3-Acetoxyaminoquinazolin-4(3H)-ones as aziridinating agents: relative rate of inversion at the exocyclic nitrogen

Abstract

Inversion at the exocyclic nitrogen in 3-acetoxyaminoquinazolinones, e.g. 2 is slow on the NMR time-scale. The associated inversion barrier could not be measured directly by NMR spectroscopy because of the thermal instability of compound 2. However, the corresponding inversion barriers for 3-isopropoxyaminoquinazolinone 5 and 3-tert-butoxyaminoquinazolinone 6, prepared by reaction of 3-acetoxyaminoquinazolinone 2 with titanium(IV) isopropoxide and titanium(IV)tert-butoxide respectively, suggest that it is sufficiently low for the rate of inversion to be fast relative to the rate of aziridination of alkenes using reagent 2. This conclusion is supported by the preparation of diastereoisomers of 3-acetoxyaminoquinazolinones 3, 16 and 21 at –20 °C and by monitoring their relative rates of aziridination of cinnamyl alcohol (by 3), and styrene (by 16) and of intramolecular aziridination (for 21) by NMR spectroscopy. In no case was there any change in the ratio of these diastereoisomers as the aziridinations progressed implying that interconversion between them was faster than the rates at which they reacted individually with the respective alkene.