Effect of β-cyclodextrin on intra and intermolecular Michael addition of some catechol derivatives

Article abstract of DOI:10.1016/j.saa.2013.09.029

The oxidation reactions of catechol, dopamine and epinephrine have been studied in the absence and presence of N-methylaniline by UV-Vis. Spectrophotometry. A variety of reaction pathways (inter and intramolecular reactions) that followed by this oxidation have been observed depending on the nature of catechol derivatives. The observed homogeneous rate constants of the reactions were estimated by fitting the absorption time profiles for each reaction. The effect of β-cyclodextrin and its inclusion complex has also been studied on the chosen reactions. The formation constants of the complexes of catechol, dopamine and epinephrine with β-cyclodextrin as well as the rate constants of the reactions of free and complexed forms have been obtained by fitting the absorption-time spectra to a proposed kinetic-equilibrium model.

Full text of DOI:10.1016/j.saa.2013.09.029

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 118 (2014) 695–701
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Effect of b-cyclodextrin on intra and intermolecular Michael addition
of some catechol derivatives
b
a
Lida Khalafi a, , Mohammad Rafiee , Sahar Fathi
⇑
a Department of Chemistry, Shahr-e-Qods Branch, Islamic Azad University, Tehran, Iran
b Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran
h i g h l i g h t s
g r a p h i c a l a b s t r a c t
ꢀ
ꢀ
ꢀ
ꢀ
Oxidation of catecholamines were
studied in the presence of N-
methylaniline.
Interplay between inter and
intramolecular reactions of
catecholamines were observed.
Substituent effect on the absorption
band of quinonic products were
observed.
Effect of b-cyclodextrin on the
reaction were studied.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 May 2013
Received in revised form 25 August 2013
Accepted 1 September 2013
Available online 18 September 2013
The oxidation reactions of catechol, dopamine and epinephrine have been studied in the absence and
presence of N-methylaniline by UV–Vis. Spectrophotometry. A variety of reaction pathways (inter and
intramolecular reactions) that followed by this oxidation have been observed depending on the nature
of catechol derivatives. The observed homogeneous rate constants of the reactions were estimated by fit-
ting the absorption time profiles for each reaction. The effect of b-cyclodextrin and its inclusion complex
has also been studied on the chosen reactions. The formation constants of the complexes of catechol,
dopamine and epinephrine with b-cyclodextrin as well as the rate constants of the reactions of free
and complexed forms have been obtained by fitting the absorption-time spectra to a proposed kinetic-
equilibrium model.
Keywords:
Catechol
Catecholamine
Oxidation
Inclusion complex
N-methylaniline
Ó 2013 Elsevier B.V. All rights reserved.
Introduction
Considering this biological importance CA and its derivatives have
been widely studied [4–7]. Moreover catecholamines with a
Catechol (CA) was first isolated more than 180 years ago by
Reinsch through the distilling catechin [1] and nowadays is known
as a basic organic compound. It mainly used as precursor of pesti-
cides, flavors and fragrance. CA structure exist also in a variety of
naturally occurring polyphenolic compounds as well as neuro-
transmitters [2,3]. CA and its natural derivatives exist widely in
higher plants such as fruits, vegetables, green tea and tobacco.
catechol skeleton in their structure are biochemically significant
hormones/neurotransmitters. Dopamine (DP) is the most impor-
tant neurotransmitter and its hydrochloride salt is being used in
the treatment of acute congestive failure and renal failure [8].
Epinephrine (EP) or adrenaline is the other most well-known
catecholamine which has many functions in the human body;
regulating of heart rate, blood vessel and air passage diameters
as hormone and neurotransmitter [9].
Upon exposure to many oxidizing agent even the air oxygen;
the CA and its derivatives are oxidized to their relative conjugated
⇑
Corresponding author. Tel.: +98 21 46896463.
E-mail address: l_khalafi@yahoo.com (L. Khalafi).
1386-1425/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.saa.2013.09.029

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L. Khalafi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 118 (2014) 695–701
and colored o-quinone derivatives. The o-quinones as electron-
deficient and reactive species undergo some electrophilic reactions
[10]. Several studies have reported on the reactivity and reactions
of o-quinones which have been derived by chemical or electro-
chemical oxidation of catechols. For example the cyclization of
catecholamines via nucleophilic addition of their side chain amine
groups is one of the interesting examples of these reactions [11].
CA oxidation that followed by some desired reactions has been uti-
lized as a successful protocol for the derivatization of CA contain-
ing molecules and synthesis of more new catechol derivatives [12].
On the other hand, cyclodextrins (CDs) are torus-like
macro-rings made from glucopyranose units. They are able to form
inclusion complexes with a wide variety of guest molecules [13].
The interaction of solutes with b-cyclodextrin (b-CD) leads to
apparent changes in their both equilibrium and kinetic properties
[14]. The aim of this research is the oxidation of CA, DP and EP in
the presence of N-methylaniline (NM) as a nucleophile and the
study of the interplay between inter and intramolecular Michael
addition. Moreover the effect of b-CD on the kinetic and patterns
of these reactions will be studied.
O
O
OH
OH
NH2
-
IO4
(1)
1
3
2
+
NH
-H+
+H+
pKa=4.84
N
(2)
(3)
4
OH
OH
NH
+
O
O
k1
5
3
2
N
O
O
N
OH
OH
-
IO4
(4)
6
5
Scheme 1.
Experimental
performed at 25 °C. All of the calculations were performed in MAT-
LAB 7.5 (Math Works, Cochituate Place, MA).
Reagents
Catechol, dopamine, epinephrine, N-methylaniline and b-cyclo-
dextrin were purchased from Fluka and were used without further
purification. Sodium periodate, sodium acetate, acetic acid, hydro-
chloric acid, sodium dihydrogen phosphate, disodium hydrogen
phosphate and phosphoric acid were reagent-grade materials,
from E. Merck. The stock solutions of, CA, DP, EP and NM were
prepared fresh, daily by dissolving them in distilled water. The
buffered solutions were prepared based on Kolthoff tables, and
the concentration of the prepared buffers was 0.15 M [15]. The ki-
netic experiment was initiated by addition of aliquot amount of
stock solution of sodium periodate to the CA, DP and EP solutions
with desired pH and b-CD concentrations in a 5 ml volumetric
flask. All of the solutions were thermostated at 25 °C before mix-
ing. Measurements were also performed at this temperature. The
reaction mixture was shaken and transferred to the spectropho-
tometer quartz cell immediately. The cell placed in cell holder
and reaction monitored by full spectral scan with time. The first
spectrum recorded 10 s after mixing for each reaction.
Results and discussion
Kinetic study of the reactions
As the base and model molecule, chemical oxidation of CA has
been studied in the absence and presence of NM initially. Fig. 1I,
curve a, shows the UV–Vis. spectrum of CA in the presence of per-
iodate (IOꢁ4 ) in acetate buffer solution (pH = 4). In the presence of
IOꢁ4 , as a strong oxidizing agent, the oxidation reaction of CA to
its corresponding o-quinone took place very fast [16] and an
absorption band with the kmax at 390 nm appeared immediately.
In the presence of NM and IOꢁ4 , a new absorption band appeared
at 520 nm and reached to its maximum value in 1 min (Fig. 1I,
curves b–n). The observed changes are in good agreement with
the reaction of NM to o-quinone via an intermolecular Michael
addition to produce the desired catechol derivative. The reaction
product which believed to be also a catechol derivative underwent
rapid oxidation with IOꢁ4 to produce the conjugated and colored fi-
nal product. The aqueous solution of CA, NM and IOꢁ4 did not show
any absorption at the wavelength region more than 330 nm
(Fig. 1I, curves o–q).
Apparatus
Absorption spectra were obtained with a Scinco UV–Vis. spec-
trophotometer S2100. In each experiment, the sample placed in a
1 mm path length quartz cells, and the measurements were
Fig. 1II, shows the UV–Vis. spectra of CA in the presence of IO4ꢁ
and NM at pH = 3; the increase in the height of absorption band
with kmax 520 nm took place more slowly than pH 4. This pH
Fig. 1. Absorption spectra for 0.5 mM CA in the presence of 1.5 mM IOꢁ4 (a) in the absence (b) to (n) in the presence of 0.5 mM NM (I) pH = 4 and (II) pH = 3, interval times
from (b) to (n) are 30 s, the absorption spectra of IOꢁ4 , CA and NM (o) to (q) respectively.

L. Khalafi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 118 (2014) 695–701
697
dependence proves that the rate determining step of the overall
reaction is the Michael addition reaction. Scheme 1 shows the most
probable mechanism for the reaction of CA and NM in the presence
of IOꢁ4 .
The observed considerable Bathochromic shift (130 nm) during
the reaction is due to the wider conjugated system of final product
(6) rather than the parent o-quinone structure (2).
equilibrium cause to cyclization reaction and formation of 11 as
the final or thermodynamic product. Unfortunately the isolation
of the proposed products (11 and 13) and their characterization
by spectrophotometric techniques was not possible. However,
the electro-active character of products and their different half-
wave potentials made it possible to utilize the electrochemical
techniques for obtaining further evidences for proposed mecha-
nism. Fig. 3 curves (a–h) show the Differential Pulse Voltammo-
grams (DPV) of 1.0 mM solution of DP and NM in the presence of
3.0 mM IOꢁ4 those recorded over time.
Oxidation of DP has been also performed in the same condition
as CA. Fig. 2I, shows that an absorption band with the kmax at
390 nm appeared immediately after mixing of the reagents at
pH = 4. It is also related to rapid oxidation of DP to corresponding
o-quinone as well. Monitoring of the reaction over time showed
that new absorption bands appeared (kmax 458 nm) and its height
increased with a relatively slow rate. This absorbance change is
due to the reaction of side chain amine group of DP with its o-qui-
none moiety via an intramolecular Michael addition [6,11]. The
product of this reaction has also a catechol ring, therefore its
formation followed by a rapid oxidation by IOꢁ4 to produce the
absorptive final product (Scheme 2). Due to the resonance elec-
tron-donating property of the substituted amine group; a batho-
chromic shift (68 nm) in absorption band of this product (11) is
also observed, but the shift is less than those observed for 6.
The absorption-time of DP and NM in the presence of IOꢁ4 are
shown in Fig. 2II. At the initial time o-quinone derivative of DP
showed the absorption band with kmax of 390 nm. Upon initiation
of the reaction, this absorption peak disappeared whereas an
absorption band at 520 nm appeared and its height increased with
time up to 2 min.
Thereafter, the height of the peak with kmax of 520 nm de-
creased slightly and spectral band position shifted to shorter wave-
lengths. Astonishingly, at the end of the reaction, one peak with
kmax of 458 nm remained that its position and half-wave are ex-
actly matched with the kmax of the product of intramolecular cycli-
zation of DP. Based on the above changes; Scheme 2 is proposed for
the oxidation of DP in the absence and presence of NM. Based on
the proposed mechanism and the observed absorbance with kmax
390, 520 and 458 nm are related to o-quinone derivatives of DP
(8), the oxidized product of intermolecular (13) and intramolecular
reactions (11) respectively.
After the mixing of DP, NM and IOꢁ4 one cathodic peak appeared
in the DPV of solution. The potential of this peak is in good agree-
ment with those obtained for the oxidation of CA in the presence of
NM [18]. At longer time, parallel to consecutive decrease of this
cathodic peak, a new cathodic peak appeared at more negative
potentials and its height increased. The half-wave potential of this
peak is exactly same as the previously reported potential for the
product of cyclization of DP [11].
Study of the oxidation of EP at the same condition showed an
immediate appearance of the absorption band of cyclization prod-
uct (kmax 482 nm). It clearly shows that the cyclization of EP took
place very fast which may be due to the presence of methyl group
that enhance the nucleophilicity of amine group [19]. The cycliza-
tion reaction of EP takes place very fast at all of the studied pH
values, 3–8, and the kinetic study of the reaction is not possible
at this pH range. Moreover the absorption changes that followed
by oxidation of EP in the presence of NM is exactly same as its ab-
sence. It demonstrates that all of the produced oxidized intermedi-
ate (o-quinone of EP) was consumed completely by the cyclization
reaction and NM could not undergo the competitive reaction with
side chain amine group of EP. Monitoring of the reaction during
longer time periods showed the decrease of absorption due to
the degradation of the proposed product (19) (see Fig. 4).
The most probable degradation reaction is the addition of water
molecules to the oxidized product of cyclization reaction which is
also a quinone derivative [9]. The proposed mechanism for the oxi-
dation of EP is shown in Scheme 3, this mechanism can be consid-
ered as the main route in the absence and even in the presence of
NM.
NM as an aryl-amine has very weak basic character, pKb = 9.16
[17]. At the pH value of 4.5; 68% of NM molecules are in deproto-
nated form whereas the side chain amine group of DP is fully
protonated with good estimation. Therefore the dominant reaction
is nucleophilic addition of NM (4) to 8 that produces 13 as the ki-
netic product. But this product is not the final product, the partially
deprotonation of side chain amine group of DP and presence of the
Effect of b-CD
As demonstrated above; oxidation of these catechol derivatives
followed by a wide variety of chemical reactions. The other aim of
this paper was the study of b-CD effect on each reaction pattern.
Fig. 5 shows the absorption time profile of CA oxidation in the
Fig. 2. Absorption spectra for 0.5 mM DP in the presence of 1.5 mM IOꢁ4 (I) in the absence and (II) in the presence of 0.5 mM NM at pH 4.5, interval times from (a) to (x) are
30 s.

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L. Khalafi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 118 (2014) 695–701
OH
OH
-
O
O
IO4
(1)
(2)
(3)
+
+
NH3
NH3
8
7
O
O
O
O
−H+
+H+
pKa=8.89
+
NH3
NH2
NH2
9
8
O
O
O
OH
OH
-
IO4
k2
N
N
H
O
H
9
11
10
+
NH3
+H3N
+H3N
O
O
OH
OH
O
O
k3
-
+
IO4
(4)
(5)
NH
N
N
4
8
12
13
+H3N
O
NH2
N
O
O
−H+
OH
O
+H+
+
OH
k4
N
N
H
NH
14
4
10
13
OH
OH
O
O
-
IO4
(6)
N
N
H
H
10
11
Scheme 2.
withdrawing from the o-quinone ring and enhances its nucleo-
philic character and accelerates its reaction [20,21]. It also may
be due to the better and real hydrogen bonding between the hyr-
oxy group of product of this step and b-CD.
A catalytic effect was also observed for the cyclization reaction
of DP in the presence of b-CD and the same reasons can be consid-
ered for the catalytic effect of b-CD on it. This catalytic effect has
been discussed in more details in our previous paper [20].
The absorption-time spectra of oxidation of DP in the presence
of NM show that the rates of both inter and intramolecular reac-
tions affected and enhanced in the presence of b-CD. But the
obtaining of a simple absorption-time profile for each reaction
Fig. 3. Differential Pulse Voltammograms of 1.0 mM DP and NM in the presence of
3.0 mM IOꢁ4 at pH = 4, interval times from (a) to (h) are 120 s.
presence of NM and b-CD at the kmax of 6 (520 nm). The absorption
wavelengths and absorption coefficient of the products did not
change considerably in the presence of b-CD (Fig. 5 inset).
But comparing the absorption time profile of product with
those obtained in the absence of b-CD clearly demonstrates that
the overall rate constant of the reaction has been increased in
the presence of b-CD. As discussed above the rate determining step
of the mechanism is the Michael addition reaction (Scheme 1 Eq.
(3)) and then it can be claimed that b-CD accelerates this nucleo-
philic addition. The catalytic effect of the b-CD on this reaction
may be due to the hydrogen bonding between carbonyl group of
o-benzoquinone with hydroxyl groups of b-CD. It causes electron
Fig. 4. Absorption spectra for 0.5 mM EP in the presence of 1.5 mM IOꢁ4 at pH = 4
and interval times from (a) to (x) are 60 s.

L. Khalafi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 118 (2014) 695–701
699
OH
OH
OH
OH
-
O
O
IO4
(1)
(2)
+
+
NH2
NH2
OH
15
16
OH
O
O
O
O
−H+
+H+
+
NH2
NH
16
17
OH
HO
HO
O
O
O
O
OH
OH
-
IO4
(3)
(4)
NH
N
N
17
19
18
HO
O
Degradation k5
Side Products
Fig. 7. Experimental (d) and fitted (line) absorption-time profile for 0.5 mM CA and
NM in the presence of 1.5 mM IOꢁ4 at pH 3, wavelength 520 nm.
N
O
19
product was not possible due to the spectral overlaps. More quan-
titative results will be present after the kinetic evaluation.
Finally the effect of b-CD has been studied on the reaction of EP
in the presence of IOꢁ4 . In the presence of b-CD the rate of cycliza-
tion reaction did not show any change, or in better words, the
detection of change in reaction rate was not possible using
UV–Vis. Spectrophotometry. But the absorption coefficient of the
reaction product shows a considerable increase in the presence
of b-CD (Fig. 6I) which is a good confirmation for the formation
of inclusion complex between EP and b-CD. Moreover there was
an interesting and significant effect on degradation reaction of its
final quinonic product. Comparing the absorption-time profile at
the kmax of reaction product in the absence and presence of b-CD
demonstrate that o-quinone of EP (19) has found considerable sta-
bility in the presence of b-CD (Fig. 6II).
Scheme 3.
One of the best well-known and effective driving forces of for-
mation of inclusion complex between b-CD and organic molecules
is the hydrophobic nature of b-CD interior and affinity of organic
molecules for formation of inclusion complex and expulsion of
water from the b-CD cavity. In better word during the complex for-
mation, the existing water molecules inside the b-CD cavity are re-
placed by the desired guest molecule. The hosted organic molecule
can be also isolated from the water environment due to formation
of inclusion complex. Therefore, the relative stability of 6 may be
related to its isolation and protection from the reactive aqueous
media by b-CD.
Fig. 5. Absorption-time profiles for 0.5 mM DP and NM in the presence of 1.5 mM
periodate (a) in the absence and (b) in the presence of 0.01 M b-CD, inset: (c) to (h)
absorbance spectra in the presence of b-CD.
Fig. 6. (I) Absorption spectra for 0.5 mM EP in the presence of 1.5 mM IOꢁ4 and 0.01 M b-CD at pH = 4, interval times from (a) to (x) are 60 s, (II) absorption-time profile in the
absence ( ) and presence (d) of b-CD, wavelength 482 nm.

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L. Khalafi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 118 (2014) 695–701
Table 1
Kinetic evaluation
Observed rate constant of the desired reactions in the absence of b-CD.
There are two possible situations for obtaining the quantitative
study of the reactions and obtaining their related rate constants.
The first situation is in the absence of b-CD and the other one is
in its presence. Even in the absence of b-CD, the rate determining
steps of reaction are coupled with a fast acid base reaction of
amines (as nucleophile) and presence of both equilibrium and ki-
netic reactions follow complicated reaction pathways. For example
consumption of NM by the Michael addition reaction (Scheme 1
Eq. (3)) shifts its fast acid–base equilibrium (Scheme 1 Eq. (2)) to
the production of NM. Then, the kinetic profiles were obtained
by numerical integration using MATLAB’s solver, ode45, which is
the standard Runge–Kutta algorithm [22]. The values of the rate
constants as nonlinear parameters were calculated by fitting the
experimental kinetic profile using the Newton–Gauss algorithm.
This consists of finding a set of parameters (rate constants) for
which the sum of squares over all of the elements of the error ma-
trix (i.e., the differences between the elements of the model and
the experimental data) is minimal [23]. The result of this procedure
is a set of nonlinear parameters (the best obtained rate constants)
which define the concentration profiles of absorptive species. Fig. 7
shows the experimental and fitted absorption-time profile (in the
kmax of product) related to the analysis of the data of the oxidation
of CA in the presence of NM.
As seen in Fig. 7, the calculated absorption-time profile is con-
sistent with the absorbance change in the collected data. The same
method has also been applied for the degradation reaction of the
product of oxidation and cyclization of EP (19). However for the
reaction of DP in the presence of NM; there was no selective wave-
length for the monitoring of the reaction. Then obtaining an
absorption time profile and its analysis was not possible. Moreover,
there are two consecutive reactions as the rate determining steps
and deriving the rate constants of reactions needs more than single
wavelength absorption time profile. Therefore the whole absorp-
tion time spectra have been used for the quantitative study of
the reaction. A two-way data matrix Y can be formed by measuring
absorbance under different wavelengths at a series of chosen times
(kinetic spectra). This matrix can be decomposed into the product
of matrix C, column wise, containing the concentration profiles of
the absorbing species and matrix A, row wise, containing their mo-
lar absorptivities. Matrix E is the residual.
Reagent
Reaction (rate constant)
Rate
constant
Catechol
Intermolecular addition of NM (k1)
Intramolecular cyclization (k2)
Intermolecular addition of NM (k3)
0.81 Mꢁ1 sꢁ1
11.5 sꢁ1
Dopamine
Dopamine
Dopamine
0.65 Mꢁ1 sꢁ1
Intramolecular cyclization of intermediate (k4) 3.91 sꢁ1
Epinephrine Degradation of cyclization product (k5)
0.07 sꢁ1
as the above mentioned method and the molar absorptivities of the
13 and 11 were known and have been used during the fitting pro-
cess. Fig. 8I illustrates the concentration profiles of the absorptive
components and kinetic-spectra that obtained during the fitting
process for the reaction of DP in the presence of NM. Comparing
the simulated (Fig. 8II) and experimental (Fig. 2II) kinetic spectra
prove that there is a good consistency between them.
Table 1 shows the rate determining step of each reaction(s) and
obtained rate constants for it (them).
As the final aim of the paper, the quantitative studies have been
performed in the presence of b-CD. As shown above, presence of b-
CD can have changed the rate of reactions due to formation of
inclusion complex. Formation of inclusion complex as an equilib-
rium reaction and difference in the rate of reaction for complexed
and free forms can be considered again as a ‘‘kinetic-equilibrium’’
model. For example the following model (Scheme 4) can be consid-
ered for the cyclization reaction of oxidized form of DP in the pres-
ence of b-CD. Based on the proposed reaction mechanism and
difference in the rate of reactions, the observed reaction rates are
roughly proportional to the equilibrium concentration of free and
complex forms.
Consumption of each reactant shifts the equilibriums to coun-
teract the imposed changes. The rate constants of the desired reac-
tions and the formation constant of the reactants that involved in
these reactions have been obtained based on the proposed model.
The observed rate constants of the chemical reactions in the ab-
sence of b-CD entered as known parameters during this step of fit-
ting process. The obtained values are listed in Table 2, the small
lack of fits, they were less than 3% for all of the fitting processes
are also good evidences for the validity of the underlying models.
As demonstrated in Table 2 and comparing those appeared in
Table 1; it can be concluded that b-CD has a catalytic effect on Mi-
chael addition of the o-quinones and their conversion to catechol
derivatives. It has been demonstrated that the difference in hydro-
gen bond formation of reactants and product is an important deriv-
ing force for this effect. The catalytic effect is more significant for
the intramolecular reactions. It seems that the cavity of b-CD as a
Y ¼ CA þ E
Purpose of the fitting; consists of finding a set of parameters for
which the sum over all the squares, ssq, over all the elements of the
error matrix, E, is minimal. The kinetic profiles were obtained same
Fig. 8. (I) Simulated absorption spectra of DP and NM in the presence of IOꢁ4 and concentration profiles of absorptive components 8 (d), 14 (j) and 11( ).

L. Khalafi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 118 (2014) 695–701
701
presence of NM. An intramolecular cyclization reaction were de-
tected for EP as the main route in the absence and presence of
NM that followed by the degradation of final product with rela-
tively slow rate. The effect of b-CD has been studied on all of the
observed reaction mechanism. Overally, conversion of o-quinone
to the desired catechol derivatives, through nucleophilic addition,
accelerated in the presence of b-CD whereas, the degradation reac-
tion of the products by water molecules slow-down in its presence.
In conclusion, the kinetic-spectrophotometric method has been
proposed for the study of the weak and reversible complexation
b-CD and the effect of inclusion on various reaction path-
ways.AcknowledgementsThis work was supported by Iran Na-
tional Science Foundation (INSF).
Acknowledgements
Scheme 4.
This work was supported by Iran National Science Foundation
(INSF).
Table 2
Observed rate constant of the desired reactions in the presence of b-CD.
References
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Reaction (rate constant)
Rate
constant
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Intermolecular addition of NM (k03)
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1.12 Mꢁ1 sꢁ1
14.6 sꢁ1
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‘‘molecular reactor’’ provide a better media for the intramolecular
reaction in which both reactive site located on one included mole-
cule. Among the whole inter and intramolecular reactions which
have studied here; the degradation of the product of EP oxidation
have been slow down considerably in the presence of b-CD. It
may be due to this fact that encapsulated guest in the hydrophobe
cavity of b-CD is isolated from the aqueous media and protected
from the nucleophilic addition of water molecules.
Conclusion
Spectrophotometric study of oxidation of CA, DP and EP has
been performed in the presence IOꢁ4 as strong oxidizing agent
and NM as nucleophile. In the presence of strong oxidizing agents
such as IOꢁ4 , the oxidation reaction of the chosen catechol deriva-
tives to their corresponding o-quinones took place very fast. The
in situ generation of o-quinone and three patterns of reactivities
were observed depending on the structure of catechol derivatives.
Oxidation of CA in the presence of NM followed only by an inter-
molecular nucleophilic addition. Two steps consecutive inter and
intramolecular reactions were observed for oxidation of DP in the
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