A rapid and green method for expedient multicomponent synthesis of N-substituted decahydroacridine-1,8-diones as potential antimicrobial agents

Abstract

An efficient, green, high yielding, and quick method for the synthesis of N-substituted decahydroacridine-1,8-diones was achieved by multicomponent reaction between various aromatic aldehydes (1a–q), dimedone (2), and various aromatic amines (2a–d) using ChCl:Urea deep eutectic solvent as a recyclable organocatalyst and medium. The reaction conditions are relatively mild and do not require additional metals, acid catalysts, or organic solvents. The mild reaction conditions, experimental simplicity, straightforward purification procedures, excellent yields with short reaction times, as well as the application of green chemistry principles, are the advantages of this methodology. This simple ammonium deep eutectic solvent, easily synthesized from choline chloride and urea, is relatively inexpensive and biodegradable, making it applicable for industrial use. The deep eutectic solvent was easily separated and reused without loss of activity, and thus provides a good alternative. The synthesized 10-(substituted phenyl)-9-(substitutedphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8 (2H,5H)-diones (4a–l) were screened for their in vitro antimicrobial activity against four bacterial Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and three fungal strains (Candida albicans, Aspergillus niger and Aspergillus flavus). Among them, the 9-(N,N-Dimethylphenyl)-3,3,6,6-tetramethyl-10-(3-pyridyl)-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (4f), 10-(4-Bromophenyl)-9-(3-hydroxy-4-methoxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (4i) and 9-(4-Nitrophenyl)-3,3,6,6-tetramethyl-10-phenyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (4k) show good antimicrobial activity.