Synthesis and Biological Activity of Some New Oxadiazoles

• Main Author: V. Nair, Deepti
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2007
• Subjects: Analgesics; Anti-inflammatory agents; Anticonvulsants; Antimicrobial agents; Biological activity; Carbon; Caustic soda; Chloride; Cooling; Dyes; Ethanol; Iodine; Medical imaging; Microbiology; Nitrogen; NMR; Nonsteroidal anti-inflammatory drugs; Nuclear magnetic resonance; Pharmaceutical sciences; Polymer chemistry; Polymers; Potassium; Radiation; Sodium; Solvents
• ISBN: 9798380222327

ObjectiveOxadiazoles have found a variety of uses as pharmaceuticals, pesticides, color developers, stabilizers in photography, dyes, protective against UV radiation, liquid solution scintillators, and thermostable polymers.Consequently, a number of synthetic approaches to the 1,3,4-oxadiazoles system have been developed and most of these involve the use of hydrazine or its derivatives.In view of the above facts, it is worthwhile to synthesis:1. A series of different oxadiazoles derivatives with different substitiuents2. Characterization by IR, 1 HNMR and mass spectroscopic method.3. Screening for antimicrobial activity.MethodologyThe starting compound ethyl{2-[(2,6-dichlorophenyl)amino]benzyl}acetate(3) and ethyl{2-[(2,6-dimethylphenyl)amino]phenyl}acetate(7) required for the synthesis of substituted oxadiazoles was prepared from{2-[(2,6-dichlorophenyl)amino] benzyl}acetic acid(diclofenac acid)(1) and {2-[ (2,6-dimethylphenyl) amino] phenyl}acetic acid(mefenamic acid)(6) respectively by the reaction with H2SO4 in ethanol for 6 hrs reflux. The compound (3) and (7) on reaction with hydrazine hydrate was refluxed for 18 hrs produced respective hydrazides, 2-{2-[(2,6-dichlorophenyl)amino]benzyl}acetohydrazide(4) and 2-{2-[(2,6-dimethylphenyl) amino]phenyl}acetohydrazide(8) The compound (4) and (8)on reaction with different substituted aromatic acids and phosphorous oxychloride undergoes cyclization furnished to oxadiazole derivatives of biological interest.ExperimentalMelting points are degree Celsius. These were determined in open capillary tubes and are uncorrected. The purity of the compounds was checked by TLC using suitable solvent system. The IR spectra were recorded on Perkin-Elmer and FT-IR 1000 spectrophotomers using KBr pellets wave numbers are expressed in cm-1HNMR spectra were recorded on ACF 200, Supercon-switzerland spectrophotometer using CDC13 or DMSO-d6 as solvent and TMS as internal standard reference, chemical shifts are expressed in δ values (ppm). The mass spectra were recorded on LCMS-2010A (SHIMADZU) mass spectrophotometers.Antimicrobial activityAll the compounds were synthesized during the course of present work have been screened for antibacterial and antifungal activities. The organisms used for antibacterial activity are Staphylococcus Epidermatitis, Escherichia Coli, Pseudomonas Aeruginosa and Bacillus Subtilis for antifungal activity are Aspergillus Niger and Candida Albicans.Oxadiazoles are five membered heterocyclic systems containing two nitrogen and one oxygen atoms, only one divalent hetero atom can be incorporated into a simple five-membered, aromatic heterocyclic. These systems are named with the nonnitrogen atom number as 1, and the positions of the nitrogen atoms shown with reference to the divalent atom 1,2,4- oxadiazoles, 1,3,4- oxadiazoles and 1,2,5- oxadiazoles are well known, but the 1,2,3- oxadiazoles system, which calculations indicate to be unstable relative to its ring-open diazoketone tautomer.Ring Synthesis:1, 2, 4- oxadiazoles can be prepared by acylation of amidoximes. A variation of this method gives a one-pot synthesis from the amidoxime, an organic and a peptide coupling agent is used. 1,2,4-oxadiazoles can also be prepared from amides via acylamidines, or via the cycloaddition of nitrile oxides to nitriles or to o-methyl oximes.