Synthesis and crystal structure of the dinuclear cyclopalladated compounds of methyl (E)-4-(benzylideneamino)benzoate with acetato and chlorido bridge ligands: Study of their splitting reactions with pyridine

Article abstract of DOI:10.1016/j.jorganchem.2016.05.003

Reaction of methyl (E)-4-(benzylideneamino)benzoate C₆H₅CH=N(C₆H₄-4-CO₂Me) with Pd(OAc)₂ produced the dinuclear acetato bridge ortho-cyclopalladated compound [Pd{C₆H₄CH=N(C₆H₄-4-CO₂Me)-κC_ortho,κN}]₂(μ-OAc)₂ (1). Compounds [Pd{C₆H₄CH=N(C₆H₄-4-CO₂Me)-κC_ortho,κN}]₂(μ-Cl)₂ (2) and [Pd{C₆H₄CH=N(C₆H₄-4-CO₂Me)-κC_ortho,κN}(py)(X)] [3 (X = OAc); 4 (X = Cl)] were also prepared and isolated in good yields by substitution reactions. ¹H and ¹³C{¹H} NMR in CDCl₃ solution of compounds 3 and 4 revealed that they consisted of a mixture of trans- and cis-N,N isomers. Addition of pyridine-d₅ to solutions of 1 and 2 in CDCl₃ in a molar ratio pyridine-d₅/1 or 2 ≈50-55 gave solutions A and B, respectively, which contained compounds 5 and 6 analogous to 3 and 4, but with pyridine-d₅ rather than pyridine in their structural formula. In these solutions, the trans- and cis-N,N geometrical isomers of compounds 5 and 6 were interconverting between them in a dynamic equilibrium. In addition, an exchange between free and coordinated pyridine-d₅ was also taking place in solutions A and B. The NMR data for solution A showed that the dynamic equilibrium between the cis- and trans-N,N isomers of compound 5 was shifted to the trans-N,N isomer. However, the NMR data for solution B suggested that in this solution the equilibrium between the cis- and trans-N,N isomers of compound 6 was shifted to the cis-N,N isomer. Interconversion between the trans- and cis-N,N isomers of compounds 5 and 6 in solutions A and B plausibly proceeded through the intermediate ionic complexes [Pd{C₆H₄CH=N(C₆H₄-4-CO₂Me)-κC_ortho,κN}(py-d₅)₂]X [7 (X = OAc), 8 (X = Cl)]. Ionic complexes 7 and 8 were not observed in CDCl₃ solution but were the major species in D₂O solutions containing compounds 1 and 2 and pyridine-d₅ in a molar ratio pyridine-d₅/1 or 2 ≈50-55. The crystal structure of the adduct 1·2(CH₃COOH) and that of compound 2 were determined by single crystal X-ray diffraction. A theoretical study on the difference in free Gibbs energy in CHCl₃ solution between the cis- and trans-N,N isomers of compounds 3 and 4 is also included in this work.

Full text of DOI:10.1016/j.jorganchem.2016.05.003

Journal of Organometallic Chemistry 815-816 (2016) 44e52
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis and crystal structure of the dinuclear cyclopalladated
compounds of methyl (E)-4-(benzylideneamino)benzoate with
acetato and chlorido bridge ligands: Study of their splitting reactions
with pyridine
Joan Albert a b, , Ramon Bosque , Lucía D’Andrea **, Jos eꢀ Antonio Dur aꢀ n a,
,
*
a
,
b
a,
Jaume Granell , Merc eꢁ Font-Bardia , Teresa Calvet c
Departament de Química Inorg aꢁ nica, Facultat de Química, Universitat de Barcelona, Martí i Franqu ꢁe s 1-11, 08028 Barcelona, Spain
Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain
Departament de Cristal·lografia, Mineralogia i Dip oꢁ sits Minerals, Universitat de Barcelona, Martí i Franqu ꢁe s s/n, 08028 Barcelona, Spain
a,
b
c, d
a
b
c
d
Unitat de Difracci oꢀ de RX, Centre Científic i Tecnol oꢁ gic de la Universitat de Barcelona, Sol ꢀe i Sabarís 1-3, 08028 Barcelona, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 March 2016
Received in revised form
Reaction of methyl (E)-4-(benzylideneamino)benzoate C H CH]N(C H -4-CO Me) with Pd(OAc) pro-
6
5
6
4
2
2
duced the dinuclear acetato bridge ortho-cyclopalladated compound [Pd{C
N}] -OAc) (1). Compounds [Pd{C CH]N(C -4-CO Me)-
CH]N(C -4-CO Me)-
N}(py)(X)] [3 (X ¼ OAc); 4 (X ¼ Cl)] were also prepared and iso-
lated in good yields by substitution reactions. H and C{ H} NMR in CDCl
revealed that they consisted of a mixture of trans- and cis-N,N isomers. Addition of pyridine-d
solutions of 1 and 2 in CDCl in a molar ratio pyridine-d /1 or 2 z 50e55 gave solutions A and B,
respectively, which contained compounds 5 and 6 analogous to 3 and 4, but with pyridine-d rather than
6
H
4
CH]N(C
6
H
4
2
-4-CO Me)-
k
C
ortho
,k
2
(
m
2
6
H
4
6
H
4
2
k
C
ortho
,k
N}] -Cl)
2
(
m
2
(2) and [Pd
21 April 2016
{C
6
H
4
6
H
4
2
ortho
kC ,k
Accepted 4 May 2016
Available online 6 May 2016
1
13
1
3
solution of compounds 3 and
to
4
5
3
5
Keywords:
Cyclometallation
Palladium(II)
Splitting reaction
Pyridine
5
pyridine in their structural formula. In these solutions, the trans- and cis-N,N geometrical isomers of
compounds 5 and 6 were interconverting between them in a dynamic equilibrium. In addition, an ex-
change between free and coordinated pyridine-d was also taking place in solutions A and B. The NMR
5
Geometrical isomerization
data for solution A showed that the dynamic equilibrium between the cis- and trans-N,N isomers of
compound 5 was shifted to the trans-N,N isomer. However, the NMR data for solution B suggested that in
this solution the equilibrium between the cis- and trans-N,N isomers of compound 6 was shifted to the
cis-N,N isomer. Interconversion between the trans- and cis-N,N isomers of compounds 5 and 6 in solu-
tions A and B plausibly proceeded through the intermediate ionic complexes [Pd{C
CO Me)- N}(py-d
]X [7 (X ¼ OAc), 8 (X ¼ Cl)]. Ionic complexes 7 and 8 were not observed in
CDCl solution but were the major species in D O solutions containing compounds 1 and 2 and pyridine-
in a molar ratio pyridine-d /1 or 2 z 50e55. The crystal structure of the adduct 1$2(CH COOH) and
that of compound 2 were determined by single crystal X-ray diffraction. A theoretical study on the
6 4 6 4
H CH]N(C H -4-
2
k
C
ortho
,k
5 2
)
3
2
d
5
5
3
difference in free Gibbs energy in CHCl
3
solution between the cis- and trans-N,N isomers of compounds 3
and 4 is also included in this work.
©
2016 Elsevier B.V. All rights reserved.
1. Introduction
In recent years, it has been shown that some N-donor cyclo-
metallated palladium(II) compounds present anticancer activity,
both in vitro and in vivo in mouse models [1e4]. The anticancer
activity of these compounds can be modulated by modifying the
substituents at the N-donor cyclometallated ligand or by changing
through substitution reactions the co-ligands of the palladium(II)
*
Corresponding author. Departament de Química Inorg aꢁ nica, Facultat de Quí-
mica, Universitat de Barcelona, Martí i Franqu eꢁ s 1-11, 08028 Barcelona, Spain.
** Corresponding author.
E-mail addresses: joan.albert@qi.ub.es (J. Albert), luciadandrea@hotmail.com
(
L. D’Andrea).
http://dx.doi.org/10.1016/j.jorganchem.2016.05.003
022-328X/© 2016 Elsevier B.V. All rights reserved.
0

J. Albert et al. / Journal of Organometallic Chemistry 815-816 (2016) 44e52
45
center [5,6]. Substitution reactions at palladium(II), in which the
entering ligand is a DNA nitrogen base or a thiol function of an
enzyme, such as Cathepsin B, or oxidation by palladium(II) of
mitochondrial membrane protein thiol functions to disulphide
groups, seem to be the starting reactions that could explain the
cytotoxicity of this type of compounds towards cancer cells [4,7,8].
In addition, cyclopalladated compounds present application as
precatalysts for carbon-carbon and carbon-heteroatom coupling
reactions [9,10] and as Lewis acid catalysts for some organic re-
actions [9,11], between many other applications [12]. Furthermore,
in recent years the cyclopalladation reaction has been successfully
introduced in catalytic cycles that transform CeH bonds in CeC and
C-heteroatom bonds [13e15]. Therefore, the study of the synthesis,
reactivity and properties of cyclopalladated compounds is a subject
of interest [12].
which was consistent with the coordination of the iminic nitrogen
to the palladium(II) center [17]. The asymmetric and symmetric
stretchings of the acetato carboxylic functions of 1 produced broad
ꢀ
1
intense bands at 1574 and 1415 cm , indicating that the acetato
ligands of 2 presented a bridging coordination mode [18]. The C]O
stretching of the ester function for compounds 1 and 2 appeared at
ꢀ1
1717 and 1719 cm , respectively. In addition, the LDI-TOF (þ) mass
spectra of compounds 1 and 2 produced intense peaks for the
þ
cations [MꢀX] , where X was acetate for 1 and chloride for 2, in
agreement with their dinuclear structure with acetato and chlorido
bridge ligands [19].
The main features of the 1H NMR of compound 1 in CDCl
so-
3
lution were i) the high-field shift of the methinic proton in relation
to the free imine by 0.72 ppm, ii) the high-field shift of the H2
proton (6.58 ppm) in relation to the free ligand (7.53e7.47 ppm),
and iii) the presence of only one singlet produced by the methyl
protons of the acetato ligands and by the protons of the methox-
ycarbonyl functions, which appeared at 1.86 and 3.95 ppm,
respectively. Overall the precedent characterization data for com-
In this work, we deal with i) the synthesis and characterization
of the dinuclear ortho-cyclopalladated compounds [Pd{C
N(C -4-CO Me)- N}] -X)
(X ¼ Cl), derived from methyl (E)-4-(benzylideneamino)benzoate
CH]N(C -4-CO Me), ii) the synthesis and characterization
mononuclear derivatives [Pd
N}(L)(X)], compounds
L ¼ pyridine, X ¼ OAc), 4 (L ¼ pyridine, X ¼ Cl), 5 (L ¼ pyridine-d
6
H
4
CH]
6
H
4
2
kC
ortho
,k
2
(m
2
, compounds 1 (X ¼ OAc) and
2
C
H
6 5
6
H
4
2
ortho
pound 1 were consistent with a kC ,kN bidentate chelate coor-
of their pyridine and pyridine-d
CH]N(C -4-CO Me)-
5
dination mode for its imine ligands and with this compound
adopting a trans-folded dinuclear structure with acetato ligands
bridging the palladium(II) centers [19e22].
{
C
6
H
4
H
6 4
2
kC
ortho
,
k
3
(
5
,
13
1
X ¼ OAc) and 6 (L ¼ pyridine-d
5
, X ¼ Cl), iii) the study of the ste-
3
The C{ H} NMR in CDCl of compound 1 produced a single set
reochemistry and behaviour in solution of compounds 3e6, and iv)
of signals, which presented as principal features i) the low-field
shift of the methinic and the metallated carbon atoms in relation
to the free imine by 11.8 and 3.6 ppm, respectively, and ii) the single
set of signals afforded by the carbon atoms of the acetato ligands,
which appeared at 180.6 and 24.2 ppm, and by the carbon atoms of
the methoxycarbonyl functions, which resonated at 166.4 and
a computational study related with the difference in free Gibbs
energy in CHCl
3
solution between the cis- and trans-N,N isomers of
compounds 3 and 4.
2
. Results and discussion
ortho
52.3 ppm. These data were consistent with the kC ,kN coordi-
Scheme 1 outlines the methods of preparation of the com-
nation mode of the imine ligands in compound 1 and with its trans
pounds under study and gives their numbering, and that of their
hydrogen and carbon atoms for the discussion that follows. Com-
stereochemistry [19].
1
The H NMR of compound 2 in CDCl
3
at 298 K produced one set
1
13
1
plete assignment of the signals of the H and C{ H} NMR for
methyl (E)-4-(benzylideneamino)benzoate CH]N(C -4-
CO Me), compound 1 and the trans- and cis-N,N isomers of com-
of signals, most of them broad, except the methinic protons, which
afforded a singlet at 8.01 ppm, 0.43 ppm high-field shifted in
relation to the free imine, and the protons of the methoxycarbonyl
functions, which produced a singlet at 3.96 ppm. The broadening of
the proton NMR signals of dinuclear cyclopalladated compounds
C
6
H
5
6 4
H
2
1
1
pounds 3 and 4, was achieved by two-dimensional He H and
He C NMR experiments.
1
13
Methyl (E)-4-(benzylideneamino)benzoate was synthesized by
with chlorido bridge ligands in CDCl
namic equilibrium between their cis and trans isomers [23].
X-ray quality yellow crystals of the adduct 1$2(CH CO H) and of
compound 2 were obtained by slow evaporation at room temper-
ature of a solution in acetic acid of 1 and of a solution in chloroform
3
has been ascribed to a dy-
a condensation reaction between equimolecular amounts of
benzaldehyde and methyl 4-aminobenzoate. The acetato bridge
cyclopalladated compound (1) was prepared by a cyclopalladation
3
2
reaction between equimolecular amounts of Pd(OAc)
2
and methyl
(E)-4-(benzylideneamino)benzoate. A metathesis reaction between
3 2
of complex 2, respectively. Adduct 1$2(CH CO H) and compound 2
compound 1 and an excess of LiCl was carried out to produce the
chlorido bridge cyclopalladated complex (2). Details on the prep-
aration of these compounds are given in Scheme 1 and in the
experimental part.
crystallized in the triclinic P-1 with Z ¼ 2 and in the orthorhombic
Pccn with Z ¼ 4 space groups, respectively. Details on the X-ray
crystallographic structure determinations are given in the
Supplementary Material.
Methyl (E)-4-(benzylideneamino)benzoate was a pale yellow
Figs. 1 and 2 show ball and stick models for the XRD molecules
of compounds 1 and 2, respectively, together with some distances
and angles for them. In the crystal of 1$2(CH CO H), the two halves
3 2
of the molecule of 1 were not equivalent and differed between
them only in small differences in distances and angles. On the other
hand, in the crystal of 2, both halves of the molecule of 2 were
equivalent since the molecule was situated over a crystallographic
center of inversion.
3
solid soluble in CDCl , and in solution in this solvent afforded a
1
13
1
single set of signals both in the H and in the C{ H} NMR. These
results suggested that methyl (E)-4-(benzylideneamino)benzoate
consisted of only the E-stereoisomer in relation to the imine
function [16]. The methinic proton and the methinic carbon atom of
methyl (E)-4-(benzylideneamino)benzoate appeared at 8.44 and
1
61.7 ppm, respectively, and the C]N and C]O stretchings of the
imine and ester functions produced intense bands at 1628 and
Bond distances and angles around of the palladium(II) centers
for the molecules of 1 and 2 were between the normal intervals
[5,19,24e26]. The chelate bite angles at palladium(II) showed the
ꢀ1
1
717 cm , respectively. In addition, the ESI (þ) mass spectrum of
methyl (E)-4-(benzylideneamino)benzoate gave an intense signal
at 240.1 m/z, which corresponded to [MþH] .
þ
ꢁ ꢁ
largest deviations from the ideal angle of 90 , being 80.0(2) and
ꢁ
ꢁ
Compounds 1 and 2 were red and yellow solids, and were quite
80.7(2) for 1 and 81.6 (4) for 2. The five-membered metallacycles
were planar and maximum deviated atoms from the five-
membered planar metallacycles were N(1) [0.008(5) Å] and N(2)
[ꢀ0.022(5) Å] for 1 and C(3) [0.054(13) Å] for 2. In 1 and 2, the PdeO
3
and slightly soluble in CDCl , respectively. The C]N stretching of
ꢀ
1
compounds 1 and 2 appeared at 1609 and 1605 cm , as an intense
band shifted to lower wavenumbers in relation to the free imine,

46
J. Albert et al. / Journal of Organometallic Chemistry 815-816 (2016) 44e52
ꢁ
Scheme 1. i) Pd(OAc)
temperature, molar ratio pyridine/1 or 2 z 3; iv) pyridine-d
pyridine-d
0 mg (30
2
, HOAc, 60 C, molecular ratio methyl (E)-4-(benzylideneamino)benzoate/Pd(OAc)
2
¼ 1; ii) LiCl excess, acetone, room temperature; iii) pyridine, CH
2
Cl
2
, room
5
, CDCl , room temperature, molar ratio pyridine-d
3
5
/1 or 2 z 50e55, v) pyridine-d
5
, D
2
O, room temperature, molar ratio
3
5
/1 or 2 z 50e55. Reactions in deuterated solvent were performed treating ca. 6 mg of compound 1 or 2 with 1 cm of the corresponding deuterated solvent and ca.
3
5
mL) of pyridine-d .
and PdeCl bonds trans to the metallated carbon atoms were longer
than the corresponding bonds trans to the iminic nitrogen atom
The angle between the palladacycles in compound 1 was
30.8(2) and the distance between palladium atoms was
ꢁ
[
Pd(1)eO(1) ¼ 2.161(4) Å and Pd(2)eO(4) ¼ 2.156(4) Å but Pd(1)
2.9175(13) Å. This distance was too long for being considered a
palladiumepalladium single bond [28]. In compound 2, the palla-
dacycles and the chlorido bridging ligands defined a plane (plane
1). For compound 1, the angles between the phenyls bonded to the
iminic nitrogen atoms and the metallacycles were 50.8(3) and
eO(3) ¼ 2.041(4) Å and Pd(2)eO(2) ¼ 2.050(4) Å for 1, and
Pd1eCl2i ¼ 2.464 (3) Å but Pd1eCl2 ¼ 2.337 (3) Å for 2]. These
results were in agreement with the greater trans influence of the
palladated carbon atom in relation to the iminic nitrogen atom [27].

J. Albert et al. / Journal of Organometallic Chemistry 815-816 (2016) 44e52
47
function, the C]N stretching of the imine function and the C]N
stretching of the pyridine ligand, respectively. The MALDI-TOF (þ)
for compound 3 and 4 produced an intense signal for the cation
þ
[
MꢀX] , where X was acetate for compound 3 and chloride for
compound 4. In addition, compound 4 produced also intense sig-
þ
þ
nals for the cations [2MꢀCl] and [2MꢀClꢀpy] .
Interestingly, compounds 3 and 4 isolated from the solution
2 2
resulting from the reaction in CH Cl of compounds 1 and 2 with
pyridine in a molar ratio pyridine/1 or 2 z 3 consisted of a mixture
of trans- and cis-N,N isomers (Scheme 1). The relative integral of the
signals of the ortho protons of the coordinated pyridine allowed to
establish the ratio between the trans and cis isomers of compounds
Fig. 1. XRD molecular structure of compound 1. Hydrogen atoms and solvent mole-
cules have been omitted for clarity. Selected bond distances (Å) and angles ( ): Pd(1)
eC(5) 1.993(6), Pd(1)eO(3) 2.041(4), Pd(1)eN(1) 2.052(4), Pd(1)eO(1) 2.161(4), Pd(1)
ePd(2) 2.9175(13), Pd(2)eC(20) 1.982(5), Pd(2)eO(2) 2.050(4), Pd(2)eN(2) 2.054(5),
Pd(2)eO(4) 2.156(4), N(1)eC(11) 1.298(7), N(2)eC(26) 1.299(7), C(25)eC(26) 1.444(7),
C(10)eC(11) 1.425(7), C(20)eC(25) 1.364(7), C(5)eC(10) 1.411(8), C(5)ePd(1)eO(3)
ꢁ
3
and 4 in CDCl
compound 4. The ratio between the geometrical isomers of 3 and 4
in CDCl solution was unaltered after maintaining the precedent
3
, which were 1.0:0.8 for compound 3 and 1.0:0.6 for
92.4(2), C(5)ePd(1)eN(1) 81.0(2), O(3)ePd(1)eN(1) 173.13(17), C(5)ePd(1)eO(1)
175.28(18), O(3)ePd(1)eO(1) 88.60(17), N(1)ePd(1)eO(1) 97.84(17), C(20)ePd(2)
3
eO(2) 91.8(2), C(20)ePd(2)eN(2) 80.7(2), O(2)ePd(2)eN(2) 172.53(17), C(20)ePd(2)
eO(4) 175.24(18), O(2)ePd(2)eO(4) 88.15(16), N(2)ePd(2)eO(4) 99.25(17), C(10)eC(5)
ePd(1) 112.4(4), C(5)eC(10)eC(11) 115.4(5), N(1)eC(11)eC(10) 117.2(5), C(11)eN(1)
ePd(1) 113.9(4), C(26)eN(2)ePd(2) 112.7(4), N(2)eC(26)eC(25) 117.6(5), C(20)eC(25)
eC(26) 114.5(5), C(25)eC(20)ePd(2) 114.3(4).
solutions at room temperature for two days. Interestingly, the cis-
N,N isomer of compounds 3 and 4 produced somewhat broad sig-
nals for the ortho protons of the coordinated pyridine, suggesting
that an exchange between the coordinated pyridine trans to the
palladated carbon atom and an adventitious free L ligand (water or
pyridine) was taking place in these solutions. The strong trans effect
produced by the metallated carbon atom into the coordinated
pyridine in the cis-N,N isomer of compounds 3 and 4 should favour
this exchange [29].
Addition of pyridine-d
mg of compound 1 in 1 cm of CDCl
z 50e55 gave solution A. Solution A contained as observable
5
to a solution of compound 1 in CDCl
3
(ca.
5
/
3
6
1
3
) in a molar ratio pyridine-d
1
palladium(II) compound by H NMR at 400 MHz and at room
temperature, compound 5, which was analogous to compound 3
but with a pyridine-d ligand rather than a pyridine ligand in its
5
structural formula. Doublet signals at 7.83 and 6.63 ppm and a
singlet at 3.89 ppm were assigned to methyl 4-aminobenzoate (4-
2 6 4 2
H NC H CO Me). The molar ratio between compound 5 and
methyl 4-aminobenzoate was ca. 20. Noteworthy, compound 5 in
solution A consisted of only the trans-N,N geometrical isomer by H
NMR at 400 MHz and at room temperature. Thus, a large excess of
Fig. 2. XRD molecular structure of compound 2. Hydrogen atoms have been omitted
for clarity. Selected bond distances and angles: Pd1eC3 1.980 (13), Pd1eN10 2.089 (9),
Pd1eCl2 2.337 (3), Pd1eCl2i 2.464 (3), C9eN10 1.304 (15), C8eC9 1.414 (17), C3eC8
1
1
.428 (16), C3ePd1eN10 81.6 (4), C3ePd1eCl2 93.7 (3), N10ePd1eCl2 174.6 (3),
pyridine-d
. The precedent results indicated that the cis- and trans-N,N iso-
mers of compound 5 (or 3) were the kinetic and thermodynamic
control products, respectively, for the reaction 1 þ 2 py-d (or 2
py) / 5 (or 3) (reaction ). For reaction , the cis-N,N isomer
5
promoted the cis / trans isomerization of compound
C3ePd1eCl2i 177.1 (4), N10ePd1eCl2i 100.5 (3), Cl2ePd1eCl2i 84.08 (10), Pd1e-
Cl2ePd1i 95.92 (10), C11eN10ePd1 127.9 (7), N10eC9eC8 119.6 (10), C9eC8eC3 114.6
5
(
11), C8eC3ePd1 112.4 (9).
5
a
a
ꢁ
should be the kinetic control product of the reaction due to the
strong trans effect produced by the metallated carbon atoms into
the acetato O-donor atoms trans to them in the initial compound 1
4
1.0(3) , and for compound 2, the angle between the phenyls
ꢁ
bonded to the iminic nitrogen atoms and plane 1 was 5.89(13) . For
compounds 1 and 2, the methoxycarbonyl functions and the phenyl
groups bonded to the methoxycarbonyl functions were coplanar.
Compounds 3e8 were prepared by splitting reactions between
the corresponding compound 1 or 2 and pyridine (compounds
e4) or pyridine-d
isolated and fully characterized, whereas compounds 5e8 were
studied by NMR in CDCl solution (compounds 5 and 6) or in D
solution (compounds 7 and 8) in both cases in presence of free
pyridine-d
[29].
The signals of the aromatic protons of compound 6 in solution B
at 500 MHz and at 298 K were broad but only one palladium(II)
species was observed. Solution B was analogous to solution A but
contained ca. 6 mg of compound 2 rather than 6 mg of compound 1.
3
5
(compounds 5e8). Compounds 3 and 4 were
1
In the H NMR of solution B at 500 MHz and at 298 K, the H10 and
3
2
O
H9 protons of compound 6 produced broad signals at 7.97 and
7.12 ppm. These chemical shifts were between the chemical shifts
5
.
of the H10 and H9 protons of the cis-N,N (7.76 and 7.00 ppm) and
the trans-N,N (8.09 and 7.51 ppm) isomers of compound 4. These
results indicated that the cis- and trans-isomers of compound 6
were in a fast dynamic equilibrium between them in solution B. The
lack of a signal of an aromatic proton in the interval between 7.00
and 6.00 ppm and the fact that the chemical shift of the H9 protons
Compounds 3 and 4 were isolated, as yellow and pale-yellow
solids in 82 and 97% yield, respectively. These compounds pro-
duced satisfactory elemental analyses, IR and MALDI-TOF-(þ) mass
spectra. In the IR spectrum of compound 3, bands at 1720, 1604 and
ꢀ
1
1586 cm
were assigned to the C]O stretching of the ester
function, the C]N stretching of the imine function and the C]O
stretching of the carboxylate function of the terminal acetato
ligand, respectively. The C]N stretching of the pyridine ligand of
compound 3 was obscured by the strong band corresponding to the
C]O stretching of the carboxylate function of the terminal acetato
ligand. In the IR spectrum of compound 4, bands at 1715, 1604 and
(7.12 ppm) was closer to the chemical shift of the H9 protons of the
cis-N,N isomer (7.00 ppm) than that for the H9 protons of the trans-
N,N isomer (7.51 ppm) suggested that the cis-N,N isomer of com-
pound 6 was the major species in solution B. It should be noted that
the exchange between coordinated and free pyridine-d in the cis-
5
N,N isomer of compound 6 in solution B could also be contributing
to the broadening of the signals. The strong trans effect produced by
ꢀ
1
1586 cm
were assigned to the C]O stretching of the ester

48
J. Albert et al. / Journal of Organometallic Chemistry 815-816 (2016) 44e52
the palladated carbon atom on the coordinated pyridine-d
cis-N,N isomer of compound 6 should favour this latter exchange
5
in the
kinetic control product of the reaction due to the strong trans effect
produced by the metallated carbon atoms into the chlorido bridge
ligands trans to them in the initial compound 2 [29].
[
29].
1
13
1
Interestingly, the H NMR of a solution of ca. 6 mg of compound
in 1 cm of CDCl
In the C{ H} NMR at 101 MHz of solution B and at room
temperature, the carbon signals of the coordinated pyridine-d , the
3
2
3
and containing a molar ratio between pyridine-
5
d
5
and compound 2 of ca. 4 (solution B′) or by reducing the tem-
carbon bonded to the palladium atom, and the carbons of the
00
perature of solution B to 223 K (solution B ), produced separated
signals for the cis- and trans-N,N isomers of compound 6, as
established by H NMR at 400 MHz in the first case, and at 500 MHz
phenyl bonded to the iminic nitrogen atom of compound 6 were
1
not observed. On the other hand, the H NMR of solution A at
1
400 MHz and at room temperature produced narrow signals for the
13
1
in the second. Diagnostic signals for the cis- and the trans-N,N
isomers of compound 6 were the broad signals at 7.80 ppm (H10
protons of the cis-N,N isomer) and at 6.12 ppm (H2 proton of the
trans-N,N isomer). From the ratio between the integral of the H2
proton at 6.12 ppm of the trans-N,N isomer of compound 6 and the
integral of the protons of the methoxycarbonyl function of com-
pound 6, which afforded only one sharp signal for the cis- and
trans-isomers of compound 6 at 3.90 ppm in all solutions B, it was
trans-N,N isomer of compound 5, and in its C{ H} NMR at
13
101 MHz and at room temperature, all the C signals were
observed, except those of the coordinated pyridine-d . Thus, an
exchange between free and coordinated pyridine-d was also tak-
5
5
ing place in solutions A and B, but this exchange was taking place at
a slower rate in solution A [19]. The weaker trans effect produced by
the iminic nitrogen on the coordinated pyridine-d
isomer of compound 5, in relation to the trans effect produced by
the palladated carbon atom on the coordinated pyridine-d on the
5
on the trans-N,N
00
established that in solutions B′ and B the ratio between the cis-
and trans-N,N isomers of compound 6 was ca. 1.
5
cis-N,N isomer of compound 6 should explain this result [29]. In
addition, the bulkier acetato terminal ligand in compound 5 in
relation to the chlorido terminal ligand in compound 6, could also
decrease the rate of the exchange in solution A in relation to so-
lution B.
In order to obtain more information on the relative stability of
the cis- and trans-N,N isomers of compounds 3 and 4, the difference
between their electronic energy, absolute enthalpy and absolute
1
1
00
A H e H COSY recorded on solution B at 500 MHz, confirmed
the assignment of the proton at 6.12 ppm to the H2 proton of the
trans-N,N isomer of compound 6, since this proton in the COSY
experiment showed a sequential correlation with three more aro-
matic protons, the last identified as the H5 proton of the ortho-
palladated phenyl ring of the trans-N,N isomer of compound 6. The
H2 proton of the trans-N,N isomer of compound 6 was shifted at
high-field because it was located in the shielding zone of the co-
ordinated pyridine-d
aromatic region of the He H COSY experiment of solution B at
00 MHz showing the COSY signals between the protons of the
ortho-palladated ring of the trans-N,N isomer of compound 6.
5
[19,25,30,31]. Fig. 3 gives an expansion of the
1
1
00
Table 1
Energy differences calculated at the DFT/B3LYP level between the cis- and trans-N,N
5
ꢀ
1
isomers for compounds 3 and 4 in kcal mol . Positive values indicate that the trans-
N,N isomer is more stable than the cis-N,N isomer.
E ¼ electronic energy(cis-
N,N) ꢀ electronic energy(trans-N,N). H ¼ absolute enthalpy(cis-N,N) ꢀ absolute
enthalpy(trans-N,N).
G ¼ absolute Gibbs free energy(cis-N,N) ꢀ absolute Gibbs free
energy(trans-N,N). v ¼ vacuum. CHCl ¼ chloroform solution.
D
00
NMR data for solutions B, B′ and B indicated that a large excess
of pyridine-d promoted the geometrical isomerization of com-
D
5
D
pound 6 and, noteworthy, suggested that the cis-N,N isomer of
compound 6 (or 4) was simultaneously the kinetic and thermo-
3
Compound
D
E(v)
DE(CHCl
3
)
D
H(v) H(CHCl
D
3
)
D
G(v)
3
DG(CHCl )
dynamic control product for the reaction 2 þ 2 py-d
5
(or 2py) / 6
3
4
ꢀ0.66
0.05
ꢀ2.31 ꢀ0.78
ꢀ0.74 ꢀ0.03
ꢀ2.40 ꢀ0.87
ꢀ1.57 ꢀ0.87
ꢀ2.88 ꢀ1.35
(
or 4) (reaction ). For reaction , the cis-N,N isomer should be the
b
b
Fig. 3. Expansion of the aromatic region of the 1He H COSY experiment at 500 MHz of solution B (solution B at 223 K). * Residual CHCl
1
00
3
3 5 4
in CDCl . ** Residual p-C HD N in pyridine-
d
5
. *** Residual m-C HD N in pyridine-d
5
4
5
.

J. Albert et al. / Journal of Organometallic Chemistry 815-816 (2016) 44e52
49
Gibbs free energy in vacuum and in CHCl
3
solution were calculated.
It should be noted that the proposed mechanism for the
geometrical isomerization of the discussed square planar palla-
dium(II) is the most usual mechanism for the geometrical isomer-
Table 1 summarizes the results. Mol files for the optimized geom-
etries for the trans- and cis-isomers of compounds 3 and 4 and the
details of the computational calculations are given in the
Supplementary Material. Only the difference of absolute Gibbs free
energy in chloroform solution between the cis- and trans-N,N iso-
mers of compounds 3 and 4 (the last column in Table 1) is discussed
ization of square planar complexes of formula [ML
2
X
2
] (M ¼ Pt(II)
or Pd(II), L ¼ neutral monodentate ligand, X ¼ monoanionic mon-
odentate ligand), and it is termed the consecutive displacement
mechanism [32].
because the experimental studies were performed in CDCl
3
solu-
In summary, the experimental data indicated that in solutions A
and B the trans- and cis-N,N isomers of compounds 5 and 6 were
interconverting between them in a dynamic equilibrium. In addi-
tion. It should be noted that although the computational study
predicted that for both compounds the cis-N,N isomer was the most
stable one, experimentally the more stable isomer for compound 5
was the trans-N,N isomer. However, the computational study pre-
dicted in agreement with what was suggested by the experimental
work that i) the thermodynamic preference for the cis-N,N isomer
for compound 4 (with a terminal chlorido ligand) was higher than
for compound 3 (with a terminal acetato ligand), and ii) the dif-
5
tion, an exchange between free and coordinated pyridine-d was
also taking place in these solutions. In solution A, the dynamic
equilibrium between the cis- and trans-N,N isomers of compound 5
was shifted to the trans-N,N isomer. However, NMR data for solu-
tion B suggested that in this solution the dynamic equilibrium
between the cis- and trans-N,N isomers of compound 6 was shifted
to the cis-N,N isomer. Interconversion between the trans- and cis-
N,N isomers of compounds 5 and 6 in solutions A and B could
proceed through the intermediate ionic complexes of formula [Pd
3
ference between the absolute Gibbs free energy in CHCl solution
for the cis and trans isomers of compounds 3 and 4 was small.
Relevant to understand the mechanism of the geometrical
isomerization of compounds 5 and 6, compounds 1 and 2 (ca.
{C
and 8 (X ¼ Cl). Ionic complexes 7 and 8 were not observed in CDCl
solution but were the major species detected by NMR in D O so-
lutions containing compounds 1 and 2 (ca. 6 mg of 1 or 2 in 1 cm of
O) and pyridine-d in a molar ratio pyridine-d /1 or 2 z 50e55.
A reviewer suggested that a -stacking interaction between the
6
H
4
CH]N(C
6
H
4
-4-CO
2
Me)-
k
C
ortho
,
k
N}(py-d
5
)
2
]X, 7 (X ¼ OAc)
3
6
mg), reacted with pyridine-d
5
in D
2
O (1 cm ) in a molar ratio
3
pyridine-d
5
/1 or 2 z 50e55 to form solutions C and D, which
2
3
contained as major compounds, the ionic mononuclear cyclo-
palladated complexes 7 (X ¼ OAc) and 8 (X ¼ Cl) of formula [Pd
D
2
5
5
{
C
6
H
4
CH]N(C
H
6 4
-4-CO
2
Me)-kC
ortho
,
kN}(py-d
)
5 2
]X (Scheme 1).
p
The ionic complexes 7 and 8 were not isolated but were charac-
terized in D O solution by mono- and bidimensional NMR experi-
aryl ring bonded to the iminic nitrogen and the pyridine could
2
stabilize the cis-N,N isomers of compounds 3 and 4. We have found
2
ments. Ortho-palladated benzaldehyde and methyl 4-
aminobenzoate were also observed by NMR in solutions C and D.
The molar ratio between compounds 7 or 8, ortho-palladated
benzaldehyde and methyl 4-aminobenzoate in solutions C and D
was ca. 1.0: 0.2: 0.2. For the ionic complexes 7 and 8, the H2 and H9
protons were shifted at high-field (6.19 and 7.02 ppm for compound
five crystal structures of an sp N-donor cyclopalladated compound
2
containing an aryl group attached to the sp N-donor nitrogen and
a pyridine ligand trans to the palladated carbon atom [33e36]. In
2
these crystal structures, the aryl ring attached to the sp N-donor
atom and the pyridine are in a face-to-face conformation. Table 2
gives the distances between the centroids of the aryl ring
2
7
in solution C and at 6.12 and 6.96 ppm for compound 8 in solution
D) because both type of protons were located in the shielding zone
of a pyridine-d ligand [19,25,30,31].
attached to the sp N-donor nitrogen (aromatic ring X) and that of
the pyridine (aromatic ring Y) in these crystal structures. Table 2
shows that only two of these distances are in the range expected
5
In solutions, C and D, the ortho-palladated benzaldehyde affor-
ded a singlet signal for the proton of the aldehyde function at ca.
for a significant p-stacking interaction (CCDC numbers 732584 and
848290).
10.5 ppm and an aromatic system corresponding to a 1,2-
disubstituted phenyl ring. On the other hand, methyl 4-
aminobenzoate produced signals at ca. 7.7 and 6.7 for the aro-
matic protons and at 3.8 ppm for the methoxycarbonyl protons. The
exchangeable amino protons of methyl 4-aminobenzoate were not
2.1. Experimental part
1
13
1
1
1
H and C{ H} NMR spectra and bidimensional He H and
1He C NMR experiments were recorded in a Varian Mercury 400.
The H NMR at 223 K and the He H COSY experiment at 223 K
13
1
1
1
observed in D
The
2
O.
N bidentate chelate coordination mode of the imine
k
C
ortho
,k
were registered at 500 MHz in a Bruker DMX 500 instrument.
Chemical shifts were measured relative to SiMe
sidual solvent peaks for C. Chemical shifts are reported in ppm
and coupling constants in Hz. C, H, N microanalyses were per-
formed with a Carlo-Erba EA 1108 instrument. IR spectra were
collected with a Nicolet Avatar 300 FT-IR spectrometers using KBr
1
ligand in compounds 3 and 4 and compounds 5e8 in solutions A e
D was consistent with the high-field shift of the methinic proton of
these compounds ca. 0.30e0.40 ppm in relation to the free imine
ligand [5,6,19,21,22,25] and with the fact that the metallated and
the methinic carbon atoms appeared low-field shifted ca.
4
for H and to re-
13
1
0e20 ppm relative to the free imine ligand [19].
The detection in solutions C and D of the ionic complexes 7 and
suggested that the geometrical isomerization experimented by
discs. MALDI-TOF(þ) mass spectra were registered with
a
VOYAGER-DE-RP spectrometer using dithranol (DTH), 2,5-
dihydroxybenzoic acid (DHB) or trans-2-[3-(4-tert-butylphenyl)-
2-methyl-2-propenylidene]malononitrile (DCTB) as matrix. ESI(þ)
mass spectra were acquired with a LC/MSD-TOF mass spectrometer
8
compounds 5 and 6 in solutions A and B proceed through the
reversible consecutive displacement mechanism given in Fig. 4. The
ionic complex 7 or 8 would not be an observable intermediate in
using H
2 3
O/CH CN (1:1) as eluent. Chemical compounds were
1
CDCl
3
by H NMR but at a high concentration of pyridine-d
5
the
commercial and were used as received.
thermodynamic equilibrium between the geometrical isomers of
compounds 5 and 6 in solutions A and B would be attained through
the intermediate ionic complexes 7 and 8. The reversible character
of the reactions I and II (Fig. 4) was in agreement with the fact that
when compound 1 reacted with pyridine in dichloromethane at
room temperature for one day in a molar ratio pyridine/1 z 50e55,
the isolated compound 3 from this reaction consisted of a mixture
of trans- and cis-N,N isomers.
6 5 6 4 2
2.1.1. Preparation of C H CH]N(C H -4-CO Me)
Methyl (E)-4-(benzylideneamino)benzoate was synthesized by
dissolving methyl 4-aminobenzoate (1465 mg, 9.69 mmol) in
3
methanol (60 cm ) followed by addition of benzaldehyde (1038 mg,
9.78 mmol). The resultant mixture was maintained under reflux for
two hours, after which time the crude was allowed to cool down to
room temperature. The solution was concentrated in vacuum (to

50
J. Albert et al. / Journal of Organometallic Chemistry 815-816 (2016) 44e52
Fig. 4. Consecutive reversible reactions between the species present in solutions A and B, which could explain the geometrical isomerization taking place in these solutions.
Table 2
sym st). MS-LDI TOF (þ) (CHCl
), m/z: 746.9 (calcd. 747.0)
Pd : C 50.57%, H 3.74%, N
3
Distances in Å between the centroids of the aromatic rings
X and Y (see the text for the definition of the aromatic rings
X and Y).
þ
[
M ꢀ OAc] . Anal. Calcd. for C34
H
30
N
2
O
8
2
3
2
0
.47%. Found: C 50.4%, H 3.8%, N 3.5%.
CCDC number
Cg(X)-Cg(Y)
.1.3. Preparation of compound 2
A mixture formed by acetato-bridge complex 1 (200 mg,
.25 mmol), lithium chloride (42 mg, 1 mmol) and acetone (10 cm )
1
6
6
7
8
299836
21235
03386
32584
48290
4.003(2)
4.703(4)
4.161(5)
3.733(4)
3.777(2)
3
was stirred at room temperature for 2 h. Afterwards, the solvent of
the orange mixture formed was eliminated under vacuum, and the
residue eluted through a silica gel-60 column chromatography
using dichloromethane:methanol (100:2) as eluent. The yellowish
band was collected and concentrated in vacuum. Addition of
3
about 20 cm ) until precipitation was observed. The pale yellow
3
diethylether (5 cm ) to the residue produced the precipitation of
solid obtained was filtered off and air-dried (1530 mg, 66% yield).
1
compound 2 as a yellow solid, which was filtered and dried in
3
H NMR (400 MHz, CDCl , 298 K), d (ppm): 8.44 (s, 1H, 7), 8.08 (d,
1
3JHH ¼ 8.6 Hz, 2H, 10), 7.92 (dd, JHH ¼ 7.7 Hz, JHH ¼ 1.8 Hz, 2H, 1),
3
4
vacuum (99 mg, 53% yield). H NMR (400 MHz, CDCl
3
, 298 K),
3
3
d
(ppm): 8.11 (br d, JHH ¼ 7.6 Hz, 2H, 10), 8.01 (s, 1H, 7), 7.44 (br d,
7
3
1
1
.53e7.47 (m, 3H, 2, 3 and 5), 7.21 (d, JHH ¼ 8.6 Hz, 2H, 9), 3.93 (s,
3
13
1
J
2
HH ¼ 7.3 Hz, 2H, 9), 7.35e7.33 (m, 2H, metallated ring), 7.10 (br s,
3
H, 13). C-{ H} NMR (101 MHz, CDCl , 298 K), d (ppm): 166.8 (12),
H, metallated ring), 3.96 (s, 3H, 13). Solubility in chloroform was
61.7 (7),156.2 (8),135.7 (6),131.9 (3),130.9 (10),129.1 (1),128.9 (2),
27.4 (11), 120.7 (9), 52.0 (13). IR (KBr, selected data), y (cm ): 1717
C]O st), 1628 (C]N st), 1275 (CeCeO as st), 1114 (CeCeO sym st).
ꢀ
1
insufficient to obtain carbon NMR data. IR (KBr, selected data), y
ꢀ
1
(
cm ): 1719 (C]O st), 1605 (C]N st), 1284 (CeCeO as st), 1116
(
þ
(CeCeO sym st). MS-LDI TOF (þ) (acetone), m/z: 722.8 (calcd.
MS-ESI (þ) {H
2
O:CH
Anal. Calcd. for C15
3
H
CN (1:1)}, m/z: 240.1 (calcd. 240.1) [MþH] .
þ
7
3
22.9) [M ꢀ Cl] . Anal. Calcd. for C30
H24Cl
2
N
2
O
4
Pd
2
: C 47.39%, H
2
13NO : C 75.30%, H 5.48%, N 5.85%. Found: C
.18%, N 3.68%. Found: C 47.6%, H 3.3%, N 3.6%.
7
4.6%, H 5.3%, N 5.9%.
2
.1.4. Preparation of compound 3
100 mg of complex 1 (0.124 mmol) were treated with 6 cm of a
3
2.1.2. Preparation of compound 1
A solution formed by palladium(II) acetate (226 mg, 1.01 mmol),
2 2
solution of pyridine in CH Cl 0.064 M (0.384 mmol of pyridine).
methyl (E)-4-(benzylideneamino)benzoate (241 mg, 1.01 mmol)
The solution was allowed to stir at room temperature for 2 h, and
thereafter volatiles were evaporated under reduced pressure. Upon
addition of diethyl ether (4 cm ) a light yellow precipitate formed,
which was collected by filtration and air-dried (98 mg, 82% yield).
Compound 3 consists of a mixture of trans-N,N and cis-N,N isomers
in a 1.0 : 0.8 ratio. A similar result was obtained reacting 100 mg
3
ꢁ
and 10 cm of glacial acetic acid was heated to 60 C for 24 h. Af-
terwards, the solvent of the orange suspension formed was
removed under vacuum and the residue subjected to column
chromatography (silica gel-60) using a 100: 4 chloroform: meth-
anol mixture as eluent. The red coloured band was collected and
3
evaporated. Addition of the minimum amount of diethyl ether (ca.
(0.124 mmol) of compound 1 with 399 mg (ca. 5 mmol) of pyridine
3
3
4
cm ) gave the target complex as a yellow orangey solid (195 mg,
in10 cm of CH
case, the H NMR in CDCl
3
2
Cl
2
stirring at room temperature for 24 h. In this
solution of the isolated compound 3
showed that it consisted of a mixture of trans- and cis-N,N isomers
8% yield). 1H NMR (400 MHz, CDCl
, 298 K),
d
(ppm): 7.86 (d,
1
4
3
3
3
J
HH ¼ 8.6 Hz, 2H, 10), 7.72 (s, 1H, 7), 7.28 (dd,
J
HH ¼ 7.5 Hz,
4JHH ¼ 1.4 Hz, 1H, 5), 7.11 (td, JHH ¼ 7.4 Hz, JHH ¼ 1.0 Hz, 1H, 4), 6.94
3
4
in 1 : 0.56 ratio. H NMR (400 MHz, CDCl
1
, 298 K),
d (ppm): [trans-
3
3
4
3
3
(
6
3
td, JHH ¼ 7.6 Hz, JHH ¼ 1.5 Hz, 1H, 3), 6.86 (d, JHH ¼ 8.6 Hz, 2H, 9),
N,N] 9.04 (d, J
HH ¼ 8.0 Hz, 2H, o-py), 8.09 (s, 1H, 7), 8.08 (d,
3
4
3
3
4
.58 (dd, JHH ¼ 7.8 Hz, JHH ¼ 0.8 Hz, 1H, 2), 3.95 (s, 3H, 13), 1.86 (s,
J
HH ¼ 8.6 Hz, 2H, 10), 7.88 (tt, JHH ¼ 7.6 Hz, JHH ¼ 1.6 Hz, 1H, p-py),
H, 15). 13C{ H} NMR (101 MHz, CDCl
1
, 298 K),
d
(ppm): 180.6 (14),
7.49 (d,
3
J
HH ¼ 8.6 Hz, 2H, 9), 7.47e7.44 (m, 2H, m-py), 7.42 (dd,
3
3
4
173.5 (7), 166.4 (12), 155.7 (1), 150.9 (8), 145.3 (6), 132.5 (2), 131.2
J
HH ¼ 7.4 Hz, JHH ¼ 1.5 Hz, 1H, 5), 7.12e7.07 (m, overlapped with 4
3 4
(
2
3), 131.1 (10), 129.6 (11), 128.9 (5), 128.2 (4), 124.2 (9), 52.3 (13),
of cis-N,N,1H, 4), 7.01 (td, JHH ¼ 7.5 Hz, JHH ¼ 1.5 Hz,1H, 3), 6.29 (d,
ꢀ1
3
4.2 (15). IR (KBr, selected data),
y
(cm ): 1717 (C]O st, ester),
J
HH ¼ 7.6 Hz, 1H, 2), 3.93 (s, 3H, 13), 1.55 (s, 3H, 15); [cis-N,N] 8.60
3
1609 (C]N st), 1574 (COO as st, bridging carboxylato), 1415 (COO
(br d, 2H, o-py), 7.86 (d, JHH ¼ 8.6 Hz, partially overlapped with p-
3
sym st, bridging carboxylato), 1282 (CeCeO as st), 1114 (CeCeO
py of trans-N,N, 2H, 10), 7.72 (s, 1H, 7), 7.67 (tt,
JHH ¼ 7.8 Hz,

J. Albert et al. / Journal of Organometallic Chemistry 815-816 (2016) 44e52
51
4JHH ¼ 1.7 Hz, 1H, p-py), 7.29e7.26 (m, partially overlapped with
4JHH ¼ 0.9 Hz, 1H, 4), 7.01 (td, JHH ¼ 7.6 Hz, JHH ¼ 1.5 Hz, 1H, 3),
3
3
3
13
1
CHCl
3
, 3H, 5 þ m-py), 7.12e7.07 (m, overlapped with 4 of trans-N,N,
6.29 (d, JHH ¼ 7.5 Hz, 1H, 2), 3.93 (s, 3H, 13), 1.56 (s, 3H, 15). C{ H}
3
4
1
J
3
H, 4), 6.94 (td,
J
HH ¼ 7.6 Hz,
J
HH ¼ 1.5 Hz, 1H, 3), 6.86 (d,
NMR (101 MHz, CDCl
3
þ py-d
5
, 298 K), d (ppm) (compound 5): 177.6
3
3
3
HH ¼ 8.6 Hz, 2H, 9), 6.58 (dd, JHH ¼ 7.8 Hz, JHH ¼ 0.7 Hz, 1H, 2),
(s, 14), 175.9 (s, 7), 166.4 (s, 12), 157.3 (s, 1), 151.9 (s, 8), 146.7 (s, 6),
133.0 (s, 2),131.5 (s, 3),130.2 (s,10),129.2 (s,11),129.1 (s, 5),124.5 (s,
4), 123.1 (s, 9), 52.2 (s, 13), 24.5 (s, 15). Due to the rapid exchange
13
1
.95 (s, 3H, 13), 1.86 (s, 3H, 15). C{ H} NMR (101 MHz, CDCl
3
,
2
98 K), (ppm): [trans-N,N] 177.6 (14), 175.9 (7), 166.4 (12), 157.4
d
(
1
5
(
1), 153.4 (o-py), 151.9 (8), 146.7 (6), 138.1 (p-py), 133.0 (2), 131.5 (3),
30.2 (10), 129.2 (11), 129.1 (5), 125.4 (m-py), 124.6 (4), 123.1 (9),
2.2 (13), 24.5 (15); [cis-N,N] 180.6 (14), 173.5 (7), 166.4 (12), 155.7
1),150.9 (8),149.9 (br s, o-py),145.3 (6),136.0 (br s, p-py),132.5 (2),
between coordinated and free pyridine-d
5
, carbon NMR signals of
coordinated pyridine-d were not observed.
5
1
31.1 (3), 129.6 (10), 128.9 (11), 128.1 (5), 124.2 (4), 123.8 (br s, m-
2.1.7. Preparation of solution B
Solution B was prepared by adding ca. 30 mg (30
to a suspension of compound 2 (ca. 6 mg) in 1 cm of CDCl
3
ꢀ1
py), 123.2 (9), 52.3 (13), 24.2 (15). IR (KBr, selected data),
y
(cm ):
mL) of pyridine-
3
1720 (C]O st, ester), 1604 (C]N st), 1586 (C]O st, terminal ace-
d
5
1
tato), 1378 (CeO st, terminal acetato), 1271 (CeCeO as st), 1108
(molar ratio pyridine-d
(400 MHz, CDCl
þ py-d
5
/compound
2
z
50e55).
H NMR
(
4
4
CeCeO sym st). MS-MALDI TOF (þ) (DHB), m/z: 422.9 (calcd.
3
5
, 298 K),
d
(ppm) (compound 6): 8.12 (s,
þ
23.0) [M ꢀ OAc] . Anal. Calcd. for C22
H
20
N
2
O
4
Pd: C 54.73%, H
1H, 7), 7.98 (br d, 2H, 10), 7.43 (m, 1H, 5), 7.31 (br signal, 2H), 7.11 (br
13
1
.18%, N 5.80%. Found: C 54.7%, H 4.3%, N 6.1%.
d, 2H, 9) 3.89 (s, 3H, 13). C{ H} NMR (101 MHz, CDCl
98 K), (ppm) (compound 6): 176.8 (s, 7), 166.2 (s, 12), 146.4 (s, 6),
131.8 (s, 3), 130.1 (br s, 2), 129.1 (s, 5), 124.9 (s, 4), 52.2 (s, 13). Due to
the rapid exchange between coordinated and free pyridine-d
carbon NMR signals of coordinated pyridine-d and some carbon
3
þ py-d
5
,
2
d
2.1.5. Preparation of compound 4
3
0
.100 g (0.132 mmol) of compound 2 were treated with 6 cm of
5
,
a solution pyridine in CH
2
Cl
2
0.064 M (0.384 mmol of pyridine). The
5
solution was allowed to stir at room temperature for 2 h, and
thereafter volatiles were evaporated under reduced pressure. Upon
addition of diethyl ether (4 cm ) a light yellow precipitate formed,
peaks of the cyclopalladated ligand could not be observed (C1 and
C8 e C11).
3
which was collected by filtration and air-dried (107 mg, 97% yield).
Compound 4 consists of a mixture of trans-N,N and cis-N,N isomers
in a 1.0 : 0.5 ratio. A similar result was obtained reacting 100 mg
2.1.8. Preparation of solution C
Solution C was prepared by adding ca. 30 mg (30
mL) of pyridine-
(
0.132 mmol) of compound 2 with 417 mg (ca. 5.3 mmol) of pyri-
d to a suspension of acetato-bridge cyclopalladated compound 1
5
3
3
dine in 10 cm of CH
2
Cl
this case, the H NMR in CDCl
showed that it consisted of a mixture of trans- and cis-N,N isomers
2
stirring at room temperature for 24 h. In
(6 mg, approx.) in deuterated water (ca. 1 cm ) (molar ratio pyri-
1
1
3
solution of the isolated compound 2
5 2
dine-d /compound 1 z 50e55). H NMR in D O revealed the
presence of the cationic complex 7, together with ortho-palladated
benzaldehyde and methyl 4-aminobenzoate in a 1.0 : 0.2 : 0.2 ratio.
1
in 1.0 : 0.6 ratio. H NMR (400 MHz, CDCl
3
, 298 K),
d
(ppm): [trans-
3
1
N,N] 8.93 (d,
J
HH ¼ 5.0 Hz, 2H, o-py), 8.12 (s, 1H, 7), 8.09 (d,
H NMR (400 MHz, D
2
O þ py-d
5
, 298 K), d (ppm); compound 7: 8.22
3
3
3
3
J
HH ¼ 9.2 Hz, 2H, 10), 7.88 (t,
J
HH ¼ 7.5 Hz, 1H, p-py), 7.51 (d,
(s, 1H, 7), 7.69 (d,
J
HH ¼ 8.8 Hz, 2H, 10), 7.58 (dd,
J
HH ¼ 7.5 Hz,
3JHH ¼ 8.4 Hz, 2H, 9), 7.60e7.41 (m, overlapped with 5 of cis-N,N,
4
J
HH ¼ 1.2 Hz, 1H, 5), 7.24 (td, JHH ¼ 7.5 Hz, JHH ¼ 1.0 Hz, 1H, 4), 7.11
3
4
3
4
3
3
H, m-py þ 5), 7.15e7.11 (m, overlapped with m-py, 9 and 4 of cis-
(td, JHH ¼ 7.6 Hz, JHH ¼ 1.5 Hz, 1H, 3), 7.02 (d, JHH ¼ 8.8 Hz, 2H, 9),
3
3
3 4
N,N, 1H, 4), 7.05 (t, JHH ¼ 7.6 Hz, 1H, 3), 6.20 (d, JHH ¼ 7.6 Hz, 1H, 2),
6.19 (dd, JHH ¼ 7.6 Hz, JHH ¼ 0.8 Hz, 1H, 2), 3.83 (s, 3H, 13), 1.90 (s,
3H, 15); ortho-palladated benzaldehyde: 10.50 (s, 1H, CH]O), 8.02
3
.92 (s, 3H, 13); [cis-N,N] 8.36 (br d, 2H, o-py), 8.16 (s, 1H, 7), 7.76 (br
3
3
3
4
d, 10), 7.60 (br t, JHH ¼ 7.4 Hz, 1H, p-py), 7.52e7.41 (m, overlapped
(d, JHH ¼ 7.5 Hz, 1H), 7.53 (dd, JHH ¼ 7.6 Hz, JHH ¼ 1.3 Hz, 1H), 7.30
3
3
4
4
with m-py, 10 and 5 of trans-N,N, 1H, 5), 7.24 (t, JHH ¼ 7.6 Hz, 1H, 3),
(td,
JHH ¼ 7.7 Hz,
J
HH ¼ 1.6 Hz, 1H), 7.13e7.06 ( JHH ¼ 1.1 Hz,
7
.15e7.11 (m, overlapped with 4 of trans-N,N, 3H, m-py þ 4 and 2),
partially obscured by 3 of 7, 1H), 1.90 (s, 3H, 15); methyl 4-
.00 (d, 3
101 MHz, CDCl
58.7 (1), 153.2 (o-py), 152.5 (8), 146.4 (overlapped with 6 of cis-
N,N, 6), 138.2 (p-py), 132.2 (2), 131.8 (3), 130.0 (10), 129.3 (11), 129.1
overlapped with 5 of cis-N,N, 5), 125.6 (m-py), 124.9 (overlapped
with m-py of cis-N,N, 4), 123.8 (9), 52.1 (13); [cis-N,N] 176.8 (7),
65.9 (12), 157.0 (1), 152.2 (8), 150.6 (o-py), 146.4 (overlapped with
of trans-N,N, 6), 137.5 (br s, p-py), 136.7 (2), 131.7 (3), 130.4 (10),
29.1 (overlapped with 5 of trans-N,N, 5), 128.9 (11), 124.9 (over-
lapped with 4 of trans-N,N, m-py), 124.6 (4), 122.5 (9), 52.3 (13). IR
J
HH ¼ 8.0 Hz, 2H, 9), 3.89 (s, 3H, 13). C{ H} NMR
13
1
aminobenzoate: 7.73 (d, JHH ¼ 8.9 Hz, 2H), 6.74 (d, JHH ¼ 8.9 Hz,
3
3
7
(
1
3
, 298 K), (ppm): [trans-N,N] 176.9 (7), 166.4 (12),
d
2H), 3.79 (s, 3H). Signal of exchangeable amino protons was not
2
observed in D O.
(
2.1.9. Preparation of solution D
1
6
1
Solution D was prepared by adding ca. 30 mg (30 mL) of pyri-
dine-d
5
to a suspension of chlorido-bridge cyclopalladated com-
3
pound 2 (ca. 6 mg) in deuterated water (ca. 1 cm ) (molar ratio
pyridine-d /compound 2 z 50e55). H NMR in D O revealed the
5 2
1
ꢀ
1
(
KBr, selected data),
y
(cm ): 1715 (C]O st), 1604 (C]N st), 1587
presence of the cationic complex 8, together with ortho-palladated
(
C]N st pyridine), 1277 (CeCeO as st), 1113 (CeCeO sym st). MS-
benzaldehyde and methyl 4-aminobenzoate in a 1.0 : 0.2 : 0.2 ratio.
þ
1
ESI (þ) {H
2
O:CH
3
OH (1:1)}, m/z: 881.0 (calcd. 881.0) [2 MꢀCl] ,
H NMR (400 MHz, D
2
O þ py-d
5
, 298 K),
d (ppm); compound 8: 8.16
þ
þ
3
8
02.0 (calcd. 802.0) [2 MꢀCl e py] , 423.0 (calcd. 423.0) [MꢀCl] .
Anal. Calcd. for C20 17ClN Pd: C 52.31%, H 3.73%, N 6.10%. Found:
C 51.9%, H 3.8%, N 6.3%.
(s, 1H, 7), 7.64 (d,
J
HH ¼ 8.4 Hz, slightly overlapped with 2H of
3
H
2 2
O
methyl 4-aminobenzoate, 2H, 10), 7.56 (d, JHH ¼ 7.5 Hz, 1H, 5), 7.22
3
(t,
J
HH ¼ 7.5 Hz, 1H, 4), 7.09e7.04 (m, overlapped with 1H of
3
metallated aldehyde, 1H, 3), 6.96 (d, JHH ¼ 8.4 Hz, 2H, 9), 6.12 (d,
3
2
.1.6. Preparation of solution A
J
HH ¼ 7.8 Hz, 1H, 2), 3.80 (s, 3H, 13); ortho-palladated benzalde-
3
Solution A was prepared by adding ca. 30 mg (30
to a suspension of compound 1 (ca. 6 mg) in 1 cm of CDCl
m
L) of pyridine-
hyde: 10.45 (s, 1H, CH]O), 7.98 (d,
J
HH ¼ 7.2 Hz, 1H), 7.47 (d,
HH ¼ 7.6 Hz, 1H), 7.09e7.04 (m, over-
lapped with 3 of 8, 1H); methyl 4-aminobenzoate: 7.68 (d,
3
3
3
d
5
3
J
HH ¼ 7.6 Hz, 1H), 7.27 (t,
J
1
(
(
1
molar ratio pyridine-d
400 MHz, CDCl
þ py-d
5
/compound
1
z
50e55).
H
NMR
3
3
5
, 298 K),
d
(ppm) (compound 5): 8.12 (s,
J
HH ¼ 8.5 Hz, slightly overlapped with 10 of 8, 2H), 6.72 (d,
3
3
3
H, 7), 8.08 (d, JHH ¼ 8.6 Hz, 2H, 10), 7.50 (d, JHH ¼ 8.6 Hz, 2H, 9),
JHH ¼ 8.5 Hz, 2H, 9), 3.76 (s, 3H, 13). Signal of exchangeable amino
3 4 3
7
.42 (dd, JHH ¼ 7.4 Hz, JHH ¼ 1.3 Hz, 1H, 5), 7.09 (td, JHH ¼ 7.4 Hz,
2
protons was not observed in D O.

5
2
J. Albert et al. / Journal of Organometallic Chemistry 815-816 (2016) 44e52
[12] J. Dupont, C.S. Consorti, J. Spencer, Chem. Rev. 105 (2005) 2527e2571.
Acknowledgments
[
[
13] J.J. Topczewski, M.S. Sanford, Chem. Sci. 6 (2015) 70e76.
14] D. Aguilar, L. Cuesta, S. Nieto, E. Serrano, E.P. Urriolabeitia, Curr. Org. Chem. 15
We are grateful to the Ministerio de Economía y Competitividad
for financial support (grant number CTQ2015-65040-P) and to the
Centres Científics i Tecnol oꢁ gics de la Universitat de Barcelona for
the facilities given for the structural determination of the
compounds.
(2011) 3441e3464.
[15] J.Q. Yu, R. Giri, X. Chen, Org. Biomol. Chem. 4 (2006) 4041e4047.
[
[
[
16] R. Knorr, Chem. Ber 113 (1980) 2441e2461.
17] H. Onoue, I. Moritani, J. Organomet. Chem. 43 (1972) 431e436.
18] K. Nakamoto, Infrared and Raman Spectra of Inorganic and Coordination
Compounds, fifth ed., Wiley, New York, 1997.
[19] J. Albert, R. Bosque, L. D’Andrea, J. Granell, M. Font-Bardia, T. Calvet, Eur. J.
Inorg. Chem. (2011) 3617e3631.
Appendix A. Supplementary data
[20] P.G. Evans, N.A. Brown, G.J. Clarkson, C.P. Newman, J.P. Rourke, J. Organomet.
Chem. 691 (2006) 1251e1256.
[
[
21] J. Albert, J. Granell, J. Sales, J. Organomet. Chem. 273 (1984) 393e399.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.jorganchem.2016.05.003.
22] J. Albert, M. G oꢀ mez, J. Granell, J. Sales, X. Solans, Organometallics 9 (1990)
1405e1413.
[23] D.C.R. Hockless, P.A. Gugger, P.H. Leung, R.C. Mayadunne, M. Pabel, S.B. Wild,
Tetrahedron 53 (1997) 4083e4094.
References
[
[
24] M. Ghedini, A. Crispini, Comments Inorg. Chem. 21 (1999) 53e68.
25] J. Albert, L. D’Andrea, J. Granell, R. Tavera, M. Font-Bardia, X. Solans,
J. Organomet. Chem. 692 (2007) 3070e3080.
26] S. Castro-Juiz, A. Fern aꢀ ndez, M. L oꢀ pez-Torres, D. V aꢀ zquez-García, A.J. Su ꢀa rez,
J.M. Vila, J.J. Fern ꢀa ndez, Organometallics 28 (2009) 6657e6665.
27] T.G. Appleton, H.C. Clark, L.E. Manzer, Coord. Chem. Rev. 10 (1973) 335e422.
28] T. Murahashi, H. Kurosawa, Coord. Chem. Rev. 231 (2002) 207e228.
29] F. Basolo, Coord. Chem. Rev. 154 (1996) 151e161.
30] A.D. Ryabov, L.G. Kuz’mina, V.A. Polyakov, G.M. Kazankov, E.S. Ryabova,
M. Pfeffer, R. van Eldik, J. Chem. Soc. Dalton Trans. (1995) 999e1006.
31] J. Vicente, I. Saura-Llamas, Comments Inorg. Chem. 28 (2007) 39e72.
32] G.K. Anderson, R.J. Cross, Chem. Soc. Rev. 9 (1980) 185e215.
[
[
[
1] A.R. Kapdi, I.J.S. Fairlamb, Chem. Soc. Rev. 43 (2014) 4751e4777.
2] I. Omae, Coord. Chem. Rev. 280 (2014) 84e95.
3] N. Cutillas, G.S. Yellol, C. de Haro, C. Vicente, V. Rodríguez, J. Ruiz, Coord. Chem.
Rev. 257 (2013) 2784e2797.
[
[
[
[
[
[
[
4] A.C.F. Caires, Anti-Cancer Agents Med. Chem. 7 (2007) 484e491.
5] J. Albert, J. Granell, R. Qadir, J. Quirante, C. Calvis, R. Messeguer, J. Badía,
L. Baldom aꢁ , M. Font-Bardia, T. Calvet, Organometallics 33 (2014) 7284e7292.
6] J. Albert, R. Bosque, M. Cadena, L. D’Andrea, J. Granell, A. Gonz ꢀa lez, J. Quirante,
C. Calvis, R. Messeguer, J. Badía, L. Baldom aꢁ , T. Calvet, M. Font-Bardia, Or-
[
[
[
[
ganometallics 33 (2014) 2862e2873.
[
[
[
7] J. Spencer, A. Casini, O. Zava, R.P. Rathnam, S.K. Velhanda, M. Pfeffer,
S.K. Callear, M.B. Hursthoused, P.J. Dyson, Dalton Trans. (2009) 10731e10735.
8] V.W.R. Moraes, A.C.F. Caires, E.J. Paredes-Gamero, T. Rodrigues, Cell Death Dis.
33] M. Pfeffer, N. Sutter-Beydoun, A. De Cian, J. Fischer, J. Organomet. Chem. 453
(1993) 139e146.
[
[
34] C. Xu, J.F. Gong, Y.H. Zhang, Y. Zhu, Y.J. Wu, Aust. J. Chem. 60 (2007) 190e195.
35] J.F. Gong, C. Xu, Y.H. Zhang, Y. Zhu, Y.J. Wu, Transit. Metal Chem. 32 (2007)
4
(2013) e658.
9] N. Selander, K.J. Szab oꢀ , Chem. Rev. 111 (2011) 2048e2076.
1000e1004.
[
[
10] R.B. Bedford, C.S.J. Cazin, D. Holder, Coord. Chem. Rev. 248 (2004) 2283e2321.
11] T.K. Hollis, L.E. Overman, J. Organomet. Chem. 576 (1999) 290e299.
[
36] K. Gopi, N. Thirupathi, Organometallics 30 (2011) 572e583.