247, and 255 nm
for 2c; at 220 and 240 nm for 3b; and at 205 and 224 nm for 4c.
HPLC data were monitored at 240 nm for 2b, 2c, and 3b and at
220 nm for 4c. Other HPLC conditions were C-8 reverse-phase
column, 50/50-60/40 MeOH/H2O, 1 mL/min flow rate, 20 µL
injections. These same HPLC conditions were used for product
analyses at the end of kinetic runs and during isolation experiments.
Most UV and HPLC data were fit by nonlinear least-squares
methods to the standard first-order rate equation. If initial reaction
products were unstable, UV absorbance and HPLC peak area data
for the unstable product were fit to the standard equation for
consecutive first-order reactions. HPLC peak area data for the
reactants always fit the first-order rate equation well, as did UV
absorbance data for cases in which the products were stable. HPLC
was always used to verify the magnitude of the rate constant for
disappearance of the reactant (kobs) in cases in which the UV
absorbance data had to be fit to the consecutive first-order rate
equation. Rate constants for very slow reactions (kobs < 5 × 10-6
s-1) were determined by fitting UV absorbance or HPLC peak area
versus time for the first 5% of the reaction to a linear equation and
dividing the slope by either the total UV absorbance change or by
the initial HPLC peak area. The experimental conditions and
calculation methods for each rate constant obtained are provided
in Tables S1-S4 in the Supporting Information.
Calculations. Detailed descriptions of the calculation methods
have been published.17 Geometries and energies for 1a, 1d, 1e, 6a,
6d, and 6e have been published.15,16 The same procedures were
followed for 1b, 1c, 6b, and 6c utilizing Spartan 04 for Macintosh
Version 1.0.1 and Spartan Version 5.30 Geometries were optimized
at the HF/6-31G* level. Frequency analyses were performed at this
level to verify that all geometries corresponded to true stationary
points. These geometries were used to obtain energies at the density
functional level B3LYP/6-31G*//HF/6-31G*. Optimized HF/6-
31G* geometries and energies at all levels calculated for 1b, 1c,
6b, and 6c are presented in the Supporting Information.
The isodesmic reaction of Scheme 6 was used to evaluate the
hydration energies of 1a-e relative to the parent phenyloxenium
ion. Calculations of isodesmic reactions were carried out by use of
(1) HF/6-31G* energies without electron correlation or (2) B3LYP/
6-31G*//HF/6-31G* with electron correlation.
Acknowledgment. We thank the Donors of the American
Chemical Society Petroleum Research Fund for support of this
research (Grant 43176-AC4). The 500 MHz NMR spectrometer
and the LC/MS were provided by grants to Miami University
by the Hayes Investment Fund of the Ohio Board of Regents.
J.N.D. received a summer research internship from the Depart-
ment’s NSF-REU grant. J.M.E. received a grant for research
supplies from Miami’s Undergraduate Research Awards Pro-
gram.
Supporting Information Available: Synthesis and character-
ization of 2b, 2c, 3b, and 4c; Tables S1-S4, containing rate
1
constants for all reactions of 2b, 2c, 3b, and 4c; complete H and
13C NMR assignments for 5b and 11b; Figure S1, spectrophoto-
metric titration of 4c; Figure S2, product yields for the decomposi-
tion of 4c as a function of pH; 1H and 13C NMR spectra for 2b, 2c,
3b, 4c, 5b, 5c, 6b, 11b, 14, and 15; and optimized geometries for
1b, 1c, 6b, and 6c at the HF/6-31G* level with energies at the
HF/6-31G* and B3LYP/6-31G*//HF/6-31G* levels. This material
is available free of charge via the Internet at http://pubs.acs.org.
Detection and quantification of tert-butanol, 12, generated during
the decomposition of 2c was performed by gas chromatography
with the following GC conditions: 0.25 mm × 30 m VF-35ms
column, 2 µL injections at 250 °C and 5/1 split, initial 50 °C column
for 5 min increasing by 10 °C/min to 250 °C, 0.3 mL/min flow
rate, FID detection with 250 °C detector oven, n-decanol internal
standard. Reactions were run at pH 1.0 and 7.0 in solutions identical
to those used for kinetics except that CH3CN was not included.
Reaction was initiated by adding sufficient solid 2c to 2 mL of the
reaction mixture stirred in a 5 mL conical vial to bring the initial
concentration to ca. 2 × 10-2 M. Reaction mixtures were incubated
JO701853E
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9962 J. Org. Chem., Vol. 72, No. 26, 2007