Synthesis of Novel Coamarin Derivatives as Potential Antibacterial Agents

Compounds containing a coumarin, a thiazoline, a their zolidinone or an oxazole moiety may have a variety of biological effects, including antimicrobial activity. The search for developing novel heterocyclic antimicrobial agent that has a potent activity, led the authors to prepare series of coumarinyl thiazolines, coumarinyl thiazolidines and oxazolocoumarins.Coumarinyl thiazolines and thiazolidinones (VI, VII) :These were obtained by the elaboration of thiazoline or thiazolidine rings on a substituted-8-aminocoumarin. Reduction of 7-ethoxy-8-nitrocoumarin (III), obtained by the etherification of 0-hydroxynitroccumarin (IIb), yielded 8-aminoderivative (IV), which on condensation with different isothiocyanates afforded the corresponding 8-substituted thiouriedocumarins (V). Condensation of these thioureas with different a-haloketones was found to give the designed compounds (VII). On the other hand, reaction of haloacetic acid derivatives and the intermediates (V) to give 2-alkylimino-5-substituted-3-(7-ethoxy-4-methylcoumarin-8-yl)-thiazolidin-4-ones (VII) was carried out.Oxazolocoumarins (X-XIX) :Vic-aminohydroxycoumarins (VIII a, b) , the key starting materials, were subjected to various reactions to yield 2 or 3-substituted-oxazolocumarins.2-Amino-derivative (x) was either obtained from (VIIIb) by reaction with cyanogens bromide or from 9-thiouriedocums in (IX), the condensation product of 8-amino-7-hydroxy-4-methylocumarin (VIIIb) and potassium thiocyanate, by treatment with lead oxide.2-Oxo-oxazolocumarin (XI) was prepared through fusion of urea with (VIIIb) or by acid hydrolysis of the preceding 2-amino analogue (x). A series of N-substituted derivatives (XII) was obtained by alkylations of (XI) with various alkyl halides.