Alfred Rindlisbacher

The discovery of thiamethoxam: a second-generation neonicotinoid†

Neonicotinoids represent a novel and distinct chemical class of insecticides with remarkable chemical and biological properties. In 1985, a research programme was started in this field, in which novel nitroimino heterocycles were designed, prepared and assayed for insecticidal activity. The methodology for the synthesis of 2-nitroimino-hexahydro-1,3,5-triazines, 4-nitroimino-1,3,5-oxadiazinanes and 4-nitroimino-1,3,5-thiadiazinanes is outlined. Bioassays demonstrated that 3-(6-chloropyridin-3-ylmethyl)-4-nitroimino-1,3,5-oxadiazinane exhibited better insecticidal activity than the corresponding 2-nitroimino-hexahydro-1,3,5-triazine and 4-nitroimino-1,3,5-thiadiazinane. In most tests, this compound was equally or only slightly less active than imidacloprid. A series of structural modifications on this lead structure revealed that replacement of the 6-chloro-3-pyridyl group by a 2-chloro-5-thiazolyl moiety resulted in a strong increase of activity against chewing insects, whereas the introduction of a methyl group as pharmacophore substituent increased activity against sucking pests. The combination of these two favourable modifications led to thiamethoxam (CGA 293 343). Thiamethoxam is the first commercially available second-generation neonicotinoid and belongs to the thianicotinyl sub-class. It is marketed under the trademarks Actara for foliar and soil treatment and Cruiser for seed treatment. The compound has broad-spectrum insecticidal activity and offers excellent control of a wide variety of commercially important pests in many crops. Low use rates, flexible application methods, excellent efficacy and the favourable safety profile make this new insecticide well-suited for modern integrated pest management programmes in many cropping systems.

Synthesis and insecticidal activity of CGA 293′343 – a novel broad-spectrum insecticide

CGA 293′343 is a novel broad-spectrum insecticide currently under world-wide development by Novartis Crop Protection. CGA 293′343 belongs to a new class of highly active compounds – the neonicotinoids – and provides excellent control of a wide variety of commercially important pests. It possesses contact, stomach and systemic activity. The long-lasting residual effect is a special benefit of this compound. In general, CGA 293′343 shows biological activity in the laboratory equal to or better than the neonicotinoids so far introduced to the market. Synthetic aspects, structure–activity relationships and the biological profile are discussed. © 1999 Society of Chemical Industry

Synthesis and structure-activity relationships of benzophenone hydrazone derivatives with insecticidal activity.

A broad range of benzophenone hydrazone derivatives was prepared and tested against selected chewing insect pests, allowing the analysis of structure-activity relationships. Good activity was found only when the aromatic rings were substituted at the 4-positions with an halogen atom and a triflate or perhaloalkoxy group. In contrast, a number of substituents on the hydrazone part led to active compounds, the best results being achieved with acyl-type substituents. The excellent laboratory and greenhouse activity of the best representatives was confirmed in semi-field trials against Spodoptera littoralis.

Synthesis and insecticidal evaluation of imidacloprid analogs

Imidacloprid analogues containing a nitroalkylidene instead of a nitroguanidine unit have been prepared and evaluated for investigation as potential insecticides. No nitroalkylidene analogue showed significant activity against the test insects.

Chemical Modification of Thiangazole A in the Oxazole and Styryl Region

The partial synthesis of 54 derivatives of thiangazole A (1a), a new polythiazoline antibiotic from Polyangium spec. (myxobacteria), is described. Derivatives with chemical modification of the carboxamide group in the oxazole region were prepared either by N-alkylation to amides 5–14 or by methanolysis to ester 15, and its transformation products 16, 19, 20. Oxidation of the C-5 methyl group of 1a with molecular oxygen led to the hydroxymethyl derivative 21, and two by-products lacking the C-5 methyl group (22), or the entire oxazole ring (23). Key intermediate for analogues with modifications in the styryl region is the aldehyde 27, obtained by direct cleavage of the C-21/C-22 double bond. 27 was transformed into the oximes 37–42 and by Wittig reaction to (21Z)-thiangazole (43) and analogues 44–46 with proton and alkyl residues replacing phenyl. 21,22-Didehydrothiangazole (50) was synthesized in a multi-step reaction from 27 via the 20-alkinyl intermediate 49. The insecticidal activities and inhibition of the respiratory chain (complex I) by the thiangazole analogues were determined and compared with the natural product.

Insecticidal natural products: new rocaglamide derivatives from Aglaia roxburghiana†

An Erratum for this article has been published in Pest Management Science 56(5) 493 (2000). In the course of the screening for novel, naturally occurring pesticides from the plant family Meliaceae, an extract of the stem bark of Aglaia roxburghiana was found to exhibit significant insecticidal activity. In addition to rocaglamide, a known insecticide isolated from several species of the genus Aglaia, 15 new natural products were isolated from this plant. Isolation and structure elucidation of the natural products is described. The outstanding insecticidal activities of some of the compounds as well as a structure–activity relationship study are presented. © 1999 Society of Chemical Industry

Synthesis and insecticidal activity of 4-perhaloalkoxy (or thioalkyl) benzophenonehydrazone derivatives†

Benzophenonehydrazone derivatives containing a mesylate or triflate substituent are known to exhibit insecticidal activity. In the present study, such substituents have been replaced by perhaloalkoxy groups. High levels of activity against lepidopteran pests were observed in greenhouse trials. For optimum activity, the substituents should be relatively small. In semi-field trials, however, none of the compounds tested showed sufficient persistence to warrant further development.

The insecticidal activity of derivatives of the ionophore X-206

The naturally-occurring ionophore X206, originally isolated for its antibacterial activity, also exhibits broad insecticidal and acaricidal activity. This summary reports structure/activity studies with X206 and 34 derivatives as well as mode of action studies. Although many compounds showed promising insecticidal activity, it was only of a contact activity nature; furthermore, the acute LD50 of the compounds in rats precluded further development of these compounds. © 1999 Society of Chemical Industry