MXPA00006888A - Process for trifluoroacetate esters and thioesters - Google Patents

Abstract

The present invention provides a process for preparing esters or thioesters of trifluoroacetic acid from trifluoroacetyl chloride and an alcohol or a thiol with the ester or thioester being present as the solvent. Esters and thioesters of trifluoroacetic acid are fine chemical intermediates which can be used in the manufacture of pharmaceuticals, agricultural chemicals, liquid crystals, dyes and industrial chemicals. Trifluoroacetate esters and thioesters can also be used as solvents in the manufacture of other fine chemicals, pharmaceuticals, agricultural chemicals, liquid crystals, industrial chemicals and dyes.

Description

PROCESS FOR PREPARING ESTERES AND TIOESTERS OF TRIFLUOROACETATE The present invention relates to a process for preparing esters or thioesters of trifluoroacetic acid, from trifluoroacetyl chloride and an alcohol or a thiol. The esters or thioesters of trifluoroacetic acid are fine chemical intermediates, which can be used in the manufacture of pharmaceuticals, agricultural chemicals, liquid crystals, dyes and industrial chemicals. The trifluoroacetate esters can also be used as solvents in the manufacture of other fine chemicals, pharmaceuticals, agricultural chemicals, liquid chemicals, dyes and industrial chemicals. There are several processes, previously described, that can be used to produce the trifluoroacetate esters. US Patent 4,916,256 teaches vapor phase reactions which must employ a substantial stoichiometric excess of the toxic and relatively expensive trifluoroacetyl chloride to react with an alcohol and produce a trifluoroacetate ester. US Patent 5,405,991 teaches the reaction of an acid chloride with an alcohol, to form a trifluoroacetate ester, but with the need to have a catalyst present, which is an alkali metal salt or an onium salt of the carboxylic acid , which corresponds to the starting material of the acid chloride. US Patent 4,701,551 discloses the reaction of trifluoroacetic acid with an alcohol, to form trifluoroacetate esters, but liquid HF is required as a catalyst. US Patent 4,730,082 discloses a multi-step process for producing methyl trifluoroacetate from trifluoroacetic acid and methanol; a catalytic amount of a strong acid is required in one of the stages. WO 96/26185 A1 discloses the formation of thioesters by the reaction of trifluoroacetic anhydride with trolls, in the presence of pyridine and 4-dimethylaminopyridine (DMAP). None of these references, individually or collectively? teach or suggest the process of the present invention. We have found in the process of the present invention that the product trifluoroacetate ester or the thioester itself is an excellent solvent for the reaction. This reaction is carried out at a relatively low temperature, from room temperature to something below the boiling point of trifluoroacetyl chloride. No other catalyst or reagent is required. The hydrogen chloride, which is a by-product of the reaction, is removed at the end of the reaction, by heating the reaction mixture to room temperature, with stirring. The product of ester or thioester, obtained by this process is already of high purity, but this purity can be increased to more than 99% by distillation. The advantages resulting from the process of the present invention include: (i) the ease of purification of the desired ester or thioester product, since no other solvent is present, which should be removed using distillation or other techniques; (ü) The solubility of the trifluoroacetyl chloride in the desired ester or thioester is high, which results in concentrated reaction mixtures and higher kilograms of the ester or thioester product per reactor. (iii) the high solubility of the trifluoroacetyl chloride in the desired ester or thioester results in a safe process, since the process control to prevent the toxic trifluoroacetyl chloride from boiling-off (the boiling point is -27) ° C) is not just dependent on the cooling of the reactor; and (iv) no other reagent or catalyst is required for the desired formation of the ester or thioester. Therefore, this invention provides a process for the preparation of a trifluoroacetate compound, of the formula (I), from the trifluoroacetyl chloride and a compound of the formula (II): 0 O 0 F3C XR (I) F3C and Cl + RXH F3C XR + HCl (II) (I) wherein: R is alkyl or alkyl substituted with alkoxy or haloalkoxy, and X is an oxygen atom c of sulfur, which comprises the steps of: (i) reacting the trifluoroacetyl chloride with a compound of the formula (II), in the initial presence of an amount of the trifluoroacetate compound, of the formula (I), at a temperature of 20 ° C or less, to produce the trifluoroacetate compound, of the formula (I), and (ii) degassing the mixture, at room temperature, to remove the byproduct of HCl and any residual trifluoroacetyl chloride. As used herein, the term "alkyl" refers to straight or branched aliphatic hydrocarbon chains, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, secondary butyl, tertiary butyl, isoamyl and n- hexyl. When the alkyl group has an asymmetric carbon atom, the term alkyl also includes its enantiomeric form or a mixture thereof. The term "alkoxy" refers to a straight or branched aliphatic hydrocarbon chain attached to an oxygen atom, for example, methoxy, ethoxy, isopropoxy, n-butoxy and the like. The term "haloalkoxy" refers to an alkoxy group substituted with one or more halogen groups, for example, chloromethoxy, chlorodisulfuromethoxy, trifluoroethoxy, perfluoroethoxy, 2-bromoethoxy and the like. The term "halogen" refers to a fluorine, chlorine or bromine atom. In a preferred process of this invention, R is alkyl (C _-C 6) or alkyl (C _-C 6) substituted with alkoxy (C _-CU). In a more preferred process of this invention, R is alkyl (C.-C_). In a still more preferred process of the invention, R is methyl, ethyl or isopropyl. In an especially preferred process of the invention, R is ethyl. More specifically, the process for the preparation of esters or thioesters of trifluoroacetic acid of this invention involves reacting the trifluoroacetyl chloride with an alcohol or a thiol, at a low temperature, in the presence of the desired product of the formula (I) as a solvent, in a first stage and, at the end of the desired reaction, degassing the mixture at room temperature to remove the byproduct of hydrogen chloride and any residual trifluoroacetyl chloride. These gases are usually treated by passing them through a scrubber or, in the case of trifluoroacetyl chloride, the gases can be recycled, for example, by capturing them in a scrubber filled with the ester or thioester of trifluoroacetic acid, which will be used as solvent in the subsequent reaction or by condensation. The ester or thioester of trifluoroacetic acid produced in this reaction is already of high purity, but the purity can be increased to more than 99% by distillation. The alcohol (ROH) or thiol (RSH) can be selected from alcohols or thiols having 1 to -fia-carbon atoms. The alkyl groups R can be straight-chain or branched. The group R can be substituted with alkoxy groups and with haloalkoxy groups. The reaction stage (i) is carried out at a temperature which is close to the boiling point of the trifluoroacetyl chloride. Typical reaction temperatures range from about -40 ° C to 20 ° C, preferably from -30 ° C to 0 ° C, and more preferably from about -25 ° C to -15 ° C.

The process is carried out as follows: the sec reactor is charged with recycled material (recycled material, usually from the previous reaction batch) of the ester or thioeste of the desired product and cooled to room temperature. The first reagent, which can be either the trifluoroacetyl chloride or the compound of the formula II), adds. The second reagent is added to a regimen to maintain the internal temperature of the reactor at the desired temperature. After the reaction is complete, the mixture is brought to room temperature to degas it to remove the hydrogen chloride and any residual trifluoroacetyl chloride. The reactor now contains the desired ester or thioester of trifluoroacetic acid. The purity can be further improved by distillation at atmospheric pressure or under reduced pressure. The order of addition is variable. Preferably, the trifluoroacetyl chloride is dissolved in the recycled material of the trifluoroacetate ester or thioester and then treated with the alcohol or thiol, as appropriate. However, the reaction can also be carried out by dissolving the alcohol or thiol in the recirculated material of the trifluoroacetate thioester ester and then adding the trifluoroacetyl chloride to that mixture. The charges of the trifluoroacetyl chloride and compound of the formula (II) are usually made in a molar ratio close to 1: 1. Any reagent can be used in a slight excess, depending on costs and convenience. Thus, the molar ratio of the compound of the formula (II) to the trifluoroacetyl chloride is conveniently in the range of 1.10 to 0.90, preferably in the range of 1.05 to 0.98. For example, the compound of the formula (II) can be used in excess in a molar ratio of 1.01 to 1.10. More convenient is the use of a lower excess of the compound of the formula (II), at a molar ratio of 1.01 to 1.02, since the residual compound of the formula (II) can be easily removed during the distillation, when used in a smaller excess. Alternatively, the trifluoroacetyl chloride may be used in a slight excess (ie, the molar ratio of the compound of the formula (II) to the trifluoroacetyl chloride is 0.99 to 0.90) and removed from the product ester or thioester during degassing. If a larger excess is used, the excess trifluoroacetyl chloride may be either recycled by condensation and returned to the next batch, or captured in a scrubber loaded with the trifluoroacetate ester or thioester, to be used as the recycled material in a Subsequent batch. The molar ratio of the desired trifluoroacetate ester or thioester, used as the solvent, to the amount of the trifluoroacetyl chloride, can vary quite widely. A molar ratio of about 0.5 to 2 is a preferred range. The process is usually done as a reaction in batches, but can be done as a continuous process. It is also possible to carry out the reaction under a slight pressure of the trifluoroacetyl chloride, preferably not higher than 3.5 kg / cm2. The reaction under pressure can be carried out at the upper end of the described temperature range, without losing reagents and products in the scrubber. Although other solvents, such as aromatics, for example toluene, or ethers, esters or alkanes, can be used for this process, instead of the desired trifluoroacetate ester or thioester, the solubility of trifluoroacetyl chloride in these solvents, at the Reaction temperatures tends to be lower, resulting in decreased productivity. Additionally, the solvents will then be separated from the ester or thioester product, in order to supply a product of high purity. The following examples and experimental procedures are provided for additional guidance to the practitioner.

Example 1: Preparation of Ethyl Trifluoroacetate A recycle material of 187 g of ethyl trifluoroacetate was cooled to -19 ° C. To this was added 199 g of the trifluoroacetyl chloride and the mixture was maintained at -19 ° C to -25 ° C. Then 55.8 of ethanol were added in 60 minutes, followed by an additional charge of 14 g of ethanol in 45 minutes. The mixture was then allowed to warm to room temperature, with stirring and using a scrubber filled with a 10% aqueous solution of sodium hydroxide. The resultant 396 g of ethyl trifluoroacetate were transferred to a distiller and distilled at atmospheric pressure to provide 360 of ethyl trifluoroacetate, with more than 99% strength.

Example 2: Preparation of Ethyl Trifluoroacetate A recycle material of 237 g of ethyl trifluoroacetate was cooled to -19 ° C. To this, 132.5 g of trifluoroacetyl chloride were added and the mixture was kept at -19 ° C to -25 ° C. Then 37 g of ethanol were added in 60 minutes, followed by an additional charge of 9.5 g of ethanol in 45 minutes. The mixture was then allowed to warm to room temperature, with stirring using a scrubber filled with a 10% aqueous solution of sodium hydroxide. The resulting ethyl trifluoroacetate was transferred to a distiller and distilled at atmospheric pressure to provide 128 g of ethyl trifluoroacetate, with purity greater than 99%.

Example 3: Preparation of Isopropyl Trifluoroacetate A 180g recycled material of isopropyl trifluoroacetate was cooled to -19 ° C. To this 132.5 g of trifluoroacetyl chloride was added and the mixture was kept at -19 ° C to -25 ° C. Then 48.6 g of isopropanol were added in 60 minutes, followed by an additional charge of 12.1 g of isopropanol in 45 minutes. The mixture was then allowed to warm to room temperature, with stirring and using a scrubber filled with a 10% aqueous solution of sodium hydroxide. The resulting isopropyl trifluoroacetate weighed 282.6 g and had a purity greater than 97%.

Example 4: Preparation of Ethyl Trifluoroacetate A recycle material of 237 g of ethyl trifluoroacetate was cooled to -30 ° C. To this 132.5 g of trifluoroacetyl chloride was added and the mixture was kept at -30. Then 37 g of ethanol were added in 60 minutes, followed by an additional charge of 9.5 g of ethanol in 45 minutes. The mixture was then allowed to warm to room temperature, with stirring and using a scrubber filled with a 10% aqueous solution of sodium hydroxide. The resultant 379 g of ethyl trifluoroacetate was transferred to a distiller and distilled at atmospheric pressure to provide 360 g of ethyl trifluoroacetate, with purity greater than 99%.

Example 5: Preparation of Methyl Trif * Luoroacetate A recycle material of 128 g of methyl trifluoroacetate was cooled to -20 ° C. To this 132.5 g of trifluoroacetyl chloride were added and the mixture was kept at -20 ° C to -25 ° C. Then 25.9 g of methanol were added in 60 minutes, followed by an additional charge of 6.4 g of methanol in 45 minutes. The mixture was then allowed to warm to room temperature, with stirring and using a scrubber filled with a 10% aqueous solution of sodium hydroxide. The resulting 256 g of methyl trifluoroacetate was transferred to a distiller and distilled at atmospheric pressure to provide 243 g of ethyl trifluoroacetate, with purity greater than 99%.

Example 6: Preparation of Ethyl Trifluoroacetate A reactor was adjusted so that the first scrubber contained 100 g of ethyl trifluoroacetate, and a second scrubber contained a 1% aqueous solution of sodium hydroxide. A recycle material of 187 g of ethyl trifluoroacetate was cooled to -10 ° C. To this was added 199 g of the trifluoroacetyl chloride and the mixture was kept at -10 ° C. Then 55.8 g of ethanol were added in 6 minutes, followed by an additional charge of 14 g of ethanol in 45 minutes. The mixture was then allowed to warm to room temperature, with stirring. The resulting 396 g of ethyl trifluoroacetate was transferred to a distiller and distilled at atmospheric pressure, to provide 338 g of ethyl trifluoroacetate, with purity greater than 99%. Ethyl trifluoroacetate, from the first scrubber, which now contains some of the trifluoroacetyl chloride, was used as the recycle material for the next reaction.

Example 7: Preparation of S-Ethyl Trifluoroacetate A recycling material of 158 g of S-ethyl trifluoroacetate was cooled to -25 ° C. To this was added 199 g of trifluoroacetyl chloride and the mixture was kept at -25 ° C. Then 75.1 g of ethanethiol were added in 60 minutes, followed by an additional charge of 18.8 g of ethanethiol in 45 minutes. The mixture was then allowed to warm to room temperature, with stirring and using a scrubber filled with a 10% aqueous solution of sodium hydroxide. The resultant 391 g of S-ethyl trifluoroacetate was transferred to a distiller and distilled at atmospheric pressure, to provide 375 g of S-ethyl trifluoroacetate, with purity greater than 99%.

Claims (10)

1. CLAIMS 1. A process for the preparation of a trifluoroacetate compound, of the formula (I), from the trifluoroacetyl chloride and a compound of the formula (II): O O or F3C XR (i) F3C Cl + RXH F3C XR + HCl (II) (I) wherein: R is alkyl or alkyl substituted with alkoxy or haloalkoxy, and X is an oxygen or sulfur atom, which comprises the steps of: (i) reacting the trifluoroacetyl chloride with a compound of the formula (II), in the initial presence of an amount of the trifluoroacetate compound, of the formula (I), at a temperature of 20 ° C or less, to produce the trifluoroacetate compound, of the formula (I), and (ii) degassing the mixture, at room temperature, to remove the byproduct of HCl and any residual trifluoroacetyl chloride.
2. 2. The process of claim 1, wherein R is (C _ -C 6) alkyl or (C _ C 6) alkyl substituted with (C 1 -C 4) alkoxy.
3. The process of claim 2, wherein R is alkyl ( C? -C4).
4. 4. The process of claim 3, wherein R is methyl, ethyl or isopropyl.
5. 5. The process of claim 4, wherein R is ethyl.
6. 6. The process of any of the preceding claims, wherein the molar ratio of the compound of the formula (II) to the trifluoroacetyl chloride, in step (i) is from 1.10 to 0.90.
7. 7. The process of claim 6, wherein the molar ratio is from 1.05 to 0.98.
8. 8. The process of claim 7, wherein the molar ratio is from 1.02 to 1.01.
9. 9. The process of claim 6, wherein the molar ratio of the trifluoroacetate compound, of the formula (I), initially present in step (i), to the trifluoroacetyl chloride, is 0.5 to 2.
10. 10. The process of claim 6, wherein step (i) is carried out at a temperature of -30 ° C to 0 ° C.