Kinetics and mechanistic study of the reaction of cyclic anhydrides with substituted phenols. Structure-reactivity relationships

Article abstract of DOI:10.1021/jo048183l

(Chemical Equation Presented) The kinetic of the reactions of phthalic and maleic anhydrides with different substituted phenols (Z-PhOH with Z = H, m-CH₃, p-CH₃, m-Cl, p-Cl, and m-CN) were studied in aqueous solution. Two kinetic processes well separated in time were observed. The fast one is attributed to the formation of the aryl ester in equilibrium with the anhydride and allows the determination of the rate of nucleophilic attack of the phenol on the anhydride (k_-A). From the slow kinetic process, the equilibrium constant for this reaction was determined. The Broensted-type plots for the nucleophilic attack of substituted phenols on the anhydrides were linear with slopes β_Nuc of 0.45 and 0.56 for phthalic and maleic anhydride, respectively. The results are consistent with a mechanism involving rate-determining nucleophilic attack and also with a concerted mechanism. The calculated effective charge on the atoms involved in the reactions and the Broensted β values are consistent with a mechanism involving a concerted or enforced concerted mechanism where a tetrahedral intermediate with significant lifetime is not formed along the reaction coordinate. The latter mechanism is preferred over the stepwise process.

Full text of DOI:10.1021/jo048183l

Kinetics and Mechanistic Study of the Reaction of Cyclic
Anhydrides with Substituted Phenols. Structure-Reactivity
Relationships
Gabriel O. Andre´s and Rita H. de Rossi*
Instituto de Investigaciones en Fı´sico Quı´mica de Co´rdoba (INFIQC), Facultad de Ciencias Qu´ımicas,
Departamento de Quı´mica Orga´nica, Universidad Nacional de Co´rdoba, Ciudad Universitaria,
5000 Co´rdoba, Argentina
ritah@dqo.fcq.unc.edu.ar
Received October 14, 2004
The kinetic of the reactions of phthalic and maleic anhydrides with different substituted phenols
(Z-PhOH with Z ) H, m-CH3, p-CH3, m-Cl, p-Cl, and m-CN) were studied in aqueous solution. Two
kinetic processes well separated in time were observed. The fast one is attributed to the formation
of the aryl ester in equilibrium with the anhydride and allows the determination of the rate of
nucleophilic attack of the phenol on the anhydride (k-A). From the slow kinetic process, the
equilibrium constant for this reaction was determined. The Bro¨nsted-type plots for the nucleophilic
attack of substituted phenols on the anhydrides were linear with slopes âNuc of 0.45 and 0.56 for
phthalic and maleic anhydride, respectively. The results are consistent with a mechanism involving
rate-determining nucleophilic attack and also with a concerted mechanism. The calculated effective
charge on the atoms involved in the reactions and the Bro¨nsted â values are consistent with a
mechanism involving a concerted or enforced concerted mechanism where a tetrahedral intermediate
with significant lifetime is not formed along the reaction coordinate. The latter mechanism is
preferred over the stepwise process.
Introduction
occur with a mixture of nucleophilic an general base-
catalyzed mechanisms, where the different terms cannot
readily be separated.5,6
The study of both forward and reverse reaction for the
nucleophilic reaction of anhydrides with phenols (eq 1)
can give relevant information regarding the mechanism
of the reaction particularly concerning the discussion of
concerted vs stepwise mechanisms of ester hydrolysis.
This is a subject which has been widely discussed for
The detailed mechanism of addition of nucleophiles to
reactive carbonyl compounds is a subject of continuing
interest.1-3 The reaction of substituted phenols with
anhydrides is a common and practical approach to the
synthesis of esters and it is also important for the
understanding of the hydrolysis mechanism of esters.4
Detailed mechanistic analysis of a reaction is assisted
by information from studies of the reverse reaction. The
nucleophilic attack by carboxylate ion on esters is ob-
served for aqueous solution only in the case of intra-
molecular reactions because the intermolecular reaction
(5) Ba-Saif, S.; Luthra, A. K.; Williams, A. J. Am. Chem. Soc. 1987,
109, 6362.
(6) Ba-Saif, S.; Maude, A. B.; Williams, A. J. Chem. Soc., Perkin
Trans. 2 1994, 2395.
(7) Stefanidis, D.; Cho, S.; Dhe-Paganon, S.; Jencks, W. P. J. Am.
Chem. Soc. 1993, 115, 1650.
(1) Castro, E. A.; Pavez, P.; Santos, J. G. J. Org. Chem. 2002, 67,
4494.
(8) Williams, A. Chem. Soc. Rev. 1994, 23, 93.
(9) Castro, E. A.; Angel, M.; Pavez, P.; Santos, J. G. J. Chem. Soc.,
Perkin Trans. 2 2001, 2351.
(2) Tundo, P.; Selva, M. Acc. Chem. Res. 2002, 35, 706.
(3) Castro, E. A. Chem. Rev. 1999, 99, 3505.
(4) Williams, A. Free energy relationship in organic and bio-organic
chemistry; The Royal Society of Chemistry: Cambridge, 2003.
(10) Andre´s, G. O.; Granados, A. M.; de Rossi, R. H. J. Org. Chem.
2001, 66, 7653.
10.1021/jo048183l CCC: $30.25 © 2005 American Chemical Society
Published on Web 01/26/2005
J. Org. Chem. 2005, 70, 1445-1449
1445

Andre´s and de Rossi
TABLE 1. Effect of Phenol Concentration on the
Observed Rate Constant of the Slow Kinetic Process
(τ2-1) for the Reaction of Phthalic Anhydride at pH 8.90a
SCHEME 1. Hydrolysis of Phthalic Anhydride in
the Presence of Substituted Phenols
[phenol], 10-3
M
τ2-1, 10-3 s-1
0.60
1.46
1.67
1.88
2.16
6.7 ( 0.1
3.3 ( 0.2
2.93 ( 0.04
2.68 ( 0.09
2.21 ( 0.05b
a Ionic strength 0.5 M, temperature 25 °C, buffer CO32-/CO3H-
0.04 M. The errors are the standard deviation of the fit as
calculated by the software used. b Phenyl hydrogen phthalate
under the same conditions.
intermolecular reactions7-9 but not so much for intra-
molecular reactions.10
as starting substrates under otherwise similar reaction
conditions (Table 1; Figure S1, Supporting Information)
confirm this proposal. The value of the observed rate
constant for Scheme 1 can be derived by standard
procedures11 and is given by eq 2, which inverted give
eq 3.12
kAkh
-1
τ2
)
(2)
(3)
We reported previously the effect of the substituents
on the aryl ring of the phenol leaving group on the
hydrolysis of monoesters of phthalic acid (kA). The intra-
molecularly catalyzed hydrolysis of aryl esters proceeds
with carboxylate assistance to give the anhydride and
the substituted phenol; this reaction is quite sensitive
to the pKa of the leaving group (âlg ) -1.15), indicating
a significant bond breaking in the transition state.10
In the present work, we report a study of the reactions
of substituted phenoxide ions with phthalic and maleic
anhydride in aqueous solution. The results are important
for the determination of âEq of eq 1, and these data will
be useful to interpret values of âNuc and âlg for those reac-
tions and to shed some light on the mechanism of intra-
molecular catalysis in esters hydrolysis. It is important
to note that there have not been previously reported
studies regarding the equilibrium described in eq 1.
k-A[Z-PhO-] + kh
k-A
kAkh[Z-PhO-]
1
kh
τ2 )
+
The plot of τ2 vs phenol concentrations is linear (Figure
S1, Supporting Information) and has a reasonable cor-
relation with a slope of (17.8 ( 0.3) × 104 M-1 s. This
value must be divided by the fraction of phenolate ion
which was 0.095 to give k-A/kAkh. To check for consistency
of the results, we measured kh under otherwise similar
reaction conditions. This value was 0.62 s-1, and it can
be combined with the slope of the plot in Figure S1
(Supporting Information) to yield k-A/kA ) 11.6 × 105 M-1
in good agreement with the value obtained from the fast
process (see below, Table 2).
-1
The observed rate constant for the slow process (τ2
)
Results and Discussion
was also measured for the reactions of maleic anhydride
with several Z-PhOH (Z ) H, p-Me, m-Cl, and m-CN)
(Table S2, Supporting Information). In all cases, reason-
ably linear plots (not shown) were obtained when τ2 was
plotted vs Z-PhO- concentration. From the slope of these
plots and the value of kh, independently determined, the
values of k-A/kA were obtained (Table 2).
Fast Process. The rate constants for the fastest
observed relaxation time were linearity dependent on the
phenolate ion concentration. In Figure 1 is shown rep-
resentative data for phthalic anhydride, and the complete
set of data is collected in Tables S3-S6 (Supporting
Information).
Rate constants for the addition of substituted phenols
(Z-PhOH with Z ) H, p-CH3, m-CH3, p-Cl, m-Cl, and
m-CN) to phthalic and maleic anhydrides were obtained
by measuring the change in absorbance at a convenient
wavelength under pseudo-first-order conditions.
The kinetic study was carried out in the presence of
substituted phenols (pKa between 8.60 and 10.20) at
constant pH. Two kinetic processes well separated in time
were observed in all cases. The observed rate constant
for the fast kinetic process (1/τ1) increases with the phenol
concentration whereas the slow kinetic process (1/τ2)
decreases (see the Supporting Information).
Slow Process. The rate constant decreases as phenol
concentration increases (Table 1), and the plot of τ2
vs phenol concentration is linear (Figure S1, Support-
ing Information). Similar results were obtained using
m-cyanophenol as nucleophile (Table S1, Supporting
Information).
This process is attributed to the equilibration reaction
-1
shown in eq 1; therefore, the observed rate constant (τ1
)
is given by eq 411
τ1-1 ) kA + k-A[Z-PhO-]
(4)
We attribute this process to the reaction described in
Scheme 1, where the phthalic anhydride is in steady-
state concentration.
The fact that the same rate constant was obtained
using phthalic anhydride or phenyl hydrogen phthalate
(11) Bernasconi, C. F. Relaxation Kinetics; Academic Press, Inc.:
New York, 1976.
(12) It should be noticed that kh in Scheme 1 represents the rate
constant for the hydrolysis of phthalic anhydride. It is not an elemental
rate constant, and it involves terms for HO- and buffer-catalyzed
pathways.
1446 J. Org. Chem., Vol. 70, No. 4, 2005

Reaction of Cyclic Anhydrides with Substituted Phenols
TABLE 2. Rate and Equilibrium Constants for the Phenolysis of Anhydridesa
Z-phenol
phthalic anhydride
maleic anhydride
Z
pKa
k-A,b 103 s-1 M-1
kA,c s-1
k-A/kA, 105 M-1
k-A,d 104 s-1 M-1
k-A/kA,e 105 M-1
p-CH3
m-CH3
H
10.26
10.08
9.88
9.38
9.02
8.61
87 ( 8
0.0228
0.0333
0.0443
0.229
0.55
38
23 ( 1
16.5 ( 0.9
10.7 ( 0.5
9.6 ( 0.3f
3.65 ( 0.05f
i
46 ( 7
61 ( 7
18
43 ( 2
9.7
11 ( 1
p-Cl
36 ( 2
1.57
0.40
0.062
m-Cl
22 ( 3
0.37 ( 0.03f
m-CNg
13.0 ( 0.6f
2.1h
0.075 ( 0.009f
a pH ) 8.50, ionic strength 0.5 M, temperature 25 °C, acetonitrile 4.25%. Rate constant calculated from eq 4. b λ ) 300 nm. c Reference
10. d λ ) 250 nm. e Value calculated from τ2 using eq 3 and kh ) 0.26 s-1 at pH 8.5 and 0.14 at pH 8.2; both rate constants were determined
independently in this work. f pH ) 8.20. g λ ) 265 nm. h Obtained as the intercept from lineal plot of τ1-1 vs m-cyanophenol concentration.
i Cannot be determined under these conditions (see ref 14).
The values of the second-order rate constants obtained
are the same within experimental error (Table S7,
Supporting Information) indicating that the buffer has
no effect on the rate. These results are in good agreement
with reported data on the nucleophilic reaction of phen-
oxide ions with methyl aryl carbonates15 and with 4-nitro-
phenyl acetate,5 which do not show evidence of general
base catalysis. Therefore, the reactions of different
substituted phenols have been carried out at pH 8.50 or
8.20 (when the kinetics were too fast) at 0.03 M buffer
concentration for all the other Z-PhOH with phthalic and
maleic anhydrides. The reaction of m-cyanophenol with
maleic anhydride could not be measured because kA is
too high and even at the lowest m-cyanophenol concen-
tration using the fast process has a very small ampli-
tude16 under the conditions of our studies.
In Table 2, the rate and equilibrium constants for the
reactions are summarized; also included in Table 2 are
the pKa of the phenol nucleophiles taken from the
literature.17
A Bro¨nsted-type plot18 (Figure 2) for k-A using all the
data has a reasonable correlation coefficient and gives
âNuc of 0.45 ( 0.04 and 0.56 ( 0.10 for phthalic and maleic
anhydride, respectively.
The values obtained are similar to those reported by
FIGURE 1. Dependence of the pseudo-first-order rate con-
Williams6 for the concerted phenolysis reaction of acetic
stants for the reaction of phthalic anhydride with substituted
anhydride (âNuc ) 0.56 ( 0.06). In that case, the equi-
phenols on the phenol concentration. Z ) 2, m-CH3, 1, p-CH3,
9, p-Cl, b, m-CN.
librium constant for the reaction in water could not be
determined because the reverse reaction (nucleophilic
attack of acetate on phenyl ester) is a mixture of
nucleophilic and general base catalysis, although the
values of the reverse reaction were obtained by an
indirect route. Ideally, rate constants for the forward and
reverse processes need to be known for reactions under
the same conditions in order to determine equilibrium
constants accurately. We had determined previously10 the
rate of nucleophilic attack by the neighboring carboxylate
group (kA, eq 1) in the hydrolysis of Z-aryl hydrogen
The values of k-A were obtained as the slope of linear
plots of τ1-1 vs [Z-PhO-] at constant pH. The intercept of
the plots represents kA, but in most cases, these values
have large errors since they are very small compared with
the slope. However, for the phthalic anhydride reactions
(Figure 1) they are of the same order of magnitude as
the kA determined in previous work,10 giving support to
the mechanism.13 For the reaction of m-cyanophenol with
phthalic anhydride the value of kA was obtained from the
intercept of the linear plot according to eq 4 (see Figure
1 and Table 2).
To determine the effect of the buffer concentration on
the rate constant, the reactions were carried out at
constant pH and phenol concentrations and with variable
concentrations of 1,4-diazabicyclo[2.2.2]octane (DABCO),
from 1 to 10 mM (Tables S3 and S5, Supporting Informa-
tion, for phthalic and maleic anhydrides, respectively).
(14) A decrease in the pKa of nucleophile leads a considerable
increase in the value of kA; therefore, the equilibrium constant for eq
1 lies very much on the left-hand side and the observed rate constant
is completely determined by kA which it is too high for the stopped-
flow technique.
(15) Castro, E. A.; Pavez, P.; Santos, J. G. J. Org. Chem. 2001, 66,
3129.
(16) The amplitude is defined as the total change in optical density
during one kinetic process. See ref 11, Chapters 6 and 7.
(17) Handbook of Chemistry and Physics, 72nd ed.; Lide, D. R., Ed.;
CRC Press: Boca Raton, FL, 1991-1992; pp 8-30-8-35.
(18) This is not formally a Bro¨nsted plot and the slope values are
not related to general base catalysis. Jenck has used the expression
“âNuc” for this parameter.23c
-1
(13) Note that in Figure 1 the value of τ1 at zero Z-phenol
concentration is the value determined in previous work (ref 10) for Z
) m-CH3, p-CH3, and p-Cl.
J. Org. Chem, Vol. 70, No. 4, 2005 1447

Andre´s and de Rossi
SCHEME 2 a
a Key: (a) transition state for the nucleophilic attack of substi-
tuted phenol on phthalic anhydride; (b) transition state for the
hydrolysis of aryl trifluoroacetates, calculated from data in ref 22;
(c) transition state for the reaction of nucleophiles with aryl
acetates, ref 7; (d) transition state for the hydroxyl attack on aryl
esters; (e) and (f) taken from ref 19.
The Bro¨nsted âEq value can be used to calculate the
change of effective charge19 on the phenyl oxygen from
reactant to transition state relative to that from reactant
to product; this is the Leffler’s R parameter. The RN value
gives an estimate of the degree of bond formation between
aryl oxygen and the carbonyl carbon in the transition
state (RN ) âNuc/âEq ) 0.27 for k-A). This result indicates
a small degree of bond formation in the forward direction
and agrees with the data previously published,10 which
indicates a high degree of bond rupture for the leaving
group in the reverse reaction (kA in eq 1).
FIGURE 2. Bro¨nsted plot for the nucleophilic attack of
phenolate ions (k-A) on phthalic (9) and maleic (b) anhydrides.
The similarities between the â values for the two
anhydrides indicate that the position of the transition
state of the rate-determining step on the reaction coor-
dinate does not change significantly among the two
anhydrides. It is interesting to note that anhydrides of
different structure such as acetic, maleic, and phthalic
anhydrides have similar âNuc for the reactions with
phenols, although the reactivity is quite different; for
instance, the second-order rate constants for the reactions
with m-chlorophenol are 626, 2.2 × 104, and 3.65 × 104
M-1 s-1 for acetic,6 phthalic, and maleic anhydrides,
respectively.
The effective charge on the oxygen of the nucleophile
(Z-PhO-) in the transition state is calculated as -0.55
for phthalic anhydride (a in Scheme 2). Similar effective
charges were observed in the transition state of different
acyl-transfer reactions.4,21 For example, the hydrolysis of
trifluoromethyl acetate esters (b in Scheme 2)22 and the
reaction of nucleophiles with aryl acetates (c in Scheme
2).7 In all these cases a concerted or enforced concerted
mechanism was proposed for the reactions.
FIGURE 3. Bro¨nsted plot for the equilibrium in the reaction
of maleic anhydride with substituted phenols.
phthalates (Z ) H, p-CH3, m-CH3, p-Cl, m-Cl) by a direct
route; therefore, the equilibrium constants for formation
of esters from Z-phenoxide anions and phthalic anhydride
can be determined (Table 2). From a Bro¨nsted-type
correlation (plot not shown) for the equilibrium constants
(k-A/kA) of phthalic anhydride a value of âEq ) 1.66
( 0.04 was obtained. The value of âEq can also be
calculated from the difference between âNuc and âlg, âEq
) âNuc - âlg ) 1.6 ( 0.1. A similar value was reported
for acyl transfer19 (âEq ) 1.7) in aqueous solution. For
the reactions of maleic anhydride the Bro¨nsted plot for
k-A/kA (Figure 3) gave a slope of âEq ) 1.69 ( 0.01.
The charge on the ether oxygen atom, as measured by
âEq, is +0.7 (âEq - 1). This appears not to be very
indicative of reactivity at the carbonyl carbon of the ester.
For instance, ethyl N-benzoylglycinate has a rate con-
stant of 1.1 M-1 s-1 and ethyl acetate has a rate constant
of 0.0061 M-1 s-1 toward the attack by hydroxide ion,
and both compounds have an effective charge of +0.7 on
the oxygen of the ester.20
On the other hand, the transition state for the forma-
tion of the tetrahedral intermediate was associated to
asmall charge development (between 0.1 and 0.3);23
however, a stepwise mechanism for the title reaction
cannot be completely discarded.
(20) Chrystiuk, E.; Jusoh, A.; Santafianos, D.; Williams, A. J. Chem.
Soc., Perkin Trans. 2 1986, 163.
(21) Castro, E. A.; Pavez, P.; Santos, J. G. J. Org. Chem. 1999, 64,
2310.
(22) Fernandez, M. A.; de Rossi, R. H. J. Org. Chem. 1999, 64, 6000.
(23) (a) Hupe, D. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 451.
(b) Satterthwait, A. C.; Jencks, W. P. J. Am. Chem. Soc. 1974, 96, 7018.
(c) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 6963.
(19) Williams, A. Acc. Chem. Res. 1984, 17, 425.
1448 J. Org. Chem., Vol. 70, No. 4, 2005

Reaction of Cyclic Anhydrides with Substituted Phenols
containing the fully hydrolyzed anhydride in the presence of
substituted phenols with one at the same concentration
prepared with phthalic or maleic acid and the corresponding
phenol.
SCHEME 3. Effective Charge Map for the
Phenolysis of Phthalic Anhydride Involving a
Putative Tetrahedral Intermediate
Aqueous solutions were made up from water purified in a
Millipore apparatus. Acetonitrile was dried on silica gel 10%
p/v as described in the literature.29
Kinetic Procedures. Most reactions were carried out in a
stopped-flow apparatus with unequal mixing. The appropriate
anhydride dissolved in dry acetonitrile was placed in the
smaller syringe (0.1 mL). The larger syringe (2.5 mL) was filled
with a water solution containing all the other ingredients.
Considering the possibility of formation of a tetrahe-
dral intermediate with finite lifetime (Scheme 3) and
assuming that leaving group expulsion is the rate-
determining step,24 the value of âNuc determined in the
present work correspond to â1. Taking into account data
from the literature (see d-f in Scheme 2), the effective
charge on the oxygen in the intermediate can be esti-
mated as approximately +0.4 which leads to âEq1 1.4 and
â-1 -0.95. Considering conservation of effective charges4
the value of âEq2 is estimated as 0.3. A small value for
âEq2 is reasonable because the substituent on the aryl
group should not have any significant influence on either
the rate of the leaving group (â2) or the rate for nucleo-
philic attack by the neighboring carboxylate group (â-2).25
The linearity of the Bro¨nsted plots and the value of
their slopes are not enough evidences to either prove or
disprove a concerted mechanism. The best demonstration
of a concerted process is the lack of a Bro¨nsted break at
the pKa expected for a change in rate-determining step
if the reaction were stepwise.8,9 For the phenolysis of
anhydrides the center of the Bro¨nsted curvature (break-
point) for a stepwise reaction should be around pKa 3
(pKa of aryl hydrogen phthalates10). Unfortunately, this
pKa is far lower than the pKa range used in this
investigation. The formation of the tetrahedral interme-
diate is expected to be rate limiting in the phenolysis of
phenyl esters when the nucleophile has a pKa greater
than that of the leaving group.26 It has been suggested27
that the alkaline hydrolysis of p-nitrophenyl esters
proceeds toward the anionic tetrahedral intermediate
with a nearly tetrahedral transition-state structure, and
the expulsion of the leaving group from the tetrahedral
intermediate does not create a significant barrier of
activation.28 We do not have any reason to suppose that
the expulsion of carboxylate with pKa ≈ 3 has an
important barrier of activation for substituted phenoxides
with pKa higher than 7. Therefore, we think that a
concerted or enforced concerted mechanism more ad-
equately describes these reactions.
The slow reactions were measured in the cell, with temper-
ature control, of a conventional spectrophotometer by adding
the substrate dissolved in acetonitrile to a solution containing
all of the other ingredients in the required proportions to have
the same amount of the organic solvent as in the stopped-flow
experiments.
The substituted phenols concentration was varied between
1 and 2 × 10-3 M. The total acetonitrile concentration was
4.25% v/v. The solutions of the substrate for the kinetic
determinations were freshly prepared in dry acetonitrile in
the appropriate concentration to get a final concentration of
1.2 × 10-4 M.
All reactions were run at 25.0 ( 0.1 °C and at constant ionic
strength (0.5 M) using NaCl as the compensating electrolyte.
The pH measurements were made with a pH meter at
controlled temperature and calibrated with buffers prepared
according to the literature.30
The observed rate constants were determined by measuring
the change in absorbance at 250, 265, or 300 nm, depending
on the anhydride and substituted phenol, and the wavelength
was chosen so as to have the best signal-to-noise ratio. In some
of the experiments, the pH of the solution was checked after
the reaction by measuring it in the discarded solution, and
the changes observed were always less than 0.03 pH units.
The kinetic traces were fitted to one exponential equation
using the software of the SF apparatus.
The pKa of substituted phenols were taken from the litera-
ture,17 since in previous work we found that there are few
differences in the pKa of the phenols measured at 0.5 and 1 M
ionic strength.10
Acknowledgment. This research was supported in
part by the Consejo Nacional de Investigaciones Cien-
t´ıficas y Te´cnicas (CONICET), the Agencia Co´rdoba
Ciencia, Agencia Nacional de Ciencia y Tecnolog´ıa
(FONCYT), Fundacio´n Antorchas, and the Universidad
Nacional de Co´rdoba, Argentina. G.O.A. is a grateful
recipient of a fellowship from CONICET.
Experimental Section
-1
Supporting Information Available: Table S1 with τ2
Materials. Phthalic and maleic anhydrides were sublimed
before use.29 The purity of the products was also checked by
comparing the UV-vis absorption spectrum of a solution
for the reactions of phthalic anhydride with m-cyanophenol,
Table S2 τ2 for the reactions of maleic anhydride with all
-1
the phenols, Tables S3 and S4 with data for phthalic anhydride
with all the other Z-PhOH used, Tables S5 with τ1-1 for maleic
anhydride with phenol at different buffer concentrations, Table
S6 with the data for all the other Z-PhOH, and Table S7 with
the second-order rate constants for the reactions of maleic and
phthalic anhydride with phenol at different buffer concentra-
tions. Figure S1: plot of τ2 vs phenol concentration for the
reaction of phthalic anhydride with phenol. This material is
available free of charge via the Internet at http://pubs.acs.org.
(24) Leaving group expulsion in the reverse direction in Scheme 3
could be rate determining if bond rupture to regenerate the ester is
faster that expulsion of the phenolate anion. This is a reasonable
possibility since the pKa of the carboxylate group is much lower than
that of the phenol.
(25) Fife, T. H.; Hutchins, J. E. C. J. Am. Chem. Soc. 1981, 103,
4194.
(26) (a) Colthurst, M. J.; Williams, A. J. Chem. Soc., Perkin Trans.
2 1997, 1493. (b) Ba-Saif, S.; Luthra, A. K.; Williams, A. J. Am. Chem.
Soc. 1989, 111, 2647. (c) Williams, A. Acc. Chem. Res. 1989, 22, 387.
(27) Shames, S. L.; Byers, L. D. J. Am. Chem. Soc. 1981, 103, 6170.
(28) This is defined as an enforced concerted mechanism.7
(29) Perrin, D. D.; Armarego, W. L. G. Purification of Laboratory
Chemicals, 3rd ed.; Butterworth-Heinemann Ltd: Great Britain, 1994.
JO048183L
(30) See ref 17.
J. Org. Chem, Vol. 70, No. 4, 2005 1449