芳香族肼化合物為合成一些吲哚（Indole）、吡唑（Pyrazole）、β-環內酯（β-Lactam）、喹口咢啉（Quinazoline）及其一些其他雜環化合物的前驅物，這些都是已知有生物活性的物質。而芳香族伸肼基化合物可轉換成芳香族肼與胺化合物，更進一步的可以繼續做衍生合成反應。本實驗室利用芳香族溴化合物、活化鎂（1,2-二溴乙烷當活化劑）與偶氮基化合物（DEAD）進行超音波化學誘導巴比艾爾型式反應生成芳香族伸肼基化合物。
另一個研究方向，許多抗腫瘤藥物、抑制劑、螢光物質和有機發光二極體（OLED）都可以找到以1,3-苯幷硫唑為中心的架構；其衍生物在藥性和工業化學上一直是研究上重要的課題之ㄧ。本實驗室發展利用天然脯胺酸（L-Proline）催化且在微波加熱的反應條件下，2-胺基苯硫吩與醛和酸類化合物進行縮合反應，生成1,3-苯幷硫唑化合物。

Aryl hydrazides are important precursors for synthesis of a variety of heterocycles such as indoles, pyrazoles, β-lactams, quinazolines and others, they are well known to be biologically active. In addition, aryl hydrazides can be transformed to aryl hydrazines and aryl amines, which can be further applied to synthesize heterocyclic compounds. Herein, our laboratory wish to report a novel synthetic method for preparation of aryl hydrazide from arylbromide, magnesium powder, 1,2-dibromoethane and diethyl azodicarboxylate via sonochemical Barbier-type reaction.
In another part, the benzothiazole-based compounds which were the core structural moiety of antitumour agents, inhibitive agents and orangic light emitting diodes(OLED’s). Our laboratory developed a microwave-assisted method for synthesis of benzothiazoles from the direct condensation reaction of aryl- or alkyl- aldehyde or carboxylic acid with 2-aminothiophenol in the presence of L-proline as catalyst.

目錄
中文摘要................................................. I
英文摘要................................................ II
第一章 緒論.............................................. 1
1-1 伸肼基化合物的合成................................... 1
1-1-1 肼基化合物（Hydrazine）的應用...................... 2
1-1-2 伸肼基化合物的合成方法............................. 6
A. 利用有機金屬試劑進行反應合成.......................... 6
B. 利用硼酸化合物與偶氮基化合物進行反應合成.............. 7
C. 利用催化劑與偶氮基化合物進行反應合成.................. 7
D. 利用烯醇化合物與偶氮基化合物進行反應合成.............. 7
1-1-3 巴比艾爾（Barbier）型式反應........................ 8
A. 金屬活化之巴比艾爾（Barbier）型式反應................. 8
B. 超音波誘導（Sonochemistry）之巴比艾爾（Barbier）型
式反應.................................................. 12
1-2 1,3-苯幷硫唑化合物的合成............................ 20
1-2-1 1,3-苯幷硫唑化合物的重要性........................ 21
A. 在材料方面的重要性................................... 21
B. 在生物活性方面的重要性............................... 22
1-2-2 1,3-苯幷硫唑化合物的合成方法...................... 24
A. 直接縮合成環反應..................................... 24
B. Pd 催化耦合反應...................................... 29
C. 鹼性條件和CAN 促進成環反應........................... 29
D. 利用DMP 進行分子內環化反應........................... 31
1-2-3 微波促進反應合成方法.............................. 32
第二章 結果與討論....................................... 42
2-1 合成伸肼化合物之結果探討............................ 42
2-2 合成1,3-苯幷硫唑之結果探討.......................... 49
第三章 結論............................................. 62
第四章 實驗與儀器步驟................................... 64
4-1 實驗溶劑............................................ 64
4-2 實驗儀器與測試方法.................................. 65
4-3 實驗步驟............................................ 68
第五章 光譜部份......................................... 72
第六章 參考資料........................................ 119
圖表目錄
Scheme 1-1 Fischer indole synthesis........................... 2
Scheme 1-2 Pyrazole 方面的合成............................. 3
Scheme 1-3 Pyrazole 方面的合成............................. 3
Scheme 1-4 β-Lactam 方面的合成............................ 4
Scheme 1-5 Quinazoline 方面的合成.......................... 5
Scheme 1-6 利用有機鋅試劑進行反應........................ 6
Scheme 1-7 利用有機鋰或有機鎂試劑進行反應.................6
Scheme 1-8 利用硼酸化合物與偶氮基化合物進行反應...........7
Scheme 1-9 利用催化劑與偶氮基化合物進行反應.............. 7
Scheme 1-10 利用烯醇化合物與偶氮基化合物進行反應......... 7
Scheme 1-11 金屬活化之巴比艾爾型式反應................... 8
Scheme 1-12 Barbier 型式反應之反應機構..................... 8
Scheme 1-13 Single Electron Transfer process................... 9
Scheme 1-14 Rieke’s method................................ 10
Scheme 1-15 金屬轉移電子於萘............................ 10
Scheme 1-16 金屬轉移電子於蒽............................ 11
Scheme 1-17 其他還原方法................................ 11
Scheme 1-18 超音波頻率的界定............................ 12
Scheme 1-19 體表面附近氣泡的不對稱陷縮.................. 13
Scheme 1-20 超音波洗滌槽................................ 14
Scheme 1-21 探針式超音波裝置............................ 15
Scheme 1-22 應用鋰超音波巴比艾爾型式反應................ 16
Scheme 1-23 麥可加成反應................................ 16
Scheme 1-24 超音波誘導巴比艾爾型式反應製備有機錫化合物.. 17
Scheme 1-25 超音波誘導巴比艾爾型式反應製備芳香基矽化合物17
Scheme 1-26 超音波誘導巴比艾爾型式反應製備芳香基酯化合物17
Scheme 1-27 製備二級芳香基醯胺.......................... 18
Scheme 1-28 雷福馬斯基反應.............................. 18
Scheme 1-29 布雷斯反應.................................. 18
Scheme 1-30 丙烯基鋅金屬化合物.......................... 19
Scheme 1-31 超音波合成3,4-雙芳香族取代α-亞甲基五環內酯...19
Scheme 1-32 1,4-加成反應................................. 19
Scheme 1-33 Epoxy 開環形成Cyclopropylmethanol............. 19
Scheme 1-34 Benzothiazole 在材料方面的應用.................21
Scheme 1-35 Benzothiazole 在生物活性方面的應用.............22
Scheme 1-36 Benzothiazole 在生物活性方面的應用.............23
Scheme 1-37 直接縮合成環反應............................ 24
Scheme 1-38 直接縮合成環反應............................ 24
Scheme 1-39 直接縮合成環反應............................ 25
Scheme 1-40 直接縮合成環反應............................ 25
Scheme 1-41 直接縮合成環反應............................ 25
Scheme 1-42 直接縮合成環反應............................ 26
Scheme 1-43 直接縮合成環反應............................ 26
Scheme 1-44 直接縮合成環反應............................ 27
Scheme 1-45 直接縮合成環反應............................ 27
Scheme 1-46 直接縮合成環反應............................ 27
Scheme 1-47 直接縮合成環反應............................ 28
Scheme 1-48 推測直接縮合成環之反應機構.................. 28
Scheme 1-49 2-胺基苯硫吩與β-Chlorocinnamaldehydes 反應.....28
Scheme 1-50 Heck Reaction type.............................29
Scheme 1-51 Suzuki Coupling............................... 29
Scheme 1-52 鹼性條件和CAN 促進成環反應................. 30
Scheme 1-53 推測CAN 促進成環之反應機構................. 30
Scheme 1-54 利用DMP進行分子內環化反應................. 31
Scheme 1-55 推測利用DMP進行分子內環化反應之反應機構... 31
Scheme 1-56 微波頻率的界定…............................ 33
Scheme 1-57 微波之組成.................................. 34
Scheme 1-58 傳統傳導加熱示意圖.......................... 34
Scheme 1-59 微波加熱示意圖.............................. 35
Scheme 1-60 化學反應形式................................ 37
Scheme 1-61 微波加熱常用之溶劑.......................... 39
Scheme 2-1 超音波誘導巴比艾爾型式反應製備有機錫化合物... 42
Scheme 2-2 超音波誘導巴比艾爾型式反應製備有機矽化合物... 42
Scheme 2-3 製備伸肼基化合物............................. 44
Scheme 2-4 水解成聯胺化合物的鹽類....................... 47
Table 2-1. 不同偶氮化合物與反應條件之測試................ 43
Table 2-2. 終止反應步驟對產率之影響...................... 44
Table 2-3. 超音波巴比艾爾反應製備伸肼基化合物............ 46
Table 2-4. 超音波巴比艾爾反應製備伸肼基化合物............ 48
Table 2-5. 傳統與微波加熱之間L-Proline 對反應的影響........ 50
Table 2-6. L-Proline 當量數對產率的影響..................... 51
Table 2-7. 微波促進芳香族醛合成1,3-苯幷硫唑.............. 53
Table 2-8. 2-(5-bromothiophen-2-yl)benzo[d]thiazole 反應條件測試54
Table 2-9. 傳統與微波加熱之間L-Proline 對反應的影響........ 55
光譜圖目錄
diethyl 1-phenylhydrazine-1,2-dicarboxylate....................72
diethyl 1-(4-methoxyphenyl)hydrazine-1,2-dicarboxylate..........75
diethyl 1-(4-(trifluoromethyl)phenyl)hydrazine-1,2-dicarboxylate...78
diethyl 1-(3-chlorophenyl)hydrazine-1,2-dicarboxylate.........81
diethyl 1-(naphthalen-1-yl)hydrazine-1,2-dicarboxylate..........84
diethyl 1-(thiophen-2-yl)hydrazine-1,2-dicarboxylate.............87
diethyl 1-(5-chlorothiophen-2-yl)hydrazine-1,2-dicarboxylate......90
diethyl 1-(benzo[d][1,3]dioxol-5-yl)hydrazine-1,2-dicarboxylate....93
diethyl 1-(3-formylphenyl)hydrazine-1,2-dicarboxylate...........96
2-(thiophen-2-yl)benzo[d]thiazole............................99
2-(5-bromothiophen-2-yl)benzo[d]thiazole....................100
2-phenylbenzo[d]thiazole..................................101
2-(4-fluorophenyl)benzo[d]thiazole..........................102
2-(4-bromophenyl)benzo[d]thiazole..........................104
2-(4-methoxyphenyl)benzo[d]thiazole.......................106
4-(benzo[d]thiazol-2-yl)-N,N-dimethylbenzenamine.............107
2-(naphthalen-1-yl)benzo[d]thiazole.........................109
2-(pyridin-3-yl)benzo[d]thiazole.............................111
2-(pyridin-2-yl)benzo[d]thiazole............................113
2-(furan-2-yl)benzo[d]thiazole..............................114
2-(1H-pyrrol-2-yl)benzo[d]thiazole..........................115
2-heptylbenzo[d]thiazole..................................117

1 “Encyclopedia of Reagents for Organic Synthesis,” ed. by L. A. Paquette, Wiley (1995), Vol. 6, p 3979.
2 Dufresne, C.; Leblanc, Y.; Berthelette, C.; Mc Cooeye, C. Synth. Commun. 1997, 27, 3612.
3 Zaltsgendler, I.; Leblanc, Y.; Bernstein, M. W. Tetrahedron Lett. 1993, 34, 2441.
4 Quin, L. D.; Pinion, D. O. J. Org. Chem. 1970, 35, 3134.
5 Nishiyama, H.; Arai, H.; Kanai, Y.; Kawashima, H.; Itoh, K. Tetrahedron Lett. 1986, 27, 361.
6 Sharma, S. D.; Pandhi S. B.; J. Org. Chem. 1990, 55, 2196.
7 Abbotto, A.; Bradamante, S.; Facchetti, A.; Pagani, G. A. J. Org. Chem. 2002, 67, 5753.
8 Velarde-Ortiz, R.; Guijarro, A.; Rieke, R. D. Tetrahedron Lett. 1998, 39, 9157.
9 Demer, J. P.; Klaubert, D. H. Tetrahedron Lett. 1987, 28, 4933.
10 Uemura, T.; Chatani, N. J. Org. Chem. 2005, 70, 8631-8634.
11 Carlin, R. B.; Moores, M. S. J. Am. Chem. Soc. 1962, 84, 4107.
12 Yadav, J. S.; Reddy, B. V. S.; Veerendhar, G.; Srinivasa Rao, R.; Nagaiah, K. Chem. Lett. 2002, 3, 318.
13 Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. Tetrahedron, 1988, 44, 5525.
14 Blomberg, C. The Barbier Reaction and Related One-Step Processes, Spring-Verlag: New York, 1993.
15 Luche, J.-L.; Damiano, J.-C. J. Am. Chem. Soc. 1980, 102, 7926.
16 Mukaiyanna, T.; Harada, T. Chem. Lett. 1981, 1527.
17 Shono, T.; Ishifune, M.; Kashimura, K. Chem. Lett. 1990, 449.
18 Naruta, Y.; Nishigaichi, Y.; Maruyama, K. Chem. Lett. 1986, 1857.
19 Dupuy, C.; Petrier, C.; Sarandeses, L. A.; Luche, J.-L. Synth. Commun., 1991, 21, 643.
20 Molle, G.; Bauer, P. J. Am. Chem. Soc. 1982, 104, 3481.
21 Cintas, P. Activated Metals in Organic Synthesis, CRC : Boca Raton; 1993.
22 Ley, S. V.; Low, C. M. R. Ultrasound in Synthesis, Spring-Verlag: New York, 1989.
23 Luche, J.-L.; Petrier, C.; Gemal, A. L.; Zirka, N. J. Org. Chem. 1982, 47, 3805.
24 Lee, A. S.-Y.; Dai, W.-C. Tetrahedron Lett. 1996, 37, 495.
25 Lee, A. S.-Y.; Dai, W.-C. Tetrahedron, 1997, 53, 859. 120
26 Lee, A. S.-Y.; Chang, Y.-T.; Chu, S.-F.; Tsao, K.-W. Tetrahedron Lett. 2006, 47, 7058.
27 Lee, A. S.-Y.; Wu, C.-C.; Lin, L.-S.; Hsu, H.-F. Synthesis, 2004, 4, 568.
28 Einhorn, J.; Luche, J.-L. Tetrahedron Lett. 1986, 27, 501.
29 Furstner, A. Synthesis 1989, 571 and reference cited therein.
30 Lee, A. S.-Y.; Cheng R.-Y.; Pan, O.-G. Tetrahedron Lett. 1997, 38, 443.
31 Lee, A. S.-Y.; Wu, C.-W. Tetrahedron, 1999, 55, 12531.
32 Lee, A. S.-Y.; Chang, Y.-T.; Wang, S.-H.; Chu, S.-F. TetrahedronLett. 2002, 43, 8489.
33 Sarandeses, L. A.; Mourino, A.; Luche, J.-L. J. Chem. Soc. Chem. Commun. 1992, 1798.
34 Sarandeses, L. A.; Mourino, A.; Luche, J.-L. J. Chem. Soc. Chem. Commun. 1992, 798.
35 Chang, W.-C.; Hu, A. t.; Duan, J.-P.; Rayabarapu, D. K.; Cheng, C.-H. J. Organomet. Chem. 2004, 689, 4882.
36 Bénéteau, V.; Besson, T.; Guillard, J.; Léonce S.; Pfeiffer, B. Eur. J. Med. Chem. 1999, 34, 1053.
37 Malcolm F. G.; Westwell, A. D. Bioorg. Med. Chem. Lett. 2003, 13, 471.
38 Li, Y.; Wang, Y.-L.; Wang, J.-Y. Chem. Lett. 2006, 35, 460-461.
39 Kodomari, M.; Tamaru, Y.; Aoyama, T. Synth. Commun. 2004, 34, 3029.
40 Itoh, T.; Nagata, K.; Ishikawa, H.; Ohsawa, A. Heterocycles, 2004, 62, 197.
41 Ranu, B. C.; Jana, R.; Dey, S. Chem. Lett. 2004, 33, 274.
42 Hein, D. W.; Alheim, R. J.; Leavitt, J. J. J. Am. Chem. Soc. 1957, 79, 427.
43 Chakraborti, A. K.; Selvam, C.; Kaur, G.; Bhagat, S. Synlett, 2004, 851.
44 Brembilla, A.; Roizard, D.; Lochon, P. Synth. Commun. 1990, 20, 3379.
45 Chakraborti, A. K.; Rudrawar, S.; Kaur, G.; Bharma, L. Synlett, 2004, 1533.
46 Matsushita, H.; Lee, S. H.; Joung, M.; Clapham, B.; Janda, K. D. Tetrahedron Lett. 2004, 45, 313.
47 Abbotto, A.; Bradamante, S.; Facchetti, A.; Pagani G. A. J. Org. Chem. 2002, 67, 5753.
48 Paul, S.; Gupta, M.; Gupta, R. Synth. Commun. 2002, 32, 3541.
49 Alagille, D.; Baldwin, R. M.; Tamagnan, G. D. Tetrahedron Lett. 2005, 46, 1349. 121
50 Majo, V. J.; Prabhakaran, J.; Mann, J. J.; Dileep Kumar, J. S., Tetrahedron Lett. 2003, 44, 8535.
51 Tale, R. H. Org. Lett. 2002, 4, 1641.
52 Bose, D. S.; Idrees, M. J. Org. Chem. 2006, 71, 8261.
53 Hayes, B. L. Microwave Synthesis-Chemistry at the Speed of Light, CEM Publishing: U.S.A., 2002.
54 Hayes, B. L. Microwave Synthesis-Chemistry at the Speed of Light, 2002, CEM Publishing, p.35.
55 Lee, A. S.-Y.; Lin, L.-S. TetrahedronLett. 2000, 41, 8803.
56 Crawford, R. J.; Takagi, K. J. Am. Chem. Soc. 1972, 94, 7406.
57 Gillis, B. T.; Beck, P. E. J. Org. Chem. 1962, 27, 1947.
58 Evans, D. A.; Britton, T. C.; Dorow, R, L.; Dellaria, J. F. J. Am. Chem. Soc. 1986, 94, 6395.
59 Trimble, L. A.; Vederas, J. C. J. Am. Chem. Soc. 1986, 94, 6397.
60 Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F.; Tetrahedron, 1988, 44, 5525.
61 Carlin, R. B.; Moores, M. S. J. Am. Chem. Soc. 1962, 84, 4107.
62 Gedye, R.; Smith, F.; Westaway, K.; Ali, H.; Baldisera, L.; Laberge, L.; Rousell, J. Tetrahedron Lett. 1986, 27, 279.
63 Giguere, R. J.; Bray, T. L.; Duncan, S. M.; Majetich, G. Tetrahedron Lett. 1986, 27, 4945.
64 Li, Y.; Wang, Y.-L.; Wang, J.-Y. Chem. Lett. 2006, 35, 460.