臺灣博碩士論文加值系統

Proline 及其衍生物 prolinamide 已被大量應用在不對稱 aldol 加成反應。在有機合成中，aldol 反應是生成碳-碳鍵最重要的方法之一，而不對稱的 aldol 反應是建構複雜的掌性醇體系結構的最有效的方法之一，其高選擇性在有機合成中已被大量應用在藥物及天然物的製備。異相觸媒具有容易從產物中分離、可以重複使用等優點。本研究將 prolinamide 的結構修飾成帶有 allyloxy 官能基，與帶有 thiol 官能基的介孔洞材料 SBA-15 ( SH-SBA-15 )，利用 AIBN 作為起始劑，進行 thiol-ene 自由基加成反應而可將 prolinamide 結構固定在介孔洞材料表面上，達到將 prolinamide 異相化的目的。
有機光驅化合物 allyloxy-N-Boc-prolinamide 由 trans-4-hydroxy-L-proline 經一系列修飾而得；含硫醇官能基的介孔洞材料 SBA-15 乃由三區塊共聚物 ( P123 ) 作為模板試劑，將 tetraethyl orthosilicate (TEOS)、(3-mercartopropyl)trimethoxysilane ( MPTMS ) 在酸性環境下進行水解與共縮合反應，合成出具有不同外觀及不同孔道長度之含硫醇基的介孔洞材料 SBA-15。其 XRD 顯示孔洞具有良好排列的二維六角堆積結構。氮氣吸脫附恆溫曲線圖顯示材料的 BET 比表面積、孔洞體積、與孔徑在 allyloxy-prolinamide 鍵結在 SBA-15 材料表面上後有下降趨勢，顯示有機物存在孔洞中；硫的 K-edge 光譜圖顯示材料有 C-S-C 鍵的存在，顯示 allyloxy-prolinamide 與 SH-SBA-15 是以共價鍵鍵結；SEM 與 TEM 圖顯示材料的外觀與孔洞性不隨 prolinamide 的引入而改變。
將含有 prolinamide 結構的 SBA-15 介孔洞材料觸媒應用在不對稱 aldol 加成反應，並藉由改變介孔洞材料其孔道長度、孔洞大小、催化反應溶劑、反應物的比例以及反應溫度等探討其觸媒反應活性。

Prolinamide, prepared from proline and aromatic amine, has been found to be an efficient organocatalyst for asymmetric aldol reaction, which is a key carbon–carbon bond-forming reaction in nature and in the repertoire of the synthetic chemist. For the purpose of easy separation from the reaction mixture and reuses of the catalyst, prolinamide organocatalysts were immobilized on mesoporous silica by covalent bonding.
In the present study, thiol group functionalized SBA-15 ( SH-SBA-15 ) was prepared by one-pot co-condensation of tetraethyl orthosilicate ( TEOS ) and (3-mercartopropyl)trimethoxysilane ( MPTMS ) using P123 copolymer as surfactant in strong acidic environment. 4-O-allyl-hydroxyprolinamide prepared from trans-4-hydroxy-L-proline was modified with allyl group then linked with thiol groups by thiol-ene addition using Azobisisobutyronitrule ( AIBN ) as an initiator. Small-angle XRD patterns showed that the materials contained well-ordered mesopores arranged in 2-D hexagonal arrays. N2 sorption data showed their surface area, pore volume, and pore diameter decreased after prolinamide was immobilized. 29Si MAS NMR spectra confirmed that the organic silane is incorporated as a part of the silica wall structure. Sulfur K-edge XANES spectra showed the existence of C-S-C bond. 13C CP-MAS NMR spectra confirmed the existence of prolinamide structure. SEM and TEM images showed the morphology and mesoporosity did not change after prolinamide immobilization.
The immobilized catalysts were highly efficient in the asymmetric aldol reactions. The effects of solvents and different ketones reacting with 4-nitrobenzaldehyde were examined. The effect of mesostructure on the molecular diffusion during the heterogeneous catalytic reaction was studied.

中文摘要 i
ABSTRACT ii
目錄 iii
圖目錄 vi
表目錄 ix
第1章 緒論 1
1.1 介孔材料的簡介 1
1.2 介孔材料的表面修飾 6
1.2.1 嫁接法 6
1.2.2 共縮合法 7
1.2.3 週期性介孔有機矽材(Periodic Mesoporous Organosilicas, PMO) 8
1.3 不對稱合成的重要性 9
1.4 不對稱Aldol加成反應的發展及反應機制 11
1.4.1 分子間aldol加成反應的機制 12
1.4.2 Proline的結構改良 13
1.4.3 反應中加入水改善催化表現 15
1.5 Thiol-ene自由基加成反應 17
1.6 同相觸媒之異相化 18
1.6.1 同相觸媒異相化之課題 18
1.6.2 Proline及其衍生物異相化之例子 21
1.7 研究目的 23
第2章 實驗方法 24
2.1 化學藥品 24
2.2 材料製備 26
2.2.1 含硫醇基之SBA-15之合成 26
2.2.2 合成具尾端雙鍵之L-prolinamide衍生物 28
2.2.3 將具尾端雙鍵之L-prolinamide固定於含硫醇機之介孔材料中 30
2.2.4 催化反應 31
2.3 鑑定材料之儀器與方法 32
2.3.1 X -光粉末繞射儀 ( Powder X-ray Diffraction, XRD ) 32
2.3.2 氮氣吸附-脫附等溫曲線 ( N2 Adsorption-desorption Isotherm ) 32
2.3.3 元素分析儀 ( Elemental Analyzer, EA ) 34
2.3.4 液態核磁共振光譜儀 ( Nuclear Magnetic Resonance, NMR ) 34
2.3.5 固態核磁共振光譜儀 ( Solid-State Nuclear Magnetic Resonance, NMR ) 35
2.3.6 掃描式電子顯微鏡 ( Scanning Electron Microscopy, SEM ) 35
2.3.7 穿透式電子顯微鏡 ( Transmission Electron Microscopy, TEM ) 35
2.3.8 熱重分析 ( Thermogravimetric Analysis, TGA ) 35
2.3.9 X光近緣吸收光譜 ( X-ray near edge spectrum, XANES ) 35
2.3.10 高效液相層析 ( High Performance Liquid Chromatography, HPLC ) 36
第3章 結果與討論 39
3.1 含硫醇基SBA-15介孔洞材料結構鑑定 39
3.1.1 含硫醇基之不同表面形貌SBA-15介孔材料 39
3.1.2 不同比例硫醇基之介孔材料 48
3.2 Prolinamide結構鑑定 55
3.3 固定Prolinamide於介孔材料SBA-15中 58
3.3.1 固定Prolinamide於不同表面形貌SBA-15之材料鑑定 58
3.3.2 固定Prolinamide於各比例硫醇基SBA-15之材料鑑定 66
第4章 催化反應 72
4.1 丙酮與 4-nitrobenzaldehyde 不對稱 aldol 加成反應 72
4.1.1 不同反應溶劑對催化活性的影響 72
4.1.2 丙酮/DMSO比例對催化活性影響 73
4.2 環己酮與 p-nitrobenzaldehyde 不對稱 aldol 加成反應 75
4.2.1 不同反應溶劑對催化活性的影響 75
4.2.2 環己酮/H2O比例對催化活性影響 76
4.2.3 探討反應物環己酮與丙酮對催化活性影響 77
4.2.4 不同反應物 (p-nitrobenzaldehyde) 的量對催化活性影響 78
4.2.5 乙醇再次萃取對催化活性影響 79
4.2.6 不同掌性催化劑含量對催化活性影響 81
4.2.7 不同反應溫度對催化活性影響 82
4.2.8 不同表面形貌之載體對催化活性影響 84
4.2.9 空白及勻相催化測試 89
4.2.10 觸媒回收利用對催化活性影響 90
第5章 結論 92
第6章 參考文獻 93

[1]J. Y. Ying, C. P. Mehnert, M. S. Wong, Angew. Chem. Int. Ed. 1999, 38, 56.
[2]F. Hoffmann, M. Cornelius, J. Morell, M. Froba, Angew. Chem. Int. Ed. 2006, 45, 3216.
[3]M. E. Davis, C. Y. Chen, S. L. Burkett, H. X. Li, Microporous Mater. 1993, 2, 27.
[4]D. Y. Zhao, J. L. Feng, Q. S. Huo, N. Melosh, G. H. Fredrickson, B. F. Chmelka, G. D. Stucky, Science 1998, 279, 548.
[5]D. Y. Zhao, Q. S. Huo, J. L. Feng, B. F. Chmelka, G. D. Stucky, J. Am. Chem. Soc. 1998, 120, 6024.
[6]S. Y. Chen, L. Y. Jang, Soofin Cheng, Chem. Mater. 2004, 16, 4174.
[7]S. Y. Chen, C. Y. Tang, W. T. Chuang, J. J. Lee, Y. L. Tsai, C. C. Chan, C. Y. Lin, Y. C. Liu, Soofin Cheng, Chem. Mater. 2008, 20, 3906.
[8]T. Asefa, M.J. MacLachan, N. Coombs, G.A. Ozin, Nature 1999, 402, 867.
[9]S. Inagaki, S. Guan, Y. Fukushima, T. Ohsuna, O. Terasaki, J. Am. Chem. Soc. 1999, 121, 9611.
[10]B.J. Melde, B.T. Holland, C.F. Blanford, A. Stein, Chem.Mater. 1999, 11, 3302.
[11]S. Inagaki, S. Guan, T. Ohsuna, O. Terasaki, Nature 2002, 416, 304.
[12]Calne, D. B.; Sandlar, M. Nature 1970, 226, 21.
[13]E.R. Jarvo, S.J. Miller, Tetrahedron 2002, 58, 2481.
[14]K. Nakamura, R. Yamanka, T. Matsuda, T. Harada, Tetrahedron: Asymmetry 2003, 14, 2659.
[15]W. Hotz, F. Tanaka, C.F. Barbas III, Acc. Chem. Res. 2004, 37, 580.
[16]U. Eder, G. Sauer, R. Wiechert, Angew. Chem. Int. Ed. 1971, 10, 496.
[17]B. List, Tetrahedron, 2002, 58, 5573.
[18]B. List, R. A. Lerner, C. F. Barbas, J. Am. Chem. Soc. 2000, 122, 2395.
[19]M. Arno, L. R. Domingo, Theor. Chem. Acc. 2002, 108, 232.
[20]N. Zotova, L. J. Broadbelt, A. Armstrong, D. G. Blackmond, Bioorg. Med. Chem. Lett. 2009, 19, 3934.
[21]B. List, P. Pojarliev, C. Castello, Org. Lett. 2001, 3, 573.
[22]Z. Tang, F. Jiang, X. Cui, L. Z. Gong, A. Q. Mi, Y. Z. Jiang, Y. D. Wu, PNAS 2004 ,101 ,5755.
[23]S. S. Chimni , S. Singh, D. Mahajan, Tetrahedron: Asymmetry 2008, 19, 2276.
[24]J. Casas, H. Sundn, A. C_rdova, Tetrahedron Lett. 2004, 45, 6117 .
[25]M. Gruttadauria, F. Giacalone, A. Mossuto Marculescu, R. Noto, Adv. Synth. Catal. 2008, 350, 1397.
[26]M. Gruttadauria, F. Giacalone, A. Mossuto Marculescu, A. M. P. Salvo, R. Noto, ARKIVOC 2009, viii, 5.
[27]B. Wang, X. W. Liu, L. Y. Liu, W. X. Chang, J. Li, Eur. J. Org. Chem. 2010, 5951.
[28]H. Yang, R. G. Carter, Synlett 2010, 19, 2827.
[29]C. E. Hoyle, T. Y. Lee, T. Roper J. Polym. Sci. Part A: Polym. Chem. 2004, 42, 5301.
[30]A. Zamboulis, N. Moitra, J. J. E. Moreau, X. Cattoen, M. W. C. Man, J. Mater. Chem. 2010, 20, 9322.
[31]A. Zamboulis, N. J. Rahier, M. Gehringer, X. Cattoen, G. Niel, C. Bied, J. J. E. Moreau, M. W. C. Man, Tetrahedron: Asymmetry 2009, 20, 2880.
[32]E. A. Prasetyanto, S. M. Jeong, S. E. Park, Top Catal 2010, 53, 192.
[33]S. E. Park, E. A. Prasetyanto, Top Catal 2009, 52, 91.
[34]Q. Chen, C. Xin, L. L. Lou, K. Yu, F. Ding, S. Liu, Catal. Lett. 2011, 141, 1378.
[35]E. G. Doyaguez, F. Calderon, F. Sanchez, A. Fernandez-Mayoralas, J. Org. Chem 2007, 72, 9353.
[36]J. Gao, J. Liu, D. Jiang, B. Xiao, Q. Yang, Journal of Molecular Catalysis A: Chemical 2009, 313, 79.
[37]Amalia Monge-Marcet, Xavier Cattoen, Diego A. Alonso, Carmen Najera, Michel Wong Chi Manb and Roser Pleixats, Green Chem. 2012, 14, 1601.
[38]J. Agarwal, R. K. Peddinti, J. Org. Chem. 2011, 76, 3502.
[39]陳志昌，國立台灣大學化學碩士論文，2004。
[40]A. Prange, N. Kuhlsen, B. Birzele, I. Arzberger, J. Hormes, S. Antes, P. Kohler, Eur. Food. Res. Technol. 2001, 212, 570.
[41]J. Cuif, Y. Dauphin, J. Doucet, M. Salome, J.Susini, Geochimica et Cosmochimica Acta 2003, 67, 75.
[42]G. Sarret, J. Connan, M. Kasrai, G. M. Bancroft, A. Charrie-Duhaut, S. Lemoine, P. Adam, P. Albrecht, L. Eybert-Berard, Geochimica et Cosmochimica Acta 1999, 63, 3767.
[43]C. M. Yang, B. Zibrowius, W. Schmidt, F. Schuth, Chem. Mater. 2004, 16, 2918.
[44]R. J. P. Corriu, A Mehdi, C. Reye, C. Thieuleux, Chem. Mater. 2004, 16, 159.
[45]A. Sakthivel, J. Zhao, G. Raudaschl-Sieber, M. Hanzlik, A. S.T. Chiang, F. E. Kuhn, Applied Catalysis A: General 2005, 281, 267.
[46]鍾欣潔，國立台灣大學化學碩士論文，2008。
[47]Z. Jiang, H. Yang, X. Han, J. Luo, M. W.Wong, Y. Lu, Org. Biomol. Chem. 2010, 8, 1368.
[48]J. G. Hernandez, E. Juaristi, Tetrahedron 2011, 67, 6953.