WO1999010310A1 - Procede de production de diphenylethers et d'esters - Google Patents

Procede de production de diphenylethers et d'esters Download PDF

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Publication number
WO1999010310A1
WO1999010310A1 PCT/US1998/017873 US9817873W WO9910310A1 WO 1999010310 A1 WO1999010310 A1 WO 1999010310A1 US 9817873 W US9817873 W US 9817873W WO 9910310 A1 WO9910310 A1 WO 9910310A1
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Prior art keywords
group
acid
substituted
ketone
ester
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PCT/US1998/017873
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English (en)
Inventor
Gerhardus Johannes Lourens
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The Dow Chemical Company
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Priority to AU91247/98A priority Critical patent/AU9124798A/en
Priority to EP98943452A priority patent/EP1007501A1/fr
Publication of WO1999010310A1 publication Critical patent/WO1999010310A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
    • C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/257—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings
    • C07C43/295—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings containing hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
    • C07C45/46—Friedel-Crafts reactions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
    • C07C49/84—Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/39—Preparation of carboxylic acid esters by oxidation of groups which are precursors for the acid moiety of the ester
    • C07C67/42—Preparation of carboxylic acid esters by oxidation of groups which are precursors for the acid moiety of the ester by oxidation of secondary alcohols or ketones

Definitions

  • Nitration of 1 ,4-dichlorobenzene gives one main product, 2,5-dichloronitrobenzene.
  • the electron-withdrawing nitro-group activates the ortho-chlorine for selective nucleophilic displacement; the meta-chlorine is not activated.
  • the diphenylether is formed in good yield due to the activating effect of the nitro-group. Some dioxins may form under the conditions of condensation.
  • Reduction of the nitro-group can be effected in many ways, for example catalytic hydrogenation, or by reduction with hydrazine.
  • Trichlorodibenzofuran forms through nucleophilic arylation by the neighbouring phenyl group on the carbon bearing the diazonium group:
  • This invention relates to a process for the production of the bacte ⁇ ostat 2,4,4' t ⁇ chloro-2'-hydroxyd ⁇ phenylether
  • the process involves the oxidation of a 2'-acyl-2,4,4'- t ⁇ chlorodiphenylether to the corresponding 2-acyloxy derivative under Baeyer-Vilhger conditions
  • the ester is transestenfied or hydrolyzed to the desired phenol
  • Advantages of the process include high yields in the final synthetic steps, absence of dibenzofuran impurities and ease of purification of the product
  • R 1 is selected from H, linear or branched, substituted or unsubstituted, aliphatic or ahcyclic groups consisting of one to twenty carbon atoms, including linear or branched primary alkyl groups and aralkyl groups, and carboxyl groups having the formula -C0 2 R" wherein R" is H, alkyl, alkoxy, aryloxy
  • R 1 include substituted or unsubstituted methyl, ethyl, propyl, isopropyl, isobutyl, butyl, pentyl, cyclopentyl and cyclohexyl groups
  • Suitable substituents are those that allow the oxidation of the aryloxyphenylketone (or aldehyde) to an ester, such as carboxyl, carbalkoxy, carbamino, halogen, ammo, blocked ammo, nitro, hydroxyl, alkyloxy and aryloxy groups R 2 , R 3 ,
  • Suitable substituents again are those that allow the oxidation of the aryloxyphenylketone (or aldehyde) to an ester, such as carboyxl, carbalkoxy, carbamino, halogen, amino, blocked amino, nitro, hydroxyl, alkyloxy and aryloxy groups.
  • R 2 , R 3 , R 4 and R 5 are hydrogen or chloro, most preferably chloro.
  • the method includes the oxidation of a substituted diphenylether aldehyde or ketone of the general formula:
  • R ⁇ R 2 , R 3 , R 4 and R 5 have the meanings given above, with a peroxy reagent such as a simple or complex peroxide, an alkylhydroperoxide, a dialkylperoxide (a peroxyether), an acylhydroperoxide (a peroxyacid), or a diacylperoxide (a peroxyanhydride), under conditions of oxidation, commonly known in the art as the Baeyer-Villiger oxidation, under neutral, basic or acidic conditions.
  • Simple and complex peroxides include hydrogen peroxide and perborate and persulfate salts.
  • Suitable alkylhydroperoxides icnlude isopropyl, triphenylmethyl- and tertiary butylhydroperoxide.
  • the dialkylperoxide may be di-tert- butylperoxide.
  • Suitable acylhydroperoxides include performic acid, peracetic acid, perpropionic acid, perbenzoic acid, substituted perbenzoic acid such as m-chloroperbenzoic acid, perphthalic acid, pertrifluoroacetic acid, perfumaric acid and permaleic acid. Diacylperoxides corresponding to the peracids listed may be selected.
  • the ketone to be oxidized such as 2'-acyl-2,4,4'-trichloro-diphenylether
  • the ketone to be oxidized may be masked as a derivative of the aldehyde or ketone such as an acetal or a ketal group or an imino group, a ketalgroup, or an iminogroup that will undergo oxidation to an ester directly, or via an intermediate aldehyde or ketone formed in situ under the conditions of the reaction;
  • the acetal or ketal will have the general formula:
  • R ⁇ R 2 , R 3 , R 4 and R 5 have the meanings as above and R 6 and R 7 may be linear or branched aliphatic groups such as methyl, ethyl, propyl or isobutyl groups, preferablyl methyl, ethyl or propyl, and may form part of a cyclic acetal or ketal structure of 5 or 6 members such as a dioxolane group or a 1 ,3-dioxane group, and the imino compound may have the general formula:
  • R 1 , R 2 , R 3 , R 4 and R 5 may have the meanings as above and R 6 includes alkoxy- groups such as methoxy and ethoxy.
  • the invention further includes the circumstances in which a diphenylether such as 2,4,4'-trichlorodiphenylether bearing an alkyl, substituted alkyl or carboxyalkyl substituent in the 2'-position may be oxidised, or be otherwise converted into a 2'-ketone prior to performance of the Baeyer-Villiger oxidation procedure.
  • a diphenylether such as 2,4,4'-trichlorodiphenylether bearing an alkyl, substituted alkyl or carboxyalkyl substituent in the 2'-position
  • a diphenylether such as 2,4,4'-trichlorodiphenylether bearing an alkyl, substituted alkyl or carboxyalkyl substituent in the 2'-position
  • a diphenylether such as 2,4,4'-trichlorodiphenylether bearing an alkyl, substituted alkyl or carboxyalkyl substituent in the 2'-position
  • this ester is produced via the oxidation of 2'-acetyl-2,4,4'-trichlorodiphenylether (which is a known substance described by DC Atkinson ef al in Journal of Medicinal Chemistry 26 (1983) 1353 - 1360); Scheme II.
  • Another aspect of the invention includes the further step of converting the ester of the phenolic diphenyl ether to the corresponding phenol, in particular the conversion of 2'-acetoxy-2,4,4'-tr ⁇ chlorod ⁇ phenylether (triclosan acetate) to 2,4,4'-tr ⁇ chloro-2'- hydroxydiphenylether (triclosan).
  • the hydrolysis may be affected in aqueous solvents using an acidic catalyst such as a mineral acid, a sulphonic acid, a Lewis acid, or a solid acid such as an acidic ion exchange resin.
  • Suitable mineral acids include hydrogen chloride, hydrogen bromide, sulphuric acid and nitric acid
  • Suitable sulphonic acids include methanosulphonic acid and p-toluenesulphonic acid.
  • Suitable Lewis acids include aluminum chloride, aluminum bromide, boron t ⁇ fluo ⁇ de, boron trichloride, ferric chloride, tin chloride and titanium tetrachlonde.
  • Suitable ion exchange resins include strong acid ion exchange resins such as Dow 50, Amber te IR120, Amberlyst 15 and Amberlyst 36.
  • the conversion of the ester into the phenol is accomplished by transesterification using an alcohol as the recipient of the acyl group and an acid catalyst which may be a mineral acid, a sulphonic acid, a Lewis acid, a solid acid such as an acidic ion exchange resin, or a titanium tetra-alkoxide.
  • an acid catalyst which may be a mineral acid, a sulphonic acid, a Lewis acid, a solid acid such as an acidic ion exchange resin, or a titanium tetra-alkoxide.
  • the phenol may also be obtained from the ester by aminolysis using ammonia or a primary amme in a suitable solvent, such as anhydrous ammonia in hexane or heptane.
  • a method for the synthesis of an acylated substitued diphenylether by condensation of a halogen substitued aromatic aldehyde or ketone with a salt of a substituted phenol The general formula for the aldehyde or ketone is:
  • the hydrogen substitued aromatic ketone may be an 1-acyl-2,5-d ⁇ chlorobenzene as represented by the general formula:
  • the salt of the substituted phenol is a metal salt, or a quaternary ammonium salt, or any other salt including salts formed in phase transfer catalysis.
  • the method for condensation further provides for the use of catalysts in the formation of the diphenylether.
  • catalysts employe in the Ullmann ether condensation apply; these include metallic copper, cuprous (Cu I) and cupric (Cu II) salts, such as oxides, hydroxides, halides, alkanoates, sulphates, nitrates. Also included is the use of these copper catalysts conjugated on carrier matrixes such as clays, silicates and other mineral carriers.
  • the invention extends to the condensation of 2,5- dichloroacetophenone with salts of 2,4-dichlorophenol under conditions of the Ullmann condensation as described above (Scheme II).
  • the selectivity of the condensation resides in the electron-withdrawing character of the acyl-substituent, which renders the 2-chloro-atom of the substituted 2,5-dichloroketone much more susceptible to nucleophilic substitution by the attacking phenolate ion than the 5-chloro-atom.
  • This principle is prevalent in all 1 -acyl-2,5-dichlorobenzenes referred to above.
  • a further aspect of the invention provides a method for the oxidation of a substituted diphenyletherketone particularly 2'-acyl-2,4,4'-trichlorodiphenylether, under Baeyer-Villiger conditions, by use of commercial peroxy-reagents preferably peracids, or peracids generated in situ.
  • This method also includes the steps of oxidizing an organic anhydride with aqueous hydrogen peroxide to form an organic peracid.
  • the thus generated peracid solution is rendered anhydrous by reacting the water present in the peracid solution with an added organic anhydride in a hydrolysis step.
  • the anhydride used to form the peracid is selected from acetic anhydride, maleic anhydride and trifluoroacetic anhydride and the anhydride employed in the hydrolytic removal of water is selected from the same anhydrides.
  • the reaction may be performed in a melt of the reactants, or in a solvent selected from toluene, xylene, butanols, ethylene glycol, polyethylene glycol, N-methylpyrrolidone, N,N-dimethylformamide, or dimethylsulfoxide.
  • the reaction temperature may be between 100 and 150 Q C and the reaction time may be 15 to 100 hours.
  • the molar ratio of 2,4-dichlorophenol to 2,5-dichloroacetophenone employed may be between 1 :1 and 5:1 , preferably 2:1 and most preferably 1.1 :1 .
  • the molar ratio of base employed to the quantity of 2,5-dichloroacetophenone used may be 0.5:1 to 5:1 in the case of the carbonates and 1 :1 to 10:1 in the case of the hydroxides; preferably this ratio will be betwen 0.55:1 and 1 :1 for the carbonates and between 1.1 :1 and 1 .1 :2 for the hydroxides; most preferably the ratio will be 0.55:1 for the alkali metal carbonates and 1 .1 :1 for their hydroxides; that is, most preferably the quantity of base employed will be chemically equivalent to the quantity of 2,4-dichlorophenol used.
  • the quantity of copper catalyst used may be between 0.5g and 10g of Cu per mole of 2,4- dichloroacetophenone employed, preferably between 1 and 5g per mole and most preferably between 2 and 3g of Cu per mole.
  • 3-Chloro-6-(2,4'-dichlorophenoxy)aceotphenone is a new molecular entity and forms part of the claims of this invention.
  • no contaminating dibenzofurans are formed and with the preferred temperature of the reaction (120 - 130 s ) the formation of other undesired by-products, such as dioxins, is minimal.
  • the intermediate is readily purified by a single crystallization.
  • acetyl-group of 3-chloro-6-(2',4'-dichlorophenoxy)acetophenone is oxidized to an acetoxy-group by means of a peroxy reagent.
  • the common Baeyer- Villiger oxidants such as percarboxylic acids, alkylhydroperoxides, inorganic peracids or complex peroxygen carriers may be employed in solvents such as organic carboxylic acids, aliphatic hydrocarbons, chlorinated hydrocarbons and alcohols. Catalysts such as inorganic acids, sulphonic acids, or metal ions may be employed.
  • 6-(2',4'-dichlorophenoxy)acetophenone to oxidant may be 1 :0.2 to 1 :5 oxidation in 1 to 8 volumes of solvent at a temperature of between 20 and 80°C and a reaction time of between 5 and 50 hours.
  • the oxidation of 3-chloro-6-(2',4'- dichlorophenoxy)acetophenone is performed with one or more of permaleic acid, peracetic acid, perphthalic acid or pertrifluoroacetic acid at a molar ratio of 1 :2 to 1 :3 in two or four volumes of a chlorinated aliphatic solvent such as dichloromethane, dichloroethane or chloroform at a temperature of between 35 and 45°C and a reaction time of between 12 and 24 hours; the reaction mixture may contain carboxylic acids or carboxylic acid anhydrides which may have been employed in the in situ generation of the essentially anhydrous peracid.
  • a chlorinated aliphatic solvent such as dichloromethane, dichloroethane or chloroform
  • 3-chloro-6-(2' ,4'- dichlorophenoxy)acetophenone is oxidized with anhydrous permaleic acid in a molar ratio of 1 :2 in 2.5 volumes of dichloromethane at 40°C for 16 hours.
  • the transesterification is effected by treatment of one molar equivalent of the ester in 2 to 50 molar equivalents of an aliphatic primary alcohol containing 0.02 to 1 molar equivalents of acid catalyst at a temperature of between 20°C and the boiling point of the alcohol for 4 to 12 hours.
  • the transesterification is performed in 6 to 8 molar equivalents of methanol, ethanol or propanol containing 0.02 to 0.05 molar equivalents of mineral acid or sulphonic acid at a temperature of between 50°C to the boiling point of the alcohol for between 5 to 9 hours.
  • the reaction is performed by refluxing 1 molar equivalent of the ester in 7 molar equivalents of methanol containing 0.03 equivalents of hydrochloric acid for 6 hours.
  • a 3-necked, one liter flask was placed in a heatable oil bath and fitted with a reflux condenser topped with a calcium chloride drying tube, an efficient stirrer and a dropping funnel.
  • the flask was charged with 49.5g (336.7 mmoles, 1 equivalent) of 1 ,4- dichlorobenzene and 1 12.5g (843 mmoles, 2.5 equivalents) of anhydrous aluminum chloride.
  • the mass was warmed to 47 9 C and stirred.
  • To the mixture was added dropwise 40g (509.5 mmoles, 1.5 equivalents) of acetyl chloride at a rate (ca 1 hour) that would maintain the exothermic reaction temperature at approximately 60 Q C.
  • the flask was charged with 269g (1.65 moles) of 2,4-dichlorophenol, 225 ml of xylene and 114g (0.825 moles) of anhydrous potassium carbonate.
  • the stirred mixture was heated to 120 Q C while a slow stream of nitrogen was introduced and 283.5g (1.5 moles) of 2,5-dichloroacetophenone was added.
  • the mixture was refluxed gently and azeotroped water was collected during 2 hours (6 ml total). The rate of product formation was followed by gas chromatographic analysis. The reaction was complete 8 hours after addition of the copper catalyst.
  • the mixture was cooled to 25 9 C and filtered.
  • the filter cake was washed with 200 ml of xylene.
  • the solvent was evaporated in vacuum.
  • the remaining brown oil crystallized on stirring with 250 ml of hexane at 5°C.
  • the product was collected on a filter and washed with four 50 ml portions of hexane (5 9 C).
  • the filter cake was resuspended in 250 ml hexane, stirred at the boiling point, cooled to 5 9 C and again collected on a filter.
  • the dried product (228.5g; 48.5 percent yield; 97 percent purity by gas chromatography) was suitable for further transformation.
  • a three-necked three liter reaction vessel, equipped with a stirrer, thermometer and dropping funnel was charged with 136.8g (1 .98 moles; 4.4 equivalents) of 49.2 percent aqueous hydrogen peroxide.
  • To the stirred solution was added 175.5g (1 .8 moles, 4 equivalents) of solid maleic anhydride over 30 minutes. The internal temperature was maintained at 23 + 2°C with occasional external cooling. Stirring was continued at this temperature for 90 minutes.
  • a 500ml three-neck flask was equipped with a magnetic stirred, a 5 9 C condenser and a thermometer.
  • the flask was charged with 80g of dichloromethane and 179g (1.8 mole) of maleic anhydride.
  • the stirred mixture was heated to 25 9 C and 47.9g (0.88 mol; 4.4 mol. parts) of 62.5 percent aqueous hydrogen peroxide was added dropwise over 30 minutes.
  • the mixture was refluxed for 90 minutes, cooled to 30°C and 65g (0.2 mole; 1 mole part) of 3-chloro-6-(2',4'-dichlorophenoxy)acetophenone was added in small portions during 40 minutes.
  • the reaction mixture was stirred under reflux for 16 hours.
  • Crystalline maleic acid was filtered off and the cake was washed with 50ml of dichloromethane.
  • the filtrate was treated successively with aqueous sodium bisulphite until free of peroxides and with aqueous sodium bicarbonate to neutrality.
  • the solvent was evaporated and the residue crystallized from methanol to give 63.5g (96.2 percent; purity 99.4 percent by gas chromatography) of colourless crystals.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

On décrit une synthèse améliorée de diphényléthers et plus particulièrement du bactériostatique 2,4,4'-trichloro-2'-hydroxydiphényléther, dans laquelle du 2'-acétyle-2,4,4'-trichlorodiphényléther est oxydé dans des conditions Baeyer-Villiger pour produire du 2'-acétoxy-2,4,4'-trichlorodiphényléther avec un rendement pratiquement quantitatif. Les meilleures conditions d'oxydation comprennent l'utilisation d'acide permaléique anhydre produit in situ. L'ester est purifié rapidement par recristallisation simple, étant donné qu'aucun dibenzofuranne n'est produit et que seulement de petites quantités de sous-produits sont formées dans le processus. L'ester est converti par hydrolyse ou par transestérification sous forme du diphényléther phénolique halogéné désiré, 2,4,4'-trichloro-2'-hydroxydiphényléther. Le produit final est purifié à un degré élevé par distillation sous vide et cristallisation pour correspondre aux normes de pureté actuelles relatives aux applications.
PCT/US1998/017873 1997-08-29 1998-08-28 Procede de production de diphenylethers et d'esters WO1999010310A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU91247/98A AU9124798A (en) 1997-08-29 1998-08-28 Process for producing diphenylethers and esters
EP98943452A EP1007501A1 (fr) 1997-08-29 1998-08-28 Procede de production de diphenylethers et d'esters

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US92097197A 1997-08-29 1997-08-29
US08/920,971 1997-08-29

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WO1999010310A1 true WO1999010310A1 (fr) 1999-03-04

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0857711A1 (fr) 1997-02-05 1998-08-12 Ciba SC Holding AG Procédé pour la préparation de composés hydroxy diphényls halogénés
WO2001083418A1 (fr) * 2000-05-04 2001-11-08 Ciba Specialty Chemicals Holding Inc. Processus de preparation de composes hydroxydiphenyle halogenes
WO2004092106A2 (fr) * 2003-04-18 2004-10-28 Endura S.P.A. Procede de preparation d'alcoxy- et d'aryloxy-phenols
CN115490578A (zh) * 2022-09-23 2022-12-20 江苏理工学院 一种碳同位素标记的三氯生的制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4950809A (en) * 1987-12-11 1990-08-21 Rhone-Poulenc Chimie Process for preparing hydroxylated aromatic derivatives by the Baeyer-Villiger reaction
EP0384043A2 (fr) * 1989-02-21 1990-08-29 The Dow Chemical Company Procédés pour la fabrication de produits intermédiaires bromés
EP0857711A1 (fr) * 1997-02-05 1998-08-12 Ciba SC Holding AG Procédé pour la préparation de composés hydroxy diphényls halogénés

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4950809A (en) * 1987-12-11 1990-08-21 Rhone-Poulenc Chimie Process for preparing hydroxylated aromatic derivatives by the Baeyer-Villiger reaction
EP0384043A2 (fr) * 1989-02-21 1990-08-29 The Dow Chemical Company Procédés pour la fabrication de produits intermédiaires bromés
EP0857711A1 (fr) * 1997-02-05 1998-08-12 Ciba SC Holding AG Procédé pour la préparation de composés hydroxy diphényls halogénés

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DAVID C. ATKINSON ET AL.: "Substituted (2-Phenoxyphenyl)acetic Acids with Antiinflammatory Activity.1", JOURNAL OF MEDICINAL CHEMISTRY, vol. 26, no. 10, 1983, pages 1353 - 1360, XP002034909 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0857711A1 (fr) 1997-02-05 1998-08-12 Ciba SC Holding AG Procédé pour la préparation de composés hydroxy diphényls halogénés
US6215029B1 (en) 1997-02-05 2001-04-10 Ciba Specialty Chemicals Corporation Process for the preparation of halogenated hydroxydiphenyl compounds
WO2001083418A1 (fr) * 2000-05-04 2001-11-08 Ciba Specialty Chemicals Holding Inc. Processus de preparation de composes hydroxydiphenyle halogenes
US6706930B2 (en) 2000-05-04 2004-03-16 Ciba Specialty Chemicals Corporation Process for the preparation of halogenated hydroxydiphenyl compounds
WO2004092106A2 (fr) * 2003-04-18 2004-10-28 Endura S.P.A. Procede de preparation d'alcoxy- et d'aryloxy-phenols
WO2004092106A3 (fr) * 2003-04-18 2004-12-09 Endura Spa Procede de preparation d'alcoxy- et d'aryloxy-phenols
CN115490578A (zh) * 2022-09-23 2022-12-20 江苏理工学院 一种碳同位素标记的三氯生的制备方法
CN115490578B (zh) * 2022-09-23 2023-12-22 江苏理工学院 一种碳同位素标记的三氯生的制备方法

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EP1007501A1 (fr) 2000-06-14

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