2- Hydroxy diphenyl ether

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. 

The most widely used active ingredient for PVC is OBPA, based on 10, 10 oxybisphenoxarsine. Until recently it had a 50% market share but usage of arsenic compounds is becoming less popular. Other important biocides include OFT (2- -octyl-4-isothiazolin-3-one), 2, 4, 4 -trichloro-2 -hydroxy-diphenyl ether, zinc pyrithione, iV-butyl-1,2-... 

Numerous halogen and zinc compounds are available, such as Folpet (iV-trichloromethylthio), phthalimide, 2,4,4 -trichloro-2 -hydroxy diphenyl ether, zinc borate and zinc pyrithione. The last-mentioned is a broad-spectrum biocide that can be used instead of OBPA in many applications. 

The effectiveness of the antimicrobial activity can be enhanced by combining zinc citrate with triclosan [22-24]. Triclosan, or 2,4,4 -trichloro-2-hydroxy diphenyl ether, is an aromatic, trichlorinated synthetic componnd. It can be obtained by reaction of 2,4-dichlorophenol with 2,5-dichloronitrobenzene in the presence of alkali and reduction of the 2,4,4 -trichloro-2 -nitrodiphenyl ether into 2,4,4 -trichloro-2 -aminodiphenyl ether. This is diazotized with sodium nitrite with excess sulfnric acid. After hydrolization, 2,4,4 -trichloro-2 -hydroxydiphenyl ether is extracted with xylene and purified [20-25]. 

Hydroxy diphenyl Ether (Catechol phenyl ether)... 

A bacteriostat should be of low human toxicity, compatible with the relevant polymer, should withstand normal temperatures, and when incorporated in the polymer should withstand repeated washings with water and detergent solutions. Among products currently in use are certain mercury compounds (which may present a toxic hazard), hexachlorophene and 2,4,4 -trichloro-2 -hydroxy-diphenyl ether. 

Two brominated phenoxyphenols, active against both gram-neg. and gram-pos. organisms, have been found in Disidea herbacea 166) and structures (32) and (33) were assigned. Both structures were based on the conversion of these substances by catalytic hydrogenolysis into the known 2-hydroxy diphenyl ether, and on analyses of their n. m. r. spectra. 

Regarding the degradation of PBDEs by white-rot fungi, the first evidence of their ability to degrade a PBDE compound corresponds to a study published by Hundt et al. [27], which studied the degradation of 4-bromo-BDE by Trametes versicolor. The degradation occurs initially by hydroxylation reaction with the possible formation of three different isomers of hydroxy-diphenyl ether followed... 

Dichloro-3 - (carboxymethyl) -4 hydroxy diphenyl ether, see Bifenox... 

A mixture of 48 parts by weight of diethyl[(3,4-methylenedioxyanilino)methylene] malonate and 500 parts by weight of diphenyl ether is refluxed for 1 hour. The mixture is allowed to cool to about 25°C with stirring and 500 parts by weight of petroleum ether are added. Filtration gives 3-carbethoxy-6,7-methylenedioxy-4-hydroxy-quinoline as a brown solid, MP 276° to 281°C. Several recrystallizations from dimethylformamide gives almost colorless analytical material, MP 285° to 286°C, (decomposes). 

Detailed discussion of these findings will be presented elsewhere. Here we only wish to point out that responses to a hydrogen donor tend to be critically affected by minor structural differences between the compounds. Thus, while diphenyl ether remains substantially unaffected by the donor, its hydroxy-derivatives (phenoxy phenols) often display fairly high reactivity. Taken in conjunction with the failure of low-rank coals (7) and phenoxy phenols (10) to suffer reductive cleavage when treated with sodium in liquid ammonia, this lends some support for the existence of phenoxy phenol entities in low rank coals. 

Synthesis of 153 began with 4-hydroxy-lH-quinolin-2-one 156 which was heated in refluxing diphenyl ether (boiling point = 259 °C) with p-anisidinc... 

When Schiff s bases (242), derived from ketones and tm-butylamine, were reacted with dimethyl methoxymethylenemalonate in diphenyl ether at 80-130°C for 1-15 hr, then at 190-250°C for 1-3 hr, 2-hydroxy-3-pyridinecarboxylates (243) were obtained by a one-pot procedure. In the first step of the reaction, the beta-carbon of the enamine moiety was involved instead of the amino group (89JHC773). 

Anthraquinonylaminomethylenemalonates (658, R = H, OMe) and 1,5-bis(aminomethylenemalonate) (191) in boiling diphenyl ether readily gave tetracyclic and pentacyclic pyridine derivatives (659 and 660) in good yields (59MI2). At the same time, the thermal cyclization of the 4-hydroxy derivative (658, R = OH) and 1,4-bis(aminomethylenemalonate) [658, R = —NHCH=C(COOEt)2] did not yield the expected condensed tetracyclic pyridine derivatives. 

A solution of diethyl (2,3,4-trifluorophenylamino)(p-methoxybenzyl-thio)methylenemalonate in diphenyl ether was added to diphenyl ether at 110°C, and the reaction mixture was then stirred at 250-260°C for 20 min under nitrogen to give ethyl 4-hydroxy-2-(/>-methoxyphenylthio)-6,7,8-trifluoroquinoline-3-carboxylate in 82% yield (88EUP286089). 

Chloroaniline was reacted with diethyl acetylmalonate at room temperature in vacuo over anhydrous CaCl2 for 10 days. The resulting cro-tonate (803) was cyclized in boiling diphenyl ether for 40 min to give 7-chloro-4-hydroxy-2-methylquinoline-3-carboxylate in 17% yield (73USP3755332). 

Dihydroxy-1,8-naphthyridine was prepared in 50% yield by the cy-clization of N-(6-hydroxy-2-pyridyl)aminomethylenemalonic acid in boiling diphenyl ether for 9 hr (84AJC1065). 

The reaction of 2-pyridylhydrazine and EMME in diphenyl ether at 190°C for 30 min give ethyl 5-hydroxy-l-(2-pyridyl)pyrazole-4-carboxylate in 6% yield (89MI435). 

The heating of diethyl N-(3-hydroxy-2-methoxyphenyl)aminometh-ylenemalonate in boiling diphenyl ether in the presence of water afforded decarboxylated 4,7-dihydroxy-8-methoxyquinoline in 61% yield (89MI5). 

PBBs and PBDEs may also cause toxicity by other mechanisms of action. For example, some PBB congeners can be metabolized to reactive arene oxides (Kohli and Safe 1976 Kohli et al. 1978) that may alkylate critical cellular macromolecules and result in injury. PBDEs may disrupt thyroid hormones by induction of hepatic microsomal UDPGT, which increases the rate of T4 conjugation and excretion, or by mimicking T4 or T3 PBDEs and their hydroxy metabolites are structurally similar to these thyroid hormones which are also hydroxy-halogenated diphenyl ethers (see Section 3.5.2). Clinical interventions designed to interfere with this mechanism or the metabolism of PBBs have yet to be developed. 

Table 3 shows the maxima of the B-bands of phenol, o-hydroxy-diphenyl, o-hydroxybenzonitrile, m-hydroxybenzaldehyde and m-nitrophenol and their methyl ethers in hexane and ethanol as well as the displacements D(Me H) and D(H-bond). 

There have been some further examples of the use of the Conrad-Limpach reaction on substituted 5-aminoquinolines for the synthesis of 4-hydroxy-1,7-phenanthrolines, although the products (see Section IV,F,1) should properly be designated as phenanthrolinones.169 Hot diphenyl ether is often employed as the medium for ring closure.170 Ethyl trifluoro-acetoacetate has been used successfully in place of ethyl aceto-acetate, and this variation has allowed entry to 2-trifluoromethyl-substituted 1,7-phenanthrolines.96 Extensions of the Conrad-Limpach type of synthesis starting with m-phenylenediamine (20) and utilizing diethyl ethoxymethylene malonate or ethyl ethoxalylacetate, reagents frequently used in quinoline syntheses, have afforded, after hydrolysis,... 

Applications of the Conrad-Limpach reaction to the synthesis of 1-hydroxy-4,7-phenanthrolines or, more correctly, l-oxo-l,4-dihydro-4,7-phenanthrolines, from p-phenylenediamine or 6-aminoquinolines continue to be reported. l,10-Dihydroxy-3,8-dimethyl-4,7-phenanthroline has again been prepared from p-phenylenediamine,234 hot diphenyl ether being used to effect the cyclization. Other examples include the new or improved preparations of l-hydroxy-3-methyl-, 10-amino-l-hydroxy-3-methyl-,232 2-(y-chlorocrotonyl)- l,10-dihydroxy-3,8-dimethyl-, and 2,9-bis (y- chlorocrotonyl)-1,10- dihydroxy - 3,8 - dimethyl - 4,7 - phenanthro-lines.235 Compounds prepared in this way have been patented as antiasthmatic agents.178 A closely related synthesis employing poly-phosphoric acid as cyclizing agent has yielded l-hydroxy-3-phenyl-4,7-phenanthroline.236... 

A few extensions of the Conrad-Limpach synthesis have been applied to the synthesis of 4,7-phenanthrolines. Unlike o-phenylenediamine, which gives a quinoxaline derivative, p-phenylenediamine reacts with excess of ethyl ethoxalylpropionate to give an intermediate bisanil, which cyclizes in hot diphenyl ether to afford 3,8-dicarboethoxy-l,10-dihydroxy-2,9-dimethyl-4,7-phenanthroline in high yield.237 With diethyl ethoxymethylenemalonate as condensing agent, 6-amino-8-methoxy-quinoline has been converted into 2-carboethoxy-l-hydroxy-6-methoxy-4,7-phenanthroline.238 A related condensation affording 1-... 

Numerous patents78,79 have recorded the preparation of malonates (71 X = C02Et), which afforded 4-hydroxy or 4-chloro derivatives (72 R3 = OH, Cl) when refluxed with diphenyl ether or phosphorous oxychloride. The reaction has provided 2-substituted isomers80,81 from 3-aminopyrazoles and, by using the appropriate reagent (70 X = COR), the corresponding 5-ketones (72) can be obtained.82-87... 

Hydroxy derivatives of biphenyl can be prepared from diazonium salts, such as the chloride or sulfate, and phenols if no alkali is added.28- 29, 30 31-32 From a solution of diazotized aniline in a large excess of-phenol, a good yield of a mixture of 2- and 4-hydroxybiphenyl is obtained in addition to diphenyl ether. 

Treatment of l-acyl-3-amino-5-pyrazolones (417) with an equimolar amount of an enol ether, such as ethoxymethylenecyanoacetate or ethoxymethylenemalononitrile in DMSO at 70-80 C for 3 h furnishes pyrazoleacrylonitriles (418) in good yields. The use of other solvents decreases the yields considerably. Heating the intermediates (418) in diphenyl ether at 200 °C promoted cyclization to give 2-acyl-6-amino-3-hydroxy-2//-pyrazolo[3,4-b]pyridines (419) (Scheme 47) <94JHC925>. 

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