Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C67/00—Preparation of carboxylic acid esters
  • C07C67/14—Preparation of carboxylic acid esters from carboxylic acid halides
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
  • C07B61/00—Other general methods
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C67/00—Preparation of carboxylic acid esters
  • C07C67/48—Separation; Purification; Stabilisation; Use of additives
  • C07C67/62—Use of additives, e.g. for stabilisation
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
  • C07C69/62—Halogen-containing esters
  • C07C69/63—Halogen-containing esters of saturated acids

Definitions

• the present invention relates to a process for preparing difluoroacetic acid esters.
• the invention relates to the preparation of the alkyl and cycloalkyl esters of difluoroacetic acid.
• the invention more particularly relates to the preparation of methyl or ethyl difluoroacetate.
• esters of difluoroacetic acid are known products described in the literature.
• An access route consists of reacting an alcohol RiOH with a difluoroacetyl fluoride of formula H-CF 2 -COF.
• a difluoroacetyl fluoride of formula H-CF 2 -COF Reference can be made in particular to the preparation described in EP-A-0 694 523.
• the alcoholysis reaction is in a continuous mode, conducted in the absence of catalyst. However, when the reaction is carried out according to a batch process, the presence of a reaction catalyst is required in order to have a reaction time compatible with industrial operation.
• EP-A 0 694 523 recommends the use as catalyst of a tertiary amine and more particularly triethylamine.
• Another disadvantage of this process is that it leads to highly polluting discharges due to the presence of amines.
• the Applicant proposes a method for overcoming the aforementioned drawbacks.
• a process for the preparation of a difluoroacetic acid ester characterized in that it comprises the reaction of difluoroacetyl fluoride with an alcohol aliphatic or cycloaliphatic, in the presence of a heterogeneous mineral base.
• an aliphatic or cycloaliphatic alcohol hereinafter referred to as "alcohol”
• alcohol an aliphatic or cycloaliphatic alcohol
• R 1 represents a hydrocarbon group, substituted or unsubstituted, which may be an alkyl or cycloalkyl group.
• alkyl a linear or branched hydrocarbon chain having 1 to 15 carbon atoms and preferably 1 or 2 to 10 carbon atoms.
• Examples of preferred alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl and t-butyl.
• cycloalkyl is meant a cyclic, monocyclic hydrocarbon group comprising from 3 to 8 carbon atoms, preferably a cyclopentyl or cyclohexyl group.
• one or more hydrogen atoms may be replaced by a substituent (e.g., halogen), as long as it does not interfere with obtaining the desired product.
• a substituent e.g., halogen
• the hydrocarbon chain may preferentially carry one or more fluorine atoms.
• R 1 can represent a fluorinated or perfluorinated alkyl group comprising from 1 to 10 carbon atoms and from 1 to 21 fluorine atoms, preferably from 3 to 21 fluorine atoms.
• R 1 represents an alkyl group having from 1 to 4 carbon atoms.
• alcohols corresponding to formula (I) mention may be made more preferably of methanol, ethanol, isopropanol, 2,2,2-trifluoroethanol, 2,2-difluoroethanol, 1,1,1-trifluoroethanol, difluoroethanol, pentafluoroethanol, hexafluoroisopropanol and cyclohexanol.
• difluoroacetyl fluoride the latter may be available alone or as a mixture with hydrofluoric acid: the amount of hydrofluoric acid present may be such that the ratio between the number of moles of hydrofluoric acid and the number moles of difluoroacetyl fluoride may reach a value equal to 10, and is preferably between 1 and 7. According to the process of the invention, the reaction is carried out between difluoroacetyl fluoride and the alcohol, in the presence of a base.
• the ratio between the number of moles of alcohol and the number of moles of difluoroacetyl fluoride may vary between 0.8 and 2, and is preferably between 0.95 and 1.05.
• a base whose function is to trap the hydrofluoric acid formed by the reaction.
• the base implemented is a heterogeneous mineral base.
• mineral base in the present text, a mineral salt having at least one pK a greater than 8, preferably between 8 and 14.
• Pk a is defined as the ionic dissociation constant of the acid / base pair when water is used as the solvent. It is defined at 20 ° C.
• heterogeneous is meant that the mineral salt is insoluble in the reaction medium.
• a salt of a monovalent metal and / or a divalent metal preferably an alkali metal and / or alkaline earth metal.
• salts include alkali metal carbonates, hydrogen carbonates, phosphates, hydrogen phosphates, preferably sodium, potassium or cesium; an alkaline earth metal, preferably magnesium, calcium, barium; a metal of group MB preferably zinc.
• sodium or potassium carbonate is preferably chosen.
• the metal hydroxides are bases to exclude for the implementation of the method of the invention.
• the base is used in a solid form, generally in the form of a powder and more particularly in a ground form in order to have a finer granulometry.
• the grinding operation of the base can be carried out in any type of crusher resistant to corrosion of the base (for example stainless steel).
• the amount of base used is such that the ratio between the number of moles of base and the number of moles of fluoride difluoroacetyl preferably varies between 0.5 and 3, and more preferably between 1 and 2.
• the reaction can be conducted in the presence or absence of an organic solvent.
• a solvent is chosen which is inert under the reaction conditions.
• a solvent is preferred which solubilizes the product obtained.
• Suitable solvents are nonpolar organic solvents such as aromatic hydrocarbons, aliphatic, cycloaliphatic or aromatic hydrocarbons, halogenated or not, or more polar organic solvents such as, in particular, ether-oxides, nitriles.
• aromatic hydrocarbons such as, in particular, benzene, toluene, xylenes, ethylbenzene, diethylbenzenes, trimethylbenzenes, petroleum fractions consisting of a mixture of alkylbenzenes, especially the cuts. Solvesso® type.
• perchlorinated hydrocarbons such as in particular tetrachlorethylene
• partially chlorinated hydrocarbons such as dichloromethane, trichloromethane, dichloroethane, tetrachloroethane, trichlorethylene, 1-chlorobutane, 1,2-dichlorobutane
• trifluoromethylbenzene trifluoromethoxybenzene.
• the ethers can also be used as solvents.
• solvents examples which may be mentioned are aliphatic, cycloaliphatic or aromatic ether-oxides and, more particularly, methyl-tert-butyl ether, dipentyl ether, diisopentyl ether and ethylene glycol dimethyl ether (or 1,2-dimethoxyethane). ), dimethyl ether of diethylene glycol (or 1,5-dimethoxy-3-oxapentane), anisole, veratrole or cyclic ethers, for example, dioxane, tetrahydrofuran.
• nitrile solvent preferably alpha or aromatic nitrites, preferably acetonitrile, propionitrile, butanenitrile, isobutanenitrile, pentanenitrile, 2-methylglutaronithle, adiponitrile, benzonitrile, tolunitrile, malonitrile, 1, 4-benzonitrile.
• alpha or aromatic nitrites preferably acetonitrile, propionitrile, butanenitrile, isobutanenitrile, pentanenitrile, 2-methylglutaronithle, adiponitrile, benzonitrile, tolunitrile, malonitrile, 1, 4-benzonitrile.
• the amount of organic solvent used is preferably chosen such that the weight concentration of difluoroacetyl fluoride in the solvent is between 20 and 100% by weight, preferably between 20 and 80%.
• the reaction is generally carried out at a temperature of between 0 ° C. and 10 ° C. when it is conducted under atmospheric pressure.
• the temperature may be chosen between 0 ° C. and 100 ° C., preferably between 0 ° C. and 40 ° C., under autogenous pressure of the reactants.
• the alcoholysis reaction is generally carried out preferably under a controlled atmosphere of inert gases. It is possible to establish an atmosphere of rare gases, preferably argon, but it is more economical to use nitrogen.
• the method of the invention is simple to implement.
• Reagents can be introduced in many variations but some are preferred.
• a preferred embodiment consists in preparing a foot consisting of the alcohol, optionally the organic solvent and the mineral base and then gradually introducing, preferably by bubbling, the difluoroacetyl fluoride.
• an ester of difluoroacetic acid corresponds to the following formula:
• Ri has the meaning given above.
• the product obtained is recovered in a conventional manner.
• salts formed by the solid / liquid separation techniques are first separated, preferably by filtration.
• the salts may be in particular the excess of mineral base and the salts formed by the reaction, most often a sodium or potassium fluoride.
• the ester formed can be recovered from the separated liquid phase in a conventional manner and more particularly by distillation.
• the process of the invention is advantageously carried out in equipment capable of withstanding the corrosion of the reaction medium.
• materials are chosen for the part in contact with the corrosion-resistant reaction medium such as alloys based on molybdenum, chromium, cobalt, iron, copper manganese, titanium, zirconium, aluminum, carbon and tungsten sold under the HASTELLOY ® brands or nickel alloys, chromium, iron, copper additive-containing manganese and / or molybdenum marketed under the trademark INCONEL ® and more particularly alloys HASTELLOY C 276 or INCONEL 600, 625 or 718.
• alloys based on molybdenum, chromium, cobalt, iron, copper manganese, titanium, zirconium, aluminum, carbon and tungsten sold under the HASTELLOY ® brands or nickel alloys, chromium, iron, copper additive-containing manganese and / or molybdenum marketed under the trademark INCONEL ® and more particularly alloys HASTELLOY C 276 or INCONEL 600, 625 or 718.
• Stainless steels such as austenitic steels can also be selected [Robert H. Perry et al, Perry's Chemical Engineers' Handbook, Sixth Edition (1984), page 23-44]. and more particularly 304, 304 L, 316 or 316 L stainless steels.
• the 304 and 304 L steels have a nickel content ranging between 8 and 12% and the 316 and 316 L steels have a nickel content ranging between 10 and 14%.
• 316L steels are more particularly chosen.
• Teflon Teflon
• PFA perfluoroalkyl resins
• the method of the invention is particularly interesting to be implemented discontinuously.
• the process of the invention involves an inexpensive mineral base which does not imply its recovery for recycling.
• the conversion ratio (TT) corresponds to the ratio between the number of moles of difluoroacetyl fluoride converted and the number of moles of difluoroacetyl fluoride employed.
• the yield (RR) corresponds to the ratio between the number of moles of difluoroacetic acid ester formed and the number of moles of difluoroacetyl fluoride employed.
• the various analyzes are carried out by 1 H NMR and 19 F.
• the autoclave is closed and the temperature of the medium is lowered to 5 ° C.
• a gaseous flow of difluoroacetyl fluoride (mass flow rate of 190 g / h) is then introduced into the medium for 30 minutes while maintaining the temperature below 15 ° C.
• the amount of difluoroacetyl fluoride added was 95 g (0.97 mol).
• reaction medium is then filtered and the salts are then rinsed with 100 ml of dichloromethane.
• the filtrates are combined and distilled at atmospheric pressure.
• the fraction harvested has a boiling point between 96 and 99 ° C.
• the yield is 77% by weight.
• the autoclave is closed and the temperature of the medium is lowered to 5 ° C.
• a gaseous flow of difluoroacetyl fluoride (mass flow rate of 190 g / h) is then added to the medium for 94 minutes while maintaining the temperature below 15 ° C.
• the amount of difluoroacetyl fluoride added was 256 g (2.5 mol).
• reaction medium is then filtered and the salts are then rinsed with 250 ml of dichloromethane.
• the filtrates are combined and distilled at atmospheric pressure.
• the fraction harvested has a boiling point between 85 and 86 ° C.
• the yield is 69% by weight.
• the autoclave is closed and the temperature of the medium is lowered to 5 ° C.
• the amount of difluoroacetyl fluoride added is 105 g
• the reaction medium is distilled at atmospheric pressure.
• the fraction harvested has a boiling point of between 96 and 98 ° C.
• the yield is 65% by weight.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

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• 2009
  • 2009-08-03 FR FR0903826A patent/FR2948659B1/fr not_active Expired - Fee Related
• 2010
  • 2010-07-29 RU RU2012108073/04A patent/RU2012108073A/ru unknown
  • 2010-07-29 US US13/388,831 patent/US20120190884A1/en not_active Abandoned
  • 2010-07-29 WO PCT/EP2010/061064 patent/WO2011015518A1/fr active Application Filing
  • 2010-07-29 KR KR1020127002921A patent/KR20120045002A/ko not_active Application Discontinuation
  • 2010-07-29 EP EP10736740A patent/EP2462102A1/fr not_active Withdrawn
  • 2010-07-29 JP JP2012523294A patent/JP2013501022A/ja not_active Abandoned
  • 2010-07-29 CN CN2010800347553A patent/CN102471217A/zh active Pending

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