Palladium (II) Complexes Containing 2-Phenylpyridine Derivatives: Synthesis, Molecular Structures, and Catalytic Activity for Suzuki–Miyaura Cross-Coupling Reactions

Article abstract of DOI:10.1134/S0022476620030130

The preparation and characterization of a series of new 2-phenylpyridine derivative ligands consisting of 2-(R) pyridine (R = mesityl (L1), 2,6-dimethylphenyl (L2), o-tolyl (L3), m-tolyl (L4), p-tolyl (L5), o-methoxyphenyl (L6), and p-methoxyphenyl (L7)) and their Pd complexes [PdCl₂L₂] (L1–L7) is investigated using a combination of X-ray diffraction spectroscopy, GC-MS, and NMR. The crystal structures show that the Pd complexes adopt a square planar geometry, and the monodentate ligand is coordinated through the N donor of the pyridine ring to the Pd atom. The catalytic activities of the synthesized complexes are investigated. The square planar Pd complex trans-[(2-mesitylpy)₂PdCl₂)] shows a high efficiency in promoting Suzuki-Miyaura cross coupling in an aqueous solvent under aerobic conditions.

Full text of DOI:10.1134/S0022476620030130

ISSN 0022-4766, Journal of Structural Chemistry, 2020, Vol. 61, No. 3, pp. 466-475. © Pleiades Publishing, Ltd., 2020.
Text © The Author(s), 2020, published in Zhurnal Strukturnoi Khimii, 2020, Vol. 61, No. 3, pp. 489-497.
PALLADIUM (II) COMPLEXES CONTAINING
2-PHENYLPYRIDINE DERIVATIVES: SYNTHESIS,
MOLECULAR STRUCTURES, AND CATALYTIC ACTIVITY
FOR SUZUKI–MIYAURA CROSS-COUPLING REACTIONS
1
A. Adamson , Y. P. Budiman , I. Mkhalid *,
1
1
1
R. Muhammad , M. N. Arshad , M. R. Alhaddad ,
2
1
1
and A. M. Asiri
The preparation and characterization of a series of new 2-phenylpyridine derivative ligands consisting of
2-(R) pyridine (R = mesityl (L1), 2,6-dimethylphenyl (L2), o-tolyl (L3), m-tolyl (L4), p-tolyl (L5),
2 2
o-methoxyphenyl (L6), and p-methoxyphenyl (L7)) and their Pd complexes [PdCl L ] (L1–L7) is
investigated using a combination of X-ray diffraction spectroscopy, GC-MS, and NMR. The crystal
structures show that the Pd complexes adopt a square planar geometry, and the monodentate ligand is
coordinated through the N donor of the pyridine ring to the Pd atom. The catalytic activities of the
2 2
synthesized complexes are investigated. The square planar Pd complex trans-[(2-mesitylpy) PdCl )] shows
a high efficiency in promoting Suzuki–Miyaura cross coupling in an aqueous solvent under aerobic
conditions.
DOI: 10.1134/S0022476620030130
Keywords: phenylpyridine, Pd, Suzuki–Miyaura coupling.
INTRODUCTION
Pyridine heterocyclic compound synthesis continues to attract much attention due to its diverse applicability to
various fields, including pharmaceutical and organic synthesis [1-6]. Transition metals such as Pd and copper complexes have
been used successfully for the preparation of very active hypertension drugs such as Losartan and Valsartan [7-11]. The use
of Pd as a catalyst for the synthesis of carbon-carbon bonds is particularly interesting due to its unique properties [12, 13]. In
recent years, the use of Pd with phosphine or carbene ligands has been found to be very promising due to the high efficiency
of their coupling reactions [14, 15]. Phosphorous-containing ligands are predominantly used in cross-coupling reactions;
however, some drawbacks have also been recorded in their usage. Phosphine has been found to be very sensitive to both
moisture and air [16]. Carbene ligands also have the disadvantage of the requirement of multiple steps in the preparation
procedure, but they are more stable than phosphorus-containing ligands [17-20]. Improvements in the use of non-phosphine
ligands, such as pyridine, for Pd-catalyzed cross-coupling were recently reported [21], and successes in the use of nitrogen
1
Department of Chemistry, King Abdulaziz University, Jeddah, Saudi Arabia; *ibrahemmkhalid@gmail.com.
2
Center of Excellence for Advanced Materials Research (CEAMR) King Abdulaziz University, Jeddah, Saudi Arabia.
Original article submitted September 11, 2019; revised October 15, 2019; accepted October 21, 2019.
466
0022-4766/20/6103-0466 © 2020 by Pleiades Publishing, Ltd.

chelating agents, such as porphyrin [22], diketiminate [23], and (bipyridine) pyridine compounds [24-31], have resulted in
numerous advances in Pd-catalyzed cross-coupling. In the quest to synthesize a more efficient catalyst, the combination of
Pd- and nitrogen-containing ligands is promising due to their stability in air, non-toxicity, and convenient handling [32].
We report herein the synthesis of a new class of Pd complexes containing 2-phenylpyridine derivatives, including
2-(R) pyridine (R = mesityl; 2,6-dimethylphenyl; o-tolyl; m-tolyl; p-tolyl; o-methoxyphenyl; p-methoxyphenyl) and
investigate their use in a Suzuki reaction of 2-bromopyridine and 2,6-dibromopyridine with steric phenyl boronic acid in an
aqueous solvent in a homogeneous catalysis system.
EXPERIMENTAL
Materials and methods. The synthesis of ligands 1, 2, 3, 4, and 6 was performed under N
techniques with [Pd(PPh ] as a catalyst [33], whereas the synthesis of ligands 5 and 7 was performed under aerobic
conditions, and a [Pd(OAc) ] catalyst was used [34]. Reagents for the reactions, phenylboronic acid, all solvents and pyridine
halides were procured from Aldrich. [PdCl (CH CN) ], bis(acetonitrile) di-chloroPd(II), [Pd(PPh ], and tetrakis
triphenylphosphine) Pd(0) were prepared according to protocols described in previous studies [35].
2
using Schlenk
3 4
)
2
2
3
2
3 4
)
(
Thin layer chromatography (TLC) was performed on silica gel GF254. Additionally, 1H (600 MHz) and
C (151 MHz) NMR spectra were acquired on a Bruker AV-600 spectrometer equipped with a 5 mm H, broadband inverse
13
13
(BBI) probe to observe 1H and a cryo dual probe optimized for C detection. All NMR spectra were recorded at room
temperature. NMR peaks were assigned by a MestreNova 9.1 NMR processing program (see http://mestrelab.com/) and
ACD/NMR Processor Academic Edition (see http://acdlabs.com/). GC-MS analyses were performed on a Shimadzu Series II
gas chromatograph equipped with a 5971 mass selective detector. A fused silica capillary column (10 m or 12 m cross-linked
5% phenylmethylsilicone) was used, and the oven temperature was ramped from 50 °C to 280 °C at a rate of 20 °C/min.
Ultrahigh purity grade helium was used as the carrier gas.
Synthesis of 2-mesitylpyridine (L1). 2-Bromopyridine (1 g, 1 equiv, 6.33 mmol), mesitylboronic acid (1.29 g,
1
.2 equiv, 7.86 mmol), K
flask containing toluene/ethanol/water (120 mL/15 mL/10 mL) under an N
reaction lasted for 48 h at 120 °C. The mixture was then cooled and diluted with ethylacetate and H
MgSO ) was used to remove any water present. After filtration, the mixture was concentrated using a rotary evaporator.
2
CO
3
(1.75 g, 2 equiv, 12.66 mmol), and Pd(PPh
3
)
4
(0.22 g, 5 mol%) were added to a round bottom
atmosphere using Schlenk techniques. The
O. Magnesium sulphate
2
2
(
4
Column chromatography was used for purification of the product. All volatiles were removed, and a yellow oily product with
1
a yield of 85% was obtained (1.06 g, 5.37 mmol) with the following properties: H NMR (600 MHz, CDCl
3
) δ 8.69 (ddt,
J = 5.0, 1.9, 1.0 Hz, 1H), 7.73 (td, J = 7.6, 1.8 Hz, 1H), 7.23 (ddd, J = 7.7, 4.9, 1.2 Hz, 1H), 7.21 (dt, J = 7.7, 1.1 Hz, 1H),
13
3
6.92 (d, J = 1.2 Hz, 2H), 2.31 (s, 3H), 2.00 (s, 6H). C NMR (151 MHz, CDCl ), δ 160.10, 149.70, 137.81, 137.52, 136.36,
+ +
35.77, 128.34, 124.06, 121.59, 21.20, 18.3; MS (EI): m/z 196.2 [M] , 181.2 [M–Me] .
1
Synthesis of 2-(2,6-dimethylphenyl)pyridine (L2). 2-Bromopyridine (1 g, 1 equiv, 6.33 mmol), 2,6-dimethyl-
2 3 3 4
phenylboronic acid (1.14 g, 1.2 equiv, 7.60 mmol), K CO (1.75 g, 2 equiv, 12.66 mmol), and Pd(PPh ) (0.370 g, 5 mol%)
were added to a round bottom flask containing toluene/ethanol/water (120 mL/15 mL/10 mL), and similar procedures as in
L1 were performed. A liquid product was obtained with a yield of 44% (0.51 g, 2.78 mmol) with the following properties:
1
H NMR (600 MHz, CDCl
3
) δ 8.78 (ddd, J = 4.9, 1.9, 1.0 Hz, 1H), 7.81 (td, J = 7.7, 1.9 Hz, 1H), 7.31 (ddd, J = 7.6, 4.9,
1
.1 Hz, 1H), 7.29 (dt, J = 7.7, 1.1 Hz, 1H), 7.25 (d, J = 1.0 Hz, 1H), 7.18-7.16 (m, 1H), 7.15 (q, J = 0.7 Hz, 1H), 2.10 (d,
13
3
J = 0.8 Hz, 6H). C NMR (151 MHz, CDCl ), δ 160.02, 149.77, 140.56, 136.36, 135.85, 127.94, 127.60, 124.54, 121.74,
+ +
0.29; MS (EI): m/z 182.2 [M] , 167.2 [M–Me] .
2
Synthesis of 2-o-tolylpyridine (L3). 2-Bromopyridine (1 g, 1 equiv, 6.33 mmol), o-tolylboronic acid (1.03 g,
2 3 3 4
1.2 equiv, 7.58 mmol), K CO (1.75 g, 2 equiv, 12.66 mmol), and Pd(PPh ) (0.37 g, 5 mol%) were added to a round bottom
flask containing toluene/ethanol/water (120 mL/15 mL/10 mL), and similar procedures as in L1 were performed. A yellow
1
oily product was obtained with a yield of 78% (0.84 g, 4.96 mmol) with the following properties: H NMR (600 MHz,
467

CDCl ) δ 8.70 (ddd, J = 4.9, 1.9, 1.0 Hz, 1H), 7.80 (dt, J = 8.0, 1.1 Hz, 1H), 7.76 (dd, J = 7.6, 1.8 Hz, 1H), 7.69 (ddd, J = 8.0,
3
7.5, 1.9 Hz, 1H), 7.37 (ddd, J = 8.3, 7.4, 1.8 Hz, 1H), 7.20 (ddd, J = 7.4, 4.9, 1.2 Hz, 1H), 7.08 (td, J = 7.5, 1.1 Hz, 1H), 7.00
13
3
(dd, J = 8.3, 1.0 Hz, 1H), 3.85 (s, 3H). C NMR (151 MHz, CDCl ), δ 157.05, 156.22, 149.51, 135.75, 131.25, 129.97,
+ +
29.26, 125.22, 121.75, 121.17, 111.45, 55.98; MS (EI): m/z 168.2 [M] , 167.1 [M–H] .
1
Synthesis of 2-m-tolylpyridine (L4). 2-Bromopyridine (1 g, 1 equiv, 6.33 mmol), m-tolylboronic acid (1.03 g,
2 3 3 4
1.2 equiv, 7.58 mmol), K CO (1.75 g, 2 equiv, 12.66 mmol), and Pd(PPh ) (0.37 g, 5 mol%) were added to a round bottom
flask containing toluene/ethanol/water (120 mL/15 mL/10 mL), and similar procedures as in L1 were performed. A yellow
1
oily product was obtained with a yield of 83% (0.97 g, 5.73 mmol) with the following properties: H NMR (600 MHz,
13
3 3
CDCl ) δ C NMR (151 MHz, CDCl ), δ 157.54, 149.43, 139.16, 138.29, 136.71, 129.64, 128.54, 127.59, 123.95, 121.94,
+ +
20.67, 21.40; MS (EI): m/z 169.2 [M] , 168.2 [M–H] .
1
Synthesis of 2-(p-tolyl)pyridine (L5). 2-Bromopyridine (0.5 g, 1 equiv, 3.16 mmol), p-tolylpboronic acid (0.52 g,
3 4 2
1.2 equiv, 3.82 mmol), K PO ⋅3H O (1.69 g, 2 equiv, 6.35 mmol), and Pd(II) acetate (0.02 g, 3 mol%), which was used as
a catalyst, were mixed in a round bottom flask containing isopropanol:water (40:30 mL). The reaction lasted for 48 h at
20 °C. The mixture was stirred continuously using a magnetic stirrer, and both TLC and GC were performed. The mixture
was cooled and diluted with ethylacetate and H O. Magnesium sulphate (MgSO ) was used to remove any water present.
1
2
4
After filtration, the mixture was concentrated using a rotary evaporator. Column chromatography was performed to purify the
product. All volatiles were removed, and a yellow oily product with a yield of 55% was obtained (0.30 g, 1.77 mmol) with
1
3
the following properties: H NMR (600 MHz, CDCl ) δ 8.67 (ddd, J = 4.8, 1.8, 1.0 Hz, 1H), 7.9-7.88 (m, 2H), 7.74-7.68 (m,
13
3
2H), 7.29-7.27 (m, 2H), 7.19 (ddd, J = 7.0, 4.8, 1.6 Hz, 1H), 2.41 (s. 3H). C NMR (151 MHz, CDCl ) δ 157.58, 149.67,
+ +
39.02, 136.80, 136.69, 129.50, 126.90, 121.94, 120.44, 21.33; MS (EI): m/z 169.2 [M] , 168.2 [M–H] .
1
Synthesis of 2-(2-methoxyphenyl)pyridine (L6). 2-Bromopyridine (1 g, 1 equiv, 6.33 mmol), 2-(2-methoxyphenyl)
2 3 3 4
boronic acid (1.20 g, 1.2 equiv, 7.90 mmol), K CO (1.75 g, 2 equiv, 12.66 mmol), and Pd(PPh ) (0.370 g, 5 mol%) were
added into a round bottom flask containing toluene/ethanol/water (120 mL/15 mL/10 mL), and similar procedures as in L1
were performed. A yellow oily product was obtained with a yield of 46% (0.49 g, 2.64 mmol) and the following properties:
1
3
H NMR (600 MHz, CDCl δ 8.69 (ddd, J = 4.9, 1.8, 1.0 Hz, 1H), 7.74 (td, J = 7.7, 1.8 Hz, 1H), 7.42-7.37 (m, 2H), 7.32-
13
3
7.23 (m, 4H), 2.36 (s, 3H). C NMR (151 MHz, CDCl ), δ 160.12, 149.30, 140.56, 136.26, 135.91, 130.80, 129.74, 128.35,
+ +
26.03, 124.16, 121.70, 20.43; MS (EI): m/z 184.2 [M] , 154.1 [M–OMe] .
1
Synthesis of 2-(4-methoxyphenyl)pyridine (L7). 2-Bromopyridine (1 g, 1 equiv, 6.33 mmol), (p-methoxyphenyl)
3 4 2 2
boronic acid (1.15 g, 1.2 equiv, 7.57 mmol), K PO ⋅3H O (3.371 g, 2 equiv, 12.66 mmol) and [Pd(OAc) ] (0.04 g, 3 mol%),
which was used as a catalyst, were mixed in a round bottom flask containing isopropanol:water (40:30 mL), using similar
procedures as in L1. A white solid product was obtained upon cooling with a yield of 58% (0.37 g, 1.99 mmol) and the
following properties: proton NMR (600 MHz, Chloroform-d), δ 8.65(ddd, J = 4.8, 1.8, 1.0 Hz, 1H), 7.96-7.93 (m, 2H),
7
3
5
.71 (ddd, J = 8.0, 7.3, 1.9 Hz, 1H), 7.67 (dt, J = 8.0, 1.1 Hz, 1H), 7.17 (ddd, J = 7.3, 4.8, 1.2 Hz, 1H), 7.05-6.94 (m, 2H),
13
.87 (s, 3H). C NMR (151 MHz, Chloroform-d), δ 160.68, 157.33, 149.69, 136.85, 132.16, 128.28, 121.56, 119.95, 114.24,
+ +
5.61. MS (EI): m/z 185.1 [M] , 170.1 [M–Me] . M.P. (53.6-54.8 °C).
Synthesis of PdCl (L1) (1). Sample L1 (0.11 g, 2.2 equiv, 0.56 mmol) and [PdCl (PhCN) ] (1 equiv, 0.1 g,
2 2 2 2
2 2
2.60 mmol) were dissolved with CH Cl (30 mL), stirred for 24 h, and then cooled. Then, petroleum ether was added to
promote precipitation. After 15 minutes, a yellow precipitate was filtered with petroleum ether. A product consisting of
1
a yellow complex was obtained with a 72% yield (0.11 g, 0.19 mmol) and the following properties: H NMR (600 MHz,
DMSO-d
6
) δ 8.61 (ddd, J = 4.9, 1.9, 1.0 Hz, 2H), 7.81 (td, J = 7.7, 1.9 Hz, 2H), 7.30 (ddd, J = 7.6, 4.9, 1.2 Hz, 4H), 7.21 (dt,
J = 7.7, 1.2 Hz, 2H), 6.96 (s, 2H), 6.88 (s, 4H), 2.23 (s, 6H), 1.87 (s, 12H).13C NMR (151 MHz, DMSO-d
6
) δ 159.09,
1
49.43, 139.70, 137.86, 136.52, 134.97, 128.00, 124.62, 121.91, 20.71, 19.88.
Complexes 2-7 were prepared in a similar way to complex 1, and their yields and data analysis results are reported
in the supporting material.
468

TABLE 1. Selected Bond Lengths for Complex Molecule 1
Bond
Length, Å
Bond
Length, Å
Pd1—Cl2
Pd1—Cl1
Pd1—N2
Pd1—N1
N2—C15
N2—C19
N1—C5
2.310(4)
2.305(4)
2.034(12)
2.024(11)
1.33(2)
Pd2—Cl4
Pd2—Cl3
Pd2—N4
Pd2—N3
N4—C43
N4—C47
N3—C29
N3—C33
2.295(4)
2.295(4)
2.050(10)
2.048(11)
1.319(19)
1.355(17)
1.330(19)
1.358(17)
1.36(2)
1.363(19)
1.34(2)
N1—C1
X-ray analysis. Suitable crystals for all compounds were selected under a microscope and mounted on an Agilent
SuperNova (dual source) Agilent Technologies diffractometer equipped with graphite-monochromatic Cu/MoK radiation for
α
data collection. The samples were fixed on a glass tip on a magnetic base copper rod using glue. Data collection was
accomplished using the CrysAlisPro software [36] at 296 K under Mo (for compound 1) and Cu (for compounds 2-5)
α
K radiation. The crystallographic parameters for both molecules are given in Table 1. The structure of the solution was
2
determined using SHELXS-97 [37] and refined by full-matrix least-squares methods of F using SHELXL-97 [37] with an
in-built X-Seed [38]. All non-hydrogen atoms were refined anisotropically by full-matrix least squares methods [37]. The
C–H hydrogen atoms were positioned geometrically and treated as riding atoms, where C–H = 0.93 Å with
U
iso(H) = 1.2Ueq(C) for aromatic carbon atoms and C–H = 0.96 Å with Uiso(H) = 1.5Ueq(C) for methyl carbon atoms. The
figures were generated using Olex2 [39]. Crystals 1, 2, 3, 4, and 5 were grown by slow evaporation of the dichloromethane
solution of the complexes at room temperature. The CCDC numbers for compounds 1-5 are 1892837-1892841, respectively.
RESULTS AND DISCUSSION
NMR spectra of the complexes tended to be invisible, except for complex 5, when using CDCl
the lack of solubility. To acquire the NMR spectra, the remaining complexes were dissolved in DMSO-d
X-ray crystallographic analysis successfully detected single crystals for complexes 1-5. The crystals were obtained
by slow evaporation of the CH Cl solution from the complexes at room temperature.
3
as a solvent due to
6
using a heat gun.
2
2
Complex 1 was crystalized in a monoclinic crystal system as two independent molecules, A (C1–C28) and B (C29–
C56), per unit cell. In both molecules, the Pd metal adopted a square planar geometry, and ligands were in the trans position.
The torsion angles between pyridine and the aromatic rings in molecule A were 77.03(5)° and 37.23(6)° and 74.56(5)° and
39.93(5)° in molecule B. Both molecules used the intermolecular hydrogen bonding to generate inversion dimers through the
C–H…Cl type interaction (Figs. 1, 2).
The torsion angles between the pyridine and rings in each molecule were 59.12(2)°, 78.42(1)°, 45.19(2)° and
39.48(3)° for molecules 2, 3, 4 and 5, respectively (Fig. 3).
Catalytic testing. To test the catalytic activities of complexes 1-7 in the coupling reaction, 2,6-dibromopyridine (1a)
and o-tolylpyridine (2a) were chosen as substrates for the model reaction. Complex 1 generally worked well at 0.3 mol%,
although di-coupling with o-tolylboronic acid was steric (94.52%), and an excellent yield was obtained using a mol% greater
than 1 (entry 1), as shown in Table 2. Product 3a with a high yield (99%) was obtained with methanol (entry 1). However, for
nonpolar 1,4 dioxane, a low yield (50%) was obtained (entry 2), and toluene showed poor activity (11%) (entry 3). Notably,
no coupling activity was observed in water (entry 4). From the aforementioned data, we can conclude that the solvent system
plays a significant role in the solubility of the reagents, aiding entry into the catalytic cycle. For the purpose of this study,
methanol was used because it is inexpensive, readily available and has the highest efficiency.
469

Fig. 1. View showing intermolecular hydrogen bonding
dashed lines).
(
Fig. 2. ORTEP diagram for complex 1.
Fig. 3. ORTEP diagram of complexes 2, 3, 4, and 5.
470

a
TABLE 2. Suzuki–Miyaura Coupling of 2,6-Dibromopyridine
b
c
Entry
Catalyst
Solvent
Time, h
Yield, %
99
1
1
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
2
3
4
5
6
7
1
1
1
1
1
MeOH : H
MeOH : H
MeOH : H
2
2
2
O
O
O
1
1
99 (1 mol % of Pd catalyst)
1
95 (0.3 mol % of Pd catalyst)
1,4-dioxane : H
Toluene : H
2
O
16
16
16
1
50
11
0
2
O
2
H O
MeOH : H
MeOH : H
MeOH : H
MeOH : H
MeOH : H
MeOH : H
MeOH : H
MeOH : H
MeOH : H
MeOH : H
MeOH : H
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
98
63
46
53
97
51
16
16
16
16
16
16
16
1
10
11
12
13
14
15
97 (Using K
87 (Using NaOH)
86 (Using Cs CO
85 (Under argon)
76 (Under N
2 3
CO )
2
3
)
16
16
2
)
a
3 4 2
General conditions: 3 mol % Pd catalyst, 1.00 mmol of 1a, 2.20 mmol of 2b, 2.00 mmol of K PO 3H O, aerobic
conditions.
b
The ratio of solvent to water = 5:1.
c
Yield isolated after TLC.
Under optimized conditions and using methanol as a solvent, the best result for the reaction was obtained when
complex 1 was used. A yield of 99% of 3a was recovered (entry 1). Complex 2, which contains L2 as a ligand, gave a high yield
of 98% (entry 5). However, a decrease in the coupling product to 63% was observed when complex 3 was used (entry 6).
Complex 4 having L4 as a ligand, showed the lowest yield of the coupling product: only 46% (entry 7). Complex 5 was also
found to be not suitable for this reaction; a yield of only 53% was obtained (entry 8). Interestingly, complex 6 containing L6 as
a ligand gave a very good isolated yield of 97% but after 16 h (entry 9). The trends of the reactions examined above supported
the theory that hindrance of electron-rich ligands is more favorable for oxidative addition of Pd(0) with aryl halides [40].
The presence of a base is important for the trans-metalation stage to occur between Ar–Pd–X and incoming acids
[41]. Of the bases tested, only K
3 4 2 2 3
PO ⋅3H O produced a high yield of 99% (entry 1), and K CO gave a less yield of 97%
(entry 11). NaOH, a good base for Suzuki cross-coupling, gave a yield of 87% (Table 2, entry 12). Another base Cs CO gave
2 3
the lowest yield but was considered to be relatively effective (Table 2, entry 13). Interestingly, the presence of gas influenced
the coupling reaction. A large amount of the coupling product (99%) was obtained when the reaction ran under aerobic
471

TABLE 3. Coupling of Pyridyl Halides
Boronic acid Product
b
Entry
Pyridylbromide
Time, h
Yield,%
1
1
99
2
3
4
1
1
1
99
99
85
5
6
7
2
63
43
49
16
16
8
2
2
2
85
22
64
9
10
a
Conditions: 2.2 mmol boronic acid coupling with 1 mmol of 2,6-dibromopyridine and 1.2 mmol boronic acid
coupling with the derivatives of 1 mmol monobromopyridine; 2 equiv of K PO ⋅3H O, 3 mol% of catalyst 1, in
3 4 2
MeOH:H O (6:1, 36 mL), 80 °C.
2
b
Isolated yield.
472

conditions after 1 h (entry 1). However, a low yield was obtained when the reaction was conducted under argon (85%) (entry
14) and nitrogen (76%) (entry 15) 6%.
Scope of the catalytic activity of complex 1 in Suzuki coupling. Based on the catalytic efficiency of each complex
in the reaction and analysis of their structure, complex 1 was chosen for the further study. Complex 1 generally worked well
for di-coupling, such as when using simple substrates 1a and 2b to produce 3b (99%) (Table 3, entry 2). An excellent yield of
3a was obtained (99%) even though di-coupling substrate 2a was more steric than 2b (Table 3, entry 1). Substrates 1a and 2c
produced an excellent yield of di-coupling product 3c (99%) (Table 3, entry 3), and this reaction was more effective than
electronically activated aryl heterocyclics such as 2d, which produced an 85% yield of di-coupling product 3d (Table 3, entry 4).
Substrate 2a coupled with 1b to produce a moderate yield of 3e (63%) (Table 3, entry 5), but steric hindered
substrates such as 2e and 2f coupled with 1b and produced coupling products of 3f and 3g (43% and 49%) (Table 3, entries 6
and 7). Consistent with the previously described example regarding the effect of steric substrates, coupling of 1c and 2a
produced a high yield of product 3h (85% (Table 3, entry 8) but hindered substrates such as 2f in performing coupling
reactions with 1c, resulting in a low yield of product 3i (22%) (Table 3, entry 9). These findings imply that a steric hindrance
affects the yield of coupling reactions. In addition, coupling product 3j produced a moderate yield (64%) in coupling with
substrates 1d and 2a (Table 3, entry 10). Interestingly, after comparing the di- and mono-coupling reactions according to the
obtained yield, di-coupling of substrate 1a with 2a (Table 3, entry 1) showed a very high yield of 3a (99%), and the mono-
coupling of 1b gave similar results to boronic acid and 2a when coupling with product 3e (63%) (Table 3, entry 5). This is
not unusual because a greater electron withdrawal of halide, i.e., Br on pyridyl makes oxidative addition easier [42]. As
a result, 2,6-dibromopyridine is more favorable for oxidative addition than 2-bromopyridine in the catalytic cyclic process.
CONCLUSIONS
Stable and efficient complexes were prepared, characterized, and applied for the Suzuki coupling reaction of both di-
and monobromo pyridine with various types of phenylboronic acid to obtain a high product yield. Crystal structures of the
catalysts show a square planar geometry around Pd atoms with monodentate ligand coordination to Pd using a nitrogen donor
2 2
atom of the pyridine ring. The square planar Pd complex trans-[(2-MesPy) ⋅Pd]Cl is highly efficient at promoting the
Suzuki–Miyaura cross-coupling reaction in an aqueous solvent under oxygen, and the complex is stable in the air. Therefore,
-mesitylpyridine, as a result of its effectiveness in the coupling reaction, can serve as alternative to phosphine ligands.
2
ACKNOWLEDGMENTS
The authors acknowledge DSR for technical and financial support. Abdulmuizz Adamson is thankful to King
Abdulaziz University for providing a scholarship.
FUNDING
This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under
grant no. 1438/130/227.
CONFLICT OF INTERESTS
The authors declare that they have no conflict of interests.
473

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