Transition-state effects in acid-catalyzed aryl epoxide hydrolyses

Article abstract of DOI:10.1021/jo040160j

The hydronium ion-catalyzed hydrolyses of 5-methoxyindene 1,2-oxide and of 6-methoxy-1,2,3,4-tetrohydronaphthalene-1,2-epoxide were each found to yield 75-80% of cis diol and only 20-25% of trans diol as hydrolysis products. The relative stabilities of the cis and trans diols in each system were determined by treating either cis or trans diols with perchloric acid in water solutions and following the approach to an equilibrium cis/trans mixture as a function of time. These studies establish that the trans diol in each system is more stable than the corresponding cis diol. Thus, acid-catalyzed hydrolysis of each epoxide, which proceeds via a carbocation intermediate, yields the less stable cis diol as the major product. Transition-state effects, presumably of a hydrogen-bonding nature, selectively stabilize the transition state for attack of water on the intermediate 2-hydroxy-1-indanyl carbocation leading to the less stable cis diol in this system. Transition-state effects must also be responsible for formation of the less stable cis diol as the major product in the acid-catalyzed hydrolysis of 5-methoxy-1,2,3,4-tetrahydronaphthalene 1,2-epoxide. However, in this system steric effects at the transition state may be more important than hydrogen bonding in determining the cis/trans diol product ratio. The synthesis of 5-methoxyindene 1,2-oxide and a study of its rate of reaction as a function of pH in water and dioxane-water solutions are reported. Both an acid-catalyzed reaction leading to only diol products and a pH-independent reaction yielding 71% of 5-methoxy-2-indanone and 29% of diols are observed; the half-life of its pH-independent reaction in water is only 2.4 s.

Full text of DOI:10.1021/jo040160j

Tr a n sition -Sta te Effects in Acid -Ca ta lyzed Ar yl Ep oxid e
Hyd r olyses
Kyere Sampson, Augustine Paik, Bridget Duvall, and Dale L. Whalen*
Department of Chemistry and Biochemistry, University of Maryland, Baltimore County,
Baltimore, Maryland 21250
whalen@umbc.edu
Received March 25, 2004
The hydronium ion-catalyzed hydrolyses of 5-methoxyindene 1,2-oxide and of 6-methoxy-1,2,3,4-
tetrohydronaphthalene-1,2-epoxide were each found to yield 75-80% of cis diol and only 20-25%
of trans diol as hydrolysis products. The relative stabilities of the cis and trans diols in each system
were determined by treating either cis or trans diols with perchloric acid in water solutions and
following the approach to an equilibrium cis/trans mixture as a function of time. These studies
establish that the trans diol in each system is more stable than the corresponding cis diol. Thus,
acid-catalyzed hydrolysis of each epoxide, which proceeds via a carbocation intermediate, yields
the less stable cis diol as the major product. Transition-state effects, presumably of a hydrogen-
bonding nature, selectively stabilize the transition state for attack of water on the intermediate
2-hydroxy-1-indanyl carbocation leading to the less stable cis diol in this system. Transition-state
effects must also be responsible for formation of the less stable cis diol as the major product in the
acid-catalyzed hydrolysis of 5-methoxy-1,2,3,4-tetrahydronaphthalene 1,2-epoxide. However, in this
system steric effects at the transition state may be more important than hydrogen bonding in
determining the cis/trans diol product ratio. The synthesis of 5-methoxyindene 1,2-oxide and a
study of its rate of reaction as a function of pH in water and dioxane-water solutions are reported.
Both an acid-catalyzed reaction leading to only diol products and a pH-independent reaction yielding
71% of 5-methoxy-2-indanone and 29% of diols are observed; the half-life of its pH-independent
reaction in water is only 2.4 s.
In tr od u ction
varying cis/trans ratios.6-9 For example, the cis/trans diol
ratio from acid-catalyzed hydrolysis of 1,2,3,4-tetrahy-
dronaphthalene 1,2-epoxides is highly sensitive to the
electronic effects of substituents in the 6-position of the
aromatic ring (Scheme 1).6 Acid-catalyzed hydrolysis of
1a yields 5% of cis diol 3a and 95% of trans diol 4a ,
whereas acid-catalyzed hydrolysis of 1b gives 80% of cis
diol 3b and only 20% of trans diol 4b. These results have
been rationalized by a mechanism in which there are two
conformations of the carbocation intermediate 2, each
reacting with solvent to yield diols in different cis/trans
ratios.
The acid-catalyzed hydrolyses of para-substituted 1-phe-
nylcyclohexene oxides yield mixtures of cis and trans
diols, and the percent of cis diol is reported to increase
systematically with the increasing electron-donating
ability of the para-substituent from only 7.5% for a nitro
substituent to 95.2% for a methoxyl substituent.8 A later
study of the hydrolyses of these epoxides under conditions
in which the diols were stable showed that the acid-
catalyzed hydrolyses of the H-, CH3-, and CH3O-substi-
tuted epoxides indeed yield cis diol as the major product
The acid-catalyzed reactions of epoxides to form diols
and other compounds have been extensively studied.1 In
this reaction, the C-O bond that undergoes the greater
extent of cleavage is generally the one between oxygen
and the more highly substituted carbon.2 In the hydroly-
sis of 1,2-disubstituted epoxides, the diol product can
potentially be the result of syn or anti hydration. Acid-
catalyzed hydrolyses of alkene oxides such as cis- and
trans-2-butene oxides3 and cycloalkene oxides such as
cyclohexene oxide4 yield only diols resulting from anti
hydration. It is thought that these epoxide hydrolysis
reactions occur by an A-2 mechanism in which epoxide
C-O bond cleavage and attack of water on protonated
epoxide are concerted.5
Acid-catalyzed hydrolyses of aryl and vinyl epoxides,
in contrast, yield mixtures of cis and trans diols in
* Corresponding author. Tel: 410-455-2521. Fax: 410-455-1874.
(1) For comprehensive early reviews, see: (a) Parker, R. E.; Isaacs,
N. S. Chem. Rev. 1959, 59, 737-799. (b) Rosowsky, A. In Heterocyclic
Compounds with Three- and Four-membered Rings; Weissberber, A.,
Ed.; Interscience: New York, 1964; Part 1, pp 1-523. (c) Buchanan,
J . G.; Sable, H. Z. In Selective Organic Transformations; Thyagarajan,
B. S., Ed.; Wiley-Interscience: New York, 1972; Vol. 2, pp 1-95.
(2) Long, F. A.; Pritchard, J . G J . Am. Chem. Soc. 1956, 78, 2663-
2670.
(6) Gillilan, R. E.; Pohl, T. M.; Whalen, D. L. J . Am. Chem. Soc.
1982, 104, 4481-4482.
(7) Mohan, R. S.; Whalen, D. L. J . Org. Chem. 1993, 58, 2663-2669.
(8) Croti, Battistini, C.; Balsamo, A.; Berti, G.; Crotti, P.; Macchia,
B.; Macchia, F. J . Chem. Soc., Chem Commun. 1974, 712-713.
(9) Doan, L.; Bradley, K., Gerdes, S.; Whalen, D. L. J . Org. Chem.
1999, 64, 6227-6234.
(3) Wilson, C. E.; Lucas, H. J . J . Am. Chem. Soc. 1936, 58, 2396-
2402.
(4) Winstein, S. J . Am. Chem. Soc. 1942, 64, 2792-2795.
(5) Wohl, R. A. Chimia 1974, 28, 1-5.
10.1021/jo040160j CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/09/2004
5204
J . Org. Chem. 2004, 69, 5204-5211

Transition-State Effects in Acid-Catalyzed Aryl Epoxide Hydrolyses
SCHEME 1
SCHEME 2
F IGURE 1. Plots of log kobsd versus pH for reaction of 5b in
water, 10:90 dioxane-water and 25:75 dioxane-water (v/v),
0.1 M NaClO4, 25.0 ( 0.2 °C. The solid lines are theoretical,
based on eq 1 and the rate parameters listed in Table 1.
Resu lts
5-Methoxyindene oxide (5b) was prepared in excellent
yield by stirring a solution of trans-2-bromo-5-methoxy-
indan-1-ol in anhydrous THF with powdered potassium
hydroxide. The epoxide is conveniently isolated by filtra-
tion of the reaction mixture to remove suspended KOH/
KBr salts and removal of the solvent from the filtrate by
rotary evaporation.
Plots of log kobsd for reaction of 5b vs pH in water,
10:90 dioxane-water, and 25:75 dioxane-water are
provided in Figure 1. A pH-independent reaction of 5b
in water is the principal reaction above pH 6, with a half-
life of ∼2.4 s. At pH 5.5 the rate is slightly faster,
suggesting the incursion of an acid-catalyzed reaction.
However, at pH less than 5.5, the rate of reaction is too
great to accurately measure by simple mixing technique.
The rate of the pH-independent reaction is slowed
significantly in dioxane-water solutions, however, whereas
the bimolecular rate constant for the acid-catalyzed
reaction is very similar in all three solvents. As a result,
the changeover in mechanism from the pH-independent
reaction to the acid-catalyzed reaction occurs at higher
pH in solutions containing more dioxane, and the pH
region for the acid-catalyzed reaction becomes more
pronounced.
(>65%) but that the cis/trans diol product ratio does not
change significantly as the para substituent is changed
from hydrogen to the more electron-donating substituents
methyl and methoxyl.9 From rate-product studies of the
hydrolysis of 1-(p-methoxyphenyl)cyclohexene oxide in
solutions containing varying concentrations of sodium
azide, it was concluded that an intermediate carbocation
is formed in a rate-limiting step and that the diol
products are formed from attack of water on a carbocation
intermediate. It was also determined from equilibration
studies that the cis diol in this system is more stable than
the trans diol, and therefore it was suggested that factors
that contribute to the greater stability of the cis diol
product also contributed to the lowering of the transition
state energy for attack of water on the carbocation
leading the to major cis diol product.9
To ascertain whether product stability plays an im-
portant role in determining the cis:trans diol ratio from
the acid-catalyzed hydrolysis of aryl epoxides in general,
we have established the relative stabilities of cis- and
trans-5-methoxy-1,2-indandiols and of cis- and trans-6-
methoxy-1,2,3,4-tetrahydronaphthalene-1,2-diols and have
compared the equilibrium cis/trans ratios of the stereo-
isomeric diols with the ratio of cis and trans diols formed
from acid-catalyzed hydrolysis of the corresponding ep-
oxides. The acid-catalyzed hydrolysis of indene oxide 5a
is reported to yield cis and trans diols 7a and 8a (Scheme
2) in a 75:25 ratio,10,11 but the preparation and study of
the reactions of 5-methoxyindene oxide 5b have not been
reported. We have therefore synthesized 5b and also
report a study of its hydrolysis reactions along with the
equilibration study of its cis and trans diol hydrolysis
products.
The rate data summarized in Figure 1 for the reaction
of 5b were fit to eq 1, where kH is the second-order rate
constant for the acid-catalyzed reaction and ko is the first-
order rate constant for the pH-independent reaction. A
summary of the rate constants for reaction of 5b is
provided in Table 1.
kobsd ) kH[H+] + ko
(1)
Products from the acid-catalyzed hydrolysis of 5b at
pH 3.2, where >98% of the reaction is acid-catalyzed, are
cis and trans diols 7b and 8b in a 80:20 cis/trans ratio.
This ratio of diols is very similar to that from acid-
catalyzed hydrolysis of indene oxide (5a ) (cis/trans diol
ratio75:25).11
Substitution of a methoxyl group at the 5-position
results in increased rate constants for the acid-catalyzed
(∼102) and pH-independent reactions (>103) but does not
(10) Balsamo, A.; Berti, G.; Crotti, P.; Ferretti, M.; Macchia, B.;
Macchia, F. J . Org. Chem. 1974, 39, 2596-2598.
(11) Whalen, D. L.; Ross, A. M. J . Am. Chem. Soc. 1976, 98, 7859-
7861.
J . Org. Chem, Vol. 69, No. 16, 2004 5205

Sampson et al.
TABLE 1. Su m m a r y of Ra te Con sta n ts for Rea ction of
5-Meth oxyin d en e Oxid e (5b) in Wa ter , 10:90
Dioxa n e-Wa ter a n d 25:75 Dioxa n e-Wa ter Solu tion s, 25
°C, 0.1 M Na ClO4
solvent
kH (M-1s-1
)
ko (s-1
)
watera
6 × 104
(2.93 ( 0.04) × 10-1
10:90 dioxane-water (5.92 ( 0.20) × 104 (1.70 ( 0.20) × 10-1
25:75 dioxane-water (5.25 ( 0.27) × 104 (5.17 ( 0.11) × 10-2
a
Because of the high reactivity of 1b in water, there were
insufficient rate data at pH < 5.5 for calculation of an accurate
value for kH. A value of 6 × 104 M-1s-1 was assumed for this rate
constant.
alter significantly the relative yields of products from
each reaction.
p H-In d ep en d en t Rea ction of 5-Meth oxyin d en e
Oxid e (5b). In water, the rate of reaction of 5b does not
change throughout the pH range 6-9. The reaction of
5b that occurs in this pH range yields 71% of 5-methoxy-
2-indanone as the major product and cis- and trans-5-
methoxyindan-1,2-diols as minor products in a 75:25
ratio. Whereas the half-life for reaction of 5b at pH > 6
in water is only 2.4 s, its half-life in 25:75 dioxane-water
is 13.4 s.
F IGURE 2. Plots of percent cis diol 7b versus time in the
equilibration reactions starting from either a mixture of 80%
cis diol (7b)/20% trans diol (8b) or pure trans diol (8b) in 0.05
M HClO4 water solution, 25.0 ( 0.2 °C. The lines are
theoretical, based on eq 3.
-
The observation that the pH-independent reaction of
5b yields ketone as a major product and both cis and
trans diols as minor but significant products is intriguing.
Similar products and product yields are formed from the
pH-independent reactions of indene oxide 5a and of
6-methoxy-1,2,3,4-tetrahydronaphthalene-1,2-epoxide (1b).
Rate-limiting hydrogen migration on the ketone-forming
reaction of 1b has been proposed.12 However, the pH-
independent reaction of 1,2,3,4-tetrahydronaphthalene-
1,2-oxide (1a ) yields only trans diol.13 The mechanism of
pH-independent epoxide reactions therefore depend mark-
edly on the structure of the epoxide. More detailed studies
of the pH-independent reactions of these epoxides are in
progress.
Acid -Ca ta lyzed Equ ilibr a tion of cis- a n d tr a n s-
5-Meth oxyin d a n -1,2-d iols a n d of cis- a n d tr a n s-6-
Meth oxy-1,2,3,4-tetr a h yd r on a p h th a len e-1,2-d iols in
Wa ter Solu tion s. The approaches to an equilibrium
mixture of cis- and trans-5-methoxyindan-1,2-diols from
both the trans diol and a mixture of 80% cis diol/20%
trans diol in 0.05 M HClO4 solutions at 25 °C were
monitored by HPLC as functions of time. In a similar
manner, the approaches to an equilibrium cis/trans diol
mixture starting from both pure cis- and pure trans-6-
methoxy-1,2,3,4-tetrahydronaphthalene-1,2-diol in 0.10
M HClO4 solutions were measured. Plots of % cis diol vs
time for the approaches of each diol system to a cis/trans
diol equilibrium mixture follow excellent pseudo-first-
order kinetics and are given in Figures 2 and 3.
The isomerization of cis diol (3b or 7b) and trans diol
(4b or 8b) is catalyzed by hydronium ion (eq 2), and the
observed pseudo-first-order rate constant for approach
to equilibrium from either side is equal to the sum of the
forward and reverse pseudo-first-order rate constants.
Therefore, kobsd ) (k1 + k-1)[H+]). Thus, the observed rate
constants kobsd for approach to equilibrium from either
F IGURE 3. Plots of percent cis diol 3b versus time in the
equilibration reactions starting from either cis diol (3b) or
trans diol (4b) in 0.10 M HClO4 water solution, 25.0 ( 0.2
°C. The lines are theoretical, based on eq 3.
-
side in the acid-catalyzed equilibration of either system
are the same within experimental error, cf. Figures 2-3.
k1
cis diol (3b or 7b) + H+
{ }
k-1
trans diol (4b or 8b) + H+ (2)
Dividing kobsd by [H+] gives the average second-order
rate constants of 0.15 M-1 min-1 and 0.26 M-1 min-1 for
the acid-catalyzed approaches to equilibrium (k1 + k-1
)
for cis- and trans-5-methoxyindan-1,2-diols and for 6-meth-
oxy-1,2,3,4-tetrahydronaphthalene-1,2-diols, respectively.
Extrapolation of the percent composition versus time
data in Figures 2 and 3 yields calculated equilibrium
mixtures containing 72% trans/28% cis diols for the
methoxyindan system (7b, 8b) and 63% trans/37% cis
diols for the methoxytetrahydronaphthalene system (3b,
4b). The equilibrium constants (Keq ) k1/k-1) are calcu-
lated from the equilibrium cis:trans diol concentrations
for each system, and from the equilibrium constants and
values of (k1 + k-1), values for k1 and k-1 are calculated.
(12) Gillilan, R. E.; Pohl, T. M.; Whalen, D. L. J . Am. Chem. Soc.
1982, 104, 4482-4484.
(13) Becker, J . R.; J anusz, J . M.; Bruice, T. C. J . Am. Chem. Soc.
1979, 101, 5679-5687.
5206 J . Org. Chem., Vol. 69, No. 16, 2004

Transition-State Effects in Acid-Catalyzed Aryl Epoxide Hydrolyses
TABLE 2. Su m m a r y of Secon d -Or d er Ra te Con sta n ts
a n d Equ ilibr iu m Con sta n ts for Acid -Ca ta lyzed
Equ ilibr a tion of cis- a n d
tr a n s-1,2,3,4-Tetr a h yd r on a p h th a len e-1,2-d iols (3b, 4b)
a n d of cis- a n d tr a n s-5-Meth oxyin d a n -1,2-d iols (7b, 8b) in
Wa ter Solu tion s, 25 °C
sufficient lifetimes in water solution to be trapped
by external nucleophiles faster than they react with
water.7,9,14-16 Unsubstituted benzyl carbocations are much
less stabilized, but there is evidence that they, too, exist
as intermediates in water solutions.13,14,17,18
Evidence that both cis and trans diol products from
the acid-catalyzed hydrolysis of 5-methoxyindene oxide
(5b) are formed from attack of water on an intermediate
carbocation comes from an analysis of the product
mixtures from hydrolysis of 5b in the absence and
presence of azide ion at pH 5.0 and 8.0 in water solutions.
The rates of reaction of 5b in water solutions are too fast
to be determined accurately, but product studies provide
important information. At pH 5.0, 65-70% of 5b reacts
by the acid-catalyzed route and 30-35% reacts by the
pH-independent route. At pH 8.0, >99% of 5b reacts by
the pH-independent route. At pH 5, in water solution
containing 0.025 M total azide concentration, the yield
of diol products from reaction of 5b is reduced by 55%,
but the ratio of cis and trans diols is not changed. At pH
8.0 in water solution containing 0.025 M total azide
concentration, the yield of diols from reaction of 5b is
reduced by only 13%, and there is a corresponding
reduction in yield of ketone product. These results
suggest that azide ion acts as a nucleophile in its reaction
with 5b at pH 8. At pH 5.0, where the reaction of 5b is
calculated to be increased due to the acid-catalyzed
pathway, the reduction in the yield of diol products due
to nucleophilic attack of azide ion on 5b should be
significantly <13%. The observation that the yield of diols
is instead reduced by a much greater amount (55%)
suggests that in the acid-catalyzed hydrolysis of 5b, azide
ion must be reacting with a carbocation intermediate,
since attack of azide ion on a protonated benzylic epoxide
(or its kinetic equivalence) has not been observed in other
systems.7,9,19,20 The fact that the cis/trans diol ratio does
not change rules out a concerted mechanism in which
the water molecule formed from reaction of hydronium
ion with 5b collapses without dissociation to form cis diol.
Were this to happen, the cis/trans diol product ratio from
reaction of 5b in azide solution would be different than
that formed from the acid-catalyzed reaction of 5b in the
absence of azide ion.
compd
k1 (M-1 min-1
)
k-1 (M-1 min-1
)
Keq
3b, 4b (X ) OCH3)a
7b, 8b (X ) OCH3)b
1.6 × 10-1
9.6 × 10-2
1.7
2.6
1.1 × 10-1
4.2 × 10-2
a
Calculated from average values of kobsd for approach to
equilibrium from both 3b and from 4b in 0.10 M HClO4 solution.
Calculated from average values of kobsd for approach to equilib-
rium from both a mixture of 80% 7b/20% 8b and from 8b in 0.05
M HClO4 solution.
b
A summary of these rate and equilibrium constants is
provided in Table 2.
Discu ssion
Diol Equ ilibr a tion Stu d ies. 5-Methoxyindan-1,2-
diols and 6-methoxy-1,2,3,4-tetrahydronaphthalene-1,2-
diols readily undergo acid-catalyzed isomerization in
dilute perchloric acid-water solutions, and in each case
the trans diol is slightly more stable than its isomeric
cis diol. This result contrasts with an earlier study of the
isomerization of 1-phenylcyclohexane-1,2-diols, which
showed that for this system the cis diol was more stable
than its isomeric trans diol. In the isomerization of
1-phenylcyclohexane-1,2-diols, change of the substituent
in the para position of the phenyl ring from methoxyl to
methyl did not affect the position of the equilibrium
mixture of cis and trans diols. We assume, therefore, that
the positions of the equilibrium mixtures of cis- and
trans-indan-1,2-diols (7a , 8a ) and of cis- and trans-
1,2,3,4-tetrahydronaphthalene-1,2-diols (3a , 4a ) will be
very similar to those of the corresponding methoxyl-
substituted systems, respectively.
Com p a r ison of Cis/Tr a n s Diol P r od u ct Ra tios
fr om Acid -Ca ta lyzed Hyd r olysis of In d en e Oxid es
w ith Equ ilibr iu m Cis/Tr a n s Diol Ra tios. The cis/
trans diol ratio from acid-catalyzed hydrolysis of 5-meth-
oxyindene oxide (80:20) is very similar to that from acid-
catalyzed hydrolysis of indene oxide (75:25). Therefore,
substitution of an electron-donating methoxyl group in
the aromatic ring has little effect on the cis/trans diol
product ratio in this system. Although acid-catalyzed
hydrolyses of indene oxide (5a ) and 5-methoxyindene
oxide (5b) each yield cis diol as the major product,
equilibration studies of 7b and 8b (and presumably 7a
and 8a ) show that the trans diol is the more stable. Thus,
the acid-catalyzed hydrolysis of these epoxides each yields
the less stable cis diol as the major product. Therefore,
the differences in transition state energies leading to cis
and trans diols from hydrolyses of 1a ,b and of 5a ,b do
not reflect the differences in energy of the products.
In the acid-catalyzed hydrolysis of 1 and 5, benzyl C-O
bond cleavage occurs to yield benzylic carbocations, which
undergo attack of water on both faces of the carbocation
to yield cis and trans diols. The fact that acid-catalyzed
hydrolysis of both indene oxide (5a ) and its 5-methoxyl
derivative (5b) yield only cis and trans diols in very
similar cis/trans diol ratios suggest that the product
forming steps are reaction of the solvent with carbocat-
ion intermediates. p-Methoxybenzyl carbocations have
Quantum chemical calculations at semiempirical, ab
initio, and DFT levels of theory suggest that there is only
one energy minimum structure for the 2-hydroxy-1-
indanyl carbocation 6 (cf Figure 4 for 6b) formed from
reaction of indene oxides 5a and 5b and that the five-
membered ring of the carbocation is very nearly planar.
The fact that the less stable cis diol is the major product
from reaction of solvent with the intermediate carbo-
cation indicates that there must be some effect that
selectively stabilizes the transition state for cis attack of
(14) Richard, J . P.; Rothenberg, M. E.; J encks, W. P. J . Am. Chem.
Soc. 1984, 106, 1361-1372.
(15) Blumenstein, J . J .; Ukachukwu, V. C.; Mohan, R. S.; Whalen,
D. L. J . Org. Chem. 1993, 58, 924-932.
(16) Amyes, T. L.; Richard, J . P. J . Am. Chem. Soc. 1990, 112, 9507-
9512.
(17) Berti, G.; Bottari, F.; Ferrarini, P. L.; Macchia, B. J . Org. Chem.
1965, 30, 4091-4096.
(18) Lin, B.; Whalen, D. L. J . Org. Chem. 1994, 59, 1638-1641.
(19) Islam, N. B.; Gupta, S. C.; Yagi, H.; J erina, D. M.; Whalen, D.
L. J . Am. Chem. Soc. 1990, 112, 6363-6369.
(20) Lin, B.; Friedman, S.; Yagi, H.; J erina, D. M.; Whalen, D. L. J .
Am. Chem. Soc. 1998, 120, 4327-4333.
J . Org. Chem, Vol. 69, No. 16, 2004 5207

Sampson et al.
bond in the transition-state cis attack of water on 6b is
expected to be stronger than that between the two
hydroxyl groups of the cis 1,2-diol product 7b because of
the partial positive charge on the water molecule at the
transition state.
In the two principal conformations of cis diol 7b, the
O-O distances are calculated at the density functional
B3LYP/6-31G* level of theory to be 2.695 and 2.675 Å,
with O-H hydrogen bond distances of 2.070 and 2.023
Å, respectively. The O-O distance in the pseudo-diequa-
torial conformation of trans diol 8b, in which the two
hydroxyl groups are closest, is calculated to be 3.115 Å,
with an O-H hydrogen bond distance calculated to be
2.848 Å. Therefore, intramolecular hydrogen bonding in
the trans diol should not be as favorable as that in the
cis diol and cannot be responsible for the greater stability
of the trans diol. The greater stability of the trans diol is
therefore most likely due to the fact that it possesses one
less gauche butane interaction than is present in the cis
diol, and the strain energy introduced by the additional
gauche butane interaction in the cis isomer must be
greater than any stabilization resulting from intramo-
lecular hydrogen bonding.
F IGURE 4. Structure of carbocation 6b, calculated at the
DFT B3LYP/6-31G* level of theory.
F IGURE 5. Transition structure for cis attack of water on
carbocation 6b, calculated at the MP2/6-31G* level of theory.
The Marcus intrinsic barrier for cis attack of water on
carbocation 6 (Figure 5) leading to the less stable cis diol
must be lower than the intrinsic barrier for trans attack
of water on 6 (Figure 6) leading to the more stable trans
diol.21 The difference in the energies of the intrinsic
barriers for cis and trans attacks of water on 6b may be
in part due to different degrees of imbalance between the
loss of resonance stabilization and lowering of energy due
to bond formation at the transition states. Differences
in solvation, perhaps including favorable intramolecular
hydrogen bonding in the transition state for cis attack
of water, may also contribute to lowering of the intrinsic
barrier for cis attack of water. Although the gas-phase
transition structures (Figures 5 and 6) calculated for cis
and trans attacks of water on carbocation 6b do not take
into account solvation or additional hydrogen bonding of
the transition states to nearby water molecules, some
insight on several factors that would affect intrinsic
barriers is apparent from analysis of the structures. The
calculated bond length between the benzylic carbon and
the attacking water molecule at the transition state for
cis attack (2.073 Å) is significantly longer than the
corresponding calculated bond length for trans attack of
water (1.823 Å). Also, the calculated C(7)-C(8)-C(1)-
O(1) dihedral angle for trans attack of water (60.54°) is
significantly reduced from the dihedral angle that the
p-orbital of the benzylic carbon of carbocation 6b makes
with the aromatic ring (∼90°), whereas the calculated
C(7)-C(8)-C(1)-O(1) dihedral angle for cis attack of
water (-88.39°) is not significantly changed from the
dihedral angle that the benzylic p-orbital of 6b makes
with the aromatic ring. Thus, the benzylic carbon atom
in the transition structure for trans attack of water on
6b is calculated to have undergone a greater change in
hybridization than it does for cis attack of water. The
greater change in hybridization for trans attack of water
would result in a greater imbalance between loss of
resonance stabilization and lowering of energy due to
F IGURE 6. Transition structure for trans attack of water on
carbocation 6b, calculated at the MP2/6-31G* level of theory.
water on 6 or destabilizes the transition state for trans
attack of water on 6, and this differential effect must be
reduced or absent in the products.
A possible explanation for the fact that the transition
state leading to the less stable cis diol is selectively
stabilized is that there is a relatively strong hydrogen
bonding interaction between the attacking water mol-
ecule and the adjacent hydroxyl group at the transition
state for cis attack of water on 6, whereas hydrogen
bonding between the attacking water molecule and the
hydroxyl group at the transition state for trans attack of
water on 6 is not possible. Transition structures calcu-
lated at the MP2/6-31G* level of theory for cis attack of
water on carbocation 6 and for trans attack of water on
carbocation 6 in the gas phase are given in Figures 5 and
6, respectively. The H‚‚‚O hydrogen bond distance be-
tween the attacking water molecule and the C2 hydroxyl
group in the transition structure for cis attack of water
7 is calculated to be 1.97 Å (O-O distance 2.60 Å). The
closest hydrogen bond distance in the transition structure
for trans attack of water is 3.15 Å.
Hydrogen bonding between the attacking water mol-
ecule and the water solvent is also expected to occur. For
the above interpretation to be correct, the intramolecular
hydrogen bond for cis attack of water (Figure 5) would
have to be energetically more favorable than the hydro-
gen bonding between the attacking water molecule and
solvent for trans attack of water (Figure 6). The hydrogen
(21) Richard, J . A.; Amyes, T. L.; Toteva, M. M. Acc. Chem. Res.
2001, 34, 981-988.
5208 J . Org. Chem., Vol. 69, No. 16, 2004

Transition-State Effects in Acid-Catalyzed Aryl Epoxide Hydrolyses
SCHEME 3
intramolecular hydrogen bonds, this transition state
involves more favorable orbital overlap of the reaction
center with the aromatic π-orbitals and would lead to
product that would occupy an energetically favorable
half-chair conformation.22,23 Thus, conformational and
resonance effects at the transition state may be more
important than hydrogen bonding effects in determining
the cis/trans diol ratio in the acid-catalyzed hydrolysis
of tetrahydronaphthalene epoxides.
In applying the same considerations for attack of water
on carbocation conformation 2(Eq)+, “axial” attack of
water on 2(Eq)+ to yield cis diol would be energetically
favorable because this pathway would lead to product
occupying a half-chair conformation, and some further
stabilization might be derived from intramolecular hy-
drogen bonding between the attacking water molecule
and the adjacent hydroxyl group. “Equatorial” attack of
water on 2(Eq)+ leading to trans diol would lead to
product occupying a half-boat conformation, and in-
tramolecular hydrogen bonding between the attacking
water molecule and the adjacent hydroxyl group is not
possible. The observation that the less stable cis diol 3b
is the major product from acid-catalyzed hydrolysis of 1b
may be primarily due to unfavorable nonbonding interac-
tions at the transition state leading to trans diol, but
intramolecular hydrogen bonding in the transition state
leading to cis diol may contribute to making this pathway
more energetically favorable.
bond formation at the transition state, which would
contribute to an increase in the intrinsic barrier.21
Intramolecular hydrogen bonding may therefore affect
transition state structure in the gas phase and may also
contribute to lowering transition state energy in solution.
Acid -Ca ta lyzed Hyd r olysis of Tetr a h yd r on a p h -
th a len e 1,2-Ep oxid es. The mechanisms of acid-cata-
lyzed hydrolysis of 1a and 1b are complicated by the fact
that the intermediate carbocation has two conformations,
one in which the hydroxyl group is in a pseudoaxial
position and a second in which the hydroxyl group is in
a pseudoequatorial position (Scheme 3).6 Also, 1a hydro-
lyzes to mostly (∼95%) trans diol 4a , whereas 1b
hydrolyzes to form cis diol 3b as the major (∼80%) diol
product. A mechanism that has been proposed6 to explain
these observations is that epoxide 1a reacts from its more
stable conformation with H+ via axial C-O bond cleavage
to form carbocation 2(Ax)+ in which the hydroxyl oc-
cupies an axial position. This carbocation conformation
then reacts by energetically favorable axial attack of
water to yield trans diol 4 faster than it rearranges to a
more stable conformation 2(Eq)+, in which the hydroxyl
group occupies an equatorial position. An explanation for
the observation that acid-catalyzed hydrolysis of 1b yields
mostly cis diol 3b is that the methoxyl-stabilized car-
bocation has a sufficient lifetime for the more stable
conformation 2(Eq)+ to be formed, and axial attack of
water on 2(Eq)+ yields the major cis diol product 3b.
Whether the diol products in the acid-catalyzed hydroly-
sis of 1b are formed from reaction of solvent with a single
carbocation conformation or two interconverting carbo-
cation conformations, the transition state leading to the
cis diol must be stabilized by some factor that is not
present in the diol products.
Su m m a r y
5-Methoxyindene 1,2-oxide (5b), 5-methoxyindan-cis-
1,2-diol and 5-methoxyindan-trans-1,2-diol were synthe-
sized. The cis stereochemistry is assigned to the diol
resulting from the reaction of 5-methoxyindene with
osmium tetroxide, followed by a reductive workup. This
procedure is known to yield only cis diols.24 Rate and
product studies of the hydrolysis of 5b over the pH range
5.5-9 are summarized. The hydronium ion-catalyzed
hydrolyses of 5-methoxyindene 1,2-oxide (5b) and of
6-methoxy-1,2,3,4-tetrohydronaphthalene 1,2-epoxide (1b)
yield 75-80% of cis diol and only 20-25% of trans diol
as hydrolysis products, although the trans diol in each
system is the more stable. Transition- state effects that
selectively stabilize the transition state leading to cis diol
and/or destabilize the transition state leading to the trans
diol must therefore be important. Energetically favorable
intramolecular hydrogen bonding of the attacking water
molecule with the adjacent hydroxyl group in the transi-
tion state for cis attack of water on the 2-hydroxyindan-
1-yl carbocation provides a rationale for the observation
that the less stable cis diol is the major product from acid-
catalyzed hydrolysis of 5-methoxyindene oxide. If so, this
transition-state stabilization for cis attack of water on a
carbocation may play a role in all epoxide hydrolysis
reactions where such hydrogen bonding is possible.
Transition-state effects that favor cis diol formation in
the acid-catalyzed hydrolysis of 6-methoxy-1,2,3,4-tetro-
hydronaphthalene 1,2-epoxide, however, may be due
mainly to unfavorable steric interactions at the transition
We have not calculated structures for “cis” and “trans”
attacks of water on carbocation conformations 2(Ax)+ and
2(Eq)+. Although the transition state for attack of water
on carbocation conformation 2(Ax)+ to yield cis diol
(“equatorial attack”) might be energetically favored by
intramolecular hydrogen bonding between the attacking
water molecule and the adjacent hydroxyl group, this
“cis” attack of water would generate substantial non-
bonding interactions at the transition state and would
force the product into an energetically unfavorable half-
boat conformation.22,23 Although “axial” attack of water
on 2(Ax)+ to yield trans diol may not be stabilized by
(23) Goering, H. L.; Vlazny, J . C. J . Am. Chem. Soc. 1979, 101,
1801-1805.
(24) Fieser, M.; Fieser, L. F. Reagents for Organic Synthesis; J ohn
Wiley and Sons: New York, 1967; pp 759-764.
(22) Goering, H. L.; J osephson, R. R. J . Am. Chem. Soc. 1962, 84,
2779-2785.
J . Org. Chem, Vol. 69, No. 16, 2004 5209

Sampson et al.
No peak (<1%) with the retention time of 5-methoxy-2-
state for trans attack of water on the intermediate
carbocation. Intramolecular hydrogen bonding at the
transition state for cis diol formation in the acid-catalyzed
hydrolysis of this epoxide may still play a role in
determining the cis:trans diol ratio, but steric effects at
the transition states may play a greater role.
indanone (21.1 min) could be detected.
P r ep a r a tive. A solution of 0.35 g of 5-methoxyindene oxide
in 2 mL of acetone was added over several minutes to 18 mL
of a stirred water solution, pH 2.9, and the resulting mixture
was stirred for 5 min at rt. The reaction mixture was extracted
with ethyl acetate (2 × 50 mL). The ethyl acetate extracts were
combined and dried over calcium sulfate. The ethyl acetate
solvent was removed at aspirator pressure to yield 0.44 g of
Exp er im en ta l Section
1
oil that solidified upon standing. Comparison of the H NMR
spectrum of this diol product mixture with the 1H NMR spectra
of authentic cis- and trans-5-methoxyindan-1,2-diols prepared
independently showed that it contained both cis and trans diols
in a 4:1 ratio.
Ma ter ia ls a n d Meth od s. Dioxane and THF were distilled
from sodium prior to use. All other reagents were purchased
from commercial sources. Quantum-chemical calculations were
performed with the molecular modeling programs Titan and
Spartan04 (Wavefunction, Inc.). The pH values given through-
out are those measured by the glass electrode, and for 10:90
and 25:75 dioxane-water solutions correspond to apparent pH
values. The activity of hydrogen ion measured by the glass
electrode was assumed to be equal to the concentration of
hydrogen ion.
P r ocedu r e for Mon itor in g Rates of Reaction of 5-Meth -
oxyin d en e Oxid e (5b). For each kinetic run, approximately
10-15 µL of a stock solution of 5b in dioxane (1 mg/mL) was
added to 2.0 mL of water or dioxane-water solution in the
thermostated cell compartment (25.0 ( 0.2 °C) of a UV-vis
spectrophotometer. Reactions were monitored at 230 nm, and
pseudo-first-order rate constants were calculated by nonlinear
regression analysis of the absorbance vs time data.
5-Met h oxyin d en e. The acid-catalyzed dehydration of
5-methoxy-1-indanol was accomplished by a slight modification
of the procedure of Winter, Godse, and Gessner,25 and this
procedure is supplied as Supporting Information. The resulting
5-methoxyindene was converted to the known trans bromo-
hydrin26 by reaction with N-bromoacetamide in 3:1 THF-
water, and this procedure is also supplied as Supporting
Information.
Rea ction s of 5-Meth oxyin d en e Oxid e in Sod iu m Azid e
Solu tion s. Aliquots (25 µL) of a solution of 5-methoxyindene
oxide in dioxane (2.3 mg/mL) were added to water solutions
containing 0.1 M NaClO4 and 0.025 M NaN3-0.075 M NaClO4
in which the pH was adjusted to 5.0. At this pH, it is estimated
that 65-70% of the reaction of 5b occurs via the acid-catalyzed
route and 30-35% occurs via the pH-independent route. After
the reactions were allowed to stand at rt for 5 min, 15 µL of a
solution containing 2.5 mg of trans-acenaphene-7,8-diol in 1.0
mL of methanol was added to serve as a standard, and the
pH of the reaction solution was then adjusted to 5-7. These
solutions were analyzed by HPLC as outlined above in the
analytical procedure. By comparing the areas of the diol
product peaks with the area of the standard compound for the
reactions of 5b in the absence of NaN3 and in 0.025 M NaN3,
it was calculated that the yield of diols from reaction of 5b in
0.025 M NaN3 solution is reduced by 55% compared to the yield
of diols from 5b when NaN3 is absent. The trans/cis diol ratio
is 0.21 when NaN3 is not present and 0.22 when [NaN3] is
0.025 M.
Similar product studies were carried out for the reactions
of 5b in the presence and absence of 0.025 M NaN3 at pH 8.0-
8.1, where > 99% of the reaction if via the pH-independent
reaction. After addition of aliquots of 5b in dioxane, the
reaction solutions were allowed to stand at rt for 2 min.
Standard was added, and the solutions were analyzed by
HPLC. The yield of diols from the reaction of 5b in 0.025 M
NaN3 was reduced by only 13% compared to the yield of diols
from 5b in the absence of azide at the same pH. The yield of
ketone product from reaction of 5b at pH 8 in 0.025 M NaN3
solution was reduced by 11%.
p H-In d ep en d en t Rea ction of 5-Meth oxyin d en e Oxid e.
An aliquot of 25 µL of a solution of 2.3 mg of 5-methoxyindene
oxide in 1.0 mL of dioxane was added to 1.0 mL of 0.1 M
NaClO4 solution in which the pH had been adjusted to 8.0.
The reaction mixture was swirled and allowed to stand at rt
for 5 min. An aliquot (15 µL) of a solution containing 2.5 mg
of trans-acenaphene-7,8-diol in 1.0 mL of methanol was added
to serve as a standard, and the resulting solution was analyzed
by HPLC under the same conditions used for analysis of the
products from acid-catalyzed hydrolysis of 5b. The retention
times of cis diol 7b, trans diol 8b, 5-methoxyindan-2-one, and
acenaphthene diol standard were 6.8, 5.2, 21.1, and 12.5 min.
The relative areas of 7b, 8b, and 5-methoxy-2-indanone in the
HLPC tracing were 5.0:19.9:75.1. Since the relative extinction
coefficients of diols and ketone at 265 nm were not determined,
the relative areas of cis and trans diol HPLC peaks from
reactions of 5b at pH 8.5 and at pH 3.2 were compared with
the area of the standard acenaphene diol HPLC peak. With
the assumption that the yield of diols from the acid-catalyzed
hydrolysis of 5b is 100%, the yields of cis diol 7b and trans
diol 8b from the pH-independent hydrolysis of 5b are calcu-
lated to be 23.0% and 5.8%, respectively. The remainder of
the product (71%) from reaction of 5b at pH 8.5 is assumed to
be 5-methoxy-2-indanone.
5-Meth oxyin d en e Oxid e (5b). A mixture 3.65 g of freshly
ground potassium hydroxide pellets (85%, ground under a
nitrogen atmosphere) and 1.01 g of trans-5-methoxy-trans-2-
bromo-1-indanol in 50 mL of THF was vigorously stirred at rt
for 1 h. The solid salts were filtered and washed with diethyl
ether. The solvent was removed from the filtrate under reduced
pressure to yield 0.66 g of clear oil, which was distilled in a
short-path distillation apparatus at an oil bath temperature
of 110 °C (0.5 mm) to yield 0.61 g (90%) of 5-methoxyindene
oxide: 1H NMR (CDCl3, 200 MHz) δ 7.40 (d, J ) 8.1 Hz, 1 H),
6.79 (1 H), 6.71 (dd, J ) 8.1, 2.4 Hz, 1 H), 4.22 (d, J ) 2.9 Hz,
1 H), 4.12 (t, J ) 2.9 Hz, 1 H), 3.78 (s, 3 H), 3.18 (d, J ) 18.3
Hz, 1 H), 2.96 (dd, J ) 18.3, 2.9 Hz, 1 H). Anal. Calcd for
C
10H10O2: C, 74.05; H, 6.22. Found: C, 73.83; H, 6.24
Acid -Ca ta lyzed Hyd r olysis of 5-Meth oxyin d en e Oxid e.
An a lytica l. A solution (25 µL) of 2.3 mg of 5-methoxyindene
oxide in 1.0 mL of dioxane was added to 1.0 mL of 0.1 M
NaClO4 solution in which the pH had been adjusted to 3.2.
The reaction mixture was swirled and allowed to stand at room
temperature for 5 min. An aliquot (15 µL) of a solution
containing 2.5 mg of trans-acenaphene-7,8-diol in 1.0 mL of
methanol was added to serve as a standard, and the pH of
the reaction solution was then adjusted to 5-7. The resulting
solution was analyzed by reversed-phase HPLC on a C18
column with 35:65 methanol-water as eluting solvent. Prod-
ucts were monitored by UV detection at 265 nm. The cis diol
7b (retention time 6.8 min) and trans diol 8b (retention time
5.2 min) were the major products, formed in a 79:21 ratio. The
retention time of the acenaphthene diol standard was 12.5 min.
A very minor peak (∼2%) having a retention time of 20.1 min
was also present in the HPLC tracing of the reaction mixture.
(25) Winter, J . C.; Godse, D. D.; Gessner, P. K. J . Org. Chem. 1965,
5-Meth oxy-cis-1,2-in d a n d iol (7b). A solution of 221 mg
(1.51 mmol) of 5-methoxyindene and 360 mg (1.42 mmol) of
osmium tetraoxide in 3.5 mL of pyridine was stirred at rt for
30, 3231-3233.
(26) Trikojus, V. M.; White, D. E. J . Proc. R. Soc. N.S.W. 1940, 74,
82-86.
5210 J . Org. Chem., Vol. 69, No. 16, 2004

Transition-State Effects in Acid-Catalyzed Aryl Epoxide Hydrolyses
2.5 h. The reaction mixture was diluted with a solution of 0.63
g of sodium bisulfite, 0.3 mL of water, and 6.4 mL of pyridine
and stirred at rt for 4 h. The reaction solution was extracted
three times with ethyl acetate (total 200 mL), and the
combined extracts was washed with 25 mL of water and dried
over calcium sulfate. The solvent was removed at reduced
pressure and the residue was sublimed (0.1 mm, 110 °C oil
bath temperature) to yield 100 mg (39%) of cis diol 7b, mp
95-97 °C. Recrystallization of this material from ether-ethyl
acetate solution yielded 7b: mp 99-101 °C; 1H NMR (DMSO-
d6, 200 MHz) δ 7.18 (d, J ) 7.9 Hz, 1 H), 6.7 (2 H), 4.82 (d, J
) 6.4 Hz, 1 H), 4.67 (apparent triplet, J avg ) 5.6 Hz, 1 H),
4.56 (d, J ) 5.3 Hz, 1 H), 4.19 (apparent pentet, J avg ) 5.1
Hz), 3.70 (s, 3 H), 2.88 (dd, J ) 15.8, 5.9 Hz, 1 H), 2.71 (dd, J
) 15.8, 4.4 Hz, 1 H). Anal. Calcd for C10H12O3: C, 66.69; H,
6.66. Found: C, 66.48; H, 6.87.
solution containing 5 mg/mL of 5-methoxy-trans-1,2-indandiol
in methanol was added to 12 mL of 0.05 M HClO4 in water,
maintained at 25.0 ( 0.2 °C, in a constant temperature water
bath. Aliquots (1.0 mL) of the reaction solution were with-
drawn at given times and quenched with 0.5 mL of 1.0 M
NaOH solution. These solutions were analyzed by reversed
phase HPLC on a C18 column with 30:70 (v/v) methanol-water
as eluent at a flow rate of 1.0 mL/min and monitored by UV
detection at 265 nm. Under these analytical conditions, the
retention time of trans diol was 8.3 min and that of cis diol
12.7 min. The results of this experiment and a similar one
starting from pure 5-methoxy-trans-indandiol are graphically
illustrated in Figure 2.
obsdt
(% cis)t ) [(% cis)o - (% cis)eq]e-k
+ (% cis)eq (3)
5-Meth oxy-tr a n s-1,2-in d a n d iol Diben zoa te. A solution
of 2.34 g of iodine in 45 mL benzene was added dropwise to a
stirred mixture of 4.20 g silver benzoate in 35 mL benzene
under a nitrogen atmosphere. The mixture was stirred an
additional 30 min at rt. A solution of 1.33 g of 5-methoxyindene
in 10 mL benzene was then added dropwise with continued
stirring of the reaction mixture. The resulting mixture was
heated at reflux for 4 h. The reaction mixture was cooled and
filtered. The benzene solvent was removed at aspirator pres-
sure to yield 4.04 g of a viscous oil. 1H NMR (CDCl3, 200 MHz)
δ 6.62 (d, J ) 3.0 Hz, 1 H), 5.86 (apparent pentet, J avg ) 3.6
Hz, 1 H), 3.82 (s, 3 H), 3.74 (dd, partially overlapping with
absorption at δ 3.82, J ) 17.0, 7.4 Hz, 1 H), 3.07 (dd, J ) 17.0,
4.2 Hz, 1 H). The crude dibenzoate, without purification, was
hydrolyzed to the trans diol 8b.
5-Meth oxy-tr a n s-1,2-in d a n d iol (8b). A mixture of 1.1 g
of crude 5-methoxy-trans-1,2-indandiol dibenzoate, 2.0 mL of
6.7 M KOH in water, and 25 mL of methanol was stirred and
heated at reflux for 1 h 15 min. The reaction mixture was
cooled, and most of the methanol was removed at aspirator
pressure. An additional 10 mL of water was added, and the
mixture was extracted twice with ethyl acetate (total 70 mL).
The solvent was removed at aspirator pressure, and the diol
product was sublimed (0.2 mm, oil bath temp 150-170 °C) to
yield trans diol 8b in 77% overall yield from 5-methoxyindene.
The sublimed product was recrystallized from ethyl acetate
to yield pure 5-methoxy-trans-1,2-indandiol: mp 152-153 °C;
1H NMR (DMSO-d6, 200 MHz) δ 7.18 (d, J ) 9.3 Hz, 1 H),
6.7-6.8 (2 H), 5.26 (d, J ) 5.9 Hz, 1 H), 5.13 (d, J ) 4.9 Hz, 1
H), 4.63 (apparent triplet, J avg ) 5.6 Hz, 1 H), 4.06 (m, 1 H),
3.71 (s, 3 H), 3.06 (dd, J ) 15.6, 6.8 Hz, 1 H), 2.56 (dd, J )
15.6, 6.4 Hz, 1 H). Anal. Calcd for C10H12O3: C, 66.69; H, 6.66.
Found: C, 66.67; H, 6.63.
The percent of cis diol in the reaction during the equilibra-
tion experiments is given by eq 3, where (% cis)t is the percent
of cis diol at a given time, (% cis)o is the initial concentration
of cis diol, (% cis)eq is the equilibrium concentration of cis-diol,
and kobsd is the pseudo-first-order rate constant for the ap-
proach to equilibrium. In the equilibrium experiment starting
from trans diol 8b, fitting of (% cis)t to eq 3 yielded values of
7.2 ( 0.6 × 10-3 min-1 for kobsd and 27.3 ( 0.5% for (% cis)eq.
In the equilibration experiment starting from a mixture of 80%
of cis diol 7b and 20% of trans diol 8b, fitting of (% cis)t to eq
3 yielded values of 8.2 ( 0.3 × 10-3 min-1 for kobsd and 28.8 (
0.8% for (% cis)eq. An average value of kobsd ) 7.7 × 10-3 min-1
was used to calculate the rate and equilibrium parameters
given in Table 2.
In similar experimental method, the approaches to equilib-
rium from either pure 6-methoxy-1,2,3,4-tetrahydronaphtha-
lene-cis-1,2-diol (3b) or its corresponding trans isomer (4b) in
0.10 M HClO4 solution were monitored as a function of time
by reverse phase HPLC with the same conditions as noted in
the previous paragraph, except that 40:70 (v/v) methanol-
water was used as eluent. The retention times of cis and trans
diols 3b and 4b under these conditions were 8.9 and 7.4 min,
respectively. These results are summarized graphically in
Figure 3. In the approach to equilibrium from cis diol 3b,
fitting of (% cis)t to eq 3 yielded values of (2.7 ( 0.1) × 10-2
min-1 for kobsd and 37.0 ( 0.7% for (% cis)eq. Starting from trans
diol 8b, fitting of (% cis)t to eq 3 yielded values of (2.5 ( 0.1)
× 10-2 min-1 for kobsd and 37.5 ( 0.3% for (% cis)eq. An average
value of kobsd ) 2.6 × 10-2 min-1 was used to calculate the
rate and equilibrium parameters given in Table 2.
Ack n ow led gm en t is made to the Donors of the
American Chemical Society Petroleum Research Fund
and to the National Institutes of Health, National
Research Service Award GM 08663 from the Minority
Access to Research Careers Undergraduate Student
Training in Academic Research (MARC U*STAR) Pro-
gram at UMBC.
5-Meth oxy-2-in d a n on e. A solution of 150 mg of 5-meth-
oxy-1,2-indene oxide in 2.0 mL of dioxane was added to 20 mL
of 0.1 M NaClO4 in 1:3 dioxane-water, pH 7.23, and the
resulting mixture was stirred for 5 min at rt. The solution was
extracted with 75 mL of diethyl ether, and the ethereal extract
was washed with water and dried over calcium sulfate.
Removal of the solvent at reduced pressure yielded 100 mg of
product, which was filtered through a column of 10 g of neutral
alumina (III, 6% water) and sublimed (oil bath temperature
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for the syntheses of 5-methoxyindene and trans-2-
bromo-6-methoxyindan-1-ol; calculated structures and Carte-
sian coordinates for carbocation 6b (B3LYP/6-31G*); calculated
transition structures and Cartesian coordinates for cis and
trans attacks of water on carbocation 6b (MP2/6-31G*);
calculated structures and Cartesian coordinates for cis and
trans 5-methoxyindan-1,2-diols (B3LYP/6-31G*). This material
is available free of charge via the Internet at http://pubs.acs.org.
1
40-55 °C, 100 mmHg): mp 77-79 °C; H NMR (CDCl3, 200
MHz) δ 7.20 (d, J ) 8.3 Hz), 6.8 (2 H), 3.81 (s, 3 H), 3.54 (2
H), 3.50 (2 H). Anal. Calcd for C10H10O2: C, 74.09; H, 6.17.
Found: C, 73.87; H, 6.36.
P r oced u r e for Mon itor in g Ra tes of Equ ilibr a tion of
5-Meth oxy-1,2-in d a n d iols a n d of 6-Meth oxy-1,2,3,4-tet-
r a h yd r on a p h th a len e-1,2-d iols. The following procedure is
an example of the method used to monitor the approach to
equilibrium of a cis:trans diol mixture. A 120-µL portion of a
J O040160J
J . Org. Chem, Vol. 69, No. 16, 2004 5211