2- Chlorophenol, products

Effects in Humans. In chlorophenol production, irritation symptoms of the nose, eyes, respiratory tract, and skin resulting ia chloroacne have been observed. The results of epidemiology studies on the long-term effects of chlorophenols are quite contradictory and have not allowed the experts to reach any firm conclusions (54). 

Overall, the chlorophenol market is ia decline. Table 2 gives worldwide production figures for 1989, excluding China, India, and Russia. Part of Western Europe s production is exported to Russia for reasons of quaUty. The main producers are brought together ia Table 3 according to the nature of their chlorophenol production. 

Milliken CE, Meier GP, Sowers KR, May HD (2004) Chlorophenol Production by Anaerobic Microorganisms Transformation of a Biogenic Chlorinated Hydroquinone Metabolite. Appl Environ Microbiol 70 2494... 

TCDD and other congeners during the BASF AG accident, and Fingerhut et al. (1991) found a significantly increased risk of cancer mortality in phenoxy herbicide and chlorophenol production workers. More complete descriptions of significant findings in the mortality studies are presented in the appropriate effect portions of Section 2.1. 

Vena J, Boffetta P, Becher H, et al. 1998. Exposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers. Environ Health Perspect 106(Suppl 2) 645-653. 

Radioimmunassay (RIA) is used to detect and quantify minute quantities of an antigen in biological or environmental samples. RIA is commonly used to measure nonprotein antigens such as drugs and toxicants. This immunoassay is highly quantitative. An example of the use of RIA in toxicology would be the analyses of dioxin levels in the blood of employees from a chlorophenol production plant. 

Chlorophenols are a class of pesticide substances, e.g. fungicides, used for wood preservation, in pulp production and other miscellaneous applications. The substances were introduced in the 1930s and have been used in very large amounts. Today, the consumption has decreased and the substances are banned in many countries. The main active substance in chlorophenol products is pentachloro-phenol (PCP Figure 3.10). The substance is moderately lipophilic and persistent, yet readily absorbed and accumulated in biota and expresses a rather high acute toxicity. The metabolism and breakdown of this envirotoxicant in biota and in the environment are rather slow, resulting in successively dechlorinated metabolites. 

In contrast to air pollutants such as volatile hydrocarbons, PCDD have very low vapor pressure so that the vapor phase does not represent a major exposure route for dioxin. Finally, unlike pollution problems caused by chemicals produced for useful purposes, dioxin Is a minute, unwanted byproduct of chlorophenol production and of combustion processes. 

Larson, R. A. and A. L. Rockwell. 1979. Chloroform and chlorophenol production by decarboxylation of natural acids during aqueous chlorination. Environ. Sci. Technol. 13 325-329. 

Phenolics. Phenol (qv) and the chlotinated phenoHcs formerly comprised the largest class of iadustrial antimicrobials (see Chlorophenols). Table 5 shows the remaining phenoHcs of importance. Use of pentachlorophenol has been severely restricted only one manufacturer suppHes product for the wood preservation market. 

The most common use of 2-(2, 4 -dichlorophenoxy)-5-chlorophenol (2,4,4 -trichloro 2 -phenoxyphenol) is in the personal care products market, where it is commonly known as triclosan and is the active antibacterial in underarm deodorants. It has also found some acceptance as an antibacterial component of plastic mattress covers. 

Reductive DechIorina.tion. Such reduction of chlorinated aUphatic hydrocarbons, eg, lindane, has been known since the 1960s. More recentiy, the dechlorination of aromatic pesticides, eg, 2,4,5-T, or pesticide products, eg, chlorophenols, has also been documented (eq. 10) (20). These reactions are of particular interest because chlorinated compounds are generally persistent under aerobic conditions. 

By the procedure described in the preceding experiment, 30 g (0.11 mole) of tri-phenylphosphine dissolved in 100 ml of acetonitrile is converted to triphenylphosphine dibromide. After the addition of the bromine has been completed, the cooling bath is removed, the flask is set up for vacuum distillation, and the solvent is removed. To the residue is added /7-chlorophenol (10.3 g, 0.08 mole), and the flask is heated at 200° (mantle, wax bath, or sand bath) until HBr ceases to be evolved (about 2 hours). The flask is cooled and the contents are steam distilled affording crude / -chlorobromo-benzene in about 90% yield. Recrystallization from benzene gives the pure product, mp 65-66°. 

Harano and colleagues [48] found that the reactivity of the Diels-Alder reaction of cyclopentadienones with unactivated olefins is enhanced in phenolic solvents. Scheme 6.28 gives some examples of the cycloadditions of 2,5-bis-(methoxycar-bonyl)-3,4-diphenylcyclopentadienone 45 with styrene and cyclohexene in p-chlorophenol (PCP). Notice the result of the cycloaddition of cyclohexene which is known to be a very unreactive dienophile in PCP at 80 °C the reaction works, while no Diels-Alder adduct was obtained in benzene. PCP also favors the decarbonylation of the adduct, generating a new conjugated dienic system, and therefore a subsequent Diels-Alder reaction is possible. Thus, the thermolysis at 170 °C for 10 h of Diels-Alder adduct 47, which comes from the cycloaddition of 45 with 1,5-octadiene 46 (Scheme 6.29), gives the multiple Diels-Alder adduct 49 via decarbonylated adduct 48. In PCP, the reaction occurs at a temperature about 50 °C lower than when performed without solvent, and product 49 is obtained by a one-pot procedure in good yield. 

PCDFs are similar in many respects to PCDDs but have been less well studied, and will be mentioned only briefly here. Their chemical structure is shown in Figure 7.1. Like PCDDs, they can be formed by the interaction of chlorophenols, and are found in commercial preparations of chlorinated phenols and in products derived from phenols (e.g., 2,4,5-T and related phenoxyalkanoic herbicides). They are also present in commercial polychlorinated biphenyl (PCB) mixtures, and can be formed... 

Dichlorodibenzo-p-dioxin was prepared from isotopic potassium 2,4-dichlorophenate uniformly labeled with Ullman conditions gave a 20.5% yield. Small amounts of dichlorophenoxy chlorophenol were removed from the product by extraction with sodium hydroxide before purification by fractional sublimation and recrystallization from anisole. Chlorination of 2,7-dichlorodibenzo-p-dioxin in chloroform solution containing trace amounts of FeCls and 12 yielded a mixture of tri-, tetra-, and pentachloro substitution products. Purification by digestion in boiling chloroform, fractional sublimation, and recrystallization from anisole was effective in refining this product to 92% 2,3,7,8-tetrachloro isomer, which also contained 7% of the tri- and 1% of the penta-substituted dibenzo-p-dioxin. Mass spectroscopy was used exclusively to monitor the quality of the products during the synthesis. 

Uniformly labeled 2,4-dichlorophenol- C (purchased from New England Nuclear Corp, Boston, Mass.) was used in the tracer preparation. This provided a label at all carbon positions in the dibenzo-dioxin structure. 2,7-Dichlorodibenzo-p-dioxin- C after initial cleanup by fractional sublimation, contained approximately 5% of an impurity, detected by thin layer chromatography (TLC) which gave mass peaks at 288, 290, 292, and 294 in the mass spectrometer, consistent with a trichloro-hydroxydiphenyl oxide. This is probably the initial condensation product of the Ullman reaction and is most likely 2-(2,4-dichlorophenoxy)-4-chlorophenol. It was removed easily by extractions with aqueous... 

PCP presents a different picture from that of the lower chlorophenols and their derivatives. The corresponding dioxin shows much more stability to light than does TCDD, enough to permit its prolonged existence at low concentrations in a photoreactor. As a phenol it can directly yield dioxins, a process favored by its normal mode of application as the sodium salt. Although octachlorodibenzo-p-dioxin has much lower mammalian toxicity than TCDD (6), its formation, properties, and effects demand additional investigation. Technical preparations of PCP are frequently mixtures of tetra- and pentachlorophenols consequently, hepta-and possibly hexachlorodibenzo-p-dioxins might be expected as photolysis products in addition to the octachloro derivative. 

Industrial workers involved in chlorinated aromatic production including chlorophenol suffered dioxin-induced chloracne 2,3). Chloracne and other serious health disturbances have been attributed to polychloro-dibenzo-p-dioxins in workers involved in manufacturing 2,4,5-T 4, 5). Dioxins are toxic to chick embryos, guinea pigs, rabbits, and monkeys 6, 7, 8, 9, 10). 

The objectives of the soil persistence experiments were (1) to learn the effect of soil type and concentration on the TCDD degradation rate, (2) to isolate and characterize degradation products from DCDD and TCDD, and (3) to determine whether chlorodioxins could be formed from chlorophenol condensation in the soil environment. This last study was essential since quality control at the manufacturing level could reduce or eliminate the formed dioxin impurity. But the biosynthesis of chlorodioxins by chlorophenol condensation in the soil environment could not be controlled and would have connotations for all chlorophenol-de-rived pesticides if formation did occur. The same question needed to be answered for photochemical condensation reactions leading to chloro-... 

The most convenient and successful synthetic preparation of octa-chlorodibenzo-p-dioxin has been described by Kulka (13). The procedure involves chlorination of pentachlorophenol in refluxing trichlorobenzene to give octachlorodibenzo-p-dioxin in 80% yield. Kulka has explained the reaction as coupling between two pentachlorophenoxy radicals. Large amounts (5—15%) of heptachlorodibenzo-p-dioxin were observed in the unpurified product. Since the pentachlorophenol used in this study contained 0.07% tetrachlorophenol, we feel that tetrachloro-phenol may be produced in situ (Reaction 4). Such a scheme would be analogous to the formation of 2,4-dichlorophenol and 3-chlorophenol produced from 2,4,4 -trichloro-2 -hydroxydiphenyl ether (Reaction 2). The solubility of octachlorodibenzo-p-dioxin was determined in various solvents data are presented in Table II. 

Dichlorodibenzo- -dioxin. 2-Bromo-4-chlorophenol (31 grams, 0.15 mole) and solid potassium hydroxide (8.4 grams, 0.13 mole) were dissolved in methanol and evaporated to dryness under reduced pressure. The residue was mixed with 50 ml of bEEE, 0.5 ml of ethylene diacetate, and 200 mg of copper catalyst. The turbid mixture was stirred and heated at 200°C for 15 hours. Cooling produced a thick slurry which was transferred into the 500-ml reservoir of a liquid chromatographic column (1.5 X 25 cm) packed with acetate ion exchange resin (Bio-Rad, AG1-X2, 200-400 mesh). The product was eluted from the column with 3 liters of chloroform. After evaporation, the residue was heated at 170°C/2 mm for 14 hours in a 300-cc Nestor-Faust sublimer. The identity of the sublimed product (14 grams, 74% yield) was confirmed by mass spectrometry and x-ray diffraction. Product purity was estimated at 99- -% by GLC (electron capture detector). 

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