Synthesis, electrochemistry and anticancer activity of novel ferrocenyl phenols prepared via azide-alkyne 1,3-cycloaddition reaction

Article abstract of DOI:10.1016/j.jorganchem.2012.05.042

A series of monophenols and diphenols containing the ferrocene-C _triazolyl and ferrocene-N_triazolyl bond were prepared in a cycloaddition reaction of ethynylferrocene with aryl and benzyl azides and in a reaction of azidoferrocene with phenylacetylenes, respectively. The anticancer activity of the prepared compounds against hormone-dependent (MCF-7) and hormone-independent (HCC38) breast cancer cell lines was studied. The investigated compounds exhibited moderate anticancer activity against hormone-independent (IC50 ～ 15-48 μM) cancer cell line and low activity against hormone-dependent cancer cell line (IC50 ～ 84-98 μM).

Full text of DOI:10.1016/j.jorganchem.2012.05.042

Journal of Organometallic Chemistry 715 (2012) 102e112
Contents lists available at SciVerse ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis, electrochemistry and anticancer activity of novel ferrocenyl phenols
prepared via azide-alkyne 1,3-cycloaddition reaction
a
,
b
b
c
*
_
_
_
Damian Plazuk , B1azej Rychlik , Andrzej B1auz , S1awomir Domaga1a
a
ꢀ
ꢀ
University of Łódz, Faculty of Chemistry, Department of Organic Chemistry, ul. Tamka 12, 91-403 Łódz, Poland
University of Łódz, Faculty of Biology and Environmental Protection, Department of Molecular Biophysics, Cytometry Lab, ul. Banacha 12/16, 90-237 Łódz, Poland
University of Łódz, Faculty of Chemistry, Department of Inorganic Chemistry, ul. Tamka 12, 91-403 Łódz, Poland
b
c
ꢀ
ꢀ
ꢀ
ꢀ
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of monophenols and diphenols containing the ferrocene-Ctriazolyl and ferrocene-Ntriazolyl bond
were prepared in a cycloaddition reaction of ethynylferrocene with aryl and benzyl azides and in
a reaction of azidoferrocene with phenylacetylenes, respectively. The anticancer activity of the prepared
compounds against hormone-dependent (MCF-7) and hormone-independent (HCC38) breast cancer cell
lines was studied. The investigated compounds exhibited moderate anticancer activity against hormone-
Received 12 March 2012
Received in revised form
24 May 2012
Accepted 30 May 2012
independent (IC50 w 15e48
cell line (IC50 w 84e98 M).
m
M) cancer cell line and low activity against hormone-dependent cancer
Keywords:
Ferrocene
Click reaction
m
Ó 2012 Elsevier B.V. All rights reserved.
Azide-alkyne cycloaddition reaction
1H-1,2,3-Triazole
HCC38 cell
MCF-7 cell
1. Introduction
antimalarial [27e30] and antibacterial [31] activities. The most
promising ferrocenyl anticancer-active compounds are ferrocifen
and its derivatives. Jaouen et al. prepared and investigated the
anticancer activity of the ferrocenyl analogue, of an active metab-
olite of tamoxifene (Scheme 2). Studies on the structureeactivity
relationship of hydroxyferrocifene indicate that: (i) the most
active ferrocifenes contain only one ferrocenyl group and two para-
A significant increase in the level of interest in the click reaction
has been observable in the past ten years. One of the widely
investigated click reactions is the metal-catalysed azide-alkyne
1,3-cycloaddition reaction (Huisgen reaction, CuAAC, Scheme 1)
[1e3]. An intensive rise in the number of applications of the CuAAC
reaction has been observed, mainly due to the simple reaction
conditions, high yield of product formation and excellent functional
group tolerance [4]. Furthermore, the 1,2,3-triazole ring has
successfully been used as a bioisosteric group with the amide [5,6]
and trans-alkene moiety [7].
Ferrocene is a redox-active, chemically stable and non-toxic
molecule that is neutral in biological media. In 1978 Brynes et al.
[8] reported the anticancer activity of ferrocenyl compounds
against the lymphocytic leukaemia P388 cell line. Since then many
different types of anticancer-active ferrocenyl derivatives have
been prepared (e.g. ferrocene conjugated with azoles [9,10],
peptides [11], nucleobases [12], vitamins [13,14], DNA intercalators
[15], enzyme inhibitors [16,17] or taxanes [18]). Many of these
hydroxyphenyl groups [32,33], (ii)
p-conjugation between ferro-
cenyl and the phenol moiety significantly increases anticancer
activity [34,35]. However, the presence of the ferrocenyl group in
the structure does not guarantee anticancer activity [36].
In search of novel ferrocenyl compounds with potent cytotoxic
activities, we decided to prepare a series of ferrocenyl phenols
containing the 1H-1,2,3-triazolyl moiety, which is bioisosteric with
the ethylene group, as a linker of ferrocenyl and the phenol groups
(Scheme 3). Herein we report on their synthesis, electrochemical
properties and in vitro cytotoxicity.
2. Results and discussion
compounds
exhibited
significant
cytotoxic
[19e26]and
2.1. Chemical synthesis
Synthesis of ferrocenyl phenols was performed in two steps: (i)
protected phenols were synthesised in a CuAAC cycloaddition
* Corresponding author. Tel.: þ48 42 6355760; fax: þ48 42 6786583.
_
E-mail address: damplaz@uni.lodz.pl (D. Plazuk).
0022-328X/$ e see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jorganchem.2012.05.042

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D. Plazuk et al. / Journal of Organometallic Chemistry 715 (2012) 102e112
103
Cu-source
R1
R2
N3 R2
R1
N
N N
Scheme 1. Azide-alkyne 1,3-cycloaddition reaction.
NMe2
O
N
O
n
Scheme 4. Synthesis of azidoferrocene.
respectively. A further reduction of benzoates 8a and 8b with lithium
aluminium hydride gave corresponding alcohols in a 64% and 62%
yield, respectively. The absence of the carbonyl group in NMR and IR
spectroscopy confirmed completeness of the reduction of esters to
alcohols. Benzyl alcohols 9a and 9b were converted to the corre-
sponding benzyl azides, via benzyl bromide, first in a reaction with
phosphorus tribromide followed by an overnight reaction with
sodium azide in DMSO, thus giving the corresponding azides 10a and
10b in a 47e51% overall yield. Crude products were used in the next
step without further purification. The presence of the azide group in
theprepared compoundswas confirmedby IR spectroscopy (astrong
band was observed at 2100e2115 cmꢀ1).
Fe
OH
OH
Hydroxytamoxifene
Hydroxyferrocifene
Scheme 2. Structures of hydroxytamoxifene and hydroxyferrocifene.
reaction of azides with alkynes, (ii) the protecting group was
cleaved, affording the corresponding phenols. Our studies showed
that demethylation of readily available triazolyl phenol methyl
ethers in reaction with an excess of boron tribromide gave corre-
sponding phenols only in low yield. We used the methyl group as
a protective group only for synthesis 23. In other cases we used the
tert-butyldimethylsilyl group as a protective group.
2.1.2. Synthesis of alkynes
Alkynes were prepared from the corresponding aldehydes in
the CoreyeFuchs reaction [40]. 4-tert-Butyldimethylsilylox-
yphenylacetylene 11a [20] and 3,5-bis-(tert-butyldimethylsily-
loxy)-phenylacetylene 11b [41] were prepared according to the
methods described previously, and slightly modified in the case of
11b (Scheme 6). Our studies showed that silylation of 3,5-
dihydroxybenzaldehyde with tert-butyldimethylsilyl chloride in
the presence of imidazole as a base in DMF at RT gave a corre-
sponding silyl ether 13b as a sole product in an excellent yield,
whereas the method of silylation as described previously [21]
failed in our hands. The reaction of silylated aldehydes with
carbon tetrabromide and triphenylphosphine followed by LDA
gave the corresponding phenylacetylenes 11a and 11b in a good
yield. The structure of the products was confirmed by NMR
(a triplet at 2.1 ppm confirmed the presence of the ^CeH group)
and IR spectroscopy (a weak or medium band at 2110 cmꢀ1 ^CeH
bond was observed).
2.1.1. Synthesis of azides
1-Azido-4-tert-butyldimethylsilyloxybenzene
1 [37], 4-azidoa
nisole 2 [7], 1-azido-3,5-dimethoxybenzene 3 [16] and 1-azido-4-
benzyloxybenzene 4 [38] were prepared as described previously.
Azidoferrocene 5 is usually prepared by monolithiation of
ferrocene followed by a reaction with an azide source (e.g. 2,4,6-
triisopropylbenzenesulfonyl azide [39]). The lithiation of ferro-
cene leads to a mixture of mono- and dilithioferrocene. The sole
formation of monolithioferrocene requires special reaction condi-
tions. Furthermore, hazardous and expensive reagents and strictly
anhydrous conditions must be used. Because of these difficulties,
we applied the previously described method of synthesis of 1,10-
diazidoferrocene [40] for a synthesis of 5, which was prepared in
a 78% yield from commercially available bromoferrocene by reac-
tion with sodium azide and copper chloride in ethanol at room
temperature for 72 h (Scheme 4). The presence of the azido group
in the product was confirmed by IR spectroscopy. A strong band
2.1.3. Metal-catalysed azide-alkyne 1,3-cycloaddition reaction
Metal-catalysed azideealkyne cycloaddition reactions (‘click’
reactions) are usually carried out in the presence of metallic
copper or copper salts [42,44,45]. First, we optimised the
was observed at 2114 cmꢀ1
.
4-tert-Butyldimethylsilyloxybenzyl azide 10a and 3,5-bis(tert-
butyldimethylsilyl)benzyl azide 10b were prepared according to
Scheme 5. The benzyl azides 10a and10b were obtained in a five-step
reactionstarting fromcommerciallyavailable4-hydroxybenzoicacid
and3,5-dihydroxybenzoicacid. First, methyl4-hydroxybenzoateand
methyl 3,5-dihydroxybenzoate reacted with tert-butyldimethylsilyl
chloride in thepresenceof imidazolein DMFat roomtemperature for
24 h to afford silyl ethers 8a and 8b in a 97% and 96% yield,
Scheme 3. Ferrocifene and its 1H-1,2,3-triazolyl analogues.
Scheme 5. Synthesis of benzyl azides.

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D. Plazuk et al. / Journal of Organometallic Chemistry 715 (2012) 102e112
104
temperature for 72 h (the progress of reactions was checked by
TLC). Pure 1,2,3-triazoles were isolated by chromatography on silica
gel in a good or excellent yield. Desilylation of the phenol silyl
ethers was carried out under typical conditions in reaction with
a large excess of tetrabutylammonium fluoride in tetrahydrofurane
at ambient temperature. The desired phenols were obtained in
a good yield (Schemes 9 and 10).
It was interesting to note that in the reaction of 3,5-
bis(tert-butyldimethylsilyloxy)benzyl azide 10b with ethynylferro-
cene 14, we observed the formation of 18b as a major product
(47% yield, based on 1H NMR) and 1-(3,5-dihydroxybenzyl)-4-
ferrocenyl-1H-1,2,3-triazole 19b in a 16.7% yield as a product of
desilylation of 18b. Due to complications with the purification of
TBDMS ether 18b, we decided to perform the desilylation of crude
18b, which allowed us to obtain a pure phenol 19b in a 49% overall
yield.
For the synthesis of 23 we chose a methyl group as a protective
group. The product of click reaction 22 was prepared in a good
yield from ethynylferrocene and 1-azido-3,5-dimethoxybenzene 3
according to the optimised procedure. The demethylation of methyl
ether was carried out in the reaction of 22 with a large excess of
boron tribromide (10 eq) at RT. The desired diphenol 23 was
obtained in a 15% yield (Scheme 11).
Scheme 6. Synthesis of phenylacetylenes.
Table 1
Reaction of ethynylferrocene with 4-azidoanisole under different conditions. The
bold text indicate the best yield of the product formation which was observed under
this reaction conditions.
Entry Cu-source
% of Cu Ligand L Solvent/time
[% mol]
Yield of
15 [%]
1
2
Cu-wire/CuCl
CuSO4, sodium
ascorbate
100a
30
None
None
tBuOH/EtOH/water/24 h
EtOH/water/24 h
0
72%
3
4
CuI
9
1
TTTAb
TTTAb
THF/16 h
MeOH/H2O/24 h
50%
50%
CuSO4, sodium
ascorbate
Cu(CH3CN)4PF6
CuSO4, sodium
ascorbate
5
6
1
1
TTTAb
TTTAb
MeOH/H2O/72 h
MeOH/H2O/72 h
93%
96%
The formation of the desired regioisomers as sole products in
the CuAAC reaction was confirmed by 1D and 2D NMR spectros-
copy. In the 1H NMR spectra, a broad singlet of triazolyl-proton was
observed at 7e8.5 ppm.
a
Calc. based on CuCl.
TTTA e tris((1-(tert-butyl)-1H-1,2,3-triazol-4-yl)methyl)amine.
b
reaction conditions of cycloaddition of ethynylferrocene 14 with
4-azidoanizole 2. The reaction optimisation results are presented in
Table 1 (Scheme 7).
2.1.4. CeH arylation of 4-ferrocenyl-1H-1,2,3-triazole
Incorporation of a second p-hydroxyphenyl group into the
5-position of the triazole moiety was successfully performed in the
CeH arylation reaction of 1-aryl-4-ferrocenyl-1H-1,2,3-triazole in
a slightly modified reaction as described previously [46]. In the
reaction of 16 with 4-tert-butyldimethylsilyloxy-1-bromobenzene
in the presence of Pd(PPh3)2Cl2 and tetrabutylammonium acetate
in N-methylpyrrolidone (NMP), we observed desilylation of the
starting material and formation of a phenol 17 as a sole product
(46% yield) (Scheme 12). Because of this, we changed the protective
group to the benzyl moiety.
The benzyl ether 25 was prepared in the reaction of ethy-
nylferrocene with 1-azido-4-benzyloxybenzene under the same
conditions as described above in a 90% yield. The reaction of 24
with 4-benzyloxy-1-bromobenzene under the same conditions as
above afforded 25 in a 81% yield. The simple and effective hydro-
genolysis of 25 with hydrogen generated in situ from triethylsilane
in the presence of palladium on active carbon [47] gave a diphenol
26 in a good yield (Scheme 13).
In the simplest case (Table 1, entry 1), when a copper wire and
copper(I) chloride were used as a Cu-source, the desired product
was not formed. The use of a high load of copper sulphate and
sodium ascorbate gave 1H-1,2,3-triazole 15 after 24 h in a good
yield (72% yield, Table 1, entry 2). As was previously described, the
use of a TTTA ligand increased the yield of formation of 1,2,3-
triazole [43,44] in the CuAAC reaction. The best reaction yield
was observed when of copper (1%mol) was used together with the
TTTA ligand (Table 1, entries 5 and 6). The highest reaction yield
was observed when a reaction was carried out for 72 h instead of
24 h. Finally, we decided to use a mixture of copper(II) sulphate and
sodium L-ascorbate as a catalyst together with the TTTA ligand
(prepared according to Scheme 8).
As was mentioned before, our first attempts in the synthesis of
ferrocenyl phenols using methyl group as a protective group failed.
As a result, we used the tert-butyldimethylsilyl group (TBDMS) as
a protective group. It is well known that the TBDMS group can be
easily cleaved in a reaction with a fluoride anion [45]. Two series of
ferrocenyl 1H-1,2,3-triazolyl phenols were prepared in the CuAAC
reaction. A series of 1-aryl-4-ferrocenyl-1H-1,2,3-triazoles were
prepared in the reaction of ethynylferrocene with aryl or benzyl
azides. The reaction of azidoferrocene with phenylacetylenes gave
a series of 4-aryl-1-ferrocenyl-1H-1,2,3-triazoles. All click reactions
2.2. Electrochemical study of ferrocenyl 1,2,3-triazol phenols
The cyclic voltammetry technique was used for the study of
the redox properties of ferrocenyl phenols. The measurements
were carried out in acetonitrile solution. Since phenols are able to
were carried out in
a methanolewater solution at room
Scheme 7. Optimisation of the azideealkyne reaction of ethynylferrocene with 4-azidoanisole.

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D. Plazuk et al. / Journal of Organometallic Chemistry 715 (2012) 102e112
105
Scheme 8. Synthesis of the TTTA ligand.
undergo deprotonation, we measured the electrochemical proper-
ties of the prepared phenols in the presence of imidazole. For
comparison, we examined the electrochemical properties of methyl
phenol 15, which exhibited redox potential at 444 mV. The addition
of imidazole to 15 did not influence its redox potential (deproto-
nation of 15 by imidazole is impossible). The data are shown in
Table 2.
The extent of their diminution was affected by the number of
the hydroxyl group in the phenol moiety. When the 3,5-
dihydroxyphenols group was present in the molecule (19b, 21b
and 23), the addition of the excess of imidazole led to an increase
in the irreversibility of the redox system (Fig. 1), whereas the
addition of imidazole to a compound containing one or two
4-hydroxyphenyl moieties (17, 19a, and 21a) gave a less reversible
redox system (Fig. 2).
All prepared phenols exhibited reversible or quasi-reversible
one-electron oxidation-reduction of the ferrocenyl moiety. As can
be seen, their redox potentials in comparison to that of ferrocene
were shifted anodically, from 46 mV in the case of 19b to up to
192 mV for 21b. For the series of 1-aryl-4-ferrocenyl-1H-1,2,3-
triazoles 27 (Scheme 14) the redox potential was almost the same
(the average value for 17, 19a and 23 is 445 mV), whereas the
average redox potential of the series of 4-aryl-1-ferrocenyl-
1H-1,2,3-triazoles 28 was as high as 575 mV. The redox potential of
monophenol 17 compared to isomeric monophenol 21a (from
series 28) is shifted anodically by 134 mV. The same trend is
observable in the series of 3,5-diphenol 23 (series 27) as compared
to 3,5-diphenol 21b (series 28), which exhibited a redox potential
shifted anodically by 129 mV. The introduction of another para-
hydroxyphenyl group to 5-position of the triazole moiety
increased the redox potential by 12 mV as compared to mono-
phenol 17. The phenol moiety was not oxidised in our conditions
(up to 1 V).
2.3. Anticancer activity
Although tamoxifen is considered to be mainly a cytostatic
agent, it also exhibits cytotoxicity when present in higher (ꢁ10
mM)
concentrations [48]. Tamoxifen’s cytotoxic effect does not signifi-
cantly depend on the estrogen receptor expression status (ibidem).
Since a ferrocenyl moiety promotes an antibiotic mode of action,
we focused on the toxic effects of the investigated phenols on
HCC38 (human breast carcinoma cell line negative for the expres-
sion of the estrogen receptor) and MCF-7 (human breast adeno-
carcinoma cell line positive for the expression of the estrogen
receptor) cancer cell lines. The IC50 values were determined by
MTT-reduction assay [49] in the phenol concentration range from
10 nM up to 100 mM. The summarised cytotoxicity data are pre-
sented in Table 3. Viability curves in the presence of the prepared
phenols are shown in Fig. 3.
Since the deprotonation of phenols in the living cell is possible,
we investigated the redox potentials of the phenols in the presence
of large excess of imidazole (100 mM) as a base. The effect of
imidazole addition on the redox potential of the prepared phenols
was similar for all compounds. The intensity of the anodic peak
increased, whereas the intensity of the cathodic peak decreased.
As can be seen, some of the prepared compounds exhibited
good cytotoxic activity against the hormone-independent HCC38
breast cancer cell line. The most active compound was 17, con-
taining one para-hydroxyphenyl group (IC50 ¼ 15.3
introduction of another para-hydroxyphenyl moiety provides
two times less active compound 26 (IC50 30.6 M).
mM). The
a
¼
m
Scheme 9. Synthesis of 4-ferrocenyl-1-(hydroxyaryl)-1H-1,2,3-triazoles.

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D. Plazuk et al. / Journal of Organometallic Chemistry 715 (2012) 102e112
Scheme 10. Synthesis of 1-ferrocenyl-4-(hydroxyaryl- or hydroxybenzyl)-1H-1,2,3-triazoles.
Replacement of the 4-hydroxyphenyl (17) or 3,5-dihydroxyphenyl
(23) groups with 4-hydroxybenzyl (19a) or 3,5-dihydroxybenzyl
(19b) groups led to a significant decrease in anticancer activity in
both cases.
The hormone-dependent MCF-7 line was moderately affected.
In general, the IC50 values were at least twice higher for MCF-7
than for the HCC38 cell line, whereas the toxicity of tamoxifen
was similar for both cell types. Only two compounds, 21a and 23,
exhibited cytotoxic activity against the hormone-dependent MCF-7
much less active than 17 (redox potential 57 mV). This suggests that
the biological effectiveness of the ferrocenoyl phenol analogues of
tamoxifen depends not only on their ability to disturb the cellular
redox status, but also on the influence of the signalling pathways
and the metabolic machinery of the cell.
4. Experimental section
cancer cell lines at high concentrations (IC50 ¼ 98.8 and 84.0
mM,
4.1. General
respectively).
1H and 13C NMR spectra were recorded on a Bruker ARX
600 MHz. Chemical shifts for the 1H NMR spectra were referenced
relatively to a residual proton in the deuterated solvent (CDCl3
7.27 ppm for 1H and 77.00 ppm for 13C, DMSO-d6 2.50 ppm for 1H
and 39.51 ppm for 13C). The spectra were recorded at room
temperature (291 K), chemical shifts are in ppm and coupling
constants in Hz. Thin-layer chromatography (TLC) was performed
on aluminium sheets precoated with Merck 5735 Kieselgel 60F254.
Column chromatography was carried out either with FLUKA 60752
Silica gel 60 for flash chromatography (0.040e0.063 mm
230e400 mesh). Dichloromethane was distilled from calcium
hydride and stored over activated molecular sieves 4A
(8e12 mesh). All reactions (if necessary) were carried out using the
standard Schlenk technique. Chemicals, biochemicals and solvents
(HPLC grade) were purchased from SigmaeAldrich or AK Scientific
(USA) and used as received.
The anticancer activity of the prepared 1H-1,2,3-triazoles
strongly depended on the structure of the phenols. In both cases,
the triazoles 21a and 21b containing a ferrocene-N1-triazolyl bond
exhibited much lower activities than the corresponding ferrocenyl-
C4 isomers 17 and 23, respectively. 21a is three times less active
against HCC38 and 21b is inactive up to 100 mM (no influence of 21b
on the viability of the HCC38 and MCF-7 cancer cell lines was
observed e Fig. 3). At high concentrations two compounds, 19a and
21b, exhibited the proliferation-promoting effect.
3. Conclusion
New types of ferrocenyl phenols containing a 1H-1,2,3-triazolyl
moiety as a linker of the ferrocenyl and phenol groups were
prepared, and their anticancer activities were studied. The 1H-
1,2,3-triazolyl moiety, which is simple to prepare, was successfully
used as a bioisosteric group of the ethylene bond. All of the
prepared active compounds containing the ferrocenyl-C4-triazolyl
bond exhibited anticancer activities against the hormone-
independent cancer cell line HCC38, whereas the isomeric 1H-
1,2,3-triazole containing the ferrocenyl-N1-triazolyl bond exhibited
much lower cytotoxic activities (IC50 for 21a is 3 times lower than
4.1.1. Azidoferrocene (5)
A solution of 523 mg (8.0 mmol) of sodium azide in 1.5 cm3 of
water was added to a solution of 1.06 g (4.0 mmol) of bromo-
ferrocene and 430.7 mg (4.3 mmol) of copper(I) chloride in 15 cm3
of ethanol, and the resulting mixture was stirred at RT in the dark
for 72 h. The product was then extracted with petroleum ether
(3 ꢂ 100 cm3) and the organic layer was washed with water, brine
and then dried over sodium sulphate. Evaporation of the solvent
gave 5 in a 78% yield (0.6 g). The crude product was used in the next
step without further purification. 1H NMR and IR spectra confirmed
the structure of the product [50].
for 17). The most active compound was 17 (IC50 ¼ 15.3 M against
m
HCC38) and 23 (IC50 ¼ 22.3
m
M against HCC38 and 84.0 mM against
MCF-7). On the other hand, we did not observe a good correlation
between the electrochemical properties of the prepared phenols
and their anticancer activities. Some of the prepared phenols with
the lowest redox potential (63 mV for 19a and 46 mV for 19b) were
Scheme 11. Synthesis of 1-(3,5-dihydroxyphenyl)-4-ferrocenyl-1H-1,2,3-triazole.

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D. Plazuk et al. / Journal of Organometallic Chemistry 715 (2012) 102e112
107
dimethylsulfoxide was added, and the resulting solution was stirred
at RT for 24 h. The resulting mixture was poured on 200 cm2 of
water/ice and the product was extracted with diethyl ether. The
crude product (90.8% yield, 2.3 g) was used in the next step without
further purification.
4.1.4. 3,5-Bis(tert-butyldimethylsilyloxy)benzyl azide (10b)
It was prepared using the same method as described for 10a in
a 47.5% overall yield, starting with 4.53 g of 9b. The crude product
was used in the next step without further purification.
Scheme 12. Reaction of 16 with 4-tert-butyldimethylsilyloxy-1-bromobenzene in the
presence of Pd(PPh3)2Cl2.
4.1.5. Tris((1-(tert-butyl)-1H-1,2,3-triazol-4-yl)methyl)amine
(TTTA)
4.1.2. 4-tert-Butyldimethylsilyloxybenzyl alcohol (9a)
A solution of 200 mg of copper sulphate and 300 mg of sodium
10 cm3 (20 mmol) of the solution of lithium aluminium hydride
(c ¼ 2 M) was added over 10 min at 0 ꢃC to a solution of 5.32 g
(20 mmol) of methyl tert-butyldimethylsilyloxybenzoate 8a [51] in
35 cm3 of anhydrous THF. Then the cooling bath was removed and
the resulting solution was stirred at RT for 20 h. Next, 50 cm3 of
water was added and the product was extracted with diethyl ether
(3 ꢂ 100 cm3). The organic layer was washed twice with water,
brine and dried over sodium sulphate. Evaporation of the solvent
gave 3.06 g of a crude product as a colourless oil [52]. It was used in
the next step without further purification.
L
-ascorbate in 15 cm3 of water was added to a solution of 1.575 g
(12.0 mmol, 1.46 cm3) of tripropargylamine and 4.60 g (46.4 mmol)
of tert-butylazide [53] in a mixture of 40 cm3 of tetrahydrofurane
and 30 cm3 of methanol. The resulting mixture was stirred at RT for
72 h. Then the reaction was quenched by addition of 50 cm3 of
water and 50 cm3 of 10% potassium cyanide (warning: highly
poisonous) and 100 cm3 of ethyl acetate. The resulting mixture was
vigorously stirred for 10 min and the product was extracted with
ethyl acetate (2 ꢂ 100 cm3). The organic solution was washed with
water, brine and dried with sodium sulphate. The solvents were
evaporated and 50 cm3 of diethyl ether was added to the crude
product. The suspension was sonicated for 2 min and the white
solid was filtered off, washed twice with 50-cm3 portions of diethyl
ether and freeze-dried to give pure TTTA in a 43% yield (2.21 g) as
4.1.3. 4-tert-Butyldimethylsilyloxybenzyl azide (10a)
3.33 g (12.3 mmol, 1.16 cm3) of phosphorous tribromide was
added to a solution of 2.93 g (12.3 mmol) of 4-tert-butyldi-
methylsilyloxybenzyl alcohol 9a and 1 cm3 of anhydrous pyridine in
100 cm3 of anhydrous diethyl ether, and the resulting mixture was
stirred at room temperature for 20 h. Then 100 cm3 of water was
added, the organic layer was separated and the aqueous layer was
extracted with diethyl ether (3 ꢂ 50 cm3). The extracts were
combined, washed twice with water, brine and dried with sodium
sulphate. Evaporation of the solvents gave 3 g of a crude 4-tert-
butyldimethylsilyloxybenzyl bromide. It was used in the next step
immediately, without further purification. To 40 cm3 of anhydrous
dimethylsulfoxide, 0.8 g (12.3 mmol) of sodium azide was added and
the mixture was stirred at RT for 24 h. Then 2.9 g (9.62 mmol) of 4-
white crystals. 1H NMR (600 MHz, DMSO-d6)
d
¼ 1.63 (s, 9H); 3.67
(s, 2H); 8.05 (s, 1H); 13C NMR (151 MHz, DMSO-d6)
d
¼ 29.4; 47.3;
58.5; 120.8; 143.1.
4.1.6. Standard procedure for CuAAC cycloaddition reaction
4.1.6.1. 4-Ferrocenyl-1-(4-methoxyphenyl)-1H-1,2,3-triazole (15).
Mixture of copper sulphate (c ¼ 0.1 M, V ¼ 100
m
l, 10
mol) and TTTA (c ¼ 0.01 M,
mmol) were added to a solution of 210 mg (1.0 mmol) of
mmol), sodium
ascorbate (c ¼ 0.1 M, V ¼ 100
ml, 10 m
V ¼ 1 cm3,10
ethynylferrocene 14 and 164.1 mg (1.1 mmol) of 4-azidoanisole 2 in
a mixture of 20 cm3 of methanol and 1 cm3 of water and the resulting
solution was stirred at RT for 72 h. Then 50 cm3 of water was added
and the product was extracted with ethyl acetate. The organic
solution was washed with water, brine and dried with sodium
sulphate. The pure product was isolated by chromatography on
silica gel (50 cm3) using dichloromethaneeethyl acetate 19e1 in
a 96% yield of a pure 15 as an orange solid.1H NMR (600 MHz, DMSO-
tert-butyldimethylsilyloxybenzyl
bromide
in
40
cm3
d6)
d
¼ 3.85 (s, 3H), 4.09 (s, 5H), 4.36 (s, 2H), 4.80 (s, 2H), 7.16 (d, 2H,
J ¼ 9.03 Hz), 7.83 (d, 2H, J ¼ 9.03 Hz), 8.71 (s,1H); 13C NMR (151 MHz,
DMSO-d6)
146.9, 159.7; IR (KBr)
d
¼ 56.1, 67.0, 68.9, 69.8, 75.9, 115.4, 118.9, 122.0, 130.7,
n
[cmꢀ1]: 3125, 3090, 1519, 1443, 1305, 1252,
1232, 1208, 1172, 1106, 1042, 1023, 830, 820; Elemental analysis.
Calculated for C19H17FeN3O e C-63.53, H-4.77, N-11.70; found: C-
63.52, H-4.77, N-11.63.
4.1.6.2. 4-Ferrocenyl-1-((4-tert-butyldimethylsilyloxy)phenyl)-1H-
1,2,3-triazole (16). The title compound was prepared in a 90%
yield as an orange solid. 1H NMR (600 MHz, CDCl3)
d
¼ 0.27 (s, 6H),
1.04 (s, 9H), 4.15 (s, 5H), 4.37 (s, 2H), 4.82 (s, 2H), 7.00 (d, 2H,
J ¼ 8.66 Hz), 7.65 (d, 2H, J ¼ 9.03 Hz), 7.83 (s, 1H), 13C NMR
(151 MHz, CDCl3)
d
¼ ꢀ4.4, 18.3, 25.7, 66.8, 68.8, 69.6, 75.2, 116.8,
121.0, 121.9, 131.1, 147.3, 156.1; IR (KBr) n
[cmꢀ1]: 3122, 2953, 2932,
1515, 1270, 910; Elemental analysis. Calculated for C24H29FeN3OSi
e C-62.72, H-6.36, N-9.15; found: C-62.87, H-6.31, N-9.23.
4.1.6.3. 4-Ferrocenyl-1-((4-tert-butyldimethylsilyloxy)benzyl)-1H-
Scheme 13. CeH Arylation of 24 and hydrogenolysis of benzyl ether 25.
1,2,3-triazole (18a). The title compound was prepared in a 55%

_
D. Plazuk et al. / Journal of Organometallic Chemistry 715 (2012) 102e112
108
Table 2
Cyclic voltammetry data for 17, 19a, 19b, 21a, 21b, 23, 26 (10ꢀ3 M solutions in
CH3CN/nBu4NPF6, scan rate 100 mV/s). E1/2 vs. ferrocene/ferrocenium cation (vs. SCE
in brackets).
Compound
Additive - None
Additive - Imidazole
E1/2 [mV]
D
E [mV]
E1/2 [mV]
DE [mV]
Scheme 14. Series of ferrocenyl-1H-1,2,3-triazoles.
Ferrocenea
0 (383)
102
e
OH
1515, 1041, 910; Elemental analysis. Calculated for C24H29FeN3OSi
e C-62.72, H-6.36, N-9.15; found: C-63.01, H-6.23, N-9.21.
N
N
17
57 (440)
128
48 (431)
190
N
Fe
4.1.6.5. 1-Ferrocenyl-4-(3,5-bis(tert-butyldimethylsilyloxy)phenyl)-1H-
1,2,3-triazole(20b). Thetitlecompoundwaspreparedina54%yieldas
a yellow solid and was recrystallised from the mixture of DCMen-
OH
N
N
pentane. 1H NMR (600 MHz, CDCl3)
d
¼ 0.25 (s, 12H), 1.02 (s, 18H),
19a
63 (446)
46 (429)
127
106
71 (454)
40 (423)
153
209
N
Fe
4.25 (s, 5H), 4.29 (t, 2H, J ¼ 1.88 Hz), 4.89 (t, 2H, J ¼ 1.88 Hz), 6.35 (t,1H,
J ¼ 2.26 Hz), 7.01 (d, 2H, J ¼ 2.26 Hz), 7.88 (s,1H); 13C NMR (151 MHz,
OH
CDCl3)
d
¼ ꢀ4.3, 18.2, 25.7, 62.2, 66.7, 70.2, 93.8, 111.0, 111.9, 119.2,
132.0, 147.4, 157.0; IR (KBr)
n
[cmꢀ1]: 3131, 3092, 2957, 2929, 2857,
N
N
OH19b
N
1608,1588,1519,1463,1254,1225,1172,1031, 917, 831, 781; Elemental
analysis. Calculated for C30H43FeN3O2Si2 e C-61.10, H-7.35, N-7.13;
found: C-61.15, H-7.67, N-7.21.
Fe
OH
4.1.6.6. 4-Ferrocenyl-1-(3,5-dimethoxyphenyl)-1H-1,2,3-triazole (22).
21a
191 (574)
98
199 (582)
202
N
N
The title compound was prepared in a 94% yield as an orange solid.1H
N
Fe
NMR (600 MHz, CDCl3)
4.79 (br. s., 2H), 6.51 (br. s., 1H), 6.94 (br. s., 2H), 7.86 (s, 1H); 13C NMR
(151 MHz, CDCl3)
¼ 55.7, 66.8, 68.8, 69.6, 75.0, 98.8, 100.3, 116.7,
138.5, 147.5, 161.5; IR (KBr)
[cmꢀ1]: 3120, 3080, 1613, 1578, 1475,
1433, 1335, 1300, 1230, 1198, 1159, 1064, 1043, 837, 511; Elemental
analysis. Calculated for C20H19FeNO e C-61.72, H-4.92, N-10.80;
found: C-61.77, H-5.03, N-11.05.
d
¼ 3.87 (s, 6H), 4.12 (s, 5H), 4.34 (br. s., 2H),
d
HO
N
n
OH
21b
192 (575)
66 (449)
62
74
e
N
N
Fe
HO
4.1.6.7. 4-Ferrocenyl-1-(4-benzyloxyphenyl)-1H-1,2,3-triazole (24).
The title compound was prepared in a 78% yield as an orange solid.
Chromatography on silica gel was performed using chloroformeethyl
acetate (gradient 0e25% of ethyl acetate) as an eluent. 1H NMR
OH
N
N
23
15 (398)
194
247
N
Fe
(600 MHz, DMSO-d6)
d
¼ 4.10 (s, 5H), 4.36 (t, J ¼ 1.88 Hz, 2H), 4.79 (t,
J ¼ 1.88 Hz, 2H), 5.22 (s, 2H), 7.25 (d, J ¼ 9.03 Hz, 2H), 7.34e7.39 (m,
1H), 7.43(t, J ¼ 7.53 Hz,2H), 7.50 (d, J¼ 7.15 Hz, 2H), 7.85 (d, J¼ 9.03Hz,
HO
OH
2H), 8.79 (s, 1H); 13C NMR (151 MHz, DMSO-d6)
d
¼ 66.4, 68.3, 69.2,
N
26
69 (452)
79
33 (416)
69.6, 75.4, 115.7, 118.5, 121.3, 121.4, 127.9, 128.6, 130.2, 136.7, 146.3,
N
[cmꢀ1]: 3119, 1586, 1516, 1453, 1314, 1229, 1043, 831,
N
158.1; IR (KBr)
n
Fe
814, 734; Elemental analysis. Calculated for C25H21FeN3O e C-68.98,
H-4.86, N-9.65; found: C-68.97, H-4.86, N-9.52.
a
References.
yield as an orange solid. 1H NMR (600 MHz, CDCl3)
0.78 (s, 9H), 3.92 (br. s. 5H), 4.16 (br. s. 2H), 4.57 (br. s. 2H), 5.24 (s,
d
¼ 0.00 (s, 6H),
2H), 6.64 (d, 2H, J ¼ 7.53 Hz), 6.96 (d, 2H, J ¼ 7.91 Hz), 7.06 (s, 1H);
13C NMR (151 MHz, CDCl3)
d
¼ ꢀ4.4,18.2, 25.6, 53.7, 67.0, 69.0, 70.1,
77.0, 118.8, 120.6, 127.5, 129.4, 147.1, 156.1; IR (KBr) n
[cmꢀ1]: 3127,
2961, 2929, 2896, 2859, 1607, 1511, 1263, 914; Elemental analysis.
Calculated for C25H31FeN3OSi e C-63.42, H-6.60, N-8.80; found: C-
63.55, H-6.67, N-8.92.
4.1.6.4. 1-Ferrocenyl-4-(4-(tert-butyldimethylsilyloxy)phenyl)-1H-
1,2,3-triazole (20a). The title compound was prepared in a 51%
yield as a yellow solid and was recrystallised from the mixture of
DCMen-pentane. 1H NMR (600 MHz, CDCl3)
d
¼ 0.25 (s, 6H), 1.02
(s, 9H), 4.13 (s, 5H), 4.35 (s, 2H), 4.80 (s, 2H), 6.98 (d, 2H,
J ¼ 8.66 Hz), 7.63 (d, 2H, J ¼ 9.03 Hz), 7.80 (s, 1H); 13C NMR
(151 MHz, CDCl3)
d
¼ ꢀ4.4, 18.3, 25.7, 66.8, 68.8, 69.6, 75.2, 116.8,
Fig. 1. Voltammogram of 23 in the absence and in the presence of imidazole. Ferrocene
for comparison.
121.0, 121.9, 131.1, 147.3, 156.1; IR (KBr) n
[cmꢀ1]: 3122, 2953, 2932,

_
D. Plazuk et al. / Journal of Organometallic Chemistry 715 (2012) 102e112
109
in 5 cm3 of tetrahydrofurane, and the resulting solution was
stirred at RT for 2 h. The progress of reaction was checked by TLC
using dichloromethaneeethyl acetate 9e1 as an eluent. The
reaction was quenched by the addition of 50 cm3 of water and the
product was extracted with several portions of ethyl acetate. The
pure product was isolated by chromatography on silica gel
(50 cm3) using dichloromethaneeethyl acetate 9e1 as an eluent.
Pure 17 was obtained as an orange powder in a 87% yield (60 mg).
1H NMR (600 MHz, DMSO-d6)
d
¼ 4.09 (s, 5H), 4.35 (t, J ¼ 1.69 Hz,
2H), 4.79 (t, J ¼ 1.69 Hz, 2H), 6.97 (d, J ¼ 9.03 Hz, 2H), 7.71 (d,
J ¼ 8.66 Hz, 2H), 8.72 (s, 1H), 9.92 (s, 1H); 13C NMR (151 MHz,
DMSO-d6)
146.1, 157.5; IR (KBr)
d
¼ 66.4, 68.3, 69.3, 75.6, 116.0, 118.4, 121.5, 128.8,
n
[cmꢀ1]: 3142, 3074, 2934, 1596, 1522, 1386,
1281, 1225, 1101, 1063, 1003, 877, 836, 512, 498; Elemental
analysis. Calculated for C18H15FeN3O e C-62.63, H-4.38, N-12.17;
found: C-62.80, H-4.31, N-12.15.
Fig. 2. Voltammogram of 21a in the absence and in the presence of imidazole.
Ferrocene for comparison.
4.1.7.2. 4-Ferrocenyl-1-(4-hydroxybenzyl)-1H-1,2,3-triazole (19a).
The title compound was prepared in a 82% yield as an orange solid.
1H NMR (600 MHz, DMSO-d6)
d
¼ 4.01 (s, 5H), 4.28 (d, J ¼ 1.51 Hz,
4.1.7. Standard procedure for desilylation of silyl phenol ethers
4.1.7.1. 4-Ferrocenyl-1-(4-hydroxyphenyl)-1H-1,2,3-triazole (17).
659.4 mg, (2.09 mmol) of tetrabutylammonium fluoride trihy-
drate was added to a stirred solution of 96 mg (0.209 mmol) of 16
2H), 4.70 (d, J ¼ 1.51 Hz, 2H), 5.44 (s, 2H), 6.76 (d, J ¼ 8.66 Hz, 2H),
7.17 (d, J ¼ 8.28 Hz, 2H), 8.12 (s, 1H), 9.49 (s, 1H); 13C NMR (151 MHz,
DMSO-d6)
145.4, 157.2; IR (KBr)
d
¼ 52.5, 66.2, 68.1, 69.1, 76.0, 115.4, 120.3, 126.3, 129.3,
n
[cmꢀ1]: 3432, 3126, 3016, 2807, 1618, 1595,
1523, 1435, 1282, 1254, 1223, 1173, 1103, 1063, 811, 511; Elemental
analysis. Calculated for C19H17FeN3O e C-63.53, H-4.77, N-11.70;
found: C-63.61, H-4.91, N-11.69.
Table 3
Cytotoxic activities of prepared phenols. IC50 values, n ¼ 6.
Compound
Tamoxifen
HCC38 [
14.9
mM]
MCF-7[
mM]
4.1.7.3. 4-Ferrocenyl-1-(3,5-dihydroxybenzyl)-1H-1,2,3-triazole (19b).
It was prepared in a 37.8% overall yield in two steps without
isolation of the TBDMS. Ether 18b was prepared using the same
method as 15 starting from 433 mg of 3,5-bis(tert-butyldime-
thylsilyloxy)benzyl azide 10b instead of 2. The crude product,
isolated by extraction with ethyl acetate from the reaction mixture,
was used in the next step without further purification. Desilylation
of the crude product was carried out as described for 17. Pure 19b
was obtained as an orange solid (142 mg) by chromatography on
silica gel (100 cm3) using dichloromethaneeethyl acetate 9e1. 1H
13.1
OH
N
17
15.3
NA
N
N
e
F
OH
N
N
19a
19b
>100
>100
NA
N
Fe
Fe
NMR (600 MHz, DMSO-d6)
d
¼ 4.03 (s, 5H), 4.29 (t, J ¼ 1.69 Hz, 2H),
OH
OH
4.72 (t, J ¼ 1.69 Hz, 2H), 5.39 (s, 2H), 6.10 (d, J ¼ 1.88 Hz, 2H), 6.14
(t, J ¼ 2.07 Hz, 1H), 8.15 (s, 1H), 9.29 (s, 2H); 13C NMR (151 MHz,
N
N
>100
N
DMSO-d6)
d
¼ 52.7, 66.2, 68.1, 69.2, 76.0, 102.0, 105.3, 120.7, 138.1,
145.5, 158.6; IR (KBr)
n
[cmꢀ1]: 3126, 1623, 1604, 1485, 1464, 1362,
1336, 1231, 1167, 1064, 1016, 847, 825, 760, 669, 507; Elemental
analysis. Calculated for C19H17FeN3O2 e C-60.82, H-4.57, N-11.20;
found: C-60.59, H-4.72, N-11.03.
OH
21a
48.9
98.8
N
N
N
Fe
4.1.7.4. 1-Ferrocenyl-4-(4-hydroxyphenyl)-1H-1,2,3-triazole (21a).
The title compound was prepared in a 98% yield as an orange solid.
HO
N
1H NMR (600 MHz, DMSO-d6)
d
¼ 4.25 (s, 5H), 4.37 (t, J ¼ 1.7 Hz,
OH
2H), 5.04 (t, J ¼ 1.9 Hz, 2H), 6.88 (d, J ¼ 8.3 Hz, 2H), 7.74 (d, J ¼ 8.7
21b
23
NA
NA
Hz, 2H), 8.81 (s, 1H), 9.60 (s, 1H); 13C NMR (151 MHz, DMSO-d6)
N
N
Fe
d
¼ 62.1, 67.0, 70.4, 94.1, 116.1, 119.8, 121.9, 127.2, 147.5, 157.9; IR
(KBr)
n
[cmꢀ1]: 3423, 3132, 3113, 2925, 1701, 1617, 1561, 1496, 1443,
HO
1276, 1222, 1173, 1107, 1037, 877, 837, 813, 489; Elemental analysis.
Calculated for C18H15FeN3O e C-62.63, H-4.38, N-12.17; found:
C-62.56, H-4.31, N-12.01.
OH
N
N
22.9
84.0
N
Fe
4.1.7.5. 1-Ferrocenyl-4-(3,5-dihydroxyphenyl)-1H-1,2,3-triazole (21b).
The title compound was prepared in a 93% yield as an orange solid. 1H
HO
OH
NMR (600 MHz, DMSO-d6)
d
¼ 4.23 (s, 5H), 4.36 (t, 2H, J ¼ 1.69 Hz),
N
N
5.05 (t, 2H, J ¼ 1.69 Hz), 6.23 (t, 1H, J ¼ 2.07 Hz), 6.80 (d, 2H,
26
30.6
>100
N
J ¼ 2.26 Hz), 8.83 (s, 1H), 9.36 (s, 2H); 13C NMR (151 MHz, DMSO-d6)
Fe
d
n
¼ 61.6, 66.5, 69.9, 93.5,102.4,103.7,120.5,131.9,147.0,158.8; IR (KBr)
[cmꢀ1]: 3096, 2923, 1618, 1453, 1382, 1226, 1153, 1105, 1051, 1001,

_
110
D. Plazuk et al. / Journal of Organometallic Chemistry 715 (2012) 102e112
Fig. 3. Viability of cancer cell lines in the presence of tamoxifen and prepared phenols.
880, 842, 687, 505; Elemental analysis. Calculated for C18H15FeN3O2 e
C-59.86, H-4.19, N-11.63; found: C-59.93, H-4.32, N-11.82.
1628, 1610, 1485, 1431, 1306, 1157, 1106, 1052, 1005, 881, 846, 818,
507; Elemental analysis. Calculated for C18H15FeN3O2 e C-59.86,
H-4.19, N-11.63; found: C-59.95, H-4.24, N-11.68.
4.1.7.6. 4-Ferrocenyl-1-(3,5-dihydroxyphenyl)-1H-1,2,3-triazole (23).
1 cm3 of boron tribromide was added dropwise at ꢀ78 ꢃC to
a solution of 150 mg (0.385 mmol) of 22 in 10 cm3 of anhydrous
dichloromethane. The resulting solution was stirred at ꢀ78 ꢃC, then
the cooling bath was removed and the stirring was continued at RT
for a further 23 h. The reaction was then quenched by addition of
75 cm3 of saturated sodium hydrogen carbonate, and the product
was extracted with ethyl acetate. The organic solution was washed
with water, brine and dried with sodium sulphate. The pure product
was isolated by column chromatography on silica gel (50 cm3) using
ethyl acetate in dichloromethane (gradient 50e100% of ethyl
acetate) as an eluent. The yield was 16% (21.2 mg) of a yellow
4.1.7.7. 4-Ferrocenyl-1,5-bis(4-benzyloxyphenyl)-1H-1,2,3-triazole
(25). 218 mg (0.5 mmol) of 24 and 302 mg (1 mmol) of tetra-n-
butylammonium acetate and 197.3 mg (0.75 mmol) of 4-benzyloxy-
1-bromobenzene were placed in the Schlenk tube and 1.5 cm3
of anhydrous 1-methyl-2-pyrrolidinone was added. 18 mg of
bis(triphenylphosphine)dichloropalladium (0.025 mmol, 20%mol)
was added andthe tubewas placedin an oilbath preheated to 100 ꢃC.
The reaction mixture was stirred at 100 ꢃC for 2 h and the solvent was
evaporated to dryness. The pure product was isolated by two chro-
matographies on silica gel (the first chromatography was performed
using 50 cm3 of silica, for the second chromatography 100 cm3 of
silica gel was used) using chloroform as an eluent. Pure 25 was
obtained as an orange foam in an 81% yield (257 mg). 1H NMR
powder. 1H NMR (600 MHz, DMSO-d6)
d
¼ 4.08 (s, 5H), 4.34 (t,
J ¼ 1.69 Hz, 2H), 4.79 (t, J ¼ 1.69 Hz, 2H), 6.32 (t, J ¼ 1.88 Hz, 1H),
6.78 (d, J ¼ 2.26 Hz, 1H), 7.35 (d, J ¼ 1.51 Hz, 2H), 8.75 (s, 1H), 9.79
(600 MHz, DMSO-d6)
(s, 2H) 5.15 (s, 2H) 7.07 (d, J ¼ 9.03 Hz, 2H) 7.14 (d, J ¼ 8.66 Hz, 2H)
d
¼ 4.03 (s, 5H) 4.25 (s, 2H) 4.40 (s, 2H) 5.12
(s, 2H); 13C NMR (151 MHz, DMSO-d6)
d
¼ 68.3, 69.2, 75.3, 98.0,
102.2, 118.2, 128.2, 146.2, 159.2; IR (KBr)
n
[cmꢀ1]: 3091, 2924,
7.32e7.37 (m, 6H) 7.38e7.43 (m, 4H) 7.43e7.46 (m, 2H) 7.48 (d,

_
D. Plazuk et al. / Journal of Organometallic Chemistry 715 (2012) 102e112
111
J ¼ 7.15 Hz, 2H); 13C NMR (151 MHz, DMSO-d6)
d
¼ 66.4, 68.3, 69.2,
the Iuventus Plus grant for the years 2010e2011). The Polish
Ministry of Science and Higher Education had no impact on study
design; on the collection, analysis and interpretation of data; on the
writing of the report; and on the decision to submit this article for
publication.
69.6, 75.4, 115.7, 118.4, 118.5, 121.3, 121.4, 127.7, 127.9, 128.4, 130.2,
136.7, 146.3, 158.1; IR (KBr)
n
[cmꢀ1]: 3090, 3033, 1617, 1515, 1452,
1383, 1291, 1250, 1173, 1078, 991, 831, 734, 694; Elemental analysis.
Calculated for C38H31FeN3O2 e C-73.91, H-5.06, N-6.80; found: C-
73.94, H-5.14, N-7.03.
References
4.1.7.8. 1,5-Bis(4-hydroxyphenyl)-4-ferrocenyl-1H-1,2,3-triazole (26).
To a slurry of 153 mg (0.242 mmol) of 25 and 60 mg of 10%
palladium on active carbon in 10 cm3 of methanol, 1 cm3 of trie-
thylsilane was added dropwise under a balloon. The resulting
slurry was rapidly stirred at RT until the starting material dis-
appeared (2 h). The palladium on carbon was filtered off, washed
with methanol and the filtrate was evaporated to dryness. The
product was isolated by chromatography on silica gel (50 cm3)
using dichloromethaneemethanol (0 / 2% of methanol) as an
eluent. Pure 26 was obtained in a 64% yield (68.8 mg) as an orange
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powder. 1H NMR (600 MHz, DMSO-d6)
d
¼ 4.01 (s, 5H) 4.23 (t,
J ¼ 1.88 Hz, 2H) 4.41 (t, J ¼ 1.69 Hz, 2H) 6.77 (d, J ¼ 8.66 Hz, 2H) 6.85
(d, J ¼ 8.66 Hz, 2H) 7.17 (d, J ¼ 2.63 Hz, 2H) 7.18 (d, J ¼ 3.01 Hz, 2H)
9.83 (br. s., 2H); 13C NMR (151 MHz, DMSO-d6)
d
¼ 66.3, 68.0, 69.0,
76.1, 115.4, 115.4, 117.7, 126.7, 127.8, 131.7, 133.0, 142.4, 157.7,
158.1; IR (KBr)
n
[cmꢀ1]: 3304, 3110, 2926, 1617, 1519, 1459,
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Acknowledgements
The authors are grateful to the Polish Ministry of Science and
Higher Education for financial support (financial support through

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