Synthesis and characterisation of mixed ligand Pt(ii) and Pt(iv) oxadiazoline complexes

Article abstract of DOI:10.1039/b807410k

The nitrile ligands in trans-[PtX₂(PhCN)₂] (X = Cl, Br, I) undergo sequential 1,3 dipolar cycloadditions with nitrones R ¹R²C=N⁺(Me)-O^- (R¹ = H, R² = Ph; R¹ = CO₂Et, R² = CH ₂CO₂Et) to selectively form the Δ⁴-1,2,4- oxadiazoline complexes trans-[PtX₂(PhCN) {N=C(Ph)-O-N(Me)-CR ¹R²}] or trans-[PtX₂{N=C(Ph)-O-N(Me)-CR ¹R²}₂] in high yields. The reactivity of the mixed ligand complexes trans-[PtX₂(PhCN){N=C(Ph)-O-N(Me)-CR ¹R²}] towards oxidation and ligand substitution was studied in more detail. Oxidation with Cl₂ or Br₂ provides the Pt(iv) species trans-[PtX₂Y₂(PhCN){N=C(Ph)-O-N(Me)- CH(Ph)}] (X, Y = Cl, Br). The mixed halide complex (X = Cl, Y = Br) undergoes halide scrambling in solution to form trans-[PtX_(4-n)Y _n(PhCN){N=C(Ph)-O-N(Me)-CH(Ph)}] as a statistical mixture. Ligand substitution in trans-[PtCl₂(PhCN){N=C(Ph)-O-N(Me)-CR ¹R²}] allows for selective replacement of the coordinated nitrile by nitrogen heterocycles such as pyridine, DMAP or 1-benzyl-2- methylimidazole to produce mixed ligand Pt(ii) complexes of the type trans- [PtX₂(heterocycle){N=C(Ph)-O-N(Me)-CR¹R²}]. All compounds were characterised by elemental analysis, mass spectrometry, IR and ¹H, ¹³C and ¹⁹⁵Pt NMR spectroscopy. Single-crystal X-ray structural analysis of (R,S)-trans-[PtBr ₂{N=C(Ph)-O-N(Me)-CH(Ph)}₂] and trans-[PtCl ₂(C₅H₅N){N=C(Ph)-O-N(Me)-CH(Ph)}] confirms the molecular structure and the trans configuration of the heterocycles relative to each other. The Royal Society of Chemistry.

Full text of DOI:10.1039/b807410k

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Synthesis and characterisation of mixed ligand Pt(II) and Pt(IV) oxadiazoline
complexes†
Julien Sarju,a Jannine Arbour,a James Sayer,a Benjamin Rohrmoser,b Wolfgang Schererb and
Gabriele Wagner*a
Received 1st May 2008, Accepted 19th June 2008
First published as an Advance Article on the web 21st August 2008
DOI: 10.1039/b807410k
The nitrile ligands in trans-[PtX2(PhCN)2] (X = Cl, Br, I) undergo sequential 1,3 dipolar cycloadditions
1
2
+
-
1
2
1
2
=
with nitrones R R C N (Me)–O (R = H, R = Ph; R = CO2Et, R = CH2CO2Et) to selectively
4
1
2
=
form the D -1,2,4-oxadiazoline complexes trans-[PtX2(PhCN) {N C(Ph)–O–N(Me)–CR R }] or
1
2
=
trans-[PtX2{N C(Ph)–O–N(Me)–CR R }2] in high yields. The reactivity of the mixed ligand complexes
1
2
=
trans-[PtX2(PhCN){N C(Ph)–O–N(Me)–CR R }] towards oxidation and ligand substitution was
studied in more detail. Oxidation with Cl2 or Br2 provides the Pt(IV) species trans-[PtX2Y2-
=
(PhCN){N C(Ph)–O–N(Me)–CH(Ph)}] (X, Y = Cl, Br). The mixed halide complex (X = Cl, Y = Br)
=
undergoes halide scrambling in solution to form trans-[PtX(4-n)Yn(PhCN){N C(Ph)–O–N(Me)–CH-
1
=
(Ph)}] as a statistical mixture. Ligand substitution in trans-[PtCl2(PhCN){N C(Ph)–O–N(Me)–CR -
R2}] allows for selective replacement of the coordinated nitrile by nitrogen heterocycles such as
pyridine, DMAP or 1-benzyl-2-methylimidazole to produce mixed ligand Pt(II) complexes of the type
1
2
=
trans- [PtX2(heterocycle){N C(Ph)–O–N(Me)–CR R }]. All compounds were characterised by
elemental analysis, mass spectrometry, IR and 1H, 13C and 195Pt NMR spectroscopy. Single-crystal
=
X-ray structural analysis of (R,S)-trans-[PtBr2{N C(Ph)–O–N(Me)–CH(Ph)}2] and
=
trans-[PtCl2(C5H5N){N C(Ph)–O–N(Me)–CH(Ph)}] confirms the molecular structure and the trans
configuration of the heterocycles relative to each other.
particularly suited for medicinal applications. Moreover, there
Introduction
are a number of synthetic strategies that allow for further
diversification of the ligand spectrum and for the synthesis of
mixed ligand Pt(II) oxadiazoline complexes. The easiest route starts
from a mixed ligand precursor such as [PtCl2(sulfoxide)(nitrile)],
which reacts with nitrones to form [PtCl2(sulfoxide)(oxadiazoline)]
complexes.9 Alternatively, the difference in reactivity of the initially
equivalent nitrile ligands in PtCl2(RCN)2 can be used. Hence, the
reaction with one equivalent of a nitrone leads to mixed nitrile–
oxadiazoline Pt(II) complexes,10,11 whereas sequential addition of
two different nitrones allows for the synthesis of Pt(II) complexes
bearing two different oxadiazolines.11 The striking selectivity of
this reaction is related to the fact that Lewis acids promote the
cycloaddition of nitrones to nitriles,12 and the first cycloaddition
is affected to a higher extent because the PtCl2(RCN) moiety
acts as a stronger Lewis acid than the PtCl2(oxadiazoline)
fragment. Other reactions such as nucleophilic additions are
also able to differentiate between the two nitriles, e.g. addition
of the hydroxide ion provides mixed nitrile–amide complexes,13
and base-catalysed addition of methanol leads to mixed nitrile–
iminoether complexes.14 Recently, it has been recognised that the
nucleophilic addition of oximes also discriminate between the
nitrile ligands and mixed iminoether–oxadiazoline complexes have
been prepared.15
Trans-configured platinum compounds with a PtCl2N2 coordina-
tion pattern have found increasing interest as potential anticancer
drugs, with the view of overcoming resistance to currently available
cis-configured drugs like cisplatin, carboplatin or oxaliplatin.1
Among the most intensely studied examples are [PtCl2(L1)(L2)]
complexes where L1 and L2 can be aromatic nitrogen heterocycles
or aliphatic amines,2,3 or ligands of the imine and iminoether type,4
and also trans-Pt(IV) complexes with NH3 and aliphatic amine
ligands have been considered.5
Following this pioneering work, we recently discovered that
trans-[PtCl2(D4-1,2,4-oxadiazoline)2] and trans-[PtCl2(nitrile)(D4-
1,2,4-oxadiazoline)] complexes exhibit substantial in vitro cytotox-
icity in platinum-sensitive and resistant human cancer cell lines.6
Compounds of this type are easily accessible by cycloaddition of
7
∫
nitrones across the C N bond of Pt(II)-coordinated nitriles, and
the same strategy can be applied to Pt(IV)-coordinated nitriles
for the synthesis of [PtCl4(D4-1,2,4-oxadiazoline)2] complexes.8
The substitution pattern of the oxadiazoline ligands can be
varied fairly freely for further fine-tuning of pharmacologically
relevant parameters, which could render this class of compounds
aChemical Sciences, FHMS, University of Surrey, Guildford, Surrey, UK
GU2 7XH. E-mail: gwasurrey@hotmail.com; Fax: +44 (0) 1483 686851;
Tel: +44 (0) 1483 686831
Mixed nitrile–oxadiazoline (Pt(II) complexes are also promising
starting materials for selective ligand exchange reactions, although
this has never been explored on this particular type of compounds.
Nitriles are generally know as being relatively labile and can be
replaced by stronger ligands.16 This process can be remarkably
bInstitute of Physics, University of Augsburg, Universita¨tsstr. 1, D-86135
Augsburg, Germany
† CCDC reference numbers 686813–686814. For crystallographic data in
CIF or other electronic format see DOI: 10.1039/b807410k
5302 | Dalton Trans., 2008, 5302–5312
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selective, as in the case of the reaction of [PtCl2(PhCN)2]
with 2-aryl-dibenzo-1,2-oxaphosphorines to form mixed ligand
[PtCl2(PhCN)(oxaphosphorine)] complexes by ligand exchange
of one of the nitriles in the presence of the other.17 In terms
of exchange kinetics, Pt-bound nitriles are less labile than Pd-
bound ones,18 and exchange reactions at a Pt center are often
comparatively slow. Oxadiazoline ligands can be replaced from
Pt(II) and Pt(IV) centers and this allows for their isolation after
synthesis in the coordination sphere of the metal.7–9
trans-isomer of PtCl2(PhCN)2 very closely with respect to their
spectroscopic data and also in their chromatographic behaviour.
The TLC shows only one spot at approximately the same Rf value
as trans-PtCl2(PhCN)2, whereas the cis isomer would be expected
at a much lower Rf value. In agreement with the high symmetry of
the complex, the IR spectra of 2b and 2c are very simple and nearly
∫
identical with that of trans-PtCl2(PhCN)2. The C N stretch occurs
at almost the same wavenumber, suggesting that the electronic
∫
properties of the C N bond depend very little on the halogen
The halogen ligands are also labile and give scope for further
diversification of complexes. They can be exchanged by other
halides under certain conditions,16a,19 and hydrolysis of the PtCl
bond under formation of hydroxo- or aquo-complexes is a
common reaction which plays a particularly important role in
aqueous and halide deficient cell media.20
Herein, we report about three synthetic approaches to mixed lig-
and platinum oxadiazoline complexes, by (a) mono-cycloaddition
to PtX2(PhCN)2 bearing halides other than Cl as ligand X; (b)
oxidation of the mixed nitrile–oxadiazoline Pt(II) complexes to
provide the first mixed ligand Pt(IV) oxadiazoline complexes;
and (c) selective ligand exchange of the nitrile in mixed nitrile–
oxadiazoline Pt(II) complexes by nitrogen heterocycles. The latter
experiments can also give evidence about how mixed nitrile–
oxadiazoline Pt(II) complexes might interact with nucleobases of
the DNA in a cell medium.
atom, as expected if the halogen ligand is coordinated in the cis
position to it. The 1H and 13C NMR spectra of the three complexes
2a-2c are nearly identical, except for the 13C chemical shift of the
nitrile carbon (116.8 ppm for trans-2a;11,23 119.1 ppm for trans-2b;
122.8 ppm for trans-2c). The 195Pt NMR chemical shift, however,
is clearly different and is characteristic of the halogen bound to the
platinum atom (-2350 ppm for trans-2a; -2860 ppm for trans-2b;
-3935 ppm for trans-2c).
Cycloaddition of one equivalent of C-phenyl-N-methyl-nitrone
1a to one of the nitrile ligands in 2b or 2c occurs at room temper-
ature (25 ◦C) to provide the corresponding mono-oxadiazoline
=
complexes trans-[PtBr2(PhCN){N C(Ph)–O–N(Me)–CH(Ph)}]
=
(3b) and trans-[PtI2(PhCN){N C(Ph)–O–N(Me)–CH(Ph)}] (3c)
in 73% and 76% yield. The reactivity of 2b and 2c is similar to
that of the chloro compound 2a studied previously,11 and the
reaction is complete after approximately 20 h in all cases. Taking
into account that the halogen ligands are in the cis-position to the
nitrile, one would indeed expect little electronic communication
Results and discussion
∫
to the nitrile. The reactivity of the C N bond is rather determined
by the electronic influence the trans-positioned nitriles exert
onto each other. Nitrone 1d, prepared by Michael addition of
N-methylhydroxylamine to diethyl acetylenedicarboxylate, is
less reactive than 1a, and mono-cycloaddition to 2a requires
longer reaction times or higher reaction temperatures. The IR,
1H and 13C NMR data of the products 3b, 3c and 3d are in good
agreement with the ones of the corresponding trans-configured
dichloro compound 2a. A cis-configuration for 3b–3d can be
excluded because the cis-compounds exhibit a very characteristic
low chemical shift of the ortho-protons at the benzonitrile ligand
(7.17 ppm in cis-3a,11 as compared to 7.68 ppm in trans-3a,
7.69 ppm in trans-3b, 7.67 ppm in trans-3c and 7.74 ppm in
The starting complexes trans-[PtCl2(PhCN)2] (2a), trans-
[PtBr2(PhCN)2] (2b) and trans-[PtI2(PhCN)2] (2c), shown in
Scheme 1, were prepared from PtCl2, PtBr2 or PtI2 and hot
benzonitrile using the method described by Kharash21 and
Uchiyama.22 This method was chosen to favour formation of
the trans-configured compound due to thermal conversion of
the kinetic cis- into the thermodynamically more stable trans-
form (or an equilibrium mixture of them).22–24 The cis- and trans-
forms of PtBr2(PhCN)225,26 and PtI2(PhCN)227 have been prepared
previously, but their characterisation involved IR and Raman
spectroscopy only. Using our protocol, uniform samples of trans-
2b and trans-2c are obtained, which resemble the corresponding
Scheme 1 Successive cycloadditions of nitrones to trans-[PtX2(PhCN)2] (a, d: X = Cl;11 b: X = Br; c: X = I; a, b, c: R1 = H, R2 = Ph; d: R1 = CO2Et,
R2 = CH2CO2Et).
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trans-3d). The 195Pt NMR signal appears at lower field than in
the corresponding bis-nitrile complexes (trans-3a: -2237 ppm;
trans-3b: -2693 ppm; trans-3c: -3695 ppm; trans-3d: -2232 ppm).
The synthesis of the bis-oxadiazoline complexes 4b–4d by
reaction of two equivalents of the nitrone with the two coordinated
nitrile ligands requires significantly harsher reaction conditions
(60 ◦C, 48 h) than for mono-cycloaddition, and an excess of
Table 1 Crystal data and structure refinement for (R,S)-trans-
[PtBr2{N–C(Ph)–O–N(Me)–CH(Ph)}2] (R,S-4b) and trans-[PtCl2-
=
(C5H5N){N C(Ph)–O–N(Me)–CH(Ph)}] (6a)
R,S-4b
6a
Chemical formula
Formula weight/g mol-1
Temperature/K
C30H28Br2N4O2Pt C20H19Cl2N3OPt
831.44
295
583.36
295
1
nitrone was used to bring the reaction to completeness. The H
˚
l/A
0.71073
P21/n (No. 14)
11.5694(9)
7.9671(9)
16.1920(12)
96.953(6)
1481.5(2)
2
0.71073
P21/c (No. 14)
16.4796(10)
8.9290(6)
15.4594(10)
113.062(4)
2093.0(2)
4
NMR spectrum of the bromo complex 4b displays very broad
signals throughout the spectrum at room temperature, which we
attribute to a combination of hindered rotations of the phenyl
groups relative to the heterocycle and the ◦heterocycles around the
N–Pt bond. At higher temperatures (55 C) the signals sharpen
and reveal the presence of two diastereoisomeric products, as
in the case of the corresponding chloro compound.7 The chloro
compound, however, did not display such temperature dependent
line broadening, indicating that the steric effects of the bromo
ligand are significantly larger than that of the chloro ligands.
Consequently, one would expect rotations to be frozen in the
iodo complex 4c, and this is in agreement with the sharp NMR
signals observed at room temperature. However, four isomers (two
diastereomers existing in two rotameric forms each) should be
present whereas only two species were observed. These isomers
were tentatively assigned to the two diastereomeric forms of the
complex on the basis of their NMR pattern being similar to those
of the chloro complex 4a, but the presence of rotameric forms can
not be excluded at that stage.
Space group
˚
a/A
˚
b/A
˚
c/A
b/◦
V/A
3
˚
Z
r
calcd/g cm-3
1.864
1.851
m/mm-1
Transmission (min/max)
7.466
0.20/0.43
6.974
0.27/0.45
13 473
Number of measured reflections 10 019
Number of unique reflections
3018 (2487,
I<2s(I))
26.3
0.031
1.06
0.0259
0.0578
4222 (3504,
I<2s(I))
26.4
0.042
1.082
0.0356
0.0788
qmax
Rint
Goodness-of-fit
a
R1
b
wR2
a R1 = RꢀFo| - |Fcꢀ/R|Fo| (where Fo > 2s(Fo2)) b wR2 = {R[w(Fo
-
2
2
1/2
Fc2)2]/R[w(Fo2)2]}
.
An X-ray structural analysis was performed for 4b (Fig. 1,
Table 1 and 2). The platinum atom marks the crystallographic
inversion center of 4b and displays a slightly distorted square
planar coordination geometry. The oxadiazoline ligands occupy
trans positions and adopt an envelope conformation where N2
points out of the (C8, N1, C1, O1) plane. This situation is similar
to the one observed for uncoordinated D4-1,2,4-oxadiazolines
described in the literature,29 but in contrast to that in the closely
related chloro analogue of 4b. Here, the heterocycle adopts a
twist conformation with the N2 and C8 atoms pointing out
◦
˚
Table 2 Selected bond lengths (A) and bond angles ( ) for (R,S)-trans-
[PtBr2{N–C(Ph)–O–N(Me)–CH(Ph)}2] (R,S-4b)
Pt(1)–Br(1)
2.4348(5)
2.011(2)
1.268(5)
1.354(4)
1.477(4)
90.93(8)
180
N(2)–C(8)
N(1)–C(8)
1.470(5)
1.486(5)
1.479(6)
1.488(7)
1.507(7)
103.9(3)
108.4(3)
130.7(3)
114.3(3)
103.1(4)
110.7(4)
112.2(3)
112.3(3)
Pt(1)–N(1)
N(1)–C(1)
C(1)–C(2)
C(1)–O(1)
O(1)–N(2)
N(2)–C(15)
C(8)–C(9)
Br(1)–Pt(1)–N(1)
Br(1)–Pt(1)–Br(1#)a
N(1)–Pt(1)–N(1#)a
Pt(1)–N(1)–C(1)
Pt(1)–N(1)–C(8)
N(1)–C(1)–O(1)
C(1)–O(1)–N(2)
O(1)–N(2)–C(8)
N(2)–C(8)–N(1)
C(1)–N(1)–C(8)
N(1)–C(1)–C(2)
O(1)–C(1)–C(2)
O(1)–N(2)–C(15)
C(8)–N(2)–C(15)
N(1)–C(8)–C(9)
N(2)–C(8)–C(9)
180
132.3(3)
119.3(2)
114.9(4)
106.3(3)
103.4(3)
a Operation used to generate symmetry equivalent atoms #: 2 - x, -y, -z.
of the NC2 plane of the heterocycle.7 The t1(C1–N1–Pt–Br1)
torsional angle of -66.3◦ indicates a significant twist between the
heterocycle and the PtBr2N2 coordination plane. This twist is less
pronounced in the bromo compound as compared to the same
torsion angle t1 of 86.1◦ in the chloro compound. This difference
is most likely due to steric reasons since a larger twist between
the heterocycle and the PtBr2N2 moiety would force an even
shorter non-bonding Br ◊ ◊ ◊ C14 contact than the one displayed
˚
by 4b (3.825 A). Also the relative orientation of the phenyl group
attached to the sp2 hybridised C1 carbon atom is different in 4b
and its chloro analogue. In the bromo compound this Ph group
adopts a t2(C7–C2–C1–N1) torsional angle of -28.8◦, causing
=
a significantly reduced conjugation with the C1 N1 moiety of
the heterocycle relative to the choro analogue (t2 = -16.5◦).
Fig. 1 PLATON28 view of (R,S)-trans-[PtBr2{N–C(Ph)–O–N(Me)–CH-
(Ph)}2], (R,S)-4b, with atomic numbering scheme.
The second phenyl group of the oxadiazoline ligand attached to
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the chiral center (C8) is in both complexes nearly perpendicular
oriented with respect to the (C8, N1, C1, O1) ligand plane. Even
in the optimised solid state conformation of 4b we still note the
presence of steric hindrance between pairs of phenyl groups of the
two trans positioned oxadiazoline ligands as indicated by the short
hydrogen contacts (e.g. H6 ◊ ◊ ◊ H11a = 2.779). Steric congestion
might also account for a hindered rotation of these groups and
the resulting broad signals observed in the 1H NMR spectrum in
solution.
Synthesis of mixed ligand Pt(IV) complexes by chlorination and
bromination
The synthesis of Pt(IV) complexes by oxidation of their Pt(II)
counterparts with halogens is well established. Thus, the reaction
of Pt(II) nitrile complexes with Cl2 or Br2 is described,30 and
also the chlorination of PtCl2(oxadiazoline)2 complexes has been
successful.7 Accordingly, the mixed nitrile oxadiazoline com-
pounds 3a and 3b react with chlorine or bromine almost instan-
taneously, at room temperature in CH2Cl2 or CDCl3 solution, to
provide the mixed ligand Pt(IV) species 5a, 5b and 5c shown in
Scheme 2.
Fig. 2 1H NMR signal of the N–CH–N proton of the coordinated oxadi-
azoline after reaction of [PtBr2(PhCN)(oxadiazoline)] 3a with chlorine at
approximately 30 min reaction time: (a) [PtBr3Cl(PhCN)(oxadiazoline)];
(b) [PtBr2Cl2(PhCN)(oxadiazoline)]; (c) [PtBrCl3(PhCN)(oxadiazoline)];
(d) [PtCl4(PhCN)(oxadiazoline)].
broadened as the number of bromo ligands increases. The expected
signal of [PtBr4(PhCN)(oxadiazoline)] 5b at 7.01 ppm is not seen
due to the poor solubility of this complex. Precipitation of this
complex also leads to an enhanced presence of the chloro-rich
species in solution.
Accordingly, the 195Pt NMR shows signals of 5a (-341 ppm),
PtCl3Br(nitrile)(oxadiazoline) (-649 ppm), 5c (-976 ppm) and
PtClBr3(nitrile)(oxadiazoline) (-1325 ppm), and these provide
a good linear correlation with the number of chloro ligands
exchanged by bromo ligands (see Fig. 3). The mixed halogen
complex 5c might exist as cis/trans isomers (with respect to
the halogens), but these are expected to have quite similar 195Pt
chemical shifts, e.g. the signals for cis- and trans-[PtCl4Br2]2- differ
by 1 ppm only.32 The slightly larger half height linewidth of the
195Pt signal of 5c (320 Hz) as compared to the one of 5a and 5b
(220 Hz each) could be explained in such terms if the signals of
the cis- and trans-forms were about 3 ppm apart.
Scheme 2 Oxidation of trans-[PtX2(PhCN)({N–C(Ph)–O–N(Me)–CH-
(Ph)}] (a: X = Y = Cl; b: X = Y = Br; c: X = Cl, Y = Br).
The deep yellow tetrachloro complex 5a, synthesised from 3a
and Cl2, is stable as a solid and in solution under anhydrous con-
ditions. Its 195Pt chemical shift of -341 ppm is in good agreement
with the linear predicted one from trans-PtCl4(EtCN)2 (-530 ppm,
in DMSO)31 and trans-PtCl4(oxadiazoline)2 (-126 ppm).7 The 1H
NMR signal of the oxadiazoline N–CH–N appears at 6.68 ppm, at
lower field than in the corresponding Pt(II) complexes but at nearly
the same chemical shift observed for other oxadiazolines bound
to a PtCl4(N) fragment.7,8 The reaction of 3b with Br2 provides
the orange-red tetrabromo complex 5b. Due to its poor solubility
in halogenated solvents, NMR data were acquired during the
reaction before the precipitation set in. The 195Pt signal of 5b is
observed at significantly lower chemical shift (-1651 ppm) than
in 5a, and the oxadiazoline N–CH–N proton is more deshielded
1
and appears at 7.01 ppm in the H NMR spectrum. The mixed
halide complex 5c is formed, initially as the sole product, by either
reaction of the chloro complex 3a with bromine or by addition
of chlorine to the bromo species 3b. Its 195Pt signal at -976 ppm
and the N–CH–N proton in the 1H NMR at 6.84 ppm are both at
average positions between the corresponding ones of 5a and 5b.
The mixed halide complex, however, is unstable and undergoes
halide scrambling over a period of 1 h. This is clearly visible in
1
Fig. 3 Correlation of the 195Pt chemical shift of PtCl(4-n)Brn(PhCN)-
(oxadiazoline) complexes 5 and the number of chloro ligands replaced by
bromo ligands. Linear regression: y = -329.6x - 329.2 with R2 = 0.9996.
the H NMR signals of the N–CH–N protons (see Fig. 2). Four
out of the expected five signals can be seen, all of which exhibit
satellites due to a 4J(195Pt,1H) coupling. These become increasingly
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The synthesis of 5a has also been attempted by mono-
cycloaddition of nitrone 1a to PtCl4(PhCN)2. However, a mixture
of oxadiazoline complexes was produced, which could not be
separated. A weighted subtraction of the 1H and 13C NMR spectra
of the bis-oxadiazoline complex7 from the ones of the crude
reaction mixture allowed identification of the remaining product
as the Pt(IV) mono-oxadiazoline complex 5a, with signals identical
to the ones discussed above. We attribute the poor selectivity of
the cycloaddition mainly to the low solubility of this particular
Pt(IV) nitrile complex, resulting in a high excess of nitrone relative
to the Pt(IV) species in solution.
within 24 h, and the metal-free oxadiazoline could be isolated
in 82% yield. It is worth mentioning that the synthesis of this
heterocycle by cycloaddition of the nitrone to the uncoordinated
◦
nitrile could not be achieved, even at temperatures up to 200 C
and microwave irradiation. However, if 3a and 3d are reacted
with only one equivalent of pyridine, under otherwise the same
conditions, selective replacement of the nitrile ligand took place
to provide the mixed oxadiazoline–pyridine complexes 6a and 6b in
good yields of 67% and 77%, respectively. All analytical data such
as elemental analysis, IR, MS and 1H and 13C NMR spectra agree
with the proposed structure. A linear extrapolation between the
195Pt chemical shifts of the complexes trans-PtCl2(oxadiazoline)2
(-2111 to -2161 ppm) and trans-PtCl2(R-pyridine)2 (-1948 to
-1973 ppm)34,35 predicts d values in a range of -2029 to -2067 ppm
for the mixed ligand complexes 6a and 6b. The experimentally
observed values of -2023 (for 6a) and -2044 (for 6b) are in
very good agreement with the predicted ones, suggesting that the
complexes 6a and 6b are trans-configured. This was also confirmed
for 6a by 1H NOESY experiments where NOE cross peaks between
the pyridine ortho-protons and the ortho-protons of the two phenyl
groups attached to the oxadiazoline were observed as the only inter
ligand NOE’s. These protons are expected to be close in the trans-
complex. For the cis-configured complex far more inter ligand
NOE signals would be expected.
The Pt(IV) complexes 5a and 5b can be reduced back
to their Pt(II) counterparts 3a and 3b upon reaction with
=
Ph3P CHCOOMe, as previously described for other Pt(IV)
complexes.33 Reduction of 5c, after halide scrambling, provides
a mixture of the Pt(II) complexes 3a, 3b and the mixed halide
compound PtClBr(PhCN)(oxadiazoline), as evidenced from the
195Pt spectrum (3a: -2237 ppm, mixed halide complex -2470 ppm,
3b: -2693 ppm).
Ligand substitution reactions
In the following, the reactivity of the mono-oxadiazoline com-
plexes 3a and 3d with nitrogen heterocycles was studied, as shown
in Scheme 3. From this, we expected to gain access to new mixed
ligand complexes, and also to obtain some first insight about the
way complexes of this type might interact with the nucleobases
of the DNA, as an important prerequisite for cytotoxicity against
cancer cells. We have demonstrated that a similar complex indeed
showed potent in vitro activity, not only against a number of Pt-
sensitive but also against resistant cell lines,6 although the precise
mode of action is not yet clear.
Crystals of 6a suitable for X-ray diffraction were grown by
slow evaporation of a CDCl3 solution. The compound crystallises
in the P21/c space group and the molecular structure of the
complex is shown in Fig. 4 with bond distances and angles
presented in Table 3. As expected, the platinum atom displays
a slightly distorted square planar coordination sphere, with the
two chloro ligands in a trans position to each other. The two
˚
individual Pt–Cl distances differ slightly by 0.015 A (Pt–Cl1 =
˚
2.311(2) and Pt–Cl2 = 2.296(2) A). The Pt–N distances (Pt–N1 =
˚
2.012(5), Pt–N3 = 2.004(5) A) are both slightly longer than in
7
36
˚
trans-PtCl2(oxadiazoline)2 (1.999 A) or trans-PtCl2(pyridine)2
˚
(1.977 A). The bond distances within the organic moieties occur
in the expected value range.37 The oxadiazoline ligand adopts
a conformation, which can be best described as an envelope
Scheme 3 Selective substitution of the nitrile ligand by nitrogen hetero-
cycles (6a, 7: R1 = Ph, R2 = H; 6b, 8: R1 = CO2Et, R2 = CH2CO2Et).
Fig. 4 PLATON28 view oftrans-[PtCl2(C5H5N){N C(Ph)–O–N(Me)–CH-
In the reaction of 3d with an excess of pyridine (e.g. 5 equiva-
=
lents) at 60 ◦C both nitrile and oxadiazoline ligands are replaced
(Ph)}] (6a) with atomic numbering scheme.
5306 | Dalton Trans., 2008, 5302–5312
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◦
˚
part of nucleobases, also selectively displaces the benzonitrile
ligand in 3d under formation of the mixed imidazole–oxadiazoline
complex 8. This complex has similar analytical characteristics as
the pyridine complex 6b. Inter ligand 1H NOE signals are observed
between the ortho protons of the phenyl group at the oxadiazoline
and the methyl and one of the aromatic protons of the imidazole
moiety. The 195Pt NMR resonance at -2074 ppm is at a slightly
lower chemical shift than in 6b, suggesting that the electron rich
imidazole ring is shielding the Pt center.
Table 3 Selected bond lengths (A) and bond angles ( ) for trans-
=
[PtCl2(C5H5N){N C(Ph)–O–N(Me)–CH(Ph)}] (6a)
Pt(1)–Cl(1)
Pt(1)–Cl(2)
Pt(1)–N(1)
Pt(1)–N(3)
O(1)–N(2)
O(1)–C(2)
N(1)–C(2)
N(1)–C(3)
2.3111(18)
2.296(2)
2.012(5)
2.004(5)
1.491(7)
1.341(7)
1.281(8)
1.496(7)
1.462(9)
179.22(7)
90.27(15)
89.65(15)
89.54(15)
90.56(15)
177.82(19)
105.2(5)
132.2(4)
119.5(4)
108.3(5)
105.5(5)
103.2(5)
113.6(6)
120.8(4)
121.3(5)
117.9(5)
N(2)–C(3)
N(3)–C(16)
N(3)–C(20)
C(2)–C(4)
C(3)–C(10)
C(16)–C(17)
C(17)–C(18)
C(18)–C(19)
1.478(9)
1.340(8)
1.355(8)
1.462(8)
1.503(9))
1.368(10)
1.382(10)
1.374(13)
1.395(11)
114.9(5)
115.3(6)
129.8(5)
102.0(5)
112.9(5)
111.2(5)
122.0(7)
122.0(7)
119.0(6)
122.3(7)
123.0(6)
119.6(7)
118.3(7)
119.6(7)
121.5(7)
N(2)–C(1)
C(19)–C(20)
Cl(1)–Pt(1)–Cl(2)
Cl(1)–Pt(1)–N(1)
Cl(1)–Pt(1)–N(3)
Cl(2)–Pt(1)–N(1)
Cl(2)–Pt(1)–N(3)
N(1)–Pt(1)–N(3)
N(2)–O(1)–C(2)
Pt(1)–N(1)–C(2)
Pt(1)–N(1)–C(3)
C(2)–N(1)–C(3)
O(1)–N(2)–C(1)
O(1)–N(2)–C(3)
C(1)–N(2)–C(3)
Pt(1)–N(3)–C(16)
Pt(1)–N(3)–C(20)
C(16)–N(3)–C(20)
O(1)–C(2)–N(1)
O(1)–C(2)–C(4)
N(1)–C(2)–C(4)
N(1)–C(3)–N(2)
N(1)–C(3)–C(10)
N(2)–C(3)–C(10)
C(2)–C(4)–C(9)
C(2)–C(4)–C(9)
C(3)–C(10)–C(11)
C(3)–C(10)–C(15)
N(3)–C(16)–C(17)
C(16)–C(17)–C(18)
C(17)–C(18)–C(19)
C(18)–C(19)–C(20)
N(3)–C(20)–C(19)
Concluding remarks
In this work a number of strategies for the selective synthesis of
mixed ligand platinum compounds, starting from a symmetrical
precursor have been introduced. Firstly, it could be confirmed
that ligand differentiation in complexes of the type trans-
Pt(halogen)2(nitrile)2 is quite a general feature whose potential is
far from being fully exploited. Pt(II) mono-oxadiazoline complexes
obtained by selective 1,3-dipolar cycloaddition to only one of the
coordinated nitriles are versatile starting materials for a variety
of new mixed ligand complexes. Thus, Pt(IV) mono-oxadiazoline
complexes are obtained by oxidation of the corresponding Pt(II)
precursors, and halide scrambling allows for further diversification
of the product spectrum. Furthermore, the lability of the nitrile
ligand in trans-PtX2(nitrile)(oxadiazoline) can be used for selective
replacement by other nitrogen heterocycles. This does not only
give easy access to new Pt(II) mixed ligand complexes, but can
also be considered as a model situation for the binding of
PtX2(nitrile)(oxadiazoline) complexes to the DNA nucleobases
to give first evidence about their reactivity and potential for
medicinal applications. Based on our recent observation that Pt(II)
mono- and bis-oxadiazoline complexes exhibit in vitro cytotoxicity
against a series of platinum-sensitive and resistant human cancer
cell lines,6 with a potency comparable to that of cisplatin and
superior to carboplatin, we propose that compounds such as
those presented in this work could also have potential, particularly
because further tailoring and fine-tuning of the pharmacological
properties should be easily possible. In vitro studies on human
cancer cell lines are currently ongoing in our group.
where N2 points out of the ring plane, as in uncoordinated
oxadiazolines29 and complex 4b. The least-squares planes of
both heterocycles are rotated out of the PtN2Cl2 coordination
plane of the metal, the pyridine ligand by 65.4◦ (compared
to 56.17◦ in trans-PtCl2(pyridine)2) and the oxadiazoline by
71.6◦ (vs. 84.2◦ in trans-PtCl2(oxadiazoline)2). Overall, the two
coordinated heterocycles do not form a propeller like structure
as in trans-PtCl2(oxadiazoline)2, but rather resemble the complex
trans-PtCl2(pyridine)2 where both ligands are tilted in a conro-
tatory fashion with respect to the PtN2Cl2 plane and are nearly
co-planar.
Similar to the reaction with one equivalent of pyridine, 4-
dimethylaminopyridine (DMAP) succeds in replacing the ben-
zonitrile ligand from the platinum complex 3a with high selectivity,
and no release of the oxadiazoline ligand has been detected. The
formation of a mixture of products was observed when the reaction
was monitored by 1H NMR spectroscopy, but only one product,
7 in Scheme 3, could be isolated in 27% from the mixture by
column chromatography. Its analytical data strongly suggest that
DMAP is bonded to the platinum center through its heterocyclic
nitrogen and the complex is trans-configured, as in the case of
6a and 6b. The 1H NOE spectra display the same pattern of
inter ligand NOE signals between the ortho protons of the phenyl
groups at the oxadiazoline and the protons in the 2-position of
the aromatic ring of DMAP. The methyl groups in the NMe2
moiety are equivalent in 1H and in 13C NMR, which might not be
expected if the amine nitrogen was coordinated to the metal. The
195Pt signal at -2036 ppm is also in very good agreement with those
of 6a and 6b, thus confirming the proposed structure of 7. DMAP
and related compounds generally prefer coordination through the
aromatic nitrogen, independent on whether the metal fragment is
a platinum compound38 or another transition metal moiety.39
1-Benzyl-2-methylimidazole, as an example for an electron rich
five-membered nitrogen heterocycle and a model for the imidazole
Experimental
Materials and instrumentation
Solvents and reagents were obtained from commercial sources and
used as received. C, H and N elemental analyses were carried out
on a Leeman CE 440 automatic analyser. Infrared spectra (4000–
400 cm-1) were recorded using a Perkin Elmer 2000 FTIR and
Nicolet Avatar 320 FTIR spectrometers in KBr pellets. Positive
FAB-MS spectra of the samples in 3-nitrobenzyl alcohol (NBA)
matrices were acquired on a Thermoquest MAT 95XL instrument
and ESI+-MS spectra were obtained from the mass spectrometry
facilities of the Chemistry Research Group at the University
1
of Oxford. H, 13C and 195Pt NMR experiments were acquired
on a Bruker DRX 500 and Bruker AV 300 spectrometers at
ambient temperature. 195Pt chemical shifts are given relative to
aqueous K2[PtCl4] = -1630 ppm, with half height line widths in
parenthesis.
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X-Ray crystallography: crystal growing, data collection and data
reduction†
OCH2CH3). 13C NMR (125.7 MHz, CDCl3) d (ppm) 14.0 and 14.2
(OCH2CH3), 34.4 (CH2), 53.9 (NCH3), 60.5 and 62.1 (OCH2CH3),
=
=
135.3 (C N), 161.6 and 168.2 (C O).
Crystals of 4b (and 6a) were obtained as yellow needles by
slow evaporation of a CDCl3 solution. A crystal fragment with
dimensions 0.22 ¥ 0.16 ¥ 0.11 mm (0.20 ¥ 0.15 ¥ 0.12) was
glued inside a 0.01 mm thin-walled capillary and mounted on
a STOE imaging plate detector system; values for 6a are given
in brackets in the following. Preliminary examination and final
data collection at ambient temperatures were carried out with
Preparation of the Pt(II) bis-benzonitrile complexes
Trans-PtCl2(PhCN)2, trans-PtBr2(PhCN)2 and trans-[PtI2-
(PhCN)2] were prepared by using a variation of a published
method.21,22 A suspension of PtCl2, PtBr2 or PtI2 (50 mg) in
benzonitrile (2 mL) was stirred at 100 ◦C for 3 d until all the
starting material had disappeared. The reaction mixture was
cooled to room temperature and petroleum ether was added.
The precipitate was filtered and washed with petrol ether. For
further purification, the crude product was extracted into CH2Cl2,
insoluble residual platinum(II) halide was filtered off and the
solvent was evaporated. The chloro and bromo complexes were
purified by chromatography (SiO2, eluent CH2Cl2), the iodo
complex was used as obtained.
˚
graphite-monochromated Mo Ka radiation (l = 0.71073 A)
from a sealed X-ray tube. Intensity data were collected in a 1◦
j-scan (0◦ < j < 180◦) with a detector-to-sample distance of
120(90) mm and an exposure time of 5(3) min. The measurement
time was 24(18) h. No significant variation of the mean intensity
caused by degradation and/or absorption was observed during the
measurement. A total of 10 019(13 473) reflections [6.6◦ < 2H <
53.5◦, h: (-13/14), k: (-10/10), l: (-20/20)] ([5.3◦ < 2H < 52.7◦,
h: (-20/20), k: (-11/11), l: (-19/19)]) were collected. The unit cell
was determined in a least-squares refinement from 19481(23750)
Trans-[PtCl2(PhCN)2] (2a). Yellow powder, yield 88%. For
analytical data see ref. 11, 20.
◦
reflection positions with 3.56◦ < 2H < 54.2◦ (4.56 < 2H <
◦
61.4 ) using the program CELL.40 The data were corrected
Trans-[PtBr2(PhCN)2] (2b). Orange-red powder, yield 86%.
Anal. calcd for C14H10Br2N2Pt: C 29.97, H 1.80, N 4.99. Found:
C 29.83, H 1.68, N 4.81. FAB+-MS, m/z: 561.8 [M]+, 480.9 [M -
for polarisation effects and anomalous dispersion. Positions of
all heavy atoms were refined along with the corresponding
anisotropic thermal parameters. H atoms were calculated in an
idealised geometry and refined using a riding model. The structure
refinements converged to yield shift/error < 0.001 and residual
HBr]+, 459 [M - PhCN]+, 400 [M - 2HBr]+. IR spectrum (selected
-1
∫
bands), cm : 3093, 3060, 3033, 3000 w n(C–H), 2288 m n(C N),
1
1593 m, 1446 m, 1200 m, 760 s, 682 m, 550 m, 536 m. H NMR
-3
˚
electron densities Dr equalled +1.0/-0.65(+1.4/-0.95) e A . The
(500 MHz, CDCl3) d (ppm) 7.57 (t, 7.9 Hz, 4H), 7.74 (t, 7.7 Hz,
weighting scheme applied throughout the refinement was w-1
=
2H) and 7.79 (d, 7.4 Hz, 4H, Ph). 13C NMR (125.7 MHz, CDCl3)
2
2
s (Fo2) + (0.028P)2 (w-1 = s (Fo2) + (0.042P)2), P being equal
∫
d (ppm) 109.4 (Cq), 119.1 (C N), 129.7 (m-CH), 133.9 (p-CH)
2
2
and 135.5 (o-CH)(Ph). 195Pt NMR (107.3 MHz, CDCl3) d (ppm)
-2860 (750 Hz).
to (Fo + 2Fc )/3. All calculations were carried out on a Linux
PC using SIR92,41SHELX,42 PLATON,43 and ORTEP344 program
packages.
Trans-[PtI2(PhCN)2] (2c). Orange-brown powder, yield 56%.
Anal. calcd for C14H10I2N2Pt: C 25.67, H 1.54, N 4.28. Found: C
25.17, H 1.36, N 4.08. FAB+-MS, m/z: 655.6 [M]+, 526.8 [M -
HI]+, 551.9 [M - PhCN]+. IR spectrum (selected bands), cm-1:
Preparation of the nitrones.
C-phenyl-N-methyl-nitrone (1a). This compound was pre-
pared according to a published method from benzaldehyde and N-
methyl-hydroxylamine hydrochloride.45 Yield 66%. For analytical
data see ref. 46
∫
3055 w n(C–H), 2287 m n(C N), 1592 m, 1445 m, 1202 m, 755 s,
1
682 m, 538 m. H NMR (300 MHz, CDCl3) d (ppm) 7.57 (t,
8.0 Hz, 4H), 7.73 (t, 7.8 Hz, 2H) and 7.78 (d, 7.2 Hz, 4H, Ph).
13
∫
C NMR (75 MHz, CDCl3) d (ppm) 109.4 (Cq), 122.8 (C N),
129.5 (m-CH), 133.5 (p-CH) and 135.2 (o-CH)(Ph). 195Pt NMR
(107.3 MHz, CDCl3) d (ppm) -3935 (700 Hz).
C-(ethoxycarbonyl)(ethoxycarbonylmethyl)-N -methyl-nitrone
(1d). This compound was prepared by a variation of a published
method.47 A solution of N-methyl-hydroxylamine hydrochloride
(0.42 g, 5.0 mmol) and Na2CO3 (0.32 g, 3.0 mmol) in aqueous
ethanol (5 mL, H2O : EtOH 1 : 1) was stirred at room temperature
for 5 min. Diethyl acetylenedicarboxylate (0.88 mL, 5.5 mmol)
was then added via a syringe over a period of 5 min. After 30 min
at room temperature the mixture was taken up in ethyl acetate
(50 mL), washed with brine (2 ¥ 5 mL) and dried over Na2SO4.
The mixture was filtered and the solvent evaporated. The brown
oily residue was purified by chromatography (SiO2, eluent hexane–
ethyl acetate 7 : 3, Rf = 0.44).
Preparation of the Pt(II) mono-oxadiazoline complexes
Trans-PtX2(PhCN)2 2a, 2b or 2c (0.1 mmol) and nitrone 1a or 1d
(0.1 mmol) were dissolved in chloroform (1 mL) and stirred at
room temperature for 24–72 h. After evaporation of the solvent
the crude products were purified by chromatography on SiO2 using
CH2Cl2 (3a, 3b, 3c) or CH2Cl2–ethyl acetate 98 : 2 (3d) as the eluent.
=
Trans-[PtCl2(PhCN){N C(Ph)–O–N(Me)–CH(Ph)}]
(3a).
Yield 68%. For analytical data see ref. 11.
Yield 96%. Anal. calcd for C9H15NO5: C 49.79, H 6.96, N 6.45.
Found: C 49.49, H 6.88, N 6.37. Accurate ESI+-MS, m/z: calcd for
=
Trans-[PtBr2(PhCN){N C(Ph)–O–N(Me)–CH(Ph)}]
(3b).
C9H15NNaO5 [M + Na]+: 240.0842. Found: 240.0841. IR spectrum
Yield 73%. Anal. calcd for C22H19Br2N3OPt: C 37.95, H 2.75, N
6.03. Found: C 38.48, H 2.79, N 5.93. FAB+-MS, m/z: 696.8 [M]+,
615.9 [M - HBr]+, 569 [M - nitrone]+, 535 [M - 2HBr]+, 432.2
-1
=
(selected bands), cm : 2984 w n(C–H), 1717 s n(C O), 1541 m–w
1
=
n(C N). H NMR (500 MHz, CDCl3) d (ppm) 1.28 (t, 6.9 Hz,
3H) and 1.32 (t, 7.0 Hz, 3H, OCH2CH3), 3.75 (s, 2H, CH2), 4.25
(s, 3H, NCH3), 4.18 (q, 7.0 Hz, 2H) and 4.27 (q, 7.0 Hz, 2H,
[M - 2HBr - PhCN]+. IR spectrum (selected bands), cm-1: 2291
1
∫
=
w n(C N), 1622 w n(C N). H NMR (500 MHz, CDCl3) d (ppm)
5308 | Dalton Trans., 2008, 5302–5312
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3.08 (s, 3H, NMe), 6.00 (s, 1H, N–CH–N), 7.45 (m, 3H) and
7.73 (d, 7.4 Hz, 2H, CH–Ph), 7.59 (t, 7.7 Hz, 2H), 7.66 (m, 1H)
diastereoisomer: 2.99 (s, 3H, NMe), 5.98 (s, broad, 1H, N–
CH–N), 7.66 (m, 3H) and 7.44 (m, 5H)(CH–Ph), and 8.68
=
=
and 9.00 (d, 8.1 Hz, 2H, N C–Ph), 7.50 (t, 7.7 Hz, 2H), 7.66 (m,
(d, 6.9 Hz, 2H, N C–Ph)(). (R,R)/(S,S)-diastereoisomer (as a
1H) and 7.69 (m, 2H, N CPh). 13C NMR (125.7 MHz, CDCl3) d
mixture with (R,S)-diastereoisomer): 2.99 (s, 3H, NMe), 5.81 (s,
broad, 1H, N–CH–N), 7.51 (m, 5H) and 7.59 (m, broad, 3H,
∫
∫
(ppm) 46.4 (NMe), 95.6 (N–CH–N), 110.2 (Cq, N CPh), 118.5
∫
=
=
(N C), 122.5 (Cq, N CPh), 128.7 (CH), 128.8 (CH), 129.3 (CH),
CH–Ph), and 8.83 (m, broad, 2H, N C–Ph). Other signals are
129.4 (CH), 130.1 (CH), 131.1 (CH), 133.7 (CH), 134.2 (CH),
134.9 (CH, CHPh, N CPh and N CPh), 135.6 (Cq, CHPh),
164.4 (C N). 195Pt NMR (107.3 MHz, CDCl3) d (ppm) -2693
overlapping with the signals of the (R,S)-diastereoisomer. 13C
NMR (125.7 MHz, CDCl3) d (ppm) 46.5 (NMe), 95.8 (N–CH–N),
=
∫
=
=
123.0 (Cq, N CPh), 128.7 (CH), 128.8 (CH), 129.3 (CH), 129.4
(750 Hz).
(CH), 130.1 (CH), 131.1 (CH), 133.7 (CH), 134.2 (CH), 134.9 (CH,
=
∫
=
CHPh, N CPh and N CPh), 136.2 (Cq, CHPh), 163.5 (C N).
=
Trans-[PtI2(PhCN){N C(Ph)–O–N(Me)–CH(Ph)}]
(3c).
195Pt NMR (107.3 MHz, CDCl3) d (ppm) -2523 (1500 Hz).
Yield 76%. Anal. calcd for C22H19I2N3OPt: C 33.44, H 2.42, N
5.32. Found: C 33.30, H 2.38, N 5.08. FAB+-MS, m/z: 790.9 [M]+,
=
Trans-[PtI2{N C(Ph)–O–N(Me)–CH(Ph)}2] (4c). Two dias-
661.9 [M - HI]+, 533.9 [M - 2HI]+, 431.0 [M - 2HI - PhCN]+. IR
tereoisomers, 1 : 1, yield 68%. Anal. calcd for C30H28I2N4O2Pt:
C 38.94, H 3.05, N 6.05. Found: C 38.42, H 3.02, N 5.75. FAB+-
MS, m/z: 925.8[M+], [M - HI]+, [M - 2HI]+, [M - 2HI - 2PhCN]+.
-1
∫
=
spectrum (selected bands), cm : 2290 w n(C N), 1622 w n(C N).
1H NMR (500 MHz, CDCl3) d (ppm) 3.11 (s, 3H, NMe), 6.07
(s, 1H, N–CH–N), 7.46 (m, 3H) and 7.75 (m, 2H, CH–Ph), 7.57
(t, 7.2 Hz, 2H), 7.66 (m, 1H) and 8.93 (d, 8.0 Hz, 2H, N C–Ph),
7.49 (m, 2H), 7.65 (m, 1H) and 7.67 (m, 2H, N CPh). 13C NMR
-1
1
=
IR spectrum (selected bands), cm : 1635 and 1623 s n(C N). H
NMR (500 MHz, CDCl3) d (ppm) 3.00 and 3.03 (s, 3H, NMe), 5.82
and 6.18 (broad) (s, 1H, N–CH–N), 7.31 (t, 1H) and 7.45 (m, 4H),
7.55 (m, 1H), 7.64 (m, 2H, CH–Ph), and 8.60, 8.73 (d, 16.5 Hz,
2H, N C–Ph). 13C NMR (125.7 MHz, CDCl3) d (ppm) 46.1, 46.3
(NMe), 96.4, 97.2 (N–CH–N), 122.7, 123.2 (Cq, N CPh), 128.1
(CH), 128.2 (CH), 128.4 (CH), 128.6 (CH), 129.6 (CH), 129.8
(CH), 129.9 (CH), 130.0 (CH), 130.6 (CH), 130.7 (CH), 130.8
(CH), 133.1 (CH), 133.2 (CH), 133.8 and 131.0, either/or (CH,
=
∫
(75 MHz, CDCl3) d (ppm) 46.1 (NMe), 96.4 (N–CH–N), 110.2
∫
∫
=
(Cq, N CPh), 121.9 (N C), 122.6 (Cq, N CPh), 128.4 (CH),
=
128.6 (CH), 129.3 (CH), 129.7 (CH), 130.1 (CH), 131.0 (CH),
133.3 (CH), 133.9 (CH), 134.7 (CH, CHPh, N CPh and N CPh),
135.3 (Cq, CHPh), 164.4 (C N). 195Pt NMR (107.3 MHz, CDCl3)
=
=
∫
=
d (ppm) -3695 (750 Hz).
=
=
∫
CHPh, N CPh and N CPh), and/or (Cq, CHPh), and 163.4,
=
Trans-[PtCl2 (PhCN){N C(Ph)–O–N(Me)–C(CO2Et)(CH2-
164.1 (C N). 195Pt NMR (107.3 MHz, CDCl3) d (ppm) -3445
CO2Et)}] (3d). Yield 74%. Anal. calcd for C23H25Cl2N3O5Pt:
C 40.07, H 3.65, N 6.09. Found: C 40.10, H 3.67, N 5.83.
Accurate ESI+-MS, m/z: calcd for C23H25Cl2N3NaO5Pt [M + Na]+:
711.0713. Found: 711.0717. IR spectrum (selected bands), cm-1:
2289 w n(C N), 1739 s n(C O), 1623 m n(C N). 1H NMR
(500 MHz, CDCl3) d (ppm) 1.31 (t, 7.1 Hz, 3H) and 1.33 (t, 7.1 Hz,
3H, 2 ¥ OCH2CH3), 3.06 (s, 3H, NMe), 3.56 (d, 17.5 Hz, 1H) and
4.88 (d, 17.5 Hz, 1H, CH2), 4.27 (m, 3H) and 4.34 (m, 1H, 2 ¥
OCH2CH3), 7.53 (t, 8.0 Hz, 2H), 7.70 (m, 1H) and 7.74 (d, 8.0 Hz,
2H, PhC N), 7.61 (t, 7.5 Hz, 2H), 7.70 (m, 1H) and 8.85 (d, 7.5 Hz,
2H, N C–Ph). 13C NMR (125.7 MHz, CDCl3) d (ppm) 14.1 and
14.4 (2 ¥ OCH2CH3), 39.7 (CH2), 42.0 (NMe), 61.6 and 63.3 (2 ¥
OCH2CH3), 92.2 (N–C–N), 109.9 (Cq, N CPh), 116.8 (N C),
(750 Hz) and -3450 (750 Hz).
=
Trans-[PtCl2{N C(Ph)–O–N(Me)–C(CO2Et)(CH2CO2Et)}2]
(4d). Two diastereoisomers 1 : 1, yield 46%. Anal. calcd
for C32H40Cl2N4O10Pt: C 42.37, H 4.45, N 6.18. Found: C
43.22, H 4.30, N 6.01. Accurate ESI+-MS, m/z: calcd for
∫
=
=
C32H40Cl2N4NaO10Pt [M + Na]+: 929.1658. Found: 929.1657. IR
-1
=
=
spectrum (selected bands), cm : 1738 s n(C O), 1625 m n(C N).
1H NMR (500 MHz, CDCl3) d (ppm) 1.29 (m, 3H) and 1.33
(m, 3H, 2 ¥ OCH2CH3), 2.99 and 3.03 (s, 3H, NMe), 3.23 and
3.50 (d, 17.5 Hz, 1H), 4.62 and 4.66 (d, 17.5 Hz, 1H, CH2), 4.10
to 4.38 (m, 4H, 2 ¥ OCH2CH3), 7.60 to 7.70 (m, 3H), 8.72 and
∫
=
∫
∫
8.79 (d, 7.5 Hz, 2H, N C–Ph). 13C NMR (125.7 MHz, CDCl3) d
=
=
∫
=
122.5 (Cq, N CPh), 129.0 (CH, N CPh), 129.6 (CH, N CPh),
131.2 (CH, N CPh), 133.8 (CH, N CPh), 134.7 and 135.1 (CH,
N CPh and N CPh), 167.9 (C N), 165.9 and 168.1 (C O). 195Pt
(ppm) 14.1, 14.2, 14.3 and 14.4 (2 ¥ OCH2CH3), 39.5 and 39.6
(CH2), 42.1 (NMe), 61.7, 61.8 63.1 and 63.3 (2 ¥ OCH2CH3),
91.9 (broad, N–C–N), 123.0 and 120.1 (Cq, N CPh), 129.6 (CH),
131.0, 131.1 (CH), 133.7 and 134.0 (CH, N CPh), 167.4 (C N),
165.9, 166.0, 168.1 and 168.2 (C O). 195Pt NMR (107.3 MHz,
=
=
∫
∫
=
=
=
NMR (107.3 MHz, CDCl3) d (ppm) -2232 (950 Hz).
∫
=
=
Preparation of the Pt(II) bis-oxadiazoline complexes
CDCl3) d (ppm) -2161 (1050 Hz).
Trans-PtX2(PhCN)2 2a, 2b or 2c (0.1 mmol) and nitrone 1a or 1d
Preparation of the Pt(IV) mono-oxadiazoline complexes
(0.25 mmol) were dissolved in chloroform (1 mL) and stirred at
◦
60 C for 48 h (for 4b and 4d). The reaction to 4c was complete
=
Trans-[PtX2(PhCN){N C(Ph)–O–N(Me)–CH(Ph)}] 3a or 3b
after 18 h. After evaporation of the solvent the crude products
were purified by column chromatography on SiO2 using CH2Cl2
(4b, 4c) or CH2Cl2–ethyl acetate 95 : 5 (4d) as the eluent.
(0.1 mmol) was dissolved in chloroform (2 mL). (a) For chlo-
rinations: dry chlorine was bubbled through the solution until
there was an obvious change in colour from pale yellow to intense
yellow (typically 20 s). Then dry nitrogen gas was passed through
the reaction mixture for 2 min to remove the excess of chlorine. (b)
For brominations: a freshly prepared solution of bromine in chlo-
roform (10% by volume, approx. 2 mmol mL-1) was added using
a micropipette (50 mL, 0.1 mmol). The product was precipitated
with petrol ether (5 mL), filtered and washed with diethyl ether.
=
Trans-[PtBr2{N C(Ph)–O–N(Me)–CH(Ph)}2] (4b). Two di-
astereoisomers, 1 : 1, yield 71%. Anal. calcd for C30H28Br2N4O2Pt:
C 43.34, H 3.39, N 6.74. Found: C 43.18, H 3.26, N 6.68. FAB+-
MS, m/z: 831.8[M+], 750.9 [M - HBr]+, 670.0 [M - 2HBr]+,
464.0 [M - 2HBr - 2PhCN]+. IR spectrum (selected bands), cm-1:
1
=
1628 s n(C N). H NMR (500 MHz, CDCl3) d (ppm) (R,S)-
This journal is
The Royal Society of Chemistry 2008
Dalton Trans., 2008, 5302–5312 | 5309
©

View Article Online
-1
1
=
The preparation of the mixed halide compound 5c was performed
in deuterated chloroform. This product decomposes rapidly so
characterisation was obtained immediately after halogen addition.
bands), cm : 1625 w n(C N), 1450, 1348, 1118, 693. H NMR
(500 MHz, CDCl3) d (ppm) 3.07 (s, 3H, NMe), 6.03 (s, 1H,
N–CH–N), 7.22 (t, 6.7 Hz, 2H), 7.71 (m, 1H), 8.74 (d, 6.5 Hz,
2H, pyridine), 7.45 (m, 3H) and 7.76 (d, 7.4 Hz, 2H, CH–Ph),
7.59 (t, 7.7 Hz, 2H), 7.67 (m, 1H) and 9.05 (d, 8.5 Hz, 2H,
=
Trans-[PtCl4(PhCN){N C(Ph)–O–N(Me)–CH(Ph)}]
(5a).
Yield 70%. Anal. calcd for C22H19Cl4N3OPt: C 38.94, H 2.82, N
N C–Ph). 13C NMR (125.7 MHz, CDCl3) d (ppm) 46.4 (NMe),
95.0 (N–CH–N), 125.3, 128.9 and 153.8 (CH, pyridine), 128.8,
130.9 and 133.8 (CH, N C–Ph), 122.8 (Cq, N C–Ph), 128.7,
=
6.19. Found: C 38.54, H 2.72, N 6.02. FAB+-MS, m/z: 678 [M+],
639 [M - 2Cl]+, 569 [M - 4Cl]+. IR spectrum (selected bands), cm-1:
=
=
1
∫
=
2314 s n(C N), 1629 m n(C N). H NMR (500 MHz, CDCl3)
d (ppm) 3.19 (s, 3H, NMe), 6.68 (s + d, JPt–H = 13.4 Hz, 1H,
N–CH–N), 7.36 (m, 1H), 7.39 (m, 2H), 7.55 (m, 5H), 7.67 (m,
2H), 7.74 (m, 1H), 7.81 (d, 7.5 Hz, 2H) and 8.27 (d, 7.4 Hz, 2H,
CHPh, N CPh and N CPh). 13C NMR (125.7 MHz, CDCl3) d
(ppm) 46.7 (NMe), 92.6 (N–CH–N), 107.1 (Cq, N CPh), 117.2
=
128.9 and 129.8 (CH, CH–Ph), 136.3 (CH, CH–Ph), C N
not detected. 195Pt NMR (107.3 MHz, CDCl3) d (ppm) -2023
(1070 Hz).
=
∫
=
Trans-[PtCl2(C5H5N){N C(Ph)–O–N(Me)–C(CO2Et)(CH2-
∫
CO2Et)}] (6b). Yield 67%. Anal. calcd for C21H25Cl2N3O5Pt: C
37.89, H 3.79, N 6.32. Found: C 36.99, H 3.53, N 6.62. Accurate
ESI+-MS, m/z: calcd for C21H25Cl2N3NaO5Pt [M + Na]+:
∫
=
(N C), 123.2 (Cq, N CPh), 127.9 (CH), 128.7 (CH), 129.3 (CH),
129.8 (CH), 129.8 (CH), 132.3 (CH), 134.6 (CH), 135.0 (CH),
688.0704. Found: 688.0699. IR spectrum (selected bands), cm-1:
=
∫
136.7 (CH), (CHPh, N CPh and N CPh), 138.1 (Cq, CHPh),
173.2 (C N). 195Pt NMR (107.3 MHz, CDCl3) d (ppm) -341
=
=
=
1
=
1737 s n(C O), 1624 m n(C N), 1613 and 1600 m–w n(C C). H
NMR (500 MHz, CDCl3) d (ppm) 1.28 (t, 7.2 Hz, 3H) and 1.33 (t,
7.4 Hz, 3H, 2 ¥ OCH2CH3), 3.06 (s, 3H, NMe), 3.58 (d, 17.6 Hz,
1H) and 4.91 (d, 17.6 Hz, 1H, CH2), 4.25 (m, 3H) and 4.34 (m,
1H, 2 ¥ OCH2CH3), 7.26 (t, 6.9 Hz, 2H), 7.76 (t, 7.7 Hz, 1H) and
8.83 (d, 6.9 Hz, 2H, C5H5N), 7.60 (t, 7.8 Hz, 2H), 7.70 (t, 7.7 Hz,
(220 Hz).
=
Trans-[PtBr4(PhCN){N C(Ph)–O–N(Me)–CH(Ph)}]
(5b).
Yield 70%. Anal. calcd for C22H19Br4N3OPt: C 30.86, H 2.24,
N 4.91. Found: C 30.58, H 2.22, N 4.99. IR spectrum (selected
-1
bands), cm : 2315 s n(C N), 1627 m n(C N). 1H NMR
(500 MHz, CDCl3) d (ppm) 3.29 (s, 3H, NMe), 7.01 (s + d,
JPt–H = 11.8 Hz, 1H, N–CH–N), 7.46 (m, 3H), 7.39 (m, 1H), 7.55
(m, 4H), 7.67 (m, 2H), 7.73 (m, 1H), 7.79 (d, 5.2 Hz, 2H) and
∫
=
1H) and 8.91 (d, 7.5 Hz, 2H, N C–Ph). 13C NMR (125.7 MHz,
CDCl3) d (ppm) 14.0 and 14.3 (2 ¥ OCH2CH3), 39.6 (CH2), 42.0
(NMe), 61.4 and 63.1 (2 ¥ OCH2CH3), 92.3 (N–C–N), 123.0 (Cq,
N CPh), 128.7, 131.3 and 134.3 (CH, N CPh), 125.3, 138.4 and
153 (CH, pyridine), 167.4 (C N), 166.1 and 168.2 (C O). 195Pt
=
=
=
8.35 (d, 7.5 Hz, 2H, CHPh, N CPh and N CPh). 13C NMR
=
∫
=
=
(125.7 MHz, CDCl3) d (ppm) 47.1 (NMe), 95.7 (N–CH–N), 108.0
NMR (107.3 MHz, CDCl3) d (ppm) -2044 (850 Hz).
∫
∫
=
(Cq, N CPh), 118.9 (N C), 123.8 (Cq, N CPh), 128.1 (CH),
128.8 (CH), 129.3 (CH), 130.0 (CH), 130.2 (CH), 132.2 (CH),
=
Trans-[PtCl2(4-Me2N–C5H4N){N C(Ph)–O–N(Me)–CH(Ph)}]
=
∫
134.7 (CH), 134.9 (CH), 136.6 (CH, CHPh, N CPh and N CPh),
(7). Yield is 27%. Anal. calcd for C22H24Cl2N4OPt: C 42.16,
H 3.86, N 8.95. Found: C 41.66, H 3.39, N 8.77. FAB+-MS,
m/z: (M is 626.18) 590.0 [M - HCl]+, 553.0 [M - 2HCl]+, 547.0
137.1 (Cq, CHPh), 174.2 (C N). 195Pt NMR (107.3 MHz, CDCl3)
=
d (ppm) -1651 (220 Hz).
[M - HCl - NMe2]+, 503.0 [M - dmap]. IR spectrum (selected
=
Trans-[PtCl2Br2(PhCN){N C(Ph)–O–N(Me)–CH(Ph)}] (5c).
-1
=
bands), cm : 1622 n(C N), 1542, 1448, 1390, 1338, 1223, 1205,
1162, 1121, 1065, 1028. H NMR (500 MHz, CDCl3) d (ppm)
2.87 (s, 6H, NMe2), 3.05 (s, 3H, NMe), 6.20 (s, 1H, N–CH–N),
5.82 (d, 7.2 Hz, 2H) and 7.08 (d, 7.3 Hz, 2H, dmap), 7.34 (m, 3H)
and 7.70 (d, 7.0 Hz, 2H, PhCH–N), 7.58 (t, 7.2 Hz, 2H), 7.66
(t, 7.3 Hz, 1H) and 9.12 (d, 7.5 Hz, 2H, N C–Ph). 13C NMR
(125.7 MHz, CDCl3) d (ppm) 39.5 (NMe2), 47.1 (NMe), 94.6
(N–CH–N), 107.3 (CH), 150.9 (CH) and 153.7 (Cq, dmap), 128.5
(CH), 129.2 (CH), 129.7 (CH) and 137.2 (Cq, PhCH–N), 122.5
(Cq), 129.1 (CH), 129.7 (CH) and 134.0 (CH, PhC N), 163.0
(C N). 195Pt NMR (107.3 MHz, CDCl3) d (ppm) -2036 (730 Hz).
=
Prepared by bromination of trans-[PtCl2(PhCN){N C(Ph)–O–
1
1
N(Me)–CH(Ph)}]. H NMR (500 MHz, CDCl3) d (ppm) 3.26
(s, 3H, NMe), 6.84 (s + d, JPt–H = 12.0 Hz, 1H, N–CH–N), 7.45
(m, 3H), 7.39 (m, 1H), 7.55 (m, 5H), 7.65 (m, 1H), 7.71 (m, 1H),
=
7.80 (d, 7.4 Hz, 2H) and 8.32 (d, 7.4 Hz, 2H, CHPh, N CPh and
=
N CPh). 13C NMR (125.7 MHz, CDCl3) d (ppm) 46.8 (NMe),
∫
∫
∫
93.8 (N–CH–N), 107.6 (Cq, N CPh), 118.1 (N C), 123.2 (Cq,
=
N CPh), 127.9 (CH), 128.6 (CH), 129.1 (CH), 129.6 (CH), 129.8
(CH), 131.9 (CH), 134.5 (CH), 134.7 (CH), 136.7 (CH, CHPh,
=
N CPh and N CPh), 137.7 (Cq, CHPh), 173.8 (C N). 195Pt NMR
=
∫
=
=
(107.3 MHz, CDCl3) d (ppm) -976 (320 Hz).
=
=
=
Trans - [ PtCl2 (N C(Me)–N(CH2Ph)–CH CH) {N C(Ph)–O–
N(Me)–C(CO2Et)(CH2CO2Et)}] (8). Yield 62%. Anal. calcd for
C27H32Cl2N4O5Pt: C 42.73, H 4.25, N 7.39. Found: C 43.15, H 4.30,
N 7.61. Accurate ESI+-MS, m/z: calcd for C27H32Cl2N4NaO5Pt
[M + Na]+: 781.1279. Found: 781.1280. IR spectrum (selected
Ligand substitution of the Pt(II) mono-oxadiazoline complexes
The Pt(II) mono-oxadiazoline complex 3a or 3d (0.1 mmol) was
dissolved in chloroform (1 mL), one equivalent of the nitrogen
heterocycle (pyridine, 4-dimethylaminopyridine or 1-benzyl-2-
methylimidazole) was added, and the reaction mixture was left
at 60 ◦C for 24 h. After evaporation of the solvent the product was
purified by column chromatography on SiO2 using CH2Cl2–ethyl
acetate 98 : 2 (6a, 6b, 8) or CH2Cl2–methanol 4 : 1 (7) as the eluent.
-1
1
=
=
bands), cm : 1737 s n(C O), 1626 m n(C N). H NMR (500 MHz,
CDCl3) d (ppm) 1.28 (t, 7.1 Hz, 3H) and 1.33 (t, 7.1 Hz, 3H, 2 ¥
OCH2CH3), 2.74 (s, 3H, CH3 imidazole), 3.04 (s, 3H, NMe), 3.59
(d, 17.6 Hz, 1H) and 4.96 (d, 17.6 Hz, 1H, CH2), 4.24 (m, 3H)
and 4.33 (m, 1H, 2 ¥ OCH2CH3), 5.02 (s, 2H, CH2Ph imidazole),
6.68 (d, 1.7 Hz, 1H) and 7.08 (d, 1.7 Hz, 1H, imidazole), 7.06 (d,
7.5 Hz, 2H) and 7.35 (m, 3H, CH2Ph imidazole), 7.57 (t, 7.6 Hz,
=
Trans-[PtCl2(C5H5N){N C(Ph)–O–N(Me)–CH(Ph)}]
(6a).
Yield 77%. FAB+-MS, m/z: 584.0 [M]+, 547.0 [M - HCl]+,
510.1 [M - 2HCl]+, 481.1 [M - PhCN]+. IR spectrum (selected
2H), 7.67 (t, 7.6 Hz, 1H) and 8.97 (d, 7.6 Hz, 2H, N C–Ph). 13C
=
5310 | Dalton Trans., 2008, 5302–5312
This journal is The Royal Society of Chemistry 2008
©

View Article Online
NMR (125.7 MHz, CDCl3) d (ppm) 13.8 (CH3, imidazole), 14.1
and 14.4 (2 ¥ OCH2CH3), 39.7 (CH2), 42.0 (NMe), 51.3 (CH2Ph,
imidazole), 61.5 and 63.1 (2 ¥ OCH2CH3), 92.4 (N–C–N), 120.0
and 129.3 (CH, imidazole), 146.1 (Cq, imidazole), 127.3, 128.8
and 129.2 (CH, CH2Ph imidazole), 134.0 (Cq, CH2Ph imidazole),
4 (a) A. Boccarelli, M. Coluccia, F. P. Intini, G. Natile, D. Locker and
M. Leng, Anti-Cancer Drug Des., 1999, 14, 253; (b) A. Boccarelli, F. P.
Intini, R. Sasanelli, M. F. Sivo, M. Coluccia and G. Natile, J. Med.
Chem., 2006, 49, 829.
5 (a) L. R. Kelland, C. F. J. Barnard, K. J. Mellish, P. M. Goddard, M.
Valenti, A. Bryant, B. A. Murrer and K. R. Harrap, Cancer Res., 1994,
54, 5618; (b) K. J. Mellish, C. F. J. Barnard, B. A. Murrer and L. R.
Kelland, Int. J. Cancer, 1995, 62, 717.
∫
=
128.3, 130.9 and 133.8 (CH, N CPh), 123.0 (Cq, N CPh), 167.0
(C N), 166.2 and 168.4 (C O). 195Pt NMR (107.3 MHz, CDCl3)
=
=
6 H. M. Coley, J. Sarju and G. Wagner, J. Med. Chem., 2008, 51, 135.
7 G. Wagner, M. Haukka, J. J. R. Frau´sto da Silva, A. J. L. Pombeiro and
V. Yu. Kukushkin, Inorg. Chem., 2001, 40, 264.
d (ppm) -2074 (930 Hz).
8 G. Wagner, A. J. L. Pombeiro and V. Yu. Kukushkin, J. Am. Chem.
Soc., 2000, 122, 3106.
9 G. Wagner and M. Haukka, J. Chem. Soc., Dalton Trans., 2001, 2690.
10 (a) B. Desai, T. N. Danks and G. Wagner, Dalton Trans., 2003, 2544;
(b) G. Wagner, T. N. Danks and B. Desai, Tetrahedron, 2008, 64, 477.
11 B. Desai, T. N. Danks and G. Wagner, Dalton Trans., 2004, 166.
12 G. Wagner, Chem.–Eur. J., 2003, 9, 1503.
13 R. Cini, F. P. Fanizzi, F. P. Intini, L. Maresca and G. Natile, J. Am.
Chem. Soc., 1993, 115, 5123.
14 F. P. Fanizzi, F. P. Intini and G. Natile, J. Chem. Soc., Dalton Trans.,
1989, 947.
15 J. Lasri, M. A. J. Charmier, M. F. C. Guedes da Silva and A. J. L.
Pombeiro, Dalton Trans., 2007, 3259.
16 (a) F. Kessler, N. Szesni, C. Maass, C. Hohberger, B. Weibert and H.
Fischer, J. Organomet. Chem., 2007, 692, 3005; (b) S. A. Johannesen,
B. O. Petersen, J. O. Duus and T. Skrydstrup, Inorg. Chem., 2007, 46,
4326; (c) C. K. Lai, A. A. Naiini and C. H. Brubaker, Jr., Inorg. Chim.
Acta, 1989, 164, 205.
17 G. Keglevich, H. Szelke, A. Kerenyi, T. Imre, K. Ludanyi, J. Dukai, F.
Nagy and P. Aranyi, Heteroat. Chem., 2004, 15, 459.
18 G. Wagner, Inorg. Chim. Acta, 2004, 357, 1320.
19 (a) A. J. Nawara, T. Shima, F. Hampel and J. A. Gladysz, J. Am. Chem.
Soc., 2006, 128, 4962; (b) X. L. R. Fontaine, D. P. Markham and B. L.
Shaw, J. Organomet. Chem., 1990, 391, 123.
20 (a) G. McGowan, S. Parson and P. J. Sadler, Inorg. Chem., 2005, 44,
7459; (b) A. C. G. Hotze, Y. Chen, T. W. Hambley, S. Parsons, N. A.
Kratochwil, J. A. Parkinson, V. P. Munk and P. J. Sadler, Eur. J. Inorg.
Chem., 2002, 1035.
21 M. S. Kharasch, R. C. Seyler and F. R. Mayo, J. Am. Chem. Soc., 1938,
60, 882.
22 T. Uchiyama, Y. Toshiyasu, Y. Nakamura, T. Miwa and S. Kawaguchi,
Bull. Chem. Soc. Jpn., 1981, 54, 181.
23 F. D. Rochon, R. Melanson, E. Thouin, A. L. Beauchamp and C.
Bensimon, Can. J. Chem., 1996, 74, 144.
Release of the oxadiazoline ligand from Pt(II) mono-oxadiazoline
complexes
The Pt(II) mono-oxadiazoline complex 3a or 3d (0.1 mmol) was
dissolved in chloroform (1 mL), 5 equivalents of pyridine (40 mg,
40.5 mL, 0.5 mmol) was added, and the reaction mixture was left
at 60 ◦C for 24 h. After evaporation of the solvent the product was
purified by column chromatography on SiO2 using CH2Cl2–ethyl
acetate 95 : 5 as the eluent.
=
[N C(Ph)–O–N(Me)–CH(Ph)] (9a). Yield 77%. For analytical
data see ref. 48
=
[N C(Ph)–O–N(Me)–C(CO2Et)(CH2CO2Et)]
(9b). Yield
82%. Anal. calcd for C16H20N2O5: C 59.99, H 6.29, N 8.75.
Found: C 59.33, H 6.11, N 8.54. Accurate ESI+-MS, m/z: calcd
for C16H20N2NaO5 [M + Na]+: 343.1264. Found: 343.1263.
-1
=
IR spectrum (selected bands), cm : 1737 s n(C O), 1650 m
1
=
n(C N). H NMR (500 MHz, CDCl3) d (ppm) 1.32 (m, 6H, 2 ¥
OCH2CH3), 2.86 (s, 3H, NMe), 3.08 (d, 17.0 Hz, 1H) and 3.21
(d, 17.0 Hz, 1H, CH2), 4.17 (q, 7.2 Hz, 2H) and 4.31 (m, 2H, 2 ¥
OCH2CH3), 7.43 (t, 7.8 Hz, 2H), 7.52 (t, 7.5 Hz, 1H) and 7.94 (d,
7.5 Hz, 2H, N C–Ph). 13C NMR (125.7 MHz, CDCl3) d (ppm)
=
13.9 and 14.0 (2 ¥ OCH2CH3), 40.9 (CH2), 41.2 (NMe), 60.9 and
=
62.2 (2 ¥ OCH2CH3), 93.3 (N–C–N), 125.0 (Cq, N CPh), 128.5,
=
=
129.0 and 132.5 (CH, N CPh), 163.0 (C N), 168.5 and 169.2
=
(C O).
24 F. P. Fanizzi, F. P. Intini, L. Maresca and G. Natile, J. Chem. Soc.,
Dalton Trans., 1990, 199.
25 (a) R. A. Walton, Spectrochim. Acta, 1965, 21, 1795; (b) R. A. Walton,
Can. J. Chem., 1966, 44, 1480.
Acknowledgements
We are grateful to the UK Engineering and Physical Science
Research Council (EPSRC), Johnson Matthey Plc and the Proof
of Concept Fund of the University of Surrey, the Deutsche
Forschungsgemeinschaft (SPP1178) as well as NanoCat, an In-
ternational Graduate Program within the Elitenetzwerk Bayern
for supporting this work.
26 (a) R. A. Walton, Can. J. Chem., 1968, 46, 2347; (b) M. J. Church and
M. J. Mays, J. Inorg. Nucl. Chem., 1971, 33, 253.
27 H. H. Eysel, E. Guggolz, M. Kopp and M. L. Ziegler, Z. Anorg. Allg.
Chem., 1983, 499, 31.
28 A. L. Spek, http://www.cryst.chem.uu.nl/platon/; see alsoA. L. Spek,
J. Appl. Crystallogr., 2003, 36, 7.
29 (a) J. M. M. Smits, P. T. Beurskens, J. R. M. Smits, R. Plate and
H. Ottenheijm, J. Crystallogr. Spectrosc. Res., 1988, 18, 15; (b) L.
Eberson, C. M. Hartshorn, M. P. Hartshorn and J. J. McCullough,
Synth. Commun., 1997, 27, 3779; (c) L. Eberson, J. J. McCullough,
C. M. Hartshorn and M. P. Hartshorn, J. Chem. Soc., Perkin Trans. 2,
1998, 41.
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