Cyclic β-hydroxy-α-nitrosulfone isomers readily interconvert via open-chain aldehyde forms.

Abstract

Two structurally diverse cyclic β-hydroxy-α-nitrosulfones have been prepared and their isomerisation reactions studied. These cyclic β-hydroxy-α-nitrosulfones undergo isomer equilibration via open-chain aldehyde forms under a variety of mild conditions. Michael condensation of 1,1'-[(1,3-dinitro-1,3-propanediyl)bis(sulfonyl)]bis(benzene) with propenal and subsequent cyclisation afforded 2,4-dinitro-2,4-bis(phenylsulfonyl)cyclohexanol in 98% yield as a mixture of four diastereomers. Sequential chromatography and recrystallization afford pure (1R,2R,4S)-rel-2,4-dinitro-2,4-bis(phenylsulfonyl)cyclohexanol based on spectroscopic and X-ray crystallographic data. This diastereomer equilibrates with the other three possible diastereomers under a variety of mild conditions: during silica gel chromatography, when dissolved in basic solution, and when dissolved in neutral polar solvents. Open-chain aldehyde forms are implicated as intermediates in isomer interconversion. Condensation of 1-methyl-4-[(nitromethyl)sulfonyl]benzene and pentanedial gives 2-(4-methylphenylsulfonyl)-2-nitrocyclohexane-1,3-diol as predominantly two diastereomers. Purification affords pure racemic diastereomer in 55% yield. This racemic diastereomer interconverts with several other isomers during silica gel chromatography. These isomers were identified as one, likely two, diastereomeric meso 2-(4-methylphenylsulfonyl)-2-nitrocyclohexane-1,3-diol isomers and four cyclic hemiacetal constitutional isomers. When dissolved in neutral polar solvents, the racemic diastereomer also interconverts with meso diastereomers and cyclic hemiacetals showing a marked solvent dependence. Reaction of the racemic diastereomer with triethylamine in dichloromethane results in isomerisation as well as substantial reversion to 1-methyl-4-[(nitromethyl)sulfonyl]benzene and pentanedial. Reaction with triethylamine in DMSO as well as simply warming in DMSO results in ring opening and concomitant dehydration to afford (E)-6-(4-methylphenylsulfonyl)-6-nitrohex-4-enal.

• Authors: Peter A Wade, Ruchi Tandon, Patrick J Carroll
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 21 Issue 24 Pg. 5033-5039 (Jun 21 2023) ISSN: 1477-0539 [Electronic] England
• PMID: 37264923 (Publication Type: Journal Article)