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.

Date of Award	1972
Original language	English