2.4.5- trichlorophenol production

The environmental burden of waterways with polychlorinated dibenzo-p-dioxins (PCDD) has been at the forefront of public and regulatory concern, because of the toxicity associated with particularly the 2,3,7,8-(laterally) substituted congeners, which have a tendency to bioaccumulate throughout the trophic food chain. Contamination of aquatic sediments by dioxins includes both non-point (e.g., atmospheric deposition) and point sources (e.g., industrial effluents, combined sewage overflows), and is generally characterized by a dominance of hepta- and octa-CDD, with minor contributions of hexa- to tetra-CDD [429]. Elevated concentrations of the 2,3,7,8-TCDD isomer tend to be associated with direct discharge from sources such as 2,4,5-trichlorophenol production [54,430]. 

The Seveso disaster began on July 10, 1976 at the Industrie Chimiche Meda Societa Azionaria (ICMESA) chemical plant in Meda, Italy. This event became internationally known as the Seveso disaster, after the name of the most severely affected community. An increase in pressure due to an exothermic reaction in a 2,4,5-trichlorophenol-production reactor caused the rupture disk of the safety valve to burst. About 3000 kg of chemicals were released into the air. The release included 2,4,5-trichlorophenol, used in the manufacture of herbicides, and possibly up to 30 kg of the dioxin TCDD (2,3,7,8-tetrachloro-dibenzo-p-dioxin). Dioxin first came to widespread public notice during the Vietnam War, when it was identified as a component of the defoliant Agent Orange. Dioxin has also been considered to be the most toxic human-made substance. 

From 1935 to 1978, workers world-wide were exposed during periodic explosions at trichlorophenol production facilities as well as during their daily production activities. Table II illustrates some major industrial accidents which yielded published reports of health effects. Table III lists some major health outcomes reported following exposures to products contaminated with 2,3,7,8-TCDD. The primary dermal effect of exposure is chloracne, a persistent form of acne caused by exposure to a number of chlorinated organic compounds. Chloracne occurred in some exposed persons in all accidents, as well as in children in Seveso (2-4). Chloracne appeared with and without other health effects and persisted in some persons up to 28 years after exposure (5-6). 

PCBs) folliculitis and xerosis (TCAB, TCAOB) and actinic elastosis (TCDD). Erythema and edema of the exposed face and extremities associated with trichlorophenol production was also seen in the Seveso cases. These pre-chloracne lesions were also accompanied by vesiculobullous and necrotic lesions on finger tips and palms, and papulonodular lesions, all of which resolved within a few weeks. Hyperkeratotic, infiltrative erythematous granuloma annulare or erythema elevatum diutinum-like lesions were also seen in association with chloracne 2 months after the explosion. Axillary involvement and follicular hyperkeratosis are linked with inhalation or ingestion of chloracnegens (Taylor 1979 Tindall 1985). 

C12H4CI4O2. A by-product in the preparation of 2,4,5-trichlorophenol from 1,2,4,5-tetrachlorobenzene, sodium hydroxide and ethylene glycol. Causes chloracne in humans. 

Several antimicrobials have been banned or severely restricted by the EPA based on documented or suspected toxicity or environmental problems. Others have been discontinued in the face of testing costs required by the EPA reregistration program mandated by the Pederal Insecticide, Pungicide, and Rodenticide Act (PIPRA) of 1988 (10). Some of the significant products that have become obsolete are 2,4,5-trichlorophenol/P3 -5 3 -47, sodium... 

Oxidation of saligenin with chromic acid or silver oxide yields saUcyladehyde as the first product. Further oxidation results in the formation of sahcyhc acid, which is also obtained when saligenin is heated with sodium hydroxide at 200—240°C. Chlorination of an aqueous solution of the alcohol gives 2,4,6-trichlorophenol, and bromination in an alkaline medium yields 2,4,6-tribromophenol and tribromosaligenin. When saligenin is heated with one mole of resorcinol in the presence of anhydrous zinc chloride, 3-hydroxyxanthene forms. 

With the discontinuation of some herbicides, eg, 2,4,5-trichlorophenol [39399-44-5] based on the higher chlorinated benzenes, and DDT, based on monochlorobenzene, both for ecological reasons, the production of chlorinated benzenes has been reduced to just three with large-volume appHcations of (mono)chlorobenzene, o-dichlorobenzene, and -dichlorobenzene. Monochlorobenzene remains a large-volume product, considerably larger than the other chlorobenzenes, in spite of the reduction demanded by the discontinuation of DDT. 

In the chlorination of 2,4-dichlorophenol it has been found that traces of amine (23), onium salts (24), or triphenylphosphine oxide (25) are excellent catalysts to further chlorination by chlorine ia the ortho position with respect to the hydroxyl function. During chlorination (80°C, without solvent) these catalysts cause traces of 2,4,5-trichlorophenol ( 500 1000 ppm) to be transformed iato tetrachlorophenol. Thus these techniques leave no 2,4,5-trichlorophenol ia the final product, yielding a 2,4,6-trichlorophenol of outstanding quaUty. The possibiUty of chlorination usiag SO2CI2 ia the presence of Lewis catalysts has been discussed (26), but no mention is made of 2,4,5-trichlorophenol formation or content. 

The plant s product was hexachlorophene, a bactericide, with trichlorophenol produced ns an intermediate. During normal operation, a very small amount of TCDD (2,3,7,8 telrachlomdib zoparadioxin) is produced in the reactor as an undesirable side product. TCDD is perhaps the most ]in(enl toxin known to man. Studies have shown TCDD to be fatal in doses as small as lE-9 times die body weight, it insolubility in water makes decontamination very difficult. Nonlethal doses of TCDD result in chloracne, an acne-like disea.se that can persist for several years. 

Tetrachlorodibenzo-p-dioxin (TCDD) (I), an occasional contaminant in 2,4,5-T and other trichlorophenol derivatives, is the most toxic of the commonly-encountered dioxins (8) and it received most of our attention. Its low solubility in common solvents and water (ca. 2 ppb) limited our experiments since the products were difficult to identify by the conventional techniques of organic chemistry. However, TCDD has an absorption maximum at 307 nm in methanol—well within the solar spectrum observed at the earth s surface and near the region of maximum intensity (310-330 nm) of the UV lamps used in previous experiments (H 29). 

Oevere toxicological responses have been associated with certain chloro- dibenzodioxins. One of these responses is chloracne, a folliculosis first associated with skin contamination by chlorohydrocarbons in 1899 (3). Serious outbreaks of chloracne-like lesions associated with runaway reactions in the production of 2,4,5-trichlorophenol occurred in Germany in the early 1950 s (5). 2,4,5-Trichlorophenol itself does not cause acne (S), but the contaminants which may be formed in the uncontrolled production of 2,4,5-trichlorophenol are extremely potent acnegens (5). 2,3,7,8-Tetrachlorodibenzo-p-dioxin and tri- and tetra-... 

Reagents. Substituted phenols, obtained commercially, were used unless otherwise noted phenols were analyzed by GLC to ensure 99+% purity. 2,4,5-Trichlorophenol and pentachlorophenol were purified by sublimation and recrystallization to yield product of 99+% purity. 

Bromo-3,4,6-trichlorophenol. 2,4,5-Trichlorophenol (20 grams, 0.10 mole) was dissolved in 40 ml of glacial acetic acid (HOAc). Bromine (17 grams, 0.11 mole) dissolved in HOAc was added to the phenol, and the mixture was heated to 100°C. The color of bromine persisted until 30 ml of water were added. The reaction mixture yielded yellow-tinted crystals upon cooling. The product formed an oil when dissolved in methanol or HOAc—H2O. The phenol was converted to its potassium salt by adding KOH and evaporating the solvent. 

Bromo-4,5,6-trichlorophenol. 2,3,4-Trichlorophenol (20 grams, 0.10 mole) was dissolved in 30 ml of HO Ac and titrated with bromine (18 grams, 0.11 mole) dissolved in HOAC-H2O (30 ml each). The last few drops of bromine caused the characteristic color of bromine to persist. The product was precipitated by adding water to the reaction mixture. The filtered product was recrystallized from methanol-water solvent yielding 27 grams (98% yield) of white crystals. 

Tetrachlorodiben2o- >-dioxin. Purified 2,4,5-trichlorophenol (50 grams, 0.26 mole) was converted to its potassium salt and dissolved in 100 ml of bEEE. After addition of the copper catalyst and ethylene diacetate, the mixture was transferred to the bottom of a 300-ml sub-limer with chloroform. Sublimation (200°C/2 mm) yielded 14 grams (39% yield) of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Mass spectral analysis revealed trace quantities of pentachlorodibenzo-p-dioxin, tetrachloro-dibenzofuran, and several unidentified substances of similar molecular weight. The combined impurity peaks were estimated to be <1% of the total integrated GLC area. The product was further purified by recrystallizations from o-dichlorobenzene and anisole. The final product had an estimated 260 ppm of trichlorodibenzo-p-dioxin as the only detected impurity. 

Hexachlorodibenzo-l -dioxin. 2,3,4,6-Tetrachlorophenol was purified by distillation and recrystallization to yield a product containing <0.1% trichlorophenol impurity. The phenol was dissolved in toluene and mixed with an equimolar amount of aqueous caustic. Water was azeotropically... 

Octachlorodibenzo- -dioxin. Pentachlorophenol was purified by sublimation and recrystallization to yield a product with the following composition trichlorophenol, 0.04% tetrachlorophenol, 0.07% and pentachlorophenol, 100.4 1%. Pentachlorophenol (300 grams, 1.13 mole) was dissolved in 900 ml of trichlorobenzene and chlorinated anhydrously for 18 hours at reflux. Ghlorine addition was stopped and the mixture was heated for 28 more hours at reflux. The crystalline product was washed with 2-liter portions of chloroform, IN NaOH, methanol, and water. Analysis by GLG suggested the presence of 5-15% heptachloro-dibenzo-p-dioxin. The mixture was carefully added to a cleaning solution of 200 ml water, 3.5 liters sulfuric acid, and 125 grams sodium dichromate. The mixture was heated at 150 °G for six hours. The product was recrystallized from hot o-dichlorobenzene and then from anisole. The purified product (160 grams, mp 329.8° 0.5°G) contained <0.1% heptachlorodibenzo-p-dioxin, determined by GLG. 

A spore-forming strain of Desulfitobacterium chlororespirans was able to couple the dechlorination of 3-chloro-4-hydroxybenzoate to the oxidation of lactate to acetate, pyruvate, or formate (Sanford et al. 1996). Whereas 2,4,6-trichlorophenol and 2,4,6-tribro-mophenol supported growth with the production of 4-chlorophenol and 4-bromophenol, neither 2-bromophenol nor 2-iodophenol was able to do so. The membrane-bound dehalogenase contains cobalamin, iron, and acid-labile sulfur, and is apparently specific for ortho-substituted phenols (Krasotkina et al. 2001). 

Chlorinated phenols have been traditionally applied in the production of wood preservatives, insecticides and disinfectants. Common chlorinated phenols found in wood preservatives are 2,3,4,6-tetrachlorophenol (TeCP), 2,4,6-trichlorophenol... 

TCP), and pentachlorophenol (PCP), in order of abundance. Minor amounts of other trichlorophenols and dichlorophenols may also be present, as well as recalcitrant polychlorinated phenoxyphenols (PCPPs) and PCDD/Fs as impurities [75, 76]. In Finland, approximately 30,000 tons of CP products were used between 1934 and 1988, when they were banned because of their potential toxicity to humans and the environment [77, 78]. The careless manufacturing and application of wood preservatives together with the lack of suitable waste disposal caused massive contamination of river sediments and sawmill sites. For example, the river Kymijoki in southern Finland was identified as the largest source of dioxins accumulating in fish in the entire Baltic area. Similar products were used in other European countries, especially Nordic countries with a large forestry industry, such as Sweden [79]. 

Seveso is a small town of approximately 17,000 inhabitants, 15 miles from Milan, Italy. The plant was owned by the Icmesa Chemical Company. The product was hexachlorophene, a bactericide, with trichlorophenol produced as an intermediate. During normal operation, a... 

On July 10,1976, the trichlorophenol reactor went out of control, resulting in a higher than normal operating temperature and increased production of TCDD. An estimated 2 kg of TCDD was released through a relief system in a white cloud over Seveso. A subsequent heavy rain washed the TCDD into the soil. Approximately 10 square miles were contaminated. 

A reaction at the interface caused by a loss of mixing can eventually lead to a runaway itself. Examples include nitration processes and the well-known Seveso incident where agitation stopped in a reactor during the manufacture of trichlorophenol this led to higher than normal temperatures and increased production of the undesirable side product 2,3, 7,8-tetrachlorodibenzo-p-di-oxin (commonly referred to as "dioxin"), ultimately resulting in a vapor release to the atmosphere. 

EPA. 1988b. Computer printout (CIS) 1977 production statistics for chemicals in the Federal Register. 1979. Petition to remove ethylbenzene, phenol, 2,4-dichlorophenol, 2,4,5- trichlorophenol and pentachlorophenol from the 307(a)(1) list of toxic pollutants. US. Environmental Protection Agency. Fed Reg 44 64555-64559. 

All accidents concerned with PCDD/F are related to the production of chlorophenols. The most famous accident happened in Seveso close to Milan, Italy, on July 10, 1976. ICMESA Corp. manufactured 2,4,5-trichlorophenol for production of phenoxy-herbizides by alkaline hydrolysis of 1,2,4,5-tetrachlorobenzene (see Figure 8.1). This... 

---