Establishing a Closed-Loop System in Mitsunobu Reaction: Recycling of TPPO, Calcium Bromide and Water

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陳哲偉(Jhe-Wei Chen) 查詢紙本館藏

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化學工程與材料工程學系

論文名稱

(Establishing a Closed-Loop System in Mitsunobu Reaction: Recycling of TPPO, Calcium Bromide and Water)

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至系統瀏覽論文 (2025-8-31以後開放)

摘要(中)

光延反應是由日本的化學家Oyo Mitsunobu於1967年發表，有機合成化學中常用於形成碳-碳 (C-C) 和碳-雜原子 (C-X) 鍵，也可使一個帶羥基的手性碳原子發生構型翻轉。因其溫和的反應條件，而且可以置換多種的官能基，在現在的有機合成中是很常見的反應。先前的文獻多注重於底物的選擇以藉由光延反應合成出新分子，但考慮到新型工業化的其中一個最重要的元素，是協助產業從源頭減少污染，更可節能降耗，為企業帶來經濟效益。尤其光延反應的副產物更是含有磷元素，這代表有必要將其回收，因為若是隨意丟棄可能會造成水質優養化，此外，地球上的磷資源有限，如果不加以利用將會加快磷資源的枯竭。因此，本研究主要為探討光延反應後副產物的回收及反應物的再利用。一開始我們將反應中所有的成分進行初步的檢驗，發現三苯基氧化磷的新多晶型，接著在本研究中我們根據先前的研究使用鹵化鹽(溴化鈣)來沉澱副產物三苯基氧化磷，將原本實驗室規模的製程移至0.5公升玻璃攪拌槽中進行了製程放大，同時將原本18小時的製程縮短至3小時，並且透過液相層析法從中監控反應物、產物、副產物的濃度變化再加以轉換為重量以確認質量平衡。我們還將沉澱出來的化合物透過水來拆解以回收三苯基氧化磷，反應時間只需要2小時且產率高達95.7 ± 11.8%，再通過減壓蒸餾來回收水及溴化鈣。總體來說，本研究具有改良製程以應用於大規模製造及在製程中縮短反應時間、節約能源和回收副產物和反應物等特點。

摘要(英)

The Mitsunobu reaction was published by Japanese chemist Oyo Mitsunobu in 1967, is frequently employed in organic synthesis for forming carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds. It can also invert the configuration of a chiral carbon atom with a hydroxyl group. Due to its mild reaction conditions and ability to replace various functional groups, the Mitsunobu reaction is widely used in modern organic synthesis. Previous literature has often focused on the selection of substrates to synthesize new molecules via the Mitsunobu reaction. However, considering one of the most critical elements of new industrial processes is to help industries reduce pollution at the source, save energy, and lower consumption, thereby bringing economic benefits to enterprises. The by-product of the Mitsunobu reaction contains phosphorus and needs to be recycled. Discarding these by-products indiscriminately can lead to water eutrophication. Additionally, since phosphorus resources on Earth are limited, failing to utilize them will accelerate the depletion of those resources. Initially, we conducted a use test of all the components in the reaction and discovered a new polymorph of triphenylphosphine oxide. Therefore, this study primarily explores the recovery of by-products and the reuse of reactants from the Mitsunobu reaction. We utilized halide salts (calcium bromide) based on previous research to precipitate by-product triphenylphosphine oxide (TPPO), scaling up the process from laboratory scale to a 0.5 liter common stirred tank. The original 18 h process was reduced to 3 h, and concentrations of reactants, products, and by-products were monitored using liquid chromatography, which were then converted to weights to ensure mass balance. Furthermore, the precipitated compounds were cracked with water to recover triphenylphosphine oxide, achieving a 95.7 ± 11.8% yield in just 2 h. The water and calcium bromide were then recovered through vacuum distillation. Overall, this study demonstrates improved processes for large-scale manufacturing, shortened reaction times, energy savings, and the recovery of by-products and reactants.

關鍵字(中)

★ 漿料結晶
★ 多晶型
★ 芐基苯基醚
★ 烷基化肼衍生物
★ 三苯基膦

關鍵字(英)

★ Slurry crystallization
★ Polymorph
★ Benzyl phenyl ether
★ Alkylated hydrazine derivative
★ Triphenylphosphine

論文目次

摘要 i
Abstract ii
Acknowledgment iv
Table of Contents vi
List of Figures ix
List of Tables xi
List of Schemes xii
Chapter 1 Introduction 1
1.1 The Importance of Recycling TPPO 1
1.2 Mitsunobu Reaction 3
1.3 Removal of TPPO 6
1.4 Conceptual Framework 8
Chapter 2 Experimental Methods 10
2.1 Materials 10
2.1.1 Chemicals 10
2.1.2 Solvents 11
2.2 Experimental Methods 13
2.2.1 Initial Solvent Screening 13
2.2.2 Mitsunobu Reaction of Benzyl Phenyl Ether 14
2.2.3 Solubility Measurements of TPPO and BPE in THF 16
2.2.4 Small-Scale Preparation of CaBr2-TPPO 17
2.2.5 Complexation of CaBr2-TPPO 18
2.2.6 Recovery of TPPO from CaBr2-TPPO Complex 20
2.2.7 Recovery of CaBr2 and Water 21
2.3 Analytical Instruments 22
2.3.1 Optical Microscopy (OM) 22
2.3.2 Fourier Transform Infrared Spectroscopy (FT-IR) 22
2.3.3 Thermogravimetric Analysis (TGA) 23
2.3.4 Differential Scanning Calorimetry (DSC) 23
2.3.5 Powder X-ray Diffraction (PXRD) 24
2.3.6 High-Temperature X-ray Diffractometer (HT-PXRD) 24
2.3.7 High Performance Liquid Chromatography (HPLC) 25
2.3.8 Solution Nuclear Magnetic Resonance (NMR) 26
2.3.9 Digital Refractometry 26
Chapter 3 Results and Discussion 27
3.1 Analysis and Characterization for Use Test 27
3.1.1 Use Test of TPPO 28
3.2 The Establishment of HPLC Calibration Line 33
3.3 Small-Scale Preparation of CaBr2-TPPO 36
3.4 Mitsunobu Reaction of Benzyl Phenyl Ether 37
3.5 Complexation of CaBr2-TPPO 42
3.6 Recovery of TPPO from CaBr2-TPPO Complex 48
3.7 Recovery of CaBr2 and Water 51
Chapter 4 Conclusions and Future Works 52
4.1 Conclusions 52
4.2 Future Works 53
Appendices 54
References 74

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指導教授

李度(Tu Lee)

審核日期

2024-7-23

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