Synthesis and Antimicrobial Activities of Some novel 1,3,4-Oxadiazoles Carrying Alkylthio and Alkylsulphonyl phenoxy Moieties

Abstract

A series of new 2-[(4-alkylthio/alkylsulfonyl phenoxy) methyl]-5-substituted-1,3,4-oxadiazoles 4a–y , 5a–h ) have been synthesized from 4-alkylthio phenol ( 1a–b ) through a multi-step reaction sequence. Compounds 1a–b reacted with ethyl chloroacetate to give ethyl [4-(alkylthio) phenoxy] acetate ( 2a–b ) which on oxidation yielded ethyl [4-(alkylsulfonyl)phenoxy]acetate ( 2c–d ). They were readily converted to the corresponding hydrazides 3a–d , and then cyclized to the title compounds 2-{[4-(alkylthio/alkylsulfonyl) phenoxy] methyl}-5-aryl-1,3,4-oxadiazoles ( 4a–y ) by condensing with aromatic carboxylic acids. Further, 3a–b , on condensation with carbon disulphide afforded the title compounds 2-{[4-(alkylthio) phenoxy]methyl}-1,3,4-oxadiazole-5-thiols( 5a–b ), which on alkylation yielded the title compounds 2-[(4-alkylthio phenoxy) methyl]-1,3,4-oxadiazole-5-alkyl thiols ( 5c–f ), while with chloroacetic acid gave the target compounds 2-[(4-alkylthio phenoxy) methyl]-1,3,4-oxadiazole-5-thioacetic acid ( 5g–h ). The structures of new compounds 4a–5h were established on the basis of their elemental analysis and IR, ¹ H NMR, ¹³ C NMR & MASS spectral data. All the title compounds were subjected to in vitro antibacterial testing against four pathogenic strains and antifungal screening against three fungi. Preliminary results indicate some of them exhibited promising activities and they deserve more consideration as potential antimicrobials.

Keywords:

• 2-{ [4-(Alkylthio/alkylsulfonyl) phenoxy] methyl}-5-aryl-1,3,4-oxadiazoles
• 2-{[4-(alkylthio) phenoxy]methyl}-1,3,4-oxadiazole-5-thiols
• 5-{[4-(alkylthio) phenoxy] methyl}-1,3,4-oxadiazole-2-substituted thiols
• antibacterial &
• antifungal screening

We are grateful to the Heads of Chemistry Department, National Institute of Technology Karnataka, Surathkal, and Strides Research & Specialty Chemicals Ltd., New Mangalore, for providing laboratory facilities. The authors are also thankful to Prof. A. Srikrishna, IISc Bangalore and the Head, SAIF, CDRI for providing ¹H NMR, ¹³C NMR, and Mass spectral facilities.