EP0993440A1 - Etherifizierungsreaktion von einem aminophenol unter verwendung eines phasentransfersystems - Google Patents

Etherifizierungsreaktion von einem aminophenol unter verwendung eines phasentransfersystems

Info

Publication number
EP0993440A1
EP0993440A1 EP98933705A EP98933705A EP0993440A1 EP 0993440 A1 EP0993440 A1 EP 0993440A1 EP 98933705 A EP98933705 A EP 98933705A EP 98933705 A EP98933705 A EP 98933705A EP 0993440 A1 EP0993440 A1 EP 0993440A1
Authority
EP
European Patent Office
Prior art keywords
protected
function
aminophenol
phenol
advantageously
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP98933705A
Other languages
English (en)
French (fr)
Inventor
Jean-Roger Desmurs
Jean-Francis Spindler
Harivelo Gérard RAJOHARISON
Alain Roustan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Rhodia Chimie SAS
Original Assignee
Rhodia Chimie SAS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Rhodia Chimie SAS filed Critical Rhodia Chimie SAS
Publication of EP0993440A1 publication Critical patent/EP0993440A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/06—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups

Definitions

  • the subject of the present invention is an etherification reaction of an aminophenol using a phase transfer system. It relates more particularly to a technique for the etherification of an aminophenol in which the aniline function is in the form of an anilide.
  • the etherification reactions of aminophenols are generally carried out in basic medium and using expensive solvents such as so-called polar aprotic solvents.
  • this basic medium weakens the molecule and leads to colored or toxic impurities.
  • the nucleus is rich in electrons, this leads to taking restrictive precautions to avoid contact with oxygen (air).
  • it is poor in electrons, and when it carries good leaving groups such as fluorine, parasitic reactions lead to the elimination of the leaving group from the molecule.
  • phase transfer techniques is little known for this type of molecule and most of the time requires iodides whose cost is often prohibitive on an industrial scale, the use of sulfonates (such as mesylate [methanesulfonate] or tosylate [toluènesulfonate]) does not necessarily save iodide while being more expensive. It also requires the use of a very high amount of sodium hydroxide very largely on stoichiometric to obtain a good anionization of the aminophenol. When the phenol function is protected, the usual techniques involve a release of the phenol before the etherification.
  • sulfonates such as mesylate [methanesulfonate] or tosylate [toluènesulfonate]
  • one of the aims of the present invention is to provide a method which makes it possible to avoid all or part of the above drawbacks.
  • an object of the present invention is to provide a process of the above type which makes it possible to avoid consumption of sodium hydroxide which is largely overstoichiometric.
  • Another object of the present invention is to provide a process of the above type which makes it possible to directly treat the protected phenols without going through an independent step of releasing the phenol from its protection.
  • this form of aniline on the one hand facilitates the reaction when it takes place in phase transfer, but still the use of a strong base does not react the amide function: it neither cuts nor alkylates.
  • the reaction can be carried out without excess, or with a small excess stroechiometric.
  • GP represents a hydrogen or a protective group where Xi is chosen from hydrogen and advantageously light halogens (chlorine or fluorine), preferably fluorine; • where X2 and the electron-withdrawing groups (GEA), advantageously by inducing but not mesomeric effect; in particular they can be a perhalogenated alkyl (preferably perfluorinated) at least on the carbon linked to the nucleus, an advantageously light halogen (chlorine or fluorine), preferably fluorine; • where and advantageously light aryls (at most 6 carbon atoms) and halogens;
  • Xi is chosen from hydrogen and advantageously light halogens (chlorine or fluorine), preferably fluorine; • where X2 and the electron-withdrawing groups (GEA), advantageously by inducing but not mesomeric effect; in particular they can be a perhalogenated alkyl (preferably perfluorinated) at least on the carbon linked to the nucleus, an advantageously light
  • -CO-R2 represents an acyl group of at most 15 carbon atoms, advantageously at most 10 carbon atoms.
  • and R3 are chosen from hydrogen and alkyls of at most 4 carbon atoms.
  • GAA advantageously by inducing but not mesomeric effect [perhalogenated alkyl (preferably perfluorinated) at least on the carbon bound to the nucleus, an advantageously light halogen (chlorine or fluorine), preferably fluorine].
  • MOH represents the alkali hydroxide and R4-Y said halide or pseudo- halide of alkyl (R4)
  • ALCO-y / e is taken in its etymological sense of hydrocarbon residue of an ALCO-O / after ignorance of the alcohol (or ol) function.
  • the amount of alkali hydroxide is at most equal to 2 times the QS (that is to say stoichiometric), advantageously 1, 5 times, preferably 1, 2 times.
  • the stoichiometric quantity corresponds to the equation
  • the phenol function of said aminophenol is protected by a radical which, linked to a hydroxyl, constitutes an acid whose pKa is at most equal to 6, advantageously to 5, preferably to 4.
  • the phenol function of said aminophenol is advantageously protected by a radical releasing an alkaline pseudo-halide, advantageously at most 20 carbon atoms, preferably at most 10 carbon atoms.
  • a pseudo-halogen is considered to be a radical [in general, this radical has a light chalcogen (sulfur or preferably oxygen) by which it is linked to the rest of the molecule] which, by leaving, constitutes an anion of which the associated acid has an acidity measured by the Hammett constant at least equal to that of acetic acid.
  • acyloxyl radicals corresponding to perhalogenated acids in alpha of the acyloxyl function such as trifluoroacetyloxyl (CF3-CO-0-) and especially the sulfonyloxyl radicals, and especially those in which the sulfur-bearing carbon is perfluorinated, the paradigm of which is trifluoromethylsulfonyloxyl.
  • the alkoxycarbonyloxyls are also targeted, which have an acceptable lipophilicity and an electron-withdrawing effect, while being inexpensive.
  • the best electron-withdrawing agents are those which, on leaving, have an acidity at least equal to that of sulfonic acids such as tosylic (paradigm of arylsulfonic acids) or mesylic (paradigm of alkylsulfonic acids).
  • sulfonic acids such as tosylic (paradigm of arylsulfonic acids) or mesylic (paradigm of alkylsulfonic acids).
  • said protected phenol function is protected by a radical releasing an alkaline pseudo-halide corresponding to protection by an acyl.
  • the carbon number of such a hydrocarbyloxycarbonyl radical is advantageously at least equal to 3, preferably to 4. It advantageously has at most 20 carbon atoms, preferably at most 10 carbon atoms.
  • said protected phenol function is protected by a radical releasing an alkaline pseudo-halide corresponding to protection by an alkoxycarbonyl, advantageously at most 20 carbon atoms, preferably at most 10 carbon atoms .
  • the phase transfer catalyst is chosen from the following compounds: quaternary ammoniums, phosphoniums, crown ethers, cryptates and other chelating agents. The catalyst must be chosen so as to have extraction characteristics allowing:
  • the most suitable industrial phase transfer catalysts are quaternary ammoniums.
  • the preferred substituent groups are alkyls or aryls comprising from 2 to 15 carbon atoms per substituent (typically: NBu4, NBu3Bz, NEt3Bz ).
  • the counter ion is either a hydroxide, halide or any other conjugate base of an acid having a pKa less than or equal to 4.
  • the molar ratio between water and hydroxide (H 2 O / OH " ) is at most equal to approximately 20, advantageously 10, preferably 5.
  • alkyl halide or pseudo-halide is, during the major part of the reaction, approximately stoichiometric or superstoichiometric with respect to that of the hydroxide or phenol which is in limiting quantity (expressed in stoichiometry).
  • the lipophilic medium can in particular be a weakly polar solvent or one of the excess reagent, in particular said aniline, alone or dissolved in a weakly polar solvent.
  • said aniline has a pKa at most equal to 5, advantageously to 4, preferably to 3.
  • the solubility in slightly polar media also plays an important role for the implementation of the present invention . It is therefore desirable that the solubility of said aminophenol in benzene is at least slightly soluble ( ⁇ or d), advantageously at least soluble (s), preferably very soluble (v).
  • the symbols are those used in the Handbook of Chemistry and Physics reference book.
  • the water-repellent medium or solvent lipophilic
  • water can only dissolve at most 10% of the solvent, or of what plays the role of solvent; this limit is advantageously at most 5%, preferably at most 2% by mass and this advantageously even in the presence of the substrate as a third solvent.
  • the solvent can only dissolve at most 10% of water, advantageously at most 5%, preferably at most 2% by mass and this advantageously even in the presence of the substrate as a third solvent. They are generally not very polar solvents.
  • slightly polar solvent a solvent whose dielectric constant [which changes little depending on the temperature, but which is advantageously measured around 20 ° C., for the constant values dielectric one can refer to the fourth edition of the work published at John WILEY and sons "TECHNIQUES OF CHEMISTRY; ORGANIC SOLVENTS, physical properties and methods of purification", of John A RIDDICK, William B. BUNGER, Théodore K. SAKANO] is at most equal to about 10 (relative dielectric constant ⁇ ). This value of ⁇ is valid for the main constituent of the solvent, but it is preferable that the whole solvent meets this constraint.
  • the maximum value of ⁇ is at most equal to 10 (two significant figures), preferably to 5 (value of chlorobenzene).
  • the main constituent of the solvent is not very basic, that is to say that its donor index or donor number is at most equal to approximately 20 (in the present description the term "approximately” is used to highlight the fact that, when the rightmost digit (s) of a number are zeros, these zeros are position zeros and not significant digits, except of course if specified otherwise), preferably at most 20 (two significant digits).
  • the lower bound is not critical.
  • solvents can be mixtures, including petroleum fractions. Naturally, under the operating conditions the solvents must be inert with respect to the substrates and the reagents used.
  • the preferred families of solvents are chosen from the group consisting of hydrocarbons, aromatic derivatives, ethers, esters and halogenated solvents.
  • halogenated aliphatic derivatives dichloromethane, dichloro-1, 2-ethane, trichloro-1, 1, 1 - ethane, as aromatic derivatives toluene and as aromatic halogen derivatives chlorobenzene , as esters ethyl acetate and isopropyl acetate, as ethers, tert-butyl methyl oxide as well as anisole and heavy alcohols, that is to say meeting the constraints of immiscibility as specified above.
  • the solvent is distillable under atmospheric pressure or under primary or secondary vacuum.
  • said slightly polar solvent is chosen from solvents of aromatic character, that is to say from solvents which have at least one aromatic nucleus.
  • This aromatic ring can either be present in a minor or major constituent of the solvent, or, when the solvent consists of a single compound, be present in this compound (for example toluene, xylene).
  • the solvent should be chosen so that its melting point is lower than the temperature at which the reaction is to take place.
  • the slightly polar solvent is a solvent chosen from aliphatic and / or aromatic carbides of halogenated aromatic derivatives, esters, phenol ethers and their mixtures.
  • the solvent it is advantageous to choose the solvent so that its starting boiling temperature is lower than the boiling (or sublimation) temperature of aminophenol; and where appropriate, other reagents used in the process.
  • the organic phase is chosen from aromatic carbides. And in particular those corresponding to a substituted benzene ring and containing at most about 10 carbon atoms, such as xylene, toluene, ethylbenzene, trimethylbenzene.
  • the reaction is carried out in the absence of iod (ur) e (that is to say at most 1 mol% relative to the substrate, advantageously 1% o, preferably 100 ppm).
  • the reaction is advantageously carried out at a temperature between 20 and 150 ° C, preferably between 30 and 120 ° C.
  • Said alkylating agent is advantageously chosen from alkyl halides.
  • sulfonic acids such as tosylic (paradigm of arylsulfonic acids) or mesylic (paradigm of acids alkyl sulfonates). Mention should also be made of those which correspond to perfluoroalkylsulphonic acids which exhibit both a good electron-withdrawing effect and a good increase in lipophilicity.
  • Said alkylating agent is advantageously chosen from alkyl halides.
  • said alkylating agent is chosen from an alkyl bromide.
  • Said alkyl (designated by R 4 in the formula) has from 1 to about 20 carbon atoms, preferably from 2 to about 10. The reaction gives good results for cyclic and / or secondary alkyls.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
EP98933705A 1997-06-24 1998-06-24 Etherifizierungsreaktion von einem aminophenol unter verwendung eines phasentransfersystems Withdrawn EP0993440A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9707871 1997-06-24
FR9707871A FR2764888B1 (fr) 1997-06-24 1997-06-24 Reaction d'etherification d'un aminophenol en utilisant un systeme de transfert de phase
PCT/FR1998/001333 WO1998058906A1 (fr) 1997-06-24 1998-06-24 Reaction d'etherification d'un aminophenol en utilisant un systeme de transfert de phase

Publications (1)

Publication Number Publication Date
EP0993440A1 true EP0993440A1 (de) 2000-04-19

Family

ID=9508355

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98933705A Withdrawn EP0993440A1 (de) 1997-06-24 1998-06-24 Etherifizierungsreaktion von einem aminophenol unter verwendung eines phasentransfersystems

Country Status (6)

Country Link
EP (1) EP0993440A1 (de)
JP (1) JP2002504922A (de)
CN (1) CN1261346A (de)
AU (1) AU8343398A (de)
FR (1) FR2764888B1 (de)
WO (1) WO1998058906A1 (de)

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6117524A (ja) * 1984-07-04 1986-01-25 Mitsui Toatsu Chem Inc ベンジルプロピルエ−テル誘導体の製造方法
US5424277A (en) * 1990-07-17 1995-06-13 Sagami Chemical Research Center Benzene derivatives substituted with heterocyclic ring, and herbicides containing same as active ingredients
EP0496347B1 (de) * 1991-01-22 1996-09-04 Sagami Chemical Research Center Verfahren zur Herstellung von Fluorbenzolderivaten und verwandter Verbindungen
JPH0692913A (ja) * 1992-09-11 1994-04-05 Sagami Chem Res Center アニリン誘導体の製造方法
DE4317322A1 (de) * 1993-05-25 1994-12-01 Bayer Ag Verfahren zur Herstellung von Difluormethoxy- und Difluormethylhioarenen

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9858906A1 *

Also Published As

Publication number Publication date
WO1998058906A1 (fr) 1998-12-30
FR2764888A1 (fr) 1998-12-24
JP2002504922A (ja) 2002-02-12
CN1261346A (zh) 2000-07-26
FR2764888B1 (fr) 2000-05-05
AU8343398A (en) 1999-01-04

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