Synthesis of Some Novel Sulfonamide-Imines as Potential Antimicrobial Agents

(E-pub Ahead of Print)

Author(s): Ahmad Reza Massah, Keivan Beheshtimaal*, Touba Khazaeili, Nahad Assakere, Fereshte Mousavi.

Journal Name:Letters in Organic Chemistry

Volume 14 , 2017


Background: Sulfonamide derivatives belong to the most important structural classes of drug molecules. This functional group constitutes the largest class of antibacterial agents. Antibacterial agents with a sulfonamide structure, e.g. sulfadiazine have been therapeutically used for many decades. Approved drugs with a sulfonamide structure have found widespread utility in a number of pharmacology and medicine applications. Literature on sulfonamides highlights the employment of molecular hybridization through conjugation with other pharmacologically interesting scaffolds for enhancement of medicinal properties. Methods: The synthesis started by the preparation of N-(4-methoxy phenyl) acetamide by the acetylation of p-anisidine with acetic anhydride under solvent-free conditions. Then the product was sulfonated with chlorosulfonic acid. The synthesized sulfonylchloride was reacted with different amines under solvent-free conditions and sulfonamide-amides (3a-j) were obtained in high yield. The products were hydrolysis to the corresponding sulfonamide-amines (4a-j) in acidic conditions. Finally, the amine group was converted to the imine group in ethanol in the presence of acetic acid. The synthesized sulfonamide-amines (4a-j) have been evaluated for their in vitro antibacterial activities against two spp. of Gram positive pathogenic bacteria and 3 spp. of Gram negative bacteria. Results: A series of novel sulfonamide-imines were synthesized starting from p-anisidine with high yields under mild conditions and were screened for in vitro antimicrobial activity against two Gram-positive spp. and three Gram-negative spp. The methicillin resistant Staphylococcus aureus (MRSA) showed significant sensitivity against the compounds (( 5-((2-chlorobenzylidene)amino)-2-methoxy-N-(2-methoxyphenyl)benzene sulfonamide (5b), N-(4-bromophenyl)-5-((2-chlorobenzylidene)amino)-2-methoxybenzene sulfonamide (5d), 5-((2-chlorobenzylidene)amino)-N-(2-chlorophenyl)-2-methoxybenzene sulfonamide (5g), 5-((2-chlorobenzylidene)amino)-2-methoxy-N-phenethylbenzene sulfonamide (5i) and 5-((2-chlorobenzylidene)amino)-N-cyclohexyl-2-methoxybenzene sulfonamide (5j). Conclusion: In conclusion, we have described a facile, efficient and eco-friendly approach for the preparation of several structurally varied novel sulfonamide-imines in five steps. The reactions are characterized by simple reaction procedures, ease of separation, high yields and purity. Furthermore, the antibacterial activity of the synthesized sulfonamide-imines was evaluated against some Gram-positive and Gram-negative microorganism. The methicillin resistant Staphylococcus aureus (MRSA) showed significant sensitivity against some of the synthesized compounds.

Keywords: Sulfonamide; Imine; p-Anisidine; Antibacterial activity

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Article Details

Year: 2017
(E-pub Ahead of Print)
DOI: 10.2174/1570178614666170707152357
Price: $95