Synthesis of Fatty 1,2,4-Trioxanes by Peracetalization of β-Hydroxy Hydroperoxides

Abstract The peracetalization of a β-hydroxy hydroperoxide derived from methyl oleate was studied using benzaldehyde as model substrate to give the corresponding fatty 1,2,4-trioxane. desired product obtained mixture regioisomers but only one diastereoisomer each formed. nature acid catalyst and both p-toluene sulfonic (PTSA) Amberlyst A35 (A35) were found be efficient homogeneous heterogeneous catalysts, respectively. solvent also investigated ethereal solvents such 2-methyltetrahydrofuran (2-MeTHF), tert-butyl ether (MTBE) cyclopentyl (CPME) gave best NMR yield (85%) for preparation trioxane. optimized conditions applied range aromatic aliphatic aldehydes, 1,2,4-trioxanes isolated with 30–91% yields (21 examples). antimalarial activity three trioxanes against Plasmodium falciparum, however, no significant detected (IC50 >1600 nM).