Synthesis, single crystal X-ray structure and W-band (95 GHz) EPR spectroscopy of a new anionic isoindoline aminoxyl: synthesis and characterisation of some derivatives

Here we describe the improved synthesis and full characterisation, includin g W-band EPR analysis and X-ray crystallography, of an anionic isoindoline aminoxyl, 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl 6 (CTMIO), which is more water soluble than the parent 1,1,3,3-tetramethylisoindolin-2-ylox yl 1 (TMIO). We also report the synthesis and characterisation of three nov el CTMIO derivatives: the n-hexyl ester 9, anhydride 10, and N-hydroxysucci nimide ester 11. Selective AlCl3-catalysed bromination of 2-benzyl-1,1,3,3-tetramethylisoind oline 2 produces the aminoxyl precursor, 5-bromo-1,1,3,3-tetramethylisoindo line 3 in high yield. Lithiation and subsequent carboxylation of this speci es generates 5-carboxy-1,1,3,3-tetramethylisoindoline 5, which undergoes tu ngstate-H2O2 oxidation to give the target aminoxyl, CTMIO 6. The analogous synthesis of 5-formyl-1,1,3,3-tetramethylisoindolin-2-yloxyl 8 is also desc ribed. W-band (95 GHz) EPR studies of toluene solutions of CTMIO, both liquid and frozen, indicate that aggregates are formed: the liquid state was used to m easure the equilibrium dimer formation constant (30 +/- 40 M-1 at 298 K); t he solid state was used to estimate the distance (19.3 Angstrom) between th e two aminoxyl groups in the dimer. A single crystal X-ray examination reve als that there is short-range intermolecular hydrogen bonding between amino xyl and carboxylic groups, and that the aminoxyl groups are separated by 10 .2 Angstrom. However, it is concluded from the EPR spectral evidence that, in toluene solution, the dimers are formed by hydrogen bonding between pair s of carboxylic groups. Using the molecular dimensions determined by X-ray analysis, the distance between the aminoxyl groups in the dimer in frozen s olution was estimated to be 17 Angstrom.