Reactions within Association Complexes: The Reaction of Imidazole with Substituted Phenyl Acetates in the Presence of Detergents in Aqueous Solution

Article abstract of DOI:10.1021/jo991887o

The bimolecular rate constants for reaction of imidazole with phenyl acetates complexed with sodium dodecyl sulfate (SDS) or cetyltrimethylammonium bromide (CTAB) micelles obey Bronsted equations with β_lg similar to that of the reaction in aqueous solution. The dissociation constants of ester (K_S) and the hypothetical dissociation constant (K_TS) of the transition state of the micelle complexes obey Hansch equations with similar sensitivities (p) to π (-0.66 and -0.589 for K_S and -0.735 and -0.495 for K_TS, respectively). The slopes also indicate that the microsolvation environments associated with the transition state and the complexed ester have aqueous character. The relative values of K_TS and K_S indicate that the transition state of the reaction of imidazole with ester is more weakly complexed to both micelles than is the reactant ester. Log K_TS values are linear functions of log K_S for reactions with both CTAB and SDS; the slopes are, respectively, -0.893 and -1.19 consistent with a slightly more "water-like" medium for the transition state than for the site of binding of ester with CTAB-micelle and slightly less for the SDS-micelle. The results for ester and transition state are consistent with the location of the phenyl residue in a hydrophobic region that possesses water molecules. It is concluded that the acetyl group in the complexed transition state is located in an aqueous part of the Stern region, whereas the phenyl residue is in a part of the Stern region that possesses alkane components. The derived kinetic and complexation parameters in these experiments refer to micelles with Stern regions that have been maintained at constant ionic compositions.

Full text of DOI:10.1021/jo991887o

J . Org. Chem. 2000, 65, 2537-2543
2537
Rea ction s w ith in Associa tion Com p lexes: Th e Rea ction of
Im id a zole w ith Su bstitu ted P h en yl Aceta tes in th e P r esen ce of
Deter gen ts in Aqu eou s Solu tion
Necmettin Pirinccioglu, Flora Zaman, and Andrew Williams*
University Chemical Laboratory, Canterbury, Kent CT2 7NH, U.K.
Received December 7, 1999
The bimolecular rate constants for reaction of imidazole with phenyl acetates complexed with sodium
dodecyl sulfate (SDS) or cetyltrimethylammonium bromide (CTAB) micelles obey Brønsted equations
with âlg similar to that of the reaction in aqueous solution. The dissociation constants of ester (KS)
and the hypothetical dissociation constant (KTS) of the transition state of the micelle complexes
obey Hansch equations with similar sensitivities (p) to π (-0.66 and -0.589 for KS and -0.735 and
-0.495 for KTS, respectively). The slopes also indicate that the microsolvation environments
associated with the transition state and the complexed ester have aqueous character. The relative
values of KTS and KS indicate that the transition state of the reaction of imidazole with ester is
more weakly complexed to both micelles than is the reactant ester. Log KTS values are linear
functions of log KS for reactions with both CTAB and SDS; the slopes are, respectively, -0.893 and
-1.19 consistent with a slightly more “water-like” medium for the transition state than for the
site of binding of ester with CTAB-micelle and slightly less for the SDS-micelle. The results for
ester and transition state are consistent with the location of the phenyl residue in a hydrophobic
region that possesses water molecules. It is concluded that the acetyl group in the complexed
transition state is located in an aqueous part of the Stern region, whereas the phenyl residue is in
a part of the Stern region that possesses alkane components. The derived kinetic and complexation
parameters in these experiments refer to micelles with Stern regions that have been maintained
at constant ionic compositions.
In tr od u ction
90 detergent molecules, is up to 3 nm. There is sufficient
space within the hydrophobic core to accommodate at
least one substrate molecule without disrupting the
overall structure of the micelle. Owing to the charged
Stern region, the SDS and CTAB micelles are subject to
ion-exchange phenomena; it is very important to keep
the ion compositions of the bulk solutions constant
throughout any concentration variations of the detergent
in order that any derived kinetic and complexation
constants are ascribed to a micelle with a Stern region
of constant ionic atmosphere.
We present here a study of the effect of micelles on
the first step of the reaction of imidazole with substituted
phenyl acetates (Scheme 1); these esters do not possess
long aliphatic side chains capable of binding in the
interior of the micelle and able to force the phenyl
component of the bound ester into the Stern layer. The
hydrophobic effect of the substituent (π)6,7 as well as the
electronic effect8 on the transition-state binding are
studied to elucidate the possible location of the transition
state of the reaction. Study of the bimolecular reaction
between ester and imidazole has the advantage that the
imidazole has a very small log P value and therefore has
little propensity to partition into the hydrophobic core
of the micelle. When hydroxide ion acts as a nucleophile
the reaction is complicated by an ion-exchange compo-
nent in CTAB and in SDS by a substantial electrostatic
repulsion.
Micelles are self-organized aggregates of detergent
molecules that contain both polar (often charged) hydro-
philic groups and a hydrophobic group, usually a long-
chain aliphatic component.1-5 The polar headgroup of the
detergent tends to associate with the bulk aqueous
solvent, and the hydrophobic part aggregates with that
of other detergent molecules to form a fluxional structure,
the micelle. The shape of the micelle can be roughly
spherical but at high detergent concentrations can take
on more extended forms such as rods, tubes, or laminar
forms. Whatever is the shape of a particular micelle, it
has a hydrophobic region and a hydrophilic surface
(interface with bulk solvent); the micelle can complex a
reactive organic molecule thus lowering its concentration
and inhibiting its reaction in the bulk aqueous phase.
Reactions of complexed substrates could occur within the
hydrophobic region of the micelle or at the interface with
the bulk solvent. Reaction in the micellar pseudophase
may be accelerated or decelerated depending on the
nature of the headgroup and the reactant species.5 The
diameter of the roughly spherical micelle, which in the
case of sodium dodecyl sulfate (SDS) and cetyltrimethyl-
ammonium bromide (CTAB) possesses between 80 and
* To whom correspondence should be addressed. Phone: (44) (0)-
1227-82-3693. Fax: (44) (0)1227-82-7724. E-mail: aw@ukc.ac.uk.
(1) Fendler, J . H.; Fendler, E. J . Catalysis in Micelles and Macro-
molecular Systems; Academic Press: New York, 1975.
(2) Cordes, E. H.; Gitler, C. Prog. Bioorg. Chem. 1973, 2, 1.
(3) Menger, F. M. Acc. Chem. Res. 1979, 12, 111.
(4) Kunitake, T.; Shinkai, S. Adv. Phys. Org. Chem. 1980, 17, 435.
(5) Bunton, C. A.; Savelli, G. Adv. Phys. Org. Chem. 1986, 22, 213.
(6) Fujita, T.; Iwasa, J .; Hansch, C J . Am. Chem. Soc. 1964, 86, 5175.
(7) Leo, A. J .; Hansch, C.; Elkins, D. Chem. Rev. 1971, 71, 525.
(8) Williams, A. Adv. Phys. Org. Chem. 1992, 27, 1.
10.1021/jo991887o CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/25/2000

2538 J . Org. Chem., Vol. 65, No. 8, 2000
Pirinccioglu et al.
Sch em e 1. Rea ction of Im id a zole w ith Su bstitu ted P h en yl Aceta tes in Aqu eou s Solu tion
Ta ble 1. Ra te P a r a m eter s for Rea ction of Im id a zole w ith Su bstitu ted P h en yl Ester s in th e P r esen ce of SDS a t 25° a
100kc/
[ester] ×
λ
103kobs
m
c
j
g,n
phenyl ester
ku/M-1s-1
Ks/mMb
M-1 s-1
KTS/Md pKa
πl
104/Mp /nmh Ne
/s-1
rf
substituted phenyl acetates
1
2
3
4
5
6
7
8
9
4-nitro
3-nitro
4-cyano
3-cyano
4-acetyl
2-chloro
3-chloro
4-chloro
parent
0.554 ( 0.010
0.202 ( 0.004
0.264 ( 0.002
0.127 ( 0.003
0.159 ( 0.002
0.0577 ( 0.001
0.052 ( 0.001
0.023 ( 0.0004
33.1 ( 4.3
70.6 ( 9.8
47.4 ( 0.002
42.0 ( 5.9
45.1 ( 4.1
6.86 ( 0.54
11.5 ( 1.4
7.81 ( 0.98
2.87 ( 0.16
0.639
>1.30
>3.12
>1.11
>1.67
0.0682 8.48
0.427 9.02
0.0898 9.38
0.439 9.99
0.0305 7.51
0.0175 6.92
0.0122 7.55
0.0405 7.71
0.0203 8.62
7.14
8.38
7.95 -0.33
8.61 -0.31
8.05 -0.39
0.22
0.11
0.442
1.77
0.695
1.14
0.288
1.69
1.97
2.44
5.99
1.01
400
350
290 11
6
6
27.7-5.34
10.1-1.42
13.2-2.11
0.9978
0.9975
0.9991
<1.1
<0.4
<0.48
<0.43
294
330
290
280
280
260
300
310
305
295
295
6
6
7
8
7
6
7
8
7
6
7
6.37-0.966 0.9973
7.96-0.834 0.9989
2.89-0.40
2.58-0.237 0.9948
1.15-0.116 0.9985
0.24-0.0445 0.9995
0.58 ( 0.069
0.76
0.77
0.73
0.00
1.49
2.26
2.27
1.53
1.50
0.9980
0.14 ( 0.01
0.200 ( 0.03
0.0325 ( 0.0084
3.13 ( 0.12
3.8 ( 0.37
6.43 ( 0.4 × 10-3 22.2 ( 1.61
10 2,5-dichloro
11 2,3,4-trichloro 0.42 ( 0.004
12 3,4,5-trichloro 0.538 ( 0.002
13 2,3-dichloro
14 3,4-dichloro
0.318 ( 0.002
3.00 ( 0.18
1.58 ( 0.43
0.855 ( 0.105
2.81 ( 0.28
2.1 ( 0.8
15.9-1.65
21.4-1.77
26.9-2.01
11.4-1.02
0.9998
0.9992
0.9999
0.9999
0.735
0.869
1.09
3.76 ( 0.13
1.58 ( 0.14
0.971 ( 0.162
0.228 ( 0.002
0.0938 ( 0.0022
2.03
4.69-0.489 0.9987
substituted phenyl hexanoate
1.99 ( 0.4 0.0247
4-nitro
0.346 ( 0.008
1.42 ( 0.2
0.539
400
9
17-1.2 0.9980
a
Conditions of measurement: solution held at pH 8.92 ( 0.02 with borate buffer (Na2B4O7) at 0.05 M, total [Na+] ) 0.22 M, free
imidazole at 0.05 M. Disssociation constant of the ester-micelle complex (in terms of detergent molecule concentration). c Second-order
b
d
rate constant for reaction of imidazole with ester-micelle complex. Dissociation constant of the transition state of the reaction between
imidazole and ester-imidazole complex. e Number of data points not including duplicates. f Correlation coefficient of fit of kobs/[free imidazole]
g
h
j
to the concentration ([detergent] - cmc) according to eq 1. Range of observed rate constants. Wavelength of the kinetic studies. pKa
l
m
n
of the leaving phenol from refs 37 and 38. The value of π is taken from ref 39. Ester concentration. Refers to the SDS concentration
range of 0-0.2 M.
mL of buffered solution, contained in a 1 cm path length silica
cuvette in the thermostated cell compartment of a Pye Unicam
SP 8-200 UV/vis spectrophotometer. The pH’s of the solutions
were measured before and after each kinetic run using a
Radiometer PHM62 pH meter with a Russell CMAWL com-
bined electrode, calibrated with BDH buffers; data for experi-
ments where the pH changed by more than 0.1 units were
discarded. Wavelengths for studying the kinetics of the reac-
tions were determined initially by repetitively scanning the
spectrum during a reaction and are recorded in Tables 1 and
2. The reactions were followed kinetically by measuring the
absorbance (At) at the optimal wavelength as a function of
time.
Exp er im en ta l Section
Ma ter ia ls. Sodium dodecyl sulfate was obtained from BDH
and cetyltrimethylammonium bromide from Sigma. Substi-
tuted phenyl acetates were available from a previous study9
or prepared by the method of Chattaway.10 3-Nitrophenyl
acetate was donated by Dr. A. B. Maude. Imidazole was
recrystallized from benzene. All solutions were prepared with
water double-distilled from glass and degassed. Buffer materi-
als and salts to maintain cation or anion concentrations were
either of A. R. grade or purified before use.
Meth od s. A series of buffered solutions for studies of rates
at different SDS concentrations (0-0.2 M) were prepared by
dilution of a stock solution containing the SDS with a diluent
solution (identical in respect of imidazole concentration, pH
and ionic strength) but without SDS. A similar protocol was
employed for the variation of CTAB concentration (0-0.05 M).
When the effect of imidazole concentration was being studied,
the detergents were kept at a standard concentration in both
buffers and imidazole was omitted from the diluent buffer. The
component concentrations are recorded in Tables 1 and 2.
In the case of the SDS studies, the sodium ion concentration
was maintained at 0.22 M, and in the case of CTAB, the
bromide ion concentration was kept at 0.05 M. In the case of
SDS, it is essential to keep the imidazolium ion concentration
as low as possible so that as little as possible ion exchange
occurs between the sodium ion in the Stern layer and the
imidazolium ion in the bulk. The consequences of not paying
due regard to these protocols are outlined in the Results.
Reactions were initiated by the addition of an aliquot (0.01-
0.05 mL) of a solution of the substrate (in acetonitrile) to 2.5
Pseudo-first-order rate constants were obtained by fitting
the value of At (which increases with time in these cases) to
the equation At ) A∞ - (A∞ - Ao) exp(-kt). Data were fit to
theoretical equations by use of standard software.
Resu lts
Monitoring the reaction between imidazole and sub-
stituted phenyl acetate in micellar solutions by UV-
absorption spectrocopy demonstrated the release of a
phenol and formation of the acetyl imidazole intermedi-
ate. In the case of the nonmicellar reactions, this reaction
has been very well documented,11,12 and there is no
evidence that the micellar solutions are changing the
nature of the reaction. The hydrolysis of the acetyl
imidazole is not measured and it is therefore not a
complicating feature. In the case of some esters, the UV-
spectral changes demonstrated that acetyl imidazole
(9) Ba-Saif, S. A.; Colthurst, M.; Waring, M. A.; Williams, A. J .
Chem. Soc., Perkin Trans. 2 1991, 1901.
(10) Chattaway, F. D. J . Chem. Soc. 1931, 2495.
(11) Kirsch, J . F.; J encks, W. P. J . Am. Chem. Soc. 1964, 86, 837.
(12) Williams, A.; Naylor, R. A. J . Chem. Soc. B 1971, 1967.

Reactions within Association Complexes
J . Org. Chem., Vol. 65, No. 8, 2000 2539
Ta ble 2. Ra te P a r a m eter s for Rea ction of Im id a zole a n d Hyd r oxid e Ion w ith Su bstitu ted P h en yl Ester s in th e P r esen ce
of CTAB a t 25 °C
ester
4-nitro
3-cyano
4-acetyl
2-chloro
3-chloro
4-chloro
parent
KS/mMb
103kc/M-1 s-1 c
KTS/Md
Ne
rf
103kobs/s-1 g,i
λ/nmh
substituted phenyl acetates with imidazolea
1
4
5
6
7
8
9
10
11
12
19.6 ( 3.7
4.98 ( 0.23
25.0 ( 1.4
4.26 ( 0.42
3.15 ( 0.38
5.25 ( 0.65
7.72 ( 1.2
2.33 ( 0.22
0.242 ( 0.031
0.513 ( 0.004
87.8 ( 3.2
20.8 ( 0.69
15.6 ( 3.6*
7.62 ( 1.1
8.13 ( 0.98
2.66 ( 0.49
1.33 ( 0.13
34.1 ( 5.2
42 ( 2.1
0.124
0.0304
0.255
0.0323
0.0201
0.0454
0.0373
0.0217
2.41 10-3
6.11 10-3
6
6
5
8
9
8
6
6
9
9
0.9978
0.99998
0.9900
0.9992
0.9964
0.9976
0.9979
0.9989
0.9996
0.9989
26.9-10.2
7.01-1.00
7.68-3.3
3.14-0.554
2.8-0.531
1.12-0.220
0.353-0.128
15.3-1.98
21.0-2.16
24.5-2.11
400
294
330
280
280
260
280
300
310
295
2,5-dichloro
2,3,4-trichloro
3,4,5-trichloro
45.2 ( 4
4-nitrophenyl acetate with hydroxide ionk
219 ( 28 1 ( 0.01
18 ( 0.68
7
0.9887
1.87-9.70
400
4-nitrophenyl hexanoate with imidazolea
with imidazolea
0.303 ( 0.007
3.8 ( 0.29
25.7 ( 0.3
with hydroxide ionm
4.08 × 10-3
5
8
0.99999
0.9899
22.1-1.91
2.27-33.5
400
400
198 ( 21
1.5 ( 0.33
a
Conditions of measurements: pH maintained at pH 7.04 ( 0.02 with imidazole buffer at a fraction of base ) 0.5 (total imidazole
concentration ) 0.1 M). Bromide ion concentration maintained at 0.05 M with KBr. Ester concentrations, π, and pKa values as given in
b-h
i
k
Table 1.
Footnotes as in footnotes to Table 1. Refers to concentration range from CTAB at 0-0.05 M. pH 10.05 maintained with
0.025M borate buffer. Bromide ion concentration maintained at 0.005M with KBr. Value of ku for hydroxide ion attack is 14.6 ( 1.6M-1s-1
.
m
pH 10.45 maintained with 0.025M borate buffer. Bromide ion concentration maintained at 0.005M with KBr. Value of ku for hydroxide
ion attack is 8.2 ( 0.24M-1s-1
.
F igu r e 2. Reactivity of 2-chlorophenyl acetate (kobs/[free
imidazole]) in the presence of SDS and imidazole(0.05 M free)
at pH 8.92 and in the presence of CTAB and imidazole (0.05
M free) at pH 7.03. Lines are theoretical, calculated from the
parameters in Tables 1 and 2.
F igu r e 1. Dependence of kobs on free imidazole concentration
for the reaction with 2-chlorophenyl acetate in the presence
of SDS at 0.16 M or CTAB at 0.04 M. Lines are least-squares
fits.
intermediate was formed and was starting to hydrolyze
during the experiments. The wavelengths were chosen
so that the decay of the acetylimidazole did not interfere
with the measurement of accurate kinetics of its forma-
tion.
Equation 1 is predicted by Scheme 2,13 and the condi-
tions employed for the experiments are given in Tables
1 and 2. We have treated the partitioning of ester into
micelle as if it were a regular one to one complexation
process; this is acceptable if the overall detergent con-
centration far exceeds that of the ester (see Tables 1 and
2). It is reasonable to assume that only a very small
number of ester molecules is absorbed in one micelle
particle at the concentration levels of detergent employed
in this study, that cmc values are not significantly
perturbed, and that there is little intermolecular interac-
tion between ester molecules complexed in a single
micelle. The values of the critical micelle concentrations
The reactions of imidazole with substituted phenyl
acetates to yield acetyl imidazole give good pseudo-first-
order kinetics up to about 90% of the total reaction. At a
given concentration of detergent, the observed first-order
rate constants are proportional to the free imidazole
concentration, and examples of this relationship are
illustrated for the 2-chlorophenyl acetate reacting in the
presence of SDS and CTAB (Figure 1). The reaction of
imidazole with substituted phenyl acetates is inhibited
by the detergents (Figure 2). The observed pseudo-first-
order rate constants for the inhibition reaction of imida-
zole with substituted phenyl acetates in a series of
detergent concentrations follow eq 1.
(cmc’s) for SDS and CTAB are taken as 1.35 × 10-3
M
and 0.8 × 10-3 M, respectively, and the aggregation
(13) Menger, F. M.; Portnoy, C. E. J . Am. Chem. Soc. 1967, 89, 4698.

2540 J . Org. Chem., Vol. 65, No. 8, 2000
Pirinccioglu et al.
Sch em e 2. Mech a n ism for Rea ction of Im id a zole
w ith Su bstitu ted P h en yl Aceta tes in th e P r esen ce
of Deter gen t Molecu les (w ) Bu lk Aqu eou s P h a se;
Mic ) Micelle P seu d op h a se)
numbers are 93 and 85.14-17
F igu r e 3. Brønsted correlations for ku, kc (CTAB), and
kc(SDS). Data are taken from Tables 1 and 2, and the lines
are calculated from the parameters in eqs 2, 3, and 4,
respectively. Identities of the ester points are from Table 1.
kobs/[imidazole]free ) (ku[KS] + kc[detergent - cmc])/
(KS + [detergent - cmc]) (1)
Neglect of the cmc term in eq 1 introduces differences
in the resultant kinetic parameters less than the stan-
dard deviations. This was noted previously for similar
systems by Tee and Fedortchenko18 and by us;19,20 it is a
useful point as cmc’s and aggregation numbers vary with
the conditions and it is likely that small variations will
occur within the ranges of detergent concentrations
employed. Further, it is not clear how much the increas-
ing concentrations of micelle will alter the concentration
of free, unaggregated detergent molecules.
The derived kinetic parameters for the reaction of
imidazole with substituted phenyl acetates in the pres-
ence of the detergents are shown in Tables 1 and 2
together with the experimental conditions. Second-order
rate constants for the reaction of imidazole with acetates
(ku) correlate with the pKa of the leaving phenol (eq 2)
and agree with those from previous studies.11,12 Second-
order rate constants for the reaction of imidazole with
acetates in the presence of micelles (kc) also obey Brøn-
sted-type equations (3) and (4) (Figure 3). The units of
KS quoted in Tables 1 and 2 are in molar concentration
of detergent rather than the molar concentration of the
micellar particles because this would require an accurate
knowledge of the aggregation numbers. Even if the
aggregation number were known for a detergent, varia-
tion of its concentration is likely to cause a change in
this number. If the micelle were to be treated as a
molecule the molar dissociation constant would be given
by the term KS/N, where N is the aggregation number of
the micellar particle. The use of the molar concentrations
of detergent does not introduce the ambiguity that could
arise due to a possible change in shape of the micelles
as the concentration of detergent is decreased. It is not
possible to compare the results with much of the previous
work because of the general lack of cation or anion control
generally obtained in the literature. In studies of the
alkaline hydrolysis of 4-nitrophenyl acetate where the
F igu r e 4. Hansch correlations of KS and KTS for SDS. Data
are taken from Table 1, and lines are calculated from the
parameters in eqs 5 and 7, respectively. Identities of the ester
points are from Table 1.
ionic atmosphere was controlled,18,21 KS values agree with
those of the present report. Dissociation constants of the
ester from the ester-micelle complexes (KS) fit Hansch
equations (5) and (6) against π and are illustrated in
Figures 4 and 5.
Hypothetical dissociation of the transition state in the
micelle complex to give free micelle and “free” transition
state gives rise to the apparent dissociation constant
(KTS ) kuKS/kc).22-24 Log KTS correlates with Hansch
π-parameters (eqs 7 and 8) as illustrated in Figures 4
and 5. Log KTS is also linearly related with log KS for both
SDS- and CTAB-mediated reactions of ester with imida-
zole (eqs 9 and 10, Figure 6).
In the case of CTAB, the total bromide ion concentra-
tion was maintained constant; the effect on the kinetics
of not doing this was reported earlier for CTAB19 and it
was shown how to obtain rate constants that referred to
a standard ionic composition. In the case of SDS at pH’s
in the region of 7, ion exchange between the imidazolium
(14) Bennion, B. C.; Tong, L. K. J .; Holmes, L. P.; Eyring, E. M. J .
Phys. Chem. 1969, 73, 3288.
(15) Rosen, M. J . Surfactants and Interfacial Phenomena, 2nd. ed.;
J . Wiley and Sons: New York, 1989.
(16) Takeda, K.; Yasunaga, T. J . Colloid. Interfac. Sci. 1972, 40,
127; 1973, 45, 406.
(17) Tartar, H. V. J . Coll. Sci. 1959, 14, 115.
(21) Almgren, M.; Rydholm, R. J . Phys. Chem. 1979, 83, 360
(22) Kurz, J . L. Acc. Chem. Res. 1972, 5, 1.
(18) Tee, O. S.; Fedortchenko, A. A. Can. J . Chem. 1997, 75, 1434.
(19) Al-Awadi, N.; Williams, A. J . Org. Chem. 1990, 55, 2001.
(20) Al-Awadi, N.; Williams, A. J . Org. Chem. 1990, 55, 4359.
(23) Tee, O. S. Adv. Phys. Org. Chem. 1994, 29, 1.
(24) Page, M. I.; Williams, A. Organic and Bio-organic Mechanisms;
Addison-Wesley Longman: Harlow, 1997; p 74.

Reactions within Association Complexes
J . Org. Chem., Vol. 65, No. 8, 2000 2541
negative π values because of the relatively large KS
values. In view of the necessity of keeping the sodium
ion concentration constant, it is not possible to use SDS
concentrations in excess of the chosen molarity of the
sodium ion. It would be possible to use a higher sodium
ion concentration but it would then not be possible to
compare the results with those for the lower concentra-
tion. The lower limits obtained for KTS may be obtained
from the errors in determining kc. It is interesting that
these values, when incorporated with the accurately
measured KTS values, do not significantly alter equations
(7) and (9) (Table 3). Scheme 3 illustrates the effective
charge map for the systems.
Discu ssion
F igu r e 5. Hansch correlations of KS and KTS for CTAB. Data
are taken from Table 2, and lines are calculated from the
parameters in eqs 6 and 8, respectively. Identities of the ester
points are from Table 1.
Rate constants for the reaction of hydroxide ion with
substituted phenyl dodecanoates in CTAB solutions are
independent of Hansch π parameters for the substituents
on the aromatic ring of the phenyl esters19 consistent with
a transition state where the undecanyl side chain of the
ester substrate lies within the hydrophobic interior of the
micelle and the phenolate leaving residue and ester
function are located in the Stern region. Calculations
show that the log P value of 4-nitrophenyl acetate is some
five units smaller than that of 4-nitrophenyl dodeca-
noate.25a When there is no long-chain alkyl group at-
tached to the reacting substrate, the only binding avail-
able is that for the leaving group, and there is therefore
less hydrophobic force available for complexation than
in the dodecanoate case. It is likely that the phenyl
component of the complexed acetate lies in a hydrophobic
region at the surface in the Stern region. Tee and
Fedortchenko18 showed that there is a monotonic increase
in transition state binding as a function of the acyl group
chain length in a series of 4-nitrophenyl alkanoate
substrates in agreement with these conclusions. Broxton
and co-workers also concluded that compounds with
single phenyl groups complex at the interface in posi-
tively charged micelles.25b,c
F igu r e 6. Relationships between log KTS and log KS for the
ester reaction with imidazole in the presence of SDS and
CTAB. Lines are calculated from eqs 9 and 10, respectively.
Identities of the ester points are from Table 1. For clarity, the
SDS line is shifted 1 log KS unit to the left.
The values of log KS for CTAB- and SDS-mediated
reactions of acetate esters correlate with Hansch’s π
values (eqs 5 and 6) rather than with the pKa of the
leaving phenol; this indicates that the complexation of
ester with micelle is governed only by partitioning
interactions and has no significant component due to the
polarity of the substituent. The slopes of the Hansch
correlations are less than unity and therefore indicate
that the microscopic medium of the complexed ester is
more water-like than n-octanol26 consistent with a bind-
ing region that possesses both alkane chain as well as
water molecules. 4-Nitrophenyl hexanoate binds with
both SDS and CTAB much more efficiently than the
corresponding acetate and this is ascribed to the extra
hydrophobic character of the pentyl chain of the ester
lending extra components to the overall log P value. The
low value of log P for imidazole (-0.08)29 indicates that
it would be reluctant to complex with a micelle and this
explains why there is no observable curvature in the plot
of kobs against free imidazole.
ion and sodium ion at the Stern layer gives rise to a
variant ionic composition at the Stern layer; this is
overcome by using a pH (∼9.0) where there is little free
imidazolium ion and also by compensating for the change
in sodium ion concentration by the use of sodium chloride
in the diluent used in making up solutions of different
SDS concentrations. It was found that, as the concentra-
tion of SDS is increased without compensating for the
sodium ion in the presence of 0.1 M total imidazole (FB
) 0.5), the pH rises substantially (typically from 7 up to
8) due to the ion exchange of the imidazolium ion into
the Stern layer reducing its concentration in the bulk
water and increasing the fraction of base. A further
manifestation is that kobs is not necessarily proportional
to the free imidazole concentration unless the ionic
composition of the micelle’s Stern layer is maintained
constant. Arranging the experimental conditions so that
ion exchange is constant also simplifies the mathematical
equations for the kinetics so that fewer disposable
parameters (such as degree of cation binding or ion-
exchange constants) need be included; the consequence
of this is that the accuracy of the resultant kinetic and
dissociation constants is improved.
(25) (a) The fragmentation technique described by Leo27 was em-
ployed to calculate log P values for 4-nitrophenyl acetate (1.26),
4-nitrophenyl hexanoate (3.61), and 4-nitrophenyl dodecanoate (6.55).
(b) Broxton, T. J .; Christie, J . R.; Sango, X. J . Org. Chem. 1987, 52,
4814. (c) Broxton, T. J .; Christie, J . R.; Chung, R. P. T. J . Org. Chem.
1988, 53, 3081.
Perusal of Table 1 indicates that it has proved impos-
sible to measure kc accurately for esters with low or

2542 J . Org. Chem., Vol. 65, No. 8, 2000
Pirinccioglu et al.
Ta ble 3. Lin ea r F r ee En er gy Rela tion sh ip s for th e Kin etic a n d Bin d in g P a r a m eter s of th e Rea ction of Im id a zole w ith
P h en yl Aceta tes in Wa ter a n d Aqu eou s Solu tion s of CTAB or SDS
reaction in water:
log ku ) -0.606((0.058)pKa + 4.11((0.48)
log kc ) -0.666((0.071)pKa + 3.38((0.59)
log kc ) -0.540((0.066)pKa + 2.63((0.55)
(r ) 0.9488; n ) 14)
(r ) 0.9575; n ) 10)
(r ) 0.9453; n ) 10)
(r ) 0.9639; n ) 14)
(2)
(3)
(4)
(5)
reaction in solution of SDS:
reaction in solution of CTAB:
dissociation constant of the
ester-SDS micelle complexes:
dissociation constant of the
ester-CTAB micelle complexes:
dissociation constant of the
transition state-SDS micelle complexes:
log KS ) -0.660((0.053)π - 1.51((0.06)
log KS ) -0.589((0.097)π - 1.98((0.12)
(r ) 0.9074; n ) 10)
(r ) 0.9120; n ) 10)
(6)
(7)
log KTS ) -0.735((0.117)π - 0.293((0.16)
[log KTS ) -0.852((0.083)π - 0.106((0.097)
(r ) 0.9476; n ) 14)]a
(r ) 0.8297; n ) 10)
dissociation constant of the
(8)
transition state-CTAB micelle complexes:
relationship between KS and KTS
for the SDS micelle reaction:
relationship between KS and KTS
for the CTAB micelle reaction:
log KTS ) -0.495((0.117)π - 1.17((0.14)
log KTS ) -1.19((0.11) log KS - 1.60((0.25)
log KTS ) -0.893((0.077) log KS + 0.62((0.19)
(r ) 0.9695; n ) 10)
(r ) 0.9713; n ) 10)
(9)
(10)
a
This regression includes the lower limits for KTS determined by employing the upper limits of kc for 3-nitro-, 4-cyano-, 3-cyano-, and
4-acetylphenyl acetates (see Table 1).
Sch em e 3. Effective Ch a r ge Ma p a n d Ha n sch p Ma p for th e Rea ction of Im id a zole w ith Su bstitu ted
P h en yl Aceta tes in th e P r esen ce of CTAB a n d SDS Micellesa
a
Values of p (given in square brackets) are the slopes of the Hansch correlation against π; the Hansch p value for water is defined as
zero and that for n-octanol as unity.
The values of kc for reaction of imidazole with 4-nitro-
phenyl hexanoate and acetate are similar within an order
of magnitude (Tables 1 and 2) for both micellar species.
Since the reaction of the hexanoate involves attack when
the ester residue is in the Stern region it is likely that
the same goes for the acetate reaction. The conclusion
that reaction of the acetate occurs in the Stern region is
also supported by the observation18 of only a small
decrease in kc (which mirrors that in ku) for the alkaline
hydrolysis of 4-nitrophenyl alkanoates in CTAB micelles
and by the low value of log P for imidazole.
The present data do not favor any particular micelle
model but could be interpreteted according to a Dill-
Flory lattice-type model30 where the location of both
transition state and reactant ester binding site would be
in the surface where alkane side chain and headgroups
exist side by side.
(26) The slope of a linear Hansch correlation with π may be
employed as a measure of the nature of the complexation medium by
comparing it with the slopes for complexation into standard media.
Thus, the plot of log P versus π will have a slope of unity that is the
standard for partitioning into the n-octanol phase from aqueous
solution; a zero slope is obtained for the identity partitioning from
water into water. The approach is the same as that employed by Leffler
(see ref 24, p 52), who compared R values for rate constants with those
for equilibrium constants to measure the progress of reaction as a
function of reactant and product. A Hansch p value of zero for transfer
between two states (such as complexed ester and complexed transition
state) indicates that there is no change in microsolvation environment
between the two states. A value for p of unity for transfer from water
to the complexed system indicates that the medium in the complex
has the attributes toward hydrophobic interactions such as n-octanol.
A value of p of zero for such a system indicates that the part of the
substrate where π varies resides in an aqueous environment in the
complexed system.
The Brønsted dependence for the second-order rate
constants of the reaction in water (ku) (eq 2) and the
micelle (kc) (eqs 3 or 4) measures the change in effective
charge8 on the leaving oxygen of phenolate from the
ground state to the transition state in water and the
micelle, respectively, as illustrated in the effective charge
map (Scheme 3). The Brønsted slopes for the reaction in
the micelles are approximately the same as that in water,
indicating similar charge development in the transition
states and a near normal water activity at the interface.
Previous workers came to the same conclusion by show-
ing that the extent of hydration of counterions incorpo-
rated into the Stern region is about the same as that in
bulk aqueous solvent.31-33 The insensitivity of kc to π
(27) Leo, A. J . Chem. Rev. 1993, 93, 1281.
(28) Menger, F. M. In Surfactants in Solution (Proc. Int. Symp.,
1982); Plenum Press: New York, 1984; p 347.
(29) Menger, F. M. J . Phys. Chem. 1979, 83, 893.
(30) Dill, K. A.; Flory, P. J . Proc. Nat. Acad. Sci. U.S.A. 1981, 78,
676.

Reactions within Association Complexes
J . Org. Chem., Vol. 65, No. 8, 2000 2543
Sch em e 4. Sch em a tic of th e Loca tion , in th e
In ter fa ce of a n SDS-Micelle, of th e Tr a n sition
Sta te for Acetyl Im id a zole F or m a tion
indicates that there is no change in hydrophobic com-
plexing capacity in the medium between reactant state
and the transition state. Although the transition state
may be in the Stern region, for the reasons already given
the results indicate that the substituted phenyl group
must have substantial hydrophobic interactions with the
micelle and that its locus in the transition state has
similar polarity to that of the ester binding.
The dissociation constants (KTS) for both SDS and
CTAB reactions (Tables 1 and 2) indicate weaker binding
of the transition state to the micelle than that of the ester
substrate. The values of the transition-state dissociation
constants provide an alternative way of indicating the
micro-solvation environment of the locus of the transition
state. The values of log KTS are linearly related to the
corresponding log KS value (Figure 6 and eqs 9 and 10).
The slope is significantly less than unity for CTAB,
indicating that the site of the transition state is more
aqueous-like than that for ester binding. In the SDS case
the slope is slightly greater than unity indicating that
the binding of the phenyl residue of the substrate in the
transition state is slightly more hydrophobic than the
locus of binding of binding the reactant state.
The inhibition caused by the SDS micelles is undoubt-
edly due to the preferential complexation of the ester
compared with that for the reactant imidazole, although
the observation of a significant kc parameter indicates
that the imidazole is not completely excluded from the
micellar pseudo phase. The results of this study refer to
limited ranges of ester, imidazole, and detergent concen-
trations. When these ranges are greatly exceeded, there
is little doubt that the rate laws will change due to the
likely massive changes in the structures of the micelles.
The lower value of kc compared with that of ku would also
be expected due to the greater steric requirements for
nucleophilic attack at the complexed ester.
A Hansch dependence has been observed for the
dissociation constant between esters of substituted phen-
yl acetates and the micelle of the imidazolyl containing
detergent, dimethyl[2-(4-imidazolyl)ethyl]octadecylam-
monium chloride (DIEODC).34 The values of KS for the
acetates and of (p) compare with those found here and
for the dissociation constants of aromatic substrates and
inhibitors from chymotrypsin.35 The results of this study
enable an effective molarity to be determined for the
intramolecular reaction of imidazolyl group with the
complexed ester in the DIEODC micelle. Division of the
first-order rate constant for reaction of the complexed
ester in DIEODC by the second-order rate constant for
reaction of imidazole with CTAB complexed ester gives
an average value of 4.9 for the acetates (1, 5, 8, and 9).
This is a relatively low effective molarity for an intramo-
lecular reaction of an acyl function with a nucleophile36
and is similar to those values found for intramolecular
proton-transfer reactions. Low effective molarities are
consistent with a high degree of disorder in the intramo-
lecular reaction between complexed ester and the imi-
dazolyl group of the detergent; this might be expected
for micelle-catalyzed reactions.
The conclusions that can be made from this study that
the location of the transition state is close to the Stern
layer of the micelle are reasonable as it would prove
difficult for the imidazole to penetrate into the hydro-
phobic interior. The Hansch and Brønsted dependencies
also indicate that the orientation of the ester part of the
transition state in both micellar types is such that the
substituted phenyl component resides in the Stern region.
We represent this conclusion in the schematic structure
of Scheme 4. The conclusions agree with those of Tee and
Fedortchenko18 for the reaction of hydroxide ion with
4-nitrophenyl esters mediated by CTAB where there is
even more reason for the reagent, hydroxide ion, not to
enter the core region of the micelle.
Ack n ow led gm en t. The University of Dicle (N.P.)
and the SERC (quota award 92301379 to F.Z.) are
thanked for studentships and NATO for a travel grant
(910922). We are grateful for helpful discussions with
Dr. G. Cevasco and Professor S. Thea of the University
of Genoa.
J O991887O
(31) Gustavsson, H.; Lindman, B. J . Am. Chem. Soc. 1975, 97, 3923.
(32) Oakes, J . J . Chem. Soc., Faraday Trans. 2 1973, 69, 1321.
(33) Robb, I. D.; Smith, R. J . Chem. Soc., Faraday Trans. 1 1974,
70, 287.
(34) Tagaki, W.; Fakushima, D.; Eiki, T.; Yano, Y. J . Org. Chem.
1979, 44, 555.
(36) Kirby, A. J . Adv. Phys. Org. Chem. 1980, 17, 183.
(37) Ba-Saif, S. A.; Waring, M. A.; Williams, A. J . Am. Chem. Soc.
1990, 112, 8115.
(38) Bourne, N.; Chrystiuk, E.; Davis, A. M.; Williams, A. J . Am.
Chem. Soc. 1988, 110, 1890.
(39) Norrington, F. E.; Hyde, R. M.; Williams, S. G.; Wootton, R. J .
Med. Chem. 1975, 18, 604.
(35) Hansch, C. Accs. Chem. Res. 1969, 2, 232.