Design, Synthesis, and Biological Activities of Novel 1,3,5-Trimethylpyrazole-Containing Malonamide Derivatives.

Qi-Bo Li,Tong Feng,Shang-Zhong Liu,Min Liao,Zhi-Yuan Xu,Chang-Hui Rui,Qing Liu

doi:10.3390/molecules24030562

Abstract

New 1,3,5-trimethylpyrazole-containing malonamide derivatives based on pyflubumide were designed, synthesized, and characterized using 1H-NMR, 13C-NMR, and high-resolution mass spectra (HRMS). The results of preliminary bioassays showed that the target compounds possessed good activities against Tetranychus cinnabarinus, Plutella xylostella, and Aphis craccivora. Most of the target compounds exhibited moderate to good acaricidal activity against Tetranychus cinnabarinus at a concentration of 400 µg/mL, and some showed moderate activity at a concentration of 200 µg/mL; in particular, compounds 8m and 8p exhibited 70.0% mortality. In addition, some of the target compounds exhibited good insecticidal activities against Plutella xylostella at a concentration of 200 µg/mL, especially compounds 8i and 8o, which achieved 100.0% mortality at a concentration of 100 µg/mL. Interestingly, some of the target compounds exhibited potent anti-aphid activity against Aphis craccivora at a concentration of 200 µg/mL; furthermore, compounds 8p and 8q demonstrated 100.0% anti-aphid activity at a concentration of 50 µg/mL. The preliminary analyses of the structure–activity relationships (SAR) indicated that the acaricidal and insecticidal activities varied significantly depending on the type of substituent and substitution pattern, which provides guidance for the further investigation of such structural modifications.

Highlights

The synthetic route to the target compounds 8a~8t is outlined in Scheme 1; these compounds were prepared in four steps
The examination of the base, solvent, and temperature led to the following informative observations: (i) potassium t-butoxide was the ideal base; (ii) N-methyl pyrrolidone (NMP) was the suitable solvent; (iii) the product yield was highest at 0 to 5 ◦ C
It was observed that the steric effect and electronic effect of substituents (R2 ) had a significant effect on the yield of target compounds

Summary

Introduction

Amide bonds are an important functional group in many of the active ingredients of agrochemicals, such as the representative amide herbicides acetochlor and metolachlor [1,2]and the succinate dehydrogenase inhibitor (SDHI) fungicides boscalid and thifluzamide [3,4,5].The nitrogen-containing heterocycle pyrazole ring is important in the field of medicinal chemistry [6,7,8], and endows many pesticide molecules with versatile biological activities, as exemplified by fipronil, tebufenpyrad, pyraclostrobin, and pyroxasulfone [9,10,11,12,13].Due to the discovery of the excellent performance of flubendiamide A (Figure 1), chlorantraniliprole B (Figure 1), and pyflubumide (Figure 2) against pest insects and phytophagous mites in crop protection and their subsequent commercialization, the design and synthesis of new compounds containing diamide groups has become a major trend in the search for potential compounds with insecticidal and acaricidal activities [14,15].Molecules 2019, 24, 562; doi:10.3390/molecules24030562 www.mdpi.com/journal/moleculesMolecules 2018, 23, x FOR PEER REVIEW (D). Amide bonds are an important functional group in many of the active ingredients of agrochemicals, such as the representative amide herbicides acetochlor and metolachlor [1,2]. The nitrogen-containing heterocycle pyrazole ring is important in the field of medicinal chemistry [6,7,8], and endows many pesticide molecules with versatile biological activities, as exemplified by fipronil, tebufenpyrad, pyraclostrobin, and pyroxasulfone [9,10,11,12,13]. Due to the discovery of the excellent performance of flubendiamide A (Figure 1), chlorantraniliprole B (Figure 1), and pyflubumide (Figure 2) against pest insects and phytophagous mites in crop protection and their subsequent commercialization, the design and synthesis of new compounds containing diamide groups has become a major trend in the search for potential compounds with insecticidal and acaricidal activities [14,15].

Methods

Results

Conclusion