Microwave assisted synthesis of 2,5-distyryl-1,3,4-oxadiazole derivatives as anti microbial agents

A new series of 2,5-distyryl-1,3,4-oxadiazoles derivatives have been synthesized from cinnamic hydrazide on reaction with various cinnamic acid derivatives. The structures of synthesized compounds have been elucidated by spectral studies like IR, 1 HNMR, Mass and also Elemental Analysis. Furthermore, all synthesized compounds were screened for in vitro anti microbial activity against the gram positive ( Staphylococcus aureus , Pseudomonas aeruginosa ) and gram negative ( Escherichia coli ) bacterial strain. In which some the compounds show potential inhibition against the test organisms.


INTRODUCTION
Oxadiazole exists in different isomeric form such as 1,2,4; 1,2,3; 1,2,5 and 1,3,4. Particularly 1,3,4-oxadiazole ring was thermally stable and have played an important role in medicinal chemistry. They are building blocks for the synthesis of biologically active scaffold. Various remarkable biological activity of 1,3,4-oxadiazoles derivative were reported in literature such as antimicrobial [1][2][3], antifungal [4,5], anticonvulsant [6], Monoamine oxidase inhibitor [7] and anti-proliferative [8], Hypoglycemic [9] and also they are very good bio isosteres of esters and amides, which can contribute significantly in increasing pharmacological activity by in hydrogen bonding interaction with the receptors [10]. B. Narayana and et al have reported synthesis via modified Fischer Indole method and the antiinflammatory activity [11]. The synthetic adaptability of 1,3,4-oxadiazole has led to the wide-ranging use of this compound in organic synthesis and have attracted the researcher to work on this type of scaffold and study their biological application.
Therefore, considering that the cinnamic acid derivatives and 1,3,4-oxadiazole are important building blocks for the development of new series of heterocycles for pharmacological interest, we have embarked upon development of various new 1,3,4oxadiazole derivatives which have been described in following sections.

EXPERIMENTAL
Melting points of the synthesized compounds were taken in open capillaries tubes. The purity of the compounds was checked by thin layer chromatography (TLC). The IR spectra were recorded on a Perkin-Elmer 1800 FTIR spectrometer in KBr pellets. The 1 HNMR spectra were recorded in DMSO-d 6 solutions on a Bruker Avance Ultra shielded 400 MHz NMR spectrometer using TMS as the internal standard. The mass spectra were recorded on a Shimadzu GCMS-QP 1000 EX. Elemental analysis of the all the synthesized compounds were carried out in Euro EA 3000 Elemental Analyzer and the results are in agreements with the structures assigned. The necessary chemicals were purchased from Spectrochem, Sisco, Loba Chemie, and Sigma Aldrich.
Substituted aromatic aldehyde (10 m mol), malonic acid (15 m mol), piperidine (4 m mol) and pyridine as solvent were taken in 100 ml two necked round bottom flask and refluxed for 6 hours. After the completion the reaction, the reaction mixture was allowed to cool ambient temperature and it was poured on to the mixture of 1:1 HCl: cold water. The separated product was filtered and washes with diluted HCl and crystallized from methanol. The product was enough pure and taken for next step without further purification. Yield 75 % to 88 %.
Cinnamic acid (0.1 mol) was taken in dried 250 ml RBF and cooled it to 0-5 °C then thionyle chloride (12 ml) was added drop wise with the time period of 40 minute and stirred for 1 hour. Excess thionyle chloride was distilled off under reduced pressure and then added hydrazine hydrate (0.1 mol). After the addition of hydrazine hydrate, reaction mixture was stirred at ambient temperature for 2 hour. The progress and the completion of the reaction were checked by thin layer chromatography. After completion of reaction, reaction mass was poured on to the crushed ice, filtered separated product and washed with cold water. Product was crystallized from glacial CH 3 COOH. M.P. 116-118 °C, Yield was 89 %.
International Letters of Chemistry, Physics and Astronomy Vol. 29

CONCLUSION
In present report , we have developed an efficient, simple, rapid and eco-friendly microwave-indused method for preparation of asymmetric 2,5-disyryl-1,3,4-oxadiazole derivatives which give the higher yield and also redused the reaction time. From the result of biological data, compound 5g, 5h, 5n, showed excellent activity against Staphylococcus aureus, while compound 5e and 5k showed maximum bacterial activity against Pseudomonas aeruginosa and compound 5o, 5h maximum activity against Escherichia coli. Antibacterial activity was compared with ofloxacin as a standard drug. All the compounds were less potent than the standard drugs ofloxacin. The compound having the halogen group shows greater antimicrobial activity.