Pyrethroid insecticide production

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 are used primarily for the control of household and agricultural insect pests, and secondarily in industrial, stored product, and veterinary applications. They are especially advantageous for use in northern climates because their toxicity is enhanced at low temperatures (Smith and Stratton 1986). Synthetic pyrethroid insecticides, including fenvalerate, are used as alternatives... 

Arena AC, Femadez CD, Porto EM et al (2008) Fenvalerate, a pyrethroid insecticide, adversely affects sperm production and storage in male rats. J Toxicol Environ Health A 71 1550-1558... 

Nakamura Y, Sugihara K, Sone T, Isobe M, Ohta S, Kitamura S (2007) The in vitro metabolism of a pyrethroid insecticide, permethrin, and its hydrolysis products in rats. Toxicology 235 176-184... 

The main devices used for mosquito protection in households have been mosquito coils, electric mosquito mats, and liquid vaporizers, all of them methods that vaporize insecticides into the air using heating by means of fire or electricity to control the insects. In recent years, new anti-mosquito products have been commercialized such as fan vaporizers, paper strip type emanators, and resin net type emanators which vaporize insecticides without heating. In all of these products pyrethroid insecticides are used as active ingredients because they are superior in what is called knockdown effect, where noxious insects are rapidly paralyzed and cannot bite, and have a high level of safety for humans. 

During studies on pyrethroid insecticides methyl permethrate 1 (a mixture of cis and trans isomers) was pyrolysed at 260-270°C in the expectation that a vinylcyclopropane-to-cyclopentene rearrangement would occur. The product, however, was found to be methyl o-toluate (78%). 

In conclusion, the combination of an enzymatic optical resolution and subsequent chemical transformations of epimerization or racemization of the asymmetric center of the unwanted antipodes have led to the successful development of processes for preparation of the two optically active pyrethroid insecticides. This work will provide a novel feature in the application of enzymes, especially lipases for the industrial production of chiral compounds. 

For the production of various pyrethroid insecticides the (S)-4-hydroxy-3-methyl-2-(2-propynyl)-2-cyclopenten-l-one was required. Arthrobacter lipase hydrolysed only the P-enantiomer of the racemic acetate and, after extraction, the mixture of the alcohol and acetate were submitted to methanesulfonyl chloride and triethylamine. The thus-obtained acetate/mesylate mixture was hydrolysed/ inverted yielding 82% of (S)-4-hydroxy-3-methyl-2-(2-propynyl)-2-cyclopenten-l-one with an ee of 90% (Scheme 6.17 B). The procedure was also proved to work with other secondary alcohols and instead of the mesylate a Mitsunobu inversion could be applied [35]. 

Plague control also requires large amounts of insecticides in certain countries. In Madagascar, 41825 kg of pyrethroid products were purchased for plague vector control in 1996 and an additional 5000 kg in 1997, while in Namibia, 18540kg of insecticide products were used between 1993 and 1997. 

Rhodium compounds and complexes are also commercially important catalysts. The hydroformylation of propene to butanal (a precursor of hfr(2-ethyUiexyl) phthalate, the PVC plasticizer) is catalyzed by hydridocarbonylrhodium(I) complexes. Iodo(carbonyl)rhodium(I) species catalyze the production of acetic acid from methanol. In the flne chemical industry, rhodium complexes with chiral ligands catalyze the production of L-DOPA, used in the treatment of Parkinson s disease. Rhodium(II) carboxylates are increasingly important as catalysts in the synthesis of cyclopropyl compounds from diazo compounds. Many of the products are used as synthetic, pyrethroid insecticides. Hexacyanorhodate(III) salts are used to dope silver halides in photographic emulsions to reduce grain size and improve gradation. 

When certain cyclodipeptides are used as catalysts for the enantioselective formation of cyanohydrins, an autocatalytic improvement of selectivity is observed in the presence of chiral hydrocyanation products [80]. A commercial process for the manufacture of a pyrethroid insecticide involving asymmetric addition of HCN to an aromatic aldehyde in the presence of a cyclic dipeptide has been described [80]. Besides HCN itself, acetone cyanohydrin is also used (usually in the literature referred to as the Nazarov method), which can be activated cata-lytically by certain lanthanide complexes [81]. Acetylcyanation of aldehydes is described with samarium-based catalysts in the presence of isopropenyl acetate cyclohexanone oxime acetate is hydrocyanated with acetone cyanohydrin as the HCN source in the presence of these catalytic systems [82]. 

Special Problems New Compounds. A major challenge presently is to make certain that our current knowledge and understanding of pesticide risks be effectively put to use in the development of new materials. The synthetic pyrethroid insecticides which are rapidly replacing many of the older products may be used to illustrate the point. While these compounds are insecticidal at almost unbelievably low rates, their mode of action is the same or similar to that of DDT (4). When chlorinated, as is the case with some of the more effective ones, they indeed become chlorinated hydrocarbons and, as such, they must be scrutinized just as carefully as if DDT itself was the compound under consideration. One trusts that this is being done, but it is important that the low-rate phenomenon not be allowed to have an undue influence as the overall toxicology of these new pesticides are being assessed. 

In this way, esters of chrysanthemic acid (2) [15,16,18] and permethrinic acid [17,18], which are important precursors for the synthesis of pyrethroid insecticides, can be prepared in >90% ee. Although enantioselective cyclopropanation cannot compete with conventional industrial syntheses of optically active pyrethroids, a technical process for the cyclopropanation of 2-methylpropene was successfully implemented at Sumitomo [18]. The product, ethyl (-l-)-2,2-dimeth-ylcyclopropanecarboxylate, serves as a starting material for the production of cilastatin, a dehydropeptidase inhibitor used as a drug to suppress the degradation of the P-lactam antibiotic iminipenem. 

The selective propionylation of benzodioxole 37 at posihon 5 with propanoic anhydride can be performed in the presence of catalyhc amount of aqueous perchloric acid (20% mol) (Scheme 3.9). The reaction is performed in cyclohexane or decalin for 3 h at room temperature. Compound 38, obtained in 65% yield, represents an intermediate for the industrial production of pyrethroid insecticides. A typical batch reactor for this process is depicted in Figure 3.3. 

MAJOR USES Used in the production of herbicides, pyrethroid insecticides, antioxidants, disinfectants, fumigants, photographic developers, explosives. 

C.A. Spinks, B. Wang, E.N.C. Mills, M.R.A. Morgan, Production and Characterization of Monoclonal Antiidiotype Antibody Mimics for the Pyrethroid Insecticides and the Herbicide Paraquat , Food Agric. Immunol, 5, 13 (1993). 

Phototransformations in the presence of soils and clays have been reported by several authors. The penetration of light into soils and sediments is greatly inhibited below the first 0.2 mm or so (Hebert and Miller, 1989), but often surface photoreactions can proceed at significant rates. For example, sediment-sorbed DDE (6) photo-lyzes faster than when it is dissolved, and the product mixture differs in a way that suggests an environment rich in H-donors, probably organic matter (Miller and Zepp, 1979 Zafiriou et al., 1984). Parathion (7) has been shown to be rapidly photolyzed on the surfaces of dust and soil particles to paraoxon (8), a more toxic substance (Spencer et al., 1980). The pyrethroid insecticide fenpropathrin (9) was rapidly photolyzed (ti/j about 1 day) on soils high in organic carbon (Takahashi et al., 1985). 

Synthetic pyrethroid insecticides are photostable analogs of the natural pyrethrins of botanical origin they consist of a series of related esters derived from alcohols and acids that maintain critical isosteric relations with the natural product prototype. Small changes in substituents and stereochemistry are sufficient... 

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