Montmorillonite─Eco-friendly and Effective Catalyst in the Synthesis of Biologically Active Compounds with Bicyclo[3.3.1] Moiety

Prins cyclization is a key method for synthesizing oxygen-containing heterocycles with biological activity involving the reaction of alkenes and aldehydes under mild acidic conditions. This process is valuable for producing compounds such as 2,2,6-trimethyl-4-(1-propenyl)-3-oxabicyclo[3.3.1]-non-6-ene, a bioactive bicyclic ether synthesized from limonene and crotonaldehyde. Compounds with bicyclo[3.3.1]-nonene structures are interesting due to their fragrance properties and potential estrogen receptor activity. This study evaluates montmorillonite (MMT), a low-cost, environmentally friendly clay, as a heterogeneous acid catalyst for this reaction. Acid treatment of MMT (treated with HNO₃, HCl, H₂SO₄, and H₃PO₄) had a positive influence on limonene conversion compared with nonmodified MMT, and limonene conversions >85% and selectivity >70% were obtained (24 h). Reaction parameters such as temperature, solvent, catalyst amount, and limonene-to-crotonaldehyde ratio significantly influenced conversion and selectivity. Higher temperatures and lower crotonaldehyde ratios improved the achieved limonene conversion, though selectivity decreased with temperature. Montmorillonite-supported heteropoly acids (HPW and HPMo) increased conversion but reduced selectivity and showed inefficient catalyst utilization at higher loadings. The initial reaction rate increased and selectivity decreased with catalyst acidity. Overall, acid-treated MMTs are more effective and economical than heteropoly acid-modified variants, offering a viable path for synthesizing bicyclic ethers via green chemistry.