Preparation and Properties of Azetidine-2-Ones

Abstract

The preparation and properties of some known azetidine~2-ones are reviewed, and the biological properties are summarised. A series of new azetidinones have been synthesised. The cycloaddition of diphenylketene or ketene to Schiff's bases yielded the 3,3-disubstituted and the 3-unsubstituted azetidinones respectively whilst the action of acid chlorides with Schiff's bases in the presence of triethylamine yielded the 3-phenyl and 3-phenyl-3-chloro azetidinones. Anils prepared from 9-fluorenone and aromatic amines yielded spiroazetidinones. In general it was found that diphenylketene and the fluorenone anils were the most reactive compounds. The mechanism of these reactions are discussed in the light of the experimental results and the theoretical foundation of the Woodward-Hoffman rules for the Conservation of Orbital Symmetry. Some nucleophilic ring opening reactions of azetidine~2-ones with sodium hydroxide, lithium aluminium hydride and methyl magnesium bromide are described and possible mechanisms for the reactions outlined. Azetidine~2-ones have been shown to undergo acid-catalysed rearrangements to yield a variety of products. The reaction of 1—phenyl azetidinones with concentrated sulphuric acid yielded 3,4-dihydroquinoline-2(1H)-ones. In the presence of boron trifluoride etherate and toluene as solvent the rearrangement of azetidine-2-ones results in the formation of a propionamide by ring opening of the azetidinone and electrophilic substitution of the intermediate into the aromatic ring of the solvent. Anisole has also been shown to undergo this reaction. 4,3,3,4-Tetraphenylazetidine-2-one also undergoes rearrangement in the presence of boron trifluoride etherate in toluene to yield the 2,3-diphenylindene- 4-one rather than the propionamide by intramolecular electrophilic attack with the extrusion of aniline. Rearrangement of 1,-diphenylazetidine-2-one in the presence of boron trifluoride etherate in an inert aromatic solvent leads to rapid B ~elimination of the proton to yield cinnamanilide. The mass spectra of a selection of azetidinones and 3,4-dihydroquinoline- 2(1H)-ones are recorded and possible fragmentation pathways are suggested for these compounds.