METHOD FOR PRODUCING POLYFLUORINATED TERTIARY ALCOHOLS

Abstract

A method is disclosed for producing polyfluorinated alcohols of formula (I)

##STR00001##

starting from a ketone of formula (II),

##STR00002##

and a carboxylic acid salt of formula (III) (R.sup.3COO).sub.xY. The substituents R.sup.1 and R.sup.2 can be selected from C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.6-C.sub.14 aryl, and C.sub.5-C.sub.14 heteroaryl. The substituents may be unsubstituted or partially or completely fluorinated. R.sup.3 is a partially or completely fluorinated C.sub.1-C.sub.10 alkyl, Y is a cation of K, Li, Na, Cs, Mg, Ca, Fe, Cu, Ag, and Zn, and x is 1 or 2. In the method, the R.sup.3 group of the carboxylic acid salt is transferred to the carbonyl carbon of the ketone of formula (II) with the release of CO.sub.2.

Claims

1. A method for producing polyfluorinated alcohols of formula (I) ##STR00015## wherein R.sup.1 is selected from the group consisting of C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.6-C.sub.14 aryl, and C.sub.5-C.sub.14 heteroaryl, wherein the substituents may be unsubstituted or partially or completely fluorinated; R.sup.2 is selected from the group consisting of C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.6-C.sub.14 aryl, and C.sub.5-C.sub.14 heteroaryl, wherein the substituents may be unsubstituted or partially or completely fluorinated; R.sup.3 is a partially or completely fluorinated C.sub.1-C.sub.10 alkyl; starting from a ketone of formula (II), ##STR00016## wherein: R.sup.1 is selected from the group consisting of C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.6-C.sub.14 aryl, and C.sub.5-C.sub.14 heteroaryl, wherein the substituents may be unsubstituted or partially or completely fluorinated; R.sup.2 is selected from the group consisting of C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.6-C.sub.14 aryl, and C.sub.5-C.sub.14 heteroaryl, wherein the substituents may be unsubstituted or partially or completely fluorinated; and a carboxylic acid salt of formula (III) (R.sup.3COO).sub.xY, wherein R.sup.3 is a partially or completely fluorinated C.sub.1-C.sub.10 alkyl; Y is a cation selected from the group consisting of K, Li, Na, Cs, Mg, Ca, Fe, Cu, Ag, and Zn; x is 1 or 2; and the R.sup.3 group of the carboxylic acid salt is transferred to the carbonyl carbon of the ketone of formula (II) with the release of CO.sub.2.

2. The method according to claim 1, wherein the reaction is carried out in a solvent selected from the group consisting of DMF, NMP, DMAc, and DMSO.

3. The method according to claim 2, wherein DMF is the solvent.

4. The method according to claim 1, wherein the reaction temperature is in the range of 100 C. to 150 C.

5. The method according to claim 1, wherein the reaction temperature is in the range of 135 C. to 145 C.

6. The method according to claim 1, wherein the reaction is carried out under anhydrous conditions.

7. The method according to claim 1, wherein the reaction is carried out in the presence of a catalyst.

8. The method according to claim 7, wherein the catalyst is an iron catalyst.

9. The method according to claim 7, wherein the iron catalyst is selected from the group consisting of FeCl.sub.2, FeCl.sub.3, FeBr.sub.3, FeF.sub.3, FeTFA.sub.3, FeSO.sub.4, and Fe.sub.2(SO.sub.4).sub.3.

10. The method according to claim 9, wherein the quantity of iron catalyst ranges from 10 to 75 mol %, and preferably from 15 to 45 mol %.

11. The method according to claim 1, wherein R.sup.1 is a C.sub.1-C.sub.10 alkyl, which may be unsubstituted or partially or completely fluorinated.

12. The method according to claim 1, wherein R.sup.3 is a C.sub.1-C.sub.10 alkyl, which may be unsubstituted or partially or completely fluorinated.

13. The method according to claim 1, wherein R.sup.1 is selected from the group consisting of CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, CH.sub.2CH.sub.3, CH.sub.2CH.sub.2F, CH.sub.2CHF.sub.2, CH.sub.2CF.sub.3, CF.sub.2CF.sub.3, CF(CF.sub.3).sub.2, C(CF.sub.3).sub.3, and CF.sub.2CF.sub.2CF.sub.3.

14. The method according to claim 1, wherein R.sup.2 is selected from the group consisting of CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, CH.sub.2CH.sub.3, CH.sub.2CH.sub.2F, CH.sub.2CHF.sub.2, CH.sub.2CF.sub.3, CF.sub.2CF.sub.3, CF(CF.sub.3).sub.2, C(CF.sub.3).sub.3, and CF.sub.2CF.sub.2CF.sub.3.

15. The method according to claim 1, wherein R.sup.3 is selected from the group consisting of CF.sub.3, CF.sub.2CF.sub.3, CF(CF.sub.3).sub.2, C(CF.sub.3).sub.3, and CF.sub.2CF.sub.2CF.sub.3.

Description

EXAMPLE 1: PRODUCTION OF C(CF.SUB.3.).SUB.3.OH WITHOUT USING A CATALYST STARTING FROM HEXAFLUOROACETONE

##STR00012##

[0087] The production of the aforementioned tertiary alcohol can be carried out according to the following methods:

Method 1: Reaction Process in Crimped Cap Vials

[0088] A kiln-dried 20 ml glass vial with a magnetic stirrer core was filled inside the glovebox with a mixture of pre-dried potassium trifluoroacetate (0.36 mmol, 1.00 equiv.), 30 l of 1,4-difluorobenzene as an internal NMR standard (0.29 mmol), and 1 ml of dimethylformamide (DMF) before being sealed with a septum cap. In this method, the septum cap is perforated. The excess amount of hexafluoroacetone (approx. 1.1 mmol, approx. 3.00 equiv.) is condensed in the vial, and the reaction is stirred for 16 hours at 140 C. The reaction mixture is then acidified with HCl, and a sample is analyzed using .sup.19F NMR spectroscopy.

[0089] The yield of the desired product is 78%.

Method 2: Reaction Process in Pressure-Resistant Crimped Cap Vials

[0090] A kiln-dried 20 ml glass vial with a magnetic stirrer core was filled inside the glovebox with a mixture of pre-dried potassium trifluoroacetate (0.36 mmol, 1.00 equiv.), 30 l of 1,4-difluorobenzene as an internal NMR standard (0.29 mmol), and 1 ml of dimethylformamide (DMF) before being sealed with a septum cap. In this method, the septum cap is not perforated. The excess amount of hexafluoroacetone (approx. 1.1 mmol, approx. 3.00 equiv.) is condensed in the vial, and the reaction is stirred for 16 hours at 140 C. The reaction mixture is then acidified with HCl, and a sample is analyzed using .sup.19F NMR spectroscopy.

[0091] The yield of the desired product is 73%.

Method 3: Reaction Process in Crimped Cap Vials, Dosing of the Substrate Using a Gas Burette

[0092] A kiln-dried 20 ml glass vial with a magnetic stirrer core was filled inside the glovebox with a mixture of pre-dried potassium trifluoroacetate (0.6 mmol, 1.00 equiv.), 100 l of 1,4-difluorobenzene as an internal NMR standard (0.963 mmol), and 1 ml of dimethylformamide (DMF) before being sealed with a septum cap. In this method, the septum cap is not perforated. The excess amount of hexafluoroacetone is measured using a gas burette, condensed in the vial, and the reaction is stirred for 16 hours at 140 C. The reaction mixture is then acidified with HCl, and a sample is analyzed using .sup.19F NMR spectroscopy.

[0093] The yield of the desired product is 76%.

Method 4: Autoclave

[0094] An autoclave (70 ml volume) is loaded in the glovebox with potassium trifluoroacetate (2.08 mmol, 1.00 equiv.) and 3.5 ml of dimethylformamide, and equipped with a magnetic stirrer core. After sealing, the excess amount of hexafluoroacetone outside the gloveboxmeasured using a gas buretteis condensed in the autoclaves and sealed. The reaction is stirred for 16 hours at 140 C. After the reaction is complete, the excess HFA is removed, and the autoclave is opened and flushed. The mixture is then acidified with HCl, and 100 l of 1,4-difluorobenzene is added as an internal standard. A sample is analyzed using .sup.19F NMR spectroscopy.

[0095] The method was carried out multiple times using different reaction pressures, and the following yields were achieved:

[0096] The yield is 58% at a reaction pressure of 0.7 bar.

[0097] The yield is 57% at a reaction pressure of 1.1 bar.

[0098] The yield is 71% at a reaction pressure of 3.0 bar.

[0099] The yield is 57% at a reaction pressure of 6.5 bar.

EXAMPLE 2: PRODUCTION OF C(CF.SUB.3.).SUB.3.OH USING A CATALYST STARTING FROM HEXAFLUOROACETONE

##STR00013##

[0100] The production of the aforementioned tertiary alcohol can be carried out according to the following methods:

Method 1: Reaction Process in a Crimped Cap Vial

[0101] A kiln-dried 20 ml glass vial with a magnetic stirrer core was filled inside the glovebox with a mixture of pre-dried potassium trifluoroacetate (0.36 mmol, 1.00 equiv.), iron (III) chloride, 30 l of 1,4-difluorobenzene as an internal NMR standard (0.29 mmol), and 1 ml of dimethylformamide (DMF) before being sealed with a septum cap. In this method, the septum cap is perforated. The excess amount of hexafluoroacetone (approx. 1.1 mmol, approx. 3.00 equiv.) is condensed in the vial, and the reaction is stirred for 16 hours at 140 C. The reaction mixture is then acidified with HCl, and a sample is analyzed using .sup.19F NMR spectroscopy.

[0102] The method was carried out multiple times using different quantities of FeCl.sub.3, and the following yields were achieved:

[0103] The yield is 95% at a quantity of 10 mol % FeCl.sub.3.

[0104] The yield is 99% at a quantity of 20 mol % FeCl.sub.3.

[0105] The yield is 95% at a quantity of 25 mol % FeCl.sub.3.

[0106] The yield is 96% at a quantity of 30 mol % FeCl.sub.3.

[0107] The yield is 86% at a quantity of 40 mol % FeCl.sub.3.

Method 2: Reaction Process in a Crimped Cap Vial, 0.6 Mmol

[0108] A kiln-dried 20 ml glass vial with a magnetic stirrer core was filled inside the glovebox with a mixture of pre-dried potassium trifluoroacetate (0.6 mmol, 1.00 equiv.), iron (III) chloride, 30 l of 1,4-difluorobenzene as an internal NMR standard (0.29 mmol), and 1 ml of dimethylformamide (DMF) before being sealed with a septum cap. In this method, the septum cap is not perforated. The excess amount of hexafluoroacetone (approx. 1.1 mmol, approx. 3.00 equiv.) is condensed in the vial, and the reaction is stirred for 16 hours at 140 C. The reaction mixture is then acidified with HCl, and a sample is analyzed using .sup.19F NMR spectroscopy.

[0109] The method was carried out multiple times using different quantities of FeCl.sub.3, and the following yields were achieved:

[0110] The yield is 62% at a quantity of 10 mol % FeCl.sub.3.

[0111] The yield is 75% at a quantity of 20 mol % FeCl.sub.3.

[0112] The yield is 67% at a quantity of 30 mol % FeCl.sub.3.

[0113] The yield is 79% at a quantity of 40 mol % FeCl.sub.3.

Method 3: Dosing of the Substrate Using a Gas Burette

[0114] A kiln-dried 20 ml glass vial with a magnetic stirrer core was filled in the glovebox with a mixture of pre-dried potassium trifluoroacetate (0.6 mmol, 1.00 equiv.), catalyst, 100 l of 1,4-difluorobenzene as an internal NMR standard (0.963 mmol), and 1 ml of dimethylformamide (DMF) and sealed with a septum cap. In this method, the septum cap is not perforated. The excess amount of hexafluoroacetone is measured using a gas burette, condensed in the vial, and the reaction is stirred for 16 hours at 140 C. The reaction mixture is then acidified with HCl, and a sample is analyzed using .sup.19F NMR spectroscopy.

[0115] The method was carried out multiple times using different catalysts, and the following yields were achieved:

[0116] The yield is 77% at a quantity of 10 mol % K.sub.2CO.sub.3.

[0117] The yield is 56% at a quantity of 10 mol % KOtBu.

EXAMPLE 3: PRODUCTION OF PHC(CF.SUB.3.).SUB.2.OH USING A CATALYST STARTING FROM TRIFLUOROACETOPHENONE

##STR00014##

[0118] A kiln-dried 20 ml glass vial with a magnetic stirrer core was stirred in the glovebox with a mixture of trifluoroacetophenone (0.30 mmol, 1.00 equiv.) with potassium trifluoroacetate (0.36 mmol, 1.20 equiv.), catalyst, and 30 l of 1,4-difluorobenzene as an internal NMR standard (0.29 mmol, 0.963 equiv.) for 12 hours at 140 C. in 1 ml of dimethylformamide and then acidified with HCl.

[0119] The method was carried out multiple times using different catalysts, and the following yields were achieved:

[0120] The yield is 53% at a quantity of 30 mol % FeCl.sub.2.

[0121] The yield is 63% at a quantity of 30 mol % FeBr.sub.3.

[0122] The yield is 63% at a quantity of 30 mol % GaBr.sub.3.

[0123] The method was carried out multiple times using different quantities of FeCl.sub.3, and the following yields were achieved:

[0124] The yield is 45% at a quantity of 15 mol % FeCl.sub.3.

[0125] The yield is 81% at a quantity of 30 mol % FeCl.sub.3.

[0126] The yield is 85% at a quantity of 45 mol % FeCl.sub.3.

[0127] The yield is 73% at a quantity of 60 mol % FeCl.sub.3.

[0128] The yield is 71% at a quantity of 75 mol % FeCl.sub.3.

[0129] The method was carried out with 30 mol % of FeCl.sub.3, whereby different ligands were used:

[0130] The yield is 77% at a quantity of 30 mol % FeCl.sub.3 and bpy as a ligand.

[0131] The yield is 89% at a quantity of 30 mol % FeCl.sub.3 and TMEDA as a ligand.

[0132] The yield is 42% at a quantity of 30 mol % FeCl.sub.3 and [2.2.2]cryptand as a ligand.

[0133] While exemplary embodiments have been disclosed hereinabove, the present invention is not limited to the disclosed embodiments. Instead, this application is intended to cover any variations, uses, or adaptations of this disclosure using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains and which fall within the limits of the appended claims.