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

Abstract

Here we describe the improved synthesis and full characterisation, including 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-yloxyl 1 (TMIO). We also report the synthesis and characterisation of three novel CTMIO derivatives: the n-hexyl ester 9, anhydride 10, and N-hydroxysuccinimide ester 11. Selective AlCl3-catalysed bromination of 2-benzyl-1,1,3,3-tetramethylisoindoline 2 produces the aminoxyl precursor, 5-bromo-1,1,3,3-tetramethylisoindoline 3 in high yield. Lithiation and subsequent carboxylation of this species generates 5-carboxy-1,1,3,3-tetramethylisoindoline 5, which undergoes tungstate–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 described. 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 measure the equilibrium dimer formation constant (30 ± 40 M−1 at 298 K); the solid state was used to estimate the distance (19.3 A) between the two aminoxyl groups in the dimer. A single crystal X-ray examination reveals that there is short-range intermolecular hydrogen bonding between aminoxyl and carboxylic groups, and that the aminoxyl groups are separated by 10.2 A. However, it is concluded from the EPR spectral evidence that, in toluene solution, the dimers are formed by hydrogen bonding between pairs of carboxylic groups. Using the molecular dimensions determined by X-ray analysis, the distance between the aminoxyl groups in the dimer in frozen solution was estimated to be 17 A.