Metal free synthesis ò furo (3,2 c) coumarins from 4 hydroxycoumarins and oximes

VIETNAM NATIONAL UNIVERSITY - HO CHI MINH CITY UNIVERSITY OF TECHNOLOGY FACULTY OF CHEMICAL ENGINEERING TRAN THI NGOC TU METAL-FREE SYNTHESIS OF FURO[3,2-c]COUMARINS FROM 4-HYDROXYCOUMARINS AND OXIMES Major: Chemical engineering Major ID: 60 52 03 01 M ENG THESIS HO CHI MINH CITY, JAN 2019 CƠNG TRÌNH ĐƯỢC HỒN THÀNH TẠI TRƯỜNG ĐẠI HỌC BÁCH KHOA – ĐHQG – HCM Cán hướng dẫn khoa học 1: TS Trương Vũ Thanh (Ghi rõ họ, tên, học hàm, học vị chữ ký) Cán hướng dẫn khoa học 2: …………………………… (Ghi rõ họ, tên, học hàm, học vị chữ ký) Cán chấm nhận xét 1: PGS.TS Nguyễn Thị Phương Phong (Ghi rõ họ, tên, học hàm, học vị chữ ký) Cán chấm nhận xét 2: TS Nguyễn Thanh Tùng (Ghi rõ họ, tên, học hàm, học vị chữ ký) Luận văn thạc sĩ bảo vệ Trường Đại học Bách Khoa, ĐHQG TP HCM ngày 12 tháng 01 năm 2019 Thành phần Hội đồng đánh giá luận văn thạc sĩ gồm: (Ghi rõ họ, tên, học hàm, học vị Hội đồng chấm bảo vệ luận văn thạc sĩ) PGS.TS Phạm Thành Quân PGS.TS Nguyễn Thị Phương Phong TS Nguyễn Thanh Tùng PGS.TS Nguyễn Đình Thành TS Lê Vũ Hà Xác nhận Chủ tịch Hội đồng đánh giá luận văn Trưởng Khoa quản lý chuyên ngành sau luận văn sửa chữa (nếu có) CHỦ TỊCH HỘI ĐỒNG TRƯỞNG KHOA KTHH ĐẠI HỌC QUỐC GIA TP.HCM TRƯỜNG ĐẠI HỌC BÁCH KHOA CỘNG HÒA XÃ HỘI CHỦ NGHĨA VIỆT NAM Độc lập - Tự - Hạnh phúc NHIỆM VỤ LUẬN VĂN THẠC SĨ Họ tên học viên: TRẦN THỊ NGỌC TÚ MSHV: 1770011 Ngày, tháng, năm sinh: 08/04/1993 Nơi sinh: Tiền Giang Chuyên ngành: Kỹ thuật hóa học Mã số : 60520301 TÊN ĐỀ TÀI: I Metal-free synthesis of Furo[3,2-c]coumarins from 4-hydroxycoumarins and oximes NHIỆM VỤ VÀ NỘI DUNG: II Tổng hợp O-acetyloxime dẫn xuất O-acetyloxime Khảo sát hoạt tính xúc tác I2 lên phản ứng tổng hợp Furo[3,2-c]coumarin từ 4-hydroxycoumarin O-acetyloxime Tối ưu phản ứng Tổng hợp dẫn xuất Furo[3,2-c]coumarin từ dẫn xuất 4hydroxycoumarin O-acetyloxime III NGÀY GIAO NHIỆM VỤ : 15/01/2018 IV NGÀY HOÀN THÀNH NHIỆM VỤ: 02/12/2018 V CÁN BỘ HƯỚNG DẪN : TS Trương Vũ Thanh Tp HCM, ngày 22 tháng 12 năm 2019 CÁN BỘ HƯỚNG DẪN CHỦ NHIỆM BỘ MÔN ĐÀO TẠO TRƯỞNG KHOA KỸ THUẬT HÓA HỌC ABSTRACT A metal-, ligand-, oxidant- and base-free method for the synthesis of furo[3,2c]coumarins from commercially available 4-hydroxycoumarin and O-acyl oximes was successfully developed This novel, efficient and facile reaction swimmingly promoted via molecular iodine catalyst which proceeded to one-pot sequential coupling/cyclization route Additionally, the use of molecular iodine as green catalyst and mesitylene as green solvent contributed to green chemistry and sustainable development i CONTENTS LIST OF FIGURES iv LIST OF SCHEMES v LIST OF TABLES vii LIST OF ABBREVIATIONS .viii CHAPTER LITERATURE REVIEW 1.1 Introduction 1.2 The synthesis of furo[3,2-c]coumarins 1.2.1 Previous methods for the synthesis of furocoumarin scaffold 1.2.2 Previous methods for the synthesis of heterocycles from Oximes 12 1.3 Our approach 15 CHAPTER EXPERIMENTAL SECTION 16 2.1 Material and instrumentation 16 2.2 Procedure for preparation of O-acyl oximes 17 2.3 Procedure for synthesis of furo[3,2-c]coumarins 21 2.4 GC yield determination 23 2.5 Isolated yield determination 25 CHAPTER 3.1 RESULT AND DISCUSSION 26 Investigation of reaction conditions 26 3.1.1 Effect of different types of solvents on the reaction yield 26 3.1.2 Effect of types of catalysts on the reaction yield .27 3.1.3 Effect of reaction environment on the reaction yield 28 3.1.4 Effect of temperature on the reaction yield .29 3.1.5 Effect of catalyst equivalent on the reaction 30 3.1.6 Effect of molar ratio of reactants on the reaction yield .31 ii 3.1.7 Effect of solvent volume on the reaction yield 32 3.1.8 Effect of time on the reaction yield 34 3.2 Reaction scope 35 3.3 Reaction Mechanism 38 3.4 Identification of products 39 CHAPTER CONCLUSION 49 REFERENCES 50 APPENDICS 58 iii LIST OF FIGURES Figure 1-1 Biologically active compounds that have a furocoumarin moiety Figure 2-1 Synthesis ketoxime derivatives 18 Figure 2-2 Synthesis ketoxime esters 20 Figure 2-3 Procedure of furo[3,2-c]coumarin framework 22 Figure 2-4 Calibration curve of furo[3,2-c]coumarin 24 Figure 3-1 Effect of different solvent on the reaction yield 26 Figure 3-2 Effect of various types of catalyst on the reaction yield 28 Figure 3-3 Effect of reaction environment on the reaction yield 29 Figure 3-4 Effect of temperature on the reaction yield 30 Figure 3-5 Effect of catalyst equivalent on the reaction yield 31 Figure 3-6 Effect of molar ratio of reactants on the reaction yield 32 Figure 3-7 Effect of solvent volume on the reaction yield 33 Figure 3-8 Effect of reaction time on the reaction yield 34 Figure 3-9 ORTEP representation of the asymmetric unit of phenyl-4H-furo[3,2c]coumarin displayed with 50% probability Atom colors: O, red; C, grey; H, white 40 iv LIST OF SCHEMES Scheme 1-1 One-pot synthesis of furocoumarins through cascade addition– cyclization–oxidation Scheme 1-2 New strategy for synthesis of 4H-furo[3,2-c]chromen-4-one Scheme 1-3 One-pot synthesis of furocoumarins via sequential Pd/Cu-catalyzed alkynylation and intramolecular hydroalkoxylation Scheme 1-4 Synthesis of 3-bromo-4-hydroxycoumarins and their derivatives Scheme 1-5 Synthesis of furo[3,2-c]coumarin derivatives using visible-light promoted radical alkyne insertion with bromocoumarins Scheme 1-6 Synthesis of furocoumarins via cascade palladium catalyzed oxidative alkoxylation of 4-oxohydrocoumarinsand alkenes Scheme 1-7 FeCl3/ZnI2-catalyzed regioselective synthesis of angularly fused furans Scheme 1-8 Synthesis of substituted furo[3,2‑c]chromen-4-ones via four component reaction Scheme 1-9 Synthesis of functionalized furo[3,2-c]coumarins via a one-pot oxidative pseudo three-component reaction in poly(ethylene glycol) 10 Scheme 1-10 The synthesis of furo[3,2-c]coumarins via I2/TBHP-mediate reaction of 4-hydroxycoumarins with terminal alkynes 11 Scheme 1-11 Rhodium(III)-catalyzed synthesis of isoquinolines from aryl ketone Oacyloxime derivatives and internal alkynes 12 Scheme 1-12 Copper-catalyzed 5-endo-trig cyclization of ketoxime carboxylates: a facile synthesis of 2-arylpyrroles 13 Scheme 1-13 Metal-free assembly of polysubstituted pyridines from oximes and acroleins 13 Scheme 1-14 Transition-metal-free N-O reduction of oximes: A modular synthesis of fluorinated pyridines 14 Scheme 1-15 Conversion of oxime ethers into 2-arylbenzofurans 14 Scheme 1-16 Synthesis furan from aldehyde and oxime ethers 14 Scheme 1-17 Metal,ligand, and base-free reaction for the generation of 15 Scheme 3-1 Investigation of reaction condition by changing types of solvent 26 Scheme 3-2 Investigation of reaction condition by changing types of catalyst 27 v Scheme 3-3 Investigation of reaction condition by changing reaction environment 28 Scheme 3-4 Investigation of reaction condition by changing temperature 29 Scheme 3-5 Investigation of reaction condition by changing catalyst equivalent 30 Scheme 3-6 Investigation of reaction condition by changing molar ratio of reactants 31 Scheme 3-7 Investigation of reaction condition by changing volume of mesitylene 32 Scheme 3-8 Investigation of reaction condition by changing reaction time 34 Scheme 3-9 Control experiments 38 Scheme 3-10 Plausible mechanism 39 Scheme 4-1 Metal-free synthesis of furo[3,2-c]coumarins from oximes and 4hydroxycoumarins 49 vi ... reaction time 34 Scheme 3-9 Control experiments 38 Scheme 3-10 Plausible mechanism 39 Scheme 4- 1 Metal- free synthesis of furo[ 3,2-c ]coumarins from oximes and 4hydroxycoumarins ... THUẬT HÓA HỌC ABSTRACT A metal- , ligand-, oxidant- and base -free method for the synthesis of furo[ 3,2c ]coumarins from commercially available 4- hydroxycoumarin and O-acyl oximes was successfully... Chuyên ngành: Kỹ thuật hóa học Mã số : 60520301 TÊN ĐỀ TÀI: I Metal- free synthesis of Furo[ 3,2-c ]coumarins from 4- hydroxycoumarins and oximes NHIỆM VỤ VÀ NỘI DUNG: II Tổng hợp O-acetyloxime dẫn