Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
  • C07C227/02—Formation of carboxyl groups in compounds containing amino groups, e.g. by oxidation of amino alcohols

Definitions

• the present invention relates to a process for the carboxylation of an aminonaphthol in order to prepare hydroxynaphthoic acids and derivatives.
• the invention relates to the carboxylation of 5-aminonaphthol in order to prepare 1-hydroxy-5-amino-2-naphthoic acid.
• a process for the carboxylation of an aminonaphthol which consists in preparing a salt of aminonaphthol by reaction of the aminonaphthol and of a base, then carrying out the carboxylation of the salt obtained, characterized in that the aminonaphthol salt is prepared in an organic solvent having a boiling point below 160 ° C and forming an azeotrope with water; that water is removed by azeotropic distillation and then carbon dioxide is introduced, in order to obtain the carboxylated compound.
• An advantageous variant of the process of the invention consists in gradually introducing the base into the reaction medium comprising the aminonaphthol and the organic solvent, while eliminating the water from the medium as it is introduced and formed.
• the process of the invention has many advantages. It can be run without shielding the reactor.
• the solvent used in the salification reaction and in the carboxylation reaction being the same, the two reactions can be linked together and carried out in the same reactor.
• the difficulty of working in an anhydrous medium is circumvented by the implementation of the preferred variant of continuous introduction of the base and simultaneous distillation of water.
• aminonaphthol denotes a naphthalene compound, one of the aromatic rings of which carries a hydroxyl group, and of which one of the hydrogen atoms of one of the aromatic rings is replaced by an optionally substituted amino group.
• the subject of the present invention is a process for the carboxylation of an aminonaphthol of general formula (I):
• - n is a number from 0 to 3
• - p and p ' identical or different, represent a number equal to 0 or 1
• - Ri represents:
• an alkyl radical optionally carrying one or more halogen atoms having from 1 to 30 carbon atoms,
• a heteroatom for example, oxygen or nitrogen
• a functional group and / or carrying a substituent for example, a halogen, a trifluoromethyl group or an ester function.
• radical R 1 represents a ring such as benzene or the like, it is possible that there are substituents on this ring. Any substituent can be present. It is most often a lower alkyl radical
• C1-C4 a lower aikoxy radical C1-C4, a hydroxyl group, a nitro group and / or a halogen atom, in particular fluorine or chlorine.
• - p and p ' identical or different, represent a number equal to 0 or 1
• R-- represents one of the following atoms or groups:
• a hydrogen atom is 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 aikoxy radical having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms such as the methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy radicals,
• acetamido group preferably a fluorine, chlorine or bromine atom, a trifluoromethyl radical
• R 5 represents an alkyl radical having from 1 to 12 carbon atoms, a trifluoromethyl radical, an optionally substituted phenyl or benzyl radical.
• aci ⁇ es implemented may optionally be in a salified form, in particular in the form of sodium or potassium salt.
• the aminonaphthol salt in suspension in an organic solvent is prepared.
• an organic solvent is used, the characteristic of which is to have a boiling temperature below 160 ° C., and to form an azeotrope with water.
• organic solvents suitable for the invention mention may in particular be made of benzene, preferably alkylbenzenes, toluene, o xylene, m-xylene, p-xylene and their mixtures or isopropanol. It is also possible to use a mixture of organic solvents. Among the aforementioned solvents, toluene is preferably used.
• the amount of organic solvent to be used is determined according to the nature of the organic solvent chosen.
• the concentration of the substrate in the organic solvent is preferably between 10 and 30% by weight.
• the aminonaphthol which is involved in the process of the invention is in salified form. They are preferably the salts of the metallic elements of group (la) of the periodic table or an ammonium salt.
• the elements reference is made below to the Periodic Table of the Elements published in the Bulletin of the Chemical Society of France, n ° 1 (1966).
• sodium or potassium salts are used.
• a base which is preferably an inorganic 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.
• the bases preferably sodium or potassium hydroxide.
• 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 aminonaphthol. If the said compound has salifiable functions other than the hydroxyl group, the quantity of base necessary to salify all the salifiable functions is therefore introduced.
• the amount of base expressed relative to aminonaphthol varies between 90 and 100% of the stoichiometric amount.
• Aminonaphthol is prepared in salified form by reacting it with the base at a temperature advantageously between room temperature and 200 ° C, preferably between 50 ° C and 160 ° C.
• ambient temperature is meant a temperature generally between 15 ° C and 25 ° C.
• the salification step is carried out under a controlled atmosphere of inert gases.
• a preferred variant of the process of the invention consists in gradually introducing the base into the reaction medium comprising the aminonaphthol and the organic solvent, while removing water from the medium as it is introduced and formed. After elimination of the last traces of water, a variant of the invention consists in introducing an alkali metal carbonate.
• alkali metal is meant an element from group (1a) of the periodic table of elements, preferably sodium or potassium.
• potassium carbonate is used, preferably used in solid form.
• the amount of carbonate used preferably represents from 0 to 50% by mole of substrate and even more preferably from 10 to 30% by mole.
• the aminonaphthol in salified form and the carbon dioxide are reacted in an organic solvent te! qu ⁇ defined.
• the quantity of carbon dioxide to be used expressed by the molar ratio between carbon dioxide and aminonaphthol varies between 1 and 50, and more preferably between 1 and 2.
• the process of the invention is advantageously carried out at a temperature between 100 ° C and 200 ° C, preferably between 100 ° C and 180 ° C. It is possible to carry out the reaction under pressure of carbon dioxide varying between atmospheric pressure and about 100 bar. We prefer a pressure between 1 and 20.
• Carbon dioxide in the form of a sweep, can be used to control the atmosphere at the start of the reaction.
• the Applicant has found that it is desirable to conduct the salification and carboxylation reactions, in the presence of a reducing compound in order to reduce the secondary oxidation reactions.
• the reducing compounds which can be used are of varied nature.
• the alkali metal salts of sulfur acids are used in which the sulfur is at an oxidation state of 2+ to 4+, such as the alkali metal salts of sulfurous acid, thiosulfuric acid, l dithionous acid.
• the alkali metal salts indicated above are sodium salts.
• sodium dithionite, sodium hydrogen sulfite, sodium sulfite, sodium thiosulfate are particularly suitable.
• reducing compounds hydrazine hydrochloride can also be used.
• organic sulfur compounds examples include organic sulfides such as thionanisole, diphenyl sulfide, phenyl and 4-chlorophenyl sulfide, di (4-chlorophenyl) sulfide,
• phenyl and stearyl suide dihexyl sulfide, ethyl sulfide and hexyl sulfide, dioctyl sulfide, propyl and 4-methylcyclohexyl sulfide, methyl sulfide and 4-chlorocyclohexyl.
• organic phosphites such as triphenyl phosphite, 0 tris phosphites (chlorophenyl), tris phosphites (dichlorophenyl), tris phosphites (trichlorophenyl), phosphite trimethyl, triethyl phosphite, tributyl phosphite, trioctyl phosphite, tris (nonylphenyl) phosphites, 2,4-ditertiobutylphenyl phosphite, tribenzyl phosphite, tris (phenethyl) phosphite, phosphite tris (2-ethoxyethyl), tricyclohexyl phosphite; organic phosphinites such as methyl diphenylphosphinite; phosphines such as triphenyl
• the amount of reducing compound used is generally small. It most often represents from 0.1 to 5% of the weight of the aminonaphthol and preferably about 1%.
• a first embodiment consists in putting the substrate (possibly a reducing compound) in suspension in the solvent.
• the base is preferably added in aqueous solution.
• the mixture is heated in order to remove the water by azeotropic distillation.
• an alkali metal carbonate is introduced.
• the medium is then brought to the chosen carboxylation temperature.
• the carbon dioxide is introduced at the desired pressure and maintained until there is no more consumption of carbon dioxide.
• the duration of the reaction is obviously variable depending on the nature of the substrate. It usually varies between 1 and 8 hours.
• Another embodiment of the invention is to put the substrate (optionally a reducing compound) in the organic solvent, to bring the suspension obtained to the reflux temperature of the solvent.
• the base is gradually introduced, in aqueous solution, while ⁇ is iiani gradually the azeotrope water / organic solvent so as to eliminate the water continuously.
• an alkali metal carbonate is introduced.
• An aminonaphthol carrying a carboxylate group is obtained. It is located in position 2 or 4 with respect to a hydroxyl group in position ⁇ and in position 1, 3 or 6 with respect to a hydroxyl group in position ⁇ .
• the product is suspended in the solvent which comprises the substrate and the product obtained.
• the product is separated according to conventional solid / liquid separation techniques, preferably by filtration.
• the carboxylated aminonaphthol is recovered from the reaction medium, in a manner known per se.
• the product in acid form it is suspended in water and the pH is brought below 6, preferably between 2.0 and 5.0, by adding an aqueous solution of a mineral acid such as for example hydrochloric, sulfuric or nitric acid. Hydrochloric acid or sulfuric acid are preferred.
• the concentration of the acid 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 acid obtained is recovered from the reaction medium according to conventional solid / liquid separation techniques, preferably by filtration.
• the carboxylated compound is obtained in acid form. It is possible to very easily prepare the esters of the acid obtained, in particular the C1-C4 alkyl esters and the aryl esters, preferably phenyl.
• the process of the invention allows easy access to 1-hydroxy-5-amino-2-naphthoic acid.
• the mixture is allowed to reflux for 1 hour to remove the last traces of water.
• reaction medium is filtered.
• toluene 50 ml of toluene are also introduced into the base of the Dean-Stark® assembly. The agitation is started and the medium is inerted with nitrogen.
• the medium is heated to toluene reflux and then poured in 2 hours, 40.3 g of a 49.3% potash solution or 0.3598 mol of potash; the water supplied being distilled simultaneously.
• the mixture is again heated at reflux for 2 hours in order to completely dry the medium, then the latter, after cooling to room temperature, is transferred into a 1 liter autoclave equipped with a Ruchston® turbine. 0.2 g of sodium dithionite is added to the medium.
• the autoclave is purged with carbon dioxide and the medium is heated to 150 ° C. Carbon dioxide is then injected into the autoclave over a period of
• Example 3 Into a 1 liter glass reactor equipped with a stirrer, a Dean-Stark® distillation assembly and an addition funnel are introduced:
• the agitation is started and the medium is inerted with nitrogen.
• the medium is heated to toluene reflux and then poured over 3 hours, 55.0 g of a 49.6% potassium hydroxide solution, ie 0.491 mol of potassium hydroxide; the water supplied being distilled simultaneously.
• the mixture is again heated at reflux for 2 hours in order to completely dry the medium, then the latter, after cooling to room temperature, is transferred into a 1 liter autoclave equipped with a Ruchston® turbine.
• the autoclave After starting the stirring, the autoclave is purged with carbon dioxide and the medium is heated to 170 ° C.
• Carbon dioxide is then introduced into the autoclave over a period of
• the medium is filtered on a No. 3 frit glass and then dried on a rotary evaporator at 55 ° C. for 2 hours 30 minutes at 20 mbar and 129 g of product containing ( en masse):

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• 1996
  • 1996-09-10 FR FR9611039A patent/FR2753194B1/fr not_active Expired - Fee Related
• 1997
  • 1997-09-10 EP EP97940212A patent/EP0927153A1/de not_active Withdrawn
  • 1997-09-10 WO PCT/FR1997/001598 patent/WO1998011055A1/fr not_active Application Discontinuation
  • 1997-09-10 JP JP51331798A patent/JP2001504089A/ja active Pending

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