Studies on isocyanides and related compounds; A facile synthesis of 4-phenyl-1-(2H)phthalazinone-2-alkanoic acid amides

A convenient synthesis of the title compounds by means of the Ugi four-comp onent condensation (Ugi 4-CC) is reported. The reaction between acetaldehyd e azine (3a), 2-benzoylbenzoic acid (4), and cyclohexyl isocyanide (5) spon taneously afforded N-cyclohexyl 2-(1,2-dihydro-1-oxo-4-phenylphthalazin-2-y l)propionamide (la) upon loss of acetaldehyde from the intermediate Ugi 4-C C adduct 6a. Starting from the less reactive azines 3c-f arising from keton es, the Ugi 4-CC adducts 6c-f did not spontaneously cyclize, whereas phenyl acetaldehyde azine (3b) afforded a mixture of the Ugi 4-CC adduct 6b and cy clized product Ib. In all of the cases, the adducts 6b-f were easily cycliz ed to 1b-f in acidic medium.