Method for producing polyfluorinated tertiary alcohols

Abstract

The invention relates to a method for producing polyfluorinated alcohols of the formula (I) starting from a ketone of the formula (II) and a carboxylic acid salt of the formula (III) (R3COO)xY, wherein the substituents R1 and R2 are selected from the group consisting of: C1C10-alkyl, C3-C10-cycloalkyl, C6-C14-aryl and C5-C14-heteroaryl, wherein said substituents can be unsubstituted or partially or completely fluorinated, R3 is partially or completely fluorinated C1-C10-alkyl, Y is a cation selected from the group comprising: K, Li, Na, Cs, Mg, Ca, Fe, Cu, Ag, Zn and x is 1 or 2. According to the method, the R3 group of the carboxylic acid salt is transferred to the carbonyl carbon of the ketone of formula (II) with release of CO2.

Description

[0001]Process for the preparation of polyfluorinated tertiary alcohols Description The present invention relates to a process for the preparation of polyfluorinated tertiary alcohols. Furthermore, the present invention relates to the use of polyfluorinated alcohols prepared by the above-mentioned process. Polyfluorinated alcohols are used as starting materials for the synthesis of chemical compounds that are used in numerous consumer products. However, no elegant, one-step synthesis for the preparation of polyfluorinated tertiary alcohols is known from the prior art. US 3,317,616 A, on the other hand, discloses a stepwise synthesis of polyfluorinated tertiary alcohols starting from polyfluoroalkyl ketones. The usual route to prepare polyfluorinated alcohols is based on the addition of Me3SiCF3 (Ruppert's reagent). In an addition to aldehydes, as in R. Filler, RM Schure, J. Org. Chem.1967, 32, 1217–1219, a secondary alcohol is formed. Addition to ketones, as described in GKS Prakash, M. Mandal, Journal of Fluorine Chemistry 2001, 112, 123–131, however, leads to tertiary alcohols. This synthetic strategy, consisting of trifluoromethylation of ketones or aldehydes with preformed polyfluoroalkyl nucleophiles such as Me3SiCF3 (Ruppert's reagent), is disadvantageous, however, due to the high cost of such reagents. Chang et al. in Journal of Fluorine Chemistry 2005, 126 (6), 937–940 and Tetrahedron Letters 2005, 46, 3161–3164 report a method that does not require Ruppert's reagents. This is a decarboxylative polyfluoroalkylation in which the polyfluoroalkyl nucleophile is generated in situ by decarboxylation from polyfluorocarboxylate salts and is added to aldehydes and ketones.According to this method, benzaldehyde can be converted into the corresponding alcohol in the presence of stoichiometric amounts of a Cu(I) halide with trifluoroacetates: 1) CF3COONa, CuX, DMF, 160 - 180 °C, 2 - 6 h 2) H3O. + Starting from benzaldehyde (R 2 = H), the corresponding secondary alcohol was produced with a very high yield of 99%. In attempted reactions of ketones (R 2 = CH3) and esters (R 2 However, only traces of the desired product, the tertiary alcohol, were detected. Gooßen et al. reported in European Journal 2015, 21, 17220–17223 and Journal of Fluorine Chemistry 2017, 198, 89–93 that the presence of iron catalysts and the use of DMF as solvent favored decarboxylative perfluoroalkylations. The above-mentioned documents only disclosed reactions with aldehydes, which were converted to secondary alcohols. The achieved yield was approximately 60%: In view of the above-mentioned disadvantages of the known syntheses and the high demand for polyfluorinated tertiary alcohols, the object of the present invention was therefore to provide a new, effective, and cost-effective synthesis for the preparation of polyfluorinated tertiary alcohols. Accordingly, a process for the preparation of polyfluorinated alcohols of the formula (I) where R 1 is selected from the group consisting of: C1-C 10 -Alkyl, C3-C 10 -Cycloalkyl, C6- C 14 -aryl and C5-C 14 -Heteroaryl, where the substituents mentioned may be unsubstituted or partially or fully fluorinated; R 2 is selected from the group consisting of: C1-C10 alkyl, C3-C10 cycloalkyl, C6-C14 aryl and C5-C14 heteroaryl, where said substituents may be unsubstituted or partially or fully fluorinated; R 3is partially or fully fluorinated C1-C10 alkyl; starting from a ketone of formula (II) where R 1 is selected from the group consisting of: C1-C 10 -Alkyl, C3-C 10 -Cycloalkyl, C6- C 14 -aryl and C5-C 14 -Heteroaryl, where the substituents mentioned may be unsubstituted or partially or fully fluorinated; R 2 is selected from the group consisting of: C1-C 10 -Alkyl, C3-C 10 -Cycloalkyl, C6-C14-aryl and C5-C14-heteroaryl, where the substituents mentioned may be unsubstituted or partially or fully fluorinated, and a carboxylic acid salt of the formula (III) (R 3 COO)xY, where R 3 is partially or fully fluorinated C1-C10 alkyl; Y is a cation selected from the group comprising: K, Li, Na, Cs, Mg, Ca, Fe, Cu, Ag, Zn; x is 1 or 2; characterized in that the R 3Group of the carboxylic acid salt is transferred to the carbonyl carbon of the ketone of formula (II) with release of CO2. The process according to the invention is very cost-effective and efficient due to the one-step execution without the addition of expensive reagents. It enables the production of polyfluorinated tertiary alcohols on a large scale. The term "polyfluorinated alcohols" in the sense of the present invention comprises alcohols of formula (I) in which at least one carbon atom of the substituent R 1 , R 2 or R 3at least two hydrogen atoms have been replaced by fluorine atoms. The term “C1-C10 alkyl” in the sense of the present invention encompasses linear or branched saturated hydrocarbon groups having one to ten carbon atoms. These include in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, 2,2-dimethylpropyl, n-hexyl, isohexyl, 2-ethylhexyl, n-heptyl, isohexyl, n-octyl, isooctyl, n-nonyl, n-decyl and the like. The term “C2-C10 alkenyl” in the sense of the present invention encompasses unsaturated linear or branched hydrocarbon groups having two to ten carbon atoms, wherein the hydrocarbon groups have at least one CC double bond. These include in particular ethenyl, 1-propenyl, 2-propenyl, 1-n-butenyl, 2-n-butenyl, iso-butenyl, 1-pentenyl, 1-hexenyl, 1-heptenyl, 1-octenyl, 1-nonenyl, 1-decenyl and the like.For the purposes of the present invention, the term "C3-C10 cycloalkyl" encompasses cyclic, saturated hydrocarbon groups having three to ten carbon atoms. These include, in particular, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclohexyl, cyclononyl, and cyclodecanyl. The term "C6-C." 14 Aryl" in the context of the present invention encompasses aromatic hydrocarbon groups with six to fourteen ring-shaped carbon atoms. These include, in particular, phenyl (C6H5 group), naphthyl (C10H7 group) and anthracyl (C14H9 group). The term "C 5- C 14For the purposes of the present invention, "heteroaryl" encompasses aromatic hydrocarbon groups having five to fourteen ring-positioned hydrocarbon atoms in which at least one hydrocarbon atom is replaced or exchanged by a nitrogen, oxygen, or sulfur atom. These include, in particular, pyrrolyl, furanyl, thiophenyl, pyrridinyl, pyranyl, thiopyranyl, and the like. All of the aforementioned hydrocarbon groups are bonded to the central atom according to formula (I) via the oxygen atom. An advantageous development of the process according to the invention provides that the reaction is carried out in a solvent selected from the group comprising: DMF, NMP, DMAc, DMSO. The above-mentioned solvents are solvents suitable for stabilizing the fluorinated carbanion during the reaction, although the invention is not limited to these.The term “fluorinated carbanion” in the sense of the present invention comprises a negatively charged carbon atom whose hydrogen atoms have been replaced by fluorine atoms. The abbreviations: DMF, NMP, DMAc, DMSO mean the following in the sense of the present invention: DMF - N,N-dimethylformamide NMP - N-methyl-2-pyrrolidone DMAc - N,N-dimethylacetamide DMSO - dimethyl sulfoxide A further advantageous development of the process according to the invention provides that the reaction is carried out in DMF or DMSO as the solvent. A most preferred development of the process according to the invention provides that the reaction is carried out in DMF. The reaction temperature in the process according to the invention is preferably from 100 to 150°C, more preferably from 130 to 150°C, most preferably from 135 to 145°C. A most preferred development of the process according to the invention provides that the reaction temperature is 140°C.A further advantageous development of the process according to the invention provides that the reaction is carried out in the absence of moisture. This measure ensures that the highly sensitive polyfluorinated ketones used as reactants in the reaction do not convert to the corresponding hydrates in the presence of traces of water, which thermally decompose to form carboxylic acids, thus preventing any negative impact on the yield of the desired tertiary polyfluorinated alcohols. Furthermore, this also prevents the CF3 anion from being oxidized due to its very high pK. Svalue is converted directly to HCF3 and the reaction is prevented in the presence of strong bases. A further advantageous development of the process according to the invention provides that the reaction is carried out in the presence of a catalyst. This embodiment of the invention has proven particularly advantageous with less reactive starting materials in order to be able to achieve a higher yield. For the purposes of the present invention, all catalysts known from the prior art and suitable for this purpose, in particular Lewis acids, can be used as the catalyst. A further advantageous development of the process according to the invention provides that the reaction is carried out in the presence of an iron catalyst. The iron catalyst in the process according to the invention is preferably selected from the group consisting of: FeCl2, FeCl3, FeBr3, FeF3, FeTFA3, FeSO4, Fe2(SO4)3, particularly preferably FeCl2, FeCl3.FeCl3 is particularly preferred as a catalyst. When FeCl3 is used as a catalyst, BPy (2,2'-bipyridine), TMEDA (N,N,N',N'-tetramethylethylenediamine), or [2.2.2]cryptand can be added as ligands to the reaction in a 1:1 ratio. The amount of iron catalyst in the process according to the invention is preferably 10 to 75 mol%, more preferably 15 to 45 mol%. A most preferred development of the process according to the invention provides that the amount of iron catalyst is 20 to 30 mol%. A further advantageous development of the process according to the invention provides that the catalyst is selected from the group comprising: KOtBu, K2CO3, KCl, ZnCl2, CoCl2, MnCl2, InCl3, GaBr3, CuI, CuBr, AgBF3, Sc(OTf)3. The amount of catalyst in the process according to the invention is preferably 10 to 75 mol%, more preferably 10 to 30 mol%.In the case of a gaseous reactant, the process according to the invention can be carried out using the following methods, but is not limited to them: crimp-cap vessels, gas burettes, and autoclaves. When using an autoclave, the reaction pressure is 0.5 to 6.5 bar, preferably 2.0 to 4.0 bar, most preferably 3.0 bar. The reaction time is 1 to 24 hours. The process according to the invention is suitable for the preparation of polyfluorinated alcohols of formula (I). where R 1 is C1-C 10 -alkyl, which may be unsubstituted or partially or fully fluorinated; R 2 is C1-C 10 -alkyl, which may be unsubstituted or partially or fully fluorinated; R 3 is partially or fully fluorinated C1-C 10 -Alkyl. The process according to the invention is well suited for the preparation of polyfluorinated alcohols of the formula (I) where R 1 is C1-C 10-alkyl which may be partially or fully fluorinated; R 2 is C1-C 10 -alkyl which may be partially or fully fluorinated; R 3 is partially or fully fluorinated C1-C 10 -Alkyl. The process according to the invention is particularly suitable for the preparation of polyfluorinated alcohols of the formula (I) where R 1 is C1-C 10 -alkyl which is fully fluorinated; R 2 is C1-C 10 -alkyl which is fully fluorinated; R 3 is fully fluorinated C1-C 10 -Alkyl. The process according to the invention is best suited for the preparation of polyfluorinated alcohols of the formula (I) where R 1 is selected from the group consisting of CF3, CF2CF3, CF(CF3)2, C(CF3)3or CF2CF2CF3; R 2 is selected from the group consisting of CF3, CF2CF3, CF(CF3)2, C(CF3)3or CF2CF2CF3; R 3is selected from the group consisting of CF3, CF2CF3, CF(CF3)2, C(CF3)3, or CF2CF2CF3. The process according to the invention is most suitable for the preparation of polyfluorinated alcohols: I-1a to I-156a, in which R 3 is CF3and the respective combination of R 1 and R 2 can be found in Table 1; I-1b to I-156b where R 3 is CF2CF3and the respective combination of R 1 and R 2 can be found in Table 1; I-1c to I-156c where R 3 is CF(CF3)2and the respective combination of R 1 and R 2 can be found in Table 1; I-1d to I-156d where R 3 is C(CF3)3and the respective combination of R 1 and R 2 can be found in Table 1; I-1e to I-156e where R 3 is CF2CF2CF3.and the respective combination of R 1 and R 2 can be found in Table 1; Table 1 The above-mentioned compounds can be used to produce electrolytes for battery cells. The process according to the invention is illustrated below by examples, although it is not limited to these: Example 1: Production of C(CF3)3OH without the use of a catalyst starting from hexafluoroacetone The preparation of the above-mentioned tertriary alcohol can be carried out according to the following methods: Method 1: Reaction in crimp-cap vessels. An oven-dried 20 ml glass vessel with a magnetic stirrer bar was filled in a glove box with a mixture of pre-dried potassium trifluoroacetate (0.36 mmol, 1.00 equiv.), 30 µl of 1,4-difluorobenzene as an internal NMR standard (0.29 mmol), and 1 ml of dimethylformamide (DMF) and sealed with a septum cap. The septum cap in the present method is perforated. Excess hexafluoroacetone (approx. 1.1 mmol, approx. 3.00 equiv.) was condensed into the vessel, and the reaction was stirred for 16 hours at 140 °C. The reaction mixture was then acidified with HCl, and a sample was taken using 19F-NMR. The yield of the desired product is 78%. Method 2: Reaction in pressure-resistant crimp-cap vessels. An oven-dried 20 ml glass vessel with a magnetic stirrer bar was filled in a glove box with a mixture of pre-dried potassium trifluoroacetate (0.36 mmol, 1.00 equiv.), 30 µl of 1,4-difluorobenzene as an internal NMR standard (0.29 mmol), and 1 ml of dimethylformamide (DMF) and sealed with a septum cap. The septum cap in the present method is not perforated. Excess hexafluoroacetone (approx. 1.1 mmol, approx. 3.00 equiv.) was condensed into the vessel, and the reaction was stirred for 16 hours at 140 °C. The reaction mixture was then acidified with HCl, and a sample was taken using 19F-NMR. The yield of the desired product is 73%. Method 3 Reaction in crimp-cap vessels, dosing of the substrate via gas burette. An oven-dried 20 ml glass vessel with a magnetic stirrer bar was filled in the glove box with a mixture of pre-dried potassium trifluoroacetate (0.6 mmol, 1.00 equiv.), 100 µl of 1,4-difluorobenzene as an internal NMR standard (0.963 mmol), and 1 ml of dimethylformamide (DMF) and sealed with a septum cap. The septum cap in the present method is not perforated. Excess hexafluoroacetone was measured via a gas burette, condensed into the vessel, and the reaction stirred for 16 hours at 140 °C. The reaction mixture was then acidified with HCl, and a sample was taken using 19F-NMR analysis. The yield of the desired product is 76%. Method 4: Autoclave An autoclave (~70 ml volume) was filled with potassium trifluoroacetate (2.08 mmol, 1.00 equiv.) and 3.5 ml of dimethylformamide in the glove box and equipped with a magnetic stirrer bar. After sealing, excess hexafluoroacetone outside the glove box – measured via a gas burette – was condensed into the autoclave and sealed. The reaction was stirred for 16 hours at 140 °C. After the reaction was complete, excess HFA was removed, the autoclave opened, and rinsed. The autoclave was then acidified with HCl, and 100 µl of 1,4-difluorobenzene was added as an internal standard, and a sample was analyzed using 19F-NMR spectroscopy was used. The method was repeated several times at different reaction pressures, and the following yields were achieved: At a reaction pressure of 0.7 bar, the yield was 58%. At a reaction pressure of 1.1 bar, the yield was 57%. At a reaction pressure of 3.0 bar, the yield was 71%. At a reaction pressure of 6.5 bar, the yield was 57%. Example 2: Production of C(CF3)3OH with a catalyst starting from hexafluoroacetone The preparation of the above-mentioned tertriary alcohol can be carried out according to the following methods: Method 1: Reaction in a Crimp Cap Vessel An oven-dried 20 ml glass vessel with a magnetic stirrer bar was filled in a glove box with a mixture of pre-dried potassium trifluoroacetate (0.36 mmol, 1.00 equiv.), iron(III) chloride, 30 µl of 1,4-difluorobenzene as an internal NMR standard (0.29 mmol), and 1 ml of dimethylformamide (DMF) and sealed with a septum cap. The septum cap in the present method is perforated. Excess hexafluoroacetone (approx. 1.1 mmol, approx. 3.00 equiv.) was condensed into the vessel, and the reaction was stirred for 16 hours at 140 °C. The reaction mixture was then acidified with HCl, and a sample was taken using 19F-NMR spectroscopy was used. The method was repeated several times with different amounts of FeCl3, and the following yields were achieved: At 10 mol% FeCl3, the yield was 95%. At 20 mol% FeCl3, the yield was 99%. At 25 mol% FeCl3, the yield was 95%. At 30 mol% FeCl3, the yield was 96%. At 40 mol% FeCl3, the yield was 86%. Method 2: Reaction in a Crimp-Cap Vessel, 0.6 mmol An oven-dried 20 ml glass vessel with a magnetic stirrer bar was placed in a glove box and filled with a mixture of pre-dried potassium trifluoroacetate (0.6 mmol, 1.00 equiv.), iron(III) chloride, 30 µl of 1,4-difluorobenzene as an internal NMR standard (0.29 mmol), and 1 ml of dimethylformamide (DMF). The reaction was sealed with a septum cap. The septum cap in this method is not perforated. Excess hexafluoroacetone (approx. 1.1 mmol, approx. 3.00 equiv.)) was condensed into the vessel and the reaction stirred for 16 hours at 140 °C. The reaction mixture was then acidified with HCl and a sample was taken using 19F-NMR spectroscopy was used. The method was repeated several times with different amounts of FeCl3, and the following yields were achieved: At 10 mol% FeCl3, the yield was 62%. At 20 mol% FeCl3, the yield was 75%. At 30 mol% FeCl3, the yield was 67%. At 40 mol% FeCl3, the yield was 79%. Method 3: Dosing of the substrate using a gas burette. An oven-dried 20 ml glass vial with a magnetic stirrer bar was filled in a glove box with a mixture of pre-dried potassium trifluoroacetate (0.6 mmol, 1.00 equiv.), catalyst, 100 µl of 1,4-difluorobenzene as an internal NMR standard (0.963 mmol), and 1 ml of dimethylformamide (DMF). The mixture was sealed with a septum cap. The septum cap used in this method is not perforated. Excess hexafluoroacetone was measured using a gas burette, condensed into the vial, and the reaction was stirred for 16 hours at 140 °C.The reaction mixture was then acidified with HCl and a sample was taken using. 19 F-NMR analysis was performed. The method was repeated several times with different catalysts, and the following yields were achieved: At 10 mol% K2CO3, the yield was 77%. At 10 mol% KOtBu, the yield was 56%. Example 3: Preparation of PhC(CF3)2OH with a catalyst starting from trifluoroacetophenone OHO CF3P h CF 3 Ph CF3An oven-dried 20 mL glass vial with a magnetic stirrer bar was treated in a glove box with a mixture of trifluoroacetophenone (0.30 mmol, 1.00 equiv.) with potassium trifluoroacetate (0.36 mmol, 1.20 equiv.) as catalyst, and 30 µL of 1,4-difluorobenzene as an internal NMR standard (0.29 mmol, 0.963 equiv.) in 1 mL of dimethylformamide for 12 h at 140 °C and then acidified with HCl. The method was repeated several times with different catalysts, and the following yields were achieved: With a quantity of 30 mol% FeCl2, the yield was 53%. With a quantity of 30 mol% FeBr3, the yield was 63%. With a quantity of 30 mol% GaBr3, the yield was 63%. The method was repeated several times with different amounts of FeCl3, and the following yields were achieved: At 15 mol% FeCl3, the yield was 45%. At 30 mol% FeCl3, the yield was 81%. At 45 mol% FeCl3, the yield was 85%.At 60 mol% FeCl3, the yield is 73%. At 75 mol% FeCl3, the yield is 71%. The method was performed with 30 mol% FeCl3 using different ligands: At 30 mol% FeCl3 and BPy as the ligand, the yield is 77%. At 30 mol% FeCl3 and TMEDA as the ligand, the yield is 89%. At 30 mol% FeCl3 and [2.2.2]cryptand as the ligand, the yield is 42%.

Claims

Claims 1. Process for the preparation of polyfluorinated alcohols of formula (I) where R 1 is selected from the group consisting of: C1-C 10 -Alkyl, C3-C 10 -Cycloalkyl, C6- C 14 -aryl and C5-C 14 -Heteroaryl, where the substituents mentioned may be unsubstituted or partially or fully fluorinated; R 2 is selected from the group consisting of: C1-C 10 -Alkyl, C3-C 10 -Cycloalkyl, C6- C 14 -aryl and C5-C 14 -Heteroaryl, where the substituents mentioned may be unsubstituted or partially or fully fluorinated; R 3 is partially or fully fluorinated C1-C10 alkyl; starting from a ketone of formula (II) where R 1 is selected from the group consisting of: C1-C 10 -Alkyl, C3-C 10 -Cycloalkyl, C6- C 14 -aryl and C5-C 14-Heteroaryl, where said substituents may be unsubstituted or partially or fully fluorinated; R 2 is selected from the group consisting of: C1-C 10 -Alkyl, C3-C 10 -Cycloalkyl, C6- C 14 -aryl and C 5- C 14 -Heteroaryl, where the substituents mentioned may be unsubstituted or partially or fully fluorinated; and a carboxylic acid salt of the formula (III) (R 3 COO)xY, where R 3 is partially or fully fluorinated C1-C10 alkyl; Y is a cation selected from the group comprising: K, Li, Na, Cs, Mg, Ca, Fe, Cu, Ag, Zn; x is 1 or 2; characterized in that the R 3group of the carboxylic acid salt is transferred to the carbonyl carbon of the ketone of the formula (II) with release of CO2.

2. Process according to claim 1, characterized in that the reaction is carried out in a solvent selected from the group comprising: DMF, NMP, DMAc, DMSO.

3. Process according to claim 2, characterized in that the solvent is DMF.

4. Process according to one of claims 1 to 3, characterized in that the reaction temperature is between 100°C and 150°C.

5. Process according to one of claims 1 to 4, characterized in that the reaction temperature is between 135°C and 145°C.

6. Process according to one of claims 1 to 5, characterized in that the reaction is carried out in the absence of moisture.

7. Process according to one of claims 1 to 6, characterized in that the reaction is carried out in the presence of a catalyst.

8. The process according to claim 7, characterized in that the catalyst is an iron catalyst.

9. The process according to claim 7 or 8, characterized in that the iron catalyst is selected from the group consisting of: FeCl2, FeCl3, FeBr3, FeF3, FeTFA3, FeSO4, Fe2(SO4)3.

10. The process according to any one of claims 7 to 9, characterized in that the amount of iron catalyst is 10 to 75 mol%, preferably 15 to 45 mol%.

11. The process according to any one of claims 1 to 10, characterized in that R 1 C1-C10-alkyl, which may be unsubstituted or partially or fully fluorinated.

12. A process according to any one of claims 1 to 11, characterized in that R 3 C1-C10-alkyl, which may be unsubstituted or partially or fully fluorinated.

13. A process according to any one of claims 1 to 12, characterized in that R 1is selected from the group consisting of: CH3, CH2F, CHF2, CF3, CH2CH3, CH2CH2F, CH2CHF2, CH2CF3, CF2CF3, CF(CF3)2, C(CF3)3, CF2CF2CF3.

14. The method according to any one of claims 1 to 13, characterized in that R 2 is selected from the group consisting of: CH3, CH2F, CHF2, CF3, CH2CH3, CH2CH2F, CH2CHF2, CH2CF3, CF2CF3, CF(CF3)2, C(CF3)3, CF2CF2CF3.

15. The method according to any one of claims 1 to 14, characterized in that R 3 is selected from the group consisting of: CF3, CF2CF3, CF(CF3)2, C(CF3)3, CF2CF2CF3.

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