Chemistry of Heterocyclic Compounds

, Volume 42, Issue 2, pp 184–190 | Cite as

Quantum-chemical investigation of the mechanism of cyclocondensation of 4-hydroxy-4-methylpentan-2-one with cyanoacetamide using the AM1 method

  • M. Fleisher
  • D. Jansone
  • L. Leite
  • E. Lukevics


The mechanism of formation of 4,6,6-trimethyl-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile from 4-hydroxy-4-methylpentan-2-one and cyanoacetamide in the presence of ammonium acetate has been studied by the AM1 method. It was found that, under the reaction conditions, the amide is readily converted to an iminol tautomeric form which takes part in subsequent reaction. It was shown that the reaction is a cascade process forming two intermediates. The final product 4,6,6-trimethyl-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile is formed from the product of a Knoevenagel condensation via an intramolecular nucleophilic substitution mechanism. On the basis of the activation energies obtained it can be deduced that the limiting stage is the deprotonation process of the cyanoacetiminol.


lactam cascade reaction AM1 method cyclocondensation Knoevenagel reaction quantum-chemical calculations 


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • M. Fleisher
    • 1
  • D. Jansone
    • 1
  • L. Leite
    • 1
  • E. Lukevics
    • 1
  1. 1.Latvian Institute of Organic SynthesisRiga

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