1,2,3,4,5,6- Hexachlorocyclohexane

A chlorinated benzene derivative, which is only of historical importance now in the major industrialized countries, is hexachlorocyclohexane, of which the y-iso-mer, lindane, was for some time widely used as a plant protection agent. Hexachlorocyclohexane (HCH) was first produced by Michael Faraday in 1825 by adding chlorine to benzene under the action of sunlight. In 1940, I Cl discovered the insecticidal effect of hexachlorocyclohexane. 

Technical hexachlorocyclohexane contains around 65% of the a-isomer, 7% of the P-isomer, 14% of the y-isomer, 4% of the 8-isomer and 10% of the remaining isomers. 

Hexachlorocyclohexane is produced industrially by the reaction of an excess of benzene with chlorine at 15 to 25 °C in a glass reactor under the influence of UV light at atmospheric pressure. Care must be taken to exclude oxygen and catalysts, such as iron, which favor substitution. When 5 to 8% of the benzene has been chlorinated, the fi-isomer begins to precipitate. After benzene and unreacted chlorine have been evaporated at temperatures of from 85 to 88 °C, a hexachlorocyclohexane mixture with a y-isomer content of 12 to 14% remains. The y-isomer is recovered by fractional crystallization. The other isomers are converted into tri-and tetrachlorobenzenes by thermal or catalytic dechlorination tri- and tetra-chlorobenzenes are used as the precursors for 2,4,5-trichlorophenol (see Chapter 5.3.4.5). 

Because of the poor biodegradability and the tendency to concentrate in the food cycle, the importance of hexachlorocyclohexane as an insecticide has declined sharply. World wide production is currently estimated at only 10,000 tpa. 

As early as 1825 Faraday prepared the addition product of benzene and three molecules of chlorine, formed in sunlight. From this product, which contains various isomers of hexachlorocyclohexane (benzenehexachloride, BHC, 31), Linden was the first to isolate the single isomers in 1912. In 1936, Bender discovered the insecticidal properties of hexachlorocyclohexane and took out a patent. However, his important discovery attracted little attention at the time, so that rediscovery of the insecticidal properties of hexachlorocyclohexane, and its application as an insecticide took place only at the beginning of the 1940s, and was the work of several research groups working independently (Dupire and Rancourt, 1943 Slade, 1945 Haller and Bowen, 1947). The important discovery that, among the various isomers formed, the y-isomer of BHC (31a) is the carrier of insecticidal properties is linked with the name of Thomas (Slade, 1945). 

A number of different methods for the manufacture of BHC are known, all of them being based on an additive chlorination of benzene under the influence of ultraviolet light or in the presence of a chemical activator. 

Free radicals formed in the cleavage of unstable compounds (e.g. sodium hypochlorite, boron trichloride and organic peroxides) may serve as chemical activators. Ultraviolet light used in photocatalytic processes and the chemical activators are used to shift the chlorination reaction from substitution to addition, and ultimately to furnish the energy necessary for homolysis of the chlorine 

The unsubstituted cyclohexane has two strainless conformations the chair (C) and the twisted boat TB) forms (Barton, 1970). The chair form possesses the higher stability, due to the absence of both Baeyer tension and Pitzer tension. 

three of its six chlorine atoms have an axial (a), and three an equatorial (e) orientation (aaaeee). 

IUPAC name 1,2,3,4,5,6-hexachloro-cyclohexane-mixed isomer Molecular formula CeHgCb, 

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Cm.OROCARBONSANDCm.OROHYDROCARBONS - TOXIC AROMATICS] (Void) b-Hexachlorocyclohexane... 

The performance of SCWO for waste treatment has been demonstrated (15,16). In these studies, a broad number of refractory materials such as chlorinated solvents, polychlorinated biphenyls (PCBs), and pesticides were studied as a function of process parameters (17). The success of these early studies led to pilot studies which showed that chlorinated hydrocarbons, including 1,1,1-trichloroethane /7/-T5-6y,(9-chlorotoluene [95-49-8] and hexachlorocyclohexane, could be destroyed to greater than 99.99997, 99.998, and 99.9993%, respectively. In addition, no traces of organic material could be detected in the gaseous phase, which consisted of carbon dioxide and unreacted oxygen. The pilot unit had a capacity of 3 L/min of Hquid effluent and was operated for a maximum of 24 h. 

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). 

HERBAZIN 500 BR , siniazine, 74 HERBI D-480 , 2,4-D, 74 HERBIMIX SC , atraziiie + semazine, 74 HERBIPAK 500 BR , ametryn, 74 HERBITRIN 500 BR , atraziiie, 74 HERBOXONE , 2,4-D, 74 HERBURON 500 BR , diui-on, 74 Hercules Eic., 232 Herdillia Chemicals Ltd., 172 Heterene Iiic., 232 Hexachlorobenzene, 74 Hexachlorobutadiene, 74 Hexachlorocyclohexanes, 74 Hexachlorocyclopentadiene, 74 Hexachloroethane, 75 Hexachloronaphthalene, 75 Hexachlorophene, 75 Hexafluoroacetone, 75 Hexafluoroethane, 75 Hexaniethylenedianiine, 75 Hexaniethylene diisocyanate, 75 Hexaniethylphosphoric trianiide, 75 n-Hexane, 75 Hexanol, 75 Hexazinone, 75 1-Hexene, 75... 

That benzene hexachloride isomer mixture is then the raw material for lindane production. The production of lindane per se is not a chemical synthesis operation but a physical separation process. It is possible to influence the gamma isomer content of benzene hexachloride to an extent during the synthesis process. Basically, however, one is faced with the problem of separating a 99%-plus purity gamma isomer from a crude product containing perhaps 12 to 15% of the gamma isomer. The separation and concentration process is done by a carefully controlled solvent extraction and crystallization process. One such process is described by R.D. Donaldson et al. Another description of hexachlorocyclohexane isomer separation is given by R.H. Kimball. 

There are eight diastereomers of 1,2,3,4,5,6-hexachlorocyclohexane. Draw each in its more stable chair conformation. One isomer loses HC1 in an E2 reaction nearly 1000 times more slowly than the others. Which isomer reacts so slowly, and why ... 

Gamma hexachlorocyclohexane, radiation resistance, 196 Gamma-rays, 188, 193, 194, 197, 202 Gamma-space, 320 Gas hydrates, 3, 20, 22, 25, 34 mechanism of formation, 4 thermodynamic properties, 15 x-ray work, 3... 

Heterogeneous polymerization, 163 Hexachlorobenzene, influence of radiation on, 198, 200 quadrupole spectrum, 197 Hexachlorocyclohexane resonance lines, 191... 

Rings with more than two differently substituted carbons can be dealt with on similar principles. In some cases, it is not easy to tell the number of isomers by inspection. The best method for the student is to count the number n of differently substituted carbons (these will usually be asymmetric, but not always, e.g., in 68) and then to draw 2" structures, crossing out those that can be superimposed on others (usually the easiest method is to look for a plane of symmetry). By this means, it can be determined that for 1,2,3-cyclohexanetriol there are two meso compounds and a dl pair and for 1,2,3,4,5,6-hexachlorocyclohexane there are seven meso compounds and a dl pair. The drawing of these structures is left as an exercise for the student. 

The mechanism is usually electrophilic (see p. 972), but when free-radical initiators (or UV light) are present, addition can occur by a free-radical mechanism. Once Br-or Cl- radicals are formed, however, substitution may compete (14-1 and 14-2). This is espiecially important when the alkene has allylic hydrogens. Under free-radical conditions (UV light) bromine or chlorine adds to the benzene ring to give, respectively, hexabromo- and hexachlorocyclohexane. These are mixtures of stereoisomers (see p. 161). ... 

Lastly, we will describe how these methods have been used to characterize the effects of hexachlorocyclohexanes on neutrophil functions. Although we are limiting this to a discussion of neutrophils, these approaches are completely generalizable to other cell types and have already been applied to some. We hope this summary will be useful to workers who wish to extend these techniques to the cell systems of interest to them. 

There are several isomers of 1,2,3,4,5,6-hexachlorocyclohexane (HCH). The Y isomer is insecticidally active, whereas most of the others are relatively inactive. These compounds have been shown to activate inflammatory functions of neutrophils (35,36). Using Indo-1, we have characterized intracellular Ca mobilization in response to these compounds. Figure 9 shows the responses of cells labeled with Indo-1 to stimulation by y, < " P , and 6-HCH at a concentration of 260 pH. 

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