221368-74-7Relevant articles and documents
Approaches to the synthesis of a water-soluble carboxy nitroxide
Thomas, Komba,Chalmers, Benjamin A.,Fairfull-Smith, Kathryn E.,Bottle, Steven E.
, p. 853 - 857 (2013/03/29)
The robust and diversely useful isoindoline nitroxide, 5-carboxy-1,1,3,3- tetramethylisoindolin-2-yloxyl (1; CTMIO), has previously been synthesised in low-to-moderate yields from phthalic anhydride (3). Recent interest in its biological potential as a potent antioxidant and in other areas has seen an increased demand for its production. Herein, three new synthetic routes to CTMIO are presented and their efficiencies assessed. Two routes, via the nitrile 9 and the formyl compound 11, derive from 5-bromo-1,1,3,3-tetramethylisoindoline (6). The third approach starts from the readily accessible starting material, 4-methylphthalic anhydride (12), and proceeds by a methylarene oxidation with potassium permanganate. The three new approaches yield CTMIO in comparable overall yields (16-18 %); however, the synthetic efficiency is most improved when employing the nitrile intermediate 9. Copyright
Brominated isoindolines: precursors to functionalised nitroxides
Micallef, Aaron S.,Bott, Raymond C.,Bottle, Steven E.,Smith, Graham,White, Jonathon M.,et al.
, p. 65 - 72 (2007/10/03)
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-H2S04 results in bromination of the aromatic ring in varying yield, while rapid treatment with peroxide-tungstate causes debromination, generating 1,1,3,3-tetra-methylisoindoline 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.
