Single electron methodology for the synthesis of disubstituted quinolines by chemical and electrochemical catalysis

  • Author / Creator
    Aloisio, Mark D.
  • Radical cation catalyzed methodology was adapted for the synthesis of disubstituted quinolines, to address the requirements for continuous oxygen sparge and high reaction temperatures. Using previously reported aldehydes and 5,6,7,8-tetrahydronaphthylamine, the reaction required optimization of radical cation salt and reaction conditions. A series of radical cation salts were synthesized by the Buchwald-Hartwig amination of para-substituted iodobenzene derivatives screened using similar para-substituted anilines. The triarylamines were oxidized to the radical cations using triphenylammonium hexachloroantimonate (TPASbCl6), tris(p-methylphenyl)ammonium hexachloroantimonate (TTASbCl6), tris(4-biphenyl)ammonium hexachloroantimonate (TBPhASbCl6), and triphenylammonium hexafluorophosphate (TPAPF6), to compare with commercial tris(4-bromophenyl)ammonium hexachloroantimonate (TBPASbCl6). After optimizing other reaction variables, the best results were obtained using TPASbCl6 as the catalyst.

    This method of radical catalysis was compared to our previously optimized acid/iodide methodology with a series of aniline substrates. Radical cation catalysis was comparable to the HI method, with some substrates providing increased yields. Bidirectional MCR reactions were evaluated using 1,5-diaminonaphthalene to target the formation of tetrasubstituted 4,10-diazachrysene compounds under the radical cation conditions. These reactions were successful, but resulted in isolation of the dihydroquinoline as product, which does not undergo aerobic oxidation to the fully aromatic ring system.

    Preliminary exploration of an electrochemical method for generating the aniline radical cation was pursued. The electrochemical cell allows for oxidation of a soluble redox mediator, leading to the same radical cation mediated MCR quinoline synthesis. Initial results were poor, but lithium bromide as electrolyte provided improved but still modest yields. The dual role of lithium bromide as the electrolyte and the amine redox mediator requires more investigation to better understand its purpose in the reaction process.

  • Subjects / Keywords
  • Graduation date
    Fall 2021
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.