Timothy C. Johnson

Penoxsulam—Structure–activity relationships of triazolopyrimidine sulfonamides

The discovery of the sulfonamide herbicides, which inhibit the enzyme acetolactate synthase (ALS), has resulted in many investigations to exploit their herbicidal activity. One area which proved particularly productive was the N-aryltriazolo[1,5-c]pyrimidine sulfonamides, providing three commercial herbicides, cloransulam-methyl, diclosulam and florasulam. Additional structure-activity investigations by reversing the sulfonamide linkage resulted in the discovery of triazolopyrimidine sulfonamides with cereal crop selectivity and high levels of grass and broadleaf weed control. Research efforts to exploit these high levels of weed activity ultimately led to the discovery of penoxsulam, a new herbicide developed for grass, sedge and broadleaf weed control in rice. Synthetic efforts and structure-activity relationships leading to the discovery of penoxsulam will be discussed.

SAR studies directed toward the pyridine moiety of the sap-feeding insecticide sulfoxaflor (Isoclast™ active).

Sap-feeding insect pests constitute a major insect pest complex that includes a range of aphids, whiteflies, planthoppers and other insect species. Sulfoxaflor (Isoclast™ active), a new sulfoximine class insecticide, targets sap-feeding insect pests including those resistant to many other classes of insecticides. A structure activity relationship (SAR) investigation of the sulfoximine insecticides revealed the importance of a 3-pyridyl ring and a methyl substituent on the methylene bridge linking the pyridine and the sulfoximine moiety to achieving strong Myzus persicae activity. A more in depth QSAR investigation of pyridine ring substituents revealed a strong correlation with the calculated logoctanol/water partition coefficient (SlogP). Model development resulted in a highly predictive model for a set of 18 sulfoximines including sulfoxaflor. The model is consistent with and helps explain the highly optimized pyridine substitution pattern for sulfoxaflor.

Expanding the structure–activity relationship of sulfoxaflor: the synthesis and biological activity of N‐heterocyclic sulfoximines

BACKGROUND Sulfoxaflor, a new insect control agent developed by Dow AgroSciences, exhibits broad-spectrum control of many sap-feeding insect pests, including aphids, whiteflies, leafhoppers, planthoppers and lygus bugs. During the development of sulfoxaflor, structure-activity relationship (SAR) exploration of the sulfoximine functional group revealed that the nature of the sulfoximine nitrogen substituent significantly affects insecticidal acitivity. As part of the investigation to probe the various electronic, steric and lipophilic parameters at this position, a series of N-heterocyclic sulfoximines were synthesized and tested for bioactivity against green peach aphid. RESULTS Using a variety of chemistries, the nitrile substituent was replaced with different substituted five- and six-membered heterocycles. The compounds in the series were then tested for insecticidal acitivty against green peach aphid in foliar spray assays. In spite of the larger steric demand of these substituents, the resulting N-heterocyclic sulfoximine analogs displayed good levels of efficacy. In particular, the N-thiazolyl sulfoximines exhibited the greatest activity, with LC50 values as low as 1 ppm. CONCLUSIONS The novel series of N-heterocyclic sulfoximines helped to advance the current knowledge of the sulfoxaflor SAR, and demonstrated that the structural requirement for the sulfoximine nitrogen position was not limited to small, electron-deficient moeities, but rather was tolerant of larger functionality.

Synthesis and Biological Potency of Anilino‐Triazine Insecticides

BACKGROUND An insecticide screening effort identified N-(4-bromophenyl)-4,6-bis(2,2,2-trifluoroethoxy)-1,3,5-triazine-2-amine as having weak potency against two lepidopteran species, Helicoverpa zea and Spodoptera exigua. A structure-activity relationship study about the trifluoroethoxy substituents and the aniline of this compound was carried out in an effort to improve insecticidal potency. RESULTS Initially, a series of analogs bearing various substituents on the aniline were prepared, and the insecticidal potency was evaluated against H. zea and S. exigua in greenhouse diet feeding assays. The results showed that electron-withdrawing substituents, such as Cl, Br and CF3 , were preferred over electron-donating substituents, such as methoxy, and that potency was significantly better when the substituent was in the para-position. Additional investigations showed that bis(anilino)trifluoroethoxytriazines were more potent. Replacement of the remaining trifluoroethyl group in the bis(anilino)triazine series with an alkyl amine lead to compounds of equal or superior efficacy. CONCLUSION The work presented showed that electron-withdrawing substituents in the para-position of the aniline ring of the initial hit delivered the best levels of insecticidal potency against the two insect species tested. Further investigations showed that potency could be improved by replacing one of the two trifluoroethoxy groups with additional 4-substituted aniline. This level of potency was maintained or further improved when the remaining trifluoroethoxy was replaced with a substituted amine.