Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
  • C07C51/15—Preparation of carboxylic acids or their salts, halides or anhydrides by reaction of organic compounds with carbon dioxide, e.g. Kolbe-Schmitt synthesis

Definitions

• the present invention relates to a process for the carboxylation of a phenol ether.
• the invention relates to the carboxylation of guaiacol (or 2-methoxyphenol) and of guetol (or 2-ethoxyphenol).
• the carboxylation is carried out according to the Kolbe-Schmitt or Marasse reactions.
• EP-A 327 221 which describes the carboxylation of sodium guaiacolate at 250 ° C under CO2 pressure. Such a process is suitable when it is desired to obtain 2-hydroxy-3-methoxybenzoic acid, that is to say to carry out a carboxylation in the ortho position of the hydroxyl group. It has also been proposed to conduct the reaction according to the conditions of
• the objective of the present invention is to provide a para carboxylation process of a phenol ether which makes it possible to overcome the aforementioned drawbacks.
• phenol ether denotes an aromatic compound, the aromatic nucleus of which carries a hydroxyl group, a hydrogen atom in para position of the OH group and of which a hydrogen atom directly linked to the aromatic nucleus is replaced by an ether group.
• aromatic means the classic notion of aromaticity as defined in the literature, in particular by Jerry MARCH, Advanced Organic Chemistry, 4 istrym ⁇ edition, John Wiley an Sons, 1992, pp 40 and following.
• the subject of the present invention is a process for the carboxylation of a phenol ether of general formula (I):
• - R represents a hydrogen atom or one or more identical or different substituents
• R - R ' represents a hydrocarbon radical having from 1 to 24 carbon atoms, which may be a linear or branched saturated or unsaturated acyclic aliphatic radical; a saturated, unsaturated or aromatic, monocyclic or polycyclic cycloaliphatic radical; a saturated or unsaturated, linear or branched aliphatic radical carrying a cyclic substituent,
• - n is a number less than or equal to 3.
• ether group denotes, in a simplified manner, groups of the R'-O- type in which R 'has the meaning given above.
• R 'therefore represents both an acyclic or cycloaliphatic, saturated, unsaturated or aromatic aliphatic radical as well as a saturated or unsaturated aliphatic radical carrying a cyclic substituent.
• the phenol ether which is involved in the process of the invention corresponds to the formula (I) in which R "represents an acyclic, saturated or unsaturated, linear or branched aliphatic radical.
• R ' represents a linear or branched alkyl radical having from 1 to 12 carbon atoms, preferably from 1 to 6 carbon atoms, the hydrocarbon chain possibly being interrupted by u heteroatom (for example, oxygen), by a functional group (for example -CO-) and / or carrying a substituent (for example, a halogen).
• acyclic, saturated or unsaturated, linear or branched aliphatic radical may optionally carry a cyclic substituent.
• ring preferably means a saturated, unsaturated or aromatic carbocyclic ring, preferably cycloaliphatic or aromatic, in particular cycloaliphatic comprising 6 carbon atoms in the ring or benzene.
• the acyclic aliphatic radical can be linked to the ring by a valential bond, a heteroatom or a functional group and examples are given above.
• the ring can be optionally substituted and, by way of examples of cyclic substituents, it is possible, among others, to consider substituents such as R, the meaning of which is specified for formula (la).
• R 'can also represent a saturated carbocyclic radical or comprising 1 or 2 unsaturations in the ring, generally having from 3 to 8 carbon atoms, preferably 6 carbon atoms in the ring; said cycle being able to be substituted with substituents such as R.
• R 'can also represent an aromatic carbocyclic radical, preferably a monocyclic radical generally having at least 4 carbon atoms, preferably 6 carbon atoms in the ring; said cycle being able to be substituted with substituents such as R.
• R ′ represents a linear or branched alkyl radical having from 1 to 4 carbon atoms or a phenyl radical.
• R ′ represents a linear or branched alkyl radical having from 1 to 4 carbon atoms or a phenyl radical.
• radicals R 'preferred according to the invention mention may be made of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl or phenyl radicals.
• the residue A may represent the remainder of an aromatic, monocyclic carbocyclic compound having at least 4 carbon atoms and preferably 6 carbon atoms or the remainder of a polycyclic carbocyclic compound which can be constituted by at least 2 aromatic carbocycles and forming between them ortho- or ortho- and pericondensed systems or by at least 2 carbocycles of which at least one of them is aromatic and forming between them ortho- or ortho- and pericondensed.
• the remainder A can carry one or more substituents on the aromatic ring.
• substituents R are given below, but this list is not limiting. Any substituent can be present on the cycle as long as it does not interfere with the desired product.
• the remainder A can, inter alia, carry several alkoxy groups, it is possible according to the process of the invention to carboxylate polyalkoxylated compounds.
• - n is a number less than or equal to 3, preferably equal to 0 or 1,
• the radical R ′ represents an alkyl radical, linear or branched, having from 1 6 carbon atoms, preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-buty or phenyl,
• radical (s) R represent one of the following atoms or groups:
• an alkyl radical linear or branched, having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, such as methyl ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,
• a linear or branched alkoxy radical having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms such as l methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, se butoxy, tert-butoxy, radicals.
• a halogen atom preferably a fluorine atom, bromine chlorine, a trifluoromethyl radical.
• the radicals R 'and R and the 2 successive atoms of the benzouq ring can form between them, a ring having from 5 to 7 atoms, possibly included another heteroatom.
• n is greater than or equal to 1
• the radicals R ′ and R and the 2 successive atoms of the benzene ring can be linked together by a radi alkylene, alkenylene or alkenylidene having from 2 to 4 carbon atoms in order to form a saturated heterocycle, unsaturated or aromatic having 5 to 7 carbon atoms.
• One or more carbon atoms can be replaced by another heteroatom, preferably oxygen.
• the radicals R 'and R can represent a methylene dioxy or ethylene dioxy radical.
• the process of the invention is particularly applicable to ethers of phenols of formula (la) in which n is equal to 1, the radicals R and R ′ both representing, identical or different, alkoxy radicals. It is more preferably suitable for the phenol ethers of formula (la) in which n is equal to 0, the radical R ′ representing an alkoxy radical.
• - monoethers such as guaiacol, 3-methoxyphenol, guetol, 3-ethoxyphenol, 2-isopropoxyphenol, 3-isopropoxyphenol, 2-methoxy-5-methylphenol, 2-methoxy-6-methylphenol, 2-methoxy-6-tert-butylphenol, 3-chloro-5-methoxyphenol, 2,3-dimethoxy-5-methylphenol, 2-ethoxy-5- (1-propenyl) phenol, 2-methoxy-1-naphthol, - diethers such as 2,3-dimethoxyphenol, 2,6-dimethoxyphenol,
• the compounds to which the process according to the invention applies more particularly advantageously are guaiacol and guetol.
• the phenol ethers are involved in the process of the invention in salified form. They are preferably the salts of the metallic elements of group (la) of the periodic table or an ammonium salt.
• a polar aprotic organic solvent which exhibits certain characteristics of polarity and basicity; the presence of said solvent making it possible to improve the regio-selectivity of the reaction.
• organic solvent A first characteristic of the organic solvent is that it is aprotic and stable in the reaction medium.
• aprotic solvent a solvent which, in Lewis theory has no protons to release.
• a polar organic solvent is used.
• An organic solvent is chosen, in accordance with the invention, which has a dielectric constant greater than or equal to 15. The upper bound has no critical character. It is preferred to use an organic solvent having a high dielectric constant, preferably between 25 and 7.
• Another condition which governs the choice of solvent is that it must meet certain basicity characteristics. Indeed, said solvent must be basic.
• a pola organic solvent is chosen having a donor number greater than 20, preferably greater than or equal to 25.
• the upper limit has no critical character.
• An organic solvent is preferably chosen having a donor number of between 25 75 and preferably between 25 and 50.
• linear or cyclic carboxamids such as N, N-dimethylacetamide (DMAC). , N, diethylacetamide, dimethylformamide (DMF), diethylformamide or methyl-2-pyrrolidinone (NMP); dimethyl sulfoxide (DMSO) hexamethylphosphotriamide (HMPT); tetramethylurea. It is also possible to use a mixture of solvents.
• linear or cyclic carboxamides are preferably used.
• the amount of organic solvent to be used is determined depending on the nature of the organic solvent chosen. It is determined so that the concentration of the substrate in the organic solvent is preferably between 1 and 50% by weight and more preferably between 10 and 40%.
• the phenol ether in the salified form and the carbon dioxide are reacted in an organic solvent as defined.
• a salified form of an extemporaneously prepared phenol ether can be used, but it can also be prepared in situ by reacting the phenol ether and the base.
• a strong base is preferably chosen, that is to say a base having a pKb greater than 12: the pKb being defined as the cologarithm of the dissociation constant of the base measured, in aqueous medium, at 25 ° C.
• inorganic bases such as the alkali metal salts, preferably an alkali metal hydroxide which may be sodium or potassium hydroxide.
• quaternary ammonium hydroxide use is preferably made of tetralkylammonium or trialkylbenzylammonium hydroxides in which the identical or different alkyl radicals represent a linear or branched alkyl chain having from 1 to 12 carbon atoms, preferably from 1 to 6 carbon atoms.
• Tetramethylammonium hydroxide, tetraethylammonium hydroxide or tetrabutylammonium hydroxide is preferably chosen.
• trialkylbenzylammonium hydroxides and in particular trimethylbenzylammonium hydroxide.
• the concentration of the basic starting solution is not critical.
• the alkali metal hydroxide solution used has a concentration generally between 10 and 50% by weight.
• the amount of base introduced into the reaction medium takes account of the amount necessary to salify the hydroxyl function of the phenol ether. If the said compound has salifiable functions other than hydroxyl grou, the quantity of base necessary to salify all the salifiable functions is therefore introduced.
• the amount of base expressed relative to the ether of phe varies between 90 and 120% of the stoichiometric amount.
• the phenol ether is prepared in salified form by reacting it with base at a temperature advantageously between 25 ° C and 100 ° C.
• the water formed at the neck of the salification reaction is removed by distillation under atmospheric pressure under a reduced pressure of between 1 mm of mercury and atmospheric pressure or by drying. When there is no more water in the medium, introduce carbon dioxide.
• the quantity of carbon dioxide to be used varies between 1,100 and more preferably between 1 and 2.
• the process of the invention is advantageously carried out at a temperature of less than 150 ° C, and preferably less than 140 ° C and still more preferably less than 120 ° C.
• the reaction temperature is chosen between 90 ° C and 110 ° C. It is generally carried out at atmospheric pressure, causing carbon dioxide to bubble in the reaction medium maintained under agitation.
• a preferred practical embodiment of the invention consists in using the solvent, the phenol ether, the base, in removing the water by distillation and then introducing the carbon dioxide.
• the carboxylated phenol ether is recovered para from the reaction medium, in a manner known per se.
• the pH is brought to between 5.0 and 8.0, by adding an aqueous solution of a mineral acid such as, for example, hydrochloric, sulfuriq or nitric acid.
• a mineral acid such as, for example, hydrochloric, sulfuriq or nitric acid.
• Hydrochloric acid or sulfuric acid are preferred.
• acid concentration is not critical. It preferably corresponds to the concentration of the commercial form, for example, 37% by weight for hydrochloric acid, 92 or 96% for sulfuric acid.
• the unreacted phenol ether settles. It is eliminated by separation of the organic and aqueous phases.
• the aqueous residual solution is acidified to a pH below 3, preferably between 1 and 2, by addition of an acidic aqueous solution as previously described so as to precipitate the substituted 4-hydroxybenzoic acid.
• the acid obtained is recovered from the reaction medium according to conventional solid / liquid separation techniques, preferably by filtration.
• the process of the invention allows easy access to 4-hydroxybenzoic acids, the aromatic nucleus of which carries at least one ether group, which can be used, as intermediates for the manufacture of the corresponding 4-hydroxybenzaldehydes, by reduction of the carboxylic function to aldehyde function.
• Another variant application of the invention consists in preparing the alkyl esters having from 1 to 8 carbon atoms and preferably from 1 to 4 carbon atoms, 4-hydroxybenzoic acids in which the aromatic nucleus carries at least one ether group. obtained according to the process of the invention, according to any method known to those skilled in the art.
• esters There are several ways of preparing esters.
• a first variant consists in reacting said acid with the appropriate alcohol.
• organic solvent is chosen such that it forms an azeotrope with water and that the boiling point of its azeotrope with water is lower than that of the alcohol involved.
• solvents that may be mentioned include toluene, cumene or pseudocumene.
• it is chosen to use a direct esterification process, in the absence of organic solvent, for alcohols having from 1 to 5 carbon atoms.
• esters of 4-hydroxybenzoic acids the aromatic nucleus of which carries at least one ether group, in particular the preferably methyl esters of p-vanic acid and of 4-hydroxy-ethoxybenzoic acid.
• the water / toluene azeotrope is distilled. After distilling 91% of the committed and formed water, the medium is pasty: agitation is difficult. Cooled under a stream of nitrogen.
• guaiacol and 500 ml of toluene are loaded into a 1000 ml three-necked flask equipped with a central agitation, a vigorous column and a 100 ml dropping funnel.
• 65.2 g of an aqueous sodium hydroxide solution at 30.8% by weight are poured in at 0.25 h at room temperature.
• the reactor is purged by a stream of CO2. There is a slight exotherm.
• the mixture is heated at 100 ° C for 7 h 00, while maintaining the CO2 pressure at 20 bar.
• Acetonitrile is added in order to make the reaction medium homogeneous.
• a 5N hydrochloric acid solution is poured in until a p of approximately 2.0 is obtained. There is precipitation.
• Acetonitrile is added in order to make the reaction medium homogeneous.
• test c - weakly polar and slightly basic aprotic solvent such as toluene
• test d - weakly polar and basic aprotic solvent such as pyridine
• N-dimethylacetamide 20 100 Na 7 h 00 27.5 5.1 84 b 1-butanol 20 100 Na 7 h 00 7.5 0 0 ec toluene 20 100 Na 7 h 00 4.4 8.8 33 d pyridine 20 100 Na 7:00 a.m. 1, 2 9.6 1 1

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• 1995
  • 1995-02-20 FR FR9501927A patent/FR2730731B1/fr not_active Expired - Fee Related
• 1996
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  • 1996-02-14 CN CN 96190099 patent/CN1146761A/zh active Pending
  • 1996-02-14 JP JP8525442A patent/JPH09512285A/ja active Pending
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