Synthesis, crystal structures, and catalytic activities of palladium imidazole complexes formed by 2-hydroxyethyl group cleavage

Article abstract of DOI:10.1007/s11243-012-9598-z

N-4,6-dimethyl-2-pyrimidinylimidazole 1 and its hydroxyethyl derivative 1-(2-hydroxyethyl)-3-(4,6-dimethyl-2-pyrimidinyl)imidazolium chloride 2 have been synthesized and characterized. The attempted synthesis of bis(N-heterocyclic carbene)palladium complexes via the direct reaction of 2 with Pd(OAc)₂ results in the unexpected formation of a bis(N-arylimidazole) palladium complex 3. Additionally, the analogous bis(N-methylimidazole) palladium complex 4 has also been synthesized by the above method. Compounds 1-4 were characterized by elemental analysis, IR, and ¹H NMR. Additionally, their crystal structures have been determined by X-ray diffraction. Complexes 3 and 4 were found to be efficient catalysts for the Suzuki reaction.

Full text of DOI:10.1007/s11243-012-9598-z

Transition Met Chem (2012) 37:373–378
DOI 10.1007/s11243-012-9598-z
Synthesis, crystal structures, and catalytic activities of palladium
imidazole complexes formed by 2-hydroxyethyl group cleavage
•
Chen Xu Zhen Li Lu-Meng Duan
•
•
•
•
•
Zhi-Qiang Wang Wei-Jun Fu Xin-Qi Hao
Mao-Ping Song
Received: 31 December 2011 / Accepted: 14 March 2012 / Published online: 30 March 2012
Ó Springer Science+Business Media B.V. 2012
Abstract N-4,6-dimethyl-2-pyrimidinylimidazole 1 and
its hydroxyethyl derivative 1-(2-hydroxyethyl)-3-(4,6-
dimethyl-2-pyrimidinyl)imidazolium chloride 2 have been
synthesized and characterized. The attempted synthesis
of bis(N-heterocyclic carbene)palladium complexes via the
direct reaction of 2 with Pd(OAc)2 results in the unexpected
formation of a bis(N-arylimidazole) palladium complex 3.
Additionally, the analogous bis(N-methylimidazole) palla-
dium complex 4 has also been synthesized by the above
method. Compounds 1–4 were characterized by elemental
analysis, IR, and 1H NMR. Additionally, their crystal
structures have been determined by X-ray diffraction.
Complexes 3 and 4 were found to be efficient catalysts for
the Suzuki reaction.
new generation of strong r-donor ligands and widely used
in organometallic chemistry and homogeneous catalysis
[4, 5]. Most significantly, NHC-palladium complexes
derived from imidazolium precursors have been success-
fully developed as highly active precatalysts for such cou-
pling reactions [6–8]. Synthetic procedures leading to the
precursor imidazolium salts have been elucidated [9], and
NHC ligands have been shown not merely to be innocent
spectators, but reactive intermediates in themselves, with a
number of new products being formed [10, 11]. In recent
years, part of our research effort has focused on the syn-
thesis and application of palladium complexes [12–14]. In
the course of our research into NHC-palladium complexes
[15], we sought to synthesize such complexes via the direct
reaction of imidazolium salts with Pd(OAc)2. In this work,
we have prepared a new N-arylimidazole ligand 1 and its
imidazolium salt 2, and we also observed the two unex-
pected formation of palladium imidazole complexes 3 and 4
from the imidazolium salt 2 (Scheme 1). The ability of
complexes 3 and 4 to catalyze the Suzuki reaction was also
investigated. The results are presented in this paper.
Introduction
Palladium-catalyzed coupling reactions such as the Suzuki
coupling have become an extremely powerful method in
organic synthesis for the formation of carbon–carbon bonds
[1–3]. Thus, the design and development of new palladium
catalysts is an important research topic. In the past decade,
N-heterocyclic carbenes (NHCs) have been developed as a
Experimental
Solvents were dried and freshly distilled prior to use. All
other chemicals were commercially available expect for
1-(2-hydroxyethyl)-3-methylimidazolium chloride [16] and
4,6-dimethyl-2-iodopyrimidine [17], which were prepared
according to the published procedures. Elemental analyses
were determined with a Thermo Flash EA 1112 elemental
analyzer. IR spectra were collected on a Bruker VEC-
TOR22 spectrophotometer using KBr pellets. 1H NMR
spectra were recorded on a Bruker DPX-400 spectrometer
in CDCl3 with TMS as an internal standard.
C. Xu (&) ꢀ Z.-Q. Wang ꢀ W.-J. Fu
College of Chemistry and Chemical Engineering,
Luoyang Normal University, Luoyang 471022, Henan, China
e-mail: xubohan@163.com
Z. Li ꢀ L.-M. Duan ꢀ X.-Q. Hao ꢀ M.-P. Song
Department of Chemistry, Zhengzhou University,
Zhengzhou 450052, Henan, China
123

374
Transition Met Chem (2012) 37:373–378
1,322, 1,199, 1,093, 1,065, 1,028, 855, 754. 1H NMR.
(400 MHz, CDCl3): d 9.13 (s, 1H, NCHN), 7.83 (s, 1H,
PyH), 7.53 (s, 1H, NCHCHN), 6.98 (s, 1H, NCHCHN),
2.51 (s, 6H, CH3).
R1
R1
Cl
OH
RI
N
N
N
N
N
OH
HN
N
Cl-
2
1
HO
Cl
Pd(OAc)2
THF
R2
R2
N
N
Pd
N
Cl
Pd
Cl
N
N
R2
General procedure for the Suzuki reaction
Cl
N
N
3 and 4
N
A prescribed amount of the catalyst, aryl bromide
(0.5 mmol), aryl boronic acid (0.75 mmol), base (1.0 mmol),
and solvent (3.0 mL) were placed in a Schlenk tube under
nitrogen. The reaction mixture was heated at 100 °C for
12 h, then cooled and quenched with water. The mixture was
extracted three times with CH2Cl2, and then the combined
organic layers were washed with water, dried over MgSO4,
and evaporated to dryness. The products were isolated by
flash chromatography on silica gel using petroleum ether
as eluent and identified by comparing melting points or 1H
NMR spectra.
R2
R1
=
N
OH
not observed
Scheme 1 Synthesis of compounds 1–4. R2 = R1 or Me
Preparation of compounds 1 and 2
A solution of 4,6-dimethyl-2-iodopyrimidine (1 mol),
imidazole (1.1 mol), NaOH (2 mol), and Bu4NBr (0.1 mol)
in benzene/H2O (50 mL/10 mL) was heated at 100 °C with
stirring for 36 h. The solvent was removed on a rotary
evaporator. The product 1 was separated by passing
through a short silica gel column with dichloromethane as
eluent. Then, a mixture of 1-chloroethanol (0.6 mol) and 1
(0.5 mol) was heated at 100 °C with stirring for 24 h. The
crude product was recrystallized from MeOH to give a
white solid 2. 1: Yield 83 %. Found (%): C, 62.3; H, 5.5;
N, 32.5. Calc. (%) for C9H10N4: C, 62.1; H, 5.8; N, 32.2. IR
(KBr, cm-1): 3,107, 1,597, 1,545, 1,473, 1,427, 1,385,
1,326, 1,247, 1,181, 1,106, 1,016, 898, 848, 782, 766.
1H NMR. (400 MHz, CDCl3): d 8.61 (s, 1H, NCHN), 7.89
(s, 1H, PyH), 7.13 (s, 1H, NCHCHN), 6.89 (s, 1H,
NCHCHN), 2.49 (s, 6H, CH3). 2: Yield 71 %. Found (%):
C, 51.7; H, 5.8; N, 22.3. Calc. (%) for C11H15ClN4: C,
51.9; H, 5.9; N, 22.0. IR (KBr, cm-1): 3,195, 1,582, 1,512,
1,451, 1,370, 1,344, 1,259, 1,061, 1,025, 882, 821, 804,
Crystal structure determination
Crystallographic data for compounds 1–4 were collected on
a Bruker SMART APEX-II CCD diffractometer equipped
with a graphite monochromator at 296 K using Mo–Ka
˚
radiation (k = 0.071073 A). The data were corrected for
Lorentz polarization factors as well as for absorption. The
structures were solved by direct methods and refined by
full-matrix least-squares methods on F2 with the SHELX-
97 program [19]. All non-hydrogen atoms were refined
anisotropically, while hydrogen atoms were placed in
geometrically calculated positions. The CCDC reference
numbers are 859298–859301 for 1–4, respectively. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
1
791. H NMR. (400 MHz, D2O): d 8.65 (s, 1H, NCHN),
7.97 (s, 1H, PyH), 7.63 (s, 1H, NCHCHN), 7.45 (s, 1H,
NCHCHN), 4.52 (t, 2H, CH2), 3.98 (t, 2H, CH2), 2.46
(s, 6H, CH3).
Results and discussion
General method for the synthesis of complexes 3 and 4
Synthesis and characterization
A Schlenk tube was charged with Pd(OAc)2 (1 mmol) and
the corresponding imidazolium salt (2.2 mmol) under
nitrogen. Dry THF was added via a cannula and the mix-
ture was stirred at 80 °C for 8 h. The solvent was removed
on a rotary evaporator, and the residue was dissolved in
CH2Cl2 and washed three times with water. The crude
product was recrystallized from CH2Cl2 to give 3 or 4 as
yellow solids (complex 4 was obtained in yield 67 %, and
its characterization data have been reported in the literature
[18]). 3: Yield 70 %. Found (%): C, 41.4; H, 3.6; N, 21.7.
Calc. (%) for C18H20Cl2 N8Pd: C, 41.1; H, 3.8; N, 21.3. IR
(KBr, cm-1): 3,152, 1,600, 1,541, 1,484, 1,418, 1,370,
Imidazolium salts can be obtained from imidazole by
stepwise aryl-/alkylation (Scheme 1). Firstly, we prepared
1 by reaction of 4,6-dimethyl-2-iodopyrimidine with
imidazole, in the presence of NaOH and Bu4NBr. The
imidazolium salt 2 was synthesized by refluxing 1 with
1-chloroethanol. Both compounds were characterized by
1
elemental analysis, IR, and H NMR. Additionally, their
crystal structures have been determined by X-ray diffrac-
tion. The structures of the molecules are shown in Figs. 1
and 2. The crystal structure of 1 reveals two molecules in
the asymmetric unit with some differences in geometry.
Intermolecular C–HꢀꢀꢀN hydrogen bonds link the molecules
123

Transition Met Chem (2012) 37:373–378
375
Fig. 1 Molecular structure of 1
Fig. 2 Molecular structure
of 2ꢀH2O
into a one-dimensional chain structure. In the crystal of
2ꢀH2O, there are many types of intermolecular C(O)–HꢀꢀꢀCl
and C–HꢀꢀꢀO hydrogen bonds (Fig. 3); water molecules and
chloride anions link to each other to form parallelogram
structures.
1:1:1. The downfield NCHN signal is still present, clearly
showing that a carbene complex has not been formed.
Remarkable downfield chemical shifts were observed for
the protons of the imidazole ring in the product compared
to those of the free ligand 1. This effect is common in such
complexes, due to the induction of electron density by the
metal resulting in effective deshielding the ligand protons
in close proximity. These results indicate that the main
product is a bis(N-arylimidazole) palladium complex.
However, the expected NHC-palladium complex was not
isolated from the reaction. In order to further investigate
Next, we studied the direct reaction of 2 with Pd(OAc)2
in THF. We expected that this reaction should produce the
NHC-palladium complex [Pd(NHC)2Cl2] as the main
product. It was surprising that the 1H NMR spectrum of the
main product was very similar to that of 2. It exhibits
similar peaks for the imidazole ring, with a proton ratio of
123

376
Transition Met Chem (2012) 37:373–378
Fig. 3 Packing diagram of
2ꢀH2O showing the hydrogen
bonds. Non-hydrogen bonding
H atoms are omitted for clarity
the nature of the product, its structure has been determined
by single crystal X-ray diffraction.
atom in each complex is coordinated by two N-substituted
imidazole ligands and two chloride atoms in a square-
planar fashion. The two N-substituted imidazoles are
mutually trans. The Pd–N and Pd-Cl bond lengths of
complexes 3 and 4 are similar to those of related palladium
imidazole complexes [18, 25, 26]. The crystal structure of
complex 3 includes p-p stacking interactions between the
imidazole and pyrimidine rings, which are used to con-
struct the one-dimensional lamellar structure (Fig. 4).
As expected from the spectroscopic analysis, the main
product 3 is a bis(N-arylimidazole) palladium complex.
During the reaction, the 2-hydroxyethyl group from the
imidazolium cation was lost, suggesting that the C–N bond
can be split with relative ease in the presence of palladium.
Although the exact mechanism of nitrogen deprotection is
not clear, it is probable that nucleophilic attack of OAc- on
the CH2 next to the positive charge is the first step of this
transformation, and a few similar N-substituent cleavage
reactions of imidazolium salts have been reported [18, 20–
24]. We have observed this type of reaction with the related
imidazolium salt [1-(2-hydroxyethyl)-3-methylimidazo-
lium chloride] and Pd(OAc)2. The analogous bis(N-methyl-
imidazole) palladium complex 4 has also been synthesized.
Even though the base KtOBu was used, the main products
of the above reactions were still 3 and 4, and no NHC-
palladium complexes were observed. In addition, an
attempt to employ the silver carbene transfer route was
unsuccessful. The molecular structures of complexes 3 and
4 are shown in Figs. 4 and 5, respectively. Selected bond
Application in Suzuki coupling reactions
Although NHCs palladium complexes have been success-
fully used as highly active catalysts for coupling reactions,
N-substituted imidazole palladium complexes have not
been widely explored in this field [18, 26–29]. Initially,
complex 3 was tested as a catalyst in the model coupling
reaction of 4-bromotoluene with phenylboronic acid to
ascertain the optimum conditions (Table 2). On screening a
variety of bases (entries 1–5), Cs2CO3 was found to give
the best results (98 % yield). A similar survey of solvents
indicated that dioxane was much better than other solvents
such as THF and DMF (entries 6–7). Toluene also afforded
o
˚
lengths (A) and angles ( ) are listed in Table 1. The Pd
Fig. 4 Packing diagram of 3
showing the p–p stacking
interactions. H atoms are
omitted for clarity
123

Transition Met Chem (2012) 37:373–378
377
Fig. 5 Molecular structure of 4.
Symmetry code: A 1 - X,
1 - Y, -Z
˚
Table 1 Selected bond lengths (A) and angles (°) for complexes 3
and 4
Table 3 Suzuki coupling of aryl bromides with heteroaryl–B(OH)2
catalyzed by 3
Cat 3;dioxane
ƒƒƒƒƒƒ!
HeteroarylꢁBðOHÞ þAr ꢁ Br
HeteroarylꢁAr
1
2
1
Complex
3
4
Cs2CO3
Yielda (%)
Pd(1)–Cl(1)
2.3023(9)
2.2959(9)
2.028(3)
2.024(3)
89.39(8)
91.07(8)
89.61(8)
89.94(7)
2.3026(15)
2.3027(15)
2.011(4)
Entry
Heteroaryl
Ar1
Pd(1)–Cl[(2) or (1A)]
Pd(1)–N(1)
1
Pyridin-3-yl
Pyridin-3-yl
Pyridin-3-yl
Pyridin-3-yl
Pyridin-3-yl
Pyridin-3-yl
Pyridin-3-yl
Pyridin-4-yl
Pyridin-4-yl
Pyridin-4-yl
Thiophen-2-yl
Furan-2-yl
Ph
96
94
93
91
87
90
95
94
92
97
82
86
2
p-MeC6H4
Pd(1)–N[(5) or (1A)]
N(1)–Pd(1)–Cl[(2) or (1A)]
N(1)–Pd(1)–Cl(1)
2.011(4)
3
p-OMeC6H4
o-MeC6H4
2,6-Me2C6H3
p-NO2C6H4
Pyridin-2-yl
Ph
90.06(14)
89.94(14)
89.94(14)
90.06(14)
4
5
6b
N[(5) or (1A)]–Pd(1)–Cl(1)
N[(5) or (1A)]–Pd(1)–Cl[(2) or (1A)]
7
8
9
p-MeC6H4
Pyridin-2-yl
Ph
Table 2 Optimization of reaction conditions for the Suzuki coupling
of 4-bromotoluene with phenyl boronic acid
10
11
12
Entry
Catalyst (mol%)
Base
Solvent
Yielda (%)
Ph
1
2
3
4
5
6
7
8
9
3(1)
3(1)
3(1)
3(1)
3(1)
3(1)
3(1)
3(1)
4(1)
K3PO4
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
THF
86
72
93
98
65
42
27
95
97
Reaction conditions: catalyst 3 (1 mol%), Ar1Br (0.5 mmol), het-
eroaryl–B(OH)2 (0.75 mmol), Cs2CO3 (1.0 mmol), dioxane (3 mL),
100 °C, 12 h
Na2CO3
K2CO3
Cs2CO3
NatOBu
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
a
Isolated yields
b
0.1 mol% 3
DMF
reaction conditions (Table 3). Reaction of 3-pyridinebo-
ronic acid with bromobenzene gave high yield (96 %, entry
1). Good yields were also obtained for 4-bromotoluene and
4-bromoanisole (entries 2–3). Ortho substituents were tol-
erated and even the very sterically hindered 2-bromo-m-
xylene provided the product in 87 % yield (entries 4–5).
The electron-deficient 4-nitrobromobenzene could be cou-
pled very efficiently with a catalytic loading as low as
0.1 mol% (entry 6). 2-Bromopyridine was found to be an
efficient coupling partner in this system, giving 95 % yield
(entry 7). Furthermore, the reactions of 4-pyridineboronic
acids with aryl bromides proceeded smoothly to provide
the desired products in good yields (entries 8–10). Finally,
the couplings of thiophen-2-ylboronic acids and furan-2-
ylboronic acids with bromobenzene also gave good yields
(entries 11–12).
Toluene
Dioxane
Reaction conditions: 4-bromotoluene (0.5 mmol), PhB(OH)2 (0.75 mmol),
base (1.0 mmol), solvent (3 mL), 100 °C, 12 h
a
Isolated yields
good coupled product yield (95 %, entry 8). Furthermore,
complex 4 also showed comparable activity, producing the
product in excellent yield (97 %, entry 9).
In contrast to arylboronic acids, the Suzuki coupling
reactions of heteroarylboronic acids have been relatively
less reported [30–32]. Thus, in the following experiments,
we investigated the Suzuki coupling of a variety of elec-
tronically and structurally diverse aryl bromides with pyr-
idyl–B(OH)2 catalyzed by complex 3 under the optimized
123

378
Transition Met Chem (2012) 37:373–378
12. Xu C, Zhang YP, Wang ZQ, Fu WJ, Hao XQ, Xu Y, Ji BM
(2010) Chem Commun 6852
Conclusion
13. Xu C, Wang ZQ, Zhang YP, Dong XM, Hao XQ, Fu WJ, Ji BM,
Song MP (2011) Eur J Inorg Chem 4878
14. Xu C, Lu YX, Lou XH, Wang ZQ, Fu WJ, Ji BM (2011) Tran-
sition Met Chem 36:637
15. Xu C, Hao XQ, Li Z, Dong XM, Duan LM, Wang ZQ, Ji BM,
Song MP (2012) Inorg Chem Commun. doi:10.1016/j.inoche.
2011.12.009
16. Branco LC, Rosa JN, Ramos JJM, Afonso CAM (2002) Chem
Eur J 8:3671
17. Xu C, Wang ZQ, Fu WJ, Lou XH, Li YF, Cen FF, Ma HJ, Ji BM
(2009) Organometallics 28:1909
18. Szulmanowicz MS, Zawartka W, Gniewek A, Trzeciak AM
(2010) Inorg Chim Acta 363:4346
In summary, we have prepared and characterized two new
carbene ligand precursors. The attempted synthesis of
bis(NHC)palladium complexes via imidazolium salts with
Pd(OAc)2 resulted in unexpected palladium imidazole
complexes, formed from C–N bond cleavage. These com-
plexes were found to be efficient catalysts for the Suzuki
reaction. Further research will focus on the reaction
mechanism and the applications involving such complexes
in other reactions.
Acknowledgments We are grateful to the National Natural Science
Foundation of China (No. 20902043) and the Natural Science
Foundation of Henan Province and Henan Education Department,
China (Nos. 102300410220 and 2009B150019) for financial support
of this work.
19. Sheldrick GM (2008) Acta Crystallogr A 64:112
20. Batey RA, Shen M, Lough AJ (2002) Org Lett 4:1411
21. Caddick S, Cloke FGN, Hitchcock PB, Lewis AKK (2004)
Angew Chem Int Ed 43:5824
22. Wang ZG, Sun HM, Yao HS, Shen Q, Zhang Y (2006) Orga-
nometallics 25:4436
23. Liu LJ, Wang F, Shi M (2009) Eur J Inorg Chem 1723
24. Sabiah S, Lee CS, Hwang WS, Lin IJB (2010) Organometallics
29:290
References
´
25. Kurdziel K, Olejniczak S, Okruszek A, Glowiak T, Kruszynski
1. Miyaura N, Suzuki A (1995) Chem Rev 95:2457
2. Suzuki A (2002) J Organomet Chem 653:83
3. Phan NTS, Sluys MVD, Jones CW (2006) Adv Synth Catal
348:609
4. Herrmann WA (2002) Angew Chem Int Ed 41:1290
5. Ender D, Niemeier O, Henseler A (2007) Chem Rev 107:5606
6. Nolan SP (ed) (2006) N-Heterocyclic carbenes in synthesis.
Wiley-VCH, Weinheim
7. Kantchev EAB, O’Brien CJ, Organ MG (2007) Angew Chem Int
Ed 46:2768
8. Fortman GC, Nolan SP (2011) Chem Soc Rev 40:5151
9. Benhamou L, Chardon E, Lavigne G, Bellemin-Laponnaz S,
Materazzi S, Potrzebowski MJ (2006) J Organomet Chem 619:
869
26. Xi CJ, Wu YW, Yan XY (2008) J Organomet Chem 693:3842
27. Mathews CJ, Smith PJ, Welton T (2003) J Mol Catal A: Chem
206:77
28. Mathews CJ, Smith PJ, Welton T (2004) J Mol Catal A: Chem
214:27
29. Kawamura K, Haneda S, Gan Z, Eda K, Hayashi M (2008)
Organometallics 27:3748
30. Kudo N, Perseghini M, Fu GC (2006) Angew Chem Int Ed
45:1282
31. Billingsley KL, Anderson KW, Buchwald SL (2006) Angew
Chem Int Ed 45:3484
32. Billingsley KL, Buchwald SL (2007) J Am Chem Soc 129:3358
´
Cesar V (2011) Chem Rev 111:2705
10. Crudden CM, Allen DP (2004) Coord Chem Rev 248:2247
11. Schuster O, Yang LR, Raubenheimer HG, Albrecht M (2009)
Chem Rev 109:3445
123