Efficient and recyclable Cu2(BDC)2(BPY)-catalyzed oxidative amidation of terminal alkynes: Role of bipyridine ligand

Article abstract of DOI:10.1039/c4cy01074d

We have described an efficient method for oxidative cross coupling reactions between activated N-H amines and terminal alkynes using heterogeneous Cu₂(BDC)₂(BPY) as recyclable catalyst (BDC = benzene-1,4-dicarboxylate; BPY = 4,4′-bipyridine). The optimal conditions involved the use of inexpensive NaHCO₃ base and oxygen as terminal oxidant in toluene solvent at 80°C. Reactions proceeds efficiently, and high selectivity with only trace amount of diynes as well as good yields were achieved in a short reaction time. The Cu₂(BDC)₂(BPY) exhibited excellent catalytic activity and selectivity as compared to other Cu-MOFs on a broad reaction scope. Interestingly, the presence of bipyridine ligand was shown to enhance the catalyst stability. Thus, the Cu₂(BDC)₂(BPY) could be facilely separated from the reaction mixture by simple centrifugation and could be reused several times with only a slight decrease in catalytic activity.

Full text of DOI:10.1039/c4cy01074d

View Article Online
View Journal
Catalysis
Science &
Technology
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: T. Truong, N. T. S.
Phan, H. T. N. Le and T. V. Tran, Catal. Sci. Technol., 2014, DOI: 10.1039/C4CY01074D.
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. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it 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/catalysis

Page 1 of 24
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01074D
Efficient and Recyclable Cu2(BDC)2(BPY)-Catalyzed Oxidative Amidation of
Terminal Alkynes: Role of Bipyridine Ligand
Hanh T. N. Le, Thuan V. Tran, Nam T.S. Phan, Thanh Truong*
Department of Chemical Engineering, HCMC University of Technology, VNUꢀHCM,
268 Ly Thuong Kiet, District 10, Ho Chi Minh City, Viet Nam
*Email: tvthanh@hcmut.edu.vn
Ph: (+84 8) 38647256 ext. 5681
Fx: (+84 8) 38637504
Abstract
We have described an efficient method for oxidative cross coupling reactions between
activated N-H amines and terminal alkynes using heterogeneous Cu2(BDC)2(BPY) as
recyclable catalyst (BDC = benzeneꢀ1,4ꢀdicarboxylate; BPY = 4,4’ꢀbipyridine). The
optimal conditions involved the use of inexpensive NaHCO3 base and oxygen as terminal
o
oxidant in toluene solvent at 80 C. Reactions proceeds efficiently and high selectivity
with only trace amount of diynes as well as good yields were achieved in short reaction
time. The Cu2(BDC)2(BPY) exhibited excellent catalytic activity and selectivity as
compared to other CuꢀMOFs on broad reaction scope. Interestingly, the presence of
bipyridine ligand was showed to enhance the catalyst stability. Thus, the Cu2(BDC)2(4,4’ꢀ
BPY) Cu2(BDC)2(BPY) could be facilely separated from the reaction mixture by simple
centrifugation and could be reused several times with only a slight decrease in catalytic
activity.
Keywords: Metalꢀorganic framework; oxidative coupling, alkynylation, amidation,
copper catalysis
1

Catalysis Science & Technology
Page 2 of 24
View Article Online
DOI: 10.1039/C4CY01074D
1. Introduction
Ynamines [1ꢀaminoꢀalkynes or Nꢀalkynyl amines] has increasingly gained importance
because of their frequent utility in valuable organic and pharmaceutical synthesis.1,2
Therefore, research in developing more efficient protocols for their preparation has much
been paid attention.3,4 Traditional methods in accessing ynamines employ the sequential
two step processes involving alkyne halogenation or alkyne metalation with borane
followed by CꢀN bond formation under copper catalysis.5ꢀ7 Recently, Stahl has presented
a direct oxidative coupling reaction between terminal alkynes and N-H amides using
CuCl2 catalyst.8 However, large excess amount of amide coupling components and slow
addition of alkynes were required to achieve good yields and selectivity. A few reports
using heterogeneous catalytic systems have been described.9ꢀ12 Mizuno employed
Cu(OH)x/TiO2 as catalyst for alkynylation of N-H oxazolidinone and sulfonamide
derivatives.9 Fan and coꢀworkers performed the reaction between phenylacetylene and 2ꢀ
oxazolidinone under Cuꢀmetallamacrocycleꢀbased 3D MOFs (MOFs = metalꢀorganicꢀ
frameworks) catalysis with slow addition of phenylacetylene.10 A preliminary
investigation of catalytic activity of Cuꢀbiphenylcarboxylate MOF catalysts was also
conducted and the significant damage of catalyst was observed.11 Recently, an elegant
works from Corma group indicated that Cu(BDC) was optimal catalysts for above
transformation among several tested heterogeneous copper catalysts by structurally
rendering the dimerization GlaserꢀHay reactions.12 However, only reactions between
phenylacetylene and 2ꢀoxazolidinone were demonstrated. In additional, catalyst
heterogeneity and recyclability has not been reported. Therefore, the heterogeneous
2

Page 3 of 24
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01074D
protocol development with more thorough investigation and higher generality on the
broader scope should be targeted.
MetalꢀOrganicꢀFrameworks (MOF have emerged as a fascinating class of crystalline
porous materials with ultrahigh porosity and enormous internal surface areas.13ꢀ16
Structurally, MOFs possess infinite network built with multitopic organic ligands and
metal ions. Thus, the possibilities in combination of two components, metal ion or cluster
and organic linker, provide MOFs with unique chemical versatility along with tunable
pore size and adjustable surface properties. These enable MOFs of interest for potential
applications in various fields including gas storage, separation, membranes, sensor,
biomedical imaging, and catalysis.17,18 Although the application of MOFs in catalysis is a
relative new research area, many MOFs have been investigated as heterogeneous
catalysts or catalyst supports for organic reactions, mostly conventional
transformations.19ꢀ21 By taking advantage of the transition metals presenting in the
structure, it has recently been reported that to many MOFs were employed for transitionꢀ
metalꢀcatalyzed reactions, which are routinely used in the synthesis a variety of valuable
compounds.12, 22ꢀ27 It is worth mentioning that one of the challenges in using MOFs in
catalysis is their low stability towards heating, moisture, and chemical environment due
to their nature of bonding. Recent studies addressing this problem pointed out that high
bond strengths between the metal oxide clusters and the organic linkers often ensure the
inertness of MOFs with external parameter.28ꢀ30 As previously mention, though Cuꢀ
carboxylate MOFs showed great activity and selectivity in ynamine synthesis reactions,
instability of these catalysts were observed.11 We hypothesized that immobilization of
ligands on Cuꢀcarboxylate MOFs would increase their stability. Herein we present the
3

Catalysis Science & Technology
Page 4 of 24
View Article Online
DOI: 10.1039/C4CY01074D
chemically stable and recyclable Cu2(BDC)2(BPY) as efficient catalyst for oxidative
coupling reactions of terminal alkynes and wide range of N-H amides forming ynamide
products. Moreover, profound investigation on reaction parameters and reactions scope
with respect to two coupling components was also investigated.
2. Experimental section
2.1. Materials and instrumentation
All reagents and starting materials were obtained commercially from SigmaꢀAldrich and
Merck, and were used as received without any further purification unless otherwise
noted. Nitrogen physisorption measurements were conducted using a Micromeritics 2020
volumetric adsorption analyzer system. Samples were pretreated by heating under
o
vacuum at 150 C for 3 h. A Netzsch Thermoanalyzer STA 409 was used for
o
thermogravimetric analysis (TGA) with a heating rate of 10 C/min under nitrogen
atmosphere. Xꢀray powder diffraction (XRD) patterns were recorded using a Cu Kα
radiation source on a D8 Advance Bruker powder diffractometer. Scanning electron
microscopy studies were conducted on a S4800 Scanning Electron Microscope (SEM).
Transmission electron microscopy studies were performed using a JEOL JEM 1400
Transmission Electron Microscope (TEM) at 100 kV. The Cu2(BDC)2(BPY) sample was
dispersed on holey carbon grids for TEM observation. Elemental analysis with atomic
absorption spectrophotometry (AAS) was performed on an AAꢀ6800 Shimadzu. Fourier
transform infrared (FTꢀIR) spectra were obtained on a Nicolet 6700 instrument, with
samples being dispersed on potassium bromide pallets. The chemisorption experiments
were studied in a Micromeritics 2020 analyzer. For hydrogen temperature programmed
4

Page 5 of 24
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01074D
o
reduction (H2ꢀTPR), the sample was outgassed at 100 C for 30 min with helium, then
cooled down to room temperature, and exposed to 50 ml/min of 10% H2/Ar as the
temperature ramped at 2.5oC/min to 600oC. The amount of hydrogen consumption was
determined from TCD signal intensities, which were calibrated using an Ag2O reference
sample.
Gas chromatographic (GC) analyses were performed using a Shimadzu GC 2010ꢀPlus
equipped with a flame ionization detector (FID) and an SPBꢀ5 column (length = 30 m,
inner diameter = 0.25 mm, and film thickness = 0.25 ꢁm). The temperature program for
o
o
GC analysis held samples at 100 C for 1.5 min; heated them from 100 to 280 C for 4.5
o
minutes; held them at 280 C for 2.5 min. Inlet and detector temperatures were set
o
constant at 280 C. Diphenyl ether was used as an internal standard to calculate reaction
conversions. GCꢀMS analyses were performed using a Hewlett Packard GCꢀMS 5972
with a RTXꢀ5MS column (length = 30 m, inner diameter = 0.25 mm, and film thickness =
0.5 ꢁm). The temperature program for GCꢀMS analysis heated samples from 60 to 280 oC
o
o
at 10 C/min and held them at 280 C for 10 min. Inlet temperature was set constant at
280 oC. MS spectra were compared with the spectra gathered in the NIST library. The 1H
and 13C NMR were recorded in CDCl3 using residual solvent peak as a reference on a
Bruker spectrophotometer at 500 MHz and 125 MHz, respectively.
2.2. Synthesis of the metal-organic framework Cu2(BDC)2(BPY)
A crystalline porous metalꢀorganic framework Cu2(BDC)2(BPY) was synthesized by
solvothermal method with modification with reported conditions.31,32 In a typical
experiment, solution of Cu(NO3)2.3H2O (0.968 g, 4 mmol) in N,Nꢀdimethylformamide
5

Catalysis Science & Technology
Page 6 of 24
View Article Online
DOI: 10.1039/C4CY01074D
(DMF, 80mL) was dropwise added to a beaker (350 mL) containing solution of H2BDC
(benzeneꢀ1,4ꢀdicarboxylic acid) (0.664 g, 4 mmol) and 4,4’ꢀbypyridine (0.312 g, 2 mmol)
in DMF (160 mL) under stirring condition at room temperature. Then, the mixture
(approximately 240mL) was divided into 24 vials (10 mL vials). These vials were capped
o
and heated at 120 C for 24 hours. After natural cooling (in period of 1 hour), green
crystals were collected from10 vials and soaked in DMF (3 days, 40 mL per day) and
then in methanol (3 days, 40 mL per day). The Cu2(BDC)2(BPY) was then dried and
activated under reduced pressure at 170oC in 12 hours to afford 1.578 g of desired MOFs
(75% yield calculated by Cu).
2.3. Catalytic studies
In a typical experiment, 2ꢀoxazolidinone (91.64 mg, 1.0 mmol, 5 eqv), NaHCO3 (33.6
mg, 0.4 mmol, 2 eqv), Cu2(BDC)2(BPY) (10.4 mg, 0.04 mmol, 20 mol%), 1.7 mL of
toluene, phenylacetylene (20.82 mg, 0.2 mmol, 1 eqv), diphenyl ether (as an internal
standard, 32.1 mg, 30 µL). A stream of oxygen was supplied by needle at 1 atm for first
15 minutes and then disconnected. The vial heated up to 80 oC and stirred during 4 hours.
After every 40 minutes, 20 µL of sample was regularly taken out via syringe, washed
with 2 mL of pure water, extracted by 2 mL of ethyl acetate and dried over anhydrous
Na2SO4. These samples were analyzed by GCꢀShimazu 2010 plus machine to determine
conversion of reaction. The product identity was further confirmed by GCꢀMS and NMR.
6

Page 7 of 24
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01074D
To investigate the recyclability of the Cu2(BDC)2(BPY), solids included CuꢀMOF,
NaHCO3, reactants and products were washed with toluene and then dichloromethane in
many times until reactants and products have been removed (confirmed by GC analysis).
Then, remaining solids was continued to be washed with methanol (3x10 mL) before
being used for the next runs. In leaching test, after 40 minutes, the reaction was stopped
and cooled down to room temperature. Solid were completely separated by centrifuge
(3000/min of rate, 10 min). The filtrate was added into another sealed vial containing
NaHCO3 (33.6 mg, 2 equiv.). The reaction solution was then stirred for a further 200
minutes at 80 oC. Reaction progress, if any, was monitored by GC.
3. Results and discussion
3.1 Catalyst synthesis and characterization
The synthesized metalꢀorganic framework Cu2(BDC)2(BPY) was characterized by
several techniques, including XRD, SEM, TEM, TGA, FTꢀIR, AAS, H2ꢀTPR, and
nitrogen physisorption measurements (Fig. S21 – Fig. S27). In general, all structural
characterization results are in good agreement with previous studies.31,32 The SEM and
XRD results indicated that Cu2(BDC)2(BPY) was formed in rectangular shape and highly
crystalline. Moreover, ligand 4,4’ꢀbipyridine was showed to be presence in the structure.
In particular, the percentage of 20.83 % copper by ICP obey the formula of
Cu2(BDC)2(BPY). In addition, FTꢀIR revealed the peak at 1615 cmꢀ1 of C=N bond in
pyridine.
7

Catalysis Science & Technology
Page 8 of 24
View Article Online
DOI: 10.1039/C4CY01074D
3.2. Catalytic studies
In optimization screening, the Cu2(BDC)2(BPY) was used as catalyst for the reaction of
phenylacetylene with 2ꢀoxazolidinone. It is well known that phenylacetylene, under
aerobic conditions, undergoes dimerization to form corresponding undesirable diynes
GlaserꢀHay product.33ꢀ35 Thus, reaction selectivity toward C-N coupling is carefully
considered as reaction outcome along with conversion during condition development.
Table 1. Optimization of reaction conditions with respect to solvent and basea
Entry
Temperature
(oC)
Solvent
Base
Conversion
Selectivity
(2 equiv.)
1
2
3
80
80
1,4ꢀDioxane
Acetonitrile
DMF
NaHCO3
NaHCO3
NaHCO3
5
0
0
0
0
80
80
80
80
80
80
80
80
80
80
80
80
80
90
70
60
42
4
5
Toluene
Dichloroethane
DMSO
NaHCO3
NaHCO3
NaHCO3
NaOAc
Na2CO3
Cs2CO3
K2CO3
100 (90)
94
95
53
56
13
79
0
6
96
7
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
100
100
10
8
9
10
11
12
13
14
15
16
17
18
30
0
KHCO3
K3PO4
83
84
51
60
52
53
66
61
73
61
Et3N
100
100
100
100
96
DBU
DABCO
NaHCO3
NaHCO3
NaHCO3
64
8

Page 9 of 24
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01074D
aVolume of solvent 2 mL, 0.2 mmol scale. Conversion by GC analysis. 2ꢀoxazolidinone /phenylacetylene
= 5:1.Numbers in parenthesis indicate the isolated yields.
o
The conditions employing molecular oxygen oxidant at 80 C were used to investigate
the effect of other parameters including solvents, bases, and temperature (Table 1). It was
found that solvent play a remarkable impact on reaction efficiency. Particularly, in 1,4ꢀ
dioxane, acetonitrile, and DMF the coupling reactions are insufficient (entries 1ꢀ3).
Optimal results were obtained in aromatic solvent toluene with complete conversion and
95 % selectivity (entry 4). Though high reaction rate was observed in 1,2ꢀdichloroethane
and DMSO, poor selectivity was achieved (entries 5, 6). The results were consistent with
previous reports in which nonꢀpolar aromatics solvents exhibited the better yields as
compared to aprotic and protic polar solvents.8ꢀ12 With respect to bases, various
inexpensive inorganic and organic bases were examined. Despite full conversion were
obtained in NaOAc and Na2CO3, substantial amount of dimerized products were obtained
(entries 7, 8). Reactions with K2CO3 and CS2CO3 recovered starting material in majority
(entries 9, 10). Moderate conversion and selectivity was observed in K3PO4 (entry 12).
Additionally, reaction using KHCO3, which was used in previous works, afforded 83%
conversion with 84% selectivity (entry 11). In organic bases such as Et3N, DBU, and
DABCO, selectivity of about 55 % was achieved with quantitative reaction conversion
(entries 13ꢀ15). It was studied that organic bases accelerated the formation of undesirable
o
diynes GlaserꢀHay products.36 Furthermore, increasing temperature to 90 C resulted in
significant drop in reaction selectivity (entry 16). It is worth mentioning that all previous
works using heterogeneous systems by Corma, Mizuno, Arai, optimal conditions was
carried out at 100 oC .9,11,12 In addition, reactions conducted at lower temperature than 80
9

Catalysis Science & Technology
Page 10 of 24
View Article Online
DOI: 10.1039/C4CY01074D
oC afforded more diynes as well as lower conversion (entries 17, 18). To confirm the
reaction selectivity, the C-N bond formation product was isolated by flash
chromatography and the characterization was carried out using NMR (1HꢀNMR and 13Cꢀ
NMR). Interestingly, reaction isolated yield was 90 %, which is significantly higher than
previous report on the same reactions using Cu(BDC).12 Therefore, NaHCO3 base in
toluene solvent at 80 oC were employed for further studies.
Reactions with variety of different oxidant were investigated (Table 2). It is worth
mentioning that reaction under air atmosphere significantly decrease the reaction
conversion as well as reaction selectivity (entry 1). When 2,2,6,6ꢀtetramethylpiperidinꢀ1ꢀ
yl)oxy (TEMPO) was employed, only 52 % selectivity toward C-N bond formation was
observed (entry 2). All tested peroxides are inactive, giving either low conversion or poor
selectivity (entries 3ꢀ6). Similarly, inorganic oxidant K2S2O8 was completely insufficient
(entry 7). Furthermore, reactions with NꢀmethylmorpholineꢀN-oxide (NMO) afforded
reasonable conversion with poor selectivity (entry 8). From green chemistry aspects, the
direct coupling reactions from sp CꢀH and NꢀH using molecular oxygen oxidant is highly
desired since H2O is the only wasteꢀproduct in reaction mixture.
10

Page 11 of 24
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01074D
Table 2. Effect of oxidant
Entry
Oxidant
Conversion
Selectivity
1
2
Air
28
99
12
25
53
20
0
43
52
0
TEMPO
3
4
5
6
7
8
Tertꢀbutyl peroxybenzoate
Tertꢀbutylhydroperoxide
Diꢀtertꢀbutylhydroxide
Cumene hydroperoxide
K2S2O8
0
40
0
0
NꢀMethylmorpholineꢀN-oxide (NMO)
58
54
aVolume of solvent 2 mL, 0.2 mmol scale. Oxidant 3 equiv. Conversion by GC analysis. 2ꢀoxazolidinone
/phenylacetylene = 5:1.
Further experiments under air environment were carried out to clarify the function of
oxygen oxidant and examine the effect of other components in air to reaction efficiency
(Table 3). In particular, reaction under oxygen atmosphere resulted in significant drop in
selectivity with only 77 % when 0.1 mg of H2O was added (entry2). Increasing amount of
H2O in reaction mixture led to the further decreasing in reaction selectivity (entry 3).
Reaction under N2 atmosphere afforded less than 10 % conversion and dimer product was
observed in majority (entry 4). Moreover, good conversion (80 %) and selectivity (93 %)
were obtained when dried air was employed (entry 5). Interestingly, reaction with
continuously supply of dried air enhanced the reaction efficiency and similar results were
achieved as compared to reaction using pure oxygen under optimal conditions (entry 6).
Therefore, oxygen is the actual reaction oxidant and the presence of H2O in reaction
mixture is likely to decrease the reaction selectivity.
11

Catalysis Science & Technology
Page 12 of 24
View Article Online
DOI: 10.1039/C4CY01074D
Table 3. Effect of other components in air to reaction efficiency
Entry
Environment
Conversion
Selectivity
1
2a
3b
4
Air
O2
28
99
43
77
45
<2
93
95
O2
99
N2
<10
80
5
6c
Dried Air
Dried Air
99
o
aVolume of toluene 2 mL, 0.2 mmol scale, 80 C, 4h. Gas was supplied for first 15 minutes and then
a
disconnected. Conversion by GC analysis. 2ꢀoxazolidinone /phenylacetylene = 5:1. Reaction with added
a
c
H2O (0.1 mg). . Reaction with added H2O (0.2 mg). Reaction with continuous flow of dried air during
reaction time.
Further investigation of the effect of reaction reagent loading on reaction rates was
kinetically examined. The tested conditions involved the use of NaHCO3 base (2 equiv.)
o
in toluene solvent at 80 C under oxygen atmosphere. Initial studies addressed the
catalyst percentage (Fig. 1). The experimental results revealed that only 46 % conversion
and poor selectivity were obtained under 10 % catalyst loading. Reaction proceeded at
significantly higher rate when 15 % catalyst was applied. However, reaction selectivity
was almost intact as compared to that of 10 % catalysts. As mentioned earlier, a
quantitative conversion of phenylacetylene was achieved after 240 min for the
transformation using 20 mol% Cu2(BDC)2(BPY) catalyst. It should be noted that almost
no reaction occurred in the absence of the Cu2(BDC)2(BPY), indicating the necessity of
copper catalyst. In the effort to reduce the amount of catalyst loading, pyridine was added
as reaction additive.8 Interestingly, 2 equiv. of pyridine was showed to enhance the
reaction rate as well as selectivity at 10 % catalyst loading with 95 % conversion and 92
% selectivity. As previously mentioned, low reaction selectivity was observed when other
organic bases were used (Table 1, Entry 13ꢀ15). Furthermore, reaction in pyridine
12

Page 13 of 24
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01074D
without inorganic base NaHCO3 gave only 15 % conversion (See Supporting
Information). Therefore, it is unlikely that pyridine played as base. In Stahl works,
pyridine was proposed as the nitrogen donor ligands.8 Under our reported conditions,
further studies are needed to clarify the actual function of pyridine in reaction
mechanism. However, with respect to green chemistry perspectives and reaction
condition simplicity, conditions using 20 % catalyst without pyridine additives was used
for further investigation.
20 mol%
10 mol%
15 mol%
0 mol%
a)
%
b)
Conversion (%)
Selectivity (%)
100
80
60
40
20
0
100
80
60
40
20
0
0
40
80
120
160
200
240
0 mol%
10 mol%
15 mol%
20 mol%
Time (min)
Fig. 1. Effect of catalyst loading on reaction conversion (a) and selectivity (b)
In previous studies with homogeneous CuCl2 catalyst and Cuꢀmetallamacrocycleꢀbased
3D MOFs, slow addition of phenylacetylene was required for good selectivity.10 Corma
and Mizuno works involved the use of 3 equiv. of 2ꢀoxazolidinone with respect to
phenylacetylene coupling partner.11,12 Therefore, the effect of molar ration between 2ꢀ
oxazolidinone and phenylacetylene was then investigated (Fig. 2). It was found that
reactions using ratio of oxazolidinone/phenylacetylene at 3/1 or 1/1 were not suitable
13

Catalysis Science & Technology
Page 14 of 24
View Article Online
DOI: 10.1039/C4CY01074D
since low conversions and poor selectivity were observed under tested conditions. In
addition, reaction rate was remarkable enhanced when 7 equiv. of oxazolidinone was
employed. Specifically, quantitative conversion was obtained after 160 minutes.
However, there was only slight improvement on reaction selectivity.
a)
Conversion (%) Selectivity (%)
%
b)
1:7
1:5
1:3
1:1
100
80
60
40
20
0
100
80
60
40
20
0
0
40
80
120
Time (min)
160
200
240
1:1
1:3
1:5
1:7
Ratio of Reagent
Fig. 2. Effect of reagent ratio on reaction conversion (a) and selectivity (b)
Table 4. Reactivity of other catalystsa
Selectivity
Entry Type
Catalyst
GC yield (%)
1
2
3
4
5
6
7
CuꢀMOFs
Cu2(BDC)2(BPY)
Cu2(BDC)2(DABCO)
Cu(BDC)
Cu(BDC) 2nd run
Cu2(OBA)2(BPY)
Cu3(BTC)2
100 (TOFb = 41.3) 95
100
92
56
58
39
4
85
84
51
75
47
0
Common salts Cu(OAc)2
14

Page 15 of 24
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01074D
8
Cu(NO3)2
98
100
99
99
25
0
73
9
CuCl2
33
32
71
39
10
11
12
13
14
15
16
17
CuBr
CuCl
CuSO4
Other MOFs
Ni2(BDC)2(BPY)
Co2(BDC)2(DABCO)
Mn2(BDC)2(DMF)2
Fe3O(BDC)3
0
0
0
ZIFꢀ67
0
b
aVolume of solvent 2 mL, 0.2 mmol scale. Calculated at initial reaction rate as moles of product formed
per hour and per mole of Lewis acidic active site (hꢀ1).
To gain more information about the catalyst reactivity, modification on catalyst structures
as well as variety of other catalysts were tested (Table 4). When ligand 4,4’ꢀbipyridine
(BPY) was replaced by DABCO, reaction rate was unchanged while only 85 % of
selectivity was achieved (entry 2). By removing BPY ligand, Cu(BDC) afforded only 92
% conversion and 84 % selectivity under our optimal condition (entry 3). In addition,
similar to previous works, catalyst damage was observed when recyclability test was
carried out with Cu(BDC) (entry 4). As observed in previous studies, changing BDC
linker to OBA or BTC linkers resulted in significantly decrease in reaction efficiency
(entries 5, 6). Several common copper salts were also catalytically examined. Excellent
conversions were achieved when Cu(NO3)3, CuCl2, CuBr, CuCl was employed.
However, substantial amount of dimer byꢀproduct was observed (entries 8ꢀ11).
Moreover, CuSO4 and Cu(OAc)2 were showed to be insufficient under tested conditions
(entries 7, 12). No trace amount of products was obtained when other MOFs with
15

Catalysis Science & Technology
Page 16 of 24
View Article Online
DOI: 10.1039/C4CY01074D
different linkers and metal clusters were applied (entries 13ꢀ17) indicating the necessity
of copper catalyst.
Standard
Solid catalyst was removed from reaction mixture
100
80
60
40
20
0
0
40
80
120
160
200
240
Time (min)
Fig. 3. Leaching test with catalyst removal after first 40 minutes
In leaching test, a control experiment was carried out using a simple hot filtration during
the course of the reaction. The direct oxidative CꢀH/NꢀH coupling reaction was then
conducted under optimal conditions involving the use of NaHCO3 base (2 equiv.),
o
oxygen oxidant in toluene solvent at 80 C in 6 hours. After 40 min with a conversion of
24 % being detected, the CuꢀMOF catalyst was removed from the reaction mixture by hot
filtration. The liquid phase was then transferred to a new reactor vessel, and magnetically
o
stirred for an additional 200 minutes at 80 C with aliquots being sampled at different
time intervals, and analyzed by GC. It was observed that no further conversion was
detected in the reaction mixture after the CuꢀMOFs catalyst was separated from the
16

Page 17 of 24
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01074D
reaction mixture (Fig. 3). In addition, ICPꢀMS revealed less than 30 ppm of copper in the
filtrate from reaction mixture. Therefore, it is likely that reactions could only proceed in
the presence of the solid Cu2(BDC)2(BPY) catalyst, and there should be no contribution
from leached active copper species in the liquid phase.
%
Conversion (%)
Selectivity (%)
100
80
60
40
20
0
1
2
3
Run
4
5
Fig. 4. Catalyst recycling studies.
As for all organic transformations using solid catalysts, the ability to recover and reuse
catalysts should be carefully considered. We therefore decided to investigate the
recoverability and reusability of the Cu2(BDC)2(BPY) catalyst by repeatedly separating
the CuꢀMOF catalyst from the reaction mixture after the reaction. The cross coupling
o
reactions was carried out using 2 equiv. of NaHCO3 in toluene at 80 C for 240 min, in
the presence of 20 mol% Cu2(BDC)2(BPY) catalyst. After the experiment, the CuꢀMOF
catalyst was separated from the reaction mixture by simple centrifugation, washed with
copious amounts of toluene, dichoromethane, and methanol and reused in further
reactions under identical conditions to the first run. It was found that the
17

Catalysis Science & Technology
Page 18 of 24
View Article Online
DOI: 10.1039/C4CY01074D
Cu2(BDC)2(BPY) catalyst could be recovered and reused several times without a
significant degradation in catalytic activity. Indeed, a conversion of more than 92 % with
about 90 % selectivity was still achieved in the 5th run (Fig. 4). As compared to the FTꢀIR
result of the fresh Cu2(BDC)2(BPY), the spectra of reused CuꢀMOF exhibited a similar
absorption (Fig. 5). Moreover, the XRD result of the recovered Cu2(BDC)2(BPY)
indicated that the crystallinity of the CuꢀMOF could be maintained, though slight
difference in the diffractogram was observed (Fig. 6).
Fig. 5. FTꢀIR spectra of the fresh (a) and reused (b) Cu2(BDC)2(BPY) catalyst.
18

Page 19 of 24
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01074D
Fig. 6. Xꢀray powder diffractograms of the fresh (a) and reused (b) Cu2(BDC)2(BPY)
catalyst.
As mentioned above, in previous studies using CuꢀMOFs catalyst, only the reaction
between phenylacetylene and 2ꢀoxazolidinone was tried.10ꢀ12 The generality of reported
conditions on other substrate scope has not been mentioned. In this study, other
derivatives of two coupling components were employed under optimal conditions and
isolated product yields were presented (Table 5). Phenylacetylene with substituents on it
such as methyl or methoxy were also active and cross coupling products were achieved in
excellent yields (entries 2, 3). It is well known that terminal alkynes possessing hydrogen
at C3 facilely undergo isomerization in presence of base and oxidant.37 Interestingly,
under our optimal conditions, amidation of aliphatic terminal alkynes was also possible.
In particular, alkynylation by cyclohexyl and cyclopentyl acetylene afforded products in
48 % and 40 % yields, respectively (entries 4, 5). Acyclic alkynes such as 1ꢀoctyne was
19

Catalysis Science & Technology
Page 20 of 24
View Article Online
DOI: 10.1039/C4CY01074D
amidatated in 96 % yield (entry 6). Crossꢀcoupling reactions of phenylacetylene with
different amides were also described. 2ꢀOxazolidinone derivative was alkynylated in
moderate yield (entry 7). In is worth mentioning that the erosion of enantioenriched
center was negligible. Amidation by sulfonamide was conducted and product was
obtained in 93 % yield (entry 8). Gratifyingly, optimal conditions were also applicable
for activated NꢀH amines. Specifically, 3ꢀacetoindole was cross coupled with
phenylacetylene and product was achieved in reasonable yield (entry 9). In addition,
diphenylamine was active and the corresponding alkynylated product for the first time
synthesized by this pathway was isolated in 70 % yields (entry 10).
Table 5. Reactions scope with respect to coupling partners
Isolated
Entry
1
Amides/amines
Alkynes
Product
yields
(%)
O
O
90
85
86
HN
O
O
2
3
HN
O
O
HN
20

Page 21 of 24
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01074D
O
O
O
O
4
5
6
48
40
96
HN
O
HN
O
HN
7
93
O
O
8
9
31
32
HN
Ph
10
70
o
Conditions: Reaction volume (2 mL), alkyne (0.2 mmol), amide/alkyne = 5/1, 80 C, 6h. See
Supporting Information for details.
21

Catalysis Science & Technology
Page 22 of 24
View Article Online
DOI: 10.1039/C4CY01074D
4. Conclusions
In summary, the metalꢀorganic framework Cu2(BDC)2(BPY) was synthesized, and
characterized by several techniques including XRD, SEM, TEM, FTꢀIR, TGA, AAS, and
nitrogen physisorption measurements. The Cu2(BDC)2(BPY) could be used as an
efficient heterogeneous catalyst for oxidative cross coupling reactions between wide
range of terminal alkynes and activated NꢀH bonds. The optimal conditions involved the
use of inexpensive NaHCO3 base and oxygen as terminal oxidant in toluene solvent at 80
oC in 4 hours. The Cu2(BDC)2(BPY) catalyst offered high activity and selectivity since
only trace amount of diyens byꢀproducts were observed. Studies on catalyst modifying
indicated that bipyridine ligand enable the stability of catalyst while BDC was the
optimal linker. No product was detected for the reaction using other MOFs possessing
other first transition metal clusters indicating the importance of copper sites for the
transformation. Leaching copper species into liquid phase was showed to be unlikely.
Consequently, the Cu2(BDC)2(BPY) catalyst could be simply separated from the reaction
mixture by centrifugation reused several times without a significant degradation in
catalytic activity.
Acknowledgements
The Vietnam National University – Ho Chi Minh City (VNUꢀHCM) is acknowledged for
financial support through project No. B2013ꢀ20ꢀ05
22

Page 23 of 24
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01074D
References
1. A. D. Kyle, L. Hongyan, G. L. Andrew, H. Ryuji, L. Zhenjie, Y. Zhang, P. H.
Richard, Chem. Rev. 2010, 110, 5064–5106.
2. S. Oppilliart, G. Mousseau, L. Zhang, G. Jia, P. Thue´ry, B. Rousseau, J.ꢀC.
Cintrat, Tetrahedron, 2007, 63, 8094ꢀ8098
3. J. A. Mulder, K. C. M. Kurtz, R. P. Hsung, Synlett, 2003, 1379.
4. A. R. Katritzky, R. Jiang, S. K. Singh, Heterocycles, 2004, 63, 1455.
5. P. Murch, B. L. Stang, P. J. Williamson, Synthesis 1994, 1255.
6. J. R. Dunetz, R. L. Danheiser, Org. Lett. 2003, 5, 4011ꢀ4014.
7. D. Buissonneaud, J.ꢀC. Cintrat, Tetrahedron Lett., 2006, 47, 3139.
8. T. Hamada, X. Ye, S.S Stahl, J. Am. Chem. Soc., 2008, 130, 833–835.
9. X. Jin, K. Yamaguchi, N. Mizuno, Chem. Commun., 2012, 48, 4974.
10. Xu, Q. Wang, H. Li, W. Meng, Y. Han, H. Hou, Y. Fan, Chem. Commun., 2012,
48, 5736.
11. T. Arai, N. Kawasaki, H. Kanoh, Synlett, 2012, 23, 1549ꢀ1553.
12. G.ꢀG. Pila, M. Müller, A. Corma, Chem. Sci., 2014, 5, 2979ꢀ3007.
13. S. Kitagawa, R. Kitaura, S. Noro, Angew. Chem. Int. Ed., 2004. 43(18), 2334ꢀ
2375.
14. J. L.C. Rowsell, O. M. Yaghi., Microporous and Mesoporous Materials, 2004,
73, 3ꢀ14.
15. G. Férey, Chem. Soc. Rev., 2008, 37, 191ꢀ214.
16. C. Janiak and J. K. Vieth, New J. Chem., 2010, 34, 2366ꢀ2388.
17. M. O’Keeffe, Chem. Soc. Rev., 2009, 38, 1215ꢀ1217.
18. H.ꢀC. Zhou, J. R. Long, O. M. Yaghi, Chem. Rev., 2010, 112(2), 673ꢀ674.
19. A. Corma, H. García and F. X. Llabrés i Xamena, Chem. Rev., 2010, 110(8),
4606ꢀ4655.
20. M. Yoon, R. Srirambalaji,. and K. Kim, Chem. Rev., 2012. 112(2), 1196ꢀ1231.
21. J. Y. Lee, O. K. Fahra, J. Roberts, K. A. Scheidt, S. B. T. Nguyen and J. T. Hupp,
Chem. Soc. Rev., 2009, 38, 1450ꢀ1459.
22. J. Gascon, A. Corma, F. Kapteijn, F. X. L. i Xamena, ACS Catal., 2014, 4 (2),
361–378.
23

Catalysis Science & Technology
Page 24 of 24
View Article Online
DOI: 10.1039/C4CY01074D
23. I. Luz, F.X.L.i. Xamena, A. Corma, J. Catal. 2012, 285, 285ꢀ291.
24. N.T.S. Phan, C.K. Nguyen, T.T. Nguyen, T. Truong, Catal. Sci. Technol. 2014, 4,
369ꢀ377.
25. G. H. Dang, T. D. Nguyen, D. T. Le, T. Truong, N.T. S. Phan, ChemPlusChem,
2014, DOI 10.1002/cplu.201402090.
26. T. Truong, C. K. Nguyen, T. V. Tran, T. T. Nguyen, N. T. S. Phan, Catal. Sci.
Technol. 2014, 4, 1276ꢀ1285.
27. H. T.N. Le, T. T. Nguyen, P. H.L. Vu, T. Truong, N.T.S. Phan, J. Mol. Catal. A:
Chem. 2014, 391, 74 – 82.
28. S. Jhung, N. A. Khan, Z. Hasan, Cryst Eng Comm., 2012, 21, 7099ꢀ7109.
29. M. P. Suh, H. J. Park, T. K. Prasad and D. W. Lim, Chem. Rev., 2012, 112(2),
782ꢀ835.
30. K. Sumida, D. L. Rogow, J. A. Mason, T. M. McDonald, E. D. Bloch, Z. R.
Herm, T.ꢀH. Bae and J. R. Long, Chem. Rev., 2012, 112, 724ꢀ781.
31. G. L. Han, K. Zhou, A. N. Lai, Q. G. Zhang, A. M. Zhu, Q. L. Liu, J. Membr. Sci.
2014, 454, 36ꢀ43.
32. Y. Sakata, S. Furukawa, M. Kondo, K. Hirai, N. Horike, Y. Takashima, H.
Uehara, N. Louvain, M. Meilikhov, T. Tsuruoka, S. Isoda, W. Kosaka, O. Sakata,
S. Kitagawa, Science 2013, 339, 193–196.
33. C. Glaser. Ber. Dtsch. Chem. Ges. 1869, 2, 422ꢀ424.
34. A. S. Hay, J. Org. Chem. 1962, 27, 3320ꢀ3321.
35. P. Siemsen, R. C. Livingston, F. Diederich. Angew. Chem., Int. Ed. 2000, 39,
2632ꢀ2657.
36. K. Balaraman, V. Kesavan, Synthesis, 2010, 3461ꢀ3466.
37. Y. Makioka; Y. Taniguchi; T. Kitamura; Y. Fujiwara; A. Saiki, Bull. Soc. Chim. Fr 1997,
134, 349.
24