Application of quinoxaline based diimidazolium salt in palladium catalyzed cross-coupling reactions

Article abstract of DOI:10.1007/s12039-015-0844-8

Abstract The reaction of 2,3-bis(bromomethyl)quinoxaline with imidazole afforded the quinoxaline bridged diimidazolium salt (1) in good yield. Diimidazolium salt (1) in conjunction with Pd(OAc)₂ was employed as a catalyst for C-C cross-coupling reactions. The diimidazolium salt was found to be efficient in catalyzing Suzuki-Miyaura cross-coupling reaction in ethanol under ambient conditions. Moderate to good selectivity of the trans product was observed in the Heck cross-coupling reaction. The molecular structure of 1 was confirmed by single crystal X-ray diffraction study. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s12039-015-0844-8

c
J. Chem. Sci. Vol. 127, No. 5, May 2015, pp. 879–884. ꢀ Indian Academy of Sciences.
DOI 10.1007/s12039-015-0844-8
Application of quinoxaline based diimidazolium salt in palladium
catalyzed cross-coupling reactions
MUJAHUDDIN M SIDDIQUI, MOHAMMED WAHEED, SAJAD A BHAT
and MARAVANJI S BALAKRISHNA∗
Phosphorus Laboratory, Department of Chemistry, Indian Institute of Technology Bombay,
Powai, Mumbai 400 076, India
e-mail: krishna@chem.iitb.ac.in
MS received 01 November 2014; revised 22 January 2015; accepted 24 January 2015
Abstract. The reaction of 2,3-bis(bromomethyl)quinoxaline with imidazole afforded the quinoxaline bridged
diimidazolium salt (1) in good yield. Diimidazolium salt (1) in conjunction with Pd(OAc)2 was employed as
a catalyst for C–C cross-coupling reactions. The diimidazolium salt was found to be efficient in catalyzing
Suzuki-Miyaura cross-coupling reaction in ethanol under ambient conditions. Moderate to good selectivity of
the trans product was observed in the Heck cross-coupling reaction. The molecular structure of 1 was confirmed
by single crystal X-ray diffraction study.
Keywords. Carbene; Imidazolium salt; Suzuki-Miyaura coupling; Mizoroki-Heck coupling; Palladium (II).
1. Introduction
extra donor sites or pendant donor arms: for example,
tridentate pincer ligand with two carbene arms (I), hybrid
pincer ligands with amine (II) or phosphine (III) donor
arms7 or heteroatom functionalized dicarbene ligands
with aromatic heterocyclic bridging units have been
documented in the literature (chart 1).8 The strong
σ-donor ability of NHC ligands in comparison with
phosphines results in stronger metal-ligand bonding,
thereby stabilizing the metal centre during the cat-
alytic process by neutralizing the charge deficit at the
metal centre.9,10 The dicarbene ligands of the type
(IV) lead to dinuclear complexes with metal centres
located in close proximity. Contrary to this, the dicar-
bene ligands of the type (V) places the metal cen-
tres in remote positions which can be seen as the
dinuclear version of the picoline or benzoimidazoline
functionalized carbene complexes (VI).11 As a part of our
continuous efforts towards designing novel and cheap
catalysts for cross-coupling reactions,12a−e we recently
reported the diamino-diol based palladium catalysts for
Suzuki-Miyaura cross coupling reaction.12f Herein, we
describe the synthesis of quinoxaline bridged imidazo-
lium salt and its in situ generated palladium catalyst in
Suzuki-Miyaura and Mizoroki-Heck coupling reactions.
Transition metal catalyzed cross-coupling reactions have
emerged as the most efficient and versatile methods in
academic research as well as in industry for the synthesis
of natural products, pharmaceutical drugs, fine chemicals
and advanced materials.1 Palladium catalyzed Suzuki-
Miyaura and Mizoroki-Heck are the most powerful
C–C bond formation reactions available to synthetic
chemists due to the broad tolerance of functional groups
and relatively mild reaction conditions.2 Apart from the
well-known [Pd(PPh3)4] as a catalyst, a vast number of
palladium complexes containing bulky as well as elec-
tron rich phosphines have been designed and success-
fully employed in different cross-coupling reactions.3
However, phosphine-based auxiliary catalysts are expen-
sive, toxic, necessitate a tedious method to prepare and
require inert atmosphere and often mild reaction con-
ditions. For a catalyst to be attractive or popular in the
industrial sector, the ligands have to be cheaper, stable
to moisture, readily available or involve simple methods
of preparation. In this context, several phosphine-free
catalytic systems with nitrogen as donor ligands such as
amines,4a imines4b and oxazolines4c as well as NHCs4d−h
have been designed and employed in various catalytic
reactions.
2. Experimental
Similar to phosphines, functionalized NHCs are becom-
ing popular in recent years.5,6 NHC ligands having
1-methyl Imidazole, bromo compounds, phenyl boronic
acid and styrene were purchased from Aldrich. Anhy-
drous K2CO3 was purchased from S.D. Fine chemicals,
∗For correspondence
879

880
Mujahuddin M Siddiqui et al
860, 776. 1H-NMR (400 MHz, DMSO-d6): δ 4.0 (s, 6H,
CH3), 6.17 (s, 4H, CH2), 7.85–7.87 (m, 4H, Ar), 7.92–
7.95 (m, 4H, Ar), 9.42 (s, 2H, NCHN). 13C-NMR (400
MHz, DMSO-d6): δ 36.03 (imidazolium-NCH3), 50.39
(quinoxaline-CH2N), 123.54, 123.71 (imidazolium-C),
128.50, 130.91 (quinoxaline-C), 137.94 (imidazolium-
NCN), 140.08, 147.93 (quinoxaline-C). ESI-MS:m/z
399.0954 [M−Br]+.
and used as received without further purification. All
1
other reagents were used as received. The H and 13C
NMR spectra were taken in DMSO-d6 with reference to
TMS. GCanalyseswereconductedusingan Agilent Gas
Chromatograph 6890 Series, Hewlett Packard equipped
with an HP5-MS capillary column (30 m × 0.25 mm ×
0.25μm) and an FID detector. All GCMS analyses were
done by Agilent 7890A GC system connected with
5975C inert XL EI/CI MSD (with triple axis detector).
2.2 General method for Suzuki cross-coupling reaction
2.1 Synthesis of 2,3-bis(imidazolylmethyl)quinoxalium
bromide (1)
In a two-neck round-bottomv flask, a mixture of palla-
dium acetate (1 mol%), 1 (1 mol%), K2CO3 (1 mmol),
A mixture of 1-methyl imidazole (0.26 g, 3.11 mmol) aryl bromide (0.5 mmol), and phenyl boronic acid
and2,3-bis(bromomethyl)quinoxaline(0.5g, 1.58 mmol) (0.75 mmol) were allowed to reflux in ethanol at 78◦C.
inacetonitrilewas refluxed over night at 80◦C. The solu- The course of reaction was monitored by GC analysis.
tionwasfilteredunderreducedpressuretoobtainabrown Ethanol was removed under reduced pressure and the
precipitate, which was washed with petroleum ether and residue was dissolved in dichloromethane and passed
the residue obtained was recrystallized from ethanol to through celite. An aliquot was taken with a syringe and
give colourless crystals of 1. Yield: 75%. M.p.: 265–268◦C subjected to GC analysis. Yields were calculated with
(dec). IR (KBr) υmax (cm−1): 3408, 3046, 1567, 1174, aryl halides as internal standards.
E
E
E
N
N
N
N
N
N
M
X
NR2
M
X
PPh2
M
X
N
N
R
R
R
R
I
II
E = C, N
III
R
N
MLn
N
N
N
N
N
N
N
N
N
N
N
M
M
MLn
R
N
Ln
Ln
R
N
N
R
MLn
IV
VI
V
R
Chart 1. Different coordination modes.
2 Br
MeN
N
N
N
N
Br
Br
CH3CN
Reflux
2
NMe
N
N
N
N
Me
1
Scheme 1. Preparation of 2,3-bis(imidazolylmethyl)quinoxalium bromide (1).

Quinoxaline based diimidazolium salt
881
2.3 General method for Heck cross-coupling reaction 2.4 X-ray structure determination of 1
Heck coupling reactions were carried out using aryl Diffraction data for 1 was obtained on a Rigaku
bromides (1.0 mmol), styrene (1.4 mmol), and K2CO3 Saturn724+ (4 x 4 bin mode) diffractometer equipped
asbase(2 mmol) dissolved in 5 mL of N,N-dimethylfor- with a rotating anode using Mo Ka radiation (λ =
mamide(DMF). Anappropriateamount of 1 (1.0 mol%) 0.7107 Å). The diffraction data were measured at 293 K
and palladium acetate (2.0 mol%) were added to this in the range 3.30 < 2θ < 24.99. Structure solution and
reaction mixture. The reaction mixture was heated to refinement were achieved with standard Patterson and
130◦C for the selected reaction time. Coupling product Fourier techniques.All non-hydrogen atoms were refined
yieldswerecalculatedfromGCdatarelative to the resid- with anisotropic displacement parameters. Hydrogen
ual aryl halide. The product identity was confirmed by atoms were added to the structure models at calculated
GC–MS.
positions.
Selected crystallographic details for 1
Mol. Formula = C18H20Br2N6, Colourless crystals,
M = 480.22, Tetragonal, space group P43212, a =
11.969(3), b = 11.969(3), c = 14.415(4) Å, a = β =
γ = 90◦, V = 2065.05 Å3, Z = 4, Dc = 1.544 g cm−3,
μ(Mo Kα) = 3.939 mm−1, F(000) = 960, T = 293 K,
GoF = 0.98, final R1 = 0.0282 and wR2 = 0.0642 for
I > 2σ(I), R1 = 0.0707, wR2 = 0.0965 for all data.
CCDC Number: 1035187.
3. Results and Discussion
Figure 1. Molecular structure of 2,3 bis-(imidazolylmethyl)
quinoxilium bromide (1). Hydrogen atoms and the bromide
counterions have been omitted for clarity; thermal ellipsoids
are drawn at 50% probability level. Selected bond angles (Å)
and bond distances (◦): C1–N1 = 1.323(4) Å, C1–N2 =
1.332(4), C2–N1 = 1.373(4), C4–N1 = 1.477(5); N1–
C1–N2 = 108.0(3), C1–N1–C2 = 108.6(3), C3–N2–C5 =
124.5(3).
The reaction of 2,3-bis(bromomethyl)quinoxaline with
two equivalents of 1-methyl imidazole in acetonitrile
under reflux conditions afforded 2,3 bis-(imidazolyl-
methyl)quinoxaline(1)asbrowncoloursolid(scheme 1).
The crude product was purified by recrystallization from
ethanol to get colourless crystals in 75% yield.13 The
Figure 2. Intermolecular hydrogen bonding (2.71 Å) and π–πstacking (3.69
Å) interactions leading to polymeric structure in the crystal lattice of 1.

882
Mujahuddin M Siddiqui et al
Pd(OAc)2, 1
Br
(HO)2B
K2CO3, EtOH
2h, Ref lux
R
R
Scheme 2. Suzuki-Miyaura cross-coupling reaction.
Table 1. Suzuki–Miyaura reaction of phenylboronic acid with aryl halides.
Entry
Aryl halide
Arylboronic acid
Product
Conversion
OHC
MeOC
NC
OHC
(HO)2B
(HO)2B
(HO)2B
(HO)2B
Br
1
2
3
4
96%
90%
93%
85%
MeOC
NC
Br
Br
MeO
MeO
Br
Br
(HO)2B
(HO)2B
OHC
OHC
5
6
82%
80%
Br
MeOC
MeOC
(HO)2B
(HO)2B
N
Br
Br
N
7
8
65%
58%
S
S
rings are almost perpendicular to the plane of the
quinoxaline ring. The carbene carbon (NCHN) of both
the imidazolyl groups are aligned in opposite direc-
tion to each other as observed in pyrazine based diim-
idazolium salts. The C1–N1 [1.323(4) Å] and C1–N2
[1.332(4) Å] bond distances as well as the N1–C1–N2
bond angle [108.0(3)◦] are comparable with the same
observed in arene bridged diimidazolium salts.11
2 Br-
O
N
N
N
N
N
2 Br-
Pd
N
O
O
N
N
N
N
O
O
Pd
Pd
O
O
N
N
N
N
N
N
N
Pd
N
O
The crystal structure of 1 shows interesting (C–H)+····
Br− ionic hydrogen bonding. The imidazolium moiety
of the ligand is involved in hydrogen bonding with
the bromide ion with the bromide ion with C1–H1····
Br1 = 2.716 Å and C1–H1–Br1 = 150.2◦. The bromide
ion is further involved in hydrogen bonding with one
of the hydrogen of the methylene group [C5–H5····
Br1 = 2.839 Å, < C5–H5····Br1 = 152.9◦]. As both the
imidazolyl groups are pointing in opposite directions,
the H-bonding leads to the formation of a polymeric
structure in the solid state. Furthermore, intermolecu-
lar π-π stacking interaction is observed between one
of the imidazoles and quinoxaline ring as shown in
figure 2 (distance = 3.69 Å).
VIII
VII
Figure 3. Proposed structures for complexes VII and VIII.
1H NMR spectrum of the diimidazolium salt 1 showed
thesignalforNCHNprotonsat 9.42 ppm, which is in the
range of NCHN protons of imidazolium and ben-
zoimidazolium salts. The resonances for N-Methyl and
methylene protons appear as singlets at 4.00 ppm and
6.17 ppm, respectively (figure 1).
The compound 1 crystallizes in tetragonal crystal
system with P43212 space group. The two imidazolyl

Quinoxaline based diimidazolium salt
883
3.1 Suzuki-Miyaura cross coupling reaction
reaction is proposed to be VII (figure 3), a dimeric com-
plex where two Pd centres are bridging between two
imidazolyl-carbene ligands, as observed in the case of
benzmidazolium derivative.14
Attempts to isolate the Pd-complex of quinoxaline-
imidazolium salt by transmetallation method using
Ag2O and by also direct deprotection method have been
unsuccessful. Thus,a mixture of diimidazolium salt 1 and
Pd(OAc)2 was employed as the catalytic system for
Suzuki-Miyaura and Mizoroki-Heck coupling reactions.
3.2 Mizoroki-Heck cross-coupling reaction
The Pd-catalyzed Suzuki-Miyaura coupling reaction of Heck coupling reactions were carried out with a
para-bromo benzaldehyde and other aryl bromides with 1:2 mixture of diimidazolium salt 1 and palladium
phenyl boronic acid has been carried out (scheme 2). acetate as catalyst precursor by choosing 4−bromo ben-
All the reactions were carried out under reflux condi- zaldehyde and styrene as the cross-coupling partners
tions in air by using environmentally benign EtOH as (scheme 3). Under the optimized conditions (1.0 mol%
solvent and K2CO3 as base. Chromatographic analysis of diimidazolium salt 1, 2.0 mol% of [Pd(OAc)2] and
of the reaction mixture revealed 96% conversion in 2 h 2.0 mmol of K2CO3 in dimethylformamide at 130◦C
under reflux conditions.
over a reaction period of 24 h, almost quantitative con-
To expand the scope of catalytic investigation, several versions were achieved. Electron withdrawing aryl bro-
meta and para substituted aryl bromides with phenyl mides showed better conversions. However moderate
boronic acid as the coupling partner were employed conversions were obtained with electron donating aryl
under the given reaction conditions. Good to excellent halides. In all the cases moderate to good selectivity
conversions were observed for the desired biphenyl pro- towards the trans product was observed (table 2). The
duct with conversion ranging from 80–93% (table 1, in situ generated catalyst in the Heck cross-coupling
entry 2–6). Moderate to good conversions were also reaction is proposed to be VIII (figure 3), where the Pd
observed for heteroaromatic bromides such as 2-bromo centres are coordinated to (C, N) hetero-donor carbene
pyridine and 2-bromo thiophene (table 1, entry 7–8). ligand. The metal centres in this case are in remote posi-
Homo-coupling product was not observed in all the cases. tions which can be seen as the dinuclear version of the pico-
The in situ generated catalyst in this cross-coupling line or benzoimidazoline functionalized carbene complexes.
R
Pd(OAc)2, 1
Br
R
K2CO3, DMF
24 h, 130
R
°
C
Trans
Cis
Scheme 3. Mizoroki-Heck cross-coupling reaction.
Table 2. Mizoroki–Heck reaction of styrene with various aryl halides.
Entry
Aryl halide
Olefin
Trans
Cis
Conversion (%)
OHC
Br
1
2
3
4
89.5
70
10.5
30
100
99
MeOC
NC
Br
Br
54
46
84
MeO
Br
66
37
70
Br
5
85
15
81

884
Mujahuddin M Siddiqui et al
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for the Heck cross-coupling reaction is lower than those
foundfor well-definedpalladium complexes with mixed
carbene/phosphine, pincer-type ligands which exhibit
better conversion rates for shorter reaction times, even
with low catalyst loading.15
4. Conclusions
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We have demonstrated the use of in situ prepared
palladium catalyst with quinoxaline bridged diimida-
zolium salt (1) in Suzuki as well as Heck cross-coupling
reactions. This is a versatile catalytic system which
effectively catalyses Suzuki cross-coupling reactions
at ambient conditions for a wide range of substrates
using environmentally benign ethanol as solvent. Mod-
erate to good selectivity towards the trans-product was
observed in Mizoroki-Heck reactions. The coordination
chemistry and further exploration of the catalytic activ-
ity of diimidazolium salt is under active investigation.
8. (a) Lee K-M, Chen J C C and Lin I B J 2001 J.
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Supplementary Information
9. Albert K, Gisdakis
P
and Rosch
N
1998
1H, 13C NMR and ESI-MS Spectral data for 1 are pro-
vided. The electronic supplementary information can be
seen at www.ias.ac.in/chemsci. Crystallographicdatafor
1 has been deposited at the Cambridge Crystallographic
Data Centre with CCDC no. 1035187. This data can be
obtained free of charge at www.ccdc.cam.ac.ul/conts/
retrieving.html[orfromtheCambridgeCrystallographic
Data Centre (CCDC), 12 Union Road, Cambridge CB2
1EZ, UK; fax: +44(0)1223-336033; E-mail: deposit@
ccdc.cam.ac.uk +44(0)1223-3360].
Organometallics 17 1608
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Acknowledgements
We are grateful to the Science & Engineering Research
Board, New Delhi, India for financial support of this
work through grantNo. SB/S1/IC-08/2014. MMSthanks
the Council of Scientific Industrial Research (CSIR),
New Delhi, for Senior Research Fellowship (SRF).
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