# Synthesis and Biological Activity of 1,3,4-Oxadiazoles Used in Medicine and Agriculture
## 5 Investigation of the Synthesis of New, Biologically Active 1,3,4-Oxadiazoles
proposed two methods of obtaining 2-(2-arylethenyl)-1,3,4-oxadiazole derivatives (Scheme 9). The first was based on the use of the appropriate 3-aryacrylhydrazides (**41a-d**) and an aromatic aldehyde which were reacted with \(p\)-toluenesulfic acid (\(p\)-TsOH), and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in the presence of dry toluene. The reaction mixture was heated to reflux until the starting hydrazide was completely consumed. The obtained final products were purified by silica gel column chromatography (benzene:EtOAc 3:1) to give the 2-(2-arylethenyl)-1,3,4-oxadiazol derivatives (**42a-k**) with 69-96% yields. The second method was based on dissolving the 3-aryacrylhydrazide in a mixture of the appropriate triethyl orthoester and glacial acetic acid. The reaction mixture was held at reflux until the substrate disappeared completely. The crude products were purified by recrystallization from benzene/hexane to give the final products (**42l-o**) with 74-92% yields. The advantages of using these methods for the preparation of 1,3,4-oxadiazol include a reaction time of 3-7 h and high yields of the final products [105]. The obtained 2-(2-arylethenyl)-1,3,4-oxadiazol derivatives were tested in vitro for their antibacterial and antifungal activity using the broth microdilution method in accordance with the standards of the European Committee on Antimicrobial Susceptibility Testing (ECAST) and the Clinical and Laboratory Standards Institute (CLSI). Tests were performed against Gram-positive bacteria (_Staphylococcus aureus_ ATCC 25923, _Staphylococcus aureus_ ATCC 43300, _Staphylococcus aureus_ ATCC 6538, _Staphylococcus epidermidis_ ATCC 12228, _Bacillus subtilis_ ATCC 6633, _Bacillus cereus_ ATCC 10876 _Microoccus luteus_ ATCC 10240), Gram-negative bacteria (_Escherichia coli_ ATCC 25922, _Klebsiella pneumoniae_ ATCC 13883, _Proteus mirabilis_ ATCC 12453, _Bordetella bronchiseptica_ ATCC 4617, _Salmonella typhimurium_ ATCC 14028, _Pseudomonas aeruginosa_ ATCC 9027) and fungi (_Candida albicans_ ATCC 2091, _Candida albicans_ ATCC 10231, _Candida parapsilosis_ ATCC 22019). Commercially available _Ciprofloxacin_ with antimicrobial activity and _Fluconazole_ with antifungal activity were used as reference compounds. The studies showed that the obtained compounds **42a-f**, **h-j** and **n-o** did not exhibit an inhibitory effect on the growth of all bacterial strains. The broadest spectrum of antibacterial activity was shown by the derivative of 5-ethyl-2-[2-(2-thienyl)]thehenyl!- 1,3,4-oxadiazole (**41l**). The remaining compounds, i.e., **42g**, **42k**, and **42m**, showed moderate antibacterial activity against Gram-positive and Gram-negative bacteria. In the studies devoted to antifungal activity, compound **411** showed the best activity against all _Candda_ spp. Compounds **42f** and **42m** showed mild activity against some of the tested _Candida_ spp. species. The remaining oxadiazoles were inactive [105]. [PERSON] et al. proposed a method for the synthesis of 5-(2-aroyl)aryloxymethyl-2-phenyl-1,3,4-oxadiazole derivatives with the use of microwave radiation. The cyclization reaction was carried out on the previously obtained hydrazide derivatives (**45a-e**), obtained by a standard procedure using hydrazine dissolved in ethanol (Scheme 10). The main synthesis step was performed using benzoic acid and clay, which were mixed with the hydrazide by means of a vortex mixer. The prepared mixture was irradiated in an unmodified domestic microwave oven at 50% power for about 10 min. After extraction, pure 5-(2-aroyl)aryloxymethyl-2-phenyl-1,3,4-oxadiazole derivatives (**46a-e**) were obtained with a yield of 70-78%. The advantage of this method is the fast reaction time and the limited use of organic solvents [106]. The activity of 5-(2-aroyl)aryloxymethyl-2-phenyl-1,3,4-oxadiazole derivatives was tested against the downy mildew pathogen (_Sclerospora graminicola_) in Pearl Millet (_Pennisetum glaucum_). Initial phytotoxicity studies were also conducted by assessing seed germination and seedling vigour.