HETEROCYCLIC NONIONIC X-RAY CONTRAST AGENTS .3. THE SYNTHESIS OF AZOLIDINYL]-2,4,6-TRIIODO-1,3-BENZENEDICARBOXAMIDE DERIVATIVES

The syntheses of 2,4,6-triiodo-1,3-benzenedicarboxamide analogs, 12c, 12e, and 17c, of interest as X-ray diagnostic agents and in which the 5 position is linked to the N atom of a 4-(hydroxymethyl)-oxazolidin-2 -one moiety, are described. The heterocycle was built from suitably pr otected 5-amino-2, 4,6-triiodo-1,3-benzenedicarboxylic acid derivative s by a three-step procedure consisting of (1) phosgene treatment to ob tain the corresponding isocyanates, (2) phenylmercuric chloride-cataly zed addition of glycidol (10) resulting in glycidyl carbamates, and (3 ) pyridine-catalyzed intramolecular N-alkylation, followed by deprotec tion, to obtain the oxazolidin-2-ones. The intramolecular N-alkylation reaction was highly regioselective and was not appreciably accompanie d by O-alkylation products under the experimental conditions employed. The two carboxamide nitrogen atoms in the intermediates and end produ cts carry either 2,3-dihydroxypropyl or 1,3-dihydroxypropyl residues. These highly congested benzenoid compounds exhibited interesting NMR s pectral features due to atropisomerism arising from hindrance to free rotation about the three single bonds that link the aromatic moiety to the N-containing functionalities.