Benzo-1,4-dioxines

Benzo- 1,4-dioxin 6,7-Dicarboxy-2,3-dihydro- IV/lb, 611 Peroxid Acetyl-(2-carboxy-benzoyl)-E13/1, 890 ( —CO—O—CO— + Persaure)... 

Experimental values of BSAF for 2,3,7,8-tetrachlorodi-benzo[ 1,4] dioxin and 2,3,7,8-tetrachlorodibenzofuran in contaminated sediments were obtained from exposure of the polychaete Nereis virens in a flow-through system for 28 day followed by a 24-h depuration period. The results were used to calculate the tissue concentrations of these contaminants at another site (Schrock et al. 1997). Although there was good agreement between the measured and predicted levels, it was pointed out that validation of this procedure would depend on the study of a more extensive data set. 

Figure 2. Photoreduction of 2,3,7,8-tetrachlorodi-benzo- -dioxin (I) (2 mg/liter in methanol) as compared with that of the 2,3,7-trichloro-homolog (II) (20), 1971 by AAAS...

Photooxygenations of 1,4-dioxins and their benzo- and naphtho derivatives as well as the ozonolyses of 1,4-benzo-dioxins and the cycloaddition of dithiins and 1,4-benzodithiins have been reported <1996CHEC-II(6)447>. In more recent reports, 2-chloro-l,4-benzodithiin-l,l,4,4-tetraoxide 67 was employed as a very reactive dienophile <19970393, 2005JOC5221> and was suggested as a mild alternative to the use of benzyne in [4-1-2] cycloaddition reactions (Scheme 7) <1996T14247>. 

Gas chromatography-mass spectrometry has been used to determine 2,3,7,8-tetrachloro-p-benzo dioxin in soil [226]. 

The first report on the peroxidase transformation of dioxins was published by Hammel et al. in 1986 [116]. They transformed dibenzo[p]dioxin and 2-chlorodi-benzo / dioxin with lignin peroxidase from P. chrysosporium. Later on, with the aim to elucidate the pathway for the fungal degradation of 2.7-dichlorodi ben7.0-p-dioxin. the oxidation products generated by lignin peroxidase and manganese peroxidase... 

SYNS DECAHYDRO-4a,7,9-TRIHYDROXY-2-METHYL-6,8-BIS(METHYLAmNO)-4H-PYRANO(2.3-b)(l,4)BENZO-DIOXIN-4-ONE DIHYDROCHLORIDE, (2R-(2-a,4a-P,5a-... 

Azzaoui, K., Lafosse, M., Lazar, S., Thiery, V. and Morinallory, L. (1995a). Separation of Benzo-dioxinic Isomers in LC. A Molecular Modeling Approach for the Choice of the Stationary Phase. J. Liquid Chromat., 18, 3021-3034. 

Abbreviations used in text AA, arachidonic acid AhR, aryl hydrocarbon receptor Amt, AhR nuclear translocator BR, bilirubin BV, biliverdin CYP1A1, cytochrome P4501A1 DRE, dioxin responsive element FICZ, 6-formylindolo(3,2b)carbazole HAH, halogenated aromatic hydrocarbon I3C, indole 3-carbinol ICZ, indolo-(3,2,-b)-carbazole PAH, polycyclic aromatic hydrocarbon RAR, retinoic acid receptor TCDD, 2,3,7,8-tetrachlorodi benzo-/>-dioxin Trp, tryptophan UGT 01, UDP-glucuronosy 1 transferase 01... 

Alternatively, a recent study by Dulin and coworkers ( ) found no photoproducts for 2,3,7,8-TCDD in either water or hexane, despite a careful analysis of the reaction solution for 2,3,7-trichlorodi-benzo- -dioxin. They suggested that cleavage of one Ar-0 bond is an alternative photochemical pathway which may predominate during 2,3,... 

The oxidation of 1,4-benzodioxins has been well investigated. Thus, oxidation of the 1,4-benzo-dioxin (42) by w-chloroperbenzonic acid afforded the 1,2-benzoquinone (43) in moderate yields. On the other hand, when (42) was oxidized by a -butyl hydroperoxide-vanadium catalyst system, followed by treatment with potassium carbonate, 1,2-benzoquinone (43) was obtained in good yield, because of the suppression of the formation of nucleophilic by-products <87JHC785>. 

As above (Section 6.09.5.2.1), the oxygenated ring of benzodioxin is relatively unstable towards electrophilic agents. However, reaction of ethyl 1,4-benzodioxin-2-carboxylate (39) and 1,4-benzo-dioxin-2-carbonitrile (47) with acyl chlorides in the presence of aluminum chloride in an inert solvent affords regiospecifically the corresponding acylated products (48) and (49), in excellent yields <95T2619>. 

Hydroxymethyl-1,4-benzodioxin (137) obtained in 80% yield by reduction of ethyl 1,4-benzo-dioxin-2-carboxylate (39) with lithium aluminum hydride in refluxing ether <91TL5525> reacted with zinc azide bis-pyridine complex under Mitsunobu conditions (triphenylphosphine, diisopropyl azodicarboxylate) to yield exclusively compound (138) in 75% yield. Otherwise, (137) was first reacted with zinc iodide under the same conditions until complete transformation of the starting material into the mixture of regioisomers (139) and (140) excess of dry piperidine was then added to the crude reaction medium to yield the alkenic analogue (141) of Piperoxan <89TL1637>. 

The lethal doses of the various very toxic compounds can vary over a wide range the LD50 value of the well-known Seveso poison 2,3,7,8-tetrachloro-di-benzo-dioxin (TCDD) indicates higher toxicity than potassium cyanide by a factor of 10 000, but it is less toxic than botulinus toxin by nearly the same factor. 

Less is known about 2,3-dihydro-5 -l,4-benzodioxepins. The parent member of this class of compounds (69) and its halogenated derivatives (68) and (70) could be obtained from 1,4-benzo-dioxin (66) by dihalogencarbene addition, thermolysis, and reduction (Scheme 6) <83AG(E)64>. 

The crystal structures of four chlorinated derivatives of di-benzo-p-dioxin have been determined by x-ray diffraction from diffractometer data (MoKa radiation). The compounds, their formulae, cell dimensions, space groups, the number of molecules per unit cell, the crystallographic B.-factors, and the number of observed reflections are given. The dioxin crystal structures were performed to provide absolute standards for assignment of isomeric structures and have been of considerable practical use in combination with x-ray powder diffraction analysis. 

Figure 7. ESR spectrum of 2,3-dichlorodi-benzo-p-dioxin in TFMS acid...

Chlorinated dibenzo ip-dioxins are contaminants of phenol-based pesticides and may enter the environment where they are subject to the action of sunlight. Rate measurements showed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is more rapidly photolyzed in methanol than octachlorodi-benzo-p-dioxin. Initially TCDD yields 2,3,7-trichlorodiben-zo-p-dioxin, and subsequent reductive dechlorination is accompanied by ring fission. Pure dibenzo-p-dioxin gave polymeric material and some 2,2 -dihydroxybiphenyl on irradiation. Riboflavin-sensitized photolysis of the potential precursors of dioxins, 2,4-dichlorophenol and 2,4,5-trichloro-phenol, in water gave no detectable dioxins. The products identified were chlorinated phenoxyphenols and dihydroxy-biphenyls. In contrast, aqueous alkaline solutions of purified pentachlorophenol gave traces of octachlorodibenzo-p-dioxin on irradiation. 

Female Wistar rats treated orally with 0.125-16 jug/kg/day of 2,3,7,8-tetrachlorodibenzo-p-dioxin (8-D), 50-800 jug/kg/day of 1,2,3,4-tetra-chlorodibenzo-p-dioxin (4-D , and 250-2000 /xg/kg/day of 2,7-dichloro-dibenzo-p-dioxin (2-D) and 1,000-2,000 /xg/kg/day of 2,3-dichlorodi-benzo-p-dioxin or 2-chlorodibenzo-p-dioxin during 6—15 days of gestation (first morning of a positive vaginal smear was designated as day 1) were assessed for prenatal effects of the compounds on their progeny. 

Combustion of wood or paper treated with pentachlorophenol resulted in no increase and more probably a decrease in octachlorodi-benzo-p-dioxin concentrations while octachlorodibenzo-p-dioxin increased slightly in paper treated with sodium pentachlorophenate. The pho-tolytic degradation of sodium pentachlorophenate at pH 8 is very rapid. Under these controlled conditions formation of no more than 0.03% octachlorodibenzo-p-dioxin was observed. The 2,3,7,8 isomer, one of the most active chloracnegens is seemingly stable towards air oxidation but... 

Chlorinated dibenzo-ip-dioxins were prepared on the gram scale for use as toxicological standards, 2,7-Dichlorodi-henzo-p-dioxin was prepared by catalytic condensation of potassium 2-bromo-4-chlorophenate in 70% yield. Thermal condensation of the potassium salt of 2,4,4 -trichloro-2 -hydroxy diphenyl ether gave a mixture of the 2,8- and 2,7-dichlorodibenzo-p-dioxins which were separated by fractional recrystallization. 2,3,7,8-T etrachlorodibenzo-p-dioxin of 99.9- -% purity was prepared by catalytic condensation of potassium 2,4,5-trichlorophenate. An isomeric mixture of hexachlorodibenzo-p-dioxins was prepared by pyrolytic condensation of sodium 2,3,4,6-tetrachlorophenate. Chlorination of pentachlorophenol (containing < 0.07% tetrachlorophenol) in trichlorobenzene gave octachlorodi-benzo-p-dioxin in 80% yield contaminated by 5-15% heptachlorodibenzo-p-dioxin. Oxidative methods were used to produce octachlorodibenzo-p-dioxin at 99.9% purity. 

Whereas the degradation of the carboxylates of the monocyclic furan, thiophene, and pyrrole is initiated by hydroxylation, degradation of their benzo analogs is generally carried out by dioxygenation. The degradation of the analogs dibenzofuran and dibenzo-[l,4]-dioxin is discussed in Part 2 of this chapter. 

The oxidation behavior of 3-oxa-chromanols was mainly studied by means of the 2,4-dimethyl-substituted compound 2,4,5,7,8-pentamethylM /-benzo[ 1,3]dioxin-6-ol (59) applied as mixture of isomers 27a it showed an extreme dependence on the amount of coreacting water present. In aqueous media, 59 was oxidized by one oxidation equivalent to 2,5-dihydroxy-3,4,6-trimethyl-acetophenone (61) via 2-(l-hydroxyethyl)-3,5,6-trimethylbenzo-l,4-quinone (60) that could be isolated at low temperatures (Fig. 6.41). This detour explained why the seemingly quite inert benzyl ether position was oxidized while the labile hydroquinone structure remained intact. Two oxidation equivalents gave directly the corresponding para-quinone 62. Upon oxidation, C-2 of the 3-oxa-chroman system carrying the methyl substituent was always lost in the form of acetaldehyde. 

Owing to the fact that ethyl ethers are especially effective substrates for CYP1A1 [184], the probe possesses an ethyl group on the phenolic oxygen of the trimethyl lock. In vitro, fluorescence was manifested by CYP1A1 isozyme with Kcat/KM 8.8 x 103 M-1s 1 and KM 0.09 pM. In cellulo, the probe revealed the induction of cytochrome P450 activity by the carcinogen 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD), and its repression by the chemoprotectant resveratrol. 

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