Effect of micelles on cyclization reactions: The use of N-hexadecyl-2- chloropyridinium iodide as an amphiphilic carboxyl-activating agent in lactonization and lactamization

Article abstract of DOI:10.1021/jo00081a022

Lactonization and lactamization with a novel carboxyl-activating agent, N- hexadecyl-2-chloropyridinium iodide (C₁₆PyCl,I), were investigated. The organization of this agent in micelles in the reaction medium facilitates cyclization giving rise to a micellar effect. Under these conditions, the corresponding lactam is produced from the ω-amino acid 12-aminododecanoic acid in good yield (double that obtained with the Mukaiyama reagent, N- methyl-2-chloropyridinium iodide C₁PyCl,I). On the other hand, the yield of lactone from 16-hydroxyhexadecanoic acid was the same with either carboxyl- activating agent. These results were accounted for in terms of substrate- dependent micellar effects. Because of solubility effects, the ω-amino acids and ω-hydroxy acids are not localized in comparable ways vis a vis the interface and, thus, have different reactivities. Moreover, hydrolysis of the reagents, C₁₆PyCl,I and C₁PyCl,I, was also detected. The interference of this reaction with the cyclization process was also found to depend on a micellar effect with C₁₆PyCl,I that is not observed with C₁PyCl,I.