Palladium(II) Complexes of N-Heterocyclic Carbene Amidates Derived from Chalcogenated Acetamide-Functionalized 1 H-Benzimidazolium Salts: Recyclable Catalyst for Regioselective Arylation of Imidazoles under Aerobic Conditions

Article abstract of DOI:10.1021/acs.organomet.8b00246

The chalcogenated acetamide-functionalized 1H-benzimidazolium salt precursors [1-(CH₂C(O)NH(CH₂)₂S/SePh)-3-R-C₇H₅N₂]⁺ X (L1-L4; R = Me, CH₂Ph; X = Br, I) to C,N,S/Se l

Full text of DOI:10.1021/acs.organomet.8b00246

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Palladium(II) Complexes of N‑Heterocyclic Carbene Amidates
Derived from Chalcogenated Acetamide-Functionalized
1H‑Benzimidazolium Salts: Recyclable Catalyst for Regioselective
Arylation of Imidazoles under Aerobic Conditions
Renu Bhaskar, Alpesh K. Sharma, and Ajai K. Singh*
Department of Chemistry, Indian Institute of Technology Delhi, New Delhi 110016, India
S
* Supporting Information
ABSTRACT: The chalcogenated acetamide-functionalized 1H-benzimidazolium salt precursors [1-(CH2C(O)NH(CH2)2S/
SePh)-3-R-C7H5N2]+ X (L1−L4; R = Me, CH2Ph; X = Br, I) to C,N,S/Se ligands were synthesized by reaction of 1H-
benzimidazole with 2-bromo-N-(2-phenylthio/seleno)ethyl)acetamide (A1/A2), followed by treatment with methyl/benzyl
bromide/iodide. The reaction of L1−L4 with Ag2O followed by treatment with [Pd(CH3CN)2Cl2] resulted in complexes
̅
̅
−
̅
[Pd(C,N,E)Cl] (C1−C4), where the C,N ,E pincer ligand was derived from L1−L4. L1−L4 and C1−C4 were characterized
by elemental analyses, HR-MS, and 1H, 13C{1H}, and 77Se{1H} NMR spectroscopy. Single-crystal structures of L2 and C1−C3
established with X-ray diffraction reveal the geometry of palladium as being nearly square planar and alignment of NHC rings as
being nearly perpendicular to the coordination plane of Pd. In C1−C3 the Pd−C bond distances are in the range 1.974(5)−
1.982(2) Å. The Pd−S bond lengths for C1 and C3 are 2.369(10) and 2.357(7) Å, respectively. In C2, the Pd−Se bond
distance is 2.464(7) Å. C1−C4 can be stored under ambient conditions for several months without decomposition, indicating
their air and moisture insensitivity. Complexes C1−C4 were all found to be efficient for regioselective C-5 arylation of
imidazoles under aerobic conditions. The optimum catalyst loading for good conversion was found to be 0.5−1 mol %. A wide
range of ArCl/Br can be used with the present catalysts. Complexes C3 and C4 appear to be more efficient than C1 and C2.
Similarly the complexes of selenium-containing ligands are more efficient as catalysts in comparison to their sulfur counterparts.
C1−C4 were found to be recyclable up to six times for regioselective arylation of imidazole with very little decrease in
efficiency. The products of regioselective arylation of imidazole with few ArX were identified by X-ray diffraction on their single
crystals.
PPh3,6 AsPh3,7 PCy3,8 P(n-Bu)Ad2,9 X-phos,10 Xantphos,11
INTRODUCTION
■
and 1,10-phenanthroline.12 N-heterocyclic carbenes (NHCs),
due to their strong σ donation and tunable steric properties,
are considered advantageous as ligands over phosphines.13
Probably due to this σ donation their complexes are usually
resistant to decomposition.14 However, examples of palladium
NHC complex catalyzed direct C−H arylation of imidazoles
with aryl halides are few15 and most of them suffer from two
shortcomings: (i) limited scope of substrate (ArX or
The atom-economical and environmentally friendly palladium-
catalyzed direct arylation of heteroarenes with aryl halides is
important in the context of pharmaceuticals, polymers, natural
products, functional materials, and biological science.1−4 In the
case of imidazoles the C4 position is inactive for palladium-
catalyzed direct arylation, whereas the C2 and C5 positions are
reactive.5 Nonpolar solvents in the presence of copper salt or
strong base are reported suitable for C2 arylation and polar
solvents (DMF or DMA) for C5 arylation in the presence of
acetate or pivalate. The common catalytic system for arylation
of imidazole is Pd(OAc)2 associated with ligands such as
Received: April 20, 2018
© XXXX American Chemical Society
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Scheme 1. Synthesis of L1−L4 and Their Pd(II) Complexes C1−C4
imidazole) and (ii) high loading (up to 5 mol % of Pd) of
complex required for efficient catalysis. The arylation of C−H
bond with palladium NHC complexes is challenging under
aerobic conditions16 because many times the real catalytic
species with oxygen forms the peroxo derivative LPd(O2)
rapidly, blocking the catalytic activity. Thus, an anhydrous and
oxygen-free environment is needed for catalytic reactions.
NHCs functionalized with donor groups become chelating
(sometimes pincer) type ligands. They have interesting
properties17a and give metal complexes17 of increased stability
that are advantageous in catalysis. The combination of amidate
and S/Se donor group can enhance the stability even in a
nucleophilic solvent, as amidate N and S/Se would increase the
electron density on palladium, shown to be advantageous in
several catalytic reactions.20,21b Some N-heterocyclic carbene
amidates have been reported in the past decade. Lee and co-
workers18 reported in 2007 palladium(II) and nickel(II)
complexes of anionic amidate NHC ligands. Ghosh and co-
workers synthesized nickel(II), palladium(II), gold(I), and
silver(I) complexes of amido-functionalized NHCs.19 Jung and
co-workers have concluded that tridentate anionic amidate
NHC ligands enhance the stability of Pd(II) complexes,20
important in catalyst design. Some catalytic applications of
palladium complexes of anionic amidate NHC ligands are
known.21 However, there has been only one report on direct
C−H activation of imidazole with aryl bromides catalyzed by
Pd complexes (2 mol %) of amidate NHC ligand.15b
found promising for C−C coupling. In 2017, Singh and co-
workers reported Hg(II) and Pd(II) complexes of a
selenoether-bridged bis-carbene ligand23 and explored them
to catalyze Heck coupling. Thus, in continuation of our
interest in selenium-containing NHCs and with the motivation
of the better catalytic results with a selenium-containing NHC,
it was thought worthwhile to design chalcogenated amidate
NHC ligands. The advantages of both coordination with
chalcogen (resulting efficient catalyst) and an amidate
functionality (enhancing stability) appear to be tailored in
such NHC ligands reported herein (Scheme 1). Their Pd
complexes were explored as catalysts for the regioselective C−
H arylation of imidazole under aerobic and mild reaction
conditions and found to be reusable. To the best of our
knowledge, such Pd complexes of selenated/sulfated NHC
amidate ligands as catalysts for regioselective C−H arylation of
imidazole are reported for the first time. Of course there has
been a report on applications of Pd(II) complexes of C,N,O
type donors as a catalyst for C−H arylation.15b
RESULTS AND DISCUSSION
■
The preparations of amide-functionalized 1H-benzimidazolium
salts L1−L4 and palladium(II) complexes C1−C4 derived
from them are shown in Scheme 1. A1/A2 (Scheme 1) was
prepared by nucleophilic substitution reaction of 2-(phenyl-
thio/seleno)ethanamine with bromoacetyl bromide at 0 °C.
The treatment of A1/A2 with 1H-benzimidazole in the
presence of potassium carbonate in DMF gave B1/B2, which
was subjected to methylation/benzylation to obtain the
chalcogenated amide-functionalized 1H-benzimidazolium salts
L1−L4 in nearly quantitative yield (93−95%). L1−L4 have
good solubility in common organic solvents such as DMSO,
DMF, CHCl3, CH2Cl2, and CH3CN and are insoluble in
Chalcogenated ligands have emerged as attractive alter-
natives to phosphines, as their transition-metal complexes are
generally air and moisture insensitive.22 The presence of a
thioether group in an NHC ligand introduces hemilability
suitable for catalysis. In 2013, our group reported the first
selenium-containing NHC, and its Pd(II) complex22a was
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diethyl ether and hexane. They were authenticated with HR-
1
1
MS and H, 13C{1H}, and 77Se{1H} NMR spectra. The H
NMR spectra show a characteristic singlet due to −NCH3 for
L1 and L2 and −NCH2Ph for L3 and L4 (see the
Experimental Section and Figures S5−S8 in the Supporting
1
Information). The signals of H11 observed in the H NMR
spectra of L1−L4 are in agreement with the signal of a similar
proton, reported earlier, in the spectrum of a related
benzimidazolium salt20,22a and indicate its high acidity. The
Ag2O acting as a mild base predominantly replaces the
carbenic proton24 of azolium salt without deprotonation of
other acidic protons. Thus, H11 is substituted by Ag, giving the
Ag-NHC complex as a white solid on treating benzimidazo-
lium salts L1−L4 with Ag2O in CH2Cl2 a under nitrogen
atmosphere and in the absence of light (Scheme 1). On
addition of the Ag-NHC complex to a suspension of
[Pd(CH3CN)2Cl2] in CH3CN at room temperature [Pd-
(C,N−,E)Cl] (C1−C4) resulted.
Figure 1. Molecular structure of L2. Selected bond distances (Å):
Se(1)−C(6) 1.911(5); Se(1)−C(7) 1.954(5); O(1)−C(9) 1.224(5);
N(3)−C(9) 1.333(5); N(3)−C(8) 1.463(6). Selected bond angles
(deg): C(6)−Se(1)−C(7) 101.1(2); C(11)−N(1)−C(10) 125.7(4);
C(9)−N(3)−C(8) 120.6(4); O(1)−C(9)−N(3) 125.0(4); O(1)−
C(9)−C(10) 120.4(4); N(3)−C(9)−C(10) 114.6(4).
C1−C4, isolated as yellow solids, were found to be air and
moisture insensitive and storable for several months as solids
under ambient conditions. They are readily soluble in polar
solvents such as CH2Cl2, CH3CN, DMF, and DMSO and
sparingly in nonpolar solvents such as n-hexane and diethyl
ether. C1−C4 were characterized with 1H, 13C{1H}, and
1
77Se{1H} NMR spectra and HR-MS. Their H and 13C{1H}
spectral data (see the Experimental Section and Figures S9−
S12 and S34−S38 in the Supporting Information) are
consistent with their molecular structures depicted in Scheme
1. The deshielding of signals in 77Se{1H} NMR spectra implies
coordination of Se with palladium(II). The signal of carbene
(around 165 ppm) in the 13C{1H} NMR spectra of C1−C4
(Figures S34−S36 and S38 in the Supporting Information)
supports palladation at the carbene carbon atom.22a In HR-MS
of L1−L4, peaks appearing at m/z 326.1321, 374.0766,
402.1637, and 450.1076, respectively, are ascribed to
benzimidazolium cations (Figures S43−S46 in the Supporting
Information). In HR-MS of C1, the peak appearing at m/z
448.0306 may be ascribed to [M − Cl + H2O]+ (Figure S47 in
the Supporting Information), and for C2−C4, peaks appearing
at m/z 477.9641, 506.0520, and 553.9975 may be ascribed to
their cationic fragments [M − Cl]+ (Figures S48−S50 in the
Supporting Information).
Figure 2. Molecular structure of C1. Selected bond distances (Å):
Pd(1)−C(11) 1.978(3); Pd(1)−N(3) 2.008(3); Pd(1)−Cl(1)
2.317(9); Pd(1)−S(1) 2.369(10). Selected bond angles (deg):
N(3)−Pd(1)−C(11) 87.50(12); C(11)−Pd(1)−Cl(1) 95.75(9);
N(3)−Pd(1)−S(1) 85.31(8); Cl(1)−Pd(1)−S(1) 91.61(3); N(3)−
Pd(1)−Cl(1) 176.00(8); C(11)−Pd(1)−S(1) 171.82(9).
Crystal Structures. Single crystals of C1−C3 suitable for
X-ray diffraction were grown by slow evaporation of their
concentrated solutions made in CH2Cl2/diethyl ether under
ambient conditions. The single crystal of L2 was obtained by
layering its solution in CH2Cl2 with diethyl ether at ambient
temperature. Figures 1−4 show the molecular structures of L2
and complexes C1−C3 along with their selected bond lengths
and angles relevant to the geometry of the central atom. Their
crystal data and structure refinement parameters are
summarized in Tables S1−S4 in the Supporting Information.
In complexes C1−C3, palladium has a distorted-square-planar
geometry, as bond angles on Pd are close to 90 and 180°. The
ligands are coordinated to palladium in a tridentate mode by
amido nitrogen, chalcogen, and the carbene carbon, forming
one five-membered and another six-membered chelate ring.
The NHC ring is nearly perpendicular to the coordination
plane of Pd. The Pd−N bond lengths in C1−C3 are 2.008(3),
2.012(4), and 2.014(18), Å respectively, consistent with those
of an amidate NHC Pd complex (1.992(3) Å).25a The Pd−N
bond length reported for a neutral amine NHC Pd complex is
2.058(12) Å.25b In an anionic amide NHC Pd complex the
Figure 3. Molecular structure of C2. Selected bond distances (Å):
Pd(1)−C(11) 1.974(5); Pd(1)−N(3) 2.012(4); Pd(1)−Cl(1)
2.312(14); Pd(1)−Se(1) 2.464(7). Selected bond angles (deg):
N(3)−Pd(1)−C(11) 87.32(19); C(11)−Pd(1)−Cl(1) 96.00(15);
N(3)−Pd(1)−Se(1) 85.61(12); Cl(1)−Pd(1)−Se(1) 91.17(4);
N(3)−Pd(1)−Cl(1) 175.87(13); C(11)−Pd(1)−Se(1) 172.51(14).
Pd−N bond length is reported as 2.006(4) Å,25c consistent
with the length of the Pd−N bonds in complexes C1−C3. The
geometry around N3 is approximately trigonal planar, as
shown by the sums of bond angles at N3 of 357.9° (C1),
C
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thioether-functionalized imidazolium salt.25d The Pd−Cl
bond distances of C1−C3, 2.317(9), 2.312(14), and
2.311(6) Å, respectively, are consistent with the range
2.303(18)−2.330(10) Å reported for amidate NHC Pd
complexes.25a
In the crystals of C1−C3, supramolecular structural patterns
(Figures S101−S103 in the Supporting Information) develop
due to secondary interactions (Table S5 in the Supporting
Information for interatomic distances) arising most probably
due to packing.
Catalytic Regioselective Arylation of C−H Bond of
Imidazole. Complexes C1−C4 were explored as catalysts for
direct C−H bond arylation of imidazole with aryl halides,
under ambient conditions. The conversions were monitored
1
with H NMR spectroscopy. The arylation of 1-methyl-1H-
Figure 4. Molecular structure of C3. Selected bond distances (Å):
Pd(1)−C(11) 1.982(2); Pd(1)−N(3) 2.014(18); Pd(1)−Cl(1)
2.311(6); Pd(1)−S(1) 2.357(7). Selected bond angles (deg):
N(3)−Pd(1)−C(11) 87.53(8); C(11)−Pd(1)−Cl(1) 97.72(6);
N(3)−Pd(1)−S(1) 85.90(6); Cl(1)−Pd(1)−S(1) 88.88(3); N(3)−
Pd(1)−Cl(1) 173.61(6); C(11)−Pd(1)−S(1) 173.39(6).
imidazole with 4-bromobenzonitrile was chosen as a model
reaction. In the presence of pivalic acid, K2CO3, and 0.5 mol %
of catalyst loading under aerobic conditions, good conversion
(Table 1; entry 5) resulted. The yield of regioselective
arylation at the C5 position was 97% with catalyst C2. The
yield became poor when K2CO3 was replaced with other bases:
viz., Cs2CO3, KOH, KOtBu, and KOAc (Table 1; entries 1−4).
Probably K2CO3 and PivOH provide a suitable combination of
acid and base to generate coordinatively unsaturated Pd
species, as proposed in the tentative mechanism in Scheme S1
(section B in the Supporting Information). The influence of
solvent on direct C−H bond arylation of imidazole was
studied. Polar aprotic solvents such as DMSO, DMA, DMF,
1,4-dioxane, and N-methylpyrrolidone (NMP) were examined,
as their interaction with Pd via oxygen can stabilize the Pd-
containing intermediates as proposed in tentative mechanism
358.18° (C2), and 354.6° (C3). The Pd−C bond distances
1.978(3), 1.974(5) and 1.982(2) Å in C1−C3, respectively,
are similar to the values 1.978(4)−1.989(4) Å reported for
[PdCl2(S,CNHC)ligand] complexes.26 The Pd−Se bond dis-
tance (2.464(7) Å) in C2 is longer than the value of
2.3909(15) Å reported for Pd(II) complexes of selenium-
containing N-heterocyclic carbenes.22a The Pd−S bond
distances of C1 and C3 (2.369(10) and 2.357(7) Å,
respectively) are consistent with the value 2.3079(3) Å
reported for a Pd−S bond of a Pd(II) complex of a
a
Table 1. Optimization of Reaction Conditions for Direct Arylation Reaction
b
b
entry no.
base (2 mmol)
additive
catalyst (mol %)
solvent (3 mL)
yield (%)
selectivity (%)
1
2
3
4
5
6
7
8
KOAc
Cs2CO3
KOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
-
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
2
DMA
DMA
DMA
DMA
DMA
DMSO
DMF
Dioxane
NMP
Toluene
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
57
11
18
10
97
nd
72
11
70
9
>99
>99
80
69
nd
nd
9
92
96
94
94
98
KOtBu
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
K2CO3
96
94
95
95
98
98
98
98
9
10
11
12
13
14
15
16
17
1
0.1
0.05
0.5
0.5
0.5
0.5
PhCOOH
PhCOOH
PivOH
95
c
18
nd
a
Reaction conditions: 4-bromobenzonitrile, 1 mmol; 1-methyl-1H-imidazole, 2 mmol; complex C2, 0.05−2 mol %; additives, 0.3 mmol; bath
b
c
1
temperature, 110 °C; reaction time, 10 h; under aerobic conditions. Determined with H NMR. Control experiment without C2: time, 24 h.
D
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a
Table 2. Direct Arylation of 1-Methyl-1H-imidazole with Aryl Halides
a
Reaction conditions unless specified otherwise: aryl halide, 1 mmol; 1-methyl-1H-imidazole, 2 mmol; catalyst, 0.5 mol %; PivOH, 0.3 mmol;
b
DMA, 3 mL; bath temperature, 110 °C; reaction time, 10 h under aerobic conditions; isolated yield. Reaction conditions: aryl chloride, 1 mmol:
catalyst, 1 mol %; reaction time, 20h.
in Scheme S1 (section B in the Supporting Information). The
use of DMA resulted in an excellent yield (Table 1; entry 5), as
it gives optimum stability and is more reducing in nature than
the other solvents explored. No coupled product was obtained
in DMSO (Table 1; entry 6). In the case of DMF and NMP,
70−72% yield was obtained (Table 1; entries 7 and 9). In 1,4-
dioxane, the yield was poor (Table 1; entry 8). The use of a
nonpolar solvent gives poor conversion (Table 1; entry 10).
The amount of catalyst was optimized. A loading of 0.5 mol %
gave the maximum conversion (Table 1; entry 5). When the
catalyst loading was lowered to 0.1 and 0.05 mol %, the yield
dropped to 80% and 69%, respectively (Table 1; entries 13 and
14). The additive pivalic acid (PivOH) was found to be
essential, as in its absence no product was obtained (Table 1;
entry 15). Its role is to generate coordinatively unsaturated Pd
as its proton neutralizes the anionic nitrogen of the amidate
fragment, which helps in cleavage of the Pd−N bond, and that
of a proton shuttle during aryl C−H bond cleavage.27 A 0.3
mmol amount of pivalic acid was used, consistent with a
concerted metalation−deprotonation (CMD) pathway of
catalytic arylation of the C−H bond of imidazole.27,31 The
yield was negligible when PivOH was replaced with benzoic
acid (Table 1; entry 16). Using other bases such as Cs2CO3
also resulted in poor yields in the presence of the additive
benzoic acid (Table 1; entry 17). Benzoic acid being stronger
than pivalic acid stabilizes the intermediate and does not allow
further catalysis (see tentative mechanism in Scheme S1,
section B in the Supporting Information). In the absence of
catalyst, no product was obtained even after 24 h (Table 1,
entry 18).
The conditions 1 mmol of 1-methyl-1H-imidazole, 0.5 mol
% of Pd as a catalyst (complex C2), 2 mmol of K2CO3 as a
base, 0.3 mmol of PivOH as an additive, 3 mL DMA as a
solvent, and 110 °C as a reaction temperature under aerobic
conditions gave the maximum yield in a reaction time of 10 h.
However, in the course of the present catalytic reaction, C-4
arylation of the imidazole and homocoupling of the aryl
bromides were observed to a very small extent.
With the optimized reaction conditions, the catalytic activity
of all complexes C1−C4 was explored for direct arylation of 1-
methyl-1H-imidazole with aryl halides (Table 2). It was found
that aryl halides with a wide range of functional groups such as
chloro, aldehyde, acetyl, cyano, and nitro gave good to
excellent yields (71−97%) (Table 2, 1b−d,g,i−k). Heteroaryl
bromides, viz. 3-bromopyridine (Table 2, 1a), 3-bromoquino-
line (Table 2, 1e) also resulted in 70−93% yield when C1−C4
E
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a
Table 3. Direct Arylation of 1,2-Dimethyl-1H-imidazole with Aryl Halides
a
Reaction conditions unless specified otherwise: aryl halide, 1 mmol; 1,2-dimethyl-1H-imidazole, 2 mmol; catalyst, 0.5 mol %; PivOH, 0.3 mmol;
b
DMA, 3 mL; bath temperature, 110 °C; reaction time, 10 h; under aerobic conditions; isolated yield. Reaction conditions: aryl chloride, 1 mmol;
catalyst, 1 mol %; reaction time, 20 h.
were used as catalysts. With sterically hindered 1-naphthyl
bromide an excellent yield of 91% of the coupled product was
obtained with C4 (Table 2, 1f). The 1-naphthyl group
optimizes the stability of CMD transition state for catalysis.
Substrates with electron-donating substituents afforded the
desired coupled products in moderate yields of 70−84%
(Table 2, 1h). Such an effect is due to an increase in the
stability of Ar−X bond. Moreover, the position of substituent
relative to halogen (ortho, meta, and para) (Table 2, 1i−k) on
the aromatic ring also affected the efficiency of the catalyst. An
ortho-substituted derivative gave low yields of 68−75% (Table
2, 1i), followed by meta (74−85% yield) (Table 2, 1j). The
maximum yield was obtained in case of para-substituted
derivatives (88−95% yield) (Table 2, 1k). An ortho subsituent
has the highest steric influence and a para substituent the least.
The yield with 1-bromobenzene was 68−77% (Table 2, 1l).
The reaction was feasible with ArCl (Table 2, 1c) and gave the
desired product albeit in low yield (52−64%) with 1 mol %
catalyst loading and in a reaction time of 24 h. This is due to
high ArCl bond energy. 1b,f,g,l are important intermediates of
bioactive compounds and functional materials.28 Another
substituted imidazole, 1,2-dimethyl-1H-imidazole, was inves-
tigated for direct arylation with aryl and heteroaryl halides
(Table 3) having various substituents (sterically hindering,
electron donating, and withdrawing). The C5-monoarylated
imidazole was obtained as the predominant product (yield up
to 97%) in the process catalyzed with C1−C4. The
regioselectivity of C5-arylated products is supported by the
single-crystal structures of 1f,g and 2k established by X-ray
diffraction (Figures 5−7 for molecular structures and Tables
Figure 5. Molecular structure of 1g.
S6 and S7 in the Supporting Information for details of crystal
data and refinement). With ArCl the reaction was carried out
for a longer time (20 h) to obtain a respectable yield. However,
the yield was better than that of 1-methyl-1H-imidazole.
The catalytic performance of C3 and C4 is better in
comparison to C1 and C2. The efficiency of a catalyst having
Se (C2 and C4) was somewhat higher than that of their sulfur
analogues (C1 and C3), as reported earlier.22b Among
F
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temperature, and time are 2 mol %, 140 °C, and 18 h,
respectively.15b Thus, complexes C1−C4 for regioselective
arylation of imidazole are very promising under aerobic
conditions, as the optimum loading is low and the reaction
time is short.
The recyclability of complexes C1−C4 for arylation of 1-
methyl-1H-imidazole and 1,2-dimethyl-1H-imidazole was
studied. A fresh lot of 1-methyl-1H-imidazole/1,2-dimethyl-
1H-imidazole, 4-bromobezonitrile, pivalic acid, and base was
added to the reaction vessel after completion of a cycle of the
arylation reaction (see the Experimental Section). The
complex catalyst showed good catalytic activity until the
sixth cycle with some decrease in efficiency. The results of
recycling experiments with complex C1, with respective yields
after each run, are depicted in Figure 8. With the other three
complexes the results of recyclability tests were found to be
similar.
Figure 6. Molecular structure of 1f.
Figure 7. Molecular structure of 2k.
complexes C1−C4, the more efficient performance of C3 and
C4 having a benzyl group suggests that an increase in bulkiness
at N2 of the benzimidazole moiety would stabilize the L′Pd0
species on exposure to air and thus facilitate the reductive
elimination process in the transformation. The arylation of 1-
methyl-5-nitroimidazole, in which the C-5 position of the 1-
methylimidazole was blocked with a nitro group, the expected
C-4-arylated product resulted in <5% yield. With 1,4,5-
trimethyl-1H-imidazole, in which both the C-4 and C-5
positions were blocked by methyl groups, the product having
arylation at the C-2 position was not detected.
Figure 8. Catalytic life of C1 tested under optimum conditions.
A comparison of the catalytic efficiency of C1−C4 for
arylation of imidazole with those of other Pd(II) complexes
reported earlier for the same purpose has been made.
Palladium phosphine functionalized NHC complexes (2.5
mol %, 140 °C, 18 h, N2 atmosphere)15a and the dipalladium
triazolidinediylidene complex trans-[PdBr2(CH3CN)]2(μ-ditz)
(ditz = 1,2,4-trimethyltriazolidine-3,5-diylidene (2.5 mol %,
140 °C, 18 h, N2 atmosphere)15c are less efficient than C1−
C4. Liu and co-workers have reported tetraarylimidazolium
carbene Pd PEPPSI complexes to be efficient as catalysts for
arylation of imidazole at 1 mol % loading,1a which is higher
than those of C1−C4. Recently Liu and co-workers
synthesized a series of bulky bis(imino)acenaphthene
(BIAN)-supported Pd PEPPSI complexes and applied them
to direct arylation of azoles,29a but they were found to show
low efficiency for chloro derivatives and nonrecyclability. An
NHC Pd(II) Im complex is claimed to be efficient for C−H
arylation with aryl chlorides, but the catalyst loading for good
yields is 2−4 mol % and the reaction requires an inert
atmosphere.29b Palladium(II) acetate complexes with phos-
phine and carbene ligands, Pd(L)(PR3)(OAc)2 (R = Ph/Cy; L
= 1,3-dibenzylimidazol-2-ylidene), developed by Lee and co-
workers are effective for direct C5-arylation of imidazoles with
aryl chlorides when the catalyst loading is 2.5 mol %.15d The
catalyst loading of C1−C4 is lower than most of these Pd
complexes reported for regioselective arylation of imidazole.
However, there has been a very recent report on direct C−H
functionalization of heterocyclic compounds with aryl
bromides in which Pd(II) complexes of anionic amidate
NHC ligands are catalysts. The optimum loading, reaction
Nature of Catalysis. To ascertain the nature of catalytic
reactions (homogeneous or heterogeneous), mercury and PPh3
poisoning tests30 were carried out. The presence of an excess
of mercury (Pd/Hg (1/400), 5 mol % of PPh3) in arylation of
imidazole catalyzed by C1−C4 under optimum reaction
conditions showed a negligible inhibitive effect on the
conversion (Table S8 in the Supporting Information). Thus,
the present catalysis appears to be homogeneous in nature.
CONCLUSION
■
A simple method for the synthesis of [Pd(C,N−,S/Se)Cl]
(C1−C4), the first Pd(II) complexes of tridentate chalco-
genated amide functionalized NHCs derived from N-alkyl-N′-
(2-(phenylthio/selanyl)ethylacetamide)benzimidazolium salts
(L = L1−L4) via a transmetalation reaction with silver, is
reported. The carbene precursors L1−L4 were synthesized by
an easy route, and the Pd(II) complexes C1−C4 were
authenticated with HR-MS and multinuclei NMR. Single-
crystal structures of L2 and C1−C3 were established with X-
ray diffraction. The geometry of Pd in C1−C3 is nearly square
planar. The ligands behave as S/Se,N−,CNHC donors. The air-
and moisture-stable complexes C1−C4 effectively catalyze
direct regioselective C−H functionalization reactions between
imidazoles and aryl halides under aerobic conditions. With a
low Pd loading the yield is good to excellent. In the substrates
both electron-rich and -poor substituents are well tolerated:
i.e., the yield is good to high. The catalyst remains active even
in the sixth reaction cycle, for the regioselective arylation of
imidazole.
G
DOI: 10.1021/acs.organomet.8b00246
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(0.354 g, 3.0 mmol) and K2CO3 (0.442g, 3.2 mmol) were added and
the reaction mixture was stirred at room temperature for 10 h. After
completion of the reaction, the mixture was poured into water and
extracted with ethyl acetate (3 × 25 mL). The organic layer was dried
with anhydrous sodium sulfate. The solvent was evaporated off on a
rotary evaporator, resulting in a white solid (B1/B2).
EXPERIMENTAL SECTION
■
Materials and Instrumentation. Palladium chloride, silver
oxide, bromoacetyl bromide, diphenyl diselenide, 2-chloropropyl-
amine hydrochloride, and sodium borohydride were procured from
Sigma-Aldrich (USA). Thiophenol, benzimidazole, methyl iodide,
base, pivalic acid, 1-methyl-1H-imidazole, 1,2-dimethyl-1H-imidazole,
and various aryl halides were procured from local sources. 2-
(Phenylthio)ethylamine22d/2-(phenylseleno)ethylamine32 and [Pd-
(CH3CN)2Cl2]22a were prepared by following the procedure reported
earlier. Commercial nitrogen gas was used after passing it successively
through traps containing solutions of alkaline anthraquinone, sodium
dithionite, alkaline pyrogallol, concentrated H2SO4, and KOH pellets.
Yields reported are of isolated coupled products which have purity
B1: white solid, yield 0.914 g (98%). 1H NMR (300 MHz, DMSO-
d6, 25 °C, TMS): δ (ppm) 3.05 (t, 2H, J = 6 Hz, H7), 3.30 (t, 2H, J =
6 Hz, H8), 4.93 (s, 2H, H10), 7.19−7.23 (m, 2H), 7.26−7.38 (m, 5H),
7.44 (d, 1H, J = 6.9 Hz), 7.66 (d, 1H, J = 6.9 Hz), 8.16 (s, 1H), 8.58
(s, 1H). 13C{1H} NMR (75 MHz, DMSO-d6, 25 °C, TMS): δ (ppm)
31.4 (C7), 38.4 (C8), 46.7 (C10), 110.2, 119.3, 121.5, 122.3, 125.8,
128.1, 129.1, 134.2, 135.5, 143.2, 144.8, 166.7 (C9). HR-MS: [M +
H]+ m/z 312.1170; calcd value for C17H18N3OS 312.1165 (ppm error
δ: 1.5).
1
1
≥95% (established by H NMR). The H, 13C{1H}, and 77Se{1H}
NMR spectra were recorded on a Bruker Spectrospin DPX-300 NMR
spectrometer at 300.13, 75.47, and 57.24 MHz, respectively, with
chemical shifts reported in ppm relative to internal standards. Carbon-
13 DEPT NMR experiments were used routinely to determine the
number of hydrogen atoms linked to a carbon atom. Thin-layer
chromatography (TLC) was performed using silica gel plates 60 F254
visualized with short-wavelength UV light (254 nm). Silica gel (100−
200 mesh) was used for column chromatography. All reactions were
carried out in glassware dried in an oven. Melting points were
determined in an electrically heated apparatus by taking the sample in
a glass capillary sealed at one end. High-resolution mass spectral (HR-
MS) measurements were performed with an Bruker Micro TOF-Q II
instrument, based on electron spray ionization (10 eV, 180 °C source
temperature, and sodium formate as calibrant), taking the sample in
CH3CN. Single-crystal X-ray diffraction studies were carried out on a
Bruker SMART APEX CCD diffractometer and Bruker D8 Quest
CMOS diffractometer using a Mo Kα (λ = 0.71073 Å) sealed tube.
The data frames were collected at T = 298 K using the program
APEX3 and processed using the SAINT routine in APEX3. The
structures were solved by direct methods and refined by full-matrix
least squares on F2 using the SHELXTL-2014/7 program. All
hydrogen atoms were included in idealized positions, and a riding
model was used for the refinement. Images were created using the
program Diamond.
B2: white solid, yield 1.053 g (98%). 1H NMR (300 MHz, DMSO-
d6, 25 °C, TMS): δ (ppm) 3.03 (t, 2H, J = 9 Hz, H7), 3.40 (t, 2H, J =
9 Hz, H8), 4.92 (s, 2H, H10), 7.21−7.32 (m, 5H), 7.43−7.52 (m, 3H),
7.67 (d, 1H, J = 6.6 Hz), 8.17 (s, 1H), 8.58 (s, 1H, N−H). 13C{1H}
NMR (75 MHz, DMSO-d6, 25 °C, TMS): δ (ppm) 25.7 (C7), 39.3
(C8), 46.8 (C10), 110.3, 119.4, 121.6, 122.4, 126.7, 129.3, 129.6,
131.4, 134.3, 143.2, 144.9, 166.7 (C9). 77Se{1H} NMR (DMSO-d6, 25
°C, Me2Se): δ (ppm) 268.74. HR-MS: [M + H]+ m/z 360.0618; calcd
value for C17H18N3OSe 360.0610 (ppm error δ: 2.3).
Synthesis of L1−L4. In a 50 mL round-bottom flask equipped
with a magnetic stirrer were placed B1 (0.934 g, 3.0 mmol)/B2
(1.075 g, 3.0 mmol) with methyl iodide (0.426 g, 3.0 mmol)/benzyl
bromide (0.513 g, 3.0 mmol) and acetonitrile (1 mL). The mixture
was stirred at room temperature for 10 h under an N2 atmosphere.
The white solid obtained was filtered, washed with THF, and dried in
vacuo to obtain L1−L4.
L1: white solid, yield 1.291 g (95%). Anal. Calcd for C18H20IN3OS:
1
C, 47.69; H, 4.45; N, 9.27. Found: C, 47.68; H, 4.45; N, 9.26. H
NMR (300 MHz, DMSO-d6, 25 °C, TMS): δ (ppm) 3.09 (t, 2H, J =
6.9 Hz, H7), 3.37 (t, 2H, J = 6.9 Hz, H8), 4.15 (s, 3H, H18), 5.32 (s,
2H, H10), 7.19−7.22 (m, 1H), 7.30−7.39 (m, 4H), 7.69−7.72 (m,
2H), 7.91 (t, 1H, J = 2.4 Hz), 8.04 (t, 1H, J = 2.4 Hz), 8.79 (br, 1H),
9.73 (s, 1H). 13C{1H} NMR (75 MHz, DMSO-d6, 25 °C, TMS): δ
(ppm) 31.9 (C7), 33.9 (C8), 39.0 (C18), 48.9 (C10), 113.9, 114.1,
126.4, 127.0, 127.2, 128.7, 129.6, 131.9, 132.0, 135.8, 144.1, 165.2.
HR-MS: [M − I]+ m/z 326.1320; calcd value for C18H20IN3OS =
326.1321 (ppm error δ: 0.3).
L2: white solid, yield 1.410 g (94%). Anal. Calcd for
C18H20IN3OSe: C, 43.22; H, 4.03; N, 8.40. Found: C, 43.20; H,
4.02; N, 8.39. 1H NMR (300 MHz, DMSO-d6, 25 °C, TMS): δ
(ppm) 3.05 (t, 2H, J = 6 Hz, H7), 3.41 (t, 2H, J = 6 Hz, H8), 4.15 (s,
3H, H18), 5.30 (s, 2H, H10), 7.26−7.33 (m, 3H), 7.50 (d, 2H, J = 7.2
Hz), 7.69−7.72 (m, 5H), 7.89−7.91 (m, 2H), 8.05 (d, 1H, J = 8.1
Hz), 8.79 (s, 1H), 9.71 (s, 1H). 13C{1H} NMR (75 MHz, DMSO-d6,
25 °C, TMS): δ (ppm) 26.1 (C7), 33.9 (C8), 39.8 (C18), 48.8 (C10),
113.9, 114.1, 126.9, 127.2, 127.2, 129.8, 129.9, 131.8, 131.9, 132.0,
144.1, 165.1. 77Se{1H} NMR (DMSO-d6, 25 °C, Me2Se): δ (ppm)
269.26. HR-MS: [M − I]+ m/z 374.0766; calcd value for
C18H20IN3OSe 374.0767 (ppm error δ: 0.2).
L3: white solid, yield 1.374 g (95%). Anal. Calcd for
C24H24BrN3OS: C, 59.75; H, 5.01; N, 8.71. Found: C, 59.74; H,
5.01; N, 8.70. 1H NMR (300 MHz, DMSO-d6, 25 °C, TMS): δ
(ppm) 3.09 (t, 2H, J = 6.0 Hz, H7), 3.33−3.36 (br, 2H, H8), 5.37 (s,
2H, H18), 5.87 (s, 2H, H10), 7.17−7.22 (m, 1H), 7.29−7.44 (m, 7H),
7.52 (d, 2H, J = 6.0 Hz), 7.64−7.69 (m, 2H), 7.94 (t, 1H, J = 6.0 Hz),
8.00 (t, 1H, J = 6.0 Hz), 8.95 (s, 1H), 9.99 (s, 1H). 13C{1H} NMR
(75 MHz, DMSO-d6, 25 °C, TMS): δ (ppm) 31.4 (C7), 38.5 (C8),
48.6 (C18), 49.8 (C10), 113.8, 113.9, 125.9, 126.7, 126.857, 128.2,
128.8, 129.0, 129.1, 130.5, 131.8, 133.9, 135.4, 143.6, 164.8. HR-MS:
[M − Br]+ (m/z) = 402.1637; calcd. value for C24H24N3OS =
402.1635 (ppm error δ: 0.7).
Synthesis of 2-Bromo-N-(2-(phenylthio/seleno)ethyl)-
acetamide (A1/A2). Bromoacetyl bromide (1.211 g, 6.0 mmol)
was added dropwise (with a dropping funnel) at 0 °C to a solution of
2-(phenylthio)ethylamine (0.919 g, 6.0 mmol)/2-(phenylseleno)-
ethylamine (1.200 g, 6.0 mmol) in CH2Cl2 (30 mL) placed in a 50
mL round-bottom flask equipped with a magnetic stirrer. After the
reaction mixture was stirred for 3 h at 0 °C, water (20 mL) was added.
The aqueous layer was separated and extracted with CH2Cl2 (30 mL).
The organic layer was washed with brine and dried over anhydrous
Na2SO4, and its solvent was evaporated off under reduced pressure on
a rotary evaporator, resulting in a white solid of A1/A2 which was
used further without any purification.
A1: white solid, yield 1.612 g (98%). 1H NMR (300 MHz, DMSO-
d6, 25 °C, TMS): δ (ppm) 3.03 (t, 2H, J = 6.6 Hz, H7), 3.27 (t, 2H, J
= 6.6 Hz, H8), 3.85 (s, 2H, H10), 7.19−7.22 (m, 1H), 7.29−7.38 (m,
4H), 8.54 (s, 1H, N−H). 13C{1H} NMR (75 MHz, DMSO-d6, 25 °C,
TMS): δ (ppm) 29.4 (C7), 31.2 (C8), 39.2 (C10), 125.8, 128.1, 129.1,
135.5 (C6), 166.1 (C9). HR-MS: [M + Na]+ m/z 295.9721; calcd
value for C10H12BrNNaOS 295.9715 (ppm error δ: 2.0).
1
A2: light yellow solid, yield 1.887 g (98%). H NMR (300 MHz,
DMSO-d6, 25 °C, TMS): δ (ppm) 2.99 (t, 2H, J = 6 Hz, H7), 3.33 (t,
2H, J = 6 Hz, H8), 3.84 (s, 2H, H10),7.24−7.33 (m, 3H), 7.48−7.52
(m, 2H), 8.55 (s, 1H, N−H). 13C{1H} NMR (75 MHz, DMSO-d6, 25
°C, TMS): δ (ppm) 25.8 (C7), 29.9 (C8), 40.0 (C10), 127.1, 129.7,
130.1 (C6), 131.8, 166.5 (C9). HR-MS: [M + Na]+ m/z 343.9158;
calcd value for C10H12BrNNaOSe 343.9156 (ppm error δ: 0.4).
Synthesis of 2-(1H-Benzimidazol-1-yl)-N-(2-(phenylthio/
seleno)ethyl)acetamide (B1/B2). In a 100 mL round-bottom
flask, 2-bromo-N-(2-(phenylthio)ethyl)acetamide (0.882 g, 3.0
mmol)/2-bromo-N-(2-(phenylselenyl)ethyl)acetamide (A1/A2;
0.963 g, 3.0 mmol) was taken and stirred with DMF (4 mL) on a
magnetic stirrer at room temperature. Subsequently benzimidazole
L4: White solid, Yield: 1.477 g (93%); Anal. Calcd for
C24H24BrN3OSe: C, 54.46; H, 4.57; N, 7.94. Found: C, 54.43; H,
4.56; N, 7.93. 1H NMR (300 MHz, DMSO-d6, 25 °C, TMS): δ
(ppm) 3.05 (t, 2H, J = 6.0 Hz), 3.40 (t, 2H, J = 6.0 Hz), 5.35 (s, 2H),
H
DOI: 10.1021/acs.organomet.8b00246
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
5.86 (s, 2H), 7.25−7.32 (m, 3H), 7.39−7.44 (m, 3H), 7.48−7.53 (m,
4H), 7.65 (t, 2H, J = 6.0 Hz), 7.92 (br, 1H), 8.00 (t, 1H, J = 6.0 Hz),
8.95 (s, 1H), 9.98 (s, 1H). 13C{1H} NMR (75 MHz, DMSO-d6, 25
°C, TMS): δ (ppm) 25.6 (C7), 40.1 (C8), 48.6 (C18), 49.9 (C10),
113.8, 113.9, 126.7, 126.8, 127.3, 128.2, 128.8, 129.0, 129.3, 129.4,
130.5, 131.4, 131.7, 133.9, 143.5, 164.6. 77Se{1H} NMR (DMSO-d6,
25 °C, Me2Se): δ (ppm) 269.73. HR-MS: [M − Br]+ m/z 450.1076;
calcd value for C24H24N3OSe 450.1080 (ppm error δ: 5.9).
Synthesis of Complexes C1−C4. L1/L2/L3/L4 (0.272/0.300/
0.289/0.317 g, 0.60 mmol) was dissolved in dry CH2Cl2 (30 mL).
Under a nitrogen atmosphere solid Ag2O (0.139 g, 0.60 mmol) was
added. The reaction mixture was stirred at room temperature for 5 h
with exclusion of light and then filtered with a Celite pad. The filtrate
obtained was concentrated to 15 mL on a rotary evaporator.
Thereafter, a suspension of [Pd(CH3CN)2Cl2] (0.156 g, 0.60
mmol) in CH3CN at room temperature under a nitrogen atmosphere
was added to the filtrate. The reaction mixture was further stirred for
6 h and filtered with a Celite pad. Thereafter, the filtrate was
evaporated to dryness on a rotary evaporator to give a yellow solid.
Dichloromethane was added slowly to the yellow solid until it
dissolved completely. Thereafter diethyl ether (30 mL) was added,
resulting in the formation of a yellow precipitate of C1−C4 which was
filtered and dried in vacuo.
monitored by TLC was carried out until maximum conversion to
product occurred. After completion of the reaction, the mixture was
cooled to room temperature and 30 mL of water was added. This
mixture was extracted with dichloromethane (3 × 15 mL). The
combined extract was washed with water and dried over anhydrous
Na2SO4. The solvent of the extract was removed under reduced
pressure with a rotary evaporator to obtain the product. The crude
products were purified by column chromatography on silica gel using
dichloromethane/methanol (20/1) as an eluent. The isolated cross-
coupled products were authenticated with 1H and 13C{1H} NMR
spectra given in Figures S51−S98 in the Supporting Information. For
X-ray crystallography suitable crystals of 1f,g and 2k were grown by
diffusion of ether vapor into a dichloromethane solution of these
compounds.
General Procedure for Reusability of Complex C1. In a 50
mL round-bottom flask, 4-bromobenzonitrile (1.0 mmol), 1-methyl-
1H-imidazole/1,2-dimethyl-1H-imidazole (2.0 mmol), pivalic acid
(0.30 mmol), K2CO3 (2.0 mmol), and catalyst C1 (0.5 mol %) in
DMA (3 mL) were heated on a bath (110 °C) for 10 h. Thereafter
the mixture was cooled to room temperature. An aliquot (100 μL)
1
was taken for analysis by H NMR spectroscopy, and a new batch of
4-bromobenzonitrile (1.0 mmol) and 1-methyl-1H-imidazole/1,2-
dimethyl-1H-imidazole (2.0 mmol) with other reagents was added.
The reaction mixture was stirred at 110 °C for another 10 h. The
aliquot analysis by 1H NMR and fresh substrate addition with
reagents was repeated six times.
C1: light yellow solid, yield 0.235 g (84%). Anal. Calcd for
C18H18ClN3OPdS: C, 46.36; H, 3.89; N, 9.01. Found: C, 46.32; H,
1
3.86; N, 9.08. Mp: 196 °C. H NMR (300 MHz, DMSO-d6, 25 °C,
TMS): δ (ppm) 2.87 (t, 2H, J = 6 Hz), 3.58 (br, 2H), 4.25 (s, 3H),
4.98 (s, 2H), 7.43−7.54 (m, 5H), 7.75−7.78 (m, 1H), 7.90−7.93 (m,
1H), 8.10−8.13 (m, 2H). 13C{1H} NMR (75 MHz, DMSO-d6, 25 °C,
TMS): δ (ppm) 29.0, 34.8, 50.1, 51.9, 111.4, 111.7, 124.0, 124.3,
129.7, 130.3, 132.3, 132.6, 133.8, 164.8, 166.6. HR-MS: [M − Cl +
H2O]+ m/z 448.0306; calcd value for C18H20N3O2PdS = 448.0312
(ppm error δ: 1.3).
C2: yellow solid, yield 0.271 g (88%). Anal. Calcd for
C18H18ClN3OPdSe: C, 42.13; H, 3.54; N, 8.19. Found: C, 42.19;
H, 3.51; N, 8.18. Mp: 210 °C. 1H NMR (300 MHz, DMSO-d6, 25 °C,
TMS): δ (ppm) 2.82 (br, 2H), 3.10 (br, 2H), 4.25 (s, 3H), 4.95 (s,
2H), 7.32−7.50 (m, 6H), 7.76 (br, 1H), 7.91 (br, 1H), 8.13 (br, 1H).
13C{1H} NMR (75 MHz, DMSO-d6, 25 °C, TMS): δ (ppm) 34.1,
34.7, 51.2, 51.9, 111.3, 111.7, 123.9, 124.2, 126.8, 129.4, 129.9, 131.6,
133.2, 133.8, 164.9, 166.8. 77Se{1H} NMR (DMSO-d6, 25 °C,
Me2Se): δ (ppm) 404.93. HR-MS: [M − Cl]+ m/z 477.9641; calcd
value for C18H18N3OPdSe 477.9656 (ppm error δ: 3.1).
Procedure for Hg/PPh3 Poisoning Test. In a round-bottom
flask, 4-bromobenzonitrile (1.0 mmol), 1-methyl-1H-imidazole (2.0
mmol), pivalic acid (0.30 mmol), and K2CO3 (2.0 mmol) were added
to DMA (3 mL). An excess of Hg/PPh3 (Hg/Pd 400/1)/(PPh3/Pd
5/1) was added. Thereafter the complex catalyst (one of C1−C4: 0.5
mol %) was added and the reaction carried out for 10 h under
optimum conditions. After standard workup of the reaction mixture,
1
percent conversion was determined with H NMR.
NMR Data of Arylated Products. 3-(1-Methyl-1H-imidazol-5-
yl)pyridine (1a).29a Pale yellow oil. H NMR (300 MHz, CDCl3, 25
1
°C, TMS): δ (ppm) 3.70 (s, 3H), 7.17 (s, 1H), 7.37−7.45 (m, 1H),
7.58 (s, 1H), 7.71−7.74 (m, 1H), 8.60−8.68 (m, 2H). 13C{1H} NMR
(75 MHz, CDCl3, 25 °C, TMS): δ (ppm) 32.5, 123.5, 123.6, 125.9,
129.0, 129.9, 135.5, 139.9, 149.2.
5-(4-Chlorophenyl)-1-methyl-1H-imidazole (1b).1a Pale yellow
1
solid. H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 3.65 (s,
3H), 7.08 (s, 1H), 7.31 (d, 2H, J = 8.4 Hz), 7.40 (d, 2H, J = 8.4 Hz),
7.51 (s, 1H). 13C{1H} NMR (75 MHz, CDCl3, 25 °C, TMS): δ
(ppm) 32.3, 128.0, 128.1, 128.7, 129.4, 132.0, 133.6, 139.1.
C3: yellow solid, yield 0.283 g (87%). Anal. Calcd for
C24H22ClN3OPdS: C, 53.15; H, 4.09; N, 7.75. Found: C, 53.16; H,
4-(1-Methyl-1H-imidazol-5-yl)benzaldehyde (1c).1a Off-white
1
4.09; N, 7.76. Mp: 200 °C. H NMR (300 MHz, DMSO-d6, 25 °C,
1
solid. H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 3.76 (s,
TMS): δ (ppm) 2.84 (t, 2H, J = 6 Hz), 3.56 (br, 2H), 5.03 (s, 2H),
6.21 (s, 2H), 7.30−7.47 (m, 10H), 7.70 (d, 1H, J = 7.5 Hz), 7.93 (d,
1H, J = 7.5 Hz), 8.00 (d, 2H, J = 7.5 Hz). 13C{1H} NMR (75 MHz,
DMSO-d6, 25 °C, TMS): δ (ppm) 40.2, 49.6, 51.7, 52.1, 111.7, 112.1,
124.0, 124.4, 127.3, 127.8, 128.0, 128.6, 129.1, 129.6, 130.1, 132.3,
133.0, 136.6, 165.5, 166.8. HR-MS: [M − Cl]+ m/z 506.0520; calcd
value for C24H22N3OPdS 506.0521 (ppm error δ: 3.9).
3H), 7.25 (s, 1H), 7.59 (d, 3H, J = 8.1 Hz), 7.96 (d, 2H, J = 8.4 Hz),
10.05 (s, 1H). 13C{1H} NMR (75 MHz, CDCl3, 25 °C, TMS): δ
(ppm) 32.9, 128.2, 129.7, 130.1, 132.2, 135.2, 135.8, 140.4, 191.5.
1-(4-(1-Methyl-1H-imidazol-5-yl)phenyl)ethanone (1d).1a Light
1
yellow solid. H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm)
2.64 (s, 3H), 3.73 (s, 3H), 7.22 (s, 1H), 7.51 (d, 2H, J = 8.4 Hz), 7.57
(s, 1H), 8.02 (d, 2H, J = 8.1 Hz). 13C{1H} NMR (75 MHz, CDCl3,
25 °C, TMS): δ (ppm) 26.6, 32.9, 128.0, 128.8, 129.3, 132.4, 134.4,
136.1, 140.2, 197.4.
C4: yellow solid. yield 0.287 g (80%). Anal. Calcd for
C24H22ClN3OPdSe: C, 48.92; H, 3.76; N, 7.13. Found: C, 48.91;
H, 3.75; N, 7.12. Mp: 220 °C. 1H NMR (300 MHz, DMSO-d6, 25 °C,
TMS): δ (ppm) 3.14 (br, 2H), 3.36 (br, 2H), 3.49 (br, 2H), 5.01 (s,
2H), 7.27−7.50 (m, 11H), 7.73 (d, 1H, J = 6.9 Hz), 7.94 (d, 1H, J =
8.4 Hz), 8.04 (d, 2H, J = 8.4 Hz). 13C{1H} NMR (75 MHz, DMSO-
d6, 25 °C, TMS): δ (ppm) 34.5, 50.0, 51.8, 52.6, 112.1, 112.6, 124.4,
124.8, 126.9, 127.9, 128.3, 129.1, 129.9, 130.2, 133.3, 133.4, 133.6,
137.0, 166.1, 167.5. 77Se{1H} NMR (DMSO-d6, 25 °C, Me2Se): δ
(ppm) 409.20. HR-MS: [M − Cl]+ m/z 553.9975; calcd value for
C24H22N3OPdSe 553.9971 (ppm error δ: 0.8).
General Procedure for Arylation Reaction. An oven-dried flask
(50 mL) was charged with 1-methyl-1H-imidazole (2.0 mmol) or 1,2-
dimethyl-1H-imidazole (2.0 mmol), aryl halide (1.0 mmol), base (2.0
mmol), acid additive (0.30 mmol), catalyst (one of C1−C4), and 3
mL of solvent. The flask was placed in an oil bath at 110 °C under
aerobic conditions, and the reaction mixture was stirred. The reaction
3-(1-Methyl-1H-imidazol-5-yl)quinoline (1e).33a Light yellow oil.
1H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 3.75 (s, 3H),
7.28 (s, 1H), 7.59−7.61 (m, 2H), 7.71−7.77 (m, 1H), 7.85 (d, 1H, J
= 8.1 Hz), 8.12−8.15 (m, 2H), 8.97 (d, 1H, J = 2.1 Hz). 13C{1H}
NMR (75 MHz, CDCl3, 25 °C, TMS): δ (ppm) 32.5, 122.9, 127.1,
127.3, 127.6, 129.1, 129.2, 129.6, 129.9, 134.1, 139.8, 147.0, 149.8.
1-Methyl-5-(naphthalen-1-yl)-1H-imidazole (1f).1a Yellow oil. 1H
NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 3.41 (s, 3H), 7.16
(s, 1H), 7.43−7.56 (m, 4H), 7.65 (d, 2H, J = 6.3 Hz), 7.92−7.94 (m,
2H). 13C{1H} NMR (75 MHz, CDCl3, 25 °C, TMS): δ (ppm) 31.9,
125.2, 125.4, 126.1, 126.7, 127.2, 128.3, 129.0, 129.2, 129.4, 131.1,
132.8, 133.6, 138.4.
4-(1-Methyl-1H-imidazol-5-yl)benzonitrile (1g).33b Off-white
1
solid. H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 3.71 (s,
I
DOI: 10.1021/acs.organomet.8b00246
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
3H), 7.20 (s, 1H), 7.50 (d, 2H, J = 8.4 Hz), 7.56 (s, 1 H), 7.71 (d,
2H, J = 8.1 Hz). 13C{1H} NMR (75 MHz, CDCl3, 25 °C, TMS): δ
(ppm) 32.8, 111.2, 118.5, 128.2, 129.8, 131.6, 132.5, 134.3, 140.5.
5-(4-Methoxyphenyl)-1-methyl-1H-imidazole (1h).33a Light yel-
5-(4-Methoxyphenyl)-1,2-dimethyl-1H-imidazole (2h).33b Pale
yellow solid. H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm)
1
2.44 (s, 3H), 3.48 (s, 3H), 3.84 (s, 3H), 6.89 (s, 1H), 6.96 (d, 2H, J =
8.4 Hz), 7.25−7.28 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3, 25 °C,
TMS): δ ppm: 12.8, 31.1, 55.3, 114.2, 122.0, 123.1, 130.2, 130.3,
145.3, 159.6.
1,2-Dimethyl-5-(2-nitrophenyl)-1H-imidazole (2i). Yellow solid.
1H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 2.45 (s, 3H),
3.32 (s, 3H), 6.90 (s, 1H), 7.43 (d, 1H, J = 7.2 Hz), 7.56−7.70 (m,
2H), 8.04 (d, 2H, J = 7.8 Hz). 13C{1H} NMR (75 MHz, CDCl3, 25
°C, TMS): δ (ppm) 13.4, 30.9, 124.5, 125.1, 126.5, 128.1, 129.8,
132.9, 133.7, 146.3, 149.4.
1
low solid. H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 3.63
(s, 3H), 3.85 (s, 3H), 6.97 (d, 2H, J = 8.4 Hz,) 7.03 (s, 1H), 7.31 (d,
2H, J = 8.4 Hz), 7.50 (s, 1 H). 13C{1H} NMR (75 MHz, CDCl3, 25
°C, TMS): δ (ppm) 32.3, 55.3, 114.2, 122.2, 127.5, 129.9, 133.2,
138.6, 159.4.
1-Methyl-5-(2-nitrophenyl)-1H-imidazole (1i). Yellow solid. 1H
NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 3.47 (s, 3H), 7.03
(s, 1H), 7.44−7.47 (m, 1H), 7.59−7.70 (m, 3H), 8.06−8.09 (dd,
1H). 13C{1H} NMR (75 MHz, CDCl3, 25 °C, TMS): δ (ppm) 31.9,
124.6, 127.7, 128.8, 130.1, 133.0, 133.8, 139.1, 149.6.
1,2-Dimethyl-5-(3-nitrophenyl)-1H-imidazole (2j). Yellow solid.
1H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 2.48 (s, 3H),
3.60 (s, 3H), 7.08 (s, 1H), 7.62 (d, 1H, J = 7.8 Hz), 7.71 (d, 1H, J =
7.8 Hz), 8.19−8.23 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3, 25 °C,
TMS): δ (ppm) 13.7, 31.5, 122.2, 122.6, 127.4, 129.8, 131.2, 132.2,
134.0, 147.3, 148.4.
1-Methyl-5-(3-nitrophenyl)-1H-imidazole (1j). Yellow solid. 1H
NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 3.65 (s, 3H), 7.24
(s, 1H), 7.59−7.66 (m, 2H), 7.75 (d, 1H, J = 7.5 Hz), 8.22−8.27 (m,
2H). 13C{1H} NMR (75 MHz, CDCl3, 25 °C, TMS): δ (ppm) 32.7,
122.5, 122.6, 129.5, 129.8, 131.0, 131.5, 134.0, 140.2, 148.5.
1-Methyl-5-(4-nitrophenyl)-1H-imidazole (1k).1a Yellow solid. 1H
NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 3.78 (s, 3H), 7.23
(s, 1H), 7.59 (d, 3H, J = 8.7 Hz), 8.31 (d, 2H, J = 8.7 Hz). 13C{1H}
NMR (75 MHz, CDCl3, 25 °C, TMS): δ (ppm) 33.0, 124.2, 128.3,
130.3, 131.4, 136.3, 140.9, 146.9.
1,2-Dimethyl-5-(4-nitrophenyl)-1H-imidazole (2k).33a Yellow
1
solid. H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 2.49 (s,
3H), 3.62 (s, 3H), 7.13 (s, 1H), 7.53 (d, 2H, J = 8.7 Hz), 8.29 (d, 2H,
J = 6.9 Hz). 13C{1H} NMR (75 MHz, CDCl3, 25 °C, TMS): δ (ppm)
13.7, 31.8, 124.1, 128.1, 128.3, 131.5, 136.9, 146.6, 148.1.
1,2-Dimethyl-5-phenyl-1H-imidazole (2l).1a Yellow oil. H NMR
1
1-Methyl-5-phenyl-1H-imidazole (1l).1a Light yellow solid. 1H
NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 3.67 (s, 3H), 7.11
(s, 1H), 7.33−7.47 (m, 5H), 7.52 (s, 1H). 13C{1H} NMR (75 MHz,
CDCl3, 25 °C, TMS): δ (ppm) 32.5, 127.9, 128.1, 128.5, 128.7, 129.8,
133.4, 139.1.
(300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 2.44 (s, 3H), 3.52 (s, 3H),
6.95 (s, 1H), 7.34−7.37 (m, 3H), 7.39−7.45 (m, 2H). 13C{1H} NMR
(75 MHz, CDCl3, 25 °C, TMS): δ (ppm) 13.7, 31.3, 125.8, 127.6,
128.6, 128.7, 130.6, 133.6, 145.9.
3-(1,2-Dimethyl-1H-imidazol-5-yl)pyridine (2a).29a Pale yellow
oil. 1H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 2.45 (s, 3H),
3.53 (s, 3H), 7.02 (s, 1H), 7.33−7.38 (m, 1H), 7.64−7.68 (m, 1H),
8.57−8.63 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3, 25 °C, TMS):
δ (ppm) 13.6, 31.3, 123.5, 126.6, 126.8, 130.0, 135.6, 146.9, 148.6,
149.0.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.8b00246.
5-(4-Chlorophenyl)-1,2-dimethyl-1H-imidazole (2b).1a Off-white
1
HR-MS and NMR spectra of ligands, complexes, and
products of catalysis and X-ray data tables (PDF)
solid. H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 2.45 (s,
3H), 3.51 (s, 3H), 6.95 (s, 1H), 7.28 (d, 2H, J = 8.67 Hz), 7.39 (d,
2H, J = 8.43 Hz). 13C{1H} NMR (75 MHz, CDCl3, 25 °C, TMS): δ
(ppm) 13.7, 31.3, 126.2, 128.9, 129.1, 129.7, 132.4, 133.6, 146.3.
4-(1,2-Dimethyl-1H-imidazol-5-yl)benzaldehyde (2c).1a Yellow
Accession Codes
CCDC 1837276−1837282 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
1
solid. H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 2.47 (s,
3H), 3.60 (s, 3H), 7.09 (s, 1H), 7.42−7.54 (m, 2H), 7.92−7.95 (m,
2H), 10.03 (s, 1H). 13C{1H} NMR (75 MHz, CDCl3, 25 °C, TMS):
δ (ppm) 13.8, 31.8, 127.7, 128.3, 130.2, 132.5, 135.1, 136.5, 147.6,
191.5.
1-(4-(1,2-Dimethyl-1H-imidazol-5-yl)phenyl)ethanone (2d).1a
1
Light yellow solid. H NMR (300 MHz, CDCl3, 25 °C, TMS): δ
(ppm) 2.46 (s, 3H), 2.62 (s, 3H), 3.57 (s, 3H), 7.05 (s, 1H), 7.45 (d,
2H, J = 8.4 Hz), 8.02 (d, 2H, J = 8.4 Hz). 13C{1H} NMR (75 MHz,
CDCl3, 25 °C, TMS): δ (ppm) 13.7, 26.6, 31.7, 127.2, 128.0, 128.8,
132.6, 135.1, 135.8, 147.2, 197.5.
AUTHOR INFORMATION
■
Corresponding Author
*A.K.S.: e-mail, aksingh@chemistry.iitd.ac.in, ajai57@hotmail.
com; fax, +91 11 26581102; tel, +91 11 26591379.
3-(1,2-Dimethyl-1H-imidazol-5-yl)quinoline (2e).29a Light yellow
1
solid. H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 2.43 (s,
ORCID
3H), 3.55 (s, 3H), 7.08 (s, 1H), 7.53−7.55 (m, 1H), 7.65−7.68 (m,
1H), 7.79 (d, 1H, J = 8.1 Hz), 8.03−8.09 (m, 2H), 8.89 (d, 1H, J =
2.1 Hz). 13C{1H} NMR (75 MHz, CDCl3, 25 °C, TMS): δ (ppm)
13.6, 31.3, 123.7, 127.1, 127.3, 127.5, 127.7, 129.2, 129.6, 130.1,
134.1, 146.9, 147.0, 150.2.
Renu Bhaskar: 0000-0002-9558-8104
Alpesh K. Sharma: 0000-0001-5950-4818
Ajai K. Singh: 0000-0003-1650-6316
Notes
1,2-Dimethyl-5-(naphthalen-1-yl)-1H-imidazole (2f).1a Yellow
1
The authors declare no competing financial interest.
oil. H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 2.50 (s,
3H), 3.27 (s, 3H), 7.02 (s, 1H), 7.41−7.55 (m, 4H), 7.69 (d, 1H, J =
7.8 Hz), 7.91 (d, 1H, J = 8.1 Hz). 13C{1H} NMR (75 MHz, CDCl3,
25 °C, TMS): δ (ppm) 13.5, 30.8, 125.1, 125.5, 125.9, 126.5, 127.0,
127.9, 128.2, 128.8, 128.9, 130.9, 132.7, 133.5, 145.3.
ACKNOWLEDGMENTS
■
A.K.S. thanks the Department of Science and Technology
(Nanomission), India, Department of Atomic Energy (BRNS),
India, and Council of Scientific and Industrial Research, India,
for research projects. R.B. thanks the University Grants
Commission (India) for JRF/SRF. A.K.S. thanks the CSIR,
India, for JRF/SRF.
4-(1,2-Dimethyl-1H-imidazol-5-yl)benzonitrile (2g).1a Off-white
1
solid. H NMR (300 MHz, CDCl3, 25 °C, TMS): δ (ppm) 2.47 (s,
3H), 3.59 (s, 3H), 7.07 (s, 1H), 7.48 (d, 2H, J = 8.4 Hz), 7.72 (d, 2H,
J = 8.4 Hz). 13C{1H} NMR (75 MHz, CDCl3, 25 °C, TMS): δ (ppm)
13.7, 31.7, 110.9, 118.6, 127.7, 128.3, 131.8, 132.5, 135.1, 147.7.
J
DOI: 10.1021/acs.organomet.8b00246
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