Tetraalkylammonium-based ionic liquids for a RuCl3 catalyzed C–H activated homocoupling

Article abstract of DOI:10.1016/j.tet.2020.131314

[BuEt₃N][NTf₂] can be a superior ionic liquid in a RuCl₃ catalyzed oxidative C–H activation reaction compared to standard imidazolium-based ionic liquids. The tetraalkylammonium-based ionic liquid resulted in higher yields

Full text of DOI:10.1016/j.tet.2020.131314

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Tetraalkylammonium-based ionic liquids for a RuCl catalyzed C–H activated
3
homocoupling
Maren Muntzeck, Felix Pippert, René Wilhelm
PII:
S0040-4020(20)30468-3
https://doi.org/10.1016/j.tet.2020.131314
TET 131314
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 2 April 2020
Revised Date: 21 May 2020
Accepted Date: 25 May 2020
Please cite this article as: Muntzeck M, Pippert F, Wilhelm René, Tetraalkylammonium-based
ionic liquids for a RuCl catalyzed C–H activated homocoupling, Tetrahedron (2020), doi: https://
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Tetraalkylammonium-Based Ionic Liquids
for a RuCl3 Catalysed C-H-Activated
Homocoupling
Leave this area blank for abstract info.
Maren Muntzeck, Felix Pippert, René Wilhelm
Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstr. 6, 38678 Clausthal-Zellerfeld,
Germany

1
Tetrahedron
journal homepage: www.elsevier.com
Tetraalkylammonium-Based Ionic Liquids for a RuCl3 Catalyzed C-H Activated
Homocoupling
Maren Muntzecka, Felix Pippertb and René Wilhelmb
aDepartment of Chemistry, University of Paderborn, Warburger Str. 100, 33098 Paderborn, Germany
bInstitute of Organic Chemistry, Clausthal University of Technology, Leibnizstr. 6, 38678 Clausthal-Zellerfeld, Germany
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
[BuEt3N][NTf2] can be a superior ionic liquid in a RuCl3 catalyzed oxidative C-H activation
reaction compared to standard imidazolium-based ionic liquids. The tetraalkylammonium-based
ionic liquid resulted in higher yields. This could be due to the absence of a possible C-H
activation on the tetraalkylammonium-based ionic liquid itself. This side reaction could occur
with imidazolium-based ionic liquids. The ionic liquid could be recycled and different oxidation
agents could be used in the reaction. The best results were obtained with FeCl3 · 6 H2O and with
a combination of LiCl under an oxygen atmosphere. Up to 83% yield were obtained in the
homocoupling of 2-arylpyridines.
Available online
Keywords:
C-H-Activation
Ionic Liquid
Ruthenium catalysis
Green chemistry
2009 Elsevier Ltd. All rights reserved
.
———
Corresponding author. Tel.: +49-5323-72-2040; fax: +49-5323-72-2834; e-mail: rene.wilhelm@tu-clausthal.de

2
Tetrahedron
synthesis of biaryl moieties was used,25 to evaluate different
1. Introduction
ionic liquids in an oxidative C-H activation reaction for a C-
C bond formation. The best oxidants for oxidative C-C bond
formations are environmental friendly compounds like
oxygen or salts based on iron which are non-toxic, cheap,
easy to handle and readily available.26 In comparison to
other techniques no additional steps are needed to introduce
reacting functional groups in C-H activations. This way time
and materials can be saved and waste is avoided.27 The
biaryl moiety is an essential part for a variety of natural
products, agrochemicals, ligands or pharmaceuticals.28
Hence, environmental friendly and resource saving methods
for the synthesis of these moieties are highly desirable.
The application of ionic liquids (ILs) in catalytic reactions
has grown continuously over the years due to their unique
features.1 Ionic liquids have been used as solvents in a
variety of reactions such as Diels-Alder,2 Friedel-Crafts,3
Heck,4
Suzuki
coupling,5 hydroformylation6
and
hydrogenation reactions.7 Also many electrolytes based on
ionic liquids have been developed.1 Their application as
electrolytes shows their potential in electrochemical
reactions and solvents for oxidative reactions. Examples for
the latter are the Ni(acac)2-catalysed aerobic oxidation of
aromatic aldehydes,8 the TEMPO catalyzed aerobic
oxidation of alcohols,9 the palladium-catalyzed oxidation of
styrene10
and
benzyl
alcohol11
and
the
N-
hydroxyphthalimide-catalyzed oxidative production of
phthalic acids from xylenes.12 The application as solvents in
these reactions is beneficial, since problematic and harmful
molecular solvents can be exchanged with the ionic liquids.
In comparison to many conventional used solvents many
ionic liquids have a low vapor pressure, excellent solvation
properties for salts, are not flammable or explosive, can be
easily handled and recycled.13
2. Results and discussion
The oxidative homocoupling reaction was investigated with
2-phenylpyridine (
1), a ruthenium catalyst and iron(III)
chloride as oxidant which gives the product 2,2'-di(pyridin-
2-yl)-1,1'-biphenyl (
protocol towards
2
2
) (Scheme 1). An improved reaction
would be desirable since so far
chlorobenzene and a sensitive ruthenium complex catalyst
were reported as optimal conditions for this reaction.29
Although ionic liquids can be used as solvents for many
reactions, there can be limits to their application due to their
own reactivity with some reagents under certain reaction
conditions.14 Especially the most common used ILs based on
1,3-dialkylimidazolium ions can be deprotonated under
basic conditions14a-c or oxidized via C-H bond activation to
give carbene species and carbene complexes in the presence
of a metal.14d,14e Hence, ionic liquids are rarely applied as
solvents in oxidative C-H functionalizations.15 Yet, with
Cp*-Rhodium complexes C-H bond activations in
[BMIM][NTf2] are possible.16 In addition, a manganese
complex in [HMIM][OTf] could be applied as a catalyst in
Scheme 1
an
oxime-directed
C-H
amidation.17
For
First, the impact of different ionic liquids (Scheme 2) on the
homocoupling of
1 was examined. The results are
tetraalkylammonium salts dealkylations have been reported
for harsh conditions, which can be of thermal or chemical
nature.18 In the catalytic hydrodimerization of butadiene, Pd-
(II) species are used as catalysts, which are immobilized in
ILs. In this case, dealkylations of imidazolium-based ILs
could be observed at higher temperatures.19 In case of the
base-catalyzed Baylis-Hillman reaction the ionic liquids
based on 1-butyl-3-methylimidazolium cations are
deprotonated to their corresponding carbenes, which react
with benzaldehyde resulting in the inhibition of the desired
reaction and make the recycling of the ILs impossible.20
summarized in Table 1. In order to obtain a baseline for the
study, a literature known procedure was repeated with 5
mol% RuCl3 as catalyst and FeCl3 as oxidant in
chlorobenzene as solvent. A yield of 6% was obtained
(Table 1, Entry 2) which is slightly lower compared to a
reported 27% in the literature for these conditions (Table 1,
Entry 1).29 With the established reference point initially the
oxidizing agent FeCl3 was replaced with different iron-based
ionic liquids, since the later were catalyzing an oxidation in
a
preceding
[THTDP][FeCl4] (
reaction. Both ILs increased the yields of the reaction to
24% with and 42% with (Table 1, Entries 3-4).
[BMIM][Fe2Cl7] ( ) with a higher FeCl3 content resulted in
work.24
) were applied as oxidants in the
[BMIM][FeCl4]
(
3)
and
4
Yet, the base-initiated deprotonation of the C-2 position for
the generation of N-heterocyclic carbenes is desired, if the
latter are used as ligands in transition-metal-catalyzed
reactions.21 E.g. Pd-catalyzed cross-couplings in ILs are
improved via this process.22 However, under these condition
the recycling of the ILs is compromised, and in some cases
the carbene complexes may also hinder the reaction.
3
4
5
a yield of 33 % (Table 1, Entry 6). After exploring the iron-
based ILs as oxidants, the influence of water on the reaction
had to be considered. By changing from anhydrous FeCl3 to
its hexahydrate analogue a yield of 78% was isolated (Table
1, Entry 6), which makes the latter system more efficient for
the oxidation than the applied metallic ionic liquids. Hence,
As part of our effort on ionic liquids14c,23 we recently
reported the application of an iron-based IL as catalyst and
oxidant in a dehydrogenation reaction.24 In the presented
work a transition metal catalyzed C-H bond activation
followed by a C-C bond formation for the resource saving
.
for further reactions FeCl3 6 H2O was the oxidant of choice.
In order to start the examination of different ionic liquids in
the oxidative C-C bond formation via C-H activation the
problematic30 and volatile chlorobenzene was replaced with

3
various ionic liquids. While [BMIM][Cl] (
), and [BMIM][OAc] ( ) did not support the reaction
(Table 1, Entries 7-9) and no conversion was observed.
[BMIM][BF4] ( ) gave a yield of 60% (Table 1, Entry 10)
6), [BMIM][PF6]
(7
8
9
and [BMIM][NTf2] (10) a yield of 66% with a reaction time
of 48 h (Table 1, Entries 10,11).
Table 1. Homocoupling reaction of 2-phenylpyridine
1
.
Entrya
1c
Oxidant
Solvent
t [h]
16
16
16
16
16
16
16
16
16
48
48
16
16
16
16
16
24
48
72
48
16
48
Yield [%]b
FeCl3
C6H5Cl
27
6
2
FeCl3
C6H5Cl
3
3
C6H5Cl
24
42
33
78
-
4
4
C6H5Cl
5
5
C6H5Cl
6
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
C6H5Cl
7
[BMIM][Cl] 6
[BMIM][PF6] 7
[BMIM][OAc] 8
[BMIM][BF4] 9
[BMIM][NTf2] 10
EAN 11
8
-
9
-
10
11
12
13
14
15
16
17
18
19
20
21
22
60
66
-
[TBP][Cl] 12
[THTDP][NTf2] 13
[THTDP][Cl] 14
[BuEt3N][NTf2] 15
[BuEt3N][NTf2] 15
[BuEt3N][NTf2] 15
[BuEt3N][NTf2] 15
[BuEt3N][PF6] 16
[BuEt3N][HSO4] 17
[PrEt3N][NTf2] 18
-
-
17
45
60
83
66
12
-
63
a
reaction was performed with 0.5 mmol 2-phenylpyridine 1, 0.4
mmol oxidant, 5 mol% RuCl3 and 1 mL chlorobenzene or 0.5 mL
ionic liquid; b isolated yields; c result from Li et al.29
Taking into account that [BuEt3N][NTf2] (15) resulted in the
highest yield, further studies were conducted with this ionic
liquid and are summarized in Table 2. To gain a better inside
on the influence of water, once pure water and once a
mixture of [BuEt3N][NTf2] (15) and water was applied as
solvent. In both cases no product was found with a reaction
temperature of 100 °C (Table 2, Entries 1-2). Hence, a small
amount of moisture is beneficial for the reaction yet an
excess of water has the opposite effect. For optimization of
the temperature one reaction was carried out at 80 °C and
another at 130 °C. In the first case a strong decrease of the
yield to 17% was found and in the second a small decrease
to 71% was observed compared to the optimum yield at 110
°C (Table 2, Entries 3-4). The decrease was due to the
formation of by-products via decomposition.
Scheme 2
Since imidazolium-based ionic liquids are known for their
capability to form carbene species via deprotonation or C-H
activation,31,14d,19 which could decrease the yield for the
reaction, the influence of non-imidazolium-based ionic
liquids as solvents was explored. The protic IL EAN (11
)
did not support the reaction (Table 1, Entry 12) and neither
did [TBP][Cl] (12) or [THTDP][NTf2] (13) (Table 1, Entries
13-14). Only starting material could be recovered.
Interestingly, [THTDP][Cl] (14) gave a yield of 17 % (Table
1, Entry 15). A significant increase of the yield to 45% after
16 h was found with [BuEt3N][NTf2] (15). The extension of
the reaction time to 48 h gave a maximum yield of 83%. A
longer reaction time of 72 h decreased the yield to 66% due
to decomposition and possible subsequent side reactions
(Table 1, Entries 17-19). Applying [BuEt3N][PF6] (16) gave
a yield of 12% with a reaction time of 48 h, while the
reaction with [BuEt3N][HSO4] (17) failed to give the desired
product (Table 1, Entries 20-21), showing a tendency that
lipophilic anions support the reaction. Finally,
Table 2. Variation of reaction conditions for the
homocoupling of 2-phenylpyridine 1.
[ProEt3N][NTf2]
(18) with a slightly smaller cation
compared to 15 gave a lower yield of 63% after 48 h (Table
1, Entry 22).

4
Tetrahedron
Entrya
Catalyst
Oxidant
Solvent
Yield
of the catalytic ruthenium species. To determine the
influence of chloride further, different chloride salts were
explored in the reaction under air or oxygen. Under air and 2
eq lithium chloride as substitute for the oxidant a yield of
19% was obtained (Table 2, Entry 14). The amount of
lithium chloride was chosen in order to maintain a chloride
level close to FeCl3. This is a significant improvement to the
absence of a chloride salt under air which gave no product
(Table 2, Entry 10). Additional water in the reaction with
LiCl gave no product, while a run under an atmosphere of
oxygen with LiCl improved the yield to 76 % (Table 2,
Entries 15-16). The absence of product with lithium
bis(trifluoromethylsulfonyl)amide as a replacement for LiCl
supported the importance of chloride anions further (Table
2, Entry 17). Other chloride salts like sodium chloride or
potassium chloride were decreasing the yield (Table 2,
Entries 18-19). Further optimization studies were conducted
[%]b
1
2
3c
4d
5
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeNO3 · 9 H2O
K3[Fe(CN)6]
Fe(OAc)2 · 4 H2O
H2O2
H2O
15/H2O
15
-
-
13
71
-
15
15
6
15
-
7
15
6
8
15
36
43
9
FeCl3 · 6 H2O /
H2O2
15
10
11e
12
13
14
15
16
17
18
19
20f
21g
22
23
24
25
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
CoCl2
CuCl
-
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
-
56
80
33
19
-
FeCl3 · 6 H2O
FeCl3 · 6 H2O / O2
O2
LiCl
LiCl / H2O
LiCl / O2
76
-
.
.
with FeCl3 6 H2O as oxidation agent. Reducing FeCl3
H2O from 0.8 eq to 0.5 eq decreased the yield to 75 % and
0.25 eq to 41 % (Table 2, Entries 20-21).
6
LiNTf2
NaCl
21
-
KCl
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
75
41
-
Finally, other possible catalysts were also explored as
substitutes for RuCl3. No product was formed with CoCl2,
CuCl, CuCl2, RhCl3 . 3 H2O, iridium(I) chloride-1,5-
cyclooctadiene complex (19) and PtCl2 (Table 2, Entries 24-
27). PdCl2 gave a low yield of 13 % (Table 2, Entry 28).
-
CuCl2
RhCl3 · 3
H2O
Ir (I) 19i
PtCl2
-
-
26
27
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
FeCl3 · 6 H2O
15
15
15
15
15
15
-
Hence, the optimum conditions for the reaction with 2-
-
phenylpyridine (1) and [BuEt3N][NTf2] (15) as solvent were
28
PdCl2
RuCl3
RuCl3
RuCl3
13
81
77
71
5 mol% RuCl3 as catalyst, 0.8 eq FeCl3 . 6 H2O as oxidant at
110 °C for 48 h under air. Simple recycling of the ionic
liquid was possible during the purification of the product via
column chromatography. Alternatively, the reaction mixture
was added directly to ethyl acetate and the organic phase
was washed with an aqueous solution of potassium
hydrogencarbonate to remove ruthenium and iron salts as
well as remains of HCl. After the removal of ethyl acetate,
the product was extracted from the ionic liquid with diethyl
ether. The ionic liquid was dried and obtained in pure form
and could be reused (Table 2, Entry 29).
29h
30j
31k
a
reaction was performed with 0.5 mmol 2-phenylpyridine 1, 0.4
mmol oxidant, 5 mol% catalyst and 0.5 mL ionic liquid at a
b
c
temperature of 110 °C for 48 h; isolated yield; reaction
temperature 80 °C; reaction temperature 130 °C; under N2;
0.5 eq FeCl3 6 H2O; 0.25 eq FeCl3 6 H2O; recycled ionic
liquid was used; i bis(1,5-cyclooctadiene)diiridium(I) dichloride; j
a scale up reaction with 5 mmol 1 was carried out; k reaction with
5 mmol 1 and recycled ionic liquid
d
e
f
.
g
.
h
Next, different oxidation agents were evaluated. Different
iron salts as well as H2O2 and also the absence of an
oxidation agent resulted always in lower or no yields
compared to FeCl3 . 6 H2O (Table 2, Entries 5-10). The
application of deoxygenated ionic liquid under a nitrogen
In Scheme 3 a possible reaction mechanism is depicted as it
has been suggested by several groups.29 Initially, RuCl3
reacts with 2-phenylpyridine
complex . Next, intermediate
elimination to form complex
undergoes the same process and the intermediate
formed after the release of HCl. Finally, the oxidative
coupling product is formed via reductive elimination. The
1
via a C-H activation to
A
A loses HCl in a reductive-
.
B
. A second 2-phenylpyridine
is
atmosphere with FeCl3 6 H2O decreased the yield to 56 %
1
C
(Table 2, Entry 11). When the reaction was conducted with
.
FeCl3 6 H2O under an atmosphere of oxygen, a yield of 80
2
% was obtained comparable to the result with air (Table 2,
Entry 12). A reaction under oxygen but in the absence of
any other oxidant furnished a yield of 33% (Table 2, Entry
13). Hence, the presence of oxygen is beneficial for the
reaction as is an iron salt with a chloride counter anion. The
conversion of 33% without an oxidant besides oxygen,
showed that a substoichiometric use of FeCl3 in further
experiments was sufficient.
ruthenium catalyst is regenerated by the oxidant FeCl3. The
formation of HCl can be observed by the decrease of the pH
value. The reaction mixture becomes gradually more and
more acidic. Obviously, the product is being protonated by
the HCl. In its protonated ionic form, the product cannot be
extracted from the ionic liquid. This causes the necessity to
use a base like triethylamine or KHCO3 in the work up
procedure in order to obtain the non-protonated product. For
the regeneration of the catalytic active RuCl3 are next to the
oxidation the presence of two chloride anions necessary. In
general, these could come from the released HCl and the
The importance of chloride can be attributed to the proposed
mechanism with RuCl3 as catalyst (Scheme 3). In this
mechanism the chloride anion is necessary for the recycling

5
formed pyridinium salts, however, it appears that a chloride
source from FeCl3 or LiCl is more efficient, since some HCl
could be lost as gas. Furthermore, it is possible that the iron
is reoxidized by oxygen or maybe it functions especially as a
source for chloride anions and the oxidation to the product is
mainly performed by oxygen. The oxidation of iron(II)
could be also promoted by presence of water in the reaction.
Entrya
1
2-Arylpyridine
Product
Yield [%]b
83
1
2
2
3
58
69
20
27
OMe
N
MeO
N
21
28
4
68
22
29
30
5
6
75
39
23
24
31
7c
22
58
25
26
32
33
8c
a
reaction was performed with 0.5 mmol 2-phenylpyridine 1, 0.4
mmol oxidant, 5 mol% catalyst and 0.5 mL ionic liquid at a
temperature of 110 °C for 48 h; isolated yield; c 72 h reaction
b
time.
Scheme 3
3. Conclusions
After the studies on the influence of various parameter on
the reaction were completed, different 2-aryl-pyridines were
coupled under the optimized conditions as shown in Table 3.
In general, different analogues with electron withdrawing
and donating groups can be applied in the reaction.
However, the yields decreased more when electron
withdrawing substituents were present in the aryl rings. An
explanation for this could be a less stable intermediate due
to the absence of ligands for the ruthenium complexes.
It was possible to demonstrate that [BuEt3N][NTf2] (15) is
an efficient ionic liquid in an oxidative C-H activation
reaction. The ionic liquid resulted in higher yields compared
to imidazolium-based ionic liquids. This could be due to the
fact that a C-H activation on the ionic liquid 15 is not
possible compared to imidazolium-based systems. In
addition, also lithium chloride in combination with an
oxygen atmosphere was found as a suitable oxidation system
for the RuCl3 catalyst. Up to 83% yield were obtained in the
homocoupling of 2-arylpyridine and the ionic liquid could
be recycled. This finding will lead to further applications of
tetraalkylammonium-based ionic liquids in these kinds of
reactions.
Table 3. Application of 2-arylpyridines under optimized
conditions.

6
Tetrahedron
4. Experimental section
7.
Brown, R. A.; Pollet, P.; Mckoon, E.; Eckert, C. A.; Liotta, C.
L.; Jessop, P. G. J. Am. Chem. Soc. 2001, 123, 1254-1255.
Howarth, J. Tetrahedron Lett. 2000, 41, 6627-6629.
Ansari, I. A.; Gree, R. Org. Lett. 2002, 4, 1507-1509.
Namboodiri, V. V.; Varma, R. S.; Sahle-Demessie, E.; Pillai,
U. R. Green Chem. 2002, 4, 170-173.
General methods: [BuEt3N][NTf2] (15), [BuEt3N][PF6]
8.
(
16) and [BuEt3N][HSO4] (17) and [ProEt3N][NTf2] (18
were prepared according to the literature from triethylamine,
bromobutane or bromopropane.32 [BMIM][FeCl4]
),
[BMIM][Fe2Cl7] ( ) and [THTDP][FeCl4] ( ) were prepared
26 were
)
9.
10.
(
3
11.
Jiang, N.; Ragauskas, A. J. Tetrahedron Lett. 2005, 46,
3323-3326.
5
4
according to the literature.24 The 2-arylpyrdines 20
-
prepared according to literature procedures.33 All other
reagents were commercially available and used as supplied
without further purification. IR spectra were recorded on a
12.
13.
Yavari, I.; Karimi, E. Synth. Commun. 2009, 39, 3420-3427.
(a) Shelke, K. F.; Badar, A. D.; Devhade, J. B. Chem. Bio.
Interface 2016, 6, 157-161; (b) Mou, F.; Sun, Y.; Jin, W.;
Zhang, Y.; Wang, B.; Liu, Z.; Guo, L.; Huang, J.; Liu, C. RSC
Adv. 2017, 7, 23041-23045; (c) Muzalevskiy, V. M.;
Shastin, A. V.; Shikhaliev, N. G.; Magerramov, A. M.;
Teymurova, A. N.; Nenajdenko, V. G. Tetrahedron 2016,
72, 7159-7163.
(a) Chowdhury, S.; Mohan, R. S.; Scott, J. L. Tetrahedron
2007, 63, 2363-2389; (b) Dupont, J.; Spencer, J. Angew.
Chem. Int. Ed. 2004, 43, 5296-5297; (c) Jurčík, V.; Wilhelm,
R. Green Chem. 2005, 7, 844-848; (d) Clement, N. D.;
Cavell, K. J.; Jones, C.; Elsevier, C. J. Angew. Chem. Int. Ed.
2004, 43, 1277-1279; (e) McGuinness, D. S.; Cavell, K. J.;
Yates, B. F. Chem. Commun. 2001, 355-356.
1
Bruker VERTEX 70 FT-IR spectrometer. The H-NMR and
13C-NMR spectra were recorded at 500 MHz or 125 MHz on
a Bruker Avance 500 spectrometer using the deuterated
solvent as the lock and the residual solvent or TMS as the
internal reference. Mass spectra were obtained on a Bruker
Esquire 3000 plus mass spectrometer (Bruker-Franzen
Analytik GmbH, Bremen, Germany) equipped with an ESI
interface and an ion trap analyzer. High-resolution mass
spectra (ESI) were recorded on a Waters Quadrupole-ToF
Synapt 2G. The reactions were followed by thin layer
chromatography on silica gel.
14.
15.
16.
Santhoshkumar, R.; Cheng, C.-H. Chem. Eur. J. 2019, 25,
9366-9384.
General experimental for the preparation of 2,2'-di(2-
pyridinyl)-1,1'-biphenyl 2. 2-Phenylpyridine (77.5 mg,
0.5 mmol, 1 eq), RuCl3 (2.6 mg, 0.0125 mmol, 5 mol%),
(a) Lv, S.; Y. Li; Yao, T.; Yu, X.; Zhang, C.; Hai, L.; Wu, Y. Org.
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.
FeCl3 6 H2O (108 mg, 0.4 mmol) and [BuEt3N][NTf2] (15
)
(0.5 mL) were added under an atmosphere of air to a 10 mL
round bottom flask. The reaction was stirred for 48 h at 110
°C. After completion of the reaction it was cooled to room
temperature and then ethyl acetate (1 mL) and triethylamine
(1 mL) were added and the mixture was allowed to stir for
30 min. The purification was performed by flash
17.
18.
chromatography (diethylether/ n-hexane = 1 : 1) to afford
5
1
(64 mg, 21 mmol, 83 %). H NMR (500 MHz, CDCl3) δ:
8.34 (ddd, J=5 Hz, 2 Hz, 1Hz, 2H), 7.54 – 7.57 (m, 2H),
7.37–7.43 (m, 6H), 7.33 (ddd, J=7.5 Hz, 7.5 Hz, 2 Hz, 2H),
7.01 (ddd, J=7.5 Hz, 5 Hz, 1 Hz, 2H), 6.80 (ddd, J=7.5 Hz, 1
Hz, 1 Hz, 2H) ppm; 13C NMR (125 MHz, CDCl3) δ: 157.1,
148.9, 139.9, 139.8, 135.1, 131.3, 130.0, 128.4, 127.7,
124.4, 121.1 ppm. The spectral data of the product was
consistent with literature values.29
19.
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Supplementary Material
Supplementary material as a pdf file with NMR spectra are
available online.
23.
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Highlights
• Tetraalkylammonium based ionic liquids as green reaction medium.
• Ionic Liquids for C-H bond activation reactions.
• Robust simple RuCl3 as catalyst for a C-H Activated Homocoupling.

Declaration of interests
☒ The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.
☐The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests: