Sixteen novel pyrazole acyl thiourea derivatives 6 were synthesized from monomethylhydrazine (phenylhydrazine) and ethyl acetoacetate. The key 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl chloride intermediates 4 were first generated in four steps through cyclization, formylation, oxidation and acylation. Thess were then reacted with ammonium thiocyanate in the presence of PEG-400 to afford 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl isothiocyanates 5. Subsequent reaction with fluorinated aromatic amines resulted in the formation of the title compounds. The synthesized compound were unequivocally characterized by IR, ¹H-NMR, ¹³C-NMR and elemental analysis and some of the synthesized compounds displayed good antifungal activities against Gibberella zeae, Fusarium oxysporum, Cytospora mandshurica and anti-TMV activity in preliminary antifungal activity tests.

Background: Plant fungi (e.g., Pellicularia sasakii, Gibberella zeae, Fusarium oxysporum, and Cytospora mandshurica and Phytophthora infestans) and bacteria (e.g., Ralstonia solanacearum) are extremely difficult to manage in agricultural production. The high incidence of plant mortality and the lack of effective control methods make P. sasakii and R. solanacearum two of the world’s most destructive plant pathogens. Pathogenic fungi and bacteria are responsible for billions of dollars in economic losses worldwide each year. Thus, we designed an active amide structure and synthesized a series of novel amide derivatives containing a triazole moiety to discover new bioactive molecules and pesticides that can act against fungi and bacteria. Results: A series of amide derivatives containing a triazole moiety were synthesized. All the obtained compounds were characterized through proton and carbon nuclear magnetic resonance spectroscopy, infrared spectroscopy, and elemental analysis. Preliminary antifungal activity test showed that some of the synthesized compounds exhibited moderate antifungal activity against P. sasakii, G. azeae, F. oxysporum, C. mandshurica, and P. infestans at 50 mg/L. Compound 4u displayed more potent antifungal activity against P. sasakii and G. azeae than hymexazol. Preliminary antibacterial activity results showed that some of the synthesized compounds exhibited high anti-bacterial activity against R. solanacearum at 200 mg/L. Compounds 4m and 4q displayed high antibacterial activity against R. solanacearum, with 71% and 65% inhibitory rates, respectively. Conclusions: A series of novel amide derivatives containing 1,2,4-triazole moiety were synthesized through the reaction of intermediate 3 with different acyl chlorides and anhydrous potassium carbonates in anhydrous tetrahydrofuran at 50°C, using 2,4-dichloroacetophenoneas as a starting material. The title compounds exhibited high inhibitory effects against P. sasakii, R. solanacearum, and G. azeae.

An effective method has been developed for the preparation under mild conditions of novel pyridazine derivatives from the easily accessible starting materials mucochloric acid and benzene. All the synthesized compounds were fully characterized and some of them displayed good antifungal activities against G. zeae, F. oxysporum and C. mandshurica in preliminary antifungal activity tests.

A series of novel chiral thioureas 3a-n bearing leucine and phosphonate moieties were synthesized in excellent yields. The structures of the compounds were completely characterized by elemental analysis, IR, ¹H-, ¹³C-, ³¹P- and ¹⁹F-NMR spectral data. A half-leaf method was used to determine the in vivo protective and curative efficacies of the title products against tobacco mosaic virus (TMV). The compounds 3l and 3n displayed good in vivo protection and curative effects against TMV with inhibitory rates of 60.1, 62.8% (protection) and 56.7, 53.6% (curative) at 0.5 mg/mL, respectively. To the best of our knowledge, this is the first report on the antiviral activity of chiral thioureas containing leucine and phosphonate moieties.

Background: Ralstonia solanacearum, one of the most important bacterial diseases on plants, is a devastating, soil-borne plant pathogen with a global distribution and an unusually wide host range. In order to discover new bioactive molecules and pesticides acting on tobacco bacterial wilt, we sought to combine the active structure of hydrazone and pyridine together to design and synthesize a series of novel hydrazone derivatives containing a pyridine moiety. Results: A series of hydrazone derivatives containing a pyridine moiety were synthesized. Their structures were characterized by ¹ H-NMR, ¹³ C-NMR, IR, and elemental analysis. The preliminary biological activity tests showed that compound 3e and 3g exhibited more than 80% activity against Ralstonia solanacearum at 500 mg/L, especially compound 3g displayed relatively good activity to reach 57.0% at 200 mg/L. Conclusion: A practical synthetic route to hydrazone derivatives containing a pyridine moiety by the reaction of intermediates 2 with different aldehydes in ethanol at room temperature using 2-chloronicotinic acid and 2-amino-5-chloro-3-methylbenzoic acid as start materials is presented. This study suggests that the hydrazone derivatives containing a substituted pyridine ring could inhibit the growth of Ralstonia solanacearum.

Background: The plant pathogenic fungus (such as Gibberella zeae, Fusarium oxysporum and Cytospora mandshurica) causes devastating disease in agriculture. The pathogenic fungus is responsible for billions of dollars in economic losses worldwide each year. In order to discover new fungicidal molecule with good fungicidal activity against G. zeae, F. oxysporum, and C. mandshurica, we sought to combine the active sub-structure of hydrazone and pyrazole amide derivatives together to design and synthesize novel pyrazole amide derivatives containing a hydrazone moiety. Results: A series of novel pyrazole amide derivatives bearing hydrazone moiety were synthesized. Their structures were characterized by ¹ H-NMR, ¹³ C-NMR, IR, and elemental analysis. The preliminary biological assays revealed that most of the synthesized compounds exhibit favorable antifungal activities against G. zeae. The activity of compounds 7a, 7f, 7g, 7h, 7i, 7j, 7l and 7q were 40.82%, 47.78%, 50.32%, 40.82%, 49.05%, 48.73%, 40.19% and 45.89%, respectively, and the synthesized compounds showed certain antifungal activities against F. oxysporum and C.mandshurica. Conclusion: A practical synthetic route to pyrazole amide derivatives containing a hydrazone moiety were synthesized by the condensation of intermediates 5-chloro-N-(4-subsititued-2-(hydrazinecarbonyl)-6-methylphenyl)-1,3-dimethyl-1 H-pyrazole-4-carboxamide with different aldehydes or ketones in ethanol at room temperature is presented, the results of the study suggested that the pyrazole amide derivatives containing hydrazone moieties could inhibit the growth of G. zeae, F. oxysporium and C. mandshurica to a certain extent.