Synthesis, characterization and cytotoxic effect of ring-substituted and ansa-bridged vanadocene complexes

Article abstract of DOI:10.1016/j.ica.2011.03.034

The cytotoxic effect of vanadocene dichloride (Cp₂VCl ₂, 1) and its ring-substituted, (η⁵-C ₅H₄Me)₂VCl₂ (2), (η⁵-C₅Me₅)₂VCl₂ (3), (η⁵-C₅H₄R)₂VCl₂ (4: R = MeOCH₂CH₂-, 5: R = 2-MeOC₆H ₄CH₂-, 6: R = 4-MeOC₆H₄CH ₂-) and ansa-bridged analogs Me₂C(η⁵-C ₅H₄)₂VCl₂ (7) and Me ₄C₂(η⁵-C₅H₄) ₂VCl₂ (8) was investigated. Synthesis of two new methoxy-functionalized compounds (4 and 5) is described. They were characterized by spectroscopic methods and X-ray diffraction analysis. The cytotoxicity studies were performed with leukemic cells MOLT-4.

Full text of DOI:10.1016/j.ica.2011.03.034

Inorganica Chimica Acta 373 (2011) 1–7
Contents lists available at ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Synthesis, characterization and cytotoxic effect of ring-substituted
and ansa-bridged vanadocene complexes
a,
a
a
a
b
⇑
ˇ
ˇ
ˇ
ˇ
Jan Honzícek , Iva Klepalová , Jaromír Vinklárek , Zdenka Padelková , Ivana Císarová ,
c
c
ˇ
ˇ
Pavel Šiman , Martina Rezácová
a Department of General and Inorganic Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic
b Department of Inorganic Chemistry, Faculty of Natural Science, Charles University in Prague, Hlavova 2030, 128 40 Praha 2, Czech Republic
c Department of Medical Biochemistry, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, 500 01 Hradec Králové, Czech Republic
a r t i c l e i n f o
a b s t r a c t
The cytotoxic effect of vanadocene dichloride (Cp2VCl2, 1) and its ring-substituted, (g
5-C5H4Me)2VCl2 (2),
Article history:
(g (g
5-C5Me5)2VCl2 (3), 5-C5H4R)2VCl2 (4: R = MeOCH2CH2–, 5: R = 2-MeOC6H4CH2–, 6: R = 4-MeO-
Received 2 September 2010
Received in revised form 16 February 2011
Accepted 5 March 2011
C6H4CH2–) and ansa-bridged analogs Me2C(g g
5-C5H4)2VCl2 (7) and Me4C2( 5-C5H4)2VCl2 (8) was investi-
gated. Synthesis of two new methoxy-functionalized compounds (4 and 5) is described. They were
characterized by spectroscopic methods and X-ray diffraction analysis. The cytotoxicity studies were per-
formed with leukemic cells MOLT-4.
Available online 13 March 2011
Keywords:
Ó 2011 Elsevier B.V. All rights reserved.
Bent metallocene
Vanadocene dichloride
Cytotoxicity
Antitumor agent
X-ray structure
Leukemia
1. Introduction
carboxylate, thiolate, amino acid led to limited improvements be-
cause putative active species ‘‘Cp2M’’ stay unchanged. However, this
Chemotherapy is the major strategy in the treatment of human
leukemia. This area has experienced intensive advance during
recent years. For example, the frequency of complete response
achieved with initial treatment of chronic lymphocytic leukemia
has increased from less than 5% with single-agent alkylators to
more than 50% with multiagent chemoimmunotherapy over the
past 20 years [1]. But even now, the prognosis of some leukemia
types is not satisfactory. Resistant forms of chronic lymphocytic
leukemia still exist. The adults suffering from the acute lympho-
blastic leukemia almost universally relapse after the conventional
chemotherapeutical protocols [2]. Therefore new chemotherapeu-
tical strategies are desperately needed.
Bent metallocene complexes (Cp2MX2; M = Ti, V, Mo;
X = halide) are known as the potent antitumor agents with low gen-
eral toxicity [3,4]. So far the main attention has been focused on
titanocene dichloride (Cp2TiCl2; TDC). It has given promising results
in preclinical [5] and phase I of the clinical trials [6]. However,
disappointing results from phase II of the trials [7,8] stimulated
enhanced interest in the modified compounds. The modifications
ofthedihalides Cp2MX2 done by exchangeofX for X0 = pseudohalide,
type of substitution can overcome the problems of the parent com-
pounds with biological incompatibility [9] and low water solubility
[10].
Modification of the cyclopentadienyl rings is a more promising
approach for solving above mentioned problems. Moreover, it
could be a potent tool for drug design enabling a fine tuning of
the cytostatic effects or
a design of the bifunctional drugs
[11,12]. Indeed, recent preclinical tests made with some new
titanocene compounds show improved activity toward the cis-
platin resistant tumor cell lines depending on the substituents
used [13–16]. The Cp ring modifications could be also used for
studies elucidating the mechanism of antitumor action. For this
purpose, the compounds with luminescent markers connected to
Cp rings were designed [17]. In the case of the group V and group
VI metallocenes, only few ring-substituted compounds were the
subjects of the biological studies [18–20].
Currently ongoing comprehensive study of the antitumor
activity mechanism of bent metallocenes [21–28] and our long-
standing interest in chemistry of Cp2VCl2 (1) led us to examine
its cytotoxic activity toward T-lymphocytic leukemia cells MOLT-
4. This study is focused on the substitution effect. It includes
methyl-substituted (
methoxy-substituted
g
5-C5H4Me)2VCl2 (2), (
g
5-C5Me5)2VCl2 (3),
⇑
Corresponding author. Fax: +420 46603 7068.
E-mail address: jan.honzicek@upce.cz (J. Honzícek).
(g
5-C5H4R)2VCl2 (4: R = MeOCH2CH2–,
ˇ
0020-1693/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2011.03.034

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J. Honzícek et al. / Inorganica Chimica Acta 373 (2011) 1–7
2
5: R = 2-MeOC6H4CH2–, 6: R = 4-MeOC6H4CH2–), ansa-bridged
vanadocene dichlorides Me2C(
5-C5H4)2VCl2 (7) and Me4C2(g5
C5H4)2VCl2 (8), Scheme 1. While this work was in progress, Tacke
et al. reported two largely complementary studies of the antitumor
properties of the six methoxybenzyl-substituted vanadocene
derivatives [18,19], one of which (6) is among those investigated
here.
tonation of methoxy-substituted cyclopentadienes (9–11) with
MeMgCl produces appropriate cyclopentadienides that react
with V(acac)3 to give appropriate vanadocene(III) monochlorides
g
-
(g
5-C5H4R)2VCl. These intermediates were not isolated. They were
treated with PCl3 to give desired dichloride compounds 4–6. Of
course, one may expect appearance of acetylacetonates
(g
5-C5H4R)2V(acac) as the intermediates instead of monochlorides.
However, the previous study on ansa-vanadocenes have shown
that the vanadocene(III) acetylacetonates are very reactive toward
ligand exchange. If they appear they readily react with MgCl2 to
give chloride analogs [34].
2. Results and discussion
2.1. Preparation and characterization
Starting cyclopentadiene 9 was prepared from sodium cyclo-
pentadienide and 2-chloroethyl methyl ether according to proce-
dure published elsewhere [35]. Fulvene protocol was used for
synthesis of cyclopentadienes 10 and 11, see Scheme 3 [36]. Meth-
oxybenzaldehydes 12 and 13 react with cyclopentadiene in pres-
ence of pyrrolidine to give fulvenes 14 and 15, respectively.
These were obtained in high yield and characterized by NMR spec-
troscopy. The addition of LiAlH4 to fulvenes 14 and 15 produces
cyclopentadienes 10 and 11, respectively. The NMR spectroscopic
measurements prove that CDCl3 solutions of cyclopentadienes 10
and 11 consist of 1- and 2-isomer in molar ratio 1:1, see Scheme
3. Both these cyclopentadienes show two signals of the cyclopenta-
diene CH2 protons (10: 3.29 and 3.23 ppm; 11: 3.00 and 2.88 ppm)
in 1H NMR spectrum. No information about the assignment of the
signals among 1- and 2-isomer was obtained.
Literature procedures were used for synthesis of vanado-
cene(IV) dichlorides 1–3 and 7–8 [29–33]. Compounds 4–6 were
prepared according to the procedure previously used for the prep-
aration of ansa-vanadocene compounds (Scheme 2) [32,34]. Depro-
New methoxy-substituted compounds 4 and 5 were character-
ized by EPR and IR spectroscopy. The EPR spectra measured in
dichloromethane showed expected eight-line hyperfine coupling
(HFC), corresponding to the nuclear spin value of 51V (I = 7/2), see
Fig. 1. Isotropic HFC constant and isotropic g-factor (4:
|Aiso| = 69.4 ꢀ 10ꢁ4 cmꢁ1, giso = 1.990; 5: |Aiso| = 69.5 ꢀ 10ꢁ4 cmꢁ1
,
giso = 1.991) were found to be in the narrow range close to the val-
ues of the unsubstituted analog
1
(|Aiso| = 69.1 ꢀ 10ꢁ4 cmꢁ1
,
giso = 1.989). The substitution in the cyclopentadienyl ring has only
low effect on these parameters, because the unpaired electron
occupies the orbital that is antibonding to the bonds V–Cl [27,30].
Infrared spectra of the compounds 4 and 5 show a pattern that
is consistent with proposed structures. The presence of the substi-
tuted
g
5-bonded cyclopentadienyl rings is evident mainly from
medium absorption bands of C–H stretching (mC–H ꢂ 3105 cmꢁ1).
The methoxyethyl compound 4 shows the band of C–O stretching
at ꢂ1113 cmꢁ1. The spectrum of the compounds 5 show C–C
stretching of benzene ring at ꢂ1600 cmꢁ1 and C–O stretching at
ꢂ1245 cmꢁ1. These vibration bands are characteristic for methoxy-
benzyl-substituted compounds.
Scheme 1. Vanadocene complexes used in the cytotoxicity study.
2.2. X-ray structures of compounds 4 and 5
Structures of the compounds 4 and 5 were determined by single-
Scheme 2. Synthesis of ring-substituted vanadocene dichlorides 4–6.
crystal X-ray diffraction analysis, see Figs.
2 and 3. These
Scheme 3. Synthesis of cyclopentadienes 9–11.

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3
Fig. 1. EPR spectrum of dichloromethane solution of compound 4 (m = 9.428 GHz).
Fig. 3. ORTEP drawing of the compound 5 with atom numbering (ellipsoids: 50%
probability). Selected bond lengths (Å) and angles (deg): Cg(C1–C5)–V1 1.9743(7),
V1–Cl1 2.4135(4), C8–O1 1.3664(16), C13–O1 1.4302(17), Cg(C1–C5)–V1–Cg(C1–
C5) 132.23(3), Cl1–V1–Cl1a 86.76(2), C8–O1–C13 116.71(11). Cg – centroid of the
cyclopentadienyl ring.
methoxyethyl group above the Cl–V–Cl moiety and the second
group placed on the side of the molecule.
2.3. Cytotoxicity studies
We used standard WST-1 viability assays [39] to examine the
cytotoxic activity of vanadocene dichloride (1) and its derivatives
2–8. Cytotoxic effect was evaluated on human T-lymphocytic leu-
kemia cells MOLT-4 in exponential grow phase, 24 h after the incu-
bation with the cytostatic drugs.
It was observed that substitution with methyl groups in the
cyclopentadienyl rings causes significant decrease of cytotoxicity
as was evidenced at compounds 2 and 3 (Fig. 4). Both dimethyl-
(2) and decamethyl- (3) derivatives showed lower cytotoxic effect
Fig. 2. ORTEP drawing of the compound 4 with atom numbering (ellipsoids: 30%
probability). Selected bond lengths (Å) and angles (°): Cg(C1–C5)–V1 1.9812(12),
Cg(C9–C13)–V1 1.9811(12), V1–Cl1 2.4018(7), V1–Cl2 2.3868(7), C7–O1 1.417(3),
C8–O1 1.420(3), C15–O2 1.364(4), C16–O2 1.442(4), Cg(C1–C5)–V1–Cg(C9–C13)
132.21(5), Cl1–V1–Cl1 86.70(3), C7–O1–C8 111.43(19), C15–O2–C16 111.6(3). Cg –
centroid of the cyclopentadienyl ring.
(2: IC50 = 96 12
unsubstituted analog 1 (70
substituent on cytotoxicity is very similar. The IC50 value of the
compound 4 was found to be 105 10 mol/L (Fig. 4).
lmol/L; 3: IC50 = 152 10
lmol/L) than the
7
lmol/L). Effect of methoxyethyl
l
The highest cytotoxic effect was detected at methoxybenzyl
derivatives 5 and 6 (Fig. 5). Both ortho- (5) and para- (6) deriva-
tives have shown increased cytotoxic effect with IC50 values
compounds have a distorted tetrahedral coordination around vana-
33 11
l
mol/L and 11
7 lmol/L, respectively. This observation
dium(IV) with two
g
5-bonded substituted cyclopentadienyl rings
is in line with the recently published tests on cell line LLC-PK
(long-lasting cells-pig kidney) with compound 6 [19] and analo-
gous titanocene derivative [40]. Our experiment clearly shows
the importance of the methoxy group position in the benzene ring,
since the compound 6 has three times lower IC50 value compared
to the compound 5.
The effect of the connection of the cyclopentadienyl rings by
interannular bridge was studied on the ansa-vanadocenes 7 and
8 (Fig. 6). Both compounds exhibit similar cytotoxic effect (7:
and two chlorides. The distances V–Cg(Cp) (4: 1.9811(12),
1.9812(12) Å; 5: 1.9743(7) Å), V–Cl (4: 2.3868(7), 2.4018(7) Å;
5: 2.4135(4) Å) and the bond angles Cg(Cp)–V–Cg(Cp) (4:
132.21(5)°; 2: 132.23(3)°) and Cl–V–Cl (4: 86.70(3)°; 5: 86.76(2)°)
were found to be in the range usual for vanadocene dichloride
[37] and its ring-substituted analogs [18,19,38]. The Cp rings of
the compounds 4 and 5 are in the staggered conformation. The
compound 5 has a rigorous overall C2 molecular symmetry with
the methoxybenzyl groups placed far apart on the sides of the mol-
ecule. The compound 4 shows different conformation with one
IC50 = 80 10
vanadocene analog 1.
lmol/L; 8: IC50 = 65 14 lmol/L) to the unbridged

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J. Honzícek et al. / Inorganica Chimica Acta 373 (2011) 1–7
Fig. 4. Cytotoxicity curves showing the effect of the compounds 1–4 on the viability of the leukemic cells MOLT-4.
Fig. 5. Cytotoxicity curves showing the effect of the compounds 5, 6 on the viability of the leukemic cells MOLT-4.
than parent compound (1). This discrepancy led us to search for
3. Conclusions
the differences in hydrolytic behavior of the most effective vanado-
cene (5) and its unsubstituted vanadocene 1.
Recently published studies have shown that substitution with
various methoxybenzyls in the cyclopentadienyl generates vana-
docene compounds with increased cytotoxicity and brings promis-
ing candidates for anticancer drugs [19,20].
The obvious assumption that the increased cytotoxicity could
be promoted with the better cell uptake of more lipophilic com-
pounds led us to investigate a larger set of the modified com-
pounds with various unpolar groups. However, the improved
properties were observed only for the methoxybenzyl-substituted
compounds 5 and 6. The other modified vanadocenes under this
study have shown similar (7 and 8) or lower cytotoxicity (2–4)
Previous experiments have shown that compound 1 hydrolyzes
immediately after dissolution in water to give appropriate aqua-
complexes [Cp2V(OH2)2]2+ [41,32]. The behavior in the mixtures
DMSO/water in the air atmosphere is very similar. Our EPR mea-
surements have shown appearance [Cp2V(OH2)Cl]+ (|Aiso| = 71.9 ꢀ
10ꢁ4 cmꢁ1
,
giso = 1.985) and [Cp2V(OH2)2]2+ (|Aiso| = 74.0 ꢀ
10ꢁ4 cmꢁ1, giso = 1.979). As expected, the degree of hydrolysis
depends on the DMSO/water ratio.
Hydrolysis of compound 5 was studied only in the mixtures
DMSO/water because benzyl-substituted vanadocenes are insoluble

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5
Fig. 6. Cytotoxicity curves showing the effect of the compounds 7 and 8 on the viability of the leukemic cells MOLT-4.
in water. The EPR spectroscopic measurements have proven lower
stability of the (
5-C5H4R)2V moiety in case of the compound 5 in
incubator at 37 °C and a controlled 5% CO2 atmosphere. The cell
lines in the maximal range of up to 20 passages have been used
for this study.
g
the air atmosphere. The expected hydrolytic products [(g5
-
C5H4R)2V(OH2)Cl]+ (|Aiso| = 72.0 ꢀ 10ꢁ4 cmꢁ1
,
giso = 1.983) and
Cytotoxicity of the compounds 1–8 was evaluated by the WST-1
cell viability test (Roche, Germany) according to manufacturer’s
instructions. The assay is based on the reduction of WST-1 (4-[3-
(4-Iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene
disulfonate) by viable cells. The reaction produces a colored solu-
ble formazan salt [39]. The absorbance at 440 nm was measured
using multiplate reader (Tecan Infinite 200). Compounds 1–8 were
dissolved in DMSO and diluted by cultivation medium to desired
concentrations. The MOLT-4 cells were seeded in 96-wells plate,
incubated in 1–1000 lmol/L solutions of the compounds 1–8 for
24 h, then washed in pure media and incubated for 180 min in
WST-1 solution. The same cells incubated in the cultivation media
only were used as the control. High concentrations (>300 lmol/L)
[(
g
5-C5H4R)2V(OH2)2]2+ (|Aiso| = 74.0 ꢀ 10ꢁ4 cmꢁ1, giso = 1.980) are
formed only as minor products. The major products have consider-
ably higher |Aiso| constants than the known vanadocene complexes.
[VO(H2O)3Cl]+ (|Aiso| = 101.0 ꢀ 10ꢁ4 cmꢁ1, giso = 1.973) is formed at
high DMSO concentrations. The full hydrolysis was observed at
low
DMSO
concentrations.
It
gives
[VO(H2O)4]2+
(|Aiso| = 106.7 ꢀ 10ꢁ4 cmꢁ1, giso = 1.968) as the major product.
The experiments described here suggest that benzyl-substituted
vanadocenes have different mechanism of the cytotoxic action on
the molecular level than unsubstituted vanadocene dichloride. Of
course, it is not conclusive, which of the hydrolytic products
([Cp02V(OH2)2]2+, [VO(H2O)4]2+ or Cp0H) is the ‘‘active species’’ or
the precursor of the ‘‘active species’’ that reaches the target in the
tumor cell. Nevertheless, this study has proven that the substitution
in the cyclopentadienyl can considerably change not only the bio-
logical properties of the metallocene complexes but also their
hydrolytic behavior.
of the compounds 5 and 6 form significant clouding and therefore
could not be measured. However, the compounds are cytotoxic in
the concentrations below these limits.
4.3. Synthesis of 6-(2-methoxyphenyl)fulvene
Pyrrolidine (25 mL, 0.3 mol) was added dropwise to the mixture
of freshly monomerized cyclopentadiene (42 mL, 0.5 mol) and
2-methoxybenzaldehyde (27.2 g, 0.2 mol) of in 200 mL of metha-
nol. After the addition was complete, the solution was stirred at
room temperature for 60 min and then 18 mL (0.32 mol) of acetic
acid was added. The dark red reaction mixture was diluted with
diethyl ether and water. The aqueous layer was washed twice with
pentane. The combined organic portions were washed three-times
with saline and dried over anhydrous MgSO4. The volatiles were
evaporated in vacuo. The crude product (dark red liquid) was used
without further purification. Yield: 35.8 g (97%). 1H NMR (CDCl3): d
7.73 [d, 1H, C6H4], 7.71 [s, 1H, CpCHPh], 7.44 [t, 1H, C6H4], 7.11 [t,
1H, C6H4], 6.98 [d, 1H, C6H4], 6.78 [s, 2H, C5H4], 6.65 [d, 1H, C5H4],
6.51 [d, 1H, C5H4], 3.93 [s, 3H, OCH3)2].
4. Experimental
4.1. Methods and materials
All operations were performed under nitrogen using conven-
tional Schlenk-line techniques. The solvents were purified and
deoxygenated by standard methods [42]. Cp2VCl2 (1) [29],
(g
5-C5H4Me)2VCl2 (2) [30], (
g -
5-C5Me5)2VCl2 (3) [31], Me2C(g5
C5H4)2VCl2 (7) [32], Me4C2(
g
5-C5H4)2VCl2 (8) [33], 6-(4-methoxy-
phenyl)fulvene [43] and methoxyethylcyclopentadiene (9) [35]
were prepared according literature procedures. IR spectra were re-
corded in the 4000–400 cmꢁ1 region on a Nicolet Magna 550 FT-IR
spectrometer using KBr pellets or Nujol mull between KBr win-
dows. 1H NMR spectra were recorded on Bruker 360 and
500 MHz spectrometers at room temperature. The EPR spectra
were recorded on Miniscope MS 200 and Miniscope MS 300 spec-
trometers at X-band at ambient temperature.
4.4. Synthesis of (2-methoxybenzyl)cyclopentadiene (10)
6-(2-Methoxyphenyl)fulvene (18.4 g, 0.1 mol) of was added
dropwise to the mixture of LiAlH4 (3.8 g, 0.1 mol) in ether
(250 mL) at 0 °C. After the addition was complete, the mixture
was stirred at room temperature for 12 h. The reaction mixture
was then slowly poured onto the mixture ice-water. The organic
layer was separated. The water layer was then washed with
200 mL of diethyl ether. The combined organic portions were
washed four times with saline, dried over anhydrous MgSO4 and
4.2. Cytotoxicity studies
The studies were performed on the human T-lymphocytic leu-
kemia cells MOLT-4 obtained from the American Type Culture Col-
lection (USA). The cells were cultured in Iscove’s modified
Dulbecco’s medium supplemented with a 20% fetal calf serum
and 0.05% L-glutamine (all Sigma–Aldrich, USA) in a humidified

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J. Honzícek et al. / Inorganica Chimica Acta 373 (2011) 1–7
Table 1
concentrated in vacuo. The product was distilled at 40 °C (50 Pa)
giving light orange liquid. Yield: 12.7 g (68%). 1H NMR(CDCl3): d
7.52, 7.46 [2 ꢀ t, 2H of A and 2H of B, C6H4], 7.22 [t, 1H of A and
1H of B, C6H4], 7.17, 7.16 [2 ꢀ d, 1H of A and 1H of B, C6H4], 6.82
[m, 1H of A or B, C5H5], 6.75 [m, 1H of A or B, C5H5], 6.74 [m, 1H
of A or B, C5H5], 6.59 [d, 2H of A or B, C5H5], 6.50 [s, 1H of A or B,
C5H5], 6.35 [s, 1H of A or B, C5H5], 4.11, 4.10 [2 ꢀ s, 2H of A and
2H of B, CpCH2Ph], 4.09 [s, 3H of A and 3H of B, OCH3], 3.29, 3.23
[2 ꢀ m, 2H of A and 2H of B, C5H5].
Crystallographic data for the compounds 4 and 5.
Compounds
4
5
Formula
Crystal system
Space group
a (Å)
b (Å)
c (Å)
C
16H22Cl2O2V
C26H26Cl2O2V
monoclinic
C2/c
23.7980(6)
6.82004(10)
14.6928(4)
113.7262(12)
4
monoclinic
P21/c
20.5657(5)
6.9761(5)
11.3962(13)
99.506(4)
4
b (°)
Z
l
(mmꢁ1
)
0.947
1.517
0.721
1.498
4.5. Synthesis of (4-methoxybenzyl)cyclopentadiene (11)
Dx (g cmꢁ3
)
Crystal size (mm)
Crystal color
Crystal shape
h range (°)
0.26 ꢀ 0.20 ꢀ 0.14 0.40 ꢀ 0.27 ꢀ 0.25
The steps of synthesis followed the procedure for compound 10.
Reagents: 6-(4-methoxyphenyl)fulvene (18.4 g, 0.1 mol), LiAlH4
(3.8 g, 0.1 mol). The product was distilled at 45 °C (50 Pa) giving
light orange liquid. Yield: 16.9 g (91%). 1H NMR(CDCl3): d 7.17,
7.14 [2 ꢀ d, 2H of A and 2H of B, C6H4], 6.89, 6.87 [2 ꢀ d, 2H of A
and 2H of B, C6H4], 6.47 [d, 1H of A or B, C5H5], 6.46 [d, 2H of A
or B, C5H5], 6.31 [dd, 1H of A or B, C5H5], 6.20 [t, 1H of A or B,
C5H5], 6.04 [t, 1H of A or B, C5H5], 3.78 [s, 3H of A and 3H of B,
OCH3], 3.74, 3.70 [2 ꢀ s, 2H of A and 2H of B, CpCH2Ph], 3.00,
2.88 [2 ꢀ d, 2H of A and 2H of B, C5H5].
green
green
block
prism
2.0–27.5
ꢁ24/26, ꢁ9/8,
ꢁ14/14
13 459
1.9–27.5
ꢁ30/30, ꢁ8/8,
ꢁ18/18
14 682
h, k, l range
Number of reflections measured
Number of unique reflections; Rint
Number of observed reflections
a
3600, 0.044
2923
2502, 0.026
2279
[I > 2r(I)]
Number of parameters
190
142
Sb all data
1.033
1.025
Rc, wRc
0.0399, 0.0885
1.697, ꢁ0.525
0.0268, 0.0631
0.294, ꢁ0.354
Dq )
, maximum, minimum (e Åꢁ3
a
b
c
4.6. Synthesis of (MeOCH2CH2C5H4)2VCl2 (4)
Rint
S = [
R(F) =
=
R
R
|F2o ꢁ F2o;mean|/
R
F2o .
(w(F2o ꢁ F2c )2)/(Ndiffrs ꢁ Nparams)] for all data.
½
R
||Fo| ꢁ |Fc||/
R
|Fo|
for
observed
data,
wR(F2) = [
R
(w(F2o ꢁ F2c )2)/
MeMgCl (9.6 mL, 3 M solution in THF) was added dropwise to
the solution of the compound 9 (3.6 g; 28 mmol) in THF (80 mL).
The reaction mixture was stirred overnight. This solution was
added via cannula to the suspension of V(acac)3 (5 g, 14 mmol) in
THF (100 mL) precooled at ꢁ78 °C. The reaction mixture charged
to dark brown. After stirring for 1 h at the room temperature, the
reaction mixture was heated at reflux for 30 min. The solvents
were removed in vacuo and the solid residuum was extracted with
diethyl ether. The brown extract was treated with PCl3 (3.8 g,
28 mmol) and stirred overnight. The green precipitate of the com-
plex 4 was collected on the glass frit and washed with diethyl ether
(2 ꢀ 20 mL). The crude product was recrystallized from CH2Cl2/
hexane. Yield: 0.91 g (17%). Anal. Calc. for C16H22Cl2O2V: C, 52.19;
H, 6.02. Found: C, 52.12; H, 6.09%. EPR(CH2Cl2): giso = 1.990,
w(F2o)2)] for all data.
½
(
R
4.9. Crystallography
The X-ray data for crystals of 4 and 5 were obtained at 150 K
using Oxford Cryostream low-temperature device on a Nonius
KappaCCD diffractometer with Mo K
graphite monochromator, and the and
a
radiation (k = 0.71073 Å), a
scan mode. Data reduc-
u
v
tions were performed with DENZO-SMN [44]. In the case of 4, the
absorption was corrected by integration methods [45]. Structures
were solved by direct methods (SIR92) [46] and refined by full ma-
trix least-square based on F2
(SHELXL97) [47]. Crystallographic data
are summarized in Table 1.
Hydrogen atoms were mostly localized on a difference Fourier
map, however to ensure uniformity of treatment of crystal, all
hydrogen were recalculated into idealized positions (riding model)
and assigned temperature factors Hiso(H) = 1.2 Ueq(pivot atom) or
of 1.5 Ueq for the methyl moiety with C–H = 0.96, 0.97, and
0.93 Å for methyl, methylene and hydrogen atoms in Cp ring,
respectively.
|Aiso| = 74.8 G; IR(cmꢁ1
, Nujol mull): 3109m, 3097m, 3085m,
1113vs.
4.7. Synthesis of (2-MeOC6H4CH2C5H4)2VCl2 (5)
The steps of synthesis followed the procedure for compound 4.
Reagents: 10 (5.4 g, 28 mmol), 9.6 mL of MeMgCl (3 M solution in
THF), V(acac)3 (5 g, 14 mmol), PCl3 (3.8 g, 28 mmol). The crude
product was recrystallized from CH2Cl2/hexane. Yield: 1.22 g
(17%). Anal . Calc. for C26H26Cl2O2V: C 63.43; H 5.32. Found: C,
Acknowledgements
This work was supported by Czech Science Foundation (No.
GACR/203/09/P100) and Ministry of Education of the Czech Repub-
lic (No. MSM 0021627501).
63.24; H, 5.29%. EPR(CH2Cl2): giso = 1.991, |Aiso| = 74.8 G; IR(cmꢁ1
,
KBr pellet): 3105m, 2963m, 2928m, 2838s, 1629m, 1600s,
1494vs, 1246vs. IR(cm–1, Nujol mull): 3109m, 1598m, 1585m,
1244vs. Single crystal of 5 suitable for X-ray diffraction analysis
was prepared by careful layering of the CH2Cl2 solution with dou-
ble volume of hexane.
Appendix A. Supplementary material
CCDC 747083 and 747084 contain the supplementary crystallo-
graphic data for compounds 5 and 4, respectively. These data can
be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Supplemen-
tary data associated with this article can be found, in the online
version, at doi:10.1016/j.ica.2011.03.034.
4.8. Synthesis of (4-MeOC6H4CH2C5H4)2VCl2 (6)
The steps of synthesis followed the procedure for compound 4.
Reagents: 11 (5.4 g, 28 mmol), 9.6 mL of MeMgCl (3 M solution in
THF), V(acac)3 (5 g, 14 mmol), PCl3 (3.8 g, 28 mmol). Yield: 1.08 g
(15%). Anal. Calc. for C26H26Cl2O2V: C, 63.43; H, 5.32. Found: C,
References
63.31; H, 5.28%. EPR(CH2Cl2): giso = 1.990, |Aiso| = 74.8 G. IR(cmꢁ1
,
KBr pellet): 3101m, 3077s, 2964s, 2936m, 2838m, 1610s, 1583m,
1512vs, 1247vs.
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