Ruthenium(η6,η1-arene-CH2-NHC) catalysts for direct arylation of 2-phenylpyridine with (hetero)aryl chlorides in water

Article abstract of DOI:10.3390/molecules23030647

A series of new benzimidazolium halides were synthesized in good yields as unsymmetrical N-heterocyclic carbene (NHC) precursors containing the N–CH₂–arene group. The benzimidazolium halides were readily converted into ruthenium(II)–NHC complex

Full text of DOI:10.3390/molecules23030647

molecules
Article
Ruthenium(η6,η1-arene-CH2-NHC) Catalysts for
Direct Arylation of 2-Phenylpyridine with
(Hetero)Aryl Chlorides in Water
Nazan Kalog˘lu 1,2, Ismail Özdemir
˙
Pierre H. Dixneuf 4
*
ID , Nevin Gürbüz 1,2 ID , Hakan Arslan 3 and
1,2,
ID
1
˙
Department of Chemistry, Faculty of Science and Arts, Inönü University, 44280 Malatya, Turkey;
nzntemelli@hotmail.com (N.K.); nevin.gurbuz@inonu.edu.tr (N.G.)
2
3
˙
Catalysis Research and Application Center, Inönü University, 44280 Malatya, Turkey
Faculty of Arts and Science, Department of Chemistry, Mersin University, 33343 Mersin, Turkey;
hakan.arslan@mersin.edu.tr
Institut des Sciences Chimiques de Rennes, Université de Rennes 1, 35042 Rennes, France;
pierre.dixneuf@univ-rennes1.fr
4
*
Correspondence: ismail.ozdemir@inonu.edu.tr; Tel./Fax: +90-422-341-0212
Received: 16 February 2018; Accepted: 7 March 2018; Published: 13 March 2018
Abstract: A series of new benzimidazolium halides were synthesized in good yields as unsymmetrical
N-heterocyclic carbene (NHC) precursors containing the N–CH2–arene group. The benzimidazolium
halides were readily converted into ruthenium(II)–NHC complexes with the general formula
,η
[RuCl2(η6 1–arene–CH2–NHC)]. The structures of all new compounds were characterized by 1H
NMR (Nuclear Magnetic Resonance), 13C NMR, FT-IR (Fourier Transform Infrared) spectroscopy and
elemental analysis techniques. The single crystal structure of one benzimidazole ruthenium complex,
2b, was determined. The complex is best thought of as containing an octahedrally coordinated
Ru center with the arene residue occupying three sites, the remaining sites being occupied by a
(carbene)C–Ru bond and two Ru–Cl bonds. The catalytic activity of [RuCl2(η6 1–arene–CH2–NHC)]
,η
complexes was evaluated in the direct (hetero)arylation of 2-phenylpyridine with (hetero)aryl
chlorides in water as the nontoxic reaction medium. These results show that catalysts 2a and
2b were the best for monoarylation with simple phenyl and tolyl chlorides. For functional aryl
chlorides, 2d, 2e, and 2c appeared to be the most efficient.
Keywords: homogeneous catalysis; ruthenium; N-heterocyclic carbene; 2-phenylpyridine; direct
arylation; single crystal structure
1. Introduction
The prevalence and importance of biaryl compounds in natural products, advanced materials,
and pharmaceuticals have made the preparation of C(sp2)–C(sp2) bond among the core interests of
organic synthesis [
are useful synthetic routes to biaryl compounds [
biaryl cross-coupling reactions, which generally employ aryl halides and organometallics as coupling
partners, have served as the most common methods for constructing biaryl unions (Figure 1a) [ ].
1]. Transition metal-catalyzed cross-coupling reactions of aromatic compounds
2–7
]. By far, traditional transition metal-catalyzed
8,9
Despite the large scope of reactions and opportunities opened by these traditional methodologies,
the starting organometallic reagents are often not commercially available. Moreover, the amount of
byproducts produced, whether in the synthesis of the organometallic reagent or during the coupling
step itself, remains significant. Recently, there has been much interest in transition metal-catalyzed
direct cross-coupling C–C bond formation of aromatic compounds with aryl halides as electrophilic
Molecules 2018, 23, 647; doi:10.3390/molecules23030647
www.mdpi.com/journal/molecules

Molecules 2018, 23, 647
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partners involving the activation of normally unreactive aromatic C–H bond, in terms of synthesis
efficiency and minimization of reaction steps waste (Figure 1b) [10 12]. Therefore, direct arylation
–
reactions through cleavage of C–H bonds represent an environmentally and economically more
attractive strategy.
Figure 1. Coupling reactions: (a) Traditional cross-coupling; and (b) direct arylation.
The direct C–C bond formation reactions generally involve directing-group-assisted activation
of sp2 C–H bonds of ortho aromatic C–H bonds. Many directing groups, such as acetyl, acetamino,
carboxylic acid, oxazolyl, pyridyl, hydroxyl, imino, and cyano moieties, have been used for C–H bond
activation [13–24]. The first example of a functional group assisted ruthenium-catalyzed C–H bond
functionalization was reported by Lewis in 1986 [25]. Further pioneering work by Murai, Kakiuchi
and Chatani on ruthenium-catalyzed hydroarylations showed the ability of ruthenium catalysts to
activate C–H bonds selectively, via assistance of a coordinating functional group [26]. In 2001, the first
ruthenium(II)-catalyzed chelation-assisted direct arylation with aryl bromides was performed by Oi,
Inoue and co-workers [27]. In addition, Prades and Peris also reported the acetate-assisted arylation of
2-phenylpyridine using N-heterocyclic carbene-ruthenium complexes [28].
Recently, different direct arylations catalysed by ruthenium-based complexes have been described
by the groups of Ackermann [29
–
31], Dixneuf [32], Davies [33] and others [34
–38]. Several
ruthenium-catalyzed direct arylations were also reported by our group [39
–41]. Most of these reported
direct arylations were performed either in NMP (N-methyl-2-pyrrolidone) or toluene as solvent.
However, the demand for a more environmentally friendly chemistry opens a new horizon for the
extended application of “green solvents” in direct C–H bond functionalizations as well [42]. In this
connection, several ruthenium-catalyzed direct arylations in water or diethylcarbonate (DEC) as green
solvent using an additive were reported by Dixneuf’s group [43–49].
We now described the synthesis and characterization of new unsymmetrical
benzimidazolium halides (1a
–
e
) and five new ruthenium(II) complexes of the general formula
). All new compounds were
[RuCl2(η 6 1–1-arylmethyl–3–butylbenzimidazol–2–ylidene)] (2a
,
η
–e
characterized by 1H NMR, 13C NMR, FT-IR spectroscopy and elemental analysis techniques. The single
crystal structure of the benzimidazole ruthenium complex 2b was also determined. These new
complexes with KOAc partner were evaluated as catalyst precursors for the direct mono orthoarylation
of 2-phenylpyridine with (hetero)aryl chlorides in water, without the need of surfactant.
2. Results and Discussion
2.1. Preparation of Benzimidazolium Halides
Benzimidazolium halides 1a, 1b, 1d and 1e were synthesized by reacting N-(alkyl)benzimidazole
with alkyl halide in dimethylformamide (DMF) at 80 ◦C for 24 h. The benzimidazolium chloride 1c
was obtained as we previously described [40]. These products were isolated as crystalline solids in
high yields (78–87%). The benzimidazolium halides 1a–e are air- and moisture-stable both in the
solid state and in solution and are soluble in chlorinated solvents, ethyl alcohol and water (Scheme 1).
The benzimidazolium halides were characterized using 1H NMR, 13C NMR, and FT-IR spectroscopy
and gave satisfactory elemental analysis. The FT-IR data clearly indicated that the benzimidazolium
halides 1a–e
exhibit a characteristic ν(NCN) band typically between 1553–1560 cm−1. In the 13C NMR

Molecules 2018, 23, 647
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spectra of compounds 1a
–
e
, the characteristic peak of the imino carbon (NCHN) resonance was
detected in the area δ , 1b, 1d and 1e further
143.2–143.6 ppm. The 1H NMR spectra of compounds 1a
supported the assigned structures. The resonances for C(2) –H were observed as sharp singlets at
δ
10.53–11.53 ppm and consistent with NMR values of other benzimidazolium halides [50].
Scheme 1. Synthesis of benzimidazolium halides, 1a–e.
2.2. Preparation of Ruthenium(II)-NHC Complexes Containing the η6,η1–NHC Mixed Chelating Ligand
The carbene ligands formed by deprotonation of benzimidazolium salts 1a
were reacted with [RuCl2(p–cymene)]2 in toluene at 110 ◦C for 5 h to give good yield of
[RuCl2(η6 1–1-arylmethyl–3–butylbenzimidazol-2-ylidene)] (Scheme 2). Selective crystallization
by solvent diffusion technique (CH2Cl2/Hexane) allowed the formation of suitable orange-brown
crystalline solids in yields of 70 82%. The air- and moisture-stable complexes 2a are soluble in
–e using Cs2CO3
,η
−
–e
solvents such as dichloromethane, chloroform, toluene, and tetrahydrofuran. The ruthenium(II)–NHC
1
complexes 2a
–
e
were characterized using H NMR, 13C NMR, and FT-IR spectroscopy and gave
satisfactory elemental analysis. The FT-IR data clearly indicated that the exhibit a characteristic ν(NCN)
band typically within 1400–1407 cm−1. NMR analysis confirmed the loss of the p-cymene ligand and
the coordination of the (arene-CH2-NHC)arene. 13C NMR chemical shifts provide a useful diagnostic
tool for this type of metal carbene complex. The chemical shifts for the carbene carbon atom are located
in δ 181.3–185.2 ppm range and are similar to those found in other ruthenium(II)–NHC complexes [51].
The analytical data are in good agreement with the compositions proposed for all the compounds we
prepared, and are summarized in Table 1.
Table 1. Physical and spectroscopic properties of new compounds 1 and 2.
M.p.
v(CN)
Isolated
Yield (%)
1H NMR
H(2) (ppm)
13C NMR
C(2) (ppm)
Compound
Formula
(Metlting
(Frequency)
◦
−1
Point) ( C)
(cm
)
1a
1b
1d
1e
2a
2b
2c
C19H23ClN2
C22H29ClN2
C22H29BrN2
C26H29ClN2O
C19H22Cl2N2Ru
C22H28Cl2N2Ru
C23H30Cl2N2Ru
C22H28Cl2N2Ru
C26H28Cl2N2ORu
78
83
80
87
87
80
82
71
76
198–199
176–177
184–185
191–192
231–232
311–312
319–320
298–299
310–311
1558
11.49
10.86
11.45
11.53
-
-
-
-
-
143.2
142.9
142.6
143.6
181.3
184.9
186.0
186.1
185.2
1553
1560
1557
1401
1400
1406
1403
1407
2d
2e

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Rn
Rn
N
Cs2CO3
N
Cl
Cl
+) X-
N
[RuCl2(p-cymene))2
+
)
Ru
N
Toulene, reflux, 5 h
R
R
1a-e
2a-e
N
Cl
Cl
N
Cl
Cl
N
Cl
Ru
N
Cl
Cl
N
Cl
Cl
Ru
Ru
)
)
Ru
)
Ru
)
)
N
N
N
N
Cl
N
OMe
2a
2d
2b
2e
2c
Scheme 2. Synthesis of [Ru-Cl2(η6,η1-arene-CH2-NHC)] complexes, 2a–e.
2.3. Single Crystal X-ray Diffraction and Structure Analysis of Complex 2b
The ligand in compound 2b has both benzimidazolylidene and arene rings, which are connected
chelating via a CH2 bridge (Figure 2). Further details concerning data collection and refinements
are given in the Supplementary Materials. This configuration leads to a system with very little
apparent strain on coordinating the ruthenium atom. The complex is best described as containing
an octahedrally coordinated Ru center with the arene residue occupying three sites, the remaining
sites being occupied by an Ru–C(carbene) bond, derived from the benzimidazole ring, and two Ru–Cl
bonds. The small steric demand of the benzimidazolylidene ligand is reflected in the C(1)–Ru(1)–C(13),
◦
C(1)–Ru(1)–Cl(1) and C(1)–Ru(1)–Cl(2) angles of 78.59(12), 92.94(9) and 89.64(8) , respectively, a result
that reflects the situation we found in related Ru complexes (Table 2) [52–55]. The atoms comprising the
tetramethylbenzyl ring are coplanar, the mean deviation from their least squares plane being 0.017(2) Å.
The five- and six-membered rings (N1/C1/N2/C7/C2) and (C2–C7) of the benzimidazolylidene
group are almost co-planar with maximum deviations of 0.010(2) Å for N1 and 0.010(2) Å for
C5, respectively. The dihedral angle between benzimidazolylidine and tetramethylbenzyl rings
is 84.49 (16)◦. The Ru-carbene distance, Ru(1)–C(1), of 2.040(3) Å, matches the literature data [52–54]
.
The Ru(1)–Cl(1) and Ru(1)–Cl(2) single bond lengths are 2.4267(9) and 2.4222(8) Å. The values of the
geometrical parameters of compound 2b agree with those reported for similar compounds [52–54].
Figure 2. The molecular structure of compound 2b. Displacement ellipsoids are drawn at the 50%
probability level.

Molecules 2018, 23, 647
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◦
◦
Table 2. Selected bond lengths (Å), angles ( ) and torsion angles ( ) for compound 2b.
Bond Lenght
Bond Angles
Torsion Angle
C(1)–N(2)
C(1)–N(1)
C(1)–Ru(1)
C(2)–N(1)
C(2)–C(7)
C(7)–N(2)
1.360(4)
1.361(4)
2.040(3)
1.386(4)
1.394(5)
1.393(4)
1.466(4)
1.466(4)
1.517(4)
2.109(3)
2.190(3)
1.426(5)
1.513(4)
2.241(3)
2.274(3)
2.267(3)
2.196(3)
2.4267(9)
2.4222(8)
N(2)–C(1)–N(1)
N(2)–C(1)–Ru(1)
N(1)–C(1)–Ru(1)
N(1)–C(12)–C(13)
C(14)–C(13)–Ru(1)
C(18)–C(13)–Ru(1)
C(12)–C(13)–Ru(1)
C(1)–N(1)–C(2)
C(1)–N(1)–C(12)
C(2)–N(1)–C(12)
C(1)–N(2)–C(7)
C(1)–N(2)–C(8)
C(7)–N(2)–C(8)
——
105.2(3)
138.3(2)
116.5(2)
106.3(2)
73.54(17)
73.77(18)
116.3(2)
111.6(3)
121.5(3)
126.7(3)
111.1(3)
124.5(3)
124.3(3)
N(2)–C(1)–Ru(1)–Cl(2) −53.0(3)
N(1)–C(1)–Ru(1)–Cl(2) 129.7(2)
N(2)–C(1)–Ru(1)–Cl(1)
N(1)–C(1)–Ru(1)–Cl(1) −141.1(2)
N(2)–C(1)–N(1)–C(12) 176.2(3)
Ru(1)–C(1)–N(1)–C(2) 177.82(19)
36.1(3)
C(8)–N(2)
C(12)–N(1)
C(12)–C(13)
C(13)–Ru(1)
C(14)–Ru(1)
C(15)–C(16)
C(15)–C(20)
C(15)–Ru(1)
C(16)–Ru(1)
C(17)–Ru(1)
C(18)–Ru(1)
Cl(1)–Ru(1)
Cl(2)–Ru(1)
——
——
——
——
——
2.4. Optimization Conditions of Direct Arylation of 2-Phenylpyridine with (hetero)Aryl Chlorides with
Catalysts 2
The catalytic activity of the [RuCl2(η6
,η
1–1–arylmethyl–3-butylbenzimidazole–2–ylidene)]
complexes 2a
–
e
for the activation of phenylpyridine towards (hetero)arylation of sp2 C–H bonds
was investigated by the reaction of (hetero)aryl chloride and 2-phenylpyridine as a standard reaction.
The reaction was carried out using 2-phenylpyridine, (hetero)aryl chloride and Cs2CO3 in the presence
of complex 2c as the catalyst in water with Cs2CO3 as a base and a carboxylate RCO2K as additive.
The results of varying the reaction parameters, including base, additive and reaction time are given in
Table 3.
It has been shown by Dixneuf’s group [43–49] that carboxylates were efficient partners for
ruthenium(II) C–H bond activation at room temperature, especially in water [44] The mechanism of
the catalytic cycle showed that a carboxylate was crucial to deprotonate the C–H bond of aromatic
systems [48
,
49]. Thus, pivalate and acetate additives were evaluated. When KOPiv was used as
◦
additive, the reaction gave low conversion of only 9% with Cs2CO3 after 5 h at 100 C, and 100%
(Table 3, entry 1). However, when K2CO3 and Na2CO3 were used as bases under similar conditions, no
reaction took place (Table 3, entries 2 and 3). ◦In the presence of KOAc as additive, the conversion was
increased to 15% with Cs2CO3 after 5 h at 100 C, to give mono-alkylated product, A, was also observed
(Table 3, entry 4). When the reaction time was increased from 5 h to 10 h, the conversion was improved
to 47% and 100% yield (Table 3, entry 5). Similarly, when the reaction time was increased from 10 to
20 h, the conversion was improved to 95% and 100% yield of product A was also observed (Table 2,
entry 6). However, when the reaction time was increased from 20 to 24 h, no significant difference
was observed in the conversion (Table 3, entry 7). These conditions (Table 3, entry 6) were selected
for mono ortho-heteroarylation of phenylpyridine. As a result, the scope of the direct arylation of
2-phenylpyridine was investigated with 2-chlorothiophene applying our best experimental conditions
(Table 3, entry 6). When 4-chlorotoluene was used as model coupling partner, the reaction gave full
conversion (100% yield of mono-alkylated product A, was observed) with Cs2CO3 as base at different
durations (5–20 h) at 100 ◦C (Table 3, entries 8–10). Eventually, the scope of the direct arylation of
2-phenylpyridine was investigated with 4-chlorotoluene applying our best experimental conditions
(Table 3, entry 10). This shows that ortho-arylation is much easier than heteroarylation.

Molecules 2018, 23, 647
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Table 3. Arylation of 2-phenylpyridine with (hetero)aryl chlorides: A search for optimal catalytic conditions a.
i) Catalyst 2c (2.5 mol%)
ii) RCO2K additive (5 mol%)
Ar(Het)
(Het)ArCl
Base, H2O, 100 oC
N
N
N
(Het)Ar
(Het)Ar
B
A
Yield (%)
Entry
(Het)ArCl
Time (h)
Conversion (%)
Base
Additive
A
B
1
2
3
4
5
6
7
8
9
2-Chlorothiophene
2-Chlorothiophene
2-Chlorothiophene
2-Chlorothiophene
2-Chlorothiophene
2-Chlorothiophene
2-Chlorothiophene
4-Chlorotoluene
4-Chlorotoluene
4-Chlorotoluene
KOPiv
KOPiv
KOPiv
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
Cs2CO3
K2CO3
5
5
5
9
-
-
15
47
95
97
100
100
100
100
-
-
100
100
100
100
100
100
100
-
-
-
-
-
-
-
-
-
-
Na2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
5
10
20
24
20
10
5
10
a Reaction conditions: Additive (0.05 mmol), ruthenium(II)-NHC complex, 2c (0.025 mmol), H2O as solvent (2 mL), r.t.
for 1 h, then 2-phenylpyridine (0.5 mmol), (hetero)aryl chloride (1.25 mmol), base (1.5 mmol). The conversions were
based on the 2-phenylpyridine by GC (Gas chromatography) and GC-MS (Gas chromatography-Mass Spectrometry).
2.5. Direct Arylation of 2-Phenylpyridine with (Hetero)Aryl Chlorides
Based on this preliminary study, the scope of the direct arylation of 2-phenylpyridine was
investigated with various (hetero)aryl chlorides applying our best experimental conditions to produce
◦
new potential bidentate ligands. With KOAc as additive, Cs2CO3 as base in water at 100 C for different
durations, ruthenium complexes 2a–e were examined in the direct arylations of 2-phenylpyridine
with six aryl chloride and thiophenyl chloride. In all of the reactions between different (hetero)aryl
chlorides and 2-phenylpyridine, mono ortho-arylated product (A) was formed selectively. In addition,
high conversion of ortho-arylated products was observed, and the selectivity was in high ratio
towards to A. Although the other aryl chlorides showed good conversion in 5 h, chlorobenzene
showed full conversion after 1 h. For example, when 2a and 2b complexes were used as catalyst,
ortho-arylated product observed full conversion (selectivity of A 100%), (Table 4, entries 1 and 2).
When the reaction of 2-phenylpyridine with 4-chlorotoluene was performed by compounds 2a, 2b
and 2c, ortho-arylated products (A and B) obtained full conversion (selectivity of A 100%), (Table 4,
entries 6–8). When the reaction of 2-phenylpyridine with 4-chlorobenzaldehyde was performed by
compounds 2a–e, ortho-arylated products (A and B) obtained full conversion (Table 4, entries 11–15).
When compound 2e was used as catalyst, high conversion (>80%) was observed (selectivity of A >85%)
(Table 4, entries 20 and 30). Heteroaryl derivative such as 2-chlorothiophene was also applicable to this
direct arylation system (Table 4, entries 31–35). When compound 2c was used as catalyst, ortho-arylated
product was observed in conversion of 95% (selectivity of A 100%), (Table 4, entry 33). These results
show that catalysts 2a–2b were the best for monoarylation with simple phenyl and tolyl chlorides.
For functional aryl chlorides ClC6H4Y, 2d (Y = CHO), 2e (Y = COMe and Y = CN), 2c (thiophenyl
chloride) appeared the most efficient.

Molecules 2018, 23, 647
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Table 4.
Direct arylation of 2-phenylpyridine with (hetero)aryl chlorides catalyzed by
ruthenium(II)-NHC complexes 2a–e a.
Yield (%)
Entry
(Het)ArCl
Time (h)
Conversion (%)
Ru-NHC
A
B
1
2
3
4
5
2a
2b
2c
2d
2e
1
1
1
1
1
100
100
80
90
85
100
100
80
90
87
-
-
20
10
13
6
7
8
9
10
2a
2b
2c
2d
2e
5
5
5
5
5
100
100
100
100
90
100
100
100
88
-
-
-
12
5
95
11
12
13
14
15
2a
2b
2c
2d
2e
5
5
5
5
5
100
100
100
100
100
70
80
72
92
86
30
20
28
8
14
16
17
18
19
20
2a
2b
2c
2d
2e
5
5
5
5
5
76
72
71
70
80
76
72
71
70
85
24
28
29
30
15
21
22
23
24
25
2a
2b
2c
2d
2e
5
5
5
5
5
72
77
70
79
74
72
77
70
79
75
28
23
30
21
25
26
27
28
29
30
2a
2b
2c
2d
2e
5
5
5
5
5
76
71
88
85
89
76
71
88
85
90
24
29
22
15
10
31
32
33
34
35
2a
2b
2c
2d
2e
20
20
20
20
20
90
88
95
89
83
90
95
100
97
10
5
-
3
15
85
a
Reaction conditions: KOAc (0.05 mmol), ruthenium(II)-NHC complexes 2a–e (0.025 mmol), H2O as solvent (2 mL),
r.t. for 1 h, then 2-phenylpyridine (0.5 mmol), (Het)ArCl (1.25 mmol), Cs2CO3 (1.5 mmol).

Molecules 2018, 23, 647
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3. Materials and Methods
3.1. General
All reactions for the preparation benzimidazolium halides (1a–e) and (arene)ruthenium(II)-(NHC)(Cl)2
complexes (2a–e) were carried out under argon in flame-dried glassware using standard Schlenk
techniques. Chemicals and solvents were purchased from Sigma-Aldrich (Istanbul, Turkey) and
Merck (Istanbul, Turkey). The solvents used were purified by distillation over the drying agents
indicated and were transferred under Argon, Et2O (Na/K alloy), CH2Cl2 (P4O10), hexane, and
˙
toluene (Na). Microanalyses were performed by Inönü University Scientific and Technological Research
Center (Malatya, Turkey). Melting points were determined in glass capillaries under air with an
Electrothermal-9200 melting point apparatus (Cole-Parmer, Istanbul, Turkey). FT-IR spectra were
recorded on ATR (Attenuated Total Reflection) unit in the range of 400–4000 cm−1 with Perkin Elmer
Spectrum 100 Spectrophotometer (Istanbul, Turkey). Routine 1H NMR and 13C NMR spectra were
recorded using a Bruker Avance AMX spectrometer (Ankara, Turkey) operating at 300 and 400 MHz
for 1H NMR, and at 75 and 100 MHz for 13C NMR in CDCl3 with tetramethylsilane as an internal
reference. Chemical shifts (
1H NMR spectra are referenced to CDCl3 (
relative to deuteriated solvent ( = 77.16 ppm for CDCl3). All catalytic reactions were monitored on
δ
) and coupling constants (J) are reported in ppm and in Hz, respectively.
δ
= 7.26 ppm for CDCl3), 13C chemical shifts are reported
δ
an Agilent 6890N Gas Chromatography (Ankara, Turkey) and Schimadzu 2010 Plus GC-MS system
(Ankara, Turkey) by GC-FID (Flame Ionization Dedector) with a HP-5 column of 30 m length, 0.32 mm
diameter and 0.25
(70–230 mesh).
µm film thickness. Column chromatography was performed using silica gel 60
3.2. General Procedure for the Preparation of Benzimidazolium Halides 1a–e
To a solution of 1-(n-butyl)benzimidazole (5.0 mmol) in DMF (5 mL) was added benzyl halide
(5.0 mmol) and the resulting mixture was stirred at 80 ◦C for 5 h. After completion of the reaction,
the solvent was removed by vacuum and diethylether (15 mL) was added to obtain a white crystalline
solid, which was filtered off. The solid was washed with diethyl ether (3
×
10 mL) and dried under
vacuum. The crude product was recrystallized from EtOH/Et2O mixture (1:2, v/v) and dried under
vacuum. The 1H NMR and 13C NMR spectrums of new benzimidazolium halides (1a
, 1b, 1d and 1e)
are available supporting information (Figures S1–S4).
1-(3-Methylbenzyl)-3-(n-Butyl)Benzimidazolium Chloride, 1a: (1.228 g, yield 78%) 1H NMR (400 MHz,
CDCl3, 25 ◦C):
δ
= 0.90 (t, 3J = 7.4 Hz, 3H, CH2CH2CH2CH3); 1.38 (hext, 3J = 7.5 Hz, 2H,
3
CH2CH2CH2CH3); 1.97 (pent, J = 7.5 Hz, 2H, CH2CH2CH2CH3); 2.22 (s, 3H, CH2C6H4(CH3)-3);
4.57 (t, 3J = 7.4 Hz, 2H, CH2CH2CH2CH3); 5.79 (s, 2H, CH2C6H4(CH3)-3); 7.04 (d, 3J = 7.5 Hz, 1H, arom.
CH, NC6H4N and CH2C6H4(CH3)-3); 7.13–7.21 (m, 3H, arom. CH, NC6H4N and CH2C6H4(CH3)-3);
7.47–7.57 (m, 3H, arom. CH, NC6H4N and CH2C6H4(CH3)-3); 7.67 (d, J = 8.2 Hz, 1H, arom. CH,
NC6H4N and CH2C6H4(CH3)-3); 11.49 (s, 1H, NCHN) ppm. 13C NMR (100 MHz, CDCl3, 25 C):
3
◦
δ = 13.5 (CH2CH2CH2CH3); 19.8 (CH2CH2CH2CH3); 21.3 (CH2C6H4(CH3)-3); 31.3 (CH2CH2CH2CH3);
47.5 (CH2CH2CH2CH3); 51.3 (CH2C6H4(CH3)-3); 113.1, 113.9, 125.3, 127.0, 127.1, 128.8, 129.1, 129.8,
131.2, 131.5, 132.9, 139.1 (arom. C, NC6H4N and CH2C6H4(CH3)-3); 143.2 (NCHN) ppm (Figure S1).
Elemental analysis calcd (%) for C19H23ClN2 (Molar Mass (Mr) = 314.90): C 72.48, H 7.36, N 8.90;
found (%): C 72.54, H 7.38, N 8.93.
1
1-(2,3,5,6-Tetramethylbenzyl)-3-(n-Butyl)Benzimidazolium Chloride, 1b: (1.481 g, yield 83%) H NMR
(300 MHz, CDCl3, 25 ◦C): = 0.87 (t, 3J = 7.0 Hz, 3H, CH2CH2CH2CH3); 1.33 (hext, 3J = 6.9 Hz, 2H,
δ
CH2CH2CH2CH3); 1.91 (pent, 3J = 6.5 Hz, 2H, CH2CH2CH2CH3); 2.16 (s, 12H, CH2C6H(CH3)4-2,3,5,6);
4.61 (t, 3J = 6.3 Hz, 2H, CH2CH2CH2CH3); 5.85 (s, 2H, CH2C6H(CH3)4-2,3,5,6); 6.98 (s, 1H, arom. CH,
3
CH2C6H(CH3)4-2,3,5,6); 7.22 (d, J = 8.2 Hz, 1H, arom. CH of benzimidazole, NC6H4N); 7.40 (t,
3J = 7.7 Hz, 1H, arom. CH of benzimidazole, NC6H4N); 7.53 (t, 3J = 7.4 Hz, 1H, arom. CH

Molecules 2018, 23, 647
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3
of benzimidazole, NC6H4N); 7.69 (d, J = 8.0 Hz, 1H, arom. CH of benzimidazole, NC6H4N);
10.86 (s, 1H, NCHN) ppm. 13C NMR (75 MHz, CDCl3, 25 ◦C):
= 13.5 (CH2CH2CH2CH3);
δ
16.0 (CH2C6H(CH3)4-2,3,5,6); 19.7 (CH2CH2CH2CH3); 20.5 (CH2C6H(CH3)4-2,3,5,6); 31.3
(CH2CH2CH2CH3); 47.5 (CH2CH2CH2CH3); 47.8 (CH2C6H(CH3)4-2,3,5,6); 113.1, 113.8, 127.0, 127.2,
127.9, 131.4, 131.5, 133.4, 134.0, 134.9 (arom. C, NC6H4N and CH2C6H(CH3)4-2,3,5,6); 142.9 (NCHN)
ppm (Figure S2). Elemental analysis calcd (%) for C22H29ClN2 (Mr = 356.90): C 74.03, H 8.19, N 7.85;
found (%): C 74.00, H 8.16, N 7.81.
1-(4-tert-Butylbenzyl)-3-(n-Butyl)Benzimidazolium Bromide, 1d: (1.605 g, yield 80%) 1H NMR (400 MHz,
◦
3
CDCl3, 25 C):
δ = 0.99 (t, J = 7.4 Hz, 3H, CH2CH2CH2CH3); 1.26 (s, 9H, CH2C6H4(C(CH3)3)-4);
1.48 (hext, 3J = 7.7 Hz, 2H, CH2CH2CH2CH3); 2.07 (pent, 3J = 7.6 Hz, 2H, CH2CH2CH2CH3);
4.64 (t, 3J = 7.4 Hz, 2H, CH2CH2CH2CH3); 5.88 (s, 2H, CH2C6H4(C(CH3)3)-4); 7.37–7.39 (m,
2H, arom. CH, NC6H4N and CH2C6H4(C(CH3)3)-4); 7.47–7.49 (m, 2H, arom. CH, NC6H4N
and CH2C6H4(C(CH3)3)-4); 7.57–7.64 (m, 2H, arom. CH, NC6H4N and CH2C6H4(C(CH3)3)-4);
7.68–7.74 (m, 2H, arom. CH, NC6H4N and CH2C6H4(C(CH3)3)-4); 11.45 (s, 1H, NCHN) ppm.
◦
13C NMR (100 MHz, CDCl3, 25 C):
δ = 13.5 (CH2CH2CH2CH3); 19.9 (CH2CH2CH2CH3); 31.2
(CH2C6H4(C(CH3)3)-4); 31.3 (CH2CH2CH2CH3); 34.7 (CH2C6H4(C(CH3)3)-4); 47.6 (CH2CH2CH2CH3);
51.1 (CH2C6H4(C(CH3)3)-4); 113.1, 113.9, 126.3, 127.1, 127.2, 128.2, 129.8, 131.3, 131.5, 152.4 (arom. C,
NC6H4N and CH2C6H4(C(CH3)3)-4); 142.6 (NCHN) ppm (Figure S3). Elemental analysis calcd (%) for
C22H29BrN2 (Mr = 401.40): C 65.83, H 7.28, N 6.98; found (%): C 65.75, H 7.29, N 6.95.
1-(2,3,5,6-Tetramethylbenzyl)-3-(3-Methoxybenzyl)Benzimidazolium Chloride, 1e: (1.831 g, yield 87%) 1H
◦
NMR (300 MHz, CDCl3, 25 C):
δ = 2.25 and 2.26 (s, 12H, CH2C6H(CH3)4-2,3,5,6); 3.76 (s, 3H,
CH2C6H4(OCH3)-4); 5.88 (s, 2H, CH2C6H4(OCH3)-4); 5.89 (s, 2H, CH2C6H(CH3)4-2,3,5,6); 6.86
(d, 3J = 8.6 Hz, 2H, arom. CH, NC6H4N and CH2C6H4(OCH3)-4); 7.08 (s, 1H, arom. CH,
3
CH2C6H(CH3)4-2,3,5,6); 7.20 (d, J = 8.1 Hz, 1H, arom. CH, NC6H4N and CH2C6H4(OCH3)-4);
7.38–7.51 (m, 4H, arom. CH, NC6H4N and CH2C6H4(OCH3)-4); 7.61 (d, 3J = 8.1 Hz, 1H, arom. CH,
◦
NC6H4N and CH2C6H4(OCH3)-4); 11.53 (s, 1H, NCHN) ppm. 13C NMR (75 MHz, CDCl3, 25 C):
δ
= 16.2 and 20.6 (CH2C6H(CH3)4-2,3,5,6); 47.9 (CH2C6H(CH3)4-2,3,5,6); 51.1 (CH2C6H4(OCH3)-4);
55.3 (CH2C6H4(OCH3)-4); 113.6, 113.8, 114.6, 114.7, 125.1, 126.9, 127.0, 127.7, 129.9, 131.6, 133.6, 134.1,
135.1, 160.1 (arom. C, NC6H4N, CH2C6H(CH3)4-2,3,5,6 and CH2C6H4(OCH3)-4); 143.6 (NCHN) ppm
(Figure S4). Elemental analysis calcd (%) for C26H29ClN2O (Mr = 421.00): C 74.18, H 6.94, N 6.65;
found (%): C 74.24, H 6.96, N 6.67.
3.3. General Procedure for the Preparation of Ruthenium(II)NHC Complexes 2a–e
A suspension of the benzimidazolium halide (1.10 mmol), Cs2CO3 (1.10 mmol) and
[RuCl2(p-cymene)]2 (0.50 mmol) in degassed toluene (20 mL) was heated under reflux for 5 h.
The reaction mixture was then filtered while hot, and the volume was reduced to about 10 mL before the
addition of n-hexane (15 mL). The precipitate formed was crystallized from CH2Cl2/hexane mixture
(1:3, v/v) to give red-brown crystals. The 1H NMR and 13C NMR spectrums of new ruthenium(II)-NHC
complexes (2a–e) are available supporting information (Figures S5–S9).
Dichloro-[1-(3-methylbenzyl)-3-(n-butyl)Benzimidazol-2-ylidene]ruthenium(II), 2a: (0.391 g, yield 87%) 1H
NMR (300 MHz, CDCl3, 25 ◦C): = 0.95 (t, 3J = 7.4 Hz, 3H, CH2CH2CH2CH3); 1.45 (hext, 3J = 7.6 Hz,
δ
2H, CH2CH2CH2CH3); 1.87 (pent, 3J = 7.8 Hz, 2H, CH2CH2CH2CH3); 2.23 (s, 3H, CH2C6H4(CH3)-3);
4.39–4.51 (m, 2H, CH2CH2CH2CH3); 4.89 (dd, J = 66.5, 11.6 Hz, 2H, CH2C6H4(CH3)-3); 5.07 (s, 1H,
arom. CH, CH2C6H4(CH3)-3); 5.40 (d, 3J = 5.6 Hz, 1H, arom. CH, CH2C6H4(CH3)-3); 5.79 (d, 3J = 6.0 Hz,
1H, arom. CH, CH2C6H4(CH3)-3); 5.93 (t, 3J = 5.8 Hz, 1H, arom. CH, CH2C6H4(CH3)-3); 7.32–7.37 (m,
3H, arom. CH of benzimidazole, NC6H4N); 7.42–7.46 (m, 1H, arom. CH of benzimidazole, NC6H4N)
ppm. 13C NMR (75 MHz, CDCl3, 25 ◦C):
δ = 13.9 (CH2CH2CH2CH3); 19.0 (CH2CH2CH2CH3); 20.0
(CH2C6H4(CH3)-3); 32.3 (CH2CH2CH2CH3); 47.8 (CH2CH2CH2CH3); 50.8 (CH2C6H4(CH3)-3); 87.4,
99.8, 100.6, 109.7, 111.9, 114.4, 123.4, 124.0, 132.8, 134.7 (arom. C, NC6H4N and CH2C6H4(CH3)-3);

Molecules 2018, 23, 647
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181.3 (Ru-Ccarbene) ppm (Figure S5). Elemental analysis calcd (%) for C19H22Cl2N2Ru (Mr = 450.40):
C 50.67, H 4.92, N 6.22; found (%): C 50.74, H 4.95, N 6.26.
Dichloro-[1-(2,3,5,6-tetramethylbenzyl)-3-(n-butyl)benzimidazol-2-ylidene]ruthenium(II), 2b: (0.393 g, yield
80%) 1H NMR (300 MHz, CDCl3, 25 ◦C):
δ
= 0.94 (t, 3J = 7.4 Hz, 3H, CH2CH2CH2CH3); 1.44 (hext,
3J = 7.5 Hz, 2H, CH2CH2CH2CH3); 1.85 (pent, 3J = 7.5 Hz, 2H, CH2CH2CH2CH3); 1.99 and 2.13 (s, 12H,
CH2C6H(CH3)4-2,3,5,6); 4.42–4.48 (m, 2H, CH2CH2CH2CH3); 5.06 (s, 2H, CH2C6H(CH3)4-2,3,5,6); 5.54
(s, 1H, arom. CH, CH2C6H(CH3)4-2,3,5,6); 7.32–7.38 (m, 2H, arom. CH of benzimidazole, NC6H4N);
7.41–7.44 (m, 2H, arom. CH of benzimidazole, NC6H4N) ppm. 13C NMR (75 MHz, CDCl3, 25 ◦C):
δ
= 13.8 (CH2CH2CH2CH3); 13.9 and 18.3 (CH2C6H(CH3)4-2,3,5,6); 20.0 (CH2CH2CH2CH3); 32.3
(CH2CH2CH2CH3); 45.9 (CH2C6H(CH3)4-2,3,5,6); 47.7 (CH2CH2CH2CH3); 84.5, 90.7, 97.5, 109.6, 110.2,
111.7, 123.1, 123.5, 133.0, 135.0 (arom. C, NC6H4N and CH2C6H(CH3)4-2,3,5,6); 184.9 (Ru-Ccarbene) ppm
(Figure S6). Elemental analysis calcd (%) for C22H28Cl2N2Ru (Mr = 492.40): C 53.66, H 5.73, N 5.69;
found (%): C 53.64, H 5.72, N 5.68.
Dichloro-[1-(2,3,4,5,6-Pentamethylbenzyl)-3-(n-Butyl)Benzimidazol-2-Ylidene]Ruthenium(II), 2c: (0.415 g,
1
◦
3
yield 82%) H NMR (300 MHz, CDCl3, 25 C):
δ = 0.94 (t, J = 7.4 Hz, 3H, CH2CH2CH2CH3);
1.44 (hext, 3J = 7.5 Hz, 2H, CH2CH2CH2CH3); 1.84 (pent, 3J = 7.5 Hz, 2H, CH2CH2CH2CH3);
2.03, 2.09 and 2.21 (s, 15H, CH2C6(CH3)5-2,3,4,5,6); 4.42–4.47 (m, 2H, CH2CH2CH2CH3); 5.05 (s,
2H, CH2C6(CH3)5-2,3,4,5,6); 7.29–7.38 (m, 2H, arom. CH of benzimidazole, NC6H4N); 7.39–7.42
(m, 2H, arom. CH of benzimidazole, NC6H4N) ppm. 13C NMR (75 MHz, CDCl3, 25 ◦C):
δ
= 13.9 (CH2CH2CH2CH3); 14.9, 15.0 and 15.7 (CH2C6(CH3)5-2,3,4,5,6); 20.0 (CH2CH2CH2CH3);
32.3 (CH2CH2CH2CH3); 46.4 (CH2C6(CH3)5-2,3,4,5,6); 47.6 (CH2CH2CH2CH3); 86.0, 94.5, 97.9, 107.9,
109.5, 111.5, 123.0, 123.4, 133.2, 135.0 (arom. C, NC6H4N and CH2C6(CH3)5-2,3,4,5,6); 186.0 (Ru-Ccarbene
)
ppm (Figure S7). Elemental analysis calcd (%) for C23H30Cl2N2Ru (Mr = 506.50): C 54.54, H 5.97,
N 5.53; found (%): C 54.57, H 5.98, N 5.54.
Dichloro-[1-(4-tert-butylbenzyl)-3-(n-butyl)benzimidazol-2-ylidene]ruthenium(II), 2d: (0.349 g, yield 71%)
1H NMR (300 MHz, CDCl3, 25 ◦C):
δ
= 0.97 (t, 3J = 7.1 Hz, 3H, CH2CH2CH2CH3); 1.26
(s, 9H, CH2C6H4(C(CH3)3)-4); 1.46 (hext, 3J = 6.4 Hz, 2H, CH2CH2CH2CH3); 1.93–1.95 (m,
2H, CH2CH2CH2CH3); 4.65 (m, 2H, CH2CH2CH2CH3); 5.40 (dd, J = 52.0, 14.7 Hz, 2H,
CH2C6H4(C(CH3)3)-4); 5.44 (s, 1H, arom. CH, CH2C6H4(C(CH3)3)-4); 5.71–5.84 (m, 3H, arom.
CH, CH2C6H4(C(CH3)3)-4); 7.32–7.58 (m, 4H, arom. CH of benzimidazole, NC6H4N) ppm.
13C NMR (75 MHz, CDCl3, 25 ◦C):
δ = 13.7 (CH2CH2CH2CH3); 19.9 (CH2CH2CH2CH3); 31.2
(CH2C6H4(C(CH3)3)-4); 31.7 (CH2CH2CH2CH3); 34.6 (CH2C6H4(C(CH3)3)-4); 48.0 (CH2CH2CH2CH3);
52.0 (CH2C6H4(C(CH3)3)-4); 81.6, 96.5, 112.8, 113.9, 126.0, 126.3, 126.4, 128.3, 130.5, 131.4, 131.5, 151.7
(arom. C, NC6H4N and CH2C6H4(C(CH3)3)-4); 186.1 (Ru-Ccarbene) ppm (Figure S8). Elemental analysis
calcd (%) for C22H28Cl2N2Ru (Mr = 492.40): C 53.66, H 5.73, N 5.69; found (%): C 53.74, H 5.78, N 5.76.
Dichloro-[1-(2,3,5,6-tetramethylbenzyl)-3-(4-methoxybenzyl)benzimidazol-2-ylidene]ruthenium(II), 2e: (0.422
g, yield 76%) 1H NMR (300 MHz, CDCl3, 25 ◦C):
δ = 2.04 and 2.16 (s, 12H, CH2C6H(CH3)4-2,3,5,6);
3.74 (s, 3H, CH2C6H4(OCH3)-4); 5.12 (s, 2H, CH2C6H(CH3)4-2,3,5,6); 5.59 (s, 1H, arom. CH
CH2C6H(CH3)4-2,3,5,6); 5.68 (s, 2H, CH2C6H4(OCH3)-4); 6.77 (d, 3J = 8.7 Hz, 2H, arom. CH, NC6H4N
and CH2C6H4(OCH3)-4); 6.99 (d, J = 8.1 Hz, 1H, arom. CH, NC6H4N and CH2C6H4(OCH3)-4);
7.06–7.12 (m, 1H, arom. CH, NC6H4N and CH2C6H4(OCH3)-4); 7.20–7.28 (m, 3H, arom. CH, NC6H4N
3
and CH2C6H4(OCH3)-4); 7.42 (d, J = 8.0 Hz, 1H, arom. CH, NC6H4N and CH2C6H4(OCH3)-4)
ppm. 13C NMR (75 MHz, CDCl3, 25 ◦C):
δ = 13.9 and 18.3 (CH2C6H(CH3)4-2,3,5,6); 46.0
(CH2C6H(CH3)4-2,3,5,6); 52.3 (CH2C6H4(OCH3)-4); 55.2 (CH2C6H4(OCH3)-4); 84.4, 90.6, 98.0,
109.5, 110.6, 113.0, 113.6, 123.1, 123.5, 129.0, 129.3, 133.2, 135.0, 158.8 (arom. C, NC6H4N,
CH2C6H(CH3)4-2,3,5,6 and CH2C6H4(OCH3)-4); 185.2 (Ru-Ccarbene) ppm (Figure S9). Elemental
analysis calcd (%) for C26H28Cl2N2ORu (Mr = 556.50): C 56.12, H 5.07, N 5.03; found (%): C 56.16, H
5.06, N 5.03.

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3.4. General Procedure for the Direct Catalytic Arylation of 2-Phenylpyridine with (Hetero)Aryl Chlorides
Each [RuCl2(η6 1-arene-CH2-NHC)] complex (2a
) (0.025 mmol) and KOAc (0.05 mmol) was
,η
–e
stirred in water (2 mL) at room temperature for 1 h, and then 2-phenylpyridine (0.5 mmol), (hetero)aryl
chloride (1.25 mmol) and Cs2CO3 (1.50 mmol) were added. The resulting mixture was stirred at
100 ◦C for different durations. After completion of the reaction, the reaction mixture was cooled to
room temperature. Dichloromethane was added to this mixture and organic phase was extracted.
The extracted organic phase was dried over MgSO4 and concentrated under vacuum. The remaining
residue was purified by column chromatography on silica gel (pentane/diethylether mixture, 1:5 v/v).
The ortho-arylated products A and B conversion and ratio were determined by GC and GC-MS analyses.
3.5. Single Crystal X-ray Diffraction and Structure Analysis
A crystal of compound 2b with dimensions of 0.31
a glass fiber using epoxy and placed on a Bruker SMART 1000 CCD (Atlanta, GA, USA) sealed tube
diffractometer with graphite monochromated MoK (0.71073 Å) radiation. Data were measured at
×
0.13
×
0.07 mm3 was mounted on the tip of
α
373(2) K using a series of combinations of phi and omega scans. Data collection, indexing and initial
cell refinements were all carried out using SMART software [55]. Frame integration and final cell
refinements were done using SAINT software [56]. The structure was solved using Direct methods and
difference Fourier techniques (SHELXTL, V6.12) [57]. Hydrogen atoms were placed in their expected
chemical positions using the HFIX command and were included in the final cycles of least squares with
isotropic Uijs related to the atoms ridden upon. All non-hydrogen atoms were refined anisotropically.
Structure solution, refinement, graphics and generation of publication materials were performed using
the software SHELXTL, Version 6.12 [57].
4. Conclusions
The above described reactions demonstrate that water can be used as solvent for direct C–H bond
functionalization. It is noteworthy that, in addition to its role as safe, clean, and recoverable solvent,
water also plays the role of a positive catalyst partner, as in the direct selective mono(hetero)arylation
of 2-phenylpyridine
and five new [RuCl2(η6
showed good catalytic activity for the direct arylation of 2-phenylpyridine with (hetero)aryl chlorides in
water. The catalytic activity of [RuCl2(η6 1-arene-CH2-NHC)] for mono heteroarylation of heterocyclic
.
We have synthesized and characterized new benzimidazolium halides (1a
–e)
,η
1-arene-CH2-NHC)] complexes (2a
–
e
). Complexes 2a with KOAc partner
–e
,
η
arene (pyridine arene) has the potential to reach bidentate new ligands in the future. There is no
serious doubt that this field of research will increase significantly in the future, hopefully making
another step towards more environmentally friendly and energy/resources saving processes.
Supplementary Materials: Supplementary materials are available online. CCDC-1823696 contains the
supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.
cam.ac.uk/data_request/cif, or by e-mailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44(0)1223-336033.
Acknowledgments: This work was financially supported by the Technological and Scientific Research Council of
˙
Turkey TÜBITAK-BOSPHORUS (109T605).
Author Contributions: All authors contributed equally to this work.
Conflicts of Interest: The authors declare that they have no conflict of interest.
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Sample Availability: Samples of the compounds 1a–e and 2a–e are available from the authors.
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