Suzuki-Miyaura cross-coupling of aryl chlorides catalyzed by palladium precatalysts of N/O-functionalized pyrazolyl ligands

Article abstract of DOI:10.1016/j.ica.2010.04.006

A series of palladium complexes, trans-[1-(R)-pz3,5-Me2]2PdCl₂ {R = CH₂CONH(2,6-i-Pr₂-C₆H₃) (1b) and 2-(OH)-C₆H₁₀ (2b)}, supported over N/O-functionalized pyrazole derived ligands effectively catalyzed the more challenging Suzuki-Miyaura cross-coupling of a variety of activated aryl chlorides with phenyl boronic acid in air in a mixed-aqueous medium (DMF:H₂O, v/v = 9:1) in moderate to excellent yields. Besides the commonly encountered C _sp2-C_sp2 coupling, the 1b and 2b precatalysts also catalyzed the relatively difficult C_sp2-C_sp3 coupling of benzyl chloride with phenyl boronic acid. The 1b and 2b complexes were synthesized by the direct reaction of the respective N/O-functionalized pyrazolyl ligands, 1a and 2a, with (COD)PdCl₂ in 62-66% yields. The stability of the pyrazole-palladium interaction in the 1b and 2b complexes has been attributed to the deeply buried N_pyrazole-Pd interaction as evidenced from the density functional theory (DFT) studies.

Full text of DOI:10.1016/j.ica.2010.04.006

Inorganica Chimica Acta 363 (2010) 3113–3121
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Suzuki–Miyaura cross-coupling of aryl chlorides catalyzed by palladium
precatalysts of N/O-functionalized pyrazolyl ligands
Alex John a, Mobin M. Shaikh b, Prasenjit Ghosh a,
*
a Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India
b National Single Crystal X-ray Diffraction Facility, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India
a r t i c l e i n f o
a b s t r a c t
A series of palladium complexes, trans-½1-ðRÞ-pz3;5-Me ꢀ2PdCl2 {R = CH2CONH(2,6-i-Pr2-C6H3) (1b) and 2-
(OH)-C6H10 (2b)}, supported over N/O-functionalized pyrazole derived ligands effectively catalyzed the
more challenging Suzuki–Miyaura cross-coupling of a variety of activated aryl chlorides with phenyl
boronic acid in air in a mixed-aqueous medium (DMF:H2O, v/v = 9:1) in moderate to excellent yields.
Besides the commonly encountered Csp2–Csp2 coupling, the 1b and 2b precatalysts also catalyzed the rel-
atively difficult Csp2–Csp3 coupling of benzyl chloride with phenyl boronic acid. The 1b and 2b complexes
were synthesized by the direct reaction of the respective N/O-functionalized pyrazolyl ligands, 1a and 2a,
with (COD)PdCl2 in 62–66% yields. The stability of the pyrazole–palladium interaction in the 1b and 2b
complexes has been attributed to the deeply buried Npyrazole–Pd interaction as evidenced from the den-
sity functional theory (DFT) studies.
2
Article history:
Received 28 January 2010
Received in revised form 8 March 2010
Accepted 6 April 2010
Available online 10 April 2010
Dedicated to Animesh Chakravorty
Keywords:
Pyrazole
Suzuki–Miyaura
N/O-functionalized
Density functional theory
Catalysis
Ó 2010 Elsevier B.V. All rights reserved.
Aryl chlorides
1. Introduction
Though phosphines like PPh3 have been traditionally used in
the Suzuki–Miyaura cross-coupling reaction, the introduction of
Among the various C–C bond forming reactions, vigorous activ-
ities are seen in the area of developing newer and better catalysts
for the construction of biaryl frameworks employing the Suzuki–
Miyaura cross-coupling methodology. The Suzuki–Miyaura cross-
coupling reaction offers numerous advantages like the use of less
toxic boronic acid and ester starting materials, mild and operation-
ally easy reaction conditions, use of aqueous inorganic bases, func-
tional group tolerance, coupling of sterically hindered substrates
and high regio- and stereo-selectivities [1–4] over the other related
protocols like Hiyama [5–7], Stille [8–10] and Negishi [11] cou-
plings available for synthesizing various biaryl frameworks [12].
The wide diversity, easy availability and low cost of aryl chlorides
compared to the bromide or iodide analogs, make them more valu-
able a substrate for the Suzuki–Miyaura cross-coupling reaction
[13–16]. However, a formidable challenge lies in the low reactivity
of the aryl chlorides that arises from the high C–Cl bond energy
[bond dissociation energy (kcal/mol) for Ph-X: Cl (95), Br (80), I
(65)] [17,18], and consequently aryl chlorides are inherently reluc-
tant towards undergoing oxidative addition, the first step in the
cross-coupling reaction.
new ligands has significantly improved the efficiency as well as
the selectivity of the coupling reaction. For example, strongly
r
-donating and sterically demanding N-heterocyclic carbenes
[19–24] as well as the less basic N-donor ligands [25–27] have
been successfully employed in designing catalysts for the
Suzuki–Miyaura coupling of aryl chlorides. In this regard, the
efforts are directed towards designing cost-effective catalysts that
are readily accessible, moisture and air stable and function under
ambient conditions.
Though the N-based ligands display excellent tendency for
the complexation with palladium and the resultant palladium
precatalysts have been employed in various cross-coupling reac-
tions [28–30], only a few reports are known of their use in the
coupling of aryl chlorides, the most of which are of pyridyl
based systems [25,27,31]. Quite significantly, a recent study
highlighted the promising potential of pyrazole based precata-
lysts by demonstrating that the substitution of a N-heterocyclic
carbene moiety in a benzimidazole ligand supported palladium
precatalyst by a pyrazole moiety led to significant enhance-
ments in the catalytic activity in the Suzuki–Miyaura cross-cou-
pling of aryl chlorides [32]. Because of the aforementioned
reasons, we became interested in exploring the utility of pyra-
zole based palladium complexes in the Suzuki–Miyaura coupling
of aryl chlorides.
* Corresponding author. Tel.: +91 22 2576 7178; fax: +91 22 2572 3480.
E-mail address: pghosh@chem.iitb.ac.in (P. Ghosh).
0020-1693/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2010.04.006

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A. John et al. / Inorganica Chimica Acta 363 (2010) 3113–3121
One of our research interests lies in advancing the chemistry of
chloroacetamide in the presence of Na2CO3 as a base in 46% yield.
The hydroxyl-functionalized pyrazole ligand 2a was synthesized
by a modified literature procedure [53].
N-heterocyclic carbenes (NHCs) [33–43] by exploring their utility
in a variety of C–C bond forming reactions like the palladium med-
iated Suzuki–Miyaura [44–46], Sonogashira [47–50] and Hiyama
[49] couplings to the nickel mediated Michael [51,52] addition
reactions. With regard to the Suzuki–Miyaura reaction, we have re-
cently reported several palladium precatalysts of N/O-functional-
ized N-heterocyclic carbenes for the cross-coupling of aryl
bromide and iodide substrates [44–46]. Progressing further along
this theme of research, we became interested in designing Suzu-
ki–Miyaura precatalysts for the more challenging aryl chloride
substrates and proposed to do so by employing N/O-functionalized
pyrazolyl ligand based catalysts for the same.
Here in this contribution, we report two new palladium precat-
alysts, 1b and 2b, supported over N/O-functionalized pyrazolyl li-
gands that conveniently carried out the Suzuki–Miyaura coupling
of activated aryl chloride substrates with phenyl boronic acid in
air in a mixed-aqueous medium [Fig. 1 and Eq. (1)]. The nature
of bonding in the 1b and 2b complexes as probed by density func-
tional theory (DFT) studies revealed the presence of reasonably
The palladium complexes 1b and 2b have been characterized by
1H and 13C{1H} NMR, infrared spectroscopy, elemental analysis and
the X-ray diffraction studies. Notable is the 1H NMR spectrum of 1b
in which the methyl substituents on the pyrazole ring of the ligand
appeared as two singlets at 2.94 ppm and 2.42 ppm, while the
amido-NH moiety appeared downfield shifted at 8.33 ppm. The
infrared spectrum of 1b showed the characteristic amido stretch
(m
CONH) at 1689 cmꢁ1. Similarly for the 2b complex, the methyl
resonances of the pyrazole ring appeared at 2.45 ppm and
2.32 ppm. The characteristic OH stretch (
m
OH) of the cyclohexyl ring
.
in the 2b complex appeared at 3447 cmꢁ1
The molecular structures of 1b and 2b, as determined by X-ray
diffraction studies, revealed the monomeric nature of these com-
plexes bearing a 2:1 ligand to metal stoichiometry with the metal
center residing in a square-planar environment (Figs. 2 and 3, and
Table 1). The two pyrazolyl ligands as well as the two chlorine
atoms in both the palladium 1b and 2b complexes were at mutu-
ally trans dispositions to each other presumably due to steric rea-
strong
r-bonding Npyrazole–Pd interactions in these complexes.
Cl
B(OH)2
Cl
R
ð1Þ
1b or 2b
1b or 2b
R
R = NO2, CHO, COPh, CN, CF3, COCH3, H
sons. The Pd–N distances in 1b [2.009(2) Å] and 2b [2.011(3) Å]
2. Results and discussion
compared well with the sum of the individual covalent radii of pal-
ladium and nitrogen (2.07 Å) [54] and also with the other related
structurally characterized pyrazole based palladium complexes
like, trans-(3,5-di-tert-butyl-pyrazole)2PdCl2 [2.020(2) Å and
2.013(2) Å] [55] and trans-(3,5-di-tert-butyl-pyrazole)2Pd(Me)Cl
[2.035(3) Å and 2.041(3) Å] [55]. Along the similar lines, the ob-
served Pd–Cl distances [2.2925(9) Å (1b) and 2.3007(12) Å (2b)]
too compared well with the sum of the covalent radii of palladium
and chlorine (2.38 Å) [54]. As a final point, the two pyrazole rings
in the palladium 1b and 2b complexes were found to be coplanar
to each other.
With the intent of gaining deeper insight into the nature of the
pyrazole–palladium interaction in the 1b and 2b complexes, de-
tailed density functional theory (DFT) studies were undertaken.
Specifically, single-point calculations were performed on the 1b
and 2b complexes at the B3LYP/SDD, 6-31G(d) level of theory using
atomic coordinates adopted from X-ray analysis using Natural
Bond Orbital (NBO) method for a greater understanding of the elec-
tronic properties of these complexes (see Supplementary material
Tables S1 and S2). Importantly, the electron donation from the pyr-
azolyl ligand moiety to the palladium center in the 1b and 2b com-
plexes is evident from both the natural and Mulliken charge
analyses that revealed significant enhancements in the electron
density at the metal center in 1b and 2b, as compared to that in
the PdCl2 fragment (see Supplementary material Tables S3 and
S4). In addition, the NBO analysis revealed that the electron dona-
tion from the pyrazolyl ligand occurred on to the 5s orbital of the
palladium center in the 1b and 2b complexes (see Supplementary
material Table S5).
Two N/O-functionalized pyrazole derived ligands namely,
1-[(N-2,6-diisopropylphenyl)-2-acetamido]-3,5-dimethylpyrazole
(1a) and 1-(2-hydroxy-cyclohexyl)-3,5-dimethylpyrazole (2a),
were employed in designing suitable palladium precatalysts 1b
and 2b for use in the Suzuki–Miyaura cross-coupling of aryl chlo-
rides substrates with phenyl boronic acids. Specifically, the palla-
dium complexes 1b and 2b were synthesized from the respective
ligands, 1a and 2a, by the direct reaction with (COD)PdCl2 in
refluxing benzene in 62–66% yields (Schemes 1 and 2). The
amido-functionalized pyrazolyl ligand 1a was synthesized by the
reaction of 3,5-dimethylpyrazole with N-2,6-diisopropylphenyl-2-
HN
O
HO
Cl
Cl
N
N
N
Pd
N
N
Pd
N
N
N
Cl
Cl
OH
O
NH
(2b)
(1b)
An estimate of the strength of pyrazole–palladium interaction
in the 1b and 2b complexes was obtained by computing the
Fig. 1. Palladium complexes of N/O-functionalized pyrazolyl ligands.

A. John et al. / Inorganica Chimica Acta 363 (2010) 3113–3121
3115
HN
O
H
HN
N
Cl
O
Cl
N
(COD)PdCl2
O
HN
N
N
N
Pd
N
N
Na2CO3
N
Cl
O
NH
(1b)
(1a)
Scheme 1.
HO
HO
Pd
O
Cl
N
(COD)PdCl2
HN
N
N
N
N
N
N
Cl
OH
(2a)
(2b)
Scheme 2.
Fig. 2. ORTEP of 1b. Selected bond lengths (Å) and angles (°): Pd1–N1 2.009(2), Pd1–Cl1 2.2925(9), N1–N2 1.361(3), N1–Pd1–N1 180.00(11), Cl1–Pd1–Cl1 180.00, N1–Pd1–
Cl1 89.28(7).

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A. John et al. / Inorganica Chimica Acta 363 (2010) 3113–3121
Fig. 3. ORTEP of 2b. Selected bond lengths (Å) and angles (°): Pd1–N1 2.010(3), Pd1–Cl1 2.3043(11), N1–N2 1.365(5), N1–Pd1–N1 180.0(2), Cl1–Pd1–Cl1 180.00(9), N1–Pd1–
Cl1 91.88(11).
Table 1
31G(d) level of theory, which pointed towards a reasonably strong
interaction (see Supplementary material Table S6). Additional
X-ray crystallographic data for palladium 1b and 2b complexes.
Compound
1b
2b
understanding of the pyrazole–Pd interaction in 1b and 2b was ob-
tained from the molecular orbital (MO) correlation diagram, con-
structed from the interaction of the individual fragment
molecular orbitals (FMOs) of the pyrazolyl ligand fragment with
the PdCl2 fragment in these complexes using AOMIX software [56].
Lattice
triclinic
triclinic
C22H36Cl2N4O2Pd
565.87
Formula
Formula weight
Space group
a (Å)
b (Å)
c (Å)
C
40H59Cl4N6PdO3
920.13
ꢀ
ꢀ
P1
P1
11.2709(5)
11.6167(5)
18.2802(8)
78.777(4)
85.015(3)
85.450(4)
2334.01(18)
2
150(2)
0.71073
1.309
0.667
32.6381
8221
8.2440(6)
8.3641(7)
11.2128(8)
104.313(7)
104.015(6)
102.973(7)
692.81(9)
2
120(2)
0.71073
1.579
1.084
32.5485
2424
Of particular relevance is the
r-interaction between the pyrazole
moiety and the palladium center in the 1b and 2b complexes as
represented by the following molecular orbitals (MOs), HOMO-59
(1b) and HOMO-35 (2b) (Figs. 4 and 5 and see Supplementary
material Figs. S1 and S2). Worth pointing out that the deep-seated
nature of the molecular orbitals (MO’s) depicting pyrazole–Pd
a
(°)
b (°)
c
(°)
V (Å3)
Z
T (K)
r
-interaction in these complexes indicate towards
a stable
Radiation (k, Å)ꢁ3
ligand–metal interaction.
q
l
(calcd.) (g cm )
(Mo K
Significantly enough, both the palladium 1b and 2b complexes
efficiently catalyzed the Suzuki–Miyaura cross-coupling of aryl
chlorides with phenyl boronic acid in air in a mixed-aqueous med-
ium. In particular, when a mixture of the aryl chloride and phenyl
boronic acid were heated at 120 °C in presence of 2 mol% of the
precatalysts, 1b and 2b, along with tetrabutylammonium bromide
(TBAB) in DMF:H2O (9:1 v/v) in air, the cross-coupled products
were obtained in a relatively short reaction period of 5 h (Eq.
(1)). Remarkably enough, a wide variety of activated aryl chloride
substrates, namely o/p-ClC6H4X (X = NO2, CN, COPh, CHO, CF3,
a
) (mmꢁ1
)
h max (°)
No. of data
No. of parameters
R1
wR2
511
0.0355
0.0832
0.928
208
0.0484
0.1286
1.084
Goodness-of-fit (GOF)
Npyrazole–Pd bond dissociation energies, De/(Pd–pyrazole), 1b
(48.14 kcal/mol) and 2b (47.18 kcal/mol), at the B3LYP/SDD, 6-

A. John et al. / Inorganica Chimica Acta 363 (2010) 3113–3121
3117
O
O
N
N
N
N
N
H
N
Cl
H
Cl
Pd
N
H
Pd
N
H
N
N
Cl
N
Cl
-6
-7
N
O
O
5 %
LUMO
27 %
HOMO-13
HOMO-13
HOMO-29
-8
-9
6 %
11 %
HOMO-5
-10
-11
-12
-13
HOMO-29
HOMO-49
HOMO-53
12 %
HOMO-49
HOMO-53
HOMO-59
7 %
6 %
HOMO-61
HOMO-61
Fig. 4. Simplified orbital interaction diagram showing major contributions to the pyrazole–palladium bond in 1b.
COCH3 and H), were converted to the respective biaryl products in
moderate to excellent yields (23% to >99%) (Table 2). Apart from
the commonly explored Csp2–Csp2 coupling, the palladium 1b and
2b complexes also catalyzed the more challenging Csp2–Csp3 cou-
pling of benzyl chlorides with phenyl boronic acid in good to excel-
lent yields (55% to >99%) (Table 2). In order to underscore the
practical efficacy of biaryl synthesis using the Suzuki–Miyaura
cross-coupling of aryl chlorides catalyzed by these palladium 1b
and 2b complexes, the isolated yields were obtained for a repre-
sentative precatalyst 1b (Table 2).
tive (82–100%) yields at a loading of 1–3 mol% at 80 °C in dioxane
[69]. We are aware of only one report of a pyrazole based palladium
precatalyst namely, [2-(1-propylbenzimidazolylmethyl)-3,5-di-
tert-butyl-pyrazole]PdCl2, that performed the Suzuki–Miyaura
coupling of aryl chlorides in moderate to good yield (32–52%) at a
catalystloadingof 0.2–2.0 mol% in CH3OH under ambient conditions
[32]. Thus, in the backdrop of the paucity of pyrazole based palla-
dium precatalysts for the cross-coupling of aryl chlorides substrates,
the N/O-functionalized pyrazole based 1b and 2b precatalysts
assume significance.
Indeed, the considerable enhancement of up to 84% obtained
with the palladium 1b and 2b precatalysts over the control experi-
3. Conclusions
ment, performed using
a simple precursor like (COD)PdCl2,
highlighted the presence of significant ‘‘ligand-influence” in the
cross-coupling reactions of these catalysts. The homogeneous nat-
ure of catalysis by the 1b and 2b complexes was ascertained by car-
rying out the ‘classical Hg-drop’ test [57,58] that showed trivial
effect on the catalysis results (see Supplementary material Table S7).
Important among the palladium complexes reported for the
Suzuki–Miyaura cross-coupling reaction of aryl chlorides are the
ones of the N-heterocyclic carbene [59–62], phosphine [63–65]
and of the various N-donor [66,67] ligands. For example, the pyrim-
idine functionalized N-heterocyclic carbene based palladium
complex, [3-(mesityl)-1-(pyrimidin-2-yl)imidazol-2-ylidene]PdCl2,
catalyzed the cross-coupling of a variety of electronically modulated
aryl chloride substrates in moderate to excellent yields (15–95%) at
1 mol% of the catalyst loading in a mixed-aqueous medium at
80–120 °C over a period of 2–12 h [68]. Analogously, the palla-
dium, cis-[1-benzyl-3-(N-phenyl-2-acetamido)-imidazo-2-ylidene]-
Pd(PCy3)Cl2 and cis-[1-benzyl-3-(N-phenyl-2-acetamido)-imidazo-
lin-2-ylidene]Pd(PCy3)Cl2, complexes carried out the coupling of
aryl chloride substrates with phenyl boronic acid in near quantita-
In summary, two new palladium precatalysts, 1b and 2b, derived
from N/O-functionalized pyrazolyl ligands have been evaluated for
their performance in carrying out the highly desirable Suzuki–Miya-
ura cross-coupling of aryl chloride substrates with phenyl boronic
acid. A wide variety of activated aryl chloride substrates, namely
o/p-ClC6H4X (X = NO2, CN, COPh, CHO, CF3, COCH3 and H), were con-
verted to the respective biaryl products in moderate to excellent
yields over a short period of reaction time of 5 h. The density func-
tional theory studies performed on the 1b and 2b complexes attrib-
uted the stability of the pyrazole–palladium interaction to the
deeply-seated nature of the Npyrazole–Pd
r-bonding orbital.
4. Experimental
4.1. General procedures
All manipulations were carried out using standard Schlenk
techniques. Solvents were purified and degassed by standard

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A. John et al. / Inorganica Chimica Acta 363 (2010) 3113–3121
HO
HO
N
Cl
Cl
N
N
N
N
N
Pd
N
Pd
N
OH
Cl
Cl
OH
-6
-7
9 %
7 %
HOMO-5
HOMO-6
HOMO-6
HOMO-5
HOMO-25
HOMO-26
-8
-9
HOMO-20
4 %
5 %
HOMO-20
HOMO-6
-10
-11
HOMO-25
HOMO-26
HOMO-27
10 %
6 %
24 %
HOMO-35
HOMO-27
Fig. 5. Simplified orbital interaction diagram showing major contributions to the pyrazole–palladium bond in 2b.
Table 2
Selected results for Suzuki–Miyaura cross-coupling reaction of aryl chlorides catalyzed by 1b and 2b.
Entry
Reagenta
Reagenta
Cross-coupled product
Yieldb
1b
2b
1
2
3
4
5
>99 (81)
>99
94 (76)
>99 (85)
93 (82)
>99 (87)
>99
>99
>99
>99
6
7
8
9
>99 (77)
>99 (72)
23
>99
>99
27
55
>99
a
Reaction conditions: 1.00 mmol of aryl chloride, 1.20 mmol of boronic acid, 1.50 mmol of Cs2CO3, 1.50 mmol of TBAB, 2 mol% of catalyst 1b–2b in 8 mL of DMF:H2O (9:1),
at 120 °C for 5 h.
b
The yields (%) were determined by GC using diethylene glycol di-n-butyl ether as an internal standard. Isolated yields for representative runs using 1b are given in the
parentheses.

A. John et al. / Inorganica Chimica Acta 363 (2010) 3113–3121
3119
procedures [70]. 2,6-Diisopropylaniline and cyclohexene oxide
4.4. Synthesis of [1-(2-hydroxy-cyclohexyl)-3,5-
dimethylpyrazole]2PdCl2 (2b)
were purchased from Sigma–Aldrich, Germany while chloroace-
tyl chloride was purchased from Spectrochem, India and used
without any further purification. The 1-(2-hydroxy-cyclohexyl)-
3,5-dimethylpyrazole (2a) [53] and N-(2,6-diisopropylphenyl)-2-
chloroacetamide [71] were synthesized by modification of the
procedures reported in literature. 1H and 13C{1H} NMR spectra
were recorded on a Varian 400 MHz NMR spectrometer. 1H
NMR peaks are labeled as singlet (s), doublet (d), triplet (t), sep-
tet (sept) and multiplet (m). Mass spectrometry measurements
were done on a Micromass Q-Tof spectrometer. Infrared spectra
were recorded on a Perkin–Elmer Spectrum One FT-IR spectrom-
eter. X-ray diffraction data were collected on a Bruker P4 diffrac-
tometer equipped with a SMART CCD detector and crystal data
collection and refinement parameters are summarized in Table
1. The structures were solved using direct methods and standard
difference map techniques, and were refined by full-matrix least-
squares procedures on F2 with SHELXTL (Version 6.10) [72,73]. GC
spectra were obtained on a Perkin–Elmer Clarus 600 equipped
with a FID. GCMS spectra were obtained on a Perkin–Elmer Cla-
rus 600 T equipped with an EI source. Elemental Analysis was
carried out on Thermo Quest FLASH 1112 SERIES (CHNS) Ele-
mental Analyzer.
A mixture of 1-(2-hydroxy-cyclohexyl)-3,5-dimethylpyrazole
(2a) (0.103 g, 0.531 mmol) and (COD)PdCl2 (0.075 g, 0.263 mmol)
was refluxed in benzene (ca. 20 mL) for 8 h, after which the reac-
tion mixture was concentrated under vacuum to yield the product
2b as a yellow solid (0.098 g, 66%). 1H NMR (CDCl3, 400 MHz, 25 °C)
d 5.97 (s, 2H, C3N2H), 3.92 (m, 2H, CH(OH)), 3.12 (m, 2H,
CH(C3N2H)), 2.82–2.79 (m, 4H, CH2), 2.45 (s, 6H, CH3), 2.32 (s, 6H,
CH3), 1.98–1.41 (m, 12H, CH2). 13C{1H} NMR (CDCl3, 100 MHz,
25 °C) d 150.8 (C3N2H), 149.0 (C3N2H), 146.3 (C3N2H), 142.8
(C3N2H), 110.6 (C3N2H), 107.9 (C3N2H), 71.3 (CH(OH)), 66.4
(CH(C3N2H)), 36.9 (CH2), 34.4 (CH2), 31.6 (CH2), 31.1 (CH2), 25.7
(CH2), 24.8 (CH2), 16.9 (CH3), 15.0 (CH3), 13.2 (CH3), 12.7 (CH3).
IR data (KBr pellet cmꢁ1): 3447 (m)
(mOH). Anal. Calc. for
C22H36O2N4PdCl2: C, 46.70; H, 6.41; N, 9.90. Found: C, 46.48; H,
6.80; N, 9.06%.
4.5. Computational methods
Density functional theory calculations were performed on the
palladium 1b and 2b complexes including their fragments using
GAUSSIAN 03 [74] suite of quantum chemical programs. The Becke
three parameter exchange functional in conjunction with Lee–
Yang–Parr correlation functional (B3LYP) has been employed in
the study [75,76]. Stuttgart–Dresden effective core potential
(ECP), representing 19 core electrons along with the valence basis
sets (SDD) is used for palladium atom [77–79]. All other atoms are
treated at the 6-31G(d) basis set [80]. Natural Bond Orbital (NBO)
analysis was performed using the NBO 3.1 [81] program imple-
mented in the GAUSSIAN 03 package.
Inspection of the metal–ligand donor–acceptor interactions was
carried out using the charge decomposition analysis (CDA) [82].
CDA is a valuable tool in analyzing the interactions between
molecular fragments on a quantitative basis, with an emphasis
on electron donation [83,84]. The orbital contributions in the sin-
gle-point structures of the palladium(II) (pyrazole)2PdCl2, 1b and
2b, complexes can be divided into three parts:
4.2. Synthesis of 1-[N-(2,6-diisopropylphenyl)-2-acetamido]-3,5-
dimethylpyrazole (1a)
A mixture of 3,5-dimethylpyrazole (0.961 g, 10.0 mmol), N-2,6-
diisopropylphenyl-2-chloroacetamide (2.53 g, 9.98 mmol) and
Na2CO3 (1.69 g, 15.9 mmol) was refluxed in acetonitrile (ca.
60 mL) for 16 h, after which the reaction mixture was cooled to
room temperature and filtered. The filtrate was concentrated un-
der vacuum to yield the crude product which was purified by re-
peated washing with hot water (ca. 3 ꢂ 30 mL) to yield the
product 1a as an off-white solid (1.43 g, 46%). 1H NMR (CDCl3,
3
400 MHz, 25 °C) d 7.55 (br, 1H, CONH), 7.13 (t, 1H, JHH = 8 Hz, p-
3
C6H3), 7.01 (d, 2H, JHH = 8 Hz, m-C6H3), 5.80 (s, 1H, C3N2H), 4.71
3
(s, 2H, CH2), 2.75 (sept, 2H, JHH = 6 Hz, CH(CH3)2), 2.27 (s, 3H,
3
CH3), 2.16 (s, 3H, CH3), 1.06 (d, 12H, JHH = 6 Hz, CH(CH3)2).
13C{1H} NMR (CDCl3, 100 MHz, 25 °C) d 167.4 (CONH), 150.0
(C3N2H), 145.9 (C3N2H), 141.0 (ipso-C6H3), 130.5 (p-C6H3), 128.6
(m-C6H3), 123.6 (o-C6H3), 106.6 (C3N2H), 52.4 (CH2), 28.9
(CH(CH3)2), 23.6 (CH(CH3)2), 13.5 (CH3), 11.1 (CH3). IR data (KBr
(i)
(ii)
r
p
-donation from the [pyrazole ligand ? PdCl2] fragment,
-back donation from [pyrazole ligand PdCl2] fragment,
and
pellet cmꢁ1): 1673 (s) (
m
CONH). HRMS (ES): Calcd. for [M+H]+
(iii) repulsive polarization (r).
314.2232, found m/z 314.2233.
The CDA calculations are performed using the AOMIX [56], using
the B3LYP/SDD, 6-31G(d) wave function. Molecular orbital (MO)
compositions and the overlap populations were calculated using
the AOMIX program. The analysis of the MO compositions in terms
of occupied and unoccupied fragment orbitals (OFOs and UFOs,
respectively), construction of the orbital interaction diagrams, the
charge decomposition analysis (CDA) was performed using the
AOMIX-CDA [85].
4.3. Synthesis of {[1-N-(2,6-diisopropylphenyl)-2-acetamido]3,5-
dimethylpyrazole}2PdCl2 (1b)
A mixture of 1-[N-(2,6-diisopropylphenyl)-2-acetamido]-3,5-
dimethylpyrazole (1a) (0.313 g, 1.00 mmol) and (COD)PdCl2
(0.142 g, 0.497 mmol) was refluxed in benzene (ca. 20 mL) for
12 h. The reaction mixture was filtered and the filtrate was concen-
trated under vacuum to yield the product 1b as a yellow solid
(0.246 g, 62%). 1H NMR (CDCl3, 400 MHz, 25 °C) d 8.33 (br, 2H,
4.6. General procedure for the Suzuki–Miyaura cross-coupling reaction
of aryl chlorides
3
3
CONH), 7.25 (t, 2H, JHH = 8 Hz, p-C6H3), 7.10 (d, 4H, JHH = 8 Hz,
m-C6H3), 6.15 (s, 2H, C3N2H), 5.90 (br, 4H, CH2), 2.94 (s, 6H, CH3),
3
2.82 (sept, 4H, JHH = 6 Hz, CH(CH3)2), 2.42 (s, 6H, CH3), 1.14 (d,
In a typical catalysis run, performed in air, a 25 mL vial was
charged with a mixture of the aryl chloride (1.00 mmol), phenyl
boronic acid (0.146 g, 1.20 mmol), Cs2CO3 (0.487 g, 1.50 mmol),
TBAB (0.484 g, 1.5 mmol) and diethyleneglycol-di-n-butyl ether
(internal standard) (0.218 g, 1.00 mmol). Palladium complexes 1b
or 2b (2 mol%) was added to the mixture followed by the solvent
(DMF/H2O, 9:1 v/v, 8 mL) and the reaction mixture was heated at
120 °C for an appropriate period of time, after which an aliquot
24H, JHH = 6 Hz, CH(CH3)2). 13C{1H} NMR (CDCl3, 100 MHz, 25 °C)
3
d 165.0 (CONH), 151.5 (C3N2H), 146.1 (C3N2H), 145.5 (ipso-C6H3),
129.9 (p-C6H3), 128.7 (m-C6H3), 123.5 (o-C6H3), 109.2 (C3N2H),
55.1 (CH2), 28.7 (CH(CH3)2), 23.7 (CH(CH3)2), 14.9 (CH3), 11.9
(CH3). IR data (KBr pellet cmꢁ1): 1689 (s) (
m
CONH). Anal. Calc. for
38H54O2N6Cl2Pdꢃ0.33C6H6: C, 57.87; H, 6.80; N, 10.12. Found: C,
57.28; H, 7.82; N, 9.91%.
C

3120
A. John et al. / Inorganica Chimica Acta 363 (2010) 3113–3121
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using diethyleneglycol-di-n-butyl ether as an internal standard.
4.7. General procedure for the Hg(0) drop test
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A 25 mL vial was charged with a mixture of the aryl chloride
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by the solvent (DMF/H2O, 9:1 v/v, 8 mL) and excess Hg(0) (ꢄ100
times). The reaction mixture was heated at 120 °C for an appropri-
ate period of time, after which an aliquot was filtered and the
product analyzed by gas chromatography using diethyleneglycol-
di-n-butyl ether as an internal standard.
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We thank DST, New Delhi, for financial support of this research.
We are grateful to the National Single Crystal X-ray Diffraction
Facility and Sophisticated Analytical Instrument Facility at IIT
Bombay, India, for the crystallographic and other characterization
data. Computational facilities from the IIT Bombay Computer Cen-
ter are gratefully acknowledged. A.J. thanks CSIR, New Delhi for re-
search fellowship.
Appendix A. Supplementary material
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graphic data for 1b and 2b. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif. Supplementary data associ-
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