Fluorine-Containing Agrochemicals CH3SO2 O
129 CH3SO2 O
Soil or plant CF3
CF3 metabolism
N
O
NC O
Isoxaflutole
Fig. 7. Metabolic conversion of the herbicide isoxaflutole to its active form.
2.1.1.2. Insecticides GABA insecticides. The N-phenylpyrazole insecticide fipronil, launched in 1993 by Rhone-Poulenc [41], is among the most successful insecticides introduced in over a decade.1 A highly versatile insecticide, it is effective against a broad spectrum of insect pests that are detrimental to crops, animals, and public health. Fipronil acts at the gamma-aminobutyric acid (GABA) receptor to block the chloride channel [42]. The product is sold as Terminators for termite control, and as Frontlines for flea and tick treatment in dogs and cats. According to the 2002 Phillips McDougall report, sales of Frontlines in 2001 were $358 million. One approach to the introduction of the trifluoromethylsulfinyl group in fipronil involves the reaction of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole and trifluoromethylsulfinyl chloride in toluene (Fig. 8) [43]. Exposure of fipronil to sunlight results in the extrusion of sulfur oxide, to give a 4-trifluoromethylpyrazole photoproduct derivative [44]. Insect growth regulators. Initially discovered in the mid-1970s, insect growth regulators (IGRs) act by inhibiting chitin synthesis in insects [45,46]. This interesting class of insecticides offers an alternative to known neurotoxic insecticides. It was originally discovered by serendipity by Dutch researchers at PhilipsDuphar in the 1970s, while they were working with the herbicides diuron and dichlobenil. Initial attempts to create a new herbicide by combining the structural features of these two herbicides failed, with the end hybrid product, shown in Fig. 9, not effective as a herbicide. Instead, the benzoyl urea turned out to have insecticide activity and exhibited unique insect symptomology [47]. A number of representatives in this class of insecticides have a N-benzoyl-N0 phenyl urea group, where the benzoyl ring has halogens in the 2 and 6 positions, and substitution in the phenyl ring varies widely from molecule to molecule. One, flufenoxuron (Cascades, Europes, Sigonas) [48], commercialized in 1993, controls insect and mite pests in vegetables, vines, citrus, cotton, and other crops. Another, bistrifluron (Hanaros) [49], is an experimental insecticide with controlling activity against lepidopterous and whiteflies in fruits.
1 [Note of the Editor: A recent article by A. Lattes and B. Sillion on the effects of Fipronil appeared in ‘‘Actualite´ Chimique’’ 294, pp. 6– 10, 2006].