- Research article
- Open Access
Synthesis, insecticidal, and antibacterial activities of novel neonicotinoid analogs with dihydropyridine
© He et al.; licensee Chemistry Central Ltd. 2013
- Received: 3 February 2013
- Accepted: 1 April 2013
- Published: 26 April 2013
Nilaparvata lugens, a major pest in rice-growing areas, is extremely difficult to manage. Neonicotinoids have increasingly been used in crop protection and animal health care against N. lugens. To discover new bioactive molecules and pesticides, we combined the active structure of cyanoacrylates, aromatic aldehydes, and substituted pyridyl (thiazolyl) methyl-2-substituted-methylidene-imidazolidine derivatives for the design and synthesis of a series of novel neonicotinoid analogs with dihydropyridine.
A series of neonicotinoid analogs with dihydropyridine were synthesized. Their structures were characterized by IR, 1H NMR, 13C NMR, and elemental analysis and their insecticidal and antibacterial activities were assessed. Preliminary biological activity tests showed that all of the title compounds feature insecticidal activities against N. lugens at 500 mg/L. Moreover, some compounds showed promising antibacterial activities against Pseudomonas solanacearum (e.g., Tobacco bacterial wilt and Tomato bacterial wilt) at a dose of 200 mg/L.
A synthetic route to obtain neonicotinoid analogs with dihydropyridine by the reaction of intermediates 2 (pyridyl (thiazolyl) methyl-2-substituted-methyl-ideneimidazolidine) and intermediates 1 (cyanoacrylates) and different aromatic aldehydes in acetonitrile under reflux conditions is presented. The effects of different solvents, bases, and reaction time on the reaction of 3a were investigated. The results of this study suggest that neonicotinoid analogs with dihydropyridine could cause N. lugens death and restrain P. solanacearum growth.
- Title Compound
- Aromatic Aldehyde
- Insecticidal Activity
- Bacterial Wilt
Yields of 3a at different reaction conditions
Structure, yield and elemental analysis data for title compounds 3a-3l
Elemental Analysis (Calcd./Found)
All of the synthesized compounds 3 were characterized on the basis of their spectroscopic data. IR absorption bands ranging were assigned as follows: 3425 to 3180 cm−1 (−CONH), 3000 to 2910 cm−1 (−CH2CH2), 1660 to 1630 cm−1 (−CO), 1560 to 1505 cm−1 (−NH2), 1368 to 1339 cm−1 (−NO2), 1220 to 1240 cm−1 (Ar–H), and 1100 to 1152 cm−1 (=CH (=CH–NO2)). In the 1H NMR spectra of 3a, the –CONH fragment displayed a singlet with a chemical shift of δ 8.21 ppm while the –CH2CH2 fragment in the imidazolidine moiety displayed a multiplet with chemical shifts ranging from δ 3.89 ppm to 4.29 ppm. Protons of –CH2 linking with a pyridine or thiazole ring were shifted downfield, ranging from δ 4.64 ppm to 4.77 ppm as a multiplet. The –CH fragment linking with C and N in the pyridine ring was shifted downfield to δ 7.47 ppm. The –NH2 fragment displayed a singlet with chemical shifts ranging from δ 7.66 ppm to 7.69 ppm.
Biological activity and structure–activity relationship
Insecticidal activities of compounds 3a to 3l against Nilaparvata lugens
The antibacterial activity of compounds 3a to 3l, Kocide against Tobacco bacterial wilt and Tomato bacterial wilt at 200 mg/L
Tobacco bacterial wilt (%)
Tomato bacterial wilt (%)
Kocide® 3000 (Cu(OH) 2 )
Melting points were determined with an X-4 digital micro-melting point meter display and are reported uncorrected. 1H NMR spectra and 13C NMR spectra were recorded with a JEOL ECX 500 NMR spectrometer at room temperature with TMS as the internal reference and DMSO-d6 as the solvent. IR spectra were recorded in KBr on a Bruker VECTOR 22 spectrometer. Elemental analyses were performed with an Elemental Vario-III CHN analyzer. Analytical TLC was performed on silica gel GF254. Column chromatographic purification was carried out using silica gel. All of the reagents and reactants were purchased from commercial suppliers and of analytical reagent grade. Intermediates 1 and 2 were prepared according to the methods described in literature [1–3, 27].
Intermediates 1 (1.25 mmol), aromatic aldehyde (1.25 mmol), and piperidine (0.10 mmol) in acetonitrile (5 mL) were refluxed with stirring for 8 h. Solutions of intermediates 2 (1.00 mmol) in acetonitrile (2 mL) were then added dropwise to the mixture of intermediates 1. The resulting solution was refluxed with stirring for 10 h until the reaction was completed. The progress of the reaction was monitored by TLC and dichloromethane/methanol was used as an eluent. The filtrate was evaporated and the residue was purified by column chromatography on silica gel (dichloromethane:methanol (v/v) = 10–20:1), yielding the corresponding products 3. Experimental details and spectroscopic data of intermediates 1 and 2 and the title compounds 3a–3l are listed in Additional file 3.
Insecticidal biological assay
P1: the mortality rate (%), K: the number of dead insects, and N: the total number of insects; Po: the blank control mortality rate (%), P2: the corrected mortality rate (%), and P t : the treatment mortality.
Antibacterial biological assay
A series of novel neonicotinoid analogs with dihydropyridine were designed and synthesized by the cyclization condensation reaction of intermediates 1 with different aromatic aldehydes and intermediates 2 in acetonitrile under reflux conditions. The effects of different solvents, bases, and reaction time on the reaction of 3a were investigated, and the best yield was obtained when intermediates 2 were treated with intermediates 1 and aromatic aldehydes in the presence of piperidine under stirring for 18 h with acetonitrile as the solvent by reflux. Antibacterial tests showed that some of the synthesized compounds possessed moderate to high activities against tobacco bacterial wilt and tomato bacterial wilt. Compound 3a revealed favorable activity against tomato bacterial wilt in vitro compared with the commercial bactericide Kocide 3000. Most of the compounds exhibited potent insecticidal activity against nilaparvata lugens. Compounds 3a, 3c, and 3e showed higher insecticidal activities than the other compounds. These primary results are promising and beneficial for further research on the development of new and more effective bactericides and pesticides. Further design studies and biological assessments of these compounds are ongoing in our laboratory.
This work was supported by the National Key Program for Basic Research (Grant No. 2010CB 126105), the Key Technologies R&D Program (Grant No. 2011BAE06B05-6), and the National Natural Science Foundation of China (Grant No. 21162004).
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