請用此 Handle URI 來引用此文件：
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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 梁文傑 | zh_TW |
| dc.contributor.advisor | Man-kit Leung | en |
| dc.contributor.author | 薛仁竣 | zh_TW |
| dc.contributor.author | Jen-Chun Hsueh | en |
| dc.date.accessioned | 2023-08-08T16:49:51Z | - |
| dc.date.available | 2023-11-09 | - |
| dc.date.copyright | 2023-08-08 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-07-21 | - |
| dc.identifier.citation | 1. Schlenk, W.; Holtz, J., Über Die Einfachsten Metallorganischen Alkaliverbindungen. Ber. Dtsch. Chem. Ges. 1917, 50 (1), 262-274.
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Masters, N. F.; Widdowson, D. A., Regiocontrolled Lithiation of Arenetricarbonylchromium (0) Complexes: Meta-Substitution of Phenols and Anilines. J. Chem. Soc., Chem. Commun. 1983, (17), 955-956. 9. Mathew, T.; Papp, A. Á.; Paknia, F.; Fustero, S.; Surya Prakash, G. K., Benzodiazines: Recent Synthetic Advances. Chem. Soc. Rev. 2017, 46 (10), 3060-3094. 10. Fröhlich, T.; Reiter, C.; Ibrahim, M. M.; Beutel, J.; Hutterer, C.; Zeitträger, I.; Bahsi, H.; Leidenberger, M.; Friedrich, O.; Kappes, B.; Efferth, T.; Marschall, M.; Tsogoeva, S. B., Synthesis of Novel Hybrids of Quinazoline and Artemisinin with High Activities against Plasmodium Falciparum, Human Cytomegalovirus, and Leukemia Cells. ACS Omega 2017, 2 (6), 2422-2431. 11. Auti, P. S.; George, G.; Paul, A. T., Recent Advances in the Pharmacological Diversification of Quinazoline/Quinazolinone Hybrids. RSC Adv. 2020, 10 (68), 41353-41392. 12. 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J., Novel Synthesis of 2,4-Diarylbenzo[h] Quinazolines. J. Heterocycl. Chem. 1973, 10 (3), 405-406. 44. Berry, D. J.; Cook, J. D.; Wakefield, B. J., Polyhalogenoaromatic Compounds. Part XXIV. The Reaction of Chloropyridyl-Lithium Compounds with Nitriles as a Route to Triazanaphthalenes. J. Chem. Soc., Perkin Trans. 1 1972, (0), 2190-2192. 45. Mikshiev, V. Y.; Antonov, A. S.; Pozharskii, A. F., Tandem Synthesis of 10-Dimethylaminobenzo[h]Quinazolines from 2-Ketimino-1,8-bis(dimethylamino)naphthalenes via Nucleophilic Replacement of the Unactivated Aromatic NMe2 Group. Org. Lett. 2016, 18 (12), 2872-2875. 46. Ma, Y.; Breslin, S.; Keresztes, I.; Lobkovsky, E.; Collum, D. B., Synthesis of a 7-Azaindole by Chichibabin Cyclization: Reversible Base-Mediated Dimerization of 3-Picolines. J. Org. Chem. 2008, 73 (24), 9610-9618. 47. Mongin, F.; Schlosser, M., Regioselective Ortho-Lithiation of Chloro and Bromo Substituted Fluoroarenes. Tetrahedron Lett. 1996, 37 (36), 6551-6554. 48. Caster, K. C.; Keck, C. G.; Walls, R. D., Synthesis of Benzonorbornadienes: Regioselective Benzyne Formation. J. Org. Chem 2001, 66 (9), 2932-2936. 49. Wang, Z.; Li, H.; Peng, Z.; Wang, Z.; Wang, Y.; Lu, P., Preparation and Photophysical Properties of Quinazoline-Based Fluorophores. RSC Adv. 2020, 10 (51), 30297-30303. 50. Boldridge, D. W.; Scott, G. W., Excited Singlet State Absorption Spectra and Relaxation Kinetics of the Azanaphthalenes. Chem. Phys. 1986, 84 (12), 6790-6798. 51. Etinski, M.; Marian, C. M., A Theoretical Study of Low-Lying Singlet and Triplet Excited States of Quinazoline, Quinoxaline and Phthalazine: Insight into Triplet Formation. Phys. Chem. Chem. Phys. 2017, 19 (21), 13828-13837. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/88218 | - |
| dc.description.abstract | 喹唑啉在藥物研究上扮演相當重要的角色，在市面上有許多以喹唑啉結構所衍生的藥物用於治療多項疾病，因為此項特性，許多科學家致力於研究如何透過具經濟效益且簡易的方式合成喹唑啉衍生物。在本論文中我們提供了一鍋化合成喹唑啉衍生物的方法，主要講述以含氟苯環與二異丙基胺基鋰反應產生鄰位導向鋰化中間產物，其產生的負電荷可與兩當量的芳香腈進行連續的親核加成反應，最後以氟原子作為離去基進行芳香環親核取代反應得到2,4-雙芳香環取代的喹唑啉衍生物，此方法所使用到的起始物皆可由市面上取得，過程中並無過渡金屬催化劑使用，且簡便的一鍋化合成方式給予了合成喹唑啉衍生物的新途徑。 | zh_TW |
| dc.description.abstract | Quinazoline plays a significant role in pharmaceutical research. Numerous quinazoline-derived drugs are available in the market for treating various diseases. Due to this characteristic, many scientists are dedicated to researching cost-effective and straightforward methods for synthesizing quinazoline derivatives. In this study, we report a one-pot synthesis of quinazoline derivatives from halofluorobenzenes and nitriles. The synthesis involves the reaction of halofluorobenzenes with lithium diisopropylamide to generate a lithiated intermediate that exhibits ortho-selectivity. The resulting aryl lithium undergoes sequential nucleophilic addition with two equivalents of aryl nitriles. Finally, a nucleophilic aromatic substitution reaction occurs with fluoride as the leaving group, resulting in 2,4-diarylquinazoline derivatives. The advantages of this approach are transition metal-free, easy to operate, and all the starting materials are commercially available, providing a new method for synthesizing quinazoline derivatives. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-08-08T16:49:51Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2023-08-08T16:49:51Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 謝辭 (i)
摘要 (ii) Abstract (iii) 目錄 (iv) 圖目錄 (v) 表目錄 (vii) 化合物結構編號與命名 viii 第一章、緒論 (1) 1.1 有機鋰試劑發展史及應用 (1) 1.2 喹唑啉衍生物介紹及應用 (4) 1.3 喹唑啉衍生物方合成方法學 (6) 1.3.1 以鄰位修飾苯胺合成喹唑啉 (6) 1.3.2 以鄰位修飾芳香基鹵化物合成喹唑啉 (7) 1.3.3 以芳基脒化合物合成唑啉衍生物 (8) 1.3.4 以有機腈類合成喹唑啉衍生物 (10) 1.4 研究動機與文獻回顧 (12) 1.4.1 實驗動機 (12) 1.4.2 文獻回顧 (14) 第二章、實驗結果與討論 (17) 2.1 反應條件優化 (17) 2.2 官能基耐受性測試 (19) 2.2.1 不同官能基之含氟苯環反應測試 (19) 2.2.2 不同官能基之芳香腈反應測試 (23) 2.3 利用正丁基鋰合成喹唑啉衍生物 (24) 2.4 利用不同芳香腈合成喹唑啉衍生物 (27) 2.5 化合物之光性質分析 (31) 2.6 化合物電化學之分析 (38) 第三章、結論 (45) 第四章、實驗合成方法與步驟 (47) 4.1 實驗儀器設備及藥品 (47) 4.2 反應合成步驟 (49) 4.3 化合物鑑定數據 (55) 第五章、附錄 (69) 5.1 化合物之1H及13C核磁共振圖譜 (69) 5.2 化合物之X-RAY晶體結構與數據表 (134) 參考文獻 (171) | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 鄰位鋰化 | zh_TW |
| dc.subject | 喹唑啉 | zh_TW |
| dc.subject | 一鍋化合成 | zh_TW |
| dc.subject | 芳香族親核取代反應 | zh_TW |
| dc.subject | Nucleophilic aromatic substitution reaction | en |
| dc.subject | Ortho-lithiation | en |
| dc.subject | One-pot synthesis | en |
| dc.subject | Quinazoline | en |
| dc.title | 鹵代氟苯與腈類藉由鄰位鋰化驅動 [2+2+2] 串聯環化反應一鍋化合成2,4-雙取代喹唑啉衍生物 | zh_TW |
| dc.title | Ortho-Lithiation Driven One-Pot Synthesis of 2,4-Disubstituted Quinazolines via [2+2+2] Cascade Annulation of Halofluorobenzenes with Nitriles | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 劉緒宗;簡敦誠 | zh_TW |
| dc.contributor.oralexamcommittee | Shiuh-Tzung Liu;Tun-Cheng Chien | en |
| dc.subject.keyword | 喹唑啉,一鍋化合成,鄰位鋰化,芳香族親核取代反應, | zh_TW |
| dc.subject.keyword | Quinazoline,One-pot synthesis,Ortho-lithiation,Nucleophilic aromatic substitution reaction, | en |
| dc.relation.page | 175 | - |
| dc.identifier.doi | 10.6342/NTU202301835 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2023-07-24 | - |
| dc.contributor.author-college | 理學院 | - |
| dc.contributor.author-dept | 化學系 | - |
| 顯示於系所單位： | 化學系 | |
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