Palladium(II) 9,10-phenanthrenequinone N-substituted thiosemicarbazone/semicarbazone complexes as efficient catalysts for N-arylation of imidazole

Article abstract of DOI:10.1080/00958972.2015.1071484

A series of palladium complexes, [PdCl(L1-₄)] (1-4) (L₁ = 9,10-phenanthrenequinone thiosemicarbazone, L₂ = 9,10-phenanthrenequinone methylthiosemicarbazone, L₃ = 9,10-phenanthrenequinone phenylthiosemicarbazone, and L₄ = 9,10-phenanthrenequinone semicarbazone), have been synthesized and characterized by elemental analyses, UV-vis, FT-IR, ¹H and ¹³C NMR, and ESI-Mass spectroscopic methods. The catalytic efficiency of the synthesized complexes was examined against N-arylation of imidazole. The system works well with the electron-rich, -neutral, and -deficient aryl halides to afford the products in good to excellent yields. Sterically congested aryl halides and heteroaryl halides have also been used as substrates to provide N-arylated heterocycles. In addition, this methodology can be applicable to other substrates with N-containing heterocycles.

Full text of DOI:10.1080/00958972.2015.1071484

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Palladium(II) 9,10-phenanthrenequinone N-
substituted thiosemicarbazone/semicarbazone
complexes as efficient catalysts for N-arylation of
imidazole
Panneerselvam Anithaa, Rajendran Manikandanab & Periasamy Viswanathamurthia
a Department of Chemistry, Periyar University, Salem-636011, India
b Department of Chemistry, KSR College of Arts and Science, Tiruchengode-637 215,
India
Accepted author version posted online: 13 Jul 2015.
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To cite this article: Panneerselvam Anitha, Rajendran Manikandan & Periasamy Viswanathamurthi (2015): Palladium(II)
9,10-phenanthrenequinone N-substituted thiosemicarbazone/semicarbazone complexes as efficient catalysts for N-
arylation of imidazole, Journal of Coordination Chemistry, DOI: 10.1080/00958972.2015.1071484
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Publisher: Taylor & Francis
Journal: Journal of Coordination Chemistry
DOI: http://dx.doi.org/10.1080/00958972.2015.1071484
Palladium(II) 9,10-phenanthrenequinone N-substituted
thiosemicarbazone/semicarbazone complexes as efficient catalysts for
N-arylation of imidazole
PANNEERSELVAM ANITHA†, RAJENDRAN MANIKANDAN†1, PERIASAMY VISWANATHAMURTHI*†
†Department of Chemistry, Periyar University, Salem-636011, India
1Present address: Department of Chemistry, KSR College of Arts and Science, Tiruchengode-637 215, India
A series of palladium complexes, [PdCl(L1-4)] (1-4) (L1 = 9,10-phenanthrenequinone
thiosemicarbazone, L2 = 9,10-phenanthrenequinone methylthiosemicarbazone, L3 = 9,10-
phenanthrenequinone phenylthiosemicarbazone and L4 = 9,10-phenanthrenequinone
semicarbazone), have been synthesized and characterized by elemental analyses, UV-Vis, FT-IR,
1H and 13C NMR and ESI-Mass spectroscopic methods. The catalytic efficiency of the
synthesized complexes was examined against N-arylation of imidazole. The system works well
with the electron-rich, -neutral, and -deficient aryl halides to afford the products in good to
excellent yields. Sterically congested aryl halides and heteroaryl halides have also been used as
substrates to provide N-arylated heterocycles. In addition, this methodology can be applicable to
other substrates with N-containing heterocycles.
Keywords: ONS/ONO Donor ligands; Pd-Catalyzed; N-Arylation; Imidazole; Aryl halides
1. Introduction
Organic molecules containing C(aryl)-N(heterocycle) linkages are found in numerous natural
products and biologically active pharmaceuticals [1]. Therefore extensive efforts are made to
develop new and efficient synthetic transformations to make these linkages [2]. Among the
synthetic transformations, transition metal complex catalyzed cross-coupling is an attractive tool
*Corresponding author. Email: viswanathamurthi72@gmail.com
1

for the synthesis of compounds containing C-N bond. Since Ohta and co-workers was first report
the direct arylation of several heteroaromatics with aryl halides using Pd(PPh3)4 as the catalyst in
1990 [3], development of this coupling has proved to be a very powerful method for synthesis of
a wide variety of arylated heterocycles [4]. This cross-coupling reaction provides cost-effective
and environmentally attractive access to the target molecules because it can eliminate the need
for the organometallic starting materials required in traditional cross-coupling methods, such as
Stille, Suzuki or Negishi couplings. Moreover, the major wastes of the reaction are a base
associated with HX and the solvent, instead of metallic salts produced under classical cross-
coupling procedures [5].
On the other hand, the environment around the coordination center is an important aspect
in catalytic activity exhibited by metal complexes. The catalytic activity of complexes can be
tuned by the coordinated ligands, either by altering the redox properties of metal or by impacting
specific activity of ligand to the complexes [6-8]. Hence, selecting ligands in the coordination
sphere of a metal is an interesting part of coordination chemistry and catalysis research.
Chemistry of thiosemicarbazones has gained importance because of their simple preparation,
unpredictable complexation properties and variety of applications [9]. The coordinating ability of
thiosemicarbazones is attributed to extended delocalization of electron density over the –NH–
C(S)–NH–N= system, which is enhanced by substitution on the terminal nitrogen. Variation in
the substituent on the azomethine carbon of the thiosemicarbazone ligands influences the mode
of their binding. On introduction of nitrogen or oxygen containing substituents on azomethine
carbon, it is anticipated that the binding ability of thiosemicarbazone becomes more capricious.
The versatility of the thiosemicarbazone ligands for binding to the metal ion has been well
documented. Besides the enormous structural diversity exhibited by the thiosemicarbazone
complexes [10], they possess a wide range of applications in biology [11] and catalysis [12]. For
the past few years, our group has been actively engaged in the synthesis and characterization of
N-substituted thiosemicarbazone complexes with various transition metals [13]. In continuation
of our efforts in understanding the coordination propensities of thiosemicarbazones, in this work,
we have carried out the synthesis and structural characterization of palladium(II) complexes
containing 9,10-phenanthrenequinone appended with derivatives of
thiosemicarbazones/semicarbazone. In addition, the catalytic performance of the synthesized
complexes was explored for arylation of nitrogen containing heterocycles with aryl halides.
2

2. Experimental
2.1. Materials and methods
All reagents used were chemically pure and AR grade. The solvents were purified and dried
according to standard procedures. The ligands HL1-4 and [PdCl2(PPh3)2] were prepared based on
literature procedures [14, 15]. Microanalyses of carbon, hydrogen, nitrogen and sulfur were
carried out using a Vario EL III Elemental analyzer at SAIF - Cochin India. IR spectra of the
ligands and their complexes were recorded as KBr pellets on a Nicolet Avatar model
spectrophotometer from 4000-400 cm-1. Electronic spectra of the complexes have been obtained
in dichloromethane using a Shimadzu UV - 1650 PC spectrophotometer from 800-200 nm.
1H and 13C NMR spectra were measured on a Jeol GSX - 400 instrument using CDCl3 as the
solvent at room temperature with TMS as the internal standard. The ESI-MS spectra were
performed with a LC-MS Q-ToF Micro Analyzer (Shimadzu) in the SAIF, Panjab University,
Chandigarh. Melting points were checked on a Technico micro heating table and are
uncorrected.
2.2. Synthesis of palladium(II) complexes
An ethanol solution (10 mL) containing HL1-4 (0.1 mmol) was added to [PdCl2(PPh3)2]
(0.1 mmol) in ethanol (10 mL) and the resulting green solution was refluxed for 4 h. After
cooling to room temperature, the green complex separated out, was filtered off and recrystallized
from ethanol. Our efforts to obtain single crystals of the complexes were unsuccessful.
2.2.1. [PdCl(L1)] (1). Yield 88%, M.p. 220 °C. Anal. calcd. for C15H10ClN3OPdS (%): C, 42.67;
H, 2.39; N, 9.95; S, 7.59. Found: C, 42.34; H, 2.23; N, 9.67; S, 7.43. FT-IR (KBr, cm-1): 1611
(quinone C=O), 1550 (C=N), 753 (C-S). UV-Vis (λmax, nm; εmax, dm3mol-1cm-1): 424 (5932), 398
(7677), 311 (9896), 250 (14325). 1H NMR (CDCl3, ppm): 9.90 (s, 1H, NH2), 10.06 (s, 1H, NH2),
7.18-7.98 (m, 8H, Ar-H). 13C NMR (CDCl3, ppm): 181.83 (quinone C=O), 169.97 (C-S), 161.18
(C=N), 124.03-136.81 (Ar-C). ESI-MS (m/z) = 422.6 [M+].
2.2.2. [PdCl(L2)] (2). Yield 85%, M.p. 214 °C. Anal. calcd. for C16H12ClN3OPdS (%): C, 44.05;
H, 2.77; N, 9.63; S, 7.35. Found: C, 44.35; H, 2.51; N, 9.49; S, 7.71. FT-IR (KBr, cm-1): 1618
3

(quinone C=O), 1551 (C=N), 761 (C-S).UV-Vis (λmax, nm; εmax, dm3mol-1cm-1): 446 (6325), 394
(7981), 334 (10112), 253 (16742). 1H NMR (CDCl3, ppm): 8.92 (s, 1H, NH-CH3), 7.19-7.71 (m,
8H, Ar-H), 3.28 (s, 3H, CH3). 13C NMR (CDCl3, ppm): 180.01 (quinone C=O), 171.23 (C-S),
161.87 (C=N), 124.77-136.61 (Ar-C), 29.92 (CH3). ESI-MS (m/z) = 436.1 [M+].
2.2.3. [PdCl(L3)] (3). Yield 87%, M.p. 225 °C. Anal. calcd. for C21H14ClN3OPdS (%): C, 50.62;
H, 2.83; N, 8.43; S, 6.43. Found: C, 50.77; H, 2.50; N, 8.61; S, 6.21. FT-IR (KBr, cm-1): 1619
(quinone C=O), 1521 (C=N), 758 (C-S). UV-Vis (λmax, nm; εmax, dm3mol-1cm-1): 426 (4739), 393
(6326), 320 (8467), 267 (12348). 1H NMR (CDCl3, ppm): 11.83 (s, 1H, NH-C6H5), 7.18-8.05 (m,
13H, Ar-H). 13C NMR (CDCl3, ppm): 179.91 (quinone C=O), 170.04 (C-S), 160.87 (C=N),
125.23-136.97 (Ar-C). ESI-MS (m/z) = 498.1 [M+].
2.2.4. [PdCl(L4)] (4). Yield 82%, M.p. 211 °C. Anal. calcd. for C15H10ClN3O2Pd (%): C, 44.36;
H, 2.48; N, 10.35. Found: C, 44.15; H, 2.60; N, 10.12. FT-IR (KBr, cm-1): 1627 (quinone C=O),
1558 (C=N), 1180 (C-O). UV-Vis (λmax, nm; εmax, dm3mol-1cm-1): 445 (5012), 381 (6946), 330
(9322), 272 (13746). 1H NMR (CDCl3, ppm): 8.84, 8.98 (s, 2H, NH2), 7.18-7.97 (m, 8H, Ar-H).
13C NMR (CDCl3, ppm): 180.01 (quinone C=O), 167.53 (C-O), 159.93 (C=N), 124.83-137.94
(Ar-C). ESI-MS (m/z) = 406.2 [M+].
2.3. Catalytic arylation of nitrogen-containing heterocycles with aryl halides
Arylhalide (1.0 mM), nitrogen-containing heterocycle (1.2 mM), KOH (2 mM) and the catalyst
(0.75 M%) were stirred in dimethyl sulfoxide (DMSO) (4 mL) at 110 °C for 10 h. After
completion of the reaction, the mixture was cooled to room temperature, diluted with ethyl
acetate (10 mL) and filtered. The filtrate was concentrated and the residue was purified by
column chromatography on silica gel using hexane/ethyl acetate (70:30) as eluent to afford the
desired product. The products have been characterized by 1H NMR spectroscopy.
1-Phenyl-1H-imidazole. 1H NMR (CDCl3, ppm): 7.90 (s, 1H), 7.38-7.56 (m, 5H), 7.18 (s, 1H),
7.08 (s, 1H).
1-(4-Formylphenyl)-1H-imidazole. 1H NMR (CDCl3, ppm): 10.01 (s, 1H), 7.82-8.04 (m, 4H),
7.70 (s, 1H), 7.27 (s, 1H), 7.21 (s, 1H).
4

1-(4-Nitrophenyl)-1H-imidazole. 1H NMR (CDCl3, ppm): 8.18-8.32 (m, 4H), 7.93 (s, 1H), 7.34
(s, 1H), 7.20 (s, 1H).
1-(4-Cyanophenyl)-1H-imidazole. 1H NMR (CDCl3, ppm): 8.02 (s, 1H), 7.61-7.78 (m, 4H),
7.29 (s, 1H), 7.21 (s, 1H).
1-(4-Acetylphenyl)-1H-imidazole. 1H NMR (CDCl3, ppm): 8.10 (s, 1H), 7.58-7.80 (m, 4H),
7.26 (d, J = 6.8 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H), 2.68 (s, 3H).
4-(1H-Imidazol-1-yl)-benzoic acid. 1H NMR (CDCl3, ppm): 10.98 (s, 1H), 8.20 (s, 1H), 7.75-
7.98 (m, 4H), 7.30 (d, J = 7.0 Hz, 1H), 7.22 (d, J = 7.2 Hz, 1H).
1-(4-Methoxyphenyl)-1H-imidazole. 1H NMR (CDCl3, ppm): 7.73 (s, 1H), 7.42-7.69 (m, 4H),
7.30 (s, 1H), 7.22 (s, 1H), 3.79 (s, 3H).
1-(4-Methylphenyl)-1H-imidazole. 1H NMR (CDCl3, ppm): 7.70 (s, 1H), 7.22-7.37 (m, 4H),
7.11 (s, 1H), 6.99 (s, 1H), 2.37 (s, 3H).
4-(1H-Imidazol-1-yl)-phenol. 1H NMR (CDCl3, ppm): 10.74 (s, 1H), 8.26 (s, 1H), 7.78-8.02
(m, 4H), 7.31 (d, J = 6.0 Hz, 1H), 7.22 (d, J = 6.2 Hz, 1H).
4-(1H-Imidazol-1-yl)-aniline. 1H NMR (CDCl3, ppm): 8.24 (s, 1H), 7.73-7.96 (m, 4H), 7.46 (d,
J = 6.8 Hz, 1H), 7.28 (d, J = 7.2 Hz, 1H), 3.88 (s, 1H).
1-(2-Methoxyphenyl)-1H-imidazole. 1H NMR (CDCl3, ppm): 7.86 (s, 1H), 7.50-7.73 (m, 4H),
7.36 (d, J = 4.4 Hz, 1H), 7.23 (d, J = 5.0 Hz, 1H), 3.87 (s, 3H).
1-(2-Methylphenyl)-1H-imidazole. 1H NMR (CDCl3, ppm): 8.12 (s, 1H), 7.74-7.88 (m, 4H),
7.44 (d, J = 5.2 Hz, 1H), 7.28 (d, J = 5.0 Hz, 1H), 2.32 (s, 3H).
2-(1H-Imidazol-1-yl)-pyridine. 1H NMR (CDCl3, ppm): 8.23 (s, 1H), 7.78-8.02 (m, 4H), 7.48
(d, J = 4.8 Hz, 1H), 7.30 (d, J = 4.2 Hz, 1H).
2-(1H-Imidazol-1-yl)-pyrimidine. 1H NMR (CDCl3, ppm): 8.18 (s, 1H), 7.80-7.94 (m, 3H),
7.52 (d, J = 4.6 Hz, 1H), 7.41 (d, J = 5.2 Hz, 1H).
1-Phenyl-1H-pyrazole. 1H NMR (CDCl3, ppm): 7.78 (d, J = 3.8 Hz, 2H), 7.12-7.53 (m, 5H),
6.86 (t, J = 3.6 Hz, 1H).
1-Phenyl-1H-pyrrole. 1H NMR (CDCl3, ppm): 7.41-7.68 (m, 4H), 6.91-7.15 (m, 5H).
1-Phenyl-1H-indole. 1H NMR (CDCl3, ppm): 7.83 (d, J = 5.8 Hz, 1H), 7.69 (d, J = 6.0 Hz, 1H),
7.33-7.46 (m, 4H), 6.98-7.18 (m, 5H).
1-Phenyl-1H-benzimidazole. 1H NMR (CDCl3, ppm): 8.08 (s, 1H), 7.57-7.73 (m, 4H), 7.13-
7.38 (m, 5H).
5

3. Results and discussion
Reactions of HL1-4 and [PdCl2(PPh3)2] in 1:1 molar ratio (scheme 1) were carried out in ethanol
to obtain four-coordinate complexes (1-4). Complex 1 was already reported by the reaction of
K2PdCl4 with HL1 in ethanol [16]. The isolated complexes are stable in air, soluble in common
solvents such as dichloromethane, chloroform, benzene, acetonitrile, ethanol, methanol, DMF
and DMSO. All the complexes were characterized by elemental analyses, IR, electronic, NMR
and ESI-Mass spectra.
O
N
O
N
Cl
Y
[PdCl2(PPh3)2]
Pd
Ethanol, reflux, 4 h
Y
HN
C
N
C
HN
R
HN
R
[PdCl(L1)] (1), Y = S, R = H
[PdCl(L2)] (2), Y = S, R = CH3
[PdCl(L3)] (3), Y = S, R = C6H5
[PdCl(L4)] (4), Y = O, R = H
Y = S, R = H (HL1)
Y = S, R = CH3 (HL2)
Y = S, R = C6H5 (HL3)
Y = O, R = H (HL4)
Scheme 1. Synthetic route of palladium(II) complexes.
3.1. FT-IR spectra
The FT-IR spectra of the ligands and the corresponding palladium(II) complexes provided
information about the metal-ligand bonding. Strong vibrations at 1593-1598 and 1630-1634 cm-1
in the ligands corresponding to azomethine ν(C=N) and quinone carbonyl ν(C=O) were shifted to
lower wavenumbers, 1521-1558 and 1611-1627 cm-1, respectively, in the complexes indicating
participation of azomethine nitrogen and quinone oxygen in bonding [17]. A sharp band at 807-
843/1674 cm-1 ascribed to ν(C=S)/ν(C=O) in the ligands disappeared in spectra of the palladium
complexes and a new band at 753-761/1180 cm-1 due to ν(C–S)/ν(C–O) indicated coordination
of the sulfur/oxygen after thio/keto enolization followed by deprotonation [18]. Further, the
hydrazinic ν(N–H) band at 3111-3148 cm-1 in the free ligands disappears in all the complexes,
suggesting deprotonation of the -NH group [19].
6

3.2. Electronic spectra
The electronic spectra of the palladium(II) complexes showed four bands from 250-451 nm. The
appearance of bands below 470 nm suggests a square planar geometry around palladium(II) in
the complexes [20, 21]. Bands in the ultraviolet region at 250-334 nm have been assigned to intra
ligand transitions. The bands at 381-398 nm have been assigned to ligand to metal charge
transfer transitions and the bands at 424-451 nm are due to metal to ligand charge transfer
transitions [22, 23].
3.3. NMR spectra
1H NMR spectra of the ligands and their complexes show signals in the expected regions. The
singlets for the hydrazinic ν(N–H) proton of the free ligands at 13.82-14.81 ppm are absent in the
complexes, supporting the enolization and coordination of the thiolate sulfur/enolate oxygen to
palladium(II). The terminal NH2 protons of HL1 and HL4 and their corresponding complexes
show two singlets at 8.35-10.06 ppm. HL2, HL3 and their corresponding complexes show one
singlet at 8.35-11.83 ppm assigned to NH methyl and NH phenyl protons. In spectra of all the
complexes, the multiplet at 7.18-8.05 ppm is assigned to aromatic protons of ligands. Methyl
protons are at 2.98-3.28 ppm (figures S1-S4).
13C NMR spectra (figures S5-S8) of the complexes show a peak at 179.91-181.83 ppm
assigned to quinone carbonyl (C=O). The azomethine (C=N) carbon has a resonance at 159.93-
161.87 ppm. A sharp peak at 29.92 ppm is expected to be methyl carbon. Peaks at 169.97-171.23
and at 167.53 ppm are assigned to thiosemicarbazone C-S and semicarbazone C-O, respectively.
The aromatic carbons are at 124.03-137.94 ppm.
3.4. Mass spectra
ESI-Mass spectral analysis of the complexes (figures S9-S12) confirm the molecular masses of
the complexes. The m/z values of the molecular ion peaks for 1-4 were obtained at 422.6, 436.1,
498.1 and 406.2 [M+], respectively. The calculated molecular masses of these complexes are
422.2, 436.2, 498.2 and 406.1, in good agreement with calculated molecular masses.
3.5. Catalysis
7

3.5.1. Screening reaction conditions for N-arylation of imidazole with iodobenzene. In order
to optimize the reaction conditions including solvent, bases, catalyst concentration and time, a
model reaction was carried out with iodobenzene and imidazole as the substrates and 1 as
catalyst in the presence of Cs2CO3 at 110 °C for 10 h in different solvents (table 1). Among the
solvents used, DMSO was most beneficial to the catalysis, giving the desired product in 60%
isolated yield (entry 6). Observation of the different bases indicated that KOH is the most
favorable base for the model reaction (entry 8). To study the effect of amount of catalyst, the
reactions were carried out at different concentration of catalyst. An excellent yield was obtained
for 0.75 M% of catalyst (entry 11) and it can be observed that even at very low catalyst loading
of 0.25 M% (entry 10), moderate yield was obtained. No coupling product was observed without
catalyst under similar reaction conditions (entry 15). To optimize the reaction time, different
time intervals (6-14 h) were employed. Reaction time of 10 h gave a higher yield (entry 11).
Finally, to choose the best catalyst among the synthesized complexes, the model reaction was
carried out using 1-4 under the above optimized conditions (table 2). From the results, 2 was the
best catalyst and showed yield of 95%. The order of reactivity of complexes with respect to
different substituents on the thiosemicarbazone fragment of the ligands is 2 > 1 > 4 > 3. Thus 2
proved to be the most efficient complex for N-arylation of imidazole with iodobenzene in terms
of yield and selectivity, 0.75 M% of catalyst loading was chosen, given the high yields and
shorter reaction time to complete the process in presence of KOH in DMSO at 110 °C (10 h).
3.5.2. N-Arylation of imidazole with various aryl halides. With the optimized reaction
conditions in hand, a number of aryl halides were screened to demonstrate the general
applicability and efficacy of this protocol and the results are summarized in table 3. We were
pleased to see that all the reactions proceeded smoothly and afforded the desired products in
moderate to excellent yields upon isolation. For example, unsubstituted aryl halides and electron-
deficient groups on the aryl halides afford coupling products in excellent yield whereas
substrates with electron-rich groups gave moderate to good yields. This reaction was less
sensitive to steric factors and gave good to excellent yields for ortho substituted aryl halides.
Among them, the coupling proceeds readily with aryl iodides giving excellent yield of the
corresponding N-aryl derivative. Heteroaryl halides also react smoothly giving an excellent
yield.
8

3.5.3. N-Arylation of nitrogen containing heterocycles with iodobenzene. In order to check
the versatility of our catalyst, we decided to study the expanded substrates scope with various
nitrogen containing heterocycles such as pyrrole, pyrazole, indole and benzimidazole (table 4).
All the heterocyclic systems gave yields from 78 to 85% (entries 1-4) under optimized
conditions. The present catalytic system works at mild reaction conditions with low reaction
time, low catalyst loading and the efficiency in terms of yield of products without side products
is higher than the existing catalytic systems [24].
3.5.4. Mechanism. The exact mechanism for the catalytic N-arylation reactions is still under
investigation. However, a proposed mechanism based on the literature [25] is provided in
scheme 2. Pd(II) catalyst undergoes an oxidative addition reaction with aryl halide across C-X in
the first step and forms an intermediate I. The palladium ion is Pd(IV) in I and reacts with
heterocyclic amine in the presence of base to form II. In this step, heterocyclic amine simply
replaces the halide ligand from I. In the final step, reductive elimination of intermediate II
results in the formation of N-arylated product followed by the regeneration of Pd(II) catalyst.
The oxidative addition and formation of intermediate I is more feasible in the more polar
solvents by polarization of the C-X bond of aryl halides (table 1).
Apart from this proposed mechanism, Pd(0)/(II) mechanism can also be suggested [26],
on which the Pd(II) catalyst undergoes a reduction to Pd(0) by the solvent in the initial step,
followed by oxidative addition as explained in previous mechanism. However, the reduction of
Pd(II) is not favorable in DMSO. Therefore, we believe that the Pd(II)/(IV) mechanism is
preferable.
9

[Pd]
Ar-N-Het
ArX
Oxidative addition
Reductive elimination
ArPdN-Het
II
ArPdX
I
HX + base
Het-NH + base
Scheme 2. Possible mechanistic pathway for palladium(II) catalyzed N-arylation of imidazole.
4. Conclusion
Four-coordinate palladium(II) complexes, [PdCl(L1-4)], have been synthesized by reacting 9,10-
phenanthrenequinone N-substituted thiosemicarbazone/semicarbazone Schiff base ligands with
[PdCl2(PPh3)2]. Analytical and spectral (FT-IR, UV–Vis, NMR, ESI-Mass) studies revealed that
the ligand is coordinated to palladium(II) through quinone oxygen, imine nitrogen and thiolate
sulfur/enolate oxygen. The synthesized complexes show good catalytic activity in N-arylation of
imidazole with aryl halides and give the corresponding N-arylimidazoles. The choice of the base
and solvent is crucial to form these products in high yields. Using KOH as the base, DMSO as
the solvent and 0.75 mol% of the catalyst, the target products were obtained in moderate to good
yields with a wide variety of aryl halides. Complex 2 was most active and hence was used for
probing the scope of possible substrates. Substituents such as methyl, methoxyl, hydroxyl,
formyl, acetyl, carboxyl, nitrile, amino or nitro group on the aryl halide are tolerated. Hindered
aryl halides or heteroaryl halides were also suitable substrates using the conditions reported
herein. In addition, the optimized catalyst efficiently catalyzes the cross-coupling reactions of
other N-containing heterocycles with iodobenzene, affording the corresponding products in good
yields. In the present catalyst system, no organometallic reagent is required, reducing the number
of steps and therefore the mass of waste products. The major waste is relatively non-toxic
10

base/HX instead of metal salts obtained in classical metal-catalyzed coupling reactions. For these
reasons, the methodology developed here is very promising for the sustainable synthesis of
N-aryl heterocycle.
Acknowledgement
The authors express their sincere thanks to Council of Scientific and Industrial Research (CSIR),
New Delhi [Grant No. 01(2437)/10/EMR-II] for financial support. One of the authors (PA)
thanks CSIR for the award of Senior Research Fellowship.
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15

Table 1. Screening reaction conditions for N-arylation of imidazole with iodobenzenea.
N
N
N
Catalyst 1
Base/Solvent
N
H
Entry
Solvent
Base
Catalyst (M%)
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
MeCN
Toluene
MeOH
DMAc
DMF
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
KOH
K3PO4
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.25
0.75
1.0
1.5
2.0
-
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
6
27
04
16
55
51
60
68
75
65
52
87
87
87
88
-
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
9
10
11
12
13
14
15
16
17
18
19
0.75
0.75
0.75
0.75
49
72
87
88
8
12
14
aReaction conditions: iodobenzene (1.0 mM), imidazole (1.2 mM), base (2 mM),
solvent (4 mL) at 110 °C. bIsolated yield by the column chromatography.
16

Table 2. Selection of favorable catalyst for N-arylation of imidazolea.
Complex
Yield (%)b
87
95
78
83
1
2
3
4
aReaction conditions: iodobenzene (1.0 mM), imidazole (1.2 mM),
KOH (2 mM), complexes 1-4 (0.75 M%) in 4 mL of DMSO were
stirred for 10 h at 110 °C. bIsolated yield by the column
chromatography.
17

Table 3. N-Arylation of imidazole with various aryl halidesa.
Arylhalide
Product
Conversion (%)b
95
N
N
N
N
N
N
I
Br
91
85
87
96
92
Cl
N
Br
N
H3COC
NC
H3COC
NC
N
N
I
N
Br
N
NC
NC
N
I
N
93
87
90
85
95
90
84
HOOC
HOOC
OHC
OHC
O2N
HOOC
HOOC
OHC
OHC
O2N
N
Br
N
N
I
N
N
Br
N
N
I
N
N
N
Br
I
N
N
O2N
O2N
H3C
H3C
18

N
Cl
N
75
82
77
80
75
81
73
H3C
H3CO
H3CO
H2N
H2N
HO
H3C
H3CO
H3CO
H2N
H2N
HO
N
N
I
N
N
Br
N
N
I
N
N
Br
N
I
N
N
Br
N
HO
HO
N
I
N
90
84
87
85
81
OCH3
OCH3
N
N
N
N
Br
N
OCH3
OCH3
I
N
N
N
CH3
CH3
CH3
CH3
CH3
Br
Cl
CH3
19

N
Cl
N
80
CHO
CHO
N
N
N
I
N
N
N
89
85
82
86
N
N
N
N
Br
Cl
N
N
N
N
N
N
Br
Cl
N
N
N
N
N
N
84
N
N
aReaction conditions: Aryl halide (1.0 mM), imidazole (1.2 mM), KOH (2 mM),
complex 2 (0.75 M%) in 4 mL of DMSO were stirred for 10 h at 110 °C.
bIsolated yield by the column chromatography.
20

Table 4. N-Arylation of nitrogen containing heterocycles with iodobenzenea.
N-Heterocycle
Product
Conversion (%)b
N
NH
N
81
N
N
NH
85
78
N
N
N
H
N
N
80
N
H
aReaction conditions: Iodobenzene (1.0 mM), N-heterocycle (1.5 mM),
KOH (2 mM), complex 2 (0.75 M%) in 4 mL of DMSO were stirred
for 10 h at 110 °C. bIsolated yield by the column chromatography.
Graphical abstract
Palladium(II) 9,10-phenanthrenequinone N-substituted thiosemicarbazone/semicarbazone
complexes as efficient catalysts for N-arylation of imidazole
X
Heterocycle-NH
+
R
O
N
Cl
Y
O
[PdCl2(PPh3)2
X = I, Br or Cl
R = H, COCH3, CN, COOH, CHO,
NO2, CH3, OCH3, NH2, OH
Pd
]
Ethanol, reflux, 4 h
Y
N
N
C
HN
C
NHR
[PdCl(L1)] (1)
[PdCl(L2)] (2)
[PdCl(L3)] (3)
[PdCl(L4)] (4)
NHR
Y = S, R = H (HL1)
Y = S, R = CH3 (HL2)
Y = S, R = C6H5 (HL3)
Y = O, R = H (HL4)
N-Heterocycle
R
i. Good substituent compatability
ii. Up to 96%yield
iii. Scalable
21