Imidazole-aryl coupling reaction via C[sbnd]H bond activation catalyzed by palladium supported on modified magnetic reduced graphene oxide in alkaline deep eutectic solvent

Article abstract of DOI:10.1016/j.catcom.2019.105890

By employing reusable heterogeneous catalyst, modified magnetic reduced graphene oxide-supported palladium catalyst (MRGO@ DAP- AO-Pd^ll), the regioselective C-5 arylation of imidazoles via C[sbnd]H bond activation pathway for the preparation of

Full text of DOI:10.1016/j.catcom.2019.105890

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Imidazole-aryl coupling reaction via C-H bond activation
catalyzed by palladium supported on modified magnetic reduced
graphene oxide in alkaline deep eutectic solvent
Monire Shariatipour, Arefe Salamatmanesh, Masoumeh
Jadidinejad, Akbar Heydari
PII:
S1566-7367(19)30351-6
DOI:
https://doi.org/10.1016/j.catcom.2019.105890
CATCOM 105890
Reference:
To appear in:
Catalysis Communications
Received date:
Revised date:
Accepted date:
14 September 2019
27 October 2019
9 November 2019
Please cite this article as: M. Shariatipour, A. Salamatmanesh, M. Jadidinejad, et al.,
Imidazole-aryl coupling reaction via C-H bond activation catalyzed by palladium
supported on modified magnetic reduced graphene oxide in alkaline deep eutectic solvent,
Catalysis Communications (2018), https://doi.org/10.1016/j.catcom.2019.105890
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Imidazole-aryl coupling reaction via C−H bond activation catalyzed by
palladium supported on modified magnetic reduced graphene oxide in
alkaline deep eutectic solvent
Monire Shariatipour, Arefe Salamatmanesh, Masoumeh Jadidinejad, Akbar Heydari*
Chemistry Department, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran
*
Phone: (+98) -21-82883444; Email: heydar_a@modares.ac.ir

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By employing reusable heterogeneous catalyst, modified magnetic reduced graphene oxide-
supported palladium catalyst (MRGO@ DAP- AO-Pdll) ), the regioselective C-5 arylation of
imidazoles via C−H bond activation pathway for the preparation of C5-arylated imidazoles has
been successfully achieved in alkaline deep eutectic solvent made of potassium carbonate and
glycerol under aerobic conditions. Compared to previous procedures, significant improvements
of this new protocol demonstrated by the high catalytic efficiency, easy recovery of catalyst,
broad substrate scope and sustainable reaction condition using green solvent.
KEYWORDS: C-H arylation, imidazole, heterogeneous catalyst, magnetic reduced graphene
oxide, palladium, deep eutectic solvent.

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1. Introduction
The palladium-catalyzed direct C-H arylation reactions of heteroarenes with aryl halides have
become as the extremely powerful method for the synthesis of biaryl or aryl-heteroaryl products.
Traditional cross coupling reactions require the preliminary synthesis of organometallic reagent
that is time consuming and provide organometallic salt (MX) as the by-product[1].In the case of
imidazole derivatives, 5-arylimidazoles are reported to be physiologically and pharmacologically
active compounds[2]. Ohta and co-workers for the first time reported regioselectively C5-
arylated imidazoles in the presence of Pd(PPh3)4, KOAc and DMA as catalyst, base and solvent,
respectively[3]. Afterwards, Miura et al. described the reaction of arylhalids with azole
compounds in the presence of Pd(OAc)2 and PPh3 in DMF using alkali metal carbonates(
Cs2CO3 and K2CO3) as bases[4]. Subsequently, other groups have reported the direct C5-
arylation of imidazoles using various palladium/ligand catalytic systems [5-8]. In 2009, a ligand-
free procedure for the regioselective C5-arylation of imidazole derivatives with aryl bromides at
low catalyst loading conditions was described by Doucet and co-worker[9]. Recently, examples
of palladium NHC complex catalyzed C5-arylation of imidazoles via C–H bond activation have
also been reported [10-15].
The major issue of Pd-catalyzed direct arylation in terms of green chemistry is related to the use
of toxic solvents such as Dimethylformamide (DMF) and Dimethylacetamide (DMA)[16]. In
recent years, several solvents such as water, polyethylene glycol, dialkyl carbonates, Biomass-
derived solvents have replaced with toxic solvents for palladium-catalyzed aromatic C−H bond
arylation[17-19]. The deep eutectic solvents (DESs) as an emergent class of solvents are
attaining increasing interest due to their fascinating properties such as low cost of components,
low toxicity, bio-degradability, simple and straightforward preparation and negligible vapor
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pressure[20]. Although DESs have been used as environmentally friendly solvents as well as
catalysts in many chemical processes including Pd-catalyzed cross-coupling reactions[21, 22],
application of DES in direct arylation reaction is in its childhood. Only, very recently, Farinola et
al, in 2017, reported the first example of palladium- catalyzed C−H bond arylation reaction in
DES[23].
In recent years, the use of heterogeneous catalysts in the field of C-H activation, especially C-H
arylation reactions has received considerable attention[24]. The pioneering achievement was
reported by Nakamura et al. in 1982 where commercially available Pd/C was introduced as a
heterogeneous catalyst for arylation of isoxazole[25]. Also, Fairlamb et al. revealed that well-
defined Pd nanoparticles (PdNPs) are rapidly formed and acted as an active catalytic species
under working Pd(OAc)2 catalyst in C-H bond functionalization reactions of
heteroarenes[26].Following the early reports, many chemists developed more efficient
methodologies via heterogeneous catalyst for Direct Csp2_H and Csp3_H arylation reactions[27,
28].Recently, a few recoverable palladium catalyst also have been reported for C-H arylation
reaction of imidazoles[29, 30].
2D graphene, consists of Sp2 hybridized carbon atom, possesses exceptional properties such as
high chemical and mechanical stability, extremely large surface area and excellent
dispersibility[31]. Several graphene-based catalysts already reported for C-H activation reaction
by a few researchers[32]. Despite their tremendous catalytic performance, for the recycling of
catalysts, traditional separation method such as filtration or centrifugation is required that is
time- consuming. To address these issues, the introduction of Fe3O4 to graphene have proven to
be an effective approach not only because this system provide high catalytic activity, but also
improve separation capability using external magnet[33].
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Based on this introduction, herein, we developed an efficient protocol for C−H arylation reaction
of imidazole with aryl bromide by introducing 2, 6-diaminopyridine (DAP) -Amidoxime (AO)
palladium complex immobilized on the magnetic reduced graphene oxide (MRGO@DAP-AO-
Pdll) as a highly efficient and reusable heterogeneous catalyst in K2CO3/Glycerol media.
2. Experimental
2.1. Typical Procedure for Direct C-5 Arylation of imidazole derivatives
1-methyl-1H-imidazole (2.0 mmol) or 1, 2- dimethyl-1H-imidazole (2.0 mmol), aryl halide (1.0
mmol), MRGO@ DAP-Pdll catalyst (25 mg, containing Pd 0.3 mol %) were weighed and placed
in a reaction tube. DES (1ml) was added. The resulting heterogeneous reaction mixture was
stirred at 130℃ under aerobic conditions. The reaction was monitored by TLC. After the
completion of reaction (17h), the mixture was cooled to room temperature and after water
addition, the catalyst separated by magnetic. This mixture was extracted with EtOAc (3×30 mL),
dried over Na2SO4 and evaporated under reduced pressure. Purification of crude product was
carried out by column chromatography (hexane: ethyl acetate= 9:1)
3. Results and Discussion
3.1. Catalyst preparation
The detailed route of synthesis of MRGO@ DAP-AO-Pdll is depicted in Scheme 1. First, Fe3O4
nanoparticles were in situ synthesized on the surface of graphene oxide (GO) to form magnetic
reduced graphene oxide (MRGO) by chemical co-precipitation method and adding hydrazine
hydrate (80%)as reducing agent. MRGO was modified by reaction of MRGO with (3-
chloropropyl) trimethoxysilane (CPTMS) followed by treatment with 2, 6 diaminopyridine
(DAP) afforded MRGO@DAP. Further, MRGO@DAP-AO was synthesized by two steps.
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MRGO @DAP was functionalized using 2-chloroacetonitrile to get the cyanomethyl group.
Then, conversion of nitrile group into amidoxime afforded MRGO@DAP-AO. Finally, the
treatment of MRGO@DAP-AO with Pd (CH3CN) Cl2 gave a heterogeneous Pd-catalyst
2
(MRGO@ DAP-AO-Pdll).
Scheme 1: A schematic illustration of the process for the preparation of the MRGO@ DAP-AO-Pdll
3.2. Catalyst characterization
The catalyst was fully characterized using various spectroscopic techniques. XRD patterns of
catalyst are shown in Figure 1. In the three curves, the diffraction characteristic peaks at 2θ
values of 10.85° and 30.69° can be attributed to the (001) and (002) planes of reduced GO,
suggesting that GO has been reduced over the preparation process of MRGO. The weak
diffraction peaks located at 2θ values of 35.33°, 41.53°, 50.67°, 63.67°, 67.85°, and 74.61° were
assigned to the (220), (311), (400), (422), (511) and (440) planes of Fe3O4 lattice, respectively,
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which matched well with the standards of Fe3O4 (JCPDS 65–3107). Furthermore, no
characteristic peaks for palladium chloride were observed in the XRD pattern of MRGO@DAP-
AO-Pdll, which may be due to the presence of well-dispersed small particles of the palladium
Figure 1: TheX-raydiffraction patterns of (a)MRGO, (b) MRGO@DAP-AO and (c) MRGO@DAP-AO-Pdll
species in the structure of the catalyst.
The Raman spectra displays four main vibrational modes (Figure 2). The characteristic
peaks at 1350 and 1590 cm_1 can be assigned as D and G bands respectively and two broad
peaks positioned at 2695 and 2933 cm−1 are related to the 2D and D+G bands. The intensity
ratio of D and G band, ID /IG, highly influences the structural transformation and expressing
the sp3/sp2 carbon ratio in carbonaceous materials. The ID/IG ratio of the MRGO
nanocomposites (1.09) showed remarkable increase over that of GO (0.97). This is due to
the removal of oxygen functional groups and the decrease of the sp2 in-plane domain
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induced by the introduction of defects and disorder of the sp2 domain upon the reduction of
the exfoliated GO. Additionally, the Raman spectrum of MRGO composite displays signals
at 200–700 cm_1, which are related to the Fe3O4 NPs. After the functionalization of MRGO,
the ID/IG of MRGO-DAP-AO increased from 1.09 to 1.14 that it can be related to the
augmentation of the sp3 hybridization carbons from the grafting DAP-AO on MRGO
(figure 2-c). Finally, ID/IG of MRGO@DAP-AO-Pdll decreases to 1.02, indicating the
palladium ions filled in defective regions of the MRGO@DAP-AO surface (Figure 2-d).
Figure 2: Ramanspectra of (a) GO, (b) MRGO, (c)MRGO@DAP-AO and(d) MRGO@DAP-AO-Pdll nanohybrids
The SEM images of the catalysts are shown in Figure S1 (a-d). The magnetite nanoparticles
have appeared in bunches on the curled and thin wrinkled sheets of graphene, having a
uniform distribution on the surface of RGO. The SEM images of MRGO@DAP-AO and
MRGO@DAP-AO-Pdll show that they remain as the nanosheet-like structures. Energy-
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dispersive X-ray (EDX) analysis was performed to confirm the presence of the expected
elements in the structure of MRGO@DAP-AO-Pdll, namely carbon, iron, silicon, oxygen,
nitrogen and palladium with wt% of 31.13, 20.53, 0.1, 40.60, 6.58 and 1.06, respectively
(Figure S1 e). Additionally, the density and distribution of the numbered elements were
evaluated by quantitative energy dispersive X-ray spectroscopy (EDS) mapping(Figure S2).
The TEM images clearly display that Fe3O4 nanoparticles as spherical particles with an
average size of 10–20 nm are uniformly dispersed on the wrinkled surfaces of RGO and no
aggregated or free particles are detected (Figure 3). Probably, the homogeneous distribution
of the palladium complex on the surface of modified MRGO is owing to the existence of
the electrostatic interaction between palladium ions and functional groups of the modified
MRGO.
Figure 3: TEM images of MRGO@DAP-AO-Pdll
Thermogravimetric analysis (TGA) were shown in Figure S3. In the three curves, the weight loss
below 200 °C is due to the loss of physically adsorbed water. The main weight loss from 200 °C
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to 630 °C is attributed to the thermal decomposition of the organic moieties including oxygen-
containing functional groups, carbon, and the complex. According to the TGA, the weight
percentage of palladium is estimated to be about 6.29 wt%. Moreover, inductively coupled
plasma (ICP) analysis was used to determine the exact loading of Pd in the structure of the
catalyst and it was evaluated to be 0.14 mmol g-1.
The magnetic measurement was carried out at room temperature. As shown in Figure S4, the
saturation magnetization (Ms) value for MRGO@DAP-AO-Pdll is 18.26 emu•g−1, demonstrating
the catalyst is paramagnetic.
3.3. Catalyst activity in C-H arylation reaction
Direct C-H arylation reaction of 1,2 -dimethyl-1H-imidazole with 4-bromobenzaldehyde was
chosen as the model reaction (Table S1). For the optimization studies, initially, we chose DMA
as the solvent, KOAc as the base and MRGO@DAP-AO-Pdll (containing 0.3 mol % Pd) as the
catalyst at 130℃ for 17h. The desired product of regioselective arylation at the C-5 position (3a)
was isolated in 78% yields (entry 1). By Switching of the base to K2CO3, yield of the product
was increased (86 % yield) (entry 2). In the case of the optimization of solvent, since the DMA
was not desirable solvent in terms of “green chemistry”, we decided to survey the effect of
greener solvents for this coupling using different DESs. Several types of choline based deep
eutectic solvents such as choline chloride/urea (1:2), choline chloride/ethylene glycol (1:2),
choline chloride/glycerol (1:2) were prepared and their efficiency was tested (entry 3-5) resulting
in 51%, 56% and 59% yields of the product, respectively (entry4 and 5). We also focus on the
different ratios molar of potassium carbonate and potassium acetate to glycerol as basic
DESs[34]. Three different DES ratios by varying glycerol molar ratio at a fixed amount of salt
(1:5, 1:7, 1:10) were prepared and their effect on yield of the model reaction was explored (entry
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6-11). A superior yield obtained when K2CO3/ glycerol(1:5) was used (entry 9). When the
palladium loading was reduced to 0.15 and 0.05 mol %, great loss of efficiency (45 % and 20 %
yields, respectively) was encountered (entry 12 and 13). Loading of 0.3 or 0.5mol% of catalyst
resulted in good yields. poor selectivity was obtained when the amount of catalyst loading
increased up to 1mol% due to the increasing of biphenyl as a by-product (25% yield) (entry 14
and 15). Thus, among the different amount of catalyst screened, a loading of 0.3 mol % was the
best choice. Moreover, screening of reaction temperature was performed. Among further
lowering of temperature to 110ºC and 90 °C, poor results were obtained with 52 % and 45 %
yields, respectively (entry 16 and 17)., in the absence of catalyst, no product was generated, even
after 24 h (entry 18). Finally, the activity of the magnetite reduced graphen oxide (solid support)
was evaluated as the unique catalyst, only trace amount of product was obtained that resulting of
inactivity of the support (entry 19).
With the optimized reaction conditions in hand, we next investigated the scope of established
protocol by applying an array of imidazoles and (hetero) aryl halides (Table 1). In all the
reactions, the C5-monoarylated imidazole was formed regioselectively, as C5 is more reactive
than C4 position in imidazoles[35]. Higher yields of the corresponding products were obtained in
the reaction of 1, 2-dimethylimidazole with different para-substituted electron deficient aryl
bromides such as 4-bromobenzaldehyde, methyl 4-bromobenzoate, and 1-bromo-4-
fluorobenzene (3a, 3b, 3c). Only 20% of arylation product was obtained when aryl chloride such
as 4-chlorobenzaldehyde was choose as coupling candidate. Since aryl bromides bearing electron
donating groups such as 4-bromoanisole and 1-bromo-4-methylbenzene stabilize Ar-X bond,
only moderate yields of 64−75 % were obtained (3d, 3e). Sterically hindered 1-naphthyl bromide
afforded the desired coupled product in compatible and satisfactory yield of 75 % (3g).
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Markedly, good yield was obtained with 2-bromopyridine as a heteroaryl bromide (3j). As
expected, the more hindered ortho-substituted aryl bromides such as 2-bromoanisole and 2-
bromoaniline gave low yields of 45 and 48%, respectively (3h, 3i). Morevere, we reacted another
substituted imidazole, 1-methyl-1H-imidazole as the coupling partners, with various aryl (hetero)
halides in the same conditions. Since both the positions 2 and 5 of this challenging substrates can
be arylated, using our procedure, the 5-arylated imidazoles were obtained regioselectivity in 57–
89 % yields and only trace amounts of C2-position was detected (4a-4f). Finally, we examined
the reaction using free (NH)-1H-imidazole with 4-bromoanisole. In the optimized reaction
conditions, the corresponding N-aryl product was obtained as the major product.
Table 1 : reaction scopea
3c: 70%
3a: 95 % (20% ) b
3b: 80%
3e: 75%
3d: 64%
3f: 65%
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3g: 75%
3h: 45%
3i: 48%
3j: 68%
4a: 85%
4b: 89%
4c: 57%
4d: 68%
4e: 79%
4f: 58%
aConditions: imidazoles (2 mmol), arylbromide (1.0 mmol), catalyst (25 mg, containing 0.3 mol %Pd), K2CO3/glycerol (1mL),
130℃, 17h in aerobic atmosphere. bwhen 4-chlorobenzaldehyde was used as the substrate(isolated yield in parenthes)
3.4. Recyclability test
The recyclability of our heterogeneous catalyst was tested in the C-H bond arylation of 4-
bromobenzaldehyde with 1, 2-dimethylimidazole under the optimized reaction conditions. After
the first run of the arylation, the reaction mixture diluted with H2O, the catalyst was removed by
external magnetic field, washed with water and ethanol respectively, dried at ambient
temperature and reused for the next run. We observed the recovered MRGO@DAP-AO-Pdll was
still adequately active catalyst after 7 runs and moderate deactivation of the catalyst has been
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noticed with the yield of 85% (figure 4a). However, we observed a drastic decrease of yield in
the 8 run (only 20% yield). ICP-MS analysis indicated that about 9.4 % of palladium on catalyst
leached into the reaction solution after the seven cycles. By studying TEM images of the
recovered catalyst, no significant morphology change on MRGO@ DAP-AO-Pdll was observed.
Therefore, the loss of catalytic activity could be attributed to leaching of palladium after seven
runs (Figure 4 b).
Figure 4: (a) The recyclabilityof MRGO@ DAP-AO-Pdll catalyst in theC-H bondarylationbetween1, 2-dimethylimidazole and4-
bromobenzaldehyde
(b) A representativeTEM image of MRGO@DAP-AO-Pdll catalyst after 7 runs.
Catalytic performance of the present catalyst was compared with previously reported catalysts in
C-H arylation reaction between 1, 2 dimethylimidazole and 4-bromobenzaldehyde (table S2). As
seen in Table S2, Although all of the listed catalysts can produce the desired C-5-arylated
imidazole in good to excellent yield, it is clearly seen that newly synthesized MRGO@DAP-AO-
Pdll as a heterogeneous catalyst is noticeably comparable with the homogeneous Palladium
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catalytic system in term of high yield of the desired product, facile magnetic recoverability, low
catalyst loading and using eco-friendly solvent.
4. Conclusion
In conclusion, we have successfully applied environmentally safe conditions for direct
regioselective C−H arylation reactions between imidazoles and aryl bromides in a deep eutectic
solvent, k2CO3/glycerol (1:5) mixture, via magnetically separable and recyclable MRGO@DAP-
AO-Pdll as a heterogeneous catalyst. Our finding suggest that replacement of reprotoxic solvent
(DMA) by DESs affords a readily accessible, inexpensive and green reaction medium.
MRGO@DAP-AO-Pdll showed good catalytic efficiency for arylation reaction of imidazoles
with several electron-deficient and electron -rich aryl bromides under these conditions. Catalyst
recycled at least 7 times without significant decreasing yield of reaction. Hot filtration and Hg
(0) poisoning test demonstrate that catalyst has heterogeneous character.
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Declaration of interests
☒ The authors declare that they have no known competingfinancialinterests orpersonal relationships
that could have appeared to influence the work reported in this paper.
☐The authors declare the followingfinancial interests/personal relationships which may be considered
as potential competinginterests:
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Graphical Abstract
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Highlights

Palladium supported on modified magnetic reduced graphene oxide (MRGO-DAP-AO-Pdll)
was well synthesized.

The catalyst was exhibited high activity in C-H arylation reaction of imidazoles with
arylbromides.


Alkaline deep eutectic solvent (K2CO3/glycerol) was applied as green solvent.
The catalyst was simply recycled and reused successfully at least for seven runs.
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