Electrochemical oxidation of substituted catechols in the presence of pyrazol-5-ones: Characterization of products and reaction mechanism

Article abstract of DOI:10.1016/j.tet.2010.10.060

The electrochemical oxidation of substituted catechol derivatives has been investigated in the presence of pyrazol-5-ones as C-H acid nucleophiles by using constant current technique in acetate buffer solution. The results indicate that different reaction

Full text of DOI:10.1016/j.tet.2010.10.060

Tetrahedron 66 (2010) 9880e9887
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Electrochemical oxidation of substituted catechols in the presence
of pyrazol-5-ones: characterization of products and reaction mechanism
,
a
Xiao-Guang Gao a, Cheng-Wen Yang a, Zheng-Zheng Zhang a, Cheng-Chu Zeng a , Xiu-Qing Song ,
*
Li-Ming Hu a, Ru-Gang Zhong a, Yuan-Bin She b
a College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China
b College of Environmental and Energy Engineering, Beijing University of Technology, Beijing 100124, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 July 2010
Received in revised form 7 October 2010
Accepted 22 October 2010
Available online 28 October 2010
The electrochemical oxidation of substituted catechol derivatives has been investigated in the presence
of pyrazol-5-ones as CeH acid nucleophiles by using constant current technique in acetate buffer so-
lution. The results indicate that different reaction mechanisms are involved and not only 1,4-Michael
adducts but also 1,6-Michael adducts are formed, depending on the nature of the starting catechols and
the nucleophiles, as well as the reaction conditions.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Electrochemical synthesis
Catechols
Pyrazol-5-ones
1,4-Addition
1,6-Addition
1. Introduction
products. In this respect, electrochemical oxidation of catechols in the
presenceofnucleophiles (suchasamines,13 thiols14 orsulfuricacids15
)
Catechols and their quinone derivatives have drawn consider-
able attention due to their abundance in nature and important roles
in many biological systems. Moreover, most of compounds in-
corporating catechol moiety exhibit antioxidant,1 anticarcino-
genic,2,3 antifungous,4 and antibacterial activities5,6 or are used as
HIV integrase inhibitors.7e9 For example, dopamine is a neuro-
transmitter in the central nervous system of human and other
vertebrate animals,10 whereas, dicaffeoyltartaric acid7 and dicaf-
feoylquinic acid7,8 exhibit HIV integrase inhibitory activity.
leads to the formation of substituted catechols or substituted
o-benzoquinones.
CeH acids are common nucleophiles and therefore also are
employed in the nucleophilic attack to the electro-generated o-
benzoquinones.18e23 However, most of the CeH acids employed are
confined to acyclic and cyclic 1,3-dicarbonyl derivatives, such as
barbituric acids,18 acetylacetone,19 cyclohexanediones,20 acetoace-
tates,21 4-hydroxycoumarins12,22 and Meldrum’s acid,23 and mainly
lead to the formation of benzofurans and coumestans. Moreover, it
is observed that only 1,4-Michael addition products are isolated in
these electrochemical transformations.
As a continuous work toward the development of potential HIV-
1 integrase inhibitors derived from polyhydroxylated aromatics, we
have investigated the electrochemical synthesis of poly-
hydroxylated aromatics.24e29 In the present work, we report the
electrochemical oxidation of catechols 1 in the presence of pyrazol-
5-ones 2 as CeH acids by constant current technique (Fig. 1). The
outcomes indicate that different reaction mechanisms (not only
1,4-Michael addition, but also 1,6-addition) are involved, which
demonstrates that a wide spectrum of products may be produced
by simply tuning the natures of the starting catechols and nucle-
ophiles, and reaction conditions.
On the other hand, electroorganic synthesis11 is regarded as an
environmental friendly strategy for chemical transformation,
whereinelectronsareusedasoxidantsandthustheutilizationof toxic
metal-based reagents is avoid. Also, such transformation is generally
performed under mild conditions. Indeed, catechols and their qui-
none derivatives can be achieved by the electrochemical synthesis of
o-benzoquinones and their in situ transformation12e23 since the
electro-generated o-benzoquinones are active intermediates and
readily undergo Michael addition reaction,12e15,18e23 with nucleo-
philes or [4þ2] cycloaddition with dienes16,17 to form various
* Corresponding author. Tel.: þ86 10 67396211; fax: þ86 10 67392001; e-mail
address: zengcc@bjut.edu.cn (C.-C. Zeng).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.10.060

X.-G. Gao et al. / Tetrahedron 66 (2010) 9880e9887
9881
indicates that the electro-generated o-benzoquinone intermediate
undergoes follow-up chemical reactions under these conditions.
H3C
R1
R2
OH
OH
N
O
N
2.2. Electrochemical oxidation of substituted catechols in the
presence of 3-methylpyrazol-5-ones
R3
2a-2e
1a-1d
2a: R3 = H,
1a: R1 = OCH3, R2 = H
1b: R1= H, R2 = t-Bu
1c: R1 = H, R2 = CH3
1d: R1 = CH3, R2 = H
2b: R3 = Ph
After examining the electrochemical properties of substituted
catechols in the absence and presence of pyrazol-5-one, pre-
parative scale of electrolyzes were carried out. At the outset, 3-
methoxy catechol 1a was subjected to anodic oxidation in the
presence of 3-methylpyrazol-5-ones. Thus, in a pilot experiment,
a solution of an equimolar quality of 1a and 2a was electrolyzed at
constant current of 12 mA (w4 mA/cm2) at pH 7.0 acetate buffer.
The reaction mixture afforded C,C-dicatechol pyrazol-5-one de-
rivative 3a in 42% yield (Scheme 1).
2c: R3 = p-CH3-Ph
2d: R3 = p-OCH3-Ph
2e: R3 = p-Cl-Ph
Fig. 1. Structures of starting substituted catechols 1 and pyrazol-5-ones 2.
2. Results and discussion
2.1. Cyclic voltammetric studies
OH
HO
OH
OCH3
OCH3
OH
HO
H3CO
H3C
Anodic oxidation
NaOAc-AcOH
The electrochemical behavior of catechols 1 in the absence and
presence of pyrazol-5-ones was examined at room temperature in
water containing 0.2 M acetate buffer (pH 7.0) as the supporting
electrolyte by cyclic voltammetry (CV).
+
N
O
N
R
OH
O
H3C
1a
3a-d
2a-2d
N
N
R
3a: R = H; 3b: R = Ph;
Taking 4-methylcatechol (1c) as an example, as shown in Fig. 2,
upon scanning anodically, 4-methylcatechol exhibits a well defined
quasi-reversible oxidation wave (peak A) at þ0.51 V versus Ag/AgCl
(KCl 3 M) and its corresponding cathodic peak (C) atþ0.30 V. Peak A
is attributed to the oxidation of 4-methylcatechol to the corre-
sponding 4-methyl o-benzoquinone and peak C to the reduction of
the quinone. The ratio of the current amplitudes between the oxi-
dation and reduction processes is equal to unity (Iopx/Ipred), indicating
that the o-benzoquinone produced at the surface of the electrode is
stable under pH 7 acetate buffer and that side-reactions, such as
hydroxylation or dimerization reactions are too slow to be observed
on the time scale of the cyclic voltammetry.13e23
3c: R = p-CH3-Ph;
3d: R = p-OCH3-Ph;
Scheme 1. Anodic oxidation of 3-substituted catechol 1a in the presence of 3-meth-
ylpyrazol-5-ones 2aed.
Subsequently, phenyl-substituted 3-methylpyrazol-5-ones
2bed were employed as CeH acid nucleophiles to react with the
electro-generated 3-methoxy o-benzoquinone (Scheme 1). Here,
due to the low solubility of phenyl-substituted 3-methylpyrazol-5-
ones, acetonitrile was added as a co-solvent. Accordingly, a mixed
solvent of acetate buffer solution and acetonitrile (3:1 ratio of ac-
etate buffer to acetonitrile, pH 7) was used as supporting electro-
lyte. It was found that analogous reaction pattern occurred with
respect to these 3-methyl-pyrazol-5-ones. As shown in Scheme 1,
when the nucleophiles were 2bed, corresponding 3b, 3c, and 3d
were isolated in 23%, 20%, and 29%, respectively. Interestingly, an
unexpected compound 4 was also isolated in 11% yield (Fig. 3),
along with 3b, from the anodic oxidation of the mixture of 1a and
2b. It is noteworthy that, structurally, compounds 3 and 4 are 1,4-
Michael addition products. For example, compounds 3 may stem
from the 1,4-Michael addition of pyrazol-5-ones to two molecules
of the electro-generated 3-methoxy o-benzoquinone.
A2
80
60
40
20
0
A
A1
c
b
B
a
OH
HO
C1
-20
-40
-60
O
H3CO
H3C
N
N
N
C
H3C
OCH3
OH
N
0
200
400
600
800
1000
1200
1400
1600
O
E/mV vs. Ag/AgCl
4
OH
Fig. 2. Cyclic voltammograms of (a) 2 mM of 4-methylcatechol (1c), (b) 2 mM of
3-methyl-1H-pyrazol-5-one (2a), and (c) a mixture of 2 mM of 2a and 2 mM of 1c, at
a glassy carbon working electrode, platinum wire counter, and Ag/AgCl reference
electrodes, in acetate buffer (0.2 M, pH 7) solution; scan rate: 100 mV/s.
Fig. 3. Structure of compound 4.
To investigate the limitation and scope of the anodic oxidation
of substituted catechols in the presence of pyrazol-5-ones, next, 4-
tert-butylcatechol (1b) was subjected to constant current electrol-
ysis in the presence of 3-methylpyrazol-5-ones 2aee (Scheme 2).
However, the benzoquinone generated from this catechol behaved
in a way quite different from o-benzoquinone generated from
3-methoxy catechol: 1,6-addition occurred on the former instead of
1,4-addition on the later. It is noticed that the formation of the type
of 1,6-addition has not been obtained in the oxidations of catechols
When 1 equiv amount of 3-methyl-1H-pyrazol-5-one 2a was
added, the voltammogram of the mixture exhibits two anodic
peaks A1 (þ0.55 V vs Ag/AgCl) and A2 (þ0.86 V vs Ag/AgCl),
whereas the cathodic peak shift to 0.19 V versus Ag/AgCl and its
cathodic current decreases dramatically (curve c, Fig. 2). Curve b in
Fig. 2 is the CV of 3-methyl-1H-pyrazol-5-one 2a, where one irre-
versible anodic wave at 0.80 V is observed. The observation that the
cathodic current of the corresponding o-benzoquinone decrease

9882
X.-G. Gao et al. / Tetrahedron 66 (2010) 9880e9887
previously reported. For example, in the case of 2a, mono adduct 5a
precipitated and was exclusively obtained in 34% yield. In a similar
manner, 5c was exclusively obtained in 44% yield from the anodic
oxidation of 1b and 2c in 3:1 volume ratio of acetate buffer to
acetonitrile as supporting electrolyte.
Subsequently, phenyl-substituted 3-methylpyrazol-5-ones 2b
were employed to react with the electro-generated 4-methyl o-
benzoquinone (Scheme 3). After the consumption of starting 4-
methylcatechol, compound 9b precipitated and was obtained in 37%
yield after recrystallization from methanol. In a similar manner,
compounds 9c, 9d, and 9e were obtained in 55%, 32%, and 62% yield,
respectively. The 1HNMR spectra of these compoundsindicatethat9
are 1,4-Michael addition products and exist as a mixture of pyrazol
9bee and their corresponding isomers 1,2-dihydropyrazol-3-one
9b0ee0.31
R
N
N
H3C
HO
OH
CH3
OH
Anodic oxidation t-Bu
NaOAc-AcOH
t-Bu
OH
OH
+
N
t-Bu
O
OH
OH
+
N
R
In addition, in the case of 3-methylcatechol (1d), C,C-dicatechol
pyrazol-5-one 10 was isolated in 38% yield, which is from the 1,4-
addition of 3-methyl-1H-pyrazol-5-one to two molecules of elec-
tro-generated 3-methyl o-benzoquinone (Scheme 4).
H3C
OH
OH
1b
2a-2e
N
H3C
N
R
5a, 5c
N
N
R
6b-6e
a: R = H; b: R = Ph; c: R = p-CH3-Ph
d: R = p-OCH3-Ph; e: R = p-Cl-Ph
OH HO
OH
CH3
CH3
HO
H3C
Scheme 2. Anodic oxidation of 4-tert-butylcatechol (1b) in the presence of 3-meth-
ylpyrazol-5-one 2aee.
H3C
Anodic oxidation
NaOAc-AcOH
OH
OH
+
N
O
N
H
Interestingly, it was observed that the reaction condition af-
fected the product composition. When the solvent-supporting
electrolyte was a 2:1 volume ratio of acetate buffer to acetonitrile,
anodic oxidation of 1b in the presence of 2c afforded exclusively
compound 6c in 17% yield, instead of 5c. The plausible reason is that
the initially formed 5c can dissolve in this supporting electrolyte to
an extent and thus underwent further oxidation followed by
a second 1,6-Michael addition to generate bis(5-hydroxypyrazol-4-
yl)catechols 6c.
O
H3C
1d
2a
N
N
H
10
Scheme 4. Anodic oxidation of 3-methylcatechol (1d) in the presence of 3-methyl-
pyrazol-5-one 2a.
2.3. Spectroscopic characterization
Similar to the anodic oxidation of the mixture of 1b and 2c, the
anodic oxidation of 1b in the presence of 2b, 2d or 2e, in 2:1 volume
ratio of acetate buffer to acetonitrile, gave 6b, 6d or 6e in 29%, 25%
or 21% yield, respectively, which was obtained by simple filtration
of the reaction mixture.
All the synthesized products 3e10 were characterized by ESI-
MS, 1H NMR, and 13C NMR. Firstly, the ESI-MS data of compounds 3
show that it is a double adduct of 3-methyl-1H-pyrazol-5-one with
two 3-methoxy o-benzoquinone molecules. The 1H NMR spectra of
compounds 3 and 10 show that the two-catechol moieties are in
the same chemical environment. Therefore, it is elucidated that
both catechol moieties are bound to C(4) of 3-methyl-1H-pyrazol-
5-one scaffold and compounds 3 and 10 are C,C-dicatechol pyrazol-
5-ones. The assignment of the structure of compounds 3 and 10 is
further demonstrated by 13C NMR spectrum where a quaternary sp3
carbon atom at about 65 Hz is observed for each C,C-dicatechol
pyrazol-5-one derivative 3 and 10. In addition, the split pattern of
the two aromatic protons (doublet, J¼2.0 Hz) of each catechol
moiety indicates that 1,4-addition reaction occurred and C(4) atom
of 3-methyl-1H-pyrazol-5-one moiety is bound to each C(5) atom
(para-position to one of the two OH groups) of the catechol
subunits.
Finally, we investigated the anodic oxidation of methyl-
substituted catechols (1c and 1d) in the presence of 3-methylpyr-
azol-5-ones. Again, different reaction pattern took place, where, not
only 1,4-addition product, but also 1,6-addition product was detec-
ted. For instance, equimolar amount of 1c and 2a were electrolyzed
at constant current to afford a mixture of compounds 7 and 8, out of
which only 7 was isolated in 20% yield aftercolumn chromatography
(Scheme 3). It was observed that the pH of the solution obviously
affected the composition of products. When the reactionwas carried
out in acidic condition (such as pH 4.0 buffer solution), compound 7
was selectively formed and isolated in 30% yield. However, com-
pound 8 was isolated as the major product in 56% yield when the
reaction was performed in basic condition (such as pH 9 buffer so-
lution). The spectroscopic data of compound 7 demonstrated that it
is stemmed from a 1,6-addition, whereas, compound 8 resulting
from the 1,4-addition of 3-methyl-1H-pyrazol-5-one to two mole-
cules of electro-generated 4-methyl o-benzoquinone.
The structure of compounds 3 and 10 are quite different from
compound 8. Although the ESI-MS data of compound 8 also show
that it is a double adduct of 3-methyl-1H-pyrazol-5-one with two
4-methyl o-benzoquinone molecules, its 1H NMR spectrum shows 4
singlets in the aromatic region (6.52, 6.61, 6.62, and 6.67 ppm),
OH
H3C
H3C
OH
OH
O
H3C
OH
Anodic oxidation
NaOAc-AcOH
H3C
OH
OH
OH
OH
OH
H3C
H3C
+
N
+
O
O
N
H
N
7
NH
1c
NH
N
2a
H3C
8
H3C
OH
OH
H3C
H3C
OH
OH
Anodic oxidation
NaOAc-AcOH
H3C
OH
OH
H3C
H3C
+
N
N
N
R
N
R
HN
N
R
OH
1c
O
9b'-9e'
2b-2e
9b-9e
Scheme 3. Anodic oxidation of 4-methylcatechol (1c) in the presence of 3-methylpyrazol-5-one 2aee.

X.-G. Gao et al. / Tetrahedron 66 (2010) 9880e9887
9883
along with 4 singlets at 8.58, 8.67, 9.03, and 9.12 ppm, attributed to
the OH groups. These results indicate that the two-catechol moie-
ties are in a quite different chemical environment. Therefore, it is
elucidated that the two catechol moieties are bound, respectively,
to C(4) and O atom of 3-methyl-1H-pyrazol-5-one scaffold. In ad-
dition, the split pattern of the two aromatic protons (singlet) of
each catechol moiety indicates that it is a 1,4-addition product.
Regarding the structures of compound 4, it was characterized
firstly by ESI-MS as an adduct of two 3-methyl-1-phenyl-1H-pyr-
azol-5-one molecules with two 3-methoxy o-benzoquinone mol-
ecules (m/e: 620.9, Mꢀꢀ1). The 1H NMR spectrum of 4 further
shows that the two-catechol moieties are in different chemical
environment. Therefore, it is elucidated that the two catechol
moieties are bound, respectively, to C(4) and O atom of the two 3-
methyl-1-phenyl-1H-pyrazol-5-one molecules, which are coupled
through C(4)eC(4) bond.
o-benzoquinone tautomers and thus nucleophilic addition takes
place readily.37,38
In the cases of 4-methylcatechol (1c) and 3-methylcatechol (1d),
the methyl group could also deactivate the 1,6-addition by elec-
tronic effects, but such electronic effect (hyperconjugation) is
rather weak. Also, the methyl group is less bulky that a tert-butyl
group. Therefore, both products of 1,4-addition (see compounds 8,
9bee in Scheme 3 and compound 10 in Scheme 4) and 1,6-addition
(see 7, Scheme 3 and Fig. 4) have been obtained and the former are
the main products. As shown in Fig. 4, the anodic oxidation of 4-
methylcatechol (1c) leads to the corresponding 4-methyl o-ben-
zoquinone 1c0. When 2a is used as nucleophile, 1,6-addition mono
adduct 7 and 1,4-addition mono adduct intermediate are formed.
The latter further undergoes 1,4-Michael addition with a second
o-benzoquinone 1c0 to afford compound 8 (C,O-double adduct)
through the hydroxyl group in the pyrazol subunit. Interestingly,
when phenyl-substituted pyrazoles 2bee were treated with 1c0,
only 1,4-addition mono adducts 9bee are produced.
2.4. Reaction mechanism
Similarly, anodic oxidation of 3-methylcatechol (1d) generates
the corresponding 3-methyl o-benzoquinone (1d0), which is
attacked by nucleophile 2a to form 1,4-addition mono adduct. Upon
ketone-type isomerization and one more 1,4-Michael addition to
a second intermediate 1d0, C,C-dicatechol pyrazol-5-ones 10 was
finally formed.
Different from that with 1a, 1c, and 1d, in the case of 4-tert-
butylcatechol 1b, catechol derivatives resulting from a 1,6-addition
of the nucleophile to the electro-generated o-benzoquinone are the
main products. This is not surprising because the carbon meta to
the tert-butyl group (1,6-addition) is much less hindered than the
carbon at the ortho-position (1,4-addition). Once the meta-position
is blocked (see 50 in Fig. 5), then the nucleophile does add at the
ortho-position, necessarily in a 1,6-fashion (there is no other pos-
sibility), to give catechols 6bee (Scheme 2).
Accordingly, the bulky tert-butyl group at C(4) position of the
o-benzoquinone caused the preferential 1,6-addition (rather than
1,4-addition behaving as 1a) of pyrazol-5-one moiety, followed by
aromatization to form mono adduct 5. Compounds 5 are by
themselves catechols and then can be in situ oxidized to the cor-
responding quinones 50, followed by a second 1,6-Michael addition
of 2 to form final compounds 6. Such result is consistent with
previous report in which high regioselective 1,6-addition product
was obtained from reaction of 4-tert-butyl o-benzoquinone and
silyl enol ethers.39
In addition, this regioselective 1,6-addition hypothesis can be
demonstrated by the reaction of 1b and 2c. As mentioned above,
when the electrochemical reaction was performed in 3: 1 volume
ratio of acetate buffer to acetonitrile as supporting electrolyte, the
reaction stopped at the mono-adduct step and 5c precipitated from
the solution due to its low solubility. However, if the volume of
acetonitrile increased to 2:1 volume ratio of acetate buffer to ace-
tonitrile, the initially-generated 5c could dissolve and was further
oxidized, followed by a 1,6-addition, to generate 6c exclusively.
As to the mechanism, it is well documented 12ꢀ23,32ꢀ36 that the
anodic oxidation of catechol and its derivatives in aqueous medium
leads to the formation of the corresponding o-benzoquinone in-
termediates. In the presence of a nucleophile (or solvent), these
intermediates are converted to other intermediates or products,
following a pattern of an EC or an ECEC mechanism. Therefore,
plausible mechanisms for the reaction between catechols and
pyrazol-5-one derivatives under electrochemical oxidation condi-
tions are proposed in Figs. 4 and 5 on the basis of the CV analysis
and structures of products.
As shown in Fig. 4, when the starting catechol is 3-methoxy
catechol 1a, its anodic oxidation leads to the corresponding 3-
methoxy o-benzoquinone 1a0, in which, the electronic factor, lone
electronic pair delocalized onto the benzene ring, is quite impor-
tant and it deactivates the 1,6-addition. In addition, the methoxy
group is less bulky than a methyl or a tert-butyl group. Conse-
quently, nucleophiles 2 selectively attack the more electropositive C
(5) position of the o-benzoquinone ring to form corresponding 1,4-
addition mono adducts (Fig. 4), no product of 1,6-addition was
obtained with 3-methoxy catechol (1a).
Once the 1,4-addition mono adducts were produced in the sol-
vent, then two different pathways may involve, in parallel or in
competitive, depending on the nature of the nucleophiles and the
reaction conditions. One pathway is that the initially formed 1,4-
addition mono adducts tautomerize to the corresponding ketone-
type isomers and subsequently its methyne C atom functions as
nucleophilic site to attack a second intermediate 1a0 in the 1,4-Mi-
chaeladditionmanner, followed byanaromatizationprocess, to form
C,C-dicatechol pyrazol-5-ones 3aed (pathway I, Fig. 4). To the best of
our knowledge, this type of reaction is known. For example, in the
presence of barbituric acids, the electrooxidation of 4-tert-butylca-
techol leads to the formation of spiropyrimidine derivatives.18
The formation of compound 4 is unique because it is a ‘tetramer’
comprised of two catechols subunits and two pyrazol subunits. Its
formation may follow a second pathway, that is, in parallel to or in
competitive with the pathway I, the 1,4-addition mono adduct was
oxidized to mono adduct quinone derivative, which undergoes
isomerization to the mono adduct quinone methide and was
attacked by a second 2b molecule. The formed ‘trimer’ intermediate
further reacts with a second active 1a0 (1,4-addition) to finally form
compound 4 (pathway II, Fig. 4). The hypothesis for the formation
of compound 4 is reasonable, because previously it was reported
that para-alkyl o-benzoquinones can isomerize to the corre-
sponding p-benzoquinone methides at rates, which depend on
the type of the substituent at the para-position. In addition, the
p-benzoquinone methides are much more electrophilic than the
3. Conclusion
In summary, the electrochemical oxidation of substituted cate-
chols in the presence of pyrazol-5-ones has been carried out by
constant current technique in acetate buffer solution. The results
indicate that the reaction is not selective. Depending on the nature
of the nucleophiles, structures of the starting catechols and re-
action conditions, different reaction pathways are involved and
thus lead to a wide spectrum of products. The anodic oxidation of 3-
methoxy catechol 1a mainly led to the formation of 1,4-addition
mono adducts, which underwent different pathway to form C,C-
dicatechol pyrazol-5-ones 3aed and unexpected ‘tetramer’ 4. In the
case of 4-tert-butylcatechol 1b, steric factor plays predominant role

9884
X.-G. Gao et al. / Tetrahedron 66 (2010) 9880e9887
R1
OH
OH
OH
OH
OH
CH3
N
N
OH
H3C
R
O
H3C
O
OH
3a-3d, 10
OH
NH
N
H3C
1a, 1c, 1d
8
R1
1c'
1a' or 1d'
-2e, -2H+
1,4-addition
R1
1,4-addition
R1
R1
R2
OH
H3C
R2
O
O
Pathway I
OH
2
H3C
N
OH
N
1,4-addition
1,4-addition
mono adducts
(9b-9e)
OH
N
H
O
OH
1a', 1c', 1d'
R
N
R
-2e, -2H+
H3C
2a
1,6-addition
Pathway II
OCH3
OCH3
O
O
H3C
OH
OH
H3C
N
OH
O
H3C
N
N
Ph
N
O
OH
OH
Ph
1,4-addition mono
N
N
H
7
1,4-addition mono
adduct quinone methide
adduct quinone
1,6-addition
mono adduct
OH
H3CO
OH
OH
CH3
N
N
H3CO
2b
OH
1a'
CH3
O
Ph
N
O
1,4-addition
N
O
N
Ph
H3C
Ph
N
N
Ph
HO
H3C
N
HO
OCH3
HO
4
Fig. 4. Plausible electrochemical reaction mechanism of substituted catechols 1a, 1c, and 1d in the presence of pyrazol-5-one derivatives 2.
4. Experimental section
t-Bu
H3C
OH
-2e, -2H+
t-Bu
OH
OH
t-Bu
O
O
2
4.1. Instruments and reagents
OH
OH
1,6-addition
1b
1b'
Cyclic voltammograms were measured by a 273 A Potentio-
stat/Galvanostat equipped with an electrochemical analysis
software, using a conventional three-electrode cell. The working
N
N
R
5
R
N
N
HO
t-Bu
O
electrode was a glassy carbon disk electrode (ca.
4
¼3 mm). The
CH3
OH
-2e, -2H+
2
auxiliary and reference electrodes in these studies were Pt wire
and saturated Ag/AgCl, respectively. Glassy carbon was polished
with polishing cloth before each measurement. All electrodes for
CV experiments were from CH Instruments, Inc. USA. Acetate
buffer solution was prepared by NaAc and HAc monitored by
a digital pH meter. Scan rate was 100 mV/s. The concentration of
1 and 2 were 2 mmol Lꢀ1, while that of the supporting electrolyte
t-Bu
O
H3C
N
1,6-addition
OH
OH
OH
H3C
N
R
6b-6e
N
N
5'
R
Fig. 5. Plausible electrochemical reaction mechanism of substituted catechol 1b in the
presence of pyrazol-5-one derivatives 2.
was 0.2 mol Lꢀ1
.
All melting points were measured with a XT4A Electrothermal
melting point apparatus and are uncorrected. IR spectra were
recorded as KBr pellets. 1H and 13C NMR spectra were recorded with
an AV 400M Bruker spectrometer (400 MHz 1H frequency, 100 MHz
d values (internal
standard: TMS). The MS spectra (ESI) were recorded on a Bruker
esquire 6000 mass spectrometer.
and 1,6-addition is preferential, hence 1,6-addition mono adducts 5
or bis-(5-hydroxypyrazolyl)-substituted catechols 6 were pro-
duced. Finally, both 1,6-addition product 7 and 1,4-addition prod-
ucts 8 (C,O-double adduct), 9 and 10 (C,C-double C-double adduct)
were obtained from anodic oxidation of methyl-substituted cate-
chol in the presence of pyrazol-5-one.
13C frequency). Chemical shifts are given as

X.-G. Gao et al. / Tetrahedron 66 (2010) 9880e9887
9885
Catechols 1, 2a, and 2b were reagent-grade from Alfa Aesar
135.9, 146.4, 148.9, 163.0, 173.9; IR (KBr):
n
3432, 2927, 1697, 1620,
China (Tianjin Co., Ltd.), whereas compounds 2cee were prepared
according to known procedure30 Other chemicals and solvents
were from Beijing Chemicals Co. and used without further purifi-
cation. Doubly distilled de-ionized water was used for preparation
of aqueous acetate buffer. All experiments were performed at room
temperature and ambient pressure.
1514, 1457; ESI-MS: m/z 462.9 (Mꢀꢀ1), 486.9 (MþþNa).
4.2.4. 4,4-Bis(3,4-dihydroxy-5-methoxyphenyl)-3-methyl-1-methox-
yphenyl-1H-pyrazol-5(4H)-one (3d). Yield: 29%; mp: 242e243 ꢂC;
1H NMR (400 MHz, DMSO-d6):
d 2.09 (s, 3H, CH3), 3.66 (s, 6H,
OCH3), 3.77 (s, 3H, OCH3), 6.19 (d, 2H, J¼2.0 Hz, AreH), 6.28 (d, 2H,
J¼2.0 Hz, AreH), 7.02 (d, 2H, J¼7.2 Hz, AreH), 7.75 (d, 2H, J¼7.2 Hz,
AreH), 8.46 (s, 2H, OH), 9.12 (s, 2H, OH); 13C NMR (100 MHz, DMSO-
4.2. General procedure for the synthesis of compounds 3e10
d6):
d 15.6, 55.8, 56.5, 67.7, 104.3, 109.7, 114.6, 121.0, 126.9, 131.5,
A 100 mL of H-type cell was equipped with a medium glass frit
as a membrane. The anode compartment contained an assembly of
seven graphite rods as the anode, whose upper rims were wrapped
by a copper wire, and a platinum wire as the counter electrode was
immersed in the cathode compartment. The current throughout
electrolysis was controlled by a DC regulated power. During elec-
trolysis, a magnetic stirrer stirred the mixture.
134.8, 146.4, 148.9, 157.1, 162.9, 173.7; IR (KBr): n 3484, 3394, 1686,
1618, 1510, 1368, 1241, 1205, 1099; ESI-MS: m/z 479 (Mꢀꢀ1), 503
(MþþNa).
4.2.5. 4-[5-(3,4-Dihydroxy-5-methoxyphenoxy)-3-methyl-1-phenyl-
1H-pyrazol-4-yl]-4-(3,4-dihydroxy-5-methoxyphenyl)-3-methyl-1-
phenyl-1H-pyrazol-5(4H)-one (4). Yield: 11%; mp: 157 ꢂC (dec); 1H
To the anode compartment, which is kept in water at room
temperature was added 50 mL acetate buffer solution. Sub-
sequently, catechols 1 (1 mmoL) and 2 (1 mmoL) were added to the
anodic compartment and electrolyzed at constant current of 12 mA
(w4 mA/cm2). The electrolysis was terminated when the starting 1
was consumed as determined by TLC. After electrolysis, the anolyte
was worked up by one of the methods shown below.
NMR (400 MHz, DMSO-d6): d 1.68 (s, 3H, CH3), 2.17 (s, 3H, CH3), 3.70
(s, 3H, OCH3), 3.74 (s, 3H, OCH3), 6.38 (d, 1H, J¼2.4 Hz, AreH), 6.43
(d, 1H, J¼2.0 Hz, AreH), 6.45 (d, 1H, J¼2.4 Hz, AreH), 6.57 (d, 1H,
J¼2.4 Hz, AreH), 7.16e7.88 (m, 10H, PheH), 8.48 (s, 1H, OH), 8.60 (s,
1H, OH), 9.15 (s, H, OH), 9.21 (s, H, OH); 13C NMR (100 MHz, DMSO-
d6):
d 13.9, 16.2, 56.6, 56.6, 61.2, 103.5, 105.2, 108.0, 108.4, 118.7,
124.4, 125.1, 125.6, 126.6, 129.0, 129.4, 134.9, 135.0, 135.8, 138.6,
In the cases of starting catechols 1 and phenyl-substituted
pyrazol-5-ones 2bee, a mixed solvent of acetate buffer solution and
acetonitrile (3:1 or 2:1 ratio of acetate buffer to acetonitrile) was
used as supporting electrolyte due to the low solubility of 2bee.
Method A: the anolyte was acidified to pH¼1 with 1 mol/L
aqueous HCl and a precipitate was generated, which were filtered
and washed with water. Pure compounds were finally obtained
after recrystallization from methanol.
146.3, 146.7, 148.8, 149.3, 156.6, 161.7, 163.4, 173.5; IR (KBr): n 3435,
1702, 1622; ESI-MS: m/z 620.9 (Mꢀꢀ1), 645.3 (MþþNa).
4.2.6. 3-(5-Hydroxy-3-methyl-1H-pyrazol-4-yl)-5-tert-bu-
tylbenzene-1,2-diol (5a). Yield: 34%; mp: 247 ꢂC (dec); 1H NMR
(400 MHz, DMSO-d6): d 1.22 (s, 9H, C(CH3)3), 2.22 (s, 3H, CH3), 6.59
(d, J¼2.4 Hz, 1H, AreH), 6.65 (d, J¼2.4 Hz, 1H, AreH), 8.42 (br s, 1H,
OH), 11.43 (br s, 3H, 2OH, and NH); 13C NMR (100 MHz, DMSO-d6):
Method B: the anolyte was acidified to pH¼1 with 1 mol/L
aqueous HCl, extracted with ethyl acetate (3ꢁ20 mL), and the or-
ganic layer was washed with water (20 mL). The separated organic
layer was dried over MgSO4, filtered and evaporated. The crude
product was purified by column chromatography on silica gel,
eluted with a mixture of petroleum ether and ethyl acetate
(v:v¼1:1).
d 12.5, 31.9, 34.1, 103.1, 110.7, 116.1, 116.7, 120.0, 141.1, 141.6, 143.2,
146.4; IR (KBr):
n
3435,1591,1530,1453; ESI-MS: m/z 260.5 (Mꢀꢀ1),
284.7 (MþþNa), 546.9 (2MþþNa).
4.2.7. 3-(5-Hydroxy-3-methyl-1-p-tolyl-1H-pyrazol-4-yl)-5-tert-bu-
tylbenzene-1,2-diol (5c). Yield: 44%; mp: 222e223 ꢂC; 1H NMR
(400 MHz, DMSO-d6):
d 1.25 (s, 9H, CH3), 2.32 (s, 3H, CH3), 2.35 (s,
3H, CH3), 6.66 (d, 1H, J¼2.4 Hz, AreH), 6.72 (d, 1H, J¼2.0 Hz, AreH),
7.32 (d, 2H, J¼8.4 Hz, AreH), 7.62 (s, 2H, J¼7.2 Hz, AreH), 8.45 (br s,
1H, OH), 10.25 (br s, 1H, OH), 12.39 (br s, 1H, OH); 13C NMR
4.2.1. 4,4-Bis(3,4-dihydroxy-5-methoxyphenyl)-3-methyl-1H-pyr-
azol-5(4H)-one (3a). Yield: 42%; mp: 173 ꢂC (dec); 1H NMR
(400 MHz, DMSO-d6):
d
1.93 (s, 3H, CH3), 3.66 (s, 6H, OCH3), 6.13 (d,
(100 MHz, DMSO-d6):
d 13.1, 21.0, 32.0, 34.2, 105.0, 111.4, 116.6,
2H, J¼2.0 Hz, AreH), 6.23 (d, 2H, J¼2.0 Hz, AreH), 8.34 (s, 2H, OH),
119.4, 121.0, 129.6, 130.0, 134.2, 135.8, 141.2, 142.0, 145.6, 146.8; IR
9.02 (s, 2H, OH), 11.14 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6):
(KBr): n 3435, 2961, 1632, 1548, 1513, 1485, 1410; ESI-MS: m/z 353.1
d
15.7, 56.4, 65.3, 104.1, 109.7, 127.4, 134.4, 146.2, 148.7, 161.8, 178.2;
(Mþþ1), 350.7 (Mꢀꢀ1), 375.0 (MþþNa), 727.2 (2MþþNa), 702.8
IR (KBr):
n
3430, 1674, 1621, 1530; ESI-MS: m/z 372.6 (Mꢀꢀ1), 396.8
(2Mꢀꢀ1).
(MþþNa), 770.9 (2MþþNa), 746.8 (2Mꢀꢀ1).
4.2.8. 4-tert-Butyl-3,6-bis(5-hydroxy-3-methyl-1-phenyl-1H-pyr-
4.2.2. 4,4-Bis(3,4-dihydroxy-5-methoxyphenyl)-3-methyl-1-phenyl-
azol-4-yl)benzene-1,2-diol (6b). Yield: 29%; mp: 263 ꢂC (dec); 1H
1H-pyrazol-5(4H)-one (3b). Yield: 23%; mp: 123e124 ꢂC; 1H NMR
NMR (400 MHz, DMSO-d6): d 1.25 (s, 9H, CH3),1.91 (s, 3H, CH3), 2.44
(400 MHz, DMSO-d6):
d
2.11 (s, 3H, CH3), 3.67 (s, 6H, OCH3), 6.21 (d,
(s, 3H, CH3), 6.81 (s, 1H, AreH), 7.18 (t, 1H, J¼7.2 Hz, AreH), 7.33 (t,
1H, J¼7.2 Hz, AreH), 7.43 (t, 2H, J¼7.6 Hz, AreH), 7.54 (t, 2H,
J¼8.0 Hz, AreH), 7.72 (br s, 2H, OH), 7.78 (d, 2H, J¼7.6 Hz, AreH),
7.80 (d, 2H, J¼7.6 Hz, AreH), 10.89 (br s, 2H, OH); 13C NMR
2H, J¼2.0 Hz, AreH), 6.29 (d, 2H, J¼2.0 Hz, AreH), 7.23 (t, 1H,
J¼7.6 Hz, AreH), 7.46 (t, 2H, J¼7.6 Hz, AreH), 7.88 (d, 2H, J¼7.6 Hz,
AreH), 8.43 (s, 2H, OH), 9.09 (s, 2H, OH); 13C NMR (100 MHz,
DMSO-d6):
d
15.7, 56.5, 67.9, 104.3, 109.7, 119.0, 125.5, 126.8, 129.5,
(100 MHz, DMSO-d6): d 13.3, 32.0, 36.0, 105.1, 115.9, 116.7, 118.2,
134.9, 138.3, 146.4, 148.9, 163.2, 174.1; IR (KBr):
n
3435, 1689, 1517;
121.0, 124.8, 126.6, 129.3, 129.7, 136.4, 140.8, 142.1, 145.7, 147.4,
ESI-MS: m/z 448.8 (Mꢀꢀ1), 450.9 (Mꢀþ1), 4773.0 (MþþNa).
160.1; IR (KBr): n 3515, 3435, 2967, 1602, 1558, 1532, 1498, 1482,
1458; ESI-MS: m/z 511.1 (Mþþ1), 533.1 (MþþNa), 508.8 (Mꢀꢀ1).
4.2.3. 4,4-Bis(3,4-dihydroxy-5-methoxyphenyl)-3-methyl-1-p-tolyl-
1H-pyrazol-5(4H)-one (3c). Yield: 20%; mp: 117 ꢂC (dec); 1H NMR
4.2.9. 4-tert-Butyl-3,6-bis(5-hydroxy-3-methyl-1-p-tolyl-1H-pyr-
(400 MHz, DMSO-d6):
d
2.10 (s, 3H, CH3), 2.31 (s, 3H, CH3), 3.67 (s,
azol-4-yl)benzene-1,2-diol (6c). Yield: 32%; mp: 312 ꢂC (dec); 1H
6H, OCH3), 6.19 (d, 2H, J¼2.0 Hz, AreH), 6.28 (d, 2H, J¼2.0 Hz,
AreH), 7.26 (d, 2H, J¼8.8 Hz, AreH), 7.75 (d, 2H, J¼8.4 Hz, AreH),
8.45 (s, 2H, OH), 9.11 (s, 2H, OH); 13C NMR (100 MHz, DMSO-d6):
NMR (400 MHz, DMSO-d6): d 1.25 (s, 9H, CH3),1.89 (s, 3H, CH3), 2.32
(s, 3H, CH3), 2.36 (s, 3H, CH3), 2.44 (s, 3H, CH3), 6.80 (s, 1H, AreH),
7.24 (d, 1H, J¼8.0 Hz, AreH), 7.35 (d, 1H, J¼8.0 Hz, AreH), 7.63e7.68
(m, 4H, AreH),10.87 (br s,1.5H, OH),12.70 (br s, 0.5H, OH); 13C NMR
d
15.7, 21.0, 56.5, 67.9, 104.2, 109.7, 119.0, 126.9, 129.9, 134.7, 134.8,

9886
X.-G. Gao et al. / Tetrahedron 66 (2010) 9880e9887
(100 MHz, DMSO-d6):
121.1, 129.6, 130.0, 133.8, 134.9, 136.2, 140.8, 142.0; IR (KBr):
d
13.1, 21.0, 21.0, 32.0, 36.0, 116.0, 116.5, 118.1,
3435,
2OH), 10.48 (br s, 0.5H, OH), 10.93 (br s, 0.5H, NH); 13C NMR
n
(100 MHz, DMSO-d6):
d
19.5, 20.9, 117.6, 118.8, 121.4, 128.6, 129.7,
3436, 2924, 1632, 1556, 1513, 1440, 1408;
3188, 2959, 2922, 2804, 1628, 1603, 1513, 1482, 1404; ESI-MS: m/z
143.1, 144.8; IR (KBr):
n
539.0 (Mþþ1), 561.0 (MþþNa), 537.0(Mꢀꢀ1).
ESI-MS: m/z 310.9 (Mþþ1), 308.7 (Mꢀꢀ1), 332.9 (MþþNa), 618.9
(2Mꢀꢀ1).
4.2.10. 4-tert-Butyl-3,6-bis(5-hydroxy-1-(4-methoxyphenyl)-3-
methyl-1H-pyrazol-4-yl)benzene-1,2-diol (6d). Yield: 21%; mp:
4.2.16. 4-(5-Hydroxy-1-(4-methoxyphenyl)-3-methyl-1H-pyrazol-4-
yl)-5-methylbenzene-1,2-diol (9d) and 4-(4,5-dihydroxy-2-methyl-
phenyl)-5-methyl-2-p-methoxyphenyl-1,2-dihydropyrazol-3-one
(9d0). Yield: 62%; mp: 279 ꢂC (dec); 1H NMR (400 MHz, DMSO-d6):
323 ꢂC (dec); 1H NMR (400 MHz, DMSO-d6):
d 1.24 (s, 9H, CH3), 1.87
(s, 3H, CH3), 2.43 (s, 3H, CH3), 3.78 (s, 3H, OCH3), 3.81 (s, 3H, OCH3),
6.79 (s, 1H, AreH), 7.01 (d, 2H, J¼8.8 Hz, AreH), 7.10 (d, 2H,
J¼8.8 Hz, AreH), 7.63 (d, 4H, J¼8.8 Hz, AreH), 10.45 (br s, 0.5H, OH),
10.45 (br s, 1H, OH), 10.86 (br s, 0.5H, OH), 11.07 (br s, 0.5H, OH),
d
1.95e2.07 (m, 6H, 2CH3), 3.78 (s, 3H, OCH3), 6.49e6.64 (m, 2H,
AreH), 7.00 (d, 2H, J¼8.4 Hz, AreH), 7.55e7.62 (m, 2H, AreH),
12.73 (br s, 0.5H, OH); 13C NMR (100 MHz, DMSO-d6):
d
32.0, 55.8,
8.62e8.70 (m, 2H, 2OH), 10.38 (br s, 0.5H, OH), 10.94 (br s, 0.5H,
55.9, 114.4, 114.9, 123.6; IR (KBr):
n
3437, 2961, 2928, 2029, 1630,
NH); 13C NMR (100 MHz, DMSO-d6):
d
13.5, 19.5, 55.8, 114.4, 114.5,
1513, 1465, 1441; ESI-MS: m/z 571.5 (Mþþ1), 593.4 (MþþNa), 569.0
117.6, 119.0, 122.3, 123.1, 123.3, 128.6, 143.1, 144.8, 146.4, 157.1; IR
(Mꢀꢀ1).
(KBr):
n 3437, 2963, 2928, 1622, 1595, 1555, 1513, 1445, 1410; ESI-
MS: m/z 326.9 (Mþþ1), 324.7 (Mꢀꢀ1), 650.8 (2Mꢀꢀ1).
4.2.11. 4-tert-Butyl-3,6-bis(1-(4-chlorophenyl)-5-hydroxy-3-methyl-
1H-pyrazol-4-yl)benzene-1,2-diol (6e). Yield: 25%; mp: 237e238 ꢂC;
4.2.17. 4-(1-(4-Chlorophenyl)-5-hydroxy-3-methyl-1H-pyrazol-4-
yl)-5-methylbenzene-1,2-diol (9e) and 4-(4,5-dihydroxy-2-methyl-
phenyl)-5-methyl-2-p-chlorophenyl-1,2-dihydropyrazol-3-one
(9e0). Yield: 32%; mp: 254 ꢂC (dec); 1H NMR (400 MHz, DMSO-d6):
1H NMR (400 MHz, DMSO-d6):
d 1.24 (s, 9H, CH3), 1.90 (s, 3H, CH3),
2.42 (s, 3H, CH3), 6.80 (s, 1H, AreH), 7.49 (d, 2H, J¼9.2 Hz, AreH),
7.61 (d, 2H, J¼8.8 Hz, AreH), 7.82 (d, 2H, J¼8.4 Hz, AreH), 7.84 (d,
2H, J¼8.8 Hz, AreH), 10.63e12.7 (br s, 2H, OH); 13C NMR (100 MHz,
d
1.92e2.17 (m, 6H, 2CH3), 6.53 (s, 1H, AreH), 6.64 (s, 1H, AreH),
DMSO-d6):
d
13.3, 32.0, 36.0, 115.9, 117.0, 118.1, 118.5, 119.6, 121.1,
7.50 (d, 2H, J¼8.4 Hz, AreH), 7.81 (d, 2H, J¼8.0 Hz, AreH), 8.64 (s,
122.2, 128.6, 129.2, 129.5, 129.6, 129.9, 130.4, 140.8, 142.1,
1H, OH), 8.74 (s, 1H, OH), 10.82 (br s, 0.5H, OH), 11.01 (br s, 0.5H,
146.6, 147.4, 156.8; IR (KBr):
n
3436, 2962, 1626, 1601, 1493; ESI-MS:
NH); 13C NMR (100 MHz, DMSO-d6):
d
13.4, 19.5, 117.6, 118.9, 120.2,
m/z 577 (Mꢀꢀ1).
121.8, 128.6, 129.3, 143.1, 145.0; IR (KBr): n 3514, 3436, 1603, 1553,
1524, 1494, 1445, 1404; ESI-MS: m/z 328.8 (Mꢀꢀ1), 352.7 (MþþNa),
658.8 (2Mꢀꢀ1).
4.2.12. 3-(5-Hydroxy-3-methyl-1H-pyrazol-4-yl)-5-methylbenzene-
1,2-diol (7). Yield: 30%; mp: 238 ꢂC (dec); 1H NMR (400 MHz,
DMSO-d6):
AreH), 6.45 (d, 1H, J¼1.6 Hz, AreH), 8.45 (br s, 1H, OH), 11.17 (br s,
3H, 2OH, and NH); 13C NMR (100 MHz, DMSO-d6):
12.4, 21.0,
d
2.15 (s, 3H, CH3), 2.20 (s, 3H, CH3), 6.42 (d,1H, J¼1.6 Hz,
4.2.18. 4,4-Bis(3,4-dihydroxy-5-methylphenyl)-3-methyl-1H-pyr-
azol-5(4H)-one (3e). Yield: 38%; mp: 163e165 ꢂC; 1H NMR
d
(400 MHz, DMSO-d6): d 1.90 (s, 3H, CH3), 2.08 (s, 6H, CH3), 3.77 (s,
102.5, 114.2, 120.4, 120.6, 127.8, 141.0, 141.1, 146.7, 161.9; IR (KBr):
n
3H, OCH3), 6.25 (d, 2H, J¼1.6 Hz, AreH), 6.42 (d, 2H, J¼2.0 Hz,
3376, 3204, 1625, 1582, 1496, 1450; ESI-MS: m/z 220.7 (Mþþ1),
AreH), 8.24 (s, 2H, OH), 9.20 (s, 2H, OH), 11.05 (s, 1H, NH); 13C NMR
218.4 (Mꢀꢀ1), 242.7 (MþþNa).
(100 MHz, DMSO-d6):
d 15.7, 16.6, 64.9, 113.7, 120.9, 124.8, 128.0,
143.3, 145.3, 161.9, 178.5; IR (KBr):
n 3420, 1668, 1601, 1501, 1300;
4.2.13. 3-Methyl-4-(4,5-dihydroxy-2-methylphenyl)-5-(4,5-dihy-
ESI-MS: m/z 341 (Mꢀꢀ1), 365 (MþþNa).
droxy-2-methylphenoxy)-1H-pyrazole (8). Yield: 56%; mp: 203 ꢂC
(dec); 1H NMR (400 MHz, DMSO-d6):
d 1.75 (s, 3H, CH3), 1.83 (s, 3H,
Acknowledgements
CH3), 2.00 (s, 3H, CH3), 6.52 (s, 1H, AreH), 6.61 (s,1H, AreH), 6.62 (s,
1H, AreH), 6.67 (s, 1H, AreH), 8.58 (s, 1H, OH), 8.67 (s, 1H, OH), 9.03
(s, 1H, OH), 9.12 (s, 1H, OH), 9.53 (br s, 1H, NH); 13C NMR (100 MHz,
This work was supported by Grants from the National Natural
Science Foundation of China (No. 20772010), the National Basic
Research Program of China (No. 2009CB930200) and fund to Z., C.C.
from Beijing City Education Committee (KM201010005009).
DMSO-d6):
d 11.0, 16.4, 19.4, 104.9, 115.6, 117.3, 117.5, 118.9, 122.9,
126.7, 128.3, 130.2, 137.9, 143.0, 143.6, 144.5, 146.0, 158.7; IR (KBr):
3527, 3435, 2961, 1608, 1571, 1542, 1492, 1452; ESI-MS: m/z 342.8
(Mþþ1), 340.6 (Mꢀꢀ1), 364.8 (MþþNa), 682.8 (2Mꢀꢀ1).
n
References and notes
4.2.14. 4-(5-Hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-5-meth-
ylbenzene-1,2-diol (9b)and 4-(4,5-dihydroxy-2-methylphenyl)-5-
methyl-2-phenyl-1,2-dihydropyrazol-3-one (9b0). Yield: 37%; mp:
1. Lo, Y. C.; Liu, Y.; Lin, Y. C.; Shih, Y. T.; Liu, C. M.; Burka, L. T. Toxicol. Appl. Phar-
macol. 2008, 228, 247e255.
2. Rao, C. V.; Desai, D.; Rivenson, A.; Simi, B.; Amin, S.; Reddy, B. S. Cancer Res.
235 ꢂC (dec); 1H NMR (400 MHz, DMSO-d6):
d 1.97e2.06 (m, 6H,
1995, 55, 2310e2315.
2CH3), 6.52e6.65 (m, 2H, AreH), 7.20 (t, 1H, J¼6.8 Hz, AreH), 7.44
(t, 2H, J¼8.0 Hz, AreH), 7.65 (d, 2H, J¼8.0 Hz, AreH), 8.60e8.72 (m,
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