Synthetic pyrethroids, insecticidal activities

Synthetic Pyrethroid Insecticides. Elucidation of the chemical stmctures of the naturally occurring pyrethmm esters, their rapid and selective insecticidal action, and their high cost stimulated the search for effective synthetic derivatives (13,17,21). Since the 1940s, stmctural optimisation has produced an array of broad-spectmm insecticides with activity 10- to 20-fold greater than other types of insecticides, and with extended residual action. These synthetic pyrethroids have become one of the most important classes of insecticides with world aimual production estimated at 6000 t (21). 

Synthetic pyrethroids now account for at least 30% of the world insecticide market and are rapidly replacing other agricultural chemicals for control of insect pests. Fenvalerate is one of the more widely used synthetic pyrethroid insecticides. It is derived from a combination of a-cyano-3-phenoxybenzyl alcohol and a-isopropyl phenylacetate ester. Technical fenvalerate is a mixture of four optical isomers, each occurring in equal amounts but with different efficacies against insect pests. Fenvalerate does not usually persist in the environment for >10 weeks, and it does not accumulate readily in the biosphere. Time for 50% loss (Tb 1/2) in fenvalerate-exposed amphibians, birds, and mammals was 6 to 14 h for reptiles, terrestrial insects, aquatic snails, and fish it was >14 h to <2 days and for various species of crop plants, it was 2 to 28 days. Fenvalerate degradation in water is due primarily to photoactivity, and in soils to microbial activity. Half-time persistence in nonbiological materials is variable, but may range up to 6 days in freshwater, 34 days in seawater, 6 weeks in estuarine sediments, and 9 weeks in soils. 

A variety of three-membered carbocycles including cyclopropylcarbonyl and -sulfonyl derivatives, cyclopropylcarbonitriles and -methanols, nitrocyclopropanes, cyclo-propanols and cyclopropylamines have been prepared via the 1,3-elimination of HX. Some representative cyclopropyl derivatives recently prepared by this method are shown in Scheme 116-18 and in equations 8-26. Conversion of chelated homoserine, 5,to chelated 2-amino-4-bromobutyrate and treatment with aqueous base directly affords chelated 1-aminocyclopropane-l-carboxylate (equation 8)19. The 1,3-elimination in 6 interestingly leads to the preferential formation of the cis isomer, from which 7, a key structural element of synthetic pyrethroid insecticides, is obtained (equation 9)20. A sulfur substituent can serve both as an activating group and as a leaving group in this type of reaction and, thus, 1,3-bis(phenylthio)propane affords cyclopropyl phenyl sulfide upon treatment with butyl-... 

Blood and various organs of humans and other animals contain esterases capable of acetylsalicylic acid hydrolysis. A comparative study has shown that the liver is the most active tissue in all animal species studied except for the guinea pig, in which the kidney is more than twice as active as the liver. Human liver is least active the enzyme in guinea pig liver is the most active. The relatively low toxicity of some of the new synthetic pyrethroid insecticides appears to be related to the ability of mammals to hydrolyze their carboxyester linkages. Thus mouse liver microsomes catalyzing (+)-/runs-resin e 111ri n hydrolysis are more than 30-fold more active than insect microsomal preparations. The relative rates of hydrolysis of this substrate in enzyme preparations from various species are mouse > > milkweed bug > > cockroach > > cabbage looper > housefly. 

Insecticides such as permethrin, benzyl benzoate, lindane, and pyrethrin have been used to treat lice. Pyrethrins are insecticides initially derived from certain species of chrysanthemum flowers. Synthetic pyrethroid insecticide is more stable with a similar activity and low mammalian toxicity and is called permethrin. Lindane (1,2,3,4,5,6 hexachlorocyclohexane) and benzyl benzoate have also been used as pediculocides. Lice infection is spread by direct contact or by wearing the clothing of an infected person. The control of secondary bacterial infection may require an antibiotic. 

Synonyms a-Cyano-3-phenoxybenzyl (S)-2-(4-difl uoromethoxy phenyl )-3-methy I butyrate 4-(Difluoromethoxy)-a-(l-methylethyl) benzeneacetic acid cyano (3-phenoxyphenyl) methyl ester Empirical C26H23F2NO4 Properties Vise, liq. sol. in acetone, xylene, 2-propanol m.w. 451.48 Toxicology LD50 (oral, rat) 67 mg/kg Uses Synthetic pyrethroid insecticide with contact and stomach poison activity... 

Szydlo, R. M., Ford, M. G., Greenwood, R. and Salt, D. W. (1985) The use of multivariate data sets in the study of structure-activity relationships of synthetic pyrethroid insecticides Part II. The relationships between pharmacokinetics and toxicity, in QSAR and Strategies in the Design of Bioactive Compounds (ed. J. K. Seydel), VCH, Weinheim. 

Another important derivative of m-cresol used in the manufacture of plant protection agents is m-phenoxytoluene, which can be produced from m-cresol and chloro- or bromobenzene at temperatures of 200 °C, with copper catalysts. m-Phenoxytoluene is converted into m-phenoxybenzoic acid methyl ester by oxidation with a cobalt acetate/KBr catalyst and subsequent esterification m-phenoxybenzoic add methyl ester serves as an intermediate in the production of m-phenoxybenzaldehyde, which is used as the raw material in the production of the synthetic pyrethroid insecticide, fenvalerate (see Chapter 6.3.2). The cyanohydrin is formed in-situ, then made to react with 2-isopropyl-(4-chlorophenyl) acetic acid chloride to yield fenvalerate, which was developed by Sumitomo Chemical in 1972. Pyrethroid insecticides are distinguished by their low toxicity and high activity. 

Fenvalerate (XXI, Hg. 7) (Pydrin, Sumicidin, Belmark) is an effective broad-spectrum synthetic pyrethroid insecticide. Fenvalerate exhibits improved photolytic stability and extended field residual activity compared to other pyrethroids. The most insecticidally active stereoisomer is of the 2S,(xS[S,S] conflguration. The racemic mixture and the pure effective insecticide were investigated... 

Resmethrin was the first synthetic pyrethroid insecticide that possessed insecticidal activity approaching the potency of pyrethrin I. In resmethrin, the furan ring replaced the cyclopentenone ring of pyrethrin I, and the benzene ring replaced the diene side chain of pyrethrin I. The success of resmethrin (four isomers, two cis-and two trans-) led to the synthesis of a form that was less toxic to mammals, bioresmethrin (lR-tra s isomer). Unfortunately, bioresmethrin per se was not more photostable than were the earlier synthetic pyrethroids, because both the furan ring and isobutenyl side chain were sites vulnerable to degradation. 

Figure 7 shows the course of development of various synthetic pyrethroids developed by retaining chrysanthemic acid as the acid moiety and modifying the alcohol moiety. Numerous useful compounds with favorable characteristics have been derived from the structural modification of natural cinerin I (7). These underlined compounds have been put into practical use as active ingredients, mainly for household insecticides. 

---