Microwave Synthesis and Preliminary Antibacterial Activities of New 5-Substituted-2-thiol/thione-1,3,4- Oxadiazoles Containing the Oxazepine and Oxazepane Moieties

Zeid Hassan Abood, Osama Hameed Rasheed, Majid Jari Mohammed

Abstract: 5- (4-aminophenyl) -2-thiol-1, 3, 4-oxadiazole 1 was synthesized via the reaction of carbon disulfide with 4-aminobenzoyl hydrazide in presence of potassium hydroxide in absolute ethanol. Compound 1 was converted to the corresponding diazonium salt which was introduced in coupling reaction with alkaline solution of 2-hydroxybenzaldehyde as coupling reagent to give azo-oxadiazole derivative 2 containing aldehyde group. The resulting aldehyde 2 was then introduced in condensation reactions with the primary aromatic amines including (4-bromoaniline, 4-chloroaniline, 2, 4-dichloroaniline, 4-nitroaniline, 3-nitroaniline, 4-methoxyaniline, 2-methoxyaniline and 4-hydroxyaniline) using microwave irradiation technique in absolute ethanol to produce eight azoimine derivatives of 1, 3, 4-oxadiazole 3a-h, respectively. Treatment of the resulting imines 3a-h with both maleic and succinic anhydrides under (2+5) cycloaddition conditions using microwave irradiation in dry benzene afforded sixteen new oxadiazoles 4a-h and 5a-h substituted with 1, 3-oxazepine and 1, 3-oxazepane moieties, respectively. Preliminary in vitro antibacterial activity of the target compounds were investigated using two types of bacteria, Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative). The results indicated that the newly synthesized oxadiazoles (compounds 4a and 5h) exhibited equipotent activities to gentamycin against Gram-positive bacteria. On the other hand, just one compound (compound 5f) showed better activity against Gram-negative bacteria when compared with that of the control drug (Gentamycin).

Keywords: Oxadiazoles, Imines, Oxazepanes, Oxazepines