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

Article abstract of DOI:10.1021/jo00119a020

Intramolecular iodocyclization of ω-alkenylanilides 6 and <ω-(alkenyloxy)alkyl>anilides 7 resulted in the formation of dihydro-2(3H)-furanylidenamines 8 and 1,4-dioxan-2-ylideneamines 9, respectively, by an amide-oxygen participative nucleophilic attack on the expected iodonium intermediate.The latter heterocyclic ring system is new.If a strong base is present, the mode of ring closure was mainly diverted to an amide-nitrogen participative nucleophilic attack, leading to (iodomethyl)pyrrolidinones 10 and (iodomethyl)morpholinones 11, from 6 and 7, respectively.Unique interconvertible syn-anti isomerism in the imino-ether 8a was demonstrated by variable temperature NMR studies.The major component in this mixture was the 8a-anti-isomer.Acetolysis of the iodocyclized products, followed by deacetylation, provided the heterocyclically substituted polyhydroxytriiodoisophthalamides 16-18.Hydrolytic studies on the imidate 16d revealed an interesting pH dependence.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 was the major product.The compounds obtained in this investigation are of interest as X-ray contrast agents.