CHAPTER 14 Synthetic Pyrethroids 14.1 Insecticidal Activity and Photostability Pyrethroids are synthetic compounds based on natural pyrethrins as models, generally arrived at by systematic variation of parts of the molecule for the purpose of improving photostability and insecticidal activity (Davies 1985). However, they differ markedly from the natural pyrethrins in their physical, chemical, and biological effects (Tables 14.1, 14.2). All pyrethroids are lipophilic compounds, almost insoluble in water; in these respects they resemble the organochlorine insecticides, but they differ from most organophosphorus and Table 14.1. Relative toxicities of some important pyrethroids and other insecticides to four species of insect by topical applicationa Compound Musca Periplaneta Glossina Boophilus domestica americana austeni microplus Biorethmethrin (standard) 100 100 100 100 LCso of standard (ng per insect) 5 2500 2.6 0.00014%b Natural pyrethrins 2 (100) (20) 170 Allethrin 3 2 Bioallethrin 6 150 12 S- Bioallethrin 10 Resmethrin 42 79 120 Cismethrin 42 500 260 Kadethrin 34 80 520 Phenothrin 30 26 Permethrin 60 290 87 200 Cypermethrin 210 350 330 Deltamethrin 1500 3000 3300 240 Fenvalerate 38 200 31 DDT 12 (15) 3 3 Dieldrin 20 (100) 26 21 Carbaryl < 5 0.1 Malathion 1 <2 Dimethoate 45 60 5.5 aResults in this table are intended for general comparison only; figures in parentheses are from very approximate comparative data, not necessarily directly against bioresmethrin. bMean lethal concentration by Shaw Immersion Technique. (Elliot et al. 1978) A. S. Perry et al., Insecticides in Agriculture and Environment © Springer-Verlag Berlin Heidelberg 1998 Synthetic Pyrethroids 93 Table 14.2. Synthetic pyrethroid insecticides Common Structure Stereochemistry Number Content name of of active isomers isomers (%) NlJturlJl Pyrethrin I lR trans; S 1 100 Pyrethrin II lR trans E; S 1 100 Cinerin I lR trans; S 1 100 Cinerin II lR trans E; S 1 100 Jasmolin I lR trans; S 1 100 Jasmolin II lR trans E; S 1 100 PhotollJbile pyrethroids Allethrin (±) cis/trans; RS 8 25 ~0 Bioallethrin lR trans; RS 2 50 Esdepallethrin lR trans; S 1 100 Barthrin (±) cis/trans 4 50 ~.-q, Butethrin (±) cis/trans; Z 4 50 0coo~ Cyphenothrin lR cis/trans; RS 4 50 20: 80 rA~o'OI... I ... Dimethrin 0COOCH2-O- (±) cis/trans 4 50 Empenthrin lR cis/trans; RS 4 50 (Vaporthrin) 0coo~ 20 : 80 Bioethanomethrin ~ lR trans 1 100 - CO~ 0 1 .., Furamethrin (±) cis/trans 4 50 Aooc",~ 0' 4- d-Furamethrin lR cis/trans 2 100 20: 80 (Contd) 94 Insecticides and the Environment Common Structure Stereochemistry Number Content name of of active isomers isomers (%) Kadethrin lR cis E 100 q=Ac~ 0 Phenothrin (±) cis/trans 4 50 0c~0'O d -Phenothrin lR cis/trans 2 100 20: 80 Prallethrin lR cis/trans; S 2 100 A~ 0 Proparthrin (±) cis/trans 4 50 0 cooCH')h. o ~ Resmethrin (±) cis/trans 4 50 ~CH'~ d-Resmethrin lR cis/trans 2 100 20: 80 Bioresmethrin A lR trans 1 100 Terallethrin ~ (±) 2 50 C , " 0 Tetramethrin (±) cis/trans 4 50 ~,~ 20: 80 0 d-Tetramethrin lR cis/trans 2 100 20: 80 Photostable or new pyrethroids Acrinathrin (CF')2Cf/OOCJ~o lR cis Z; as 1 100 ,.. ''0" Bifenthrin (±) cis Z 2 50 ' CF~l (Contd) Synthetic pyrethroids 95 Common Structure Stereochemistry Number Content name of of active isomers isomers (%) Cycloprothrin CI (±) 4 -25 ro ~~0'O~ ~ ~ Cyfluthrin (±) cis/trans 8 20-25 CI 0 40; 60 - COO >' I '0 Cl 0~"'" Beta-Cyfluthrin 1R cis/trans as 4 50 IS cis/trans aR cis/trans = 1 ; 2 Cyhalothrin (±) cis Z 4 22 00... ,.. °Alv°CFJ .. I '0 Lamda-Cyhalothrin 1R cis Z; as 2 50 1R cis Z; aR Cypermethrin (±) cis/trans 8 18-25 40; 60 - COO ... I 0'0 °0CI lv.. '" Alpha-Cypermethrin lR cis aR 2 50 IS cis aR Beta-Cypermethrin lR cis/trans as 4 50 IS cis/trans as cis/trans= 40 ; 60 Zeta-Cypermethrin (±) cis/trans as 4 50 Deltamethrin lR ciS; as 100 Br 0 - COO ... I '0 8t0lv "" Ethofenprox nonchiral 1 100 ... .... .... ~,O",I 0 ........... 0 Fenpropathrin (±) 2 50 A-c~o'(J Fenvalerate (±) 4 20-25 CI ~OO~'(J"'" I Esfenvalerate (±) S; as 1 100 (Contd) 96 Insecticides and the Environment Common Structure Stereochemistry Number Content name of of active isomers isomers (%) Fl ucythrinate (±) S; a RS 2 50 ~ coo 0 HCf"f)~J(r ~ I I '0 Flumethrin (±) trans Z 4 25 CI~:'O Fluvalinate RS; a RS 4 25 1Y~XooV'O S; a RS 2 50 CF'3 Halfenprox ~,O nonchiral 1 100 BrCi'.O '" 0 Permethrin (±) cis/trans 4 50 00 0 40: 60 CI- c~'O Silafluofen nonchiral 1 100 .,0-1'SeJ)J) I ,; -0 '" 0 Tefluthrin (±) cis Z 2 50 - I crl0)(=*' F' ~ eH, F' Tralomethrin lR cis, R'S~; as 2 100 Bt~-Ac~0'OBt '" Transfluthrin lR trans 1 100 Cl ,.. ~r carbamate insecticides. Most pyrethroids are relatively high-boiling, viscous liquids with low vapor pressures. Only a few (for example, allethrin, prothrin, and the natural pyrethrin I but not pyrethrin II) are sufficiently volatile to be useful constituents of mosquito coils. Vaporthrin is a volatile pyrethroid. These properties probably determine their fast action on insects, slow penetration into leaves, and low systemic movement in plants. Therefore, pyrethroids are effective as contact insecticides, but less effective as stomach poisons (Elliott 1977). The more stable pyrethroids (such as permethrin, cypermethrin, deltamethrin, fen valerate, ethofenprox, and others) were obtained by replacing the photolabile Synthetic Pyrethroids 97 centers of the older compounds with other chemical groups that confer on them photostability (Fig. 14.1). Reactions by which the older and newer pyrethroids are photodegraded and metabolized by various organisms have been generally established (see summary by Holmstead et al. 1977). All decomposition products obtained are of lower toxicity than the parent compounds. Hence, there is little risk that toxic residues of decomposed pyrethroi~ will accumulate and contaminate the environment, especially since application rates are as low as one-tenth of those of other commonly used insecticides. Although synthesis of analogs of the natural pyrethrins began as soon as the active constituents of pyrethrum were discovered (Staudinger and Ruzicka 1924), it was not until 1949 that the first commercially successful pyrethroid, allethrin, was introduced (Schechter et al. 1949). This constituted the first generation of the pyrethroids. Allethrin proved to be more stable and of longer residual activity than natural pyrethrins. It is very effective against flies and mosquitoes but less toxic to cockroaches and other insects. Its volatility, heat stability, and rapid knockdown makes it ideal for use in smoke coils and smoke mats for repellency, biting deterrence, and control of adult mosquitoes. It is used in aerosols for control of flying insects in households. It is used in agriculture for the control of aphids, beetles, thrips, mealybugs, loopers, leafhoppers, and other insects on many vegetable crops, on stored grain, and other commodities. The second generation pyrethroids included the synthesis of dimethrin (1961), tetramethrin (phthalthrin, 1965), resmethrin and bioresmethrin (1969), and bioallethrin (1969). Tetramethrin was found to have greater knockdown activity than allethrin and it can be strongly synergized by pyrethrum synergists. Resmethrin Unstable Stable .x . t y-c~ c CJ°0 oov°'O CI if:oo~o'O ° Pyrethrin I Permethrin Fenvalerate ~~~~ ~.~.f) Resmethrin Cypermethrin Ethofenprox a0co~o'O ~ Br Phenothrin Deltamethrin Fig. 14.1. Representative photostable and unstable pyrethroids. Arrows indicate photolabile moiety 98 Insecticides and the Envirolll:nent and, especially, bioresmethrin possess greater toxicity and much greater knockdown activity than the natural pyrethrins against most insects studied. However, they cannot be synergized by the ordinary pyrethrum synergists. Resmethrin and bioresmethrin are more stable than the natural pyrethrins, but they, too, decompose rapidly on exposure to air and sunlight, and this is the reason why they have not been used as pest control agents in agriculture. Resmethrin found its greatest use, among others of the same group, in spray and aerosol applications for control of crawling and flying insects in glasshouses and dwellings. Bioallethrin has greater efficacy than allethrin, but it is not as active as resmethrin. A number of other compounds considered for commercial use during this period included prothrin, proparthrin, and butethrin. The last in this series was phenothrin (Sumithrin) which was introduced in 1973 and is used as a domestic insecticide. The third generation pyrethroids comprise the most light-stable compounds which achieved wide application in agriculture. The first light-stable compound was fenpropathrin which was synthesized in 1971 but was commercialized as an acaricide only in 1980. During this period were introduced the most active and most photostable compounds permethrin, cypermethrin, deltamethrin, and fenvalerate. The fourth generation pyrethroids were introduced during the period 1975- 1983. Cypothrin has achieved commercial status in animal health for tick control. Flucythrinate was reported to be a broad-spectrum insecticide with activity against phytophagous mites. Fluvalinate, another compound of the same series, also proved to be effective against phytophagous mites. Cytluthrin was introduced in 1981 against cotton insects. It has a level and spectrum of activity resembling those of cypermethrin. A later compound, tlumethrin, has proved to be very effective against cattle ticks. A product of greater effectiveness and stability, cyhalothrin, has been introduced as an ectoparasiticide. Cycloprothrin and fenpyrithrin are being investigated as broad-spectrum insecticides and many other experimental compounds are in the stage of development. Pyrethroid-induced death of insects is deemed to be the result of a cascade of events starting with various forms of hyperexcitation and leading to paralysis. There seems to be no single cause that triggers death in insects having no single respiratory center.