Electrochemical oxidation of catechols in the presence of phenyl-Meldrum's acid. Synthesis and kinetic evaluation

Article abstract of DOI:10.1248/cpb.58.23

Electrochemical oxidation of catechols in the presence of phenyl-Meldrum's acid as a nucleophile in aqueous solution has been studied in detail by means of cyclic voltammetry and controlled potential coulometry. The results indicate that the o-benzoquinone derived from catechols participates in Michael addition reaction with phenyl-Meldrum's acid to form corresponding products. We derived some new highly oxygenated compounds with catechol ring with good yields based on electrochemical oxidation in the controlled potential condition in aqueous solutions, without toxic reagents and solvents at carbon electrode in an undivided cell, using an environmentally friendly method. Furthermore, the observed homogeneous rate constants (k_obs) of the chemical reaction between o-benzoquinone and phenyl-Meldrum's acid were estimated by comparing the experimental cyclic voltammetric curves with the digitally simulated ones.

Full text of DOI:10.1248/cpb.58.23

January 2010
Chem. Pharm. Bull. 58(1) 23—26 (2010)
23
Electrochemical Oxidation of Catechols in the Presence of Phenyl-
Meldrum’s Acid. Synthesis and Kinetic Evaluation
Davood NEMATOLLAHI,* Maryam BAMZADEH, and Hasan SHAYANI-JAM
Faculty of Chemistry, Bu-Ali-Sina University; P. O. Box 65174 Hamadan, Iran.
Received June 2, 2009; accepted October 10, 2009; published online October 19, 2009
Electrochemical oxidation of catechols in the presence of phenyl-Meldrum’s acid as a nucleophile in aqueous
solution has been studied in detail by means of cyclic voltammetry and controlled potential coulometry. The
results indicate that the o-benzoquinone derived from catechols participates in Michael addition reaction with
phenyl-Meldrum’s acid to form corresponding products. We derived some new “highly oxygenated compounds
with catechol ring” with good yields based on electrochemical oxidation in the controlled potential condition in
aqueous solutions, without toxic reagents and solvents at carbon electrode in an undivided cell, using an environ-
mentally friendly method. Furthermore, the observed homogeneous rate constants (kobs) of the chemical reaction
between o-benzoquinone and phenyl-Meldrum’s acid were estimated by comparing the experimental cyclic
voltammetric curves with the digitally simulated ones.
Key words catechol; phenyl-Meldrum’s acid; highly oxygenated compound; cyclic voltammetry; homogeneous rate constant;
digital simulation
Catechol, by itself, and mono-substituted catechols are ac- hibits one anodic peak (A1) and one cathodic peak (C1) that
tive in part against Pseudomonas, Bacillus, but not Penicil- shows decreasing in comparison to the cathodic peak of cate-
lium species. Many flavonoids and catechol derivatives chol (1a) in the absence of 3. In this figure, curve c is the
turned out to be as antimicrobial agents.1) In this connection, voltammogram of 3 in the absence of 1a.
in order to synthesis catechol derivatives, we studied the
The effect of potential sweep rate on shape of cyclic
electrochemical oxidation of benzenediols in the presence of voltammograms of catechol (1a) in the presence of phenyl-
CH acid nucleophiles,2—4) SH acid nucleophiles,5—9) nitrite Meldrum’s acid (3) was studied, too. It is seen that, propor-
ion10) and triphenylphosphine.11) Also, it is demonstrated tional to the augmentation of the potential sweep rate, the
that, in comparison with simple catechols, the “highly oxy- height of peak C1 increases. A similar situation is observed
genated compounds with catechol ring” exhibit interesting when the 3 to 1a concentration ratio is decreased. A plot of
biological activities.12,13) Therefore, the development of a the peak current ratio (IpC1/IpA1) versus the scan rate for a
simple synthetic route for the synthesis of “highly oxy- mixture of catechol (1a) and phenyl-Meldrum’s acid (3) con-
genated compounds with catechol ring” from readily avail- firms the reactivity of o-benzoquinone (2a) toward phenyl-
able reagents is one of the major tasks. In this direction, we Meldrum’s acid (3), appearing as an increase in the peak cur-
recently reported the synthesis of some “highly oxygenated
compounds with catechol ring.”14) This idea prompted us to
investigate the electrochemical oxidation of catechols in the
presence of phenyl-Meldrum’s acid as a nucleophile and rep-
resents a facile and one-pot electrochemical method for the
synthesis of some new “highly oxygenated compounds with
catechol ring.” Also, an additional purpose of this work is the
kinetic and mechanistic study of the electrochemical oxida-
tion of catechols in the presence of phenyl-Meldrum’s acid
and the estimation of the observed homogeneous rate con-
stants (kobs) of reaction of electrochemically generated o-ben-
zoquinones with this nucleophile by digital simulation of
cyclic voltammograms.
Results and Discussion
Electrochemical Investigations The cyclic voltammo-
gram of 1.0 mM catechol (1a) in aqueous solution containing
0.2 M acetate buffer (pHꢀ5.0) shows one anodic peak (A1)
and the corresponding cathodic peak which correspond to the
transformation of catechol (1a) to o-benzoquinone (2a) and
vice-versa, within a quasi-reversible two electron process
(Fig. 1, curve a).2—11) The electrooxidation of catechol (1a)
in the presence of phenyl-Meldrum’s acid (3) was studied in
some detail. Fig. 1, curve b, shows the first cyclic voltammo-
Fig. 1. Cyclic Voltammograms of (a) 1.0 mM Catechol (1a), (b) 1.0 mM
Catechol (1a) in the Presence of 0.1 mM Phenyl-Meldrum’s Acid (3) and (c)
0.1 mM Phenyl-Meldrum’s Acid in the Absence of 1a at a Glassy Carbon
gram obtained for a 1.0 mM solution of 1a in the presence of Electrode in Solution Containing 0.2 M Acetate Buffer (pHꢀ5.0)
Scan rate: 100 mV sꢁ1; tꢀ25ꢂ1 °C.
0.1 mM phenyl-Meldrum’s acid (3). The voltammogram ex-
© 2010 Pharmaceutical Society of Japan
∗ To whom correspondence should be addressed. e-mail: nemat@basu.ac.ir.

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Vol. 58, No. 1
rent ratio (IpC1/IpA1) at higher scan rates (Fig. 2). Further- constants (see Experimental, Characteristic of Products sec-
more, under these conditions, the current function for peak tion) in support of structures 4b and 4c.
A1, (IpA1/v1/2), changes only slightly with increasing the scan
rate.
Accordingly, the electrochemical oxidation catechols with
electron-withdrawing groups, such as 2,3-dihydroxybenzoic
Controlled-potential coulometry was performed in an
aqueous solution, containing 0.20 mmol of 1a and 0.20 mmol
of 3 at 0.35 V vs. SCE. The monitoring of electrolysis
progress was carried out by linear sweep voltammetry (Fig.
3). It shows that, proportional to the advancement of coulom-
etry, the anodic peaks A1 and A2 decreases and disappears
when the charge consumption becomes about 2eꢁ per mole-
cule of 1a (Fig. 3, inset). Comparison of these voltammo-
grams with curve c in Fig. 1 reveals that the peak A2 in Fig. 3
corresponds to the oxidation of phenyl-Meldrum’s acid (3).
Diagnostic criteria of cyclic voltammetry, the consumption
of two electrons per molecule of 1a, and the spectroscopic
1
data (IR, H-NMR, 13C-NMR and MS) of the isolated prod-
uct, indicated that the reaction mechanism of electrooxida-
tion of 1a in the presence of phenyl-Meldrum’s acid (3) is EC
(electrochemical and chemical reactions) mechanism15)
(Chart 1).
The 1,4-addition (Michael) reaction of phenyl-Meldrum’s
acid (3) to the ortho-benzoquinone intermediate 2b and 2c
can conceivably occur at C-4 and C-5 resulting in products
1
4b or 5b and 4c or 5c, respectively (Fig. 4). The H-NMR
spectra of the isolated products display two doublet peaks
(with J about 2 Hz) in each case with “no vicinal” coupling
Fig. 3. Linear Sweep Voltammograms of 0.20 mmol Catechol (1a) in the
Presence of 0.20 mmol Phenyl-Meldrum’s Acid (3) in Solution Containing
0.2 M Actate Buffer (pH 5.0) at a Glassy Carbon Electrode during Con-
trolled Potential Coulometry at 0.30 V vs. SCE
Inset: variation of peak current (IpA1) vs. charge consumed. Scan rate 100 mV sꢁ1
tꢀ25ꢂ1 °C.
;
Fig. 2. Variation of Peak Current Ratio (IpC1/IpA1) versus Scan Rate in
Electrochemical Oxidation of 1.0 mM Catechol (1a) in the Presence of
1.0 mM Phenyl-Meldrum’s Acid (3) at a Glassy Carbon Electrode in Aque-
ous Solution Containing 0.2 M Acetate Buffer (pHꢀ5.0)
tꢀ25ꢂ1 °C.
Chart 1
Fig. 4. The Possible Structures of Final Product of Electrochemical Oxidation of 3-Methylcatechol (1b) and 3-Methoxycatechol (1c) in the Presence of
Phenyl-Meldrum’s Acid (3)

January 2010
25
acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxy-benzoic acid methoxy (1c), or tert-butyl (1e) on the catechol ring causes a
and 3,4-dihydroxybenzonitrile in the presence of phenyl- decrease in kobs. In addition, the presence of substituted
Meldrum’s acid has been studied in detail by means of cyclic groups in the C-4 position of the catechol ring that is a reac-
voltammetry and controlled potential coulometry. Contrary tive site of o-benzoquinones (2) causes a decrease in the ob-
to the catechols with electron-donating groups (1a—e), our served homogeneous rate constant (kobs) (Table 1, compari-
results indicate that the final products from oxidation of cate- son of 1b and 1d). In this study, because of the electron-do-
chols with electron-withdrawing groups are “highly oxy- nating and steric characters of the tert-butyl group in the C-4
genated compounds with benzoquinone ring.”
position of the catechol ring, the least observed homoge-
Kinetic Studies A chart for the electrochemical oxida- neous rate constant (kobs) belongs to 4-tert-butylcatechol
tion of catechols in the presence of phenyl-Meldrum’s acid (1e).
(3) is proposed and tested by digital simulation. On the basis
of an EC mechanism, the observed homogeneous rate con- Conclusion
stants (kobs) of reaction of o-benzoquinones with phenyl-Mel-
In this study, we have investigated the use of the electro-
drum’s acid (3) have been estimated by comparison of the chemistry for the synthesis of some new “highly oxygenated
simulation results, (Fig. 5, curve b), with experimental cyclic compounds with catechol ring” (4a—d) via oxidation of cat-
voltammograms (Fig. 5, curve a). The transfer coefficient (a) echols 1a—d in the presence of phenyl-Meldrum’s acid (3)
was assumed to be 0.5, and the formal potentials were ob- in aqueous solutions. Final products are obtained via an EC
tained experimentally as the average of the two peak poten- mechanism, after consumption of 2eꢁ per molecule of cate-
tials observed in cyclic voltammetry. The heterogeneous rate chols (1a—d). The present results complete the previous re-
constants are estimated by use of an experimental working port on the anodic oxidation of catechols in the presence of
curve.16) The procedure is performed for achieving the best Meldrum’s and methyl-Meldrum’s acid.14) In this work, we
fit between simulated and experimental cyclic voltammo- derived products 4a—d with good yields based on electro-
grams (Table 1). The method is developed for a variety of chemical oxidation under controlled potential conditions in
scan rates and nucleophile concentrations.
aqueous solutions, without toxic reagents and solvents using
As shown in Table 1, the magnitude of the observed ho- an environmentally friendly method at a carbon electrode in
mogeneous rate constant (kobs) is dependent on the nature and an undivided cell. Also, the observed homogeneous rate con-
position of the substituted group on the catechol ring. The stants (kobs) were estimated by comparing the experimental
presence of electron-donating groups such as methyl (1b, d), cyclic voltammetric responses with the digital simulated re-
sults. The calculated observed homogeneous rate constants
(kobs) was found to vary in the order catechol (1a)ꢃ3-methyl-
catechol (1b)ꢃ3-methoxycatechol (1c)ꢃ4-methylcatechol
(1d)ꢃ4-tert-butylcatechol (1e).
Experimental
Apparatus Controlled-potential coulometry, cyclic voltammetry, and
preparative electrolysis were performed using an Autolab model PGSTAT 20
potentiostat/galvanostat. The working electrode used in the cyclic voltamme-
try experiments was a glassy carbon disc (1.8 mm2 area) and a platinum wire
was used as the counter electrode. The working electrode used in controlled-
potential coulometry and macroscale electrolysis was an assembly of four
carbon rods (31 cm2) and a large platinum gauze constituted the counter
electrode. The working electrode potentials were measured versus SCE (all
electrodes from AZAR Electrodes). The homogeneous rate constants were
estimated by analyzing the cyclic voltammetric responses, using the
DigiElch simulation software.17) C, H, N analyses were performed on a
Vario EL III elemental analyzer.
Reagents All chemicals (catechols and phenyl-Meldrum’s acid) were
reagent-grade materials. Sodium acetate, solvents and reagents were of pro-
analysis. These chemicals were used without further purification.
Electroorganic Synthesis of 4a—d In a typical procedure, 80 ml of ac-
etate buffer (pHꢀ5.0, cꢀ0.2 M) was pre-electrolyzed at potential of peak A1
Fig. 5. Cyclic Voltammograms of 1.0 mM Catechol (1a) in the Presence of
in an undivided cell, and then 1 mmol of catechol (1a—d) and 1 mmol of
1.0 mM Phenyl-Meldrum’s acid (3) in Acetate Buffer Solution (pH 5.0)
phenyl-Meldrum’s acid (3) were added to the cell. The electrolysis was ter-
0.2 M: (a) Experimental and (b) Simulated
Scan rate: 100 mV sꢁ1. Working electrode: glassy carbon electrode. tꢀ25ꢂ1 °C.
minated 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 acetic
Table 1. Calculated Observed Homogeneous Rate Constant (kobs) for Michael Addition Reaction of Electrochemically Generated o-Benzoquinones with
Phenyl-Meldrum’s Acid (3) in Aqueous Acetate Buffer (pH 5.0, cꢀ0.2 M)
Catechol
a)
kobs (Mꢁ1 sꢁ1
)
197ꢂ1.55
122ꢂ1.23
104ꢂ0.945
38ꢂ0.55
3ꢂ0.02
a) Standard deviation of five independent simulations at various scan rates.

26
Vol. 58, No. 1
acid added were added to the solution and the cell was placed in a refrigera- 130.9, 133.3, 142.1, 144.4, 166.0. MS (EI): m/z (relative intensity): 342
tor overnight. The precipitated solid was collected by filtration and washed [M]ꢄ· (3), 240 (14), 211 (20), 195(16), 165 (23), 43 (100). Anal. Calcd for
several times with water. After washing, products were characterized by IR, C19H18O6: C, 66.66; H, 5.30. Found: C, 66.87; H, 5.19.
1H-NMR, 13C-NMR, and MS. The isolated yields after washing are reported.
Characteristic of Products 5-(3,4-Dihydroxyphenyl)-2,2-dimethyl-5-
Acknowledgment We would like to thank Dr. M. Rudolph for his cyclic
voltammogram digital simulation software (DigiElch SB) and Bu-Ali Sina
University Research Council and Center of Excellence in Development of
Chemical Methods (CEDCM) for supporting this study.
phenyl-1,3-dioxane-4,6-dione (4a): mp 202—204 °C (dec.). IR (KBr) cmꢁ1
:
3377, 2923, 1756, 1715, 1612, 1531, 1436, 1395, 1383, 1316, 1269, 1201,
1129, 1097, 1049, 1024, 977, 932, 902, 871, 830, 793, 762, 715, 678, 647,
1
625. H-NMR (300 MHz, acetone-d6) d: 1.55 (s, 3H, methyl), 1.70 (s, 3H,
methyl), 6.69 (dd, Jꢀ8.3, 2.1 Hz, 1H, aromatic in catechol ring), 6.85 (d,
Jꢀ2.1 Hz, 1H, aromatic in catechol ring), 6.96 (d, Jꢀ8.4 Hz, 1H, aromatic
in catechol ring), 7.22 (m, 5H, aromatic), 8.42, 8.48 (s, s, 2H, –OH). 13C-
NMR (75.4 MHz, acetone-d6) d: 27.0, 64.8, 105.7, 115.7, 115.8, 120.2,
126.3, 128.0, 128.3, 128.9, 139.4, 145.7, 146.0, 166.7. MS (EI): m/z (rela-
tive intensity): 328 [M]ꢄ· (3), 226 (23), 197 (44), 152 (60), 115 (18), 43
(100). Anal. Calcd for C18H16O6: C, 65.85; H, 4.91. Found: C, 65.22; H,
4.80.
References and Notes
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26—30, 2002.
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5-(3,4-Dihydroxy-5-methylphenyl)-2,2-dimethyl-5-phenyl-1,3-dioxane-
4,6-dione (4b): mp 207—209 °C (dec.). IR (KBr) cmꢁ1: 3476, 2926, 1768,
1
1728, 1615, 1541, 1452, 1337, 1295, 1204, 1082, 1030, 932, 839, 711. H-
NMR (300 MHz, acetone-d6) d: 1.48 (s, 3H, methyl), 1.80 (s, 3H, methyl),
2.23 (s, 3H, methyl), 6.63 (d, Jꢀ2.0 Hz, 1H, aromatic in catechol ring), 6.70
(d, Jꢀ2.0 Hz, 1H, aromatic in catechol ring), 7.20 (m, 5H, aromatic), 7.78
(s, 1H, –OH), 8.76 (s, 1H, –OH). 13C-NMR (75.4 MHz, acetone-d6) d: 15.4,
26.8, 64.8, 105.6, 113.1, 121.8, 125.0, 125.3, 127.9, 128.1, 129.0, 139.7,
144.3, 145.0, 166.7. MS (EI): m/z (relative intensity): 342 [M]ꢄ· (1), 211
(14), 165(18), 43 (100). Anal. Calcd for C19H18O6: C, 66.66; H, 5.30. Found:
C, 67.00; H, 5.17.
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(2008).
5-(3,4-Dihydroxy-5-methoxyphenyl)-2,2-dimethyl-5-phenyl-1,3-dioxane- 10) Nematollahi D., Ariapad A., Rafiee M., J. Electroanal. Chem., 602,
4,6-dione (4c): mp 163—165 °C (dec.). IR (KBr) cmꢁ1: 3448, 2921, 1767,
1728, 1611, 1543, 1451, 1337, 1295, 1203, 1081, 1031, 931 839, 710. H-
37—42 (2007).
1
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263—265 (2000).
NMR (300 MHz, acetone-d6) d: 1.50 (s, 3H, methyl), 1.72 (s, 3H, methyl),
3.76 (s, 3H, methoxy), 6.49 (d, Jꢀ2.1 Hz, 1H, aromatic in catechol ring),
6.56 (d, Jꢀ2.2 Hz, 1H, aromatic in catechol ring), 7.22 (m, 5H, aromatic),
8.11 (br s, 1H, –OH), 8.27 (br s, 1H, –OH). 13C-NMR (75.4 MHz, acetone-
d6) d: 26.9, 55.8, 65.0, 103.9, 105.8, 109.7, 125.0, 128.0, 128.2, 128.9,
134.9, 139.5, 146.0, 148.7, 166.7. MS (EI): m/z (relative intensity): 358 14) Nematollahi D., Shayani-Jam H., J. Org. Chem., 73, 3428—3434
[M]ꢄ· (5), 256 (27), 227 (16), 181 (18), 139 (27), 59 (20), 43 (100). Anal.
Calcd for C19H18O7: C, 63.68; H, 5.06. Found: C, 63.23; H, 4.91.
(2008).
15) Bard A. J., Faulkner L. R., “Electrochemical Methods,” 2nd ed., Wiley,
New York, 2001, p. 497.
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Methods in Electrochemistry,” Ellis Horwood, New York, 1990, p.
189.
5-(4,5-Dihydroxy-2-methylphenyl)-2,2-dimethyl-5-phenyl-1,3-dioxane-
4,6-dione (C19H18O6) (4d): mp 213—215 °C (dec.). 1H-NMR (300 MHz,
acetone-d6) d: 1.21 (s, 3H, methyl), 1.79, (s, 3H, methyl), 1.95, (s, 3H,
methyl), 5.85 (s, 1H, aromatic), 6.72 (s, 1H, aromatic), 7.50 (m, 5H, aro-
matic), 7.8 (br, 1H, –OH), 7.9 (br, 1H, –OH). 13C-NMR (75.4 MHz, acetone-
d6) d: 19.0, 26.3, 64.0, 105.9, 118.1, 118.3, 127.1, 128.7, 129.5, 130.0,
17) Rudolph M., J. Electroanal. Chem., 529, 97—108 (2002) see also:
http://www.digielch.de.