Cyclodiene derivatives

One of the most important groups of chlorinated hydrocarbon insecticides is formed by the compounds belonging to the diene group. These compounds can be prepared by the diene synthesis linked with the names of Diels and Alder (1928). In the synthesis of the diene insecticides, hexachlorocyclopentadiene (40) is used as the 

3-diene partner, and various ring systems as the dienophylic partner, the single members of the group differing from one another in relation to this latter partner. 

The first member of the group to be developed was chlordane (41) which has been synthesised simultaneously in the USA and in the FRG (Riemschneider and Kuhnl, 1948 Hyman, 1945 Riemschneider, 1950 Kearns et al., 1954). 

Chlordane is prepared by reacting hexachlorocyclopentadiene (40) formed as the main product in the chlorination of cyclopentadiene (42) with hypochlorite or in the high temperature chlorination (470°C) of pentane, neopentane or cyclopentane with cyclopentadiene (Diels-Alder reaction), and chlorinating the 4,5,6,7,8,8-hexa-chloro-4,7-methano-3a,4,7,7a-tetrahydroindene (chlordene, 43) yielded by this reaction until two additional chlorine atoms are absorbed, obtaining 4,7-methano- 

While chlordene (43) has only a weak insecticidal effect, the efficiency of chlordane (41), which contains two more chlorine atoms, is 300 times greater, indicating that the efficiency of insecticides of the cyclodiene type is highly structure-specific. Even slight modifications of the molecule greatly affect the efficiency. 

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Lindane is one of eight different hexachlorocyclohexane (HCH), C H Cl, isomers and its Chemical Abstract n.2cniQ is la, 2a 3P, 4a, 5a 6P-hexachlorocyclohexane [58-89-9] (y-HCH or y-BHC, ben2ene hexachloride) (80). Commercial products containing lindane are marketed as either a mixture of isomers or as the pure y-BHC isomer. Not unexpectedly, lindane is a highly stable lipophilic compound and it has been used extensively worldwide as an insecticide. In contrast, hexachloropentadiene, C Cl, is an extremely reactive industrial intermediate used as a chemical intermediate in the synthesis of a broad range of cyclodiene-derived pesticides, which include endosulfan, endrin, heptachlor, and several different organohalogen flame retardants (81). 

DDT was first synthesized in 1874 and its insecticidal properties discovered in 1939. Technical DDT is a stable, white, amorphous powder composed of up to 14 analogs and isomers. In 1942, hexachlorocyclohexane (benzene hexachloride) was discovered to be an effective and simple insecticide. Of its isomers, y-HCH has the greatest insecticidal activity and is marketed as lindane, whereas a-HCH and )3-HCH are more toxic to mammals. Chlordane, a mixture of terpenoid compounds, was discovered in 1945 to be a highly effective residual insecticide. In 1948, the most active principle of chlordane, termed heptachlor, was developed, along with two other cyclodiene derivatives, aldrin and dieldrin. It has been subsequently shown that microbial conversion of heptachlor in the environment yields heptachlor epoxide, which exhibits toxicity equal to or greater than that of the parent compound whereas photochemical conversion yields the equally toxic photoheptachlor. Also during 1948, a product obtained by the chlorination of turpentine and containing a considerable number of chlorinated camphenes was sold as toxaphene. 

The first resins to be produced on a commercial scale were the coumarone—indene or coal-tar resins (1) production in the United States was started before 1920. These resins were dominant until the development of petroleum resins, which were estabHshed as important raw materials by the mid-1940s. Continued development of petroleum-based resins has led to a wide variety of aHphatic, cyclodiene, and aromatic hydrocarbon-based resins. The principal components of petroleum resins are based on piperylenes, dicyclopentadiene (DCPD), styrene, indene, and their respective alkylated derivatives. 

Waldmann used (R) and (5>aminoacid methyl esters and chiral amines as chiral auxiliaries in analogous aza-Diels-Alder reactions with cyclodienes.111 The diastereoselectivity of these reactions ranged from moderate to excellent and the open-chain dienes reacted similarly. Recently, the aza-Diels-Alder reaction was used by Waldmann in the asymmetric synthesis of highly functionalized tetracyclic indole derivatives (Eq. 12.45), which is useful for the synthesis of yohimbine- and reserpine-type alkaloids.112... 

As seen from the structural formulas in Figure 16.4, the organochlorine insecticides are of intermediate molecular mass and contain at least one aromatic or nonaromatic ring. They can be placed in four major chemical classes. The first of these consists of the chloroethylene derivatives, of which DDT and methoxychlor are the prime examples. The second major class is composed of chlorinated cyclodiene compounds, including aldrin, dieldrin, and heptachlor. The most highly chlorinated members of this class, such as chloredecone, are manufactured from hexachlorocyclo-pentadiene (see Section 16.3). The benzene hexachloride stereoisomers make up a third class of organochlorine insecticides, and the third group, known collectively as toxaphene, constitutes a fourth. 

The story of the discovery of the chlorinated hydrocarbon derived insecticides is one of outstanding achievement which deserves due recognition Indeed, the discovery within so few years of DDT, y-HCH ( y-BHC), the cyclodiene group and toxaphene, chlorinated insecticide types with distinct origins and synthetic principles, is truly remarkable ... 

Photolysis of 2-bromo-4,4-dimethyl-2-cyclohexenone only affords reduction, even in a nucleophilic medium343,344. Apparently, this substrate is structurally not suitable to form a vinyl cation. Formation of vinyl radical-derived products is also the main process for all vinylic halides, if their irradiation is performed in an apolar medium. Such photochemical reductive dehalogenation and especially dechlorination reactions have been extensively studied in the past, not in the least because of their importance as abiotic transformation of persistent polychlorinated environmental pollutants. Examples are the cyclodiene insecticides aldrin and dieldrin, which contain a vicinal dichloroethene chromophore. In recent... 

DDT and the cyclodiene pesticides are only a few components of a large soup of persistent environmental contaminants consisting of halogenated organics - that is, molecules with a carbon skeleton (usually aromatic) deriving some or all of their toxicological activity through the insertion of chlorine. 

Acute CH poisonings manifest with numerous symptoms (see Table 4-2). Few psychiatric effects appear in the acute stages. Most symptoms, such as irritability and confusion, result from acute physical illness and shock. The cyclodienes, not DDT or its related derivatives, produce the most severe symptoms in Table 4-2. One case report described seizures resulting from the concomitant use of lindane for treatment of head lice with dextroamphetamine for treatment of at-tention-deficit/hyperactivity disorder (ADHD) (Cox et al. 2000). 

Epoxidation or the insertion of an oxygen atom into a carbon-carbon double bond can frequently result in the formation of products with greater environmental toxicity. Various microorganisms can catalyze the reaction of the chlorinated cyclodiene insecticides aldrin, isodrin, and heptachlor to their more toxic epoxide derivatives. 

The types of monomer susceptible to metathesis polymerization reactions are limited, however, and those that are most suitable are strained ring structures. Thermodynamic considraations account for the lack of reaction with six-membraed rings, and strain-free cyclohexene derivatives or conjngated cyclodienes tend to be excluded. Newer catalysts that can polymerize polar monomers are now available. Cyclic monomers contain fnnctional groups, -OH, -COOH, -COOR, -CONHj, and -NHj, can be used with the newer catalysts that have been developed. 

From the massive rejection of the chlorinated cyclodienes, two survivors emerge, both recommended by IPM (p. 244). The first of these is endosulfan 6,48) with inbuilt biodegradability. The second is campheclor (formerly called toxaphene) said to be a mixture of about 175 polychloro derivatives of cam-phene 6.49) with an overall empirical formula ofCioHjoClg, and no double bond (Casida et al., 1974). It, too, is biodegradable. 

In the presence of rhodium [RhX(cod)]2 (where X = Cl, OSiMe3) and also RuHCl(CO)(i-PPr3)2 complexes, intramolecular condensation of divinylsubstituted silicon derivatives proceeds to open an original route for synthesizing organosilicon compounds containing organocyclotrienes, cyclodienes or cycloalkenes with jco-cyclic methylidenes. 

Electron-donating substituents activate the 1,3-cyclodiene towards electrophilic attack by singlet oxygen, which clearly demonstrates that the (4 -i- 2]-cycloaddition is controlled byHOMO (diene)-LUMO (singlet oxygen) interaction. For 1,3-cyclopentadiene derivatives, alkylation or arylation at positions 1 to 4 did... 

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