Research on Chemical Intermediates

, Volume 43, Issue 3, pp 1689–1708 | Cite as

On the formation of a side product with hexahydroaporphine-like structure in the Grewe cyclization of dextromethorphan

  • Qiao Zhao
  • Kai Zhao
  • Sheng-ying Wu
  • Bo-xue Tian
  • Leif A. Eriksson
  • Li-min Wang
  • Na An
  • Zhong-zhu Long
  • Shui-hong Cai
Article
  • 152 Downloads

Abstract

Factors leading to the formation of a hexahydroaporphine-like cyclizing side product were studied systematically for the first time and the ratio of this side product was controlled effectively. To understand better the electronic effect of substrates on the formation of side products, different 1-benzyloctahydroisoquinolines with substituted groups on nitrogen or benzene ring were compared. A plausible mechanism of cyclizing reaction was proposed, and key intermediates as well as transition states were analyzed using DFT calculations.

Keywords

Grewe cyclization Dextromethorphan Hexahydroaporphine-like side product DFT calculation 

Notes

Acknowledgments

The work was supported by the National Nature Science Foundation of China (NSFC, 21272069, 20672035), the Fundamental Research Funds for the Central Universities, the Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, the Swedish research council, and the Faculty of science at University of Gothenburg.

Supplementary material

11164_2016_2723_MOESM1_ESM.docx (4.4 mb)
Supplementary material 1 (DOCX 4478 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Qiao Zhao
    • 1
  • Kai Zhao
    • 1
  • Sheng-ying Wu
    • 1
    • 2
    • 3
    • 4
  • Bo-xue Tian
    • 2
  • Leif A. Eriksson
    • 3
    • 4
  • Li-min Wang
    • 1
  • Na An
    • 4
  • Zhong-zhu Long
    • 4
  • Shui-hong Cai
    • 4
  1. 1.Key Laboratory for Advanced Materials and Institute of Fine ChemicalsEast China University of Science and TechnologyShanghaiPeople’s Republic of China
  2. 2.Department of Pharmaceutical Chemistry, School of PharmacyUniversity of CaliforniaSan FranciscoUSA
  3. 3.Department of Chemistry and Molecular BiologyUniversity of GothenburgGöteborgSweden
  4. 4.Dongyue Pharma Ltd. Co.ShanghaiPeople’s Republic of China

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