1.4- Dichlorobenzene intermediate

Dichlorobenzene. T -Dichlorobenzene s largest and growing oudet is in the manufacture of poly(phenylene sulfide) resin (PPS). Other apphcations include room deodorant blocks and moth control, a market which is static and likely to remain unchanged but combined is currently a larger outlet than PPS. Small amounts ofT -dichlorobenzene are used in the production of 1,2,4-trichlorobenzene, dyes, and insecticide intermediates. Exports have been a principal factor in U.S. production with about 25% exported in 1988. 

Other Chlorobenzenes. The market for the higher chlorobenzenes (higher than di) is small in comparison to the combined mono- and dichlorobenzenes. Trichlorobenzenes are used in some pesticides, as a dye carrier, in dielectric fluids, as an organic intermediate and a chemical manufacturing solvent, in lubricants, and as a heat-transfer medium. These are small and decreasing markets. 

A variety of solvents was investigated for this reaction, as shown in Table 15.1. As inferred from Table 15.1, the hydrogenolysis performance is best in more polar solvents snch as acetonitrile, acetone, ethyl acetate, and acetic acid. Only in o-dichlorobenzene is the rate of reaction ranch lower than predicted by the dielectric constant. The presence of nonpolar solvents snch as hexane and the thiol product resulted in large amonnts of the disnlfide intermediate. It has been shown that the disnlfide is the intermediate in stoichiometric rednctions such as samarium diiodide reduction of alkyl thiocyanates to thiols (11) so it is reasonable to expect it as the... 

In 2001, Linder and Podlech studied the microwave-assisted decomposition of diazoketones derived from a-amino acids [340]. In the presence of imines, the initially formed ketene intermediates reacted spontaneously by [2+2] cydoaddition to form /3-lactams with a trans substitution pattern at positions C-3 and C-4 (Scheme 6.179) [340], In order to avoid the use of the high-boiling solvent 1,2-dichlorobenzene, most transformations were carried out in 1,2-dimethoxyethane under sealed-vessel conditions. Solvent-free protocols, in which the substrates were adsorbed onto an inorganic alumina support, led only to the corresponding homologated /3-amino acids. Evidently, traces of water present on the support trapped the intermediate ketene. 

Although harmine 52 is frequently obtained by isolation (or purchase order), a synthesis of this compound as well as a number of analogs has recently appeared [47,48]. The key step to this synthesis was the thermal electrocyclization of oxime intermediate 55, which was prepared by acylation of vinylindole derivative 54 followed by treatment with hydroxylamine hydrochloride. Neither oxime 55 nor its ketone precursor were isolated— instead, the crude reaction mixture was heated at reflux in o-dichlorobenzene to ultimately yield harmine in 56% yield overall starting from 54 (Fig. 18). 

Thermal decomposition of the triazolopyridinium salt 31 in dichlorobenzene at 180 °C resulted in compounds 32 and 33 (Scheme 9), providing convincing support for the intermediate formation of a nitrenium cation <1997JOC1136>. 

Uses Manufacture of ethylbenzene (preparation of styrene monomer), dodecylbenzene (for detergents), cyclohexane (for nylon), nitrobenzene, aniline, maleic anhydride, biphenyl, benzene hexachloride, benzene sulfonic acid, phenol, dichlorobenzenes, insecticides, pesticides, fumigants, explosives, aviation fuel, flavors, perfume, medicine, dyes, and many other organic chemicals paints, coatings, plastics and resins food processing photographic chemicals nylon intermediates paint removers rubber cement antiknock gasoline solvent for fats, waxes, resins, inks, oils, paints, plastics, and rubber. 

When 1,2-dichlorobenzene in hydrogen-saturated deionized water was exposed to a slurry of palladium catalyst (1%) at room temperature, benzene formed via the intermediate chlorobenzene. The reaction rate decreased in the order of MCM-41 (mesoporous oxide having a silicon aluminum ratio of 35) > alumina > Y (dealuminated zeolite having a silicon aluminum ratio of 15). It appeared the reaction rate was directly proportional to the surface area of the support catalyst used (Schiith and Reinhard, 1997). 

Chlorinated aromatics, including monochlorobenzene (MCB), o-dichloroben-zene (o-DCB), and p-dichlorobenzene (p-DCB), are the major chlorinated aromatic species produced on an industrial scale. MCB is used as both a chemical intermediate and a solvent. As an intermediate, it is used to produce chloroni-trobenzene, pesticides, and pharmaceutical products. In solvent applications, MCB is used in the manufacture of isocyanates. Its high solvency allows it to be used with many types of resins, adhesives, and coatings. The o-dichlorobenzene is used primarily for organic synthesis, especially in the production of 3,4-dichlo-roaniline herbicides. Like MCB, it can be used as a solvent, especially in the production of isocyanates. It is also used in motor oil and paint formulations. The p-dichlorobenzene is used as a moth repellent and for the control of mildew and fungi. It also is used for odor control. It is a chemical intermediate for the manufacture of pharmaceuticals and other organic chemicals. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for 1,4-dichlorobenzene. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

Other intermediate-duration oral studies with 1,4-dichlorobenzene have reported liver toxicity. In female rats dosed with 1,4-dichlorobenzene by gavage for about 6 months, doses of 188 mg/kg/day and above resulted in increased liver weights. At 376 mg/kg/day, slight cirrhosis and focal necrosis of the liver were also observed (Hollingsworth et al. 1956). No effects on the liver were seen at a dose of 18.8 mg/kg/day. Based on a minimal LOAEL (increased liver weight) of 188 mg/kg/day, an intermediate-duration MRL of 0.4 mg/kg/day was calculated as described in the footnote to Table 2-2 and Appendix A (Hollingsworth et al. 1956). 

In a series of intermediate-duration studies, groups of Fischer 344 rats were administered 1,4-dichlorobenzene at concentrations ranging from 37.5 to 1,500 mg/kg/day by gavage in com oil 5 days a week for 13 weeks. Ocular discharge was noted prior to death in males dosed with 1,200 mg/kg and in all rats exposed to 1,500 mg/kg. In parallel studies with B6C3Fi mice, no compound-related ocular effects were observed after administration of 1,4-dichlorobenzene at concentrations ranging from 84.4 to 1,800 mg/kg/day by gavage in com oil 5 days a week for 13 weeks (NTP 1987). 

In intermediate-duration studies, no compound-related effects on weight gain were noted in albino or Fischer 344 rats administered 1,4-dichlorobenzene by gavage in com oil at doses up to 600 mg/kg/day,... 

The precise mechanism of 1,4-dichlorobenzene oxidation to 2,5-dichlorophenol has not thoroughly been investigated. 1,4-Dichlorobenzene is known to be metabolized by cytochrome P-450 (Azouz et al. 1955 Hawkins et al. 1980) in order to be presented to phase II metabolic pathways to increase its water solubility for excretion. A proposed metabolic pathway involving cytochrome P-450 with intermediate formations of metabolites has been outlined for 1,4-dichlorobenzene (Den Besten et al. 1992). No... 

The metabolism of 1,4-dichlorobenzene could involve the formation of an arene oxide intermediate, as has been proposed to occur in the oxidative metabolism of many halogenated aromatic hydrocarbons (Jerina and Daly 1974). 1,4-Dichlorobenzene has not been shown to be mutagenic in microbial or mammalian systems, a result that may be viewed as further suggestive evidence that an arene oxide intermediate is not involved in its metabolism. 

In addition, several studies in animals have demonstrated that increased mortality can result from acute-, intermediate-, or chronic-duration oral exposure to 1,4-dichlorobenzene. Because 1,4-dichlorobenzene mothballs are used in many homes, they are often readily accessible in closets and storage areas. Therefore, there is a potential concern for the lethal effects of 1,4-dichlorobenzene, especially if accidentally consumed by young children. 

An MRL of 0.2 ppm has been derived for intermediate-duration inhalation exposure (15 to 364 days) to 1,4-dichlorobenzene. 

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