利用无溶剂研磨反应制备3-取代异吲哚啉-1-酮类化合物

doi:10.3866/PKU.DXHX202008040

大学化学 >> 2021, Vol. 36 >> Issue (6): 2008040.doi: 10.3866/PKU.DXHX202008040

利用无溶剂研磨反应制备3-取代异吲哚啉-1-酮类化合物

王平安(), 姚琳, 张东旭, 聂慧芳, 李穆琼, 姜茹

空军军医大学药学系, 药物化学与药物分析学教研室, 西安 710032

收稿日期:2020-08-17 录用日期:2020-09-29 发布日期:2020-11-11
通讯作者: 王平安 E-mail:ping_an1718@outlook.com
作者简介:王平安, Email: ping_an1718@outlook.com
基金资助:
国家自然科学基金(21372259)

Synthesis of 3-Substituted Isoindolin-1-ones by Solvent-Free Grinding Reaction

Pingan Wang(), Lin Yao, Dongxu Zhang, Huifang Nie, Muqiong Li, Ru Jiang

Department of Medicinal Chemistry and Pharmaceutical Analysis, School of Pharmacy, The Air Force Medical University of PLA, Xi'an 710032, China

Received:2020-08-17 Accepted:2020-09-29 Published:2020-11-11
Contact: Pingan Wang E-mail:ping_an1718@outlook.com

摘要/Abstract

摘要：

以2-氰基芳醛和活泼亚甲基化合物（如丙二酸二甲酯、乙酰乙酸乙酯等）为原料，在无水碳酸钾催化下，通过无溶剂室温研磨反应，一步得到3-取代异吲哚啉-1-酮类化合物，产物无需柱层析。产物的结构通过核磁共振波谱和质谱解析确定。该反应具有操作步骤简单、反应时间短、适用范围广、产率高、高原子经济性等优点，是绿色有机合成反应，在新药设计与合成、天然产物合成中具有应用价值。

关键词: 2-氰基芳醛, 活泼亚甲基化合物, 3-取代异吲哚啉-1-酮, 无溶剂, 研磨反应

Abstract:

A solvent-free grinding reaction for the synthesis of 3-substituted isoindolin-1-ones from 2-cyanoarylaldehydes and various activated methylene compounds (such as dimethyl malonate and ethyl acetoacetate) has been developed. All the products were obtained without the tedious column chromatographic purification and were characterized using NMR spectroscopy and mass spectrometry. This method is advantageous because of its simple manipulation, short reaction time, wide substrate scope, high product yield, and high atom economy. It also has potential uses in novel-drug designing and natural product synthesis.

Key words: 2-Cyanoarylaldehyde, Activated methylene compound, 3-Substituted isoindolin-1-one, Solvent-free, Grinding reaction

王平安, 姚琳, 张东旭, 聂慧芳, 李穆琼, 姜茹. 利用无溶剂研磨反应制备3-取代异吲哚啉-1-酮类化合物[J]. 大学化学, 2021, 36(6): 2008040.

Pingan Wang, Lin Yao, Dongxu Zhang, Huifang Nie, Muqiong Li, Ru Jiang. Synthesis of 3-Substituted Isoindolin-1-ones by Solvent-Free Grinding Reaction[J]. University Chemistry, 2021, 36(6): 2008040.

链接本文: https://www.dxhx.pku.edu.cn/CN/10.3866/PKU.DXHX202008040

https://www.dxhx.pku.edu.cn/CN/Y2021/V36/I6/2008040

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序号	碱(摩尔百分比)	研磨时间/min	产率
1	Et₃N (10%)	5	86%
2	ⁱPr₂NEt (10%)	5	85%
3	DABOC (10%)	5	87%
4	DBU (10%)	5	86%
5	PPh₃ (10%)	20	0
6	NaOH (10%)	5	结果复杂
7	Na₂CO₃ (10%)	10	75%
8	K₂CO₃ (10%)	5	> 99%
9	K₂CO₃ (10%)	1	> 99%
10	K₂CO₃ (5%)	10	84%

利用无溶剂研磨反应制备3-取代异吲哚啉-1-酮类化合物

Synthesis of 3-Substituted Isoindolin-1-ones by Solvent-Free Grinding Reaction

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