DE4313794A1 - Process for the preparation of ketones - Google Patents

Abstract

There is described a novel process for the preparation of ketones, for example of CF3C(O)CH3, CF3C(O)CH2C(O)CF3 and CF3C(O)CF2H. In this process, ss-ketoesters are transesterified with a carboxylic acid, for example trifluoroacetic acid, in the presence of an "onium" salt of a carboxylic acid, alkyl- or arylsulphonic acid or a mineral acid and decarboxylated. The process is carried out under anhydrous conditions. No acetals or hydrates are therefore formed, so a dehydration stage is unnecessary. A further advantage of the process is the simple way it is carried out.

Description

The invention relates to a method of manufacture development of ketones.

Ketones are valuable intermediates in the chemical Synthesis. For example, 1.1.1-trifluoroacetone is an important one Intermediate in the manufacture of biologically active intermediates connections, see DE-OS 40 25 188. In this disclosure the production of halogen methyl ketones from the respective halomethylnitro compound by reaction with Alcoholate and subsequent ozonization described. The pro product is obtained as a hydrate, acetal or hemiacetal. The said Laid-open specification describes further processes for ketone therapy position that take place via Grignard connections (this reac tion type requires increased safety precautions, except unwanted waste products are produced) or the acid relate to catalyzed cleavage of keto esters. In the last Other processes also produce hydrates of the ketones. Further deacylation is often observed instead of the desired De carboxylation.

The object of the present invention is a method state the immediately anhydrous ketones without De hydration and technically easy to do is. This task is accomplished by the method of the present Invention solved.

The process for the production of ketones by cataly This results in decarboxylation of keto-ester compounds characterized in that the decarboxylation with transesterification with a carboxylic acid in the presence of a catalyzed reaction  amount of an "onium" salt of a carboxylic acid and / or a concentrated acid selected from the group comprising Mineral acids, aryl sulfonic acids and alkyl sulfonic acids leads.

The term "onium" stands for cations with a positive charge nem nitrogen, for example protonated aromatic stick substance bases such as pyridinium or protonated alkyl, dialkyl or Trialkylammonium cations with up to 20 carbon atoms, or for through Cycloalkyl substituted ammonium compounds or cycloalipha table nitrogen bases such as piperidinium. The term "mineral acids "includes oxo acids of elements of the 4th to 7th major group, especially phosphoric acid, sulfuric acid, fluorosulfone acid and chlorosulfonic acid. The term "alkyl sulfonic acids" um summarizes C1-C5-alkylsulfonic acids, the alkyl group being represented by 1 or more halogen atoms may be substituted, for example methane sulfonic acid and trifluoromethanesulfonic acid. The term "Arylsul fonic acids "includes phenylsulfonic acid and sulfonic acids with a Phenyl group formed by 1 or more halogen atoms and / or can be substituted by 1 or more C1-C2-alkyl groups, e.g. B. p.toluenesulfonic acid. The amount of carbon to be used Acid is advantageously at least 0.8 moles per mole to be converted the carboxy group. It is preferred to work without water.

According to the invention, the production of Ketones of the general formula (I)

R¹C (O) CH _n R² _3-n (I)

wherein R¹ is alkyl having 1 to 10 carbon atoms, by at least 1 halogen represents atom-substituted alkyl having 1 to 10 carbon atoms; Aryl; aryl substituted by at least 1 halogen atom; Arylalkyl; R² for hydrogen, alkyl with 1 to 10 carbon atoms; Aryl; through minde at least 1 halogen atom substituted aryl; Arylalkyl, halogen or C (O) R³, in which R³ is alkyl having 1 to 10 C atoms; through minde at least 1 halogen atom substituted alkyl with 1 to 10 carbon atoms; Aryl, aryl substituted by at least 1 halogen atom; Aryl alkyl means and stands and n = 1 or 2 means by conversion  tion of a carboxylic acid with 1 to 10 carbon atoms or one at least 1 halogen atom substituted carboxylic acid with 1 to 10 carbon atoms with a keto ester compound in the form of a car boxylate or dicarboxylate compound of the general formula (II)

R¹C (O) CR² _3-n [C (O) OR⁴] _n (II)

wherein n, R¹ and R² have the meaning given above, R⁴ Al kyl with 1 to 10 carbon atoms; by at least 1 halogen atom sub substituted alkyl with 1 to 10 carbon atoms; Aryl; by at least 1 halogen atom substituted aryl, the reaction under Decarboxylation in the presence of a catalyze the reaction the amount of an "onium" salt of a carboxylic acid with 1 to 10 carbon atoms, a metal or "onium" salt one by min least 1 halogen atom substituted carboxylic acid with 1 to 10 C- Atoms, a concentrated mineral acid, an arylsulfonic acid or an alkyl sulfonic acid is carried out.

If n = 1, they are ketones of the formula R¹C (O) CHR²₂. Here the two substituents R² can be the same or have different meanings. If n = 2, you go out of dicarboxylate compounds of the formula R¹C (O) CR² [C (O) OR⁴] ₂. Here can the substituents R⁴ same or different meaning possess.

If, according to a variant of the invention, a carbon acid in the presence of an "onium" salt of a carboxylic acid sets, it can be different carboxylic acids or before act preferably the same carboxylic acids.

The mineral acid used is preferably sulfuric acid, which is particularly well suited as a mineral acid.

Excellent as a carboxylic acid salt are "onium" salts, where "onium" stands for cations with positively charged nitrogen, preferably for a nitrogen cation of the formula R ^I R ^II R ^III R ^IV N R, in which R ^I , R ^II , R ^III and R ^IV independently of one another are hydrogen, alkyl having 1 to 20 C atoms, or aralkyl, or in which R ^I and R ^III or in which R ^III and R ^IV or in which R ^I , R ^II and R ^III or in which R ^I , R ^II , R ^III and R ^IV, optionally including the nitrogen atom, form saturated or unsaturated ring systems. Salts in which "onium" represents ammonium, pyridinium or R ^{1 ′} R ^{2 ′} R ^{3 ′} R ^{4 ′} N⁺, where rin R ^{1 ′} , R ^{2 ′} , R ^{3 ′} and R ^{4 ′} , are independently hydrogen, alkyl having 1 to 15 carbon atoms, aryl or benzyl. "Aryl" here means in particular phenyl or phenyl substituted by 1 or more C1-C2-alkyl groups. Examples of such cations are pyridinium, anilium, piperidinium, benzyltriethyl ammonium and triethylammonium.

In the process according to the invention, the carboxylic acid is used preferably a carboxylic acid of formula (III), R1 COOH, where rin R¹ has the meaning given above. Preferably stands R¹ is alkyl substituted by 1 to 5 halogen atoms with 1 or 2 carbon atoms, especially for CH₂F, CHF₂ or CF₃. R² is in front preferably for hydrogen, fluorine or C (O) R³, where R³ is CH₃, CH₂F, CHF₂ or CF₃ is.

According to a preferred embodiment, R⁴ stands for gege optionally alkyl substituted by 1 or more halogen atoms with 1 to 6 carbon atoms, preferably with 1 to 3 carbon atoms, esp special methyl, ethyl, propyl, 1.1.1-trifluoroethyl or penta fluoropropyl.

According to one embodiment of the invention, n = 1. Man then produces ketones of the formula R¹C (O) CHR²₂ from R¹C (O) CR²₂COOR⁴. For example, CF₃C (O) CH₃ from CF₃C (O) CH₂COOMe, Make CF₃C (O) CH₂COOEt or CF₃C (O) CH₂COOCH₂CF₃. Analog can to produce CF₃C (O) CH₂F or CH₂FC (O) CH₂F and other ketones.

According to another embodiment, n = 2. For the manufacture Development of ketones of the formula R¹C (O) CH₂R² then starts from Di carboxylates of the formula R¹C (O) CR² [C (O) OR⁴] ₂.  

The starting point for the production of diketo compounds Keto esters of the formula R¹C (O) CR² [C (O) R³] [C (O) OR⁴] or R¹C (O) C [C (O) R³] [C (O) OR⁴] ₂.

The amount of carboxylic acid is appropriately chosen so that per mole of ester group in the compound of formula (II) at least 0.8 mol of carboxylic acid can be used. That is an advantage Molar ratio of carboxylic acid to ester groups in the compound of the formula (II) between 0.9: 1 to 1.1: 1.

The temperature when carrying out the process is present partly in the range of 70 to 130 ° C. The pressure is appropriate in the range from 0.01 bar (absolute) to 2 bar (absolute).

The "onium" salt of the carboxylic acid or mineral acid is suitably in a concentration of 50 to 900 g / l in the reaction mixture.

If desired, one can in the presence of an inert Lö working means, for example in the presence of coal hydrogen or perhalogenated compounds. If rivers sig, can also use the mineral acid used as a solvent to serve.

The keto ester verbin serving as the starting compounds Solutions are known or can be based on or analogous to standard measurements methods are produced. As the explanations above be can already be removed, you can by means of the erfindungsge According to the method also produce β-diketo compounds. To you go z. B. from compounds of the formula (IV) a, R¹C (O) CH₂C (O) OR⁴ or (IV) b, R¹C (O) CH [C (O) OR⁴] ₂, or (IV) c, R¹C (O) CHR²C (O) OR⁴.

R¹, R² and R⁴ have the meaning described above. The Proton is exchanged for an R³ (CO) group. This can for example, the compound of formula (IV) with R³C (O) Cl in the presence of a base, e.g. B. triethylamine. At for example, one can use CH₂ (COOEt) ₂ with CF₃C (O) Cl and Et₃N Implement CF₃C (O) CH (COOEt) ₂. The decarboxylation of keto-di esters using trifluoroacetic acid and sulfuric acid  CF₃C (O) CH₃. Analogously, CH₃C (O) CH₂COOEt is formed according to trifluor acetylation and decarboxylation of the compound CF₃C (O) CH₂C (O) CH₃. Such diketones are complexing agents and e.g. B. usable in metal recycling.

Analogously, other keto-ester compounds can also be used Acylation of esters or diesters are generated.

The method according to the invention can also be continuous operate. This is done by passing Car into the reaction mixture acid and keto ester compound and separates formed Ketone, optionally also the ester formed, for example wise by distillation.

The present invention has yet another aspect on. When the carboxylic acid is transesterified, an ester is formed ser carboxylic acid, which are isolated from the reaction mixture can. By using certain carboxylic acids and keto-ester Compounds with certain ester groups can be targeted agreed, may be difficult to manufacture in other ways Esters are synthesized.

The method according to the invention technically configures it fold production of keto compounds that are anhydrous len. In addition, esters can also be produced in a targeted manner. The on The reaction mixtures can be separated by distillation.

The invention will now be further explained using examples tert without its scope should be restricted.

example 1

Manufacture of as a starting product for decarboxylation required 1,1,1-trifluoro-2-oxo-3,3-diethyldicarboxylate Reaction of trifluoroacetyl chloride with diethyl malonate and triethylamine

CF₃C (O) Cl + CH₂ (COOEt) ₂ → CF₃C (O) CH (COOEt) ₂

The production was carried out analogously to that of A. F. Ermolov, A. F. Eleev, A. F. Benda and G. A. Sokol′skii in Zh. Org. Khim. 23 (1) (1987), pages 105-112. To do this approximately equimolar amounts of the starting compounds in diethyl ether reacted with 2 equivalents of triethylamine. The educated [CF₃C (O) C (COOEt) ₂) ⁻HNEt₃⁺ was added by adding sulfuric acid 1,1,1-trifluoro-2-oxo-3,3-diethyl-dicarboxylate implemented. This Compound was then removed from the reaction mixture with diethyl ether extracted and purified by distillation.

Example 2

Preparation of 1,1,1-trifluoroacetone from 1,1,1-trifluoro-2-oxo 3,3-diethyl dicarboxylate by transesterification with trifluores acetic acid / pyridinium trifluoroacetate and subsequent decarboxy lation

In a glass apparatus with a 20 cm Vigreux column with two downstream cold traps cooled to -78 ° C and KPG stirrer 35.9 g (0.45 mol) of pyridine were introduced and 149.2 g (1.30 mol) trifluoroacetic acid with gentle cooling at 50 to 70 ° C added dropwise. After the addition of 51.2 g (0.20 mol) of 1.1.1- The reaction mixture was trifluoro-2-oxo-3,3-diethyl-dicarboxylate heated in an oil bath to 120 to 140 ° C, at 90 ° C the Decarboxylation began. The yield of 1,1,1-trifluoroacetone was 72.6% of theory after a reaction time of 10 h Mix with ethyl trifluoroacetate.

Example 3

Production of 1,1,1-trifluoroacetone from ω, ω, ω-trifluoracetes ethyl acetate by transesterification with trifluoroacetic acid in concentrated sulfuric acid and decarboxylation at 90 to 120 ° C  

In a glass apparatus with a 20 cm Vigreux column with two downstream cold traps cooled to -78 ° C and KPG stirrer 100 ml of conc. H₂SO₄ and 109.5 g (0.96 mol) of trifluoroacetic acid acid presented at room temperature. After the addition of 58.9 g (0.32 mol) ω, ω, ω-trifluoroacetoacetic acid ethyl ester the Re action mixture with stirring in an oil bath to temperatures of 90 heated up to 120 ° C inside temperature, whereby at approx. 75 ° C the De carboxylation. At the beginning of the reaction, the over partially trifluoroacetic acid distilled off. The out Prey of 1,1,1-trifluoroacetone was after a reaction time from 7 h 86% d. Theory as a mixture with trifluoroacetic acid ethyl ester, for the final heating of the trifluor ethyl acetate and trifluoroacetic acid still present Oil bath temperature was increased up to 160 ° C. Subsequent Distillation over a packed column gave pure trifluor acetone.

Example 4

Preparation of 1,1,1-trifluoroacetone from 1,1,1-trifluoro-2-oxo 3,3-diethyl-dicarboxylate by transesterification with trifluoroacetic acid right / methanesulfonic acid and subsequent decarboxylation at 130 up to 160 ° C

In a glass apparatus with a 20 cm Vigreux column with two downstream cold traps cooled to -78 ° C and KPG stirrer 148.24 g (1.54 mol) of methanesulfonic acid and 68.41 g (0.60 mol) of trifluoroacetic acid at room temperature. To the addition of 51.24 g (0.20 mol) of 1,1,1-trifluoro-2-oxo-3,3-diet The reaction mixture was hyl dicarboxylate with stirring (600 rpm) in an oil bath at temperatures from 130 to 160 ° C inside heated temperature, the decarboxylation at about 90 ° C. started. At the beginning of the reaction, the excess trifluor  partially distilled off acetic acid. The yield of 1,1,1-tri fluoroacetone was 79% after a reaction time of 9 h d. Theory as a mixture with trifluoroacetic acid ethyl ester, where for final heating of the trifluoroacetic acid ethyl ester and the excess trifluoroacetic acid the oil bath temperature was increased up to 200 ° C.

Example 5

Preparation of 1,1,1-trifluoroacetone from 1,1,1-trifluoro-2-oxo 3,3-diethyl dicarboxylate by transesterification with trifluoroacetic acid in concentrated sulfuric acid and decarboxylation at 90 to 120 ° C

In a glass apparatus with a 20 cm Vigreux column with two downstream cold traps cooled to -78 ° C and KPG stirrer 100 ml of conc. H₂SO₄ and 68.41 g (0.60 mol) of trifluoroacetic acid acid presented at room temperature. After the addition of 51.24 g (0.20 mol) 1,1,1-trifluoro-2-oxo-3,3-diethyl-dicarboxylate the reaction mixture with stirring (600 rpm) in an oil bath at tem temperatures heated from 90 to 120 ° C internal temperature, whereby at approx. 90 ° C started the decarboxylation. At the beginning of the reaction de the excess trifluoroacetic acid is partially distilled off. The yield of 1,1,1-trifluoroacetone after a reak tion time of 7 h 82% d. Theory as a mixture with trifluores ethyl acetate, the final heating of the tri ethyl fluoroacetate and trifluoroacetic acid still present acid the oil bath temperature was increased up to 160 ° C.

Also a sulfuric acid / sulfolane mixture (30 ml conc. Sulfur acid / 70 ml sulfolane) was tested and delivered approximately same results. Carrying out several decarboxyly Runs with the same catalyst mixture was without Pro bleme possible. When using chloro- and fluorosulfonic acid as Catalyst component resulted in the formation of unidentified minor components. Too much trifluor at the start of the reaction  removed acetic acid, the decarboxylation takes place under Bil formation of ethylene.

The separation of the trifluoroacetone / Trifluoroacetic acid ethyl ester mixture was then carried out by distillation over a 40 cm packed column.

Example 6 Continuous production of 1,1,1-trifluoroacetone in one Endurance test

Example 3 was repeated. According to the amount of 1,1,1- Trifluoroacetone and trifluoroacetic acid ethyl ester, which from the Reaction mixture was distilled off, was continuous Educt introduced into the glass apparatus. The yield of 1,1,1- Trifluoroacetone after a test period of 15 days 95% of Theory.

Claims (13)

1. A process for the preparation of ketones by catalyzed decarboxylation of keto-ester compounds, characterized in that the decarboxylation with transesterification with a carboxylic acid in the presence of a reaction catalyzing amount of an "onium" salt of a carboxylic acid and / or concentrated acid selected from the group consisting of mineral acids, arylsulfonic acids and alkylsulfonic acids. 2. The method according to claim 1, characterized by the manufacture of ketones of the general formula (I) R¹C (O) CH _n R² _3-n (I) wherein R¹ is alkyl having 1 to 10 carbon atoms; alkyl with 1 to 10 carbon atoms substituted by at least 1 halogen atom; Aryl; aryl substituted by at least 1 halogen atom; Arylalkyl; R² is hydrogen, alkyl having 1 to 10 carbon atoms; Aryl; aryl substituted by at least 1 halogen atom; Arylalkyl, halogen or C (O) R³, wherein R³ is alkyl having 1 to 10 C atoms; alkyl having 1 to 10 carbon atoms substituted by at least 1 halogen atom; Aryl; aryl substituted by at least 1 halogen atom; Arylalkyl means and stands and n = 1 or 2, by reacting a carboxylic acid with 1 to 10 C atoms or a carboxylic acid substituted by at least 1 halogen atom with 1 to 10 C atoms with a keto ester compound in the form of a carboxylate - Or dicarboxylate compound of the general formula (II) R¹C (O) CR² _3-n [C (O) OR⁴] _n (II) wherein n, R¹ and R² have the meaning given above, R⁴ alkyl having 1 to 10 carbon atoms; alkyl with 1 to 10 carbon atoms substituted by at least 1 halogen atom; Aryl; aryl substituted by at least 1 halogen atom, the reaction with decarboxylation in the presence of a reaction which catalyzes the amount of an "onium" salt of a carboxylic acid having 1 to 10 carbon atoms, a metal or "onium" salt of one by at least 1 halogen atom substituted carboxylic acid having 1 to 10 carbon atoms, a concentrated mineral acid, arylsulfonic acid or an alkylsulfonic acid is carried out. 3. The method according to claim 1, characterized in that the reaction of the compound of formula (II) with the carbon acid in the presence of an amount catalyzing the reaction an "onium" salt of the same carboxylic acid or a conc mineral acid selected from sulfuric acid and Group comprising phosphoric acid or methanesulfonic acid leads. 4. The method according to claim 1, 2 or 3, characterized records that an "onium" salt of carboxylic acid or Schwe uses rock acid. 5. The method according to any one of the preceding claims, characterized in that a carboxylic acid is used as the carboxylic acid of formula (III), R¹COOH, wherein R¹ is the above Has meaning. 6. The method according to any one of the preceding claims, characterized in that R¹ represents from 1 to 5 halogen atoms substituted alkyl with 1 or 2 carbon atoms. 7. The method according to claim 6, characterized in that R¹ represents CH₂F, CHF₂ or CF₃. 8. The method according to any one of the preceding claims, characterized in that R² is hydrogen, fluorine or C (O) R³ is where R³ is CH₃, CH₂F, CHF₂ or CF₃. 9. The method according to any one of the preceding claims, characterized in that R⁴ optionally by halogen sub substituted alkyl with 1 to 6 carbon atoms, preferably with 1 to 3 carbon atoms means.   10. The method according to any one of the preceding claims, characterized in that R⁴ is methyl, ethyl, propyl, 1,1,1- Trifluoroethyl or Pentafluorpropyl stands. 11. The method according to any one of the preceding claims, characterized in that for the production of CF₃C (O) CH₃ Trifluoroacetic acid reacted with CF₃C (O) CH₂COOEt or CF₃C (O) CH (COOEt) ₂ in the presence of a catalytic converter amount of an "onium" salt of trifluoroacetic acid or concentrated sulfuric acid. 12. The method according to any one of the preceding claims, characterized in that the "onium" salt of the carboxylic acid or the concentrated mineral acid in a concentration of 50 to 900 g / l is present in the reaction mixture. 13. Modification of the method according to one of claims 1 to 12, characterized in that one for the continuous Implementation with separation of the ketone formed and the ge optionally formed ester, in the reaction mixture Carboxylic acid and the keto ester compound initiates.