Ullmann-type coupling reaction using metal-organic framework MOF-199 as an efficient recyclable solid catalyst

Article abstract of DOI:10.1016/j.apcata.2013.02.005

A highly porous metal-organic framework (MOF-199) was synthesized, and characterized by several methods including XRD, SEM, TEM, TGA, FT-IR, AAS, and nitrogen physisorption measurements. The MOF-199 was used as an efficient recyclable solid catalyst for the Ullmann-type reaction between aryl iodides and phenols to form diaryl ethers. High conversions were achieved for the transformation at the catalyst concentration of 5 mol%, in the presence of MeONa as a base. Due to the rare availability and the high cost, Cs ₂CO₃ should only be used for the case of deactivated aryl iodides or deactivated phenols. The MOF-199 catalyst could be facilely separated from the reaction mixture by simple filtration, and could be reused several times without a significant degradation in catalytic activity. The Ullmann-type reaction could only proceed in the presence of the solid MOF-199 catalyst, and the contribution from leached active species in the liquid phase, if any, was negligible.

Full text of DOI:10.1016/j.apcata.2013.02.005

Accepted Manuscript
Title: Ullmann-type coupling reaction using metal-organic
framework MOF-199 as an efficient recyclable solid catalyst
Authors: Nam T.S. Phan, Tung T. Nguyen, Chi V. Nguyen,
Thao T. Nguyen
PII:
S0926-860X(13)00083-5
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.apcata.2013.02.005
APCATA 14096
To appear in:
Applied Catalysis A: General
Received date:
Revised date:
Accepted date:
4-12-2012
29-1-2013
2-2-2013
Please cite this article as: N.T.S. Phan, T.T. Nguyen, C.V. Nguyen, T.T.
Nguyen, Ullmann-type coupling reaction using metal-organic framework MOF-
1
99 as an efficient recyclable solid catalyst, Applied Catalysis A, General (2013),
http://dx.doi.org/10.1016/j.apcata.2013.02.005
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Ullmann-type coupling reaction using metal-organic framework MOF-199 as an
efficient recyclable solid catalyst
a*
a
a
b
Nam T. S. Phan , Tung T. Nguyen , Chi V. Nguyen , Thao T. Nguyen
Department of Chemical Engineering, HCMC University of Technology, VNU-HCM,
68 Ly Thuong Kiet, District 10, Ho Chi Minh City, Viet Nam
a
2
b
Department of Chemical and Food Engineering, Lac Hong University, 10 Huynh Van
Nghe, Buu Long Ward, Bien Hoa, Viet Nam
*
Email: ptsnam@hcmut.edu.vn
Ph: (+84 8) 38647256 ext. 5681
Fx: (+84 8) 38637504
Highlights
MOF-199 was used as catalyst for the Ullmann-type reaction.
High conversions were achieved using catalytic amounts of the MOF-199.
The catalyst could be recovered and reused.
Abstract
A highly porous metal-organic framework (MOF-199) was synthesized, and
characterized by several methods including XRD, SEM, TEM, TGA, FT-IR, AAS, and
nitrogen physisorption measurements. The MOF-199 was used as an efficient recyclable
solid catalyst for the Ullmann-type reaction between aryl iodides and phenols to form
diaryl ethers. High conversions were achieved for the transformation at the catalyst
concentration of 5 mol%, in the presence of MeONa as a base. Due to the rare availability
and the high cost, Cs CO should only be used for the case of deactivated aryl iodides or
2
3
deactivated phenols. The MOF-199 catalyst could be facilely separated from the reaction
1
Page 1 of 37

mixture by simple filtration, and could be reused several times without a significant
degradation in catalytic activity. The Ulmann-type reaction could only proceed in the
presence of the solid MOF-199 catalyst, and the contribution from leached active species
in the liquid phase, if any, was negligible.
Keywords: Metal-organic framework; MOF-199; Ullmann-type reaction; heterogeneous
catalyst; diaryl ethers.
1
. Introduction
Diaryl ethers have emerged as important structural motifs in a variety of biologically
active natural products and pharmaceuticals as well as in monomers for the synthesis of
functional polymers [1, 2]. Conventionally, these structures are synthesized by the
Ullmann coupling reaction of phenols with aryl halides in the presence of stoichiometric
or even greater quantities of copper salts at high temperatures [3]. However, the
separation and handling of large quantities of hazardous copper-based waste produced
from these homogeneous processes would present undesirable economic, environmental,
as well as health and safety issues [4]. Recently, several palladium-catalyzed coupling
transformations of phenols with aryl halides in the presence of phosphine-based ligands
have been developed [5, 6]. However, despite the efficiency of these protocols, using
homogeneous palladium catalysts for the Ullmann-type reaction would suffer a number
of drawbacks, such as high cost, relatively rare availability, and tedious work-up in the
product isolation as well as difficulty in the removal of residual palladium from the
desired product [7, 8]. Several efforts have been made to achieve a general and efficient
2
Page 2 of 37

approach for the formation of diaryl ethers, in which the combination of copper salts with
suitable ligands has attracted significant attention [3, 4, 9]. For the development of more
environmentally benign processes, the Ullmann-type transformation using heterogeneous
copper-based catalysts should be targeted in terms of the ease of handling, simple
workup, recyclability and reusability. Moreover, the catalyst recovery also decreases
contamination of the desired products with hazardous or harmful metals [10, 11]. To the
best of our knowledge, reports on solid copper catalysts for the Ullmann-type reaction
have been very limited in the literature [12-15].
Metal-organic frameworks (MOFs) have emerged as promising materials with potential
applications in several fields [16-21]. Although the use of MOFs in catalysis is a young
research area, MOFs have been employed as solid catalysts or catalyst supports for a
variety of organic transformations [22], including the three-component coupling reaction
of aldehyde, alkyne, and amine [23], the Biginelli reaction [24], the Friedlander reaction
[25, 26], asymmetric α-alkylation of aldehydes [27], NO generation from biologically
occurring substrates [28], the arylation of aldehydes with arylboronic acids [29], the Paal-
Knorr reaction [30], Friedel-Crafts reactions between pyrroles and nitroalkenes [31],
Friedel-Crafts alkylation and acylation [32-34], oxidation of organo-sulfide [35],
oxidation [36-41], alkene epoxidation [42-44], cycloaddition of CO with epoxides [45],
2
cyanosilylation [46, 47], hydrogenation [48], Suzuki cross-coupling [49, 50], Sonogashira
reaction [51], transesterification reaction [52], Knoevenagel condensation [53-55], aldol
condensation [56, 57], aza-Michael condensation [58, 59], 1,3-dipolar cycloaddition
reactions [60], N-methylation of aromatic primary amines [61], epoxide ring-opening
3
Page 3 of 37

reaction [62-64], hydrolysis of ammonia borane [65], and cyclopropanation of alkene
66]. In this work, we wish to report the application of MOF-199 as an efficient solid
[
catalyst for the copper-catalyzed Ullmann-type coupling reaction of aryl iodides with
phenols to form diaryl ethers. The catalyst could be separated from the reaction mixture
by simple filtration, and could be reused without a significant degradation in catalytic
activity.
2
. Experimental
2
.1. Materials and instrumentation
All reagents and starting materials were obtained commercially from Sigma-Aldrich and
Merck, and were used as received without any further purification unless otherwise
noted. Nitrogen physisorption measurements were conducted using a Quantachrome
o
2
200e system. Samples were pretreated by heating under vacuum at 150 C for 3 h. A
Netzsch Thermoanalyzer STA 409 was used for thermogravimetric analysis (TGA) with
o
a heating rate of 10 C/min under a nitrogen atmosphere. X-ray powder diffraction
(
XRD) patterns were recorded using a Cu Kα radiation source on a D8 Advance Bruker
powder diffractometer. Elemental analysis with atomic absorption spectrophotometry
AAS) was performed on an AA-6800 Shimadzu. Fourier transform infrared (FT-IR)
(
spectra were obtained on a Bruker TENSOR37 instrument, with samples being dispersed
on potassium bromide pallets. Scanning electron microscopy studies were conducted on a
S4800 Scanning Electron Microscope (SEM). Transmission electron microscopy studies
4
Page 4 of 37

were performed using a JEOL JEM 1400 Transmission Electron Microscope (TEM) at
00 kV.
1
Gas chromatographic (GC) analyses were performed using a Shimadzu GC 2010 Plus
equipped with a flame ionization detector (FID) and an SPB-5 column (length = 30 m,
inner diameter = 0.25 mm, and film thickness = 0.25 μm). The temperature program for
o
o
GC analysis heated samples from 100 to 130 C at 15 C/min; heated them from 130 to
o
o
o
o
2
00 C at 50 C/min; heated them from 200 to 215 C at 1.5 C/min; then heated them
o
o
o
o
from 215 C to 300 C at 50 C/min and held them at 300 C for 3 min. Inlet and detector
o
temperatures were set constant at 300 C. n-Dodecane was used as an internal standard to
calculate reaction conversions. GC-MS analyses were performed using a Hewlett Packard
GC-MS 5972 with a RTX-5MS column (length = 30 m, inner diameter = 0.25 mm, and
film thickness = 0. 5 μm). The temperature program for GC-MS analysis heated samples
o
o
o
from 60 to 300 C at 15 C/min and held them at 300 C for 3 min. Inlet temperature was
o
set constant at 300 C. MS spectra were compared with the spectra gathered in the NIST
library.
2
.2. Synthesis of MOF-199
The procedure to prepare MOF-199 was similar to that previously reported [67, 68]. In a
typical preparation, a solid mixture of Cu(NO ) .3H O (4.38 g, 18.10 mmol) and 1,3,5-
3
2
2
benzenetricarboxylic acid (H BTC) (2.36 g, 11.20 mmol) was dissolved in a mixture of
3
DMF (30 ml), ethanol (40 ml) and water (30 ml). The resulting solution was then
o
distributed in 20 ml vials. The vials were heated at 85 C in an isothermal oven for 24 h,
5
Page 5 of 37

yielding light blue crystals. After cooling the vials to room temperature, the solid product
was obtained by decanting with mother liquor and washed with DMF (3 x 80 ml).
Solvent exchange was then carried out with methanol (3 x 80 ml) at room temperature.
o
The product was then dried under vacuum at 170 C for 6 h, yielding 2.98 g of MOF-199
as Cu (BTC)2 in the form of deep purple crystals (88% based on 1,3,5-
3
2
benzenetricarboxylic acid, Langmuir surface areas of 1970 m /g).
2
.3. Catalytic studies
The MOF-199 was used as a solid catalyst for the copper-catalyzed Ullmann-type
coupling reaction of aryl iodides with phenols. In a typical experiment, a pre-determined
amount of MOF-199 was added to the flask containing a solution of 4’-iodoacetophenone
(
0.246 g, 1.0 mmol), phenol (0.188 g, 2.0 mmol), K PO as a base (0.424 g, 2.0 mmol),
3 4
acetylacetone (0.02 ml, 0.2 mmol) as ligand, and n-dodecane (0.15 ml) as internal
standard in DMF (10 ml). The catalyst concentration was calculated based on the molar
ratio of copper/4’-iodoacetophenone. The reaction mixture was magnetically stirred at
o
1
20 C for 2 h. The reaction conversion was monitored by withdrawing aliquots from the
reaction mixture at different time intervals, quenching with an aqueous KOH solution
1%, 0.1 ml), drying over anhydrous Na SO , analyzing by GC with reference to n-
(
2
4
dodecane, and further confirming product identity by GC-MS. To investigate the
recyclability of MOF-199, the catalyst was filtered from the reaction mixture after the
experiment, washed with copious amounts of DMF and methanol, dried under vacuum at
o
1
20 C for 4 h, and reused if necessary. For the leaching test, a catalytic reaction was
stopped after 20 min, analyzed by GC, and filtered to remove the solid catalyst. The
6
Page 6 of 37

reaction solution was then stirred for a further 100 min. Reaction progress, if any, was
monitored by GC as previously described.
3
. Results and discussion
I
OH
R'
R
R'
MOF-199
+
O
R
R': H, Cl, CN, OCH CH
3
R: H, COCH , OCH , CH
3
3,
3
3
Scheme 1. The Ullmann-type coupling reaction between aryl iodides with phenols using
the MOF-199 as a solid catalyst.
The MOF-199 was synthesized by a solvothermal method, using the reaction of copper
nitrate trihydrate and 1,3,5-benzenetricarboxylic acid in DMF, according to a literature
procedure [68]. The material was then characterized by several techniques as previously
reported [59], including XRD, SEM, TEM, TGA, FT-IR, AAS, and nitrogen
physisorption measurements, and the result was in good agreement with the literature
(see Fig. S1 – Fig. S6 in supporting information). The MOF-199 was then used as a solid
catalyst for the Ullmann-type coupling reaction between 4’-iodoacetophenone with
phenol to form 4-acetyl diphenyl ether as the principal product (Scheme 1). Initial studies
addressed the effect of temperature on the reaction conversion. The coupling reaction was
carried out in DMF using 5 mol% MOF-199 catalyst, in the presence of K PO as a base
3
4
and acetylacetone as a ligand, at the 4’-iodoacetophenone:phenol molar ratio of 1:2, in
7
Page 7 of 37

o
the temperature range of 100-130 C. It was found that the reaction proceeded with
o
difficulty at 100 C, with a conversion of only 16% being observed after 2 h. As
o
expected, increasing the temperature to 110 C led to a significant enhancement in
reaction rate, affording 70% conversion after 6 h. Experimental results showed that the
reaction conversion could be improved to 82% and 89% after 6 h for the reaction carried
o
o
out at 120 C, and 130 C, respectively (Fig. 1). Indeed, several homogeneous Ullmann-
type reactions of aryl iodides with phenols were previously carried out effectively in the
o
temperature range of 80-110 C [3, 4, 7, 69].
However, the Ullmann-type
transformations using heterogeneous catalysts could require the reaction temperature of
o
o
o
o
up to 120 C [70], 130 C [8], 140 C [71], and 150 C [12]. Moreover, it should be noted
o
that the reaction using 5 mol% MOF-199 catalyst carried out at 120 C proceeded with
difficulty in the absence of acetylacetone as a ligand, with only 20% conversion being
observed after 2 h. Sun and co-workers also observed similar result, where acetylacetone
was also employed as the ligand for the Ullmann-type reaction using magnetic CuFe O4
2
nanoparticles as catalyst [72]. Further studies would be needed to elucidate the role of
this ligand in the Ullmann-type reaction.
8
Page 8 of 37

100
80
60
40
20
0
110 oC
120 oC
130 oC
100 oC
0
20
40
60
80
100
120
Time (min)
Fig. 1. Effect of temperature on reaction conversion.
With this result in mind, we then decided to investigate the effect of the reagent molar
o
ratio on the reaction conversion. The reaction was carried out at 120 C in DMF using 5
mol% MOF-199 catalyst, in the presence of K PO as the base and acetylacetone as the
3
4
ligand, at the 4’-iodoacetophenone:phenol molar ratio of 1:1, 1:1.5, and 1:2, respectively.
It was observed that the reagent molar ratio also exhibited a significant effect on the
reaction conversion. The coupling reaction proceeded slowly when one equivalent of
phenol was employed, though 56% conversion was still obtained after 6 h. As expected,
increasing the reagent ratio to 1:1.5 led to dramatic enhancement in reaction rate, with a
conversion of 70% being achieved after 6 h. The reaction conversion could be improved
to 82% when two equivalents of phenol was used for the coupling reaction (Fig. 2). It
was previously reported that most of the Ullmann-type reactions of aryl iodides with
phenols could proceed effectively when more than one equivalent of phenols was
9
Page 9 of 37

employed, depending on the nature of the catalyst system as well as the nature of the
substrate. Indeed, the reagent molar ratio could be 1:1 for the reaction using CuI and tris-
(2-aminoethyl)amine [4] or CuI and tetrabutylammonium bromide [73], 1:1.2 for the
reaction using Cu(OTf) and 1,1’-binaphthyl-2,2’-diamine [7], CuI and nitrogen-based
2
tetradentate ligand [74], or CuI and 2,2’-bipyridine [69], 1:1.5 for the reaction using
modified clay [75] or CuI and immobilized bispyridinyl ligand [76], and 1:2 for the
reaction using CuI as catalyst under microwave irradiation [77]. In some special cases,
more than one equivalent aryl iodides was employed for the Ullmann-type coupling
reaction [1, 78].
100
80
60
40
20
0
1
:1
1:2
1:1.5
0
20
40
60
Time (min)
80
100
120
Fig. 2. Effect of 4’-iodoacetophenone:phenol molar ratio on reaction conversion.
1
0
Page 10 of 37

K3PO4
CH3ONa
CH3COONa
K2CO3
Cs2CO3
NaOH
100
80
60
40
20
0
0
20
40
60
80
100
120
Time (min)
Fig. 3. Effect of different bases on reaction conversion.
As with several Ullmann-type transformations between aryl halides and phenols using
other catalysts, the presence of two equivalents of a base should be required to speed up
the transmetallation step in the catalytic cycle of the reaction [9]. Previously, a variety of
different bases were employed for the Ullmann-type coupling reaction, including K PO4
3
[1, 3, 69, 73, 74], Cs CO [1, 4, 7, 15, 78], KF [8], K CO [75, 79], KOH [1], MeONa
2 3 2 3
[75], and t-BuOK [69]. It was therefore decided to investigate the effect of different bases
on the Ullmann-type reaction using the MOF-199 catalyst. The reaction was carried out
o
at 120 C in DMF using 5 mol% MOF-199 catalyst, in the presence of acetylacetone as
the ligand, at the 4’-iodoacetophenone:phenol molar ratio of 1:2, using different bases
including K PO , Cs CO , K CO , MeONa, CH COONa, NaOH, triethylamine. It was
3
4
2
3
2
3
3
found that the nature of the base exhibited a significant effect on the reaction conversion.
1
1
Page 11 of 37

Triethylamine was found to be completely ineffective for the Ullmann-type reaction with
no trace amount of the product being detected. CH COONa was also unsuitable for the
3
reaction, affording only 49% conversion after 2 h. The reaction using K CO could afford
2
3
7
2% conversion, while this value could be improved to 82% after 2 h for the case of
K PO and NaOH, respectively. Interestingly, it was observed that the reaction rate could
3
4
be accelerated when MeONa was employed, with 94% being achieved after 2 h. As
expected, the Ullmann-type reaction using Cs CO offered highest conversion as
2
3
compared to that using other bases (Fig. 3). From experimental point of view, it should be
noted that it was difficult to observe the difference in the reaction rate when the Ullmann-
type transformation proceeded with very high conversions in all cases (i.e. for the
reaction using Cs CO as the base). It was therefore decided to use MeONa as the base
2
3
for the reaction when investigating the effect of other factors on the reaction conversion.
Moreover, the effect of different amounts of base on the reaction conversion was also
o
investigated. The reaction was carried out in DMF at 120 C using 5 mol% MOF-199
catalyst, with the 4’-iodoacetophenone:phenol molar ratio of 1:2 in the presence
acetylacetone as the ligand, using 1, 1.2, 1.5, and 2 equivalents of CH ONa as the base,
3
respectively. It was found that the reaction proceeded with difficulty in the absence of
CH ONa, affording only 4% conversion after 2 h. As expected, increasing the base
3
concentration to 1, 1.2, 1.5, and 2 equivalents led to a dramatic enhancement in reaction
rate, with 54%, 66%, 91%, and 94% conversions, respectively, being achieved after 2 h
(Fig. 4). Indeed, two equivalents of base were previously employed for several Ullmann-
type transformations [9].
1
2
Page 12 of 37

0
1
equiv.
.5 equiv.
1 equiv.
2 equiv.
1.2 equiv.
100
80
60
40
20
0
0
20
40
60
80
100
120
Time (min)
Fig. 4. Effect of base concentration on reaction conversion.
100
80
60
40
20
0
1
5
mol%
mo%
3 mol%
100
0
20
40
60
Time (min)
80
120
Fig. 5. Effect of catalyst concentration on reaction conversion.
Another factor that should be seriously addressed when investigating the Ullmann-type
reaction using the MOF-199 is effect of the catalyst concentration on the reaction
1
3
Page 13 of 37

o
conversion. The reaction was then carried out at 120 C in DMF using MeONa as the
base and acetylacetone as the ligand, in the presence of two equivalents of phenol, at the
catalyst concentration of 1 mol%, 3 mol%, and 5 mol%, respectively. The catalyst
concentration was calculated with respect to the copper/4’-iodoacetophenone molar ratio.
It was found that the reaction conversion was significantly affected by the catalyst
concentration. The Ullmann-type reaction using 1 mol% MOF-199 catalyst proceeded
with difficulty, affording only 42% conversion after 2 h. As expected, increasing the
catalyst concentration led to a dramatic enhancement in the reaction rate. A conversion of
6
6% was obtained after 2 h for the reaction using 3 mol% catalyst, while this value could
be improved to 94% for the case of 5 mol% catalyst (Fig. 5). It should be noted that no
reaction occurred in the absence of the MOF-199 catalyst. Several copper-based catalysts
were previously employed for the Ullmann-type transformation, where the copper
concentrations could vary from less than 5 mol% to more than 10 mol%, depending on
the nature of the catalyst as well as that of the substrate. These catalysts included
aminoarenethiolato-copper(I) complexes (2.5 mo%) [2], CuI and picolinic acid as ligand
(5 mol%) [3], CuI and tris-(2-aminoethyl)amine as ligand (10 mol%) [4], CuI and
tetrabutylammonium bromide as phase transfer catalyst (10 mol%) [73], CuI and
tetradentate nitrogen-based ligand (10 mol%) [74], sol-gel immobilized copper catalyst
(10 mol%) [76], nano CuO (10 mol%) [1], Cu nanoparticles (10 mo%) [80], Cu(OTf)2
and 1,1’-binaphthyl-2,2’-diamine as ligand (20 mol%) [7]. The catalyst concentrations
used for the Ullmann-type reaction in this study were therefore comparable to those in the
literature.
1
4
Page 14 of 37

100
80
60
40
20
0
DMF
DMA
p-xylene
n-butanol
0
20
40
60
80
100
120
Time (min)
Fig. 6. Effect of solvent on reaction conversion.
The effect of different solvents on the rate of an organic reaction using a solid catalyst
should also be seriously taken into consideration. In several cases, the solvent could
strongly accelerate or slow down the reaction, depending on the nature of the catalyst
material [81, 82]. Wang and co-workers previously carried the heterogeneous Ullmann-
type reaction using CuI-supported MOF-253 catalyst in different solvents, and pointed
out that the combination of DMSO as the solvent and Cs CO as the base offered highest
2
3
yield, whereas DMF was not suitable for this transformation [13]. Zhang and co-workers
also tested several solvents for the reaction using nano CuO catalyst, and found that the
reaction carried out in DMSO gave highest yield [1]. Similarly, Ling and co-workers
observed that the reaction using CuO/γ-Al O catalyst offered significantly higher
2
3
conversion in DMSO as compared to the case of DMF [12]. DMSO was also the solvent
of choice for the reaction using silica-supported CuI catalyst [8]. On the contrary,
1
5
Page 15 of 37

Choudhary and co-workers reported that DMF was the best solvent for the Ullmann-type
reaction using Cu-Fe-hydrotalcite catalyst [71]. Arundhathi and co-workers emphasized
that the combination of DMSO as the solvent and Cs CO as the base was almost
2
3
ineffective, while DMF and K CO was the most suitable solvent and base pair for the
2
3
reaction using Fe O -based catalyst [79]. However, Mulla and co-workers investigated a
3
4
series of solvents for the heterogeneous reaction using copper fluorapatite catalyst, and
reported that NMP was the best solvent, while both DMSO and DMF should not be used
[70]. We therefore decided to investigate the effect of different solvents on the reaction
o
conversion, having carried out the reaction at 120 C, using 5 mol% MOF-199 catalyst, in
the presence of acetylacetone as the ligand and MeONa as the base, at the 4’-
iodoacetophenone:phenol molar ratio of 1:2, using different solvents including DMSO,
DMF, DMA, p-xylene, and n-butanol. DMSO was found to be unsuitable for the reaction
as the MOF-199 catalyst was decomposed under the reaction condition. Experimental
results showed that the reaction proceeded with difficulty in p-xylene, and n-butanol,
affording 9% and 36% conversions, respectively, after 2 h. The conversion could be
improved to 80% for the reaction carried out in DMA. It was found that the Ullmann-type
reaction using the MOF-199 catalyst should be carried out in DMF, with 94% conversion
being achieved after 2 h (Fig. 6). Indeed, DMF previously exhibited high performance in
several homogeneous [73, 78] and heterogeneous [71, 79] Ullmann-type transformations.
Various ligands were also employed for the coupling of 4’-iodoacetophenone and phenol
using the MOF-199 catalyst (Fig. 7). From experimental point of view, it should be noted
that acetylacetone exhibited better performance than the other ligands, and should be the
ligand of choice for the Ullmann-type reaction (Fig. 8). Indeed, Sun and co-workers
1
6
Page 16 of 37

previously investigated the Ullmann-type reaction using magnetic CuFe O nanoparticles
2
4
as catalyst in the presence of different ligands, and pointed out that acetylacetone should
be used for this reaction [72].
N
N
O
N
O
O
N
N
(
1)
(2)
(3)
O
O
N
N
N
N
N
(
4)
(5)
N
(
6)
Fig. 7. Different ligands used for the Ullmann-type reaction.
(
1)
5)
(2)
(6)
(3)
(4)
(
100
80
60
40
20
0
0
20
40
60
Time (min)
80
100
120
Fig. 8. Effect of different ligands on reaction conversion.
1
7
Page 17 of 37

MOF-199
CuI
Cu(NO3)2
Cu(OAc)2
CuCl2
100
80
60
40
20
0
0
20
40
60
80
100
120
Time (min)
Fig. 9. Effect of different catalysts on reaction conversion.
To confirm the necessity of using the solid MOF-199 as the catalyst for the Ullmann-type
reaction, the two components of the MOF-199 (i.e. Cu(NO3)2 and 1,3,5-
benzenetricarboxylic acid) and some common copper salts including CuI, CuCl2,
Cu(NO ) , and Cu(OAc) were also used as homogeneous catalysts for the
3
2
2
o
transformation. The reaction was carried out at 120 C in DMF using MeONa as the base
and acetylacetone as the ligand, in the presence of two equivalents of phenol, at the
catalyst concentration of 5 mol%. Interesting, it was found that Cu(NO ) exhibited low
3
2
catalytic activity for the Ullmann-type reaction, with less than 20% conversion being
observed after 2 h. Cu(OAc) and CuCl also offered low activity for the reaction,
2
2
producing the diaryl ether in a conversion of 34% and 47%, respectively, after 2 h. As
expected, the reaction using CuI as the catalyst could proceed readily, affording 85%
conversion after 2 h. Interestingly, it was found that the MOF-199 exhibited higher
1
8
Page 18 of 37

catalytic activity than CuI, leading to a conversion of 94% after 2 h (Fig. 9). Indeed, CuI
in conjunction with different ligands were previously used as homogeneous catalysts for
several Ullmann-type transformations [3, 69, 74].
100
80
60
40
20
0
5
mol% catalyst
Leaching test
0
20
40
60
Time (min)
80
100
120
Fig. 10. Leaching test indicated no contribution from homogeneous catalysis of active
copper species leaching into reaction solution.
As for most liquid-phase organic transformations using solid catalysts, an important
problem that should be taken into accounts is the possibility that some of active sites
could dissolve into the liquid phase during the course of the reaction. In several cases, the
reaction was partially or totally catalyzed by these leached species, thus implying that the
transformation would not proceed under real heterogeneous catalysis conditions [82]. In
order to determine if active species leached from the solid MOF-199 catalyst could play a
significant role in the catalytic activity for the Ullmann-type reaction, an experiment was
performed using a simple filtration during the course of the reaction. After the MOF-199
catalyst was separated from the reaction mixture, if the Ullmann-type transformation
1
9
Page 19 of 37

continued this would indicate that the leached copper species contributed significantly to
o
the total conversion of the reaction. The reaction was carried out at 120 C in DMF using
MeONa as the base and acetylacetone as the ligand, in the presence of two equivalents of
phenol, at the catalyst concentration of 5 mol%. After 20 min reaction time, the DMF
phase was separated from the solid MOF-199 by simple filtration, and transferred to a
new reactor vessel. The reaction mixture was then stirred for an additional 100 min at 120
o
C with aliquots being sampled at different time intervals, and analyzed by GC. As
expected, experimental results showed that no further conversion was observed for the
Ullmann-type transformation after the solid MOF-199 catalyst was removed from the
reaction mixture (Fig. 10). Furthermore, the elemental analysis of the reaction residue
indicated that the copper concentration in the reaction mixture was less than 2 ppm,
corresponding to less than 0.6% of the starting copper concentration. These results
obviously confirmed that the Ulmann-type reaction could only proceed in the presence of
the solid MOF-199 catalyst, and the contribution from leached active species in the liquid
phase, if any, was negligible.
2
0
Page 20 of 37

100
80
60
40
20
0
1
2
3
4
5
Run
Fig. 11. Catalyst recycling studies.
In the view of green chemistry, important issues that should be seriously considered for
organic reactions using solid catalysts are the ease of separation as well as the
deactivation and reusability of the catalysts. It would be expected that the solid catalyst
should be facilely separated from the reaction mixture, and could be recovered and reused
several times before it eventually deactivates completely. It was therefore decided to
investigate the recoverability and reusability of the MOF-199 catalyst in the Ullmann-
type reaction by repeatedly separating the MOF-199 from the reaction mixture, washing
o
it and then reusing it. The reaction was carried out for 2 h at 120 C in DMF, using 5
mol% MOF-199 catalyst, in the presence of acetylacetone as the ligand and MeONa as
the base, at the 4’-iodoacetophenone:phenol molar ratio of 1:2. After each run, the
catalyst was separated from the reaction mixture by simple filtration, then washed with
copious amounts of methanol to remove any physisorbed reagents. The recovered MOF-
2
1
Page 21 of 37

1
99 was dried under vacuum at room temperature for 6 h, and then reused in further
reactions under identical conditions to those of the first run. Experimental results showed
that the MOF-199 could be recovered and reused several times without a significant
degradation in catalytic activity. It was observed that a conversion of 82% was still
th
achieved in the 5 run (Fig. 11). These results showed that the MOF-199 exhibited good
reusability in the Ullmann-type reaction, thus offering a greener approach to carry out
this transformation. Indeed, it was previously reported that the MOF-199 could be
recovered and reused with slight loss of activity in several organic reactions, including
the isomerization of terpene derivatives [83], the acetalization of aldehydes with
methanol [84], the oxidation reaction of cyclohexene [85], and the Aza-Michael reaction
[67].
100
80
60
40
20
0
1
st
2nd
3rd
th
5th
4
0
20
40
60
80
100
120
Time (min)
Fig. 12. Kinetic behavior in the catalyst recycling studies.
2
2
Page 22 of 37

Lin (Counts)
9
8
7
6
5
4
3
2
1
00
00
00
00
00
00
00
00
00
0
(
a)
(
b)
5
10
15
20
25
30
2-Theta-Scale
Fig. 13. X-ray powder diffractogram of the fresh (a) and reused (b) MOF-199.
160
140
120
100
(a)
80
60
40
20
0
(b)
4000
3500
3000
2500
2000
1500
1000
500
Wavenumber cm-1
Fig. 14. FT-IR spectra of the fresh (a) and reused (b) MOF-199.
2
3
Page 23 of 37

Fig. 15. TEM micrograph of the reused MOF-199.
2
4
Page 24 of 37

Fig. 16. Nitrogen adsorption/desorption isotherm of the fresh (a) and reused (b) MOF-
99. Adsorption data are shown as closed circles and desorption data as open circles.
1
Although it was previously reported that no loss of activity was observed for reused solid
catalysts in the Ullmann-type reaction using solid copper-based catalysts [13, 15, 71, 75,
7
6], no kinetic data was provided. Indeed, only conversions at the end of the experiment
were mentioned. Unfortunately, stable activity can not be proven by reporting only
similar reaction conversions at long times. Kinetic studies should be the true test of
catalyst deactivation. We therefore investigated the kinetic behavior of the MOF-199
catalyst during the catalyst reusability in the Ullmann-type reaction over five successive
runs. Experimental results indicated that the activity of the MOF-199 catalyst decreased
slightly after each run. For example, the reaction could afford 68%, 66%, 66%, 65%, and
5
8% conversions after 20 min for the first, the second, the third, the fourth, and the fifth
run, respectively. However, 83% conversion was still achieved after 2 h in the fifth run
Fig. 12). In order to confirm the recoverability and reusability of the MOF-199 in the
(
Ullmann-type reaction, the recovered MOF-199 catalyst was also characterized by XRD,
FT-IR, nitrogen physisorption measurements, TEM, and elemental analysis. XRD result
of the reused MOF-199 indicated that the crystallinity of the catalyst could be maintained
during the course of the reaction (Fig. 13). The overall FT-IR spectra of the reused MOF-
1
99 were basically similar to those of the fresh catalyst (Fig. 14). Elemental analysis by
AAS exhibited a copper loading of 4.86 mmol/g, indicating the negligible change of
copper loading in the reused MOF-199. TEM micrograph (Fig. 15) of the reused catalyst
also showed that a porous material was still obtained, though it was apparent that the pore
2
5
Page 25 of 37

structure of the MOF-99 was complex and would require further investigations. The
nitrogen physisorption measurements (Fig. 16) revealed that the porous structure of the
reused MOF-199 was slightly different as compared to that of the fresh catalyst. Indeed,
2
Langmuir surface areas of 1752 m /g were achieved for the reused MOF-199, being
2
slightly lower than those of the fresh catalyst (i.e. 1970 m /g). The slight loss of catalytic
activity could be rationalized based on the decrease of the surface areas, though the
problem still remains to be elucidated in further studies.
4
-iodoacetophenone
iodobenzene
4
4
4
4
-iodotoluene
-iodoanisole
-iodoanisole/Cs2CO3
-iodotoluene/Cs2CO3
100
80
60
40
20
0
0
20
40
60
80
100
120
Time (min)
Fig. 17. Effect of different substituents in the aryl iodides on reaction conversion.
The study was then extended to the Ullmann-type reaction of phenol with different aryl
iodides in the presence of the MOF-199 as catalyst, including 4’-iodoacetophenone,
iodobenzene, 4-iodotoluene, and 4-iodoanisole. The reaction was carried out for 2 h at
2
6
Page 26 of 37

o
1
20 C in DMF, using 5 mol% MOF-199 catalyst, in the presence of acetylacetone as the
ligand and MeONa as the base, at the aryl iodide:phenol molar ratio of 1:2. Aliquots were
sampled at different time intervals, and analyzed by GC, showing the difference in the
reaction rate of these substrates. It was found that the nature of the substituent in the aryl
iodide structure exhibited a significant effect on the reaction rate. The Ullmann-type
reaction of iodobenzene could afford 67% conversion after 2 h. The presence of an
electron-withdrawing group in the aryl iodide (i.e. 4’-iodoacetophenone) led to a
significant enhancement in the reaction rate, with 94% conversion being achieved after 2
h. As expected, the rate of Ullmann-type transformation decreased in the presence of an
electron-donating group in the aryl iodide structure. Conversions of 53% and 37% were
observed after 2 h for the reaction of 4-iodotoluene and 4-iodoanisole with phenol,
respectively (Fig. 17). This observation was in good agreement with several transition
metal-catalyzed transformations where the oxidative addition step in the catalytic cycle
was accelerated for aryl halides containing electron-withdrawing groups. Wang, Zhang
and co-workers observed similar results, in which the Ullmann-type reaction offered
higher conversions for aryl iodides with electron-withdrawing groups, and lower
conversions for the case of electron-donating groups [1, 13]. It should be emphasized
that the Ullmann-type reaction of aryl iodides containing electron-donating groups (i.e. 4-
iodotoluene and 4-iodoanisole) afforded low conversions because MeONa was used as
the base. However, when Cs CO was employed instead of MeONa, high conversions
2
3
were still achieved for these deactivated aryl iodides. It was found that the Ullmann-type
reaction of 4-iodotoluene and 4-iodoanisole with phenol could afforded a conversion of
9
6% and 98%, respectively, after 2 h in the presence of Cs CO as the base (Fig. 17).
2 3
2
7
Page 27 of 37

Indeed, Cs CO previously exhibited more efficiency than other bases, and hence it was
2
3
the base of choice for several Ullmann-type transformations [1, 4, 7, 15, 78]. However,
due to its rare availability and its high cost, Cs CO should only be used for the case of
2
3
deactivated aryl iodides, and more available bases should be used for activated substrates.
Phenol
p-cresol
4-cyanophenol
4-chlorophenol/Cs2CO3
4
2
4
-chlorophenol
-methoxyphenol
-cyanophenol/Cs2CO3
100
80
60
40
20
0
0
20
40
60
80
100
120
Time (min)
Fig. 18. Effect of different substituents in the phenols on reaction conversion.
To further extend the scope of the protocol, several phenols were also investigated for the
Ullmann-type reaction using the MOF-199 catalyst, including phenol, p-cresol, 4-
chlorophenol, 2-methoxyphenol, and 4-cyanophenol. The reaction was carried out for 2 h
o
at 120 C in DMF, using 5 mol% MOF-199 catalyst, in the presence of acetylacetone as a
ligand and MeONa as a base, at the 4’-iodoacetophenone:phenol molar ratio of 1:2. It
was found that the presence of electron-donating groups in the phenol structure exhibited
little effect on the Ullmann-type reaction using the MOF-199 catalyst, and the reaction of
2
8
Page 28 of 37

electron-rich phenols proceeded readily with high conversions being achieved. The
reaction of 4’-iodoacetophenone with phenol, p-cresol, and 2-methoxyphenol could
afford 94%, 92% and 97% conversions after 2 h, respectively. In contrast, it was
observed that phenols containing electron-withdrawing groups provided the
corresponding diaryl ethers with significantly lower conversions. A conversion of 63%
was observed after 2 h for the reaction of 4-chlorophenol, while only 8% conversion was
detected for the reaction of 4-cyanophenol (Fig. 18). Zhang and co-workers previously
reported similar results, in which no reaction occurred with a chloro substituent at the
para position of the phenol ring [1]. Wang [13], Bistri [78], Ouali [74] and co-workers
also reported that the Ullmann-type reaction of electron-deficient phenols proceeded with
difficulty. As expected, replacing MeONa by Cs CO as the base for the Ullmann-type
2
3
reaction of 4-chlorophenol, and 4-cyanophenol led to a significant enhancement in the
reaction rate, with conversions of 99% and 60%, respectively, being achieved after 2 h
(
Fig. 18). As mentioned earlier, Cs CO should only be used for the case of deactivated
2 3
phenols due to its high cost and its rare availability.
4
. Conclusions
In summary, highly crystalline porous MOF-199 was synthesized from the reaction of
copper nitrate trihydrate and 1,3,5-benzenetricarboxylic acid by a solvothermal method,
and was characterized by several techniques including FT-IR, TEM, SEM, XRD, TGA,
DLS, AAS, and nitrogen physisorption measurements. The MOF-199 exhibited high
activity in the Ullmann-type reaction between aryl iodides and phenols to form diaryl
2
9
Page 29 of 37