研究生: |
柯勝凱 Shengkai Ko |
---|---|
論文名稱: |
改良性合成具生物活性雜環分子 The improvement in the synthesis of bioactive heterocyclic molecules |
指導教授: |
姚清發
Yao, Ching-Fa 李文山 Lee, Whe-Shan |
學位類別: |
博士 Doctor |
系所名稱: |
化學系 Department of Chemistry |
論文出版年: | 2008 |
畢業學年度: | 96 |
語文別: | 英文 |
論文頁數: | 338 |
中文關鍵詞: | 雜環 、吲朵 、麥可加成 、一鍋反應 、縮合反應 、綠色化學 |
論文種類: | 學術論文 |
相關次數: | 點閱:162 下載:0 |
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Part one
六硝酸根二銨鈰 (CAN: cerium ammonium nitrate) 或碘分子可以分別在使用二甲基亞碸 (dimethyl sulfoxide) 與水 (五比一的比例) 的混合溶劑或在使用乙醚為溶劑的條件下用來催化吲哚 (indole) 或 1-甲基吲哚 (1-methylindole) 進行加成反應後而加成到, -未飽和酮或醛上。加入過量的吲哚或1-甲基吲哚可以產生中等至高產率的產物三吲哚取代產物,此結果和大部分文獻的報導略有差異。 有關上述結果,我們提出的解釋認為反應先進行麥可加成 (Michael addition or 1,4-addition) 得到中間產物,之後中間產物再繼續與過量的吲哚反應進行1,2-addition而產生最終產物-三吲哚取代的加成化合物。
Part Two
此部分報導在使用Amberlyst-15當催化劑的條件下,-萘酚可以和醛類進行一鍋化 (one-pot) 的縮合反應而生成14-substituted-14H-dibenzo[a, j]xanthenes。因反應過程中使用了便宜又市面上容易購買且對環境無害又可以重複使用的Amberlyst-15當催化劑,使得此反應具備了下面的優點:反應條件溫和且迅速、高產率、以及反應步驟非常簡單等特色。
Part Three
此部分我們報導在使用了六硝酸根二銨鈰(CAN)為催化劑的條件下,在室溫下進行一鍋到底的方式來合成polyhydroquinoline的方法,此反應除了產率極高以外同時也具備了便利及效率的特色。反應是在以CAN為催化劑的條件下將醛類、1,3-環己二酮、乙醯基乙酸乙酯以及醋酸銨等四種反應物混合後進行Hantzsch類型的縮合反應後而生成產物。此反應的特色是反應過程簡單且對環境比較無害,而且催化劑屬於便宜、可以直接購買得到的試劑。
Part Four
本部分的目的在報導從綠色化學的觀點來合成 1,4-dihydropyridine 的各種衍生物,此反應的優點包括如:屬於簡單的合成步驟、產物容易分離及純化,更重要的是在強調環保意識的時代,因不使用催化劑及不使用溶劑及的條件下來合成此類化合物,而得以減少對環境所造成的不利影響。
Part one
CAN (cerium ammonium nitrate) and iodine can catalyze the reactions of indole or 1-methylindole with ,-unsaturated ketone or aldehyde in DMSO/H2O (5 : 1) or ether solution at room temperature to obtain moderate to high yields of different products. The result was proposed to proceed through the 1,4-addition first to obtain intermedium and then intermedium can react with excess indole continuously to undergo the 1,2-addition to generate final triindolyl compounds.
Part Two
A one-pot condensation of -naphthol with aldehydes in the presence of Amberlyst-15 to synthesize 14-substituted-14H-dibenzo[a, j]xanthenes under solvent-free condition is reported. The advantages such as shorter reaction times, milder conditions, simplicity of the reaction, good product yields, and the easy procedures involved in the reaction makes the inexpensive and commercially available Amberlyst-15 to be a powerful catalyst for the synthesis of different organic compound.
Part Three
A facile and efficient one-pot synthesis of high yields of polyhydroquinoline derivatives at ambient temperature using Ceric Ammonium Nitrate (CAN) as catalyst was reported. This reaction is a four-component condensation of aldehyde with 1,3-cyclohexanedione, ethyl acetoacetate, and ammonium acetate in the presence of CAN to synthesize Hantzsch reaction products. The process is simple and environmentally benign and the catalyst is commercially available and inexpensive.
Part Four
A variety of the Hantzsch reaction products, i.e., 4-substituted-1,4-dihydropyridine derivatives, are efficiently synthesized with excellent yields under neat condition. The condensation reaction includes several advantages such as simple reaction procedures, environmental benign, eco-friendly, and the products are easily isolated and purified.
1.Sundberg, R.J. The Chemistry of Indoles; Academic Press: New York, 1970.
2.(a) Bergman, J.; Hoegberg, S.; Lindstroem, J. Tetrahedron 1970, 26, 3347. (b) Banerjee, A.; Mukhopadhyay, A. K. Indian J. Chem. 1982, 21B, 239.(c) Chen, D.; Yu, L.; Wang, P. G. Tetrahedron Lett. 1996, 37, 4467. (d) Denis, J.; Mauger, H. Vallee, Y. Tetrahedron Lett. 1997, 38, 8518. (e) Babu, G.; Sridhar, N.; Perumal, P. T. Synth. Commun. 2000, 30, 1609. (f) Chalaye-Mauger, H.; Denis, J. Averbuch-Pouchot, M.; Vallee, Y. Tetrahedron 2000, 56, 791. (g) Yadav, J. S.; Readdy, B. V. S.; Murthy, Ch. V. S. R.; Kumar, M.; Madan, Ch. Synthesis 2001, 783. (h) Chakrabarty, M.; Ghosh, N.; Basak, R.; Harigaya, Y. Tetrahedron Lett. 2002, 43, 4075. (i) Bandgar, B. P.; Shaikh, K. A. Tetrahedron Lett. 2003, 44, 1959. (j) Yadav, J. S.; Reddy, B. V. S.; Sunitha S. Adv. Synth. Catal. 2003, 349. (k) Ji, S.-J.; Zhou, M.-F.; Gu, D.-G.; Wang, S.-Y.; Loh, T.-P. Synlett. 2003, 2077. (l) Ji, S.-J.; Zhou, M.-F.; Gu, D.-G.; Wang, S.-Y.; Loh, T.-P. Eur. J. Org. Chem. 2004, 1584. (m) Bartoli, G.; Bosco, M.; Foglia, G.; Giuliani, A.; Marcantoni, E.; Sambri, L. Synthesis 2004, 6, 895. (n) Mi, X.; Luo, S.; He, J.; Cheng, J.-P. Tetrahedron Lett. 2004, 45, 4567. (o) Sharma, G. V. M.; Reddy, J. J.; Lakshmi, P. S.; Krishna, P. R. Tetrahedron Lett. 2004, 45, 7729. (p) Wang, L.; Han, J.; Tian, H. Sheng, J.; Fan, Z.; Tang, X. Synlett. 2005, 337. (q) Deb, M. L.; Bhuyan, P. J. Tetrahedron Lett. 2006, 47, 1441.
3.(a) Noland, W. E.; Hartman, P. J. J. Chem. Soc. 1954, 76, 3227. (b) Noland, W. E.; Christensen, G. M.; Sauer, G. L.; Dutton, G. G. S. J. Chem. Soc. 1955, 77, 456. (c) Lloyd, D. H.; Nichols, D. E. J. Org. Chem. 1986, 51, 4294. (d) Chakrabarty, M.; Basak, R.; Ghosh, N. Tetrahedron Lett. 2001, 41, 3913. (e) Komoto. I.; Kobayashi, S. Org. Lett. 2002, 4, 1115. (f) Chakrabarty, M.; Basak, R.; Ghosh, N.; Harigaya, Y. Tetrahedron 2004, 60, 1941.
4.(a) Yadav, J. S.; Abraham, S.; Reddy, B. V. S.; Sabitha, G. Synthesis 2001, 2165. (b) Ji, S.-J. Synlett. 2003, 2074. (c) Wang, S.-Y.; Ji, S.-J.; Loh, T.-P. Synlett. 2003, 2377. (d) Alam, M. M.; Varala, R.; Adapa, S. R. Tetrahedron Lett. 2003, 44, 5115. (e) Srivastava, N.; Banik, B. K.; J. Org. Chem. 2003, 68, 2109. (f) Arcadi, A.; Bianchi, G.; Chiarini, M.; D’ Anniballe, G.; Marinelli, F. Synlett. 2004, 944. (g) Banik, B. K.; Fernandez, M.; Alvarez, C. Tetrahedron Lett. 2005, 46, 2479. (h) Bartoli, G.; Bartolacci, M.; Bosco, M.; Foglia, G.; Giuliani, A.; Marcantoni, E.; Sambri, L.; Torregiani, E. J. Org. Chem. 2003, 68, 4594. (i) Yadav, J. S.; Reddy, B. V. S.; Baishya, G.; Reddy, K. V.; Narsaiah, A. V. Tetrahedron 2005, 61, 9541. (j) Kantam, M. L.; Laha, S.; Yadav, J.; Choudary, B. M.; Sreedhar, B. Adv. Synth. Catal. 2006, 348, 867.
5.(a)Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Umani-Ronchi, A. J. Org. Chem. 2002, 67, 5386. (b) Bandini, M.; Fagioli, M.; Melloni, A.; Umani-Ronchi, A. Adv. Synth. Catal. 2004, 573. (c) Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Umani-Ronchi, A. Angew. Chem. Int. Ed. 2004, 43, 84.
6.(a) Harrington, P.; Keer, M. A. Can. J. Chem. 1998, 76, 1256. (b) Shi, M.; Cui, S.-C.; Li, Q.-J. Tetrahedron 2004, 60, 6679. (c) Gibbs, T. J. K.; Tomkinson, N. C. O. Org. Biomol. Chem. 2005, 3, 4043. (d) Nair, V.; Vidya, N.; Abhilash, K. G. Tetrahedron Lett. 2006, 47, 2871.
7.(a) Hwu, J. R.; King, K. Y. Curr. Sci. 2001, 81, 1043. (b) Nair, V.; Panicker, S. B.; Nair, L. G.; George, T. G.; Augustine, A. Synlett. 2003, 156. (c) Sommermann, T. Synlett. 2003, 834.
8.(a) Kim, K. M.; Ryu, E. K. Tetrahedron Lett. 1996, 37, 1441. (b) Firouzabadi, H.; Iranpoor, N.; Hazarkhani, H. J. Org. Chem. 2001, 66, 7527. (c) Ramalinga, K.; Vijayalakshmi, P.; Kaimal, T. N. B. Tetrahedron Lett. 2002, 43, 879. (d) Firouzabadi, H.; Iranpoor, N.; Sobhani, S. Tetrahedron Lett. 2002, 43, 3653. (e) Yadav, J. S.; Reddy, B. V. S.; Reddy, M. S.; Prasad, A. R. Tetrahedron Lett. 2002, 43, 9703. (f) Das, B.; Banerjee, J.; Ramu, R.; Pal, R.; Ravindranath, N.; Ramesh, C. Tetrahedron Lett. 2003, 44, 5465. (g) Saeeng, R.; Sirion, U.; Sahakitpichan, P.; Isobe, M. Tetrahedron Lett. 2003, 44, 6211. (h) Ji, S.-J.; Wang, S.-Y.; Zhang, Y.; Loh, T.-P. Tetrahedron 2004, 60, 2051. (i) Yadav, J. S.; Reddy, B. V. S.; Shubashree, S.; Sadashiv, K. Tetrahedron Lett. 2004, 45, 2951. (j) Phukan, P. J. Org. Chem. 2004, 69, 4005. (k) Phukan, P. Tetrahedron Lett. 2004, 45, 4785. (l) Sun, J.; Dong, Y; Wang, X.; Wang, S.; Hu, Y. J. Org. Chem. 2004, 69, 8932. (m) Bhosale, R. S.; Bhosale, S. V.; Bhosale, S. V.; Wang, T.; Zubaidha, P. K. Tetrahedron Lett. 2004, 45, 9111. (n) Ke, B.; Qin, Y.; He, Q.; Huang, Z.; Wang, F. Tetrahedron Lett. 2005, 46, 1751. (o) Chu, C.-M.; Gao, S.; Sastry, M. N. V.; Yao, C.-F. Tetrahedron Lett. 2005, 46, 4971. (p) Ko, S.; Sastry, M. N. V.; Lin, C.; Yao, C.-F. Tetrahedron Lett. 2005, 46, 5771. (q) More, S. V.; Sastry, M. N. V.; Wang, C.-C.; Yao, C.-F. Tetrahedron Lett. 2005, 46, 6345. (r) 張占輝; 劉慶彬 化學進展(Progress in Chemistry) 2006, 18, 270.
9.(a) Brown, H. C.; Ham, G. J. Am. Chem. Soc. 1956, 78, 2735. (b) Brown, H. C.; Ichikawa, K. Tetrahedron 1957, 221. (c) Schneider, H.-J.; Thomas, F. J. Am. Chem. Soc. 1980, 102, 1424. (d) Carey, F. A.; Sundberg, R. J. Avanced Organic Chemistry, Part A: Structure and Mechanisms, 4th ed.; Kluwer Academic/Plenum Publishers, New York, 2000, pp171.
11.Lambert, R. W.; Martin, J. A.; Merrett, J. H.; Parkes K. E. B.; Thomas, G. J. Chem. Abstr., 1997, 126, p212377y, PCT Int. Appl. WO 9706178, 1997.
12.Hideo, T. Chem. Abstr., 1981, 95, 80922b, Jpn. Tokkyo Koho JP 56005480, 1981.
13.Poupelin, J. P.; Saint- Rut, G.; Foussard-Blanpin, O.; Narcisse, G.; Uchida-Ernouf, G.; Lacroix, R. Eur. J. Med. Chem., 1978, 13, 67.
14.(a) Banerjee A.; Mukherjee, A. K. Stain Technol., 1981, 56, 83. (b) Menchen, S. M.; Benson, S. C.; Lam, J. Y. L.; Zhan, W.; Sun, D.; Rosenblum, B. B.; Khan, S. H.; Ting, M. U. S. Patent, US 6583168, 2003. (c) Jiao, G.-S.; Castro, J. C.; Thoresen, L. H.; Burgess, K. Org. Lett. 2003, 5, 3675.
15.(a) Sirkeeioglu, O.; Talinli, N.; Akar, A. J. Chem. Res. (S), 1995, 502. (b) Ahmad, M.; King, T. A.; Ko, Do-K.; Cha B. H.; Lee, J. J. Phys. D: Appl. Phys., 2002, 35, 1473.
16.Knight, C. G.; Stephens, T. Biochem. J., 1989, 258, 683.
17.Ion, R. M.; Sirkecioglu, O.; Talinli, N.; The spectroscopy and associated photodynamic derivatives, The third INTERNET conference on Photobiology.
18.(a) Iron, R. M. Progr. Catal. 1997, 2, 55. (b) Iron, R. M.; Frackowiak, D.; Plannar, A.; Wiktorowicz, K. Acta Biochim, Pol. 1998, 45, 833.
19.Papini P; Cimmarusti, R. Gazz. Chim. Ital., 1947, 77, 142.
20.Sen, R. N.; Sarkar, N. J. Am. Chem. Soc., 1925, 47, 1079.
21.Allen, J. A. V.; Giannini, D., D.; Whitesides, T. H. J. Org. Chem., 1982, 47, 820.
22.Khosropour, A. R.; Khodaei, M. M.; Moghannian, H. Synlett, 2005, 955.
23.Rajitha, B.; Kumar, B. S.; Reddy, Y. T.; Reddy, P. N.; Sreenivasulu, N. Tetrahedron Lett., 2005, 46, 8691.
24.Das, B.; Ravikanth, B.; Ramu, R.; Laxminarayana, K.; Rao, B. V. J. Mol. Catal. A: Chemical 2006, 255, 74.
25.Sarma, R. J.; Baruah, J. B. Dyes and Pigments 2005, 64,91.
26.(a) Ballini R.; Petrini, M. J. Chem. Soc., Perkin Trans. 1, 1988, 2563. (b) Ramesh, C.; Banerjee, J.R.; Pal, B. Das, Adv. Synth. Catal., 2002, 345, 557. (c) Yu, W.; Hidajat, K.; Ray, A. K. Appl. Catal. A:General, 2004, 260, 191. (d) Feng, X. -L.; Guan, C. -J.; Zhao, C.-X. Syn. Comm., 2004, 34, 487. (e) Farhanullah; Sharon, A.; Maulik, P.; Ram, V. J. Tetrahedron Lett., 2004, 45, 5099. (f) Ke, B.; Qin, Y.; He, Q.; Huang, Z.; Wang, F. Tetrahedron Lett., 2005, 46, 1751. (g) Solladie-Cavallo, A.; Lupattelli, P.; Bonini, C. J. Org. Chem, 2005, 70, 1605. (h) Das, B.; Thirupathi, P.; Mahender, I.; Reddy, V. S.; Rao, Y. K. J. Mol. Catal. A: Chemical 2006, 255, 233.
27.(a) Rashidi-Ranjbar, P.; Mohajeri, A.; Mahmoudkhani, A. H. J. Phys. Org, 2001, 14,210. (b) Khoramabadi-zad, A.; Kazemi, Z.; Rudbari, H. A. J. Kor. Chem. Soc., 2002, 46, 541.
28.Mauzeral, D.; Westheimer, F. H. J. Am. Chem. Soc. 1955, 77, 2261. (b) Baraldi, P. G.; Chiarini, A.; Budriesi, R.; Roberti, M.; Casolar, A.; Manfredini, S.;. Simoni, D.; Zanirato, V.; Varani, K.; Borea, P. A. Drug Des. Deliv. 1989, 5, 13. (c) Baraldi, P. G.; Budriesi, R.; Cacciari, B.; Chiarini, A.; Garuti, L.; Giovanninetti, G.; Leoni A.; Roberti, M. Collect. Czech. Chem. Commun. 1992, 169. (d) Stilo, A. Di; Visentin, S.; Clara, C.; Gasco, A. M.; Ermondi, G.; Gasco, A. J. Med. Chem. 1998, 41, 5393. (e) Kawase, A. Shah, H. Gaveriya, N.Motohashi, H. Sakagami, M.; Varga, A.; Molnar, J. J. Bioorg. Chem. 2002, 10, 1051. (f) Suarez, M.; Verdecia, Y.; Illescas, B.; Martinez-Alvarez, R.; Avarez, A.; Ochoa, E.; Seoane, C.; Kayali, N.; Martin, N. Tetrahedron 2003, 59, 9179. (g) Shan, R.; Velazquez, C.; Knaus, E. E. J. Med. Chem. 2004, 47, 254. (h) Sawada, Y.; Kayakiri, H.; Abe, Y.; Mizutani, T.; Inamura, N.; Asano, M.; Hatori, C.; Arsmori, I.; Oku, T.; Tanaka, H. J. Med. Chem. 2004, 47, 2853.
29.(a) Tsuruo, T.; Iida, H.; Nojiri, M.; Tsukagoshi, S.; Sakurai, Y. Cancer Res. 1983, 43, 2905. (b) Chapman, R. W.; Danko, G.; Siegels, M. I. Pharmacology 1984, 29, 282. (c) Malaise, W. J.; Msthias, P. C. F. Diabetologia 1985, 28, 153. (d) Reid, J. L.; Meredith, P. A.; Pasanisi, F. J. Cardiovasc. Pharmacol. 1985, S18, 7. (e) Buhler, F. R.; Kiowski, W. J. J. Hypertens. 1987, S3, 5. (f) Krauze, A.; Germance, S.; Sturms, O. Eberlinsm I.; Klusa, V.; Duburs, G. Eur. J. Med. Chem. 1999, 34, 301. (g) Peri, R.; Padmanabhan, S.; Singh, S.; Rutledge, A.; Triggle, D. J. J. Med. Chem. 2000, 43, 2906.
30.(a) Bretzel, R. G.; Bollen, C. C.; Maeser, E.; Federlin, K. F. Drugs Fut. 1992, 17, 465. (b) Bretzel, R. G.; Bollen, C. C.; Maeser, E.; Federlin, K. F. Am. J. Kidney. Dis. 1993, 21, 53. (c) Klusa, V. Drugs Fut. 1995, 20, 135. (d) Boer, R.; Gekeler, V. Drugs Fut. 1995, 20, 499.
31.(a) Hantzsch, A. Ber. Dtsch. Chem. Ges. 1888, 21, 942. (b) Hantzsch, A. Ber. Dtsch. Chem. Ges. 1890, 23, 1747.
32.(a) Khadikar, B. M.; Gaikar, V. G.; Chitnavis, A. A. Tetrahedron Lett. 1995, 36, 8083. (b) Ohberg, L.; Westman, J. Synlett 2001, 1296. (c) Agarwal, A. ; Chauhan, P. M. S. Tetrahedron Lett. 2005, 46, 1345.
33.Sabitha, G.; Reddy, G. S. K. K.; Reddy, Ch. S.; Yadav, J. S. Tetrahedron Lett. 2003, 44, 4129.
34.Wang, L.-M.; Sheng, J.; Zhang, L.; Han, J.-W.; Fan, Z.; Tian, H.; Qian, C. -T. Tetrahedron 2005, 61, 1539.
35.Ko, S.; Sastry, M. N. V.; Lin, C.; Yao, C.-F. Tetrahedron Lett. 2005, 46, 5771.
36.Sharma, G. V. M.; Reddy, K. L.; Lakshmi, P. S.; Krishna, P. R. Synthesis 2006, 55.
37.Ko, S.; Yao, C.-F. Tetrahedron 2006, 62, 7293.
38.(a) Ji, S.-J.; Jiang, Z.-Q.; Lu, J.; Loh, T.-P. Synlett 2004, 831. (b) Sridhar, R.; Perumal, P. T. Tetrahedron 2005, 61, 2465.
39.(a) Phillips, A. P. J. Am. Chem. Soc. 1949, 71, 4003. (b) Anderson, G. J. R; Berkelhammer, G. J. Am. Chem. Soc. 1958, 80, 992. (c) Singh, H.; Chimni, D. S. S.; Kumar, S. Tetrahedron 1995, 51, 12775. (d) M. F. Gordeev, D. V. Patel and E. M. Gordon, J. Org. Chem., 1996, 61, 924. (e) J. G. Breitenbucher and G. Figliozzi, Tetrahedron Lett., 2000, 41, 4311. (f) J.-C. Liang, J.-L. Yeh, C.-S. Wang, S.-F. Liou, C.-H. Tasi and I.-J. Chen, Bioorg. Med. Chem., 2002, 10, 719. (g) R. Miri, H. Niknahad, Gh. Vesal and A. Shafiee, IL Farmaco, 2002, 57, 123. (h) A. Dondoni, A. Massi, E. Minghini, S. Sabbatini and V. Bertoasi, J. Org. Chem., 2003, 68, 6172. (i) A. Dondoni, A. Massi, E. Minghini and V. Bertoasi, Tetrahedron, 2004, 60, 2311. (j) N. Tewari, N. Dwivedi and R. P. Tripathi, Tetrahedron Lett., 2004, 45, 9011. (k) M. A. Zolfigol and M. Safaiee, Synlett, 2004, 827. (l) J. D. Moseley, Tetrahedron Lett., 2005, 46, 3179.
40.(a) More, S. V.; Sastry, M. N. V.; Yao, C.-F. Green Chem. 2006, 8, 91. (b) Ko, S.; Yao, C.-F. Tetrahedron Lett. 2006, 47, 8827.
41.(a) Wang, G.-W; Miao, C.-B.Green Chem. 2006, 8, 1080. (b) Kumar, S.; Sharma, P.; Kapoor, K. K.; Hundal, M. S. Tetrahodron 2008, 64, 536.
42.Y. Zhao, J. Zhao, Y. Zhou, Z. Lei, L. Li and H. Zhang, New J. Chem, 2005, 29, 769.
43.M. Litvic’, M. Filipan, I. Pogorelic’ and I. Cepanec, Green Chem., 2005, 771.
44.Sainani, J. B.; Shah, A. C.; Arya, V. P. Indian J. Chem. Sect. B., 1994, 33, 526.