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Current Organic Synthesis

Author(s): Manini Nayak, Kanyanjali Samal and Anita Pati*

DOI: 10.2174/1570179419666220413092052

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Design and Facile Synthesis of Spiro-s-tetrazine Derivatives of 2,4- diphenyl-3-azabicyclo[3.3.1]nonane-9-one

Page: [332 - 338] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Background: Literature survey suggested various methods of synthesis of the 3- azabicyclo [3.3.1] nonanes which include, Mannich reaction, α, α'-Annelation of Cyclic Ketones or through Enamines, Michael addition, Intramolecular Cyclizations, etc. However, a mechanism following a Michael addition path through the formation of the dibenzylidene cyclohexanone intermediate can not be ignored. Thus to ensure the mechanistic pathway for the formation of 2,4-diphenyl- 3-azabicyclo[3.3.1]nonan-9-one and to understand the reactivity of a conformationally and biologically important molecule for the synthesis of spiro-s-tetrazine derivatives and its further functionalization with thiazole and thiazolidinone derivatives the present work has been undertaken.

Methods: Direct reaction of dibenzylidene cyclohexanone and ammonium acetate has been tried to get the confirmation of Mannich/ Michael reaction pathway for the formation of 2,4-diphenyl-3- azabicyclo[3.3.1]nonan-9-one. Synthesis of the spiro-s-tetrazine derivative has been accomplished by the simple condensation reaction of azabicyclic system and thiocarbohydrazide (TCH). Simple methods have been adopted for the installation of heterocyclic moieties like thiazolidinone, thiazole.

Results: Failure of the attempts to prepare 2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-onedirectly from dibenzylidene cyclohexanone ruins the possibility of Michael addition reaction and supports the formation of the product through Mannich reaction. Synthesis of the spiro derivatives containing tetrazine, thiazole, thiazolidinone moieties were achieved by using simple techniques and products were obtained in good yield. FTIR, NMR spectroscopy are used for the characterization of all the molecules. Formation of 2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-onewas confirmed by using some additional data like mass and single crystal XRD.

Conclusion: Confirmation of the mechanistic route for the 2 2,4-diphenyl-3- azabicyclo[3.3.1]nonan-9-one was achieved and simple methods for the formation of spiro derivatives containing tetrazine, thiazole, thiazolidinone were established.

Keywords: Diphenyl-3-azabicyclo[3.3.1]nonan-9-one, spiroheterocycles, tetrazines, thiazolidinone, mannich reaction, azabicyclic ketone.

Graphical Abstract

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