A new strategy has been used to synthesize 2,3,4,4a-tetrahydroxanthen-1-one (3) in high yield. Using the Me3N-promoted domino Baylis–Hillman/oxa-Michael reaction sequence at room temperature, the reaction of salicyldehyde (1) with cyclohexanone (2) provided 3 in 88% yield, which further undergo reaction with thiosemicarbazides (4) to afford a series of new xanthene-based thiosemicarbazones (5a–5j). All the synthesized compounds were characterized by their physical and spectral data. The solid state self-assembly studies for 5d and 5i were carried out by the single crystal X-ray technique to investigate the prevalence of the thioamide dimer synthon and its role in molecular alignment in the solid state. Furthermore, the compounds (5a–5j) were tested for their antibacterial activity. The compounds 5b, 5c, 5d and 5i showed excellent antibacterial activity against one or more of the tested bacterial strains. Notably, the antibacterial activity for the compound 5c was found comparable to the standard reference drug, ciprofloxacin against Salmonella typhi.
