Electrospray ionization (ESI) fragmentations and dimethyldioxirane reactivities of three diverse lactams having full, half, and zero resonance energies

J Org Chem. 2014 Jan 17;79(2):517-28. doi: 10.1021/jo402041u. Epub 2013 Dec 30.

Abstract

Three lactams having, respectively, ~20, ~10, and 0 kcal/mol of resonance energy have been subjected to electrospray ionization mass spectrometry (ESI/MS) as well as to attempted reaction with dimethyldioxirane (DMDO). The ESI/MS for all three lactams are consistent with fragmentation from the N-protonated, rather than the O-protonated tautomer. Each exhibits a unique fragmentation pathway. DFT calculations are employed to provide insights concerning these pathways. N-Ethyl-2-pyrrolidinone and 1-azabicyclo[3.3.1]nonan-2-one, the full- and half-resonance lactams, are unreactive with DMDO. The "Kirby lactam" (3,5,7-trimethyl-1-azaadamantan-2-one) has zero resonance energy and reacts rapidly with DMDO to generate a mixture of reaction products. The structure assigned to one of these is the 2,2-dihydroxy-N-oxide, thought to be stabilized by intramolecular hydrogen bonding and buttressing by the methyl substituents. A reasonable pathway to this derivative might involve formation of an extremely labile N-oxide, in a purely formal sense, an example of the hitherto-unknown amide N-oxides, followed by hydration with traces of moisture.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Epoxy Compounds / chemistry*
  • Lactams / chemistry*
  • Molecular Structure
  • Quantum Theory
  • Spectrometry, Mass, Electrospray Ionization
  • Thermodynamics

Substances

  • Epoxy Compounds
  • Lactams
  • dimethyldioxirane