Ligand-Tuned C–H Bond Activation/Arylation of 2-Arylpyridines over Pyridine-Based N,O/N,N Ligated Ruthenium–Arene Complexes

Article abstract of DOI:10.1002/ejic.201701446

Water-soluble ruthenium(II)–arene complexes [(η⁶-arene)Ru(κ²-L)]ⁿ⁺ (n = 0, 1) ([Ru]-1–[Ru]-10) containing pyridine-based bischelating N,O/N,N donor ligands (L1–L5) are synthesized and employed for the catalytic C–H bond activation/arylation of a wide range of 2-phenylpyridines and aryl halides in water, affording the corresponding mono- and biarylated products. Exploring the reactivity of the synthesized complexes, our investigations, including time-dependent ¹H NMR spectroscopic studies with ruthenium–arene catalysts, demonstrate a remarkable structure–activity relationship for the ligand-tuned C–H activation/arylation of 2-phenylpyridine, where the complexes with bischelating N,O donor-based ligands (acteylpyridine and picolinate) outperform those with N,N donor ligands (iminopyridine). Moreover, among the N,O donor ligands, a distinct effect of the nature of the coordinating oxygen donor on the catalytic activity is also observed, where ruthenium–arene complexes having N,O donor ligands (acetylpyridine) with neutral oxygen-donor atoms exhibit enhanced catalytic activity over those with anionic oxygen-donor atoms (picolinate). The observed trend in the catalytic activity is attributed to the ligand-promoted facile deprotonation and coordination–decoordination interconversion behavior. In addition, molecular structures for a few of the representative complexes ([Ru]-2, [Ru]-4, and [Ru]-5) are authenticated by single-crystal X-ray diffraction studies.

Full text of DOI:10.1002/ejic.201701446

A Journal of
Accepted Article
Title: Ligand-tuned C-H bond activation/arylation of 2-arylpyridines over
pyridine based N,O/N,N ligated ruthenium-arene complexes
Authors: Chinky Binnani, Rohit Kumar Rai, Deepika Tyagi, Shaikh M.
Mobin, and Sanjay Kumar Singh
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To be cited as: Eur. J. Inorg. Chem. 10.1002/ejic.201701446
Link to VoR: http://dx.doi.org/10.1002/ejic.201701446

10.1002/ejic.201701446
European Journal of Inorganic Chemistry
Ligand-tuned C-H bond activation/arylation of 2-arylpyridines
over pyridine based N,O/N,N ligated ruthenium-arene
complexes
Chinky Binnani,a Rohit K. Rai,a Deepika Tyagi,a Shaikh M. Mobin,a and Sanjay K. Singh*ab
aDiscipline of Chemistry, Indian Institute of Technology Indore, Simrol, Indore-453552, Madhya Pradesh, India
bE-mail: sksingh@iiti.ac.in
Abstract
Water soluble ruthenium(II)-arene complexes [(η6-arene)Ru(κ2-L)]n+ (n = 0, 1) ([Ru]-1 – [Ru]-
10) containing pyridine based bischelating N,O/ N,N donor ligands (L1 – L5) were synthesized
and were employed for the catalytic C-H bond activation/ arylation of a wide range of 2-
phenylpyridines and arylhalides in water, to afford corresponding mono and biarylated products.
Exploring the reactivity of the synthesized complexes, our investigations including time
dependent 1H NMR studies with ruthenium-arene catalysts demonstrated a remarkable structure-
activity relationship for the ligand-tuned C-H activation/ arylation of 2-phenylpyridine, where
the complexes with bischelating N,O donor based ligands (acteylpyridine and picolinate)
outperformed over those with N,N donor ligands (iminopyridine). Moreover, among N,O donor
ligands a distinct effect of the nature of coordinating oxygen donor on the catalytic activity was
also observed, where ruthenium-arene complexes having N,O donor ligands (acetylpyridine)
with neutral oxygen donor atom exhibited enhanced catalytic activity over those with anionic
oxygen donor (picolinate). The observed trend in the catalytic activity was attributed to the
ligand promoted facile deprotonation and coordination-decoordination interconversion behavior.
In addition, molecular structures for few of the representative complexes ([Ru]-2, [Ru]-4 and
[Ru]-5) were authenticated by single crystal X-ray diffraction studies.
1
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
Introduction
C-H bond activation and functionalization is a promising and efficient strategy to synthesize a
wide range of organic compounds in a step economical way.1 C-H bond activation/
functionalization reactions not only reduce time and efforts in long and tedious organic
transformations, but also generate less waste and undesired side products. Therefore to serve this
purpose, several methodologies have been developed to activate the otherwise un-reactive C-H
bonds. Among these methodologies, the functional group directed C-H bond activation and
functionalization has emerged as an efficient way to achieve tuned regioselectivity.1-2 The key
feature of this strategy is to exploit the Lewis basic site of substrate to bring the transition metal
in the close proximity of the targeted C-H bond to facilitate deprotonation – a concerted
metalation and deprotonation mechanistic pathway.1-3 In recent years, reactions proceeded
through the directed C-H bond activation have been illustrated by the formation of
cyclometalated intermediates, an important intermediate of C-H bond activation reactions.2-3
Along with a variety of transition metals including palladium,4 iridium5 and rhodium6 which
form cyclometalated species, ruthenium based complexes have also shown appreciable reactivity
towards the formation of cyclometalated species.7 Moreover, ruthenium complexes offers
excellent water solubility which provides the opportunity to perform catalytic C-H bond
activation/functionalization under environmentally benign condition using of water as a
solvent.8,9,12,13
In particular, catalytic systems based on ruthenium-arene complexes for C-H bond
activation/ functionalization of various heteroarenes have also been vastly explored, where the
role of ligands was found to be a crucial factor.7-14 For instance, bulky phosphines have been
used to tune the selectivity of monoarylated product during the ortho arylation of heteroarenes by
2
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
Inoue et al.11a Contrary to phosphine based ligands, carboxylates, as a ligand and deprotonating
agent explored by various researchers and displayed high potential to achieve enhanced catalytic
activity with tunable selectivity for ruthenium catalyzed C-H bond activation reaction.12
Extensive kinetic studies by Jutand et al. also evidenced the active role of carboxylates as
deprotonating agents, which enhances the catalytic efficiency of reaction by autocatalytic
process.12g A remarkable example of robust ruthenium(II) catalyzed carboxylate assisted C-H
arylation of amino acids and peptides has recently been reported by Ackermann et al. which also
suggests the crucial role of carboxylates in C-H activation reaction.12i In our recent studies with
ruthenium-arene complexes containing O,O and O,N donor tropolone/ aminotropolone ligands
for C-H bond arylation of 2-phenylpyridine in water, we also investigated the interesting role of
carboxylate additives, driven by steric bulkiness, in tuning the selectivity of C-H arylation
products.13 Later, we also explored aniline based ruthenium-arene complexes for C-H bond
arylation in water, where the strength of aniline-ruthenium bond and the substitution on aniline
ligand was found to be the crucial factors to tune the selectivity of mono v/s biarylated products
during the reaction.14
Further, in our deliberate efforts to develop efficient catalytic system for C-H activation/
functionalization reactions,13,14 herein we synthesized a series of ruthenium(II)-arene complexes
containing pyridine based N,O and N,N donor ligands and systematically investigated their
catalytic performance for ortho C-H bond activation/ arylation of 2-phenylpyridine with several
arylhalides in water. Synthesized ruthenium-arene complexes were well characterized using
NMR, mass spectral analysis and the molecular structure for few of the representative complexes
were authenticated by single crystal X-ray diffraction studies. Attempts were also made to
establish a relation between the pattern of bonding of ligands to the ruthenium metal center and
3
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
the observed catalytic activity of these complexes for ortho C-H bond activation/ arylation
reaction using time-scaled 1H NMR spectroscopy.
Results and Discussion
Synthesis of water-soluble ruthenium(II)-arene complexes [Ru]-1 to [Ru]-10: Water-soluble
ruthenium-arene complexes ([Ru]-1 ̶ [Ru]-10) containing pyridine based N,O and N,N donor
ligands were synthesized in good yield by reacting respective ruthenium(II)-arene dimer with the
readily available ortho substituted pyridine based N,O/ N,N donor bidentate ligands with
substituents ranging from carboxylic (pyridine-2-carboxylic acid (L1)), acetyl (2-acetylpyridine
(L2)), ester (2-methylpicolinate (L3)) and imino groups (N-benzyl-pyridylimine (L4) and N-
butyl-pyridylimine (L5)) as shown in the Scheme 1.
Scheme 1. Synthesis of ruthenium-arene complexes [Ru]-1 – [Ru]-10 containing
pyridine based N,O and N,N donor ligands.
4
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
Ligand L3 was prepared by acid catalyzed esterification of L1 in methanol under
refluxing condition.15a Iminopyridine ligands L4 and L5 were prepared by the condensation of
pyridine-2-carboxyladehyde with benzylamine and n-butylamine respectively.15b-15d Identity and
1
purity of the synthesized ligands L3 – L5 were confirmed by H and 13C NMR.15 Complexes
[Ru]-1 – [Ru]-2, [Ru]-4 – [Ru]-7, [Ru]-9 and [Ru]-10, with general formula [(η6-
arene)RuCl(2-L)]n+, where η6-arene = C6H6 or C10H14, L = L1 – L2, L4 and L5 and n = 0, +1,
were obtained by treating respective [{(η6-arene)RuCl2}2] with ligands L1 – L2, L4 and L5 in
methanol.15d,16 Complexes [Ru]-3 and [Ru]-8 were obtained by stirring ligand L3 with [{(η6-
arene)RuCl2}2] (η6-arene = η6-C10H14 and η6-C6H6) in dichloromethane at room temperature. The
synthesized complexes were well characterized by various spectro-analytical techniques, which
further authenticated the proposed structure as shown in the Scheme 1.
1H NMR spectra of the complexes [Ru]-1 – [Ru]-10 depicted an analogous trend, where
a downfield shift in the chemical shifts of the protons associated with ligands was observed
compared to the free ligands, suggesting the coordination of ligand to the ruthenium metal
1
center. H NMR resonances for protons corresponding to ruthenium coordinated η6-arene ring
were also observed in the expected region for all the complexes.13,14,15-18 FTIR and UV-visible
spectra recorded for the synthesized complexes were also in accordance with the previous
reports.16,18 The ESI mass spectra of the complexes [Ru]-1 and [Ru]-6 showed peaks
corresponding to the [M-Cl]+ ions, while rest of the cationic complexes displayed peaks for [M]+
ions with the characteristic Ru isotopic patterns. Moreover, the synthesized complexes also
exhibited appreciably good thermal stability (up to 250 ºC), as inferred from TGA studies
(Figure S1).
Further, molecular structure of the representative complexes [Ru]-2, [Ru]-4 and [Ru]-5
was also confirmed by single crystal X-ray diffraction studies. Crystals suitable for X-ray
5
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
diffraction of the complexes [Ru]-2, [Ru]-4 and [Ru]-5 were grown by the diffusion of diethyl
ether into the methanolic solution of these complexes at room temperature. Complexes [Ru]-2
and [Ru]-4 crystallized in monoclinic crystal system with P21/c space group, whereas [Ru]-5
crystallized in triclinic crystal system with P-1 space group. The geometry around the ruthenium
metal center was pseudo-octahedral, where the η6-arene ring occupied the top of the piano-stool,
and three legs were occupied by the bidentate N,O or N,N donor ligands and one chloride ligand.
The η6-arene ring centroid was displaced from the Ru(II) center by 1.671, 1.693 and 1.695 Å for
the complexes [Ru]-2, [Ru]-4 and [Ru]-5 respectively, which is comparable to the similar arene-
Ru(II) complexes.16-18 For complex [Ru]-2, the ligand 2-acetylpyridine (L2) was coordinated
with the ruthenium metal in bidentate fashion involving the nitrogen atom of pyridine ring and
oxygen atom of acetyl. Similarly, for complexes [Ru]-4 and [Ru]-5, iminopyridine ligands L4
and L5 were coordinated with the ruthenium metal in κ2-mode through Npy and Nimine. Ru-Npy(1)
and Ru-O(1) bond distances 2.107 and 2.117 Å respectively of complex [Ru]-2 were within the
permissible ranges for analogous ruthenium-arene complexes.18 Angles between the legs of the
complex, N(1)-Ru-Cl(1) and O(1)-Ru-Cl(1), were 83.9º and 83.8º respectively, whereas bond
angle between the legs and the centroid of the η6-arene ring (Ct) were in the range of 129.6 -
133.9º for complex [Ru]-2. The N(1)-Ru-O(1) bite angle was 76.2º for complex [Ru]-2. Ru-Npy
and Ru-Nimine bond distances were 2.079 and 2.094 Å respectively for the complex [Ru]-4 and
those for [Ru]-5 were 2.0871 and 2.0708 Å respectively. Bite angles N(1)-Ru-N(2) for the
complexes [Ru]-4 and [Ru]-5 were 76.6º and 76.8º. Angles between legs of these piano-stool
complexes were in the range of 83.3º-86.1º for complex [Ru]-4 and 85.1º - 85.9º for complex
[Ru]-5. The observed bond parameters are comparable to the previous reports for related
complexes.16,18 Detailed crystal refinement data , selected bond lengths and bond angles are
given in the Table S1-S7.
6
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
Figure 1. Single crystal X-ray structure of complex [Ru]-2 with 50% probability of
thermal ellipsoids. Counter ion PF6 and all hydrogen atoms are omitted for clarity.
Selected bond lengths (Å) and selected bond angles (deg): Ru1-N1 2.107(4), Ru1-O1
2.117(4), Ru1-Cl1 2.391(14), Ru1-Ct 1.671, N1-Ru-Cl1 83.91(12), O1-Ru-Cl1 83.85(12),
N1-Ru-O1 76.21(6).
Figure 2. Single crystal X-ray structure of complex [Ru]-4 with 50% probability of
thermal ellipsoids. Counter ion PF6 and all hydrogen atoms are omitted for clarity.
Selected bond lengths (Å) and selected bond angles (deg): Ru1-N1 2.079(5), Ru1-N2
2.094(5), Ru1-Cl1 2.398(15), Ru1-Ct 1.693, N1-Ru-Cl1 86.15(16), N2-Ru-Cl1 83.30(14),
N1-Ru-N2 76.65(19).
7
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
Figure 3. Single crystal X-ray structure of complex [Ru]-5 with 50% probability of
thermal ellipsoids. Counter ion PF6 and all hydrogen atoms are omitted for clarity.
Selected bond lengths (Å) and selected bond angles (deg): Ru1-N1 2.0871(19), Ru1-N2
2.0708(19), Ru1-Cl1 2.3997(6), Ru1-Ct 1.695, N1-Ru-Cl1 85.10(6), N2-Ru-Cl1 85.93(6),
N1-Ru-N2 76.80(8).
Ruthenium-arene catalyzed ortho C-H bond arylation of 2-phenylpyridines with
arylhalides. At an outset, 2-phenylpyridine (1a) and 4-chloroanisole (2a) were chosen as model
substrates for ortho C-H bond arylation over [Ru]-1 – [Ru]-10 catalysts. The reaction of 1a (0.5
mmol) and 2a (1.25 mmol)13,19 over [Ru]-1 catalyst (5 mol %) in the presence of 3 equiv. of
K2CO3 showed a conversion of 82% with 86% selectivity (63% yield) for the monoarylated
product (3aa) in 8 h at 100 °C in water (Table 1, entry 1). Further, a remarkably high conversion
of 98% was achieved over [Ru]-2 with 73% selectivity for 3aa (65% yield) in 8 h under
analogous reaction conditions. Moreover, extending the catalytic reaction to 10 h, complete
conversion of 2-phenylpyridine can be achieved over [Ru]-2 catalyst. Notably, [Ru]-3 catalyst
also resulted in 93% conversion with 61% yield of 3aa (Table 1, entry 3). In contrary to the
higher catalytic activity of [Ru]-1 – [Ru]-3 catalysts (ruthenium-arene with N,O donor ligands),
8
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
ruthenium-arene-iminopyridine complexes ([Ru]-4 – [Ru]-5) exhibited only moderate
conversions (Table 1, entries 4 and 5).
Table 1. Catalytic activity of ruthenium-arene complexes for ortho C-H bond arylation of 2-
phenylpyridine (1a) with 4-chloroanisole (2a).a
Entry Catalyst
Conv.
(%)d
Sel.
(3aa/4aa)
(%)d Yield (%) TON/TOF
(3aa)
1
2
[(η6-p-cymene)Ru(κ2-N,O-pyridine-
2-carboxylate)Cl] [Ru]-1
82
86/14
63%
16.4/2.05
19.6/2.45
[(η6-p-cymene)Ru(κ2-N,O-2-
acetylpyridine)Cl]PF6 [Ru]-2
98
(100)b
73/27
(68/22)b
65%
(60%)c
3
[(η6-p-cymene)Ru(κ2-N,O-2-
methylpicolinate)Cl]PF6 [Ru]-3
93
42
45
76/24
86/14
88/12
89/11
87/13
84/16
80/20
86/14
61%
28%
33%
63%
72%
65%
40%
32%
18.6/2.32
8.4/1.05
9.0/1.12
16.0/2.0
19.4/2.42
17.6/2.2
12.4/1.55
9.0/1.12
4
[(η6-p-cymene)Ru(κ2-N,N-(N-
benzyl-pyridylimine)Cl]PF6 [Ru]-4
5
[(η6-p-cymene)Ru(κ2-N,N-(N-butyl-
pyridylimine)Cl]PF6 [Ru]-5
6
[(η6-benzene)Ru(κ2-N,O-pyridine-2- 80
carboxylate)Cl] [Ru]-6
7
[(η6-benzene)Ru(κ2-N,O-2-
acetylpyridine)Cl]PF6[Ru]-7
97
88
62
45
8
[(η6-benzene)Ru(κ2-N,O-2-
methylpicolinate)Cl]PF6 [Ru]-8
9
[(η6-benzene)Ru(κ2-N,N-(N-benzyl-
pyridylimine)Cl]PF6 [Ru]-9
10
[(η6-benzene)Ru(κ2-N,N-(N-butyl-
pyridylimine)Cl]PF6 [Ru]-10
aReaction conditions: 1a (0.5 mmol), 2a (1.25 mmol), K2CO3 (3 equiv.), [Ru] catalyst (5 mol%) in
b
c
d
water (5 mL) at 100 ºC for 8 h. Reaction time = 10 h. Isolated yield in 10 h. Conversion and
selectivity were determined by 1H NMR. Yield (%) represents the isolated yield of the purified product
(3aa). TON = Turn Over Number. TOF = Turn Over Frequency (h-1).
9
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
Consistent with the higher catalytic activity observed with (η6-p-cymene)Ru complexes
([Ru]-1 – [Ru]-3), analogous (η6-benzene)Ru complexes ([Ru]-6 – [Ru]-8) also exhibited
enhanced catalytic conversion, where the (η6-benzene)Ru-acetylpyridine complex ([Ru]-7)
showed 97% conversion of 1a (Table 1, entry 6). Moreover, (η6-benzene)Ru complexes
containing iminopyridine based ligands ([Ru]-9 and [Ru]-10) were also observed to be less
active than the complexes with N,O donor ligands (Table 1, entries 9,10). Therefore, it is evident
from the above results, that ruthenium-arene complexes with N,O donor pyridine based ligands
displayed superior catalytic performance over those ligated with N,N donor ligands for the ortho
C-H bond arylation of 1a. Moreover, amongst N,O donor ligands, the ruthenium-arene
complexes having N,O donor ligands with neutral oxygen donor group (acetylpyridine ligated
ruthenium-arene complexes ([Ru]-2, [Ru]-3, [Ru]-7 and [Ru]-8) outperformed over those
coordinated with anionic oxygen donor group (picolinate ligated ruthenium-arene complexes
[Ru]-1 and [Ru]-6), under analogous reaction condition. The above results suggesting a crucial
role of ligand in the observed trend in the catalytic C-H bond activation reaction. Moreover, most
of the ionic ruthenium catalysts ([Ru]-2, [Ru]-3, [Ru]-7 and [Ru]-8) exhibited superior catalytic
activity than the electroneutral catalysts ([Ru]-1 and [Ru]-6),20 but the poor performance of other
ionic catalysts ([Ru]-4, [Ru]-5, [Ru]-9 and [Ru]-10) suggesting that presumably the effect of
solvation was superseded by the dominating and crucial role of the ligands.
10
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
100
80
60
40
20
0
Figure 4. Structure-activity relationship for ortho C-H bond arylation of 2-phenylpyridine
(1a) with 4-chloroanisole (2a) over [Ru]-1  [Ru]-10 catalysts.
Notably, carboxylate additives are considered as efficient deprotonating agents in C-H
bond activation reactions, where its deprotonating properties increases with the increase in
bulkiness/ basicity and on its availability in the solution.12, 13 Therefore, the effect of carboxylate
salts, with increasing bulkiness on α-carbon, were explored over the best catalyst ([Ru]-2) under
the optimized reaction conditions: Cat. 5 mol%, 100 ºC, K2CO3 (3 equiv.) (Table 2). Results
inferred that with the increase in bulkiness of the carboxylate salts (acetate → pivalate), a
gradual decrease in the conversion of 1a was observed over ruthenium-arene-acetylpyridine
[Ru]-2 catalyst (Table 2, entries 9-12). Interestingly, the ruthenium-arene picolinate catalyst
[Ru]-1 showed a reverse pattern, where an increase in the catalytic activity was observed with
bulky carboxylates (acetate → pivalate) (Figure 5).
11
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
Figure 5. Effect of carboxylate additives on ortho C-H bond arylation of 2-
phenylpyridine with 4-chloroanisole over [Ru]-1 and [Ru]-2 catalyst. * Reaction
performed with KOAc in absence of K2CO3.
The observed trend can be attributed to the competitive coordination of the
acetylpyridine/ picolinate and the carboxylate additives to the ruthenium center. The strong
coordinating nature of pivalate compared to acetylpyridine, under catalytic reaction condition
unless otherwise mentioned, resulted in the decreases in the availability of free carboxylate in the
solution, whereas picolinate showed stronger coordination behavior than carboxylate additives
and hence ensured greater availability of carboxylate additives in the solution. Though the
observed conversion with a range of carboxylate salts (with or without K2CO3) was found to be
lower than the conversion observed with only K2CO3 base (in the absence of any carboxylate
additives) in case of both catalysts, the above observations are worth noting as it inferred the
crucial role of the ligand in controlling the catalytic activity in the studied ruthenium-arene
complexes. Therefore, further optimization experiments were performed using only K2CO3 base,
without carboxylate additives. Notably, reaction could not occur in the absence of base or
12
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
catalyst (Table 2, entries 7-8). Moreover, performing the reaction at lower temperature < 100 ºC
resulted in poor conversion over [Ru]-2 catalyst (Table 2, entries 5-6).
Table 2. Optimization table for catalytic ortho C-H bond arylation of 2-phenylpyridine over
complex [Ru]-2.a
Conv.
(%)
Sel. (%)
(3aa/4aa)
Entry Temp. (ºC) Time (h)
Base
Additive
33
>99/<1
1
100
2
K2CO3
-
2
3
4
5
6
100
100
100
70
4
6
8
8
8
8
8
8
8
8
8
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
-
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
86
92
98
12
37
n.r.
n.r.
97
84
80
63
83/17
75/25
73/27
>99/<1
>99/<1
-
-
-
-
-
-
-
-
80
7
100
100
100
100
100
100
8b
9
-
CH3COOK
CH3CH2COOK
(CH3)2CH2COOK
(CH3)3CHCOOK
57/43
76/24
81/19
89/11
10
11
12
aReaction conditions: 1a (0.5 mmol), 2a (1.25 mmol), base (3 equiv., 1.5 mmol), [Ru]-2 (5 mol%),
1
additives (0.05 mmol) in water (5 mL). Conversion and selectivity were determined by H
NMR.bwithout catalyst. n.r. = No reaction.
1
Further, time-dependent H NMR experiments for C-H bond arylation reaction were
conducted over the high performance [Ru]-2 catalyst, and the results were compared with those
of the analogous picolinate ([Ru]-1) and iminopyridine ([Ru]-4) complexes (Figure 6a). Among
all the complexes studied, [Ru]-2 exhibited higher rates (6.12 × 10-4 sec-1) during the 0-8 hours
of the catalytic reaction (Figure S2). Contrary to [Ru]-2, complexes [Ru]-1 and [Ru]-4 displayed
relatively lower kinetics 3.50 × 10-5 sec-1 and 2.63 × 10-5 sec-1, respectively (Figure S2). The
above results clearly evidenced the crucial role of the coordination environment around the Ru
13
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
center, due to N,O/ N,N donor ligands, on the catalytic efficiency of the resulting ruthenium-
arene complexes. Further, the time-dependent reaction profile over [Ru]-2 catalyst showed
>90% consumption of 1a over a period of 6 h. Though the selectivity for monoarylated product
(3aa) remains dominated throughout the reaction (2-10 h), the selectivity for the biarylated
product (4aa) increases gradually with the increase in the reaction time, suggesting the
consumption of 3aa to form 4aa (Figure 6b).
(a)
(b)
100
80
60
40
20
0
100
80
60
40
20
0
[Ru]-4
[Ru]-2
[Ru]-1
2 h
4 h
6 h
8 h
1
2
3
4
5
2 h
4 h
6 h
10 h
8 h
Time(h)
Time (h)
Figure 6. (a) Time dependent reaction profile with complexes complexes [Ru]-1, [Ru]-2
and [Ru]-4, and (b) products, monoarylated (3aa) and biarylated (4aa), distribution over
[Ru]-2 for ortho C-H bond arylation of 2-phenylpyridine (1a) with 4-chloroanisole (2a) at
100 ºC in water.
Further, the scope and generality for [Ru]-2 catalyzed C-H bond arylation of 2-
phenylpyridine (1a) using several arylhalides (2a-2k) was explored under the optimized reaction
condition (Table 3). Notably, both electron donating and electron withdrawing arylhalides were
proved to be efficient arylating agents for ortho C-H bond arylation of 1a to afford
corresponding monoarylated products (3aa-3ak) as major component, with moderate to high
selectivity and yield in 8 h. The unsubstituted chlorobenzene (2b) afforded 82% conversion for
the arylation of 1a with 78% selectivity for the monoarylated product (3ab) (Table 3, entry 2).
14
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Analogous to 4-chloroanisole (2a), reaction with electron donating arylhalides, 4-chlorotoluene
(2c) and 4-chlorophenol (2d), also afforded the respective monoarylated products with high
selectivity, 70% for (3ac) and 75% for (3ad) (Table 3, entries 3-4). Notably, 4-chlorostyrene (2e)
showed sluggish reaction, presumably due to the coordination of vinyl group to the catalyst and
thus retarded the reaction progress. Nevertheless, 91% selectivity for the monoarylated product
(3ae) was achieved with 2e (Table 3, entry 5). Further, 4-chlorobenzhydrol (2f) and 4-bromo
N,N-dimethylaniline (2g) also exhibited moderate conversion, but with high selectivity of 99%
and 82% respectively for the monoarylated products (3af) and (3ag) (Table 3, entries 6,7).
Electron withdrawing arylhalides, 4-chloromethylbenzoate (2h) and 4-chloroacetophenone (2i),
also exhibited excellent conversion of 96% and 80%, respectively with selectivities of 45% and
80% for (3ah) and (3ai) (Table 3, entries 8,9). However, (hetero)arylhalides, 2-chlorothiophene
(2j) and 2-bromopyridine (2k), showed only poor conversion, presumably due to the strong
coordination of Lewis basic heteroatoms to the ruthenium center (Table 3, entries 10,11).21
Table 3. Catalytic ortho-C-H bond arylation of 2-phenylpyridine (1a) using various arylhalides
(2a-2k).a
Entry (Hetero)arylhalide
1
Conv. (%)/ Time (h)
Sel. (%)
Yield (%)
98 (8 h)
73/27
>99 (10 h)
68/32
(3aa/4aa)
2a
3aa (63%)
3ab (58%)
2
82
78/22
(3ab/4ab)
2b
15
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3
86
70/30
(3ac/4ac)
2c
3ac (53%)
3ad (63%)
3ae (40%)
3af (56%)
4
>99
52
75/25
(3ad/4ad)
2d
5
91/9
(3ae/4ae)
2e
6
65
99/1
(3af/4af)
2f
7
37
82/18
(3ag/4ag)
2g
3ag (20%)
3ah (36%)
8
96
80
40
45/55
(3ah/4ah)
2h
9
80/20
(3ai/4ai)
2i
3ai (58%)
3aj (24%)
10
80/20
(3aj/4aj)
2j
16
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11
15
45/55
(3ak/4ak)
2k
3ak (nd)b
aReaction conditions: 1a (0.5 mmol), 2a-2k (1.25 mmol), K2CO3 (3 equiv.), [Ru]-2 (5 mol%) in water (5
mL) at 100 ºC for 8 h. Conversion and selectivity were determined by 1H NMR. Yield (%) represents the
isolated yield of the purified product. bnd = Not determined.
Moreover, the effect of the substituted 2-phenylpyridines (1a-1c) on ortho C-H bond
arylation was also investigated (Table 4). Results inferred that having an electron donating
substituent, 2-(p-tolyl)pyridine (1b) showed enhanced reactivity with >80% conversion and
appreciably good selectivity for the monoarylated products was achieved (Table 4, entries 4-6).
In contrary, 2-(4-chloro)phenylpyridine (1c) bearing electron withdrawing chloro substituent
resulted in lower conversion for ortho C-H bond arylation (Table 4, entries 7-9). Nevertheless,
monoarylated products remain the dominating product for all the reactions.
Table 4. Catalytic ortho-C-H bond arylation of substituted 2-phenylpyridines using selected
arylhalidesa
Entry Phenylpyridine
Arylhalide
Conv. (%)
>99%b
Sel. m/d (%) (Yield
(%))
68/22 b
(3aa, 60%)c
1
82%
78/22
(3ac, 58%)c
2
17
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>99%
75/25
(3ad, 53%)c
3
98%
95%
>99%
62%
53/47
4
5
6
7
(3ba, 40%)c
70/30
(3bc, 55%)c
68/32
(3bd, nd)e
80/20
(3ca, 40%)d
39%
55%
86/14
8
9
(3cc, 23%)c
49/51
(3cd, 20%)d
aReaction conditions: 1a-1c (0.5 mmol), arylhalide (1.25 mmol), K2CO3 (3 equiv.), [Ru]-2 (5 mol%) in
water (5 mL) at 100 ºC for 8 h. Conversion and selectivity for monoarylated (m) and biarylated product
(d) were determined by 1H NMR. bTime = 10 h. cIsolated yield. dCombined yield for monoarylated and
biarylated product. end = Not determined.
To investigate and identify the possible organometallic species, which may be involved
in one or many steps of the catalytic ortho C-H bond arylation reaction, several controlled
1
experiments were performed. H NMR analysis of the reaction mixture using the stoichiometric
ratio of catalyst [Ru]-2 and substrate (1a) (C:S = 1:5) after 3 h, showed the formation of 2-
phenylpyridine
coordinated
cyclometallated
species
{(η6-p-cymene)Ru(κ2-C,N-
phenylpyridine)}+ [Ru]-A. Earlier reports inferred that such organometallic species [Ru]-A are
indeed a crucial species involved in several ruthenium-arene catalyzed ortho C-H bond
activation reactions.8,12,14 The presence of cycloruthenated species ([Ru]-A) was also confirmed
18
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European Journal of Inorganic Chemistry
by mass spectrometric investigation (m/z 390.1) of the stoichiometric reaction of complex [Ru]-
2 with 2-phenylpyridine (1a), even in the absence of base K2CO3 (Figure 7), suggesting the
possible role of the ruthenium coordinated 2-acetylpyridine in C-H activation reaction.
Therefore, the above NMR and mass spectral investigations along with the reaction kinetics and
carboxylate effect experiments substantially accounted for the observed superior catalytic
activity of N,O donor ligated ruthenium-arene complexes over those with N,N donor ligands,21
and the order of catalytic activity of the studied complexes was found as (η6-arene)Ru(κ2-N,O-2-
acetypyridine) > (η6-arene)Ru(κ2-N,O-2-methylpicolinate) > (η6-arene)Ru(κ2-N,O-picolinate) >>
(η6-arene)Ru(κ2-N,N-iminopyridine). The observed trend is indeed in accordance with the
previous studies, which evidenced the crucial role of bis-chelating ligands in tuning the catalytic
C-H activation reaction pathway via coordination/decoordination mechanism and by
participating in deprotonation step.22,23 For instance, the crucial role of Pd-coordinated picolinate
in the deprotonation of arene was reported over a Pd-catalyzed C-H acetoxylation of arenes,
where interestingly, picolinate/picolinic acid remains coordinated to the Pd during this
deprotonation step.23a Moreover, compared to the picolinate ligated metal complexes, those
having N,N donor ligands exhibited lower activity.23b In contrary to the picolinate and N,N
donor ligands, studies revealed that the acetyl group participated actively in the deprotonation of
the C-H bond activation, while remain uncoordinated.22 Moreover, literature also revealed that
proton abstraction by a carbonate base requires less energy (-13.7 kcal/mol) and comparatively
favorable over hydride abstraction pathway (+28.2 kcal/mol).24. Hence, we anticipated that the
remarkable catalytic activity of acetylpyridine ligated ruthenium-arene complexes for C-H
activation/ arylation is presumably due to the active participation of the ligand in facile
deprotonation of C-H bond and efficient coordination-decoordination interconversion process
19
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
(Figure 7). On the basis of above experimental observations a plausible reaction pathway for the
ortho-C-H bond arylation of 2-phenylpyridine is illustrated in Scheme S1.
Figure 7. (A) Ligand assisted remote C-H bond deprotonation of various arene rings
with transition metal (Ref. 18a, 20) (B) C-H bond deprotonation of 2-phenylpyridine and
coordination and decoordination of carbonyl oxygen of N,O donor ligand for the
formation of deprotonated cycloruthenated species. (C) Mass spectral identification of
cycloruthenated species for the reaction of [Ru]-2 with 2-phenylpyridine (with 1:5 molar
ratio) in absence of base.
20
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Conclusions
To summarize, we systematically investigated the ligand-tuned catalytic performance of
ruthenium(II)-arene complexes ligated with N,O and N,N donor pyridine based ligands for the
ortho C-H bond arylation of phenylpyridine with a variety of arylhalides in water. Our findings
demonstrated that among all the synthesized complexes, ruthenium-arene complexes ligated with
N,O donor pyridine ligands, [Ru]-1  [Ru]-3 and [Ru]-6  [Ru]-8, outperformed with good to
moderate yields (61-77%) for the C-H bond arylated products, over those containing N,N donor
1
pyridine ligands (28-40%). Moreover, the time-dependent H NMR studies inferred higher rate
constant for [Ru]-2 (ruthenium-acetylpyridine) (k = 6.12 × 10-4 sec-1) over [Ru]-3 (ruthenium-
picolinate) (k = 3.50 × 10-5 sec-1 ) and [Ru]-4 (ruthenium-iminopyridine) (k = 2.63 × 10-5 sec-1).
The observed trend in the ligand-tuned catalytic performance of the studied complexes inferred
the crucial role of the coordinating ligands (nitrogen vs oxygen and neutral vs anionic) to
establish the structure-activity relationship for the catalytic C-H activation/ arylation reactions,
where the facile ligand to Ru center coordination-decoordination interconversion and
deprotonation of C-H bond played crucial role in the observed trend. Moreover, the mass spectral
1
and H NMR studies showed the formation of the crucial cycloruthenated species, {(6-
arene)Ru(κ2-C,N-phenylpyridine)}+ ([Ru]-A) during the C-H bond activation of 2-
phenylpyridine. In addition, molecular structures for few of the representative complexes, [Ru]-
2, [Ru]-4 and [Ru]-5, were also authenticated by single crystal X-ray diffraction studies.
Specifically, we demonstrated ligand-tuned efficient ruthenium catalyzed C-H activation/
arylation reactions, which will be helpful in exploring new possibilities in this field.
21
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Experimental Section
Materials and instrumentation. All the reactions for catalyst preparation were performed
without inert gas protection and all the catalytic reactions for C-H bond arylation of 2-
phenylpyridine with arylhalides were performed under N2 atmosphere using chemicals of high
purity purchased from Sigma Aldrich and Alfa Aesar. Ruthenium-arene precursors [{(η6-
C6H6)RuCl2}2]and [{(η6-C10H14)RuCl2}2] were synthesized according to the literature
procedures. 25, 26 1H NMR (400 MHz), 13C NMR (100 MHz), and 31P NMR (161.98 MHz)
spectra were recorded at 298 K using CDCl3, Acetone-d6 or DMSO-d6 as the solvent on a Bruker
Avance 400 spectrometer. The chemical shifts in ppm are reported relative to the center of the
singlet at 7.26 ppm for CDCl3, 2.04 ppm for Acetone-d6 and 2.49 ppm for DMSO-d6 in 1H NMR
and to the center of the triplet at 77.0 ppm for CDCl3, singlet at 206.0 ppm for Acetone-d6 and
13
multiplet at 39.50 ppm for DMSO-d6 in C NMR. Coupling constants, J values are reported in
Hertz (Hz), and the splitting patterns are designated as follows: s, singlet; d, doublet; t, triplet; m,
multiplet; sept, septet. Single-crystal X-ray structural studies of complexes were carried out
using Agilent Technologies Supernova CCD system. FTIR for complexes was recorded on
Perkin Elmer STD10 FTIR spectrometer and UV-visible spectra of all the complexes was
recorded in methanol at room temperature on Carry-60 UV-visible spectrophotometer with
concentration of 5 × 10-5 M. Elemental analysis was carried out using a Thermo Scientific
FLASH 200 elemental analyzer. High-resolution mass spectra (HRMS) were recorded on
amicrOTF-Q II mass spectrometer. Thermal gravimetric analyses (TGA) were performed on the
Mettler Toledo thermal analysis system. CCDC deposition numbers of the complexes [Ru]-2,
[Ru]-4 and [Ru]-5 are 1515543, 1518468 and 1515545 respectively.
22
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Procedure for the synthesis of arene-Ru(II) complexes ([Ru]-1-[Ru]-10) containing pyridine
based ligands.
Synthesis of [(η6-p-cymene)Ru(κ2-N,O-pyridine-2-carboxylate)Cl] ([Ru]-1). Complex [Ru]-1
was prepared by the modified procedure.16 [{(η6-p-cymene)RuCl2}2] (0.306 g, 0.5 mmol) was
suspended in methanol (25 mL) and stirred for 30 minute at room temperature, and was added
pyridine-2-carboxylic acid (0.135, 1.1 mmol). After refluxing the reaction mixture for 12 h, all
volatiles were removed on rotavaporator and the residue obtained was dissolved in a minimum
amount of dichloromethane. Upon addition of excess of diethyl ether in the above
1
dichloromethane solution, yellow solid was precipitated out. Yield: 85% (0.260 g). H NMR
(400 MHz, CDCl3) δ (ppm) = 8.99 (d, 1H, J = 8.0 Hz), 7.98-7.94 (m, 2H), 7.59 (d, 1H, J = 8.0
Hz), 5.63 (d, 2H, J = 4.0 Hz), 5.47 (d, 2H, J = 8.0 Hz), 2.88 (m, 1H), 2.28 (s, 3H), 1.23 (d, 6H, J
= 8.0 Hz). 13C NMR (100 MHz, CDCl3) δ (ppm) =171.2, 153.1 151.1, 139.4, 128.4, 127.0,
102.6, 98.6, 83.2, 83.0, 82.1, 81.1, 31.1, 22.5, 22.49, 19.1. IR (cm-1) = 1634 (υC=O). UV/vis
(MeOH, λmax/nm) (εmax/M-1 cm-1) = 252 (5400), 320 (2400), 410 (400). MS (ESI) m/z calculated:
358.02 [M-Cl]+ [C16H18NO2Ru], Found: 358.03 [M-Cl]+ [C16H18NO2Ru].
Synthesis of [(η6-p-cymene)Ru(κ2-N,O-2-acetylpyridine)Cl]PF6 ([Ru]-2). Complex [Ru]-2 was
synthesized following modified procedure,16 by refluxing [{(η6-p-cymene)RuCl2}2] (0.306 g, 0.5
mmol) and 2-acetylpyridine (124 μL, 1.1 mmol) in methanol (25 mL) for 24 h. Upon cooling to
room temperature, 3 equiv. of NH4PF6 (0.489 g) was added and the solution was stirred for 4 h at
room temperature. Then, solvent was removed on rotavapour and the obtained residue was
dissolved in a minimum amount of dichloromethane. To the filtered dichloromethane solution,
excess of diethyl ether was added to precipitate out a green solid. Yield: 89% (0.272 g). 1H NMR
(400 MHz, CDCl3) δ (ppm) = 9.26 (d, 1H, J = 8.0 Hz), 8.25 (d, 1H, J = 8.0 Hz), 8.20-8.16 (m,
23
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European Journal of Inorganic Chemistry
1H), 7.90-7.86 (m, 1H), 6.02 (d, 1H, J = 8.0 Hz), 5.90 (d, 1H, J = 4.0 Hz), 5.82 (d, 1H, J = 8.0
Hz), 5.76 (d, 1H, J = 8.0 Hz), 3.02-2.97 (sept, 1H, J = 8.0 Hz), 2.95 (s, 3H), 2.31 (s, 3H), 1.39 (d,
6H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3) δ (ppm) = 211.0, 154.4, 151.1, 140.2, 131.9,
31
130.4, 103.7, 99.4, 85.7, 83.4, 83.3, 82.5, 31.3, 30.9, 22.5, 22.1, 18.3. P NMR (161.97 MHz,
CDCl3) δ (ppm) = -144.6. IR (cm-1) = 1615 (υC=O). UV/vis (MeOH, λmax/nm) (εmax/M-1 cm-1) =
270 (4800), 370 (1400), 437 (1100). MS (ESI) m/z calculated: 392.03 [M]+ [C17H21ClNORu],
Found: 392.03 [M]+ [C17H21ClNORu].
Synthesis of [(η6-p-cymene)Ru(κ2-N,O-2-methylpicolinate)Cl]PF6 ([Ru]-3). Complex [Ru]-3
was synthesized by stirring [{(η6-p-cymene)RuCl2}2] (0.306 g, 0.5 mmol) and 2-
methylpicolinate (0.150 mg, 1.1 mmol) in dichloromethane (25 mL) at room temperature for 24
h. Volume was then reduced and 10 mL methanol was added followed by the addition of 3
equiv. of NH4PF6 (0.489 g). The resulting mixture was stirred for 4 h at room temperature.
Volume of solution was again reduced to 5 mL under vacuum and complex was dissolved in
minimum amount of dichloromethane. An excess of NH4PF6 was removed and complex was
precipitated out with excess of diethyl ether as an orange colored solid. Yield: 80% (0.244 g). 1H
NMR (400 MHz, CDCl3) δ (ppm) = 9.21 (d, 1H, J = 8.0 Hz), 8.12-8.09 (m, 2H), 7.92-7.89 (m,
1H), 6.04 (d, 1H, J = 8.0 Hz), 5.89 (d, 1H, J = 4.0 Hz), 5.83 (d, 2H, J = 4.0 Hz), 4.30 (s, 3H),
13
3.00-2.96 (sept, 1H, J = 8.0 Hz), 2.30 (s, 3H), 1.38 (d, 6H, J = 8.0 Hz). C NMR (100 MHz,
CDCl3) δ (ppm) = 202.0, 152.8, 145.1, 139.4, 128.7, 127.1, 102.6, 98.7, 82.7, 82.5, 81.7, 80.7,
31
31.0, 29.6, 22.23, 22.21, 18.6. P NMR (161.97 MHz, CDCl3) δ (ppm) = -144.6. IR (cm-1) =
1599 (υC=O). UV/vis (MeOH, λmax/nm) (εmax/M-1 cm-1) = 250 (5000), 316 (2600), 415 (600). MS
(ESI) m/z calculated: 408.03 [M]+ [C17H21ClNO2Ru], Found: 408.03 [M]+ [C17H21ClNO2Ru].
24
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Synthesis of [(η6-p-cymene)Ru(κ2-N,N-(N-benzyl-pyridylmethyleneamine))Cl]PF6 ([Ru]-4).
Complex [Ru]-4 was synthesized following the analogous procedure as used for complex [Ru]-
2, by stirring [{(η6-p-cymene)RuCl2}2] (0.306 g, 0.5 mmol) and N-benzyl-
pyridylmethyleneamine (0.215 mg, 1.1 mmol) in methanol (25 mL) at room temperature for 24
1
h. Brown solid. Yield: 89% (0.272 g). H NMR (400 MHz, CDCl3) δ (ppm) = 9.32 (d, 1H, J =
8.0 Hz), 8.04 (s, 1H), 7.99-7.95 (m, 1H), 7.82 (d, 1H, J = 8.0 Hz) 7.67-7.63 (m, 1H), 7.47 (s,
5H), 5.84 (d, 1H, J = 4.0 Hz), 5.68-5.64 (m, 2H), 5.60 (d, 1H, J = 4.0 Hz), 2.74-2.67 (sept, 1H, J
= 8.0 Hz), 2.13 (s, 2H), 1.59 (s, 3H), 1.15-1.07 (m, 6H). 13C NMR (100 MHz, CDCl3) δ (ppm) =
166.0, 155.6, 154.3, 139.3, 133.2, 130.1, 129.6, 129.5, 129.0, 128.6, 106.9, 102.1, 86.1, 85.3,
31
85.0, 84.7, 69.5, 31.1, 22.1, 21.8, 18.4. P NMR (161.97 MHz, CDCl3) δ (ppm) = -149.3. IR
(cm-1) = 1598 (υC=N imine). UV/vis (MeOH, λmax/nm) (εmax/M-1 cm-1) = 264 (3600), 330 (2200),
427 (1000). MS (ESI) m/z calculated: 467.08 [M]+ [C23H26ClN2Ru], Found: 467.08 [M]+
[C23H26ClN2Ru].
Synthesis of [(η6-p-cymene)Ru(κ2-N,N-(N-butyl-pyridylmethyleneamine))Cl]PF6 ([Ru]-5).
Ru]-5 was synthesized following the above procedure as used for complex [Ru]-2 by stirring
[{(η6-p-cymene)RuCl2}2] (0.306 g, 0.5 mmol) and N-butyl-pyridylmethyleneamine (0.178 mg,
1.1 mmol) in methanol (25 mL) at room temperature for 24 h. Brown solid. Yield: 85% (0.260
1
g). H NMR (400 MHz, CDCl3) δ (ppm) = 9.26 (d,1H, J = 8.0 Hz), 8.37 (s, 1H), 8.03-7.99 (m,
1H), 7.94 (d, 1H, J = 8.0 Hz), 7.65-7.63 (m, 1H), 5.83 (d, 1H, J = 4.0 Hz), 5.79 (d, 1H, J = 8.0
Hz), 5.70 (d, 1H, J = 4.0 Hz), 5.62 ( d, 1H, J = 4.0 Hz), 4.45-4.31 (m, 2H), 2.76-2.73 (sept, 1H, J
= 8.0 Hz), 2.21 (s, 3H), 1.09-1.96 (m, 2H), 1.44-1.41 (m, 2H), 1.15 (d, 3H, J = 8.0 Hz), 1.10 (d,
3H, J = 8.0 Hz), 0.99-0.96 (m, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm) = 165.8, 155.4, 154.4,
139.4, 128.6, 128.5, 106.9, 102.1, 86.2, 85.4, 85.3, 84.9, 67.0, 31.3, 31.1, 22.0, 21.9, 20.0, 18.5,
25
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31
13.6. P NMR (161.97 MHz, CDCl3) δ (ppm) = -149.4. IR (cm-1) = 1599 (υC=N imine). UV/vis
(MeOH, λmax/nm) (εmax/M-1 cm-1) = 272 (6400), 357 (2400), 415 (1800). MS (ESI) m/z
calculated: 433.09 [M]+ [C20H28ClN2Ru], Found: 433.10 [M]+ [C20H28ClN2Ru].
Synthesis of [(η6-benzene)Ru(κ2-N,O-pyridine-2-carboxylate)Cl] ([Ru]-6). Complex [Ru]-6
was synthesized by following the analogous procedure used for the synthesis of complex [Ru]-1
by refluxing [{(η6-benzene)RuCl2}2] (0.250 g, 0.5 mmol) and pyridine-2-carboxylic acid (0.135,
1
1.1 mmol) in methanol (25 mL) for 12 h. Brown solid. Yield: 80% (0.200 g). H NMR (400
MHz, DMSO-d6) δ (ppm) = 9.38 (d, 1H, J = 4.0 Hz), 8.08 (d, 1H, J = 8.0 Hz), 7.75 (d, 2H, J =
13
8.0 Hz), 5.93 (s, 6H). C NMR (100 MHz, DMSO-d6) δ (ppm) = 170.3, 154.1, 150.3, 139.7,
127.9, 125.3, 83.2. IR (cm-1) = 1655 (υC=O). UV/vis (MeOH, λmax/nm) (εmax/M-1 cm-1) = 250
(2200), 312 (1000), 391 (200). MS (ESI) m/z calculated: 301.97 [M-Cl]+ [C12H10NO2Ru],
Found: 301.97 [M-Cl]+ [C12H10NO2Ru].
Synthesis of [(η6-benzene)Ru(κ2-N,O-2-acetylpyridine)Cl]PF6 ([Ru]-7). Complex [Ru]-7 was
synthesized by following the analogous procedure used for the synthesis of complex [Ru]-2 by
refluxing [{(η6-benzene)RuCl2}2] (0.250 g, 0.5 mmol) and 2-acetylpyridine (124 μL, 1.1 mmol)
in methanol (25 mL) for 24 h. Green solid. Yield: 87% (0.217 g). 1H NMR (400 MHz, Acetone-
d6) δ (ppm) = 8.96 (d, 1H, J = 8.0 Hz), 7.91 (d, 1H, J = 8.0 Hz), 7.69-7.65 (m, 1H), 7.31-7.28 (m,
1H), 5.48 (s, 6H), 2.27 (s, 3H). 13C NMR (100 MHz, Acetone-d6) δ (ppm) = 213.0, 157.2, 152.0,
142.2, 133.2, 132.2, 86.4, 30.4. 31P NMR (161.97 MHz, Acetone-d6) δ (ppm) = -139.9. IR (cm-1)
= 1567 (υC=O). UV/vis (MeOH, λmax/nm) (εmax/M-1 cm-1) = 268 (3000), 380 (600), 435 (400). MS
(ESI) m/z calculated: 335.97 [M]+ [C13H13ClNORu], Found: 335.97 [M]+ [C13H13ClNORu].
26
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Synthesis of [(η6-benzene)Ru(κ2-N,O-2-methylpicolinate)Cl]PF6 ([Ru]-8). Complex [Ru]-8
was synthesized by following the analogous procedure used for the synthesis of complex [Ru]-3
by stirring [{(η6-benzene)RuCl2}2] (0.250 g, 0.5 mmol) and 2-methylpicolinate (0.150 mg, 1.1
mmol) in dichloromethane (25 mL) at room temperature for 24 h. Orange solid. Yield: 83%
1
(0.207 g). H NMR (400 MHz, Acetone-d6) δ (ppm) = 8.70 (d, 1H, J = 4.0 Hz), 7.45-7.41(m,
1H), 7.31 (d, 1H, J = 8.0 Hz), 7.13-7.10 (m, 1H), 5.30 (s, 6H), 3.37 (s, 3H). 13C NMR (100 MHz,
Acetone-d6) δ (ppm) = 206.8, 157.1, 145.7, 142.2, 133.0, 129.0, 85.2, 58.3. 31P NMR (161.97
MHz, Acetone-d6) δ (ppm) = -144.6. IR (cm-1) = 1596 (υC=O). UV/vis (MeOH, λmax/nm) (εmax/M-
1
cm-1) = 260 (5000), 320 (1600), 394 (600). MS (ESI) m/z calculated: 351.96 [M]+
[C13H13ClNO2Ru], Found: 351.97 [M]+ [C13H13ClNO2Ru].
Synthesis of [(η6-benzene)Ru(κ2-N,N-(N-benzyl-pyridylmethyleneamine))Cl]PF6 ([Ru]-9).
Complex [Ru]-9 was synthesized following a modified procedure,15d analogous to that used for
synthesis of complex [Ru]-4 by stirring [{(η6-benzene)RuCl2}2] (0.250 g, 0.5 mmol) and N-
benzyl-pyridylmethyleneamine (0.215 mg, 1.1 mmol) in methanol (25 mL) at room temperature
for 24 h. Brown solid. Yield: 88% (0.220 g). 1H NMR (400 MHz, DMSO-d6) δ (ppm) = 9.62 (d,
1H, J = 8.0 Hz), 8.38 (s, 1H), 8.19 (d, 2H, J = 8.0 Hz), 7.78 (d, 1H, J = 8.0 Hz), 7.49-7.44 (m,
13
5H), 6.10 (s, 6H), 3.31 (s, 2H). C NMR (100 MHz, DMSO-d6) δ (ppm) = 167.2, 156.0, 154.5,
139.7, 134.4, 129.7, 129.1, 128.7, 128.3, 121.9, 87.8, 68.5. 31P NMR (161.97 MHz, DMSO-d6) δ
(ppm) = -148.9. IR (cm-1) = 1601 (υC=N imine). UV/vis (MeOH, λmax/nm) (εmax/M-1 cm-1) = 270
(4600), 350 (1600), 576 (40). MS (ESI) m/z calculated: 411.01 [M]+ [C19H18ClN2Ru], Found:
411.03 [M]+ [C19H18ClN2Ru].
Synthesis of [(η6-benzene)Ru(κ2-N,N-(N-butyl-pyridylmethyleneamine))Cl]PF6 ([Ru]-10).
Complex [Ru]-10 was synthesized by following the analogous procedure used for synthesis of
27
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
complex [Ru]-5 by stirring [{(η6-benzene)RuCl2}2] (0.250 g, 0.5 mmol) and N-butyl-
pyridylmethyleneamine (0.178 mg, 1.1 mmol) in methanol (25 mL) at room temperature for 24
h. Brown solid. Yield: 82% (0.205 g). 1H NMR (400 MHz, Acetone-d6) δ (ppm) = 9.63 (d, 1H, J
= 8.0 Hz), 8.76 (s, 1H), 8.26 (d, 1H, J = 8.0 Hz), 8.21 (d, 1H, J = 8.0 Hz), 7.81 (d, 1H, J = 4.0
Hz), 6.23 (s, 6H), 4.75-4.71 (m, 1H), 4.49-4.43 (m, 1H), 2.03-1.97 (m, 2H), 1.44-1.40 (m, 2H),
0.96-0.92 (m, 3H). 13C NMR (100 MHz, Acetone-d6) δ (ppm) = 168.2, 157.3, 156.4, 141.1,
130.0, 129.3, 88.6, 68.1, 32.8, 21.2, 14.3. 31P NMR (161.97 MHz, Acetone-d6) δ (ppm) = -144.2.
IR (cm-1) = 1634 (υC=N imine). UV/vis (MeOH, λmax/nm) (εmax/M-1 cm-1) = 272 (5200), 348 (2200),
410 (1200). MS (ESI) m/z calculated: 377.03 [M]+ [C16H20ClN2Ru], Found: 377.04 [M]+
[C16H20ClN2Ru].
General procedure for catalytic ortho C−H bond arylation of 2-phenylpyridine with
arylhalides.
All the reactions were carried out under N2 atmosphere. Ortho C-H bond arylation reactions of
2-phenylpyridine were performed in a two necked round bottom flask. Flask was charged with
ruthenium catalyst (5 mol %, 0.025 mmol) and K2CO3 (3 equiv., 1.5 mmol, 0.207 g) with
distilled water (5 mL). Solution was stirred for 15 minutes and then added 2-phenylpyridine (0.5
mmol) and arylhalide (1.25 mmol). The reaction was continued to stir at 100 ºC for specified
duration and then cooled down to room temperature. Further, the reaction mixture was extracted
with ethyl acetate (3×10 mL) and the combine organic fractions was washed with 10 mL of brine
solution and dried over Na2SO4. All the volatiles were removed under vacuum to obtain the crude
product. Conversion and selectivity of the mono and biarylated products were determined by 1H
NMR. Products were purified and isolated from the crude reaction mixture by using column
chromatography on silica gel with ethyl acetate/n-hexane as eluents.
28
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10.1002/ejic.201701446
European Journal of Inorganic Chemistry
Acknowledgements
Authors thank IIT Indore, CSIR, New Delhi (01(2885)/17/EMR-II) and SERB (DST), New
Delhi (SB/FT/CS-028/2014 and EMR/2016/005783) for the financial support. Thanks to SIC,
IIT Indore for the instrumentation facility. C.B., R. K. R. and D. T. thank MHRD, Govt. of India,
CSIR, New Delhi and UGC, New Delhi respectively for their fellowships. C.B. and S.K.S.
designed the experiments and wrote the manuscript, C.B. performed the experiments, R. K. R.
and D. T. helped in the characterization of catalysts and reaction products, and S.M.M.
elucidated molecular structures by single crystal X-ray diffraction.
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