Efficient Ullmann C-N coupling catalyzed by a recoverable oligose-supported copper complex

Article abstract of DOI:10.1039/c6ra13536f

The natural compound β-cyclodextrin supported copper complex (CuIβ-CD) was prepared and employed as catalyst for an Ullmann-type C-N coupling reaction of N-nucleophiles and aryl halides under mild conditions. Reactions with different substrates were examined, and moderate to excellent yields were obtained. In addition to the high efficiency, the reaction system is also noticeable due to the excellent recoverability and reusability of the catalyst.

Full text of DOI:10.1039/c6ra13536f

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: X. Ge, X. Chen, C.
Qian and S. Zhou, RSC Adv., 2016, DOI: 10.1039/C6RA13536F.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Page 1 of 17
RSC Advances
View Article Online
DOI: 10.1039/C6RA13536F
Efficient Ullmann CꢀN coupling catalyzed by recoverable
oligoseꢀsupported copper complex
ab
b
b
c
Xin Ge , Xinzhi Chen , Chao Qian * and Shaodong Zhou *
a
School of Chemical and Material Engineering, Jiangnan University, Wuxi, P.R China
b
Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of
Chemical and Biological Engineering, Zhejiang University, Hangzhou, P.R China.
C
Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 135, 10623 Berlin,
Germany
Abstract
The natural compound βꢀCyclodextrin supported copper complex (CuI@βꢀCD) was prepared
and employed as catalyst for Ullmannꢀtype CꢀN coupling reaction of Nꢀnucleophiles and aryl
halides under mild conditions. Reactions with different substrates were examined, and moderate to
excellent yields were obtained. In addition to the high efficiency, the reaction system is also
remarked by the excellent recoverability and reusability of the catalyst.
Keywords: βꢀCyclodextrin, copper, CꢀN coupling reaction, catalysis, recoverable
*
Corresponding author. Chao Qian, Eꢀmail: qianchao@zju.edu.cn and Shaodong Zhou, Eꢀmail:
shaodong.zhou@campus.tuꢀberlin.de

RSC Advances
Page 2 of 17
View Article Online
DOI: 10.1039/C6RA13536F
Introduction
As an important CꢀN coupling strategy, transitionꢀmetal catalyzed Nꢀarylation has been widely
1
adopted in pharmaceutical and agrochemical industry during the past few decades . In addition to
2
so many examples that employ Group 10 metal complexes as catalysts , copper complex catalyzed
3
Nꢀarylation has been attracting more and more attention , which was initially proposed as
4
Ullmannꢀtype coupling . To overcome several drawbacks of the prototypical Ullmannꢀtype
o
coupling including high temperature (about 200 C), excessive usage of catalyst, fussyness about
substrate and moderate yield, great effort has been made on ligand design for the active copper
5
3a,3c,6
7
8
complex; a series of ligands were found effective, e.g. diamines
, glycol , Schiff base , amino
9
10
11
12
13
14
15
acids , diketones , phenanthroline , 2,2′ꢀbipyridine , carbohydrates , oxalamic acid , diamide .
While such effective ligands have brought improvement to the Ullmannꢀtype coupling process, the
recycling of catalyst remains challengeable. To this end, attempts have been made to immobilize
16
17
18
19
ligands on various supports such as magnetic materials, silica , polymers and fluorapatite to
achieve heterogeneous catalysis. Especially, the copperꢀexchanged fluorapatite showed
remarkably high activity in catalyzing the arylation of NꢀH heterocycles and imidazoles with aryl
chlorides and even some electronꢀpoor aryl fluorides; further investigation is highly demanding.
As green and abundant natural compounds, carbohydrates are not only employed as catalyst in
organic synthesis, but also widely used in organometallics due to the high “metal affinity” of some
20
21
22
oligoses, such as chitosan , cellulose and cyclodextrin (CD) . Up to now, oligoseꢀsupported
metal complexes have been reported capable of catalyzing some organic reactions like CꢀS
2
3
24
20a
22d
coupling, hydrogenation, Click cyclization and Suzuki crossꢀcoupling . Following the
25
interest in fineꢀtuning and design of carbohydrate structure , we studied Dꢀglucosamine promoted
Ullmannꢀtype CꢀN coupling reaction by means of combined experimental/theoretical
26
investigation . It has been found that the amino group does not count in the catalytic cycle of the
oxidative additionꢀreductive elimination mechanism and oxoꢀligated Cu complex was formed via
coordination of the hydroxyl groups with copper. Recently, we found that βꢀcyclodextrin
supported copper complex (Cu@βꢀCD) is highly active in catalyzing the Ullmannꢀtype CꢀN

Page 3 of 17
RSC Advances
View Article Online
DOI: 10.1039/C6RA13536F
coupling reaction. In addition to the high activity, Cu@βꢀCD is also remarkable due to its
excellent recoverability and reusability. Here, we describe this catalysis system in more detail.
Results and Discussion
As we have demonstrated previously, instead of the amino group, the hydroxyls affect more the
26
Dꢀglucosamine promoted Ullmannꢀtype CꢀN coupling reaction . As cyclic oligomers of
glucopyranosyl units, CDs possess the toroid exposing to secondary and primary hydroxyl
2
2a
groups . Moreover, CDs, especially αꢀ, βꢀ and γꢀCDs are able to form metal complexes via
coordination of unprotected hydroxyl groups with metal atoms. Thus we attempted to prepare
recyclable CDsꢀsupported Cu catalyst for CꢀN couplings. First, preparation of the Cu@CDs
catalyst via immobilization of copper salt on CDs was investigated. This is achieved by
suspending the commercially available CDs in neutral aqueous solution of copper salts, as well as
subsequent centrifugal separation and vacuum dry.
Performances of the prepared Cu@CDs catalysts were examined with the model reaction of
4
ꢀiodoanisole with imidazole, which was also selected for optimization of the reaction conditions;
more details can be found in Table 1. A preliminary comparison of the reactions catalyzed by
CuI@CDs with the one catalyzed by bare CuI and the one without any catalyst indicates that the
supporting on CDs dramatically promotes the activity of CuI (Table 1, Entry 1ꢀ6); CuI@βꢀCD
shows the highest catalytic activity, and βꢀCD is thus selected for further investigation. Next,
4 2
different copper sources, i.e. CuI, CuBr, CuSO and Cu(OAc) , were tested (Table 1, Entry 4, 7ꢀ9).
It turns out that the monovalent Cu salts are better copper source as compared to the divalent ones,
while CuI outstands.
a
Table 1. The coupling reaction of 4ꢀiodoanisole and imidazole catalyzed by Cu@CDs
b
Entry
Catalyst
Yield/%
1
2
CuI
ꢀ
trace
trace

RSC Advances
Page 4 of 17
View Article Online
DOI: 10.1039/C6RA13536F
3
4
5
6
7
8
9
CuI@αꢀCD
CuI@βꢀCD
54
85
67
42
41
25
17
CuI@γꢀCD
CuI@MeꢀβꢀCD
CuBr@βꢀCD
CuSO
4
@βꢀCD
@βꢀCD
Cu(OAc)
2
a
Reaction conditions: 4ꢀiodoanisole 1a (1.0 mmol), imidazole 2a (1.2 mmol), K CO (2.0 mmol) and
2
3
catalyst (copper loading 10 mol%) in the DMSOꢀwater (V/V:1/1, 5 ml) for 24 h.
b
Isolated yield.
Further, with CuI@βꢀCD as the catalyst, optimization of other reaction conditions such as
copper loading, solvent, base used and temperature, were performed. Reactions carried out in a
series of solvents were compared (Table 2); while the polar aprotic solvents DMSO and DMF
favor this coupling reaction, the solubilities of CuI@βꢀCD are limited. To solve this problem, the
mixed solvents, i.e. DMSOꢀwater (1:1) and DMFꢀwater (1:1) were also examined (Table 2, Entry
5
ꢀ6), and reaction carried out in the former gives the highest yield of all. This result indicates that
the objective coupling reaction is not sensitive to water, while the poor yield of Entry 4 in Table 2
2
7
is probably due to the rather low solubility of iodobenzene (200 mg/L ). With regard to the base
used, copper loading and temperature, they also affect much to the selected CꢀN coupling reaction
2 3
(Table 2, Entry 6ꢀ15); K CO was found the most ideal base, 10 mol% copper loading and the
o
reaction at 110 C gave the highest yield. Finally, the optimum conditions can be concluded: using
2 3
K CO as the acidꢀbinding reagent, DMSOꢀwater (1:1) as solvent, 10 mol% copper loading, 110
o
C. Further extensive experiments will be carried out on this conditions with CuI@βꢀCD as
catalyst.
a
Table 2. Optimization of the coupling reaction catalyzed by CuI@βꢀCD
H
N
N
I
CuI@ -CD
N
+
N
Solvent, Base
Temp., under air
O
O
1
a
2a
3a
b
o
c
Entry
CuI@βꢀCD
Base
Solvent
Temp/ C
Yield/%
1
2
3
10 mol%
10 mol%
10 mol%
K CO
DMF
DMSO
110
110
110
45
53
17
2
3
3
3
K
2
2
CO
CO
K
Methanol

Page 5 of 17
RSC Advances
View Article Online
DOI: 10.1039/C6RA13536F
4
5
6
7
8
9
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
5 mol%
K
K
K
2
2
2
CO
3
3
3
Water
110
110
110
110
110
110
110
110
110
80
trace
CO
CO
DMFꢀwater (1:1)
DMSOꢀwater (1:1)
DMSOꢀwater (1:1)
DMSOꢀwater (1:1)
DMSOꢀwater (1:1)
DMSOꢀwater (1:1)
DMSOꢀwater (1:1)
DMSOꢀwater (1:1)
DMSOꢀwater (1:1)
DMSOꢀwater (1:1)
DMSOꢀwater (1:1)
79
85
74
53
61
28
76
86
14
57
81
Cs
KOH
NaOH
Na CO
2
CO
3
1
0
2
3
1
1
2
3
4
5
K
2
CO
3
1
1
1
1
20 mol%
10 mol%
10 mol%
10 mol%
K
2
CO
3
3
3
3
K CO
2
K
2
2
CO
CO
100
120
K
a
Reaction conditions: 4ꢀiodoanisole 1a (1.0 mmol), imidazole 2a (1.2 mmol), base (2.0 mmol) and CuI@βꢀCD
b
c
in the solvent (5 ml) for 24 h. copper loading. Isolated yield.
The CuI@βꢀCD catalyst was characterized by Fourier transform infrared spectoscopy (FTꢀIR),
thermogravimetric analysis (TG), Xꢀray diffraction (XRD), transmission electron microscopy
(TEM) and inductively coupled plasmaꢀatomic emission spectroscopy (ICPꢀAES). The broad peak
ꢀ1
at 3450 cm in the FTꢀIR spectrum of pure βꢀcyclodextrin powder (shown as Fig.1a) corresponds
ꢀ1
to OꢀH stretching vibration. The peak at 1640 cm can be attributed to OꢀH bending vibration in
the glucose of βꢀcyclodextrin. While the coupled CꢀOꢀC stretching vibration are responsible to the
ꢀ1
ꢀ1
ꢀ1
peak at 1150 cm , presence of the peaks at 1076 cm and 1030 cm is due to the coupled
22e
CꢀO/CꢀC stretching/OꢀH bending vibrations . Differences have been found in FTꢀIR spectrum of
ꢀ1
the prepared CuI@βꢀCD (shown as Fig. 1b): the peaks turn sharper and stronger at 3450 cm ,
ꢀ1
ꢀ1
1
076 cm and 1030 cm , resulting from coordination of the hydroxyl group of βꢀcyclodextrin
ꢀ1
with atomic copper; in addition, increased intensity of the peak at 1390 cm was found, which can
be also attributed to complexation of copper with the hydroxyl group of βꢀcyclodextrin concerning
CꢀH/OꢀH bending vibrations. The TG analysis shows that the decomposition of CuI@βꢀCD was
o
o
mainly occurred from 290 C to 350 C (shown as Fig.2). Thus, CuI@βꢀCD is stable under a wide
range of temperature. The XRD patter of CuI@βꢀCD exhibits deposition of the composite film
from a dispersion of CuI in βꢀCD (Fig.S1, SI), in which CuI@βꢀCD has (111), (220) and (311)
2
8
diffraction peaks of CuI film . Further, the TEM analysis indicates well dispersion of CuI
particles on CDs, as shown in Fig.3a. Finally, the exact loading amount of copper in CuI@βꢀCD
was measured by ICPꢀAES analysis, and a content of 0.76 mmol/g was detected.

RSC Advances
Page 6 of 17
View Article Online
DOI: 10.1039/C6RA13536F
(b)
1390
(a)
1076
2930
1150
1640
1030
3450
4
000
3500
3000
2500
2000
1500
1000
500
ꢀ
1
wave number/cm
Fig.1 FTꢀIR spectral analysis of βꢀcyclodextrin (a) and CuI@βꢀCD (b).
Fig.2 TGꢀDTG analysis for CuI@βꢀCD
(
a)
(b)
Fig.3 TEM images of CuI@βꢀCD (a) and CuI@βꢀCD after being reused five times (b)

Page 7 of 17
RSC Advances
View Article Online
DOI: 10.1039/C6RA13536F
The extensive investigation was performed by varying the nucleophile and aryl halide of the
above model reaction; more details are shown in Table 3. Electron withdrawing and donating
effect of the groups substituted on aryl ring have much influence on the coupling reaction with
imidazole, comparably yields of electron withdrawing group were better than electron donating
group (Table 3, Entry 1ꢀ8). Here, either cleavage of the CꢀI bond does not correspond to the rate
limiting step or these substitution groups do not give much influence on the BDE(CꢀI). Next, we
compared the reactivities of different aryl halides with imidazole (Table 3, Entry 8ꢀ10); an order of
reactivity ArI > ArBr > ArCl was found, in line with the increasing BDE(ArꢀX) (BDE(ArI) =
2
9
2
72.0 kJ/mol < BDE(ArBr) =336.4 kJ/mol < BDE (ArꢀCl) = 397.9 kJ/mol) . Obviously, cleavage
of the CꢀX bond matters. Also, it was notice that the reactivity of metaꢀsubstituent was lower than
paraꢀsubstituent and substituent at orthoꢀposition had poor reactivity (Table 3, Entry 11ꢀ13). For
orthoꢀsubstituent, the steric hindrance inhibited its reaction with CuI@βꢀCD. Notably, when using
2
ꢀbromoꢀ and 2ꢀiodo phenethylamine as substrate, indoline was obtained by the intramolecular
CꢀN bond with medium yields (Table 3, Entry 14ꢀ15). Further, experiments with different
nucleophiles were performed; in general, the CꢀN coupling process is available with sorts of
amines as nucleophile, and moderate to excellent yields were obtained (Table 3, Entry 14ꢀ23). It is
notable that reaction with 4ꢀmethylimidazole gave obviously lower yield than that with imidazole
(
Table 3, Entry 1 and 16); the weak electronꢀdonating effect of methyl does not give clue to an
explanation; here, unknown factors affect. Some nitrogen nucleophiles such as
Hꢀbenzo[d]imidazole and indole were tried and the final products were obtained with good yields
Table 3, Entry 17 and 18). The reaction of aryl iodide with amide is more difficult than other
1
(
nucleophile (Table 3, Entry 21). Finally, the excellent yield given by the reaction with benzyl
amine can be attributed to the strong electron donating effect of benzyl that increases the electron
density of amino thus favoring the nucleophilic step (Table 3, Entry 22ꢀ23).
a
Table 3. The CꢀN coupling reaction catalyzed by CuI@βꢀCD

RSC Advances
Page 8 of 17
View Article Online
DOI: 10.1039/C6RA13536F
Nitrogen
b
Entry
1
Aryl Halides
1
Product
Yield/%
Compound
85 (3a
)
2
3
89 (3b)
94 (3c
)
4
96 (3d)
5
6
7
8
9
83 (3e)
87 (3f
)
82 (3g
)
81 (3h
57 (3h
trace
)
)
1
0
1
1
78 (3i
)
1
1
2
3
trace
c
8 (3j
)

Page 9 of 17
RSC Advances
View Article Online
DOI: 10.1039/C6RA13536F
14
15
16
ꢀ
ꢀ
53 (3k
)
36 (3k
)
69 (3l
)
17
18
72 (3m)
67 (3n
)
19
20
21
22
23
63 (3o
51 (3p
34 (3q
)
)
)
97 (3r
)
66 (3s
)
a
Reaction conditions: aryl halides
1
(1.0 mmol), nitrogen nucleophiles 2 (1.2 mmol), K CO (2.0 mmol) and
2 3
o
CuI@βꢀCD (loading 10 mol%) in the DMSOꢀwater (5 ml, 1/1:v/v), 110 C for 24 h.
b
c
Isolated yield. GC yield.
As a further advantage of CuI@βꢀCD, it is easily recoverable from the reaction system. The
separation of catalyst from reaction liquid is achievable via either centrifugation or filtration
depending on different solvation system. After that, washing the solid with ethanol and drying it
under vacuum to obtain the recovered catalyst that can be directly reused. Further, the reusability

RSC Advances
Page 10 of 17
View Article Online
DOI: 10.1039/C6RA13536F
of CuI@βꢀCD was examined with the model reaction as mentioned in Table 1, and centrifugation
was adopted in this reaction system to recover the catalyst; the results are shown in Fig.4. It is
clear that after being reused for five times, the catalytic activity of CuI@βꢀCD remains; fine
reusability and stability of the prepared catalyst are thus proved. Moreover, the TEM of
CuI@βꢀCD after being reused for five times (shown as Fig.3b) gives further evidence to its
structural stability and the content of copper was detected as 0.71 mmol/g by ICPꢀAES analysis.
Thus, it is proved that coordination of the hydroxyl group on the βꢀCD surface decreases metal
22a
leaching, in line with the previous report
.
1
00
8
6
4
2
0
0
0
0
0
1
2
3
4
5
Run
Fig.4 Recycling and reuse of catalyst CuI@βꢀCD
Conclusion
In summary, we have presented a simple and efficient protocol for Ullmannꢀtype CꢀN coupling
of Nꢀnucleophiles and aryl halides with oligose supported copper complex as catalyst.
Applicability of the catalytic system was proved by reactions of different aryl halides with various
amines, in which moderate to excellent yields of the CꢀN coupling products were obtained. In
addition to the high reactivity, the current protocol is also ecoꢀfriendly in that the catalyst is easily
recoverable and steadily reusable.

Page 11 of 17
RSC Advances
View Article Online
DOI: 10.1039/C6RA13536F
Experimental section
General methods
Melting points were determined on an X4ꢀData microscopic melting point apparatus and were
1
uncorrected. Nuclear magnetic resonance (NMR) spectra were measured at 400 MHz ( H) or at
13
1
00 MHz ( C) on a Bruker Avance DRXꢀ400 spectrometer. All reactions were monitored by
analytical thinꢀlayer chromatography (TLC) from Merck with detection by UV. The products were
purified by column chromatography through silica gel (300ꢀ400 mesh). All reagents and solvents
were general reagent grade unless otherwise stated.
General procedure of CuI@βꢀCD catalyzed coupling reaction of nucleophile and
aryl halide
To a stirred solution of DMSOꢀwater (v/v:1/1, 5 ml) were added aryl halide (1.0 mmol),
nucleophile (1.2 mmol), CuI@βꢀCD (130 mg, loading 10 mol%) and K CO (2 mmol) at room
2
3
o
temperature. Then the reaction mixture was heated to 110 C under air and stirred for 24 h. After
cooling to room temperature, the catalyst CuI@βꢀCD was separated by centrifugation. The
reaction mixture was partitioned by adding the ethyl acetate (20 ml) and water (20 ml).
Subsequently, the organic phase was separated and the aqueous phase was extracted with ethyl
acetate (20 ml) twice. The combined organic phases were washed with saturated brine, dried over
2
Na SO4, and concentrated in vacuo. Then the crude product was purified by column
chromatography through silica gel, eluting with petroleum ether/ethyl acetate solvent mixture, to
give the pure 3.
The spectral data of the products
13b
1
1
ꢀ(4ꢀMethoxyphenyl)ꢀ1Hꢀimidazole 3a. Pale yellow solid, m.p.: 60ꢀ61 °C. H NMR (400
MHz, CDCl3) δ 7.79 (s, 1H), 7.30 (d, J = 8.9 Hz, 2H), 7.20 (d, J = 6.7 Hz, 2H), 6.99 (d, J = 8.9 Hz,
2H), 3.85 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 159.00, 135.84, 130.67, 129.86, 123.25, 118.82,
+
1
14.93, 55.62. MS (EI): m/z = 174 [M] .

RSC Advances
Page 12 of 17
View Article Online
DOI: 10.1039/C6RA13536F
14b
1
1
ꢀ(4ꢀFluorophenyl)ꢀ1Hꢀimidazole 3b. Yellow oil. H NMR (400 MHz, CDCl ) δ 7.77 (d, J
3
13
=
3
15.0 Hz, 1H), 7.42 – 7.32 (m, 2H), 7.26 – 7.11 (m, 4H). C NMR (100 MHz, CDCl ) δ 162.92,
160.46, 135.78, 133.61, 130.44, 123.51 (J = 8.5 Hz), 118.61, 116.76 (J = 23.0 Hz). MS (EI): m/z =
+
1
62 [M] .
13b
1
1
ꢀ(4ꢀChlorophenyl)ꢀ1Hꢀimidazole 3c. Colorless oil. H NMR (400 MHz, CDCl3) δ 7.84 (s,
13
1
H), 7.52 – 7.42 (m, 2H), 7.35 (d, J = 8.7 Hz, 2H), 7.27 (s, 1H), 7.21 (s, 1H). C NMR (101 MHz,
+
CDCl
3
) δ 135.89, 135.53, 133.22, 130.67, 130.04, 122.72, 118.19. MS (EI): m/z = 178 [M] .
30
1
1
ꢀ(4ꢀ(1Hꢀimidazolꢀ1ꢀyl)phenyl)ethanone 3d. Pale yellow solid, m.p.: 112ꢀ114°C. H NMR
(
400 MHz, CDCl ) δ 8.09 (d, J = 8.5 Hz, 2H), 8.00 (s, 1H), 7.51 (d, J = 8.6 Hz, 2H), 7.36 (s, 1H),
3
1
3
7
1
3
.25 (s, 1H), 2.65 (s, 3H). C NMR (100 MHz, CDCl ) δ 196.54, 140.63, 135.86, 135.38, 130.77,
+
30.33, 120.77, 117.76, 26.60. MS (EI): m/z = 186 [M] .
13c
1
1ꢀ(4ꢀ(Trifluoromethoxy)phenyl)ꢀ1Hꢀimidazole 3e.
Colorless oil. H NMR (400 MHz,
CDCl
3
) δ 7.84 (s, 1H), 7.44 (d, J = 8.9 Hz, 2H), 7.35 (d, J = 8.6 Hz, 2H), 7.27 (s, 1H), 7.22 (s, 1H).
13
3
C NMR (101 MHz, CDCl ) δ 148.10, 135.90, 135.63, 130.79, 122.92, 122.54, 121.67, 119.10,
+
1
18.30. MS (EI): m/z = 228 [M] .
3
1
1
1
3
ꢀ(4ꢀ(Trifluoromethyl)phenyl)ꢀ1Hꢀimidazole 3f. Yellow oil. H NMR (400 MHz, CDCl ) δ
1
3
7
.97 (s, 1H), 7.43 (d, J = 7.4 Hz, 2H), 7.35 (d, J = 7.9 Hz, 2H), 7.25 (s, 1H), 7.20 (s, 1H).
C
NMR (101 MHz, CDCl ) δ 137.48, 135.62, 134.99, 130.26 (d, J = 21.4 Hz), 121.45, 118.37. MS
3
+
(
EI): m/z = 212 [M] .
30
1
3
ꢀ(4ꢀethoxyphenyl)ꢀ3Hꢀimidazole 3g. White solid, m.p.: 102ꢀ103°C. H NMR (400 MHz,
CDCl ) δ 7.83 (s, 1H), 7.30 (d, J = 8.9 Hz, 2H), 7.20 (d, J = 5.6 Hz, 2H), 6.98 (d, J = 8.9 Hz, 2H),
3
1
3
4
1
3
.08 (q, J = 7.0 Hz, 2H), 1.45 (t, J = 7.0 Hz, 3H). C NMR (100 MHz, CDCl ) δ 158.42, 135.80,
+
29.48, 123.23, 118.83, 115.45, 63.90, 14.74. MS (EI): m/z =188 [M] .
13b
1
1
ꢀPhenylꢀ1Hꢀimidazole 3h. Yellow oil. H NMR (400 MHz, CDCl3) δ 7.87 (s, 1H), 7.49 (t,
13
J = 7.7 Hz, 2H), 7.42 – 7.35 (m, 3H), 7.29 (s, 1H), 7.21 (s, 1H). C NMR (100 MHz, CDCl3) δ
+
1
37.40, 135.60, 130.41, 129.89, 127.50, 121.51, 118.25. MS (EI): m/z = 144 [M] .
30
1
1
ꢀ(3ꢀMethoxyphenyl)ꢀ1Hꢀimidazole 3i. White solid, m.p.: 125ꢀ127 °C. H NMR (400 MHz,
CDCl ) δ 7.87 (s, 1H), 7.42 – 7.30 (m, 1H), 7.24 (s, 1H), 7.17 (s, 1H), 6.99 – 6.91 (m, 1H), 6.90 –
3
1
3
6
1
3
.81 (m, 2H), 3.82 (s, 3H). C NMR (100 MHz, CDCl ) δ 196.54, 140.63, 135.86, 135.38, 130.77,
+
30.33, 120.77, 117.76, 26.60. MS (EI): m/z = 174 [M] .

Page 13 of 17
RSC Advances
View Article Online
DOI: 10.1039/C6RA13536F
32
1
Indoline 3k. Pale yellow oil. H NMR (400 MHz, CDCl ) δ 7.03 (d, J = 7.2 Hz, 1H), 6.93 (t,
3
J = 7.6 Hz, 1H), 6.62 (t, J = 7.4 Hz, 1H), 6.55 (d, J = 7.7 Hz, 1H), 3.44 (t, J = 8.3 Hz, 3H), 2.93 (t,
1
3
3
J = 8.3 Hz, 3H). C NMR (100 MHz, CDCl ) δ 151.64, 129.37, 127.25, 124.68, 118.71, 109.51,
+
4
7.37, 29.89. MS (EI): m/z = 119 [M] .
1
3b
1
1
ꢀ(4ꢀmethoxyphenyl)ꢀ4ꢀmethylꢀ1Hꢀimidazole 3l. White solid, m.p.: 79ꢀ80 °C. H NMR
400 MHz, CDCl ) δ 7.58 (s, 1H), 7.19 (d, J = 8.4 Hz, 2H), 6.94 – 6.80 (m, 3H), 3.76 (s, 3H), 2.21
s, 3H). C NMR (100 MHz, CDCl ) δ 158.68, 139.06, 134.81, 130.90, 122.84, 115.20, 114.85,
(
(
3
13
3
+
5
5.59, 13.65. MS (EI): m/z = 188 [M] .
ꢀ(4ꢀMethoxyphenyl)ꢀ1Hꢀbenz[d]imidazole 3m. Yellow solid, m.p.: 96ꢀ97 C. H NMR
400 MHz, CDCl ) δ 7.98 (s, 1H), 7.87 – 7.73 (m, 1H), 7.43 – 7.36 (m, 1H), 7.33 (d, J = 8.8 Hz,
H), 7.24 (p, J = 7.2 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H). C NMR (100 MHz, CDCl3)
3
3
o
1
1
(
3
1
3
2
δ 159.37, 142.55, 129.12, 125.74, 123.56, 122.63, 120.43, 115.13, 110.36, 55.64. MS (EI): m/z =
+
2
24 [M] .
3
4
o
1
1
ꢀ(4ꢀMethoxyphenyl)ꢀ1Hꢀindole 3n. White solid, m.p.:56–58 C. H NMR (400 MHz,
CDCl3) δ 7.73 (d, J = 7.1 Hz, 1H), 7.50 (d, J = 8.1 Hz, 1H), 7.48 – 7.39 (m, 2H), 7.32 (d, J = 3.2
1
3
Hz, 1H), 7.30 – 7.16 (m, 2H), 7.11 – 7.03 (m, 2H), 6.72 – 6.66 (m, 1H), 3.92 (s, 3H). C NMR
(100 MHz, CDCl3) δ 158.27, 136.37, 132.88, 128.98, 128.28, 126.00, 122.15, 121.02, 120.08,
+
1
14.75, 110.37, 102.90, 55.71. MS (EI): m/z = 223 [M] .
3
5
o
1
4
ꢀ(4ꢀMethoxyphenyl)morpholine 3o. White solid. m.p.: 72ꢀ73 C. H NMR (400 MHz,
1
3
CDCl
3
) δ 6.97 – 6.77 (m, 4H), 3.90 – 3.82 (m, 4H), 3.77 (s, 3H), 3.11 – 3.00 (m, 4H). C NMR
(
[
100 MHz, CDCl ) δ 154.00, 145.66, 117.84, 114.53, 67.06, 55.59, 50.84. MS (EI): m/z = 193
3
+
M] .
ꢀ(4ꢀMethoxyphenyl)pyrrolidine 3p. Yellow solid. m.p.: 45ꢀ46 C. H NMR (400 MHz,
CDCl ) δ 6.76 (d, J = 8.9 Hz, 2H), 6.45 (d, J = 8.9 Hz, 2H), 3.67 (s, 3H), 3.14 (t, J = 6.4 Hz, 4H),
35
o
1
1
3
1
3
1
2
3
.99 – 1.79 (m, 4H). C NMR (100 MHz, CDCl ) δ 149.75, 142.23, 114.00, 111.58, 54.98, 47.20,
+
4.35. MS (EI): m/z = 177 [M] .
Nꢀ(4ꢀmethoxyphenyl)ꢀ2ꢀpyrrolidinone 3q. White solid. m.p.: 111ꢀ112 C. H NMR (400
MHz, CDCl ) δ 7.50 (d, J = 9.0 Hz, 2H), 6.91 (d, J = 9.0 Hz, 2H), 3.98 – 3.63 (m, 5H), 2.60 (t, J =
36
o
1
3
1
3
8
3
.1 Hz, 2H), 2.24 – 2.09 (m, 2H). C NMR (100 MHz, CDCl ) δ 173.89, 156.59, 132.66, 121.84,
+
1
14.05, 55.46, 49.19, 32.45, 18.02. MS (EI): m/z = 191 [M] .

RSC Advances
Page 14 of 17
View Article Online
DOI: 10.1039/C6RA13536F
35
o
1
NꢀBenzylꢀ4ꢀmethoxybenzenamine 3r. White solid, m.p.: 49ꢀ50 C. H NMR (400 MHz,
CDCl3) δ 7.27 (q, J = 7.1 Hz, 3H), 7.18 (m, 1H), 6.70 (d, J = 8.8 Hz, 2H), 6.53 (d, J = 8.7 Hz, 2H),
1
3
4
1
.20 (s, 2H), 3.66 (d, J = 0.9 Hz, 3H). C NMR (100 MHz, CDCl
3
) δ 151.16, 141.43, 138.66,
+
27.56, 126.52, 126.14, 113.89, 113.08, 54.78, 48.22. MS (EI): m/z = 213 [M] .
37
o
1
4
ꢀMethoxyꢀNꢀphenylbenzenamine 3s. White solid, m.p.: 105ꢀ106 C. H NMR (400 MHz,
CDCl ) δ 7.14 (m, 2H), 6.99 (d, J = 8.8 Hz, 2H), 6.87 – 6.68 (m, 5H), 5.40 (s, 1H), 3.71 (s, 3H).
3
13
3
C NMR (100 MHz, CDCl ) δ 154.24, 144.14, 134.71, 128.27, 121.17, 118.53, 114.62, 113.64,
+
5
4.55. MS (EI): m/z = 199 [M] .
Acknowledgements
The authors are grateful for the financial support from the Natural Science Foundation of China
(21376213, 21476194), the Zhejiang Provincial Public Technology Research of China
(2014C31123, 2015C31038), Project Funded by China Postdoctoral Science Foundation
(2016M590536) and the Fundamental Research Funds for the Central Universities
(JUSRP115A05).
References
(
1)
2)
(a) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem Rev 2003, 103, 893(b) Voets, M.; Antes,
I.; Scherer, C.; MullerꢀVieira, U.; Biemel, K.; MarchaisꢀOberwinkler, S.; Hartmann, R. W. J
Med Chem 2006, 49, 2222(c) Wiglenda, T.; Ott, I.; Kircher, B.; Schumacher, P.; Schuster, D.;
Langer, T.; Gust, R. J Med Chem 2005, 48, 6516(d) Bambal, R. B.; Hanzlik, R. P. Chem Res
Toxicol 1995, 8, 729(e) Nair, V.; Bindu, S.; Sreekumar, V. Angew Chem Int Edit 2005, 44,
1907.
(
(a) Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angewandte Chemie-International Edition
in English 1995, 34, 1348(b) Louie, J.; Hartwig, J. F. Tetrahedron Lett 1995, 36, 3609(c)
Hartwig, J. F. Angew Chem Int Edit 1998, 37, 2046(d) Kantchev, E. A. B.; O'Brien, C. J.;
Organ, M. G. Angew Chem Int Edit 2007, 46, 2768.
(
3)
4)
(a) Klapars, A.; Antilla, J. C.; Huang, X. H.; Buchwald, S. L. J Am Chem Soc 2001, 123,
7727(b) Job, G. E.; Buchwald, L. Org Lett 2002, 4, 3703(c) Klapars, A.; Huang, X. H.;
Buchwald, S. L. J Am Chem Soc 2002, 124, 7421.
(
(a) Sainsbury, M. Tetrahedron 1980, 36, 3327(b) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz,
E.; Lemaire, M. Chem Rev 2002, 102, 1359.
(
5)
6)
Monnier, F.; Taillefer, M. Angew Chem Int Edit 2009, 48, 6954.
(a) Antilla, J. C.; Baskin, J. M.; Barder, T. E.; Buchwald, S. L. J Org Chem 2004, 69, 5578(b)
Surry, D. S.; Buchwald, S. L. Chem Sci 2010, 1, 13.
(

Page 15 of 17
RSC Advances
View Article Online
DOI: 10.1039/C6RA13536F
(
(
(
(
7)
(a) Kwong, F. Y.; Klapars, A.; Buchwald, S. L. Org Lett 2002, 4, 581(b) Yang, B.; Mao, Z. X.;
Zhu, X. H.; Wan, Y. Q. Catalysis Communications 2015, 60, 92.
8)
(a) Cristau, H. J.; Cellier, P. P.; Spindler, J. F.; Taillefer, M. Chem-Eur J 2004, 10, 5607(b)
Wang, Y.; Gao, J. Y.; Zhao, M. D.; Li, J. M. Chem Res Chinese U 2015, 31, 549.
(a) Ma, D. W.; Cai, Q. Synlett 2004, 128(b) Tang, J. M.; Xu, B. Q.; Mao, X.; Yang, H. Y.;
Wang, X. X.; Lv, X. J Org Chem 2015, 80, 11108.
9)
10)
(a) Shafir, A.; Buchwald, S. L. J Am Chem Soc 2006, 128, 8742(b) de Lange, B.;
LambersꢀVerstappen, M. H.; van de Vondervoort, L. S.; Sereinig, N.; de Rijk, R.; de Vries, A.
H. M.; de Vries, J. G. Synlett 2006, 3105.
(
11)
12)
Altman, R. A.; Buchwald, S. L. Org Lett 2006, 8, 2779.
(
Zhang, C.; Huang, B.; Bao, A. Q.; Li, X.; Guo, S.; Zhang, J. Q.; Xu, J. Z.; Zhang, R.; Cui, D.
M. Org Biomol Chem 2015, 13, 11432.
(
13)
14)
(a) Cheng, D. P.; Gan, F. F.; Qian, W. X.; Bao, W. L. Green Chem 2008, 10, 171(b) Wen, M.;
Shen, C.; Wang, L. F.; Zhang, P. F.; Jin, J. Z. RSC Adv 2015, 5, 1522(c) Suresh, P.; Pitchumani,
K. J Org Chem 2008, 73, 9121.
(
(a) Zhang, Y.; Yang, X. Y.; Yao, Q. Z.; Ma, D. W. Org Lett 2012, 14, 3056(b) Wang, Y. B.;
Zhang, Y.; Yang, B. B.; Zhang, A.; Yao, Q. Z. Org Biomol Chem 2015, 13, 4101.
Zhou, W.; Fan, M. G.; Yin, J. L.; Jiang, Y. W.; Ma, D. W. J Am Chem Soc 2015, 137, 11942.
Chouhan, G.; Wang, D. S.; Alper, H. Chem Commun 2007, 4809.
(
(
(
(
(
15)
16)
17)
18)
19)
Likhar, P. R.; Roy, S.; Roy, M.; Kantam, M. L.; De, R. L. J Mol Catal A-chem 2007, 271, 57.
Li, X. K.; Yuan, T. J.; Yang, Y.; Chen, J. M. Tetrahedron 2014, 70, 9652.
Choudary, B. M.; Sridhar, C.; Kantam, M. L.; Venkanna, G. T.; Sreedhar, B. J Am Chem Soc
2005, 127, 9948.
(20)
(a) Baig, R. B. N.; Varma, R. S. Green Chem 2013, 15, 1839(b) Dekamin, M. G.; Azimoshan,
M.; Ramezani, L. Green Chem 2013, 15, 811(c) Ifuku, S.; Matsumoto, C.; Wada, M.;
Morimoto, M.; Saimoto, H. Int J Biol Macromol 2013, 52, 72(d) Baig, R. B. N.; Nadagouda,
M. N.; Varma, R. S. Green Chem 2014, 16, 2122(e) Chao Shen; Jun Xu; Wenbo Yu; Zhang., P.
Green Chem 2014, 16, 3007.
(
21)
22)
Ye, J.; Wang, B.; Xiong, J.; Sun, R. C. Carbohyd Polym 2015, 135, 57.
(
(a) Bellia, F.; La Mendola, D.; Pedone, C.; Rizzarelli, E.; Saviano, M.; Vecchio, G. Chem Soc
Rev 2009, 38, 2756(b) Senra, J. D.; Malta, L. F. B.; da Costa, M. E. H. M.; Michel, R. C.;
Aguiar, L. C. S.; Simas, A. B. C.; Antunes, O. A. C. Adv Synth Catal 2009, 351, 2411(c)
Hapiot, F.; Ponchel, A.; Tilloy, S.; Monflier, E. Comptes Rendus Chimie 2011, 14, 149(d)
Zhang, G. F.; Luan, Y. X.; Han, X. W.; Wang, Y.; Wen, X.; Ding, C. R.; Gao, J. R. Green
Chem 2013, 15, 2081(e) Liu, X. D.; Yan, L.; Yin, W. Y.; Zhou, L. J.; Tian, G.; Shi, J. X.; Yang,
Z. Y.; Xiao, D. B.; Gu, Z. J.; Zhao, Y. L. Journal of Materials Chemistry A 2014, 2, 12296.
Shen, C.; Xu, J.; Yu, W. B.; Zhang, P. F. Green Chem 2014, 16, 3007.
(
23)
24)
(
Barskiy, D. A.; Kovtunov, K. V.; Primo, A.; Corma, A.; Kaptein, R.; Koptyug, I. V.
Chemcatchem 2012, 4, 2031.
(25)
(a) Shen, C.; Xia, H. J.; Zheng, H.; Zhang, P. F.; Chen, X. Z. Tetrahedron-asymmetr 2010, 21,
1
936(b) Shen, C.; Shen, F. Y.; Xia, H. J.; Zhang, P. F.; Chen, X. Z. Tetrahedron-asymmetr
011, 22, 708(c) Shen, C.; Shen, F.; Zhou, G.; Xia, H.; Chen, X.; Liu, X.; Zhang, P. Catalysis
2
Communications 2012, 26, 6(d) Shen, C.; Xia, H. J.; Yan, H.; Chen, X. Z.; Ranjit, S.; Xie, X.
J.; Tan, D.; Lee, R.; Yang, Y. M.; Xing, B. G.; Huang, K. W.; Zhang, P. F.; Liu, X. G. Chemical

RSC Advances
Page 16 of 17
View Article Online
DOI: 10.1039/C6RA13536F
Science 2012, 3, 2388(e) Ge, X.; Qian, C.; Chen, X. Z. Tetrahedron-asymmetr 2014, 25,
450(f) Ge, X.; Qian, C.; Chen, Y. B.; Chen, X. Z. Tetrahedron-asymmetr 2014, 25, 596.
1
(26)
(27)
(28)
(29)
Ge, X.; Chen, X. Z.; Qian, C.; Zhou, S. D. RSC Adv 2016, 6, 29638.
Tewari, Y. B.; Miller, M. M.; Wasik, S. P.; Martire, D. E. J Chem Eng Data 1982, 27, 451.
Yang, Y.; Gao, Q. M. Langmuir 2005, 21, 6866.
Luo, Y. R. Handbook of Bond Dissociation Energies in Organic Compounds; CRC Press:
Boca Raton, London, New York, Washington, D.C., 2002.
(30)
(31)
(32)
Wu, F. T.; Yan, N. N.; Liu, P.; Xie, J. W.; Liu, Y.; Dai, B. Tetrahedron Lett 2014, 55, 3249.
Li, L. Y.; Zhu, L.; Chen, D. G.; Hu, X. L.; Wang, R. H. Eur J Org Chem 2011, 2692.
Guo, D. L.; Huang, H.; Zhou, Y.; Xu, J. Y.; Jiang, H.; Chen, K. X.; Liu, H. Green Chem 2010,
12, 276.
(33)
(34)
(35)
Farahat, A. A.; Boykin, D. W. Tetrahedron Lett 2014, 55, 3049.
Rao, R. K.; Naidu, A. B.; Jaseer, E. A.; Sekar, G. Tetrahedron 2009, 65, 4619.
Zhu, X. H.; Su, L.; Huang, L. Y.; Chen, G.; Wang, J. L.; Song, H. C.; Wanlal, Y. Q. Eur J Org
Chem 2009, 635.
(
36)
37)
DeAngelis, A. J.; Gildner, P. G.; Chow, R.; Colacot, T. J. J Org Chem 2015, 80, 6794.
Zhang, H.; Cai, Q.; Ma, D. W. J Org Chem 2005, 70, 5164.
(

Page 17 of 17
RSC Advances
View Article Online
DOI: 10.1039/C6RA13536F
Graphical abstract