Synthesis of novel 1,4-benzoquinone-containing 1,2,3-triazoles: An entry into a new library

Article abstract of DOI:10.1055/s-0028-1088017

A heretofore unexplored library of 1,4-benzoquinone-containing 1,2,3-triazoles was prepared by the application of a highly regioselective copper(I)-catalyzed process. Furthermore, the utilization of this novel triazole-1,4-benzoquinone system as an intere

Full text of DOI:10.1055/s-0028-1088017

PAPER
1341
Synthesis of Novel 1,4-Benzoquinone-Containing 1,2,3-Triazoles: An Entry
Into a New Library
Synthesis of
1a
t
inone-C
i
ontain
h
ing 1,2,3-TriazolesAlgi,*a,b Metin Balci*a
a
Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
Fax +90(312)2101280; E-mail: mbalci@metu.edu.tr
b
Laboratory of Organic Materials (LOM), Çanakkale Onsekiz Mart University, 17100 Çanakkale, Turkey
E-mail: falgi@comu.edu.tr
Received 24 November 2008
the triazole moiety. Furthermore, the utilization of this
novel triazole–quinone system as an interesting class of
extended, branched molecules for the construction of new
supramolecular architectures is presented here.
Abstract: A heretofore unexplored library of 1,4-benzoquinone-
containing 1,2,3-triazoles was prepared by the application of a high-
ly regioselective copper(I)-catalyzed process. Furthermore, the uti-
lization of this novel triazole–1,4-benzoquinone system as an
interesting class of extended, branched molecules for the construc-
tion of new supramolecular architectures is presented.
Our initial exploratory efforts involved the synthesis of
the valuable 2-(azidomethyl)-substituted hydroquinone
(2a) scaffold (see Scheme 1) which bears both the masked
triazole functionality, obtainable through a copper(I)-cat-
alyzed 1,3-dipolar cycloaddition, and the benzoquinone
moiety, accessible through oxidation.
Key words: benzoquinones, azides, triazoles, copper(I) catalysis,
regioselectivity
Triazoles, attractive constructs because of their unique
chemical properties and structure, have found broad use in
agrochemicals and industrial applications such as dyes
and dyestuffs, fluorescent compounds, corrosion inhibi-
tors, and photostabilizers, and have been regarded an in-
teresting unit in terms of biological activity.1,2 In
particular, 1,2,3-triazoles have recently become popular
as a means for establishing reliable and stable connections
in organic synthesis and materials science. Several syn-
thetic methods in which azide3 plays a prominent role
have been developed recently,4–6 with the discovery that
copper(I) catalyzes6 the 1,3-dipolar cycloaddition reaction
between azides and alkynes a particular milestone, open-
ing a myriad of applications.
O
OH
OH
Br
N3
NH2
H2, Pd/C
NaN3
EtOAc, r.t.
acetone–H2O
r.t.
O
OH
OH
2b
1
2a
Scheme 1
We found that 2-(bromomethyl)-1,4-benzoquinone (1)
could be converted into the 2-(azidomethyl)-substituted
hydroquinone (2a) by the action of sodium azide
(Scheme 1).12 Azide 2a was easily converted into the cor-
responding amine 2b by catalytic hydrogenation.
On the other hand, we have recently turned our attention
to benzoquinones,7 which are ubiquitous in living systems
and represent important cofactors in electron transfer in
photosynthesis and respiration. In addition, they have
found widespread use in medicine as antitumor, antifun-
gal, and antiparasitic drugs, as well as antibiotics.8–10 We
have speculated, perhaps counterintuitively, that mole-
cules in which these structures are combined, that is, mol-
ecules that consist of a triazole ring on one side and the
quinone moiety on the other, would display the intriguing
features of both of these functional groups. Furthermore,
such compounds would be interesting in terms of elec-
tron- and/or energy-transfer (ET) systems.11 In this re-
gard, we have initiated a program aimed at introducing a
new library of 1,4-benzoquinone-containing 1,2,3-triaz-
oles. Herein, we wish to report the results of our research
concerning the regioselective synthesis of such com-
pounds with a variety of substituents at the 4-position of
To further explore the reactivity, an initial attempt was
made by the treatment of azide 2a with phenylacetylene in
the presence of copper(I) iodide as catalyst at room tem-
perature (Scheme 2; Table 1, entry 3).6c We noticed that
the reaction provided the corresponding 1,2,3-triazole 3c
with remarkable regioselectivity, favoring the 1,4-regio-
isomer, albeit in low yield (ca. 10%, by NMR, after 16 h).
Increasing the temperature (80 °C) caused a dramatic in-
crease in both the rate of the reaction and the yield (85%).
These optimizations were chosen as the standard condi-
tions for testing the scope of this route. Thus, a variety of
mono- and disubstituted alkynes including acetoxymeth-
yl-, trimethylsilyl-, aryl-, ferrocenyl-, and thienylacety-
lenes, as well as dimethyl acetylenedicarboxylate were
subjected to the reaction with hydroquinone 2a under
these conditions, to afford the corresponding 1,2,3-triaz-
oles 3a–g in moderate to good yields (Scheme 2, Table 1).
The compounds were characterized by spectroscopy (1H,
13C, DEPT, COSY, HMBC, and HMQC NMR and FTIR)
and combustion analysis.
SYNTHESIS 2009, No. 8, pp 1341–1347
x
x
.
x
x
.2
0
0
9
Advanced online publication: 16.03.2009
DOI: 10.1055/s-0028-1088017; Art ID: P13108SS
© Georg Thieme Verlag Stuttgart · New York

1342
F. Algi, M. Balci
PAPER
OH
A proposed mechanism for the formation of 1,2,3-triaz-
oles in the presence of the copper catalyst is depicted in
Scheme 3.6c At the initial stage of the catalytic cycle, the
reaction of an alkyne with copper(I) iodide produces
acetylide A. The [3+2] cycloaddition between the C–C tri-
ple bond of copper acetylide A and azide 2a takes place
readily to form intermediate B. Protonolysis of the C–Cu
bond of intermediate B affords 1,2,3-triazole 3.
OH
OH
N
N3
N
N
R1
R2
CuI (20 mol%)
MeCN, 80 °C
R1
R2
OH
2a
3
Scheme 2
The following points are worthy of comment. First of all,
it appears as if a variation in the steric environment around
Table 1 Synthesis of Novel 1,2,3-Triazoles 3 and 1,4-Benzoquinones 4
Entry
Acetylene
Triazolea
3
1,4-Benzoquinoneb
4
Yieldc (%)
85
OH
O
N
N
N
N
N
N
AcO
1
3a
4a
OAc
OAc
OH
OH
O
N
N
N
N
N
N
N
e
2
3
3bd
–
–
65 (for 3b)
TMS
TMS
OH
HO
O
N
N
N
Ph
N
N
N
3c
4c
85
Ph
Ph
O
O
HO
OH
N
N
4
3d
4d
90
OHC
OH
OH
O
O
CHO
CHO
N
N
N
N
N
N
Fc
N
N
N
5
6
7
3e
3f
4e
4f
60
Fc
Fc
OH
OH
O
O
N
N
N
90f
S
OH
OH
S
S
O
O
N
N
N
N
N
N
3g
4g
100g
MeO2C
CO2Me
MeO2C
OH
MeO2C
CO2Me
CO2Me
O
a Reagents and conditions: 2a (2 mmol), R1C≡CR2 (3 mmol), MeCN (50 mL), CuI (20 mol%), reflux, 12–26 h.
b Reagents and conditions: 3 (1 mmol), MnO2 (5 equiv), CH2Cl2, r.t., 16–32 h.
c Isolated and unoptimized yield of 4 over two steps.
d The reaction was run at r.t.
e Decomposed during oxidation (see text).
f Trace amount of 1,5-isomer was also observed.
g The reaction was run at r.t. without catalyst.
Synthesis 2009, No. 8, 1341–1347 © Thieme Stuttgart · New York

PAPER
Synthesis of 1,4-Benzoquinone-Containing 1,2,3-Triazoles
1343
R1
H
OH
O
+
CuI
N
N
N
N
N
N
MnO2
R2
R1
CH2Cl2, r.t.
R1
R2
HI
OH
O
R1
H
3
4
R1
Cu
Scheme 4
A
N
N
R2
N
3
since dipyrrins offer a number of desirable features, such
as ease of purification by conventional flash chromatogra-
phy over silica gel, intense optical absorptions, and a pro-
pensity to form stable, neutral complexes with metal
ions.13
R2
N3
R1
H
2a
R1
Cu
or
HI
N
N
R2
N
The synthesis of the bis(ligand)–metal complex 6 was
achieved through a two-step reaction sequence: acid-cata-
lyzed condensation of pyrrole with 3d gives the dipyr-
romethene-appended ligand precursor 5, which was
subsequently complexed with the metal after oxidation
B
Scheme 3
the alkyne, at least to the extent represented by the cases
investigated, had no effect on the regioselectivity of the
process, even though it caused a somewhat detrimental ef-
fect on the yield; since the lower yield values were ob-
tained with acetylenes substituted with trimethylsilyl
(Table 1, entry 2), and ferrocenyl (Table 1, entry 5).
with
2,3-dichloro-5,6-dicyano-1,4-benzoquinone
1
(Scheme 5). Unfortunately, the H NMR spectrum of 6
does not provide useful information, because the metal
ion (CuII) is paramagnetic.
However, absorption spectroscopy of the combination of
the 1,2,3-triazole–1,4-benzoquinone system and cop-
per(II) with the dipyrrin chelators was valuable, although
no significant emission was observed. The salient feature
of bis(ligand)–copper complex 6 was that a new broad ab-
sorption band (with a shoulder), ascribed to a metal–
ligand charge-transfer process, appeared at around 496
nm (Figure 1). These spectral features are consistent with
those of similar compounds reported in the literature.13
1,2,3-Triazoles 3 were converted into the corresponding
1,4-benzoquinones 4 by treatment with manganese(IV)
oxide (Scheme 4, Table 1); the reactions proceeded al-
most quantitatively, except in the case of the trimethylsi-
lyl derivative (Table 1, entry 2), where the product could
not be isolated, probably due to decomposition.
Finally, we explored the use of this novel triazole–1,4-
benzoquinone system as an interesting class of extended,
branched molecules for the construction of new supramo-
lecular architectures. For this purpose, we investigated the
incorporation of the triazole–1,4-benzoquinone system
into porphyrinogenic dipyrromethene (dipyrrin) units,
The electrochemical behavior of bis(ligand)–copper com-
plex 6 was also examined. The cyclic voltammogram ex-
hibited one reversible reduction peak with a half wave
potential of –0.41 V, as well as one irreversible reduction
OH
OH
N
N
N
TFA
N
N
N
pyrrole, r.t.
OH
OH
3d
5
CHO
N
H
NH
1. DDQ
MeCN, r.t.
2. Cu(ClO4)2
N
N
O
N
N
N
Cu
O
N
N
O
N
N
6
N
O
Scheme 5
Synthesis 2009, No. 8, 1341–1347 © Thieme Stuttgart · New York

1344
F. Algi, M. Balci
PAPER
Figure 3 ESR spectrum of 6 (10–3 M) in dichloromethane; inset: se-
cond derivative of ESR spectrum
Figure 1 UV/vis absorption spectrum of 6 (10–3 M) in dichloro-
methane
peak at –0.84 V (Figure 2), which can be attributed to re- ole–1,4-benzoquinone system as an interesting class of
duction of 1,4-benzoquinone units and the metal center in extended, branched molecules for the construction of new
complex 6, respectively.
supramolecular architectures was presented. Considering
the multitude of choices in metal selection, we are confi-
dent that this approach can be extended to a variety of
novel supramolecular architectures with practical applica-
tions in many fields. Efforts to elucidate the versatility of
1,4-benzoquinones 4 reported herein in expanded struc-
tures, and applications to electron- and/or energy-transfer
(ET) systems are currently underway in our laboratories.
Melting points were determined on a Buchi model 530 apparatus
and are uncorrected. IR spectra were recorded on a Mattson model
1000 FT-IR spectrometer. 1H and 13C NMR spectra were recorded
on an Avance-Bruker 400 MHz NMR spectrometer, operating at
400 and 100 MHz, respectively. Electroanalytical measurements
were performed on a Gamry PCI4/300 potentiostat–galvanostat. A
Pt disk (0.02 cm2) and a Pt wire were used as working and counter
electrodes, respectively, as well as Ag/AgCl, which was used in 3
M aq NaCl soln as a reference. UV/vis spectra were recorded on a
Hewlett–Packard 8453A diode array spectrometer. ESR spectra
were recorded on a Varian E12 ESR spectrometer. Column chroma-
tography was performed on silica gel (Merck, 60–200 mesh). TLC
was carried out on Merck 0.2-mm silica gel 60 F254 analytical alu-
minum plates.
Figure 2 Cyclic voltammogram of 6 in a 0.1 M solution of tetrabu-
tylammonium perchlorate in acetonitrile (scan rate, 100 mV·s–1)
2-(Aminomethyl)benzene-1,4-diol (2b)
A 100-mL, two-necked round-bottomed flask was charged with Pd/
C (50 mg, 10 mol%) and azide 2a12 (0.33 g, 2 mmol) in EtOAc (50
mL). One of the necks was attached to H2 gas by a three-way stop-
cock, and the other neck was capped with a rubber septum. The re-
actants were degassed and flushed with H2 gas, while the contents
of the flask was stirred magnetically. After 3 h (TLC), the soln was
filtered through a short pad of Celite 545 to remove the catalyst, and
the solvent was evaporated to give 2b.
The ESR spectrum of 6 also confirmed the presence of
copper(II) in the complex. As shown in Figure 3, the un-
paired electron of copper(II) interacts with the nuclear
spins of nitrogen (I = 1), leading to an ESR signal with
some hyperfine lines. Seven superhyperfine lines with
equally spaced coupling constants (12 G) for four nitrogen
atoms can be attributed to the square planar, rather than
tetrahedral, structure of complex 6.14
Yield: 0.25 g (89%); dark red oil.
IR (acetone): 3390, 3370, 2930, 2905, 2840, 1650, 1510, 1430,
1350, 1240, 1180, 1100, 863, 803 cm–1.
1H NMR (400 MHz, acetone-d6): d = 6.65–6.58 (m, 2 H), 6.50 (m,
1 H), 3.87 (s, 2 H), 2.81 (br s, 4 H).
13C NMR (100 MHz, acetone-d6): d = 150.9, 147.4, 122.2, 118.2,
115.2, 112.7, 41.2.
In summary, a heretofore unexplored library of 1,4-ben-
zoquinone-containing 1,2,3-triazoles was prepared by the
application of a highly regioselective copper(I)-catalyzed
process. Furthermore, the utilization of this novel triaz-
Synthesis 2009, No. 8, 1341–1347 © Thieme Stuttgart · New York

PAPER
Synthesis of 1,4-Benzoquinone-Containing 1,2,3-Triazoles
1345
Anal. Calcd for C7H9NO2: C, 60.42; H, 6.52; N, 10.07. Found: C,
60.16; H, 6.29; N, 10.01.
1076, 1055, 1009, 982, 879, 832, 818, 772, 744, 706, 683, 656, 616
cm–1.
1H NMR (400 MHz, acetone-d6): d = 10.02 (s, 1 H, CHO), 8.15 (s,
1 H), 8.03–7.90 (AA¢BB¢ system, 4 H, aromatic), 6.81 (d, J = 9.4
Hz, 1 H, A part of AB system), 6.74–6.72 (m, 2 H), 5.57 (s, 2 H).
13C NMR (100 MHz, CD3OD): d = 193.5, 151.4, 149.5, 147.4,
137.7, 137.4, 131.3, 127.0, 123.7, 123.2, 117.7, 117.4, 117.3, 50.6.
1,2,3-Triazoles 3; General Procedure
CuI (76 mg, 0.4 mmol) was added to a soln of azide 2a12 (0.33 g, 2
mmol) and the appropriate alkyne (3 mmol) in MeCN (50 mL), and
the homogeneous mixture was heated under reflux. After comple-
tion of the reaction (12–26 h, TLC), the mixture was allowed to cool
to r.t. and filtered through a short pad of Celite 545, and the solvent
was removed under reduced pressure. The residue was chromato-
graphed (silica gel, EtOAc–hexane, 1:4); this gave pure, solid 3.
Anal. Calcd for C16H13N3O3: C, 65.08; H, 4.44; N, 14.23. Found: C,
65.15; H, 4.50; N, 14.08.
2-[(4-Ferrocenyl-1H-1,2,3-triazol-1-yl)methyl]benzene-1,4-diol
(3e)
Brownish-red solid; mp 244–246 °C (dec).
[1-(2,5-Dihydroxybenzyl)-1H-1,2,3-triazol-4-yl]methyl Acetate
(3a)
White solid; mp 152–154 °C.
IR (acetone): 3451, 3084, 3017, 2969, 2945, 2927, 2855, 2114,
1739, 1618, 1580, 1504, 1451, 1367, 1226, 1215, 1154, 1105, 1092,
1058, 1002, 899, 879, 819, 769, 740, 669 cm–1.
1H NMR (400 MHz, acetone-d6): d = 8.09 (br s, 1 H), 7.79 (s, 1 H),
7.68 (br s, 1 H), 6.65 (d, J = 8.5 Hz, 1 H, A part of AB system), 6.54
(dd, J = 8.5–2.7 Hz, 1 H, B part of AB system), 6.45 (d, J = 2.7 Hz,
1 H), 5.38 (s, 2 H), 4.61–4.56 (m, 2 H), 4.15–4.12 (m, 2 H), 3.89 (s,
5 H).
IR (acetone): 3267, 3031, 2969, 2727, 2129, 2055, 1739, 1712,
1661, 1611, 1509, 1458, 1366, 1227, 115, 1126, 1093, 1041, 1000,
968, 921, 872, 822, 765, 736, 684, 627, 605 cm–1.
1H NMR (400 MHz, acetone-d6): d = 8.22 (br s, 1 H), 7.84 (s, 1 H),
7.83 (s, 1 H), 6.80 (d, J = 9.3 Hz, 1 H, A part of AB system), 6.70–
6.68 (m, 2 H), 5.49 (s, 2 H), 5.14 (s, 2 H), 2.01 (s, 3 H).
13C NMR (100 MHz, acetone-d6): d = 170.2, 150.4, 147.9, 142.5,
124.1, 122.0, 116.7, 116.6, 116.5, 57.4, 49.0, 20.3.
13C NMR (100 MHz, acetone-d6): d = 151.1, 149.4, 148.7, 128.5,
123.9, 120.9, 117.0, 116.8, 70.1, 69.0, 67.3, 55.5, 49.4.
Anal. Calcd for C12H13N3O4: C, 54.75; H, 4.98; N, 15.96. Found: C,
54.60; H, 5.11; N, 15.68.
Anal. Calcd for C19H17FeN3O2: C, 60.82; H, 4.57; N, 11.20. Found:
C, 60.90; H, 4.37; N,11.14.
2-{[4-(Trimethylsilyl)-1H-1,2,3-triazol-1-yl]methyl}benzene-
1,4-diol (3b)
White solid; mp 178–180 °C.
2-{[4-(3-Thienyl)-1H-1,2,3-triazol-1-yl]methyl}benzene-1,4-
diol (3f)
Brownish solid; mp 242–243 °C (dec).
IR (acetone): 2996, 2970, 2926, 2854, 2105, 1739, 1661, 1588,
1454, 1367, 1214, 1094, 1016, 844, 761, 633 cm–1.
1H NMR (400 MHz, acetone-d6): d = 8.24 (s, 1 H), 7.92 (s, 1 H),
7.83 (s, 1 H), 6.80 (d, J = 8.5 Hz, 1 H, A part of AB system), 6.68
(dd, J = 8.5, 2.9 Hz, 1 H, B part of AB system), 6.63 (d, J = 2.9 Hz,
1 H), 5.54 (s, 2 H), 0.27 (s, 9 H).
IR (acetone): 3442, 3014, 2969, 2948, 2857, 2129, 1739, 1609,
1507, 1454, 1366, 1228, 1217, 1152, 1090, 967, 891, 858, 820, 785,
740, 710, 668, 621 cm–1.
1H NMR (400 MHz, acetone-d6): d = 8.06 (br s, 1 H), 7.95 (s, 1 H),
7.70 (br s, 1 H), 7.67 (d, J = 2.2 Hz, 1 H), 7.46 (d, J = 4.9 Hz, 1 H),
7.39 (dd, J = 4.9, 3.0 Hz, 1 H), 6.79 (d, J = 8.5 Hz, 1 H, A part of
AB system), 6.69 (dd, J = 8.5–2.7 Hz, 1 H, B part of AB system),
6.66 (d, J = 2.7 Hz, 1 H), 5.53 (s, 2 H).
13C NMR (100 MHz, acetone-d6): d = 152.1, 149.4, 147.0, 131.3,
124.4, 121.9, 118.0, 117.8, 49.7, 0.0.
Anal. Calcd for C12H17N3O2Si: C, 54.73; H, 6.51; N, 15.95. Found:
C, 55.01; H, 6.48; N, 15.78.
13C NMR (100 MHz, CD3OD): d = 151.2, 149.5, 145.2, 132.7,
127.7, 126.9, 122.9, 122.4, 121.9, 118.2, 117.9, 117.7, 55.8.
2-[(4-Phenyl-1H-1,2,3-triazol-1-yl)methyl]benzene-1,4-diol (3c)
White solid; mp 216–217 °C (dec).
Anal. Calcd for C13H11N3O2S: C, 57.13; H, 4.06; N, 15.37; S, 11.73.
Found: C, 57.00; H, 3.89; N, 15.20; S, 11.56.
IR (acetone): 3220, 3138, 3064, 3026, 2970, 2948, 2852, 2224,
2122, 1739, 1658, 1609, 1579, 1508, 1456, 1366, 1292, 1214, 1154,
1081, 1055, 1030, 1000, 978, 898, 876, 819, 765, 745, 694, 655, 619
cm–1.
Dimethyl 1-(2,5-Dihydroxybenzyl)-1H-1,2,3-triazole-4,5-dicar-
boxylate (3g)
White solid; mp 94–96 °C.
1H NMR (400 MHz, acetone-d6): d = 8.14 (s, 1 H), 8.13 (br s, 1 H)
7.75 (d, J = 7.8 Hz, 2 H), 7.69 (br s, 1 H), 7.27 (t, J = 7.6 Hz, 2 H),
7.16 (t, J = 7.3 Hz, 1 H), 6.66 (d, J = 8.5 Hz, 1 H, A part of AB sys-
tem), 6.54 (dd, J = 8.5–2.9 Hz, 1 H, B part of AB system), 6.50 (d,
J = 2.9 Hz, 1 H), 5.43 (s, 2 H).
13C NMR (100 MHz, acetone-d6): d = 150.6, 147.7, 146.9, 131.4,
128.6, 127.6, 125.3, 122.8, 120.6, 116.3, 116.1, 116.0, 48.7.
IR (acetone): 3443, 3031, 3010, 2957, 2924, 2852, 2112, 1735,
1658, 1558, 1509, 1458, 1364, 1317, 1229, 1149, 1103, 1095,
1063, 964, 824, 793, 766, 737, 696, 605 cm–1.
1H NMR (400 MHz, acetone-d6): d = 8.21 (s, 1 H), 7.83 (s, 1 H),
6.74 (d, J = 8.7 Hz, 1 H, A part of AB system), 6.67 (dd, J = 8.7, 2.8
Hz, 1 H, B part of AB system), 6.55 (d, J = 2.8 Hz, 1 H), 5.76 (s, 2
H), 3.91 (s, 3 H), 3.90 (s, 3 H).
13C NMR (100 MHz, acetone-d6): d = 161.3, 159.9, 151.4, 148.6,
139.8, 132.1, 122.6, 117.2, 117.0, 116.8, 53.6, 52.5, 49.6.
Anal. Calcd for C15H13N3O2: C, 67.40; H, 4.90; N, 15.72. Found: C,
67.49; H, 4.96; N, 15.84.
Anal. Calcd for C13H13N3O6: C, 50.82; H, 4.26; N, 13.68. Found: C,
50.99; H, 4.39; N, 13.61.
4-[1-(2,5-Dihydroxybenzyl)-1H-1,2,3-triazol-4-yl]benzalde-
hyde (3d)
White solid; mp 236–237 °C.
2-(1H-1,2,3-Triazol-1-ylmethyl)-1,4-benzoquinones 4; General
Procedure
Activated MnO2 (5 equiv) was added to a soln of 3 (1 mmol) in
CH2Cl2. The heterogeneous mixture was vigorously stirred at r.t.
until all the starting material was consumed (16–32 h, TLC). After
IR (acetone): 3424, 3137, 3101, 3040, 2969, 2075, 1740, 1696,
1670, 1609, 1574, 1508, 1461, 1365, 1306, 1264, 1212, 1171, 1115,
Synthesis 2009, No. 8, 1341–1347 © Thieme Stuttgart · New York

1346
F. Algi, M. Balci
PAPER
2-{[4-(3-Thienyl)-1H-1,2,3-triazol-1-yl]methyl}-1,4-benzo-
completion, the mixture was filtered through a short pad of Celite
545 and the solvent was removed under pressure to give 4.
quinone (4f)
Brownish solid.
{1-[(3,6-Dioxocyclohexa-1,4-dienyl)methyl]-1H-1,2,3-triazol-4-
yl}methyl Acetate (4a)
Brownish oil.
IR (acetone): 3067, 3014, 2969, 2948, 2855, 2130, 1739, 1685,
1601, 1507, 1450, 1366, 1284, 1226, 1217, 1120, 1089, 1061, 1000,
965, 897, 855, 820, 785, 712, 618 cm–1.
IR (acetone): 3125, 3015, 2969, 2955, 2866, 2120, 1739, 1664,
1610, 1584, 1549, 1508, 1455, 1366, 1214, 1154, 1110, 1094, 1061,
1017, 968, 897, 845, 762, 742, 697, 656, 633 cm–1.
1H NMR (400 MHz, acetone-d6): d = 7.89 (s, 1 H), 6.75 (dd,
J = 10.1, 1.4 Hz, 1 H, A part of AB system), 6.70 (dd, J = 10.1, 1.6
Hz, 1 H, B part of AB system), 6.24 (br s, 1 H), 5.37 (s, 2 H), 5.09
(s, 2 H), 1.95 (s, 3 H).
1H NMR (400 MHz, acetone-d6): d = 8.14 (s, 1 H), 7.71 (br s, 1 H),
7.47–7.41 (m, 2 H), 6.86 (d, J = 9.9 Hz, 1 H, A part of AB system),
6.79 (d, J = 9.9 Hz, 1 H, B part of AB system), 6.37 (s, 1 H), 5.46
(s, 2 H).
13C NMR (100 MHz, acetone-d6): d = 191.7, 190.9, 149.2, 147.6,
141.9, 141.5, 138.3, 137.1, 131.4, 130.9, 126.3, 126.0, 53.9.
Anal. Calcd for C13H9N3O2S: C, 57.55; H, 3.34; N, 15.49; S, 11.82.
Found: C, 57.63; H, 3.29; N, 15.38; S, 11.56.
13C NMR (100 MHz, acetone-d6): d = 187.5, 186.6, 171.2, 143.2,
137.7, 137.2, 134.0, 126.2, 117.6, 58.2, 48.4, 21.3.
Anal. Calcd for C12H11N3O4: C, 55.17; H, 4.24; N, 16.09. Found: C,
55.40; H, 4.12; N, 16.22.
Dimethyl 1-[(3,6-Dioxocyclohexa-1,4-dienyl)methyl]-1H-1,2,3-
triazole-4,5-dicarboxylate (4g)
White solid; mp 90–92 °C.
2-[(4-Phenyl-1H-1,2,3-triazol-1-yl)methyl]-1,4-benzoquinone
(4c)
Brownish solid; mp 133–135 °C.
IR (acetone): 3011, 2968, 2956, 2848, 2126, 2024, 1881, 1738,
1661, 1603, 1556, 1456, 1364, 1320, 1277, 1226, 1220, 1152, 1097,
1064, 964, 944, 899, 845, 826, 797, 772, 740, 712, 693, 670, 617
cm–1.
1H NMR (400 MHz, acetone-d6): d = 6.79 (d, J = 10.1 Hz, 1 H, A
part of AB system), 6.72 (d, J = 10.1 Hz, 1 H, B part of AB system),
6.24 (s, 1 H), 5.58 (s, 2 H), 3.82 (s, 3 H), 3.78 (s, 3 H).
IR (acetone): 3028, 2969, 2928, 2855, 2115, 2058, 1739, 1660,
1613, 1509, 1457, 1366, 1226, 1217, 1154, 1125, 1091, 1044, 969,
898, 874, 821, 766, 739, 694, 650, 605 cm–1.
1H NMR (400 MHz, acetone-d6): d = 8.44 (s, 1 H), 7.91 (d, J = 7.6
Hz, 2 H), 7.45 (t, J = 6.0 Hz, 2 H), 7.35 (t, J = 7.2 Hz, 1 H), 6.94 (d,
J = 10.1 Hz, 1 H, A part of AB system), 6.87 (dd, J = 10.1–1.9 Hz,
1 H, B part of AB system), 6.45 (br s, 1 H), 5.56 (s, 2 H).
13C NMR (100 MHz, acetone-d6): d = 187.5, 186.5, 161.3, 159.4,
142.9, 141.0, 137.7, 137.3, 133.9, 131.2, 53.8, 52.8, 48.5.
Anal. Calcd for C13H11N3O6: C, 51.15; H, 3.63; N, 13.77. Found: C,
51.22; H, 3.48; N, 13.61.
13C NMR (100 MHz, acetone-d6): d = 187.7, 186.8, 148.2, 143.6,
137.6, 137.4, 134.0, 132.0, 129.6, 128.7, 126.3, 122.4, 48.3.
Anal. Calcd for C15H11N3O2: C, 67.92; H, 4.18; N, 15.84. Found: C,
68.08; H, 4.21; N, 15.56.
2-({4-[4-(Di-1H-pyrrol-2-ylmethyl)phenyl]-1H-1,2,3-triazol-1-
yl}methyl)benzene-1,4-diol (5)
Aldehyde 3d (0.154 g, 0.52 mmol) was dissolved in neat pyrrole (10
mL), and the soln was degassed by bubbling with N2 for 20 min.
TFA (0.01 mL, 0.09 mmol) was added, and the soln was stirred for
10 min. It was then diluted with CH2Cl2 (50 mL), washed with 0.1
N aq NaOH (50 mL) and H2O (50 mL), and subsequently dried
(MgSO4). The MgSO4 was removed by vacuum filtration and the
filtrate was evaporated to remove the CH2Cl2. The remaining pyr-
role was removed by vacuum distillation with gentle heating. The
product was purified by column chromatography (silica gel, hex-
anes–CH2Cl2, 1:1, then MeOH–CH2Cl2, 5:95).
4-{1-[(3,6-Dioxocyclohexa-1,4-dienyl)methyl]-1H-1,2,3-triazol-
4-yl}benzaldehyde (4d)
Brownish solid; mp 160–161 °C.
IR (acetone): 3005, 2968, 2929, 2856, 2739, 2115, 1737, 1701,
1660, 1609, 1574, 1454, 1423, 1365, 1284, 1214, 1170, 1121, 1075,
1046, 1013, 974, 899, 834, 743, 684, 653, 609 cm–1.
1H NMR (400 MHz, acetone-d6): d = 10.03 (s, 1 H, CHO), 8.48 (s,
1 H), 8.09–7.94 (AA¢BB¢ system, 4 H, aromatic), 6.90 (d, J = 10.1
Hz, 1 H, A part of AB system), 6.83 (dd, J = 10.1, 2.2 Hz, 1 H, B
part of AB system), 6.49 (br s, 1 H), 5.55 (s, 2 H).
Yield: 83%; yellow solid; mp 238–239 °C.
IR (KBr): 3828, 3752, 3427, 2923, 2859, 2378, 1627, 1501, 1455,
1394, 1356, 1282, 1206, 1089, 931, 810, 728, 612, 482 cm–1.
1H NMR (400 MHz, CD3OD): d = 8.16 (s, 1 H), 7.70 (d, J = 8.2 Hz,
2 H), 7.26 (d, J = 8.2 Hz, 2 H), 6.73 (d, J = 8.5 Hz, 1 H), 6.67–6.62
(m, 4 H), 6.00 (t, J = 3.0 Hz, 2 H), 5.75 (bd, J = 2.0 Hz, 2 H), 5.54
(s, 2 H), 5.44 (s, 1 H).
13C NMR (100 MHz, CD3OD): d = 151.4, 149.4, 148.8, 145.2,
134.2, 130.1, 129.7, 125.5, 123.4, 122.1, 118.0, 117.6, 117.3, 108.1,
107.6, 50.4, 45.2.
13C NMR (100 MHz, acetone-d6): d = 192.2, 187.5, 186.6, 168.2,
147.3, 143.1, 137.7, 137.3, 136.8, 134.3, 131.0, 126.8, 123.8, 48.5.
Anal. Calcd for C16H11N3O3: C, 65.53; H, 3.78; N, 14.33. Found: C,
65.60; H, 3.65; N, 14.09.
2-[(4-Ferrocenyl-1H-1,2,3-triazol-1-yl)methyl]-1,4-benzoquino-
ne (4e)
Reddish oil.
IR (acetone): 3006, 2969, 2925, 2853, 2127, 1739, 1659, 1587,
1443, 1367, 1215, 1092, 1057, 879, 817, 668 cm–1.
UV/Vis (CH2Cl2): lmax = 250, 297 nm.
1H NMR (400 MHz, acetone-d6): d = 7.78 (s, 1 H), 6.83 (d, J = 10.1
Hz, 1 H, A part of AB system), 6.72 (dd, J = 10.1, 2.1 Hz, 1 H, B
part of AB system), 6.25 (br s, 1 H), 5.35 (s, 2 H), 4.63 (m, 2 H),
4.19 (m, 2 H), 3.95 (s, 5 H).
Anal. Calcd for C24H21N5O2: C, 70.06; H, 5.14; N, 17.02. Found: C,
70.16; H, 5.08; N, 16.97.
Bis(ligand)–Copper Complex 6
A soln of DDQ (0.170 g, 0.69 mmol) in MeCN (20 mL) was added
dropwise to a stirred soln of pyrrole 5 (0.284 g, 0.69 mmol) in
MeCN (10 mL) at r.t. The reaction mixture turned dark red, and the
stirring was continued for another 30 min. Then Cu(ClO4)2 was add-
ed to the mixture, which was stirred overnight. The solvent was re-
13C NMR (100 MHz, acetone-d6): d = 185.7, 185.0, 146.2, 141.8,
135.9, 135.5, 132.2, 119.6, 74.4, 68.6, 67.7, 65.7, 46.6.
Anal. Calcd for C19H15FeN3O2: C, 61.15; H, 4.05; N, 11.26. Found:
C, 61.21; H, 4.18; N, 11.09.
Synthesis 2009, No. 8, 1341–1347 © Thieme Stuttgart · New York

PAPER
Synthesis of 1,4-Benzoquinone-Containing 1,2,3-Triazoles
1347
moved and the residue was purified by column chromatography
(silica gel, CHCl3); this afforded a dichroic red/green film.
(5) (a) Garanti, L.; Molteni, G. Tetrahedron Lett. 2003, 44,
1133. (b) Katritzky, A. R.; Singh, S. K. J. Org. Chem. 2002,
67, 9077. (c) Suzuki, H.; Nakaya, C.; Matano, Y.
Tetrahedron Lett. 1993, 34, 1055.
Yield: 0.381 g (63%); mp >300 °C.
UV/Vis (CH2Cl2): lmax = 251, 268, 496.
(6) On copper-catalyzed synthesis and/or applications of 1,2,3-
triazoles, see: (a) Rostovtsev, V. V.; Green, L. G.; Fokin,
V. V.; Sharpless, K. B. Angew. Chem. Int. Ed. 2002, 41,
2596. (b) Tornoe, C. W.; Christensen, C.; Medal, M. J. Org.
Chem. 2002, 67, 3057. (c) Jin, T.; Kamijo, S.; Yamamoto,
Y. Eur. J. Org. Chem. 2004, 3789. (d) Fazio, F.; Bryan,
M. C.; Blixt, O.; Paulson, J. C.; Wong, C. H. J. Am. Chem.
Soc. 2002, 124, 14397. (e) Wang, Q.; Chan, R. C.; Hilgraf,
R.; Fokin, V. V.; Sharpless, K. B.; Finn, M. G. J. Am. Chem.
Soc. 2003, 125, 3192. (f) Löber, S.; Rodriguez-Loaiza, P.;
Gmeiner, P. Org. Lett. 2003, 5, 1753. (g) Perez-Balderas,
F.; Ortega-Munoz, M.; Morales-Sanfrutos, J.; Hernandez-
Mateo, F.; Calvo-Flores, F. G.; Calvo-Asin, J. A.; Isac-
Garcia, J.; Santoyo-Gonzales, F. Org. Lett. 2003, 5, 1951.
(h) Rodinov, V. O.; Fokin, V. V.; Finn, M. G. Angew. Chem.
Int. Ed. 2005, 44, 2210.
(7) Balci, M.; Çelik, M.; Gültekin, M. S. In Science of Synthesis,
Vol. 28; Griesbeck, A. G., Ed.; Thieme: Stuttgart, 2006, 31–
180.
(8) O’Malley, P. J. Chem. Phys. Lett. 1997, 274, 251.
(9) Blanchard, J. S.; Marcinkeviciene, J. A. Biochemistry 1995,
34, 6621; and references cited therein.
(10) For structure–activity studies of 1,4-benzoquinones, see:
(a) Sami, S. M.; Iyengar, B. S.; Tarnow, S. E.; Remers,
W. A.; Bradner, W. T.; Schurig, J. E. J. Med. Chem. 1984,
27, 701. (b) Shaikh, I. A.; Johnson, F.; Grollman, A. P. J.
Med. Chem. 1986, 29, 1329. (c) Kunz, K. R.; Iyengar, B. S.;
Dorr, R. T.; Alberts, D. S.; Remers, W. A. J. Med. Chem.
1991, 34, 2281. (d) Arai, H.; Ashizawa, T.; Gomi, K.; Kono,
M.; Saito, H.; Kasai, M. J. Med. Chem. 1995, 38, 3025.
(e) Hernick, M.; Flader, C.; Borch, R. F. J. Med. Chem.
2002, 45, 3540.
Calcd for C48H32CuN10O4: C, 65.78; H, 3.68; N, 15.98. Found: C,
65.85; H, 3.61; N, 16.04.
Acknowledgment
We thank the Scientific and Technical Research Council of Turkey
(TUBITAK, Grant No. 107T769) and the Turkish Academy of Sci-
ences (TUBA) for financial support of this work. We are also grate-
ful to Prof. A. M. Önal and Dr. A. Cihaner for UV/vis, CV, and ESR
measurements.
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Synthesis 2009, No. 8, 1341–1347 © Thieme Stuttgart · New York