Luận án tiến sĩ Kỹ thuật hóa học: CuFe2O4 and Fe2O3 superparamagnetic nanoparticles as catalysts for some C-N crosscoupling reactions

VIETNAM NATIONAL UNIVERSITY – HO CHI MINH CITY

HO CHI MINH CITY UNIVERSITY OF TECHNOLOGY

NGUYEN THI KIM OANH

NANOPARTICLES AS CATALYSTS FOR SOME C-N COUPLING REACTIONS

CROSS-PhD THESIS

HO CHI MINH CITY - 2021

VIETNAM NATIONAL UNIVERSITY – HO CHI MINH CITY

HO CHI MINH CITY UNIVERSITY OF TECHNOLOGY

NGUYEN THI KIM OANH

NANOPARTICLES AS CATCALYSTS FOR SOME C-N CROSS-COUPLING REACTIONS

Major: Chemical Engineering Code: 9520301

Independent examiner: Assoc Prof Dr Hoang Thi Kim Dung Independent examiner: Assoc Prof Dr Tran Hoang Phuong

Examiner: Assoc Prof Dr Tran Ngoc Quyen Examiner: Assoc Prof Dr Nguyen Phuong Tung Examiner: Assoc Prof Dr Nguyen Quang Long

Advisor: Prof Dr Phan Thanh Son Nam

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PLEDGE

I assure that this is my own research The research results and conclusions in this thesis are honest, and do not reproduce from any source and in any form References to sources (if any) have been cited and the source of reference is properly regulated

PhD Candidate

Signature

Nguyen Thi Kim Oanh

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ABSTRACT

Superparamagnetic nanoparticles (NPs) have attracted attention as catalyst supports, because of their response to an applied magnetic field Magnetic separation has emerged as a robust, highly efficient and rapid catalyst separation tool with many advantages compared to other catalyst isolation techniques such as liquid-liquid extraction, chromatography, filtration or centrifugation The superparamagnetic nanoparticle materials had highly catalytic activity in many organic reactions because they contain open-type centers Specifically, two superparamagnetic nanoparticle materials include CuFe2O4 and Fe2O3 were synthesized by simple methods, having many outstanding advantages suitable for catalytic applications Moreover, these superparamagnetic nanoparticle materials were commercial materials and could be obtained at low cost

Two materials, including CuFe2O4 and Fe2O3 were used as heterogeneous catalysts for C–N cross-coupling reactions to synthesize compounds such as triphenylamines, 3-

phenylquinoxalin-2(1H)-one and yl)methanone substances The result of the reaction between benzoxazole: iodobenzene (1: 3) produced triphenylamine with a conversion rate of nearly 95% after 2 hours at 140 C in diethylene glycol solvent, 2.5 equivalent Cs2CO3 using 10 mol% catalyst of CuFe2O4 in the argon gas Fe2O3 material was used as a catalyst for the 3-

phenyl(2-phenylimidazo[1,2-a]pyrimidin-3-phenylquinoxalin-2(1H)-one compound from 2-oxo-2-phenylacetic acid (0.25 mmol)

and benzene-1,2-diamine (0.375 mmol) The results achieved a conversion of about 82% after 24 hours at 100 °C in a mixture of solvent C6H5Cl/H2O (1.5 / 0.5) (v / v), using 10 mol% catalyst of Fe2O3 In addition, CuFe2O4 was also used for phenyl(2-

phenylimidazo[1,2-a] pyrimidin-3-yl)methanone from trans-chalcone (0.3 mmol) and

2-aminopyrimidine (0.2 mmol) The results achieved a conversion of about 84% after 7 hours at 140 °C in 1,4-dioxane solvent, two equivalents of iodine using 10 mol% catalyst of CuFe2O4 in oxygen atmosphere These catalysts provided high efficiency and selectivity In addition, the function of the catalysts has also been demonstrated The superparamagnetic nanoparticle catalysts could be recovered and reused many

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times without any significant reduction in catalytic activity To our knowledge, these transformations using superparamagnetic nanoparticle catalysts have not been studied before

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TÓM TẮT LUẬN ÁN

Vật liệu nano siêu thuận từ đã thu hút sự chú ý của các nhà khoa học với vai trò là chất xúc tác hỗ trợ Sự tách từ tính ngày càng được chú ý như một phương pháp tách xúc tác, hiệu quả cao và nhanh chóng với nhiều ưu điểm hơn so với việc phân lập xúc tác bằng cách truyền thống như chiết lỏng-lỏng, sắc ký, lọc hoặc ly tâm Vật liệu này thể hiện hoạt tính xúc tác cao trong nhiều phản ứng hữu cơ vì chúng chứa các tâm kim loại mở Đặc biệt hai vật liệu gồm CuFe2O4 và Fe2O3 được tổng hợp bằng phương pháp đơn giản, có nhiều ưu điểm vượt trội phù hợp trong ứng dụng xúc tác Hơn nữa, các vật liệu nano siêu thuận từ này đã được thương mại hóa và giá thành tương đối thấp Cả hai vật liệu CuFe2O4 và Fe2O3 được sử dụng làm xúc tác dị thể cho phản ứng ghép đôi C–N trong quá trình tổng hợp các hợp chất hữu cơ như triphenylamine, 3-

phenylquinoxalin-2(1h)-one và yl)methanone Kết quả thực hiện phản ứng giữa benzoxazole : iodobenzene (1 : 3) tạo ra triphenylamine đạt hiệu suất gần 95% sau 2 giờ ở 140 C trong dung môi diethylene glycol, 2.5 đương lượng Cs2CO3 sử dụng 10 mol% CuFe2O4 trong môi trường khí argon Vật liệu Fe2O3 được sử dụng làm xúc tác cho phản ứng tổng hợp 3-

phenyl(2-phenylimidazo[1,2-a]pyrimidin-3-phenylquinoxalin-2(1h)-one từ 2-oxo-2-phenylacetic acid (0.25 mmol) và

benzene-1,2-diamine (0.375 mmol) Kết quả thực hiện phản ứng đạt hiệu suất khoảng 82% sau 24 giờ ở 100 C trong hỗn hợp dung môi C6H5Cl/H2O (1.5/0.5) (v/v), sử dụng 10 mol% xúc tác Fe2O3 Ngoài ra, vật liệu CuFe2O4 cũng được sử dụng cho phản ứng

tổng hợp phenyl(2-phenylimidazo[1,2-a]pyrimidin-3-yl)methanone từ trans-chalcone

(0.3 mmol) và 2-aminopyrimidine (0.2 mmol) Kết quả thực hiện phản ứng đạt hiệu suất khoảng 84% sau 7 giờ ở 140 C trong dung môi 1,4-dioxane, hai đương lượng iodine sử dụng 10 mol% xúc tác CuFe2O4 trong môi trường khí oxi Các xúc tác này cho hiệu suất và độ chọn lọc cao Ngoài ra, chức năng của các xúc tác cũng đã được chứng minh Các xúc tác nano siêu thuận từ có thể thu hồi và tái sử dụng nhiều lần mà hoạt tính xúc tác giảm không đáng kể Theo hiểu biết của chúng tôi, những phản ứng trên sử dụng các xúc tác CuFe2O4 và Fe2O3 chưa từng được nghiên cứu trước đây

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ACKNOWLEDGEMENTS

I would like to express our special appreciation and deep regards to my mentor, Prof Dr Phan Thanh Son Nam, who guided me throughout the process of implementing this thesis I have learned from him a lot of professional knowledge and through his guidance I have also learned how to approach and solve other scientific problems I feel so precious when I have the opportunity to receive his guidance

Next, I would like to offer our sincere thank you to Assoc Prof Dr Pham Thanh Quan, Dr Phan Thi Hoang Anh, Dr Nguyen Thanh Tung and the staff of lecturers of Organic Engineering, Faculty of Chemical Engineering, Ho Chi Minh City University of Technology have made sincere suggestions and created many favorable conditions for me to complete this thesis

Last time I had the opportunity to learn and exchange professional knowledge with the staffs in Manar laboratory (MSc Nguyen Kim Chung, MSc Nguyen Thai Anh, Đang Van Ha, Ha Quang Hiep, Pham Huy Hoang) Master's students (Ha Trong Pha, Phan Thi Phuong) and some students (Truong Kim Nhu, Phan Le Tuan Anh, Huynh Dang Khoa) helped me a lot during my time at the lab

Last but not least, I would like to express my special thanks to my families Words cannot express how grateful I are to my parents for all of the sacrifices that they have made on my behalf Their constant encouragement is my most important strength to finish this research work

1.1.2 Green and sustainable catalysis 1

1.1.3 Homogeneous and heterogeneous catalysis 2

1.1.4 Nanocatalyst and magnetic nanoparticles 3

1.2 Ferrite nanoparticles and copper ferrite nanoparticles 7

1.2.1 Ferrite nanoparticles catalyst 7

1.2.2 Copper ferrite nanoparticles catalyst 10

1.2.3 Application of superparamagnetic nanoparticles in catalyst 13

1.3 C-N cross-coupling reactions 23

1.3.1 C-N cross-coupling reaction synthesizes triphenylamines 24

1.3.2 C–N cross-coupling reactions synthesize Quinoxalin-2-ones 29

1.3.3 C-N cross-coupling reactions synthesize a]pyrimidines/aroylimidazo[1,2-a]pyridines 31

aroylimidazo[1,2-1.4 Necessity – Novelty of thesis 35

1.4.1 The necessity of the thesis 35

1.4.2 The novelty of the thesis 35

1.5 Aim and objective 36

CHAPTER 2 RESEARCH METHODS 38

2.1 Materials and instrumentation 38

2.2 Formulate for calculating yield and isolated yield 39

2.3 The catalytic activity investigation of nano CuFe2O4 for synthesis reaction of triphenylamine (TPAs) 40

2.4 The catalytic activity investigation of nanostructured Fe2O3 material for synthesis reaction of quinoxalin-2-ones 41

2.5 The catalytic activity investigation of nanostructured CuFe2O4 material for synthesis reaction of phenyl(2-phenylimidazo[1,2-a]pyrimidin-3-yl)methanone 41

CHAPTER 3 RESULTS AND DISCUSSION 43

3.1 Characteristic structure of materials 43

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3.1.1 Nanostructured CuFe2O4 material 43

3.1.2 Nanostructured Fe2O3 material 45

3.2 The catalytic activity investigation for C–N cross-coupling reactions 46

3.2.1 The catalytic activity investigation of CuFe2O4 for synthesis reaction of triphenylamine (TPAs) 47

3.2.1.1 Effect of different catalysts on the conversion reaction 47

3.2.1.2 Effect of different solvents on reaction conversion 48

3.2.1.3 Effect of different bases and base amounts on reaction conversion 50

3.2.1.4 Effects of reactant concentrations and reactants molar ratio on reaction conversion 533.2.1.5 Effect of catalyst concentrations on reaction conversion 55

3.2.1.8 Effect of homogenous catalysts and heterogeneous catalysts on reaction conversion 583.2.1.9 The mechanism proposal of reaction 60

3.2.1.10 Catalyst recycling and reusing 62

3.2.1.11 Effect of TPAs derivatives on reaction conversion 65

3.2.2 The catalytic activity investigation of Fe2O3 for synthesis reaction of quinoxalin-2-ones 74

3.2.2.1 Effect of different temperatures on the conversion reaction 74

3.2.2.2 Effect of reactant molar ratios on the conversion reaction 76

3.2.2.3 Effect of solvent volume ratios on the conversion reaction 76

3.2.2.4 Effect of catalyst amount on the conversion reaction 77

3.2.2.5 Effect of solvent types on the conversion reaction 78

3.2.2.6 Effect of different catalysts on the conversion reaction 80

3.2.2.7 The mechanism proposal of reaction 82

3.2.2.8 Effect of catalyst loading on reaction conversion 83

3.2.2.9 Catalyst recycling and reusing 85

3.2.2.10 Effect of quinoxalin-2(1H)-one derivative on reaction conversion 88

3.2.3 The catalytic activity investigation of the nano CuFe2O4 for synthesis reaction of phenyl(2-phenylimidazo[1,2-a]pyrimidin-3-yl)methanone 94

3.2.3.1 Effect of different temperatures on the conversion reaction 95

3.2.3.2 Effect of different catalytic amounts on reaction conversion 96

3.2.3.3 Effect of different ratios of the reactant on reaction conversion 97

3.2.3.4 Effect of iodine amount on reaction conversion 98

3.2.3.5 Effect of solvent types on reaction conversion 99

3.2.3.6 The effect of homogeneous and heterogeneous catalysts on reaction conversion 100 3.2.3.7 The mechanism proposal of reaction 102

3.2.3.8 Effect of catalyst loading on reaction conversion 103

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3.2.3.9 Catalyst recycling and reusing 104

3.2.3.10 Effect of a]pyrimidines and a]pyridines derivatives on reaction conversion 107

Figure 1.3: Crystallographic unit cell of different iron oxides: (a) α-Fe2O3, (b) γ-Fe2O3, (c) Fe3O4 and (d) FeO [36] 8

Figure 1.4: Magnetic separation of copper ferrite NPs [49] 11

Figure 1.5: Structure of CuFe2O4 [67] 12

Figure 1.6: Structure of TPAs 25

Figure 1.7: Structure of Quinoxalin-2(1H)-ones 29

Figure 1.8: Structures of some imidazo[1,2-a]pyridine drugs and drug candidates [142] 32

Figure 1.9: Biologically active 3-aroylimidazo[1,2-a]pyridine derivatives [142] 32

Figure 3.1: Copper-oxide-based nano-catalyst dispersed in DMSO reactive solvent (left) and after being applied to an external magnetic field (right) 44

Figure 3.2: Screening solid catalysts for the ring-opening reaction 48

Figure 3.3: Yields of 2-(diphenylamino)phenol versus solvents 50

Figure 3.4: Yields of 2-(diphenylamino)phenol versus bases 52

Figure 3.5: Yields of 2-(diphenylamino)phenol versus base amount 52

Figure 3.6: Yields of 2-(diphenylamino)phenol versus benzoxazole concentration 54

Figure 3.7: Yields of 2-(diphenylamino)phenol versus reactant molar ratios 54

Figure 3.8: Yields of 2-(diphenylamino)phenol versus catalyst concentration 55

Figure 3.9: Yields of 2-(diphenylamino)phenol versus temperatures 56

Figure 3.10: Leaching assessment verified that 2-(diphenylamino)phenol was not generated in the absence of CuFe2O4 superparamagnetic nanoparticles 58

Figure 3.11: Yields of 2-(diphenylamino)phenol using the CuFe2O4 nanocatalyst versus some homogeneous catalysts 59

Figure 3.12: Yields of 2-(diphenylamino)phenol versus heterogeneous catalyst 60

Figure 3.13: Catalyst reutilizing investigation 63

Figure 3.14: XRD results of the fresh (a) and reutilized (b) catalyst 64

Figure 3.15: TEM micrograph of the recovery catalyst 64

Figure 3.16: Yield of 3-phenylquinoxalin-2(1H)-one versus temperature 75

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Figure 3.17: Yield of 3-phenylquinoxalin-2(1H)-one versus 2-oxo-2-phenylacetic

acid:benzene-1,2-diamine molar ratio 76

Figure 3.18: Yield of 3-phenylquinoxalin-2(1H)-one versus MeCN: H2O volume ratio 77

Figure 3.19: Yield of 3-phenylquinoxalin-2(1H)-one versus catalyst amount 78

Figure 3.20: Yield of 3-phenylquinoxalin-2(1H)-one versus the solvent system 78

Figure 3.21: Yield (a) and selectivity (b) of 3-phenylquinoxalin-2(1H)-one versus heterogeneous catalysts 80

Figure 3.22: Yield (a) and selectivity (b) of 3-phenylquinoxalin-2(1H)-one using the Fe2O3 nanocatalyst versus homogeneous catalysts 82

Figure 3.23: Leaching experiment verified that the transformation proceeded under heterogeneous catalysis 84

Figure 3.24: Catalyst reutilizing studies: Yield (a), and selectivity to phenylquinoxalin-2(1H)-one (b) 85

3-Figure 3.25: XRD analysis of the new (a) and reutilized (b) catalyst 86

Figure 3.26: TEM image of the recovery catalyst 87

Figure 3.27: The effect of temperatures on the reaction conversion 96

Figure 3.28: The effect of the amount of catalyst on reaction conversion 97

Figure 3.29: The effect of ratios of the reactant on reaction conversion 98

Figure 3.30: The effect of iodine amount on reaction conversion 99

Figure 3.31: The effect of solvent types on reaction conversion 100

Figure 3.32: Yields of phenyl(2-phenylimidazo[1,2-a]pyrimidin-3-yl)methanone using the CuFe2O4 nanocatalyst versus homogeneous catalysts 101

Figure 3.33: Yields of phenyl(2-phenylimidazo[1,2-a]pyrimidin-3-yl)methanone versus heterogeneous catalysts 101

Figure 3.34: Leaching studies verified that no additional a]pyrimidin-3-yl)methanone was produced after catalyst removal 104

phenyl(2-phenylimidazo[1,2-Figure 3.35: Catalyst reutilizing studies 105

Figure 3.36: XRD patterns of the fresh (a) and reutilized (b) superparamagnetic nano CuFe2O4 catalyst 106

Figure 3.37: TEM image of the recovery catalyst 106

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LIST OF SCHEMES

Scheme 1.1: Xu’s pathway using copper ferrite NPs to form diaryl ethers [63] 14Scheme 1.2: Schematic diagram showing the formation of pFe3O4@mPANI [65] 14Scheme 1.3: β-Fe3O4@mPANI-catayzed O-arylation of phenols with aryl chlorides [65] 15Scheme 1.4: CuFe2O4-catalyzed reaction of indoles with epoxides [66] 15Scheme 1.5: CuFe2O4-catalyzed Friedel–Crafts acylation [67] 16Scheme 1.6: Propargylamine formation via a one-pot three-component reaction of N‒alkyl anilines, terminal alkynes, and TBHP over copper ferrite NPs [68] 16Scheme 1.7: The a-arylation of acetylacetone with aryl iodides using the CuFe2O4 nanoparticles as a solid catalyst [69] 17Scheme 1.8: The synthesis reaction of ynones using CuFe2O4 MNP’s [70] 17Scheme 1.9: Nano-CuFe2O4-catalyzed cross-coupling of aryl halides with diphenyl diselenide [71] 18Scheme 1.10: The cross-coupling between phenylboronic acid and sodium para-toluenesulfinate [53] 18Scheme 1.11: Reaction of iodobenzene and elemental sulfur, n-butyl acrylate using CuFe2O4 as catalyst [74] 19Scheme 1.12: Synthesis of N-aryl amides by using aldoximes and iodobenzene [75] 19Scheme 1.13: The reaction of benzyl bromide, sodium azide, and phenylacetylene [77] 20Scheme 1.14: Synthesis of spiro[indolinepyrazolopyridopyrimidine] derivatives [84]20Scheme 1.15: CuFe2O4-catalyzed synthesis of spiropyrimidine [85] 21Scheme 1.16: Copper ferrite nanoparticles catalyzed thioetherification of iodobenzene using thiourea and benzyl bromide in wet PEG 200 [39] 21Scheme 1.17: Magnetic Copper(II) Ferrite Catalyzed Cyclization of N-(2-Bromophenyl)benzamide to 2- Phenyl-1,3-benzoxazole [62] 22Scheme 1.18: Heterogeneous nano-CuFe2O4 catalyzed synthesis of xanthone derivatives [86] 22Scheme 1.19: Synthesis of dibenzodiazepinones [87] 23Scheme 1.20: Copper ferrite NPs catalyzed synthesis of 2-phenyl quinazolines [88] 23Scheme 1.21: Ullmann reaction [103] 25Scheme 1.22: Buchwald-Hartwig reaction [105] 26Scheme 1.23: Gauthier and Fréchet ‘s reactions between diphenylamine and aryl halides [107] 26Scheme 1.24: Synthesis of TPAs using tetraethyl orthosilicate as solvent [108] 27

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Scheme 1.25: Synthesis of TPAs using 8-hydroxyquinoline as ligand [115] 27

Scheme 1.26: Synthesis of TPAs using CuI NPs as catalyst [116] 27

Scheme 1.27: Synthesis of TPAs using pivalonitrile as solvent [118] 28

Scheme 1.28: Synthesis of TPAs under ligand-free [119] 28

Scheme 1.29: Photo-induced iminyl radical cyclization via N – X bond cleavage [122] 30

Scheme 1.30: The reaction of o-phenylenediamine, sodium pyruvate and benzaldehyde with sodium acetate [121] 30

Scheme 1.31: General reaction for ketimine formation and transimination to quinoxalin-2-ones [123] 31

Scheme 1.32: 3CC reaction of 2-aminopyridine, benzaldehyde, and phenylacetylene [127] 33

Scheme 1.33: Synthesis of 3-aroylimidazo[1,2-a]pyridines [128] 34

Scheme 1.34: One-pot synthesis of imidazo[1,2-a]pyridine [130] 34

Scheme 1.35: Iron-catalyzed synthesis of 3-aroylimidazo[1,2-a]pyridines from 2- aminopyridines and phenylpropiolaldehyde [124] 35

Scheme 2.1: The ring-opening reaction of benzoxazole with iodobenzene to generate 2-(diphenylamino)phenol 47

Scheme 2.2: The synthesis of quinoxalin-2-ones 74

Scheme 2.3: The oxidative cyclization between trans-chalcone and 2-aminopyrimidine utilizing CuFe2O4 superparamagnetic nanoparticles as catalyst 94

Scheme 3.1: Plausible pathway for the transformation 62

Scheme 3.2: Proposed reaction route 83

Scheme 3.3: Plausible mechanism 103

Scheme 3.4: Copper ferrite-catalyzed coupling of dibenzylideneacetone and aminopyridine 112

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LIST OF TABLES

Table 3.1 Summary of research results compare with previous reports of synthetic reaction of TPAs 65Table 3.2: Synthesis of different triphenylamines via ligand-free selective ring-opening reaction utilizing CuFe2O4 nanocatalyst 65Table 3.3 Summary of research results compare with previous reports of synthetic reaction of 3-phenylquinoxalin-2(1H)-one 87Table 3.4: Reactions of 2-oxo-2-phenylacetic acid with different diamines in the presence of the superparamagnetic Fe2O3 nanoparticles 88Table 3.5 Summary of research results compare with previous reports of synthetic reaction of phenyl(2-phenylimidazo[1,2-a]pyrimidin-3-yl)methanone 106

Table 3.6: Scope of aroylimidazo[1,2-a]pyrimidine/aroylimidazo[1,2-a]pyridine

synthesis.a 107

DSC Differential scanning calorimetry

GC/FID Gas chromatographic/flame ionization detector

GC-MS Gas Chromatographic - Mass Spectrometry

HKUST Hong Kong University of Science and Technology

HMBC Heteronuclear Multiple Bond Correlation

HSQC Heteronuclear Single Quantum Correlation

IRMOF Isorecticular Metal-Organic Framework

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THF Tetrahydrofuran

VSM Vibrating Sample Magnetometer

ZIF Zeolitic imidazole framework

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PREFACE

In the organic synthetic field, cross-coupling reactions have been a topic of interest In particular, the C–N cross-coupling reaction is one of the important reactions because they allow the formation of compounds containing C–N bonds and find wide application in organic synthesis of bioactive compounds Not only do these reactions use expensive palladium catalysts, but also associate with complexes or toxic ligands Although extensive efforts have been put in developing lower-cost transition metal catalysts to replace the palladium catalyst in C–N cross-coupling reaction, most of today's catalysts are still of homogeneous catalytic types These homogeneous catalysts, while performing well, are difficult to meet Green Chemistry's demand for recoverability and reuse for economically efficient and environmental friendly processes This calls for development of heterogeneous catalyst systems applicable in cross-coupling reactions The nanoscale is a choice of interest scientists in order to create heterogeneous catalyst systems with good activity

In fact, in the last few years, there have been some studies highlighting the catalytic ability of superparamagnetic nanoparticles for C–N coupling reactions Meanwhile, in the superparamagnetic nanoparticle field, CuFe2O4 and Fe2O3 nanoparticles are continuously reported to be capable of catalyzing many organic reactions These results motivated the goal of this thesis toward extending the use of CuFe2O4 and Fe2O3 nanomaterials in catalyzing the synthetic reactions of triphenylamine, 3-phenylquinoxalin-2(1H)-one, and phenyl(2-phenylimidazo[1,2-a] pyrimidin-3-yl) methanone compounds

Triphenylamines, 3-phenylquinoxalin-2(1H)-one, and a]pyrimidin-3-yl)methanone substances act as important intermediate compounds in the synthesis of biologically active compounds containing nitrogen and functional organic materials Many transition metal catalysts, homogeneous and heterogeneous, have been applied as catalysis for C–N cross-coupling reactions However, these processes have some limitations such as difficult reaction conditions, low product

phenyl(2-phenylimidazo[1,2-xix

performance, complex refining processes, and the use of toxic metal salts as a catalyst Therefore, the research that finds more effective processes for the synthesis of organic products is of great interest worldwide

Among the published solid catalysts, the superparamagnetic nanoparticle materials showed high catalytic activity in the organic reactions because they contained open-type centers Especially, two superparamagnetic nanoparticle materials including nanostructured CuFe2O4 material and nanostructured Fe2O3 material were commercial material, had many outstanding advantages suitable for catalytic applications Moreover, these superparamagnetic nanoparticle materials are commercially available and could be obtained at a low cost These nanoparticle materials have a thermal resistance of about 600 °C Moreover, the largest pore diameter of nanostructured CuFe2O4 material and nanostructured Fe2O3 material is the range of 7.5 - 9.0 Å which allows compounding with average diameter going inside the pore and approach the catalyst centers However, to our knowledge, the C–N cross-coupling reactions to synthesize triphenylamines, 3-phenylquinoxalin-2(1H)-one, and phenyl(2-phenylimidazo[1,2-a]pyrimidin-3-yl)methanone compounds using these superparamagnetic nanoparticle materials as catalysts have not been studied before Therefore, the first goal of the thesis is the use of these nanostructured CuFe2O4 material and nanostructured Fe2O3 material as catalysts for the C–N cross-coupling reactions to synthesize triphenylamines, 3-phenylquinoxalin-2(1H)-one, and phenyl(2-phenylimidazo[1,2-a]pyrimidin-3-yl)methanone compounds The second objective of the thesis is to study the recovery and reusability of materials in suitable conditions The third objective is the research scope that afterward expanded to the synthesis of different products via three reactions mentioned above.

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CHAPTER 1 OVERVIEW

1.1 Catalytic overview 1.1.1 Catalysis

Catalysis plays an increasingly crucial role in chemical processes, and it is widely used at the heart of innumerable chemical processes in various science fields and industrial-scale production [1] Catalysis significantly impacts chemical science, especially in organic synthesis, by greatly accelerating chemical processes, reactions, effectively and sustainably improving yields of synthetic products [2] As a result, it is difficult to realize the development of new and sustainable chemical processes for the synthesis of natural products, drugs, and biologically active molecules without the use of catalysts The catalysts play the role of reducing the activating energy without altering the balance or equilibrium state of the system Recently, catalysis and catalytic reactions have significantly attracted attention in the pharmaceutical and chemical industries [3] Catalysts have possessed a key role in improving and developing organic synthesis, especially in medical chemistry, and have become one of the most economically and ecologically impacting technologies so far [2] The modern era of organic synthesis is shifting towards the path of creative strategies which fundamentally underlines or focuses on the concept of green chemistry, especially the use of sustainable and green catalysts [1]

1.1.2 Green and sustainable catalysis

The development of green, sustainable, and economical chemical processes is one of the challenges in modern chemistry science and green chemistry [4] Green chemistry is also called sustainable chemistry, a philosophy of chemical research and engineering that encourages the design of products and processes toward minimization of the use and generation of hazardous substances [5] Green catalysis is a subchapter of green chemistry, but probably the most important one, and one of the urgently indispensable challenges facing chemists now is the design and use of environmentally benign

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catalysts [7] The concept of green chemistry, which makes catalysis science even more creative, has become an integral part of sustainability [5] From the perspective of green chemistry, an ideal and sustainable catalyst must possess a series of distinctive advantages such as low preparation cost, high activity, efficiency and selectivity, high stability, efficient recovery, and good recyclability [7]

Accordingly, the search for designing and using environmentally benign, sustainable, and efficient, reusable alternative catalytic systems has become a challenge in modern catalysis science [5]

1.1.3 Homogeneous and heterogeneous catalysis

Depending on the reaction phase in which catalysts occupy, catalysts could be classified into two types including homogeneous and heterogeneous catalysts Homogeneous catalyst operates in the same phasing as the reactants, generally dissolved in the reaction medium, but chemists are unanimous on this theory In a homogenous catalytic system, all catalytic sites are accessible because of their distribution in the reaction medium [4] As a result, it is possible to tune the chemo-, region- and enantio-selectivity of the catalyst [8] Homogeneous catalysts have a series of other advantages such as high selectivities, better yield, high turnover numbers, and easy optimization of catalytic systems by modification of ligands and metals [4,5,9] However, homogeneous catalysts also show a notable disadvantage which is the difficulty in separating homogenous catalysts from the desired products, or reaction medium is a difficulty, which is a tedious, and time-consuming task and needs a series of costly and specific techniques [11] It is essential to remove the catalyst because metal contamination is highly regulated, especially in the drug and pharmaceutical industry [5] Also, it is not compatible with the principles of green chemistry in modern catalysis science, especially from an economic standpoint [11] To address the separation problems in homogeneous catalysis, chemists focused on designing new, green, and effective heterogeneous catalytic systems A heterogeneous catalyst is a type of catalysis in which the catalysis is present in a different or separate phase The heterogeneous catalyst is a solid substance, and the reactant is gas or liquid Recently,

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support materials of active molecules (such as inorganic silica and organic polymers) are an efficient strategy for developing eco-friendly catalytic systems that facilitate the recovery and reusability of the catalysts [12] However, the activity and the selectivity of heterogeneous catalysts are lower than those of their homogeneous counterparts Besides, they have a lower dimensionality of the interaction between the components and the catalyst surface [2], [7] These shortcomings might hinder the further development of heterogeneous catalysts [2] In this respect, organic chemists are looking for new heterogeneous catalysts that possess the advantages of both homogenous catalysts (high activity and selectivity, etc.) and heterogeneous catalysts (easy catalyst separation, long catalytic life, thermal stability, and recyclability) [1]

1.1.4 Nanocatalyst and magnetic nanoparticles

Nanotechnology is the science and technology of precisely manipulating the structure of matter at the molecular level, in particular things that are <100 nm in size Nanotechnology is the key and valuable achievement of the 21st century in all sciences, especially in chemistry science During the last decade, chemistry science has witnessed the birth of a new technology revolution and created huge developments in catalysis as a nanocatalyst Nanocatalyst is a hot research topic that involves the use of nanomaterials (average size of 1–100 nm) as catalysts for a variety of catalysis applications [1] The nanocatalysts open up a new and marvelous chapter in catalysis processes and create numerous opportunities for chemists to achieve their goals Nanocatalysts are attractive alternatives to conventional catalysts because when the size of the material (catalysis or support) reaches the nanometer scale, the surface area significantly increases, and the material (catalysis or supports) can equally disperse in the reaction medium, to form a homogenous emulsion [1] To improve catalytic activity, selectivity, and stability of nanocatalysts, it is conventional to manipulate chemical and physical properties such as size, shape, composition, and morphology [14] Accordingly, the particle size and support employed for the dispersion of catalyst are two key factors that affect the efficiency of nanocatalyst processes [1] Nanocatalysts are separated and recovered through filtration or centrifugation strategies However, in most cases, isolation and recovery of nanocatalysts from the

1.1.5 Superparamagnetic nanoparticles

Superparamagnetic nanoparticles (NPs) have attracted attention as catalyst supports, because of their response to an applied magnetic field Magnetic separation has emerged as a robust, highly-efficient, and rapid catalyst separation tool with many advantages compared to catalyst isolation by use of liquid-liquid extraction, chromatography, filtration, or centrifugation Magnetic separation techniques have been used for decades in the mining and food processing industries to separate magnetic from non-magnetic materials on a wet or dry basis using eddy currents, electromagnets, and permanent magnets [26] Magnetic techniques are an inherent part of numerous material treatment operations and have undergone dramatic developments over the last 30 years [27]

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The attractive or repulsive forces between magnetic materials can be described in terms of magnetic dipoles-tiny bar magnets with opposite poles Materials can thus be classified into diamagnetic, paramagnetic, ferromagnetic, ferrimagnetic, and antiferromagnetic according to the arrangement of their magnetic dipoles in the absence and presence of an external magnetic field [28] Figure 1.1 shows schematic diagrams of these five different situations If a material does not have magnetic dipoles in the absence of an external field and has weak induced dipoles in the presence of a field, the material is referred to as diamagnetic The magnetization of a diamagnet responds in the opposite direction to the external field If the material has randomly oriented dipoles that can be aligned in an external field, it is paramagnetic The magnetization of a paramagnet responds in the same direction as the external field The magnetic interactions derived from the above two types of materials are very weak For a ferromagnetic material, the magnetic dipoles always exist in the absence and presence of an external field and exhibit long-range order Macroscopically, such material displays a permanent magnetic moment The difference in the source of the net magnetic moment can also be used to distinguish ferromagnetism from both ferrimagnetism and antiferromagnetism In a ferromagnetic material, there are always weaker magnetic dipoles aligned antiparallel to the adjacent, stronger dipoles in the absence of an external magnetic field For an antiferromagnetic material, the adjacent dipoles are antiparallel in the absence of an external field and cancel each other In general, magnetic materials are referred to as those characterized by either ferro- or ferrimagnetic features [29]

a ferro- or ferrimagnet decreases to a certain critical value rc, the particles change from

a state with multiple magnetic domains to one with a single domain As shown in Figure 1.2, if the size continues to decrease to a value r0, the thermal energy becomes comparable with that required for a spin to flip directions, leading to the randomization of the magnetic dipoles in a short period of time Such small particles do not have permanent magnetic moments in the absence of an external field but can respond to an external magnetic field They are referred to as superparamagnetic colloids

1.2 Ferrite nanoparticles and copper ferrite nanoparticles 1.2.1 Ferrite nanoparticles catalyst

Nanostructured iron oxides are used in different technological areas, such as microwave absorption, catalysis, environment protection, gas sensors, magnetic storage, clinical diagnosis, and treatment, etc Hematite is the most stable form of iron oxide polymorphs and it is important in many applications [34] Hematite is

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plentiful in nature, for example, in aquatic systems, sediments, and soils α-Fe2O3 is the most stable iron oxide under ambient conditions and has been studied extensively for its broad range of applications It crystallizes in the rhombohedral crystal system with n-type semiconducting properties (the optical band gap is 2.1 eV) [35]

Figure 1.3: Crystallographic unit cell of different iron oxide nanoparticles: (a) α-Fe2O3,

(b) γ-Fe2O3 [36]

Fe2O3 exhibits various polymorphs including α-Fe2O3 (rhombohedral), γ-Fe2O3 (cubic), β-Fe2O3 (cubic), and ε-Fe2O3 (orthorhombic), among which α-Fe2O3 is the most thermodynamically stable phase (Figure 1.3a) Both γ-Fe2O3 (space group: P4132, a = b = c = 0.8347 nm) and Fe3O4 (space group: Fd-3m, a = b = c = 0.8394 nm) share the cubic structure with close-packed oxygen atoms along the direction but vary in the oxidation state for Fe (Figure 1.3b) Magnetite contains both Fe2+ and Fe3+ ions in the crystal lattice and is sometimes formulated as FeO·Fe2O3 In the crystal structure of nano Fe3O4, half of the Fe3+ ions are located in the tetrahedral interstitial sites, and the other half of the Fe3+ ions and all the Fe2+ ions occupy the octahedral sites In γ-Fe2O3, due to the absence of Fe2+, some of the Fe positions are left unoccupied as random vacancies (Figure 1.3b) Nano FeO adopts the cubic, rock-salt structure, where Fe2+ ions are octahedrally coordinated by O2- ions The applications for iron oxides intimately depend on their ability to redox (reduction and oxidation) cycle between the +2 and +3 oxidation states However, the variable oxidation states of iron lead to a fairly complicated phase diagram of iron oxides with several easily interchangeable phases Understanding the process of nano Fe2O3 reduction has therefore been a longstanding challenge [36]

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The iron oxide (Fe2O3) is the most common oxide of iron and has important magnetically properties too From the viewpoint of the basic research, iron (III) oxide is a convenient compound for the general study of polymorphism and the magnetic and structural phase transitions of nanoparticles The most frequent polymorphs structure “alpha” (hematite) having a rhombohedral-hexagonal, prototype corundum structures and cubic spinel structure “gamma” (maghemite) have been found in nature At a temperature of 650 C, hematite turns into Fe3O4 with a high energy loss Hematite has strongly antiferromagnetic properties -Fe2O3 (maghemite) is the ferrimagnetic cubic form of Fe (III) oxide and it differs from the inverse spinel structure of magnetite through vacancies on the cation sublattice In time, at room temperature, the maghemite turns into a hematite crystalline structure Maghemite has the same crystalline structure as Fe3O4 (magnetite) The main distinctive features of maghemite are the presence of vacancies in Fe position with symmetry reduction The other polymorphs, the cubic bixbyite structure “beta” and orthorhombic structure “epsilon”, as well as nanoparticles of all forms, have been synthesized and extensively investigated in recent years Epsilon is a transition phase between hematite and maghemite The first scientific report about epsilon Fe2O3 was published in 1934 (Forestier and GuiotGuillain) The detailed structural characterization of the epsilon phase was published by Tranc in 1998 and by Klemm and Mader later Until now, the way to produce -Fe2O3 is gamma–>epsilon->alpha Fe2O3 The β-Fe2O3 with his cubic bixbyite structure has paramagnetic properties Gamma and epsilon type Fe2O3 are ferromagnetic; α-Fe2O3 is a canted antiferromagnetic while beta type Fe2O3 is a paramagnetic material Maghemite Fe2O3 is biocompatible and therefore is one of the most extensively used biomaterials for different applications like cell separation, drug delivery in cancer therapy, magnetic induced hyperthermia, MRI contrast agent, immunomagnetic separation IMC, and others Generally, the semiconductor properties of the hematite are extremely useful in solar energy conversion, photocatalysis, water splitting and the magnetic properties of maghemite play an important role in different applications of health care For this purpose, a large number of materials in bulk as

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well as in the form of nanoparticles have been created for a variety of photochemical and photoelectrochemical applications [37]

1.2.2 Copper ferrite nanoparticles catalyst

Catalysts had played a cornerstone role in the chemical industry for more than one century when more than 85% of all chemical products are manufactured in the presence of them [38] Generally, catalysts could divide into homogeneous and heterogeneous ones The formers usually offer high activity and selectivity However, they suffer from the difficulty in separating from reaction mixtures as the main drawback Meanwhile, the latter did not dissolve in the medium, which can help them to overcome this disadvantage As a result, a wide range of heterogeneous catalysts has been researched for organic transformations such as nanoparticles [39], activated

carbon [40], chitosan [41], zeolite [42], metal-organic frameworks [43], [44]

Despite the increasing attention in the employment of heterogeneous catalysts, they cannot cover the low activity, which is the issue and limits their applications [45] To solve these problems, one of the possible solutions was to keep the particle size of the catalyst within the nanometer (nm) scale to significantly improve its dispersibility in the reaction medium [46] Nevertheless, it seems to be ineffective to separate the nano-sized catalyst from the reaction mixture by conventional methods such as normally centrifugation and simple filtration [47] Subsequently, ferrite NPs have emerged more commonly as a considerably alternative catalyst owing to their unique magnetically separable features [48] This ability allows efficient separation in which the catalysis can be kept stationary in the reactor by using a magnetic field Besides, the reaction mixture could easily decant or be withdrawn (Figure 1.4) This facilitated procedure also minimizes the possible loss of catalyst as well as the heavy metal contamination in final products [49]

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Figure 1.4: Magnetic separation of copper ferrite NPs [49]

Thanks to their attractive properties, ferrite NPs have long been exploited as the supports to offer heterogeneity for a variety of precious but soluble catalysts in a huge number of reactions [50] More interestingly, the last decade witnessed the usage of ferrite NPs indirect way as catalysts without functionalization or complexion with other noble metals in many organic transformations [49] For instance, Fe2O3 NPs for Suzuki C-C coupling reactions [54], Fe3O4 NPs for three-component couplings of aldehydes, alkynes, and amines [33], CuFe2O4 NPs for N-arylations of pyrrole with aryl halides [55], CoFe2O4 NPs for C–O bond formations of different aryl halides [56], NiFe2O4 NPs for Sonogashira reactions [57], etc have been reported

Among the ferrite NPs, copper ferrite NPs (CuFe2O4 - Figure 1.5) had received significant attention in recent years [58] They have widely used for some reactions such as: C–H arylations of benzothiazoles with aryl iodides [59], C–S couplings of arylsulfinic acid salts and organohalides/boronic acids [60], C–O cross-couplings of phenols and aryl halides [61], C–C couplings of terminal alkynes with aryl halides [62], C–Se coupling reactions [63], asymmetric hydrosilylation of prochiral ketones

[64], synthesis of carbamates containing biothiazole moiety [65], etc It is worth noting

that copper ferrite NPs could well prepare from many methods using simple procedures without further functionalization or surface treatment [66], exhibited excellent thermal stability, and usually had sphere shape with particle size mainly about 20 nm [51] These additional features offer this material with low price, high

Figure 1.5: Structure of nano CuFe2O4 [67]

In particular, copper ferrite NPs have been reported as potential heterogeneous catalysts which are effective even at low concentrations, ligand-free, and can be easily recovered and reused for several reactions [57] These interesting features are highly desirable in the context of environmental and industrial concerns A more specific review of the exploitation of copper ferrite NPs in heterogeneous catalysis will be discussed in the next section

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1.2.3 Application of superparamagnetic nanoparticles in catalyst

Superparamagnetic nanoparticles have been currently reported as a powerful catalyst for many organic transformations [69] Highlighted publications in recent years will be mentioned to demonstrate this

1.2.3.1 C-O cross-coupling reactions

In 2011, Zhang et al reported the synthesis of magnetically recoverable CuFe2O4 nanoparticles through simple heating (90 C) of Fe(NO3)29H2O and Cu(NO3)22H2O in the presence of citric acid in water and then decomposition of citric acid at 300 C The transmission electron microscopy (TEM) image of the synthesized catalyst showed that the average size of the CuFe2O4 nanoparticles was about 5–10 nm The saturation magnetization is as high as 33.8 emu.g-1 at room temperature This makes possible a very fast magnetic separation of nanoparticles by simply applying an external magnetic field The catalytic activity of nano CuFe2O4 was tested for O-arylation of various phenols with substituted aryl halides in the presence of Cs2CO3 as a base in DMF at 135 C Some important information of the reactions are listed below: (i) phenols with electron-withdrawing substituents compare to phenols bearing electron-donating substituents gave lower yield of desired products; (ii) aryl iodides gave a higher yield of products than aryl bromides; and (iii) aryl chlorides were shown to be completely unreactive [61] Subsequently, in 2013, the group of Yang–Xu improved the efficiency of this protocol by performing the process in NMF employing 2,2,6,6- tetramethylheptane-3,5-dione(L) as an efficient ligand Both electron-rich and electron-poor phenols 26 and all the three kinds of substituted aryl halides (aryl iodides, bromides, and chlorides) worked well under optimized conditions [CuFe2O4- NPs (5 mol%), L (10 mol%), Cs2CO3 (2 equiv.), NMP, 135 C, 24 h] as provided corresponding diaryl ethers in high to excellent yields (63–91% for derivatives) (Scheme 1.1) [70] This study opened up a more environmentally friendly pathway to synthesize diaryl ethers, which is an important motif in many products including industrial polymers and biologically active compounds [71], [72]

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Scheme 1.1: Xu’s pathway using copper ferrite NPs to form diaryl ethers [70] In 2011, the catalytic activity of magnetic Fe3O4@- mesoporouspolyaniline core-shell nanocomposite (pFe3O4@-mPANI) in the O-arylation of phenols with less reactive aryl chlorides was studied by Arundhathi et al The nanocomposite was synthesized through the encapsulation of as prepared porous magnetite Fe3O4 nanoparticles with the mesoporous polyaniline shell by in situ surface polymerization of aniline with the use of ammonium persulfate [(NH4)2S2O8] in the presence of polyvinylpyrrolidone (PVP) as a linker and sodium dodecylbenzenesulfonate (SDBS) as the structure-directing agent (Scheme 1.2)

Scheme 1.2: Schematic diagram showing the formation of pFe3O4@mPANI [73] The coupling reactions were carried out in DMF as the solvent at 110 C and in the presence of K2CO3 as the base The expected diaryl ethers were obtained in good to very excellent yields (Scheme 1.3) This catalytic system has also been successfully used in the cross-coupling of benzylic and aliphatic alcohols with aryl chlorides under the same conditions The catalyst was recovered by easy decantation of the reaction mixture in the presence of an external magnet and reused at least five times without a loss in its activity Later, nano-sized unsupported Fe3O4 was found to be an efficient catalyst for the etherification of aryl halides with phenols under solvent-free conditions at 130 C Yields were fair to excellent (43–98% for 5 examples) [73]

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Scheme 1.3: β-Fe3O4@mPANI-catalyzed O-arylation of phenols with aryl chlorides [73]

1.2.3.2 C-C cross-coupling reactions

In 2012, Ramarao Parella et al introduced a new method using Fe3O4 NPs and

CuFe2O4 NPs as catalysts for the stereo- and regioselective reactions of epoxides with indoles/pyrroles under solvent- and ligand-free condition (Scheme 1.4) [74] Chiral epoxides gave the alkylated indoles with a complete inversion of stereochemistry

Scheme 1.4: CuFe2O4-catalyzed reaction of indoles with epoxides [74]

Traditionally, a great number of Friedel–Crafts acylation protocols have been reported and most of those methods suffer from the drawbacks such as pre-activation of the catalyst and problems with separation catalyst from the reaction mixture [75] Thus, there was still a need for improvement in new synthetic methods for carrying out the

Friedel–Crafts acylation In 2013, Parella et al introduced regioselective Friedel–

Crafts acylation of an array of anisoles/arenes with various acid chlorides using 5 - 20 mol% of CuFe2O4 NPs, which is moisture insensitive and easily separable from the reaction medium (Scheme 1.5) [75]

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Scheme 1.5: CuFe2O4-catalyzed Friedel–Crafts acylation [75]

In 2014, a protocol for oxidative cross-coupling reactions between N‒alkyl anilines and terminal alkynes forming N‒aryl‒N‒methylpropargylamines using CuFe2O4 NPs as an effective active catalyst was shown by Nam Phan’s group [76] The catalyst was separated from the reaction mixture by magnetic decantation and could be used six times without notable loss in catalytic activity (Scheme 1.6)

Scheme 1.6: Propargylamine formation via a one-pot three-component reaction of N‒

alkyl anilines, terminal alkynes, and TBHP over copper ferrite NPs [76]

Similarly, in 2014, Nam T S Phan et al were used CuFe2O4 nanoparticles as a solid

catalyst for the Cu-catalyzed a-arylation of acetylacetone and iodobenzenes to form phenylacetone as the principal product and 3-phenyl-2,4-pentanedione as the byproduct The optimal conditions employed 5% CuFe2O4 nanocatalyst, DMSO solvent, and K2CO3 base (3 equivalents) at 140 C in 3 h with a 3:1 iodoarene/acetoacetone molar ratio The recovery of the catalyst was achieved easily by simple magnetic decantation The reaction could proceed to completion with 95% selectivity to phenylacetone The CuFe2O4 nanoparticles could be reused several times for the a-arylation reaction without significant degradation in catalytic activity (Scheme 1.7) [77]

Scheme 1.8: The synthesis reaction of ynones using CuFe2O4 MNP’s [78]

1.2.3.3 Others Cross-Coupling reactions

In 2011, Kokkirala Swapna et al had developed a facile copper ferrite

nanoparticle catalyzed cross-coupling of aryl halides with diphenyl diselenide to afford diaryl selenides under ligand-free conditions This method also offers significant improvements in operational simplicity, reaction time, and general applicability to the synthesis of both aryl and alkyl selenides, with high yields of the corresponding products, involving an inexpensive, efficient, and recyclable catalytic system (Scheme 1.9) [79]

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Scheme 1.9: Nano-CuFe2O4-catalyzed cross-coupling of aryl halides with diphenyl diselenide [79]

In 2014, Bojja Sreedhar et al had developed an efficient and environmentally friendly

catalytic system using magnetically separable CuFe2O4 nanoparticles for the coupling between arylsulfinic acid salts with various alkyl or/aryl halide/and boronic acids to generate the corresponding aryl sulfones under similar reaction conditions The catalyst is magnetically separable and eliminates the requirement of nanocatalyst centrifugation after completion of the reaction, which is an additional sustainable attribute of this protocol The recyclability of the catalytic system makes the reaction economically and potentially viable for commercial applications (Scheme 1.10) [60]

cross-Scheme 1.10: The cross-coupling between phenylboronic acid and sodium toluenesulfinate [60]

para-Formerly, the C–S coupling reactions were mostly carried out in solvents that are toxic, expensive, flammable organic solvents such as hexamethylphosphoramide [80] Their use and disposal led to high risks for safety and health as well as heavy burdens for our planet [81] Recently, in 2015, to improve this situation, Mohammad Gholinejad’s team presented a new C–S coupling in PEG (polyethylene glycol) as solvent by using nano CuFe2O4 as a catalyst This protocol could afford products in 72–94% yield under relatively mild conditions Moreover, 76% of the product still formed with the catalyst being reused five times as compared to the first run (Scheme 1.11) [82]

conditions, for the synthesis of N-aryl amides by using copper ferrite NPs as a catalyst

[83] This method was a significant improvement compared to traditional amide formation reactions which usually required strong acids, and high temperatures as well as released hazardous wastes [84] Besides, this protocol could apply to various substrates and afforded a good yield from 73 to 88% (Scheme 1.12)

Scheme 1.12: Synthesis of N-aryl amides by using aldoximes and iodobenzene [83]

1.2.3.4 Three-component reactions

In 2012, Reza Bonyasi et al used CuFe2O4@Starch as a heterogeneous catalyst in

click chemistry for the three-component synthesis of 1,2,3-triazoles in the water at room temperature with low copper loading (0.1 mol%) Using this catalyst, benzylic halides, alkyl bromides, and arylboronic acids reacted with sodium azide and terminal alkynes giving 1,4-disubstituted 1,2,3-triazoles in high yields The catalyst can be easily separated from the reaction mixture using an external magnet and reused for at least 11 consecutive runs with a slight drop in its catalytic activity (Scheme 1.13)[85]–[87]

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Scheme 1.13: The reaction of benzyl bromide, sodium azide, and phenylacetylene [85] The use of water as a solvent for organic reactions has recently drawn attention due to its safety and non-toxic nature [88] However, not all heterogeneous catalysts could endure water since the interaction with water can lead to undesired degradation of their structures [87] Meanwhile, copper ferrite NPs showed excellent stability against water For that reason, in 2013, Ayoob Bazgir and co-workers conducted reactions to synthesize spiro[indolinepyrazolopyridopyrimidine] derivatives in water in the presence of CuFe2O4 NPs (Scheme 1.14) [92] In specific, products could be obtained with excellent yields after only 30 min (81–96% for derivatives) The catalyst was also reused three times without an obvious reduction in yields

Scheme 1.14: Synthesis of spiro[indolinepyrazolopyridopyrimidine] derivatives [92]

In 2013, Dandia et al reported that copper ferrite NPs could be a great catalyst for the

synthesis of spiropyrimidine scaffolds, which have received much attention thanks to their significant biological activity for the regulation of oxidative stress in parasite cells [93] After optimization using various solvents, ethanol was the most effective solvent for this type of reaction (Scheme 1.15) Moreover, the scope was extended and the yields were in the range from 52% to 82%

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Scheme 1.15: Nano CuFe2O4 catalyzed synthesis of spiropyrimidine [93]

In 2014, Mohammad Gholinejad et al have prepared copper ferrite nanoparticles with

an average size of 20–30 nm and studied their catalytic activity for one-pot odorless thioetherification of aryl bromides and iodides using alkyl bromides and thiourea The catalyst was also successfully applied for one-pot synthesis of symmetrical diaryl trithiocarbonates from the reaction of aryl iodides, carbon disulfide, and sodium sulfide under heterogeneous reaction conditions Copper ferrite nanoparticles are recoverable by an external magnet and we have recycled catalyst for five consecutive runs with retention of catalyst activity (Scheme 1.16) [47]

Scheme 1.16: Copper ferrite nanoparticles catalyzed thioetherification of iodobenzene using thiourea and benzyl bromide in wet PEG 200 [47]

1.2.3.5 Cyclization reactions

In 2014, Daoshan Yang et al have developed a simple and efficient magnetic copper

ferrite nanoparticle-catalyzed method for the synthesis of substituted benzoxazoles by Ullmanntype coupling under ligand-free conditions The protocol uses cheap, readily

available, air-stable, recyclable copper (II) ferrite as the catalyst and substituted

N-(2-halophenyl)benzamides as starting materials, and it gives the corresponding benzoxazoles in good to excellent yields under mild conditions (49–96% for