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: 60.75 MASTER THESIS HO CHI MINH CITY, AUGUST 2018 ` CÔNG TRÌNH ĐƯỢC HOÀN THÀNH TẠI TRƯỜNG ĐẠI HỌC BÁCH KHOA –ĐHQG -HCM Cán bộ hướng dẫn khoa học 1: GS. TS Phan Thanh Sơn Nam Cán bộ chấm nhận xét 1: PGS. Trần Ngọc Quyển Cán bộ chấm nhận xét 2: PGS. Nguyễn Thị Phương Phong Luận văn thạc sĩ được bảo vệ tại 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: 1. Chủ tịch: PGS. Phạm Thành Quân 2. Phản biện 1: PGS.
Trần Ngọc Quyển 3. Phản biện 2: PGS. Nguyễn Thị Phương Phong 4. Ủy viên: PGS.
Nguyễn Đình Thành 5. Lê Vũ Hà 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 ii 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: Tô Anh Tường MSHV: 1770013 Ngày sinh: 02/07/1994 Nơi sinh: TP.HCM Chuyên ngành: Kỹ thuật Hóa học Mã số: 60. 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 các dẫn xuất β- ketosulfone và furocoumarin) Nhiệm vụ và nội dung: 1.
Khảo sát hoạt tính xúc tác của MOF Cu2(OBA)2BPY cho phản ứng tổng hợp các dẫn xuất β –ketosulfone từ các ketoxime ester. Phát triển phương pháp mới 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 bộ hướng dẫn: GS. Phan Thanh Sơn Nam TP.HCM, ngày 16 tháng 06 năm 2018 CÁN BỘ HƯỚNG DẪN CHỦ NHIỆM BỘ MÔN ĐÀO TẠO TRƯỞNG KHOA KỸ THUẬT HÓA HỌC iii ACKNOWLEDMENTS I would like to thank: Advisor Prof. 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 .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 1 - Ketoxime esters as versatile building blocks in organic synthesis. Ketoxime esters under copper catalysis .2 Annulations of oxime esters under copper catalysis .3 α-functionalization of ketoxime esters under copper catalysis .11 Chapter 2 - An efficient access to β-ketosulfones via ketoxime esters .13 Our approach and objectives. 29 Materials and instrumentations .29 Preparation and characterization of Cu2(OBA)2BPY. Results and discussion.
33 Preparation and characterization of Cu2(OBA)2BPY .52 Chapter 3 - A novel pathway to furo[3,2,c]coumarins via ketoxime esters .54 Our approach and objectives. 67 Materials and instrumentation. Results and discussion. 69 Screening reaction conditions.70 Proposing the reaction mechanism .75 Expansion of the substrate scope .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]octane DBU 1,8-Diazabicyclo[5.0]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.
General pathways for N-O bond activation of oxime esters under transition- metal catalysis. Annulation of ketoxime esters and aldehydes to pyridines. Modular pyridine synthesis from oximes and enals. Three-component approach to poly-substituted pyridines.
Three-component approach to 2-aminopyridines. Pathway from ketoxime esters to pyrazolines. Three-component synthesis of pyrazoles. Synthesis of benzo-fused pyrazoles from o-bromophenyl oxime esters and amines.
Pyrazolo[1,5-a]indoles synthesis from ketoxime esters. Homo-coupling of ketoxime esters to symmetrical pyrroles. Synthesis of asymmetrically substituted pyrroles from ketoximes. Synthesis of 2-aminothiazoles from ketoxime esters.
Synthesis of 2-alkoxythiazoles from ketoxime esters. A straightforward way from pyridines to imidazo[1,2-a]pyridines. Cyclization of o-haloaryloxime acetates to construct nitrogen-containing heterocycles. Novel pathway to β-ketosulfones through ketoxime esters under copper catalysis.
Synthesis of β-ketophosphonates through α-functionalization of ketoxime esters under copper catalysis. Synthesis of enaminones via C-C cross-coupling α-functionalization of ketoxime esters. β-ketosulfones as vital intermediates in organic transformation. The summary of common pathways to prepare β-ketosulfones.
α-acylation of alkylsulfones. Sulfonylation of silyl enol ethers. Sulfonylation of α-haloketones by sodium arene sulfinates via nucleophilic substitution reaction. Oxidation of β-ketosulfides.
The oxidative coupling of alkynes and sulfinic acids. The oxidative coupling of alkynes and sulfinates in aqueous media. The oxidative coupling of alkenes and sulfinates in aqueous media. The oxidative coupling of alkenes and sulfinic acids.
The oxidative coupling of arylketones and sulfinic sodium sulfinates to prepare β-ketosulfones. The addition of arylboronics acids to (arylsulfonyl)acetonitriles followed by the hydrolysis to prepare β-ketosulfones. The two-step synthesis of (arylsulfonyl)acetonitriles. The sulfonylation of oxime acetate followed by the hydrolysis to prepare β-ketosulfones.
The preparation of oxime acetates. The general strategy of the solvothermal synthesis. Synthetic pathway to ketoxime esters. Reaction to synthesize sodium sulfinates.
The model reaction for optimization. The optimal reaction conditions. Proposed reaction mechanism. Expansion of the substrate scope.
A possible synthetic pathway of 4-hydroxycoumarins from available compounds. Conventional synthesis of furo[3,2-c]coumarins from 4-hydroxycoumarins and α-haloketones. Synthesis of α-tosyloxyketones from hypervalent iodine followed by cyclization of 4-hydroxycoumarins. Aldehydes as C-3 sources for construction of furo[3,2-c]coumarins.
Isocyanides as ring-closure partners. Furo[3,2-c]coumarin synthesis via phosphine zwitterions. Unexpected exploration from dicoumarol synthesis. One-pot pseudo three-component synthesis of furo[3,2-c]coumarins.
One-pot synthesis of furo[3,2-c]coumarins under CuBr2/O2 catalytic system. Cyclization of 4-hydroxycoumarins and nitroallylic acetates with the presence of base. Cyclization of 4-hydroxycoumarins and β-nitrostyrenes under microwave irradiation. Selective synthesis of furo[3,2-c]coumarins by reaction of 4- hydroxycoumarins and nitroallylic alcohols.
Four-component reaction producing furo[3,2-c]coumarins. Oxidative addition of 4-hydroxycoumarins to electron-rich alkenes promoted by metal oxidants. Aerobic oxidative cyclization of 4-hydroxycoumarins and alkenes. Cyclization of 3-diazo-4-hydroxycoumarins and terminal alkynes catalyzed by rhodium (II).
Two-step synthesis of furo[3,2-c]coumarins catalyzed by palladium. Sequential Pd/Cu-catalyzed alkynylation and intramolecular hydroalkoxylation. Visible-light-promoted iridium-catalyzed alkyne insertion with 3-bromo- 4-hydroxycoumarins followed by annulation. Aerobic oxidative annulation of un-activated 4-hydroxycoumarins and terminal alkynes catalyzed by FeCl3/ZnI2.
The observation from our previous study. Synthetic pathway to ketoxime esters. Model reaction and starting conditions. The optimal reaction conditions.
Plausible reaction mechanism. Expansion of the substrate scope. 77 xii LIST OF FIGURES Figure 2. (a) The components of MOF-5: the Zn4O(−CO2)6 SBU as an octahedron, the ditopic terephthalate linker as a rod and their assembly into the crystalline net.
The most commonly used methods for MOF preparation. Development of MOF catalysts in comparison to the MOF in the recent years. Link between Cu(II) ions and ligands in MOF Cu2(OBA)2BPY. The coordination modes of OBA2- anions with metal: (I) bis(chelating bidentate), (II) bis(bridging-bidentate), (III) both bis(chelating bidentate) and bis(bridging-bidentate).
The eight-membered ring chain. Structure 2D helical layers. The 3D pillared-layer structure of MOF Cu2(OBA)2BPY. (a) The 3D network with helical channels by BPY bridges in Cu2(OBA)2BPY viewed along the c-axis, all OBA2- anions are omitted for clarity.
(b) Spacefilling diagram of the helical chains in the 2D helical layer. (c) The 3D network of Cu2(OBA)2BPY viewed along the c-axis. Reaction of benzothiazole with iodobenzene using Cu2(OBA)2BPY catalyst. Our approach to β-ketosulfones synthesis.
Synthesis of Cu2(OBA)2BPY. Powder X-ray diffraction patterns of Cu2(OBA)2BPY a) The activated Cu2(OBA)2BPY; b) The simulated Cu2(OBA)2BPY .14 Effect of temperatures on the reaction yield. Effect of reactant molar ratio on the reaction yield. Effect of different solvents on the reaction yield.
Effect of reactant concentrations on the reaction yield. Effect of catalyst amount on the reaction yield. Effect of reaction times on the reaction yield. Comparison of catalytic activity of Cu2(OBA)2BPY to other copper-based MOFs.
Comparison of catalytic activity of Cu2(OBA)2BPY to other copper-based homogeneous catalysts. Leaching test results compared to optimal condition. The reutilization of the catalyst. FT-IR analyses of the new (a) and recovered (b) catalyst.
XRD determination of the new (a) and recovered (b) catalyst. Structures of some synthetic furanocoumarins. Effect of catalysts on the reaction yield. Effect of solvents on the reaction yield.
Effect of reaction molar ratios on the reaction yield. Effect of temperatures on the reaction yield. Effect of catalyst amounts on the reaction yield .74 xiv LIST OF TABLES Table 2. Synthesis of β-ketosulfones via Cu2(OBA)2BPY-catalyzed direct C-S coupling reaction followed by hydrolysis step.
Synthesis of substituted furo[3,2,c]coumarins via copper-catalyzed 4- hydroxycoumarins with ketoximes.77 xv LIST OF PUBLICATIONS Related publications: 1. Phan and Nam T. An efficient access to β- ketosulfones via β-sulfonylvinylamines: metal–organic framework catalysis for the direct C–S coupling of sodium sulfinates with oxime acetates. Phan, Thanh Truong and Nam T.
A new route to substituted furocoumarins via copper-catalyzed cyclization between 4-hydroxycoumarins and ketoximes, Organic and Biomolecular Chemistry, 2018,16, 5086-5089. Phan and Nam T. Synthesis of quinazolinones and benzazoles utilizing recyclable sulfated metal-organic framework-808 catalyst in glycerol as green solvent, Journal of Industrial and Engineering Chemistry, 2018, 64, 107-115. Direct oxidative CH amination of quinoxalinones under copper- organic framework catalysis, Catalysis Communications, 2017, 101, 20-25.
Iron-catalyzed one-pot sequential transformations: Synthesis of quinazolinones via oxidative Csp3-H bond activation using a new metal-organic framework as catalyst, submitting. xvi Chapter 1 - Ketoxime esters as versatile building blocks in organic synthesis 1. Introduction The early application of oximes started 19th century, which are well-known for the Beckmann rearrangement, the Semmler–Wolff reaction as well as for reagents in organic synthesis and applications in industry [1, 2].