# 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
An analysis of the inhibitory effect on mold growth was carried out by treating with nonbytotoxic concentrations of 5-(2-aroyl)aryloxymethyl-2-phenyl-1,3,4-oxadiazole derivatives for about 6 h before sowing in pots containing a mixture of soil, sand and manure inoculated with 40,000 zoospor/mL of pathogen. _Metalaxyl-M_ was used as a reference compound--a widely used substance for the prevention of downy mildew. The research showed that none of the 5-(2-aroyl)aryloxymethyl-2-phenyl-1,3,4-oxadiazol derivatives was phytotoxic for Pearl Millet seeds. The prevalence of downy mildew in seeds treated with 1 g/kg of seeds of compound **46a** was 65% under greenhouse conditions and 48% under field conditions. The control sample treated with sterile distilled water and methanol was 92% infected. The remaining compounds (**46b-e**) showed no activity against downy mildew [106]. Another example of the use of microwave radiation in the synthesis of 5-aryl-2-(2-methyl-4-nitro-1-imidazolomethyl)-1,3,4-oxadiazol derivatives (Scheme 11) was presented by [PERSON] et al. In carrying out the cyclization reaction, the substrate in the form of 2-methyl-4-nitro-1-imidazoloacetyldrazide (**50**), obtained in a two-step sequence of transformations starting from 2-methyl-4-nitro-imidazole (**47**), was used. In the first step, imidazole was reacted with ethylchloroacetate (**48**) in dry acetone against potassium carbonate to give imidazole acetate (**49**), which was reacted with hydrazine hydrate. The main stage of the synthesis, with the use of microwave radiation, was carried out with carboxylic acid derivatives and phosphorus oxychloride. The acid/hydrazide mixture was ground, a few drops of POCl\({}_{3}\) were added and the mixture was reacted in a 160 W microwave oven for about 5 min. The obtained crude products were purified by recrystallization from ethanol:DMF to give the final 5-aryl-2-(2-methyl-4-nitro-1-imidazolomethyl)-1,3,4-oxadiazol derivatives (**51a-l**) with a yield of 54-75%. The advantages of using microwave radiation include the fast reaction time and the absence of organic solvents [107]. The obtained 5-aryl-2-(2-methyl-4-nitro-1-imidazolomethyl)-1,3,4-oxadiazol derivatives were tested for antibacterial activity against four strains of bacteria, i.e., _Staphylococcus aureus_ (G+), _Klebsiella pneumoniae_ (G-), _Escherichia coli_ (G-) and _Pseudomonas aeruginosa_ (G-), and antifungal activity against _Aspergillus flavus_, _A. fumigatus_, _Penicillium_, _Trichophyta_, by the cup-plate method. Among the tested compounds, derivatives **51e**, and **51l** showed good activity against _E. coli_, _P. aeruginosa_, and _K. pneumoniae_ bacteria, and moderate activity against S. aureus. Moreover, derivative **51h** showed good activity against _E. coli_, and _P. aeruginosa_. Compound **51j** also showed moderate potency against _S. aureus_. When tested for antifungal activity, the **51d** molecule showed good potency against all fungi. Compound **51f** showed great activity against _A. flavus_, and _Penicillium_. Additionally, **51j** showed effective potency against _A. fumigatus_, and moderate activity against _Trichopython_. Compounds **51g** and **51i** were moderately active against _Penicillium_, and _Trichopython_. Studies related to the anti-inflammatory effects of 5-aryl-2-(2-methyl-4-nitro-1 imidazolomethyl)-1,3,4-oxadiazol derivatives were also carried out. For this purpose, the Winter method was used, which is based on the induction of edema with formalin. Rat paw volume was measured with a Buttle apparatus. Studies confirmed that all compounds exhibited anti-inflammatory effects at doses of 50 mg/kg body weight. The anti-inflammatory effects of derivatives **51b**, **51c**, and **51d** were comparable to that of _Indomethacin_ at doses of 1-5 mg/kg [107].