Pyrethroid insecticide acids, structures

Some derivatives of 56 have been investigated because they are related to the widely used pyrethroid insecticides. Pure cyhalothric acid (70) forms H-bonded centrosymmetric dimers in the crystal125. Newly discovered clathrates with aromatic molecules may facilitate the separation of isomers126. The structures of the acid 71 and of its 2/1 inclusion compound with benzene have been determined126. 

Enantioselection can be controlled much more effectively with the appropriate chiral copper, rhodium, and cobalt catalyst.The first major breakthrough in this area was achieved by copper complexes with chiral salicylaldimine ligands that were obtained from salicylaldehyde and amino alcohols derived from a-amino acids (Aratani catalysts ). With bulky diazo esters, both the diastereoselectivity (transicis ratio) and the enantioselectivity can be increased. These facts have been used, inter alia, for the diastereo- and enantioselective synthesis of chrysan-themic and permethrinic acids which are components of pyrethroid insecticides (Table 10). 0-Trimethylsilyl enols can also be cyclopropanated enantioselectively with alkyl diazoacetates in the presence of Aratani catalysts. In detailed studies,the influence of various parameters, such as metal ligands in the catalyst, catalyst concentration, solvent, and alkene structure, on the enantioselectivity has been recorded. Enantiomeric excesses of up to 88% were obtained with catalyst 7 (R = Bz = 2-MeOCgH4). 

Pyrethroid insecticides are generally classified into one of two large groups on the basis of the central neurotoxic syndrome that they produce [5, 6]. Type I pyrethroids are esters of chrysanthemic acid and an alcohol, having a furan ring and terminal side chain moieties, and absence of a cyano moiety. Allethrin was the first pyrethroid identified in 1949. Allethrin and other pyrethroids such as phenothrin and permethrin with the basic cyclopropane carboxylic ester structure are type I pyrethroids. The insecticidal activity of these synthetic pyrethroids was enhanced further by the addition of a cyano group to give ot-cyano type II pyrethroids such as deltamethrin, fenvalerate, cyfluthrin, cyhalothrin, and lambda-cyhalothrin (Fig. 137.2). 

Miyamoto J, Nishida T, Ueda K (1971) Metabolic fate of resmethrin, 5-benzyl-3-furylmethyl A -trans chrysanthemate in the rat. Pestic Biochem Physiol 1 293-306 Miyamoto J, Suzuki T, Nakae C (1974) Metabolism of phenothrin (3-phenoxybenzyl A-trans-chrysanthemumate) in mammals. Pestic Biochem Physiol 4 438-450 Moss GP, Derden JC, Patel H, Cronin MT (2002) Quantitative structure-permeability relationships (QSPRs) for percutaneous absorption. Toxicol In Vitro 16 299-317 Mugeng J, Soderlund DM (1982) Liquid chromatographic determination and resolution of the enantiomers of the acid moieties of pyrethroid insecticides as their (-)-l-(l-phenyl)ethylamide derivatives. J Chromatogr A 248(1) 143-149... 

Pyrethroids, the natural insecticides. The insecticides "pyrethroids , naturally occurring in Pyrethrum species, are the esters in which the acidic part is the cyclopentenone fatty acid, structurally similar to jasmonate ... 

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. 

Mention was made of the natural product pyrethrins and the structure of pyrethrin I was given in this chapter, Section 3.1. Because of the unique structures of these cyclopropane-containing natural products and their high insecticidal properties, syntheses of analogs have been studied. The isobutenyldimethylcyclopropanecarboxylic acid moiety, called chrysan-themic acid, has been modified by using different ester groups. As a result a number of synthetic pyrethroids are available for certain specific uses. 

Pyrethroid Esters of Benzene Acetate. These insecticides have more extensive structural optimization in both acid and alcohol moieties. Fenvalerate [51630-58-1]y 0t-cyano-(3-phenoxyphenyl)methyl (+)-(2R,T)-a-isopropyl-4-chlorophenylacetate (24) (d 1.17, vp 1.4 J,Pa at 25°C), a mixture of four isomers, is soluble in water to 0.3 mg/L The rat oral LD ( is 450 mg/kg. Esfenvalerate [66230-04-4] is the (+)-2-(3, 3)-isomer (mp 59°C). The rat LD5Qs are 75, 458 (oral), and the rabbit dermal LD50 is 2000 mg/kg. These pyrethroids are widely used general-purpose insecticides for field, vegetable, and fruit crops. 

Synthetic pyrethroids are a group of ester compounds having excellent insecticidal activities. After the discovery of allethrin (1), a variety of useful synthetic pyrethroids have been produced mainly by structural modification of an alcohol having an asymmetric center. The insecticidal activities greatly depend upon the stereoisomers. Therefore, much effort has been expended to develop technologies for obtaining optically active isomers. However, contrary to the case of chrysanthemic acid, chemical methods of optical resolution were not very effective for these alcohols. 

Pyrethroids occupy a central position among insecticides because of their high selectivity and low toxicity [34]. Chrysanthemic esters (33), the carboxylic acid components of this important class of compounds, can be synthesized by asymmetric cyclopropanation of olefins (cf Section 3.1.7) by diazoacetates in the presence of a chiral Schiff base-Cu complex (Scheme 9 and Structures 34 and 35) [35-37]. 

The insecticidal activity and structure-activity relationships of novel pyrethroids prepared by reacting methyl phenyl substituted pyrazole methanols with dichloro chrysanthemic acid chloride are reported. These pyrethroids are active on tobacco budworm, fall armyworm, southern corn rootworm, and aster leafhopper, generally in the concentration range of 1000-250 ppm. Although less active than the pyrethroid standard bifenthrin, the overall structure-activity of these pyrazole pyrethroids with regard to substitution patterns is similar to that previously observed with bifenthrin analogs. 

Permethrinic acid,3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxyl-ic acid, is another kind of cyclopropanecarboxylic acid producing insecticides of higher performance and stability [5]. The structure of permethrin, a totally synthetic pyrethroid, is shown in Fig. 2. The most effective isomer of permethrinic acid is shown to be the d-cis isomer rather than the d-trans isomer [6]. 

Given the disadvantages mentioned before, the manufacture of chrysanthe-mic acid is economically less important than that of permethric acid. Scientifically, the syntheses of both compounds are ofinterest. The aim of (mostly industrial) research was to identify the simplest and cheapest way to access this structurally demanding class of substances. Nowadays, pyrethroid research is however largely a matter of the past, the insecticide market is dominated by... 

This class of acids 259 constituted a novel feature and a deviation from the natural model compound chrysanthemic acid. Originating from structure-activity considerations on the similarity of pyrethroid and DDT by Holan [512], they improved the understanding of molecular shape and insecticidal activity. The commercial result of this ideas is cycloprothrin. 

The potentials of this and other similar chiral Schiff base complexes of copper were originally explored for the manufacture of synthetic pyre-throids, a class of highly active pesticides. Cyclopropane rings with asymmetric centers are an integral part of the molecular structures of synthetic pyrethroids. Synthetic pyrethroids were made because the natural product chrysanthemic acid, 7.69, and its derivatives have insecticidal properties. 

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