藉由 Suzuki 反應一步合成 Benzoxanthene anhydride 及其衍生物

One-pot synthesis of Benzoxanthene anhydride and its derivatives via suzuki reaction

賴姵穎(Pei-Ying Lai)

指導教授 ： 施增廉

淡江大學/理學院/化學學系碩士班/碩士(2013年)

https://doi.org/10.6846/TKU.2013.00154

摘要

1,8-naphthalimide類化合物及及衍生物都具有強烈螢光的特性。其中一衍生物 Benzoxanthene anhydride為本論文主要研究對重點。利用在結構上多苯環的平面性及共軛系統，使其具有優良的光化學穩定性、耐熱性，可用來作為新型的螢光染料、螢光標識劑，或是增加對 DNA 嵌入能力而作為新的抗腫瘤藥物。
近年來，許多科學家致力研究新穎的合成方式來合成 Benzoxanthene anhydride，但合成的報導並不多。其中一個是利用 4-bromo-1,8-naphthalic 為起始物，經由三步合成所需的目標物，但總產率並不理想，或是需要用到工業上不適用的二甲基甲醯胺(毒化物) 為溶劑，針對這些條件，我們尋找提升總產率及環境安全的合成途徑
有別於以往的文獻，我們改以 Acenaphthene 為起始物，經由鹵化、氧化後得到 4,5-dibromo-1,8-naphthalic。再利用 Suzuki 反應，成功的合成出目標物，並縮短合成步驟為一步反應，且提高總產率。

關鍵字

鈴木反應

並列摘要

Naphthalimides and their derivatives have been extensively investigated in recent years. Benzoxanthene anhydride, the most important derivative of naphthalimides, has been commonly used as fluorescent markers, anticancer drug and fluorescent dye owing to its large planar aromatic scaffold, conjugated system, high photo stability, large stroke shift and dual fluorescence properties.
Researchers have been devoted to discover novel synthetic method of benzoxanthene anhydride. A three-step synthesis of target molecule starting from 4-bromo-1,8-naphthalic anhydride has been reported. However, this method was not only inefficient but also required DMF (toxic) as the solvent, which is prohibited using in industry. In order to overcome this problem, we try to conduct a synthetic strategy to enhance the total yields and improve on environmental safety.
In comparison of previous report, we used acenaphthene as a starting material to synthesize 4,5-dibromo-1,8-naphthalic via bromination and oxidation. Finally, we employed Suzuki reaction to synthesize benzoxanthene anhydride. Based on this method, we can accomplish this synthesis in a one-step manner and increase the total yield.

並列關鍵字

1,8-naphthalimide ； Suzuki reaction

參考文獻

30. Mallory, F. B.; Mallory, C. W.; Butler, K. E.; Lewis, M. B.; Angell, Q. X.; Luzik, E. D.; Fredenburgh, L. E.; Ramanjulu, M. M.; Van, Q. N.; Francl, M. M.; Freed, D. A.; Wray, C. C.; Hann, C.; Nerz-Stormes, M.; Carroll, P. J.; Chirlian, L. E. J. Am. Chem. Soc. 2000, 122, 4108-4116.

18. Prickett, M. P.; Singh, G.; Vankayalapati, H. Tetrahedron Lett. 2000, 41, 2987-2990.

6. Khosravi, A.; Moradian, S.; Gharanjig, K.; Taromi, A. F. J. Chin. Chem. Soc. 2005, 52, 495-502.

9. Brana, M. F.; Sanz, A. M.; Castellano, J. M.; Roldan, M. C.; Roldan, C. Eur. J. Med. Chem. 1981, 16, 207-212.

21. Zhang, Y.; Oblak, E. Z.; Bolstad, E. S. D.; Anderson, A. C.; Jasinski, J