Utilizing cu mof 74 and cu2(oba)2bpy materials as heterogeneous catalysts in systhesis of 1,4 benzothiazines and 3 aroylquinolines

9 CHAPTER 2: RESEARCH OF CATALYTIC ACTIVITY OF COPPER-BASED METAL-ORGANIC FRAMEWORK Cu-MOF-74 IN THE SYNTHESIS OF 1,4-BENZOTHIAZINE .... Yield of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carb

VIETNAM NATIONAL UNIVERSITY HO CHI MINH CITY

BACH KHOA UNIVERSITY -

DANG VAN HA

MATERIALS AS HETEROGENEOUS CATALYSTS IN

SYNTHESIS OF 1,4-BENZOTHIAZINES AND

HO CHI MINH CITY, AUGUST 2018

ACKNOWLEDGEMENT

The success and final outcome of this thesis required a lot of guidance and assistance from many people and I am extremely privileged to have got this all along the completion of my project All that I have done is only owing to such supervision and assistance and I would not forget to thank them

First of all, I respect and thank our adviser, Prof Dr Phan Thanh Son Nam for providing me an opportunity to do the thesis work in Manar lab and giving me all support and guidance which made me complete the project duty I am extremely thankful to him for providing such a nice encouragement, guidance and financial support, although he had busy schedule managing the department affairs

Furthermore, our profound gratitude is expanded to all the staffs and co-workers

in our laboratory, especially Mr Ha Quang Hiep, Ms Nguyen Thi Kim Oanh, Mr Nguyen Thai Anh, Mr Nguyen Kim Chung, Mr Doan Hoai Son, for teaching me valuable lessons when I were still clueless about this field Moreover, we also want to express our fortune for having a chance to work with my friends at MANAR LAB I

do not think that I would be able to complete this work to this state without your help

Last but not least, I would like to express special thanks to my family Words cannot express how grateful I am to our parents for all sacrifices that they have made

on your behalf Their constant encouragement gave me the important strength to successfully finish this research work

ABSTRACT

A crystalline porous metal-organic framework Cu-MOF-74 and

Cu2(OBA)2(BPY) were solvothermally synthesized and then characterized by X-ray powder diffraction (XRD), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR), and Nitrogen physisorption measurements

The obtained Cu-MOF-74 was utilized as a reusable heterogeneous catalyst for the synthesis of substitued benzo[b][1,4]thiazine-4-carbonitriles from 2-aminobenzothiazole and terminal alkyne with the presence of base and oxidant The product of the reaction was separated and predicted the structure using Gas chromatography with Mass spectroscopic detector and NMR spectroscopy From the best of our knowledge, this was the first time that the reaction was carried out in under the catalysis of heterogeneous catalyst This broaden a great potential improvement of the reaction in terms of separation and reusability of the catalyst

The Cu2(OBA)2(BPY) is demonstrated as an efficient heterogeneous catalyst for the formation of 3-acylquinolines from 2-aminoaryl methanols and saturated ketones The optimal conditions employed 2, 2, 6, 6-Tetramethyl-1-piperidinyloxy (TEMPO)

as the oxidant and pyridine as ligand in N,N-dimethylformamide at 120oC Furthermore, leaching test was also conducted to investigate the heterogeneity Satisfyingly, the catalyst can be facilely recycled several times under optimal conditions without significant degradation in the catalytic activity This work dedicated to the ideal of green chemistry, which is the vision of current and future chemistry

ACKNOWLEDGEMENT i

ABSTRACT ii

CONTENTS iii

LIST OF FIGURES v

LIST OF TABLES viii

LIST OF SCHEMES ix

ABBREVIATIONS AND SYMBOLS xi

CHAPTER 1: LITERATURE REVIEWS 2

1.1 Introduction to metal-organic frameworks 2

1.1.1 General introduction 2

1.1.2 General methods for the synthesis of metal-organic frameworks 3

1.1.3 Applications of metal–organic frameworks 5

1.2 Copper-based metal-organic frameworks as heterogeneous catalyst 9

CHAPTER 2: RESEARCH OF CATALYTIC ACTIVITY OF COPPER-BASED METAL-ORGANIC FRAMEWORK Cu-MOF-74 IN THE SYNTHESIS OF 1,4-BENZOTHIAZINE 13

2.1 The Cu-MOF-74 metal-organic framework 13

2.1.1 Structure and properties 13

2.1.2 Application in catalysis 14

2.2 The 1,4-benzothiazines and conventional synthesis 16

2.3 Experimental 18

2.3.1 Chemicals and instruments 18

2.3.2 Synthesis of Cu-MOF-74 20

2.3.3 Catalytic studies on the synthesis of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile 20

2.4 Results and discussions 20

2.4.1 Synthesis of Cu-MOF-74 21

2.4.2 Catalytic studies on the synthesis of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile 25

2.5 Conclusions 45

CHAPTER 3: COPPER-CATALYZED ONE-POT DOMINO REACTIONS VIA C-H BOND ACTIVATION: SYNTHESIS OF 3-AROYLQUINOLINES FROM 2-AMINOBENZYLALCOHOLS AND PROPIOPHENONES UNDER

METAL-ORGANIC FRAMEWORK CU(OBA) 2 BPY CATALYSIS 46

3.1 The Cu 2 (OBA) 2 (BPY) metal-organic framework 46

3.1.1 Structure and Properties of Cu2(OBA)2(BPY) 46

3.1.2 Applications of Cu2(OBA)2(BPY) in catalysis 47

3.2 The quinoline derivatives 49

3.2.1 Introduction 49

3.2.2 Synthesis route of quinoline derivatives 50

3.3 Experimental 57

3.3.1 Materials and Instrumentations 57

3.3.2 Synthesis of Cu2(OBA)2(BPY) catalyst 59

3.3.3 The catalytic studies on the synthesis of phenyl(quinolin-3-yl)methanone 60

3.4 Results and discussions 61

3.4.1 Synthesis and characterization of Cu2(OBA)2(BPY) 61

3.4.2 The catalytic studies on the synthesis of phenyl(quinolin-3-yl)methanone 66

3.5 Conclusions 89

REFERENCES 90

APPENDIX A: CALIBRATION CURVE 99

APPENDIX B: GC AND MS RESULTS 102

APPENDIX C: NMR OF 1,4-BENZOTHIAZINE 105

APPENDIX D: NMR OF 3-ACYLQUINOLINES 145

LIST OF FIGURES

Figure 2.1 Crystal structure of a MOF-74 (left) and the metal oxide chains connected

by organic linkers (right) O, red; C, black; H, white; metal, blue 13

Figure 2.2 Structure of Cu-MOF-74 before and after activation 14

Figure 2.3 Antipsychotic and antihistaminic drugs from phenothiazines 16

Figure 2.4 Powder X-ray diffraction patterns of Cu-MOF-74 21

Figure 2.5 FT-IR spectra of the Cu-MOF-74 and dihydroxyterephtalic acid 22

Figure 2.6 SEM and TEM micrographs of Cu-MOF-74 22

Figure 2.7 Isotherm linear plot of Cu-MOF-74 23

Figure 2.8 Poresize distribution of Cu-MOF-74 24

Figure 2.9 TGA curve of the Cu-MOF-74 24

Figure 2.10 Yield of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile vs reaction time at different temperatures 26

Figure 2.11 Yield of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile vs time in different solvents 27

Figure 2.12 Yield of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile vs time at different catalyst concentrations 28

Figure 2.13 Yield of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile vs time at different reactant molar ratios 29

Figure 2.14 Yield of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile vs time with different oxidants 30

Figure 2.15 Yield of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile vs time at different DTBP amounts 31

Figure 2.16 Yield of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile vs time with different bases 32

Figure 2.17 Yield of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile vs time at different Cs2CO3 amounts 33

Figure 2.18 Leaching test showed that 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile was not produced after the isolation of the catalyst 34

Figure 2.19 Yield of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile vs time with

different homogeneous catalysts 35

Figure 2.20 Yield of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile vs time with different heterogeneous catalysts 36

Figure 2.21 Catalyst reutilizing studies 37

Figure 2.22 FT-IR results of the new (a) and reutilized (b) catalyst 38

Figure 2.23 XRD results of the new (a) and reutilized (b) catalyst 38

Figure 3.1 The structure of Cu(OBA)2BPY……… 47

Figure 3.2 Biologically active molecules containing 3-substituted quinolones 49

Figure 3.3 X-ray powder diffractograms of the Cu2(OBA)2(BPY) 62

Figure 3.4 FT-IR spectra of the Cu2(OBA)2(BPY), H2OBA, 4,4-bipyridine 63

Figure 3.5 TGA analysis of the Cu2(OBA)2(BPY) 64

Figure 3.6 Pore size distribution of the fresh Cu2(OBA)2(BPY) 65

Figure 3.7 Nitrogen adsorption/desorption isotherm of the Cu2(OBA)2(BPY) Adsorption data are shown as closed circles and desorption data as open circles 65

Figure 3.8 SEM (a) and TEM (b) micrograph of Cu2(OBA)2(BPY) 66

Figure 3.9 Effect of temperature on reaction yield 67

Figure 3.10 Effect of different solvents on reaction yield 69

Figure 3.11 Effect of amount of DMF on the reaction yield 70

Figure 3.12 Effect of the 2-aminobenzyl alcohol : propiophenone molar ratio on the reaction yield 71

Figure 3.13 Effect of catalyst amount on the reaction yield 72

Figure 3.14 Effect of time on the reaction yield 73

Figure 3.15 Effect of different oxidants on the reaction yield 73

Figure 3.16 Effect of oxidant amount on the reaction yield 75

Figure 3.17 Effect of different ligands on the reaction yield 76

Figure 3.18 Effect of pyridine amount on reaction yield 77

Figure 3.19 Effect of different heterogeneous catalysts on the reaction 78

Figure 3.20 Effect of different homogeneous catalysts on the reaction 79

Figure 3.21 Leaching test 81

Figure 3.22 Catalyst recycling studies 82

Figure 3.23 X-ray powder diffractograms of the fresh (a) and reused (b)

Cu2(OBA)2(BPY) catalyst 83

Figure 3.24 FT-IR spectra of the fresh (red) and reused (black) Cu2(OBA)2(BPY) catalyst 84

Figure 3.25 Yields of phenyl(quinolin-3-yl)methanone in the presence of ascorbic

acid 85

LIST OF TABLES

Table 2.1 Some physical properties of synthesised Cu-MOF-74 compared with the

literatures 23

Table 2.2 The synthesis of benzo[1,4]thiazines from 2-aminobenzothiazoles and

terminal alkynes utilizing Cu-MOF-74 catalyst 41

Table 3.1 List of the utilized substances and their providers……… 57

one-pot domino reactions 86

phenylacetylene with 2-oxazolidinone 11

Scheme 1.5 The Suzuki coupling reaction using Pd@CuBDC 11 Scheme 1.6 The aerobic cross-coupling of aromatic amines and phenyl boronic acid

(Chan–Lam coupling) through Cu2(BDC)2(BPY)–MOF 11

Scheme 1.7 The ring expansion reaction of 2-aminobenzothiazole with

phenylacetylene utilizing Cu–MOF-74 catalyst 12

Scheme 2.1 Knoevenagel condensations (top) and Michael additions (bottom) using

MOF-74……… 14

Scheme 2.2 Simplified reaction scheme for the acylation of anisole with acetyl

chloride using Cu-MOF-74 as catalyst 15

Scheme 2.3 Amidation of alkanes by amides catalyzed by Cu-MOF-74 15

3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile 16

Scheme 2.5 The exploration of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile

synthesis 17

Scheme 2.6 The synthesis 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile found

by Qiu and co-workers 17

Scheme 2.7 The three-component tandem cyclization to synthesis 1,4-benzothiazines.

Scheme 2.11 Proposed reaction pathway 39 Scheme 3.1 Reaction of benzothiazole with iodobenzene……… 48 Scheme 3.2 The direct C–S coupling reaction utilizing Cu2(OBA)2(BPY) catalyst (a),

and the hydrolysis step to form β-ketosulfone (b) 48

Scheme 3.3 One-pot phosphine-catalyzed syntheses of quinolones 50 Scheme 3.4 Synthesis of quinoline-based lead agonist and its derivatives 51 Scheme 3.5 Strategy for the synthesis of 1,2-dihydroquinolines, quinolines and

benzo[b]azepine derivatives 52

Scheme 3.6 Synthesis quinolines through modified Friedländer approach involving

SNAr/reduction/annulation cascade in one-pot in the presence of glucose 53

CuSO4-D-Scheme 3.7 Synthesis of 4-substituted 3-aroyl quinolines from o-aminoaryl ketones

and enaminones 53

Scheme 3.8 Designation on 3-acylquinoline synthesis via enaminone C=C bond 54 Scheme 3.9 Transition-metal-free synthesis of 3-ketoquinolines 55 Scheme 3.10 Synthesis of 3-acylquinolines through Cu-catalyzed double C(sp3)–H

bond functionalization of saturated ketones 55

Scheme 3.11 The cyclization of 2-aminobenzyl alcohol and propiophenone utilizing

Cu2(OBA)2(BPY) as a heterogeneous catalyst 56

Scheme 3.12 Synthetic scheme for self-assembling the light green crystal of

Cu2(OBA)2(BPY) 61

Scheme 3.13 Proposed reaction mechanism 85

ABBREVIATIONS AND SYMBOLS

GC-MS Gas Chromatography – Mass Spectrometry

HKUST Hong Kong University of Science and Technology

MDR Multidrug-resistance

MIL Matériaux de l′Institut Lavoisier

MOFs Metal-Organic Frameworks

NMP N-methyl-2-pyrrolidone

NMR Nuclear Magnetic Resonance

XRD X-ray Diffraction

rt Room temperature

SBUs Secondary Building Units

SEM Scanning Electron Microscopy

TBHP tert-butyl hydroperoxide

TEAB tetraethylammonium bromide

TEM Transmission Electron Microscopy

TEMPO 2,2,6,6-Tetramethyl-1-piperidinyloxy

TGA Thermogravimetric

TMEDA Tetramethylethylenediamine

CHAPTER 1: LITERATURE REVIEWS

1.1.1 General introduction

Metal-organic frameworks (MOFs) have received much attention in recent years especially as newly developed porous coordination polymers, have emerged as a new family of crystalline materials composed of organic linkers that connect metal ions or metal clusters to produce one-, two-, or three-dimensional networks [1] Flexibility or the rigidity

of the frameworks is greatly affected by the choice of organic linker in the structure [2] Furthermore, the tendency of metal ions can make different coordination numbers of metal, which can influence the geometric configuration of MOF structures [3] The abundant structures of MOFs (1D, 2D and 3D) are reported in the Cambridge Structural Database (CSD) (Figure 1.1)

Figure 1.1 Growth of the Cambridge structural database (CSD) from 1972 to 2016, the

red bar shows structures added annually

MOFs are constructed by joining secondary building units (SBUs) with organic linkers, using strong bonds to create open crystalline frameworks with permanent porosity

The great diversity of metal SBUs and organic linkers have led to thousands of MOFs being synthesized and studied These metal-containing SBUs are essential to the design of directionality for the construction of MOFs and to the achievement of robust frameworks The organic units are ditopic or polytopic organic carboxylates (and other similar negatively charged molecules) [4] Longer organic linkers provide larger storage space and

a greater number of adsorption sites within a given material Containing both organic linkers and metal ions in the frameworks, MOFs possess several interesting properties, such as well-defined structures, high surface areas, high porosity, structural diversity, the ability to tune the pore size, and the possibility to modify the surface hydrophobicity/ hydrophilicity [5] These unique properties have paved the way for MOFs research to grow substantially, and applications are being considered in many areas including gas storage [6, 7], separation [8], catalysis [9] and carbon capture as well as biomolecule encapsulation [10], drug delivery [11], and imaging [12]

1.1.2 General methods for the synthesis of metal-organic frameworks

Figure 1.2 Structural model of MOF (top row) and the representative SBUs (middle

row), as well as ligands (down row)

MOFs are typically synthesized by combining metal salts clusters as connectors and

organic ligands as linkers (Figure 1.2) The characteristics of the ligand (bond angles,

ligand length, bulkiness, chirality, etc.) play a crucial role in dictating what the resultant framework will be Additionally, the tendency of metal ions to adopt certain geometries also influences the structure of the MOFs Generally, MOFs are crystallized from solution The reactants are mixed in high boiling, polar solvents such as water, dialkyl formamides, dimethyl sulfoxide or acetonitrile [2]

Many methods of MOFs synthesis have been reported, such as solvothermal,

hydrothermal, microwave-assisted heating, etc (Figure 1.3) However, solvothermal is the

most popular method thanks to its ability to produce high quality single crystals adequate for structural analysis in dilute liquid phase conditions and accelerate the discovery of new MOF structures The most important parameters of solvothermal MOFs synthesis are temperature, the concentrations of metal salt and ligand (which can be varied across a large range), the extent of solubility of the reactants in the solvent, and the pH of the solution [13, 14] One of the most promising alternatives is microwave irradiation which allows

Figure 1.3 Synthesis methods of metal-organic frameworks

access to a wide range of temperatures and can be used to shorten crystallization times while controlling face morphology and particle size distribution [15, 16]

1.1.3 Applications of metal–organic frameworks

Even though more endeavors are demanded for the development of these materials, possible applications of MOFs have attracted notable attention throughout the most recent years These properties, together with the extraordinary degree of variability for both the organic and inorganic components of their structures, make MOFs of interest for potential applications in a number of fields such as storage, separation [12], optics, magnetic and catalysis [1] These are based on pore size and shape of MOFs and the interactions between host framework and guest molecules [17], as well as the choice of appropriate metal ions and organic ligands In addition, biomedical applications, sensors and devices are also involved [18]

Figure 1.4 Applications of metal–organic frameworks

Drug delivery system

MOFs have been extensively explored as drug delivery devices in the past decade for delivering loaded cargoes to desired sites Although many carriers have been reported, MOFs garnered much attention owing to their porous structure containing voids, which

provides high drug loading capacity and a controlled drug-release profile A wide range of drug molecules with hydrophilic, hydrophobic and amphiphilic natures can be encapsulated in the MOFs [19] Based on the loading approaches discussed earlier, drugs can be encapsulated in the MOFs cavity and/or tethered with the framework structure [20, 21] The drug molecules functionalized by covalent conjugation with the MOFs provide higher ability for controlled drug release action over the drugs adsorbed in the cavity of MOFs

Cancer therapy

Applications of MOFs in cancer therapy have been extensively explored for accomplishing desired targeted action for prolonged periods of time Nano MOFs are highly useful in treating diverse human cancers [22] Applications of Fe3O4-UiO66 MOFs for delivering an anticancer agent (i.e., doxorubicin) revealed improvement in the biopharmaceutical characteristics including controlled drug-release properties up to 40 days, superior anticancer activity in HeLa cells and significant reduction in the tumor volume [23]

Delivery of biomolecules

There are many applications of MOFs beyond drug delivery, thus they have gained wider attention in delivery of biological molecules like DNA, RNA, siRNA, etc [22].Recent instances of MOFs used for biomedical applications include utility of high porosity nano MOFs encapsulated with chemotherapeutic agents withpooled multidrug-resistance (MDR) gene silencing siRNAs for action against drug-resistant ovarian cancer cells In another case, the approach of delivering the prodrug of cisplatin by encapsulation within the MOF structure along with siRNA has been employed to provide improved anticancer action In this context, not only do MOFs help in protecting the siRNA from ribonuclease degradation in the body but they also enhance cellular uptake and promote escape from endosomal enzymes for silencing MDR genes, leading eventually to enhanced chemotherapeutic efficacy [24]

Gas storage

Storage of medical gases in the inert porous carriers is highly useful in biomedical applications Extremely high surface area and pore volume facilitate storage of gases within

the void space of the materials [25] Examples of MOFs include M-CPO-27, which shows exceptional ability for the delivery of medial gases like nitric oxide and hydrogen sulfide HKUST-1 MOFs have also been investigated for their applicability in the storage and delivery of nitric oxide gas [26]

Biosensors

MOFs possess excellent utility in designing the biosensing devices as diagnostic tools for disease identification [27, 28] Magnetism, photostablity, light-sensing and luminescence are the vital properties of MOFs, making them capable of biosensing applications Moreover, other useful characteristics of MOFs including channel size, specific coordination or H-bonding ability, and degree of chirality in the framework are considered to be influential on biosensing applications

Efficient heterogeneous catalysts

Figure 1.5 The active catalytic sites in MOFs

Schematic showing the generation of unsaturated metal connecting points as active catalytic sites (a), the use of functional groups in the bridging ligands as active catalysts

(b), trapping catalytic active species inside MOFs (c)

Although a number of homogeneous organometallic catalysts have been successfully adopted in industrial processes [30], they often suffer from several shortcomings including tedious separation and recycling of expensive catalysts [31] The employment of corresponding heterogeneous catalysts can thus improve the processes by offering a number of advantages over homogeneous catalysts, including easy separation, efficient recycling, minimization of metal traces in the product, and improved handling and process control [18] Moreover, heterogeneous catalysts are more selective than their homogeneous counterparts in some cases [32] Several different approaches for the development of heterogeneous catalysts have been taken including immobilization of homogeneous catalysts on solid supports and introduction of chiral modifiers on catalytically active surfaces One of the latest developments in this field involved catalysis based on metal-organic frameworks [33] Many advantages of metal- organic framework systems such as the high density of active catalytic centers, high level of porosity, crystalline nature enabling elucidation of structural details, and relatively easy immobilization as compared

to other heterogeneous systems make these materials invaluable for heterogeneous asymmetric catalysis [34]

As porous materials, MOFs may prove to be very useful in catalysis All metal cations

or functional groups on the organic bridging ligands in MOFs structure could be useful for catalytic reactions; therefore, the dispersion and the loading of active sites on the solid framework could be maximized By definition, porous metal-organic frameworks are formed by the coordinative polymerization of metal ions or clusters and polyfunctional linker molecules They can acquire catalytic activity in a variety of ways; for exhaustive compilations of all MOF-related catalysis studies, the reader is referred to a number of excellent recent reviews [33, 35] First, the metal or metal cluster connecting points can be

used to catalyze organic transformations As shown in Figure 1.6a, a metal connecting

point with a free coordinating site can be used as a Lewis acid catalyst after removal of

coordinating solvent molecules from the axial positions of the metal center [36] When the MOFs are used in oxidation or hydrogenation reactions, there can be an additional requirement for the framework to accommodate metal ions with changing coordinative demands or even oxidation states Especially when the metal ions of the MOF are alkaline earths, the MOF can also be used as a base catalyst, where the metal–ligand ensemble abstracts a proton from the reactant molecules [29] Second, active catalytic sites can be

generated from the functional groups within a MOF scaffold (Figure 1.7b). Third, the catalytic activity of MOFs can result from entrapped active catalysts, such as palladium or

ruthenium nanoparticles (Figure 1.8c) [37] Note that the catalytic performance of a solid

catalyst with low porosity or with narrow pores with respect to the substrate dimensions can be severely decreased by diffusion control of the reaction rate

As porous materials, MOFs may prove to be very useful in catalysis During the last few years, a variety of MOFs have been explored for catalysis applications, including direct oxidative C -C coupling reactions, cyclization reactions, aza-Michael reactions, Ulmann-type reactions, etc In 2003, Wang and co-workers showed that the cycloaddition of benzyl azide to phenylacetylene through Cu(2-pymo)2, Cu3(BTC)2 and Cu(BDC) [38, 39] It is intriguing to see that Cu2+-MOFs are active as this type of reaction is generally accepted to

be catalyzed by Cu+ species (Scheme 1.1) [40]

Scheme 1.1 The cycloaddition of benzyl azide and phenylacetylene using Cu-MOFs

In 2008, Dongmei Jiang and co-workers also showed that the crystallineCu(bpy)(H2O)2(BF4)2(bpy) is a highly active and selective Lewis acid catalyst in the ring-opening reaction of epoxides with methanolat room temperature [41] 93% of the desired product was achieved employing 9% Cu(bpy)(H2O)2(BF4)2(bpy) as heterogeneous catalyst, low to moderate yields were observed when using other MOFs and homogeneous

transition metal catalysts This was an evidence that the use of Cu(bpy)(H2O)2(BF4)2(bpy)

was compulsory for a range of effective organic transformations (Scheme 1.2)

Scheme 1.2 Ring-opening of styrene oxide with methanol using metal–organic

framework Cu(bpy)(H2O)2(BF4)2(bpy)

In 2013, Lien T.L Nguyen and co-workers have revealed that Cu-MOF-199 as an efficient

heterogeneous catalyst for the aza-Michael reaction (Scheme 1.3) Excellent conversions

were achieved under mild conditions in the presence of 5 mol% catalyst The

Cu-MOF-199 catalyst could be reused several times without a significant degradation in catalytic activity No contribution from homogeneous catalysis of active species leaching into the liquid phase was detected [42]

Scheme 1.3 The aza-Michael reaction using the MOF-199 catalyst

In 2015, Hanh T N Le and co-workers successfully also synthesized and applied

Cu2(BDC)2(BPY) as a catalyst for oxidative amidation reaction of terminal alkyne

(Scheme 1.4) The Cu2(BDC)2(BPY) exhibited excellent catalytic activity and selectivity

as compared to other Cu-MOFs on broad reaction scope Interestingly, the presence of bipyridine ligand was showed to enhance the catalyst stability Consequently, the

Cu2(BDC)2(BPY) catalyst could be simply separated from the reaction mixture by centrifugation reused several times without a significant degradation in catalytic activity [43]

Scheme 1.4 The Cu2(BDC)2(BPY) was used as catalyst for the reaction of

phenylacetylene with 2-oxazolidinone

In 2016, Sadegh Rostamnia and co-workers showed that the palladium ion was

coordinated onto the Schiff base-decorated Cu-BDC pore cage (Scheme 1.5)

Pd@Cu-BDC/Py-SI as a new material was found to be an efficient nanoporous MOFs with hydrophobic nature which had high capacity for the catalysis of the Suzuki- Miyaura cross-coupling reaction at reflux conditions in short reaction time Interestingly, the catalyst was investigated for recoverability and reusability in the Suzuki coupling reaction over 7 successive runs [44]

Scheme 1.5 The Suzuki coupling reaction using Pd@CuBDC

In 2017, Armaqan Khosravi’s Group has revealed that nanoporous Cu2(BDC)2MOF was used as efficient and reusable heterogeneous catalyst to effect the aerobic cross-

(BPY)-coupling of aromatic amines and phenyl boronic acid (Chan–Lam (BPY)-coupling) (Scheme 1.6)

[45] A comparison with other catalytic systems in the cross-coupling reaction of aniline with phenylboronic acids demonstrated that Cu-MOF catalyst system exhibited a higher conversion and yield under optimized reaction condition Ball-milling strategy was utilized for the first as a powerful green and energy-efficient method for the synthesis of this nanoporous metal–organic framework

Scheme 1.6 The aerobic cross-coupling of aromatic amines and phenyl boronic acid

(Chan–Lam coupling) through Cu2(BDC)2(BPY)–MOF

Recently, in 2018 Ha V Dang and co-workers reported synthesis

of benzo[1,4]thiazines via ring expansion of 2-aminobenzothiazoles with terminal alkynes

under Cu-MOF-74 (Scheme 1.7) Different from previous works, the reaction proceeded

readily in the presence of lower catalyst concentration, at lower temperature, and under ligand-free conditions This copper-based framework demonstrated higher catalytic efficiency than a series of MOF-based heterogeneous catalysts and traditional homogeneous catalysts The copper–organic framework was reutilized without a remarkable decline in catalytic efficiency although this ring expansion reaction was not previously performed with a recyclable catalyst [46]

Scheme 1.7 The ring expansion reaction of 2-aminobenzothiazole with phenylacetylene

utilizing Cu–MOF-74 catalyst

In conclusion, MOFs materials are of great interest to the chemical field Promising fields of applications are gas storage, gas purification, separations and catalysis Gas storage, gas purification and separation are the most mature fields of research Therefore,

it is most likely that the first application will come from one of these fields However, research on the catalytic properties of MOFs is gaining momentum Due to their unique properties, MOFs are likely to give new impulses to catalysis research as a whole and may also be beneficial for existing processes All in all, as an emerging class of porous materials, MOFs are being investigated more and more Consequently, an increasing number of new materials are being discovered and novel applications are being identified Since there is virtually infinite number of possible combinations of linker molecules and metal ions, it can be expected that academic and industrial research activities in this field will continue

to be vigorous In the next section, the catalytic activity of the metal-organic framework

Cu2(OBA)2(BPY) – a hopeful candidate for catalysis – is reviewed

CHAPTER 2: RESEARCH OF CATALYTIC ACTIVITY OF BASED METAL-ORGANIC FRAMEWORK Cu-MOF-74 IN THE

COPPER-SYNTHESIS OF 1,4-BENZOTHIAZINE

2.1 The Cu-MOF-74 metal-organic framework

2.1.1 Structure and properties

Cu-MOF-74 belongs to the M-MOF-74 (or M-CPO-27) series of materials which is formed from a 2.5-dihydroxyterephthalic acid (dhtp4-) organic linkers linking with metal cations (M = Cu, Fe, Mn, Co, Ni or Zn) which are of divalence The structure of these MOF-74s, of general formula M2dobdc (dobdc4- = 2.5-dioxidoterephthalate), consists of metal oxide chains connected by the dobdc4- linkers forming a 3-D structure with honeycomb-like hexagonal that contains 1-D broad channels [47] The metal ions bond with oxygen atoms in square pyramidal geometry with coordination number of five

(Figure 2.1)

Figure 2.1 Crystal structure of a MOF-74 (left) and the metal oxide chains connected by

organic linkers (right) O, red; C, black; H, white; metal, blue After synthesis, the channels of MOF-74s are lined with guest molecules such as water or DMF molecules because the metal cations coordinate oxygen atoms and guest

molecules in octahedral geometry (Figure 2.2) Upon desolvation, the metal coordination

changes from octahedral to square pyramidal without compromising the framework integrity, leaving coordinatively unsaturated metal sites open to channels [47] The desolvated MOFs are called activated because they have active metal sites on the channels

Figure 2.2 Structure of Cu-MOF-74 before and after activation 2.1.2 Application in catalysis

In the past decades, Cu-MOFs, more specifically Cu-MOF-74, have been rising as one of the most highly studied MOFs in the literature in the past years In 2014, Pieterjan Valvekens and co-workers successfully synthesized and applied MOF-74 as active catalysts in previously base-catalyzed reactions such as Knoevenagel condensations or Michael additions [64]

Scheme 2.1 Knoevenagel condensations (top) and Michael additions (bottom) using

MOF-74

In the same year, G Calleja and co-workers also showed that copper-based MOF-74 can act as effective acid catalyst in Friedel–Crafts acylation of anisol This research has pointed out that using Cu-MOF-74 as the catalyst can yield product up to 90%, and the

catalyst can be reused up to 7 times while its catalytic activity was not significantly decreased [65]

Scheme 2.2 Simplified reaction scheme for the acylation of anisole with acetyl chloride

using Cu-MOF-74 as catalyst

And recently, our group has reported the alkylation of amides via direct oxidative C(sp3)-H/N-H coupling catalyzed by Cu-MOF-74 under ligand-free condition High yields

of N-alkyl amides were achieved The Cu-MOF-74 was more catalytically active than other Cu-MOFs such as Cu3(BTC)2, Cu(BDC), Cu(EDB), Cu2(BPDC)2(BPY),

Cu2(BDC)2(DABCO), and Cu2(EDB)2(BPY) The Cu-MOF-74 also exhibited advantages

as compared to several copper-based salts, including Cu(OAc)2, CuCl2, CuBr, CuI, CuCl, Cu(NO3)2, and CuSO4 The Cu-MOF-74 catalyst could be reused several times for the amidation transformation without a noteworthy deterioration in catalytic efficiency [66]

Scheme 2.3 Amidation of alkanes by amides catalyzed by Cu-MOF-74

Overall, Cu-MOF-74 is the new member of MOF-74 analogs which had been developed recently with many advantages such as open metal sites, Lewis acid sites, and Lewis base sites As a result, Cu-MOF-74 is a potential heterogeneous catalyst with not only efficient catalytic activity but also the excellent feature of reusability and recyclability for several organic syntheses, especially in oxidative cross-coupling reactions

2.2 The 1,4-benzothiazines and conventional synthesis

Benzo[1,4]thiazine is emerged as a promising substance in pharmaceutical and

agrochemical sites, which displays a variety of functions such as antibacterial [48],

antidiabetic [49], antiarrhythmic[50], antitumor [51], and neurodegenerative diseases [52]

In addition, the similar in structure between this and phenothiazines, which are well

established drugs namely Chlorpromazine, Fluphenazine, Mesoridazine, potentially shows

the use as antipsychotic and antihistaminic drugs [53]

Figure 2.3 Antipsychotic and antihistaminic drugs from phenothiazines

Cyanamides are commonly utilized to prepare herbicides [54] and various

heterocycles [55], which are probably beneficial in manipulate the growth of tumor [56]

To illustrate the applicability of 1,4-benzothiazines several further transformations have

been carried out Accordingly, some strong antimicrobial compounds have been derivable

synthesize 1,4-benzothiazines while investigating the synthesis of

phenylbenzo[d]imidazo[2,1-b]thiazole [57] The reaction was carried out using

2-aminobenzothiazole and phenylactylene under the catalyst system of copper salt and ligand

in 1,2-dichlorobenzene at 100 oC for 6 hours The highest yield on isolated product was 82

% with CuI and 1,10-phenanthroline, meanwhile using copper (II) salt did not cause the

formation of target molecule (Scheme Error! No text of specified style in document 12)

Scheme 2.5 The exploration of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile

synthesis

In 2015, Qiu and co-workers modified the synthesis by changing the reagent from phenylacetylene to 3-phenylpropionic acid [58] The improvement of this modification was the elimination of ligand in the system However, the large amount of base need to be added

to gain good yield The result of this research suggested that homogeneous copper catalyst play an key role in the ring-opening of 2-aminobenzothiazole

Scheme 2.6 The synthesis 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile found by

Qiu and co-workers

In 2016, Chu and co-workers explored another method to prepare the substance, the Three-component tandem cyclization between 1-iodo-2-isothiocyanatobenzene with ethynylbenzene and aqueous ammonia [59] The obtained yield was up to 85% Nevertheless, there are several drawbacks which need to be considered Firstly, the three reactants posed the potential of undesired products Secondly, 1-iodo-2-

isothiocyanatobenzene is unavailable Finally, the condition used in the reaction was more sophisticated

Scheme 2.7 The three-component tandem cyclization to synthesis 1,4-benzothiazines

In the same year, a development in preparation of this valuable compound was achieved The team of Balwe successfully synthesized this under solvent free condition with microwave assistance [60] The reaction got high yield in a significantly short time

Scheme 2.8 Microwave-assisted synthesis of

3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile However, these methods to synthesize benzo[1,4]thiazine derivatives still suffers the drawback of using homogeneous catalysis, in which catalyst recovery and reusability were not mentioned as well as well the possibility of metal contamination in products could increase significantly Nowadays, the viewpoint of green chemistry have been increasingly emphasized for the sake of environment and sustainable development so that there is a need

of finding alternative heterogeneous catalysts

2.3.1 Chemicals and instruments

All reagents and starting materials were obtained commercially from SigmaAldrich, and Chemsol Chemical and used as received without any further purification unless otherwise noted

1 Copper (II) nitrate trihydrate Sigma Aldrich

2 2.5-dihydroxyterephthalic acid Aldrich

5 Cesium carbonate ReagentPlus®, Sigma Aldrich

6 Luperox® Di, tert-butyl peroxide Sigma Aldrich

In terms of instrument, Powder X-ray diffraction patterns were recorded using a Cu

Kα radiation source on a D8 Advance Bruker powder diffractometer GC analyses were performed using a Shimadzu GC 2010-Plus equipped with a flame ionization detector and

an SPB-5 column (length = 30 m, inner diameter = 0.25 mm, and film thickness = 0.25

m) The temperature program for GC analysis held samples at 160 oC for 1 min; heated them from 160 to 280oC at 40oC/min; and held them at 280 oC for 3.5 min Inlet and detector temperatures were set constant at 280 oC Diphenyl ether was used as an internal standard to calculate the GC yield GC–MS analyzes 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 m) The temperature program for GC-MS analysis held samples at 50oC for 2 min; heated samples from 50 to 280oC at 10oC/min and held them at

280 oC for 10 min Inlet temperature was set constant at 280oC MS spectra were compared with the spectra gathered in the NIST library Scanning electron microscopy studies were conducted on a S4800 scanning electron microscope Transmission electron microscopy studies were performed using a JEOL JEM 1400 transmission electron microscope at 80

kV Fourier transform infrared spectra were obtained on a Nicolet 6700 instrument, with samples being dispersed on potassium bromide pallets

2.3.2 Synthesis of Cu-MOF-74

The Cu-MOF-74 was prepared according to a slightly modified literature procedure [61] In a typical preparation, a solid mixture of H2dhtp (H2dhtp = 2.5-dihydroxyterephthalic acid; 0.495 g, 2.5 mmol), and Cu(NO3)2.3H2O (1.21 g, 5 mmol) was dissolved in a mixture of DMF (47 mL) and 2-propanol (3 mL) The suspension was stirred

to achieve a homogeneous solution The resulting solution was then distributed to ten 8 mL vials The vials were then heated at 85 oC in an oven for 18 hours After cooling the vials

to room temperature, the solid product was removed by decanting the mother liquor and daily washed with DMF for 3 days (3×20 mL) Solvent exchange was carried out with 2-propanol (3×20 mL) at room temperature The material was then evacuated under vacuum

at 150 oC for 5 hours

2.3.3 Catalytic studies on the synthesis of

3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile

In an experiment, 2-aminobenzothiazole (0.0375 g, 0.25 mmol) was added to an 8

mL cap-equipped vials, following by acetonitrile (1mL) was used to completely dissolve the white powder in order to form a colorless solution Then, Cs2CO3 (0.016 g, 0.05 mmol) was added in the vial The amount of Cu-MOF-74 was determined by using the ratio of 2-aminobenzothiazole to copper In this experiment, 5 mol % of copper catalyst was

employed Next, Di tert-butyl peroxide (0.1095g, 0.75mmol) was utilized as oxidant The

mixture was magnetically stirred in half a minute to stabilize the medium Finally, phenylacetylene (0.0765 mg, 0.75 mmol) was gradually dropped into this The vials were capped and heated at 80 oC for 3 hours After the reaction was finished, the mixture was cool to room temperature and diphenyl ether (0.0425 g, 0.25 mmol) was used as internal standard for initially calculate the yield The aliquot was then processed under liquid-liquid extraction using 5 mass % KHCO3 solution and 3 mL of ethyl acetate The organic layer was dehydrated using anhydrous sodium sulfate The organic substances were analyzed by Gas chromatography and Flame ionization detector with reference to diphenyl ether The calibration curve was shown in the appendix

2.4 Results and discussions

2.4.1 Synthesis of Cu-MOF-74

The copper-based metal-organic framework Cu-MOF-74 was synthesized according

toa description in Scheme 2.9

Scheme 2.9 Synthesis of Cu-MOF-74

After the solvent exchanging and activation, the Cu-MOF-74 as black crystal was yielded The crystals was obtained in the appearance described The characteristics of Metal–organic framework were initially analyzed using XRD, which offered the graph below

Figure 2.4 Powder X-ray diffraction patterns of Cu-MOF-74

a) The activated CuMOF-74; b) The simulated Cu-MOF-74 [61]

In the Figure 2.4, it is clearly seen that the X-ray diffraction patterns of the

Cu-MOF-74 illustrated the presence of very sharp peaks at 2 of approximately 7o and 12o, proving the highly crystallinity of the Cu-MOF-74 The simulated patterns previously reported in the literature, Sanz, R., et al Dalton Transactions, 2013 [61] strengthened the results as it had the similar to the attained graph

FT-IR spectra of the Cu-MOF-74 exhibited the stretching vibration of a strong peak

at 1560 cm−1, which was lower than the value for the C-O stretching vibration observed in free carboxylic acids observed at 1690 cm-1 (Figure 3.2 b).This strong peak of Cu-MOF-

74 was due to the stretching vibration of carboxylate anions present in the material The absence of strong absorption bands at 1760–1690 cm−1, where the –COOH group was expected to appear, indicated the deprotonation of –COOH groups in 2.5-dihydroxyterephthalic acid upon the reaction with metal ions The broad bands at 3500–

3104 cm−1 were indicative of the presence of –OH group in acid form (Figure 3.2 a)

Figure 2.5 FT-IR spectra of the Cu-MOF-74 (a), and dihydroxyterephtalic acid (b)

20 30 40 50 60 70 80 90

500 1000 1500

2000 2500

3000 3500

The morphology of Cu-MOF-74 was studied by Scanning Electron Microscopy The SEM micrograph indicates that large needle-shaped crystals of the Cu-MOF-74 were obtained Furthermore, to confirm the porosity, one of most important characteristics of MOF materials, the transmission electron microscopy test was done As expected, the TEM micrograph shows that Cu-MOF-74 has porous structure

In this work, based on nitrogen physisorption measurements, it was found that the Cu-MOF-74 has BET surface area of 816 m2/g and an average pore diameter of 8.04 Å

(Figure 2.8) These values are slightly lower than those reported in the literature This is

may be due to incomplete activation conditions

Table 2.1 Some physical properties of synthesised Cu-MOF-74 compared with the

literatures

BET Surface area (m2/g)

Pore diameter (Å)

Figure 2.8 Poresize distribution of Cu-MOF-74

Figure 2.9 TGA curve of the Cu-MOF-74

The thermal stability of the Cu-MOF-74 was also examined by the

thermalgravimetric analysis (TGA) The TGA profile in Error! Reference source not

found showed that a significant weight-loss of the Cu-MOF-74 started at 75.6 oC The initial weight loss of 16.2%, occurring from 75.6 oC to approximately 150 oC, corsresponded well to the loss of DMF, water or solvent molecule per monomer The next remarkable decreasing in weight of 42.9% began at nearly 297.8 oC, when the pyrolysis

0 0.5 1 1.5 2 2.5 3 3.5

began to occur The thermal degradation proceeded until the structure of Cu-MOF-74 was completely decomposed at about 480 oC The mass percentage of the remained Cu-MOF-

74 was about 42.4%, corresponding with the copper oxide and carbon content in the MOF-74 The TGA curve was comparable to the previous report, and confirmed the high thermal stability of the resulting Cu-MOF-74

Cu-2.4.2 Catalytic studies on the synthesis of carbonitrile

N CN

Scheme 2.10 The ring expansion reaction of 2-aminobenzothiazole with phenylacetylene

utilizing Cu-MOF-74 catalyst

The copper-organic framework was explored as heterogeneous catalyst for the ring expansion reaction of 2-aminobenzothiazole with phenylacetylene to produce 3-phenyl-

4H-benzo[b][1,4]thiazine-4-carbonitrile as major product (Scheme 2.10) Mitra et al

previously performed this reaction under air at 100 oC with 10 mol% CuI catalyst and 10 mol% 1,10-phenanthroline as ligand [64] In this work, we found that by using Cu-MOF-

74 catalyst, Cs2CO3 as base, and DTBP as oxidant, the reaction could proceeded at lower catalyst concentration, lower temperature, and without added ligand Initially, the influence

of temperature on the yield of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile was

investigated (Figure 2.10) The reaction was conducted at 5 mol% catalyst in acetonitrile

for 3 h, with 3 equivalents of phenylacetylene, in the presence of 20 mol% of Cs2CO3 as base and 3 equivalents of DTBP as oxidant, at room temperature, 40 oC, 60 oC, 80 oC, and

100 oC, respectively The reaction did not occur at 40 oC, with less than 2% yield being recorded after 3 h Boosting the temperature led to higher yield of the expected product The reaction performed at 60 oC afforded 53% yield after 3 h, while 85% yield was achieved for the reaction carried out at 80 oC Increasing the temperature to 100 oC resulted

in higher initial rate, and the reaction reached 75% yield after 3 h Indeed, GC and GC-MS

analyses indicated that a large amount of homocoupling product of phenylacetylene was produced at 100 oC, resulting in lower yield for the major product

Figure 2.10 Yield of 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile vs reaction time

at different temperatures

Reaction conditions: 2-aminobenzothiazole (0.25 mmol), phenylacetylene (0.75 mmol), DTBP (0.75 mmol), Cu-MOF-74 (5 mol%), Cs2CO3 (20 mol%), acetonitrile (1 mL)

2.4.2.2 Effect of solvents

As the ring expansion reaction of 2-aminobenzothiazole with phenylacetylene to

produce 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile, the solvent might control the

reaction rate significantly The influence of solvent on the yield of the major product was then studied, having conducted the reaction in DMA, DMF, DMSO, NMP, THF, and

acetonitrile, respectively (Figure 2.11) The reaction was carried out at 5 mol% catalyst

for 3 h, with 3 equivalents of phenylacetylene, in the presence of 20 mol% of Cs2CO3 as base and 3 equivalents of DTBP as oxidant, at 80 oC THF was noticed to be inappropriate for this reaction, producing 3-phenyl-4H-benzo[b][1,4]thiazine-4-carbonitrile in 45% yield after 3 h The reaction executed in DMA progressed to 56% yield, while 57% yield was detected for the reaction conducted in NMP Using DMF as solvent for the reaction, the

0 20 40 60 80 100