无金属催化合成3,3-二氟-2-氧化吲哚衍生物

doi:10.11944/j.issn.1000-0518.2016.11.160035

摘要/Abstract

摘要：

发展了一种合成3,3-二氟-2-氧化吲哚及其衍生物的新方法。以简单的芳香胺和溴二氟乙酸乙酯为起始原料,在无溶剂和N₂气保护下搅拌5 h,得到含二氟的氮乙酰苯胺衍生物中间体,产率85%~93%。该中间体与碘甲烷反应,得到N-甲基保护的乙酰苯胺衍生物,产率75%~90%。该衍生物在3.0化学计量促进剂次硫酸氢钠甲醛的存在下,以N,N-二甲基甲酰胺/H₂O为溶剂,发生分子内自由基关环反应,得到3,3-二氟-2-氧化吲哚及其衍生物,产率53%~72%。该方法原料便宜,不使用任何金属化合物,最后一步以水相为溶剂,较为环保,具有潜在的工业应用价值。

关键词: 乙酰苯胺, 次硫酸氢钠甲醛, 二氟氧化吲哚, 无金属催化

Abstract:

A novel method for the synthesis of 3,3-difluoro-2-oxindoles was developed. 2-Bromo-2,2-difluoro-N-phenylacetamide was prepared from neat simple aromatic amines with ethyl bromodifluoroacetate. Reflux of the product in CH₃CN with CH₃I for 24 h gave 2-bromo-2,2-difluoro-N-methyl-N-phenylacetamide in 75%~90% yields. In the presence of 3.0 chemometric number sodium formaldehyde sulfoxylate, this key intermediate undergoes intramolecular radical cyclization in aqueous solution(N,N-dimethylformamide/H₂O) and affords the final product 3,3-difluoro-1-methylindolin-2-ones in 53%~72% yields. This method can be performed in aqueous solution from commercially available and affordable starting materials without any metal catalysts. It shows potential in industrial production of 3,3-difluoro-2-oxindoles.

Key words: acetanilide, sodium formaldehyde sulfoxylate, difluoro-methylindolin-one, metal-free

买文鹏, 杨柳, 吕名秀, 王延伟, 曹毅, 卢奎. 无金属催化合成3,3-二氟-2-氧化吲哚衍生物[J]. 应用化学, 2016, 33(11): 1279-1283.

MAI Wenpeng, YANG Liu, LYU Mingxiu, WANG Yanwei, CAO Yi, LU Kui. Metal-Free Synthesis of 3,3-Difluoro-2-Oxindoles[J]. Chinese Journal of Applied Chemistry, 2016, 33(11): 1279-1283.

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