Fateme Tavakoli, Manouchehr Mamaghani*, Mehdi Sheykhan, Narjes Mohammadipour and Mehdi Rassa Pages 872 - 880 ( 9 )
Aim and Objective: Chromene scaffold is one of the most famous oxygen heterocycles that have widely found in plants playing pivotal roles in medicinal and synthetic chemistry. This study was undertaken to provide a green protocol for the synthesis of novel functionalized chromen-pyrrole hybrids by a regioselective three-component reaction via both conventional and sonochemical methods. Because of fascinating features of these individual cores, a hybride molecular structure comprising of pyrrole and chromene moieties could result in a novel single molecule with increased efficacy.
Materials and Methods: The synthesis of novel functionalized chromen-pyrrole hybrids was accomplished by regioselective three-component reaction of β-naphthol, 3-(1-methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile and diverse aromatic aldehydes catalyzed by triethylamine in H2O-EtOH via both conventional and sonochemical methods. The impact of some variants such as solvents, catalysts and temperature was also probed under both conventional heating and sonochemical methods to accomplish the optimized reaction condition. The synthesized products were screened for antibacterial activity against Gram positive (Ml, Bs, Sa) and Gram negative bacteria (Ps, Ec).
Results: In initial attempt, the reaction of equimolar amounts of 2-fluorobenzaldehyde, 3-(1-methyl-1H-pyrrol- 2-yl)-3-oxopropanenitrile and β-naphthol was selected as a model reaction. The role of various solvents, temperature and different acidic and basic catalysts on the model reaction was examined. The optimized condition was the use of 20 mol% triethylamine in H2O-EtOH (1:1) under ultrasound irradiation at 65°C. The scope of this reaction was screened with respect to various substituted aromatic aldehydes. Considering the results, the electronic features of substituents affected the performance of this condensation. The reaction with aromatic aldehydes containing electron-withdrawing groups proceeded in lower reaction time, affording the productds in high to excellent yields while aldehydes with electron-donating groups reacted more slowly. This three-component reaction also provided a suitable procedure for the synthesis of bis-(chromen-pyrrole) in excellent yield. All of the synthesized products had significant antibacterial activity against the screened bacteria (Ml, Bs, Sa, Ps, Ec).
Conclusion: A streamlined, regioselective and ecofriendly ultrasonic-promoted procedure for the synthesis of novel substituted benzo[f]chromenes from one-pot condensation of β-naphthol, 3-(1-methyl-1H-pyrrol-2-yl)-3- oxopropanenitrile and structurally diverse aldehydes catalyzed by triethylamine was developed. This green protocol furnishes all the products in reduced reaction times and high yields. In addition, the synthesized novel compounds showed narrow to wide spectral activity against the tested strains.
Three-component reaction, green synthesis, sonochemistry, chromen-pyrrole hybrids, medicinal chemistry, green chemistry.
Department of Chemistry, Faculty of Sciences, University of Guilan, P.O. Box 41335-1914, Rasht, Department of Chemistry, Faculty of Sciences, University of Guilan, P.O. Box 41335-1914, Rasht, Department of Chemistry, Faculty of Sciences, University of Guilan, P.O. Box 41335-1914, Rasht, Department of Chemistry, Faculty of Sciences, Islamic Azad University, Rasht Branch, P.O. Box 41335-3516, Rasht, Department of Biology, Faculty of Sciences, University of Guilan, P.O. Box 41335-1914, Rasht