Synthesis of low-fluoride organic compounds

Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters

Reexamination Certificate

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C562S577000, C562S578000, C562S849000

Reexamination Certificate

active

06252105

ABSTRACT:

BACKGROUND OF THE INVENTION
This invention relates to a method for the catalytic synthesis of low-fluoride organic compounds, especially fluorinated organic compounds such as carboxylic acids and derivatives thereof.
Fluorinated organic compounds are of great importance in many areas of technology. Fluorinated organic compounds (fluorinated hydrocarbons, fluorochlorohydrocarbons, fluorine-containing ethers, fluorine-containing surfactants, etc.) are used, for example, in the field of refrigeration technology, in the fire extinguisher field, and as cleaning agents. Fluorinated hydrocarbons are utilized as propellants for the production of foams or aerosols (even in the field of pharmaceutical preparations). Fluorinated organic compounds are used not only as end products as explained above, but also as intermediate products in the production of useful processed goods. Particularly in the field of agricultural technology, for example, fluorine- containing, and in some cases chlorine-containing, carboxylic acids have proved very interesting as building blocks. Carboxylic acids of this type and reactive derivatives thereof, such as carboxylic acid chlorides, can be further processed—frequently in condensation reactions—to yield interesting building blocks, for example esters or ring systems.
Many carboxylic acids and esters of carboxylic acids are used in industry as such. Acetate esters and other carboxylate esters are used, for example, as solvents or cleaning agents, while other esters, such as those of succinic acid, are used for aromatizing. Ethyl trifluoroacetate is, for example, a solvent for the chlorination of paraffins or for the polymerization of olefin oxides. Many carboxylate esters are also intermediates in chemical synthesis. The hydrogenation of methyl trifluoroacetate and of 1,1,1-trifluoroethyl trifluoroacetate results in trifluoroethanol (and possibly methanol). Trifluoroethanol is used as a solvent and as intermediate, for example, for the production of the solvent and anesthetic, isofluorane. Esters of trifluoroacetic acid and trifluoroacetoacetic acid are also used for the introduction or synthesis of biologically active compounds, which have a CF
3
group. For example, by N-acylation with methyl trifluoroacetate, peptides with hormonal activity can be synthesized. Shift reagents for NMR analysis are obtained from trifluoroethyl esters, together with camphor derivatives. After the Fries displacement with aluminum chloride, phenyl trifluoroacetate yields the corresponding trifluoroacetylated phenol, which is a building block for the synthesis of pharmaceutical drugs. Persons skilled in the art are familiar with many other applications involving esters, for example, the reactions of esters with amines to form amides, which represent building blocks for the synthesis of pharmaceutical drugs, photosensitizers and dyes.
Esters of chlorodifluoroacetic acid also are building blocks for syntheses. The ethyl ester is used, for example, for the synthesis of liquid crystals (see German Offenlegungsschrift 4 023 106) and for the synthesis of drugs (see U.S. Pat. No. 5,006,563), and the methyl ester is also used for the synthesis of liquid crystals and as a starting material for the microbial synthesis of chiral secondary alcohols (see T. Kitasume et al., J. Fluorine Chem. 56 (1992), pages 271 to 284) or for the synthesis of fluorinated enol ethers by the Wittig method (see J. P. Begue et al., J. Org. Chem. 57 (1992), page 3807 ff). The esters of chlorodifluoroacetic acid are also intermediates in the synthesis of dichlorocarbene.
Carboxylic acid chlorides, particularly fluorine-containing carboxylic acid chlorides, are reacted with ketene to form compounds of the type RC(O)CH
2
C(O)Cl, which are esterified and also are synthesis building blocks. The synthesis of acid chlorides of halogenated acetoacetic acid and their esterification is disclosed in the German Auslegeschrift 1 158 490. The esters are intermediates in dye chemistry, pharmaceutical chemistry and crop protection chemistry.
Fluorinated organic compounds can be produced, for example, by means of direct fluorination with F
2
, higher valence metal fluorides, through chlorine-fluorine exchange, HF-addition, and other processes. Insofar as hydrolyzable fluoride is obtained, whether as a result of the process used or through hydrolysis of fluorine from the molecule, this can lead to corrosion problems with glass, ceramic and metal containers or apparatus.
Hydrogen fluoride reacts with glass and ceramics and ultimately forms H
2
SiF
6
, which for its part under certain conditions reacts with water to form HF and SiO
2
again. The HF which is released again attacks glass, so that great damage can result. Corrosion of metal containers is likewise undesired.
Problems not only arise in storage/supply containers, but also in preparation of derivatives of fluorinated organic compounds, for example through condensation reactions in which HF is released, sometimes as a secondary reaction product.
However, the esterification of carboxylic acid chlorides without catalysts with alcohols leads to corrosion problems if the acid chlorides, due to the way in which they are produced, contain small amounts of carboxylic acid fluorides, free hydrogen fluoride or hydrolyzable fluoride. Such contaminants also frequently interfere in carboxylic acids or their esters because of corrosion problems.
The foregoing explanations detail the problems with fluorinated organic compounds. Such problems can also arise in compounds which are not substituted by fluorine, but which may take up fluorine as an impurity during their production.
It is surprising how often undesired corrosion can be traced back to hydrolyzable fluorides.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a method, which can be carried out easily industrially and with which organic compounds, especially fluorinated organic compounds, can be produced or purified so that they contain decreased amounts of hydrolyzable fluoride.
It is a specific object of the invention to provide a method with which carboxylic acids, carboxylic acid chlorides and derivatives thereof, especially those produced in condensation reactions, which contain little fluoride or decreased amounts of carboxylic acid fluorides and free hydrogen fluoride, can be synthesized in good yield starting from corresponding contaminated carboxylic acids, carboxylic acid chlorides or esters.
These and other objects are achieved in accordance with the present invention by providing a method for producing an organic compound with a decreased content of hydrolyzable fluoride, said method comprising the step of contacting an organic compound contaminated with hydrolyzable fluoride with at least one separating agent for hydrolyzable fluoride selected from the group consisting of inorganic oxide sorption agents and “onium” salts of carboxylic acids.
The process of the invention is suitable for purifying organic compounds which are contaminated with fluoride or hydrolyzable fluorine. This contamination may result from the production of the compound and or it may result from hydrolysis of fluorine in the molecule. Preferably fluorinated organic compounds are purified. These are compounds which contain at least one fluorine atom. Optionally, other halogen substituents can also be contained therein. The invention will be explained in further detail with reference to such embodiments.
The invention comprises two aspects: the purification of previously synthesized fluorinated organic compounds (e.g. before their use or further processing or during storage), and the synthesis of fluorinated organic compounds with simultaneous purification in accordance with the invention.
Preferably the invention is used for the synthesis or purification of fluorine-containing carboxylic acids, fluorine-containing carboxylic acid chlorides and/or for the synthesis or purification of derivatives of fluorine-containing carboxylic acids and fluorine-containing carboxylic acid chlorides. The formation of derivatives usually

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