Investigations on substituent and solvent effects on solvolysis reactions Part IX. The influence of polar substituents on the imidazole catalyzed hydrolysis of 2,4-dinitrophenyl acetates in water

Article abstract of DOI:10.1039/a901004a

The imidazole catalyzed hydrolysis of polar substituted 2,4-dinitrophenyl acetates in water has been investigated at different temperatures. The observed rates correspond to the bimolecular nucleophilic addition of the imidazole at the carboxylic carbon atom followed by a very fast hydrolysis of the N-acetylimidazole in water. The influence of polar substituents in the acid moiety of the ester molecule on the hydrolysis reaction can be described by an electrostatic dipole-dipole interaction in the same way as the neutral hydrolysis of polar substituted ethyl acetates.

Full text of DOI:10.1039/a901004a

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Investigations on substituent and solvent e†ects on solvolysis reactions
Part IX.¤ The inÑuence of polar substituents on the imidazole catalyzed
hydrolysis of 2,4-dinitrophenyl acetates in water
J. Bittner and G. Schmeer*
Institut fur Physikalische und T heoretische Chemie, Universitat Regensburg, D-93040
Regensburg, Germany. E-mail: Georg.Schmeer=chemie.uni-regensburg.de
Received 5th February 1999, Accepted 29th March 1999
The imidazole catalyzed hydrolysis of polar substituted 2,4-dinitrophenyl acetates in water has been
investigated at di†erent temperatures. The observed rates correspond to the bimolecular nucleophilic addition
of the imidazole at the carboxylic carbon atom followed by a very fast hydrolysis of the N-acetylimidazole in
water. The inÑuence of polar substituents in the acid moiety of the ester molecule on the hydrolysis reaction
can be described by an electrostatic dipoleÈdipole interaction in the same way as the neutral hydrolysis of
polar substituted ethyl acetates.
According to the neutral hydrolysis of polar substituted ethyl
acetates,4 the rate determining step of the imidazole catalyzed
hydrolysis in water is the formation of an intermediate like a
mixed ester-amide of ortho-acetic acid via a tetrahedral tran-
sition state.
According to the neutral hydrolysis of esters, one important
contribution to the Gibbs energy of activation, *Gº, should
be the electrostatic interaction energy of the dipolar nucleo-
phile molecule (water, imidazole) with the ester molecule.
Within the scope of this electrostatic model of the activation
step, the change of the Gibbs energy of activation, **Gº, in a
series of polar substituted esters with respect to the
unsubstituted 2,4-dinitrophenyl acetate (Index 0) is correlated
1
Introduction
The imidazole catalyzed hydrolysis of esters in waterÈsee Fig.
1Èproceeds via the addition of imidazole at the carboxylic
carbon atom in the sense of nucleophilic catalysis (B N)2
forming a tetrahedral intermediate. This intermediate decom-
poses by the elimination of the alcohol or phenol group, yield-
ing a very reactive N-acetylimidazole which is immediately
hydrolysed in aqueous solution. The Ðnal formation of acids
or their corresponding bases is controlled by the dissociation
constants of the respective acids (alcohols, phenols and acetic
acids).
Ac
The general base catalysis (B 3)2 by a second imidazole
Ac
molecule is of less importance3 due to the relatively high
to the change of the electric Ðeld ([grad t
ester molecule, see eqn. (2).
) of the polar
Ester
acidity of the leaving 2,4-dinitrophenol (pK \ 4.1), and is not
S
observed in water. Therefore, the reaction is purely of Ðrst
R T ln(k /k) \ **Gº \ *Gº [ *Gº
order in the ester and in imidazole (cf. eqn. (1)).
g
0
0
dc
dt
\ [N l (grad t
[ grad t
)
(2)
Ester
[
\ kc
c
(1)
A Nucl
Ester
Ester, 0
Ester Im
R is the gas constant, T the temperature, l
is the dipole
g
Nucl
moment of the nucleophile, t
is the electrostatic potential
Ester
of the polar ester molecule, and N is AvogadroÏs number;
A
and k and k are the rate constants of the respective com-
0
pounds.
The other contributions to *Gº remain nearly constant in
the series of polar substituted esters and therefore vanish in
eqn. (2). Since this simple treatment was very successful for the
description of the substituent e†ect of polar substituents on
the neutral and alkaline hydrolysis of esters, it should be
tested to see if it can also be used for the imidazole catalyzed
hydrolysis of esters in aqueous solutions.
2
Experimental
Fig. 1 Mechanism of the imidazole catalyzed hydrolysis of esters in
water.
The rate constants of the imidazole catalyzed hydrolysis of
2,4-dinitrophenyl acetate, 2,4-dinitrophenyl methoxyacetate,
and 2,4-dinitrophenyl chloroacetate have been measured in
water between 5 and 45 ¡C.
¤ Part VIII, ref. 1.
Phys. Chem. Chem. Phys., 1999, 1, 2593È2596
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Table 1 Physical data of the prepared esters R-CO C H (NO )
2 2
Table 3 Pseudo-Ðrst-order rate constants k of the imidazole cata-
2
6
3
obs
lyzed hydrolysis of polar substituted 2,4-dinitrophenyl acetates (units,
Yield (%)
Melting point (q/¡C)
c
: 10~4 mol l~1, k : 10~2 s~1).
Im
obs
R
Exptl.
Lit.
Exptl.
Lit.
c
k
c
k
Im
obs
Im
obs
CH
55
53
50
606
È
È
69.5
85.5
92.5
706
2,4-Dinitrophenyl acetate
5 ¡C
3
CH OCH
È
3
ClCH
2
2
97È987
15 ¡C
125.0 ^ 0.1
200.2 ^ 0.1
275.5 ^ 0.2
351.1 ^ 0.2
2.99 ^ 0.03
124.9 ^ 0.1
200.0 ^ 0.1
275.3 ^ 0.2
350.8 ^ 0.2
4.97 ^ 0.02
7.75 ^ 0.03
10.69 ^ 0.02
13.47 ^ 0.03
4.72 ^ 0.03
6.49 ^ 0.02
8.14 ^ 0.03
2.1 Materials
The three esters (2,4-dinitrophenyl acetate, 2,4-dinitrophenyl
methoxyacetate, and 2,4-dinitrophenyl chloroacetate) were
prepared according to Schmidt and Westheimer.5 15 mmol
2,4-dinitrophenol and 15 mmol pyridine were dissolved in 100
ml dry diethyl ether. Subsequently, 15 mmol of the com-
mercially available acetyl chloride, dissolved in 25 ml dry
diethyl ether, was added at room temperature within 30 min.
After stirring of the solution for 12 h to complete the reaction,
the precipitated pyridinium hydrochloride was Ðltrated o†
and the solvent removed under reduced pressure. The remain-
ing esters were recrystallized from chloroform/n-hexane mix-
tures (1:4) until constant melting points were achieved. All
procedures were done under dry nitrogen to prevent hydro-
lysis of the reagents and products. The physical data of the
substances are given in Table 1. 2,4-Dinitrophenyl methoxy-
acetate has not yet been described in the literature (searches in
Chemical Abstracts and Beilstein yielded negative results). Its
1H NMR data are given in Table 2. The observed lines in the
NMR spectrum are in full accordance with the molecular
structure. 1,4-DioxaneÈthe solvent of the ester stock solu-
tions for the kinetic measurementsÈwas treated with a molec-
ular sieve (Merck, 0.4 nm) for 20 days to decrease the water
content, as determined by the Karl Fischer method, from 50
to 15 ppm. The water was deionized via a Millipore column.
Imidazole (puriss., Fluka) was used without further puriÐ-
cation. The sodium hydroxide solutions were prepared from
0.1 m stock solutions (Merck) by dilution with water to the
appropriate concentration. All solutions were held under
nitrogen that was free of carbon dioxide.
25 ¡C
35 ¡C
124.7 ^ 0.1
199.6 ^ 0.1
274.7 ^ 0.2
350.0 ^ 0.2
7.83 ^ 0.01
12.45 ^ 0.06
17.01 ^ 0.03
21.52 ^ 0.06
124.3 ^ 0.1
199.0 ^ 0.1
274.2 ^ 0.2
349.0 ^ 0.2
12.06 ^ 0.03
19.08 ^ 0.10
26.29 ^ 0.08
33.03 ^ 0.07
45 ¡C
123.8 ^ 0.1
198.2 ^ 0.1
273.2 ^ 0.2
347.6 ^ 0.2
18.69 ^ 0.07
29.36 ^ 0.07
40.27 ^ 0.15
51.28 ^ 0.17
2,4-Dinitrophenyl methoxyacetate
5 ¡C
15 ¡C
8.07 ^ 0.03
15.34 ^ 0.04
22.73 ^ 0.04
29.99 ^ 0.05
4.37 ^ 0.03
8.22 ^ 0.07
12.04 ^ 0.07
16.02 ^ 0.11
8.06 ^ 0.03
15.33 ^ 0.04
22.71 ^ 0.04
29.96 ^ 0.05
6.68 ^ 0.04
12.57 ^ 0.09
18.57 ^ 0.07
24.43 ^ 0.05
25 ¡C
35 ¡C
8.04 ^ 0.03
15.29 ^ 0.04
22.66 ^ 0.04
29.90 ^ 0.05
9.93 ^ 0.07
18.89 ^ 0.09
27.7 ^ 0.2
36.4 ^ 0.2
8.02 ^ 0.03
15.25 ^ 0.04
22.60 ^ 0.04
29.81 ^ 0.05
14.62 ^ 0.10
27.4 ^ 0.3
40.5 ^ 0.6
53.1 ^ 0.3
45 ¡C
7.99 ^ 0.03
15.19 ^ 0.04
22.51 ^ 0.04
29.70 ^ 0.05
21.0 ^ 0.4
39.5 ^ 0.3
58.2 ^ 0.2
76.4 ^ 0.6
2,4-Dinitrophenyl chloroacetate
5 ¡C
2.2 Kinetic measurements
The kinetic experiments were performed in a previously
described optical apparatus with a multichannel diode array
spectrometer1 for the detection of chemical reactions with
time constants greater than 0.5 s in the wavelength range from
200 to 620 nm. After Ðlling the reaction cell with 20 ml of the
aqueous solution of imidazole and attaining the appropriate
temperature, the reaction was started by the injection of 30 ll
of the ester solution. The volume ratio of the solutions of the
esters in 1,4-dioxane to the aqueous solutions is less than
0.005 and therefore the inÑuence of the organic solvent on the
reaction is negligible. The solutions contain imidazole with at
least twentyfold excess and therefore the time dependence of
15 ¡C
1.26 ^ 0.02
2.15 ^ 0.02
3.09 ^ 0.02
3.99 ^ 0.02
5.54 ^ 0.10
9.29 ^ 0.04
13.17 ^ 0.09
17.12 ^ 0.06
1.26 ^ 0.02
2.17 ^ 0.02
3.08 ^ 0.02
3.99 ^ 0.02
8.34 ^ 0.11
14.03 ^ 0.14
19.92 ^ 0.11
25.64 ^ 0.13
25 ¡C
35 ¡C
1.27 ^ 0.02
2.16 ^ 0.02
3.08 ^ 0.02
3.98 ^ 0.02
12.81 ^ 0.06
21.5 ^ 0.2
1.26 ^ 0.02
2.16 ^ 0.02
3.08 ^ 0.02
3.97 ^ 0.02
18.7 ^ 0.2
31.7 ^ 0.2
44.9 ^ 0.2
57.2 ^ 0.6
30.56 ^ 0.12
39.0 ^ 0.2
45 ¡C
1.26 ^ 0.02
2.15 ^ 0.02
3.06 ^ 0.02
3.94 ^ 0.02
26.7 ^ 0.2
45.2 ^ 0.5
62.9 ^ 0.7
81.5 ^ 1.3
Table 2 1H NMR data for 2,4-dinitrophenyl methoxyacetatea
d (ppm)
Signal
J(HÈH)/Hz
I
Group
rel
3.57
4.44
9.00
8.56
7.53
s
s
d
dd
d
È
È
2.7
8.9, 2.7
8.9
3
2
1
1
1
ÈOÈCH
3
ÈCOÈCH ÈO
the absorbance of the solution, A(t), taken at the wavelength
of maximum absorption of the 2,4-dinitrophenolate ion (360
nm), is given by the pseudo-Ðrst-order kinetic equation, eqn.
(3)
2
ArÈH(3)
ArÈH(5)
ArÈH(6)
a Solvent: CDCl , reference: TMS. s: singlet, d: doublet, dd: double
doublet. The numbers at the aryl hydrogen atoms refer to the num-
bering of the 2,4-dinitrophenyl group. NMR spectrometer: Bruker
AC-250.
3
A(t) \ A= ] (A0 [ A=)e~kobs t
(3)
where A0 and A= are the absorbances at the beginning and at
the end of the reaction. The computer program used, mcskin1
2594
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Table 4 Rate constants k and activation parameters of the imidazole catalyzed hydrolysis of polar substituted 2,4-dinitrophenyl acetates
k/l mol~1 s~1
*Gº/
*Hº/
*Sº/
5 ¡C
15 ¡C
25 ¡C
35 ¡C
45 ¡C
kJ mol~1
kJ mol~1
J mol~1 k~1
2,4-Dinitrophenyl acetate
2.28 ^ 0.02
3.78 ^ 0.03
6.07 ^ 0.03
121.1 ^ 0.6
968 ^ 8
9.36 ^ 0.08
176.6 ^ 0.4
1423 ^ 9
14.56 ^ 0.07
254.8 ^ 0.6
2037 ^ 20
68.6 ^ 0.4
61.1 ^ 0.2
56.0 ^ 0.6
31.5 ^ 0.2
26.4 ^ 0.1
26.6 ^ 0.3
[124.2 ^ 0.8
[116.5 ^ 0.5
[98.5 ^ 0.9
2,4-Dinitrophenyl methoxyacetate
53.0 ^ 0.4
81.0 ^ 0.1
2,4-Dinitrophenyl chloroacetate
423 ^ 4 635 ^ 3
(developed in our laboratory for the non-linear optimization
E (r, h, r) \ [grad t (r, h, r)
(5b)
(5c)
1
1
of rate equations) yields the Ðtted parameters A0, A= and k
,
obs
E (O, h, r) \ 0
their standard deviations, the number of half-life periods, and
the turnover of the reaction.
1
The transition state is imbedded in a dielectric sphere with
radius a and with internal permittivity e , and surrounded by
i
the homogenous solvent with permittivity e. The acid moiety
3
Results
is characterised by k , the dipole moment of the polar bond
1
The experimental rate constants of the imidazole catalyzed
hydrolysis of polar substituted 2,4-dinitrophenyl acetates in
water are collected in Table 3. They are mean values of 6È11
measurements over at least six half-life periods.
CÈCl. The term R is the distance between the two dipoles, h
1
and h are the angles between the dipole vectors and this dis-
2
tance, and r is the dihedral angle between the two dipoles
around the axis R. The electrostatic potential W (r, h, r)
1
The second-order rate constants k, given in Table 3, are
results from the superposition of all charges within the mol-
obtained by linear least-squares Ðtting of eqn. (4)
ecule.
The solution of the Poisson equations for the potential
inside and outside of the dielectric sphere yields the potential
k
\ k
] kc
H2O Im
(4)
obs
with respect to the concentration of imidazole (the correlation
coefficients lie between 0.9997 and 0.9999). The neutral hydro-
lysis of the 2,4-dinitrophenyl acetates in aqueous solution
(k ) is more than Ðve orders of magnitude slower and, there-
fore, need not be taken into account.
t (r, h, r) and its gradient with the help of appropriate
1
boundary conditions. The resulting electrostatic energy W
,
el
eqn. (6),
H2O
k k GC e [ 2
A
R
a
B
3
D
1 2
W \
1 [
sin h sin h cos r
el
1
2
The linear temperature dependence of the rate constants
(ln(k/T ) vs. 1/T ) yields the activation parameters with corre-
lation coefficients better than 0.9999.
The activation quantities *Gº, *Hº, and *Sº are given in
the last three columns of Table 4. The negative activation
entropies are in the typical range for such reactions and show
clearly the decrease of the degrees of freedom in the tetra-
hedral transition state.
For the rate constant k of the imidazole catalyzed hydro-
lysis of 2,4-dinitrophenyl acetate the following data can be
found in the literature (6.49 l mol~1 s~1 at 26.2 ¡C in water,8
5.83 l mol~1 s~1 at 25 ¡C in waterÈ0.4% acetonitrile,3,9 and 4
l mol~1 s~1 at 25 ¡C in waterÈ3% acetonitrile10). Our result
(6.07 l mol~1 s~1) is in good agreement with the Ðrst two
data, whereas the last value shows the inÑuence of the less
solvating solvent acetonitrile. For the other two esters no
experimental values can be found in the literature.
R3
e ] 1
C
e [ 2
e ] 1
A
R
B
3
D
H
[ 2 ]
cos h cos h ] W @ (6)
1
2
a
can be subdivided into the contribution of the substituent
dipole k (e.g. k
) and the constant contribution W @ of the
residual molecule, which will vanish in the energy di†erence
with respect to the unsubstituted reference molecule.
1
ChCl
R, h , h , and r are the relative coordinates of the two
1
2
dipoles in the transition state. Due to free rotation around the
CÈC-axis in the ester, the mean value of r is D90¡, and there-
fore the Ðrst term in eqn. (6) is zero. The change in the rate
constants is then given by eqn. (7)
N k
A 2
C
e [ 2
e ] 1
A
R
a
B
3
D Ak cos h cos h
B
1
1
2
ln(k/k ) \
2 ]
*
(7)
0
RT
R3
4
Discussion
At the molecular level the Gibbs energy of activation, *Gº, is
given by the amount of work, which is necessary to bring the
imidazole molecule from inÐnite distance to its place in the
transition state, required to modify the electronic charge dis-
tribution in the tetrahedral activated complex, and to rear-
range the solvent shell around the reaction centre.
In the dielectric model of the transition state, shown in Fig.
2, the interesting contribution to this energy is the electro-
static energy, *G , necessary to transfer the imidazole dipole
el
k in the electrostatic potential t (r, h, r) of the ester molecule
2
1
from a very large distance to the Ðnal position in the tran-
sition state, as is given by eqn. (5):
Fig. 2 Model of the transition state of the imidazole catalyzed
hydrolysis of 2,4-dinitrophenyl chloroacetate (R \ C H (NO ) .
*G \ [N l (E (R, h, r) [ E (O, h, r)) \ N W
el A 2 el
(5a)
6
3
2 2
1
1
A
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Table 5 Structural data and electrostatic substituent parameters *(k cos h cos h /R3) of the esters RCO C H (NO ) . The e†ective dipole
1
1
2
2
6
3
2 2
moment of the methoxy group is calculated via the superposition of the two CÈO dipoles in the direction of the CÈO bond. (Substituent
parameter: D nm~3; rate constants k and k taken from Table 3 at 25 ¡C)
0
nCCX
(¡)
Rest R
Bonding
d/nm
R/nm
cos h
cos h
k
/D
*/(k cos cos h /R3)
log k/k
1
2
ChX
1
1
2
0
CÈC
CÈN
CÈH
OÈC
0.154
0.147
0.107
0.143
CH
CH OCH
109.5
109.5
(105)
110.0
0.376
0.383
0.362
0.402
0.892
0.882
[0.4
0.74
(1.1)
1.46
0.0
7.1
0.0
1.3
3
2
3
(OÈCH )
3
CH Cl
ClÈC
0.176
0.390
0.437
0.871
11.8
2.2
2
with the substituent parameter according to eqn. (8)
moments (k
Imidazole
\ 3.87 D14 and
k
\ 1.85 D15; 1
H2O
D B 3.335 64 ] 10~30 C m) is 2.09. The consistency of the
two values is remarkably good, taking into account that, on
the one hand, the dipole moments are determined in the gas
phase and, on the other hand, the slopes in Fig. 3 contain the
inÑuence of the solvent water on the reacting molecules and
the transition state. This result shows that the solvation e†ects
in the two series of esters remain nearly constant and play
only a minor role in the discussion of the inÑuence of polar
substituents on the reaction rate. The inÑuence of the two dif-
ferent leaving groups on the reaction rate is eliminated in the
A
k cos h cos h B Ak cos h cos h
B
1
1
2
1
1
2
*
\
R3
R3
A
k cos h cos h
B
1
1
2
[
(8)
R3
0
In this model of the substituent parameter it is assumed, that
the ratio (R/a) in eqn. (6) remains constant in the di†erent
molecules. The atomic distances, bond angles, and dipole
moments are taken from standard tables.11,12 In the scope of
this model, the geometrical parameters of stable compounds
are taken also for the unstable transition states. Because only
energy di†erences are discussed, this procedure is justiÐed.
The length R is determined as the distance between the
centre of the dipole of the imidazole and the centre of the
respective shifts of the rate constants, log(k/k ).
Recent quantum-mechanical calculations of the neutral
hydrolysis of polar substituted ethyl acetates16 at the ab initio
level in the gas phase conÐrm the assumption that electro-
negative substituents in the acyl moiety decrease the energy
barrier of the tetrahedral transition state.
0
substituent dipole CÈX (X \ OCH , Cl for the polar substi-
3
tuted esters, and H for the reference molecule with Index 0).
The former point is calculated from the bond lengths and
angles of the planar imidazole molecule13 and from its charge
distribution14 as the midpoint between the negative and the
positive charge. The latter point is calculated as the midpoint
of the CÈX bond from standard bond lengths and angles with
the assumption r \ 90¡. The relevant data for the calculations
are given in Table 5.
Acknowledgements
We are grateful to the ““Fonds der Chemischen Industrie
(Frankfurt/Main)ÏÏ for Ðnancial support.
Fig. 3 shows the function log(k/k ) \ f M*[(k cos h cos
References
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1
1
h )/R3]N according to this electrostatic model. The linearity of
2
1
G. Schmeer, C. Six and J. Steinkirchner, J. Solution Chem., 1999,
28, 211.
the function (line 1 in the Ðgure) is fulÐlled in the whole range.
Line (2) in Fig. 3 is the straight line obtained from the
neutral hydrolysis of ethyl acetates,4 which is fulÐlled over
seven decades for the rate constants.
2
3
4
5
E. K. Euranto, Ann. Acad. Sci. Fenn., A 2, 1970, 152, 1.
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2
6
D. B. Olsen, T. W. Hepburn, S. Lee, B. M. Martin, P. S. Mariano
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7
8
9
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Fig. 3 Linear dependence of the rate shift log(k/k ) at 25¡ C on the
0
electrostatic substituent parameter. Line (1) shows the linear depen-
Paper 9/01004A
dence of the imidazole catalyzed hydrolysis, line (2) that of the neutral
hydrolysis of the polar substituted ethyl acetates.4
2596
Phys. Chem. Chem. Phys., 1999, 1, 2593È2596