Kinetic study of electrochemically induced michael reactions of o-quinones with meldrum's acid derivatives. Synthesis of highly oxygenated catechols

Article abstract of DOI:10.1021/jo800115n

(Chemical Equation Presented) Electrochemical oxidation of catechols has been studied in the presence of Meldrum's acid derivatives as nucleophiles in aqueous solution, by means of cyclic voltammetry and controlled-potential coulometry. Catechols in the Michael addition reaction react with Meldrum's acids to form adducts that can undergo electrooxidation. Such products were obtained in good yields as confirmed by controlled potential electrosynthesis. Such products can be generated in aqueous solutions by means of electrosynthesis, using a carbon electrode in an undivided cell. Furthermore, the homogeneous rate constants of the chemical reaction interposed between electron transfers were estimated by comparing the experimental cyclic voltammetric curves with the digitally simulated ones.

Full text of DOI:10.1021/jo800115n

Kinetic Study of Electrochemically Induced Michael Reactions of
o-Quinones with Meldrum’s Acid Derivatives. Synthesis of Highly
Oxygenated Catechols
D. Nematollahi* and H. Shayani-jam
Faculty of Chemistry, UniVersity of Bu-Ali-Sina, Hamadan, 65174, Iran
nemat@basu.ac.ir
ReceiVed January 17, 2008
Electrochemical oxidation of catechols has been studied in the presence of Meldrum’s acid derivatives
as nucleophiles in aqueous solution, by means of cyclic voltammetry and controlled-potential coulometry.
Catechols in the Michael addition reaction react with Meldrum’s acids to form adducts that can undergo
electrooxidation. Such products were obtained in good yields as confirmed by controlled potential
electrosynthesis. Such products can be generated in aqueous solutions by means of electrosynthesis, using
a carbon electrode in an undivided cell. Furthermore, the homogeneous rate constants of the chemical
reaction interposed between electron transfers were estimated by comparing the experimental cyclic
voltammetric curves with the digitally simulated ones.
Introduction
(CNS). And accordingly, their electrochemistry has been
investigated extensively.3 Furthermore, o-quinones are of con-
siderable interest because many drugs such as doxorubicin,
daunorubicin, and mitomycin C in cancer chemotherapy contain
quinones,4 whereas various other quinones have found use in
industry.5 Some of them also exhibit antitumor and antimalarial
activities6 and many of them are also involved in enzyme
inhibition and DNA cross-linking.7 Also, it is demonstrated in
comparison with simple catechols and quinones that highly
oxygenated catechols8,9 and quinones10 exhibit interesting
biological activities. After the valuable published paper on the
electrochemical oxidation of substituted catechols by Ryan et
al. in 1980,11 in recent years we and others have investigated
the electrochemical oxidation of some catechols in the presence
Investigation of catechol derivatives may lead to the discovery
of selectively acting, biodegradable agrochemicals with a human,
animal, and plant compatibility.1,2 One of the most important
groups of catechols are catecholamines. Catecholamines are
compounds containing a catechol nucleus and amine group on
a chain of two carbon atoms meta or para to the phenolic
hydroxyl groups and are bioenergetic amines that play quite an
important role as neurotransmitters in the central nervous system
* Corresponding author. Fax: 0098-811-8272404, Phone: 0098-811-8271541.
(1) AMICBASE-EssOil, Database on Natural Antimicrobials; Review Sci-
ence: Germany (1999-2002).
(2) Pauli, A. Antimicrobial Properties of Catechol DeriVatiVes; Proceeding
of the 3rd World Congress on Allelopathy: Tsukuba, Japan, August, 2002.
3428 J. Org. Chem. 2008, 73, 3428–3434
10.1021/jo800115n CCC: $40.75 2008 American Chemical Society
Published on Web 04/09/2008

Synthesis of Highly Oxygenated Catechols
FIGURE 1. The structures of methyl-Meldrum’s acid (3) and Melder-
am’s acid (3a).
of nucleophiles for obtaining new catechols and quinone
derivatives.12–22 But the development of a simple synthetic route
for the synthesis of highly oxygenated catechols and quinones
from readily available reagents is one of the major tasks in this
paper. This idea prompted us to investigate the electrochemical
oxidation of catechols in the presence of Meldrum’s acid
derivatives as nucleophiles (Figure 1) and represents a facile
and one-pot electrochemical method for the synthesis of some
new highly oxygenated catechols and quinones. Also, an
additional purpose of this work is the kinetic and mechanistic
study of the electrochemical oxidation of catechols in the
presence of Meldrum’s acid derivatives and the estimation of
the observed homogeneous rate constants (kobs) of reaction of
electrochemically generated o-benzoquinones with these nu-
cleophiles by digital simulation of cyclic voltammograms.
FIGURE 2. Cyclic voltammograms of (a) 1.0 mM 3-methylcatechol
in the absence of methyl-Meldrum’s acid, (b) in the presence of 1.0
mM methyl-Meldrum’s acid, and (c) 1.0 mM methyl-Meldrum’s acid
in the absence of 3-methylcatechol at a glassy carbon electrode, in
phosphate buffer solution (pH 7.0, c ) 0.2 M). Scan rate: 100 mV s-1
t ) 25 °C.
.
Results and Discussion
Electrochemical Oxidation of Catechols in the Presence
of Methyl-Meldrum’s Acid. Figure 2 (curve a) shows a cyclic
voltammogram recorded for 1.0 mM 3-methylcatechol (1a) in
aqueous solution containing 0.2 M phosphate buffer (pH 7.0).
The voltammogram shows an anodic peak (A1) in the positive-
going scan and a cathodic counterpart peak (C1) in the negative-
going scan, which corresponds to the transformation of 3-me-
thylcatechol (1a) to o-benzoquinone 2a and vice versa within a
quasireversible two-electron process.11–20,23In basic solutions,
the peak current ratio (IpC1/IpA1) is less than unity and
decreases with increasing pH as well as by decreasing the
potential sweep rate. These can be related to the coupling of
anionic or dianionic forms of catechols with o-benzoquinones
(dimerization reaction).11,23,24
The oxidation of 3-methylcatechol (1a) in the presence of
methyl-Meldrum’s acid (3) as a nucleophile was studied in some
detail. Figure 2 (curves b) shows the cyclic voltammogram obtained
for a 1.0 mM solution of 1a in the presence of methyl-Meldrum’s
acid (3) in aqueous solution containing 0.2 M phosphate buffer
(pH 7.0). In this condition, the voltammogram exhibits two anodic
peaks A1 and A2 (at more positive potentials) and two cathodic
related peaks (C1 and C2).
The existence of a subsequent chemical reaction is supported
by the following evidence: (a) During the reverse scan, the peak
corresponding to the reduction of the o-benzoquinone 2a
decreases (Figure 2). This could be indicative of the fact that
o-benzoquinone 2a formed at the surface of an electrode is
removed by chemical reaction with methyl-Meldrum’s acid (3).
(b) Figure 3 presents the variation of the oxidation peak current
of 1a (A1 and A2) versus the potential scan rate in the presence
of 3. It is seen that proportional to the augmentation of potential
sweep rate, parallel to the increase in height of the C1, the height
of C2 decreases. A plot of the peak current ratio (IpC1/IpA1) versus
scan rate for a mixture of 1a and methyl-Meldrum’s acid (3)
confirms the reactivity of 2a toward methyl-Meldrum’s acid (3),
appearing as an increase in the peak current ratio (IpC1/IpA1) at
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J. Org. Chem. Vol. 73, No. 9, 2008 3429

Nematollahi and Shayani-jam
SCHEME 1
FIGURE 3. Typical cyclic voltammograms of 1.0 mM 3-methylcat-
echol in the presence of 1.0 mM methyl-Meldrum’s acid at a glassy
carbon electrode, in phosphate buffer solution (pH 7.0, 0.2 M). Scan
rates from curves a-c are 25, 50, and 100 mV s-1, respectively. t )
25 °C.
V
1/2), decreases slightly with increasing the scan rate. (c) The
intensity of the oxidation peak A2 (and its counterpart) increases
as the concentration of methyl-Meldrum’s acid (3) increases.
Also, electrochemical oxidation of 3-methylcatechol (1a) in
the presence of methyl-Meldrum’s acid (3) was studied at
various pH values. The low pKa of methyl-Meldrum’s acid
(3)25,26 allowed the use of neutral condition (phosphate buffer,
pH 7.0, 0.2 M) for electrochemical study of catechols in the
presence of methyl-Meldrum’s acid (3).
Controlled-potential coulometry was performed in aqueous
solution (0.2 M phosphate buffer, pH 7.0) containing 0.25 mmol
of 1a and 0.25 mmol of 3 at 0.15 V versus SCE. Cyclic
voltammetric analysis carried out during the electrolysis shows
the progressive formation of anodic peak A2, parallel to the
disappearance of peak A1. Peak A1 disappears when the charge
consumption becomes about 2e- per molecule of 1a.
These observations allow us to propose an ECE′ pathway in
Scheme 1 for the electrochemical oxidation of 1a in the presence
of methyl-Meldrum’s acid (3). Generation of o-benzoquinone
2a is followed by a Michael addition of 3 to the o-benzoquinone
2a, producing the catechol derivative 4a as the final product.
The oxidation of this compound (4a) is more difficult than the
oxidation of the parent starting molecule (1a) by virtue of the
presence of methyl-Meldrum’s acid group with electron-
withdrawing character on the catechol ring.
curve a). The transfer coefficient (R) was assumed to be 0.5,
and the formal potentials were obtained experimentally as the
average of the two peak potentials observed in cyclic voltam-
metry. The heterogeneous rate constants are estimated by use
of an experimental working curve.27
The procedure is performed based on achieving the best fit
between simulated and experimental cyclic voltammograms
(Table 1). The method is developed for a variety of scan rates
and nucleophile concentrations.
As shown in Table 1, the magnitude of observed homoge-
neous rate constants (kobs) is dependent on the nature and
position of the substituted group on the catechol ring. The
presence of electron-donating groups such as methyl (1a),
methoxy (1b), or tert-butyl (1e) on the catechol ring causes a
decrease in kobs. In contrast, in the case of 1i the presence of
the nitrile group with electron-withdrawing character causes an
increase in kobs. In addition, the presence of substituted groups
in the C-4 (R1 ) H, R2 * H) position of the catechol ring that
is a reactive site of o-benzoquinones 2 causes a decrease in the
observed homogeneous rate constant (kobs) (Table 1, comparison
of 1a and 1c or 1f and 1g). The observed homogeneous rate
According to our results, the anodic peaks of the voltammo-
grams presented in Figure 2 (A1 and A2) pertain to the oxidation
of catechols 1a and 4a to the o-benzoquinones 2a and 5a,
respectively. Obviously, the cathodic peaks C1 and C2 cor-
respond to the reduction of o-benzoquinones 2a and 5a,
respectively.
A scheme for the electrochemical oxidation of catechols in
the presence of methyl-Meldrum’s acid (3) is proposed and
tested by digital simulation. On the basis of an ECE′ mechanism,
the observed homogeneous rate constants (kobs) of reaction of
o-benzoquinones with methyl-Meldrum’s acid (3) have been
estimated by comparison of the simulation results, (Figure 4
curve b), with experimental cyclic voltammograms (Figure 4
(25) Arnett, E. M.; Maroldo, S. G.; Schilling, S. L.; Harrelson, J. A., Jr.
J. Am. Chem. Soc. 1984, 106, 6759.
FIGURE 4. Cyclic voltammograms of 1.0 mM 3-methylcatechol in
phosphate buffer solution (pH 7.0, c ) 0.2 M): (a) experimental and
(b) simulated. Scan rate: 100 mV s-1. Working electrode: glassy carbon
electrode. t ) 25 ( 1 °C.
(26) Arnett, E. M.; Harrelson, J. A., Jr. J. Am. Chem. Soc. 1987, 109, 809.
(27) Greef, R.; Peat, R.; Peter, L. M.; Pletcher, D.; Robinson, J. Instrumental
Methods in Electrochemistry; Ellis Horwood: Chichester, UK, 1990; p 189.
3430 J. Org. Chem. Vol. 73, No. 9, 2008

Synthesis of Highly Oxygenated Catechols
TABLE 1. The Observed Homogeneous Rate Constant (kobs) of
the Reaction of Electrochemically Generated o-Benzoquinones with
Methyl-Meldrum’s Acid
electron
consumption (mol)
kobs
b
catecholsa
E1/2 vs SCE
(M-1 s-1
)
1a
1b
1c
1d
1e
1f
1g
1h
1i
0.107
0.102
0.097
0.158
0.107
0.182
0.228
0.258
0.284
2.1
2.2
2.1
2.3
2.1
2.2
2.4
2.4
2.3
615 ( 36
756 ( 52
43 ( 3
982 ( 68
18 ( 1
712 ( 42
6800 ( 580
8400 ( 621
18200 ( 1150
a R1 ) CH3, R2 ) H (1a). R1 ) OCH3, R2 ) H (1b). R1 ) H, R2
CH3 (1c). R1 ) H, R2 ) H (1d). R1 ) H, R2 ) C(CH3)3 (1e). R1 ) H,
)
FIGURE 6. E1/2-σ plot for catechols.
R2 ) -COOH (1f). R1 ) -COOH, R2 ) H (1g). R1 ) H, R2
)
-COOEt (1h). R1 ) H, R2 ) -CN (1i). b Standard deviation of four
independent simulations at various scan rates.
FIGURE 7. Cyclic voltammograms of 1.0 mM 3,4-dihydroxybenzoic
acid: (a) in the absence and (b and c) first and second scan in the
presence of 1.0 mM Meldrum’s acid at a glassy carbon electrode, in
FIGURE 5. Hammett plots for electrochemical oxidation of catechols
in the presence of methyl-Meldrum’s acid.
phosphate buffer solution (pH 7.0, c ) 0.2 M). Scan rate: 100 mV s-1
t ) 25 °C.
.
constant (kobs) can be related to the Hammett parameters, where
the Hammett equation is log ki ) log k0 + σF, where ki is the
rate constant for substituted catechol, k0 is the rate constant for
catechol, σ is a constant characteristic of a given substituent
group,28 and F is the slope of the log ki-σ graph. The Hammett
plots are shown in Figure 5. In this figure, σm and σp are used
for C-3 (R2 ) H, R1 * H) and C-4 (R1 ) H, R2 * H)
compounds, respectively. The F values in both plots are positive.
These positive F values mean that the transition states have
substantial negative charge, because the reaction rates are
increased significantly for electron-withdrawing substituents.12,29–33
This result is consistent with the attack of the anion enolate of
methyl-Meldrum’s acid (3) to the o-benzoquinone 2. Also, as
shown in Figure 5, the F value for C-4 (R1 ) H, R2 * H)-
substituted catechols (3.22) is greater than that for C-3 (R2 )
H, R1 * H)-substituted catechols (2.28). This means that the
effect of substituents on C-4-substituted catechols is much larger
than that on the C-3-substituted catechols.
slope value means that the E1/2 is increased significantly for
electron-withdrawing substituents.34–38
Electrochemical Oxidation of 4-Substituted Catechols in
the Presence of Meldrum’s Acid. As in the previous case,
voltammetric experiments were carried out in aqueous phosphate
buffer solution (pH 7.0, c ) 0.2 M). Figure 7 (curve a) shows
a typical voltammetric curve for a 1.0 mM solution of
3,4-dihydroxybenzoic acid (1f). One anodic peak (A1) and the
related cathodic peak (C1) which corresponds to the transfor-
mation of 1f to o-benzoquinone 2f and vice versa within a
quasireversible two-electron process39,40 are observed. The
oxidation of 1f in the presence of Meldrum’s acid (3a) as a
nucleophile was studied in some detail. Figure 7 (curve b) shows
the cyclic voltammogram obtained for a 1.0 mM solution of 1f
in the presence of Meldrum’s acid (3a). In this condition, the
voltammogram exhibits one anodic peak (A1) and two cathodic
peaks (C1 and C0). The second cyclic voltammogram shows
that one new anodic peak A0 appears at less positive potentials.
Furthermore, it is seen that proportional to the increase of
potential sweep rate, parallel to the increase in height of the
Also, the half-wave potential (E1/2) of catechols is quite
sensitive to substituent effects as is shown in Table 1. A plot
of E1/2 versus σ confirms the sensitivity of E1/2 to the
characteristic of the substituent group (Figure 6). The positive
(34) Zuman, P. Substituents Effects in Organic Polarography; Plenum Press:
New York, 1967.
(28) Hansch, C.; Leo, A.; Taft, R. W. Chem. ReV. 199l, 91, 165.
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Electrochim. Acta 1991, 36, 1219.
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J. Org. Chem. Vol. 73, No. 9, 2008 3431

Nematollahi and Shayani-jam
TABLE 2. Experimental and Simulated Parameters for Catechols
in the Presence of Meldrum’s Acid
SCHEME 3
electron
consumption (mol)
kobs
b
catechola
(M-1 s-1
)
1a
1b
1c
1d
1e
1f
1g
1h
1i
6.05
6.09
4.02
6.03
4.06
4.10
6.15
4.11
4.12
151 ( 9
195 ( 13
20.3 ( 1
225 ( 10
5.7 ( 0.3
173 ( 13
1500 ( 90
2100 ( 189
6000 ( 480
a 1c, 1e, 1f, 1h, and 1i have been simulated according to the ECE
mechanism. 1a, 1b, 1d, and 1g have been simulated according to the
ECECE mechanism. b Standard deviation of four independent simulations
at various scan rates.
SCHEME 2
Meldrum’s acid group with electron-donating (contrary to
methyl-Meldram’s acid) character on the catechol ring.
According to our results, the anodic peaks A1 and A0 pertain
to the oxidation of catechols 1f and 4f to the o-benzoquinones
2f and 5f, respectively. Obviously, the cathodic peaks C1 and
C0 correspond to the reduction of o-benzoquinones 2f and 5f,
respectively.
The most important difference between this case and the
previous case is the number of transferred electrons during
controlled-potential coulometry. Contrary to the previous case,
the results show that the consumed charge is about 4e- per
molecule of 3,4-dihydroxybenzoic acid (1f). This is related to
the electron-donating character of Meldrum’s acid (in intermedi-
ate 4f) (Scheme 3), in comparison with the electron-withdrawing
character of methyl-Meldrum’s acid (in intermediate 4a) giving
rise to the presence of two acidic protons in 3a (Figure 1) or
one acidic proton in intermediate 4f (Scheme 3).
As shown in Scheme 3, contrary to 4a, intermediate 4f can
be converted to anion enolate 4f′′. This transformation caused
that Meldrum’s acid (3a) to act as an electron-donating sub-
stituent.
On the basis of an ECE mechanism, the observed homoge-
neous rate constants (kobs) of the reaction of o-benzoquinones
2c, 2e, 2f, 2h, and 2i with Meldrum’s acid (3a) have been
estimated by comparison of the simulation results, with experi-
mental cyclic voltammograms, under the above-mentioned
conditions (Table 2). The procedure is performed based on
achieving the best fit between simulated and experimental cyclic
voltammograms.
C1, the height of C0 decreases. A similar situation is observed
when the Meldrum’s acid (3a) to 1f concentration ratio is
decreased. A plot of the peak current ratio (IpC1/IpA1) versus
scan rate for a mixture of 3,4-dihydroxybenzoic acid (1f) and
Meldrum’s acid (3a) confirms the reactivity of 2f toward
Meldrum’s acid (3a), appearing as an increase in the peak
current ratio (IpC1/IpA1) at higher scan rates. On the other hand,
the current function for peak A1 (IpA1/V1/2) decreases with an
increase in the scan rate.
Electrochemical Oxidation of 3-Substituted Catechols
in the Presence of Meldrum’s Acid. Cyclic voltammograms
recorded for 1.0 mM 2,3-dihydroxybenzoic acid (1g) in aqueous
solutions show an anodic peak (A1) and a cathodic counterpart
peak (C1) which corresponds to the transformation of 1g to
o-benzoquinone 2g and vice versa within a quasireversible two-
electron process.39,40 The oxidation of 1g in the presence of
Meldrum’s acid (3a) was studied in some detail. Figure 8 shows
the cyclic voltammogram obtained for a 1.0 mM solution of 1g
in the presence of Meldrum’s acid (3a) in aqueous solution
containing 0.2 M phosphate buffer (pH 7.0). In this condition,
the voltammogram exhibits one anodic peak (A1) and three
cathodic peaks (C1, C0, and C00). The second cyclic voltam-
mogram shows that two new anodic peaks A0 and A00 appear
at less positive potentials.
Controlled-potential coulometry was performed in aqueous
solution (phosphate buffer, c ) 0.2 M, pH 7.0) containing 0.30
mmol of 3,4-dihydroxybenzoic acid (1f) and 0.30 mmol of 3a
at peak A1 potential. Cyclic voltammetric analysis carried out
during the electrolysis shows the progressive formation of a
new anodic peak (A0), parallel to the disappearance of peak
A1. The anodic peak A1 and cathodic peak C1 disappear when
the charge consumption becomes about 4e- per molecule of 1f
(Table 2). Contrary to the previous case, these observations are
indicative of an ECE (Electron transfer-Chemical reaction-
Electron transfer) mechanism and allows the proposal of the
pathway for the electrooxidation of 3,4-dihydroxybenzoic acid
(1f) in the presence of Meldrum’s acid (3a) (Scheme 2).
Accordingly, the 1,4-addition (Michael) reaction of 3a to the
o-benzoquinone 2f leads to intermediate 4f. The oxidation of
4f is easier than the oxidation of 1f by virtue of the presence of
Also, it is seen that proportional to the augmentation of
potential sweep rate, parallel to the increase in height of the
3432 J. Org. Chem. Vol. 73, No. 9, 2008

Synthesis of Highly Oxygenated Catechols
SCHEME 4
FIGURE 8. Cyclic voltammograms (first and second scans) of 1.0 mM
2,3-dihydroxybenzoic acid (1g) in the presence of 1.0 mM Meldrum’s
acid (3a) at a glassy carbon electrode, in phosphate buffer solution
(pH 7.0, c ) 0.2 M). Scan rate: 100 mV s-1. t ) 25 °C.
mmol of 1g and 0.25 mmol of Meldrum’s acid (3a) at 0.25 V
(versus SCE). The monitoring of electrolysis progress was
carried out by cyclic voltammetry. It shows that proportional
to the advancement of coulometry, the anodic peak A1 decreases
and disappears when the charge consumption becomes about
6e- per molecule of 1g. Coulometric results for various cat-
echlols have been shown in Table 2.
FIGURE 9. Variation of peak current ratio (IpC1/IpA1) of 2,3-dihy-
droxybenzoic acid versus pH (a) in the absence of Meldrum’s acid,
(b) in the presence of Meldrum’s acid, and (c) the difference between
peak current ratio (IpC1/IpA1) in the presence and absence of Meldrum’s
acid (curve a - curve b).
These observations allow us to propose an ECECE mecha-
nism for electrochemical oxidation of 2,3-dihydroxybenzoic acid
(1g) and other C-3-substituted catechols in the presence of
Meldrum’s acid (3a) (Scheme 4).
C1, the heights of C0 and C00 decrease. A similar situation is
observed when the 3a to 1g concentration ratio is decreased. A
plot of peak current ratio (IpC1/IpA1) versus scan rate for a mixture
of 1g and 3a, appearing as an increase in the peak current ratio
(IpC1/IpA1) at higher scan rates, confirms the reactivity of 2g
toward 3a. On the other hand, the current function for peak A1
(IpA1/V1/2) decreases with an increase in the scan rate.
According to our results, it seems that the Michael addition
reaction of the anion enolate of 3a to o-benzoquinone 2g (eq
2) is faster than other side reactions and leads to intermediate
4g. The oxidation of compound 4g is easier than the oxidation
of parent-starting molecule 1g by virtue of the presence of an
electron-donating group (eq 3). In the next step, o-benzoquinone
5g, via an intramolecular Michael reaction, is converted to
intermediate 6g (eq 4). Further oxidation converts intermediate
6g into the final product 7g. Also, according to our results, the
anodic peaks A1, A0, and A00 pertain to the oxidation of
catechols 1g, 4g, and 6g to the o-benzoquinone 2g, 5g, and 7g,
respectively. Obviously, the cathodic peaks C1, C0, and C00
correspond to the reduction of o-benzoquinones 2g, 5g, and 7g,
respectively.
The electrochemical oxidation of catechols in the presence
of Meldrum’s acid is proposed and tested by digital simulation.
On the basis of an ECECE mechanism, the observed homoge-
neous rate constants (kobs) of the reaction of o-benzoquinones
2a, 2b, 2d, and 2g with Meldrum’s acid have been estimated
by comparison of the simulation results, with experimental cyclic
voltammograms. The calculated homogeneous rate constants are
In addition, electrochemical oxidation of 1g in the presence
of Meldrum’s acid (3a) (pKa ) 4.97)41 was studied at various
pH values (Figure 9, curve b). The results indicate that the peak
current ratio (IpC1/IpA1) increases with decreasing pH. This can
be related to protonation of Meldrum’s acid (3a) and inactivation
of it toward the Michael addition reaction with o-benzoquinone
2g. This indicates that the rate of the coupling reaction is pH
dependent and enhanced by increasing pH in the range of 5-7.
In this range, the difference between the peak current ratio (IpC1
/
IpA1) in the presence (curve b) and absence of Meldrum’s acid
(3a) (curve a) is maximum (curve c). In this study, a solution
containing phosphate buffer (pH 7.0, c ) 0.2 M) has been
selected for electrochemical study of catechols in the presence
of Meldrum’s acid (3a).
Controlled-potential coulometry was performed in aqueous
solution (c ) 0.2 M phosphate buffer, pH 7.0) containing 0.25
(41) Pihlaja, K.; Seilo, M. Acta Chem. Scand. 1969, 23, 3003.
J. Org. Chem. Vol. 73, No. 9, 2008 3433

Nematollahi and Shayani-jam
1
1104, 997, 977, 936, 901, 867, 844, 699, 623 cm-1; H NMR (90
given in Table 2. As shown in Table 2 and as discussed before,
the magnitude of the observed homogeneous rate constant (kobs
MHz DMSO-d6) δ 1.63 (s 3H), 1.82 (s 3H), 1.97 (s 3H), 3.40 (s
)
3H), 6.55 (s, 1H), 6.84 (s, 1H), 8.94 (br).
is dependent on the nature and position of the substituted group
on the catechol ring. In this study, because of the electron-
donating and steric characters of the tert-butyl group and its
presence in the C-4 position of the catechol ring, the least
observed homogeneous rate constant (kobs) belongs to 4-tert-
butylcatechol. A comparison of the observed homogeneous rate
constants (kobs) of Tables 1 and 2 has revealed that kobs for the
reaction of anion enolate of methyl-Meldrum’s acid (3) with
o-quinones 2a-i is greater than kobs for reaction of anion enolate
of Meldrum’s acid (3a). This can be related to the higher
reactivity of the anion enolate of methyl-Meldrum’s acid (3) in
comparison with the anion enolate of Meldrum’s acid (3a).
Compound 4c: mp 257-259 °C dec; IR(KBr) 3433, 3000, 2952,
1764, 1725, 1698, 1609, 1526, 1510, 1456, 1399, 1383, 1280, 1241,
1201, 1160, 1134, 1064, 1016, 980, 901, 869, 857, 845, 802, 752,
724, 661, 616, 582 cm-1; 1H NMR (90 MHz DMSO-d6) δ 1.56 (s,
3H), 1.76, (s, 3H), 1.82, (s, 3H), 2.01 (s, 3H), 6.58 (s, 1H), 6.88 (s,
1H), 7.92 (br). 13C NMR, δ (90 MHz acetone-d6): 18.9, 23.3, 27.5,
28.9, 51.7, 106.1, 115.3, 119.2, 125.5, 127.2, 143.3, 144.9, 168.1.
Conclusion
We have investigated the use of the electrochemistry for the
synthesis of some new catechol derivatives (4a-c) by oxidation
of catechols 1a-c in the presence of methyl-Meldrum’s acid
(3) in aqueous solutions. The overall reaction mechanism for
anodic oxidation of catechols, in the presence of methyl-
Meldrum’s acid (3), is presented in Scheme 1. The kinetics of
the reaction of electrochemically generated o-benzoquinones
with the methyl-Meldrum’s acid (3) is studied by the cyclic
voltammetriy and the simulation of obtained voltammograms
under the ECE′ mechanism. Also, the effects of the substituted
groups on the catechol ring in kobs (Hammett plot) have been
studied. In addition, the reaction of electrochemically generated
o-benzoquinones 2a-i with Meldrum’s acid (3a) has been
studied. Contrary to the previous case, the results indicate that
the reaction mechanism is ECE and ECECE in the case of C-4
and C-3 catechols, respectively. The overall reaction mecha-
nisms for anodic oxidation of catechols (1a-i) in the presence
of Meldrum’s acid (3a) are presented in Schemes 2 and 4. Also,
based on ECE and ECECE mechanisms, the homogeneous rate
constants were estimated by comparing the experimental cyclic
voltammetric responses with the digital simulated results. There
is good agreement between the simulated voltammograms
and those obtained experimentally. Furthermore, the effect of
nucleophile on the oxidation pathway of catechols has been
discussed.
Experimental Section
Apparatuse and Reagents. Reaction equipment is described in
the Supporting Information. The homogeneous rate constants were
estimated by analyzing the cyclic voltammetric responses, using
the DigiElch simulation software.42 An excellent fit between the
experimental and simulated data was obtained over this range of
experimental conditions for the following kinetic parameter values.
All chemicals (catechols, methyl-Meldrum’s acid, and Meldrum’s
acid) were reagent-grade materials, and phosphate salts were of
pro-analysis grade. These chemicals were used without further
purification
Electroorganic Synthesis of 4a-c. In a typical procedure, 80
mL of solution containing 0.2 M phosphate buffer (pH 7.0) was
pre-electrolyzed at 0.20 V vs SCE, in an undivided cell; then 2
mmol of catechol (1a-c) and methyl-Meldrum’s acid (3) (2 mmol)
were added to the cell. The electrolysis was terminated when the
decay of the current became more than 95%. The process was
interrupted during the electrolysis and the graphite anode was
washed in acetone to reactivate it. At the end of electrolysis, a few
drops of phosphoric acid were added to the solution and the cell
was placed in the refrigerator overnight. The precipitated solid was
collected by filtration and washed with water. After washing,
1
products were characterized by IR, H NMR, 13C NMR, and MS.
The isolated yields of 4a-c are 66%, 49%, and 40%, respectively.
Characteristic of Products. Compound 4a: mp 260-262 °C
dec; IR(KBr) 3432, 3350, 2991, 2936, 1767, 1715, 1618, 1603, 1528,
1498, 1432, 1395, 1376, 1307, 1257, 1204, 1161, 1107, 1074, 1030,
Acknowledgment. We would like to thank Dr. M. Rudolph
for his cyclic voltammogram digital simulation software (DigiElch
SB) and the authors acknowledge the Bu-Ali Sina University
Research Council and Center of Excellence in Development of
Chemical Methods (CEDCM) for support this work.
1
997, 978, 936, 902, 874, 840, 740, 716, 699, 624, 602 cm-1; H
NMR, δ (90 MHz acetone-d6) 1.26 (s, 3H), 1.62 (s, 3H), 1.66 (s,
3H), 2.16 (s, 3H), 6.57 (d, 1H), 6.67 (d, 1H), 7.35 (br), 8.61 (br);
13C NMR (90 MHz, CDCl3) δ 15.7, 26.1, 27.1, 29.4, 55.0, 106.1,
110.1, 119.9, 125.0, 127.7, 143.4, 144.0, 168.3; MS m/e (rel
intensity) 280 (46), 178 (61), 167 (26), 150 (100), 43 (35).
Compound 4b: mp 281-283 °C dec; IR(KBr) 3467, 3000, 2944,
1775, 1740, 1673, 1633, 1614, 1515, 1453, 1431, 1379, 1240, 1206,
Supporting Information Available: Copies of 1H, 13C NMR,
FT-IR and MS of all compounds (4a-c), as well as cyclic
voltammograms of 1f and 1g in the presence of Meldrum’s acid
in various scan rates, and during controlled potential coulometry
(in the case of 1g). This material is available free of charge via
the Internet at http://pubs.acs.org.
(42) (a) Rudolph, M. J. Electroanal. Chem. 2002, 529, 97. (b) Also, see:
http://www.digielch.de.
JO800115N
3434 J. Org. Chem. Vol. 73, No. 9, 2008