Kinetic study of the hydrolysis of phthalic anhydride and aryl hydrogen phthalates

Article abstract of DOI:10.1021/jo010499v

The kinetics of the hydrolysis of phthalic anhydride and X-phenyl hydrogen phthalate (X = H, p-Me, m-Cl, and p-Cl) were studied. Several bases accelerate the reaction of phthalic anhydride: acetate, phosphate, N-methyl imidazole, 1,4-diazabicyclo[2,2,2]octane (DABCO), and carbonate. Phosphate, DABCO, and N-methyl imidazole react as nucleophiles, whereas the data do not allow the determination of whether the other bases react in the same way or as general bases catalyzing the water reaction. The rate constants for all of them including water and HO^- define a Broensted plot with β = 0.46. The kinetics of the hydrolysis of the esters were studied below pH 6.20, and the mechanism involves the formation of phthalic anhydride, which then is hydrolyzed to the phthalic acid. Phenoxide ion has a very high rate constant for the reaction with phthalic anhydride, so above pH 6.20 it competes significantly with the hydrolysis of the anhydride. The reactions of the esters as a function of pH allow the determination of the kinetic pK_a which are 3.06, 3.02, 2.95, and 2.93 for X = H, p-Me, m-Cl, and p-Cl, respectively. The data also show that the catalysis by the neighboring carboxy group takes place only when it is ionized (i.e., as carboxylate).

Full text of DOI:10.1021/jo010499v

J . Org. Chem. 2001, 66, 7653-7657
7653
Kin etic Stu d y of th e Hyd r olysis of P h th a lic An h yd r id e a n d Ar yl
Hyd r ogen P h th a la tes
Gabriel O. Andr e´ s, Alejandro M. Granados, and Rita H. de Rossi*
Instituto de Investigaciones en F ı´ sico Qu ı´ mica de C o´ rdoba (INFIQC), Facultad de Ciencias Qu ´ı micas,
Departamento de Qu ı´ mica Org a´ nica, Universidad Nacional de C o´ rdoba, Ciudad Universitaria,
5
000 C o´ rdoba, Argentina
ritah@dqo.fcq.unc.edu.ar
Received May 17, 2001
The kinetics of the hydrolysis of phthalic anhydride and X-phenyl hydrogen phthalate (X ) H,
p-Me, m-Cl, and p-Cl) were studied. Several bases accelerate the reaction of phthalic anhydride:
acetate, phosphate, N-methyl imidazole, 1,4-diazabicyclo[2,2,2]octane (DABCO), and carbonate.
Phosphate, DABCO, and N-methyl imidazole react as nucleophiles, whereas the data do not allow
the determination of whether the other bases react in the same way or as general bases catalyzing
-
the water reaction. The rate constants for all of them including water and HO define a Br o¨ nsted
plot with â ) 0.46. The kinetics of the hydrolysis of the esters were studied below pH 6.20, and the
mechanism involves the formation of phthalic anhydride, which then is hydrolyzed to the phthalic
acid. Phenoxide ion has a very high rate constant for the reaction with phthalic anhydride, so
above pH 6.20 it competes significantly with the hydrolysis of the anhydride. The reactions of the
esters as a function of pH allow the determination of the kinetic pK which are 3.06, 3.02, 2.95,
a
and 2.93 for X ) H, p-Me, m-Cl, and p-Cl, respectively. The data also show that the catalysis by
the neighboring carboxy group takes place only when it is ionized (i.e., as carboxylate).
The study of intramolecular catalysis in model systems
gives important information about enzyme mechanisms.1
In connection with our studies of the effect of cyclodextrin
in intramolecularly catalyzed reactions,4 we became
interested in the study of the effect of a neighboring
carboxylic group on the hydrolysis of esters.
change in absorbance adjusted very well to a single-
exponential curve. At pH 6.20 and 7.24, H PO /HPO
2 4 4
-3
-
2-
was used as buffer, and two kinetic processes, well
separated in time, can be detected. The rate constant for
the slower process cannot be measured because it is too
slow for the stopped-flow technique. In one experiment
carried out in a conventional spectrophotometer at pH
obs
The hydrolysis of monoesters of phthalic acids was
shown to be catalyzed by the neighboring carboxy group
6.20 with total buffer concentration 0.08 M, a k value
-
3
-1
when the pK
a
of the alcohol leaving group is higher than
of 1.26 × 10
s
was determined.
1
3.5 and by the carboxylate when the leaving group has
2-
The reaction of phthalic anhydride with HPO
4
is
5
a
a lower pK . In this paper, we report the effect of
known to form phthaloyl monophosphate with rate
substituents on the aryl ring of the phenol leaving group.
It was found that the reaction is quite sensitive to the
-1 -1
constant 1.23 M
s , and then the mixed anhydride is
6
hydrolyzed with a slower rate. From the slopes of the
linear plots of kobs for the fast process versus total buffer
concentration (not shown) at pH 6.2 and 7.24 and the
pK of the leaving group (âlg ) -1.15), indicating a
a
significant bond breaking in the transition state. Since
phthalic anhydride is a known intermediate in this type
a
pK of the phosphate monoanion (6.28 at ionic strength
5
of reaction, we also include here a study of the kinetics
7
0
.5 M), the second-order rate constant for the reaction
of the hydrolysis of this compound under the same
conditions used for the esters.
2
-
of HPO
4
with phthalic anhydride is calculated as 1.02
-
1
-1
and 1.21 M
s
in good agreement with the literature
value mentioned above. The intercepts of the plots are
the same within experimental error at pH 6.20 and 7.24.
Resu lts a n d Discu ssion
P h th a lic An h yd r id e. The rate of hydrolysis of this
compound was determined at different pHs in the range
.63-10.50 at 25 °C and in water containing a small
amount of acetonitrile. In the pH range 0.63-3, HCl was
used to regulate the pH, and above pH 3, several buffers
were used (see Table S1 in the Supporting Information).
At pH 5.0 and 5.7 there was a small catalysis using
acetic/acetate as buffer (Table S1), but the observed
At pH 6.20, 6.80, and 7.80, N-methyl imidazole was
used as buffer. Only one kinetic process was detected in
this case, and the observed rate constants are collected
in Table S2. It can be seen in Figure 1 that at pH 7.80
there is a nonlinear dependence between the observed
rate constant and the total buffer concentration. These
results can be interpreted as shown in Scheme 1, where
B represents the buffer base, in this case N-methyl
imidazole.
0
(1) Kirby, A. J .; Lancaster, P. W. J . Chem. Soc., Perkin Trans. 2
1
972, 1206.
(2) Suh, J .; Chun, K. H. J . Am. Chem. Soc. 1986, 108, 305.
(3) Menger, F. M.; Ladika, M. J . Am. Chem. Soc. 1988, 110, 6794.
(4) Granados, A. M.; de Rossi, R. H. J . Org. Chem. 2001, 66, 1548.
(5) Thanassi, J . W.; Bruice, T. C. J . Am. Chem. Soc. 1966, 88, 747.
(6) Higuchi, T.; Flynn, G. L.; Shah, A. C. J . Am. Chem. Soc. 1967,
89, 616.
(7) Bernasconi, C. F.; Gehriger, C. L.; de Rossi, R. H. J . Am. Chem.
Soc. 1976, 98, 8451.
1
0.1021/jo010499v CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/23/2001

7
654 J . Org. Chem., Vol. 66, No. 23, 2001
Andr e´ s et al.
Ta ble 1. Ra te Con sta n ts for th e Hyd r olysis of P h th a lic
An h yd r id e in th e P r esen ce of Ba ses
k, M- s-1
1
base
pKa
-
4 a
H2O
AcO
-1.74
4.75
6.28
7.20
9.22
9.78
15.7
1.67 × 10
1.61 × 10
1.1c
-
-2 b
HPO4 2
-
d
N-methyl imidazole
0.277
d
DABCO
11.5
2
-
106e
CO3
HO
-
f
10636
a
Calculated from the average of the rate constants extrapolated
at zero buffer concentration obtained at pHs between 0.63 and
c
5
.7 divided by 55. b Calculated from data at pH 5.00 and 5.7. This
d
is kB in Scheme 1, data obtained at pH 6.2 and 7.8. This
e
represents KBk1, Scheme 1, data obtained at pH 7.8. Calculated
from the data at 8.9, 9.5, and 10.5. f Taken from the slope of a
-
(14-pH)
plot of kobs at zero buffer concentration vs 10
range 8-10.5.
in the pH
Using 1,4-diazabicyclo[2,2,2]octane (DABCO) as buffer
at pH 7.8, the observed rate constant has a linear
F igu r e 1. Observed rate constant for the hydrolysis of
phthalic anhydride as a function of total N-methyl imidazole
concentration at 25 °C, pH 7.8, and ionic strength 0.5 M. The
dependence with the buffer concentration in the range
-2
0
s
.0087-0.08 M concentration. The intercept 1.44 × 10
-
2
-1
line was calculated using eq 1 with k
o
) 1.59 × 10
) 0.074 s , and the fraction of N-methyl imidazole
as base ) 0.799.
s
, K
B
)
-1
represents k , and this value is in reasonably good
o
-1
-1
3
.75 M , k
1
agreement with the value measured at the same pH with
N-methyl imidazole (see above). The slope of this plot is
-
1
-1
Sch em e 1
11.5 M
correspond to k
be much higher. The rate constant for the aminolysis of
phthalic anhydride is independent of the pK of the amine
for morpholine
in Scheme 1 for
) 9.2)12 should be of this order of magni-
s
, and it should be k
1 B
K . This value cannot
B
in Scheme 1 because it is expected to
a
8
for nucleophiles of pK
a
> 8. The value k
B
5
-1 -1 8
(
pK
a
) 8.7) is 2.1 × 10 M
s
, so k
B
DABCO (pK
a
tude.
At pH between 8.90 and 10.50, CO 2
-/HCO -
was used
3
3
as buffer (Table S3). In this case, only one kinetic process
2
-
is observed. The slope of the plot of kobs versus CO
concentration is 106 M
3
-1
-1
s . We did not detect, as in the
case of the phosphate reaction, any slow process, so we
cannot say whether the catalysis by carbonate represents
basic catalysis or the nucleophilic reaction with the
anhydride.
By considering Scheme 1 and assuming that the
formation of the intermediate 1 is in fast equilibrium
with the reactants, the observed rate constant in the
presence of N-methyl imidazole is given by eq 1 where
The second-order rate constants for reactions of all the
bases are collected in Table 1. A Br o¨ nsted plot (Figure
2
) using all the data has a reasonable correlation coef-
K
B
B
) k /k-B
ficient and gives â ) 0.46 despite the fact that the rate
constants do not have the same mechanistic meaning in
all cases. The reaction of water represents the addition
k + K k [B]
o
B 1
kobs
)
(1)
1
+ K [B]
13
B
of water catalyzed by a water molecule, the reaction of
2
-
HPO
4
represents the nucleophilic addition of this
The reaction of phthalic anhydride with nucleophiles is
well documented in the literature.6,8
species on the carbonyl group, and the reactions of
N-methyl imidazole and DABCO are the products of the
equilibrium constant for the addition of the nucleophile
times the rate constant for the hydrolysis of the inter-
mediate (k k /k in Scheme 1). These results should be
a warning for the interpretation of the effect of bases in
the hydrolysis reactions, since one usually assumes that
a good Br o¨ nsted plot implies the same mechanism, and
a â value around 0.5 is attributed to general base-
Using eq 1 to fit the data for N-methyl imidazole at
-
1
-1
pH 7.80, we can calculate k
o
) 0.0159 s , K
) 0.074 s . The initial slope of the plot of kobs
versus N-methyl imidazole concentration gave K
B
) 3.75 M ,
-
1
and k
1
1
B
-B
B
k
1
)
-1
-1
0
.287 M
s
in good agreement with the value obtained
by nonlinear fitting. At pH 6.80 and by using the same
-2
-1
value of K
is a reasonable value compared with that obtained at pH
.80. The value of k is about 8 times higher than the
B
, k
1
) (6.3 ( 0.7) × 10
s
is calculated. This
7
1
(
9) The rate constant of the water reaction for acetic anhydride is
rate constant for the hydrolysis of phthalic anhydride,
-1
-1
0
.17 min (ref 10) and that of N-methylacetyl imidazole is 2.8 min
(ref 11).
(10) Kirsch, J . F.; J encks, W. P. J . Am. Chem. Soc. 1964, 86, 837.
while the relative rate of reaction of acetyl N-methylimi-
dazole and acetic anhydride is 16.9-11
(
(
11) Wolfenden, R.; J encks, W. P. J . Am. Chem. Soc. 1961, 83, 4390.
12) Sayer, J . M.; J encks, W. P. J . Am. Chem. Soc. 1969, 91, 6353.
(
8) Hall, W. E.; Higuchi, T.; Pitman, H. I.; Uekama, K. J . Am. Chem.
(13) Gandour, R.; Coyne, M.; Stella, V. J .; Schowen, R. L. J . Org.
Chem. 1980, 45, 1733.
Soc. 1972, 94, 8153.

Kinetic Study of Hydrolysis of Phthalic Anhydride
J . Org. Chem., Vol. 66, No. 23, 2001 7655
Ta ble 2. Ra te Con sta n ts for th e F a st P r ocess (τ1) in th e
a
Rea ction of P h en ol w ith P h th a lic An h yd r id e
H2PO4 /HPO4 0.01 Mb
-
2-
H2PO4 /HPO4 0.05 Mb
-
2-
phenol], 10-
3
M
τ1-1, s-1
[phenol], 10-3
M
τ1-1, s-1
[
0
0.0227
0.201
0.231
0.244
0.280
0
0.067
0.229
0.268
0.299
0.340
1
1
1
1
.15
.22
.42
.62
1.0
1.2
1.4
1.6
a
pH 7.24, ionic strength 0.5 M, temperature 25 °C. The values
of τ are the average of 4-10 determinations, and the standard
deviation is less than 2%. b Total buffer concentration.
kinetic processes (τ
1
2
and τ ) well separated in time. Each
of them was independently adjusted to a monoexponen-
tial function, and the observed rate constant was calcu-
lated.
1
The faster relaxation time (τ ) is attributed to the
reaction of the anhydride with buffer, with the solvent,
and with phenol. Using phosphate as buffer, the intercept
-
1
of the plots of τ
1
versus phenol concentration is in good
agreement with the expected value as measured inde-
pendently at the same pH and buffer concentration but
without phenol. Besides, the slopes of the plots at the
two phosphate concentrations are the same within experi-
mental error, and from these slopes, a value of (7.2 (
F igu r e 2. Br o¨ nsted plot for the hydrolysis of phthalic
anhydride catalyzed by bases (data from Table 1).
4
-1
-1
0
.2) × 10
M
s
is calculated for the second-order
-
18
reaction of PhO with phthalic anhydride. The reactiv-
ity of the phenoxide anion is far above the value expected
from the Br o¨ nsted line drawn with all the other bases.
Comparing the rate of hydrolysis of acetic and phthalic
anhydrides, we found that the former is 3.3 times more
reactive than the latter when water is the nucleophile,
but the relative reactivity of the two anhydrides is in the
opposite direction with stronger nucleophiles such as
phenoxide and hydroxide ions.1 It is interesting to note
that when comparing a series of carbonyl derivatives of
increasing reactivity such as p-nitrophenyl and 2,4-
dinitrophenyl acetate 1-acetoxy-4-methoxy-pyridinium
perchlorate16 and phthalic anhydride, the relative reac-
9,20
-
-
tivity between PhO and HO increases, and this is
-
mainly because the reactivity of PhO increases more
than that of HO as the reactivity of the substrate
-
F igu r e 3. pH rate profile for the hydrolysis of phthalic
increases. This result may indicate that desolvation of
the nucleophile becomes important when the substrate
is very reactive. The importance of desolvation in the
anhydride at 25 °C and ionic strength 0.5 M. The line was
-
(14-pH)
calculated using log(0.0092 + 10 640 × 10
).
2
1
reactions of nucleophiles is well documented.
catalyzed reactions rather than to nucleophilic
reactions.1
The second kinetic process (τ ) is related to the hy-
drolysis of phenyl hydrogen phthalate formed during the
2
4-16
Using the data of the observed rate constants extra-
polated to zero buffer concentration, the pH profile shown
in Figure 3 is obtained. The average value of the flat
first kinetic process, but at the pH of this study (7.24), it
does not shows a pure first-order behavior, and it will
not be discussed further.
Ar yl Hyd r ogen P h th a la te. The hydrolysis reaction
of phenyl, p-methylphenyl, m-chlorophenyl, and p-chloro-
phenyl hydrogen phthalate was studied at pH above 0.60
and below 5.70. With the exceptions mentioned below, it
shows two kinetic processes which are identified with the
-3
-1
region of the pH profile is 9.2 × 10
s
, and it is in good
agreement with the value reported for slightly different
-
3
-1 5
reaction conditions, namely 12.3 × 10
s
and 10.5 ×
-
3
-1 13
1
0
s .
The rate of hydrolysis of phthalic anhydride
1
7
is 23 times that of benzoic anhydride, and this differ-
ence in reactivity may be attributed to ring strain in the
former.
(18) To calculate this value, the slopes of the lines drawn using the
-
data reported in Table 2 were divided by the fraction of PhO 2.29 ×
The reaction of phthalic anhydride was also studied
in the presence of phenol at pH 7.24 at two buffer
concentrations (Table 2). In this case, there are two
-3
1
0
a
calculated with the pK of phenol determined at ionic strength
0.5 M which is 9.88.
19) The second-order rate constant for the reaction of acetic
(
-
3
-1 -1
anhydride with HO is 10
ion is also 10
M
s
(ref 10) and that of the phenoxide
3
-1
s-1 (ref 20).
M
(14) Bruice, P. Y.; Bruice, T. C. J . Am. Chem. Soc. 1974, 96, 5523.
(15) Fersht, A. R.; Kirby, A. J . J . Am. Chem. Soc. 1967, 89, 4853.
(16) J encks, W. P.; Gilchrist, M. J . Am. Chem. Soc. 1968, 90, 2622.
(17) Bunton, C. A.; Fendler, J . H. J . Org. Chem. 1966, 31, 3764.
(20) Basaif, S. A.; Maude, A. B.; Williams, A. J . Chem. Soc., Perkin
Trans. 2 1994, 2395.
(21) Terrier, F.; Moutiers, G.; Xiao, L.; Le Gu e´ vel, E.; Guir, F. J .
Org. Chem. 1995, 60, 1748-54.

7
656 J . Org. Chem., Vol. 66, No. 23, 2001
Andr e´ s et al.
Ta ble 3. Ra te Con sta n ts a n d Kin etic p Ka for th e
a
Hyd r olysis of X-Ar yl Hyd r ogen P h th a la tes
ki, 10- s-1 b
2
pKac
X
H
4.43 ( 0.07
2.28 ( 0.02
55 ( 1
3.06 ( 0.04
3.02 ( 0.02
2.95 ( 0.06
2.93 ( 0.02
p-Me
m-Cl
p-Cl
22.9 ( 0.2
a
Ionic strength 0.5 M, temperature 25 °C, acetonitrile 3.85%.
b
c
Rate constant for the ring closure reaction (see Scheme 2).
Calculated from the observed rate constant for the ring closure
reaction at different pH.
F igu r e 4. Absorbance at 300 nm vs time for the reaction of
phenyl hydrogen phthalate at pH ) 5.7 with buffer AcOH/
-
AcO (0.08 M) and 25 °C. The line is calculated by fitting the
-
t/τ1
-t/τ
-1
2
experimental data to Abs ) a
1
e
+ a
2
e
2
+ B with τ
)
-
2
-1
1
.04 × 10
s .
Sch em e 2
F igu r e 5. Rate constant vs fraction of carboxylate anion for
the four esters studied: phenyl hydrogen phthalate, p-meth-
ylphenyl hydrogen phthalate, m-chlorophenyl hydrogen ph-
thalate, and p-chlorophenyl hydrogen phthalate.
buildup and decay of phthalic anhydride, Scheme 2.
Figure 4 is a representative plot of the absorbance versus
time under these conditions.
The hydrolysis rate constant for the phenyl ester was
also measured at pH higher than 5.7, but in this case,
the backward reaction of the phenol with the anhydride
complicated the kinetics of the system, so it will not be
discussed here.
hydrolysis of the anhydride as the measured value. Both
methods gave comparable results (see Table S5), but we
think that the second is the more accurate one, and these
are the values reported in Table 3.
The observed rate constant for the ring closure reaction
plotted versus pH gives a sigmoid curve (not shown)
similar to that reported in the literature for phenyl
For phenyl and p-methylphenyl esters at pH lower
than 2, the decomposition of the intermediate is too fast,
and only one kinetic process is observed which corre-
sponds to the formation of phthalic anhydride (Table S4).
Above pH 2, the rate constant for the formation of the
5
hydrogen phthalate. From the inflection point of those
curves, the kinetic pK was calculated (Table 3). In the
a
case of the phenyl ester, the value obtained of 3.06 is in
+
anhydride increases linearly with 1/H while that of the
good agreement with the literature value, that is, 3.36
at 1 M ionic strength and 30 °C.5
hydrolysis of phthalic anhydride remains constant, so
both processes can be measured.
The observed rate constant can be plotted as a function
The ring closure reaction (k
i
) is slightly dependent on
of the fraction of substrate in the carboxylate form, x
(Figure 5). The intercept at x ) 0 is zero within
experimental error, indicating that the neutral substrate
A
buffer concentration (Table S5). Using phosphate as
buffer, the changes in absorbance fit to a three-exponen-
tial equation, while at the same pH using N-methyl
imidazole as buffer, the data are well represented by a
two-exponential equation. This is consistent with the
results obtained for the hydrolysis of phthalic anhydride
see above). To calculate the rate constants for the
system, we used a double (or triple)-exponential equation
to fit the data, or we set the value corresponding to the
A
is very unreactive. The intercept at x
2) and is shown in Table 3.
A
i
) 1 is k (Scheme
The âlg for the ring closure reaction is -1.15 that
implies a considerable C-O bond breaking in the rate-
limiting transition state. A value of âlg ) -1 was found
for the intramolecular aminolysis of 2-substituted ben-
zoate esters,22 and a value of âlg ) -1.15 was found in
(

Kinetic Study of Hydrolysis of Phthalic Anhydride
J . Org. Chem., Vol. 66, No. 23, 2001 7657
Ta ble 4. IR a n d 13C NMR for th e X-p h en yl Hyd r ogen
P h th a la tes
the carbonate catalyzed reaction in the hydrolysis of aryl
trifluoroacetates.23 The high value of the âlg probably
IR, cm-
1 a
13C NMR, ppmb
indicates that the ring closure takes place without the
formation of a tetrahedral intermediate with finite
lifetime. The results are also consistent with the rapid
X
H
1695.5 (CdO in -COOH) 172.4
166.5
132.5
129.7
126.0
166.8
133.2
130.1
129.0
150.8
1770.5 (CdO in ester)
133.0
130.0
129.0
131.1
129.5
121.3
148.6
132.4
130.0
121.0
formation of a tetrahedral intermediate that undergoes
rate-limiting elimination of phenoxide.24
p-CH3 1677.5 (CdO in -COOH) 172.3
The second-order rate constant for the reaction of
1
758.1 (CdO in ester)
136.0
131.1
129.8
-
-2
-1
-1 25
phenyl benzoate with HO is 5.56 × 10
M
s .
Assuming a â value of 0.5, we can calculate the rate
2
0.8
1713.7 (CdO in -COOH) 171.8
759.5 (CdO in ester) 132.8
31.4
129.1
1709.7 (CdO in -COOH) 171.8
1742.6 (CdO in ester)
constant for the nucleophilic reaction of a carboxylate of
-
6
-1 -1
p-Cl
166.3
132.6
130.2
122.7
166.2
149.3
131.6
129.6 sh
pK
a
3.06 as 8.5 × 10
M
s . Since the rate constant
1
for the intramolecular reaction of the carboxylate in
1
-
2
-1
phenyl hydrogen phthalate is 4.43 × 10
s , the
3
effective molarity is 5 × 10 M, a typical value for
m-Cl
151.2
131.4
129.6
119.8
intramolecular reactions.26
134.8 132.6 sh
1
1
30.3
29.0
130.2
122.1
In conclusion, we have determined that the hydrolysis
of phthalic anhydride is catalyzed by buffer bases such
as phosphate, acetate, N-methyl imidazole, DABCO, and
carbonate, and in the case of the amines and phosphate,
the nucleophilic mechanism can be inferred from the
data. Phenol is very reactive toward this electrophile, and
this fact complicates the kinetics of the hydrolysis of
phenyl hydrogen phthalate at pH higher than 5.70. The
hydrolysis of aryl hydrogen phthalate occurs with the
formation of phthalic anhydride as the intermediate, and
only the deprotonated carboxylate group is effective for
intramolecular catalysis. Besides, the reactions have a
high âlg, indicating that there is significant C-O bond
breaking in the transition state.
126.4
a
KBr pellets. b In d-chloroform.
M of phenol half-neutralized with NaOH. The pH values of
these solutions were 9.876, 9.888, and 9.882.
Kin etic P r oced u r es. Most reactions were carried out in
an Applied Photophysics SF 17MV apparatus with unequal
mixing. The substrate 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. The total acetonitrile concentration was 3.85%.
The solutions of the substrates for the kinetic determinations
were freshly prepared in dry acetonitrile in the appropriate
-
4
concentration to get a final concentration of 5 × 10 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 observed rate constants were determined by measuring
the change in absorbance at 300 nm. In some of the experi-
ments, 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 with one-, two-, or three-exponential equa-
tions using the software of the SF apparatus.
Exp er im en ta l Section
Aqueous solutions were made up from water purified in a
Millipore apparatus. Acetonitrile Merck HPLC was dried on
silica gel 10% p/v as described in the literature.27 It is very
important to have the solvent dried because with traces of
water the substrates hydrolyzes before the solution can be
used.
The pH measurements were done at controlled temperature
and calibrated with buffers prepared according to the litera-
ture.
The wavelengths used to monitor the reactions were 255
nm for phenyl hydrogen phthalate at pH 0.63, 1.06, and 1.45,
2
8
2
60 nm for p-methylphenyl hydrogen phthalate at pH 0.68,
Phthalic anhydride (Anedra) was sublimated before use. The
monoaryl esters were prepared from phthalic anhydride and
the appropriate phenol by adapting the method described in
1.45, and 2.00, and 300 nm for phenyl hydrogen phthalate at
pH 2.00 and for phthalic anhydride at pH 0.63, 1.06, 1.45, and
2.00. These reactions were measured in a cell, with temper-
ature control, of a conventional spectrophotometer adding the
substrate dissolved in acetonitrile to a solution containing all
the other ingredients in the required proportion to have the
same amount of the organic solvent as in the stopped-flow
experiments.
2
9
the literature. The products were characterized by IR and
1
3
C NMR. The spectroscopic data are collected in Table 4. The
IR of phenyl hydrogen phthalate agrees with the reported
2
9
spectrum. The purity of the products was also checked by
comparing the UV-vis absorption spectrum of a solution
containing the fully hydrolyzed ester with one at the same
concentration prepared with phthalic acid and the correspond-
ing phenol.
Ack n ow led gm en t. This research was supported in
part by the Consejo Nacional de Investigaciones Cien-
tificas y T e´ cnicas (CONICET), the Agencia Cordoba
Ciencia (ex-Consejo de Investigaciones Cient ´ı ficas y
Tecnol o´ gicas de la Provincia de C o´ rdoba), Agencia
Nacional de Ciencia y Tecnolog ´ı a (FONCYT), and the
Universidad Nacional de C o´ rdoba, Argentina. G.O.A. is
a grateful recipient of a fellowship from FOMEC and
from CONICET.
The pK
a
of phenol at ionic strength 0.5 M was determined
by measuring the pH of solutions 0.0462, 0.0305, and 0.150
(22) Fife, T. H.; Chauffe, L. J . Org. Chem. 2000, 65, 3579.
(23) Fernandez, M. A.; de Rossi, R. H. J . Org. Chem. 1999, 64, 6000.
(24) Theoretical and experimental investigations suggest that the
hydrolysis of aryl esters may occur without formation of a tetrahedral
intermediate with finite lifetime (see ref 23 and references therein),
but all these studies involve intermolecular reactions.
(
25) Kirsch, J . F.; Clewell, W.; Simon, A. J . Org. Chem. 1968, 33,
1
27.
Su p p or tin g In for m a tion Ava ila ble: Tables S1-S5, con-
taining the observed rate constant for phthalic anhydride and
aryl hydrogen phthalates as a function of pH and buffer
concentration. This material is available free of charge via the
Internet at http://pubs.acs.org.
(
(
26) Kirby, A. J . Acc. Chem. Res. 1997, 30, 290.
27) Perrin, D. D.; Armarego, W. L. G. Purification of Laboratory
Chemicals, 3rd ed.; Butterworth-Heinemann Ltd: Great Britain, 1994;
p 68.
(
28) Handbook of Chemistry and Physics, 72nd ed.; Lide, D. R., Ed.;
CRC Press: Boca Raton, FL, 1991-1992; pp 8-30-8-35.
29) Bojanowska, I.; J asinski, T. Pol. J . Chem. 1989, 63, 455.
(
J O010499V