Synthesis of New Chromenopyrimidinebenzene Sulfonate Analogs With Antibacterial Activity

ABSTRACT In this study, the synthesis of new chromenopyrimidinebenzene sulfonate derivatives was investigated. The first step of the reaction involved using 4‐hydroxy or 2‐hydroxybenzaldehyde, p ‐toluene or benzene sulfonyl chloride, and DABCO in acetonitrile to produce 2‐formylphenylbenzene ( p ‐tolyl)sulfonate derivatives. Subsequently, these derivatives were reacted with 2‐hydroxybenzaldehyde, ethyl cyanoacetate, and ammonium acetate in a deep eutectic solvent (choline chloride:urea) to synthesize chromenopyrimidine derivatives. Finally, by reacting the chromenopyrimidine derivatives with p ‐toluene or benzenesulfonyl chloride in DABCO in DMF at room temperature, new chromenopyrimidinebenzene sulfonate derivatives were obtained. Chromeno[2,3‐ d ]pyrimidine 4a and its benzenesulfonate esters 5a–5e were tested against Staphylococcus aureus and Escherichia coli . Compound 4a showed strong broad‐spectrum activity. Compound 5d containing p ‐tolyl sulfonate exhibited the highest potency against E. coli due to improved membrane permeability, while 5e was less active. Compounds 4a and 5d were identified as lead candidates for further optimization.