ĐẠI HỌC QUỐC GIA THÀNH PHỐ HỒ CHÍ MÌNH TRƯỜNG ĐẠI HỌC BÁCH KHOA ÔNG ĐỨC TOÀN INTRODUCTION OF TRIFLUOROMETHYL GROUP INTO BORONIC ACID AND ITS DERIVATIVES USING MOF CU(INA)2 CHUYÊN NGÀNH: KỸ THUẬT HÓA HỌC MÃ SỐ: 60 52 03 01 LUẬN VĂN THẠC SĨ TP. HỒ CHÍ MINH, tháng 6 năm 2017 ĐẠI HỌC QUỐC GIA THÀNH PHỐ HỒ CHÍ MINH TRƯỜNG ĐẠI HỌC BÁCH KHOA INTRODUCTION OF TRIFLUOROMETHYL GROUP INTO BORONIC ACID AND ITS DERIVATIVES USING MOF CU(INA)2 CHUYÊN NGÀNH: KỸ THUẬT HÓA HỌC MÃ SỐ CHUYÊN NGÀNH: 60 52 03 01 LUẬN VĂN THẠC SĨ Cán bộ hướng dẫn Khoa học: TS. Trương Vũ Thanh Học viên: Ông Đức Toàn MSHV: 1570005 TP. HỒ CHÍ MINH, tháng 7 năm 2017 CÔNG TRÌNH ĐƯỢC HOÀN THÀNH TẠI TRƯỜNG ĐẠI HỌC BÁCH KHOA – ĐHQG – HCM Cán bộ hướng dẫn khoa học: TS.
TRƯƠNG VŨ THANH …………………………. Cán bộ chấm nhận xét 1: PGS. NGUYỄN THỊ PHƯƠNG PHONG …………………………………………………… Cán bộ chấm nhận xét 2: PGS. NGUYỄN ĐÌNH THÀNH …………………………………………………… Luận văn thạc sĩ được bảo vệ tại Trường Đại học Bách Khoa, ĐHQG Tp.
HCM ngày 01 tháng 08 năm 2017. Thành phần Hội đồng đánh giá luận văn thạc sĩ bao gồm: 1. Chủ tịch: PGS. Phạm Thành Quân 2.
Phản biện 1: PGS. Nguyễn Thị Phương Phong. Phản biện 2: PGS. Nguyễn Đình Thành 4.
Ủy viên: TS. Tống Thành Danh 5. Thư ký: Phan Thị Hoàng Anh. Xác nhận của Chủ tịch Hội đồng đánh giá LV và Trưởng Khoa quản lý chuyên ngành sau khi luận văn đã được sửa chữa (nếu có) CHỦ TỊCH HỘI ĐỒNG TRƯỞNG KHOA KTHH PGS.
Phạm Thành Quân ĐẠI HỌC QUỐC GIA TP.HCM CỘNG HÒA XÃ HỘI CHỦ NGHĨA VIỆT NAM TRƯỜNG ĐẠI HỌC BÁCH KHOA Độc lập – Tự do – Hạnh phúc ------------ ------------ NHIỆM VỤ LUẬN VĂN THẠC SĨ Họ tên học viên: Ông Đức Toàn MSHV: 1570005 Ngày, tháng, năm sinh: 28/01/1992 Nơi sinh: Tp.HCM Chuyên ngành: Kỹ thuật hóa học Mã số: 60520301 I. TÊN ĐỀ TÀI LUẬN VĂN: Introduction of trifluoromethyl group into boronic acid and its derivatives using MOF Cu(INA)2. NHIỆM VỤ VÀ NỘI DUNG: Tổng hợp MOF Cu(INA)2. Phân tích cấu trúc MOF Cu(INA)2 bằng các phương pháp XRD, SEM, TGA, FT-IR.
Khảo sát phản ứng tổng hợp hợp chất hữu cơ chứa nhóm CF3 từ axit boronic và các dẫn xuất của axit boronic. Xác định sẩn phẩm thu được bằng các phương pháp phân tích NMR và GC-MS. NGÀY GIAO NHIỆM VỤ: 07/2016 IV. NGÀY HOÀN THÀNH NHIỆM VỤ: 06/2017 V.
CÁN BỘ HƯỚNG DẪN: TS. Trương Vũ Thanh Tp. HCM, ngày tháng năm 2017 CÁN BỘ HƯỚNG DẪN CHỦ NHIỆM BỘ MÔN ĐÀO TẠO TRƯỞNG KHOA ACKNOWLEDGEMENT I am deeply grateful to my supervisor Dr. Truong Vu Thanh, for his encouragement and guidance.
He always helps me to have a favorable condition to do my research and gives me great guidance to finish my thesis with his wonderful patience, motivation, enthusiasm, and immense knowledge. Besides, I wish to thank all of the teaching staffs of Organic Chemical Engineering Department for their meaning encouragement and help. I am grateful to my family who is always by my side to encourage me. Ho Chi Minh, June 19, 2017 Ong Duc Toan Introduction of trifluoromethyl group into boronic acid and its derivatives using MOF Cu(INA)2 2017 Contents LIST OF FIGURE.
3 LIST OF SCHEME. 4 LIST OF TABLE. 6 CHAPTER I: LITERATURE REVIEW. Trifluoromethylation of boronic acid: .2 Metal-organic frameworks (MOFs).
17 CHAPTER II: EXPERIMENTAL .1 Synthesis and characterization of the metal-organic frame work Cu(INA)2:. Materials and instrument:. Synthesis of MOF Cu(INA)2:. Materials and instrumentation:.
GC yield determination:. Isolated yield determination:. 26 1 Introduction of trifluoromethyl group into boronic acid and its derivatives using MOF Cu(INA)2 2017 2. 27 CHAPTER 3 : RESULTS AND DISCUSSIONS .1 Cu-MOF synthesis.
Characterization of Cu(INA)2: .2 Trifluormethylation of boronic acids. Effect of catalyst loading on the reaction yield. Effect of different fluoride anion to the reaction yield. Effect of temperature on the reaction yield.
Effect of TMSCF3 ratio on the reaction yield. Effect of 1,10-phenanthroline amount on the reaction yield. Effect of different solvent on the reaction yield. Effect of different copper-based catalysts on the reaction yield.
The recyclability of Cu(INA)2 .10 Substrate scope for trifluormethylation of boronic acid. 53 2 Introduction of trifluoromethyl group into boronic acid and its derivatives using MOF Cu(INA)2 2017 LIST OF FIGURE Figure 1. 1 Natural occurring fluoro-organic compounds. Several active ingredients containing trifluormethyl group10.
3 View of the crystal structure of Cu(INA)2. Synthesized procedure of MOF Cu(INA)2 ………………………………. 2 General procedure for the trifluormethylation of 4-methoxyphenyl boronic acid. 3 Calibration curve of 4-trifluormethyl anisole.
1 Powder X-ray diffraction patterns of the synthesized Cu(INA)2 (a) and the calculated pattern (b) ……………………………………………………………. 2 FT–IR spectra of the Cu(INA)2. 3 SEM micrograph of the Cu(INA)2. 4 TGA curve of the Cu(INA)2.
5 Effect of catalyst loading on reaction yield. 6 Effect of different fluoride anion to the reaction yield. 7 Effect of temperature on the reaction yield. 8 Effect of TMSCF3 amount on reaction yield.
9 Effect of 1,10-phenanthroline amount on the reaction yield. 10 Effect of different copper-based catalysts on the reaction yield. 12 Catalyst recycle studies.13 X-ray powder diffractograms of the fresh (a) and reused (b) [Cu(INA)2] catalyst. 41 3 Introduction of trifluoromethyl group into boronic acid and its derivatives using MOF Cu(INA)2 2017 LIST OF SCHEME Scheme 1.
Copper-mediated perfluoroalkylation of aromatic compounds. 2 Copper-mediated radical trifluoromethylation of boronic acids. 3 Ruthenium(II) and copper-catalyzed radical trifluoromethylation of boronic acids. Copper-catalyzed electrophilic trifluoromethylation of boronic acids.
Copper-catalyzed oxidative trifluormethylation of boronic acids. Copper-mediated oxidative trifluoromethylation of boronic acids. 7 Copper-promoted oxidative trifluoromethylation of alkyl boronic acids. Fluoroform-derivated CuCF3 for trifluoromethylation of boronic acids.
9 Cu(INA)2 as an efficient heterogeneous catalyst for the ligand-free N- arylation of heteroarenes. 10 Trifluoromethylation of boronic acids over Cu-MOF .1 Copper-mediated trifluoromethylation of 4-phenoxyphenyl boronic acid ………………………………………………………………………………….2 Proposed mechanism for the copper-mediated oxidative trifluoromethylation of boronic acids 32 4 Introduction of trifluoromethyl group into boronic acid and its derivatives using MOF Cu(INA)2 2017 LIST OF TABLE Table 1. 1 List of chemicals for MOF synthesis. 1 List of chemicals for trifluormethylation of boronic acids 21 Table 2.
2 Dilution preparation for 4-trifluormethyl anisole. 3 Calibration curve preparation for 4-trifluormethyl anisole. 1 Effect of different solvent on the reaction yield ………………………36 Table 3. 2 Reaction scope of coupling components.
42 5 Introduction of trifluoromethyl group into boronic acid and its derivatives using MOF Cu(INA)2 2017 ABSTRACT Herein, we describe the first heterogeneous and catalytic protocol for nucleophilic trifluormethylation of aryl boronic acids. In particular, a crystalline porous metal organic framework copper isonicotinate Cu(INA)2 [INA = 1,4-(NC5H4CO2)] exhibit exceptional catalytic activity toward the trifluormethylation of boronic acids. The optimal condition involves the use of Cu(INA)2 catalyst (30% mol), nucleophilic trifluormethyltrimethylsilane (TMSCF3) and CsF reagent in 1,2-dichloroethane (DCE) solvent at room temperature in 2 h. Oxygen was employed as oxidant.
Leaching tests confirmed the heterogeneity of Cu(INA)2 during reaction. In addition, Cu(INA)2 was showed to be recovered and reused several times without a significant degradation in catalytic catalyst activities, almost similar reaction yield was still obtained at 6 th run. 6 Introduction of trifluoromethyl group into boronic acid and its derivatives using MOF Cu(INA)2 2017 Tóm Tắt Luận Văn Trong phần luận văn này, chúng tôi trình bày về phản ứng trifluormethyl hóa các hợp chất hữu cơ axit boronic, lần đầu tiên sử dụng xúc tác dị thể và tác nhân fluor hóa ái nhân. Cụ thể, phản ứng được thúc đẩy bởi xúc tác MOF đồng isonicotinate Cu(INA)2 [INA = 1,4-(NC5H4CO2)].
Điều kiện phản ứng tối ưu thu được khi sử dụng 30% mol xúc tác MOF Cu(INA)2 cùng với tác nhân fluor hóa ái nhân trifluormethyltrimethylsilane (TMSCF3), và CsF trong dung môi khan 1,2-dichloroethane (DCE) tại nhiệt độ phòng trong thời gian 2h. Khí oxi được sử dụng làm tác nhân oxi hóa. Đồng thời, vai trò của xúc tác dị thể của MOF Cu(INA)2 được khẳng định bằng thí nghiệm kiểm tra leaching. Thêm vào đó, xúc tác MOF Cu(INA)2 có thể được thu hồi và tái sử dụng nhiều lần mà hiệu suất phản ứng không bị giảm đáng kể với lần thí nghiệm thứ 6.
7 Introduction of trifluoromethyl group into boronic acid and its derivatives using MOF Cu(INA)2 2017 CHAPTER I: LITERATURE REVIEW 1.1 Trifluoromethylation Fluorination chemistry has been an attractive field for many scientists due to its widespread applications in pharmaceuticals,1 agrochemicals,2 materials,3 and radiotracers for positron emission tomography (PET).4 It has been reported that 20% of pharmaceuticals and up to 30% of agrochemicals on the market are fluorine-containing compounds,1a which indicates the vital role of these compounds in numerous areas. In pharmaceutical research, introducing fluorine atom(s) into an organic compound can change its physical, distribution, metabolism and excretion properties1a while remaining the molecular size due to the similar atomic radius of fluorine to hydrogen atom. Despite fluorine is the 13th most abundant element found in the earth’s crust, the amount of natural fluorinated compounds known is very low (Figure 1.5 Therefore, there is a large interest in methodology to introduce selectively fluorine and fluorine-containing groups into organic compounds for improvements of biological activities. 1 Natural occurring fluoro-organic compounds The first metal-mediated direct perfluoroalkyllation was invented by McLoughlin and Thrower in 1965.
They successfully introduced perfluoroalkyl group into the 8 Introduction of trifluoromethyl group into boronic acid and its derivatives using MOF Cu(INA)2 2017 predetermined position of aromatic compounds bearing a wide variety of substituent (carboxy, nitro, amino, hydroxyl, etc.) with the presence of copper under 110-130 oC (Scheme 1. It was also clearly demonstrated that the copper perfluoroalkyl Cu-Rf was formed as a mediated species, which then reacted with aryl halide to produce the desired product.6 However, it was not until 1986 that the copper perfluoroalkyl comple x was first identified via spectroscopic studies. Copper-mediated perfluoroalkylation of aromatic compounds. Since 1960’s, further developments have been continuously reported, regarding the use of various transition-metal-based catalysts.8 Among that, copper-mediated trifluoromethylation has been studied most extensively because of the high efficiency and low cost of copper8.
Trifluoromethylation of boronic acid: One of the most important classes of fluorinated substances consists of compounds bearing a trifluormethyl group. The effects of trifluormethyl introduction into molecules are similar to that of fluorine, including enhancing chemical and metabolism stability, lipophilicity and binding selectivity of initial compounds.9 Hence, such these compounds are used widely as active ingredients in drugs as well as agrochemicals, some examples of them are shown in Figure 1. 9 Introduction of trifluoromethyl group into boronic acid and its derivatives using MOF Cu(INA)2 2017 Figure 1. Several active ingredients containing trifluormethyl group10.
Looking for new methods to introduce trifluormethyl group into organic molecules is also an attractive field owing to their important applications in many areas.10 Molecules bearing a trifluormethylation group represent one of the most important classes of selectively fluorinated compound. 11 In 2012, Standford and co-workers reported the copper-mediated radical trifluoromethylation of aryl boronic acids with the radical reagent sodium trifluoromethanesulfinate NaSO2CF3, in conjunction with tert-butyl hydroperoxide, proceeding under ambient conditions at room temperature (Scheme 1.12 Herein, trifluoromethyl radical could be generated from the radical reagent to participate in the reaction as a reactive species.13 One limitation of this method is the use of stoichiometric amounts of copper salt. 2 Copper-mediated radical trifluoromethylation of boronic acids 10 Introduction of trifluoromethyl group into boronic acid and its derivatives using MOF Cu(INA)2 2017 The merger of photoredox catalyst ruthenium(II) and copper catalysis was also described by Sanford et al.