Biphenyl pyrethroids, activity

Replacement of the normal pyrethroid ester by alternative linkages usually leads to diminution of biological activity. One important exception to this general phenomena is several oxime ether derivatives, in particular, 3-phenoxybenzyl derivatives of various alkyl aryl ketones. Pyrethroid esters derived from certain 2-substituted-[1,1 -biphenyl]-3-methanols have been shown to possess initial and residual activity surpassing that of esters derived from 3-phenoxybenzyl alcohol. Now it has been demonstrated that the same enhancement of activity was observed for alkyl aryl oxime ethers of certain [1,1 -biphenyl]-3-methanols compared to the corresponding 3-phenoxybenzyl alcohol derived oximes. The synthesis, biological activity, including soil activity, structure-activity relationships and toxicity of several of these biphenylmethyl oxime ethers are described. 

Pyrethroid esters derived from [1,1 -biphenyl]-3-methanol have been of interest at FMC(5-7). It has been reported that [1,1 -biphenyl]-3-methanol esterified with both cis-3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid and cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid produced esters which have initial and residual activity surpassing that of permethrin against a number of insects. It occurred to us that this same enhancement of activity might be observed with alkyl... 

In this work it was reported that the biological activity and residual properties of biphenyl-3-ylmethyl (1R,S)-cis-3-(2,2-di-chlorovinyl)-2,2-dimethylcyclopropanecarboxylate were about one-half that of the corresponding 3-phenoxybenzyl ester. The preparation of a series of substituted derivatives of biphenyl-3-ylmethyl (1R,S)-cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-carboxylates resulted in esters with significantly greater insecticidal activity and broader spectrum of biological activity than the conventional pyrethroid insecticides(7). The 2-monosubstituted derivatives were found to be the most active compounds in this series with the 2-methyl compound being the most active. This result encouraged us to combine these biphenyl-3-ylmethyl compounds with alkyl aryl methanone oximes. 

The replacement of the ester linkage of pyrethroids by alternatives was known to lead to compounds of diminished biological activity. Thiol esters and amides are two such isosteric replacements that lead to a loss in biological activitv(13.14). The exception to this trend was the replacement by the oxime function-alitv(2.3). The alkyl aryl oxime ethers are not susceptible to alkaline hydrolysis and esteric attack as are the pyrethroid esters(15). The present study details our investigation of the biological activity of [1,1 -biphenyl]-3-methanols when combined with alkyl aryl methanone oximes. 

One of the more recent results of pyrethroid research in the late 1970 s/early 1 80 s consists of biphenyl-3-methylesters of certain pyrethroid acids, having an additionally strong activity against mites (Bifenthrin). Although the unsubstituted biphenylmethyl esters are of an appreciable activity [659, 660], the higher substituted ones are more interesting, particularly if the phenyl substituent is sterically forced out of plane. For synthesis, the classical methods of biphenyl chemistry had to be optimized to quite an extent (Reaction scheme 215). 

Plummer EL, Cardis AB, Martinez AJ, Van Saun WA, Palmere RM, Pincus DS, Stewart RR (1983) Pyrethroid insecticides derived from substituted biphenyl-3-methods. Pestic Sci 14 560-570 Porcelli C, Roncaglioni A, Ghana A, Boriani E, Benfenati A (2007) A protocol for quantitative structure, activity relationship (QSAR) for regulatory purposes the example of DEMETRA. In Environmental fate and ecological effects of pesticides, symposium pesticide chemistry, 13th, Piacenza, Italy, Sept 3-6, 2007, pp 669-674. 

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