A thiosemicarbazone–palladium(II)–imidazole complex as an efficient pre-catalyst for Suzuki–Miyaura cross-coupling reactions at room temperature in aqueous media

Article abstract of DOI:10.1007/s11243-017-0174-4

Abstract: A Pd(II) complex of two sterically crowded ligands, specifically an N,S-donor thiosemicarbazone and an N-donor imidazole, has been synthesized and characterized by physicochemical and spectroscopic methods. X-ray single-crystal analysis revealed that the coordination geometry around the palladium center is distorted square planar, and the chloride ligand is involved in intermolecular bifurcated X–HY-type (where X?=?C, N and Y?=?Cl) hydrogen bonding. This complex proved to be a highly active and retrievable pre-catalyst for additive-free Suzuki–Miyaura cross-coupling reactions of arylboronic acids with aryl bromides or chlorides at room temperature and 60?°C, respectively. The reactions require a low catalyst loading and the complex is converted to ~1.5–2.0 nm-sized Pd nanoparticles (probably the real catalyst). The catalyst can be reused up to seven times without significant loss in activity. Since the reaction proceeds under mild conditions in aqueous medium and the catalyst is recoverable, it provides an environmentally benign alternative to the existing protocols for Suzuki–Miyaura reactions. Graphical abstract: Biaryls can be synthesized in high yield under greener reaction conditions in the presence of efficient pre-catalyst, thiosemicarbazone–palladium(II)–imidazole.[Figure not available: see fulltext.].

Full text of DOI:10.1007/s11243-017-0174-4

Transit Met Chem
DOI 10.1007/s11243-017-0174-4
A thiosemicarbazone–palladium(II)–imidazole complex
as an efficient pre-catalyst for Suzuki–Miyaura cross-coupling
reactions at room temperature in aqueous media
Jayantajit Baruah1 Rajjyoti Gogoi1 Nibedita Gogoi1 Geetika Borah1
•
•
•
Received: 27 April 2017 / Accepted: 7 August 2017
Ó Springer International Publishing AG 2017
Abstract A Pd(II) complex of two sterically crowded
ligands, specifically an N,S-donor thiosemicarbazone and
an N-donor imidazole, has been synthesized and charac-
terized by physicochemical and spectroscopic methods.
X-ray single-crystal analysis revealed that the coordination
geometry around the palladium center is distorted square
planar, and the chloride ligand is involved in intermolec-
ular bifurcated X–HÁÁÁY-type (where X = C, N and
Y = Cl) hydrogen bonding. This complex proved to be a
highly active and retrievable pre-catalyst for additive-free
Suzuki–Miyaura cross-coupling reactions of arylboronic
acids with aryl bromides or chlorides at room temperature
and 60 °C, respectively. The reactions require a low cata-
lyst loading and the complex is converted to *1.5–2.0 nm-
sized Pd nanoparticles (probably the real catalyst). The
catalyst can be reused up to seven times without significant
loss in activity. Since the reaction proceeds under mild
conditions in aqueous medium and the catalyst is recov-
erable, it provides an environmentally benign alternative to
the existing protocols for Suzuki–Miyaura reactions.
Introduction
Since the first report of the Suzuki–Miyaura reaction [1, 2],
this method has become one of the most powerful and
versatile procedures for the construction of unsymmetrical
biaryls that are used as building blocks in the pharmaceu-
tical, agrochemical and material industries [3, 4]. Thou-
sands of Pd(II) complexes with various ligand systems
have been reported to accelerate this coupling reaction
[5–8]. In most cases, the catalytic agent Pd(II) is converted
to Pd(0) during catalysis [8]. However, a debate on this
issue is still ongoing and it is uncertain with many Pd
complexes whether they are the actual catalyst or pre-cat-
alyst. Traditionally, Suzuki–Miyaura coupling relies on
toxic, air and/or moisture sensitive and expensive palla-
dium catalysts, usually with phosphine ligands [9–12].
Moreover, the solvents used in such reactions are mostly
not eco-friendly. Since catalysis under phosphine-free
conditions is an important challenge, in recent years a
plethora of N-based ligands such as amines [13], N-hete-
rocyclic carbenes (NHC) [14, 15], oximes [16], hydrazones
[17] and others [18, 19] have been tested as possible
alternatives to phosphines in Suzuki–Miyaura cross-cou-
pling reactions. Recently, Schiff bases have been recog-
nized as excellent alternative ligands in Suzuki–Miyaura
reactions [5–8]. There are, however, few reports of Pd
catalysts bearing thiosemicarbazone ligands in Suzuki–
Miyaura reactions [20–27]. Many of the earlier protocols
use severe reaction conditions, such as high temperature
(100–155 °C), DMF solvent, long reaction time, high cat-
alyst loading in some cases, and little or no scope for
recycling the catalyst, due to its homogeneous nature.
Since this reaction is relevant to industry, it is important to
design novel catalytic systems with air stable, less expen-
sive and robust ligands which could efficiently catalyze the
Electronic supplementary material The online version of this
article (doi:10.1007/s11243-017-0174-4) contains supplementary
material, which is available to authorized users.
& Geetika Borah
geetikachem@yahoo.co.in
Jayantajit Baruah
jayantajit09@gmail.com
1
Department of Chemistry, Dibrugarh University, Dibrugarh,
Assam, India
123

Transit Met Chem
cross-coupling reactions without employing any additives,
especially in green solvents.
apparatus. SEM images were obtained with a JEOL JSM
Model 6390 LV scanning electron microscope, operating at
an accelerating voltage of 15 kV. Transmission electron
microscopic (TEM) investigations were carried out on a
JEM-2100 instrument equipped with a high-resolution
CCD camera and an accelerating voltage of 60–100 kV in
50 kV steps. EDX spectra were also recorded on the same
instrument attached to the scanning electron microscope.
X-ray diffraction analysis (XRD) was performed on a
Bruker AXS D8 Advance Diffractometer with Cu-Ka
Thiosemicarbazones constitute an interesting class of
N,S-donor ligands because of their mixed hard–soft
character. These ligands are mainly known for their bio-
logical activity [28, 29]. They can act as bi- or multi-
dentate ligands [30–32], and can occupy two, three or four
coordination sites and thereby control the selectivity of
the catalyst [30–32]. Additional donor atoms in the ligand
can act as stabilizing groups during the course of metal-
mediated reactions and thereby improve catalytic effi-
ciency [20]. As a part of our continuing efforts to develop
efficient Pd catalysts for cross-coupling reactions [33–36],
herein, we report the synthesis of a reusable Pd(II) com-
plex with thiosemicarbazone and imidazole ligands within
the same coordination sphere, and its evaluation as a
catalyst in Suzuki–Miyaura reactions of aryl halides with
aryl boronic acids in aqueous media at room temperature.
To the best of our knowledge, this is the first example of a
Pd catalyst bearing both thiosemicarbazone and imidazole
ligands. We hoped that the presence of two bulky, elec-
tron-rich ligands within the same coordination sphere
would increase steric congestion around the Pd metal and
facilitate the rate of both oxidative addition and reductive
elimination steps in the mechanism [37]. However, Pd(0)
nanoparticles (*1.5–2.0 nm) were formed while carrying
out the reactions, and these appeared to be the real
catalyst.
˚
(k = 1.541A) radiation. X-ray photoelectron spectra (XPS)
were recorded on an XPS-AES Module, Model: PHI 5000
Versa Prob II. The C (1s) electron binding energy corre-
sponding to graphitic carbon was used for calibration of the
Pd (3d) core-level binding energy. The amount of Pd lea-
ched on the filtrate after the fifth cycle of catalysis was
analyzed by inductively coupled plasma atomic emission
spectroscopy (ICP-AES) on a Thermo Electron IRIS
Intrepid II XSP DUO instrument. The progress of the
reactions was monitored by TLC on silica gel plates (E.
Merck, silica gel 60F254), using n-hexane–ethyl acetate as
eluent. The products of the reactions were confirmed by
1
comparing H spectra with those reported in the literature.
Crystallography The X-ray crystallographic analysis
was carried out on a Bruker Apex 2 CCD diffractometer
˚
using monochromatic Mo-Ka radiation (k = 0.71073A) at
293 K. The data were corrected for Lorenz and polarization
effects. Hydrogen atoms were included in calculated
positions and refined in riding mode. The structure was
solved using the SHELXL-2014/7 package and refined by
full-matrix least squares on F2. CCDC No. 1497434 con-
tains the supplementary crystallographic data for this
paper. This file can be obtained free of charge from the
Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/ structures.
Experimental
Materials and instrumentation
All chemicals were of AnalaR grade and obtained com-
mercially. They were used as received without further
drying or purification. Solvents were purchased from
Merck. The 4-phenylthiosemicarbazide and N-methylimi-
dazole were purchased from Sigma–Aldrich, and palla-
dium(II) chloride was procured from Arora Matthey
Limited. The arylboronic acids were purchased from
Spectrochem. FTIR spectra (4000–250 cm-1) were recor-
ded using KBr disks on a Shimadzu Prestige-21 FTIR
spectrophotometer. Elemental analyses were obtained on
an Elementar Vario EL III Carlo Erba 1108 elemental
analyzer. Electrospray ionization (ESI) (?) mass spectra
were recorded on a Waters ZQ-4000 liquid chro-
matograph–mass spectrometer. 1H and 13C (100 MHz)
NMR spectra were recorded in DMSO-d6 using TMS as an
internal standard on a JEOL JNM ECS NMR spectrometer
operating at 400 MHz and an Advance DPX 300 MHz FT-
NMR spectrometer operating at 300 MHz. Melting points
were determined by using a BUCHI B450 melting point
Catalyst preparation
Synthesis of anisaldene-4–phenylthiosemicarbazone
(HL1)
HL1 was synthesized by reacting anisaldehyde (1.36 g,
10 mmol) and 4-phenylthiosemicarbazide (1.65 g,
10 mmol) in 1:1 molar ratio in EtOH (25 ml) with a few
drops of acetic acid [38]. White crystalline solid; yield:
85%; m.p. 146 °C. Anal. Calcd. for C15H15N3OS (%): C,
63.2; H, 5.3; N, 14.7; S, 11.2. Found: C, 63.6; H, 5.0; N,
14.2; S, 10.8. FW: 285 g mol-1. ESI (?) MS m/z [M]?:
285, [M ? H]?; selected IR bands (KBr, cm-1): (N3–H)
3327, (N2–H) 3152, (C=N) 1603, (N–N) 1171, (C=S) 827.
1H NMR [300 MHz, DMSO-d6, d ppm]: 11.69 (s, 1H, N2–
H), 10.04 (s, 1H, N3–H), 8.10 (s, 1H, CH=N), 6.96–7.84
123

Transit Met Chem
(m, 9H, Ph–H), 3.78 (s, 3H, OCH3). 13C NMR [100 MHz,
DMSO-d6, d ppm]: 175.5 (C=S), 160.8 (Ph–C), 142.9
(CH), 138.9 (Ph–C), 114.1–129.3(Ph–C), 55.2 (CH3).
Catalytic experiments
The Suzuki–Miyaura cross-coupling reactions were carried
out under aerobic conditions at room temperature (28 °C).
Progress of the reactions was monitored by TLC. The
products were isolated by column chromatography using
silica gel (60–120 mesh) and characterized by comparing
Synthesis of [PdL1Cl2]
PdCl2 (0.089 g, 0.5 mmol) and HL1 (0.142 g, 0.5 mmol)
were added to acetonitrile (20 ml), and the mixture was
stirred at room temperature in air for 3 h. An orange pre-
cipitate was formed. This was filtered off, washed with
acetonitrile and dried over fused CaCl2 in a desiccator.
Dark red solid; yield: 75%; d.t. 215–220 °C; selected IR
bands (KBr, cm-1): (N3–H) 3242, (N2–H) 3046, (C=N)
1591, (N–N) 1174, (C=S) 825, (Pd–N) 500, (Pd–S) 396,
(Pd–Cl) 385. 1H NMR[400 MHz, DMSO-d6, d ppm]:
10.75 (s, 1H, N2–H), 9.73 (s, 1H, N3-H), 8.29 (s, 1H,
CH=N), 8.12 (d, 2H), 7.52 (d, 2H), 7.07 (t, 1H), 7.36 (t,
2H), 7.50 (d, 2H), 3.82 (s, 3H, OCH3); 13C
1
their H NMR, mass spectral data and melting points with
authentic samples.
In a typical procedure, a mixture of aryl halide
(0.5 mmol), arylboronic acid (0.6 mmol), K2CO3 (3
equiv.) and catalyst (1.18 mol%) was added to solvent
(4 ml) and the mixture was stirred at room temperature for
the required time. After completion of the reaction, the
mixture was centrifuged. The residual solid was filtered off
and washed with three portions of the same reaction sol-
vent (4 ml). The residue was extracted from the filtrate
using water–ether mixture (1:3) followed by washing with
brine and drying over Na2SO4. The products were obtained
by column chromatography of the residue using ethyl
acetate/hexane (1:9) as eluent. For recycling experiments,
the catalyst was washed several times after each cycle with
water (3 9 5 ml) followed by diethyl ether (3 9 5 ml).
NMR[100 MHz, DMSO-d6,
d ppm]: 176.5 (C=S),
162.8(Ph–C), 143.9 (CH), 138.9 (Ph–C), 116.1–132.3 (Ph–
C), 55.0 (CH3).
o
Synthesis of [PdL1L2Cl] (C1)
After overnight drying at 120 C, the recovered catalyst
was subjected to subsequent runs under identical
conditions.
The precursor complex, [PdL1Cl2] (0.231 g, 0.5 mmol),
was dissolved in acetonitrile (10 ml). To this solution,
KPF6 (0.092 g, 0.5 mmol) and N-methylimidazole
(0.041 g, 0.5 mmol) were added. The mixture was refluxed
with stirring for 1.5 h under air. The resulting yellow
precipitate was filtered off, washed with acetonitrile and
dried under vacuum. Yellow solid; yield: 60%; d.t.
220–227 °C; FW: 508.3 g mol-1; selected IR bands (KBr,
cm-1): (N3–H) 3100, (C=N) 1593, (N–N) 1176, (C–S) 593,
Results and discussion
Synthesis and spectroscopic characterization
Our study was directed toward developing a cheap and
non-toxic Pd-based catalytic system for Suzuki–Miyaura
cross-coupling reactions under room temperature, envi-
ronmentally friendly conditions. To this end, we have
synthesized a new complex C1, [PdL1L2Cl] from [PdL1Cl2]
and N-methyl imidazole as per Scheme 1 (L1
= anisaldene-4-phenylthiosemicarbazone and L2 = N-
methyl imidazole). N-methyl imidazole was chosen as the
1
(Pd–N) 561,(Pd–S) 387, (Pd–Cl) 382; H NMR[400 MHz,
DMSO-d6, d ppm]: 8.47(s, 1H, N3–H), 7.68 (s, 1H,
CH=N1), 7.50–7.20 (m, 9H, Ph–H), 6.8 (s, 1H, CH=N4, Im-
H), 5.50 (d, 2H, Im-H), 3.82 (s, 3H, OCH3), 3.61 (s, 3H,
N5–CH3); 13C NMR[100 MHz, DMSO-d6, d ppm]: 171.1
(C–S), 160.9(Ph–C), 141.9 (CH), 55.2 (CH3).
O
O
N
HN3
S
HN3
S
N2
N1
HN2
N1
O
N
HN3
S
Me
HN2
N1
CH3CN
PdCl2
Pd
Pd
N4
HPF6/CH3CN
Cl
N5
Cl
Cl
Me
C1
Scheme 1 Synthesis of precursor complex and C1
123

Transit Met Chem
Fig. 1 Molecular structure of
[PdL1L2Cl], C1
co-ligand in order to increase the electron density at Pd
[39].
The coordination geometry around the palladium is
distorted square planar, with N(4)–Pd(1)–Cl(1), N(4)–
Pd(1)–S(1), N(1)–Pd(1)–S(1) and N(1)–Pd(1)–Cl(1) bond
angles at 87.72°(15), 91.21°(15), 84.11°(15) and
97.18°(14), respectively (Table 2). The Pd1–N1, Pd1–N4,
The precursor complex, [PdL1Cl2], and the new com-
plex C1 are both stable to air and moisture and soluble in
dichloromethane and DMSO. They were characterized by
ESI mass spectrometry, NMR (1H and 13C) and FTIR.
Moreover, the structure of the complex C1 was determined
by single-crystal X-ray diffraction analysis. In the infrared
spectra, both complexes exhibit characteristic IR bands due
to v(Pd–N) and v(Pd–S) in the ranges of 500–561 cm-1 and
387–396 cm-1, respectively, showing coordination of the
ligand to the metal. The m(C=N) band at 1600 cm-1 for the
free ligand is shifted (Dm & 7–9 cm-1) toward lower fre-
quencies on complexation, suggesting coordination to the
metal through the azomethine nitrogen [40]. The m(C=S)
band at 828 cm-1 for the free ligand is absent for complex
C1; a new, medium intensity band at 593 cm-1 is attributed
to m(C–S), indicating the presence of only thiolate sulfur in
the complex.
˚
Pd1–S1 and Pd1–Cl1 bond distances are 2.015 A(5), 2.019
˚
˚
˚
A(5), 2.2260 A(18) and 2.3407 A (18), respectively.
Interestingly, the chloride ligand is involved in inter-
molecular bifurcated hydrogen bonding, specifically N3–
˚
C19–
HÁÁÁCl1(d(HÁÁÁA) = 2.624
A)
and
˚
HÁÁÁCl1(d(HÁÁÁA) = 2.927 A) (Fig. 2) [41, 42]. The second
of these hydrogen bonds may be important for the C–H
bond activation, since the strength of C–HÁÁÁHalogen
hydrogen bonding can play an important role in deter-
mining the affinity and selectivity of catalysts for C–H
bond activation [43]. Moreover, the crystal lattice shows a
helical structure [44] through the N3–HÁÁÁCl1 hydrogen
bonds, which run along the b-axis (Fig. 3).
To determine the catalytic activity of the precursor
complex C1, a model cross-coupling reaction was investi-
gated at room temperature between 4-bromoanisole and
phenyl boronic acid. The results of these experiments are
summarized in Table 1. Screening various solvents using
K2CO3 as base showed that ethanol was the most effective
solvent (Table 1, entries 1, 11 and 22). Increasing the
temperature reduced the reaction time, but did not alter the
yield substantially (Table 1, entries 3 and 16). Upon
trialling different catalyst loadings, we found that
1.18 mol% of catalyst was efficient for the required con-
version (Table 1, entry 11). Our investigations also showed
that the base plays an essential role, since the reaction did
not proceed without base (Table 1, entry 21). We therefore
screened different bases, namely K2CO3, Na2CO3, Cs2CO3,
Description of the crystal structure of [PdL1L2Cl]
The complex C1 was crystallized from acetonitrile by slow
evaporation over a period of 5 days. The crystal has
monoclinic P21/c space group. The molecular structure of
C1 together with the atomic numbering scheme is shown in
Fig. 1. Crystallographic data are given in Table S1, and
selected bond lengths are listed in Table S2. The single-
crystal X-ray diffraction analysis confirmed coordination of
the thiosemicarbazone to palladium through thiolate sulfur
S1 and azomethine nitrogen N1. The other two coordina-
tion sites are occupied by the pyridine nitrogen N4 of the
N-methylimidazole ligand and a chloride ligand.
123

Transit Met Chem
Fig. 2 Intermolecular
bifurcated hydrogen bonding in
the complex
Fig. 3 Helical structure of C1
along the b-axis
NaOH, KOH, NaHCO3 and Na3PO4Á12H2O (Table 2); the
best results were obtained with K2CO3 (Table 2, entry 7).
Since C1 is soluble in ethanol, it could not be recovered
from this solvent. However, in aqueous medium the cata-
lyst remained as a suspension, allowing easy separation
from the organic products. Since reusability is an important
concern for a catalyst and also from the green chemistry
perspective water is the most suitable solvent, we chose
water as solvent to optimize the choice of base (Table 2)
and to also examine the scope of the reaction for various
aryl bromides and aryl boronic acids having either elec-
tron-withdrawing or electron-donating groups as coupling
partner (Table 3).
withdrawing or electron-donating groups, giving good
yields in both cases (Table 3, entries 5, 9–12). On the other
hand, 3-thienyl and 4-fluoro boronic acids required longer
reaction times and gave moderate and trace amounts of
product, respectively (Table 3, entries 15 and 16). The
primary problem associated with fluoro boronic acid might
be a slow rate of transmetalation, associated with the
electron deficiency of the aromatic ring. This protocol was
not useful for aryl chlorides at room temperature due to the
higher bond energy of C–Cl compared to C–Br; however,
at elevated temperature (60 °C) moderate isolated yields
were obtained (Table 3, entries 19, 20 and 22).
Reusability of the catalyst was checked using phenyl-
boronic acid and 4-bromoanisole as coupling partner. Since
C1 forms a colloidal solution under the reaction conditions,
it is easily recoverable by extraction with ethyl acetate and
water, washing with brine followed by centrifugal precip-
itation. The catalyst can then be reused after washing with
ethyl acetate and brine and drying. Very interestingly, the
second run reaction completed very rapidly (within 1 h)
with higher isolated yield (95%) compared to the first run
(6 h, 78% yield). However, the reaction time increased
From the substrate study reported in Table 3, it is clear
that the rate of cross-coupling depends on the functional
group present on both the aryl halide and aryl boronic acid.
The coupling between 4-substituted aryl bromides with
electron-withdrawing groups and phenyl boronic acid
(Table 3, entries 2, 3 and 8) required short reaction times
and returned good product yields. 4-Methoxyphenyl boro-
nic acid did not have any appreciable effect on the progress
of the reaction with aryl bromides bearing either electron-
123

Transit Met Chem
Table 1 Optimization of the Suzuki–Miyaura reaction of p-bromoanisole with phenylboronic acid at room temperaturea
Entry
Solvent (ml)
Catalyst (mol%)
Time (h)
Yield (%)b
1
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
H2O
[PdL1Cl2] (1.29)
[PdL1Cl2] (1.08)
[PdL1Cl2] (1.08)
[PdL1Cl2] (0.86)
[PdL1Cl2] (0.43)
[PdL1Cl2] (0.22)
[PdL1Cl2] (0.86)
[PdL1Cl2] (0.43)
[PdL1Cl2] (0.86)
[PdL1Cl2] (0.43)
C1(1.18)
C1(0.98)
C1(0.79)
C1(0.39)
C1(0.2)
C1(0.2)
C1(0.79)
C1(0.39)
C1(0.79)
3
4
90
87
89c
87
85
78
72
60
25
20
93
92
92
90
89
90c
84
78
35
30
2
3
2
4
4
5
5
6
6
7
6
8
H2O
8
9
i-PrOH
i-PrOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
H2O
24
24
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
a
3
2
4
4
2
6
H2O
6
i-PrOH
i-PrOH
EtOH
EtOH
H2O
24
24
3
C1(0.39)
C1(1.18)
PdCl2(1.00)/L1(1.00)/L2(1.00)
PdCl2(1.00)/L1(1.00)/L2(1.00)
PdCl2(1.00)/L1(1.00)/L2(1.00)
d
–
8
60
45
40
8
i-PrOH
8
Reaction conditions: p-bromoanisole (0.5 mmol), phenylboronic acid (0.6 mmol), K2CO3 (3 equiv.) solvent (4 mL), catalyst
(0.22–1.29 mol%) ca. room temperature (28 °C) in air unless otherwise noted
b
Yields are of isolated products
c
At 60 °C
No added base
d
Table 2 Optimization of base for the coupling reaction of p-bro-
moanisole with phenylboronic acid using catalyst C1 in watera
slightly in subsequent cycles (Table 4). From the turnover
frequency (TOF) determination (Table S3), it was observed
Yield (%)b
that the TOF of the second catalytic cycle (81 h-1) is
highest. After the second cycle, the slight gradual decrease
in product yield on successive reuse may be due to either
physical loss of catalyst or some decomposition of the real
catalyst. To investigate for possible catalyst leaching, we
performed ICP-AES analysis of the filtrate after the fifth
Entry
Base
Time (h)
1
2
3
4
5
6
7
a
Na2CO3
Cs2CO3
Na3PO4.12H2O
NaOH
4
9
3
4
4
4
3
73
40
85
66
65
58
92
KOH
catalytic cycle. Detection of
a negligible amount
NaHCO3
K2CO3
(0.0065 mol%) of palladium in the filtrate suggests no
significant leaching [45]. To further confirm the nature of
the catalytic system, we carried out a hot filtration test [45],
again using 4-bromoanisole and phenylboronic acid. After
15 min, the reaction was stopped and the catalyst was
Reaction conditions: p-bromoanisole (0.5 mmol), phenylboronic
acid (0.6 mmol), K2CO3 (3 equiv.), solvent (4 mL), catalyst
(1.18 mol%) ca. room temperature (28 °C)
b
Yields are of isolated products
123

Transit Met Chem
Table 3 Suzuki–Miyaura reaction of aryl halides with different arylboronic acidsa
Entry
X
R1
R2
Time (h)
Yield (%)b
1
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
4-CH3O
4-NO2
4-CHO
3-NO2
4-CHO
3-CHO
2-CHO
4-CN
H
6
2
78
2
H
90
3
H
2
85
4
4-CH3
4-CH3O
H
4
70
5
4
85
6
5
73
7
H
4
79
8
H
2
87
9
4-CH3O
3-NO2
H
4-CH3O
4-CH3O
4-CH3O
4-CH3O
3-CH3O
4-CH3CO
3-Thienyl
4-F
4
88
10
11
12
13
14
15
16
17
18
19
20
21
22
a
3
84
4
82
4-NO2
H
2
87
4
78
H
4
75
4-CH3O
3-NO2
4-NO2
4-CH3O
4-CH3O
4-CH3O
4-NO2
4-NO2
12
12
4
65
Trace
80
4-CH3CO
H
12
12
12
12
12
Trace
60c
50c
15
4-CH3O
H
H
H
72c
Reaction conditions: p-bromoanisole (0.5 mmol), phenylboronic acid (0.6 mmol), K2CO3 (3 equiv.), solvent (4 mL), catalyst (1.18 mol %) ca.
room temperature (28 °C) in air unless otherwise noted
b
Yields are of isolated products
c
At 60 °C
Table 4 Reusability of C1 in watera
No. of runs
Time (h)
%Yield
First
6
78
95
93
90
90
89
87
Second
Third
Fourth
Fifth
1
1.5
1.5
2
Sixth
2
Seventh
3
a
Reaction condition
b
Isolated yield
filtered off after centrifugation (20% yield determined by
GC–MS). The reaction was then allowed to continue for a
further 6 h without the catalyst (Fig. 4). No catalytic
activity could be seen in the filtrate (by GC analysis),
ruling out the possibility of homogeneous catalysis by
leached Pd species. Furthermore, to identify the active
catalytic species, we performed an Hg(0) poisoning test.
Hg(0) poisons heterogeneous palladium particles by
Fig. 4 Activity of the catalyst for the reaction between phenyl
boronic acid and 4-bromoanisole with hot filtration and without
filtration
forming an amalgam [46], but does not poison homoge-
neous complexes of palladium in high oxidation states.
Hence, for the mercury poisoning test, Hg(0) (molar ratio
to [Pd] *400) was taken in a reaction flask containing H2O
123

Transit Met Chem
layer of the thiosemicarbazone. As shown in the figure, the
clearly visible lattice fringes and diffraction dots observed
in the SAED image indicate the crystalline nature of the
PdNPs.
Figure S6 shows the SEM–EDX pattern of the catalyst
after the first catalytic cycle. The data reveal the palladium
content along with the N, S, C and O proportions and suggest
that the Pd nanoparticles are stabilized by the thiosemicar-
bazone ligand. The XRD pattern of C1 after the first catalytic
cycle exhibits diffraction peaks at 2h values of 40.2, 46.3 and
67.8 which correspond to the (111), (200) and (220) planes of
the face centered cubic phase of Pd(0) nanoparticles
[JCPDS46-1043]. The peak broadening suggests the pres-
ence of small particles as well as a low degree of crystallinity
(Fig. S7). This was further confirmed by TEM analysis.
Figure 6a, b shows the characteristic XPS responses of
the Pd2? and Pd0 3d core-level peaks of the catalyst before
and after the first catalytic cycle, respectively. The two
peaks at 341.2 and 346.1 eV (Fig. 6a) can be assigned to
the Pd2? 3d core-level peaks corresponding to the 5/2 and
3/2 spin–orbit components [47]. The Pd0 nanoparticles 3d
core-level spectrum (Fig. 6b) is characterized by a pair of
relatively narrow peaks corresponding to the 5/2 and 3/2
spin–orbit components located at 336.2 and 341.4 eV, in
agreement with several results previously reported [48, 49].
In order to investigate the cause of the decrease in cat-
alytic efficiency on successive cycles, we carried out a
TEM analysis of C1 recovered after the sixth catalytic
cycle. This revealed that the Pd nanoparticles of size
1.5–2.0 nm formed after the first run had aggregated to
larger particles (Fig. S8). The aggregation appears to be
responsible for the decrease in catalytic activity observed
for successive runs.
Fig. 5 Particle size distribution of C1 after the first catalytic cycle
before the addition of reactants and stirred for 0.5 h at
room temperature. To this suspension, 4-bromonitroben-
zene (0.5 mmol), phenylboronic acid (0.6 mmol), K2CO3
and the palladium catalyst recovered after first run were
added, and the mixture was stirred for the required time at
room temperature. The reaction was almost stopped (by
GC analysis) by the addition of Hg(0). This established
that the complex C1 is actually a pre-catalyst, which gets
activated to Pd(0) during the first catalytic cycle and
interacts with Hg(0) to stop the reaction. To clarify the
catalytic nature of the palladium catalyst recovered after
the first run, we have carried out TEM, SEM–EDX and
XRD analysis. Also to check the oxidation state of pal-
ladium, XPS was performed before and after the first
cycle.
The TEM image (SAED: selected area electron
diffraction, in the inset) of the catalyst [Fig. S5] after the
first run clearly shows the formation of Pd nanoparticles,
with the majority of particles within the size range of
1.5–2.0 nm, as shown in the particle size histogram pre-
sented in Fig. 5. We believe that during the course of the
reaction, the palladium–ligand bonds dissociate and form
Pd(0) nanoparticles which might be stabilized by a surface
We have compared our catalyst with some previously
reported catalysts [21–27] and found it to have some
advantages in terms of greener reaction conditions, recy-
clability and heterogeneity (Table 5). Most of the previ-
ously reported catalysts were homogeneous in nature, so
either could not be recycled or could be used for a
Fig. 6 a 3d core-level XPS
spectrum of the catalyst C1 (i.e.,
Pd2? complex before catalysis),
b 3d core-level XPS spectrum
of the recovered catalyst after
the first catalytic cycle
123

Transit Met Chem
Table 5 Comparison of C1 with other reported Pd catalysts
Catalyst (mol%)
Aryl
halide
Yield % (reaction
time)
Solvent
Temperature, base
Reference
[21]
Chloro[4-tert-butyl-benzaldehyde 4-(ß-D-
glucopyranosyl) thiosemicarbazone]palladium(II)
dimer [0.1 mol%]
PhBr
PhCl
59–90 (24 h)
No reaction
DMF
DMF
100 oC, K2CO3
100 oC, K2CO3
Palladium(II) complexes with carbohydrate derived PhCl
thiosemicarbazone and semicarbazone ligands
[0.2 mol%]
98 (1 h)
EtOH
25 oC, K2CO3
[22]
Bis(diphenylphosphino)ferrocene bridged Pd
complex [0.5 mol%]
PhBr
PhCl
PhBr
99 (24–48 h)
99 (24–48 h)
100 (2–18 h)
DMF
DMF
130 oC, K3PO4
130 oC, K3PO4
120 oC, NaOH
[23]
[24]
[Pd(NS-R)2] or [Pd(CNS-R)(PPh3)] [0.001 mol%]
Polyethylene
glycol
PhCl
PhBr
PhCl
50–100 (5–24 h)
100 (24 h)
Polyethylene
glycol
120 oC, NaOH
1-R means [Pd(L–R)(nn)] and 2–R means [Pd(L–
R)(q)] [0.1–0.001 mol%] where, nn = 1-nitroso-
2-naphthol q = quinolin-8-ol R = OCH3, CH3, H,
Cl, NO2
Polyethylene
glycol
120 oC, Cs2CO3,
NaOH
120 oC, Cs2CO3,
[25]
100 (24 h)
Polyethylene
glycol
NaOH
95–110 oC, NaOH
Pd catalyst [0.5–1 mol%]
Pd catalyst [0.001 mmol]
PhBr
[99 (9–15 h)
Ethanol–toluene
(1:1)
[26]
[27]
PhBr
PhCl
PhBr
PhCl
80–99 (1 h)
58 (12 h)
Ethanol
Ethanol
H2O
Reflux, K2CO3
Reflux, K2CO3
RT, K2CO3
[PdL1L2Cl], C1
88 (3–12 h)
72 (12 h)
This work
[1.18 mol%]
H2O
60 oC, K2CO3
maximum for three runs [27]. Moreover, some of these
reported catalysts contain expensive and toxic phosphine
ligands [23, 24].
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