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Approaches to the Synthesis of a Water‐Soluble Carboxy Nitroxide
Author(s) -
Thomas Komba,
Chalmers Benjamin A.,
FairfullSmith Kathryn E.,
Bottle Steven E.
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201201551
Subject(s) - chemistry , isoindoline , phthalic anhydride , nitrile , nitroxide mediated radical polymerization , yield (engineering) , combinatorial chemistry , organic chemistry , trifluoroacetic anhydride , copolymer , catalysis , polymer , materials science , radical polymerization , metallurgy
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 .