A convergent paired electrochemical synthesis of new heterocyclic compounds. Reaction of benzoquinones with 3-Amino-4-hydroxycoumarin

Article abstract of DOI:10.1007/BF03246201

Electrochemical oxidation of catechols (1) has been studied in the presence of cathodically generated 3-amino-4- hydroxycoumarin (3a) as a nucleophile in aqueous solutions, using cyclic voltammetry and controlled-potential coulometry. The results indicate that the o-benzoquinones derived from catechols (1) participate in Michael addition reaction with 3-amino-4- hydroxycoumarin (3a) to form the corresponding new heterocyclic compounds (7) (oxidized form of coumestan derivatives). The electrochemical process consists of a multi-step including (a) cathodic reduction of 4-hydroxy^-3-nitrocoumarin (3) to 3-amino-4- hydroxycoumarin (3a), (b) anodic oxidation of catechols (1) to related o-benzoquinone (2), (c) the Michael addition reaction of 3- amino-4-hydroxycoumarin (3a) to o-benzoquinone (2), and (d) anodic oxidation of formed adduct. The paired electrochemical synthesis of compounds 7a and 7b has been successfully performed in a one-pot process at carbon rods as working and counter electrodes in an undivided cell.

Full text of DOI:10.1007/BF03246201

J. Iran. Chem. Soc., Vol. 8, No. 1, March 2011, pp. 48-58.
JOURNAL OF THE
Iranian
Chemical Society
A Convergent Paired Electrochemical Synthesis of New Heterocyclic Compounds.
Reaction of Benzoquinones with 3-Amino-4-hydroxycoumarin
D. Nematollahi* and H. Karbasi
Faculty of Chemistry, Bu-Ali-Sina University, P. O. Box 65174, Hamedan, Iran
(
Received 14 January 2010, Accepted 13 February 2010)
Electrochemical oxidation of catechols (1) has been studied in the presence of cathodically generated 3-amino-4-
hydroxycoumarin (3a) as a nucleophile in aqueous solutions, using cyclic voltammetry and controlled-potential coulometry. The
results indicate that the o-benzoquinones derived from catechols (1) participate in Michael addition reaction with 3-amino-4-
hydroxycoumarin (3a) to form the corresponding new heterocyclic compounds (7) (oxidized form of coumestan derivatives). The
electrochemical process consists of a multi-step including (a) cathodic reduction of 4-hydroxy-3-nitrocoumarin (3) to 3-amino-4-
hydroxycoumarin (3a), (b) anodic oxidation of catechols (1) to related o-benzoquinone (2), (c) the Michael addition reaction of 3-
amino-4-hydroxycoumarin (3a) to o-benzoquinone (2), and (d) anodic oxidation of formed adduct. The paired electrochemical
synthesis of compounds 7a and 7b has been successfully performed in a one-pot process at carbon rods as working and counter
electrodes in an undivided cell.
Keywords: 4-Hydroxy-3-nitrocoumarin, Catechol, Paired electrochemical synthesis, Cyclic voltammetry, 3-Amino-4-
hydroxycoumarin
INTRODUCTION
energy consumption as compared to conventional electro-
organic syntheses [3,4]. In commercial electrosynthetic
processes, pairing electrode processes has always been
important [1]. The most prominent example of a paired
electrosynthesis is the production of adiponitrile by
electrohydrodimerisation of acrylonitrile, which is an
industrially important intermediate used in the manufacture of
nylon-6,6 [5]. In paired electrochemical synthesis, processes in
which two starting materials upon oxidation and reduction
give the same product may be employed in a convergent
process [1].
On the other hand, the importance of compounds known as
coumestans [6] has led many workers to synthesize a number
of coumestan derivatives by chemical [7-10] and
electrochemical [11-14] routes. These compounds are
derivatives of 6H-benzofuro[3,2-c][1]benzopyran-6-one and
Electrosynthesis offers a powerful tool for the formation of
anion and cation radical intermediates and for driving clean
synthetic reactions without the need for additional chemical
reagents [1]. In electro-organic synthesis, it is known that the
number of electrons added at the cathode (for reduction) must
simultaneously be removed at the anode (for oxidation).
Unfortunately, in most of the processes the product in one of
the compartments is undesirable [2]. The strategy of paired
electrochemical synthesis for the production of organic
chemicals, in which the reactions at both the anode and
cathode simultaneously contribute to the formation of the final
product(s), could result in as much as a 50% reduction in
*Corresponding author. E-mail: nemat@basu.ac.ir

Nematollahi & Karbasi
are structural compounds of many natural products such as
wedelolactone, medicagol, psoraldin, isopsoraldin, erosnin and
the estrogenic coumestrol, which possess interesting
physiological activities [15,16].
Isolated yield = 62%. MS: m/z (relative intensity); 177
(M , 23), 121 (100), 92 (29), 65 (44), 39 (45).
+
.
Electro-organic Synthesis of 7a,b
These objects prompted us to investigate the
electrochemical oxidation of catechols in the presence of 4-
hydroxy-3-nitrocoumarin and we have discovered an easy and
one-pot convergent paired electrochemical method for the
synthesis of new oxidized form of coumestan derivatives
An aqueous solution of phosphate buffer (80 ml) (pH 6.0,
c = 0.2 M) containing of catechol {1a or 1b (2 mmol) and 7,
(0.5 mmol)} and 2 mmol of 4-hydroxy-3-nitrocoumarin (3)
was electrolyzed at the 0.50 V vs. SCE in an undivided cell
equipped with graphite rods as cathode and anode. The
electrolysis was terminated when the cathodic peak that
corresponds to the reduction of 4-hydroxy-3-nitrocoumarin (3)
in cyclic voltammetry disappears. At the end of the
electrolysis, cell was placed in the refrigerator overnight. The
precipitated solid was collected by filtration and washed with
water.
(
7a,b) in high yield and purity, using this environmentally
friendly method with high atom economy.
EXPERIMENTAL
Apparatus and Reagents
Cyclic voltammetry and controlled-potential coulometry
Compound 7a. m.p.: 207-209 °C (dec), isolated yield =
76%. MS: m/z (relative intensity); 280 (8.8), 275 (6.9), 180
(4.4), 121 (53.1), 94 (100), 65 (55.5). FT-IR (KBr): ν 3186
(broad), 1728, 1608, 1553, 1490, 1444, 1279, 1209, 1105, 858,
were performed using
a Behpajoh model BHP-2062
potentiostat/galvanostat. The working electrode used in the
voltammetry experiments was a glassy carbon disc (1.8 mm
diameter) and platinum wire was used as the counter electrode.
The working electrode (cathode) used in controlled-potential
coulometry and macroscale electrolysis was an assembly of
two graphite rods (6 mm diameter and 6 cm length) and two
same graphite rods constituted the counter electrode (anode).
The working electrode potentials were measured versus
standard calomel electrode (SCE) (all electrodes from AZAR
Electrode). All chemicals (4-hydroxy-3-nitrocoumarin,
catechol, 3-methylcatechol and 4-methylcatechol) were
reagent-grade materials, from Aldrich. Phosphate salts were
proanalysis grade from E. Merck. These chemicals were used
without further purification.
-1
759 cm .
Compound 7b. m.p.: 199-201 °C (dec), isolated yield =
81%. MS: m/z (relative intensity); 295 (100), 267 (19.7), 238
(32.0), 139 (20.9), 121 (49.2), 91 (36.4), 63 (50.4). IR (KBr):
ν 3073 (broad), 1686, 1633, 1611, 1584, 1465, 1433, 1346,
-1
1288, 1212, 1151, 1112, 1040, 904, 774, 724, 669, 605 cm .
RESULTS AND DISCUSSION
Electrochemical
nitrocoumarin (3)
Study
of
4-Hydroxy-3-
Cyclic voltammograms of 1 mM solution of 4-hydroxy-3-
nitrocoumarin (3) in aqueous solutions at various pHs are
shown in Fig. 1. Over a pH range from 2.0 to 8.0, cyclic
voltammograms show one cathodic (C ) and anodic (A ) peak
Electro-organic Synthesis of 3a
An aqueous solution of phosphate buffer (80 ml) (pH 6.0,
c = 0.2 M) containing 2 mmol of 4-hydroxy-3-nitrocoumarin
1
1
which corresponds to the reduction of 4-hydroxy-3-
nitrocoumarin (3) to 3-amino-4-hydroxycoumarin (3a) and
oxidation of 3-amino-4-hydroxycoumarin (3a) to 4-hydroxy-
3-(hydroxyamino)coumarin (3b) (Scheme 1).
(
3) was electrolyzed at the -0.85 V vs. SCE in a divided cell
equipped with graphite rods as cathode and anode (an
assembly of two rods in each case). The electrolysis was
terminated when the cathodic peak that corresponds to the
As Fig. 1 shows, the peak potentials for peaks C
1
, and A
1
reduction of 4-hydroxy-3-nitrocoumarin (3) (C
1
in Fig. 2) in
shifted to the negative potentials by increasing pH. This is
expected because of the participation of protons in the
reduction of 3 to 3a and oxidation of 3a to 3b.
cyclic voltammetry disappears. At the end of the electrolysis,
cell was placed in the refrigerator overnight. The precipitated
solid was collected by filtration and washed with water.
Controlled-potential coulometry was performed in aqueous
4
9

A Convergent Paired Electrochemical Synthesis of New Heterocyclic Compounds
1
0
5
0
5
2
8
A
1
-
Starting potential
-
-
-
-
-
-
10
15
20
25
30
35
pH = 8 7 6 5
4
1
3 2
C
-1.5
-1.2
-1.0
-0.7
-0.5
-0.2
0.1
0.3
0.6
0.8
E (V vs. SCE)
Fig. 1. Cyclic voltammograms of 1 mM 4-hydroxy-3-nitrocoumarin at glassy carbon electrode (1.8 mm
-1
diameter), in various pHs (2.0, 3.0, 4.0, 5.0, 6.0, 7.0 and 8.0). Scan rate: 100 mV s ; t = 25 °C.
inset). These voltammetric and coulometric data in addition to
OH
OH
Peak C1
6e +6H
mass spectroscopic data (m/z = 177) of the final product (see
experimental section) in accompany with previous reports on
chemical or electrochemical reduction of 3 [17-19], confirm
NO
2
NH
2
-
+
+
(1)
-
2H O
O
3
O
2
O
3a
O
formation
of
3-amino-4-hydroxycoumarin
(3a)
in
electrochemical reduction of 4-hydroxy-3-nitrocoumarin (3)
(Scheme 1, Eq. 1).
ꢀ
OH
OH
Peak A1
NH
2
NHOH
O
-
2e- -2H+
(2)
+
H O
O
O
2
O
3
a
3b
Electrochemical Study of Catechols (1a and 1b) in the
Presence of 4-Hydroxy-3-nitrocoumarin (3)
The electrochemical behavior of catechol (1a) in the
presence of 4-hydroxy-3-nitrocoumarin (3) was studied in
some detail. Figure 3 shows the cyclic voltammograms
obtained for a 1 mM solution 1a in the presence of 1 mM 3,
when oxidation of catechol (1a) occurs at first stage and
reduction of 3 occurs at second stage. At this condition,
Scheme 1
solution containing 0.29 mmol of 4-hydroxy-3-nitrocoumarin
3) in a divided cell at -0.85 V (vs. SCE). Monitoring of the
progress of the electrolysis was carried out by cyclic
voltammetry (Fig. 2). As shown, during coulometry, in
parallel with the decrease in height of the cathodic peak C1, the
(
voltammogram exhibit anodic peak A and two cathodic peaks
2
height of anodic peak A
coulometry cathodic peak C
1
increases. At the end of the
disappears and only anodic peak
(C and C ). These peaks (A and C ) correspond to the
1
2
2
2
1
oxidation of catechol (1a) to o-benzoquinone 2a and vice
versa within a reversible two-electron process [20,21].
Contrary to our previous reports on the electrochemical
A remains. The cathodic peak C disappears when the charge
1
1
-
consumption becomes about 6e per molecule of 3 (Fig. 2,
5
0

Nematollahi & Karbasi
A1
50
0
Q=144
Q=96.0
I
pC1 = -0.81C+ 138.1
1
20
2
R =0.9962
n = 6.1
-50
8
4
0
0
0
Q=48.0
Q=0.0
-
-
100
150
0
50
100
150
C1
Charge (C)
-
1.5
-1.0
-0.5
0.0
0.5
1.0
E (V vs. SCE)
Fig. 2. Cyclic voltammograms of 0.29 mmol 4-hydroxy-3-nitrocoumarin in phosphate buffer solution (c = 0.2 M, pH
6
.0), at glassy carbon electrode (1.8 mm diameter) during controlled-potential coulometry at -0.85 V vs. SCE.
-1
After consumption of: 0.0, 48.0, 96.0 and 144.0 C. Scan rate 100 mV s . t = 25 ± 1 °C. Inset: variation of peak
current (IpC1) vs. charge consumed.
1
5
0
5
0
5
Starting Potential
1
A2
1
2
5
-
3
C2
A2
-10
-15
-20
-25
-30
-35
12
7
2
4
-3
-8
C
2
-
13
-
0.25
0.05
0.35
0.65
C1
E (V vs. SCE)
-1.5
-1
-0.5
0
0.5
1
E (V vs. SCE)
Fig. 3. Cyclic voltammogram of 1 mM catechol in the presence of 1 mM 4-hydroxy-3-nitrocoumarin, in phosphate
buffer solution (c = 0.2 M, pH 6.0), at glassy carbon electrode. Sweeping direction: oxidation of catechol at
-1
the first stage and reduction of 4-hydroxy-3-nitrocoumarin at the second stage. Scan rate: 50 mV s ; t = 25
1 °C. Inset; cyclic voltammogram of 1 mM catechol in the absence of 4-hydroxy-3-nitrocoumarin, in same
conditions. Arrows 1-5, show sweeping direction.
±
5
1

A Convergent Paired Electrochemical Synthesis of New Heterocyclic Compounds
oxidation of catechols in the presence of 4-hydroxycoumarin
number of electron (napp) and (c) appearing of new anodic and
cathodic peaks A and C . In this case, the peak current ratio
(I p /I p ) is less than unity and depends on the sweep rate. It
C2
A2
[
13,14], in this condition, the peak current ratio (I p /I p ) is
3
0
C2
A2
near unity. This indicates that, 4-hydroxy-3-nitrocoumarin (3)
doesn’t have any nucleophilisity. This is related to the
presence of nitro substituent, which has electron-withdrawing
property in the structure of the 4-hydroxy-3-nitrocoumarin.
Figure 4 shows the cyclic voltammograms obtained for a 1
mM solution 1a in the presence of 1 mM 4-hydroxy-3-
nitrocoumarin (3), when reduction of 3 occurs at first stage
and oxidation of 1a occurs at second stage. The reactivity of
anodically generated o-benzoquinone (2a) toward cathodically
generated 3-amino-4-hydroxycoumarin (3a) is supported by
reaches to nearly unity in higher sweep rates. Also,
disappearance of peak A in higher sweep rates is another
3
aspect of increasing of sweep rate. This peak (A ) can be
3
related to the oxidation of intermediate 6a (see Scheme 2).
Peak C is independent to the peak A and has dependency to
0
1
peak A (Fig. 5).
2
Furthermore, in the second cycle, a new anodic peak (A
which is counterpart of peak C0, appears with an Ep value of
0.01 V vs. SCE (Fig. 6). These peaks (C and A ) correspond
0
)
0
0
the following evidence: (a) Decreasing of peak C during the
to the oxidation of catechol 4a to o-benzoquinone 5a and vice
versa (see Scheme 2). The oxidation of intermediate 4a is
easier than the oxidation of catechol 1a by virtue of the
presence of an electron-donating amine group. Diagnostic
criteria of cyclic voltammetry and the mass spectrum of
2
reverse scan. This indicates that o-benzoquinone 2a is partially
removed from the surface of electrode by chemical reaction
with 3-amino-4-hydroxycoumarin (3a). (b) Increasing of peak
A current. This could be indicative of increasing of apparent
2
1
5
0
5
0
5
A
2
A
3
1
A
1
3
4
C
0
-
2
C
2
-
-
-
-
-
-
10
15
20
25
30
35
Starting Potential
1
C
1
-
1.5
-1
-0.5
0
0.5
1
E ( V vs . SCE)
Fig. 4. Cyclic voltammogram of 1 mM catechol in the presence of 1 mM 4-hydroxy-3-nitrocoumarin, in phosphate buffer
solution (c = 0.2 M, pH 6.0), at glassy carbon electrode. Sweeping direction: reduction of 4-hydroxy-3-
-1
nitrocoumarin at the first stage and oxidation of catechol at the second stage. Scan rate: 50 mV s ; t = 25 ± 1 °C.
Arrows 1-4, show sweeping direction.
5
2

Nematollahi & Karbasi
1
1
1
4
2
0
8
6
4
2
0
2
4
6
14
12
A2
A A
2
3
A3
1st Scan
nd Scan
1
0
8
6
4
2
0
3
2
3
a
A1
b
A1
A0
c
4
2
4
2
-
-
-
1
-2
C0
Starting Potential
1
C
0
-
-
4
C2
Starting Potential
C
2
6
-
0.6 -0.35 -0.1 0.15 0.4 0.65
-
0.45
-0.15
0.15
0.45
0.75
E ( V vs . SCE)
E ( V vs . SCE)
Fig. 5. Cyclic voltammograms of 1 mM catechol in the
presence of 1 mM 4-hydroxy-3-nitrocoumarin, in
phosphate buffer solution (c = 0.2 M, pH 6.0), at
glassy carbon electrode with various switching
potentials. Sweeping direction: reduction of 4-
hydroxy-3-nitrocoumarin at the first stage and
oxidation of catechol at the second stage. Scan rate:
Fig. 6. First and second cycles of cyclic voltammograms of 1
mM catechol in the presence of 1 mM 4-hydroxy-3-
nitrocoumarin, in phosphate buffer solution (c = 0.2
M, pH 6.0), at glassy carbon electrode. Sweeping
direction; reduction of 4-hydroxy-3-nitrocoumarin at
the first stage and oxidation of catechol at the second
-1
-1
stage. Scan rate: 50 mVs ; t = 25 ± 1 °C. Arrows 1-4,
show sweeping direction. The reduction peak of 4-
hydroxy-3-nitrocoumarin didn’t show.
50 mV s ; t = 25 ± 1 °C. Arrows 1-4, show
sweeping direction. The reduction peak of 4-
hydroxy-3-nitrocoumarin didn’t show.
isolated product indicate that the reaction mechanism of
electrooxidation of catechols (1a,b) in the presence of 4-
hydroxy-3-nitrocoumarin (3) is ECECE (Scheme 2).
results were obtained in the case of 3-methylcatechol (1b).
Since, oxidation potential of 3a is less than EpA of 1a (EpA1
<
EpA2), oxidation of 3a during the oxidation of 1a is possible.
According to our results, it seems that the intermolecular
Michael addition reaction of the cathodically generated 3-
amino-4-hydroxycoumarin (3a) to o-bezoquinone 2a leads to
the intermediate 4a. The oxidation of this compound (4a) is
easier than the oxidation of the parent-starting molecule
So, presentation of a new Scheme according to oxidation of 3a
in anode is also probable (Scheme 3).
According to our results, it seems that the Michael addition
reaction of 3b to o-benzoquinone 2a, leads to the intermediate
8
a. Oxidation of intermediate 8a is easier than the oxidation of
(
catechol) by virtue of the presence of an electron-donating
catechol 1a by virtue of the presence of an electron-donating
hydroxylamine group in structure of 8a. In continuation, the
intramolecular Michael addition reaction converts o-
bezoquinone 9a to compound 10a which in the next step with
amine group in the structure of 4a. The intramolecular
Michael addition reaction in next stage converts o-
bezoquinone 5a to compound 6a and in final stage and during
the preparative reaction, the over-oxidation of product 6a
converts it to its oxidized form as final product (7a). The same
removal of H O is converted to 7a.
2
5
3

A Convergent Paired Electrochemical Synthesis of New Heterocyclic Compounds
3
0
0
R
A2
OH
OH
2
A3
2e-
2H
1a,b
R
A1
b
a
-
-
+
OH
O
10
0
O
NH
2
+
O
a,b
O
2
3a
-
-
-
-
-
10
20
30
40
50
OH
OH
H
N
NO
2
R
O
3
O
C
2
O
O
OH
-
2e-
4a,b
OH
O
+6e +6H
-2H
-
+
Starting Potential
+
O
-
2H
H
OH
2
O
N
O
NH
2
OH
a,b
O
O
3a
O
R
5
O
H
N
OH
-60
O
C1
-0.8
O
OH
-
70
-1.3
6
a,b
R
2e-
2H
-0.3
0.2
0.7
-
-
O
O
+
H
N
O
O
N
OH
O
E(V vs. SCE)
O
O
O
O
R
R
7a,b
Fig. 7. Cyclic voltammograms of 1 mM 4-methylcatechol (a)
in the absence and (b) in the presence of 1 mM 4-
hydroxy-3-nitrocoumarin, in phosphate buffer solution
R= -H, -CH
3
Scheme 2
(
c = 0.2 M, pH 6.0), at glassy carbon electrode in
-1
various scan rates. Scan rate: 100 mV s ; t = 25 ± 1 °C.
Arrows show sweeping direction.
R
OH
OH
OH
NO
2
-
2e-
1a,b
R
O
3
O
+
-
2H
-
+
+
6e +6H
O
OH
-2H O
2
Electrochemical Study of 4-Methylcatechol (1c) in the
Presence of 4-Hydroxy-3-nitrocoumarin (3)
O
OH
NH
2
2a,b
O
O
NH
2
3
a
Among catechols, 4-alkylcatechols have special properties.
o-Benzoquinone, formed from oxidation of 4-alkylcatechols
can be converted to their tautomeric p-quinone methides form
O
O
2e-
3a
-
+
OH
R
-
2H
NHOH
O
O
+
[
22]. 4-Methylcatechol is a sample of 4-alkylcatechols, and
O
O
2a,b
3
b
also a model for biological molecules with biologic and
therapeutic effects [23-25]. So we chose it with the aim of
investigation of electrooxidation of 4-alkylcatechols in the
presence of 3-amino-4-hydroxycoumarin (3a).
The cyclic voltammogram of a 1 mM solution of 4-
methylcatechol (1c) in aqueous solution containing 0.2 M
phosphate buffer (pH 6.0) is shown in Fig. 7 (curve a). The
OH OH
N
R
O
O
OH
-
2e-
8a,b
OH
O
+
O
OH
O
OH
-
2H
N
N
OH
O
O
OH
a,b
O
O
10a,b
O-H
R
R
9
-
2
H O
O
O
voltammogram shows one anodic (A
) and a corresponding
2
H
N
O
O
N
OH
O
O
O
cathodic peak (C ), which corresponds to the transformation of
2
O
O
4
-methylcatechol (1c) to o-benzoquinone 2c and vice versa
R
R
7
a,b
R= -H, -CH
3
within a quasi-reversible two-electron process [26]. Figure 7
(curve b) shows the cyclic voltammogram obtained for a 1
Scheme 3
5
4

Nematollahi & Karbasi
mM solution of 1c in the presence of 1 mM 4-hydroxy-3-
nitrocoumarin (3) in same condition. Decreasing of peak C
current during the reverse scan and appearing of a new anodic
peak A are evidences for reactivity of anodically generated o-
I (μA)
2
A2
A3
A1
3
15
benzoquinone (2c) or its tautomer form toward cathodically
generated 3-amino-4-hydroxycoumarin (3a). Also, it is seen
that proportional to the increasing of the potential sweep rate,
c
-5
C0
b
C2
parallel to the increase in current of the C the height of A3
2
a
-25
decreases (Fig. 8). This peak (A ) disappears in high scan rates
3
Starting Potential
(
Fig. 8, curves e and f). These evidences reconfirm reactivity
of 2c toward 3a. After exhaustive electrolysis, the formed
product was compound 7a. Therefore, it can be suggested that
the formation of the unexpected product 7a arises from an
oxidative cleavage of the methyl group [27].
-45
a: Scan rate=50 mV/s
b: Scan rate=100 mV/s
c: Scan rate=150 mV/s
-65
It is probable that this abnormal process was accomplished
via enolization of the methyl group followed by chemical
reactions on the tautomeric quinone methide [22,28,29] (see
Scheme 4). We saw previously this unexpected type of
product in electrochemical oxidation of 4-methylcatechol (1c)
in methanol [30]. According to diagnostic criteria of cyclic
voltammetry and the mass spectrum of isolated product, we
proposed a mechanism including the generation of quinone
methide and formation of a carbocation-leaving group in
convergent paired electrochemical synthesis of 7a (Scheme 4).
According to our results, it seems that the Michael addition
reaction of 3-amino-4-hydroxycoumarin (3a) to p-quinone
methide 2d leads to intermediate 11. The oxidation of this
compound (11) is easier than the oxidation of the parent-
starting molecule (4-methylcatechol) by virtue of the presence
of an electron-donating group in structure of 11. Therefore, in
applied potential for oxidation of 1c, this intermediate
converts to o-benzoquinone 11a which then under
tautomerization reaction changes to p-quinone methide 11b. In
next step, intermolecular Michael addition reaction of 3a to p-
quinone methide 11b converts 11b to catechol 12. Such as
intermediate 11, the oxidation of 12 is easier than oxidation of
C1
-
85
-
1.3
-0.8
-0.3
0.2
0.7
E (V vs. SCE)
I (μA)
A
A1
2
1
20
-30
180
330
480
630
f
e
-
-
-
-
Starting
Potential
C2
d
d: Scan rate=2500 mV/s
: Scan rate=5000 mV/s
: Scan rate=10000 mV/s
e
f
C1
-
1.3
-0.8
-0.3
0.2
0.7
E (V vs. SCE)
1
c by virtue of the presence of two electron-donating groups in
structure of it. Oxidation, tautomerization and subsequent
intramolecular Michael addition reaction converts 12 to
catechol 13. As same as catechols 11 and 12, under oxidation
conditions, catechol 13 changes to related o-benzoquinone
Fig. 8. Cyclic voltammograms of 1 mM 4-methylcatechol in
the presence of 1 mM 4-hydroxy-3-nitrocoumarin, in
phosphate buffer solution (c = 0.2 M, pH 6.0), at
glassy carbon electrode in various scan rates. t = 25 ± 1
(
13a). Intrermolecular Michael addition reaction, oxidation
°C. Arrows show sweeping direction.
and then intramolecular Michael addition reaction together
5
5

A Convergent Paired Electrochemical Synthesis of New Heterocyclic Compounds
H
3
C
OH
OH
-
+
H C
O
O
H
2
C
OH
O
-
2e -2H
3
1
c
2c
OH
2d
OH
NH2
H C
2
3a
CH2
+
3
OH
OH
O
O
O
2d
3a
1
1
3a
3a
CH
a
CH2
-
+
CH
OH
OH
-
2e -2H
11
O
+ 3a
3a
OH
1
1a O
11b O
12
3
a
3a
C
-
+
CH
O
O
OH
-
2e -2H
12
3a
3a
O
12a
12b
3
a
3a
-
+
-
2e -2H
3a
C
OH
OH
3a
C
O
12b + 3a
3a
3a
O
13
13a
3a
3a
C
OH
OH
-
+
C
O
O
-
2e -2H
13a
+
3a
HO
HO
NH
NH
O
O
14a
14
O
O
3a
O
H
N
O
OH
C
OH
O
O
H+
+
3a
+
O
+
C
OH
NH
14b
1
5
6a
O
-
+
O
-
2e -2H
O
O
H
N
O
N
O
OH
O
O
O
O
O
7a
Scheme 4
with removal of carbocation-leaving group 15 converts 13a to
compound 6a. The over-oxidation of product 6a during the
preparative reaction, converts compound 6a to its oxidized
form as final product (7a).
Methyl group as a carbocation can not leave the molecule.
The elimination of methyl group was performed when it
converts to carbocation-leaving group 15. Also, the
elimination of methyl group can be carried out after formation
of p-quinone methides 12b or 11b (Schems 5 and 6,
respectively).
Controlled-potential coulometry of 4-methylcatechol (1c)
in the presence of 4-hydroxy-3-nitrocoumarin (3) in aqueous
solution containing 0.2 M phosphate buffer (pH 6.0) shows the
-
consumption of about 10e (n = 10.3) per molecule of 1c.
5
6

Nematollahi & Karbasi
3
a
3a
3a
3a
HC
OH
OH
-
2e -2H+
HC
O
O
-
12b
+
3a
HO
HO
NH
NH
O
O
16a
16
O
O
3
a
O
3a
H
N
O
OH
OH
HC
OH
O
H
O
H+
+
3a
+
O
C+
NH
16b
6
-
a
17
O
-
2e -2H+
O
O
O
H
N
O
O
N
O
OH
O
O
O
O
7a
Scheme 5
3a
3a
H C
OH
OH
-
+
H C
O
2
2
-
2e -2H
11b
+
3a
HO
HO
O
NH
NH
O
O
18a
18
O
O
3
a
OH
O
O
H
N
NH CH2
OH
H
C
OH
O
2
O
H+
+
+
O
O
O
OH
NH
18b
19
6a
-
+
O
-
2e -2H
O
O
O
H
N
O
N
O
OH
O
O
O
O
O
7a
Scheme 6
According to this data we think that the elimination of methyl
group can be carried out after formation of p-quinone
methides 12b (Schems 5). Also, as shown in Scheme 3, it is
possible that instead of nucleophile 3a, compound 3b as a
nucleophile participates in Michael addition reactions.
CONCLUSIONS
The results of this work show a convergent paired
electrochemical synthesis of new heterocyclic compounds 7a
and 7b. These products, which are oxidized form of
5
7

A Convergent Paired Electrochemical Synthesis of New Heterocyclic Compounds
coumestan derivatives, were obtained after two successive
(1976) 4823.
intermolecular and intramolecular Michael addition reactions
of 3-amino-4-hydroxycoumarin with quinones. The reaction
mechanism for the synthesis of compounds 7a and 7b is
presented in Schemes 2-6. In this work, a simple and efficient
paired method for synthesis of compounds 7a and 7b is
described. Furthermore, the results of this work introduce
electrochemistry as a powerful and green tool in organic
synthesis and mechanistic investigations.
[12] I. Tabakovic, Z. Grujic, Z. Bejtovic, J. Heterocyclic
Chem. 20 (1983) 635.
[13] S.M. Golabi, D. Nematollahi, J. Electroanal. Chem. 420
(1997) 127.
[14] S.M. Golabi, D. Nematollahi, J. Electroanal. Chem. 430
(1997) 141.
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Thompson, E.A. Hollwell, E.G. Beinhart, J. Anim. Sci.
1
9 (1960) 4.
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[16] M. Darbarwar, V. Sundaramurthy, N.V. Subba Rao,
Indian J. Chem. 11 (1973) 115.
The authors acknowledge to Bu-Ali Sina University
Research Council and Center of Excellence in Development of
chemical Methods (CEDCM) for supporting this work.
[17] C.F. Heubner, R.P. Link, J. Am. Chem. Soc. 67 (1945)
99.
[18] M. Trkovnik, M. Laan, Z. Stuni, D. Nahmijaz, Org.
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5
8