We report here the characterisation of eight newly synthesized thioureides of 2-(4-chlorophenoxymethyl)-benzoic acid and the evaluation of the in vitro antimicrobial activity of the new compounds against Gram-positive [Listeria monocytogenes, Staphylococcus aureus, Bacillus subtilis], Gram-negative [Psedomonas aeruginosa, Escherichia coli, Salmonella enteritidis], as well as Candida spp., using both reference and clinical multidrug resistant strains to establish the minimal inhibitory concentration (MIC) values. Our results showed that the tested compounds exhibited specific antimicrobial activities, both concerning the spectrum of antimicrobial activity and the corresponding MIC values, which ranged widely between 1024 and 32 μg/mL, depending on the nature and position of the substituents on the benzene ring. The most active compounds were N-[2-(4-chlorophenoxymethyl)-benzoyl]-N'-(2,6-dichlorophenyl)-thiourea (5g) and N-[2-(4-chlorophenoxymethyl)-benzoyl]-N'-(4-bromophenyl)-thiourea (5h), which showed a broad spectrum of antimicrobial activity against enterobacterial strains (E. coli and S. enteritidis), P. aeruginosa, S. aureus and Candida spp. All the tested compounds except 5f were highly active against S. aureus (MIC=32 μg/mL), suggesting their possible use in the treatment of MRSA infections. Four of compounds also exhibited antifungal activity (MIC =256-32 μg/mL) against C. albicans, but L. monocytogenes as well as B. subtilis were resistant to all tested compounds. Our studies thus demonstrated that among other biological activities, the thioureides of 2-(4-chlorophenoxymethyl)-benzoic acid also exhibit selective and effective antimicrobial properties that could lead to the selection and use of these compounds as efficient antimicrobial agents, especially for the treatment of multidrug resistant infections.

Thioureides (IV) (8 examples) are obtained in a condensation reaction of 2‐thenoyl‐isocyanate with heterocyclic amines under optimized conditions.

Thioureides of 2-(4-methyl-phenoxymethyl)benzoic acid have been synthesised by reaction of 2-(4-methyl-phenoxymethyl)benzoyl isothiocyanate with primary aromatic amines. The mentionated isothiocyanate was obtained in the reaction of the 2-(4-methyl-phenoxymethyl)benzoic acid chloride with ammonium thiocyanate. The acid chloride was prepared by reacting the coresponding acid, the 2-(4-methyl-phenoxymethyl)benzoic acid, with thionyl chloride and the aforementioned acid from potassium para-cresolate with phtalide. The reaction conditions were established to ensure the best yields. These new thioureides have been characterized by means of elemental analysis, IR and NMR spectral studies.

It is well known that many compounds bearing thioureide structure have been reported to have antimicrobial activity and some of these thioureide compounds are found to be associated with other therapeutical activities. The present application is a continuation of our research concerning the synthesis and characterization of 2-(4-methyl-phenoxymethyl)benzoic acid thioureides with antimicrobial activities. The new thioureides were obtained in three stages. In the first stage we prepared the 2-(4-methyl-phenoxymethyl)benzoic acid by reacting potassium para-cresolate with phtalide. The second stage consists in the synthesis of the 2-(4-methyl-phenoxymethyl)benzoic acid chloride and, in the third phase, the acid chloride aforementioned is refluxed with ammonium thiocyanate the resulting 2-(4-methyl-phenoxymethyl)benzoyl isothiocyanate being treated with primary aromatic amines to obtain the new compunds. We established the optimal reaction conditions for the new compounds synthesizing process of with high purity and yields. The new compounds, which are not mentioned in the literature concerning this domain, have been characterized by their physical properties (melting point, solubility) and the structures were confirmed by elemental analysis, 1H-NMR, 13C-NMR and IR spectral methods.

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