CA2336812A1

CA2336812A1 - Production of organic compounds which are low in fluoride

Info

Publication number: CA2336812A1
Application number: CA002336812A
Authority: CA
Inventors: Max Braun; Johannes Eicher; Francine Janssens; Kerstin Eichholz; Stefan Palsherm
Original assignee: Individual
Current assignee: Solvay Fluor GmbH
Priority date: 1998-07-06
Filing date: 1999-06-29
Publication date: 2000-01-13
Also published as: JP4621352B2; EP1481958B1; CN1207256C; EP1481958A1; HUP0102558A2; DE59910530D1; WO2000001647A2; EP1094999A2; EP1094999B1; HUP0102558A3; JP2002526385A; WO2000001647A3; HK1036971A1; DE59914714D1; CN1305446A

Abstract

Organic compounds, e.g., fluoro-organic compounds such as fluorocarboxylic acids or carboxylic acid chlorides can contain small quantities of carboxyli c acid fluorides, HF or hydrolysable fluoride. Corrosive fluorides or hydrofluoric acid are then formed during derivatization, e.g., esterificatio n. The invention relates to a method for producing especially fluoro-organic compounds such as carboxylic acids, carboxylic acid chlorides and derivative s thereof, e.g., carboxylic acid esters, from carboxylic acid chlorides containing acid fluorides or hydrolysable fluoride as appropriate, and alcohols, using the catalytic effect of "onium" salts of carboxylic acids. T he products are low in fluoride. Alternatively, an inorganic-oxidic sorbent is used. The method is particularly suitable for producing esters of trifluoroacetic acid, chlorodifluoroacetic acid and trifluoroacetoacetic aci d and difluoroacetoacetic acid.

Description

Solvay Fluor and Derivate GmbH
30173 Hannover Preparation of low-fluoride organic compounds Description The invention relates to a process for the catalysed preparation of low-fluoride organic compounds, in particular fluorine-organic compounds such as carboxylic acids and their derivatives.
Fluorine-organic compounds are of great importance in many fields of technology. Fluorine-organic compounds are used for example in the field of refrigeration, in fire-extinguishing and as cleaning agents (fluorohydrocarbons, fluorochlorohydrocarbons, fluorine-containing ethers, fluorine-containing surfactants, etc.). Fluorohydrocarbons are used as blowing agents for the production of foams or propellants for the production of aerosols (also in the field of pharmaceutics). Fluorine-organic compounds are used not only as end products, as explained above, but also as intermediate products for the production of useful further-processing products.
Carboxylic acids containing e.g. fluorine and optionally chlorine have been found to be of great interest as a building block in particular in the field of agricultural engineering.
Such carboxylic acids and reactive derivatives such as corresponding carboxylic acid chlorides may be processed further to form interesting building blocks - often in condensation reactions - for example to form esters or ring systems.
Many carboxylic acids and esters of carboxylic acids are used as such in industry. Acetic esters and other carboxylic acid esters serve, for example, as solvents or cleaning agents, and other esters, e.g. of succinic acid, are used for aromatisation. Ethyl trifluoroacetate is for example a solvent for the chlorination of paraffins or the polymerisation of olefin oxides. Many carboxylic acid esters are also intermediate products in chemical synthesis. Methyl trifluoroacetate and 1,1,1-_ trifluoroethyl trifluoroacetate yield trifluoroethanol (and optionally methanol) after hydrogenation. Trifluoroethanol is used as a solvent and as an intermediate product, for example in the preparation of the solvent and anaesthetic isoflurane.
Esters of trifluoroacetic acid and trifluoroacetoacetic acid also serve to introduce or prepare biologically active compounds which have a CF3 group. For example, peptides having hormonal activity can be prepared by N-acylation with methyl trifluoroacetate.
The trifluoroethyl ester, with camphor derivatives, provides shift reagents for NMR
analysis. Phenyl trifluoroacetate, after a Fries' rearrangement with aluminium chloride, yields the corresponding trifluoroacetylated phenol, which is a synthesis building block for pharmaceuticals. Many other applications of esters are known to the person skilled in the art, for example the reaction of esters with amines to form amides, which are synthesis building blocks for pharmaceuticals, photosensitisers and dyes.
Esters of chlorodifluoroacetic acid are likewise synthesis building blocks.
The ethyl ester serves for example to construct liquid crystals, see DE-OS 40 23 106, in the production of medicaments, see US-A 5,006,563, and the methyl ester likewise serves to construct liquid crystals, as a starting compound for the microbial preparation of chiral secondary alcohols, see T. Kitazume et al., J. Fluorine Chem. 56 (1992), pages 271 to 284, or for the preparation of fluorinated enol ethers in a Wittig synthesis, see J. P. Beque et al., J. Org. Chem. 57 (1992), page 3807 ff. The esters of chlorodifluoroacetic acid are also precursors for difluorocarbene.
Carboxylic acid chlorides, in particular fluorine-containing carboxylic acid chlorides, are reacted with ketenes to form compounds of the type RC(O)CH2C(O)CI, which are esterified and are likewise synthesis building blocks. The preparation of haloacetoacetic acid chlorides and the esterification thereof is disclosed by 158 490. The esters are intermediate products in dyestuff chemistry, pharmaceutical chemistry and plant protection chemistry.
Fluorine-organic compounds may for example be prepared by means of direct fluorination with F2, higher-valency metal fluorides, by chlorine-fluorine exchange, HF
addition and other processes. If hydrolysable fluoride is contained therein, be it due to production or due to hydrolysis of fluorine from the molecule, this may result in corrosion problems with glass, ceramic and metal containers or apparatus.

Hydrogen fluoride reacts with glass and ceramics finally to form H2SiFg, which in turn under certain conditions again forms HF and Si02 with water. The released HF
in turn attacks glass, so significant damage may be caused; corrosion on metal containers is likewise undesirable.
Problems occur not only in storage containers, but also in the derivatisation of fluorine-organic compounds, e.g. in condensation reactions in which HF - even if it is as a secondary product - is released.
The esterification of carboxylic acid chlorides without a catalyst with alcohols results, e.g., in corrosion problems if the carboxylic acid chlorides contain small amounts of carboxylic acid fluorides, free HF or hydrolysable fluoride owing to their production. The aforementioned impurity is also disruptive in carboxylic acids and their esters, also due to corrosion problems.
The above comments explain the problems with fluorine-organic compounds.
Such problems may occur even with compounds which are not substituted by means of fluorine, but during the production of which fluoride is drawn in.
What is surprising is that corrosion can frequently be ascribed to hydrolysable fluoride.
It is an object of the present invention to devise a process which is technically easy to perform, with which organic compounds, in particular fluorine-organic ones, which contain reduced amounts of hydrolysable fluoride can be purified or prepared. It is a particular object to devise a process with which carboxylic acids, carboxylic acid chlorides and their derivatives, in particular from condensation reactions, such as carboxylic acid esters, can be purified with a high yield, which are low in fluoride or contain reduced amounts of carboxylic acid fluorides and free HF, or can be prepared if one starts from correspondingly contaminated carboxylic acids, carboxylic acid chlorides or their derivatives, such as esters. This object is achieved by the process of the present invention.
The process according to the invention for the preparation of organic compounds which are low in hydrolysable fluoride provides for the fluorine-organic compounds contaminated with hydrolysable fluoride to be contacted with at least one separating agent for hydrolysable fluoride, selected from the group comprising inorganic-oxidic sorbents and "onium" salts of carboxylic acids.
The process according to the invention is suitable for the purification of organic compounds which are contaminated by fluoride or hydrolysable fluoride. This contamination may result from production methods and/or from hydrolysis of fluorine in the molecule. Preferably fluorine-organic compounds are purified. These are compounds which have at least one fluorine atom. They may optionally also contain other halogen substituents. The invention will be explained further with reference to this embodiment.
The invention comprises two aspects: the purification of already-prepared fluorine-organic compounds (e.g. before their use or further processing or during storage) and the preparation of fluorine-organic compounds with simultaneous purification according to the invention.
It is preferably applied to the preparation or purification of fluorine-containing carboxylic acids, fluorine-containing carboxylic acid chlorides and to the preparation or purification of derivatives of fluorine-containing carboxylic acids and fluorine-containing carboxylic acid chlorides. "Derivatisation" means preferably condensation reactions such as esterification of fluorine-containing carboxylic acids, carboxylic acid chlorides, condensation with hydrazine derivatives, hydrolysis, etc.
It can also be applied very effectively to organic compounds having one or more CF3-, CF2H- or CF2C1-groups.
"Hydrolysable fluoride" is also understood to mean alkali fluoride, such as may be produced e.g. in alkaline (lye)-catalysed reactions.
The process according to the invention serves preferably for the preparation or purification of carboxylic acids, carboxylic acid chlorides and carboxylic acid esters which are low in carboxylic acid fluoride, free HF or hydrolysable fluoride, from carboxylic acids, carboxylic acid chlorides and carboxylic acid esters which are contaminated with carboxylic acid fluoride, HF or hydrolysable fluoride, by contacting the latter with at least one separating agent for carboxylic acid fluoride, free HF and hydrolysable fluoride selected from the group consisting of inorganic-oxidic sorbents and "opium" salts of the corresponding carboxylic acid.
The preferred inorganic-oxidic sorbent is silicon dioxide, in particular in the form of amorphous silicon dioxide, for example precipitated as a hydrate or in the form of silica gel beads. As already stated, water is frequently released in condensation reactions. This results in formation of HF, and this in turn results in corrosion. In the purification of substances or reaction mixtures which do not contain any further amounts of water apart from this condensed water, finely divided Si02, optionally in the form of hydrate, can be used well as an HF scavenger. In systems which contain a relatively large amount of water, expediently silica gel beads (or other material of relatively coarse grain size) are used. The beads or granules or compacts can be used directly in the reactor. Advantageously, the material to be purified or the reaction mixture is circulated over a separately arranged bed of the particulate sorbent. It has been observed that the corrosion due to HF is suppressed effectively even with systems having a relatively large water content (e.g. formation of hexafluorosilicic acid or the renewed decomposition thereof).
When using "opium" salts, this HF scavenger is refreshed as soon as the molar ratio of HF to "opium" salt has exceeded the value of 2:1.
The process according to the invention is suitable in particular for the preparation (purification) of carboxylic acids of the formula R1 C(O)OH, of carboxylic acid chlorides of Formula (I) R1C(O)CI and carboxylic acid chlorides of the formula (II) R1 C(O)CH2C(O)CI, and their derivatives obtained by condensation, such as esters of Formula (III) R1 C(O)OR2 and of esters of Formula (IV) R1 C(O)CH2C(O)OR2; the meanings of R1 and R2 are explained further below. If desired, the purification can also be performed by simultaneous use of an oxidic sorbent and an "opium" salt or by successive purification with "opium" salt and oxidic sorbent in any desired sequence.
The ester can be purified by the process according to the invention after it has been prepared and optionally isolated. According to one embodiment, the separation of carboxylic acid fluorides, HF and hydrolysable fluoride is performed during the ester preparation from carboxylic acid chloride and alcohol.

This embodiment for the preparation of low-fluoride carboxylic acid esters from alcohols and carboxylic acid chlorides contaminated with carboxylic acid fluoride or HF
and hydrolysable fluoride is characterised in that the reaction is performed without water in the presence of an "opium" salt of the carboxylic acid, corresponding to the carboxylic acid chloride used, as separating agent, and/or of the inorganic-oxidic sorbent. The resulting carboxylic acid ester can then be separated off, for example by distillation. The fluoride remains in the residue.
In this case, the "opium" salt of carboxylic acid may at the same time serve as a catalyst. One possibility consists in performing the reaction of acid chloride and alcohol in the presence of the "opium" salt and circulating the reaction mixture over the sorbent. Of course, it is also possible to operate without a catalyst or with other catalysts and to provide for the reaction mixture to be circulated over the sorbent such as Si02.
The "opium" salt may if desired be prepared in situ from the carboxylic acid and the base corresponding to the "opium" cation. If it is an unstable acid - for example a ~-keto-carboxylic acid with a tendency towards decarboxylation - initially another carboxylic acid may be used. Thus, for example, initially trifluoroacetic acid may be used instead of 4,4,4-trifluoroacetylacetic acid [sic] in order to obtain the "opium" salt.
It was established that when the 4,4,4-trifluoroacetoacetic acid or an ester is added the "opium" salt of 4,4,4-trifluoroacetoacetic acid then forms in a mild manner, without decarboxylation occurring.
The addition of acid, e.g. a carboxylic acid, is not necessary, and preferably does not occur.
The process according to the invention may be applied in principle to the preparation and purification of any carboxylic acids, acid chlorides and esters of any carboxylic acids with any alcohols. One preferred embodiment provides for a carboxylic acid of the formula R1 C(O)OH or R1 C(O)CH2C(O)OH, carboxylic acid chloride of the formula R1C(O)CI (I) or R1C(O)CH2C(O)CI (II), an ester of Formula (I II) R1 C(O)OR2 or of Formula (IV) R1 C(O)OH2C(O)OR2 to be used, wherein R1 stands for alkyl with 1 to 6 C atoms which is substituted by at least 1 halogen atom, in particular by at least one fluorine atom, and R2 has the above meaning. The process is particularly well suited for application to compounds of the formula R1 C(O)OH, of Formula (I), of Formula (II) (the compounds of Formula (II) being obtainable e.g. by addition of the compounds of Formula (I) to ketenes), of Formulae (III) or (IV), in which R1 stands for polyfluorinated, perfluorinated or polyfluorochlorinated alkyl having 1 to 6 C atoms, in particular 1 to 4 C atoms. Therein, the term "polyfluorinated"
means that at least 2/3 of all the H atoms in R1 are replaced by F atoms. The term "perfluorinated" means that all the H atoms in R1 are replaced by F atoms. The term "polyfluorochlorinated" means that at least 2/3 of all the H atoms in R1 are replaced by F atoms and of the remaining H atoms at least the predominant part or all of them are replaced by CI atoms.
Furthermore, it is preferred that an ester or alcohol of the formula R20H (II) is used, wherein R2 stands for alkyl or alkenyl with 1 to 8 C atoms; alkyl or alkenyl with 1 (or in the case of alkenyl, with at least 2 C atoms) to 8 C atoms which is substituted by at least 1 halogen atom; phenyl, tolyl; benzyl; phenyl, tolyl or benzyl substituted by at least 1 halogen atom and/or at least one nitro group.
It is very particularly preferred that R1 stands for polyfluoroalkyl, perfluoroalkyl or polyfluorochloroalkyl with 1 to 4 C atoms and R2 for alkyl or alkenyl with 1 (or in the case of alkenyl, with at least 2 C atoms) to 4 C atoms; alkyl or alkenyl with 1 (or in the case of alkenyl, with at least 2 C atoms) to 4 C atoms which is substituted by at least 1 halogen atom; phenyl; phenyl substituted by at least 1 halogen atom and/or by at least one nitro group. In particular, R1 stands for perfluoromethyl, perfluoroethyl, perfluoropropyl or chlorodifluoromethyl. Particularly preferably, R2 stands for alkyl or alkenyl with 1 (or in the case of alkenyl, with at least 2 C atoms) to 3 C
atoms; alkyl or alkenyl with 1 (or in the case of alkenyl, with at least 2 C atoms) to 3 C
atoms which is substituted by at least 1 fluorine atom; phenyl; phenyl substituted by at least 1 fluorine atom and/or at least one nitro group.
Carboxylic acid chlorides substituted by fluorine and optionally chlorine can be prepared in known manner.
The term "onium" stands for cations having a positively-charged nitrogen, for example protonated aromatic nitrogen bases such as pyridinium or protonated alkyl-, dialkyl- or trialkylammonium cations having up to 20 C atoms, or for ammonium compounds substituted by cycloalkyl, or cycloaliphatic nitrogen bases such as piperidinium or quaternary ammonium cations.
Highly suitable carboxylic acid salts are "onium" salts, with "onium"
[standing]
for a cation of nitrogen of the formula RIRIIRIIIRIVN+, wherein RI, RII, RIII
and RIV
independently of each other are hydrogen, alkyl with 1 to 20 C atoms, aryl or aralkyl, or wherein RI and RI I or wherein RI II and RIV, or wherein RI, RII and RI I I
or wherein RI, RII, RIII and RIV, optionally with the inclusion of the nitrogen atom, form saturated or unsaturated ring systems. "Aryl" here stands in particular for phenyl or for phenyl substituted by 1 or more C1-C2-alkyl groups. Outstandingly suitable are salts, in which "onium" stands for ammonium, pyridinium or R1 ~ R2~ R3~ R4~ N+, wherein R1 ~, R2~, R3~
and R4~ independently of each other stand for hydrogen, alkyl with 1 to 15 C
atoms, phenyl or benzyl. Examples of such cations are pyridinium, piperidinium, anilinium, benzyltriethylammonium and triethylammonium.
The process according to the invention is particularly well suited for the preparation or purification of difluoroacetic acid, 4,4-difluoroacetoacetic acid, trifluoroacetic acid, chlordifluoroacetic acid, 4,4,4-trifluoroacetoacetic acid and 4-chloro-4,4-difluoroacetoacetic acid, their acid chlorides and their derivatives obtained by condensation reactions (hydrolysis, esterification, hydrazinolysis with formation of rings with heteroatoms), such as esters with 1,1,1-trifluoroethanol, methanol, ethanol, isopropanol, n-propanol, 4-nitro-phenol, pentafluorophenol and allyl alcohol.
In the ester preparation, the molar ratio of carboxylic acid halide and alcohol is advantageously above 0.9. The alcohol may also be used in a greater excess, and serves as a solvent, particularly if it is an alcohol substituted by electron-attracting groups, for example fluorine atoms. Expediently, the molar ratio of alcohol to carboxylic acid halide lies between 0.9:1 and 1.1:1, or if the alcohol acts as a solvent, up to 5:1.
The temperature at which the reaction (or purification) is performed is at ambient temperature (approximately 20°°C) up to the boiling point of the mixture, for example up to 100°°C. In the case of unstable acids or acid chlorides, one operates below the decarboxylation temperature. This applies, e.g. in the esterification of 4,4,4-trifluoro-, 4-chloro-4,4-difluoro- and 4,4-difluoroacetoacetic acid chloride;
in this case, esterification is carried out at room temperature or with cooling of the reaction mixture.
Operation is at ambient pressure (approximately 1 bar absolute) or if desired also at elevated pressure, for example at a pressure of up to 5 bar absolute.
The "onium" salt may be present in catalytic or molar quantities. Expediently, the molar ratio of acid halide and the carboxylic acid salt lies in the range from 1:1 to 20,000:1.
In addition to the already-mentioned distillation in order to isolate the esters, in the case of some esters the fact that two phases form can be utilised: one phase contains the very pure ester (>94% purity), the other the catalyst, the alcohol and the fluoride. Two phases form e.g. in the case of the methyl and ethyl esters of trifluoro-and chlorodifluoroacetic acid and also the n-propyl ester of chlorodifluoroacetic acid.
This has the advantage of simplified processing.
This embodiment of the process according to the invention for the preparation of methyl or ethyl esters of trifluoroacetic acid and of chlorodifluoroacetic acid and of the n-propyl ester of chlorodifluoroacetic acid provides for the acid chloride to be reacted with an excess of the alcohol in the presence of an "onium" salt of the relevant acid and the molar ratio of alcohol to acid chloride to be selected such that two phases form, wherein one phase contains the ester in a purity which can be achieved without a distillation stage, of at least 95% by weight, and the ester is isolated by separating off the ester phase from the other phase. With this procedure, the ester is thus produced in a purity which makes distillation unnecessary. One preferred embodiment of the process according to the invention therefore provides for isolation of the resulting ester without distillation.
In the preparation of the methyl ester of trifluoroacetic acid, the molar ratio of methanol to trifluoroacetyl chloride is in the range from 1.03:1 to 4:1. In the preparation of the ethyl ester of trifluoroacetic acid, the molar ratio of ethanol to trifluoroacetyl chloride is in the range from 1.01:1 to 5:1. In the preparation of the methyl ester of chlorodifluoroacetic acid, the molar ratio of methanol to chlorodifluoroacetyl chloride is in the range from 1.06:1 to 2.5:1. In the preparation of the ethyl ester of chlorodifluoroacetic acid, the molar ratio of ethanol to chlorodifluoroacetyl chloride is in the range from 1.02:1 to 2.5:1. In the aforementioned ranges, two phases are present in which, as stated, one phase comprises the ester, which is always contained in a purity of at least 95% by weight. The methyl esters always form the lower phase; the ethyl ester of chlorodifluoroacetic acid likewise forms the lower phase, and the ethyl ester of trifluoroacetic acid forms the upper phase.
The invention provides acids, acid chlorides and esters having a greatly reduced fluoride content (e.g. less than 70 ppm, or even 10 ppm and less), depending on the original content of HF, carboxylic acid fluoride and hydrolysable fluoride. On one hand, the product is thus very pure, and on the other hand there are no corrosion problems (or greatly reduced corrosion), e.g. in esterification in installations and components of installations made of ceramic or glass.
The use of "opium" salts as catalysts in esterification has already been disclosed in EP-A 623 582 (= US 5,405,991 ). The fact that in this manner not only is preparation possible in a very simple manner, but also when using starting materials containing carboxylic acid fluoride low-fluoride product is obtained and the corrosion is reduced, is not apparent from this application. The same applies to DE 197 32 031, which does not constitute a prior publication, which relates to the 2-phase method for the preparation of the methyl- and ethyl esters of CF3C(O)CI and CF2CIC(O)CI.
"Opium" salts of 4,4,4-trifluoroacetoacetic acid, 4-chloro-4,4-difluoroacetoacetic acid and 4,4-difluoroacetoacetic acid and the free acids themselves are novel, can be used for the process according to the invention and are likewise a subject of the invention.
The invention will be explained further with reference to the following examples, without limiting its scope.

General test procedure for Examples 1-3 for the preparation of low-fluoride trifluoroacetic acid ethyl esters from trifluoroacetyrl chloride and ethanol with a catalyst Batch (applies to Examples 1 - 3~
0.2 mol pyridine 15.8 g 0.2 mol trifluoroacetic acid 22.8 (TFA) g 2.0 mol reagent-grade ethanol92.1 g 1.8 mol trifluoroacetyl chloride238.5 (TFAC) g Performance:
The pyridine was placed in a 250-ml three-necked flask with magnetic stirrer rod, temperature sensor and dry-ice cooler, and TFA was added dropwise. The reaction was exothermic, and before the salt could precipitate completely, the ethanol was added in order to keep it in solution. In order to increase the reaction speed, the solution was brought to 50°C in a oil bath and the TFAC was introduced at this temperature via a glass frit.
At 20% of the required TFAC, two phases formed, the upper phase being virtually pure ethyl trifluoroacetate.
Stirring of the solution was continued for half an hour once the introduction had ended, and it was then transferred into a separating funnel. Both phases were clear after separation, and the catalyst phase was slightly yellow in colour.
Example 1:
Herein, TFAC with a fluoride content of 570 ppm was used. The test was performed as described above, and after reaction yielded an ester phase having a fluoride content of 61 ppm and a catalyst phase containing 1850 ppm F-.
The percentage distribution showed that the fluoride was found preferentially in the catalyst phase; 86.03% of the total fluoride was found therein, and the ester phase still contained 15.27%.

Example 2:
Herein, the same TFAC having a fluoride content of 570 ppm was used. The test was performed as described above, but with considerably more vigorous stirring, and after reaction yielded an ester phase having a fluoride content of 10 ppm and a catalyst phase containing 3670 ppm F'.
The percentage distribution showed that the fluoride was found preferentially in the catalyst phase; 97.28% of the total fluoride was found therein; in the ester phase, the fluoride content had been reduced to 2.72% of the original value.
Example 3:
Herein, TFAC with a fluoride content of 71 ppm was used. The test was performed as described above, and after reaction yielded an ester phase having a fluoride content of ppm and a catalyst phase containing 130 ppm F-.
The percentage distribution showed that the fluoride was found preferentially in the catalyst phase; 76.66% of the total fluoride was found therein, and the ester phase still contained 23.35% of the original value.
The examples show that the fluoride value in the ester can be reduced to very low values, both in the case of an originally very high and in the case of an originally very low fluoride content in the carboxylic acid fluoride.
Example 4:
Batch:
0.1 mol pyridine 7.9 g 0.1 mol trifluoroacetic acid 11.4 g 2.0 mol reagent-grade ethanol 92.1 g 1.8 mol trifluoroacetyl chloride 238.5 g Herein, again TFAC with a fluoride content of 570 ppm was used. The amount of catalyst was reduced to 5 mole % instead of the 10 mole % otherwise used. The test was performed as described above, only with considerably more vigorous stirring, and after reaction yielded an ester phase having a fluoride content of 32 ppm.

Example 5:
Preparation of low-fluoride trifluoroacetic acid ester using Si02 in a ceramic stirred vessel 5.1. A solution of 0.10 kg pyridinium trifluoroacetate in 1.90 kg methanol was prepared and mixed with a further 4.80 kg of methanol. 0.02 kg precipitated Si02 hydrate (product "1.00656.000 Kieselsaure gefallt reinst schwer" by Merck KGaA, Darmstadt; bulk density approximately 30-50 g/100 ml), grain size <0.1 mm, was added and 19.2 kg trifluoroacetyl chloride (1000 ppm hydrolysable fluoride) was introduced with stirring. The methyl ester contained less than 40 ppm hydrolysable fluoride after distillation. Even after many repetitions, no corrosion could be seen on the ceramic parts of the stirred vessel.
5.2 Example 5.1 was repeated. Instead of methanol, the same molar quantity of ethanol was used. The ethyl ester contained less than 30 ppm hydrolysable fluoride after distillation.
Example 6:
Separation of hydrolysable fluoride from trifluoroacetyl chloride A bed of 100 g "KC-Trockenperlen AF 125" from Engelhard Process Chemicals GmbH, Hannover was formed in a glass tube having an internal diameter of 1.5 cm.
These "Trockenperlen" consist of Si02 gel and have a diameter of between 2 and mm. The pore diameter is 125 A (12.5 nm). They are usually used as drying agents or as catalyst supports.
Trifluoroacetyl chloride containing 570 ppm hydrolysable fluoride was passed over this bed at room temperature. The product leaving the bed had a content of 98 ppm.
Examples 7-9:
Purification of ethyl 4,4,4-trifluoroacetoacetate 2.6 g HF (0.1 mol) was added to 630 g of the ester (3.4 mol) in order to simulate an ester contaminated with 4125 ppm hydrolysable fluoride.

Example 7:
Py.TFA as F-separating agent In this case, 2.1 g pyridine (0.027 mol) was placed in a 250 ml Teflon flask with magnetic stirrer rod, and 3.1 g trifluoroacetic acid (0.027 mol) was added thereto (4,4,4-trifluoroacetoacetic acid has a tendency to decarboxylate if the salt is prepared directly from pyridine and 4,4,4-trifluoroacetoacetic acid). Then 50.2 g ethyl 4,4,4-trifluoroacetoacetate were added to the pyridinium trifluoroacetate and the mixture was stirred for 3 hours at room temperature. After this time, the solution was heated for another hour at 70°C water-bath temperature and distilled off under vacuum. The bottom sample, in which the "onium" salt of 4,4,4-trifluoroacetoacetic acid was detected (19F-NMR), yielded a fluoride value of 14,500 ppm. The ester which was distilled off still contained 1460 ppm fluoride.
The "onium" salts of 4,4-difluoroacetoacetic acid and of 4-chloro-4,4-difluoroacetoacetic acid can also be prepared analogously. Isolation is possible using standard methods.
Examlale 8:
Precipitated Si02 hydrate as sorbent In this case, 50.1 g of the ethyl 4,4,4-trifluoroacetoacetate (0.27 mol) was poured into a Teflon flask with magnetic stirrer rod. 6.57 g precipitated Si02 hydrate from Merck (see Example 5) was added to the ethyl 4,4,4-trifluoroacetoacetate, and the mixture was stirred for 3 hours at room temperature. After this time, the solution was heated for another hour at 80°C water-bath temperature. The solution was filtered off hot once the stirring time had ended, and the solution was investigated for fluoride. We obtained a fluoride content of 9 ppm.

Example 9:
Si02 gel beads as sorbent In this case, 50.7 g of the ethyl 4,4,4-trifluoroacetoacetate (0.28 mol) was poured into a Teflon flask with magnetic stirrer rod. 10.2 g of "Trockenperlen AF 125"
(for further details see Example 6) was added to the ethyl 4,4,4-trifluoroacetoacetate, and the mixture was stirred for 3 hours at room temperature. After this time, ethyl 4,4,4-trifluoroacetoacetate was filtered off, fluoride content: 47 ppm.
Example 10:
Purification of trifluoroacetic acid Trifluoroacetyl chloride containing approximately 1,000 ppm hydrolysable fluoride was stirred with the virtually equimolar quantity of water. The reaction mixture was circulated continuously over "AF 125". Less than 50 ppm hydrolysable fluoride was detected in the product. Thus the Si02 sorbed the fluoride despite the water content of the reaction mixture.
Example 11:
Preparation and isolation of 4,4,4-trifluoroacetoacetic acid Batch:
4.0 mol ethyl a,a,a-trifluoroacetoacetic 736,4 g 2.0 mol trifluoroacetic acid 228.0 g 0.9 mol sulphuric acid 95-97% 90.0 g Set-up and Performance:
Ethyl a,a,a-trifluoroacetoacetate and trifluoroacetic acid were placed in a 1-litre flask with distillation attachment, and concentrated sulphuric acid was dropped carefully thereinto. The previously clear solution then became cloudy. Then it was boiled for 1.5 hours at 70°C-90°C. On observing individually-occurring gas bubbles at the bubble counter, the temperature was reduced somewhat.

After boiling, the light brown solution was taken from the oil bath and placed in an ice bath for cooling, where after a short time fine, white, needle-like crystals formed. The crystals were drawn off via a glass frit and analysed by means of NMR and mass spectrometry, and were confirmed as trifluoroacetoacetic acid.
4,4-Difluoroacetoacetic acid and 4-chloro-4,4-difluoroacetoacetic acid can be obtained analogously from the ethyl ester and trifluoroacetic acid and subsequent conventional purification operations.

Claims

1. A process for the preparation of fluorinated organic compounds which are low in hydrolysable fluoride, wherein the organic compounds contaminated with hydrolysable fluoride are contacted with at least one separating agent for hydrolysable fluoride, selected from the group comprising amorphous SiO2 and "onium" salts of carboxylic acids.

2. A process according to Claim 1, characterised in that carboxylic acids or carboxylic acid chlorides are purified.

3. A process according to Claim 1, characterised in that derivatives of carboxylic acids or carboxylic acid chlorides are purified.

4. A process according to one of Claims 1 to 3, characterised in that the derivatives of carboxylic acids or carboxylic acid chlorides are purified upon production thereof.

5. A process according to Claim 1 for the preparation of carboxylic acids, carboxylic acid chlorides and carboxylic acid esters which are low in carboxylic acid fluoride or hydrolysable fluoride, from carboxylic acids, carboxylic acid chlorides and carboxylic acid esters which are contaminated with carboxylic acid fluoride or hydrolysable fluoride, by contacting them with at least one separating agent for carboxylic acid fluoride and hydrolysable fluoride, selected from the group comprising inorganic-oxidic sorbents and "onium" salts of the corresponding carboxylic acid.

6. A process according to Claim 1, characterised in that silica gel beads or precipitated SiO2 hydrate is used.

7. A process according to Claim 5, characterised in that carboxylic acid esters are prepared in the presence of an "onium" salt of the corresponding carboxylic acid and/or of the inorganic-oxidic sorbent from carboxylic acid chloride and alcohol.

8. A process according to one of the preceding claims, characterised in that a carboxylic acid of the formula R1C(O)OH is purified or a carboxylic acid chloride of the formula R1C(O)Cl (I) or R1C(O)CH2C(O)Cl (II) is used, wherein R1 stands for alkyl with 1 to 6 C atoms which is substituted by at least 1 halogen atom; in particular polyfluoroalkyl, perfluoroalkyl or polyfluorochloroalkyl with 1 to 6 C atoms.

9. A process according to Claim 7, characterised in that an alcohol of the formula R2OH (II) is used, wherein R2 stands for alkyl or alkenyl with 1 to 8 C atoms; alkyl or alkenyl with 1 to 8 C atoms which is substituted by at least 1 halogen atom; phenyl, tolyl; benzyl; phenyl, tolyl or benzyl substituted by at least 1 halogen atom and/or at least one nitro group.

10. A process according to Claim 5, characterised in that an ester of Formula (III) R1C(O)OR2 or (IV) R1C(O)CH2C(O)OR2 is purified or prepared, wherein R1 and R2 have the above meaning.

11. A process according to one of Claims 8 to 10, characterised in that R1 stands for polyfluoroalkyl, perfluoroalkyl or polyfluorochloroalkyl with 1 to 4 C atoms and R2 for alkyl or alkenyl with 1 to 4 C atoms; alkyl or alkenyl with 1 to 4 C atoms which is substituted by at least 1 halogen atom; phenyl; phenyl substituted by at least 1 halogen atom and/or by at least one nitro group.

12. A process according to Claim 11, characterised in that R1 stands for perfluoromethyl, perfluoroethyl, perfluoropropyl or chlorodifluoromethyl.

13. A process according to Claim 12, characterised in that R2 stands for alkyl or alkenyl with 1 to 3 C atoms; alkyl or alkenyl with 1 to 3 C atoms which is substituted by at least 1 fluorine atom; phenyl; phenyl substituted by at least 1 fluorine atom and/or at least one vitro group.

14. A process according to one of the preceding claims, characterised in that the molar ratio between acid chloride and "onium" salt lies in the range from 1:1 to 20,000:1.

15. A process according to one of the preceding claims, characterised in that a pyridinium or piperidinium salt is used.

16. A process according to Claim 7, wherein the "onium"
salt is prepared in situ from the corresponding carboxylic acid and the base corresponding to the onium cation.

17. A process according to Claim 16, wherein in the case of carboxylic acids which have a tendency to decarboxylation the starting point is a carboxylic acid which is stable with respect to decarboxylation.

18. A process according to Claim 12, characterised in that R1C(O)CH2C(O)Cl which has been obtained by reacting R1C(O)Cl and ketene is used.

19. A process according to Claim 1, characterised in that CF3C(O)Cl or CF3C(O)CH2C(O)Cl is purified or prepared or is used in derivatisation, in particular ester preparation.

20. A process according to Claim 7 for the preparation of methyl or ethyl esters of trifluoroacetic acid and chlorodifluoroacetic acid, wherein the acid chloride is reacted with a stoichiometric excess of the alcohol in the presence of the "onium" salt and optionally the inorganic-oxidic sorbent and the molar ratio of alcohol to acid chloride is selected such that two phases form, wherein one phase contains the ester in a purity which can be achieved without a distillation stage, of at least 95% by weight, and the ester is isolated by separating off the ester phase from the other phase.

21. A process according to Claim 20, characterised in that the methyl ester of trifluoroacetic acid is prepared and the molar ratio of methanol to trifluoroacetyl chloride is in the range from 1.03:1 to 4:1.

22. A process according to Claim 20, characterised in that the ethyl ester of trifluoroacetic acid is prepared and the molar ratio of ethanol to trifluoroacetyl chloride is in the range from 1.01:1 to 5:1.

23. A process according to Claim 20, characterised in that the methyl ester of chlorodifluoroacetic acid is prepared and the molar ratio of methanol to chlorodifluoroacetyl chloride is in the range from 1.06:1 to 2.5:1.

24. A process according to Claim 20, characterised in that the ethyl ester of chlorodifluoroacetic acid is prepared and the molar ratio of ethanol to chlorodifluoroacetyl chloride is in the range from 1.02:1 to 2.5:1.

25. A process according to Claim 20, characterised in that the reaction mixture is circulated and is contacted with the sorbent.

26. A process according to Claim 6, characterised in that in water-containing systems silica gel beads are used and purification is effected in a circulating stream.

27. A process according to Claim l, characterised in that the molar ratio of "onium" salt to HF is at or above 1:2.

28. 4-Chloro-4,4-difluoroacetoacetic acid, 4,4-difluoroacetoacetic acid and its "onium" salts.