Copper based metal organic frameworks as efficient and recyclable catalysts for the oxidative amination reactions

UNIVERSITY OF TECHNOLOGY TRAN VAN THUAN COPPER – BASED METAL – ORGANIC FRAMEWORKS AS EFFICIENT AND RECYCLABLE CATALYSTS FOR THE OXIDATIVE AMINATION REACTIONS Major: Chemical technolo

UNIVERSITY OF TECHNOLOGY

TRAN VAN THUAN

COPPER – BASED METAL – ORGANIC FRAMEWORKS

AS EFFICIENT AND RECYCLABLE CATALYSTS FOR

THE OXIDATIVE AMINATION REACTIONS

Major: Chemical technology

Major code: 60 52 03 01

M ENG THESIS

HO CHI MINH CITY, JANUARY 2015

Supervisor: Dr Truong Vu Thanh ………

Independent opponent 2: Dr Phan Thi Hoang Anh ………

Master thesis was defended at Ho Chi Minh City University of Technology – Vietnam National University – Ho Chi Minh City on January 14th, 2015

Member of the committee included:

1 Assoc Prof Nguyen Ngoc Hanh

2 Dr Phan Thi Hoang Anh

3 Dr Nguyen Quoc Thiet

4 Dr Bui Tan Nghia

Ho Chi Minh City, January 28 th , 2015

II Thesis title

COPPER – BASED METAL – ORGANIC FRAMEWORKS AS EFFICIENT AND

RECYCLABLE CATALYSTS FOR THE OXIDATIVE AMINATION

REACTIONS

III Aim and objectives

1 Characteristics of the Cu2(BDC)2(BPY) and Cu3(BTC)2 by various techniques including XRD, FT-IR, SEM, TEM, TGA, ICP and nitrogen physisorption measurement

2 Catalytic investigation of the Cu2(BDC)2(BPY) and Cu3(BTC)2 for the oxidative amination reactions

IV Started date: January 20th, 2014

V Finished date: November 21st, 2014

VI Supervisor: Dr Truong Vu Thanh

The project was approved by the Department of Organic Chemical Engineering

Faculty of Chemical

Engineering

Prof Dr

Phan Thanh Son Nam

Organic Chem Eng Department

Assoc Prof Dr

Le Thi Hong Nhan

Supervisor

Dr Truong Vu Thanh

I wish to thank all of my friends and all students for their support during course of my study

Especially, I would like to express my sincere thankfulness to my family who are always standing by my side through the hardest times Their unconditional love and support have always accompanied with every achievement in my life

Ho Chi Minh City, January 2015

Tran Van Thuan

The utilization of both ligand 1,4-dicarboxylic acid and 4,4-bipyridine preparing for the

Cu2(BDC)2(BPY) were implemented by solvothermal method The Cu3(BTC)2 also was synthesized according to previous works The structure of this materials were characterized using several various techniques, including X-ray powder diffraction

(XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), inductively coupled plasma (ICP) analysis, and nitrogen physisorption measurements

The Cu2(BDC)2(BPY) and Cu3(BTC)2 were used as heterogeneous catalysts for the oxidative amination reactions Several essential factors including solvent, temperature, molar ratio, catalyst concentration and oxidant component were rigorously investigated

in order to establish optimal circumstances of reaction In leaching test, the catalyst was facilely separated from the reaction by centrifugation The catalyst recyclability was also specifically investigated and the reaction could be reused several times without a significant degradation in catalytic activity Under optimal reaction, reactions scope with respect to coupling partners were also determined The products were confirmed by GC-

MS, 1H NMR and 13C NMR

iii

ACKNOWLEDGEMENTS i

ABSTRACT ii

LIST OF ABBREVIATIONS v

LIST OF FIGURES vi

LIST OF TABLES ix

LIST OF SCHEMES x

CHAPTER 1: LITERATURE REVIEW 1

1.1 METAL – ORGANIC FRAMEWORKS 1

1.1.1 General background 1

1.1.2 Structural characteristics 2

1.1.3 Properties 4

1.1.4 Synthetic methods 6

1.1.5 General applications 7

1.2 MOFs AS CATALYST FOR ORGANIC REACTION 11

1.2.1 MOFs with catalytically active metal nodes in the framework 11

1.2.2 Catalytic functionalization of organic framework linkers 14

1.2.3 Homochiral MOFs 15

1.2.4 MOF-encapsulated catalytically active guests 16

1.3 C – N OXIDATIVE COUPLING REACTION 17

1.3.1 Copper-catalyzed oxidative amidation of terminal alkynes 17

1.3.2 Copper-catalyzed C-N oxidative amination of C-H/N-H 19

2.1 MATERIALS AND INSTRUMENTATION 22

2.2 SYNTHESIS OF THE METAL-ORGANIC FRAMEWORKS 23

2.2.1 Chemical catalogue 23

2.2.2 Preparation of Cu2(BDC)2(BPY) 24

2.2.3 Preparation of Cu3(BTC)2 24

2.3 Catalytic Studies 25

2.3.1 Oxidative amindation of terminal alkynes between phenylacetylene and 2 – oxazolidone 25

2.3.2 The oxidative α-amination between propiophenone and morpholine 25

2.4 Formulate for reaction calculation 26

2.4.1 Formulate for calculating conversion of reaction 26

2.4.2 Formulate for calculating selectivity of reaction 26

CHAPTER 3: RESULTS AND DISCUSSION 28

3.1 CATALYST CHARACTERIZATION 28

3.1.1 Cu2(BCD)2(BPY) 28

3.1.2 Cu3(BTC)2 33

3.2 CATALYTIC INVESTIGATION OF THE Cu2(BCD)2(BPY) FOR THE OXIDATIVE AMINDATION OF TERMINAL ALKYNES 37

3.3 CATALYTIC INVESTIGATION OF THE Cu3(BTC)2 FOR THE C-N OXIDATIVE AMINATION OF C-H/N-H 50

CONCLUSION 63

REFERENCES 64

APPENDIXIES 76

v

LIST OF ABBREVIATIONS DMF: N,N-Dimethylformamide

DCM: Dichloromethane

FT-IR: Fourier transform infrared

GC-MS: Gas chromatography-mass spectrometry

ICP-AES: Inductively coupled plasma atomic emission spectroscopy BDC: 1,4 – benzenedicarboxylic acid

BTC: 1,3,5 – benzenetricarboxylic acid

DABCO: 1,4-diazabicyclo[2.2.2]octane

IRMOF: Iso-reticular metal-organic framework

MIL: Materials of Institut Lavoisier

MOF: Metal-organic framework

SEM: Scanning electron microscopy

TBHP: Tert-butyl hydroperoxide

TEM: Transmission electron microscopy

TGA: Thermogravimetric analysis

TON: Turnover number

TOF: Turnover frequency

BPY: 4,4’ – bipyridine

DBU: 1,8-Diazabicycloundec-7-ene

H 2 BTEC: 1,4-benzenedicarboxylic acid

4-BTAPA: 1,3,5-benzene tricarboxylic acid tris[N-(4-pyridyl)amide

Page Content

SBU

(b) 1D → 2D parallel and (c) 1D → 3D inclined interpenetration

from bioactive linker and its delivery Here the bioactive linker is nicotinic acid Iron, oxygen, nitrogen, and carbon atoms are in orange, red, gray, and black, respectively

carriers; (Top right): Pore openings of the MIL-53 solid: water (left), ibuprofen (center) and open form (right); (Bottom right): Schematic view of the larger cage (left) and the smaller cage (right) of MIL – 100 Metal octahedra, oxygen and carbon atoms are in orange, red, and black, respectively

2-oxazolidinone using copper catalyst

carbonyls

acid (b) and 4,4’-bipyridine (c)

Adsorption data is shown as closed circles and desorption data as vertical bars

under vacuum pressure (b)

data is shown as closed circles and desorption data as vertical bars

35 Figure 3.13 SEM micrograph of the Cu 3 (BTC) 2

ix

LIST OF TABLES

Page Content

alkyne and nitrogen nucleophiles

electrophilic amine

CHAPTER 1: LITERATURE REVIEW

1.1 METAL – ORGANIC FRAMEWORKS

1.1.1 General background

Over the several decades, the study of porous solid materials has been arousing great attention from researches of various fields, including chemistry, physics and material science.1 From the first ideal about coordination network having a chemical formula of Ni(CN)2(NH3).C6H6 discovered by Hofmann and Küspert in 1897,2 the porous structures have illustrated with a vast number of applications in various fields such as adsorption, separation and purification as well as catalysis.3 Because of numerous features concerning about high stability and porosity, the exploration of advanced porous materials for such applications is therefore an interesting subject of scientific research Metal – Organic

Frameworks (MOFs) emerged as a new class of porous solid materials, as well as, have

unprecedentedly evolved into a potential research field.4,5

Although the first reports on MOFs began from the late 1950s,6 Robson and co-workers,7

followed by Kitagawa et al.8 also discovered many innovative structures, there was no evidence that both official definitions and considerable characteristics were indicated At the beginning 1990s, Yaghi and co-workers 9, and then Ferey et al.10 much contributed

toward boost in applicable extent Thus, new terms of Materials Institute Lavoisier (MILs), Secondary Building Units (SBUs), Meso–Porous Metal–Organic Framework (meso – MOF) and Pore size were integrally described 11 Moreover, several MOFs are nowadays

industrially prepared and marked by BASF, such as ZIF-9 (Zeolite Imidazolate

Frameworks, BASOLITETM Z2100) and Cu3(BTC)2 (HKUST-1, MOF-199, BASOLITETM

C300) Some also commercially available through Aldrich.12 In addition, reticular

chemistry forms and predetermines thousands of structure in proportion to topology in

which unit is repeated and held together by strong bonds.13 This is also one of the most highlighting and advanced features in comparison with traditional materials

1.1.2 Structural characteristics

MOFs are classified the family of porous coordination polymers built up from the

combination of an inorganic subunit (metal cluster) and organic linker (ligand) by coordination bonds 3,14 Different from other organic polymers, this material generates orderly organization in three – dimensional framework whose skeleton based on strong connection between organic components and central metal ions (often called as SBUs,

secondary building units).15

(b) The same abstracted as an octahedral

SBU

According to their definition, SBUs are categorized into two major kinds The first kind is organic linkers that may be ditopic or polytopic The second kind of SBU may be a metal atom or (most commonly) a finite polyatomic cluster containing two or more metal atoms

or an infinite unit such as a one-periodic rod of atoms Both shapes are treated slightly differently in a way that reflects their different roles in the design and synthesis process.16

Metal-containing SBUs are formed at the time of synthesis using conditions (e.g.,

temperature, pH) designed to produce just that SBU Their shape is defined by points of

extension where they connect to organic linking components.17

In particular, the latter may have the same topology but a different metric, producing, one

anticipates, an iso-reticular series of structures with the same underlying net

Figure 1.3 SBUs with (from top) eight, eight,

and 12 points of extension

Figure 1.4 Examples of tetratopic linkers: (a and b) tetrahedral and (c) square

The crystal science reaching out porous networks becomes a complicated task because of

the topology of interpenetration which can even be beneficial to porous networks,

stabilizing structures that would otherwise likely collapse upon removal of solvent.18

Furthermore, a flexible structure can fill available space a sit forms by whether through intercalation (ranging from ordered guests pieces to completely disordered, essentially liquid solvent), interdigitation (for 1D or 2D networks), or interpenetration.19

Interpenetration occurs when two or more polymeric networks are not chemically bonded

to each other but cannot be separated without the breaking of bonds.20 There are two important topological properties of interpenetrating 1D and 2D networks Firstly, the nets can interpenetrate such that they are all parallel or inclined in two or more directions Secondly, the interpenetration can produce entanglements that are either of the same dimensionality of the nets or higher Both these considerations lead to different topologies

of interpenetration

Figure 1.5 Different modes of interpenetration for 1D nets: (a) 1D → 1D parallel (b) 1D → 2D parallel and (c) 1D → 3D inclined interpenetration

There are numerous examples of interpenetrating 3D networks, the most common of which are the diamond and α-Po nets.21 Therefore, self-penetration and heterogeneous interpenetration are also mentioned.22

Figure 1.6 (a) Heterochiral and (b) homochiral interpenetration of two 3D nets

1.1.3 Property

While traditional materials such as zeolite or silica normally obtain specific surface area

no more than 500 m2/g by BET method, MOFs are with ultrahigh porosity up to 90% free volume and surface areas, for example, MOF-200 and MOF-210 extending with 8,000

Figure 1.7 Crystal structure of MOF-210, DOI: 10.1126/science.1192160

Several MOFs have open metal sites (coordinative unsaturated) that are built into the pore

“walls” in a repeating, regular fashion Indeed, the presence of open metal sites is of key importance for adsorption and catalysis, since it strongly favors the direct interaction between metal and substrate.24 Consequently, materials originally designed for adsorption may as well show good performance for the latter and vice versa, as has been demonstrated.25 For example, Yousung Jung and co-workers have implemented chemospecific affinity toward CO2 using M-MOF-74 (M = Mg, Ca, and the first transition metal elements) Report showed that Ti- and V-MOF-74 can have an enhanced affinity compared to Mg-MOF-74 by 6−9 kJ/mol Otherwise, the origin of the major affinity trend

is the local electric field effect of the open metal site that stabilizes CO2, but forward donation from the lone-pair electrons of CO2 to the empty d-levels of transition metals as

in a weak coordination bond makes Ti and V have an even higher binding strength than

Mg, Ca, and Sc.26

(1) along the crystal ographic c-axis (where, lp = large pore, np = narrow pore)

In 2007, G Férey’s group has detected the reversible “breathing” motion of MILs

concerning about behaviors of structural flexibility in which reversible transitions are

dependent on both quantity of adsorbed guest molecules and role of solvent – host interactions.27 Although mechanism of transformation and the interactions between the guests and the skeleton are sophisticated based on combination between control the nature

of the inorganic building block and computer simulation, in situ techniques show that these flexible solids are highly selective absorbents.28 For example, Fisher et al have presented

a powerful approach for the targeted manipulation of responsiveness and framework flexibility of an important family of pillared-layered MOFs based on the parent structure [Zn2(BDC)2(DABCO)]n The parent MOF is only weakly flexible; however, the substituted frameworks of [Zn2(BDC)2(DABCO)]n contract drastically upon guest removal and expand again upon adsorption of DMF, EtOH, or CO2, etc., while N2 is hardly adsorbed and does not open the narrow-pored form These “breathing” dynamics are attributed to the dangling side chains that act as immobilized “guests”, which interact with mobile guest molecules as well as with themselves and with the framework backbone.29

of low-cost, high porous crystal and fluctuating temperature of reaction only from 80 oC

to 200 oC.34 Thus, the metal source combines with organic linkers under suitable conditions of solvent, temperature, structure-directing agents and mineralizers to form crystalline material 35

The solvent is one of the most important parameters in the synthesis of MOFs Although

always incorporated in the as-synthesized MOF structures and thus act as space-filling molecules.36 For example, both Fe3+/H2BDC-NH2/solvent and Al3+/H2BDC-NH2/solvent system have a profound impact on the product formation While in acetonitrile or in methanol, at low temperatures, only Fe-MIL-88B-NH2 was observed, aluminum nitrate led in all cases to the formation of Al-MIL-53-NH2 using DMF, methanol and water as the solvent And the use of aluminum chloride in DMF resulted in the formation of both Al-MIL-53-NH2 and Al-MIL-101-NH2.37

On the other hand, one challenge in the use of organic structure-directing agents, such as

amines and ammoniumions, is their removal/exchange after the synthesis.38 Depending on the flexibility of the framework, the guest molecules can have a strong influence on the pore dimension For example, M-MIL-53 (M = Fe, Al, Cr) can switch reversibly from a

narrow pore (np) into a large pore (lp) form with up to 60% variation of their unit cell

volume without altering the framework topology and the Cr- and Al-based compounds show similar thermal and host-guest behavior.39 Removal of the guest molecules by

thermal activation leads to the high-temperature form, which is identical to the lp form

Upon cooling down to room temperature, the compounds adsorb water from air and

transform into the np form.40

Under the reaction conditions, mineralizers added to the reaction mixtures in the correct

quantities favor the formation of well-crystalline phases Similarly, in the synthesis of carboxylate-based MOFs trivalent metal ions are used as amineralizing agent to increase the crystallinity and to promote the crystal growth of the final product.41

gas capture,46 membranes,47 electrodes,47 semiconductors,49 chemical sensors,50 and thin film,51 The following content deals with novel applications of MOFs in drug delivery and enantioselective separation

Taking advantage of MOFs as a delivery drug system is one of the most innovative

applications in pharmaceutical Since the 1970s, the biomedical development of drug nanocarriers has been improved methods to protect both the organism from toxic side effects of the active pharmaceutical ingredient (API) and from biological degradation, thus also increasing drug’s efficiency and intracellular penetration.52

Figure 1.9 Schematic view of the formation of a Bio-MOF (Bio-MIL-1) built up from bioactive linker and its delivery Here the bioactive linker is nicotinic acid Iron, oxygen, nitrogen, and carbon atoms are in orange, red, gray, and black, respectively

However, the greatest challenge in traditional drug delivery system such as liposomes, nano – emulsions, nanoparticles, functional hydrogels, or micelles is the efficient delivery

of drugs in the body using nontoxic nano-carriers vehicle.53 Because the possibility of adjusting the framework’s functional groups and tuning of the pore size, MOFs can be regarded as potentially optimal drug delivery materials.54

Figure 1.10 (Left): Kinetics of delivery of ibuprofen from several porous MOFs carriers; (Top right): Pore openings of the MIL-53 solid: water (left), ibuprofen (center) and open form (right); (Bottom right): Schematic view of the larger cage (left) and the smaller cage (right) of MIL –

100 Metal octahedra, oxygen and carbon atoms are in orange, red, and black, respectively

In 2009, Taylor – Pashow and co – workers have reported the encapsulation of the hydrophobic ethoxysuccinato-cisplatin, aprodrug of the hydrophilic antitumoral drug cisplatin, with loadings up to 13 wt% into the silica covered iron terephthalate MIL-101 modified with 17 mol% of amino-terephthalate ligands.55 Recently, Ke et al also reported the encapsulation and delivery of the hydrophobic anticancer drug, nimesulide, fromamagnetic nanocomposite material made from the cupper trimesate HKUST-1 and

Fe3O4 nanorods The total amount of the loaded drug (0.2 g/g) was released after 11 days

in physiological saline medium.56 Today, tablets of ibuprofen-containing iron carboxylates MIL-53 and MIL-100, obtained using low pressures without any binder but a correct stability under simulated body fluid conditions (SBF, 37 oC), have been proposed for controlled drug release.57 Nevertheless, underground mechanism and advanced features in the encapsultion and release processes of the delivery drug system using MOFs need to be more evident On the other hand, the prospect of MOFs for continuous development and implementation in biomedical applications are demonstrated by further discussing issues including stability, toxicology, and biocompatibility

In the modern pharmaceutical, most drugs are only active in optically pure chirality form

with the opposite enantiomer often producing dangerous effects Although obvious separation methods obtain optically pure chemical products, enantiomers usually coexist

as racemic mixtures in an achiral environment, thus requiring a chiral reagent for their separation Recently, several techniques such as chromatographic techniques and electro migration have been progressive but there were many problems with high cost and complications 58 In the beginning of topological chirality available on homochiral MOFs,

enantioselective separation became feasible process through chiral pore with proper size

and shape.59

Figure 1.11 Schematic representation of the synthesis of POST – 1

The first example of enantioselective inclusion of chiral molecules into the well-defined pores of an homo chiral MOF was reported by Kimand and co-workers on [Zn3(µ3-O)(L4-H)].2H3O.12H2O (POST – 1, L = (4S, 5S) or (4R,5R)-2,2-dimethyl-5-[(4-pyridinyl-amino) carbonyl] -1,3-dioxolane-4-carboxylicacid).60 A structurally interesting feature is that part of the pyridyl groups of the ligands are not coordinated to the metal atoms, but are partially protonated and extrude into the channels The presence of large accessible chiral channels and exchangeable cations in this MOF prompted 80% of the protons on the free pyridine groups of the framework were exchanged with a 66% enantiomeric excess in favor of the isomer

Figure 1.12 The diamond – like 3D network of Cd(QA) 2 ; selective sorption in favor of S-alcohol

In 2001, Xiong et al have evolved a robust 3D homochiral MOF, Cd(QA)2 methoxyl-(8S,9R)-cinch-onan-9-ol-3-carboxylate) which has a diamond-like net containing homochiral open channels.61 As a result, the estimated enantiomeric excess (ee)

(QA=6’-value was approximately 98.2% Furthermore, the adsorbed (S)-2-butanol can be completely removed upon heating the samples up to 210 oC without destroying the framework Recently, rationally tuning micropores of homochiral MOFs by ligand modifications for enantiopure selective separation of 1-phenylethyl alcohol has also been demonstrated by Chen group.62 Two isostructural MOFs, Zn3-(CDC)3[Cu(SalPycy)] and

Zn3(BDC)3[Cu(SalPycy)] containing homochiral pores of about 6.4 Å in diameter The evaluated ee value was 21.1 % in the first use of the fresh sample It is important that after the adsorption of (S)-1-phenylethyl alcohol the MOF sample kept high crystallinity and could be regenerated by immersing into methanol Clearly, these reported results have indicated that despite being in an early stage of research, MOFs have great potential in enantioselective separations

1.2 MOFs AS CATALYST FOR ORGANIC REACTION

1.2.1 MOFs with catalytically active metal nodes in the framework

The open metal sites in MOFs contribute towards an important structural role as node

points of the framework By accepting electron pairs from reactant molecules, such open

metal sites function as Lewis acids Strategies to tune the Lewis acidity of the metal centers could also be further developed For example, the copper sites were first illustrated using cyanosilylation reactions.63

Scheme 1.1 Cyanosilylation of benzaldehyde

In 2004, Schlichte and co-workers has investigated the dependence of concentration of benzaldehyde and the product on the time for a reaction that carried out at 313 K in pentane

in the presence of Cu3(BTC)2 As a result, the yield is 57% (88.5% selectivity) after 72h while there is no more than 10 % conversion of blank experiment without adding catalyst

in comparison

Heterogeneous mechanism was demonstrated through a filtering test carried out by separating the catalyst from the reaction mixture It is clear that the reaction did not proceed further, whereas in the catalyst-containing suspension, the conversion of the substrate continued Unfortunately, the recyclability of the Cu3(BTC)2 was not reported

Scheme 1.2 Isomerization of a-pineneoxide (1) to campholenic aldehyde (2).

Furthermore, the isomerization reactions of α-pinene oxide, (+)-citronellal, and the ethylene ketal of α-bromopropiophenone obtained high yield of desired products with 84%, 66% and 75%, respectively.64 However, the activity of Cu3(BTC)2 in these reactions

is fairly low because of strong shielding effect by the four oxygen atoms surrounding the active sites.65 The Cu3(BTC)2 was resistant to leach in these reactions Catalyst deactivation was induced by progressive formation of deposits inside the pores.66

Scheme 1.3 Proposed mechanism for the formation of the epoxide using [Cu(H 2 BTEC)(BPY)] as heterogeneous catalyst

In several oxidative reactions in which MOFs as catalyst,67 not only the coordination number, but also the oxidation number of the metal may change For example, [Cu(H2BTEC)(BPY)] was employed for the epoxidation of cyclohexene and styrene with TBHP as an oxidant with yields of 65% and 24%, respectively, for 24 h at 75 oC TOFs is

as high as 79 h-1 for cyclohexene illustrating the efficiency of the catalyst The possible mechanism can begin with an expansion of the coordination number of the Cu II center by

coordination of TBHP After a nucleophilic attack of the alkene substrate on this species,

a concerted oxygen transfer takes place, leading to the departure of tert-butanol 67,68

1.2.2 Catalytic functionalization of organic framework linkers

Recently, the Knoevenagel condensation reaction has been gained great attraction Because amides can act either as hydrogen bond donors or acceptors, bonds C-N among the amides themselves could inhibit the interaction with guest molecules A high conversion of 98% was obtained for 12 h when Kitagawa utilized the [Cd(4-BTAPA)2(NO3)2].6H2O.2DMF]n containing free amide groups as guest-accessible functional organic sites for reaction of benzaldehyde and malononitrile.69

In contrast, the same reaction took place with lower efficiency when using only naked metal site In 2008, functionalization of dehydrated MIL-101 through grafting of amine molecules was reported by Hwang and co-workers As a result, up to 99 % of selectivity for trans-ethyl cyanocinnamate achieved for reaction between benzaldehyde and ethyl cyanoacetate in cyclohexane at 80 oC.70

Table 1.1 Knoevenagel condensation reaction of benzlaldehyde with substrates, catalyzed

by [Cd(4-BTAPA) 2 (NO 3 ) 2 ].6H 2 O.2DMF] n (1a)

Especially, Gascon reported both IR-MOF-3 and amino-functionalized MIL-53 were significant as base catalysts in the Knoevenagel condensation of benzaldehyde and ethyl cyanoacetate in DMF at 60 oC Therefore, the IR-MOF-3 catalyst outperformed the aniline reference homogeneous catalyst, with a conversion of 90% compared with 55% However,

a minor activity decrease of IR-MOF-3 in the second recycle was observed Leaching test was also carried out with no further conversion Ultimately, it is evident that the stability

of the heterogeneous catalyst was proved.70, 71

1.2.3 Homochiral MOFs

The active metal sites which connected via chiral linkers bring on the modest enantiomeric excess (ee) values because of the too remote position of the chiral organic groups with respect to the active site In such catalysts, the catalytically active metal centers have no structural role in the MOF lattice but are coordinated in a chiral reaction environment inside the pore The reaction takes place inside the pores, as revealed by the occurrence of reactant shapes electivity, but the relatively large distance such as between the two moieties results in a low enantioselective induction (ee 8 %) in the transesterification between 2,4-dinitrophenyl acetate and 1-phenyl-2-propanol.72

Figure 1.14 Ligand employed in POST-1 synthesis (left) and transesterification of

An interesting approach was followed for the post-synthetic modification of MIL-101 (Cr)

By grafting the open metal sites of this highly porous MOF with an L-proline- bearing ligand, asymmetric aldol condensations can be carried out with yields between 60% and

90% and ee values between 55% and 80% for the R-isomers.73

1.2.4 MOF-encapsulated catalytically active guests

The encapsulation of metalloporphyrins in the cavities of an carboxylate-based rho-zeolite-like metal–organic framework (rho-ZMOF) has been demonstrated.74 The catalytic activity of this material was assessed by cyclohexane oxidation with TBHP as the oxidant The cyclohexane conversion reached 91.5 % after 24

hydrogenation of styrene, 1-octene, and cis-cyclooctene for 24 h at 35 oC After 12 h,

>99% of ethylbenzene was obtained from styrene hydrogenation, whereas for the hydrogenation of cis-cyclooctene, <13 wt % of cyclooctane was obtained after 12h

1.3 C – N OXIDATIVE COUPLING REACTION

1.3.1 Copper-catalyzed oxidative amination of terminal alkynes

Ynamines [1-amino-alkynes or N-alkynyl amines] have recently more and more obtained significance because of their wide applications in worth organic and pharmaceutical synthesis.76, 77 Therefore, approaching these efficient methods for their preparation has strongly been paid attention.78 Traditional protocols in reaching out ynamines implement

in sequential two step processes consisting alkyne halogenation or alkyne metalation with

borane followed by C-N bond formation under copper catalysis (figure 1.17).79

Scheme 1.4 Copper-catalyzed pathways for ynamine synthesis

In 2008, Stahl has indicated a direct oxidative coupling reaction between terminal alkynes and N-H amides used CuCl2 as catalyst.81 However, large excess amount of amide coupling components and slow addition of alkynes were required to achieve good yields

and selectivity (scheme 1.4)

Figure 1.18 A model of C-N coupling reaction between phenylacetylene and 2-oxazolidinone

using copper catalyst

A few reports using heterogeneous catalytic systems have been described.82 Mizuno took advantage of Cu(OH)x/TiO2 as catalyst for alkynylation of N-H oxazolidinone and sulfonamide derivatives 82a Furthermore, Fan and co-workers performed the reaction between phenylacetylene and 2-oxazolidinone under Cu-metallamacrocycle-based 3D MOFs (MOFs = metal-organic frameworks) catalysis with slow addition of phenylacetylene.82b

Scheme 1.5 Procedures and issues summary forming C-N bond in comparison

A preliminary investigation of catalytic activity of Cu-biphenylcarboxylate MOF catalysts was also conducted and the significant damage of catalyst was observed.82c 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 Glaser-Hay reactions 82d However, only reactions between phenylacetylene and 2-oxazolidinone were demonstrated In addition, catalyst heterogeneity and recyclability have not been reported As a result, the heterogeneous protocol development with more thorough investigation and higher generality on the

Scheme 1.6 Proposed mechanism for copper-catalyzed oxidative coupling terminal alkyne and

1.3.2 Copper-catalyzed C-N oxidative amination of C-H/N-H

Transition metal catalyzed carbonyls bearing α-amino substitution have offered widespread applications in the synthesis of many valuable substrates including

pharmaceutically active compounds and complex natural products (figure 1.19).83

Figure 1.19 Common pharmacophore in medicinal agents toward α-amino carbonyls

Unfortunately, approaching the catalytic strategies toward such high-value compounds often tolerated mediate steps whether desired product was obtained poor yield or formation

of by-products appeared (scheme 1.7).84 For example, the catalytic α-amination between ketones or aldehydes (via enolate derivatives) and secondary amine involves the use of 2π-electrophile aza-substrates to deliver α-hydrazinyl or α-oxy-amino products Consequently, two structural classes that must be chemically modified prior to natural productor medicinal chemistry applications

Scheme 1.7 Traditional strategy via many protocols between nucleophilic enolate and

electrophilic amine

In 2013, MacMillan and co-workers indicated that a direct oxidative α-amination of ketones, aldehydes or esters used CuBr2 as catalyst However, 3 equiv amine was added for 12 hours On the other hand, up to 10 mol% catalyst was employed while studies toward a catalytic asymmetric variant of this new transformation need to be ongoing.85

Scheme 1.8 Procedures and issues summary forming C-N bond in comparison

Recently, system of transition metal free oxidative α-C−H amination of ketones via a radical mechanism has been developed 86 However, reaction was conducted under aerobic condition, such as strong oxidant hydroperoxide 2.0 equiv., base Na2CO3and pro-longing

18 hours The use of MOFs with transition metal clusters for α-amination have increasingly paid attention The largest advantages of such system are to contribute to rate

of reaction, under mild condition and green by-product (scheme 1.9)

Scheme 1.9 Proposed mechanism for Cu(II)-Catalyzed Carbonyl−Amine Coupling 85

CHAPTER 2: EXPERIMENTAL SECTION 2.1 MATERIALS AND INSTRUMENTATION

All reagents and starting materials were obtained commercially from Sigma – Aldrich or 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 vacuum at 150 oC for 3 h A Netzsch Thermoanalyzer STA 409 was used for thermogravimetric analysis (TGA) with a heating rate of 10 oC/min under nitrogen atmosphere X-ray 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 metal-organic framework samples was dispersed on holey carbon grids for TEM observation Elemental analysis with atomic absorption spectrophotometry (AAS) was performed on an AA – 6800 Shimadzu Fourier transform infrared (FT – IR) 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 reduction (H2-TPR), the sample was outgassed at 100 oC 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 2.5 oC/min to 600 oC 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 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 GC analysis held samples at 100 oC for 1.5 min; heated them from 100 to 280 oC for 4.5 minutes; held them at 280 oC for 2.5 min Inlet and detector

temperatures were set constant at 280 oC Diphenyl ether 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 from 60 to 280 oC at 10 oC/min and held them at 280 oC 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 FRAMEWORKS

2.2.1 Chemical catalogue

Table 2.1 List of common chemicals for experiment

Purity (%)

2.2.2 Preparation of Cu 2 (BDC) 2 (BPY)

A crystalline porous metal-organic framework Cu2(BDC)2(BPY) was synthesized by solvothermal method with modification with reported conditions.87 In a typical experiment, solution of Cu(NO3)2.3H2O (0.968 g, 4 mmol) in N,N-dimethylformamide

(DMF, 80mL) was dropwise added to a beaker (350 mL) containing solution of H2BDC (benzene-1,4-dicarboxylic 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 and heated at 120 oC 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)

with mother liquor and washed with DMF (3 × 10 mL) Solvent exchange was then carried out with methanol (3 × 10 mL) at room temperature The product was then dried under vacuum at 170 oC for 6 h, yielding 0.96 g of Cu3(BTC)2 in the form of deep purple crystals (85% based on 1,3,5-benzenetricarboxylic acid)

2.3 Catalytic Studies

2.3.1 Oxidative amindation of terminal alkynes between phenylacetylene and 2 – oxazolidone

In a typical experiment, 2 – oxazolidinone (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 GC – Shimazu 2010 plus machine

to determine conversion of reaction The product identity was further confirmed by GC –

MS and NMR To investigate the recyclability of the Cu2(BDC)2(BPY), solids included

Cu – MOF, 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 were 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 rapidly Solid was 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

2.3.2 C-N oxidative amination of C-H/N-H

The general procedure for copper-catalyzed based on metal organic framework reaction

of C-N direct coupling is illustrated by the following included propiophenone and morpholine: In a sealed vial were added Cu3(BTC)2 (20.0 mg, 0.1 mmol, 10 mol%), KBr (36.0 mg, 0.3 mmol, 30 mol%), diphenyl ether (50 µL, as an internal standard), propiophenone 98 % (137 mg, 1.0 mmol, 1 eqv) All were stirred for 5 minutes Then, morpholine (2.5 M in DMF, 131 mg, 1.5 mmol, 1.5 eqv) was dropwised during 10 minutes under air at room temperature Close septum with a syringe needle impaled After every 2 hours, 20 µL of sample was regularly taken out via syringe, washed with pure water (2 mL), extracted with ethyl acetate (2 mL), then dried over Na2SO4

anhydrous and analyzed by GC – Shimadzu 2010 plus machine to determine conversion

of reaction The product identity was further confirmed by GC – MS and NMR To investigate the recyclability of the Cu3(BTC)2, solids included Cu – MOF, KBr, reactants and products were washed with DMF and then methanol in many times until reactants and products have been removed (confirmed by GC analysis) Then, remaining solids were continued to be washed with methanol (3x10 mL) and dryed before being used for the next runs In leaching test, the reaction was stopped after 2 h Solid was completely separated by centrifuge (3000/min of rate, 10 min) The filtrate was added into another sealed vial containing KBr (36.0 mg, 30 mol%) The reaction solution was then stirred for a further 10 h at room temperature Reaction progress, if any, was monitored by GC

2.4 Formulate for reaction calculation

2.4.1 Formulate for calculating conversion of reaction