Azetidin-2-ones: structures of antimitotic compounds based on the 1-(3,4,5-trimethoxyphenyl)azetidin-2-one core

Abstract

A series of related substituted 1-(3,4,5-trimethoxyphenyl)azetidin-2-ones have been characterized: 3-(4-fluorophenyl)-4-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one, C25H24FNO5 (1), 3-(furan-2-yl)-4-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one, C23H23NO6 (2), 4-(4-methoxyphenyl)-3-(naphthalen-1-yl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one, C29H27NO5 (3), 3-(3,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one, C27H29NO7 (4) and 4,4-bis(4-methoxyphenyl)-3-phenyl-1-(3,4,5-trimethoxyphenyl)azetidin-2-one, C32H31NO6 (5). All of the compounds are racemic. The lactam and 3,4,5-trimethoxyphenyl rings are approximately co-planar and the orientation of the lactam and the 4-methoxyphenyl substituent is approximately orthogonal. The chiral centres, although eclipsed by geometry, have torsion angles ranging from −7.27 to 13.08° for the 3 position, and −8.69 to 13.76° for the 4 position of the β-lactam. The structures display intramolecular C—H...O bonding between the 3,4,5-trimethoxyphenyl ring and the lactam ketone. Further C—H...O interactions are observed and form either an opposing methoxy `buckle' to join two molecules together or a cyclic dimer.

Keywords

• β-lactam
• antimitotic
• crystal structure