Kinetics of hydrolysis of procaine in aqueous and micellar media

Article abstract of DOI:10.1002/kin.20735

The kinetics of alkaline hydrolysis of procaine under the pseudo-first-order condition ([OH^-] a [procaine]) has been carried out. N,N-Diethylaminoethanol and p-aminobenzoate anion were obtained as the hydrolysis product. The rate of hydrolysis was found to be linearly dependent upon [NaOH]. The addition of cationic cetyltrimethylammonium bromide (CTAB), dodecyltrimethylammonium bromide (DDTAB) and tetradecyltrimethylammonium bromide, and anionic sodium dodecyl sulfate (SDS) micelles inhibited the rate of hydrolysis. The maximum inhibitive effect on the reaction rate was observed for SDS micelles, whereas among the cationic surfactants, CTAB inhibited most. The variation in the rate of hydrolysis of procaine in the micellar media is attributed to the orientation of a reactive molecule to the surfactant and the binding constant of procaine with micelles. The rate of hydrolysis of procaine is negligible in DDTAB micelles. The observed results in the presence of cationic micelles were treated on the basis of the pseudophase ion exchange model. The results obtained in the presence of anionic micelles were treated by the pseudophase model, and the various kinetic parameters were determined.

Full text of DOI:10.1002/kin.20735

Kinetics of Hydrolysis of
Procaine in Aqueous and
Micellar Media
FAWZIA FALEH AL-BLEWI, HAMAD A. AL-LOHEDAN, M. Z. A. RAFIQUEE, ZUHEIR A. ISSA
Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Received 16 November 2011; revised 18 January 2012, 25 February 2012; accepted 28 February 2012
DOI 10.1002/kin.20735
Published online 20 November 2012 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: The kinetics of alkaline hydrolysis of procaine under the pseudo–first-order
−
condition ([OH ]ꢀ[procaine]) has been carried out. N,N-Diethylaminoethanol and p-
aminobenzoate anion were obtained as the hydrolysis product. The rate of hydrolysis was found
to be linearly dependent upon [NaOH]. The addition of cationic cetyltrimethylammonium bro-
mide (CTAB), dodecyltrimethylammonium bromide (DDTAB) and tetradecyltrimethylammo-
nium bromide, and anionic sodium dodecyl sulfate (SDS) micelles inhibited the rate of hydrol-
ysis. The maximum inhibitive effect on the reaction rate was observed for SDS micelles, whereas
among the cationic surfactants, CTAB inhibited most. The variation in the rate of hydrolysis
of procaine in the micellar media is attributed to the orientation of a reactive molecule to the
surfactant and the binding constant of procaine with micelles. The rate of hydrolysis of pro-
caine is negligible in DDTAB micelles. The observed results in the presence of cationic micelles
were treated on the basis of the pseudophase ion exchange model. The results obtained in the
presence of anionic micelles were treated by the pseudophase model, and the various kinetic
parameters were determined. ꢁC 2012 Wiley Periodicals, Inc. Int J Chem Kinet 45: 1–9, 2013
INTRODUCTION
circulation in a large amount [1–3]. Surfactants (also
known as amphiphiles or detergents) are frequently
used in industries and pharmaceuticals as an emulsifier,
stabilizer, wetting agent, solubilizer, preservatives, etc.
[4–6]. During pharmaceutical formulation, the studies
on surfactant–drug interactions are very important in
view of their stability and maintenance of biological ef-
ficacy. Surfactants usually have an ionic or polar head
group and a long alkyl tail. At concentrations above
a critical micellar concentration (cmc) in water, they
form normal micelles having a nearly spherical struc-
ture with the head groups in contact with water and
a hydrocarbon-like interior. The use of micelles and
other association colloids, such as microemulsions and
vesicles in water and organic solvents, has been fasci-
nating to scientists owing to their modifying effect on
reaction rates. In micellar media, most of the ionic or
polar species exist in the Stern and Guoy–Chapman
Procaine, the 2-diethylaminoethyl ester of 4-
aminobenzoic acid (PABA), is a local anesthetic drug
that causes reversible loss of pain sensation of skin
and mucous membrane. Procaine is metabolized in the
plasma through hydrolysis into PABA, which is then
excreted by the kidneys into the urine. It is a vasodilator
and is often coadministered with epinephrine for the
purpose of vasoconstriction in which it helps to reduce
bleeding and prevents the drug from reaching systemic
Correspondence to: Hamad A. Al-Lohedan; e-mail: hlohedan@
ksu.edu.sa.
Contract grant sponsor: Dean, Scientific Research, King Saud
University.
Contract grant number: RGP-VPP-148.
ꢀ
c 2012 Wiley Periodicals, Inc.

2
AL-BLEWI ET AL.
−
6
−1 −1
cm ) was
regions as counterions or coions. The micelles play
a critical role in the localization and/or dispersion of
charges on reactants and their activated states, and thus
can easily influence reaction rates, equilibrium, and
concentration, or depletion of reactants in the interfa-
cial region. These effects depend on transfer of the sub-
strate from water to micelles, the reaction mechanism,
and properties of the interfacial region, that is, local
charge, polarity, and water content. Therefore, the reac-
tion media of surfactants are capable of both catalyzing
and inhibiting the reaction rates, depending on the na-
ture of interaction between the surfactant and reactants,
micellar aggregation number, cmc values, the extent of
incorporation of reactants as counterions or coions in
micelles, etc. [7–12]. The studies on the hydrolysis of
procaine in micellar media will be helpful in determin-
ing the extent of association of drug with micelles and,
thereby, their stability in that environment. Therefore,
kinetic experiments were performed in the presence
of cationic cetyltrimethylammonium bromide (CTAB),
dodecyltrimethylammonium bromide (DDTAB) and
tetradecyltrimethylammonium bromide (TDTAB), and
anionic sodium dodecyl sulfate (SDS) micelles for the
alkaline hydrolysis of procaines to observe the role of
surfactant on the stability of drugs in the micellar me-
dia. The observed results have been discussed with the
help of the Poisson–Boltzman equation model and the
pseudophase ion exchange (PIE) model [13–16]. The
kinetic parameters were determined and are reported
herewith.
(specific conductance: (1–2) × 10
ꢀ
used as a solvent.
Kinetic Measurements
The kinetic experiments were performed spectropho-
tometrically using a Lambda 45 double-beam UV/vis
spectrophotometer (Perkin Elmer, Shelton, CT) pro-
vided with multiple cell holders and thermostated
by circulating water. The reactants (procaine and
sodium hydroxide) were equilibrated at the desired
◦
temperature (± 0.1 C) for ∼15 min in the water
bath. The reaction was started by injecting calculated
amount of procaine into the sodium hydroxide solu-
tion taken in a 3-mL quartz cuvette. All the kinetic
runs were carried out under the pseudo–first-order re-
action conditions in which [NaOH] was in high ex-
cess over [procaine]. The rate of reaction was mea-
sured by monitoring the decrease in absorbance at
λmax = 286 nm. The observed pseudo–first-order rate
−1
constant (k1, s ) was obtained from slopes of plots
ln At versus time. The kinetic experiments were per-
formed till the reaction was almost completed. The
values of correlation coefficients were quite satisfac-
2
tory (r > 0.995) for all rate constants determined.
Critical micelle concentrations for the surfactants un-
der the reaction conditions were determined using a
Kruss type 10 tensiometer (Karl Kolb Scientific Tech-
nical Supplies, Dreieich, Germany).
RESULTS AND DISCUSSION
EXPERIMENTAL
Materials
Hydrolysis of Procaine in Aqueous Medium
The repetitive scans of the mixture containing pro-
−
5
−3
caine (6.50 × 10 mol dm ) and NaOH (5.00 ×
−2
−3
Procaine hydrochloride (99%; Sigma, St. Louis, MO),
SDS (99%; BDH, Parkstone, Poole, UK), sodium
bromide (99%; BDH), and CTAB (99%, Aldrich,
Taufkirchen, Germany) were used without further pu-
rification. DDTAB and TDTAB were synthesized in
the laboratory. DDTAB was synthesized by adding
10 mol dm ) were recorded at constant intervals
of time in the UV/vis region. The spectra are shown
in Fig. 1, and a shift in maximum absorption was ob-
served from 286 to 265 nm with the increase in re-
action time. The absorbance decreased at 286 nm and
increased at 265 nm with the progress of the hydrolysis
of procaine. The spectra presented in Fig. 1 have two
well-defined isobestic points within the interest range,
indicating that the decrease in absorbance at 286 nm
is due to hydrolysis of procaine and an increase in ab-
sorbance at 265 nm is attributed to formation of the
p-nitrobenzoate anion as a hydrolysis product.
1-bromododecane (0.1 mol) to trimethylamine (0.1
mol) dissolved in 100 mL isopropyl alcohol. The mix-
ture was refluxed for 48 h. Isopropyl alcohol was re-
moved by distillation, and the remaining solvent was
evaporated by using a rotary evaporator. The dried
product was recrystallized from absolute alcohol–dry
ethyl ether. TDTAB was synthesized by using 1-
bromotetradecane instead of 1-bromododecane and
following the same procedure as for DDTAB. The
sodium salt of toluene-4-sulfonate was used from
BDH. Sodium hydroxide of AnalR grade was used dur-
ing the experiments. Deionized double-distilled water
The pseudo–first-order rate constant determined
at different concentrations of sodium hydroxide in
−
3
the range 0.10–1.40 mol dm at fixed [procaine]
−5
−3
◦
(= 6.50 × 10 mol dm ) at 25.0 ± 0.1 C shows that
−
the rate is linearly dependent upon [OH ]. The rate
of hydrolysis was decreased when an organic solvent
International Journal of Chemical Kinetics DOI 10.1002/kin.20735

KINETICS OF HYDROLYSIS OF PROCAINE IN AQUEOUS AND MICELLAR MEDIA
3
−
5
−3
−2
−3
Figure 1 Repetitive scan for the hydrolysis of procaine (6.50 × 10 mol dm ) with 5.00 × 10 mol dm NaOH at 25.0
◦
±
0.1 C. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
(
methanol, ethanol, and tetrahydrofuran) was added to
the reaction in which the charge density is higher in the
activated complex than the initial reactant molecules.
The higher polarity of the solvent stabilizes the charged
intermediate and, therefore, increases the reaction rate
by its solvation. Thus, the addition of the organic sol-
vent lowers the polarity and decreases the stability of
the transition state and, therefore, the rate of reaction
is decreased on increasing the proportion of organic
solvents.
the reaction mixture. The increase in proportion of the
organic solvent decreased the reaction rate.
During the alkaline hydrolysis of procaine, the re-
−
action starts with the attack of nucleophile OH to the
carbonyl carbon group of procaine to form a tetrahe-
dral intermediate (see Scheme 1), which, in turn, finally
gives N,N-diethylaminoethanol and p-aminobenzoate
anion [17–19].
The rate constant for the reaction followed the rela-
tionship
Hydrolysis of Procaine in Surfactant Media
a
k1 = k2[NaOH]
(1)
The addition of CTAB, DTAB, TDTAB, and SDS mi-
celles to the reactants inhibited the rate of hydrolysis
of procaine. The inhibitive effect on the rate of hydrol-
ysis of procaine by SDS is presented in Fig. 4. The
inhibitive effect of micellar solutions was observed in
the order: SDS > CTAB > TDTAB > DDTAB. The
lowering of the overall rate of the reaction in the pres-
ence of cationic and anionic micelles is indicative of
the presence of a strong interaction between procaine
and micelles. According to the pseudophase model, the
reaction proceeds at different rates in the aqueous and
micellar phases. The rate of the reaction depends on
the distribution of procaine in aqueous and micellar re-
gions and on its orientation on the micellar surface. The
model proposed by Romsted [15,16] has been used to
predict the distribution of procaine in the Stern region
of micelles. The mechanism of hydrolysis of procaine
occurring in the presence of micelles is presented in
Scheme 2 with the different values of the first-order
where k1 and k2 are the pseudo–first-order rate and
second-order rate constants, respectively. The bimolec-
ular rate constant, k2, could not be determined directly
as the disappearance of the hydroxide ion with time
could not be accurately measured due to being in large
excess over procaine. So, it has been conveniently de-
termined after obtaining the pseudo-unimolecular rate
constant k1. The slope of the plot of log k1 versus log
[
NaOH] (Fig. 2) gave the values of a (= 0.947), and
its intercept gave the values of the second-order rate
−3
−1
3
−1
constant, k2 (= 3.82 × 10 mol dm s ).
The addition of the organic solvent, namely,
methanol, ethanol, and tetrahydrofuran, to the reactants
solution decreased the rate of reaction. The inhibitive
effect on the rate of hydrolysis by the added organic
solvent is associated with the lowering of the polarity
of the solvent on increasing its fraction (Fig. 3). Ac-
cording to the Hugges–Ingold rules [20], an increase in
solvent polarity results in increased reaction rates for
ꢂ
ꢂ
rate constants k and k in micellar and aqueous me-
m
w
dia, respectively.
International Journal of Chemical Kinetics DOI 10.1002/kin.20735

4
AL-BLEWI ET AL.
O
CH2 CH3
H N
–
2
CH2
N
+
OH
CH2 CH3
O
CH2
K
O
O
CH2 CH 3
H N
2
CH2
N
CH2 CH3
CH2
-
OH
Fast
CH2 CH3
CH2 CH3
O
CH2
N
H N
2
O
CH2
HO
k1
slow
O
C
H2 CH3
+
H N
2
CH2
N
CH2 CH3
OH
O
CH2
Fast
CH2 CH3
O
CH2
N
H N
+
2
CH2 CH3
H O CH2
O
Scheme 1
In this scheme, Dn presents the micellized surfac-
Ks is given by
tant (Dn = [D] – cmc, where D is the total surfactant
concentration) and Ks is the binding constant for pro-
caine to the micelle. Sm and Sw are the concentrations
of procaine distributed in micellar and aqueous media.
[
Sm]
Ks =
(2)
[Sw][Dn]
International Journal of Chemical Kinetics DOI 10.1002/kin.20735

KINETICS OF HYDROLYSIS OF PROCAINE IN AQUEOUS AND MICELLAR MEDIA
5
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1
+log [NaOH]
Figure 2 Logarithm plot of 4 + log k1 versus 1 + log [NaOH] for the hydrolysis of procaine in aqueous medium. Reaction
−5
−3
◦
conditions: [procaine] = 6.50 × 10 mol dm , temperature = 25.0 ± 0.1 C.
1
1
1
2
1
0
9
8
7
6
5
4
3
2
1
0
10
20
30
40
50
v/v solvent (%)
Figure 3 Variation of observed rate constant, k1 versus % v/v solvent; methanol (•), ethanol (ꢀ), and tetrahydrofuran (ꢁ) for
−5
−3
−1
−3
the hydrolysis of procaine. Reaction conditions: [procaine] = 6.50 × 10 mol dm , [NaOH] = 3.00 × 10 mol dm , and
◦
temperature = 25.0 ± 0.1 C.
International Journal of Chemical Kinetics DOI 10.1002/kin.20735

6
AL-BLEWI ET AL.
35
30
25
20
15
10
5
0
0.00
0.01
0.02
0.03
0.04
-3
[
SDS] (mol dm )
Figure 4 Plot of kꢁ versus [SDS] for the hydrolysis of procaine in micellar medium. Reaction conditions: [procaine] = 6.50
−5
−3
−1
−3
◦
×
10 mol dm , [NaOH] = 3.00 × 10 mol dm , and temperature = 40.0 ± 0.1 C.
Ks
Sw
+
D n
S m
k'w
k'm
Products
Scheme 2
−
The overall rate can be expressed as
on the basis of the PIE model [21–23] in which Br
−
ions are exchanged by OH ions from the micellar
surface as its counterions. These OH ions bound to
−
ꢂ
−
v = kꢁ[ST] = k [ST] [OH ] = k [Sw] [OH ]
−
T
w
w
ꢂ
−
m
the micellar surface in the Stern region are reactive and
participate in the hydrolysis of procaine. The exchange
+
k [Sm] [OH ]
(3)
m
−
of Br and OH ions occurring at the micellar surface
m
−
where
w
can be presented by the following equation:
[
ST] = [Sw] + [Sm]
(4)
(5)
−
−
−
m
[
OH ] = [OH ] + [OH ]
−
− K
OH
B
w ꢂ
−
−
T
w
OH + Br
OH + Br
(7)
m
w
m
and
ꢂ
ꢂ
The equilibrium constant for the ion exchange process
is given by
k + k Ks[Dn]
w
m
kꢁ =
(6)
1
+ Ks[Dn]
−
−
The hydrolysis of procaine occurring in the micellar
media of CTAB, DTAB, and TDTAB can be explained
[OH ][Br ]
Br
w
−
m
K
=
(8)
OH
−
[OH ][Br ]
m
w
International Journal of Chemical Kinetics DOI 10.1002/kin.20735

KINETICS OF HYDROLYSIS OF PROCAINE IN AQUEOUS AND MICELLAR MEDIA
7
−
−
−
−
w
Table I Kinetic Parameters Obtained for the Alkaline
Hydrolysis of Procaine in Micellar Media
in which OH , OH , Br , and Br are the ions partic-
m
w
m
ipating in the equilibrium around micellar surfaces as
surfactant counterions; the subscript “w” represents the
ions in aqueous medium and “m” the micellar medium.
The fraction of the micellar head group neutralized
OH
Br
4
−1
[Surfactant]
β
K
km (10 s
)
Ks
SDS
–
–
2.24
5722
2400
2800
2000
CTAB
DDTAB
TDTAB
0.8
0.8
0.8
16
16
16
4.44 ± 0.09
8.13 ± 0.16
6.65 ± 0.36
−
−
by OH and Br may be defined in terms of β and is
m
m
given by
−
3
Reaction conditions: [NaOH] = 0.30 mol dm , [procaine] = 6.50
β = mOH + mBr
(9)
−
5
−3
−3 −1
×
10 mol dm , k
1
= 3.45 × 10
s
(in the absence of surfactant
◦
◦
at 40.0 ± 0.1 C), and temperature = 40.0 ± 0.1 C.
where mOH and mBr are the neutralized fractions of the
micellar head groups with reactive (OH ) and nonre-
active (Br ) ions:
−
−
the pseudophase model. On rearranging Eq. (6), we
obtained the following equation:
−
[
[
OH ]
m
mOH =
mBr =
(10)
(11)
1
1
1
[
Dn]
=
+
(16)
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
k − kꢁ
k − k
(k − k )Ks[Dn]
−
w
w
m
w
m
Br ]
m
[
Dn]
ꢂ
The plot of 1/(k − kꢁ) versus 1/[Dn] gave a straight
w
ꢂ
ꢂ
m
line (Fig. 6) with intercept at 1/(k − k ) and slope
w
Thus, on considering the equilibrium constant and re-
active OH ions concentrations involved during the
ion exchange process at the micellar head group,
Eq. (6) can be written as
ꢂ
ꢂ
ꢂ
=
1/(k − k )Ks. The values of k and Ks were cal-
−
w
m
m
culated using the values of the slope and intercept ob-
tained for the above plot. These values are given in
Table I. The values of Ks were found in the order SDS
>
DDTAB > CTAB > TDTAB. Tomida et al. [18]
−
reported that procaine is associated with the SDS in
both protonated (at lower pH) and free base (at higher
pH) forms, whereas it is associated with polyoxyethy-
lene ether, CTAB, and N-dodecyl betaine (NDB) mi-
celles as a free base. All the studied cationic (CTAB
and NDB), anionic (sodium lauryl sulfate, SLS), and
nonionic (polyoxyethylene lauryl ether, PLE) surfac-
tants inhibited the hydrolysis of procaine. Their order
of inhibition followed the sequence SLS > CTAB >
PLE > NDB. The inhibitive effect by cationic mi-
celles is contrary to the electrostatic theory for the
base-catalyzed hydrolysis of ester [24]. Meakin et al.
[25] described that the inhibitive effect of cationic mi-
celles for the hydrolysis of ethyl p-aminobenzoate and
p-aminophenyl acetate is due to the electron-releasing
kw[OH ] + (kmKs − kw)mOH[Dn]
T
kψ =
where
(12)
1
+ Ks[Dn]
−
−
−
m
[
OH ] = [OH ] + [OH ]
(13)
(14)
T
w
Similarly,
−
−
−
m
[
Br ] = [Br ] + [Br ]
T
w
The following quadratic gave the value of mOH at con-
stant values of [OH ] and β at varying concentrations
of surfactant [Dn]:
−
T
ꢀ
ꢃ
−
OH
−
T
[
OH ] + K [Br ]
effect of the -NH group. Eriksson and Gilberg [26] on
2
OH
T
Br
2
m
+ mOH
ꢁ
ꢂ
− β
OH
Br
K
− 1 [Dn]
the basis of NMR studies suggested that the hydrolysis
of a simple aromatic ester depends on the orientation
manner of solubilizate on the micellar surface. The ob-
served inhibitive effect of CTAB on the hydrolysis of 2-
diethylaminoethyl 4-nitrobenzoate (p-nitro substituent
of the p-amino group of procaine) [18] shows that the
substituent -NO2 does not play a significant role during
the hydrolysis. Therefore, these observations suggest
that the manner of orientation of procaine molecules
on the micellar surface plays an important role in their
rate of hydrolysis. The site of reaction, that is, the es-
ter group, is either strongly adsorbed to the micellar
ꢄ
ꢅ
−
β OH
T
−
ꢁ
ꢂ
= 0
(15)
OH
Br
K
− 1 [Dn]
Thus, with the help of the PIE model, the kꢁ–[CTAB]
profile (Fig. 5) was used to obtain various kinetic pa-
rameters, viz., km, Ks, and KBr using a computer pro-
gram. The values of these parameters were observed
to be in the similar order, as reported by Rodenas and
Vera [21,22] and are given in Table I.
The hydrolytic reaction of procaine occurring in
anionic SDS micelles is treated quantitatively by using
OH
+
+
+
cationic head group of DDTA , CTA , and TDTA ,
International Journal of Chemical Kinetics DOI 10.1002/kin.20735

8
AL-BLEWI ET AL.
1
2
0
8
6
4
2
0
1
0
20
40
60
80
100
3
–3
[
Surfactant] (10 mol dm )
Figure 5 Plot of kꢁ versus [surfactant] for the hydrolysis of procaine in micellar media of CTAB (ꢁ), TDTAB (ꢀ), and
−5
−3
−1
−3
DDTAB (•). Reaction conditions: [procaine] = 6.50 × 10 mol dm , [NaOH] = 3.00 × 10 mol dm , and temperature =
◦
4
0.0 ± 0.1 C.
550
500
450
400
350
300
0
200
400
600
800
–3
1
/[D ] (mol dm )
n
ꢂ
−5
Figure 6 Plot of 1/(kw − kꢁ) versus 1/[Dn] for the hydrolysis of procaine. Reaction conditions: [procaine] = 6.50 × 10 mol
−3
−2
−3
◦
dm , [NaOH] = 5.00 × 10 mol dm , and temperature = 25.0 ± 0.1 C.
International Journal of Chemical Kinetics DOI 10.1002/kin.20735

KINETICS OF HYDROLYSIS OF PROCAINE IN AQUEOUS AND MICELLAR MEDIA
9
surface or solubilized inside the hydrophobic interior,
and thereby decreases the rate of hydrolysis. The higher
inhibitive effect of DDTA may be due to better solu-
The project was supported by King Saud University, Dean-
ship of Scientific Research, College of Science Research
Centre.
+
bilization of the reactive ester group to the interior of
micelle by possessing the longer hydrophobic chain.
The lower inhibitive effect by TDTA micelles may
BIBLIOGRAPHY
+
1
2
. Burstein, C. L. Anesthesiology 1946, 7, 13.
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105, 259.
be attributed to its folding, resulting in weak binding
of procaine to the micellar surface.
−
The inhibition by DS micelles is the result of the
3. Raj, P. P.; Ohlweiler, D.; Hitt, B. A.; Denson, D. D.
Anesthesiology 1980, 53, 307.
preferential binding of procaine onto the micellar sur-
−
face/Stern region and expulsion of OH from the mi-
4
. Romsted, L. S. Micellization, Solubilization and Mi-
croemulsions, Mittal, K. L., Ed.; Plenum Press: New
York, 1982; Vol. 2.
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binds to the hydrophobic hydrocarbon interior of the
−
micelles, whereas negatively charged OH ions are
5. Rosen, M. J. Surfactants and Interfacial Phenomena. 3rd
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Macromolecular Systems; Academic Press: New York,
−
Thus, the micelles of DS keep the reactive center of
−
procaine and OH ions away from each other and slow
7
the rate of hydrolysis. The order of binding constant
(i.e., SDS > DDTAB > CTAB > TDTAB) for pro-
1975.
caine with micelles is not in the same order for the
rate of inhibition of the hydrolysis of procaine (i.e.,
SDS > CTAB > TDTAB > DDTAB). This may be
due to the micelles of the different surfactants hav-
ing different volume fractions in the micellar phase
8
. Al-Lohedan, H. A.; Bunton, C. A.; Mhala, M. M. J Am
Chem Soc 1982, 104, 6654.
. Al-Lohedan, H. A. J Chem Soc, Perkin Trans 1995, 2,
9
1
707.
0. Al-Lohedan, H. A. J Chem Soc, Perkin Trans 1990, 2,
401.
1
(at the same surfactant concentration). Among CTAB,
1
TDTAB, and DDTAB surfactants, the binding constant
is highest for DDTAB owing to its having a longer hy-
drocarbon chain; however, in TDTAB, the still longer
hydrocarbon chain may result in folding to have less
space for binding to procaine.
11. Broxton, T. J. Aust J Chem 1982, 35, 1357.
12. Al-Ayed, A. S.; Ali, M. S.; Al-Lohedan, H. A.; Al-
Sulaim, A. M.; Issa, Z. A. J Colloid Inter Sci 2011,
3
61, 205.
3. Menger, F. M.; Portnoy, C. E. J Am Chem Soc 1967, 89,
698.
1
4
1
1
4. Bunton, C. A. Catal Rev Sci Eng 1979, 20, 1.
5. Romsted, L. S. In Symposium on Surfactants in Solu-
tion, Lund: Sweden, 1982.
CONCLUSION
1
6. Al-Lohedan, H.; Bunton, C. A.; Romsted, L. S. J Phys
Chem 1981, 85, 2123.
The alkaline hydrolysis of procaine yields N,N-
diethylaminoethanol and p-aminobenzoate anion. The
rate of hydrolysis under the pseudo–first-order condi-
17. Higuchi, T.; Havinga, A.; Busse, L. W. J Am Pharm
Assoc, Sci Ed 1950, 39, 405.
−
tions ([OH ] ꢀ [procaine]) has been found to be lin-
18. Tomida, H.; Yotsuyanagi, T.; Ikeda, K. Chem Pharm
Bull 1978, 26, 148.
early dependent upon [NaOH]. The addition of cationic
1
2
9. Razvi, N.; Beg, A. E. J Chem Soc Pak 1981, 3, 121.
0. Reichardt, C. Solvents and Solvent Effects in Organic
Chemistry, 3rd ed.; Wiley-VCH: New York, 2003.
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2. Vera, S.; Rodenas, E. Tetrahedron 1986, 42, 143.
3. Cheong, May-Ye; Ariffin, A.; Khan, M. N. Bull Korean
Chem Soc 2007, 28, 1135.
(CTAB, TDTAB, and DDTAB) and anionic (SDS) sur-
factants to the reaction mixture (procaine and sodium
hydroxide) decreased the rate of hydrolysis. The max-
imum decrease in the rate constant was observed for
SDS micelles. Among the cationic surfactants, CTAB
inhibited the most. The orientation of reactive molecule
to the surfactant, values of the binding constant, and
volume fractions of micelles are attributed to the vari-
ation in the rate of hydrolysis of procaine in the micel-
lar media. The hydrolytic rate becomes negligible in
DDTAB micelles.
2
2
2
2
2
4. Hartley, G. S. Trans Faraday Soc 1934, 30, 444.
5. Meakin, B. J.; Winterborn, I. K.; Davies, D. J. G. J Pharm
Pharmacol 1971, 23, 25S.
26. Eriksson J. C.; Gilberg, G. Acta Chem Scan 1966, 20,
2019.
International Journal of Chemical Kinetics DOI 10.1002/kin.20735