Convenient synthesis of the 2,5-di-substituted 1,3,4-oxadiazole derivatives under microwave

We have reported some novel 1,3,4-oxadiazole synthesized by conventional method as well as microwave assisted method. The reaction of different substituted cinnamic acid 2a-o with 2-(4-chlorophenyl) acetohydrazide by using phosphoric anhydride as catalyst, yielded a series of 2,5-di-substituted 1,3,4-oxadiazole 6a-o. The structures of all synthesized compounds are well characterized by Mass, FT-IR, 1 H NMR, 13 C NMR and elemental analysis. After obtaining experimental data regarding the yield and the time taken for the synthesis by both the methods, conventional and microwave assisted method, it was proved that the microwave assisted method is convenient for synthesis of this type of 2,5-di-substituted 1,3,4-oxadiazole 6a-o.


INTRODUCTION
In the field of synthetic organic chemistry, major challenges are to develop the new method for the synthesis of five member heterocyclic compounds. Literature survey reveals five member 1,3,4-oxadiazole derivatives, which belong to an important group of heterocyclic compounds, have been the issue of wide-ranging study in the recent time. Various reports have displayed their chemistry and use [1][2][3].
However, some of these newer reported also suffer from drawbacks such as they require to heat reactants for an extended periodic time at elevated temperatures, awkward product isolation procedure, and environmental pollution. Moreover, the yield is frequently only moderate or low.
In previous we have reported this type of compounds by using phosphorous oxychloride [14], but we have observed that use of phosporic anhydried is better than phosphorous oxychloride. In view of the above-mentioned findings, the purpose of the present work was to investigate the new methodologies for the one pot synthesis of 1,3,4oxadiazole with high yield and lesser reaction time.

MATERIAL AND METHOD
Melting points were determined in open glass capillaries. Infrared spectra were recorded on a Shimadzu FT-IR-8400 spectrometer using KBr pellet method. 1 H NMR and 13 C NMR spectra were recorded on a Bruker Advance 400 MHz NMR Spectrometer using DMSO-d 6 as a solvent and TMS as a Internal standard. The type of signal is indicated by following letter: s = singlet, d = doublet, t = triplet, dd = doublet of doublet, q = quartet, m = multiplet. Mass spectra were recorded on Shimadzu GC-MS-QP-2010 model using Direct Injection Probe technique. Microanalysis was performed on Euro EA Elemental Analyser. Reaction was monitored by thin-layer chromatography (TLC).
A mixture of different substituted aromatic aldehyde (0.01 mol) and malonic acid (0.015 mol) was taken in pyridine (15 ml) and catalytic amount of piperidine was added. The reaction mixture was refluxed for 6 hours. After the completion of reaction, the reaction mass was poured on to the crushed ice: HCl (1:1) solution. Filtered the separated product and wash with diluted HCl and crystallized from methanol. The product was enough pure and taken for next step without further purification. Yield 75 % to 88 %.
A mixture of 2-(4-chlorophenyl) acetic acid was taken in methanol and adds few drops of H 2 SO 4 and refluxes it about 8 hours. Then cool the reaction mixture and poured into crushed ice, filter the separated product and use it for further step without purification.
A mixture of 2-(4-chlorophenyl) acetic ester (0.1 mol) and hydrazine hydrate (20 ml) was stirred at room temperature for 4 hours. TLC using solvent system Chloroform monitored the reaction progress: methanol (9:1). Separated product was filtered and washed with water. Recrystallized from acetic acid. Yield was 83 %
The obtained solid mass was further washed with 50 ml 10 % solution of sodium bicarbonate and followed by wash with 50 ml deminaralized water. The resulting compound was purified by column chromatography by silica gel 230-400 mesh using ethyl acetate: hexane (4: 6 v/v) as eluent. Yield : 75 %. ILCPA Volume 30 Scheme 1 a) Pyridine, Pipyridine (Catalyst), reflux for 6 hrs.