Brominated isoindolines: precursors to functionalised nitroxides

A new, convenient method for the preparation of functionalised precursors to stable tetraalkylisoindoline nitroxides (aminoxyls) is presented. Simple treatment of 2-benzyl-1,1,3,3-tetramethylisoindoline 2 with Br2 in CCl4 gives rapid oxidative debenzylation, generating benzaldehyde and an unusual bromoamine, 2-bromo-1,1,3,3-tetramethylisoindoline 4, in high yield. Treatment of the bromoamine 4 with FeSO4–H2SO4 results in bromination of the aromatic ring in varying yield, while rapid treatment with peroxide–tungstate causes debromination, generating 1,1,3,3-tetramethylisoindoline 3. Bromination of the isoindoline aromatic ring is more readily afforded by treatment of 2-benzyl-1,1,3,3-tetramethylisoindoline 2 with Br2 and AlCl3 in CCl4, producing 2,5-dibromo-1,1,3,3-tetramethylisoindoline 7 and/or 2,5,6-tribromo-1,1,3,3-tetramethylisoindoline 6 in varying yields depending upon the exact reaction conditions. Rapid treatment with peroxide–tungstate generates the corresponding bromine substituted isoindolines, 5-bromo-1,1,3,3-tetramethylisoindoline 5 and 5,6-dibromo-1,1,3,3-tetramethylisoindoline 8. Prolonged peroxide–tungstate treatment oxidises the substituted bromoamines to the corresponding nitroxides, 5-bromo-1,1,3,3-tetramethylisoindolin-2-yloxyl 9 and 5,6-dibromo-1,1,3,3-tetramethylisoindolin-2-yloxyl 10. SQUID magnetic susceptibility measurements of crystalline 10 reveal strong antiferromagnetic interradical spin coupling. The crystal structures of 10, 2-bromo-1,1,3,3-tetramethylisoindoline 4 and the hydrobromide dihydrate salt of 1,1,3,3-tetramethylisoindoline 3 (3a) have also been determined, with 10 displaying an interesting molecular packing arrangement.