Catalytic synthesis of heterocyclic compounds with a cineole moiety based on α-pinene

Abstract

Cineole is a natural compound that is used in traditional medicine and pharmaceuticals. This work describes for the first time the selective catalytic synthesis of heterocyclic compounds with a cineole fragment by condensation of 8-hydroxy-6-hydroxymethyllimonene (α-pinene based platform molecules) with thiophene-2-carbaldehyde. Acid-modified halloysite nanotubes and commercial montmorillonites K-10 and K-30 were used as heterogeneous catalysts and compared with the traditional ones. The materials were characterized by SEM, EDX, N₂ adsorption-desorption, MAS NMR, and FTIR with pyridine methods. Selectivity to the product with the 1,8-cineole moiety increased slightly with increasing solids acidity, reaching 77 % on K-10, which was the same as in the presence of BF₃·Et₂O. Over strong Brønsted acid (Amberlyst-15), mainly intramolecular cyclization of the diol occurred. Formation of the product with the 1,4-cineole fragment was more pronounced at high initial reagents concentrations, or when water was added, since it is formed through another intermediate containing two hydroxy groups. The reaction mechanism and pathways are discussed using both experimental data and DFT calculations. The use of a catalytic system based on resistant to leaching montmorillonite K-10 in methylene chloride allowed generation of the products with a 1,8-cineole moiety with selectivity up to 96 % depending on the aldehyde.