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 the 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 hydrolysed 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 Grampositive
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 Grampositive
and Gram-negative microorganism. The methicillin resistant Staphylococcus aureus (MRSA)
showed significant sensitivity against some of the synthesized compounds.