Synthesis and reactivity of platinum(II) triphenylphosphino complexes with aromatic aldoximes

Article abstract of DOI:10.1016/j.ica.2017.04.058

trans-[Pt(μ-Cl)Cl(PPh₃)]₂ reacted with arylaldoximes in 1,2-dichloroethane to afford [PtCl₂(PPh₃){N(OH)[dbnd]CHAr}] (Ar = 3,4-dimethoxyphenyl, 1-naphthyl, 9-anthryl) where aldoxime ligands are N-coordinated to p

Full text of DOI:10.1016/j.ica.2017.04.058

Accepted Manuscript
Research paper
Synthesis and reactivity of platinum(II) triphenylphosphino complexes with ar-
omatic aldoximes
Daniela Belli Dell' Amico, Marialuigia Colalillo, Luca Labella, Fabio Marchetti,
Simona Samaritani
PII:
S0020-1693(17)30328-6
http://dx.doi.org/10.1016/j.ica.2017.04.058
ICA 17563
DOI:
Reference:
To appear in:
Inorganica Chimica Acta
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Revised Date:
Accepted Date:
3 March 2017
27 April 2017
30 April 2017
Please cite this article as: D.B.D. Amico, M. Colalillo, L. Labella, F. Marchetti, S. Samaritani, Synthesis and
reactivity of platinum(II) triphenylphosphino complexes with aromatic aldoximes, Inorganica Chimica Acta (2017),
doi: http://dx.doi.org/10.1016/j.ica.2017.04.058
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Inorganica Chimica Acta
Synthesis and reactivity of platinum(II) triphenylphosphino complexes with aromatic aldoximes
Daniela Belli Dell’ Amico, Marialuigia Colalillo, Luca Labella, Fabio Marchetti, Simona
Samaritani*
Dipartimento di Chimica e Chimica Industriale and CIRCC, Università di Pisa, via Giuseppe Moruzzi 13, Pisa I-56124
th
Dedicated to Dr Carlo Mealli on occasion of his 70 birthday
Corresponding Author:
Simona Samaritani
tel. +39 050 2219 261
e.mail: simona.samaritani@unipi.it
3 2
Abstract: trans-[Pt(µ-Cl)Cl(PPh )] reacted with arylaldoximes in 1,2-dichloroethane to afford
[
PtCl (PPh ){N(OH)=CHAr}] (Ar = 3,4-dimethoxyphenyl, 1-naphthyl, 9-anthryl) where aldoxime
2
3
ligands are N-coordinated to platinum. The obtained complexes are soluble in chlorinated solvents,
where they afford equilibrium mixtures of cis,trans and/or (E),(Z) isomers. Equilibria in solution
3
1
were studied by P-NMR spectroscopy and solid state structural data were obtained by single
crystal X ray diffraction studies. The reactivity of [PtCl (PPh ){N(OH)=CHAr}] complexes with
2
3
basic aqueous solutions was studied, under liquid-liquid phase transfer catalysis conditions. The
outcome of the reaction depends on the stereochemistry of the precursors: cis,(Z)-isomers promptly
2
undergo cyclization to the corresponding dinuclear derivatives [Pt{µ-(κ -N,O)}-
3 2
{N(O)=CHAr}Cl(PPh )] , where two aldoximate ligands symmetrically bridge two metal centers.
Keywords: platinum(II); triphenylphosphine; cis-trans isomerism; cyclization; phase transfer
catalysis.
1. Introduction
Since the early discover of anticancer properties of cis-[PtCl
2
(NH
3
2
) ][1], many studies have been
carried out with the aim of elucidating the mechanism of action of platinum based drugs [2] and it is
generally accepted that the main target of these bioactive molecules is DNA. The platination of
DNA generally involves the coordination of purine bases to activated, hydrolyzed forms of the
metal complexes and can be greatly helped by additional interactions such as hydrogen bonding. As
a matter of fact, good results have been described for some platinum complexes characterized by
the presence of OH groups on coordinated ligands [3]. In the context of our studies on platinum(II)
derivatives [4], we have observed interesting antiproliferative properties for triphenylphosphino

complexes [4a-f]. In particular, trans-[PtCl
2
(PPh )(DEA)] (DEA = diethanolamine) [4d,f], where
3
the ligated amine bears two hydroxyl groups, was found more active than cisplatin towards HeLa
cells. Moreover, it is worth to note that hydroxyl functional groups are reactive towards a series of
chemical transformations, so that platinum compounds bearing OH groups could be good
precursors to more complex derivatives. We report here the synthesis, characterization and
reactivity under basic conditions of three complexes [PtCl
2
(PPh
3
){N(OH)=CHAr}] (Ar = 3,4-
3
dimethoxyphenyl, 1-naphthyl, 9-anthryl), bearing, besides PPh , a coordinated arylaldoxime.
2. Experimental
2.1. Materials and general methods
All manipulations were performed under a dinitrogen atmosphere, if not otherwise stated.
1
13
31
Solvents and liquid reagents were dried according to reported procedures [5]. H-, C-, P- and
1
95
Pt-NMR spectra were recorded with a Bruker ‘‘Avance DRX400’’ spectrometer, in CDCl
3
solution if not otherwise stated. Chemical shifts were measured in ppm (δ) from TMS by residual
1
13
31
solvent peaks for H and C, from aqueous (D
2
O) H
3
PO
4
(85%) for P and from aqueous (D
2
O)
1
95
hexachloroplatinic acid for Pt. A sealed capillary containing C
6
D
6
was introduced in the NMR
tube to lock the spectrometer to the deuterium signal when non-deuterated solvents were used.
FTIR spectra in solid phase were recorded with a Perkin–Elmer ‘‘Spectrum One’’ spectrometer,
equipped with an ATR accessory. Elemental analyses (C, H, N) were performed at Dipartimento di
Scienze e Tecnologie Chimiche, Università di Udine. Trans-[Pt(µ-Cl)Cl(PPh
according to a reported procedure. Aldoxime ligands ArCH=N(OH) [Ar = 3,4-dimethoxyphenyl
1), 1-Naphtyl (2), 9-Anthryl (3)] were prepared by a slight modification of a described
3 2
)] [4h] was prepared
(
procedure.[6] In the text the following abbreviations were used: 1,2-dichloroethane (1,2-DCE),
tetrabutylammonium chloride (TBACl).
2
.2.Synthesis of platinum complexes [PtCl
2
(PPh
3
){N(OH)=CHAr}]
(PPh )(1)], 4)
2.2.1. [PtCl (PPh ){N(OH)=CH(C H (OMe)
6
2
3
3
2
)}] ([PtCl
2
3
A sample (0.300 g) of trans-[Pt(µ-Cl)Cl(PPh
3
2
)] [4h] (0.56 mmol of Pt) was suspended in 1,2-DCE
(
15.0 mL) and treated with a solution of aldoxime 1 (0.101 g) in the same solvent (1/Pt molar ratio=
1.0). The suspension was stirred at room temperature (1h) and then treated with another portion
(
0.101 g) of ligand 1 and refluxed (84 °C). The initially orange suspension turned into a yellow
solution and a colorless solid formed. The solid was filtered and dried under vacuum (0.100 g). A
sample of this solid was crystallized from a CHCl solution, by slow diffusion of pentane vapors
and identified (single crystal X-ray diffraction) as (Z)-cis-[PtCl
3
3
1
2
3
(PPh )(1)] {(Z)-cis-4}. The P-

NMR spectrum of a freshly prepared CDCl
3
solution of the crystals showed a signal at 5.60 ppm
P-Pt = 3860 Hz). The P-NMR spectrum of another sample of the crystals dissolved in 1,2-DCE
showed after 2h four signals: 5.29 (69%), 2.46 (27%), 1.33 (4%), 7.37 (traces). The isomer
1
31
(
J
3
1
responsible of the P-NMR signal at 2.46 ppm was crystallized and identified (single crystal X-ray
diffraction) as (E)-trans-[ PtCl (PPh )(1)] {(E)-trans-4}. A second crop of product was precipitated
2
3
as a mixture of isomers (total isolated yield 51%). We report the spectroscopic characterization for
the species (Z)-cis-4 and (E)-trans-4.
(
Z)-cis-4. C27
H
28Cl
2
NO
~
4
PPt Anal. Calc.: C 44.6, H 3.9, N 1.9 %; Exp.: C 44.8, H 4.4, N 2.0. FTIR
-1
~
~
~
1
4
(
ATR, cm ): 3159 (υ OH), 3048 (υ CH), 2992 (υ CH), 1623 (υ CN). H-NMR: 8.66 (d, 1H, JH-P=4
Hz, CHN); 8.32 (bs, 1H, OH); 7.78 (s, 1H, Harom); 6.86 (d, 1H, J=8.9 Hz, Harom); 7.53-7.45 (m, 10H, Harom
+
31
1
H
arom PPh
3
); 7.36-7.32 (m, 6H, Harom PPh
3
3 3
) 4.05 (s, 3H, OCH ); 3.98 (s, 3H, OCH' ). P-NMR: 5.60 ( JP-
Pt=3860 Hz).
1
4
(
E)-trans-4. H-NMR: 10.9 (s, 1H, OH); 8.45 (d, JH-P=3 Hz, CHN); 7.82-7.78 (m, 6H, Harom PPh
3
); 7.73 (s,
1
H, Harom); 7.59 (d, 1H, J= 8.6 Hz, Harom); 7.58-7.46 (m, 9H, H arom PPh
3
); 6.94 (d, J=8.6 Hz, Harom); 3.97 (s,
31
1
3
H, OCH
3
); 3.92 (s, 3H, OCH'
3
). P-NMR: 2.54 ( JP-Pt=3658 Hz).
2
.2.2. [PtCl
2
(PPh ){N(OH)=CH(1-Naphtyl)}] ([PtCl (PPh )(2)], 5)
3 2 3
A sample (0.194 g) of trans-[Pt(µ-Cl)Cl(PPh
3
)]
2
[4h] (0.36 mmol of Pt) was suspended in 1,2-DCE
(
15.0 mL) and treated with a solution of aldoxime 2 (0.064 g) in the same solvent (2/Pt molar ratio=
1.0). The suspension was refluxed (84 °C) 24h. The initially orange suspension turned into a yellow
solution and a colorless solid formed. The solid was filtered and dried under vacuum (0.061 g) and
identified as (Z)-cis-5. The liquid phase was refluxed (12h) and treated with heptane. A second crop
of solid was obtained and identified as (E)-trans-5. The total, isolated yield was 60%. We report the
spectroscopic characterization for the species (E)-trans- and (Z)-cis-5.
(
2
Z)-cis-5. C29H24Cl NOPPt. Anal. Calc.: C 49.8, H 3.5, N 2.0 %; Exp.: C 49.4, H 4.0, N 2.0%.
-1
~
~
~
~
1
FTIR (ATR, cm ): 3117 (υ OH), 3049 (υ CH), 3006 (υ CH), 1618 (υ CN). H-NMR: 9.85 (d, 1H,
J=7 Hz, Harom); 8.81 (s, 1H, OH); 8.78 (d, 1H, CHN); 8.08 (d, 1H, J=8.4 Hz, Harom); 7.88 (d, 1H, J=8.3 Hz,
Harom); 7.78 (dd, 1H, J=J'= 7.7 Hz, Harom); 7.52 (dd, 1H, J=J'= 7.3 Hz, Harom); 7.38-7.30 (m, 10H, Harom +
3
1
1
H
arom PPh
3
3
); 7.21-7.18 (m, 6H, Harom PPh ), 6.89 (d, 1H, J=8.2Hz, Harom). P-NMR: 5.60 ( JP-Pt=3860 Hz).
1
(
E)-trans-5. H-NMR: 11.05 (d, 1H, J=3.4 Hz, OH); 9.46 (d, 1H, J= 2.5 Hz, CHN); 8.40 (d, 1H, J=7.3 Hz,
Harom); 8.14 (d, 1H, J=8.1 Hz, Harom); 8.00 (d, 1H, J=8.1 Hz, Harom); 7.90 (d, 1H, J=7.3 Hz, Harom); 7.86-7.82
1
3
(
3 3
m, 6Hz, Harom PPh ); 7.60-7.45 (m, 12H, Harom+ Harom PPh ). C-NMR: 148.7, 134.8 (d, JC-P= 10.5 Hz),

133.5, 132.1, 131.7, 131.3, 131.2, 129.7, 128.8, 128.5 (d, JC-P= 64 Hz), 128.1 (d, JC-P= 11.7 Hz), 127.5, 126.4,
31
1
195
1
1
25.0, 123.6. P-NMR: 2.38 ( JP-Pt=3678 Hz). Pt-NMR: -3610 ( JP-Pt=3678 Hz).
2
2 3 2 3
.2.3. [PtCl (PPh ){N(OH)=CH(9-Anthryl)}] ([PtCl (PPh )(3)], 6)
3 2
A sample (0.301 g) of trans-[Pt(µ-Cl)Cl(PPh )] [4h] (0.59 mmol of Pt) was suspended in 1,2-DCE
(
15.0 mL) and treated with a solution of aldoxime 3 (0.129 g) in the same solvent ([3]/[Pt] molar
ratio = 1.0). The suspension, stirred at room temperature for 4h, at first turned into a yellow solution
and successively a yellow solid formed. The solid was filtered and dried under vacuum (0.167 g). A
3
1
1
sample of the solid, dissolved in CDCl
3
, was studied spectroscopically ( P-NMR, ppm): 1.58 ( JP-Pt
1
=
3781 Hz). After 48 h the spectrum showed the signal at 1.58 (20%, JP-Pt = 3781 Hz) and a new
1
one at 2.29 (80%, JP-Pt = 3705 Hz). From this mixture the species responsible of the signal at 2.29
ppm was crystallized and identified (single crystal X-ray diffraction) as (E)-trans-6. A second crop
of solid was collected (0.065 g) for a total yield of 54%. We report the spectroscopic
characterization for the species (Z)-trans-6 and (E)-trans-6.
(
Z)-trans-6. C33
H
26Cl NOPPt. Anal. Calc.: C 52.9, H 3.5, N 1.9 %; Exp.: C 52.7, H 4.1, N 1.9%.
2
-
1
~
~
~
1
4
3
FTIR (ATR, cm ): 3188 (υ OH), 3058 (υ CH), 1627 (υ CN). H-NMR: 9.61 (d, 1H, JH-P=9.0 Hz, JH-
Pt=50 Hz, CHN); 9.45 (s, 1H, OH); 8.66 (s, 1H, Harom); 8.44 (d, 2H, J=8.7 Hz, Harom); 8.11 (d, 2H, J=8.4 Hz,
13
H
arom); 7.66 (m, 2H, Harom); 7.56 (m, 2H, Harom); 7.39-7.23 (m, 15H, Harom PPh
3
). C-NMR: 155.4, 134.5 (d,
J
C-P= 10.4 Hz), 131.2, 130.8, 130.5, 130.4, 128.7, 127.7 (d, JC-P= 11.5 Hz), 127.6 (d, JC-P= 66.7 Hz), 127.0,
31
1
195
1
1
25.7, 125.6, 123.3. P-NMR: 1.58 ( JP-Pt=3781 Hz). Pt-NMR: -3559 ( JP-Pt=3781 Hz).
1
4
3
(
E)-trans-6. H-NMR: 10.87 (s, 1H, OH); 9.69 (d, 1H, JH-P=2.0 Hz, JH-Pt=20 Hz, CHN); 8.59 (s, 1H, Harom);
8
.06 (d, 2H, J=8.4 Hz, Harom); 8.03 (d, 2H, J=8.7 Hz, Harom); 7.90-7.85 (m, 6H, Harom PPh
3
); 7.61-7.56 (m, 4H,
13
H
arom); 7.56-7.49 (m, 9H, Harom PPh ). C-NMR:152.2, 134.9 (d, JC-P= 10.3 Hz), 131.3, 131.0, 130.0, 128.9,
3
3
1
1
1
28.4, 128.1 (d, JC-P= 11.4 Hz), 128.0 (d, JC-P= 69.0 Hz), 127.0, 125.7, 125.3 (2C); P-NMR: 2.29 ( JP-
1
95
1
Pt=3691 Hz). Pt-NMR: -3614 ( JP-Pt=3691 Hz).
2.3.General procedure for the base promoted cyclodimerization reaction
A 1,2-DCE solution of [PtCl (PPh ){N(OH)=CHAr}] (0.2 mmol in 15 mL) was mixed with an
2
3
aqueous solution of NaOH (0.4 mmol in 15mL). A catalytic amount (about 10 mg) of TBACl was
added and the mixture was refluxed under vigorous stirring (2h). The disappearance of the
3
1
precursor was checked by P-NMR spectroscopy, together with the appearance of a single new
1
signal at -0.858 ( JP-Pt= 3981 Hz) and the two phases were separated. The aqueous phase was
extracted with portions of CHCl
3
(3 x 5 mL) and all the collected organic phases were dried over
anhydrous Na SO . The solution was concentrated under vacuum and then treated with heptane
2
4

under stirring. A pale yellow solid formed which was filtered and dried under vacuum. For each
compound, the precursor used, the isolated product yield and the spectroscopic characterization is
reported:
2
2
.3.1. (SP4,4; SP4,4)-(Z, Z)-[PtCl{µ-(κ -N,O)-(1‒H)}(PPh
3
)]
2
[(SP4,4; SP4,4)-(Z, Z)-7]. (Z)-cis-4
-
1
~
~
1
(
(
50% yield). FTIR (ATR, cm ): 3059 (υ CH), 1598 (υ CN). H-NMR: 8.11 (d, 1H, CHN); 7.73
m, 7H, Harom + Harom PPh
3
); 7.39-7.25 (m, 9H, Harom PPh
3
); 7.01 (s, 1H, Harom); 6.82 (d, 1H, Harom);
1
3
3
.92 (s, 3H, OCH
3 3
); 3.83 (s, 3H, OCH' ). C-NMR: 150.7; 148.3; 134.8; 134.6 (d, JC-P=10 Hz);
3
1
1
30.6; 128.4 (d, JC-P=64 Hz); 127.8 (d, JC-P=11 Hz); 124.3; 121.6; 111.3; 110.4; 56.1; 55.0. P-
1
195
1
NMR: -0.801 ( JP-Pt= 3974 Hz). Pt-NMR: -3251 ( JP-Pt= 3974 Hz).
2
2
.3.2. (SP4,4; SP4,4)-(Z, Z)-[PtCl{ µ-(κ -N,O)-(2‒H)}(PPh
3
)]
2
[(SP4,4; SP4,4)-(Z, Z)-8]. (Z)-cis-5
-
1
~
~
1
(
48 % yield). FTIR (ATR, cm ): 3057 (υ CH), 1571 (υ CN). H-NMR: 9.42 (d, 1H, Harom); 8.72 (s,
1H, CHN); 7.92 (d, 1H, Harom); 7.76 (d, 1H, Harom); 7.65 (m, 1H, Harom); 7.55-7.44 (m, 4H, Harom + Harom
1
3
PPh
3
); 7.41-7.32 (m, 7H, Harom + Harom PPh
3
);7.23-7.10 (m, 6H, Harom PPh
3
); 6.68 (d, 1H, Harom). C-
NMR: 150.1; 147.6; 140.0; 134.4 (d, JC-P=10 Hz); 133.0; 130.5; 128.5 (d, JC-P=68 Hz); 128.4;
3
1
1
195
1
28.2; 127.8; 126.5; 126.0 (2C); 125.4; 123.5. P-NMR: -1.58 ( JP-Pt= 3986 Hz). Pt-NMR: -3229
1
(
JP-Pt= 3986 Hz).
2.4. X-ray structure determination
Crystals were selected at room temperature (296 K), glued to glass fibers and analyzed with a
Bruker Smart Breeze CCD diffractometer. Table 1 summarizes the lattice parameters and the
respective space groups. Intensity data were collected in the ranges of 2θ angles reported in the
Table. After correction for Lorentz and polarization effects and for absorption, the structure
solutions were obtained using the direct methods contained in SHELXS program.[7] The
asymmetric units of all the three crystals correspond to the respective molecules but in the case of
(
Z)-cis-4 and (E)-trans-6 ones the structures are completed by a solvent molecule: chloroform and
n-pentane, respectively. The n-pentane solvent molecules are disordered and had to be introduced in
the model by fitting a molecule with an idealized geometry over the residual maxima of the
difference Fourier map and refined as a rigid group. All the hydrogen atoms were introduced in
calculated positions. The final reliability factors and some details of the refinement procedure are
listed in Table S3.
The structure refinement was done using SHELXL program,[8] other control calculations were
performed with the programs contained in the suite WINGX.[9]

3. Results and discussion
3.1 Synthesis of arylaldoxime Pt complexes.
Arylaldoxime ligands were prepared in good yields by a slight modification of a described
procedure [6] and were used to synthesize the corresponding platinum(II) complexes according to
3 2
the regio- and stereoselective ring-opening reaction of trans-[Pt(µ-Cl)Cl(PPh )] [4h] depicted in
Scheme 1.
+
L = Arylaldoxime
2 3
Scheme 1. Ring-opening reaction leading to complexes [PtCl (PPh ){N(OH)=CHAr}]
Although oxime ligands show both N- or O-coordination to metals [10], in the case of platinum(II)
N-coordination is much more frequently observed [3b,10,11], with the exception of cases where
deprotonated oximes act as anionic ligands [3a]. In our case, taking into account the strong trans
3 3 2
effect exerted by PPh , the reaction of arylaldoximes with trans-[Pt(µ-Cl)Cl(PPh )] (Scheme 1)
was expected to afford trans platinum complexes with N-coordinated oxime ligands. Nevertheless,
since square planar Pt(II) complexes often show cis/trans isomerization equilibria in solution and
arylaldoxime ligands can show (E)/(Z) isomerism as well, up to four complexes could theoretically
be observed (Scheme 2). With the aim of following the reaction and characterize spectroscopically
the species formed, a sample (30.0 mg) of trans-[Pt(µ-Cl)Cl(PPh
3
2
)] was reacted with a slight
3
1
excess of arylaldoxime 1 in CDCl
3
. P-NMR analysis clearly showed the formation, after only few
1
minutes, of a kinetic product (1.25 ppm, JP-Pt=3693 Hz), which was reasonably ascribed to (Z)-
2 3 6 3 2
trans-[PtCl (PPh ){N(OH)=CH(C H (OMe) )}] (Scheme 2, (Z)-trans-4). Indeed, the chemical shift
1
and the JP-Pt coupling constant measured in (Z)-trans-4 were very similar to those measured in
2
Pt(II) complexes were a PPh
3
group is trans to ligands coordinated via an sp nitrogen atom [4a].
On the other hand, (Z) geometry in the complex was assigned taking into account the most likely
1
(
E) geometry for the free ligand in solution. The complex was characterized in solution also by H-,
1
3
195
C- and Pt-NMR (see SI-2).

(Z)-trans
(Z)-cis
(E)-trans
(E)-cis
2 3
Scheme 2. Possible equilibria involving [PtCl (PPh ){N(OH)=CHAr}] complexes.
Besides the signal corresponding to the kinetic product (Z)-trans-4, two other minor signals with
1
1
satellites (2.54 ppm, JP-Pt=3668 Hz, 6% and 5.60 ppm, JP-Pt=3890 Hz, traces) were soon observed
3
1
in the P-NMR spectrum, clearly indicating the presence of equilibria in solution. The relative
intensities of the signals changed with time (Table S1) and, after 24h, some colorless crystals
3
1
formed, which were identified as (Z)-cis-4 by single crystal X-ray diffraction. P-NMR analysis
3
carried out on a freshly prepared solution of (Z)-cis-4 in CDCl allowed to assign to this complex
1
the resonance at 5.60 ppm ( JP-Pt=3890 Hz). When a sample of (Z)-cis-4 was dissolved in refluxing
3
1
1
,2-DCE, a yellow solution was obtained. P-NMR spectrum registered on the same solution at
1
1
room temperature showed four signals (5.29 {69%, JP-Pt=3857 Hz}, 2.46 {27%, JP-Pt=3664 Hz},
1
1
.33 {4%, JP-Pt=3700 Hz}, 7.33 {traces}). While signals at 5.29 and 1.33 belonged to the
aforementioned (Z)-cis-4 and (Z)-trans-4, the product characterized by the signal at 2.46 ppm was
crystallized and identified as (E)-trans-4 by single crystal X-ray diffraction, so that it was possible
to assign the resonance at 7.33 ppm to (E)-cis-4. When the synthesis of complex 4 was carried out
in 1,2-DCE on a preparative scale, (Z)-cis-4 precipitated out of the reaction mixture and was
recovered pure, while a second crop of solid was obtained as a mixture of isomers and the overall
yield was about 50%. Analogous preparations were carried out using arylaldoximes 2 and 3 and the
3
1
complexes were identified on the basis of their P-NMR chemical shifts and coupling constants. In
all cases studied the formation of a kinetic product was observed, followed by its isomerization.

With naphthalene derivative 2 it was possible to obtain the least soluble (Z)-cis-5 isomer in good
yield, while with the anthracene derivative 3, isomerization to cis isomers was not observed,
probably due to steric hindrance: in this case, the kinetic product (Z)-trans-6 precipitated out (54%)
from the reaction mixture and was characterized spectroscopically. A sample of (Z)-trans-6 slowly
3
isomerized in CHCl solution to (E)-trans-6, which was crystallized by addition of pentane. Its
structure was determined by single crystal X-ray diffraction. A schematic representation of the
3
1
identified isomers for complexes 4-6, with the corresponding P-NMR observed signals, is
depicted in Chart 1.
Ph3P
Cl
Cl
N
PPh3
Ph3P
Cl
Cl
N
PPh3
O H
Cl
Cl
Cl
Cl
Pt
Pt
Pt
O H
Pt
O H
Ar
O H
N
N
Ar
Ar
Ar
(Z)-cis-4
(
Z)-trans-4
(E)-trans-4
2.46 ppm (J = 3664 Hz)
X-ray structure
(
7
E)-cis-4
.33 ppm
Ar =
MeO
1.33 ppm (J = 3700 Hz) 5.29 ppm (J = 3857 Hz)
kinetic product
X-ray structure
OMe
(Z)-trans-5
(Z)-cis-5
(E)-trans-5
Ar =
1.10 ppm (J = 3760 Hz) 4.50 ppm (J = 3831 Hz)
kinetic product
1.74 ppm (J = 3715 Hz)
nd
(
Z)-trans-6
(E)-trans-6
2.23 ppm (J = 3717 Hz)
X-ray structure
Ar =
1.47 ppm (J = 3783 Hz)
kinetic product
nd
nd
3
1
Chart 1. P-NMR data in 1,2-DCE solution for complexes 4-6.
3 2
With a similar procedure trans-[Pt(µ-Cl)Cl(PPh )] was reacted with 1,3-diphenylpropan-2-one
oxime (S1). In this case only cis/trans isomerism was possible, since the oxime was obtained from a
symmetric ketone. The kinetic trans isomer (S2) was characterized in solution (Table S1), while the
less soluble cis-S2 was recovered in good yield (SI-4).
All the prepared oxime Pt(II) complexes were not soluble in water nor ethanol. They were soluble,
3
1
but not stable in DMSO. As a matter of fact, P-NMR spectra registered in DMSO solutions of
1
compounds 4-6 showed their conversion into cis-[PtCl
2
(PPh
3
)(DMSO)] (18.15 ppm, JP-Pt = 3772
Hz) [4d]. Cis isomers reacted slower than trans isomers, anyway in all cases the substitution
reaction was complete within 48h. This behavior is due to the strong trans effect exerted by PPh
3
.

3.2 Reactivity of arylaldoxime Pt complexes with NaOH under phase transfer catalysis conditions.
It is known [10,12] that the acidity of oxime hydroxyl group is enhanced upon coordination to metal
centers. This reactivity has been used [3a] to prepare dinuclear derivatives upon treatment of some
bis(oxime)dichloroplatinum complexes with silver acetate. It seemed then interesting to investigate
the behavior of arylaldoxime complexes towards bases. In a preliminary experiment, a solution of
(
E)-trans-6 in 1,2-DCE was treated with an aqueous solution of NaOH, in the presence of a
catalytic amount of tetrabutylammonium chloride. The mixture was refluxed and the reaction was
3
1
monitored by P-NMR spectroscopy. The analysis of the spectrum showed the presence of several
signals, which were not assigned. An analogous behavior was observed when (E)-trans-5 was used.
The outcome of the reaction did not change when the process was carried out at room temperature.
On the contrary, good results were obtained when (Z)-cis-4 was reacted under the same
3
1
experimental conditions. After two hours, the P-NMR signal due to (Z)-cis-4 had disappeared and
1
a single, new signal with satellites was observed (-0.807 ppm, JP-Pt=3974 Hz). A yellow solid was
1
recovered upon the usual work-up and addition of pentane. The H-NMR analysis in CDCl
3
showed
the absence of the OH signal of the precursor, while other signals were significantly shifted. The
complete conversion of the precursor was evident also in the ATR-FTIR spectrum of the recovered
-
1
solid, where the strong absorption at 3159 cm , due to OH stretching, had disappeared. The slow
diffusion of pentane vapours into a CHCl solution afforded crystals, which allowed the structural
determination (Figure S1) of the dinuclear derivative (SP4,4; SP4,4)-(Z, Z)-[PtCl{µ-(1‒H)}(PPh )]
Figure 1), where two monoanionic aldoximate ligands coordinate two platinum centers in a head-
3
3
2
(
to-tail mode. To the best of our knowledge, only another example of this kind is described.[3a] In a
similar way, a single product was obtained starting from (Z)-cis-5. Despite several attempts, it was
not possible to crystallize the complex, but its ATR-FTIR and NMR spectroscopic features, very
similar to those observed in the case of [(SP4,4; SP4,4)-(Z, Z)-7], allowed to identify it as (SP4,4;
3 2
SP4,4)-(Z, Z)-[PtCl{µ-(2‒H)}(PPh )] [(SP4,4; SP4,4)-(Z, Z)-8] (Figure 1).
These data show that the selectivity observed in the formation of dinuclear complexes 7 and 8
depends on the stereochemistry of the precursor, the cis isomers allowing the formation of the
dinuclear complex more quickly than possible other products. This data is in agreement with the
behavior previously observed in DMSO.

(
7)
8)
Ar =
(
Figure 1. Structure of dinuclear complexes 7 and 8.
3.3 Structural determinations
Figure 2. Structures of (Z)-cis-4 (A), (E)-trans-4 (B) and (E)-trans-6 (C).
The structures of complexes (Z)-cis-4, (E)-trans-4 and (E)-trans-6 are reported in Figure 2 (A, B
and C respectively), while the most significant bond lengths and angles for the three derivatives are
listed in Table S2. In all the complexes, the coordination around platinum is square planar, with
small deviations from ideality. Oxime ligands are N-coordinated to the metal, as in most of the
described oxime platinum(II) complexes. In (Z)-cis-4 the Pt‒N bond length (2.014(3) Å) is in good
agreement with data described for [PtX (N-oxime)(L)] complexes (X = halide, L = N-coordinated
2

oxime, DMSO) [13], where Pt‒N bond lengths range from 1.90(2) Å to 2.051(9) Å. The molecules
of (Z)-cis-4 are held in couples by OH⋅⋅⋅Cl interactions with O(1)⋅⋅⋅Cl(2') distance of 3.08 Å as
shown in Figure S2.
In (E)-trans-4 and (E)-trans-6 the Pt‒N bond lengths are significantly longer (2.134(3) and
2.1393(16) respectively), due to the trans influence exerted by triphenylphosphine and already
observed for some dipyridyl- and piperazino- Pt(II) complexes. [4a] Indeed, these bond lengths can
be compared with those reported for trans-hydrido(3-methylisoxazol-4,5-dion-4-oximato-
N)bis(triphenylphosphino)platinum(II) [14] (2.15(3) Å) and for some platinum acetyl(N-oxime)
derivatives [15] (bond lengths ranging from 2.104(3) to 2.137(3) Å), where the N-coordinated
oxime ligand is trans to residues (hydride and acetyl) characterized as well by a strong trans
influence. Couples of molecules of (E)-trans-6 interacts by π-stacking of phenanthryl moieties at
distance of about 3.5 Å, as shown in Figure S3.
4. Conclusions
3
New dichloroplatinum(II) complexes bearing PPh and arylaldoxime ligands were prepared starting
from trans-[PtCl(µ-Cl)(PPh )] and arylaldoximes. In each case, coordination to platinum involved
3
2
nitrogen and the kinetic (Z)-trans- product formed at first. Anyway, equilibria in solution involving
cis/trans and/or (E)/(Z) stereoisomers were observed. The study of these equilibria by NMR
spectroscopy, together with X-ray diffraction on solid samples, allowed to describe completely the
investigated systems. While (E)/(Z) isomerism involving the oxime C=N double bond was observed
in all cases studied, cis/trans equilibria were affected by steric hindrance; as a matter of fact, with
anthryl-9-carbaldoxime 3, only trans isomers were obtained. It is worth to note that cis isomers
were generally less soluble than the corresponding trans derivatives and could be obtained as pure
samples.
[
PtCl
2
(PPh ){N(OH)=CH(Ar)}] complexes reacted promptly with aqueous NaOH, under PTC
3
conditions and the outcome of the reaction was affected by stereochemistry. While trans isomers
afforded mixtures of unidentified products, (Z)-cis-4 and (Z)-cis-5 were converted cleanly into rare
3 2
dinuclear aldoximate complexes (SP4,4; SP4,4)-(Z,Z)-[PtCl{µ-(1‒H)}(PPh )] (7) and (SP4,4;
SP4,4)-(Z, Z)-[PtCl{µ-(2‒H)}(PPh )] (8). Since the process is stereospecific, the steric hindrance
3
2
of cis mononuclear precursors is maintained in the dinuclear products 7 and 8. Thus, the loss of
selectivity observed with trans isomers has to be sought in their higher reactivity, due to the strong
3
trans effect exerted by PPh . The different reactivity of the two isomers is in agreement with the

behavior previously observed in DMSO. Although for both isomers thecoordinated oxime is
substituted by DMSO, trans-4-6 reacted faster than the corresponding cis isomers. The prompt and
clean reactivity observed for the aforementioned (Z)-cis- complexes 4 and 5 under basic PTC
conditions is promising, in view of their further derivatization.
Acknowledgements. The authors thank the Università di Pisa for financial support (Fondi di Ateneo
2015). S. Samaritani is grateful to the financial support provided by Università di Pisa—Progetti di
Ricerca di Ateneo 2015—‘Sintesi e studio delle proprietà di composti di metalli di transizione come
agenti Antitumorali’ (PRA_2015_0055). Thanks are due to Dr. Martina Dell’ Acqua for preliminary
experiments.
Appendix A. Supplementary data
Experimental details concerning the preparation of 5 as well as some spectroscopic data are
reported as Supplementary Information.
CCDC 1535199-1535202 contain the supplementary crystallographic data for the derivatives (Z)-
cis-4 , (E)-trans-4 , (E)-trans-6 and [(SP4,4; SP4,4)-(Z, Z)-7]. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif
1
2
3
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Inorganica Chimica Acta
Synthesis and reactivity of platinum(II) triphenylphosphino complexes with aromatic aldoximes
Daniela Belli Dell’ Amico, Marialuigia Colalillo, Luca Labella, Fabio Marchetti, Simona Samaritani*
Dipartimento di Chimica e Chimica Industriale, Università di Pisa, via Giuseppe Moruzzi 13, Pisa I-56124
Graphical Abstract
Ph3P
Cl
Cl
N
PPh3
N
Cl
Cl
Pt
OH
Pt
R
OH
PTC
R
(
Z)-trans
(Z)-cis
H
Cl
O
O
Ph3P
Ar
PPh3
OH
Cl
Cl
Pt
N
Ar
Ph3P
Cl
Cl
N
Pt
Pt
OH
N
Pt PPh3
Cl
N
R
H
R
(E)-trans
(E)-cis

Inorganica Chimica Acta
Synthesis and reactivity of platinum(II) triphenylphosphino complexes with aromatic aldoximes
Daniela Belli Dell’ Amico, Marialuigia Colalillo, Luca Labella, Fabio Marchetti, Simona Samaritani*
Dipartimento di Chimica e Chimica Industriale, Università di Pisa, via Giuseppe Moruzzi 13, Pisa I-56124
Highlights
•
•
•
•
trans-[Pt(µ-Cl)Cl(PPh
cis,trans and/or (E),(Z)-isomers equilibria were studied in solution.
[PtCl (PPh ){N(OH)=CHAr}] reacted with NaOH(aq) under PTC conditions.
dinuclear [Pt{µ-(κ -N,O)}-{N(O)=CHAr}Cl(PPh )] were obtained from cis-(Z)-isomers.
3
)]
2
and arylaldoximes afforded [PtCl
2
(PPh ){N(OH)=CHAr}].
3
2
3
2
3
2