Hexachlorocyclohexane production

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). 

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. 

Co(TPP) has been demonstrated to act as a catalyst for the electrocarboxylation of benzyl chloride and butyl bromide with CO - to give PhCHiCfOiOCH Ph and Bu0C(0)C(0)0Bu, respectively. The propo.sed mechanism involved Co(TPP)R and [Co(TPP-N-R) as intermediates (the latter detected by spectroscopy) in the catalytic production of free R or R-, which then reacted directly with Co(TPP) precipitated on graphite foil has been successfully used for the determination of organic halides, including DDT and 1,2,3,4,5,6-hexachlorocyclohexane (lindane), to sub-ppm level in aqueous solution. Deoxygenation of the solutions is not required, and the technique is moderately insensitive to the ionic composition of the solution. ... 

Particularly the chlorinated compounds have enjoyed range of applications vinyl chloride (chloro-ethene) as monomer for the production of PVC, tetra- and trichloroethenes as solvents for degreasing, and the insecticides l,l,l-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and isomers of hexachlorocyclohexane (HCH) (benzene hexachloride). The biodegradation of fluorinated aliphatic compounds is generally different from the outlines that have emerged from investigations on their chlorinated, brominated, and even iodinated analogues. They are therefore treated separately in Part 4 of this chapter. 

For some important insect pests there are still no satisfactory chemical controls. Such problems should be given due consideration in the development program. Many of these problems appeared to be solved with the discovery of DDT, benzene hexachlo-ride (hexachlorocyclohexane), and some of the more recent insecticides. Further studies of the toxicity of some of these products to warm-blooded animals have raised the important question of the advisability of continuing their use where food and feed products are concerned. Considerable attention is being centered on finding safer analogs, such as TDE and methoxychlor, and new and better insecticides. 

Partition chromatography, developed by Martin and Synge (3) for the separation of amino acid derivatives, was employed by Ramsey and Patterson (4) for the separation of isomers of benzene hexachloride (1,2,3,4,5,6-hexachlorocyclohexane) in the technical product. The work of Ramsey and Patterson was extended by Aepli, Munter, and Gall... 

Various industrial pilot plants and full-scale operations, using radiation-chemical processing have been reported, with production rates -50 to -1000 tons per year (Spinks and Woods, 1990 Chutny and Kucera, 1974). Production rates less than -50 tons per year are not considered viable. These operations are or have been conducted in countries such as the United States, the former U.S.S.R., Japan, and France. However, some operations have also been reported in the former Czechoslovakia and Romania, especially in connection with petroleum industry. In the United States, chlorination of benzene to gammexane (hexachlorocyclohexane) was hotly pursued at one time by radiation or photoinitiation. Since the early seventies the activity has dwindled, presumably due to lack of demand and environmental considerations. 

Chlorination of aromatic compounds under irradiation has been studied extensively (Wagner, 1969). With benzene, the product is a mixture of stereoisomeric hexachlorocyclohexanes with yields 104pmol.J 1. This certainly points to chain reaction with the initiation either from a dissociation, Cl2 2C1, or from the participation of the first excited singlet state of benzene 0B2u) giving... 

Chlorination of benzene gives an addition product that is a mixture of stereoisomers known collectively as hexachlorocyclohexane (HCH). At one time, this was incorrectly termed benzene hexachloride. The mixtnre has insecticidal activity, though activity was found to reside in only one isomer, the so-called gamma isomer, y-HCH. y-HCH, sometimes under its generic name lindane, has been a mainstay insecticide for many years, and is about the only example of the chlorinated hydrocarbons that has not been banned and is still available for general use. Although chlorinated hydrocarbons have proved very effective insecticides, they are not readily degraded in the environment, they accumulate and persist in animal tissues, and have proved toxic to many bird and animal species. 

Although substitution is more common, aromatic compounds may undergo addition if forcing conditions are used. When benzene is treated with an excess of chlorine under heat and pressure (or with irradiation by light), six chlorine atoms add to form 1,2,3,4,5,6-hexachlorocyclohexane. This product is often called benzene hexachloride (BHC) because it is synthesized by direct chlorination of benzene. 

Hexachlorocyclohexane During the production of this substance from chlorine and benzene under the influence of light, various isomers are also formed, particularly the toxic substance hndane. 

Isomers of hexachlorocyclohexane (HCH) are found in air, soil, water, food and even breast milk. Lindane is used in large quantities in agriculture and forestry as a wood preservative as well as in veterinary medicine. Provided that the required safety measures are adhered to, no liver damage occurs during the production of lindane. On the other hand, liver cell necrosis was observed in animal experiments after HCH isomers were added to the feed a carcinogenic effect was seen after long-term administration. An increased toxic potential is to be expected when there is simultaneous exposure to DDT, PCB, contraceptives, etc. 

Lindane is absorbed from the gastrointestinal tract, the respiratory tract, and skin. The metabolism of lindane is complex and involves a number of pathways depending on which isomer of hexachlorocyclohexane (HCH) is involved (lindane is the gamma (y) isomer). It is nonetheless rapid. Lindane is metabolized in the liver by microsomal enzymes. The main pathways include stepwise elimination of chlorines to form tri- and tetrachloro-phenols and conjugation with sulfates or glucuron-ides and subsequent elimination. Other metabolic pathways involve the production of mercaptura-tes. These water-soluble products are eliminated in the urine. Lindane is bound by serum proteins in the blood. Storage is in adipose tissue and other... 

The reaction of Clj with a number of mixtures including butan-l-ol and butan-2-ol cyclohexanol, cyclohexanone, and hexachlorocyclohexane and phenol, chlorobenzene and dichlorobenzene (isomeric mixture) proceeded similarly. Many other similar types of mixtures are likely to undergo COCl /CCl formation under such severe conditions. Indeed, this system can be extended under such forcing conditions (550-660 "C and 80-300 atmospheres) to the reaction of Clj with mixtures of CO, CO or HjO with benzene, chlorinated benzenes, hexachlorocyclohexanes, trichloroethane, trichloroethene, or tetrachloroethene [1714]. The hydrogen in the system appears as HCl, and some perchlorinated compounds tend to be formed, but the principal carbon-containing products are COCl and CCl. ... 

Hexachlorocyclohexane has been used as an insecticide for the control of agricultural pests, for dressing of cereal seed and for the control of parasites on farm animals since the 1960s. Its use has been banned in many countries but it still remains in extensive use in others. Hexachlorocyclohexane mainly exists in the form of three different isomers, a-(3- and y-hexachlorocyclohexane, appearing in a cmde mixture after manufacture. Only one of these isomers, the y form, expresses insecticidal activity, and the refined product containing about 99% y-hexachlorocyclohexane (y-HCH) is named lindane. 

S) -S-(l-phenylethyl)-gluCaChione compounds were isolated in a 60Z yield. Hexachlorocyclohexane (lindane) has been used as starting material for synthesis of glutathione conjugates of dichlorobenzenes. Three products were isolated and characterized as the 2,5-, 3,5- and 2,3-dlchlorophenyl glutathione conjugates (121-123). 

Chlorination of benzene may lead to the formation of various chlorinated products. Commercial chlorination is generally carried out in tall cast-iron or steel tanks which have been lined with pure lead, then tile (55). The process is regulated so that chlorobenzene is the chief product. Wiegandt and Lantos (77) developed a process for improved yields of p-dichlorobenzene. Hexachlorocyclohexane is generally obtained by photochemical chlorination of benzene 40, 55). 

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