Boosted Fe(III)–porphyrin catalysis for eco-friendly synthesis of tetrazolopyrimidine–chromone derivatives by water-powered chemistry

Abstract

A green, efficient, and highly sustainable one-pot three-component synthetic protocol has been established for the preparation of novel (4,5-dihydro-tetrazolo[1,5-a]pyrimidin-7-yl)-chromen-2-one derivatives through the condensation of 3-acetyl-chromen-2-one, 5-aminotetrazole and various aromatic aldehydes catalyzed by a recyclable Fe(III)–porphyrin complex. The optimized reaction system, operating in an ethanol: water (1:3, v/v) medium at 80 °C, afforded the desired heterocycles in excellent yields (91–96%) within short reaction times (15–30 min). Systematic optimization revealed that increasing the catalyst loading from 3 to 10 mmol% significantly enhanced both product yield and reaction rate, with 10 mmol% identified as the optimal dosage. Comparative catalytic screening demonstrated that the Fe(III)–porphyrin complex markedly outperformed other Lewis acid, basic, and ionic liquid catalysts—including FeCl₃·6H₂O, Fe(OTf)₃, Mg(OTf)₂, and ZnBr₂ by achieving superior conversion efficiency and selectivity under mild, eco-friendly conditions. Hot filtration experiments confirmed that the reaction predominantly proceeds through a homogeneous catalytic pathway. The Fe(III)–porphyrin complex exhibited excellent structural stability and could be efficiently reused for at least five consecutive cycles without notable loss of activity. This environmentally benign and high-yielding strategy underscores the potential of Fe(III)–porphyrin complexes as robust, recyclable, and green catalysts for the sustainable synthesis of pharmacologically valuable heterocyclic scaffolds.