Tri- and difluoromethoxylated N-based heterocycles − Synthesis and insecticidal activity of novel F3CO- and F2HCO-analogues of Imidacloprid and Thiacloprid

Abstract

The preparation of F 3 CO-and F 2 HCO-analogues of Imidacloprid and Thiacloprid and the evaluation of their biological activity have been performed. For this purpose, a first synthetic approach allowed the preparation of a desired F 3 CO-containing key intermediate. To allow a facile access to the second F 2 HCO-containing key intermediate, the difluoromethylation of hydroxylated N-based heterocycles has been developed using difluoromethyl triflate (a liquid non-ODS reagent) under air in aqueous conditions and with very short reaction time. The broad diversity of compatible heterocycles includes a large series of substituted hydroxypyridines, but also -pyrazoles, -pyrazine, -pyridazine, and -quinolines. The couplings of both key intermediates with the required 4,5-dihydro-N-nitro-1H-imidazol-2-amine and [N(Z)]-N-2-thiazolidinylidene-cyanamide were successfully achieved using literature conditions. This work enables the preparation of valuable building blocks, which could lead to the discovery of new bioactive entities.

The Biochemical Pathways of Nicotinamide-Derived Pyridones

“…The N -methylated 6-pyridone were easily generated from their respective chloronicotinic acid precursors as were the ribosylated 6-pyridone according to published syntheses [ 6 , 29 , 30 , 31 , 32 ]. However, N -Me-2PY, 2PYR, N -Me-4PY, and 4PYR converted readily to the methylated ester instead of the amide under aqueous methanolic conditions.…”

“…1 H NMR (CDCl 3 ), δ, ppm: 8.16 (s, 1H, H6), 7.95 (dd, J = 2.44 & 2.44 Hz, 1H, H4), 6.51 (d, J = 9.56 Hz, 1H, H3), 4.25 (q, J = 7.14 Hz, 2H, -CH2), 1.28 (t, J = 7.12 Hz, 3H, Me). 13 C NMR (CDCl 3 ), δ, ppm: 165.61 (COCH 3 ), 164.00 (C2), 141.11 (C6), 139.69 (C4), 119.36 (C3), 111.44 (C5), 60.68 (-CH 2 ), 14.23 (Me) [30].…”

Late-stage difluoromethylation: concepts, developments and perspective

“…Leroux and co-workers expanded the original substrate scope reported by Hartwig to N-containing heteroaromatics. 170 They also prepared a series of OCF 2 H analogues of imidacloprid and thiacloprid, two blockbuster insecticides. Dolbier and co-workers reported that fluoroform is suitable for the difluoromethylation of phenols (15 examples, up to 88% yield) and thiophenols (4 examples, up to 76% yield).…”

Recent Progress on the Synthesis of CF2H-Containing Derivatives

“…Leroux et al developed a synthetic strategy for the preparation of hydroxy-fluorinated analogues of the insecticides imidacloprid and thiacloprid. 81 In their study, they reported on the synthetic scope for the difluoromethylation of hydroxy-pyridines, -pyrazoles, -pyrazines and -quinoline using difluoromethyl triflate as a difluorocarbene precursor in the presence of KOH to afford the corresponding products in moderate to good yields (31-76%).…”