O-Tosyl Amidoximes及Aryl Oxadiazolones與 3-Dimethylaminopropenones經由[3 + 2]環加成反應得到 2,4-Disubstituted Imidazoles之合成研究

Synthetic Studies of the 2,4-Disubstituted Imidazoles via [3 + 2] Cycloaddition Reaction of O-Tosyl Amidoximes and Aryl Oxadiazolones with 3-Dimethylaminopropenones

林子期(Lin Tzu-Chi)

指導教授 ： 簡敦誠

國立臺灣師範大學/理學院/化學系/碩士(2020年)

https://doi.org/10.6345/NTNU202000042

摘要

研究O-tosyl alkyl amidoximes與3-dimethylaminopropenone derivatives於適當金屬鹽條件下進行[3+2]環加成反應。O-tosyl alkyl amidoximes 可以由alkyl nitriles與hydroxylamine進行親核加成反應得到alkyl amidoximes，而alkyl amidoximes接著與TsCl進行O-tosylation得到。同時，3-dimethylaminopropenones可以由methyl ketones與N,N-dimethylforamide-dimethylacetal (DMF-DMA)進行反應得到。不幸地，O-tosyl aryl amidoximes不能以相同步驟被製備。找尋另一替代方式，發現oxadiazolones可以進行[3+2]環加成反應，而其可以由aryl oximes與carbonylimidazole (CDI)進行兩次親核加成與消去反應所製備。我們的研究顯示出以O-tosyl alkyl amidoximes及aryl oxadiazolones作為反應物，與3-dimethylaminopropenones進行[3+2]環加成反應，可以作為一新穎的方式得到4-acyl-2-substituted imidazoles。

關鍵字

金屬鹽 ； [3+2]環加成反應 ； 咪唑(Imidazole)

並列摘要

A systematic screening of metal ion catalysts for the [3+2] cycloaddition of O-tosyl alkyl amidoximes with 3-dimethylaminopropenone derivatives was studied. O-Tosyl alkyl amidoximes can be obtained by nucleophilic addition of hydroxylamine to alkyl nitriles followed by tosylation with TsCl. Meanwhile, 3-dimethylaminopropenones were obtained from the reaction of methyl ketones with N,N-dimethylformamide-dimethylacetal. Unfortunately, O-tosyl aryl amidoximes cannot be obtained by the same process. Alternatively, aryl oxadiazolones were obtained by nucleophilic addition and elimination of aryl oximes to carbonyldiimidazole. Our investigation showed that iron(III)-catalyzed [3+2] cycloaddition of O-tosyl alkyl amidoximes and aryl oxadiazolones with 3-dimethylaminopropenones can serve as a novel approach toward 4-acyl-2-substituted imidazoles.

並列關鍵字

O-tosyl alkyl amidoxime ； aryl oxadiazolone ； 3-dimethylaminopropenone ； imidazole ； iron(III)-catalyzed [3+2] cycloaddition

參考文獻

[1]. M. R. Grimmett Imidazole and benzimidazole synthesis; Academic press, 1997.

[2]. R. Sivek; Pytela, O.; Bureš, F. J. Heterocycl. Chem. 2008, 45, 1621.

[3]. S. Kamijo; Yamamoto, Y. Chem Asian J 2007, 2, 568.

[4]. A. D. Palkowitz; Steinberg, M. I.; Thrasher, K. J.; Reel, J. K.; Hauser, K. L.; Zimmerman, K. M.; Wiest, S. A.; Whitesitt, C. A.; Simon, R. L. J. Med. Chem. 1994, 37, 4508.

[5]. L. Labanauskas; Brukštus, A.; Gaidelis, P.; Buchinskaite, V.; Udrenaite, E.; Daukšas, V. Pharm. Chem. J. 2000, 34, 353.