Design, Synthesis and Bioactivities of Novel Isoxazole-Containing Pyrazole Oxime Derivatives

Abstract

In this study, in order to find novel biologically active pyrazole oxime derivatives, twenty-eight new pyrazole oxime compounds containing a substituted isoxazole ring were synthesized and evaluated for their acaricidaland insecticidal activities. Bioassays exhibited that some target compounds indicated good acaricidal and insecticidal activities against Tetranychus cinnabarinus, Aphis medicaginis, Mythimna separata, and Nilaparvata lugens. Especially, compounds 9c, 9h, 9u, and 9v showed 100.00%, 90.56%, 90.78%, and 90.62% insecticidal activities against A. medicaginis at the concentration of 20 μg/mL, respectively, compounds 9k and 9u had 70.86% and 100.00% insecticidal activities against M. separata at 20 μg/mL, respectively.

Keywords: bioactivity; isoxazole; pyrazole oxime; synthesis.

Figure 1

The design of the target molecules.

Scheme 1

Synthesis of the title compounds 9a–9v. Reagents and conditions: (a) substituted phenol, KOH, DMF or DMSO, 40 °C, 2–4 h, 105 °C, 8–24 h, 52–76% for 2; (b) NH₂OH·HCl, KOH, CH₃OH, reflux, 7–22 h, 61–73% for 3; (c) dimethyl oxalate, CH₃ONa, CH₃OH, 60 °C, 6–8 h, 53–65% for 5; (d) NH₂OH·HCl, CH₃OH, 60 °C, 7–10 h, 55–60% for 6; (e) LiAlH₄, THF, 0 °C, 3–6 h, 70–76% for 7; (f) SOCl₂, DMF, CH₂Cl₂, 0 °C, 4–7 h, 73–80% for 8; (g) compound 3, K₂CO₃, Cs₂CO₃, CH₃CN, reflux, 8–19 h, 47–63% for 9.

Scheme 2

Synthesis of the title compounds 13a–13f. Reagents and conditions: (a) 4-hydroxybenzaldehyde, Cs₂CO₃, CH₃CN, reflux, 5 h, 71–77% for 10; (b) LiAlH₄, THF, 0 °C, 30 min, 68–72% for 11; (c) SOCl₂, DMF, CH₂Cl₂, 0 °C, 6–8 h, 62–65% for 12; and, (d) compound 3, K₂CO₃, CH₃CN, reflux, 10–15 h, 46–56% for 13.