Base-Catalyzed cyclization of N-propargylamides to oxazoles

The base-catalyzed cyclization of some N-propargylamides to oxazoles has been studied in the presence of sodium hydride and potassium carbonate. The α-arylsubstituted propargylamides 1c-d (Ar = p-OMeC₆H₄ ( 1c ), C₆H₅ ( 1d ), and p-O₂NC₆H₄ ( 1e )) cyclized with markedly higher rates ( 1e > 1d > 1c ) than the unsubstituted and α-methyl substituted propargylamides 1a and 1b . A ¹H nmr spectroscopic experiment demonstrated the presence of an allenic intermediate in the potassium carbonate-catalyzed ring closure of 1e . The observed rank order of reactivities correlates well with the acidities of the respective propargylic hydrogens of the amides and with the ability of the ring closed intermediates to stabilize an oxazole anion. The results demonstrate that the base-catalyzed formation of oxazoles from propargylamides may proceed via an allenic intermediate.