Title of Invention

"PRODUCTION OF ALKENONES"

Abstract This invention relates to Halogen alkenone ethers can be prepared by the addition of carboxylic acid halides or anhydrides to vinyl ether. The improvement of the present invention is to do this in the present of an "onium" salt of a carboxylic acid which can be regenerated. The product is produced in a high yield. Alternatively, pyridine substituted by one or two C1 -C3 -alkyl groups or other "onium" salts may also be used.
Full Text Production of alkenones Description
The invention relates to a process for the preparation of halogenated alkenone ethers.
Halogenated alkenone ethers, for example 4-ethoxy-1,1,1-trifluoro-3-buten-2-one, are building blocks in chemical synthesis, see for example EP-0 744 400. They can be prepared by reacting an acid chloride with a vinyl ether in the presence of a base, see the above-mentioned European publication. It is an object of the present invention to devise an improved process. This object is achieved by the process of the present invention.
The process according to the invention for the preparation of alkenones of Formula (I)
R1-C(O)-C(H)=C (H)-OR2 (I),
wherein R1 stands for a C1-C4-alkyl group or for a C1-C4alkyl group which is substituted by at least 1 halogen atom, or wherein R1 stands for CF3C(O)CH2, and wherein R2 stands for aryl, substituted aryl, a C1-C4-alkyl group or for a C1-C4-alkyl group which is substituted by at least 1 halogen atom, provides that an acid anhydride or an acid halide of Formula (II)
R1-C(O)X (II),
wherein X stands for R1-C(O)-0 or F, CI or Br and R1 has the above meaning, is reacted with a vinyl ether of Formula (III)
CH=C(H)-OR2 (III),
wherein R2 has the above meaning, in the presence of an "onium" salt of a carboxylic acid, or pyridine which is substituted by 1 or 2 C1-C3-alkyl groups and is optionally chlorinated being used, or an "onium" salt of an inorganic acid being used.
According to one variant of the invention, pyridine substituted by 1, 2 or 3 C1-C3-alkyl groups, preferably picoline, collidine or lutidine (i.e. pyridine which is substituted by 1, 2 or 3 methyl groups, all isomers being usable), preferably 2-picoline, can be used. The pyridine substituted by 1 to 3 C1-C3-alkyl groups may also be substituted in the ring and/or the alkyl group(s) by one or more chlorine atoms. In that case, then chloromethyl, dichloromethyl and trichloromethyl pyridine, in particular the picolines substituted in the 2 position, are preferred. Even if the hydrochloride formed were to be burned or disposed of, this variant is advantageous compared with other amines used in the prior art owing to the higher yield which is achieved (it is however possible, by means of acid treatment, to recycle it, as described further below).
According to a further variant, an "onium" salt of any desired amine of an inorganic acid is used. It was established that adducts of amine and acid, also of inorganic acid, are effective as acid scavengers in the present invention, if the molar ratio of amine to acid is less than 3. Thus for example onium hydrochloride is capable of sequestering 2 mol HCI from the reaction. In this variant onium hydrochloride is preferred.
One particularly preferred variant provides for the use of onium carboxylates of any amines. This process has the advantage of a milder reaction and a higher yield, compared with the process of the prior art, in which a trialkylamine is used as base, and will be explained further below.
R1 preferably stands for methyl, ethyl, n-propyl or i-propyl, or methyl, ethyl, n-propyl or i-propyl substituted by at least 1 fluorine atom. Particularly preferably, R1 stands for methyl, ethyl, or methyl or ethyl substituted by at least 1 fluorine atom. Very particularly preferably, R1 stands for CF3, CF2H, CF2CI, C2F5) C3F7 or CF3C(O)CH2.
R2 may stand for aryl, for example phenyl or phenyl substituted [by] C1-C4-alkyl groups and/or halogen atoms. Preferably R2 is linear or branched C1-C4-alkyl. Very particularly preferably, R2 is methyl, ethyl, n-propyl or i-propyl.
The molar ratio of "onium" salt and acid halide or acid anhydride is advantageously between 0.1:1 and 2:1.
The acid chloride is preferred as the acid halide. The invention will be explained further with reference to this preferred embodiment.
The molar ratio of acid chloride or anhydride and vinyl ether is expediently between 0.9:1 and 1:0.8.
The reaction is performed e.g. at -15 to +80°C, and advantageously at a temperature in the range of 0° to 40°C. It may be exothermic, so the reaction mixture may optionally have to be cooled or the reaction is performed very slowly.
According to a preferred embodiment, a solvent is used in the reaction. This is particularly advantageous when first the vinyl ether and then the anhydride is added to the introduced "onium" salt or amine. For example aliphatic linear or branched hydrocarbons or aliphatic linear or branched halogenated (hydro)carbons, cyclic aliphatic hydrocarbons or esters of trifluoroacetic acid or of pentafluoropropionic acid are suitable. For example optionally halogenated (hydro)carbon compounds with 1 to 8 C atoms are well suited. For example dichloromethane, 1,1,1-trifluoro-2,2,2-trichloroethane, hexane, cyclohexane and ethyl or propyl trifluoroacetate are very well suited.
According to another preferred embodiment, no solvent is used in the reaction between anhydride and vinyl ether. This is particularly possible when first the anhydride and then the vinyl ether is added to the introduced "onium" salt or amine. The advantage is that no solvent needs to be separated off, which of course is advantageous (no recovery expense necessary, lower energy requirement).
Finally, it is also possible to perform the reaction between vinyl ether and acid halide without solvent, but then to add a solvent, e.g. CH2CI2, for better phase separation.
The anion of the carboxylic acid of the "onium" salt preferably has the formula R1C(O)0', wherein R1 has the above meaning. The carboxylic acid in the "onium" salt of the carboxylic acid used is preferably the acid which corresponds to the acid halide used.
The term "onium" stands for cations having a positively-charged nitrogen, for example protonated aromatic nitrogen bases such as pyridinium or protonated alkyl-, dialkyl- or trialkylammonium cations, or for ammonium compounds substituted by cycloalkyl, or cycloaliphatic nitrogen bases such as piperidinium or quaternary ammonium cations.
"Onium" salts are very highly suitable as carboxylic acid salt, "onium" standing for a cation of nitrogen of the formula R'R"RB,R""N+. R', R", R"' and R"", independently of each other, stand for hydrogen, alkyl with 1 to 20 C atoms, aryl or aralkyl. R' and R" or R'" and R"", or R', R" and R"' or R', R", R"' and R"" may also, optionally with inclusion of the nitrogen atom, form saturated or unsaturated ring systems. "Aryl" here stands in particular for phenyl or for phenyl substituted by 1 or more C1-C2 alkyl groups. Outstandingly suitable are salts in which "onium" stands for ammonium, pyridinium or R1R2R3R4N+, wherein R1', R2', R3' and R4' independently of each other stand for hydrogen, alkyl with 1 to 15 C atoms, phenyl or benzyl. Examples of such cations are pyridinium, piperidinium, N-methylpiperidinium, anilinium, benzyltriethylammonium and triethylammonium.
Amines substituted by hydroxyl groups, particularly cycloaliphatic amines, in particular hydroxy-substituted piperidines and N-C1-C4 alkylpiperidines, can also be used. Suitable examples are the piperidines substituted at the C4 atom such as 4-hydroxypiperidine, N-methyl-4-hydroxypiperidine, N-ethyl-4-hydroxypiperidine and N-propyl-4-hydroxypiperidine.
Cations of amines which are disclosed in German Offenlegungsschrift 101 04 663.4 can also be used. These are "onium" cations based on a mono- or bicyclic compound with at least 2 nitrogen atoms, wherein at least 1 nitrogen atom is incorporated into the ring system.
Thus "onium" cations based on monocyclic compounds may be used. These are then saturated or unsaturated 5-ring, 6-ring or 7-ring compounds. At least 1 nitrogen atom is incorporated into the ring. A further nitrogen atom may also be incorporated into the ring system. Alternatively or additionally, the ring may be substituted by one or more amino groups. Dialkylamino groups in which the alkyl groups may be identical or different and comprise 1 to 4 carbon atoms are preferred. The amino group may also represent a saturated ring system, for example a piperidino group. Representatives of monocyclic ring systems which can be used effectively are dialkylaminopyridine, dialkylaminopiperidine and dialkylaminopiperazine.
"Onium" cations of bicyclic compounds may also be used. Here too, 1, 2 or more nitrogen atoms may be integrated in the ring system. The compounds may be substituted by one or more amino groups. Dialkylamino groups, wherein the alkyl groups may be identical or different and comprise 1 to 4 C atoms or together with the nitrogen atom form a saturated ring system, such as for example the piperidinyl group, are again preferred.
It is clear from what has been stated above that in this embodiment at least 2 nitrogen atoms in the usable compounds must have basic properties and, depending on the type of bonds, are bonded to 2 or 3 carbon atoms.
"Onium" salts of carboxylic acid with bicyclic amines, in particular 1,5-diazabicyclo[4.3.0]-non-5-ene (DBN) and 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU) are very particularly preferred). Also the "onium" salts of aromatic amines, particularly those having one, two or three electron-donating groups, such as Ci-C3-alkyl groups, can be readily used, e.g. salts of 2-picoline. Salts of picoline chlorinated in the ring, e.g. in the 4-position and/or the alkyl groups, e.g.
trifluoroacetic acid adducts of 2-chloromethyl, 2-dichloromethyl and 2-trichloromethyl picoline, are liquid and can therefore even act like a solvent.
The "onium" salts of the carboxylic acids can be prepared by simply reacting the corresponding amines with the free acids.
The process according to the invention for the preparation of alkenones of Formula (I) can be carried out at elevated pressure or alternatively at ambient pressure. It may be performed batchwise or semi-continuously.
The reaction mixtures are worked up using conventional methods. For example, the desired alkenone of Formula (I) can be distilled out of the mixture once the solvent (if contained therein) has been separated off. Another possibility is to add water to the reaction mixture and to isolate the alkenone from the organic phase once water has been separated off by conventional separating agents such as sodium sulphate.
One preferred embodiment exploits working-up with formation of 2 phases. Two particularly advantageous variants are suitable for this. One variant provides for working-up with the addition of water. An organic phase forms which contains the desired product and the organic solvent used. The aqueous phase contains the spent "onium" salt. Where the acid anhydride has been used as one of the educts, the "onium" salt is present largely as the "onium" salt of the carboxylic acid corresponding to the anhydride. If the "onium" salt of the carboxylic acid has been used as acid scavenger, in this case there is an excess of acid in the aqueous phase. If it is desired to use the "onium" salt as acid scavenger again, the ratio of "onium" cation to carboxylic acid content has to be brought to the preferred range of 0.9:1 to 1:0.9. This is accomplished most easily by addition of so much alcohol, e.g. of C1-C4-aliphatic alcohols, that the acid which is present in an amount above the desired content is reacted off with esterification and can be separated off together with the water present by distillation.
If for example the acid chloride was used as educt, the "onium" salt is largely present in the aqueous phase as a hydrochloride or as a chloride-enriched onium
complex. For working-up, it is reacted with the corresponding carboxylic acid, e.g. trifluoroacetic acid, preferably in a 5 to 10-fold molar excess. At relatively high temperature, hydrochloric acid which is released is evaporated off. Since usually an excess of the carboxylic acid is used for this regeneration, then again an "onium" salt of carboxylic acid with an excess of acid is present, which is not well-suited to re-use. In that case, as already described above, an alcohol is added which reacts with the excess acid, forming ester. The ester can then be distilled off, with water being distilled off with it.
Another embodiment provides for an organic solvent to be added which causes two phases to form. To this end, solvents which cause the reaction mixture to be present in a homogenous phase are first removed. Then a solvent or solvent mixture is added which accomplishes the splitting into two phases. The following have for example proved usable: ethers, in particular dialkyl ethers, particularly diethyl ether; esters of trifluoroacetic acid, for example isopropyl trifluoroacetate; aliphatic hydrocarbons, for example hexane; cyclic hydrocarbons, for example cyclohexane; halogenated carbon compounds, for example 1,1,2-trichloro-1,2,2-trifluoroethane (CFC-113) or dichloromethane. It is a simple matter for the person skilled in the art to determine further solvents which likewise effect formation of two phases by simple trial and error.
One phase contains the solvent and the alkenone formed, and the other phase contains essentially the salt. The phase containing the alkenone is separated off, the solvent is removed and the alkenone can then be purified in conventional manner, for example by distillation, if this is necessary at all, because the product usually already occurs in a very high purity. It has been shown that with this embodiment too the yield and purity of the product is very high.
Instead of the reaction with a carboxylic acid such as trifluoroacetic acid, regeneration can also take place by addition of the anhydride of the carboxylic acid, e.g. by addition of acetic anhydride or trifluoroacetic anhydride, preferably by addition of the anhydride of the carboxylic acid which corresponds to the acid chloride used. Then the acid chloride and the "onium" salt of the carboxylic acid
form, and can then be reacted further with vinyl ethers in accordance with the process according to the invention.
The "onium" salt of the carboxylic acid can be prepared in advance by reacting the free base with the carboxylic acid. It can also be prepared during the reaction, by continuously or discontinuously introducing into the reaction mixture the carboxylic acid anhydride of the carboxylic acid which corresponds to the acid chloride.
One modification of the process according to the invention provides that, in a first stage, an aldehyde or acid chloride of the general formula (II) and a vinyl ether of the general formula (III) are reacted in the presence of an amine base, as is described for example in EP-A-0 744 400. The amine hydrochloride produced is then preferably regenerated as described above and, in this embodiment in a second stage, re-used in the process according to the invention.
A further subject of the invention is adducts of a carboxylic acid anion of the formula R1C(O)0" with a protonated cation of pyridine, which is substituted by one, two or three C1-C3 alkyl groups, preferably by one, two or three methyl groups. Those adducts with the anion of trifluoroacetic acid are preferred. These adducts may additionally contain up to 1 mole of the free acid per mole "onium" salt.
The protonated cation of the pyridine substituted by 1 to 3 C1-C3-alkyl groups may also be chlorinated, in particular in the alkyl groups. It may therefore be 2-chloromethyl, 2-dichloromethyl or 2-trichloromethyl pyridinium.
Particularly preferred is picolinium trifluoroacetate (n = 0) and its adducts with trifluoroacetic acid, in particular of the formula A-Bn, wherein A stands for picolinium trifluoroacetate, B for trifluoroacetic acid and n for 0 One further subject of the invention is the use of pyridine, substituted by 1, 2 or 3 C1-C3-alkyl groups, as acid scavenger. 2-alkylpyridine with alkyl = methyl, ethyl or propyl is preferred.
The following examples are intended to explain the invention further, without limiting its scope.
Examples
Examples 1 to 8 explain the preparation using trifluoroacetyl chloride, and Examples 9 to 12 explain the preparation using trifluoroacetic anhydride. Example 13 explains the regeneration of the spent "onium" salt with trifluoroacetic acid.
Aqueous working-occurs up in Examples 1 to 3.
Example 1:
Preparation of 4-ethoxy-1,1,1-trifluoro-3-buten-2-one (ETFBO) with pyridinium trifluoroacetate
Reaction:
CF3-COCH-CH2=CH-0-CH2-CH3 → CF3-CO-CH=CH-0-CH2-CH3
Batch:
Pyridine 0.4 mol 31.6 g
Trifluoroacetic acid (TFA) 0.4 mol 45.6 g
Ethyl vinyl ether 0.3 mol 21.6 g
Trifluoroacetyl chloride (TFAC) 0.3 mol 39.6 g
Dichloromethane 180.0 g
Performance:
First the pyridinium trifluoroacetate was prepared in a 500 ml three-necked flask with dry-ice cooler. For this, pyridine was introduced into the flask and TFA was added dropwise with stirring. So that the mixture did not become too hot (since the reaction is highly exothermic), it was cooled with a water bath. Then dichloromethane and ethyl vinyl ether were added and TFAC was introduced with stirring. The reaction temperature was kept at room temperature by means of a water bath. The batch became slightly yellowish when TFAC was introduced. Then the batch was stirred for another 2 3/4 h at room temperature and then a GC
sample was taken (sample was hydrolysed). The conversion was 97.2%, and the selectivity for 4-ethoxy-1,1,1-trifluoro-3-buten-2-one (ETFBO) was quantitative.
For working-up, water was added and the two phases which formed were separated. The dichloromethane was distilled off from the organic phase and the remaining product was precision-distilled. Trifluoroacetic acid was added to the aqueous phase and the mixture was kept at reflux to expel the HCI. Then, corresponding to the excess of trifluoroacetic acid used, ethanol was added and the trifluoroacetic acid ester which formed was distilled off together with ethanol and water as azeotrope. The remaining "onium" salt of trifluoroacetic acid was then re-used in the preparation of ETFBO.
Example 2:
Trifluoracetylation of ethyl vinyl ether with the trifluoroacetic acid(TFA) salt of 1,5-diazabicyclo[4.3.0]-non-5-ene (DBN) (deficiency of TFAC)
Reaction:
CF3-COCI+CH2=CH-0-CH2-CH3 → CF3-CO-CH=CH-0-CH2-CH3
Batch:
DBN 0.2 mol 24.8 g
TFA 0.2 mol 22.8 g
Ethyl vinyl ether 0.2 mol 14.2 g
TFAC 0.18 mol 23.8 g
Dichloromethane 120 g
Performance:
First the DBNxTFA was prepared in a 250 ml three-necked flask with dry-ice cooler. For this, DBN was introduced into the flask and TFA was added dropwise with stirring. So that the mixture did not become too hot (since the reaction is highly exothermic), it was cooled with a water bath, DBNxTFA becoming solid. Then dichloromethane and ethyl vinyl ether were added and TFAC was introduced with stirring. The reaction temperature was kept at room temperature by means of a water bath. The batch became yellow when TFAC was introduced. Then the
batch was stirred for another hour at room temperature and then a GC sample was taken (sample was hydrolysed). The conversion of EVE was quantitative, and the selectivity for ETFBO was 93.4%.
Working-up as in Example 1.
Example 3:
Trifluoracetylation of ethyl vinyl ether with DBN x TFA (TFAC equimolar)
Reaction:
CF3-COCI+CH2=CH-0-CH2-CH3 → CF3-CO-CH=CH-0-CH2-CH3
Batch:
DBN 0.05 mol 6.2 g
TFA 0.05 mol 5.7 g
Ethyl vinyl ether 0.05 mol 3.6 g
TFAC 0.05 mol 6.6 g
Dichloromethane 30 g
Performance:
First the DBNxTFA was prepared in a 100 ml three-necked flask with dry-ice cooler. For this, dichloromethane was introduced into the flask with DBN and TFA was added dropwise with stirring. So that the mixture did not become too hot (since the reaction was highly exothermic), it was cooled with a water bath. Then ethyl vinyl ether was added and TFAC was introduced with stirring. The reaction temperature was kept at room temperature by means of a water bath. The batch became yellow when TFAC was introduced. Then the batch was stirred for another 1 1/2 h at room temperature and then a GC sample was taken (sample was hydrolysed). The conversion of EVE was quantitative, and the selectivity for ETFBO was 95%.
Working-up as in Example 1.
Example 4:
Trifluoracetylation of ethyl vinyl ether with DBN x TFA with 2-phase formation
Reaction:
CF3-COCI+CH2=CH-0-CH2-CH3 → CF3-CO-CH=CH-0-CH2-CH3 + HCI
ETFBO = 4-ethoxy-1,1,1-trifluoro-3-buten-2-one
Batch:
DBN 0.20 mol 24.8 g
TFA 0.20 mol 22.8 g
Ethyl vinyl ether 0.15 mol 10.8 g
TFAC 0.15 mol 19.8 g
Dichloromethane 90 g
Performance:
First the DBNxTFA was prepared in a 250 ml three-necked flask with dry-ice cooler. For this, MeCl2 and DBN were introduced into the flask and TFA was added dropwise with stirring. So that the mixture did not become too hot (since the reaction is highly exothermic), it was cooled with a water bath. Then ethyl vinyl ether was added and TFAC was introduced with stirring. The reaction temperature was kept at room temperature by means of a water bath. The batch became orange when TFAC was introduced. The batch was then stirred for another 2 h at room temperature and then a GC sample was taken (sample was hydrolysed). The ethyl vinyl ether had completely reacted. Then the solvent dichloromethane was removed under vacuum in a rotary evaporator, and the remaining solution was divided into several partial volumes which were worked up by adding a solvent forming a second phase.
Equal volumes of the following solvents were added to the partial volumes, whereupon in each case a second phase formed:
Example 4.1: diethyl ether
Example 4.2: isopropyl trifluoroacetate
Example 4.3: hexane
Example 4.4: cyclohexane
Example 4.5: 1,1,2-trichloro-1,2,2-trifluoroethane (113)
Workinq-up:
Mainly the desired product ETFBO was found in the organic phase; the spent amine salt was found quantitatively in the other phase. The ETFBO phase was separated off and then isolated carefully on a rotary evaporator with a purity of >98% by drawing off the solvent in a vacuum.
Example 5:
Trifluoracetylation of ethyl vinyl ether with DBU x TFA
Reaction:
CF3-COCI+CH2=CH-0-CH2-CH3 → CF3-CO-CH=CH-0-CH2-CH3 + HCI
ETFBO
DBU = 1,5-diazabicyclo[5.4.0]undec-5-ene
Batch:
DBU 0.2 mol 30.4 g
TFA 0.2 mol 22.8 g
Ethyl vinyl ether 0.15 mol 10.8 g
TFAC 0.15 mol 19.8 g
Dichloromethane (MeCI2) 90 g
Performance:
First the DBU x TFA was prepared in a 250 ml three-necked flask with dry-ice cooler. For this, MeCI2 and DBU were introduced into the flask and TFA was added dropwise with stirring. So that the mixture did not become too hot (since the reaction is highly exothermic), it was cooled with a water bath. Then ethyl vinyl ether was added and TFAC was introduced with stirring. The reaction temperature was kept at room temperature by means of a water bath. The batch became orange when TFAC was introduced. The batch was then stirred for another 2 h at
room temperature and then a GC sample was taken (sample was hydrolysed). A second sample was taken the next morning (batch had darkened). The ethyl vinyl ether had completely reacted to ETFBO. The isolation took place using the two-phase method described in Example 4.
Example 6:
Trifluoracetylation of ethyl vinyl ether with pyridine x TFA
Reaction:
CF3-COCI+CH2=CH-0-CH2-CH3 → CF3-CO-CH=CH-0-CH2-CH3 + HCI
ETFBO
Batch:
Pyridine 0.4 mol 31.6 g
TFA 0.4 mol 45.6 g
Ethyl vinyl ether 0.3 mol 21.6 g
TFAC 0.3 mol 39.6 g
Dichloromethane 180 g
Performance:
First the pyridinium trifluoroacetate was prepared in a 500 ml three-necked flask with dry-ice cooler. For this, pyridine was introduced into the flask and TFA was added dropwise with stirring. So that the mixture did not become too hot (since the reaction is highly exothermic), it was cooled with a water bath. Then dichloromethane and ethyl vinyl ether were added and TFAC was introduced with stirring. The reaction temperature was kept at room temperature by means of a water bath. The batch became slightly yellowish when TFAC was introduced. Then the batch was stirred for another 2 3/4 h at room temperature and then a GC sample was taken (sample was hydrolysed). The ethyl vinyl ether had virtually completely reacted. The conversion to 4-ethoxy-1,1,1-trifluoro-3-buten-2-one (ETFBO) was 97.2%. Then MeCl2 was removed under vacuum in a rotary evaporator, and the remaining solution was again divided into partial volumes and extracted by adding a solvent forming a second phase.
The partial volumes formed a second phase with equal volumes of the following solvents:
Example 6.1: hexane
Example 6.2: cyclohexane
Example 6.3:1,1,2-trichloro-1,2,2-trifluoroethane (113)
Again, mainly the desired product ETFBO was found in this second phase; the spent amine was found quantitatively in the other phase. The ETFBO phase was then separated off and isolated carefully on a rotary evaporator with a purity of >98% by drawing off the solvent in a vacuum.
The working-up by means of the formation of two phases described in Examples 4 to 6 led to particularly high yields, but thermal loading of the reaction mixture was avoided.
Example 7:
Trifluoracetylation of ethyl vinyl ether / use of picoline
Reaction:
CF3-COCI+CH2=CH-0-CH2-CH3 → CF3-CO-CH=CH-0-CH2-CH3+HCI
Batch:
2-picoline 0.20 mol 18.6 g
TFA 0.20 mol 22.8 g
Ethyl vinyl ether 0.15 mol 10.8 g
TFAC 0.15 mol 19.8 g
Dichloromethane 90 g
Performance:
First the picoline trifluoroacetate was prepared in a 250 ml three-necked flask with dry-ice cooler. For this, dichloromethane and 2-picoline were introduced into the flask and TFA was added dropwise with stirring. So that the mixture did not become too hot (since the reaction is highly exothermic), it was cooled with a water
bath. Then ethyl vinyl ether was added and TFAC was introduced with stirring. The reaction temperature was kept at room temperature by means of a water bath. The batch became yellow when TFAC was introduced. Then the batch was stirred for another 2 1/2 h at room temperature and then a GC sample was taken (sample was hydrolysed). The ethyl vinyl ether had completely reacted. Then the batch was poured on to 150 g ice water, the organic phase was washed twice with water and distilled using a Rotavapor.
The dichloromethane was drawn off at 28°C water-bath temperature and 300 mbar.
The 4-ethoxy-1,1,1-trifluoro-3-buten-2-one passed over at 64°C water-bath
temperature and 13 mbar. According to the gas chromatogram, the purity was
98.0%.
The yield of ETFBO was 94.6%.
Example 8:
Trifluoracetylation of ethyl vinyl ether, 1st stage: free base, 2nd stage: "onium" trifluoroacetate as acid scavenger
Stage 1:
Batch 1st stage:
2-picoline 0.05 mol 4.66 g
Ethyl vinyl ether 0.15 mol 10.8 g
TFAC 0.15 mol 19.8 g
Dichloromethane 90 g
Performance of 1 st stage:
2-picoline, dichloromethane and ethyl vinyl ether were introduced into a 250 ml three-necked flask with dry-ice cooler and TFAC was introduced with stirring. The reaction temperature was kept at room temperature by means of a water bath. The batch became yellow when TFAC was introduced. After 2 1/2 h - the ethyl vinyl ether had completely reacted - the batch was poured on to 150 g ice water, washed twice with water and then the organic phase was distilled using a Rotavapor. The dichloromethane was drawn off at 24°C water-bath temperature
and 300 mbar. The 4-ethoxy-1,1,1-trifluoro-3-buten-2-one passed over at 65°C water-bath temperature and 15 mbar. According to the gas chromatogram, the purity was 97.4%. The ETFBO yield was 76.2%.
The remaining residue consisted largely of picoline hydrochloride. Trifluoroacetic acid was added to the residue, HCI was expelled, ethanol was added to react excess trifluoroacetic acid to the ester (see also Example 12c), and the picolinium trifluoroacetate formed was then used in the 2nd stage.
Stage 2:
Use of the picolinium trifluoroacetate produced in stage 1
Analogously to Example 7, the picoline and the trifluoroacetic acid were however not used separately, but in the form of the "onium" salt obtained above.
Example 9:
Trifluoracetylation of ethyl vinyl ether / use of trifluoroacetic anhydride (TFAH)
Reaction:
(CF3-CO)20 + CH2=CH-0-CH2-CH3 → CF3-CO-CH=CH-0-CH2-CH3 + CF3COOH
Batch:
2-picoline 0.20 mol 18.6 g
TFA 0.20 mol 22.8 g
Ethyl vinyl ether 0.15 mol 10.8 g
TFAH 0.15 mol 31.5 g
Dichloromethane 90 g
Performance:
First the picoline trifluoroacetate was prepared in a 250 ml three-necked flask with water-cooled condenser. For this, dichloromethane and 2-picoline were introduced into the flask and TFA was added dropwise with stirring. So that the mixture did not become too hot (since the reaction is highly exothermic), it was cooled with a water
bath. Then ethyl vinyl ether was added and TFAH was added dropwise with stirring. The reaction temperature was kept at room temperature by means of a water bath. The batch became yellow when TFAH was added. Then it was stirred for another 1 h and then a GC sample was taken (sample was hydrolysed). The next morning, a further sample was taken - the ethyl vinyl ether had completely reacted - and the batch was then poured on to 150 g ice water. The organic [phase] was washed twice more with water and then distilled using a Rotavapor.
The dichloromethane was drawn off at 24°C water bath temperature and 300 mbar.
The 4-ethoxy-1,1,1-trifluoro-3-buten-2-one passed over at 68°C water-bath
temperature and 18 mbar. According to the gas chromatogram, the purity was
97.9%.
The yield of ETFBO was 87.96%.
Example 10:
Trifluoracetylation of ethyl vinyl ether / use of trifluoroacetic anhydride and picoline
Reaction:
(CF3-CO)20 + CH2=CH-0-CH2-CH3 → CF3-C0-CH=CH-0-CH2-CH3 + CF3COOH
Batch:
Pyridine 0.20 mol 15.8 g
TFA 0.20 mol 22.8 g
Ethyl vinyl ether 0.15 mol 10.8 g
TFAH 0.15 mol 31.5 g
Dichloromethane 90 g
Performance:
First the pyridine trifluoroacetate was prepared in a 250 ml three-necked flask with water-cooled condenser. For this, dichloromethane and pyridine were introduced into the flask and TFA was added dropwise with stirring. So that the mixture did not become too hot (since the reaction is highly exothermic), it was cooled with a water bath. Then ethyl vinyl ether was added and TFAH was added dropwise with stirring. The reaction temperature was kept at room temperature by means of a
water bath. Then it was stirred for another 1 h and then a GC sample was taken (sample was hydrolysed). The next morning, a further sample was taken - the ethyl vinyl ether had completely reacted. The yield of ETFBO was 85.0%.
For working-up, water was added, the resulting organic phase was treated as described above, by distilling off the dichloromethane and precision-distilling the product. Ethanol was added to the aqueous phase and an ester/water/ethanol azeotrope was distilled off.
Example 11:
Trifluoracetylation of ethyl vinyl ether / use of DBN
Reaction:
(CF3-CO)20+CH2=CH-0-CH2-CH3 → CF3-CO-CH=CH-0-CH2-CH3+CF3-CO-OH
Batch:
DBN 0.20 mol 24.8 g
TFA 0.20 mol 22.8 g
Ethyl vinyl ether 0.15 mol 10.8 g
TFAH 0.15 mol 31.5 g
Dichloromethane 90.0 g
Performance:
First the DBN x TFA was prepared in a 250 ml three-necked flask with water-cooled condenser. For this, MeCl2 and DBN were introduced into the flask and TFA was added dropwise with stirring. So that the mixture did not become too hot (since the reaction is highly exothermic), it was cooled with a water bath. Then ethyl vinyl ether was added and TFAH was added dropwise with stirring. The reaction temperature was kept at room temperature by means of a water bath. The batch became yellow in colour. Then the batch was stirred for another 1.5 h at room temperature and then a GC sample was taken (sample was hydrolysed). The ethyl vinyl ether had completely reacted.
Then MeCI2 was removed under vacuum in a rotary evaporator at room temperature, and the remaining solution, after dividing into partial volumes, was extracted with different solvents forming two phases. Hexane, pentane, cyclohexane and 113 were used as two-phase extraction agents.
The entire isolated yield of ETFBO was 91%.
Example 12:
Working-up of "onium" hydrochloride
Example 12a:
Working-up of pyridinium hydrochloride
Reaction:
Pyridinium hydrochloride + 10 TFA → pyridine trifluoroacetate + HCI
Batch:
Pyridine hydrochloride 0.05 mol 5.8 g
TFA 0.50 mol 75.0 g
Performance:
Pyridine hydrochloride and TFA were introduced into a 100 ml three-necked flask with water-cooled condenser and boiled at reflux. After 5, 8 and 15 hours, CI" samples were taken.
CI' analyses
(Table Removed)
Example 12b:
Working-up of picolinium hydrochloride
Reaction:
Picoline hydrochloride + 10 TFA → Picoline trifluoroacetate + HCI
Batch:
Picoline hydrochloride 0.16 mol 20.6 g
TFA 1.60 mol 182.4 g
Performance:
Picoline hydrochloride and TFA were introduced into a 250 ml three-necked flask with water-cooled condenser and boiled at reflux. After 1 and 7 hours, CI" samples were taken.
CI" analyses
(Table Removed)
The chloride can be exchanged more easily than pyridine.
Example 12c:
Reaction with ethanol
The reaction product from Example 12 a) was heated and excess trifluoroacetic acid was distilled off, until picolinium trifluoroacetate was present as adduct with further trifluoroacetic acid; per mol picolinium trifluoroacetate, two mol trifluoroacetic acid (amine x 3 TFA) were present in the residue. A further separation of trifluoroacetic acid from this adduct was not possible by distillation. 1 mol ethanol was added per mol acetic acid. After distilling off the resulting ethyl trifluoroacetate, with some non-reacted ethanol and water present also passing
over, the picolinium trifluoroacetate remained, and could then be reintroduced into the reaction according to the invention.
Example 13:
Trifluoracetylation of ethyl vinyl ether without added solvent
Reaction:
(CF3-CO)20 + CH2=CH-0-CH2-CH3 → CF3-C0-CH=CH-0-CH2-CH3 + CF3COOH
Batch:
2-picoline 0.10 mol 9.3 g
TFA 0.10 mol 11.4 g
Ethyl vinyl ether 0.15 mol 10.8 g
TFAH 0.15 mol 31.5 g
Performance:
First the picoline trifluoroacetate was prepared in a 100 ml three-necked flask with water-cooled condenser, by introducing 2-picoline and adding TFA dropwise with stirring. So that the mixture did not become too hot (since the reaction is highly exothermic), it was cooled with an ice water bath. Then TFAH was added and ethyl vinyl ether was added dropwise with stirring (reaction is highly exothermic). The reaction temperature was kept at room temperature by means of a ice water bath. The reaction mixture was already yellow when TFAH was added. Then it was stirred for another hour and then a GC sample was taken (sample was hydrolysed). The conversion to ETFBO was 91.3%.
Example 14:
Trifluoracetylation in the absence of solvent, phase separation with addition of solvent
Performance:
Example 13 was repeated. The reaction was carried out without solvent, and for even better phase separation dichloromethane was then added. Again, a high conversion to ETFBO was observed.











We Claim;
1. A process for the preparation of alkenones of Formula (I)
(Formula Removed)
wherein R1 is a C1-C4-alkyl group or a C1-C4-alkyl group which is substituted by at least one halogen atom, or wherein R1 is a CF3C(O)CH2, and R2 is a aryl, substituted aryl, a C1-C4-alkyl group or for a C1-C4-alkyl group which is substituted by at least one halogen atom, wherein an acid anhydride or acid halide of Formula (II)
(Formula Removed)
wherein X is a R1-C(O)-O- or F, Cl or Br and R1 has the above meaning, is reacted with a vinyl ether of Formula (III)
(Formula Removed)
wherein R2 has the above meaning, in the presence of an "onium" salt of a carboxylic acid.
2. The process as claimed in claim 1, wherein R1 is methyl, ethyl or propyl, or for methyl, ethyl or propyl substituted by at least 1 fluorine atom.
3. The process as claimed in claim 1, wherein R1 is CF3, CF2H, CF2C1, C2F5, C3F7 or CF3C(O)CH2
4. The process as claimed in claim 1 wherein R2 is a methyl, ethyl, n-propyl or isopropyl.
5. The process as claimed in claim 1, wherein the molar ratio of "onium" salt to acid chloride is between 0.1:1 and 2:1.
6. The process as claimed in claim 1, wherein the reaction is performed at a temperature in that range of-15°C to +80°C, preferably 0°C to 40°C.
7. The process as claimed in claim 1, wherein the reaction mixture is converted into two phases, with one phase containing the alkenone product.
8. The process as claimed in claim 7, wherein a organic solvent is added to cause two phases to form, the alkenone being in the organic phase and the "onium" salt in the other phase.
9. The process as claimed in claim 7, wherein water is added to the reaction mixture, trifluoroacetic, acid is added to the onium complex enriched with "onium" chloride in the aqueous phase, resulting HC1 is expelled and then an alcohol is added to the reaction residue to form an ester from excess trifluoroacetic acid, the ester is separated off and the resulting "onium" trifluroacetate is recovered.
10. The process as claimed in claim 1, wherein resulting "onium" chloride is regenerated with carboxylic acid anhydride.
11. The process as claimed in claim 1, wherein a first step of the process is carried out in the presence of the free base corresponding to the "onium" salt of carboxylic acid; the "onium" halide formed is regenerated with formation of the "onium" salt of the carboxylic acid, and the salt is used in a subsequent step of the method.

Documents:

http://ipindiaonline.gov.in/patentsearch/GrantedSearch/viewdoc.aspx?id=fn6bsLgyVML83m482KgNsw==&loc=+mN2fYxnTC4l0fUd8W4CAA==


Patent Number 268544
Indian Patent Application Number 2477/DELNP/2004
PG Journal Number 36/2015
Publication Date 04-Sep-2015
Grant Date 02-Sep-2015
Date of Filing 25-Aug-2004
Name of Patentee SOLVAY FLUOR GMBH.,
Applicant Address HANS-BOCKLER-ALLEE 20, 30173 HANNOVER, GERMANY
Inventors:
# Inventor's Name Inventor's Address
1 MAX BRAUN VARLOH 8, 30900 WEDEMARK, GERMANY
2 UTA CLAASSEN AN DER AUE 31, 31249 HOHENHAMELN, GERMANY
PCT International Classification Number C07C 45/45
PCT International Application Number PCT/EP2003/00913
PCT International Filing date 2003-01-30
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 102 05 224.7 2002-02-08 Germany
2 102 61 471.7 2002-12-31 Germany