Synthesis of N-Heterocyclic Carbine Silver(I) and Palladium(II) Complexes with Acylated Piperazine Linker and Catalytic Activity in Three Types of C—C Coupling Reactions

Article abstract of DOI:10.1002/cjoc.202000237

Two bis-imidazolium salts LH₂·Cl₂ and LH₂·(PF₆)₂ with acylated piperazine linker and two N-heterocyclic carbene (NHC) silver(I) and palladium(II) complexes [L₂Ag₂](PF₆)₂ (1) and [L₂Pd₂Cl₄] (2) were prepared. The crystal structures of LH₂·Cl₂ and 1 were confirmed by X-ray analysis. In 1, one 26-membered macrometallocycle was generated through two silver(I) ions and two bidentate ligands L. The catalytic activity of 2 was investigated in Sonogashira, Heck-Mizoroki and Suzuki-Miyaura reactions. The results displayed that these C—C coupling reactions can be smoothly carried out under the catalysis of 2.

Full text of DOI:10.1002/cjoc.202000237

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Accepted Article
Title: Synthesis of NHC Silver(I) and Palladium(II) Complexes with Acylated
Piperazine Linker and Catalytic Activity in Three Types of C-C Coupling Reactions
Authors: Qingxiang Liu,* Xiantao Zhang, Zhixiang Zhao, Xinying Li and Wei Zhang
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Cite this paper: Chin. J. Chem. 2021, 39, XXX-XXX. DOI: 10.1002/cjoc.202100XXX
Synthesis of NHC Silver(I) and Palladium(II) Complexes with Ac-
ylated Piperazine Linker and Catalytic Activity in Three Types of
C-C Coupling Reactions
Qingxiang Liu,* Xiantao Zhang, Zhixiang Zhao, Xinying Li and Wei Zhang
Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin
300387, P. R. China.
Keywords
Silver | Palladium | N-Heterocyclic carbine | Catalytic activity | C-C Coupling reaction
Main observation and conclusion
Two bis-imidazolium salts LH2·Cl2 and LH2·(PF6)2 with acylated piperazine linker and two N-heterocyclic carbene (NHC) silver(I) and
palladium(II) complexes [L2Ag2](PF6)2 (1) and [L2Pd2Cl4] (2) were prepared. The crystal structures of LH2·Cl2 and 1 were confirmed by
X-ray analysis. In 1, one 26-membered macrometallocycle was generated through two silver(I) ions and two bidentate ligands L. The
catalytic activity of 2 was investigated in Sonogashira, Heck-Mizoroki and Suzuki-Miyaura reactions. The results displayed that these
C-C coupling reactions can be smoothly carried out under the catalysis of 2.
Comprehensive Graphic Content
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Liu et al.
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highly effective NHC-Pd(II) catalyst is still a challenge.
Background and Originality Content
Additionally, Sonogashira reaction under copper-free is one
of the things that researchers focused on. In a typical So-
nogashira procedure, the reaction is conducted using a Pd cata-
lyst with a copper additive (like CuI) as cocatalyst. Although the
copper additive can increase the cross-coupling rate, it can also
promote the occurrence of Glaser-Hay coupling as a side reac-
tion.[22] Moreover, Cu-acetylide generated in situ is extremely
sensitive to air and moisture, so inert atmospheric conditions are
required.[23] To overcome these drawbacks, some palladium cat-
alysts containing phosphine[24] or NHC[25] ligands have been de-
veloped in the absence of Cu. However, NHC-Pd(II) catalyzed
Sonogashira couplings under copper-free remain tiny compared
to P-Pd(II) complexes. Here are a few related examples, such as
Ghosh reported the complexes [(NHC)PyPdI2] (type I in Scheme
1), and these catalysts can catalyze Sonogashira coupling reac-
tions to give moderate to high yields for aromatic bromide and
aromatic iodide.[26] Yasar reported the mixed P/NHC-Pd(II) com-
plexes [(NHC)(PPh3)PdCl2] (type I in Scheme 1), and good to ex-
cellent yields for aromatic bromide and iodide were obtained.[27]
Also, Cao reported the complexes [(NHC)PyPdBr2] (type I in
Scheme 1), and the yields of 55-91% for aromatic bromide and
iodide were gained.[28] Although some good results were ob-
tained in these Sonogashira reactions, the most of cases suffer
from the problem of high catalyst loadings.
In view of this, further developing environmentally friendly,
air-stable and highly efficient catalysts for C-C cross-coupling
reactions is still highly desired. We are interested in bis-NHC lig-
ands and their metal complexes, several open bi-Pd(II) complexes
([(NHC)(CH3CN)(PdCl2)]2) with different bridging linkers (such as
alkyl, aryl or aryl ether) have been reported by us (type IV in
Scheme 1),[29] in which NHC-Pd(II) complexes were synthesized
via the metal exchange reaction of NHC-Ag(I) complexes with
PdCl2(CH3CN)2. The catalytic activities of these complexes in Su-
zuki-Miyaura or Heck-Mizoroki reactions were investigated using
MeOH/H2O or H2O as solvents with the catalyst dosages of
0.1-0.2%. In most cases, the moderate to high yields for aromatic
bromide and iodide were obtained. To explore more efficient
catalysts for C-C coupling reactions in aqueous media, herein, we
report the synthesis of two bis-imidazolium salts LH2·Cl2 and
LH2·(PF6)2 and two N-heterocyclic carbene silver(I) and palladi-
um(II) complexes [L2Ag2](PF6)2 (1) and [L2Pd2Cl4] (2) (type V in
Scheme 1). Particularly, the catalytic performance of complex 2
was studied in Suzuki-Miyaura, Heck-Mizoroki and Sonogashira
reactions. During investigation, we paid special attention to three
aspects below. Firstly, the water-soluble acylated piperazine as
bridging group was introduced in the synthesis of ligands, which
was a new attempt for the preparation of NHC metal complexes.
As expected, above three types of C-C coupling reactions can be
smoothly carried out in H2O/EtOH (1:1) under the catalysis of 2.
Secondly, we did not add any copper additive in Sonogashira
reactions, but good cross-coupling yields were obtained. Thirdly,
although the low catalyst loading (0.1 mol%) in these coupling
reactions were used, the similar yields were obtained in compar-
ison with other traditional NHC-Pd(II) catalyst using high catalyst
dosages.[30] These results indicated that complex 2 was an effec-
tive catalyst for promoting the formation of C-C bond.
After the first free stable N-heterocyclic carbene (NHC) was
discovered,[1] the metal complexes based on N-heterocyclic car-
benes have drawn considerable attention owing to their easy
access and structural variety.[2] Various kinds of relevant metal
complexes have been prepared via deprotonation of benzimidaz-
olium (or imidazolium) salts.[3] Because N-heterocyclic carbenes
possess the strong σ-donating ability, the metal complexes of
them have high stability to air, moisture and heat.[4] Among NHC
metal complexes, NHC silver(I) complexes play an important part.
On one hand, NHC silver(I) complexes can be used as carbene
transfer reagent to synthesize NHC-Ni(II), -Pd(II), -Cu(II), -Au(I),
-Rh(I), and -Ru(II) complexes.[5,6] On the other hand, NHC silver(I)
complexes are of biological activities as antimicrobial and anti-
cancer agents.[7,8] In addition, NHC palladium(II) complexes also
attracted extensive attention due to their importance as catalysts
in organic synthesis. NHC palladium(II) complexes have multiple
types of structures.[9] Among them, NHC-Pd(II) complexes with
two coordinated halogen atoms (Cl, Br or I) are a common kind of
catalyst, and they mainly contain six classes of structures as
shown in Scheme 1. (1) Mono-palladium(II) complexes bearing
two monodentate ligands (namely, two NHC ligands, or one NHC
ligand and one other ligand with heteroatom E (N, P, O, As and
Sb)),[10] (2) mono-palladium(II) complexes bearing one bidentate
chelating ligand (II),[11] (3) open bi-palladium(II) complexes bear-
ing one bis-NHC ligand (III),[12] (4) open bi-palladium(II) complex-
es bearing one bis-NHC ligand using B as bridge linker (IV), [13] (5)
cyclic bi-palladium(II) complexes bearing two bidentate chelating
ligands (V)[14] and (6) open tri-palladium(II) complexes bearing
one tri-NHC ligand (VI).[15] These catalysts have been widely
applied in some organic reactions such as Suzuki-Miyaura,
Heck-Mizorokim, olefin metathesis and Sonogashira reactions.[16]
Over the past two decades, the organic reactions in aqueous
media have been concerned by more and more researchers for
environmentally friendly and safe purposes. A number of related
reactions using P-Pd(II) [17] or NHC-Pd(II)[18] complexes as catalysts
have been reported. However, the application of P-Pd(II) com-
plexes was limited due to their toxicity and air-instability. By con-
trast, NHC-Pd(II) complexes are more favored by researchers due
to their small toxicity and good air-stability. NHC-Pd(II) catalyzed
reactions in aqueous media are relatively rare, and the main
problem is that water-solubility of most NHC-Pd(II) complexes is
poor. To solve this problem, it is necessary that introducing some
good water-soluble groups in the preparation of ligand. For ex-
+
ample, Huynh reported the complexes with -NR3 (type I in
Scheme 1), and these catalysts can catalyze Suzuki-Miyaura and
i
Mizoroki-Heck coupling reactions using PrOH/H2O as solvent to
give excellent yields for aromatic bromide, and good yields for
-
aromatic chloride.[19] Peris reported complexes with -SO3 (type I
and type II in Scheme 1), and these catalysts can catalyze Suzu-
ki-Miyaura coupling reactions using H2O as solvent to give mod-
erate to high yields.[20] Also, Cetinkaya and co-workers developed
a series of NHC-Pd(II) complexes with one carboxylate and two
carboxylates (type I in Scheme 1), and these catalysts can cata-
lyze Suzuki-Miyaura coupling reactions in water to give moderate
to high yields.[21] Even so, the preparation of water-soluble and
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Running title
Chin. J. Chem.
Scheme 1 Structures of some NHC-Pd(II) complexes with two coordi-
nated halogen atoms (Cl, Br or I)
B
B
X
NHC
X
Pd
X
NHC
E
NHC NHC
III
X
Pd
E
I
X
Pd
X
E
E
NHC
Pd
NHC
Pd
Pd
X
X
X
X
X
X
E
E
II
IV
X
B
E
Pd NHC
X
NHC
E
=
=
=
X
E
B
Cl, Br, I
NHC,
bridge
X
X
or
As Sb
NHC Pd
X
E
X
Pd
X
N, P, O,
group
X
Pd
E
X
NHC
E
Pd NHC
X
B
V
VI
Chin. J. Chem. 2021, 39, XXX－XXX
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Liu et al.
Report
showed no metal-metal interactions between two Ag+.[43] The
piperazine rings exhibited chair configuration and an inverse
symmetric center was observed in 1.
Results and Discussion
Preparation and characterization of bis-imidazolium salts
LH2·Cl2 and LH2·(PF6)2 and NHC metal complexes
[L2Ag2](PF6)2 (1) and [L2Pd2Cl4] (2)
The piperazine as a starting material was treated with chlo-
roacetyl chloride in the presence of Na2CO3 to generate
1,4-bis(2’-chloroacetyl)piperazine as shown in Scheme 2, fol-
lowed by the reaction with N-nbutylimidazole to afford
bis-imidazolium salt LH2·Cl2. Subsequent anion exchange reaction
using NH4PF6 in CH3OH was conducted to generate
1,4-bis[2’-(N-nbutylimidazoliumyl)acetyl]piperazine hexafluoro-
phosphate LH2·(PF6)2, which reacted further with Ag2O in ace-
tonitrile under N2 for 24 h to afford NHC silver(I) complex
[L2Ag2](PF6)2 (1). NHC palladium(II) complex [L2Pd2Cl4] (2) was
prepared via the metal exchange reaction of [L2Ag2](PF6)2 (1) with
PdCl2(CH3CN)2 (2 equiv.) in CH3CN under N2.
Scheme 2 Preparation of LH2·Cl2, LH2·(PF6)2, 1 and 2
nC4H9
O
N
N
Cl
nC4H9
nC4H9
2Cl-
O
O
O
O
Cl
Cl
Cl
N
N
N
N
N
HN
NH
N
N
N
N
Na2CO3
·
LH2
Cl2
nC4H9
nC4H9
NH4PF6
N
N
N
O
N
N
N
N
nC4H9
nC4H9
O
N
N
O
O
O
-
Ag2O
N
N
Ag
Ag
2PF6
N
-
2PF6
O
·(
LH2 PF6
N
N
N
N
N
)
Precursor LH2·(PF6)2 has good stability in air, and it is soluble
in CH3CN, CH2Cl2 and DMSO, and hardly soluble in petroleum
2
nC4H9
nC4H9
1
1
ether, diethyl ether and benzene. In the H NMR spectrum of
CN)2Cl2
Pd(CH3
LH2·(PF6)2 (Figure S7), the proton signal of imidazolium (NCHN)
was at δ = 9.07 ppm, and this value was similar to the signals of
known imidazolium salts.[2,3] Complexes 1 and 2 were stable in
the air, soluble in DMSO, but nearly insoluble in petroleum ether
and diethyl ether. From the 1H NMR spectra of 1 and 2 (Figure S9
and Figure S11), the proton signals of imidazolium (NCHN) have
disappeared, which indicated the formation of NHC-metal com-
plexes, and the signals of other protons were similar to those of
LH2·(PF6)2.[31-35] In the 13C NMR spectra of 1 and 2 (Figure S10 and
Figure S12), the signals of the carbonyl carbon were observed at
180.4 ppm and 179.9 ppm. The signal of carbene carbons for 1
did not observed, and this phenomenon has been reported in
some literatures of carbene-silver(I) complexes.[32] The signal of
carbene carbons for 2 was observed at 171.9 ppm, and this value
was similar to the signals of known carbene-palladium(II) com-
plexes.[5] In ESI-MS of [L2Pd2Cl4] (2) (Figure S13(a)-(c)), the signals
of losing 2Cl-, 3Cl- and 4Cl- (m/z [(M - 2Cl-)2+/2] = 556.5267, m/z
[(M - 3Cl-)3+/3] = 359.0568 and m/z [(M - 4Cl-)4+/4] = 260.0894)
were observed, which further indicated that the structure of
NHC-Pd(II) complex 2 was a macrocycle as shown in Scheme 2.
Additionally, the carbene-silver(I) complex as an intermediate of
preparing carbene-palladium(II) complex via metal exchange
reaction has been reported in some literatures,[36-38] in which the
structure of carbene-palladium(II) complexes were similar to the
structure of carbene-silver(I) complexes. We attempted to obtain
crystal structure of 2, unfortunately, it was unsuccessful.
nC4H9
nC4H9
N
N
N
N
N
N
N
O
O
O
O
PdCl2
PdCl2
N
N
N
N
N
nC4
H9
nC4H9
2
Figure 1 Perspective view of LH2·Cl2 and anisotropic displacement pa-
rameters depicting 50% probability. Some bond angles (˚) and lengths (Å):
N(2)-C(7)-N(1) 108.4(1), C(9)-N(3)-C(10) 120.0(1); C(7)-N(1) 1.323(2),
C(7)-N(2) 1.329(1), C(9)-N(3) 1.341(2), C(10)-N(3) 1.464(2). Sym. code: i:
-x, 1 - y, 1 - z. Monoclinic, space group P21/c with cell dimensions of a =
0.759(4) nm, b = 1.588(8) nm, c = 1.069(5) nm, β = 98.14(1)˚, V = 1.2765
nm3, Z = 2, μ = 2.84 cm-1.
Structures of LH2·Cl2 and [L2Ag2](PF6)2 (1)
The single crystals of LH2·Cl2 and [L2Ag2](PF6)2 (1) were gained
through diffusing diethyl ether to their solution of CH3CN. In the
cation of LH2·Cl2 (Figure 1), the N-C-N angle at imidazole ring is
108.4(1)˚, and this value is similar to those in the literatures of
known imidazolium salts.[39-42] In LH2·Cl2, two imidazole rings
were parallel, and an inverse symmetric center was observed.
The crystal structure of 1 was displayed in Figure 2, where
two ligands L and two silver(I) ions formed a 26-membered mac-
rocycle. The Ag(1)···Ag(1A) separation was 11.506(8) Å, which
Figure 2 Perspective view of 1 and anisotropic displacement parame-
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Chin. J. Chem.
ters depicting 50% probability. Some bond angles (˚) and lengths (Å):
N(2)-C(7)-N(1) 104.0(3), C(7A)-Ag(1)-C(17) 174.5(1), N(5)-C(17)-N(6)
103.9(3); C(7A)-Ag(1) 2.079(4), C(17)-Ag(1) 2.084(3), C(7)-N(1) 1.355(5),
C(7)-N(2) 1.354(5). Sym. code: i: -1 + x, 1 + y, -1 + z. Triclinic, space group
P-1 with cell dimensions of a = 1.027(7) nm, b = 1.306(1) nm, c = 1.341(1)
nm, β = 93.05(1)˚, V = 1.6140 nm3, Z = 1, μ = 7.72 cm-1.
The
cross-coupling
of
phenylboronic
acid
with
4-bromotoluene was used to test the different reaction condi-
tions (Table S2, see the supporting information). The reactions
were detected through GC analysis after the suitable intervals.
Using K2CO3 as base and H2O/EtOH (1:1) as solvent with
the catalyst loading of 0.1 mol% at 40 ˚C in air gave the same
Catalytic performance of [L2Pd2Cl4] (2) in Suzuki-Miyaura
reaction
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Table 1 Suzuki-Miyaura reaction with different aryl halides catalyzed by complex 2a
2
Complex
,
K2CO3 TBAB
+
Ar
2a-2m
Ar
X
B
(HO)2
H
40
2O/EtOH (1:1)
=
X
Br, I
Cl,
in air
°C,
O
X
H2N
X
O2N
O
O
X
2b
Br,
Cl, 14h,
2c
2e
Br,
Cl, 14h,
2a
14h,
2d
14h,
=
=
=
=
=
=
=
X
X
99%
36%
Br,
92%
87%
26%
X
Br,
Br,
93%
14h,
14h,
Br,
Br,
96%
94%
14h,
(1)
(2)
(1)
X
(2)
2f
14h,
2j
2g
18h,
2h
18h,
2i
14h,
=
=
=
X
=
=
X
87%
X
Cl, 14h, 31%
Br,
93%
X
Br,
87%
X
CHO
O2N
NO2
2m
Br,
14h,
Cl, 18h,
2k
2l
=
=
=
X
X
X
92%
33%
100%
(1)
(2)
(3)
=
=
X
trace
X
Cl, 14h,
35%
Cl, 18h,
8h,
I,
a Reaction conditions: Aryl halide (0.50 mmol), phenylboronic acid (0.60 mmol), K2CO3 (1.0 mmol), complex 2 (0.1 mol%), TBAB (10% mol), H2O/EtOH (1:1)
(3 mL), 40 ˚C, in air.
yield of 92% in 14 h or 16 h (entries 10 and 20). When the tem-
perature of reaction was changed to 25 ˚C or 60 ˚C, the yields of
56% or 92% were obtained (entries 21 and 22). When time was
reduced, the yields also descended (entries 17-19). When the
catalyst dosages were reduced, the catalytic performance was
obviously decreased (entry 24). Under the same conditions as
entry 10, the yield of 96% was obtained after adding 10 mol%
tetrabutylamonium bromide (TBAB) (entry 23, see the supporting
information). In this reaction, the palladium(0) species was gener-
ated in the catalytic process, and this substance may be the actual
catalyst. The addition of TBAB can stabilize palladium(0) and im-
prove catalytic activity of the catalyst.[44-48] Water, MeOH, EtOH,
H2O/EtOH (5:1), H2O/EtOH (1:5), DMF, 1,4-dioxane, THF and
CH3CN as solvents have also been tested, and the yields of 11-61%
were obtained (entries 1-9). By contrast, the solvent H2O/MeOH
(1:1) gave a high yield of 90% (entry 11). Different bases (Na2CO3,
NaHCO3, Et3N, K3PO4·3H2O, and NaOAc) have also been tested to
lead to poor to medium yields (entries 12-16). According to the
above results, the optimal conditions for this reaction were
H2O/EtOH (1:1) and K2CO3 as solvent and base, TBAB (10 mol%) as
co-catalyst with the catalyst loading of 0.1 mol% at 40 ˚C in air
(entry 23, see the supporting information). In entry 25, the cou-
pling reaction was carried out without the precursor, and other
conditions were the same as the optimal conditions to afford the
yield of 49%, which illustrated that the precursor played a key role
in the catalytic reaction.
of iodobenzene with phenylboronic acid to gave the yield of 100%
(2m(3)). Relative low yields (trace-36%) were gained in the cases
of aryl chlorides as substrates (2b(2), 2e(2), 2j, 2k, 2l, 2m(2)).
Catalytic performance of [L2Pd2Cl4] (2) in Heck-Mizoroki
reaction
Over the years, the Heck-Mizoroki reaction has been widely
concerned and developed.[49-53] The cross-coupling of styrene with
phenyl bromide was used to test the different reaction conditions
(Table S3, see the supporting information). Use of H2O/EtOH (1:1)
and K2CO3 as solvent and base with the catalyst loading of 0.1 mol%
at 110 ˚C in 12 h gave the yield of 87% (entry 17). Under the same
conditions, the yield of 92% was gained after adding 10 mol%
TBAB (entry 8, see the supporting information). The results of
entry 8 (the yield of 92% in air) and entry 20 (the yield of 92% in
N2) showed that the catalytic system had good tolerance to air.
Namely, the atmosphere had no obvious effect on the yield. When
the catalyst dosages were reduced, the catalytic performance was
obviously decreased (entry 18). Other solvents such as water,
MeOH, EtOH, DMF, 1,4-dioxane, THF and CH3CN were also tested,
and the yields of 11-45% were gained (entries 1-7). Some usual
bases (K3PO4·3H2O, NaOAc, Et3N, Na2CO3 and NaHCO3) were also
used to give poor to medium yields (entries 9-13). By analyzing
above results, the optimal conditions were H2O/EtOH (1:1) and
K2CO3 as solvent and base, TBAB (10 mol%) as co-catalyst with the
catalyst loading of 0.1 mol% at 110 ˚C in air (entry 8, see the sup-
porting information). In entry 19, the coupling reaction was car-
ried out without the precursor, and other conditions were same
as the optimal conditions to afford the yield of 38%, which illus-
trated that the precursor played a key role in the reaction.
As shown in Table 1, the different aryl halides as substrates
were used. In most cases, phenylboronic acid can react with the
aryl halides. 4-Nitrobromobenzene or 4-bromoacetophenone
gave the excellent yields of 99% or 96% (2b(1) and 2d).
4-Bromoanisole or 3-bromoanisole gave the good yields of 93% or
92% (2a and 2c). The catalyst was highly effective to the coupling
As displayed in Table 2, other aryl halides as substrates were
also used to test the catalytic activity. 4-Bromoacetophenone,
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3-bromoanisole, 4-bromoanisole, 4-nitrobromobenzene and
1-bromonaphthalene can react easily with styrene to afford yields
of 90-95% (3a-3c, 3d(1) and 3f). 4-Bromoaniline gave the yield of
85% (3e(1)). Aryl dibromides (9,10-dibromoanthracene,
4,4-dibromobiphenyl and 1,4-dibromonaphthalene) gave yields of
91-95% (3g-3i). Iodobenzene and bromobenzene afforded the
yields of 98% in 6 h and 92% in 12 h (3j(1) and 3j(2)). Aryl chlo-
rides gave unsatisfactory yields (from trace to 39% for 3d(2), 3e(2),
3j(3), 3k and 3l). Notably, only trans products were obtained in
the catalytic system.
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Table 2 Heck-Mizoroki reaction of aryl halides with styrene catalyzed by complex 2a
2
Complex
,
K2CO3 TBAB
+
Ar
X
Ar
H
110
2O/EtOH (1:1)
=
X
Br, I
3a-3l
Cl,
in
°C, air
O
H2N
(1)
O
N
O2
3d
3b
3a
3c
3e
O
X
=
=
=
=
=
=
=
=
=
X
X
Br, 12 95%
Br, 12 90%
X
Br, 12 92%
Br,
X
Br, 12 93%
X
X
12 85%
h,
h,
h,
(1)
(2)
h,
h,
h,
h,
12 39%
Cl,
trace
12
Cl,
(2)
3j
3f
3g
3h
=
=
3i
Br, 16 91%
X
X
6
98%
I,
h,
(1)
(2)
X
X
Br, 12 95%
h,
=
X
Br, 16 95%
=
X
Br, 16 91%
h,
h,
X
h,
trace
12
Cl,
h,
NO2
NO2
O2N
3l
3k
=
=
trace
X
12
Cl,
trace
12
h,
Cl,
h,
a Reaction conditions: aryl halide (0.50 mmol), styrene (0.75 mmol), K2CO3 (1.0 mmol), complex 2 (0.1 mol%), TBAB (10% mol), H2O/EtOH (1:1) (3 mL), 110
˚C, in air.
Table 3 Sonogashira reaction of phenylacetylene with aryl halides catalyzed by complex 2 a
2
Complex
,
Cs2CO3 TBAB
+
Ar
Ar
X
H
2O/EtOH (1:1)
80 in air
=
X
Br, I
Cl,
4a-4o
°C,
O
H2N
O2N
O
4c
4d
4a
4b
4e
=
=
=
=
=
=
X
Br, 10 92%
X
X
Br, 10 96%
=
X
Br, 10 94%
X
Br, 10 89%
h,
h,
h,
h,
h,
(1)
(2)
X
Br, 10 91%
h,
10 38%
Cl,
O
NO2
4i
10 55%
4j
4g
4f
4h
=
=
=
=
=
=
=
X
X
Br,
10 85%
X
X
Br, 10 94%
X
h,
X
Br, 10 91%
X
X
Br, 10 92%
Cl,
(1)
(2)
h,
h,
h,
h,
(1)
(2)
10 31%
h,
Cl,
10 39%
h,
Cl,
O2N
NO2
4l
10 66%
CHO
4m
=
X
10 44%
Cl,
4k
=
=
X
X
Br, 10 92%
h,
(1)
(2)
Cl,
h,
h,
10 98%
I,
h,
a Reaction conditions: aryl halide (0.50 mmol), styrene (0.75 mmol), Cs2CO3 (1.0 mmol), complex 2 (0.1 mol%), TBAB (10% mol), H2O/EtOH (1:1) (3 mL), 80
˚C, in air.
h gave the yields of 24-75% (entries 1-8). However, when mixed
solvents such as H2O/MeOH (1:1) or H2O/EtOH (1:1) were used in
the presence of Cs2CO3 at 80 ˚C in 10 h, the coupling yields of 87%
or 88% were obtained (entries 9 and 10). Other bases such as
K2CO3, NaOAc, K3PO4·3H2O, Et3N or NaHCO3 were also tested up-
on using H2O/EtOH (1:1) as solvent at 80 ˚C in 10 h, and the yields
of 26-77% were obtained (entries 11-15). When 10 mol% of TBAB
Catalytic performance of [L2Pd2Cl4] (2) in Sonogashira reac-
tion
Phenylacetylene and 4-bromoacetophenone were chosen to
screen the optimal conditions.[54,55] As illustrated in Table S4 (see
the supporting information), using single solvent (such as CH3CN,
1,4-dioxane, DMSO, H2O, DMF, MeOH, EtOH and THF) and using
Cs2CO3 as base with the catalyst loading of 0.1 mol% at 80 ˚C in 10
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Chin. J. Chem.
was added and other conditions were the same as entries 9
and 10, the yields of 90% and 92% were gained (entry 16 and
entry 17, see the supporting information). According to above
experimental results, the optimal conditions for this reaction were
H2O/EtOH (1:1) and Cs2CO3 as solvent and base, TBAB (10 mol%)
as co-catalyst with the catalyst loading of 0.1 mol% at 80 ˚C in air
(entry 17, see the supporting information). In entry 18, the cou-
pling reaction was carried out without the precursor, and other
conditions were the same as the optimal conditions to afford the
yield of 47%, which illustrated the precursor played a key role in
the reaction.
In Table 3, the different aryl halides were tested.
3-Bromoanisole, 4-bromoanisole or 4-bromoaniline coupled with
phenylacetylene to give the yields of 89-94% (4a-4c).
4-Nitrobromobenzene or 4-bromoacetophenone gave the yields
of 96% or 92% (4d(1) and 4h(1)). The couplings of
1-bromonaphthalene, 2-methylbromobenzene or bromobenzene
afforded the yields of 85-94% (4g, 4j(1), 4k(1)). The couplings of
Figure 3 Kinetic experiments of Sonogashira, Heck-Mizoroki and Suzu-
ki-Miyaura reactions.
aryl
dibromides
(4,4’-dibromobiphenyl
or
9,10-dibromoanthracene) afforded same yield of 91% (4e and 4f).
Coupling of aryl chlorides gave the yields of 55% and 66% (4i and
4l).
While
4-nitrochlorobenzene,
4-chloroacetophenone,
Conclusions
2-chlorobenzaldehyde or 2-chlorotoluene afforded the poor yields
of 36-44% (4d(2), 4h(2), 4m, 4j(2)). Iodobenzene gave the excel-
lent yield of 98% (4k(2)).
In summary, two piperazine-bridging NHC metal complexes
[L2Ag2](PF6)2 (1) and [L2Pd2Cl4] (2) have been prepared and char-
acterized. One 26-membered macrometallocycle in complex 1 was
formed by two silver(I) ions and two ligand L. Additionally, the
catalytic performance of complex 2 was studied in three types of
C-C coupling reactions. In the synthesis of ligand, the introduction
of acylated piperazine improved water solubility of complex 2.
Thus, three types of C-C coupling reactions (Sonogashira,
Heck-Mizoroki and Suzuki-Miyaura reactions) can be smoothly
carried out in H2O/EtOH (1:1) under the conditions of low catalyst
loading (0.1 mol%). In Sonogashira reaction, although no copper
additive was used, good cross-coupling yields were obtained.
These results indicated that complex 2 was an effective catalyst
for the formation of C-C bonds. Some further researches are un-
derway.
Kinetic studies
The kinetic experiments of the three coupling reactions were
carried out to research the mechanisms of reactions under the
optimal conditions (Table S2: entry 23, Table S3: entry 8 and Table
S4: entry 17, see the supporting information). The induction pe-
riods of 2 or 3 hours were observed in Figure 3. These reactions
progressed fast from 0 h, Suzuki-Miyaura and Heck-Mizoroki reac-
tions gave the yields of 82% and 78% after 8 h, and Sonogashira
reaction afforded the yield of 77% after 6 h. Thereafter, the three
reactions progressed slowly, and afforded the final yields of 96%
in 14 h, 92% in 12 h and 92% in 10 h. These experimental results
showed that the active catalytic species may be Pd(0) and the
precatalyst may be complex 2.[56, 57]
To understand whether these reactions were homogeneous
or heterogeneous, Hg drop experiments were carried out. These
three kinds of reactions were all suppressed. According to the
experimental results, Pd(0) was further confirmed to be the actual
catalytic species and these reactions were heterogeneous.[58, 59]
Experimental
General procedures
The solvents and chemicals for experiment were analytical
grade by purchasing commercially. H NMR and 13C NMR spectra
1
were collected using a Varian spectrometer. A Focus DSQI GC-MS
equipped with an integrator (C-R8A) was applied in GC analysis.
Elemental analyses were measured to apply Perkin-Elmer 2400C
Elemental Analyzer. The Accurate-Mass Q-TOF LC/MS (Agilent) at
220 ˚C was applied for recording ESI-MS spectra.
Preparation of 1,4-bis(2’-chloroacetyl)piperazine
Chloroacetyl chloride (2.010 g, 17.8 mmol) was added drop-
wise into a H2O (100 mL) solution of piperazine (0.765 g, 8.9 mmol)
and Na2CO3 (1.886 g, 17.8 mmol) under ice-water bath. The mix-
ture was stirred at room temperature for 1 h and a white precipi-
tate was formed. After the mixture was cooled for 0.5 h under
ice-water bath, the solid was collected through filtration to give
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1,4-bis(2’-chloroacetyl)piperazine. Yield: 1.851 g (87%). M.p.:
96-98 ˚C. 1H NMR (400 MHz, DMSO-d6) δ: 3.51 (d, J = 17.6 Hz, 8H,
CH2), 4.44 (s, 4H, CH2). 13C NMR (100 MHz, DMSO-d6) δ: 164.8
(C=O), 45.1 (CH2Cl), 44.7 (CH2Cl), 41.9 (CH2), 41.6 (CH2), 41.2 (CH2).
Anal. Calcd for C8H12N2O2Cl2: C, 40.18; H, 5.05; N, 11.71%. Found:
C, 40.21; H, 5.01; N, 11.69%.
moved by rotary evaporator to afford a yellow powder. This pow-
der was recrystallized through adding diethyl ether into its CH3CN
solution to give [L2Pd2Cl4] (2) as a pale yellow powder. Yield: 0.049
g (83%). M.p.: 272-275 ˚C. 1H NMR (400 MHz, DMSO-d6) δ: 7.81 (s,
4H, ArH), 7.62 (s, 4H, ArH), 5.37 (d, J = 10.0 Hz, 8H, CH2), 4.26 (t, J
= 6.0 Hz, 8H, CH2), 3.60 (d, J = 6.0 Hz, 8H, CH2), 3.51 (s, 8H, CH2),
1.82 (m, 8H, CH2), 1.28 (m, 8H, CH2), 0.92 (t, J = 7.0 Hz, 12H, CH3).
13C NMR (100 MHz, DMSO-d6) δ: 179.9 (C=O), 171.9 (Ccarbene),
126.6 (PhC), 122.6 (PhC), 50.1 (CH2), 47.9 (CH2), 33.5 (CH2), 19.8
(CH2), 13.7 (CH3). ESI-MS: m/z [(M - 2Cl-)2+/2] = 556.5267, m/z [(M
- 3Cl-)3+/3] = 359.0568, m/z [(M - 4Cl-)4+/4] = 260.0894.
Preparation of LH2·Cl2 and LH2·(PF6)2
1,4-Bis(2’-chloroacetyl)piperazine (0.956 g, 4.0 mmol) and
N-nbutylimidazole (1.104 g, 8.9 mmol) were dissolved in 50 mL of
THF, and heated to reflux with stirring. After 72 h,
1,4-bis[2’-(N-nbutylimidazoliumyl)acetyl]piperazine
dichloride
General method of Suzuki-Miyaura reaction
(LH2·Cl2) as a white solid was formed, and it was obtained through
1
filtration. Yield: 1.637 g (84%). M.p.: 150-152 ˚C. H NMR (400
For a representative reaction, 4-nitrobromobenzene (0.101 g,
0.50 mmol), phenylboronic acid (0.073 g, 0.60 mmol), TBAB (0.016
g, 10 mol%), K2CO3 (0.165 g, 1.2 mmol) and [L2Pd2Cl4] (2) (0.5 mg,
MHz, DMSO-d6) δ: 9.07 (s, 2H, 2-imiH), 7.81 (s, 2H, ArH), 7.63 (s,
2H, ArH), 5.38 (d, J = 10.8 Hz, 4H, CH2), 4.26 (t, J = 7.2 Hz, 4H, CH2),
3.59 (s, J = 5.4 Hz, 4H, CH2), 3.52 (s, 4H, CH2), 1.79 (s, J = 7.2 Hz, 4H, 0.1 mol%) were added into the solvent (3 mL, H2O:C2H5OH = 1:1,
CH2), 1.27 (d, J = 7.2 Hz, 4H, CH2), 0.93 (t, J = 7.2 Hz, 6H, CH3). 13
C
v:v), and stirred at 40 ˚C in air. After the predetermined time, 10
mL of water was added to the reaction mixture, which was ex-
tracted three times using CH2Cl2 (8 mL × 3). The oil layer was
washed three times with water (8 mL × 3), which was dried over
MgSO4. After filtration, the solution was concentrated to 3 mL.
The solution was separated through a column chromatography to
give 4-nitrobiphenyl (2b). Yield: 0.099 g (99%). 1H NMR (400 MHz,
CDCl3) δ: 8.31 (d, J = 8.8 Hz, 2H, ArH), 7.75 (d, J = 8.8 Hz, 2H, ArH),
7.64 (t, J = 4.2 Hz, 2H, ArH), 7.45 (m, 3H, ArH). 13C NMR (100 MHz,
CDCl3) δ: 147.6, 147.1, 138.7, 129.1, 128.9, 127.8, 127.3, 124.1.
NMR (100 MHz, DMSO-d6) δ: 163.9 (C=O), 137.3 (imiC), 124.1
(PhC), 121.8 (PhC), 48.6 (CH2), 31.3 (CH2), 18.6 (CH2), 13.2 (CH3).
Anal. Calcd for C22H36O2N6Cl2: C, 54.20; H, 7.44; N, 17.24%. Found:
C, 54.33; H, 7.51; N, 17.32%.
The methanol (20 mL) solution of NH4PF6 (0.619 g, 3.8 mmol)
and the methanol (20 mL) solution of LH2·Cl2 (0.974 g, 2.0 mmol)
were mixed. The mixture was stirred for 72 h at 25 ˚C, and
1,4-bis[2’-(N-nbutylimidazoliumyl)acetyl]piperazine
hexafluoro-
phosphate (LH2·(PF6)2) as a white solid was formed. LH2·(PF6)2 was
obtained through filtration. Yield: 1.235 g (87%). M.p.: 96-98 ˚C.
1H NMR (400 MHz, DMSO-d6) δ: 9.07 (s, 2H, 2-imiH), 7.81 (s, 2H,
PhH), 7.63 (s, 2H, PhH), 5.38 (d, J = 10.4 Hz, 4H, CH2), 4.26 (t, J =
6.0 Hz, 4H, CH2), 3.61 (d, J = 6.4 Hz, 4H, CH2), 3.52 (s, 4H, CH2),
1.82 (m, J = 6.6 Hz, 4H, CH2), 1.28 (m, J = 6.9 Hz, 4H, CH2), 0.93 (t, J
= 7.0 Hz, 6H, CH3). 13C NMR (100 MHz, DMSO-d6) δ: 163.9 (C=O),
137.3 (imiC), 124.1 (PhC), 121.7 (PhC), 48.6 (CH2), 31.3 (CH2), 18.7
(CH2), 13.2 (CH3). Anal. Calcd for C22H36O2N6P2F12: C, 37.40; H, 5.13;
N, 11.89%. Found: C, 37.55; H, 5.28; N, 11.78%.
General method of Heck-Mizoroki reaction
A mixture of bromobenzene (0.078 g, 0.50 mmol), styrene
(0.078 g, 0.75 mmol), TBAB (0.016 g, 10 mol%), K2CO3 (0.165 g,
1.2 mmol) and [L2Pd2Cl4] (2) (0.5 mg, 0.1 mol%) in solvent (3 mL,
H2O:C2H5OH = 1:1, v:v) was stirred at 110 ˚C in air. The other op-
erations were similar to that in Suzuki reactions, and stilbene (3j)
1
was obtained. Yield: 0.082 g (92%). H NMR (400 MHz, CDCl3) δ:
7.60 (d, J = 7.6 Hz, 4H, ArH), 7.45 (t, J = 7.6 Hz, 4H, ArH), 7.35 (t, J
= 7.4 Hz, 2H, ArH), 7.19 (s, 2H, ArH). 13C NMR (100 MHz, CDCl3) δ:
137.3, 128.6, 127.6, 126.5.
Preparation of complex [L2Ag2](PF6)2 (1)
Silver oxide (0.069 g, 0.30 mmol) reacted with
General method of Sonogashira reaction
1,4-bis[2’-(N-nbutylimidazoliumyl)acetyl]piperazine
hexafluoro-
A mixture of 4-bromoacetophenone (0.078 g, 0.50 mmol),
phenylacetylene (0.076 g, 0.75 mmol), TBAB (0.016 g, 10 mol%),
Cs2CO3 (0.390 g, 1.2 mmol) and [L2Pd2Cl4] (2) (0.5 mg, 0.1 mol%) in
solvent (3 mL, H2O:C2H5OH = 1:1, v:v) was stirred at 80 ˚C in air.
The other operations were similar to that in Suzuki reactions, and
1-(4-acetylphenyl)-2-phenylacetylene (4h) was obtained. Yield:
0.101 g (92%). 1H NMR (400 MHz, CDCl3) δ: 7.95 (d, J = 8.4 Hz, 2H,
ArH), 7.62 (d, J = 8.4 Hz, 2H, ArH), 7.56 (m, 2H, ArH), 7.37 (t, J =
3.2 Hz, 3H, ArH), 2.61 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3) δ:
197.2, 136.2, 131.7, 131.7, 128.8, 128.4, 128.2, 128.2, 122.7, 92.7,
88.6, 26.6.
phosphate (0.212 g, 0.30 mmol) in acetonitrile (30 mL) at 40 ˚C in
N2. After 12 h, the suspension was filtered and the filtrate was
concentrated to 5 mL. Upon the addition of 5 mL Et2O, a white
powder was precipitated. Isolation by filtration yields complex
1
[L2Ag2](PF6)2 (1). Yield: 0.131 g (65%). M.p.: 212-214 ˚C. H NMR
(400 MHz, DMSO-d6) δ: 7.50 (s, 4H, PhH), 7.36 (s, 4H, PhH), 5.31
(d, J = 10.4 Hz, 8H, CH2), 4.17 (d, J = 6.0 Hz, 8H, CH2), 3.62 (t, J
=11.0 Hz, 16H, CH2), 1.79 (s, 8H, CH2), 1.30 (q, J = 6.9 Hz, 8H, CH2),
0.93 (t, J = 7.0 Hz, 12H, CH3). 13C NMR (100 MHz, DMSO-d6) δ:
180.4 (C=O), 123.8 (PhC), 121.3 (PhC), 50.7 (CH2), 33.2 (CH2), 19.2
(CH2), 13.5 (CH3). Anal. Calcd for C44H68O4N12Ag2P2F12: C, 39.59; H,
5.13; N, 12.59%. Found: C, 39.44; H, 5.35; N, 12.46%.
X-ray data collection and structural determinations
Preparation of [L2Pd2Cl4] (2)
The collection of diffraction data of 1 and LH2·Cl2 was carried
out applying a Bruker Apex II CCD diffractometer.[60] The struc-
tures were solved with the SHELXS program.[61] Figures 1 and 2
were formed via employing Crystal-Maker.[62]
Pd(CH3CN)2Cl2 (0.026 g, 0.10 mmol) was added to a solution of
[L2Ag2](PF6)2 (1) (0.067 g, 0.05 mmol) in CH3CN (25 mL) under N2,
and the suspension solution was stirred for 24 h at ambient
temperature. After filtering, the solvent in the filtrate was re-
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Running title
Chin. J. Chem.
Organometallics 2016, 35, 762-770.
Supporting Information
[12] (a) Karimi, B.; Akhavan, P. F. ChemInform Abstract: Main-Chain
NHC-Palladium Polymer as a Recyclable Self-Supported Catalyst in the
Suzuki-Miyaura Coupling of Aryl Chlorides in Water. Inorg. Chem. 2011,
50, 6063-6072; (b) Zanardi, A.; Mata, J. A.; Peris, E. Domino Approach to
Benzofurans by the Sequential Sonogashira/Hydroalkoxylation Couplings
Catalyzed by New N-Heterocyclic-Carbene-Palladium Complexes. Or-
ganometallics 2009, 28, 4335-4339.
[13] (a) Dubey, P.; Gupta, S.; Sing, A. K. Trinuclear Complexes of Palladium(II)
with Chalcogenated N-Heterocyclic Carbenes: Catalysis of Selective Ni-
trile-Primary Amide, Interconversion and Sonogashira Coupling. Dalton
Trans. 2017, 46, 13065-13076; (b) Yang, J.; Li, P. H.; Zhang, Y. C.; Wang, L.
Dinuclear NHC-Palladium Complexes Containing Phosphine Spacers: Syn-
thesis, X-ray Structures and Their Catalytic Activities towards the Hiyama
Coupling Reaction. Dalton Trans. 2014, 43, 7166-7175.
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2021xxxxx.
Acknowledgements
This work was financially supported by Tianjin Natural Science
Foundation (No. 18JCZDJC99600), the National Natural Science
Foundation of China (No. 21572159) and the Program for
Innovative Research Team in University of Tianjin (TD13-5074).
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(The following will be filled in by the editorial staff)
Manuscript received: XXXX, 2021
Manuscript revised: XXXX, 2021
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Synthesis of NHC Silver(I) and Palladium(II) Complexes with Acylated Piperazine Linker and Catalytic Activity in Three Types of C-C Coupling
Reactions
Qingxiang Liu,* Xiantao Zhang, Zhixiang Zhao, Xinying Li and Wei Zhang
Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
NHC silver(I) and palladium(II) complexes were prepared, and the catalytic activity of NHC palladium(II) complex in C-C coupling reactions were inves-
tigated.
www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX
This article is protected by copyright. All rights reserved.