Smiles rearrangement as a tool for the preparation of 5-[(2-hydroxyacyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamides: Main pathway and side reactions.

In the preparation of 5-[(2-hydroxyacyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamides 1a-h from 2a-h two conditions using stoichiometric amounts of base (method A - aq NaOH at 50 degrees C; method B - MeONa in DMF at r.t.) were used. Yields are good to excellent provided that the right conditions are chosen. Primary amides 2a,b give Ia,b with method B only, whereas with method A extensive hydrolysis of the CONH2 moiety is observed. N-Methyl derivatives 2c,d afford 1c,d with either method. However, with method B long reaction times lead to the formation of large amounts of benzoxazinones, 4c,d. Under the same conditions, the pattern of side products which are formed from N-(hydroxyalkyl)phenoxyacctamides 2e-g is furtherly complicated by: i) intramolecular cyclizations leading to bicyclic (7f,g) and tricyclic structures (5) ii) N-deacylation; iii) double Smiles rearrangement reactions.