1,6-Bis[1-(2-chloro-5-thiazolylmethyl)-2-nitroiminoimidazolidin-3-yl]hexane and 1,3,5-tris[1-(6-chloronicotinyl)-2-nitroiminoimidazolidin-3-ylmethyl]benzene-Synthesis and insecticidal and neuroblocking activities in American cockroaches, Periplaneta americana

Abstract

A chlorothiazole-based hexamethylene divalent neonicotinoid and trivalent 1,3,5-tris[1-(6-chloronicotinyl)-2-nitroiminoimidazolidin-3-ylmethyl]benzene were synthesized, and tested for the insecticidal activity using American cockroaches by injection without (alone) and with synergists, piperonyl butoxide and propargyl propyl benzenephosphonate. The minimal lethal dose (MLD) in mol was 8.9 for the divalent compound alone, which was 4 times larger than that of the corresponding chloropyridylbased dimer. The MLD was 34 nmol for the trivalent compound, somewhat larger than for the divalent 1,3-xylenyl analog (20 nmol). The synergists combined enhanced their effectiveness about 8-20 times. Neurophysiological measurements were conducted using a nerve preparation containing the abdominal fifth and sixth ganglia of an American cockroach. The trivalent compound showed a pattern characteristic of neonicotinoids and its neuroblocking potency was 100 mM.

Furan-2,5-dimethylene-Tethered Bis-imidacloprid Insecticide Conferring High Potency

“…Synthesis. All tethered molecules were prepared by the coupling of IMI with the corresponding R,ω-bis-halide or bis-tosylate linker (route 1 in Scheme 1) except for compound 7, which was obtained by the double introduction of the chloropyridinyl group to 2,5-bis-(2-nitroiminoimidazolidin-1-ylmethyl)furan (17), which was available by a three-step reaction starting from furan-2,5-dialdehyde (route 2 in Scheme 1). The final products thus obtained were purified through column chromatography with ethyl acetate as the eluent, where the bis-IMI derivatives were completely separated from fast-eluted IMI.…”

“…Compound 7 was prepared via the intermediate 2,5-bis-(2-nitroiminoimidazolidin-1-ylmethyl )furan (17) by following procedure route 2 in Scheme 1. A solution of ethylenediamine (484 mg, 8.1 mmol) in ethanol (0.5 mL) was added to a solution of 2,5-diformylfuran (200 mg 1.6 mmol) in ethanol (2 mL).…”

“…Mass spectra were recorded at 70 eV with the JEOL JMS-700 instrument. Compounds 3 − 6 , 8 , 9 , and 11 − 16 were prepared according to the published procedure (route 1 in Scheme ) − , and the analytical data for structural confirmations are given in the Supporting Information.…”

“…Defined nAChR structure in neonicotinoid-bound state − has accordingly facilitated the receptor structure-guided ligand design quest for more effective insecticides with unique biological properties − . The bis-pharmacophore drug design approach has been applied to neonicotinoid insecticide, yielding N 3 , N 3 ′ -alkylene-tethered bis-imidacloprid (bis-IMI) derivatives (Figure ) − . The dimeric IMI analogues with hexamethylene, heptamethylene, and octamethylene linkers have plant-systemic insecticidal properties .…”

“…The dimeric IMI analogues with hexamethylene, heptamethylene, and octamethylene linkers have plant-systemic insecticidal properties . The number of bis-IMI methylene units determines the binding affinity to the insect nAChR − , , and the heptamethylene analogue showed optimal potency . The IMI dimer binds in a unique manner to the insect nAChR model wherein the chloropyridine moieties are embraced by two distinct and distant domains and the heptamethylene moiety suitably bridges these two subsites .…”