Nucleophilic substitution in carboxylic esters in oil-in-water microemulsions

Article abstract of DOI:10.1023/A:1020892132432

In hydrolysis and aminolysis of p-nitrophenyl esters of carboxylic acids in oil-in-water microemulsions on the basis of surfactants of various nature, a complex mechanism of the effect of the medium is operative, including shift of acid-base equilibria in the nucleophile. The rate constants of the processes studied are quantitatively related to the surface potential of the microdroplet. Varied hydrophobicity of the nucleophile and substrate changes the site of the reaction act and the relative contributions of aminolysis and hydrolysis.

Full text of DOI:10.1023/A:1020892132432

Russian Journal of General Chemistry, Vol. 72, No. 8, 2002, pp. 1261 1265. Translated from Zhurnal Obshchei Khimii, Vol. 72, No. 8, 2002,
pp. 1343 1348.
Original Russian Text Copyright
2002 by Mirgorodskaya, Kudryavtseva.
Nucleophilic Substitution in Carboxylic Esters
in Oil-In-Water Microemulsions
A. B. Mirgorodskaya and L. A. Kudryavtseva
Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center,
Russian Academy of Sciences, Kazan, Tatarstan, Russia
Received August 9, 2000
Abstract In hydrolysis and aminolysis of p-nitrophenyl esters of carboxylic acids in oil-in-water micro-
emulsions on the basis of surfactants of various nature, a complex mechanism of the effect of the medium is
operative, including shift of acid base equilibria in the nucleophile. The rate constants of the processes studied
are quantitatively related to the surface potential of the microdroplet. Varied hydrophobicity of the nucleo-
phile and substrate changes the site of the reaction act and the relative contributions of aminolysis and
hydrolysis.
Surfactant microemulsions are thermodynamically
reagents, as well as the rate and mechanism of
stable, self-organized, and macroscopically uniform chemical processes.
dispersions with aqueous and hydrocarbon phases,
Chemical processes in surfactant oil-in-water micro-
stabilized by surfactants and cosurfactants [1]. The
high solubilizing ability and the exceptionally de-
veloped interface providing effective contact between
reagents with different solubilities in the aqueous and
organic phases explain the interest in such systems as
microreactors for various chemical processes [2 4].
emulsions generally occur either on the surface of or
inside the microdroplet. By varying the hydrophobicity
of reagents, one can affect the site of their localization
and also their partners by the reaction act, which can
be exemplified by hydrolytic cleavage of p-nitro-
phenyl carboxylates in microemulsions in the presence
of primary aliphatic amines. In aqueous solutions, this
process generally occurs by two directions: aminolysis
(major reaction) and alkaline hydrolysis (side reac-
tion).
Knowledge of factors determining the rate and
direction of processes in microemulsions is very
important, allowing one to forecast and plan results
of scientific research and favoring purposeful search
for new catalytic systems. These problems are closely
related to enzymology, since most enzyme processes
occur in highly organized systems, such as cell
membranes and subcellular particles. Microemulsions
can serve as a convenient model for studying in vitro
processes in living cells [5].
R NH2
RC(O)NHR +HOC H NO -p
6
4
2
RC(O)OC H NO -p
6
4
2
OH
RC(O)OH + OC H NO -p
6
4
2
To estimate the relative contributions of these two
processes in microemulsions, we at first considered
alkaline hydrolysis of p-nitrophenyl esters in the
absence of amines. It should be noted that the kinetic
dependences of this process on the nature of micro-
emulsion-forming surfactants, the hydrophobicity of
substrate, the pH and temperature of reaction medium
are of interest in their own.
The present work is a continuation and develop-
ment of our research into the catalytic properties of
oil-in-water microemulsions in nucleophilic substitu-
tion reactions [6]. Its aim is to study the properties of
oil-in-water microemulsions on the basis of surfac-
tants of various nature and to gain insight into the
effect of these systems on hydrolysis and aminolysis
of carboxylic esters.
The apparent hydrolysis rate constants (k ) of
1
,o
p-nitrophenyl acetate (I) and p-nitrophenyl caprylate
(II) in microemulsions on the basis of cetyltrimethyl-
ammonium bromide (III), cetylpyridinium bromide
(IV), dodecylpyridinium bromide (V), cetylpyridi-
nium chloride (VI), Brij-97 (VII), and sodium do-
decyl sulfate (VIII) at pH 9.35 are listed in Table 1.
In the microemulsions studied (fraction of the disperse
As the reaction medium for nucleophilic substitu-
tions in carboxylic esters we chose microemulsions
with equal volumes of the disperse phases but dif-
ferently charged microdroplet surfaces. Varied nature
of surfactants forming microemulsions should affect
the physicochemical properties and reactivity of
1
070-3632/02/7208-1261$27.00 2002 MAIK Nauka/Interperiodica

1262
MIRGORODSKAYA, KUDRYAVTSEVA
Table 1. Apparent hydrolysis rate constants of compounds
and II in surfactant oil-in-water microemulsions
same reason is responsible for the higher sensitivity of
compound II, compared with compound I, to the
chain length and the nature of surfactant head group
and counterion (Table 1). It should be noted that
acetate I undergoes a more facile hydrolysis than
caprylate II both in all the microemulsions studied
and in molecular aqueous solutions. In this respect
microemulsions considerably differ from micellar
systems, where the micellar catalytic effect with ester
I is weak, while with ester II it is strong and results
in reactivity reversal of these two substrates [7].
I
a
(
pH 9.35)
I
II
Sur-
factant
T,
k1,o
s 1
,
,
T,
k1,o
s 1
,
C
mV
C
III
III
III
III
IV
V
VI
VII
VII
VII
25
33
41
43
25
25
25
25
31
37
43
25
32
43
51
0.00091
0.00195
0.00350
0.00387
0.00110
0.00150
0.00102
0.00028
0.00053
0.00070
0.00096
0.000123
0.00020
0.00046
0.00085
30.2
25 0.00026
33 0.00053
41 0.0010
43 0.0011
25 0.00037
25 0.0007
25 0.00034
25 0.000041
The kinetic effect of microemulsions can be divided
into two contributions: (1) nonelectrostatic which
relates to hydrophobic interactions with reagent and is
commonly modeled by the effect of nonionogenic
surfactants and (2) electrostatic which relates to inter-
action of hydroxide ion with a charged microdroplet
surface [8].
35.1
43.1
33.2
0
b
VII
ln k2, = ln k2, + e /k T.
VIII
VIII
VIII
VIII
21.1
25 0.000025
34 0.000051
41 0.000113
47 0.00015
B
Here e is the electronic charge, is the effective
surface potential, k is Boltzmann’s constant, T is the
B
absolute temperature, and k2, and k2, are the second-
order rate costants, determined in microemulsions on
the basis of ionogenic surfactants and a nonionogenic
surfactant, corrected for the phase volume. At the
same value, the k2, value for two microemulsions
a
The k
values in aqueous solutions at pH 9.35 are 0.00032,
1
1
,o
0
.0062, 0.0126, and 0.015 s at 25, 32,47, and 51 C, respecti-
1
vely, for compound I and 0.000045, 0.000080, and 0.00019 s
at 25, 35, and 47 C, respectively, for compound II.
At higher temperatures, addition of compound II to the micro-
emulsion on the basis of surfactant VII induces phase separa-
tion.
b
under comparison can be replaced by k . In our
1,o
case, for the nonionogenic surfactant we used com-
pound VII.
The effective surface potentials ( ) in microemul-
sions on the basis of ionogenic surfactants, estimated
by the above equation from the kinetic data for al-
kaline hydrolysis of ester I, proved to be 50 100 mV
lower in absolute value than those in micellar solu-
tions of the same compounds [9 11] (Table 1). This
is explained by the presence in the surface layer of the
microdroplet of the neutral 1-butanol molecules.
phase 0.13), microdroplet formation involves, along
with a surfactant (5.05 wt%), a hydrocarbon (hexane,
1
.97 wt%) that forms a nonpolar nucleus, and a co-
surfactant (1-butanol, 5.05 wt%). As follows from the
oil water partition constants {10.8 (I) and 95.9 (II)
[4]}, substrate is almost completely localized inside
microdroplet. As the volume phase we used aqueous
sodium tetraborate [c 0.05 M (pH 9.35)]. The result-
ing data suggest electrostatic interactions: concentra-
tion of hydroxide ion at a positively charged micro-
droplet surface (cationic surfactants) accelerates hydro-
lysis of esters I and II compared with aqueous solu-
tion at the same pH, a negatively charged surface
The example of the microemulsion on the basis of
surfactant III was used to trace the effect of the pH
of the medium of the apparent hydrolysis rate constant
of esters I and II (Fig. 1). It will be remembered that
the listed pH values are formal and thus unsuitable
for estimating the true nucleophile concentration and
the second-order rate constants of alkaline hydrolysis.
(
anionic surfactants) slows down the reaction, and
microemulsions on the basis of nonionogenic sur-
factants has almost no rate effect. Therewith, the
effects of the medium, measured by the ratio of the
apparent rate constants in microemulsions and in
water k (me)/k (water), are slightly better pro-
Cetylamine added to the reaction mixture localizes
in the microdroplet and competes with hydroxide in
the nucleophilic attack on the substrate ester bond.
The contribution of aminolysis increases and becomes
dominating as the amine concentration increases and
the pH of the medium decreases. The high solubiliz-
1
,o
1,o
nounced with ester II compared with ester I, probably,
on account of different localizations of these sub-
strates in the surface layer of the microdroplet. The
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 72 No. 8 2002

NUCLEOPHILIC SUBSTITUTION IN CARBOXYLIC ESTERS
ing ability of microemulsions allows such amine
1263
k1,o, s 1
concentrations to be attained that alkaline hydrolysis
of p-nitrophenyl esters is suppressed completely. The
dependences of the apparent rate constants of amino-
lysis (kapp) on amine concentration in various micro-
emulsions in the concentration range studied (to
0
.015
1
0
.05 M) are linear both with compound I and with
0
.010
compound II (Fig. 2). It should be borne in mind that
acid base equilibria in surfactant solutions are shifted
due to selective solubilizing ability of microaggre-
gates with respect to neutral and ionized forms of
compounds. This shift is primarily determined by the
surface potential of the microdroplet and results in
that, at the same pH of surfactant microemulsions, the
fraction of the neutral form of the amine ( ) increases
in cationic surfactant solutions and decreases in
0.005
2
0
9.2
9.6 10.0 10.4 10.8 11.2
pH
anionic surfactant solutions. The shift of pK can
a
contribute much into the catalytic effect by changing
the concentration of the neutral (reactive) form of the
amine.
Fig. 1. Hydrolysis rate constants (k ) of (1) p-nitro-
1
,o
phenyl acetate and (2) p-nitrophenyl caprylate vs. pH of
the medium in the microemulsion on the basis of sur-
factant III (25 C).
From the dependences of the apparent rate con-
stants of cleavage of the p-nitrophenyl esters on amine
kapp, s 1
concentration (c ) by the equation k
= (kapp
am
2,am
k )/ c we estimated the volume-averaged second-
1
,o
am
order aminolysis rate constants (k2,am) (Table 2). On
an example of reaction of ester I with cetylamine one
can see that the k2,am values in microemulsions depend
on the sign of the surface potential of the microdroplet,
0.15
1
being slightly lower that the k value for this reaction
2
2
in water and much higher that that in hexane (Table 2).
These findings suggest that aminolysis of acetate I
takes place in a fairly polar region of microemulsions,
i.e., at the interface. The hydrophobic caprylate II is
likely to react with cetylamine in the oil phase, and,
therefore, its k2,am values are almost independent on
the nature of the microemulsion-forming surfactant. It
should be noted that the apparent rate constants of
aminolysis in microemulsions on the basis of cationic
and anionic surfactants vary 30 times with ester I and
0
.10
0.05
0
3
4
5
1
0 times with ester II, whereas the k2,am values, 7 and
.5 times with esters I and II, respectively. These re-
0.01 0.02
0.03 0.04 0.05
, M
c
am
sults provide evidence for the assumption that the
main factor controlling the rate of this reaction is shift
Fig. 2. Apparent rate constants (k ) of cleavage of
app
of the pK of the amine, i.e. the amount of its reactive
ester I in the microemulsions on the basis of surfactants
(1) III, (2) VII, (4) VIII and (3) of ester II in the
microemulsion on the basis of surfactant III vs. con-
centration of cetylamine (25 C).
a
form.
When analyzing the kinetic data for cleavage of
p-nitrophenyl esters in the presence of butylamine,
one should take into account that the latter is fairly
hydrophilic and is partition between the aqueous
and oil phases. Butylamine is a strong base and, there-
fore, regardless of the fact that microemulsions on the
its neutral form is low ( 0.13), which adversely
affects experimental accuracy. We determined the rate
constant of reactions of butylamine with esters I and
II in the microemulsion on the basis of surfactant III
at various pHs. With account for the contribution of
alkaline hydrolysis and for the values, we estimated
basis of cationic surfactants reduce the pK values of
a
amines, in a buffer solution at pH 9.35 the fraction of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 72 No. 8 2002

1264
MIRGORODSKAYA, KUDRYAVTSEVA
Table 2. Apparent rate constants for cleavage of the ester bonds in compounds I and II in surfactant oil-in-water micro-
emulsions in the presence of amines (pH 9.35)a
I
II
Surfactant
kapp, s 1
k2,am
,
kapp, s 1
k2,am,
l mol 1 s 1
T,
C
T,
C
(
cam 0.01 M)
l mol 1 s 1
(cam 0.025 M)
Cetylamine
III
III
III
III
IV
V
VI
VII
VII
VII
VIII
VIII
VIII
VIII
0.95
25
0.064
0.080
0.094
0.11
6.64
8.22
9.52
11.2
5.0
25
0.010
0.42
0.53
0.67
0.92
0.43
0.37
0.42
0.70
33
41
48
25
25
25
25
31
34
25
34
41
51
33
41
48
25
25
25
25
0.0126
0.0160
0.0230
0.0101
0.0092
0.010
0.93
0.98
0.95
0.80
0.05
0.059
0.051
0.036
0.448
0.052
0.0018
0.0030
0.0038
0.00502
5.75
5.2
4.50
5.60
6.45
0.84
1.38
1.67
2.09
0.014
0.2
25
32
43
51
0.00185
0.0025
0.0031
0.0046
0.365
0.450
0.612
0.886
Butylamineb
4.60
III
0.15
25
0.0079
25
0.005
0.64
a
1
1
The k values for the reaction of ester I with cetylamine in hexane are 0.022, 0.023, and 0.021 l mol
s
at 23, 27, and 37 C,
2
b
respectively. The k
value was calculated taking into account that at amine concentrations of 0.01 and 0.025 M the pHs of the
2
,am
microemulsion are 9.55 ( 0.15) and 10.0 ( 0.25), respectively.
second-order rate constants for aminolysis of esters I
activation energy for aminolysis in much higher than
zero but much lower than for hydrolysis. This result is
probably explained by temperature- and reagent-
induced structural changes in microemulsions, by the
character of distribution of their components between
the aqueous and nonaqueous phases, as well as with
and II, which proved to be close to the k values with
2
cetylamine. These results gives us grounds to state
that aminolysis with butylamine occurs in the disperse
phase. The contribution of volume aminolysis into
the overall reaction rate appears to be small. The
reaction rates depend on the concentrations of the possible changes in reaction mechanisms. Thus, at the
nucleophile and substrate in the same phase rather
than on the hydrophobicity of the amines.
same pH, the contribution of alkaline hydrolysis in
ester cleavage increases with increasing temperature.
Consequently, in oil-in-water microemulsions, tem-
Kinetic studies on cleavage of ester bonds in micro- perature (along with hydroxide and amine concentra-
emulsions in the presence of cetylamine allowed us to
estimate activation parameters for hydrolysis and
aminolysis of esters I and II (Tale 3). The activation
tion) may prove an important parameter controlling
the amide:acid ratio in the final reaction products.
energies (E ) and preexponential terms (log A) are
To conclude, in oil-in-water microemulsions on
the basis of surfactants of various nature, a complex
mechanism of the effect of the medium on nucleo-
philic substitution in carboxylic esters is operative,
including shift of acid base equilibria in the nucleo-
phile. The hydrolysis rate constants of esters are
quantitatively related to the surface potential of the
microdroplet, and this process can serve as a probe
for estimating the latter parameter. By varying the
hydrophobicity of the nucleophile and substrate, one
can change the site of the reaction act and control the
a
apparent and depend on the thermodynamic para-
meters of intermediate equilibrium processes. Hydro-
lysis of p-nitrophenyl esters in microemulsions is
characterized by high activation energies which only
slightly depend of surfactant nature and are slightly
higher than the E values in water (Table 3). It is
a
known that aminolysis processes have low activation
energies [12]. The E value for the reaction of cetyl-
a
amine with ester I in hexane, we estimated with data
in Table 2, too, is close to zero. In microemulsions, the
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 72 No. 8 2002

NUCLEOPHILIC SUBSTITUTION IN CARBOXYLIC ESTERS
1265
Table 3. Activation parameters of cleavage of ester bonds in compounds I and II in surfactant oil-in-water microemulsions
in the absence and in the presence of cetylamine
I
II
Surfactant
a
a
E , kJ/mol
Ea, kJ/mol
log A
E , kJ/mol
Ea, kJ/mol
log A
a
a
(hydrolysis)
(aminolysis)
(aminolysis)
(hydrolysis)
(aminolysis)
(aminolysis)
III
VII
VIII
63.19
52.01
59.84
17.27
29.63
29.0
3.93
5.84
6.93
63.49
24.99
26.63
3.99
4.21
67.28
a
The log A value could not be estimated because of the lack of second-order rate constants for hydrolysis; the E values for this
a
process in aqueous solutions at pH 9.35 are 45.86 (ester I) and 52.06 kJ/mol (ester II).
relative contributions of the competing processes.
Therewith, in microemulsions, like in molecular solu-
tions, acetate I undergoes a more facile cleavage than
caprylate II, i.e. no reactivity reversal of these esters
is observed, by contrast to what happens in micellar
systems on the basis of the same surfactants. Tempera-
ture, along with nucleophile concentrations, deter-
mines the fractions of amides and acids formed by
ester cleavage.
ACKNOWLEDGMENTS
The work was financially supported by the Russian
Foundation for Basic Research (project no. 99-03-
3
2037a).
REFERENCES
1
. Mikroemul’sii: struktura i dinamika (Microemulsions:
Structure and Dynamics), Friberg, S.E. and Botorel, P.,
Eds., Moscow: Mir, 1990.
EXPERIMENTAL
2. Schwuger, M.J., Stichdom, K., and Schomacker, R.,
Chem. Rev., 1995, vol. 95. no. 4. p. 849.
The solvents, amines, and p-nitrophenyl carboxylic
esters were purified by conventional procedures. The
samples of ionogenic surfactants were twice repreci-
pitated from ethanol with diethyl ether.
3. Menger, F.M. and Elrington, A.R., J. Am. Chem. Soc.,
1
991, vol. 113, no. 25. p. 9621.
4
5
. Bhattacharya, S. and Senhalatha, K., J. Chem. Soc.,
Perkin Trans. 2, 1996, no. 9. p. 2021.
. Martinek, K., Levashov, A.V., Khmel’nitskii, Yu.L.,
and Klyachko N.L., in Fiziko-khimicheskie problemy
fermentativnogo kataliza (Physicochemical Problems
of Enzyme Catalysis), Moscow: Nauka, 1984, p. 18.
. Mirgorodskaya, A.B. and Kudryavtseva, L.A., Izv.
Ross. Akad. Nauk, Ser. Khim., 1998, no. 2, p. 272.
. Micellization, Solubilization, and Microemulsions,
Mittal, K., Ed., New York: Plenum, 1977.
Kinetic measurements were performed spectro-
photometrically on a Specord UV-Vis instrument in
temperature-controlled cells, following the optical
density at 400 nm (formation of p-nitrophenolate
6
7
8
9
anion). The initial concentration of the substrate was
5
5
10 M, conversion >90%.
. Mackay, R.A. and Hermansky, C., J. Phys. Chem.,
1
981, vol. 85, no. 6. p. 739.
The apparent pseudo-first-order rate constants (kapp
)
. Mirgorodskaya, A.B., Kudryavtseva, L.A., Zakharo-
va, L.Ya., and Bel’skii, V.E., Izv. Ross. Akad. Nauk,
Ser. Khim., 1998, no. 7, p. 1333.
were determined from the dependence log (D
.434kapp + const (D and D are the optical
densities of solutions at time and after reaction
D ) =
0
1
1
0. Bohmer, M.R., Koopal, L.K., and Lyklema, J.,
J. Phys. Chem., 1991, vol. 95, no. 23, p. 9569.
1. Mchedlov-Petrosyan, N.O., Loginova, L.P., and Kle-
shchevnikova, V.N., Zh. Fiz. Khim., 1993, vol. 67,
no. 8, p. 1649.
2. Bel’skii, V.E., Valeeva, F.G., and Kudryavtseva, L.A.,
Izv. Ross. Akad. Nauk, Ser. Khim., 1998, no. 7,
p. 1339.
completion). The kapp values were calculated by the
least-squares method.
The fractions of the neutral forms of amines at a
given pH were found by potentiometric titration with
1
0.1 N hydrochloric acid using a pH-340 pH meter in
microemulsions with an aqueous volume phase.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 72 No. 8 2002