Synthesis And Antibacterial Activities Of O-Hydroxy Phenyl Pyrazoles And Their Intermediates

Eighteen compounds were designed and synthesized by combining o-hydroxyl pheny,pyrazole and phenylhydrazone group, according to the superposition principle of biological activities. Twelve compounds and antibacterial-activity of eighteen compounds have not been reported so far. The structures of all compounds were confirmed by 1H NMR,IR and elemental analysis.Substituted aniline was diazotized and subsequently reduced to give substituted phenylhydrazine, acetophenone arylhydrazone were obtained by the condensation of acetophenone with substituted phenylhydrazine, reacted with N,N-dimethylformamide,phosphorus oxychloride, l-aryl-3-phenyl-4-formylpyrazoles were obtained. Then reacted with salicylic hydrazide to obtain N-[(1-aryl-3-phenyl-pyrazol-4-yl)methylene]-2-hydroxybenzohydrazide (I4a-I4f), verified and deduced the reaction mechanism of acquiring the1-aryl-3-phenyl-4-formyl-pyrazoles(I3a-I3f), revealed the realationships between cyclization reaction activities and electronic effect of the 1- phenyl ring substituent.Substituted aniline was diazotized and subsequently reacted with ethylacetoacetate, then condensed with salicylic hydrazide to obtain 3-(2-hydroxybenzoylhydrazono)-2-(2-phenylhydrazono)-ethyl butanoates(II3a-II3f). 1-(2-Hydroxybenzoyl)-3-methyl-4-substitued phenylhydrazono-pyrazolones(III4a-III4f) were acquired by intramolecular cyclization reaction of compounds II3a-II3f. The reaction mechanism of acquireing target compounds showed compounds II3a-II3f were difficult to maintain in acidic medium, but generated compounds III4a-III4f with rapid cyclization. So, preparation of compounds II3a-II3f should be in neutral or weak alkaline solution, but preparation of compounds II3a-II3f had better be in the acdic medium.The result of preliminary bioassay showed that the inhibitory rates against Monilia albican and Escherichia coli of N-[(1-aryl-3-phenyl-pyrazol-4-yl)methylene]-2-hydroxybenzohydrazide and 1-(2-hydroxybenzoyl)-3-methyl-4-substituted phenylhydrazono-pyrazolone compounds were high to 100 % at 0.01% mass concentration, which displayed excellent antibacterial activities. The inhibitory rates against Staphlococcus aureus were over 70%, which exhibited a certain extent antibacterial activities. inhibitory rates against Escherichia coli ofII series compounds(II3b,II3c) were high to 100 % at 0.01% mass concentration, which displayed excellent antibacterial activities. The inhibitory rates against Monilia albican and Staphlococcus aureus were over 70%, which exhibited a certain extent antibacterial activities.The analysis of structure–activity relationships showed that the antibacterial activities of compounds were reduced by electron-donating and electron-withdrawing groups of the phenyl ring, such as -OCH₃,-NO₂,-CH₃. The antibacterial activities of compounds with -OCH₃ and -CH₃ is lower than compounds with the -NO₂. the antibacterial activities of compounds were enhanced by the halogen groups of the phenyl ring, and the antibacterial activities of p-substitued compounds is higher than 0-substitued. Furthermore, the antibacterial activities of the compounds II3a-II3f,III4a-III4f were significantly different. Compared with compounds II3a-II3f, the antibacterial activities of III4a-III4f were significantly enhanced.