tóm tắt luận án cu based organic frameworks as catalysts for c c and c n coupling reactions (tiếng anh)

VIETNAM NATIONAL UNIVERSITY – HO CHI MINH CITY
HO CHI MINH CITY UNIVERSITY OF TECHNOLOGY





DANG HUYNH GIAO




Cu-BASED ORGANIC FRAMEWORKS AS CATALYSTS
FOR C–C AND C–N COUPLING REACTIONS






Major: Organic Chemical Technology
Major code: 62527505




PhD THESIS SUMMARY

HO CHI MINH CITY 2015



The thesis was completed in University of Technology –VNU-HCM




Advisor 1: Prof. Dr. Phan Thanh Son Nam
Advisor 2: Dr. Le Thanh Dung



Independent examiner 1: Prof. Dr. Dinh Thi Ngo
Independent examiner 2: Assoc. Prof. Dr. Nguyen Thi Phuong Phong



Examiner 1: Assoc. Prof. Dr. Nguyen Cuu Khoa
Examiner 2: Assoc. Prof. Dr. Nguyen Thai Hoang
Examiner 3: Assoc. Prof. Dr. Le Thi Hong Nhan




The thesis will be defended before thesis committee at

On………………………………………………………………………………






The thesis information can be looked at following libraries:
- General Science Library Tp. HCM
- Library of University of Technology – VNU-HCM



Abstract
Four highly porous Copper-based organic frameworks (Cu-MOFs) such
as Cu
3
(BTC)
2
, Cu
2
(BDC)
2
(DABCO), Cu
2
(BPDC)
2
(BPY) and Cu(BDC) were

synthesized and characterized by X-ray powder diffraction (PXRD), scanning
electron microscopy (SEM), transmission electron microscopy (TEM),
thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy
(FT-IR), inductively coupled plasma mass spectrometry (ICP-MS), hydrogen
temperature-programmed reduction (H
2
-TPR) and nitrogen physisorption
measurements. Three Cu-MOFs including Cu
3
(BTC)
2
, Cu
2
(BDC)
2
(DABCO),
Cu
2
(BPDC)
2
(BPY) were used as heterogeneous catalysts for direct CC
coupling reactions to synthesize propargylamines. Cu(BDC) was employed as
heterogeneous catalyst for CN coupling reaction to synthesize quinoxalines.
These catalytic systems offered practical approaches with high yields and
selectivity. Additionally, broad functionality was shown to be compatible. The
Cu-MOFs catalysts could be recovered and reused several times without
significant degradation in catalytic activity. To the best of our knowledge, these
transformations using Cu-MOFs catalysts were not previously mentioned in the
literature.

INTRODUCTION
Homogeneous transition metals are often employed as catalysts to
promote the transformation of an organic compound in the liquid phase.
However, difficulties in removing catalyst impurities in the final products
narrow the application of homogeneous catalytic systems, especially in
pharmaceutical industry. Metal-organic frameworks (MOFs) have recently
attracted significant attention with advantages in replacing homogeneous
catalysts in chemical process.
Propargylamines and quinoxalines have emerged as important
intermediates in the synthesis of numerous nitrogen-containing biologically
active compounds as well as a variety of functional organic materials. Many
transition-metal catalytic systems, both in homogeneous and heterogeneous
catalysis, were applied for the preparation of propargylmines and quinoxalines
via the C−C and C−N coupling reations. However, many of those processes
suffered from one or more limitations such as harsh reaction conditions, low
product yields, tedious work-up procedures, and the use of toxic metal salts as
catalysts. Consequently, study for the high-effective, sustainable synthetic
routes of proparylamines and quinoxalines is an unquestionable trend in near
future.
Among several popular MOFs, copper-based organic frameworks (Cu-
MOFs) previously exhibited high activity in various organic reactions due to
their unsaturated open copper metal sites. Especially, the Cu-MOFs including
Cu
3
(BTC)

2
, Cu(BDC), Cu
2
(BDC)
2
(DABCO) and Cu
2
(BPDC)
2
(BPY), which are
constructed from copper salts and 1,4-benzenedicarboxylic acid (BDC), 1,3,5-
benzenetricarboxylic acid (BTC) and 4,4’-biphenyldicarboxylic acid (BPDC),
exhibit many advantages for catalytic application. Those organic linkers are
commercial and relatively cheap. These Cu-MOFs have surface areas higher
than 1000 m
2
/g (except for Cu(BDC)) and thermal stability of up to 300 °C or


higher. Moreover, the largest pore apertures of Cu
2
(BDC)
2
(DABCO),
Cu
3
(BTC)
2
and Cu
2

(BPDC)
2
(BPY) are in the range of 7.5 – 9.0 Å which can
allow average size substrates to enter the pores and reach catalytic sites.
However, to the best of our knowledge, the direct C–C and C–N coupling
reactions for the synthesis of proparylamines and quinoxalines using these Cu-
MOFs were not previously mentioned in the literature.
The first purpose of this thesis is to synthesize Cu-MOFs including
Cu
3
(BTC)
2
, Cu(BDC), Cu
2
(BDC)
2
(DABCO) and Cu
2
(BPDC)
2
(BPY). The
second objective is to study their use as heterogeneous catalysts for the direct
C–C and C–N coupling reactions to form proparylamines and quinoxalines.


CHAPTER 1 LITERATURE REVIEW: Cu
3
(BTC)
2
,

Cu
2
(BDC)
2
(DABCO), Cu
2
(BPDC)
2
(BPY), Cu(BDC) AND C–C, C–N
COUPLING REACTIONS
1.1 Introduction to metal-organic frameworks
 In comparison with other porous materials, MOFs possess unique
structures, in which the metal ions combine with organic linkers
to form secondary building units (SBUs), which dictate the
final topology of a whole framework. The combination of
numerous kinds of linkers and metal ions can lead to considerable
diversity of this material.
 Many studies reported MOFs containing copper active sites as efficient
heterogeneous catalysts.
 Among organic linkers that are often used for Cu-MOFs synthesis, 1,4-
benzenedicarboxylic acid (BDC), 1,3,5-benzenetricarboxylic acid
(BTC) and 4,4’-biphenyldicarboxylic acid (BPDC) have advantages
that they are commercial and relatively cheap. In another approach,
MOFs can be constructed from mixed linkers to provide greater
flexibility in terms of surface area, modifiable pore size and chemical
environment. Linkers BDC and BPDC could be easily combined with
pillar linkers such as 1,4-diazabicyclo [2.2.2]octane (DABCO) or 4,4’-
bipyridine (BPY) to form rigid Cu-MOFs. Therefore, Cu-MOFs
constructed from BDC, BTC or BPDC recently attracted great
attention.

1.1 1.2 Cu
3
(BTC)
2
, Cu(BDC), Cu
2
(BDC)
2
(DABCO) and
Cu
2
(BPDC)
2
(BPY)
 Cu
3
(BTC)
2
, Cu(BDC), Cu
2
(BDC)
2
(DABCO) and Cu
2
(BPDC)
2
(BPY)
constitute Cu-MOFs that contain common SBUs of two 5-coordinate
copper cations bridged in a paddle wheel-type configuration (Fig. 1.4).

Fig 1.4. Common coordination geometry of paddle wheel building units of
Cu
3
(BTC)
2
, Cu
2
(BDC)
2
(DABCO), Cu
2
(BPDC)
2
(BPY), Cu(BDC) and their
framework structures (L = Carboxylate linker, P = N-containing bidentate pillar
linker and G = Guest molecule).
 Cu
3
(BTC)
2
, Cu(BDC), Cu
2
(BDC)
2
(DABCO) and Cu
2
(BPDC)

2
(BPY)
are synthesized by solvothermal methods. Their physicochemical
properties are presented in Table 1.2:
Table 1.2: Physicochemical properties of Cu
3
(BTC)
2
, Cu(BDC),
Cu
2
(BDC)
2
(DABCO) and Cu
2
(BPDC)
2
(BPY)
MOFs
Decomposition
temperature
(°C)
BET surface
area
(m
2
/g)
Pore
aperture (Å
2

)
Cu
3
(BTC)
2

300
1000-1450
8.0  9.0
Cu(BDC)
325
545-625
_
Cu
2
(BDC)
2
(DABCO)
300
1461
7.5  7.5



4.7  3.8
Cu
2
(BPDC)
2
(BPY)

320
1210
12.3  7.8



8.8  8.0


 Cu
3
(BTC)
2
, Cu(BDC), Cu
2
(BDC)
2
(DABCO) and Cu
2
(BPDC)
2
(BPY)
can be characterized by various techniques, such as single crystal X-ray
diffraction (SC-XRD), powder X-ray diffraction (PXRD), scanning
electron microscopy (SEM), Fourier transform infrared (FT-IR),
transmission electron microscopy (TEM), thermogravimetric analysis
(TGA), inductively coupled plasma mass spectrometry (ICP-MS), and
gas physisorption measurement, etc.
1.3 C–C coupling reactions
 Traditional routes to access propargylamines often suffer from

disadvantages such as hard conditions, low yields, and limited reaction
scopes.
 Difficults in removing catalysts contaminated in final products narrow
the application of homogeneous catalytic systems, especially in
pharmaceutical industry.
 Recently, the most attractive synthetic route is the use of Manich-type
reaction, a three component procedure of terminal alkynes,
formaldehyde, and secondary amines. However, the aldehyde-free,
oxidative Manich reactions have not been previously reported under
any catalysis.
1.4 C–N coupling reactions
 Traditionally, quinoxalines have been prepared by the acid-catalyzed
condensation of 1,2-aryldiamines with 1,2-diketone or 1,2-diketone
alternatives, such as epoxides, α-bromoketones, and α-hydroxyketones.
 Although the contamination of the desired products with transition
metals or other solids would be minimized under heterogeneous
catalysts conditions, developing an efficient heterogeneous catalyst
system for the quinoxaline synthesis still remains to be explored.


1.2 1.5 Aim and objectives
 Propargylamines and quinoxalines are frequently found as the versatile
intermediates for the synthesis of many nitrogen-containing
biologically active compounds.
 Cu
3
(BTC)
2
, Cu
2

(BDC)
2
(DABCO), Cu
2
(BPDC)
2
(BPY) and Cu(BDC)
have many advantages for suitable catalytic applications.
 To the best of our knowledge, the direct C–C and C–N coupling
reactions for synthesizing proparylamines and quinoxalines using these
Cu-MOFs were not previously mentioned in the literature.
 The main aim of this dissertation is using Cu
3
(BTC)
2
,
Cu
2
(BDC)
2
(DABCO), Cu
2
(BPDC)
2
(BPY) and Cu(BDC) as catalysts
for the synthesis of proparylamines and quinoxalines:
i) Synthesis and characterization of the Cu-MOFs including
Cu
3
(BTC)

2
, Cu
2
(BDC)
2
(DABCO), Cu
2
(BPDC)
2
(BPY) and Cu(BDC);
ii)Catalytic studies of Cu
3
(BTC)
2
, Cu
2
(BDC)
2
(DABCO),
Cu
2
(BPDC)
2
(BPY) on C–C coupling reactions between amine
compounds and terminal alkynes, catalytic studies of Cu(BDC) on C–N
coupling reaction between α-hydroxyacetophenone and o-
phenylenediamine.

CHAPTER 2 SYNTHESIS AND CHARACTERIZATION OF
Cu
3
(BTC)
2
, Cu
2
(BDC)
2
(DABCO), Cu
2
(BPDC)
2
(BPY), Cu(BDC)
2.1 Introduction
In this chapter, the synthesis, characterization methods, physicochemical
properties of Cu
3
(BTC)
2
, Cu
2
(BDC)
2
(DABCO), Cu
2
(BPDC)
2
(BPY) and
Cu(BDC) were studied.

2.2 Experimental
 Cu
3
(BTC)
2
, Cu
2
(BDC)
2
(DABCO), Cu
2
(BPDC)
2
(BPY) and Cu(BDC)
were synthesized by solvothermal methods.
 They were charactized by different techniques such as PXRD, FT-IR,
SEM, TEM, TGA, ICP-MS and nitrogen physisorption measurement.
2.3 Results and discussions
2.3.1 Synthesis and characterization of Cu
3
(BTC)
2

 The synthesis yield was approximately 85% based on H
3
BTC.
 The copper content in the Cu
3
(BTC)
2

was 29% (ICP-MS).
 The BET surface areas of Cu
3
(BTC)
2
were achieved approximately
1799 m
2
/g, the Langmuir surface areas were achieved approximately
2007 m
2
/g.
 The thermal stability of Cu
3
(BTC)
2
is over 300
o
C (TGA).
 The PXRD pattern of the synthesized Cu
3
(BTC)
2
was similar to the
simulated pattern previously reported in the literature (Figure 2.2).
 The SEM micrograph indicated Cu
3
(BTC)
2
exhibited a cubic octahedral

morphology (Fig. 2.4).





Figure 2.2 X-ray powder
diffractograms of the simulated
Cu
3
(BTC)
2
(a) and the synthesized
Cu
3
(BTC)
2
(b)
Figure 2.4 SEM micrograph
of the Cu
3
(BTC)
2

2.3.2 Synthesis and characterization of Cu
2
(BDC)
2
(DABCO)
 The synthesis yield was approximately 66% based on H

2
BDC.
 The copper content in the Cu
2
(BDC)
2
(DABCO) was 21.5% (ICP-MS).
 Langmuir surface areas of Cu
2
(BDC)
2
(DABCO) were achieved
approximately 1174 m
2
/g.
 The Cu
2
(BDC)
2
(DABCO) was stable up over 300 °C.


Figure 2.8 X-ray powder diffractograms of the
simulated Cu
2
(BDC)
2
(DABCO) (a) and the
synthesized Cu
2

(BDC)
2
(DABCO) (b)
Figure 2.9 SEM
micrograph of the
Cu
2
(BDC)
2
(DABCO)
 The PXRD pattern of the synthesized Cu
2
(BDC)
2
(DABCO) was in
good accordance with the simulated pattern of the optimized plausible
structure by using Cerius 2 (Fig. 2.8).


 Figure 2.9 showed that SEM micrograph of Cu
2
(BDC)
2
(DABCO)
revealed that well-shaped, high- quality cubic crystals were formed.
2.3.3 Synthesis and characterization of Cu
2
(BPDC)
2
(BPY)

 The synthesis yield was approximately 66% based on H
2
BPDC.
 The copper component in Cu
2
(BPDC)
2
(BPY) was 18% (ICP-MS).
 Langmuir surface areas of 1519 m
2
/g were achieved for the
Cu
2
(BPDC)
2
(BPY), BET surface areas were achieved 1082 m
2
/g.
 TGA result indicated that the Cu
2
(BPDC)
2
(BPY) was stable up to over
300 °C.
 PXRD pattern of the Cu
2
(BPDC)
2
(BPY) (Fig. 2. 14) showed the
presence of a sharp peak at 2θ = 6°, being consistent with the simulated

pattern of single-crystal previously reported by James and co-workers.
 The SEM micrograph of the Cu
2
(BPDC)
2
(BPY) revealed that the
formed crystals were well-shaped cubic (Fig 2.16).



Figure 2.14 X-ray powder diffractograms
of the simulated Cu
2
(BPDC)
2
(BPY) (a)
and the synthesized Cu
2
(BPDC)
2
(BPY) (b)
Figure 2.16 SEM micrograph
of the Cu
2
(BPDC)
2
(BPY)

2.3.4 Synthesis and characterization of Cu(BDC)
 The synthesis yield was approximately 66% based on H
2
BDC.
 The copper content in the Cu(BDC) was 29% (ICP-MS).
 Langmuir surface areas of 616 m
2
/g were achieved for the material.
 TGA result indicated that the Cu(BDC) was stable up to over 300 °C.
 The PXRD pattern of the Cu(BDC) was also similar to the simulated
pattern previously reported in the literature (Fig. 2.20).
 The SEM micrograph indicated the formation of the cubic
microcrystals of the Cu(BDC).
1.3


Figure 2.20 X-ray powder diffractograms of
the simulated Cu(BDC) (a) and the
synthesized Cu(BDC) (b)


Figure 2.22 SEM micrograph
of the Cu(BDC)


2.4 Conclusion
The four Cu-MOFs such as Cu
3

(BTC)
2
, Cu
2
(BDC)
2
(DABCO),
Cu
2
(BPDC)
2
(BPY) and Cu(BDC) were successfully synthesized and
characterized by PXRD, FT-IR, TGA, H
2
TPR, ICP-MS and nitrogen
physisorption measurements.


CHAPTER 3 CATALYTIC STUDIES OF Cu
3
(BTC)
2
,
Cu
2
(BDC)
2
(DABCO), Cu
2
(BPDC)

2
(BPY), Cu(BDC) ON C–C AND C–N
COUPLING REACTIONS
3.1 Introduction
 Cu
3
(BTC)
2
, Cu
2
(BDC)
2
(DABCO), Cu
2
(BPDC)
2
(BPY) and Cu(BDC)
exhibited high activity for many reactions due to their unsaturated open
metal sites.
 In this chapter, the catalytic performance of Cu
3
(BTC)
2
,
Cu
2
(BDC)
2
(DABCO), Cu
2

(BPDC)
2
(BPY) and Cu(BDC) on the C–C,
C–N coupling reactions will be discussed (Scheme 3. 1 and Scheme
3.2).

Scheme 3.1. The synthesis of propargylamines


Scheme 3.2. The synthesis of quinoxaline
1.4 3.2 Experimental
Catalytic studies of Cu
3
(BTC)
2
on C–C coupling reaction from N,N-
dimethylanilines and terminal alkynes (reaction 1); Catalytic studies of
Cu
2
(BDC)
2
(DABCO) on C–C coupling reaction from N-methylanilines and


terminal alkynes (reaction 2); Catalytic studies of Cu
2
(BPDC)
2
(BPY) on C–C
coupling reaction from Tetrahydroisoquinoline, benzaldehydes and terminal

alkynes (reaction 3); Catalytic studies of Cu(BDC) on C–N coupling reaction
from α-hydroxyacetophenone and phenylenediamine (reaction 4).
The reaction conversions were monitored by withdrawing aliquots from the
reaction mixture at different time intervals, quenching with water (1 ml), drying
over anhydrous Na
2
SO
4
, analyzing by Gas chromatographic (GC) with
reference to inernal standard. All major products from four reactions were
confirmed by
1
H NMR and
13
C NMR.
3.3 Results and discussions
3.3.1 Catalytic studies of Cu
3
(BTC)
2
on C–C coupling reaction (1)


Scheme 3.3. The direct oxidative C-C coupling reaction between N,N-
dimethylaniline and phenylacetylene using Cu
3
(BTC)
2
as catalyst.
 All optimized synthetic conditions of reaction 1 between N,N-

dimethylaniline and phenylacetylene are summaried in Table 3.2.

Reaction conditions
Results (Reaction conversion (%))
Temperature
RT (0), 100 °C (56), 110 °C (76), 120 °C
(96)
Molar ratio of Phenylacetylene :
N,N-dimethylaniline
1:1 (85), 1: 2 (96), 1:3 (93)

Catalyst amount (%)
0 % (12), 1 % (65), 3 % (83), 5 % (96), 7
%(87)
Oxidant
TBHP (96), TBHP in decane (100),


DTBP (44), CHP (96, by product),
K
2
S
2
O
8
and H
2
O (no product)
Oxidant concentration (equiv)
1 (54), 1.5 (76), 2 (82), 3 (96)

Solvent
DMA (96), Clorobenzene (45), o-xylene
(40), DMF, DEF, NMP (99, 95, 100,
byproduct)
Other Cu-MOFs, Cu salts
Similar to Cu
3
(BTC)
2

Other MOFs
No product appeared
0
20
40
60
80
100
0 25 50 75 100 125 150
Time (min)
Conversion (%)
5 mol% leaching test


0
20
40
60
80
100

1 2 3 4 5 6 7 8 9 10
Run
Conversion (%)

Figure 3.9. Leaching test
indicated no contribution from
homogeneous catalysis of active
species leaching into reaction
solution
Figure 3.12. Catalytic recycling studies
 Leaching test indicated no contribution from homogeneous catalysis of
active species leaching into reaction solution (Fig. 3.9).
 The Cu
3
(BTC)
2
catalyst could be recovered and reused ten times in the
direct C-C coupling reaction between N,N-dimethylaniline and
phenylacetylene without a significant degradation in catalytic activity.
Indeed, a conversion of 95% was still obtained after 150 min for the
transformation in the ten run (Fig. 3.12).
 XRD result confirmed that the reused Cu
3
(BTC)
2
was still highly
crystalline. Moreover, FT-IR analysis of the reused Cu
3
(BTC)
2

exhibited a similar absorption as compared to that of the fresh Cu-
MOF.
 With various coupling starting materials of N,N-dimethylanilines and
terminal alkynes, all the products were characterized by
1
H NMR. The
yields were isolated yields. The results showed that the isolated yields
were achieved from 55% to 81%.
3.3.2 Catalytic studies of Cu
2
(BDC)
2
(DABCO) on C–C coupling reaction (2)

Scheme 3.4. The direct C-C coupling reaction via methylation and C-H
functionalization of N-methylaniline and phenylacetylene.
 All optimized synthetic conditions of reaction 2 between N-
methylaniline and phenylacetylene are summaried in Table 3.4.

Reaction conditions
Results (Reaction conversion (%))
Temperature
RT (3), 100 °C (37), 110 °C (67), 120 °C
(96)
Molar ratio of Phenylacetylene :
N-methylaniline
1:1 (79), 1: 2 (96), 1:3 (96)

Catalyst amount (%)
0 % (11), 1 % (83), 3 % (89), 5 % (96), 7
%(96)
Oxidant
TBHP (96), TBHP in decane (100), DTBP
(44),
K
2
S
2
O
8
and Dilauroyl peroxide (no product)
Oxidant concentration (equiv)
1 (54), 1.5 (76), 2 (83), 3 (96)
Solvent
DMA (96), DMF (82), NMP (97, by-
product), DEF (56), Clorobenzene (57),
Diclorobenzene (73), o-xylene (54),


Mesitylene (45)
Other Cu-MOFs, Cu salts
Similar to Cu
2
(BDC)
2
(DABCO)
Other MOFs

No product appeared


0
20
40
60
80
100
0 30 60 90 120 150 180
Time (min)
Conversion (%)
Leaching test 5 mol%



0
20
40
60
80
100
1 2 3 4 5 6 7 8 9 10
Run
Conversion (%)

Figure 3.22. Leaching test
indicated no contribution from
homogeneous catalysis of active
species leaching into reaction

solution
Figure 3.24. Catalytic recycling
studies.
 Leaching test indicated no contribution from homogeneous catalysis of
active species leaching into reaction solution (Fig. 3.22).
 The Cu
2
(BDC)
2
(DABCO) catalyst could be recovered and reused ten
times in the direct C-C coupling reaction between N-methylaniline and
phenylacetylene without a significant degradation in catalytic activity.
Indeed, a conversion of 96% was still obtained after 180 min for the
transformation in the ten run (Fig. 3.24).
 With various coupling starting materials of N-methylanilines and
terminal alkynes, all the products were characterized by
1
H NMR. The
yields were isolated yields. The results showed that the isolated yields
were achieved from 58% to 77%.


 FT-IR analysis of the reused Cu
2
(BDC)
2
(DABCO) exhibited a slightly
different absorption as compared to that of the fresh Cu-MOF. The
crystallinity of the reused Cu-MOF was found to be slightly different to
that of the fresh catalyst. However, XRD result indicated that the

reused Cu
2
(BDC)
2
(DABCO) was still highly crystalline.
3.3.3. Catalytic studies of Cu
2
(BPDC)
2
(BPY) on C–C coupling reaction (3)

Scheme 3.5. The A
3
reaction of tetrahydroisoquinoline, benzaldehyde, and
phenylacetylene using Cu
2
(BPDC)
2
(BPY) catalyst.
 All optimized synthetic conditions of reaction 3 from
Tetrahydroisoquinoline, benzaldehyde and phenylacetylene are
summaried in Table 3.5.

Reaction conditions
Results (Reaction conversion (%))
Temperature
RT (10), 60 °C (20), 70 °C (46), 80 °C
(95), 90 (96)
Molar ratio of Phenylacetylene :
Benaldehyde:

Tetrahydroisoquinoline
1:1:1 (88), 1:1.1: 1.1 (95), 1:1.2: 1.2 (96),
1:1.5: 1.5 (96)
Catalyst amount (%)
0 % (10), 1 % (32), 3 % (66), 5 % (95)
Solvent
Toluene (95), p-xylene (52), metylsilene
(36), NMP (31), DMA (80), 1,4-dioxane
(39)
Pyridine (equiv)
As a catalyst poison with copper sites
Adding product
Product adsorbed on the copper sites of
Cu
2
(BPDC)
2
(BPY)
Other Cu-MOFs, Cu salts
Higher than other Cu-MOFs, similar to Cu
salts


Other MOFs
No product appeared
 Interestingly, the Cu
2
(BPDC)
2
(BPY)-catalyzed C1-alkynylation

reaction of tetrahydroisoquinoline offered high regioselectivity to the
endo-yne-product. Indeed, more than 99% of (A) was achieved, leaving
less than 1% of (B) in the product mixture.
0
20
40
60
80
100
0 30 60 90 120 150 180
Time (min)
Conversion (%)
5 mol% Leaching test

0
20
40
60
80
100
1 2 3 4 5 6 7
Run
% Selectivity


Figure 3.35. Leaching test indicated
no contribution from homogeneous
catalysis of active species leaching
into reaction solution
Figure 3.36. Catalyst recycling

studies
 Fig. 3.35 indicated that no contribution from homogeneous catalysis of
active species leaching into reaction solution after Cu
2
(BPDC)
2
(BPY)
catalyst was removed.
 The Cu
2
(BPDC)
2
(BPY) catalyst could be recovered and reused several
times for the copper-catalyzed A
3
reaction of tetrahydroisoquinoline,
benzaldehyde, and phenylacetylene without a significant degradation in
catalytic activity. Indeed, a conversion of more than 95% was still
achieved in the 7
th
run (Fig. 3.36).
 As compared to the FT-IR result of the fresh Cu
2
(BPDC)
2
(BPY), the
spectra of reused Cu-MOF exhibited a similar absorption. Moreover,
the XRD result of the recovered Cu
2
(BPDC)

2
(BPY) indicated that the


crystallinity of the Cu-MOF could be maintained, though slight
difference in the diffractogram was observed.
 The study was the extended to reactions of tetrahydroquinoline and
phenylacetylene with different aldehydes. Then, reaction scope with
respect to alkyne starting material components was kinetically
described. The results showed that the reaction conversions were
changed dramatically when electron donating groups or electron
withdrawing groups presented in aldehydes or alkynes.
3.3.4. Catalytic studies of Cu(BDC) on C–N coupling reaction (4)

Scheme 3.6. The oxidative cyclization reaction between α-
hydroxyacetophenone and phenylenediamine using Cu(BDC) catalyst.
 All optimized synthetic conditions of reaction 4 between α-
hydroxyacetophenone and phenylenediamine are summaried in Table
3.6.

Reaction conditions
Results (Reaction conversion (%))
Temperature
RT (8), 80 °C (74), 90 °C (82), 100 °C
(100)
Molar ratio of α-
hydroxyacetophenone: 1,2-
phenylenediamine
1:1.0 (98), 1: 1.1 (100), 1:1.5 (93), 1:2
(90)

Catalyst amount (%)
0 % (6), 1 % (81), 3 % (86), 5 % (100)
Solvent
Toluene (100), o-xylene (98), p-xylene
(92), mesitylene (92), clorobenzene (90),
1,4-dioxane (74)
Pyridine (equiv)
As a catalyst poison with copper sites
Oxidant
Oxygene, di-tert-butylperoxide, argon, air
Other Cu-MOFs, other MOFs
Higher than Cu-MOFs and other MOFs


Cu salts
Similar to Cu(BDC)

1.5
0
20
40
60
80
100
0 30 60 90 120 150 180
Time (min)
Conversion (%)
5 mol% leaching test

0

20
40
60
80
100
1 2 3 4 5 6 7 8
Run
Conversion (%)

Figure 3.45. Leaching test indicated
no contribution from homogeneous
catalysis of active species leaching
into reaction solution
Figure 3.49. Catalytic recycling
studies
 Fig. 3.45 indicated that the quinoxaline synthesis could only proceed in
the presence of the solid Cu(BDC) catalyst.
 The Cu(BDC) catalyst could be recovered and reused several times
without a significant degradation in catalytic activity. Indeed, a
conversion of more than 97% was still achieved in the 8
th
run (Fig.
3.49).
 The FT-IR spectra of the reused Cu(BDC) showed a similar absorption
as compared to those of the fresh Cu-MOF. The XRD result of the
recovered Cu(BDC) after washing soaking in DMF revealed that the
crystallinity of the Cu-MOF catalyst could be maintained, though slight
difference in the diffractogram was detected.
 The condition generality was examined with 4-methyl-
phenylenediamine, 4-chloro-phenylenediamine derivatives. It was

found that the presence of an electron-withdrawing group in the
benzene ring of the phenylenediamine resulted in a significant drop in
the reaction rate. For the case of the reaction between α-
hydroxyacetophenone and phenylenediamine, the desired product, 2-
phenylquinoxaline, an isolated yield of 95% was achieved with
accepted NMR purity.
3.4 Conclusion
 Cu
3
(BTC)
2
, Cu
2
(BDC)
2
(DABCO), Cu
2
(BDC)
2
(BPY) were used as
heterogeneous catalysts for direct CC coupling reactions to form
propargylamines, Cu(BDC) was employed as heterogeneous catalyst
for direct CN coupling reaction to get quinoxalines.
 The direct CC, CN coupling transformations of reaction 1, 2, 3 and
4 could only proceed in the presence of the solid Cu-MOF catalyst with
no contribution from homogeneous leached active copper species.
 These Cu-MOFs could be separated from the reaction mixture by
centrifugation or filtration, and could be recovered and reused several

times without a significant degradation in catalytic activities. Fresh Cu-
MOFs and reused Cu-MOFs were also compared by PXRD and FT-IR.



CHAPTER 4 CONCLUSION
4.1 Summary of current work
 The four Cu-MOFs consist of Cu
3
(BTC)
2
, Cu
2
(BDC)
2
(DABCO),
Cu(BDC) and Cu
2
(BPDC)
2
(BPY) were synthesized and characterized
by several techniques including XRD, SEM, TEM, FT-IR, TGA, ICP-
MS, H
2
TPR and nitrogen physisorption measurements. These Cu-
MOFs are the highly cited MOFs due to their relatively easy synthesis
by solvothermal methods, thermal stability, high surface area, open
metal sites.
 The Cu
3

(BTC)
2
was used as a heterogeneous catalyst for the direct
oxidative CC coupling reaction via CH functionalization between
N,N-dimethylanilines and terminal alkynes (reaction 1). The direct CC
coupling transformation could proceed to 96 % conversion after 180
min in the presence of 5 mol% Cu
3
(BTC)
2
catalyst at 120
o
C.
 The Cu
2
(BDC)
2
(DABCO) was used as a heterogeneous catalyst for the
direct CC coupling reaction via CH functionalization between N-
methylaniline and phenylacetylene (reaction 2). Tert-butyl
hydroperoxide also served as the methylating reagent in the
transformation, and N-methyl-N-(3-phenylprop-2-ynyl)benzenamine
but not N-(3-phenylprop-2-ynyl)benzenamine was produced as the
principal product. The direct C-C coupling reaction could proceed to 95
% conversion with a selectivity of 80 % to N-methyl-N-(3-phenylprop-
2-ynyl)benzenamine being achieved after 180 min.
 The Cu
2
(BPDC)
2

(BPY) could be used as a heterogeneous catalyst for
the copper-catalyzed A
3
reaction of tetrahydroisoquinoline, aldehydes,
and alkynes to form C1-alkynylated tetrahydroisoquinolines (reaction
3). The Cu
2
(BPDC)
2
(BPY)-catalyzed C1-alkynylation reaction of


tetrahydroisoquinoline offered high regioselectivity to the endo-yne-
product, with more than 99 % of 2-benzyl-1-(phenylethynyl)-1,2,3,4-
tetrahydroisoquinoline being achieved, leaving less than 1 % of 2-(1,3-
diphenylprop-2-ynyl)-1,2,3,4-tetrahydroisoquinoline in the product
mixture.
 The Cu(BDC) was employed as a heterogeneous catalyst for the
oxidative cyclization reaction between -hydroxyacetophenone and
phenylenediamine derivatives to form 2-arylquinoxaline as the
principal product (reaction 4). The simple optimal conditions involved
the use of air atmosphere oxidant in toluene solvent at 100
o
C in 3 h.
 These Cu-MOFs could be separated from the reaction mixture by
centrifugation or filtration, and could be recovered and reused several
times without a significant degradation in catalytic activities.
 Our results here confirm the feasibility of employing the Cu-MOFs as
recyclable heterogeneous catalysts in the field of organic synthesis,
expanding applications of these porous metal-organic frameworks from

the gas separation and storage to catalysis. The fact that available Cu-
MOFs

could be used as recyclable heterogeneous catalysts would be
interested to the chemical industry.
4.2 Contributions of this thesis
The overoarching goal of this thesis is to use four Cu-MOFs as catalysts for
direct C–C and C–N coupling reactions to synthesize propargylamines and
quinoxalines. These compounds are found as the versatile intermediates for the
synthesis of many nitrogen-containing biologically active compounds. Herein,
the following are the main research contributions of this thesis.
 Cu
3
(BTC)
2
, Cu
2
(BDC)
2
(DABCO), Cu
2
(BPDC)
2
(BPY) and Cu(BDC)
were synthesized successfully by solvothermal methods. These Cu-
MOFs were characterized by characterized by PXRD, FT-IR, SEM,