Utilization of ketoxime esters as building blocks for the sythesis of b ketosulfones and furocoumarins

VIETNAM NATIONAL UNIVERSITY - HO CHI MINH CITY BACH KHOA UNIVERSITY - TO ANH TUONG UTILIZATION OF KETOXIME ESTERS AS BUILDING BLOCKS FOR THE SYNTHESIS OF β-KETOSULFONES AND FUROCOUMARINS Major: Chemical Engineering Number: 60.52.75 MASTER THESIS HO CHI MINH CITY, AUGUST 2018 ` CƠNG TRÌNH ĐƯỢC HỒN THÀNH TẠI TRƯỜNG ĐẠI HỌC BÁCH KHOA –ĐHQG -HCM Cán hướng dẫn khoa học 1: GS TS Phan Thanh Sơn Nam Cán chấm nhận xét 1: PGS TS Trần Ngọc Quyển Cán chấm nhận xét 2: PGS TS Nguyễn Thị Phương Phong Luận văn thạc sĩ bảo vệ Trường Đại học Bách Khoa, ĐHQG Tp HCM ngày 04 tháng 08 năm 2018 Thành phần Hội đồng đánh giá luận văn thạc sĩ gồm: Chủ tịch: PGS TS Phạm Thành Quân Phản biện 1: PGS TS Trần Ngọc Quyển Phản biện 2: PGS TS Nguyễn Thị Phương Phong Ủy viên: PGS TS Nguyễn Đình Thành Thư ký: TS Lê Vũ Hà Xác nhận Chủ tịch Hội đồng đánh giá LV Trưởng Khoa quản lý chuyên ngành sau luận văn sửa chữa (nếu có) CHỦ TỊCH HỘI ĐỒNG TRƯỞNG KHOA KTHH ii ĐẠI HỌC QUỐC GIA TP.HCM CỘNG HÒA XÃ HỘI CHỦ NGHĨA VIỆT NAM TRƯỜNG ĐẠI HỌC BÁCH KHOA Độc lập – Tự – Hạnh phúc NHIỆM VỤ LUẬN VĂN THẠC SĨ Họ tên học viên: Tô Anh Tường MSHV: 1770013 Ngày sinh: 02/07/1994 Nơi sinh: TP.HCM Chuyên ngành: Kỹ thuật Hóa học Mã số: 60.52.75 I Tên đề tài Utilization of ketoxime esters as building blocks for the synthesis of β-ketosulfones and furocoumarins (Sử dụng ketoxime ester làm nguyên liệu để tổng hợp dẫn xuất βketosulfone furocoumarin) Nhiệm vụ nội dung: Khảo sát hoạt tính xúc tác MOF Cu2(OBA)2BPY cho phản ứng tổng hợp dẫn xuất β –ketosulfone từ ketoxime ester Phát triển phương pháp sử dụng ketoxime ester để tổng hợp khung furo[3,2,c]coumarin II Ngày giao nhiệm vụ: 15/01/2018 III Ngày hoàn thành nhiệm vụ: 15/06/2018 IV Cán hướng dẫn: GS.TS Phan Thanh Sơn Nam TP.HCM, ngày 16 tháng 06 năm 2018 CÁN BỘ HƯỚNG DẪN CHỦ NHIỆM BỘ MƠN ĐÀO TẠO TRƯỞNG KHOA KỸ THUẬT HĨA HỌC iii ACKNOWLEDMENTS I would like to thank: Advisor Prof Dr Phan Thanh Son Nam Co-workers Vo Hoang Yen Nguyen Thai Anh Nguyen Thi Hong Ngoc Nguyen Huynh Thanh Hai Lab members Ha Quang Hiep Duong Ngoc Tan Xuan Nguyen Dang Hieu Le Van Thanh And my family iv ABSTRACT In this master thesis, I would like to present two new protocols that exploited the potential of reactive ketoxime esters in organic synthesis Our studies also overcame some of the remaining limitations of this research field In the first work, Cu2(OBA)2BPY MOF was successfully synthesized and employed to be an efficient heterogeneous catalyst for the oxidative coupling of ketoxime esters to form β-sulfonylvinylamines, which were then hydrolyzed to obtain β-ketosulfones The Cu2(OBA)2BPY showed high catalytic activity and could be reused many times without a significant deterioration in the catalytic performance This work provided a typical example for the promising combination of copper-based MOFs as heterogeneous catalysts and reactive ketoxime esters In the second study, a novel copper-catalyzed direct Cα-O bond formation of ketoxime esters followed by cyclization to obtain furo[3,2,c]coumarins was explored The new approach featured a facile synthesis of wide range of these bicyclic skeletons in good yields form readily available materials and cheap CuBr2 catalyst, addressing the issues of previous methods v TABLE OF CONTENTS ACKNOWLEDMENTS iv ABSTRACT v TABLE OF CONTENTS .vi LIST OF ABBREVIATIONS viii LIST OF SCHEMES .x LIST OF FIGURES xiii LIST OF TABLES xv LIST OF PUBLICATIONS xvi Chapter - Ketoxime esters as versatile building blocks in organic synthesis .1 Introduction .1 Ketoxime esters under copper catalysis Annulations of oxime esters under copper catalysis α-functionalization of ketoxime esters under copper catalysis Summary .10 Thesis objectives 11 Chapter - An efficient access to β-ketosulfones via ketoxime esters 12 Literature review 12 Introduction 12 Previous approaches .13 Our approach and objectives 19 Experimental section 29 Materials and instrumentations 29 Preparation and characterization of Cu2(OBA)2BPY .30 Catalytic studies 30 vi Results and discussion 33 Preparation and characterization of Cu2(OBA)2BPY .33 Catalytic studies 34 Conclusion .52 Chapter - A novel pathway to furo[3,2,c]coumarins via ketoxime esters 53 Literature review 53 Introduction 53 Previous approaches .54 Our approach and objectives 64 Experimental section 67 Materials and instrumentation 67 Catalytic studies 67 Results and discussion 69 Screening reaction conditions .70 Proposing the reaction mechanism 75 Expansion of the substrate scope 77 Conclusion .81 Chapter - Conclusion 82 REFERENCES 83 APPENDICES .91 vii LIST OF ABBREVIATIONS Ac Acetyl Ar Aryl BET Brunauer–Emmett–Teller BPDC Biphenyl-4,4′-dicarboxylate BPY 4,4’-Bipyridine Bu Butyl CAN Cerium (IV) ammonium nitrate COF Covalent organic framework CPO Coordination polymer of Oslo Cy Cyclohexyl DABCO 1,4-Diazabicyclo[2.2.2]octane DBU 1,8-Diazabicyclo[5.4.0]undec-7-ene DCB 1,2-Dichlorobenzene DCM Dichloromethane DEC Diethyl carbonate DMAP 4-(N,N-dimethylamino)pyridine DMF N,N-dimethylformamide DMSO Dimethylsulfoxide dppf Bis(diphenylphosphino)ferrocene Et Ethyl EWG Electron withdrawing group FID Flame ionization detector FT-IR Fourier-transform infrared spectroscopy GC Gas chromatography GC-MS Gas chromatography coupled with mass spectrometry HKUST (Hong-Kong University of Science and Technology m-CPBA meta-Chloroperoxybenzoic acid Me Methyl mesoMOF Mesoporous metal organic framework viii MIL Mate´riauxs de l’Institut Lavoisier MOCN Metal-organic coordination network MOF Metal-organic framwork MPF Metal peptide framework MW Microwave NMR Nuclear magnetic resonance OBA 4,4’-oxybis(benzoate) PhCl Chlorobenzene Piv Pivaloyl Pr Propyl RPF Rare-earth polymeric framework SBU Secondary building unit SC-XRD Single crystal X-ray diffraction SEM Scaning electron microscope TEM Transmission electron microscope TEMPO 2,2,6,6-Tetramethylpiperidine-1-oxyl TGA Thermogravimetric analysis TMS Trimethylsilyl Ts Tosyl XRD X-ray diffraction ZIF Zeolitic imidazolate framework ZMOF Zeolite-like metal organic framework ix LIST OF SCHEMES Scheme 1.1 General pathways for N-O bond activation of oxime esters under transitionmetal catalysis Scheme 1.2 Annulation of ketoxime esters and aldehydes to pyridines Scheme 1.3 Modular pyridine synthesis from oximes and enals Scheme 1.4 Three-component approach to poly-substituted pyridines Scheme 1.5 Three-component approach to 2-aminopyridines Scheme 1.6 Pathway from ketoxime esters to pyrazolines Scheme 1.7 Three-component synthesis of pyrazoles Scheme 1.8 Synthesis of benzo-fused pyrazoles from o-bromophenyl oxime esters and amines Scheme 1.9 Pyrazolo[1,5-a]indoles synthesis from ketoxime esters Scheme 1.10 Homo-coupling of ketoxime esters to symmetrical pyrroles Scheme 1.11 Synthesis of asymmetrically substituted pyrroles from ketoximes Scheme 1.12 Synthesis of 2-aminothiazoles from ketoxime esters Scheme 1.13 Synthesis of 2-alkoxythiazoles from ketoxime esters Scheme 1.14 A straightforward way from pyridines to imidazo[1,2-a]pyridines Scheme 1.15 Cyclization of o-haloaryloxime acetates to construct nitrogen-containing heterocycles .8 Scheme 1.16 Novel pathway to β-ketosulfones through ketoxime esters under copper catalysis Scheme 1.17 Synthesis of β-ketophosphonates through α-functionalization of ketoxime esters under copper catalysis Scheme 1.18 Synthesis of enaminones via C-C cross-coupling α-functionalization of ketoxime esters Scheme 2.1 β-ketosulfones as vital intermediates in organic transformation 12 Scheme 2.2 The summary of common pathways to prepare β-ketosulfones .13 Scheme 2.3 α-acylation of alkylsulfones .13 Scheme 2.4 Sulfonylation of silyl enol ethers 14 Scheme 2.5 Sulfonylation of α-haloketones by sodium arene sulfinates via nucleophilic substitution reaction .14 x Appendix 69 13C NMR spectra of 3.3ag Characterization Data for 3.3ag Prepared as shown in the general experimental procedure and was purified by silica gel column chromatography using hexane/dichloromethane (1.5:1,v/v) as eluent: white solid, 49% yield 1H NMR (500 MHz, CDCl3) δ 7.92 (dd, J = 8.0, 1.5 Hz, 1H), 7.84 (s, 1H), 7.62 (dd, J = 7.5, 1.5 Hz, 1H), 7.55 – 7.49 (m, 1H), 7.44 (dd, J = 8.5, 1.0 Hz, 1H), 7.41 – 7.32 (m, 2H), 7.06 (td, J = 7.5, 1.0 Hz, 1H), 7.01 (dd, J = 8.5, 1.0 Hz, 1H) 13C NMR (125 MHz, CDCl3) δ = 158.0, 157.8, 157.2, 152.7, 143.1, 131.6, 130.8, 130.0, 124.5, 121.9, 121.0, 120.6, 118.3, 117.2, 113.1, 111.1, 109.8, 55.8 FT-IR  (cm1 ) 1748, 1628, 1573, 1498, 1245, 1021, 964, 739 HR-MS (ESI) m/z ([M+Na]+), calcd for C18H12Na1O4 315.0628, found 315.0630 158 Appendix 70 1H NMR spectra of 3.3ah 159 Appendix 71 13C NMR spectra of 3.3ah Characterization Data for 3.3ah Prepared as shown in the general experimental procedure and was purified by silica gel column chromatography using hexane/dichloromethane (1.5:1,v/v) as eluent: white solid, 76% yield 1H NMR (500 MHz, CDCl3) δ 7.90 (dd, J = 8.0, 1.0 Hz, 1H), 7.73 (s, 1H), 7.65 (d, J = 8.0 Hz, 2H), 7.55 – 7.51 (m, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.36 (t, J = 7.5 Hz, 1H), 7.26 (d, J = 8.0 Hz, 2H), 2.40 (s, 3H) 13C NMR (125 MHz, ) δ = 158.8, 158.0, 152.7, 141.1, 138.4, 130.9, 129.4, 128.7, 126.8, 126.2, 124.6, 121.1, 117.3, 112.9, 108.7, 21.4 FT-IR  (cm-1) 1731, 1624, 1498, 1441, 1116, 1038, 969, 760 HRMS (ESI) m/z ([M+Na]+), calcd for C18H12Na1O3299.0679, found 299.0679 160 Appendix 72 1H NMR spectra of 3.3ai 161 Appendix 73 13C NMR spectra of 3.3ai Characterization Data for 3.3ai Prepared as shown in the general experimental procedure and was purified by silica gel column chromatography using hexane/dichloromethane (1.5:1,v/v) as eluent: white solid, 79% yield 1H NMR (500 MHz, CDCl3) δ 7.92 (dd, J = 8.0, 1.5 Hz, 1H), 7.77 (s, 1H), 7.74 – 7.69 (m, 2H), 7.56 (ddd, J = 8.5, 7.5, 1.5 Hz, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.44 – 7.40 (m, 2H), 7.40 – 7.35 (m, 1H) 13C NMR (125 MHz, CDCl3) δ = 161.3, 159.1, 158.0, 152.8, 141.4, 134.6, 131.3, 130.1, 128.9, 127.7, 125.9, 124.7, 121.2, 117.3, 112.8, 108.4 FT-IR  (cm-1) 1744, 1629, 1543, 1485, 1394, 1091, 1070, 1048, 969, 924, 889, 826, 775, 751, 505 HR-MS (ESI) m/z ([M+Na]+), calcd for C17H9Cl1Na1O3 319.0138, found 319.0131 162 Appendix 74 1H NMR spectra of 3.3aj 163 Appendix 75 13C NMR spectra 3.3aj Characterization Data for 3.3aj Prepared as shown in the general experimental procedure and was purified by silica gel column chromatography using hexane/dichloromethane (1.5:1,v/v) as eluent: white solid, 66% yield 1H NMR (500 MHz, CDCl3) δ 7.92 (dd, J = 8.0, 1.5 Hz, 1H), 7.78 (s, 1H), 7.68 – 7.62 (m, 2H), 7.61 – 7.52 (m, 3H), 7.47 (d, J = 8.0 Hz, 1H), 7.42 – 7.34 (m, 1H) 13C NMR (125 MHz, CDCl3) δ = 159.1, 158.0, 152.8, 141.4, 131.9, 131.3, 130.4, 128.2, 125.9, 124.7, 122.8, 121.2, 117.3, 112.8, 108.4 FT-IR  (cm-1) 1746, 1628, 1541, 1482, 1101, 1070, 1047, 968, 924, 824, 776, 748, 519 HR-MS (ESI) m/z ([M+Na]+), calcd for C17H9Br1Na1O3 362.9627, found 362.9622 164 Appendix 76 1H NMR spectra of 3.3ak 165 Appendix 77 13C NMR spectra of 3.3ak Characterization Data for 3.3ak Prepared as shown in the general experimental procedure and was purified by silica gel column chromatography using hexane/dichloromethane (1.5:1,v/v) as eluent: white solid, 86% yield 1H NMR (500 MHz, ) δ 7.95 (dd, J = 3.5, 1.0 Hz, 1H), 7.90 (dd, J = 7.5, 1.5 Hz, 1H), 7.86 (s, 1H), 7.57 – 7.52 (m, 1H), 7.46 (d, J = 8.5 Hz, 1H), 7.38 – 7.34 (m, 1H), 7.31 (dd, J = 5.0, 1.0 Hz, 1H), 7.13 (dd, J = 5.0, 3.5 Hz, 1H) 13C NMR (125 MHz, CDCl3) δ = 158.9, 157.8, 152.7, 140.6, 131.2, 130.1, 129.0, 128.2, 125.4, 124.7, 121.2, 120.5, 117.3, 112.7, 108.1 FT-IR  (cm-1) 1736, 1626, 1495, 1417, 1319, 1203, 1109, 1030, 1009, 955, 901, 846, 754, 705 HR-MS (ESI) m/z ([M+Na]+), calcd for C15H8S1Na1O3 291.0086, found 291.0093 166 O O O Appendix 78 1H NMR spectra of 3.3al 167 O O O Appendix 79 13C NMR spectra of 3.3al Characterization Data for 3.3al Prepared as shown in the general experimental procedure and was purified by silica gel column chromatography using hexane/dichloromethane (1.5:1, v/v) as eluent: white solid, 73% yield 1H NMR (500 MHz, CDCl3) δ = 7.9 (dd, J = 8.0, 1.5 Hz, 1H), 7.51 – 7.46 (m, 4H), 7.44 – 7.43 (d, J = 7.5 Hz, 2H), 7.40 – 7.38 (m, 3H), 7.37 – 7.33 (m, 1H), 2.89 – 2.84 (m, 2H), 1.38 – 1.35 (m, 3H) 13C NMR (125 MHz, CDCl3) δ = 157.8, 156.7, 156.4, 152.4, 130.3, 130.1, 129.9, 128.2, 127.8, 124.3, 120.7, 119.9, 117.1, 113.0, 109.7, 20.0, 13.0 FT-IR  (cm-1) 2977, 1731, 1630, 1501, 1450, 1085, 1059, 960, 752, 704 HR-MS (ESI) m/z ([M+Na]+), calcd for C19H14Na1O3 313.0835, found 313.0838 168 Appendix 80 1H NMR spectra of 3.3am 169 Appendix 81 13C NMR spectra of 3.3am Characterization Data for 3.3am Prepared as shown in the general experimental procedure and was purified by silica gel column chromatography using hexane/dichloromethane (1.5:1, v/v) as eluent: white solid, 77% yield 1H NMR (500 MHz, CDCl3) δ = 7.99 (d, J = 8.0 Hz, 1H), 7.56 – 7.53 (m, 3H), 7.51 (dd, J = 7.0, 1.0 Hz, 2H), 7.46 – 7.42 (m, 4H), 7.38 (t, J = 7.5 Hz, 1H), 7.34 -7.30 (m, 3H) 13C NMR (125 MHz, CDCl3) δ = 157.5, 156.5, 152.7, 151.4, 130.7, 130.3, 130.2, 129.4, 128.8, 128.6, 128.6, 128.4, 126.7, 124.4, 120.9, 117.3, 112.8, 111.3 FT-IR  (cm-1) 1736, 1626, 1502, 1096, 965, 772, 744, 696 HR-MS (ESI) m/z ([M+Na]+), calcd for C23H11Na1O3 361.0835, found 361.0840 170 Appendix 82 1H NMR spectra of 3.3an 171 Appendix 83 13C NMR spectra of 3.3an Characterization Data for 3.3an Prepared as shown in the general experimental procedure and was purified by silica gel column chromatography using hexane/dichloromethane (1.5:1, v/v) as eluent: white solid, 75% yield 1H NMR (500 MHz, ) δ 7.82 (dd, J = 8.0, 1.5 Hz, 1H), 7.48 – 7.44 (m, 1H), 7.41 (dd, J = 8.5, 1.0 Hz, 1H), 7.34 – 7.29 (m, 1H), 2.82 – 2.73 (m, 4H), 1.97 – 1.90 (m, 2H), 1.86 – 1.79 (m, 2H) 13 C NMR (125 MHz, CDCl3) δ = 158.91, 156.08, 154.39, 152.31, 129.87, 124.39, 120.53, 117.28, 116.85, 113.38, 110.51, 23.28, 22.54, 22.40, 21.06 FT-IR  (cm-1) 2936, 1727, 1618, 1500, 1439, 1382, 1078, 1030, 973, 762 HR-MS (ESI) m/z ([M+Na]+), calcd for C15H12Na1O3 263.0679, found 263.0677 172 ... and built from BPY bridges between the Cu centers The other type of helices is the double-stranded helices chains in the 2D helical layer and formed by the V-shaped OBA ligands bridging Cu atoms,... of Cu2(OBA)2BPY a) The activated Cu2(OBA)2BPY; b) The simulated Cu2(OBA)2BPY Furthermore, Cu2(OBA)2BPY was also characterized by FT-IR, SEM, TEM, TGA and nitrogen physisorption measurement, and. .. thuật Hóa học Mã số: 60.52.75 I Tên đề tài Utilization of ketoxime esters as building blocks for the synthesis of β -ketosulfones and furocoumarins (Sử dụng ketoxime ester làm nguyên liệu để tổng