WO2012025548A1

WO2012025548A1 - Process for the preparation of alkenones

Info

Publication number: WO2012025548A1
Application number: PCT/EP2011/064503
Authority: WO
Inventors: Max Josef Braun
Original assignee: Solvay SA
Current assignee: Solvay SA
Priority date: 2010-08-27
Filing date: 2011-08-24
Publication date: 2012-03-01
Anticipated expiration: 2013-02-27

Abstract

The present invention relates to a process for preparing alkenone, in particular alkenone ethers, by reacting a carboxylic acid halide with a vinyl ether and eliminating hydrogen halide from said precursor to form the alkenone.

Description

Process for the preparation of alkenones

The present application claims the benefit of the European application no. 10174329.2 filed on August 27, 2010, herein incorporated by reference.

The present invention relates to a process for preparing alkenones, in particular alkenone ethers.

Halogenated alkenone ethers, such as 4-ethoxy- 1, 1, 1 -trifluoro-3 -butenone

(ETFBO), are building blocks in chemical synthesis, as disclosed, for example, in U.S. Pat. No. 5,708,175. They may be prepared by reacting an acid chloride with a vinyl ether in the presence of a base, as described in the aforementioned U.S. patent.

WO 03/066558 discloses the production of alkenones from vinyl ethers and acid halides or acid anhydrides in the presence of onium salts. In those processes, in which trifluoroacetic anhydride is added to ethyl vinyl ether, both addition of ethyl vinyl ether to a reaction medium containing trifluoroacetic anhydride and addition of trifluoroacetic anhydride to a reaction medium containing ethyl vinyl ether are described.

WO 2004/108647 discloses the production of alkenones comprising addition of carboxylic acid halides to vinyl ethers. In the examples,

trifluoroacetyl chloride is added to ethyl vinyl ether.

WO 2010/000871 discloses the manufacture of alkenones in a

continuously stirred tank reactor.

While alkenone ethers can be prepared by the known processes, these processes are still not optimal with regard to selectivity and yield of the reaction.

Thus, it is an object of the present invention to provide an improved process for the preparation of alkenones, in particular concerning the selectivity and the yield of the production. It has been found that the selectivity and the yield of the process can be significantly increased when the reaction is at least partially conducted in a microreactor. It has been found that when a carboxylic acid halide is reacted with a vinyl ether, it is of importance to keep the temperature of the reaction in the optimal range. In particular in the first seconds and minutes of the reaction most of the reaction heat (enthalpy) is set free.

Insufficient control of the temperature leads to formation of undesired byproducts. When large reaction vessels like stirred tank reactors are used, in particular at the beginning of the reaction, it has been found that formation of "hot spots" in the vessels cannot sufficiently be avoided. Surprisingly it has been found that when the reaction of a carboxylic acid halide with a vinyl ether is conducted at least partially in a microreactor (in particular at the beginning of the reaction), these hot spots are avoided and excellent yields and selectivity can be obtained.

The invention relates to a process for preparing an alkenone, which comprises the following reaction steps: (a) reacting a carboxylic acid halide with a vinyl ether to form a halogenated precursor of the alkenone and (b) eliminating hydrogen halide from said precursor to form the alkenone, wherein reaction step (a) is at least partially conducted in a microreactor.

The process according to the invention can advantageously be applied to the preparation of an alkenone of the Formula (I): Ri-C(0)-C(H)=C(H)-OR₂ (I) wherein Ri represents a Ci-Cio alkyl group which is optionally substituted by at least one halogen atom or Ri represents CF₃, CF₂C1, CF₂H; and R₂ represents aryl, substituted aryl, or a Ci-Cio alkyl group which is optionally substituted by at least one halogen atom. The alkenone of the Formula (I) is preferably obtained in reaction step (a) by reacting the carboxylic acid halide of the Formula (II): Ri- C(0)X (II) in which X represents fluorine, chlorine or bromine and Ri has the meaning given above, with a vinyl ether of the Formula (III): CH₂=C(H)-OR₂ (III) in which R₂ has the meaning given above.

Ri is preferably a fluorinated C1-C4 alkyl group. Ri more preferably represents methyl, ethyl, n-propyl, isopropyl or methyl, ethyl, n-propyl or isopropyl substituted by at least one fluorine atom. It is especially preferred if Ri represents methyl, ethyl or methyl or ethyl substituted by at least one fluorine atom. CF₃, CF₂H, CF₂C1, C₂F₅, C₃F₇ are particularly preferred as Ri . CF₃, CF₂C1 and CF₂H are more particularly preferred as Ri .

R₂ can be selected for example from aryl, for example, phenyl, C1-C4 alkyl groups and/or phenyl substituted by halogen atoms. R₂ is preferably a C1-C4 alkyl group. More preferably, R₂ represents a linear or branched C1-C4 alkyl group, and particularly preferably R₂ represents methyl, ethyl, n-propyl or isopropyl, most preferably a methyl or an ethyl group.

X is preferably selected from fluorine and chlorine, more preferably X is chlorine.

In a first particular embodiment, the carboxylic acid halide is

trifluoroacetyl chloride. In a second particular embodiment, the carboxylic acid halide is chlorodifluoroacetyl chloride.

In a third particular embodiment, the carboxylic acid halide is

difluoroacetyl chloride.

In a forth particular embodiment, the carboxylic acid halide is

trifluoroacetyl fluoride.

In a fifth particular embodiment, the carboxylic acid halide is

(trifluoroaceto)acetyl fluoride.

In one embodiment of the present invention step (a) comprises reacting a carboxylic acid halide with a vinyl ether by introducing vinyl ether into a reaction medium containing the carboxylic acid halide to form the halogenated precursor of the alkenone. In this embodiment the reaction medium contains the carboxylic acid halide, optionally an additional solvent and optionally the alkenone or the halogenated precursor to be produced.

In a preferred embodiment of the present invention step (a) comprises reacting a carboxylic acid halide with a vinyl ether by introducing the carboxylic acid halide into a reaction medium containing the vinyl ether to form the halogenated precursor of the alkenone. In this embodiment the reaction medium contains the vinyl ether, optionally an additional solvent and optionally the alkenone or the halogenated precursor to be produced.

The reaction steps (a) or (b) can be carried out in the presence of a base. The base to be used may, for example, be a nitrogen-containing heterocyclic compound such as pyridine, quinoline or picoline; or a tertiary base such as triethylamine, dimethylaniline, diethylaniline or 4-dimethylaminopyridine. Among them, pyridine, triethylamine, dimethylaniline, diethylaniline or 4- dimethylaminopyridine is preferred. Among them, pyridine is particularly preferred. These bases may be used alone or in combination as a mixture. If appropriate, the base is used usually in an amount of from 1.0 to 3.0 equivalents, preferably from 1.05 to 1.5 equivalents, per mol carboxylic acid halide.

The reaction steps (a) or (b) can be carried out in the presence of an additional solvent. "Additional solvent" is understood to denote a solvent different from the reactants and the products of said reaction. The solvent to be used can, for example, be an aromatic hydrocarbon such as benzene, toluene or xylene, an aliphatic hydrocarbon such as pentane or hexane; a halogenated hydrocarbon such as a chlorinated hydrocarbon selected in particular from methylene chloride, chloroform or ethylene dichloride or a fluorinated hydrocarbon selected in particular from 1,1, 1,3,3-pentafluoropropane or, preferably 1,1, 1,3,3-pentafluorobutane ; or an ether such as diethyl ether, dibutyl ether or tetrahydrofuran. Among them, an aromatic hydrocarbon is preferred. Particularly preferred among them, is benzene or toluene. These solvents can be used alone or in combination as a mixture. If appropriate, the solvent is used usually in an amount of from 1 to 35 parts by weight, preferably from 3 to 16 parts by weight, per part by weight of the reaction medium. Preferably, no additional solvent is present in the reaction medium.

The organic products of the reactions of step (a) and (b) in particular the halogenated precursor of the alkenone and, preferably, the alkenone to be produced can be used as solvents for the reaction steps (a) and/or (b).

Preferably, the reaction of the carboxylic acid halide with the vinyl ether in reaction step (a) is carried out in a reaction medium comprising the alkenone to be produced, in particular ETFBO. The alkenone is generally used in an amount of from 10 to 99 % by weight, preferably from 10 to 60 % by weight, more preferably from 15 to 35 % by weight relative to the total weight of the reaction medium.

In another embodiment, the reaction medium for the reaction of the carboxylic acid halide with the vinyl ether comprises a halogenated precursor of the alkenone to be produced, in particular CETFBO ( 1,1, 1 -trifluoro-4-chloro-4- ethoxybutan-2-one). The halogenated precursor is generally used in an amount of from 10 to 99 % by weight, preferably from 10 to 60 % by weight, more preferably from 15 to 35 % by weight of the halogenated precursor to the total weight of the reaction medium. The presence of the halogenated precursor of alkenone to be produced is preferred when the reaction medium comprises carboxylic acid halide.

In one preferred embodiment step (a) comprises reacting a carboxylic acid halide with a vinyl ether by introducing the carboxylic acid halide into the reaction medium containing the vinyl ether and the alkenone to be produced and/or the halogenated precursor to be produced. The alkenone preferably comprises alkenone from an earlier batch of alkenone produced according to the processes as described herein. The carboxylic acid halide to be introduced into the reaction medium can be dissolved in the alkenone to be produced and/or the halogenated precursor to be produced before introduction into the reaction medium. In the process according to the invention, when the reaction of the carboxylic acid halide with the vinyl ether in reaction step (a) is carried out by adding the vinyl ether to a reaction medium which contains carboxylic acid halide, the content of the carboxylic acid halide is typically at least 20 % by weight relative to the total weight of the reaction medium. Preferably this content is at least 50 % weight. In this embodiment of the process according to the invention when the reaction medium comprises carboxylic acid halide, the reaction medium may consist essentially of carboxylic acid halide. However, preferably the reaction medium generally contains less than 100 % by weight of carboxylic acid halide, for example less than about 99 % by weight, relative to the total weight of the reaction medium.

In another aspect of the invention, when the vinyl ether is added to the reaction medium which comprises carboxylic acid halide, the reaction medium contains at least 1 % by weight of carboxylic acid halide relative to the total weight of the reaction medium. Preferably this content is at least 5 % weight. In this embodiment, the reaction medium generally contains less than about 20 % by weight of carboxylic acid halide relative to the total weight of the reaction medium. Preferably this content is less than 10 % weight. Preferably, the reaction medium contains 5 to 10 % by weight of carboxylic acid halide relative to the total weight of the reaction medium.

It has been found that in the process according to the present invention for preparing an alkenone, step (a) as described above, which step corresponds to the preparation of a halogenated precursor of the alkenone, can advantageously be carried out in a microreactor, at least partially.

Microreactors are known in the art (cf. e.g. WO 2007/042313 A2, US

2009/0295005 Al, EP 1 481 724 A2, or WO 2007/027785 A2). "Microreactors" as used herein is understood in the broadest technical meaningful sense. In the art often "micromixer" and "microreactor" are used as synonyms. In some cases, however, a microreactor which mixes a plurality of fluids together is called a "micromixer" and a microreactor which causes a chemical reaction during the mixing of a plurality of fluids is called a "microreactor". The microreactor as used herein is a device comprising "micromixers", "microreactors" and combinations of these as used in the art. Preferably, "microreactor" as used herein is a device which comprises components, typically channels or flow ducts, having characteristic/determining geometric dimensions of 1 μιη to 2000 μιτι, and in particular preferable from 10 μιη to 1000 μιη. A microreactor is typically provided with a reaction channel which leads to a plurality of fine reaction channels or flow ducts. The equivalent diameter obtained in the section of the fine reaction channel is, converted to a circle, several micrometers to several hundreds of micrometers.

Preferably, "microreactor" as used herein includes at least one micromixer, which is preferably used in combination with a further microreactor. Further, the term "microreactor" used herein can be a device, which is referred to in the art as "minireactor", "micro heat exchanger", "minimixer" or "micromixer". Examples of these are microreactors, micro heat exchangers, and T- and Y-mixers, as available by a large number of companies (e.g. Ehrfeld Mikrotechnik BTS

GmbH, Institut fur Mikrotechnik Mainz GmbH, Siemens AG, CPC-Cellulare Process Chemistry Systems GmbH).

In a preferred embodiment, "microreactor" comprises a known static micromixer, more preferably a multi-lamination mixer, split and recombine mixers, or else mixers with a cross-sectional constriction. Preferably, the static micromixers are flowed through continuously. Examples of known static micromixers are stack mixers as described in DE 202 06 371 Ul, slotted plate mixers, as described in WO 2004/052518 A2, or else comb mixers, as described e.g. in DE 202 09 009 Ul, as available by, for example, Ehrfeld Mikrotechnik BTS GmbH. These are multi-lamination mixers, in which the two fluid streams to be mixed are fanned out into a multitude of thin lamellae or films, and these lamellae are then merged with one another in alternation, such that the diffusion and secondary flows result in rapid mixing.

As alternative micromixers, V-type mixers, as available by

Forschungszentrum Karlsruhe, split and recombine mixers, e.g. cascade mixers or faceted mixers, as available by Ehrfeld Mikrotechnik BTS GmbH, or caterpillar mixers, e.g. obtainable from the Institut fur Mikrotechnik, Mainz, can be used. In these mixers the product streams to be mixed are divided into smaller flows and these smaller flows are repeatedly combined and divided. Further alternative micromixers with a cross-sectional constriction, such as focus mixers or cyclone mixers, or else jet mixers, as described in EP 1 165 224 Bl, e.g.

obtainable from Synthesechemie, and impingement jet mixers or valve mixers, as described in WO 2005/079964 Al, available from Ehrfeld Mikrotechnik BTS GmbH, can be used. Particular preferred cascade mixers are used as micromixers in the process of the present invention. In a preferred embodiment the microreactors comprise channels with channel widths of less than 1000 μπι, preferably less than 500 μπι, more preferably less than 200 μπι, in particular less than 100 μιη. Preferably the microreactor applied in the process according to the present invention comprises a micromixer, and more preferably comprises a combination of a micromixer with a further microreactor, most preferably a sandwich type microreactor. In one preferred embodiment, the further microreactor used is a micro heat exchanger or a microreactor having an integrated static mixing function, in which the reaction can be carried out under defined flow conditions, such as low axial and good radial mixing. This results in a narrow residence time distribution, in particular in continuous operation. Preferably a sandwich type reactor from Ehrfeld Mikrotechnik BTS GmbH is used, more preferably in combination with a micromixer, in particular a cascade mixer. The temperature of the

microreactors as used herein can preferably be controlled by use of a temperature control fluid circulating through and/or around the microreactor. In a preferred embodiment "microreactor" comprises a static mixer, preferably a

microstructured static mixer, in particular the mixers as specified above, most preferably in combination with a further microreactor, in particular a sandwich type microreactor.

In a preferred embodiment known microstructured heat exchangers are used as microreactors. These known heat exchangers include micro-heat exchangers which consist of stacked thin plates provided with microchannels and welded to one another. Microstructure heat exchangers are, e.g. cross-current or counter-current plate heat exchangers as described in DE 37 09 278 Al . Such heat exchangers are available from Ehrfeld Mikrotechnik BTS GmbH. Preferably the microreactor applied in the process according to the present invention is a combination of a micromixer as described above and a microstructured heat exchanger.

In a preferred embodiment of the process according to the present invention, the microreactor, in particular the static micromixer is flowed through continuously. Thereby, the reaction mixture can advantageously be kept at the optimal reaction temperature of around 0°C to 40°C, preferably from 10°C to 30°C, more preferably about 25°C or about 20°C. The high heat transfer performance of the microreactors, in particular of the microstructured heat exchangers, thereby guarantees that the temperature can be kept in the optimal range, in particular also during the first stages of the reaction, where typically the most reaction heat (enthalpy) is generated. In the micromixers the small volumes of the reaction mixture allow exact temperature control and thereby prevent an undesired rise in the temperature which typically leads to side reactions and loss in selectivity. In addition, the efficiency of the process is enhanced, since, owing to the very high exchange area per unit volume, it is possible to work with more highly concentrated reaction and work-up mixtures. The intensive mixing of the phases additionally leads to acceleration of the preparation and work-up reaction, and to improved reaction conversion and increase in yield and selectivity of the reaction.

The process for preparing an alkenone according to the present invention is at least partially conducted in a microreactor. "Partially" as used herein means that the reaction, e.g. mixing the carboxylic acid halide with the vinyl ether is not conducted in the microreactor until completion, but that the reaction medium discharged from the microreactor contains significant amounts of the carboxylic acid halide to be reacted and/or the vinyl ether to be reacted, respectively.

Preferably the reaction is substantially completed in a continuously stirred tank reactor (CSTR), which follows the microreactor. Instead of a CSTR e.g. a bubble column reactor or a similar reactor can also be used. In the following the invention will be explained with respect to a CSTR reactor, however, all the following explanations are also valid for a bubble column reactor.

In a preferred embodiment, the process, in particular step (a), is carried out in continuous mode. In a continuous process, the starting ingredients are preferably continuously fed into the microreactor, optionally followed by feeding the product obtained from the microreactor into a continuously stirred tank reactor. In the continuously stirred tank reactor, the content of the halogenated precursor of the alkenone in the liquid reaction medium is preferably kept in a range from 50 to 99 %, preferably in a range from 60 to 99 %, more preferably in a range from 75 to 99 % by weight of halogenated precursor relative to the total weight of the reaction medium. This is particularly advantageous for a continuous process, for example in a microreactor, followed by a continuously stirred tank reactor (CSTR).

In a particularly preferred embodiment of the process for preparing an alkenone according to the present application the carboxylic acid halide is reacted with the vinyl ether in step (a) such that the residence time of the reaction mixture in the microreactor is not sufficient for a substantially complete reaction. Preferably the residence time in the microreactor is selected such that about 90% or less, more preferably about 70% or less, in particular about 50 % or less of the starting ingredient has reacted. The starting ingredient which can react completely is the carboxylic acid halide or the vinyl ether, whichever of the two is present in a lower molarity in the reaction mixture. If the molar ratio of carboxylic acid halide and vinyl ether is about 1, preferably the vinyl ether is the relevant starting ingredient.

The residence time in the microreactor is preferably less than 80%, more preferably less than 60%, in particular less than 50% of the residence time necessary to achieve substantially completion of the reaction at the respective reaction conditions. For the most preferable reactions the residence time in the microreactor is preferably less than 80 minutes, more preferably less than 40 minutes, in particular less than 20 minutes. In this embodiment, the reaction of the carboxylic acid halide with the vinyl ether in the process according to the present application is preferably continued, more preferably substantially completed in a continuously stirred tank reactor (CSTR), which reactor most preferably directly follows the microreactor. Preferably, this reaction is carried out continuously. Thus the carboxylic acid halide and vinyl ether are mixed and partially reacted in a microreactor, followed by substantial completion of the reaction in a continuously stirred tank reactor.

"Substantially complete" as used herein typically denotes an optional content of 1% by weight or less of the starting ingredient, more preferred 0.5% by weight or less, more preferred 0, 1 % by weight or less of starting ingredient relative to the weight of the end product.

Reaction step (a) of the process of the present invention can also comprise completion of the reaction step in a plug-flow reactor. The reaction mixture, which has been at least partially brought to reaction in the microreactor can be further reacted in the microreactor or a stirred tank reactor and then substantially completed (or completed) in a plug-flow reactor. In a preferred embodiment, e.g. the last 5%, preferably the last 2% or the last 1% of the reaction of reaction step (a) is carried out in a plug-flow reactor.

The CSTR reactor is usually in the turbulent state while the plug-flow reactor can be in the turbulent state or in the laminar-flow state.

Reaction of the carboxylic acid halide with the vinyl ether in a

microreactor, optionally followed by an CSTR and optionally followed by a plug-flow reactor is advantageous as the advantages of the specific reactors are combined. During the beginning of the reaction, the microreactor is particularly advantageous as it typically provides excellent heat exchange, and thereby is able to control the reaction heat (enthalpy), which is set free mostly at the beginning of the reaction. Therefore, already at the stage of the beginning of the reaction heating of the reaction mixture above the optimal temperature range of e.g. ± 20°C is avoided, whereby yield and selectivity of the reaction is increased. The completion of the reaction can then be carried out in a continuously stirred tank reactor and/or a plug-flow reactor.

In a particular embodiment, which is preferred, the reaction of step (a) or (b) is carried out in the substantial or complete absence of a base, especially when a carboxylic acid chloride as described herein before is used.

In a further particular embodiment, which is preferred, the reaction of step (a) or (b) is carried out in the substantial or complete absence of additional solvent.

In a further particular embodiment, which is preferred, the reaction of step (a) or (b) is preferably carried out in the substantial or complete absence of base and of additional solvent, as described here before.

The above particular embodiments can be advantageously combined with any of the other embodiments of the invention.

"Substantial absence" as used herein typically denotes an optional content of 1 % by weight or less, more particularly of 0.5 % by weight or less of base and/or solvent relative to the total weight of the reaction mixture.

The process according to the invention allows for particularly efficient isolation of, if desired, the halogenated precursor of the alkenone and in particular the desired alkenone, because the reaction proceeds selectively and separation is facilitated by the substantial absence of components different from the starting material and the products of the reaction.

In the process according to the invention and in the particular embodiments thereof, the molar ratio of the carboxylic acid halide to the vinyl ether preferably is from 0.8 to 1.2, and particularly preferably from 0.8: 1 to about 1. Most preferably, the molar ratio is about 1.

In the process according to the invention when the reaction medium comprises carboxylic acid halide, the vinyl ether is preferably introduced into the reaction medium at a rate of from 0.01 to 2 mol/hour/mol of carboxylic acid halide. More preferably this rate is from 0.5 to 1.5 mol/hour/mol of carboxylic acid halide. A rate of about 1 mol/hour/mol of carboxylic acid halide has provided good results. In the process according to the invention when the reaction medium comprises vinyl ether, it is desirable, in particular in a continuous process, to control the concentration of the vinyl ether in the reaction medium which is preferably fed into the microreactor. Preferably, this concentration is more than 50 % by weight relative to the total weight of the reaction medium. Often the concentration of the vinyl ether in the reaction medium is equal to or more than 80 % by weight relative to the total weight of the liquid reaction medium. More preferably, this concentration is equal to or more than 90 % by weight relative to the total weight of the reaction medium, and may be at least 95 % by weight relative to the total weight of the reaction medium.

It has been found that controlling the concentration of the vinyl ether in the reaction medium avoids particularly the formation of other unwanted compounds such as chloroethers, polymeric materials and improves the yield and purity of the alkenone.

The process according to the present invention is generally carried out at a temperature from 0°C to 40°C, preferably from 10°C to 30°C, more preferably at about 25°C or about 20°C.

In a particular aspect of this specific embodiment, which is particularly advantageous when the process is carried out in continuous mode, the vinyl ether, the carboxylic acid halide and any optional solvents are mixed in step (a) by use of a micromixer, preferably followed by introduction of the mixture into a further microreactor.

It has been found, surprisingly, that by carrying out step (a) at least partially in a microreactor, hot spots can be substantially avoided in said reaction medium, thereby improving the yield and purity of the halogenated precursor of the alkenone and of the alkenone obtained from the precursor.

For the purpose of the present invention, the term "hot spot" denotes in particular a zone of the reaction medium having a substantially higher temperature than the target temperature at which the reaction should be carried out. "Substantially higher temperature" is understood a temperature which is at least 5°C, or at least 10°C higher than the target temperature of the reaction medium.

In the process according to the present application the reaction step (a) is preferably partially, more preferably completely, carried out in a microreactor, which preferably comprises at least one micromixer. Thus, the carboxylic acid halide, the vinyl ether and the optional solvent are preferably fed into a micromixer. The micromixer is preferably a known static micromixer. Preferably the mixture obtained from the micromixer is then fed into a further microreactor, e.g. a microstructured heat exchanger and/or a sandwich type microreactor. Preferably after mixing in the micromixer the mixture is subsequently passed through an arrangement of microstructured heat exchangers with a given residence time. The arrangement is preferably configured such that the temperature profile in the flowing reaction mixture along the flow direction is adjustable by application of one or a sequence of heat exchangers or a sequence of further microreactors. Most preferably, the static micromixer is flowed through continuously, the obtained mixture is brought to a suitable temperature by means of one or more heat exchangers, and then the reaction mixture is optionally fed into one or more further microreactors, and optionally the reaction mixture is then passed to the CSTR and/or a plug-flow reactor according to the preferred embodiments as described above.

The turbulent state of the CSTR can be achieved, for example, by an operation selected from stirring, passing the reaction medium through a flow resistance or mixing the reaction medium through introduction of gas bubbles such as an inert gas (in a bubble column reactor). The stirring in the reaction medium may be realized by means of internal stirring such as a turbine or an agitator, or by means of a recirculation pipe exterior to the reactor. Typical examples of a flow resistance are for example shaped bodies which can be placed in a reactor such as glass rings and Raschig rings. Particular embodiments of CSTR as applied in the various embodiments according to the present invention include reactors which consist of one or more cylindrical or spherical tanks wherein the turbulent state of the liquid reaction medium is created by any of the means described above. When more than one CSTR reactor is used, for example 2, 3 or 4 reactors, it is advantageous to split the feed of the preferably prereacted vinyl ether from the microreactor so as to feed vinyl ether from the microreactor into each CSTR reactor. It is of course possible to use combinations of CSTR reactors and bubble column reactors.

Particular embodiments of the plug flow reactor are in the form of a cylindrical tube through which the feed enters at one end and exits at the other end.

The process according to the invention and the particular embodiments thereof, generally comprises carrying out the reaction of step (a) at a first temperature and carrying out step (b) at a second temperature higher than the first temperature.

The first temperature is generally less than 50°C, often less than 40°C, preferably 30°C or less. In one aspect, the temperature is preferably about -25°C or less. The first temperature is generally at least -50°C, often -40°C or more, preferably -30°C or more. As the use of a microreactor already gives excellent yield and selectivity at room temperature it is preferred that the first temperature is in the range of about 10°C to about 50°C, more preferably about 20°C to about 30°C.

The second temperature is generally at least 50°C, often 60°C or more, preferably 70°C or more. The second temperature is generally less than 150°C, often less than 100°C, preferably about 80°C or less.

The process according to the invention and the particular embodiments thereof, generally comprises carrying out the reaction of step (a) at a first pressure and carrying out step (b) at a second pressure lower than the first pressure.

The first pressure is generally in the range of about 1 bar abs to about 100 bar abs. The first pressure is preferably chosen to maintain the reaction medium and the reactands in the liquid state. For example, the first pressure is

advantageously about 2 bar abs or more at a reaction temperature of about -25°C to about +30°C, e.g. if trifluoroacetyl chloride is used as acid halide. The first pressure is advantageously a pressure of about 2 bar abs or more, more preferably about 5 bar abs to about 10 bar abs or more, in particular at a reaction temperature of from 20 to 30°C.

The second pressure is preferably chosen to allow for fractional distillation at least of the alkenone from the reaction medium obtained in step (a). A typical second pressure is from 1 to about 10^"3 bar abs.

In another embodiment of the process according to the invention and the particular embodiments thereof, step (a) is carried out in a first reaction zone and step (b) is carried out in a second reaction zone different from the first reaction zone.

The first reaction zone is often a microreactor, optionally followed by a continuously stirred tank reactor and/or a plug-flow reactor. The second reaction zone can be, for example, a distillation column.

In a further particular embodiment, which is preferred, the process according to the invention further comprises separating the alkenone produced in step (b) from hydrogen halide, unreacted carboxylic acid halide and unreacted halogenated precursor (and some traces of polymeric material) and optionally recycling carboxylic acid halide to step (a) and halogenated precursor to step (b).

A distillation, in particular a fractional distillation, is preferred as separation technique to separate the alkenone, in particular from the reaction mixture of step (b).

In a preferred embodiment the process for preparing an alkenone according to the present invention comprises the following steps:

(a) providing a halogenated precursor of the alkenone, by reaction of a

carboxylic acid halide and a vinyl ether in accordance with any of the processes disclosed herein before or a combination thereof, which reaction is at least partially conducted in a microreactor, and

(b) eliminating the hydrogen halide from said halogenated precursor to form the alkenone by a thermolysis treatment selected from a flash thermolysis, a vacuum thermolysis and a thermolysis under stripping with an inert gas.

For the purpose of the present invention, the term "flash thermolysis" refers to a process wherein the liquid reaction medium is heated up in a short time. Typical heating times for flash thermolysis are less than 1 hour, in particular less than 30 min, preferably about 15 minutes. Generally, the heating time is greater than Is, often greater than 15s.

In particular aspects of the process according to this embodiment, the flash thermolysis is conducted at a temperature ranging from -20° C to 140° C and a period of time ranging from 30 seconds to 1 hour, preferably at a temperature ranging from 0° C to 130° C and a period of time ranging from 30 seconds to 30 min, more preferably at a temperature ranging from 20° C to 120° C and a period of time ranging from 30 seconds to 20 min.

The thermolysis or flash thermolysis can be optionally carried out under stripping with an inert gas stream such as nitrogen gas, argon gas.

For the purpose of the present invention, the term "stripping" denotes in particular a physical separation process where one or more components, in particular HC1, are removed from the liquid reaction medium by a gas stream. The liquid and gas streams can have concurrent or countercurrent flow directions.

If appropriate, the stripping is advantageously carried out with a nitrogen stream. The process according to this embodiment, generally comprises carrying out the thermolysis at a temperature of -20° C to 140° C, preferably from 60 to 130°C, for example at about 80 °C or about 120 °C.

The thermolysis or flash thermolysis may be carried out under vacuum. In that case, the vacuum is preferably from 100 to 600 mbar.

According to one alternative, in the process according to the present invention the elimination of hydrogen halide is carried out simultaneously during the formation of the halogenated precursor of the alkenone, for example, in the presence of an acid scavenger and/or by thermally inducing the elimination of hydrogen halide. The acid scavenger to be used may, for example, be a nitrogen- containing heterocyclic compound such as pyridine, quinoline or picoline; or a tertiary base such as thiethylamine, dimethylaniline, diethylaniline or 4- dimethylaminopyridine. Among them, pyridine, triethylamine, dimethylaniline, diethylaniline or 4-dimethylaminopyridine is preferred. Among them, pyridine is particularly preferred. These acid scavengers may be used alone or in

combination as a mixture. If appropriate, the acid scavenger is used in an amount of about 1 equivalent or less, preferably about 0.8 equivalents or less, in particular about 0.5 to about 0.8 equivalents per mol carboxylic acid halide. If desired, an additional solvent may be present during the elimination of hydrogen halide. The term "additional solvent" has the same meaning as defined above.

It is understood that the different processes and embodiments disclosed herein apply in most preferred way to the manufacture of

chlorotrifluoroalkoxybutanone from alkyl-vinylether and trifluoroacetic acid halide, in particular from trifluoroacetyl chloride and ethyl vinyl ether and subsequent elimination to form trifluoroalkoxybutenone, in particular ETFBO (4-ethoxy-l, 1, l-trifluoro-3-butenone).

chlorodifluoroalkoxybutanone from alkyl-vinylether and difluoroacetic acid halide, in particular from difluoroacetyl chloride and ethyl vinyl ether and subsequent elimination to form difluoroalkoxybutenone, in particular EDFBO (4-ethoxy- 1 , 1 -difluoro-3 -butenone).

The present invention further relates to a reactor for conducting the processes as described above comprising at least one microreactor, preferably the microreactors as defined above, in particular a micromixer and/or a sandwich- type microreactor, and a stirred tank reactor, preferably a CSTR and preferably a plug-flow reactor. The microreactor and the stirred tank reactor, preferably a CSTR (and optionally the plug-flow reactor) are connected to allow the passage of the fluid, i.e. the liquid reaction medium from the microreactor into the stirred tank reactor, preferably the CSTR as described above (and if required furtheron into the plug-flow reactor). In a preferred embodiment the microreactor and the stirred tank reactor are directly connected such that no intermediate device is arranged between the microreactor and the stirred tank reactor, such that the liquid reaction medium discharged from the microreactor is directly charged into the stirred tank reactor.

Should the disclosure of any patents, patent applications, and publications which are incorporated herein by reference conflict with the description of the present application to the extent that it might render a term unclear, the present description shall take precedence.

The examples hereafter are intended to illustrate the invention without however limiting it.

In these examples and throughout this specification the abbreviations employed are defined as follows: TFAC is trifluoroacetylchloride, EVE is ethyl vinyl ether, CETFBO is 4-Chloro-4-Ethoxy-l, l, l-trifluoro-3-butan-2-one, ETFBO is Ethoxy-l, l, l-trifluoro-3-buten-2-one, and DETFBO is 4,4-Diethoxy- 1,1, 1 trifluoro-3-butan-2-one.

Example: Manufacture of 4-ethoxy-l,1 -trifliioro-3-butene-2-one in a microreactor

Step (a)

EVE and gaseous TFAC were reacted in a static mixer ("cascade-type mixer", article no. 0116, stainless steel, obtainable by Ehrfeld Mikrotechnik BTS GmbH, Wendelsheim, Germany), followed by a microreactor (sandwich type reactor 0212-1-001-F, stainless steal, obtainable by Ehrfeld Mikrotechnik BTS GmbH; volume = 30 ml).

Gaseous trifluoracetylchlorid (TFAC) was charged in a molar ratio of 1 : 1, relative to the EVE applied, into the micromixer, together with ethyl vinyl ether (EVE), or a mixture of EVE and ethoxy-l, l, l-trifluoro-3-butene-2-one

(ETFBO), respectively. The feeding rate of the TFAC was controlled via a rotameter and the feeding rate of EVE, or the mixture with of EVE with ETFBO, respectively, was controlled via a dosing pump or a HPLC-pump. The feeding rate was adjusted to obtain the residence time as indicated in the tables. The mixing of the gaseous/liquid phase was achieved in the micromixer (a split and recombine micromixer), the temperature of which can be controlled. After passing the micromixer the reaction mixture was fed into the sandwich type microreactor, which can be controlled in temperature, in order to provide the desired residence time. At the exit of the sandwich type microreactor a sample was analyzed via ONLINE-NIR (Thermo Fischer device), analysis datas in the tables below are given in masss %.

In the tables 1 - 3 shown below three series of examples are indicated, which are distinguished by different EVE concentration (vol.-%) used in the microreactor: EVE/ETFBO mixture 50:50 (examples 1 - 7), EVE/ETFBO mixture of 80:20 (examples 8 - 11) and 100 % EVE (examples 12 - 24).

In table 4 shown below an example is indicated, where a pressure retention valve was installed at the exit of the microreactor and liquid TFAC was charged into the mixer. The reactor pressure was adjusted to 5.5 bar.

Step (b)

Conversion of CETFBO by thermolysis treatment.

After the reaction step (a), as described above, a flask, fitted with reflux condenser, was heated to the desired temperature by using an oil bath. The thermolysis or flash thermolysis was performed under different conditions, at different temperatures, with or without an inert gas stream or under vacuum. The conversion of CETFBO to ETFBO was followed by gas chromatography (GC) analysis, with corrected GC-values based on NIR cross check. When the composition of the reaction mixture remained constant, the resulting reaction mixture was further subjected to a distillation in vacuo (70°C, 20 mbar) to obtain ethoxy-1, 1, l-trifluouro-3-buten-2-one (purity cis + trans > 99 %). Excellent yields, typically in the range of 90 - 98 %, relative to the EVE were achieved. Thus excellent yields and excellent selectivity can be obtained by conducting the reaction in a microreactor.

Claims

C L A I M S

1. Process for preparing an alkenone, which comprises the following reaction steps:

(a) reacting a carboxylic acid halide with a vinyl ether to form a halogenated precursor of the alkenone and

(b) eliminating hydrogen halide from said precursor to form the alkenone, wherein reaction step (a) is at least partially conducted in a microreactor.

2. Process according to claim 1, wherein reaction step (a) is partially conducted in a microreactor and completed in a stirred tank reactor.

3. Process according to claim 1 or 2, for preparation of an alkenone, wherein the alkenone has the Formula (I):

R₁-C(O)-C(H)=C(H)-OR₂ (I) wherein Ri represents a Ci-Cio alkyl group which is optionally substituted by at least one halogen atom or Ri represents CF₃C(0)CH₂; and R₂ represents aryl, substituted aryl, or a Ci-Cio alkyl group which is optionally substituted by at least one halogen atom wherein the carboxylic acid halide in reaction step (a) has the Formula (II): R₁-C(O)X (II) in which X represents fluorine, chlorine or bromine and Ri has the meaning given above, and the vinyl ether in reaction step (a) has the Formula (III):

CH₂=C(H)-OR₂ (III) in which R₂ has the meaning given above.

4. Process according to claim 3, wherein Ri is a fluorinated C1-C4 alkyl group, preferably a CF₃ group.

5. Process according to claim 3 or 4, wherein R₂ is a C1-C4 alkyl group, preferably a methyl or an ethyl group.

6. Process according to anyone of claims 1 to 5, wherein the carboxylic acid halide is trifluoroacetyl chloride.

7. Process according to anyone of claims 1 to 6, wherein the reaction of the carboxylic acid halide with the vinyl ether in reaction step (a) is carried out by introducing the carboxylic acid halide into a reaction medium comprising from 20 %, preferably from 50 % to less than 100 % by weight of vinyl ether, relative to the total weight of the reaction medium.

8. Process according to anyone of claims 1 to 7 wherein step (a) is carried out in a first reaction zone and step (b) is carried out in a second reaction zone different from the first reaction zone.

9. Process according to claim 8, wherein the first reaction zone is a microreactor optionally followed by a stirred tank reactor and the second reaction zone is a distillation column.

10. Process according to anyone of claims 1 to 9, wherein step (a) is carried out at a pressure of 2 bar abs. or more.

11. Process according to anyone of claims 1 to 10, which is carried out continuously.

12. Process according to anyone of claims 1 to 11, wherein the microreactor comprises channels having a channel width of less than 1000 μπι, preferably less than 500 μπι.

13. Process according to anyone of claims 1 to 12, wherein the microreactor comprises a micromixer.

14. Process according to anyone of claims 1 to 13, wherein the microreactor comprises a combination of a micromixer and a sandwich-type microreactor.

15. Reactor for conducting a process according to any one of claims 1 to 12, comprising at least one microreactor and an, optionally stirred, tank reactor.