Acta Chimica Sinica ›› 2012, Vol. 70 ›› Issue (21): 2236-2245.DOI: 10.6023/A12080543 Previous Articles     Next Articles


功能化烯胺的合成(I): 混合溶剂中硫脲催化α,β-邻位氨基溴转变成α,β-脱氢氨

陈战国, 王丹, 李亚男, 王英杰, 胡均利, 夏伟   

  1. 陕西省大分子科学重点实验室 陕西师范大学化学化工学院 西安 710062
  • 投稿日期:2012-08-11 发布日期:2012-09-12
  • 通讯作者: 陈战国
  • 基金资助:
    项目受陕西省自然科学基金(No. 2009JM2011)和陕西师范大学研究生创新基金(No. 2008CXB009)资助.

Synthesis of Functionalized Enamines (I): theα,β-Vicinal Bromoamine Compounds Converted into α,β-Dehydroamino Derivatives Catalyzed by Thiourea in Mixture Solvent

Chen Zhanguo, Wang Dan, Li Yanan, Wang Yingjie, Hu Junli, Xia Wei   

  1. Key Laboratory of Macromolecular Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710062
  • Received:2012-08-11 Published:2012-09-12
  • Supported by:
    Project supported by the the Natural Science Foundation of Shaanxi Province (No. 2009JM2011) and the Innovation Foundation of Postgraduate Cultivation of Shaanxi Normal University (No. 2008CXB009).

An easy and efficient new method for the synthesis of functionalized enamines from α,β-vicinal bromoamine ketones and esters has been developed. A series of α,β-vicinal bromoamine ketones and esters can be smoothly converted into corresponding α,β-dehydroamino derivatives catalyzed by thiourea (50 mol%) in mixture solvents [CH2Cl2/DMF=1∶1 (V/V)] at room temperature in nearly quantitative yield (90%~99%). This new method, the conversion of α,β-vicinal bromoamine ketones and esters into α,β-dehydroamino derivatives, has many advantages such as mild conditions, easy handling, nearly quantitative yields etc. 32 structurally different substrates were investigated. The results indicated that the protocol has applicability in a large scope of vicinal bromoamine compounds including α,β-vicinal bromoamine ketones and esters. During the elimination process of HBr from vicinal bromoamine compounds to generate corresponding functionalized enamines with assistance of thiourea, the corresponding intermediate aziridines must be formed firstly. The final products (α,β-dehydroamino derivatives) were formed via ring-open reaction of the aziridines. Herein, no matter the substrate was α-amino-β-bromo or α-bromo-β-amino in structurally, the aziridines skeleton in structurally was similar to each other formed from the intramolecular nucleophilic replacement reaction fashion. Because of ring-open reactions of aziridines have full regiospecificity, the obtained final products are full regiospecificity, too. A possible mechanism was proposed and it can explain well the full regiospecificity of the reaction. All functionalized enamines were obtained by following experimental procedure. Unless otherwise stated, all reagents were purchased from commercial sources and used without further purification. A mixture of a α,β-vicinal bromoamine ketones or esters (1.0 mmol), anhydrous K2CO3 (0.5 mmol), thiourea (0.5 mmol) was put into a dried convenience vessel. Then, 10 mL of commercial and not degassed mixture solvent [CH2Cl2/DMF=1∶1 (V/V)] was added to the vessel with stirring at room temperature without protection of inert gas. The reaction progress was monitored by TLC until the starting material was consumed, and the spot of final product was not changed (The first spot represented a corresponding aziridine. Subsequently, this aziridine spot was disappeared, and the final product spot was formed which was stable). After completion of the reaction, the reaction mixture was diluted with EtOAc (15 mL) and washed with water (15 mL×3) and brine (15 mL×3). The organic layer was dried by anhydrous Na2SO4 and concentrated under reduced pressure to give crude product, which was purified by column chromatography packed with silica gel with petroleum ether and EtOAc as eluent to afford pure product. The structures of all products were confirmed by their 1H NMR, 13C NMR and HRMS analysis.

Key words: enamine, thiourea, catalyze, α,β-vicinal bromoamine, α,β-dehydroamino