Pyrethroids

Pyrethroids consist of pyrethrum and its synthetic pyrethrum analogs called synthetic pyrethroids. Pyrethrum is a solvent extract of dried flowers of Chrysanthemum cinerariaefo-lium. The active ingredients of pyrethrum are called pyrethrins. Pyrethrins consist of four esters, namely, pyrethrins I and II and cinerins I and II, which comprise the combination of two different alcohols (pyrethrolone and cinerolone) and two different acids (chrysan-themic acid and pyrethric acid), as follows  

The structures of these alcohols and acids are depicted as follows  

The method of attachment for pyrethrin I is shown in the following text. 

Pyrethrum is a very safe insecticide (oral LD50 in rats is 1500 mg/kg) and is very fastacting on insects, causing immediate paralysis. It is commonly formulated with synergists as household sprays and aerosols because insects may recover from pyrethrum alone. 

Pyrethrum is not useful in agriculture because of its cost and instability in sunlight. Synthetic pyrethroids, however, have exceptional insecticide activity and photostability and therefore are useful in agriculture, forestry, and public health insect control. 

The pyrethroids and DDT are by far the most important insecticides in this category. According to their modes of action, they are sometimes classified into two types. Type 1 includes DDT, its analogues, and pyrethroids without a cyano group, whereas type 2 compounds include the pyrethroids with an a-cyano-3-phenoxybenzyl alcohol. In mammals, they give slightly different symptoms by poisoning. Type 1 causes whole-body tremors, whereas type 2 causes salivation and choreoathetosis. Insects also show different symptoms, but not so distinct. 

Pyrethroids form a uniform group of pesticides, some of which are naturally occurring, and many are synthetic analogues of these. The natural pyrethroids are obtained from pyrethrum, a substance that is extracted from the flowers of certain species of chrysanthemum. Pyrethrum is made up of six naturally occurring esters, two of which are sometimes referred to as pyre-thrins, the other being known as cinerins and jasmolins. 

Selective toxicity conferred by target site specificity (e.g., biores-methrin) or metabolic degradation (lower toxicity for trans- than for cis-cyclopropanecarboxylates) 

Modification of every part of the molecule with retention of activity 

Maintenance of high insecticidal potency while minimizing fish toxicity (e.g., the non-ester silafluofen) 

The organophosphates and carbamates as inhibitors of acetylcholinesterase (IRAC MoA Group lA and IB) still form the largest group of insecticides, followed by the pyrethroids, known to act on voltage-gated sodium channels. These classes are briefly covered below in terms of their mode of action and biological value. 

Organophosphates (OPs) were first introduced to the agrochemical market in 1944 and are economically still the most successful and diverse chemical class of insecticides ever invented [4]. Over 100 different active ingredients belonging to this class are known, with the best selling OP of all being chlorpyrifos. 

One of the most important chemical classes of insecticides are the pyrethroids, which act as ligands of voltage-gated sodium channels in nerve axons [8, 9]. In 

In the beginning of the eighties, synthetic pyrethroid insecticides were introduced into the wood protection market substituting organochlorine and organophosphate insecticides. The pyrethroids share similar modes of 

) in 98 % yield with 76 % ee. Enantiomerically pure its (/ )-amide is obtained by recrystallization from methanol [31]. 

A Rh catalyst with (/ ,/ )-MeDuPHOS is effective for the asymmetric hydrogenation of sterically congested functionalized olefins, a key intermediate in the synthesis of Tipranavir, an HIV protease inhibitor [32]. The cationic Rh catalyst is found to enable an highly efficient and enantioselective hydrogenation of a unique carboxylate for the 12-kg reaction scale production of candoxatril, a cardiovascular agent [33]. 

The first records of pyrethrum as an insecticide date back to Chinas late Zhou Dynasty (ca. 1046-256 BC). Since medieval times, the flowers were traded along the old Silk route through Tashkent to Persia and eventually to the Dalmatian coast. Later, during the Napoleonic Wars (1804-1815) French soldiers appreciated pyrethrum as an agent to control fleas and body hce. [63] 

The Dalmatian insect powder, as its name imphes, was prepared from the dried, crushed blooms of the Dalmatian insect-flower (Tanacetum cinerarUfoli-um, syn. Chrysanthemum cinerariifolium, Pyrethrum cinerariifolium) (Fig. 8.23). 

On the other hand the Armenian, Persian and Caucasian insect powder was obtained from the Caucasian insect-flower (Tanacetum coccineum, syn. Chrysanthemum coccineum, Pyrethrum roseum, Pyrethrum carneum), native to the Caucasus. 

In former times, either species was a genus of its own, but both are placed now in the Tanacetum genus of about 160 species of flowering plants in the family Asteraceae. 

The active material is located in the mature, fully-opened flower-head. The average content of toxic components in chrysanthemums from Kenya is 1.3%, 

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These chemorational techniques have generated great interest in, and high expectations for, the acceleration of development of innovative pesticides. However, many purportedly successful appHcations of QSAR procedures have reHed on the quaHtative insights traditionally associated with art-based pesticide development programs. Retrospective QSAR analyses have, however, been helpful in identifying the best compounds for specific uses (17). Chemorational techniques have also found some appHcations in the development of pesticides from natural product lead compounds, the best known examples being the synthetic pyrethroid insecticides (19) modeled on the plant natural product, pyrethmm. 

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). 

Pyrethroids from Chiysanthemic Acid. The unsaturated side chains of the aHethrolone alcohol moieties of the natural pyrethrins are readily epoxidized by microsomal oxidases and converted to diols, thus detoxifying the insecticides. Esterification of chrysanthemic acid (9), R = CH3, with substituted ben2yl alcohols produces usehil insecticides barthrin [70-43-9J, 2-chloro-3,4-methylenedioxyben2yl (+)-i7j ,/n7 j -chrysanthemate, and dimethrin [70-38-2] 2,4-dimethylben2yl (+)-i7j ,/n7 j -chrysanthemate. These have alimited spectmm of insecticidal activity but are of very low mammalian toxicity, ie, rat oralLD s >20,000 mg/kg. 

Pyrethroids with Modified Chrysanthemate Esters. Newer pyrethroids incorporate optimized chrysanthemic acid components to retard detoxication by microsomal oxidases and these are esterified with a variety of optimized alcohol moieties therefore increasing persistence. 

Pyrethroid Esters of Benzene Acetate. These insecticides have more extensive stmctural optimization in both acid and alcohol moieties. Fenvalerate [51630-58-17, a-cyano-(3-phenoxyphenyl)methyl (+)-(2R,5)"Ct"isoprop5i-4-chlorophenylacetate (24) d 1.17, vp 1.4 p.Pa at 25°C), a mixture of four isomers, is soluble in water to 0.3 mg/L The rat oral LD q is 450 mg/kg. Esfenvalerate [66230-04-4] is the (+)-2-(i, 5)-isomer (mp 59°C). The rat LD qS are 75, 458 (oral), and the rabbit dermal LD q is 2000 mg/kg. These pyrethroids are widely used general-purpose insecticides for field, vegetable, and fmit crops. 

The horn fly Haematobia irritans an important bloodsucking pest of catde, was found to be completely controlled by ear tags which slowly released permethrin and fenvalerate. These were found to give almost 100% control for 24 weeks. However, following almost universal appHcation of this ideal control measure, control failures of the pyrethroid insecticides were widely reported in North America in 1982 ndash 1983 and the practice is now abandoned. 

The pyrethroid permethrin is an effective repeUent for biting flies, mosquitoes, and ticks. A 30% permethrin cream is a general-purpose repeUent used by the U.S. Armed Forces. 

K. Naumaim, Synthetic Pyrethroid Insecticides Structures and Properties, Sptinger-Verlag, Berlin, 1990. 

Some of the newer compounds may contain both saturated and unsaturated rings, heteroatoms such as oxygen, nitrogen, or sulfur, and halogen substituents. Others, such as synthetic pyrethroids, may have one or more chiral centers, often needing stereospecific methods of synthesis or resolution of isomers (42). Table 4 Hsts examples of some more complex compounds. Stmctures are shown ia Eigure 1 (25). 

T. Cairns and J. Sherma, eds.. Comprehensive Analytical Profiles of Important Pesticides, CRC Press, Boca Raton, Fla., 1992, 304 pp. From the series ModemMethods for Pesticide Analysis, provides detailed information on properties and analytical methodology for nine prominent pesticides, pyrethroids, and fumigants in food. Includes formulations and uses, chemical and physical properties, toxicity data, and tolerances on various foods and feeds. Analytical information may be given in enough detail for methods to be carried out without having to consult additional Hterature sources. 

An example of a specialty olefin from an amyl alcohol is Phillips Petroleum s new process for 3-methyl-1-butene (used in the synthesis of pyrethroids) from the catalytic dehydration of 3-methyl-1-butanol (21,22). The process affords 94% product selectivity and 94% alcohol conversion at 310°C and 276 kPa (40 psig). 

Anthrahydroquinones have been patented in Japan as bird repeUents (73), and anthraquinone [84-65-1] (qv) is used widely in Europe as a spray to protect growing crops and as a wood dressing. The synthetic pyrethroid deltamethrin [52918-63-5] (27) was evaluated (74), as were other materials, including bendiocarb (20) (75) and 20,25-dia2ocholesterol dihydrochloride [1249-84-9] (Omitrol) (28), a steroid that inhibits embryo development when adsorbed or ingested as a seed treatment of bait com (55,76). 

Carboyylic acid ester hydrolysis is frequendy observed as the initial reaction for pesticides with ester bonds, such as 2,4-D esters, pyrethroids, and DCPA (dacthal) (8) (eq. 11) (16). 

Synthetic pyrethroids is one of the group of modern insecticides of cyclopropancai bonic acid derivate. The pyrethroids prepai ation is the racemic mixture of optical isomers or mixture of cis- or tran.s-isomers. 

This peculiarity of pyrethroids needs to take into account during gas chromatographic determination. 

USE OF SEMI PERMEABLE MEMBRANE DEVICES (SPMDs) TO INDOOR AIR MONITORING OF PYRETHROID INSECTICIDES... 

An easy, rapid and environmentally friendly methodology was developed for the extraetion of pyrethroid inseetieide residues from semi permeable membrane deviees (SPMD), based in a mierowave-assisted extraetion, in front of a dialysis method nowadays widely employed. Several solvent sueh as hexane, toluene, aeetonitrile, eyelohexane and ethyl aeetate were tested as mierowave-assisted extraetion solvent. Mixtures of hexane and toluene with aeetone were also assayed and provide better results than single solvents. 

Gas ehromatography mass-mass aequisition was used for the pyrethroid determination. Pyrethroids investigated were Allethrin, Prallethrin, Tetramethrin, Bifenthrin, Phenothrin, X-Cyhalothrin, Permethrin, Cyfluthrin, Cypermethrin, Flueythrinate, Fsfenvalerate, Fluvalinate and Deltamethrin. Piperonyl butoxide, main synergist eompound for pyrethroid eompounds, was also studied. 

Limits of deteetion values ranging from 0.2 to 0.8 ng/SPMD and repeatability from 2.0 % to 8.3 % were aehieved. Pyrethroid reeoveries for spiked SPMD (100 ng eaeh pyrethroid) were from (57 5) to (101 4) % for mierowave-assisted extraetion, versus from (34 3) to (91 3) % for dialysis referenee method. A substantially reduetion of solvent amount and analysis time were aehieved. 

For carrying out of given researches method of synthetic pyrethroids determination in air has been developed. Chromatographic behaviour is investigated and optimum conditions of the synthetic pyrethroids analysis with application of capillary column with stationary phase DB-5 and electron-capture detector are selected. 

In connection with a variety of disinsectants formulations (aerosols, foams, electric fumigators) on basis of pyrethroids the income of the given substances into air during application is possible as aerosols and as vapors, especially in case of electric fumigators application. 

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