Fluorinated Derivatives of Vanadocene Y
to colourless with a white precipitate formed. The precipitate was
filtered through a frit and was washed with 20 mL of diethyl ether.
The white precipitate was dried briefly under reduced pressure and
855 (s), 819 (m), 752 (m) cm–1. UV/Vis (CH2Cl2, nm): λ (ε) = 202
(336), 233 (20673), 281 (16991), 386 (13100) nm.
Synthesis of Bis{[4-(trifluoromethoxy)benzyl]cyclopentadienyl}vana-
dium(IV) Dichloride, [(η5-C5H4–CH2–C6H4–OCF3)]2VCl (3c): Su-
per Hydride (LiBEt3H) (15.0 mL,15.0 mmol, 1 solution) in THF
was concentrated by removal of the solvent by heating it to 60 °C
under reduced pressure of 10–2 mbar for 40 min and then to 90 °C
for 20 min in a Schlenk flask. The concentrated Super Hydride
was dissolved in 30 mL of dry diethyl ether to give a cloudy white
suspension. The red oil 1c (2.36 g, 9.9 mmol) was added to a
Schlenk flask and was dissolved in 90 mL of dry diethyl ether to
give a red solution. The red fulvene solution was transferred to the
Super Hydride solution via cannula. The solution was left to stir
for 8 h to give a white precipitate of the lithium cyclopentadienide
intermediate and the solution had changed colour from orange/red
to colourless with a white precipitate formed. The precipitate was
filtered through a frit and was washed with 20 mL of diethyl ether.
The white precipitate was dried briefly under reduced pressure and
was transferred to
a Schlenk flask under nitrogen. 1.83 g
(8.70 mmol, 83.7% yield) of the lithiated cyclopentadienide inter-
mediate 2a was obtained. The lithium cyclopentadienide intermedi-
ate was dissolved in 60 mL of dry THF to give a colourless solu-
tion. Vanadium tetrachloride (0.46 mL, 4.35 mmol) was added to
the lithium cyclopentadienide intermediate solution slowly at
–78 °C to give a dark red solution. The dark red vanadium solution
was refluxed for 20 h at 88 °C. After refluxing, the solution was
allowed to return to room temperature and then cooled to –78 °C
where a light green precipitate formed. The precipitate was filtered
through a frit and washed with 20 mL of THF and small quantities
of chloroform. The light green solid was then dissolved in chloro-
form and filtered through a frit to remove any remaining LiCl. The
solvent was removed under reduced pressure to yield a light green
crystalline solid (1.03 g, 1.95 mmol, 44.8% yield) 3a.
C26H24Cl2F2O2V (528.32): calcd. C 59.11, H 4.58, Cl 13.42, F 7.19;
found C 58.92, H 4.54, Cl 13.60, F 7.10. ESR (CH2Cl2 solution,
r.t.): 8-line hyperfine coupling, giso = 2.027, Aiso = 7.46 mT. MS
was transferred to
a Schlenk flask under nitrogen. 1.91 g
(7.76 mmol, 78.3% yield) of the lithiated cyclopentadienide inter-
mediate 2c was obtained. The lithium cyclopentadienide intermedi-
ate was dissolved in 60 mL of dry THF to give a colourless solu-
tion. 0.41 mL (3.88 mmol) of vanadium tetrachloride was added to
the lithium cyclopentadienide intermediate solution slowly at
–78 °C to give a dark red solution. The dark red vanadium solution
was refluxed for 20 h at 88 °C. After refluxing, the solution was
allowed to return to room temperature and the solvent was re-
moved under reduced pressure. The resulting green/brown solid was
washed with 60 mL of dry pentane and redissolved in chloroform.
The solution was then filtered through a frit to removed any re-
maining LiCl. The solvent was removed under reduced pressure
and the resulting green solid was again washed with 60 mL of dry
pentane and dried under reduced pressure to yield a green crystal-
line solid (0.82 g, 1.37 mmol, 35.7% yield) 3c. C26H20Cl2F6O2V
(600.28): calcd. C 52.02, H 3.36, Cl 11.81, F 18.99; found C 51.52,
H 3.33, Cl 11.75, F 18.86. ESR (CH2Cl2 solution, r.t.): 8-line hyper-
fine coupling, giso = 2.027, Aiso = 7.46 mT. MS (QMS-MS/MS):
(m/z, QMS-MS/MS): m/z = 492 [M – Cl]+. IR (KBr ): ν = 3108
˜
(s), 3086 (s), 2956 (w), 2914 (w), 2833 (w), 1623 (s), 1583 (m), 1506
(s), 1474 (w), 1437 (s), 1284 (s), 1261 (s), 1157 (s), 1103 (s), 1030
(s), 932 (w), 869 (s), 851 (m), 791 (m) cm–1. UV/Vis (CH2Cl2, nm):
λ (ε) = 202 (390), 231 (19895), 280 (17632), 387 (13421) nm.
Synthesis of Bis[(3-fluoro-4-methoxybenzyl)cyclopentadienyl]vanadi-
um(IV) Dichloride, [(η5-C5H4–CH2–C6H3F–OCH3)]2VCl2 (3b): Su-
per Hydride (LiBEt3H) (15.0 mL, 15.0 mmol, 1 solution) in THF
was concentrated by removal of the solvent by heating it to 60 °C
under reduced pressure of 10–2 mbar for 40 min and then to 90 °C
for 20 min in a Schlenk flask. The concentrated Super Hydride
was dissolved in 30 mL of dry diethyl ether to give a cloudy white
suspension. The red oil 1b (2.30 g,11.4 mmol) was added to a
Schlenk flask and was dissolved in 90 mL of dry diethyl ether to
give a red solution. The red fulvene solution was transferred to the
Super Hydride solution via cannula. The solution was left to stir
for 8 h to give a white precipitate of the lithium cyclopentadienide
intermediate and the solution had changed colour from orange/red
to colourless with a white precipitate formed. The precipitate was
filtered through a frit and was washed with 20 mL of diethyl ether.
The white precipitate was dried briefly under reduced pressure and
m/z = 564 [M – Cl]+. IR (KBr): ν = 3109 (m), 3088 (m), 2951 (w),
˜
2830 (w), 1509 (s), 1433 (m), 1270 (s, br), 1228 (s, br), 1152 (s),
1105 (m), 1021 (w), 876 (w), 838 (w), 813 (w) cm–1. UV/Vis
(CH2Cl2, nm): λ (ε) = 207 (657), 230 (12478), 289 (7806), 385 (3090)
nm.
was transferred to
a
Schlenk flask under nitrogen. 2.06 g
Cytotoxicity Studies: Preliminary in-vitro cell tests were performed
on the cell line LLC-PK (long-lasting cells–pig kidney), and the
human renal cell line Caki-1 in order to compare the cytotoxicity
of the compounds presented in this paper. These cell lines were
chosen based on their regular and long-lasting growth behaviour,
which is similar to the one shown in kidney carcinoma cells. They
were obtained from the ATCC (American Tissue Cell Culture Col-
lection) and maintained in Dulbecco’s Modified Eagle Medium
containing 10% (v/v) FCS (fetal calf serum), 1% (v/v) penicillin
streptomycin and 1% (v/v) -glutamine. Cells were seeded in 96-
well plates containing 200 µL microtitre wells at a density of 5000-
cells/200 µL of medium and were incubated at 37 °C for 24 h to
allow for exponential growth. Then the compounds used for the
testing were dissolved in the minimal amount of DMSO (dimethyl
sulfoxide) possible and diluted with medium to obtain stock solu-
tions of 5ϫ10–4 in concentration and less than 0.7% of DMSO.
The cells were then treated with varying concentrations of the com-
pounds and incubated for 48 h at 37 °C. Then, the solutions were
(9.8 mmol, 85.8% yield) of the lithiated cyclopentadienide interme-
diate 2b was obtained. The lithium cyclopentadienide intermediate
was dissolved in 60 mL of dry THF to give a colourless solution.
Vanadium tetrachloride (0.52 mL, 4.90 mmol) was added to the
lithium cyclopentadienide intermediate solution slowly at –78 °C
to give a dark red solution. The dark red vanadium solution was
refluxed for 20 h at 88 °C. After refluxing, the solution was allowed
to return to room temperature and then cooled to –78 °C where a
light green precipitate formed. The precipitate was filtered through
a frit and washed with 20 mL of THF and small quantities of chlo-
roform. The light green solid was then dissolved in chloroform and
filtered through a frit to remove any remaining LiCl. The solvent
was removed under reduced pressure to yield a light green crystal-
line solid (1.45 g, 2.74 mmol, 56.0% yield) 3b. C26H24Cl2F2O2V
(528.32): calcd. C 59.11, H 4.58, Cl 13.42, F 7.19; found C 59.01, H
4.58, Cl 13.51, F 7.12. ESR (CH2Cl2 solution, r.t.): 8-line hyperfine
coupling, giso = 2.027, Aiso = 7.46 mT. MS (QMS-MS/MS): m/z =
492 [M – Cl]+. IR (KBr): ν = 3135 (w), 3109 (m), 2939 (w), 2841 removed from the wells and the cells were washed with PBS (phos-
˜
(w), 1621 (w), 1584 (w), 1520 (s), 1479 (m), 1433 (m), 1394 (w), phate buffer solution) and fresh medium was added to the wells.
1319 (m), 1281 (s), 1223 (s), 1122 (s), 1025 (s), 956 (m), 869 (m), Following a recovery period of 24 h incubation at 37 °C, individual
Eur. J. Inorg. Chem. 2009, 2804–2810
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
2809
Gleeson, Brendan
