HETEROCYCLIC NONIONIC X-RAY CONTRAST AGENTS .4. THE SYNTHESIS OF DIHYDRO-2(3H)-FURANYLIDENAMINO, 5-OXO-1-PYRROLIDINYL, AND 5-OXO-4-MORPHOLINYL DERIVATIVES BY AN INTRAMOLECULAR IODOCYCLIZATION APPROACH

Intramolecular iodocyclization of omega-alkenylanilides 6 and [omega-( alkenyloxy)alkyl]anilides 7 resulted in the formation of dihydro-2(3H) -furanylidenamines 8 and 1,4-dioxan-2-ylideneamines 9, respectively, b y an amide-oxygen participative nucleophilic attack on the expected io donium intermediate. The latter heterocyclic ring system is new. If a strong base is present, the mode of ring closure was mainly diverted t o an amide-nitrogen participative nucleophilic attack, leading to (iod omethyl)-pyrrolidinones 10 and (iodomethyl)morpholinones 11, from 6 an d 7, respectively. Unique interconvertible syn-anti isomerism in the i mino-ether 8a was demonstrated by variable temperature NMR studies. Th e major component in this mixture was the 8a anti-isomer. Acetolysis o f the iodocyclized products, followed by deacetylation, provided the h eterocyclically substituted polyhydroxytriiodoisophthalamides 16-18. H ydrolytic studies on the imidate 16d revealed an interesting pH depend ence. As expected the amine 3d and the amide 22 resulted in pH values of 2 and 6. At pH 12, however, the Chapman rearrangement product 17d w as the major product. The compounds obtained in this investigation are of interest as X-ray contrast agents.