Method for purifying organic compound

Abstract

Provided is a method for purifying an organic compound, whereby it is possible to recover the organic compound at a high purity and to inexpensively purify the organic compound by a simple method. This method for purifying an organic compound comprises: a step (A) for preparing a mixture containing an organic compound, hydrogen fluoride, and an SiO2-containing material; and a step (B) in which a base is added to the mixture. As a result, it is possible to recover the organic compound with high purity and to inexpensively refine the organic compound by a simple method.

Description

[0001] This application is a divisional application of the same patent application, filed on June 1, 2017, with application number 201780033006.0. Technical Field

[0002] This invention relates to a method for purifying organic compounds. Background Technology

[0003] Difluoroacetate and other difluoroester compounds are known to be useful compounds used as intermediates in the manufacture of pharmaceuticals and pesticides, as well as battery materials, and are therefore highly valuable. Consequently, research is actively underway on technologies for the high-yield and high-purity production of difluoroester compounds. One known method for producing difluoroester compounds is, for example, 1) heating 1-alkoxy-1,1,2,2-tetrafluoroethane in the presence of a catalyst to generate difluoroacetyl fluoride, which is then reacted with a lower alcohol (e.g., Patent Document 1).

[0004] In the manufacturing method described in 1) above, the hydrogen fluoride (HF) generated in the reaction is reacted with triethylamine, and the product is purified by washing with dichloromethane solvent. During this purification process, hydrolysis may occur, potentially reducing the yield and purity of the target compound. Therefore, various purification methods have been investigated to obtain the target compound with high yield and purity. As one example, a scheme has been proposed that involves adding an aqueous solution of an inorganic compound that reacts with fluoride ions to form a fluoride in difluoroacetate containing HF, followed by removing the generated salt to purify the product (e.g., Patent Document 2). Furthermore, methods for manufacturing difluoroacetate compounds without generating difficult-to-separate HF have also been investigated. As a specific example, a scheme has been proposed that involves decomposing 1-alkoxy-1,1,2,2-tetrafluoroethane in the presence of lithium chloride and an alcohol to obtain crude difluoroacetyl fluoride, generating hydrogen chloride and lithium fluoride, and removing the acidic component from the reaction system in the form of hydrogen chloride gas (e.g., Patent Document 3).

[0005] Existing technical documents Patent documents Patent Document 1: Japanese Patent Application Publication No. 8-92162; Patent Document 2: Japanese Patent Application Publication No. 2002-179623; Patent Document 3: Japanese Patent Application Publication No. 2011-93886 Summary of the Invention

[0006] The technical problem that the invention aims to solve However, the technology disclosed in Patent Document 2 generates a large amount of insoluble salts, leading to operational difficulties. Furthermore, the recovery rate after two washing cycles is as low as 77%, and the hydrogen fluoride (HF) content after washing is as high as 300 ppm, thus raising concerns about high purity. Additionally, the technology disclosed in Patent Document 3 requires expensive lithium chloride as a byproduct and also suffers from the problem of generating difficult-to-handle solid lithium fluoride as waste.

[0007] The present invention was made in view of the above circumstances, and its object is to construct a purification process for recovering organic compounds with higher purity from organic compounds such as ester compounds containing hydrogen fluoride as impurities. Specifically, the object of the present invention is to provide a purification method for organic compounds that can recover organic compounds with high purity and can be purified in a simple and inexpensive manner.

[0008] Methods for solving technical problems To achieve the above objectives, the inventors of this invention conducted repeated and in-depth research and discovered that by performing alkaline treatment in the presence of a SiO2-containing material on a mixture containing organic compounds and hydrogen fluoride, the above objectives could be achieved, thus completing this invention.

[0009] That is, the present invention includes, for example, the subject matter described in the following items.

[0010] Item 1. A method for purifying an organic compound, comprising: Step A, which prepares a mixture comprising an organic compound, hydrogen fluoride, and a SiO2-containing material; and Step B involves adding alkali to the mixture described above.

[0011] Item 2. A method for purifying an organic compound as described in Item 1, wherein the organic compound is an ester compound represented by the following general formula (1).

[0012] R A COOR B (1) (where R) A and R B R is an organic group. A and R B Each can be the same as or different from the other. Item 3. A method for purifying an organic compound as described in Item 2, wherein, in the organic ester compound represented by formula (1) above, R A and R B It is an alkyl group, a haloalkyl group, an alkyl group containing an ether-containing oxygen atom, or an alkyl group containing an ether-containing oxygen atom that is substituted by one or more halogen atoms.

[0013] Item 4. A method for purifying an organic compound as described in any one of items 1 to 3, wherein, after adding alkali in step B, a step C is performed, which involves at least one treatment selected from distillation, filtration, and separation.

[0014] Item 5. A method for purifying an organic compound as described in any one of items 1 to 4, wherein, prior to step B, a separation step is performed where an organic solvent is added to the mixture obtained in step A for extraction treatment, and then a layer containing the organic solvent of the mixture is removed.

[0015] Item 6. A method for purifying an organic compound as described in Item 3, wherein, in general formula (1), R A HCF2, R B It is an alkyl group having 1 to 4 carbon atoms.

[0016] Item 7. A method for purifying an organic compound as described in any one of items 1 to 6, wherein the SiO2-containing material is selected from at least one of silica powder and silica gel.

[0017] Item 8. A method for purifying an organic compound as described in any one of items 1 to 7, wherein the base is selected from at least one of metal bicarbonates and metal alkoxides.

[0018] Item 9. A method for purifying an organic compound as described in any one of items 1 to 8, wherein the mixture is prepared by adding a SiO2-containing material to a mixture containing the organic compound and hydrogen fluoride.

[0019] Item 10. A method for purifying an organic compound as described in Item 5, wherein the organic solvent is at least one selected from straight-chain or branched alkanes having 8 to 16 carbon atoms and straight-chain or branched olefins having 8 to 16 carbon atoms.

[0020] Item 11. A method for manufacturing an organic compound, comprising a refining step having step A and step B as described in any one of claims 1 to 10.

[0021] The effects of the invention According to the purification method of the organic compounds of the present invention, organic compounds such as ester compounds can be recovered with high purity, and organic compounds can be obtained inexpensively and easily. Detailed Implementation

[0022] The embodiments of the present invention will now be described in detail. In this specification, the terms "containing" and "comprising" include the concepts of "containing," "comprising," "substantially constituted by," and "consisting solely of."

[0023] In the purification method of this embodiment, impurities such as hydrogen fluoride can be removed from organic compounds and the organic compounds can be recovered. In particular, the purification method of this embodiment includes: step A, which prepares a mixture containing an organic compound, hydrogen fluoride and a SiO2-containing material; and step B, which adds an alkali to the mixture.

[0024] According to the above-described purification method, organic compounds can be recovered with high purity, and organic compounds can be obtained inexpensively and easily. Therefore, the purification method of the present invention is suitable, for example, as a method for obtaining difluoroacetates and other difluoroester compounds that are useful as intermediates in pharmaceuticals and pesticides with high purity.

[0025] In step A, a mixture containing organic compounds, hydrogen fluoride, and SiO2-containing materials is prepared.

[0026] There is no particular limitation on the types of organic compounds. For example, ester compounds represented by the following general formula (1) can be exemplified as organic compounds.

[0027] R A COOR B (1) (where R) A and R B R is an organic group. A and R B Each can be the same as or different from the other.

[0028] The organic groups in formula (1) are not specifically limited.

[0029] R in the above equation (1) A and R B Specific examples of organic groups include alkyl groups, haloalkyl groups, alkyl groups containing ether oxygen atoms, or alkyl groups containing ether oxygen atoms that are replaced by one or more halogen atoms.

[0030] The alkyl group preferably has 1 to 20 carbon atoms, more preferably 1 to 12, and particularly preferably 1 to 4. Further specific examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, and octyl. The alkyl group can be either straight-chain or branched.

[0031] As the aforementioned haloalkyl group, groups in which one or more hydrogen atoms in the alkyl group are replaced by halogen atoms can be listed. There is no particular limitation on the halogen atom, but a fluorine atom is preferred. The haloalkyl group may have all its hydrogen atoms replaced by halogen atoms.

[0032] Examples of alkyl groups containing ether-containing oxygen atoms include alkoxy or alkoxyalkyl groups. The number of carbon atoms in the alkyl group containing ether-containing oxygen atoms is preferably 1 to 20, more preferably 1 to 12, and particularly preferably 1 to 4.

[0033] Furthermore, the alkyl group containing the aforementioned ether-containing oxygen atom can be a group having two or more ether-containing oxygen atoms.

[0034] As an alkyl group containing an ether-containing oxygen atom that has been substituted with one or more halogen atoms, examples include groups in which one or more hydrogen atoms of the aforementioned alkyl group containing an ether-containing oxygen atom are substituted with halogen atoms. For example, an alkyl group containing an ether-containing oxygen atom that has been substituted with a halogen atom is a halogen-containing (poly)ether group, that is, a (poly)ether group having one or more halogen atoms. There is no particular limitation on the halogen atom, but a fluorine atom is preferred. An alkyl group containing an ether-containing oxygen atom that has been substituted with one or more halogen atoms may have all its hydrogen atoms substituted with halogen atoms.

[0035] Specific examples of alkyl groups containing ether-containing oxygen atoms that are replaced by one or more halogen atoms, as described above, include fluoroalkoxy, fluoroalkoxyalkyl, perfluoroalkoxy, and perfluoroalkoxyalkyl.

[0036] Furthermore, the alkyl group containing an ether-containing oxygen atom that is replaced by one or more halogen atoms as described above can be a group having two or more ether-containing oxygen atoms.

[0037] As R in equation (1) A For example, HCF2 is preferred. In this case, the ester compound shown in formula (1) can be obtained with higher purity.

[0038] As R in equation (1) B For example, it is an alkyl group with 1 to 4 carbon atoms, preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, etc. In this case, the ester compound shown in formula (1) can be obtained with higher purity.

[0039] The SiO2-containing material used in process A can be either SiO2 alone or a material containing SiO2 as a component. When the SiO2-containing material is SiO2, the purity of SiO2 is not particularly limited, but when it is around 80% by weight or higher, the target organic compound can be obtained in high yield.

[0040] Specific examples of SiO2-containing materials include silica gel, silica, silica sand, glass, and quartz. Additionally, SiO2-containing materials can be composite oxides of SiO2 with other metals and / or metal oxides. Examples of such composite oxides include silica-titanium oxide composite oxides, silica-alumina composite oxides, and silica-alumina-iron composite oxides.

[0041] Commercially available SiO2-containing materials can be used, for example. More preferably, silica gel, silica powder, or silica sand powder are preferred materials, and at least one selected from silica powder and silica gel is particularly preferred. In this case, organic compounds can be obtained with exceptionally high purity.

[0042] The shape of SiO2-containing materials is not particularly limited. However, from the viewpoint of maintaining good reactivity, powder with a particle size of about 1 μm to 2 mm is preferred.

[0043] There are no particular limitations on the method for preparing the mixture in step A. For example, if the organic compound is an ester compound, an ester compound containing hydrogen fluoride as a byproduct can be synthesized in advance (for example, refer to "Manufacturing Method 1-1" described later). A SiO2-containing material can be added to the product containing the hydrogen fluoride and the ester compound, thereby preparing a mixture containing the ester compound, hydrogen fluoride, and a SiO2-containing material. Alternatively, when the ester compound is synthesized in advance by reaction in the presence of a SiO2-containing material (producing hydrogen fluoride as a byproduct), the product obtained by this synthesis can be used as the above-mentioned mixture (for example, refer to "Manufacturing Method 1-2" described later). Furthermore, methods for preparing the mixture used in step A include preparing the ester compound, hydrogen fluoride, and SiO2-containing material separately and mixing them in a specified amount.

[0044] Here, we will describe an example of a method for manufacturing an ester compound as shown in formula (1) above. As a method for manufacturing an ester compound, for example, a compound as shown in general formula (2) below can be used as a starting material.

[0045] R A CF2OR B (2) (where R) A and R B The meaning is the same as that of equation (1), R A and R B Each can be the same as or different from the other.

[0046] Specifically, the aforementioned ester compound can be obtained by reacting the starting material shown in formula (2) in the gas phase in the presence of a metal oxide catalyst, followed by treatment with an alcohol. Hereinafter, this method will be referred to as "manufacturing method 1-1". This manufacturing method 1-1 can be carried out, for example, in the same manner as described in Patent Document 1.

[0047] As a metal oxide catalyst, a metal oxide that enables the above reaction to proceed efficiently is preferred. Examples of metal components in this metal oxide include aluminum, zirconium, and titanium. The metal oxide catalyst is preferably selected from at least one of alumina (Al₂O₃), zirconium oxide (ZrO₂), and titanium oxide (TiO₂), and alumina is particularly preferred from the perspective of reactivity and catalyst lifetime.

[0048] Furthermore, metal oxide catalysts can contain atoms other than the metal component and oxygen. Examples of these other atoms include fluorine atoms and chlorine atoms. Other atoms can be, for example, partially fluorinated alumina, partially chlorinated alumina, partially fluorinated chlorinated alumina, partially fluorinated zirconium oxide, partially fluorinated titanium oxide, etc. The ratio of chlorine to fluorine atoms in the metal oxide catalyst is not particularly limited.

[0049] The metal oxide catalyst can be activated before the reaction. Conventional methods can be used for activation, and there are no particular limitations. A preferred activation method involves thoroughly dehydrating the metal oxide catalyst in a nitrogen stream at approximately 250°C to 300°C, and then activating it with dichlorodifluoromethane (hereinafter referred to as R12), dichlorodifluoromethane, or hydrogen fluoride.

[0050] In the manufacturing method 1-1 described above, an inert gas may be present in the reaction system. Examples of such inert gases include nitrogen and rare gases, with nitrogen and argon being preferred from the perspectives of ease of operation and availability.

[0051] The temperature of the gas-phase reaction varies depending on the type of catalyst and the raw materials, and can be set to approximately 100–300°C. The reaction time can be set within the range of 0.1 seconds to 24 hours. There is no particular limitation on the reaction pressure; atmospheric pressure, reduced pressure, or pressurized pressure are all acceptable. For example, the reaction pressure can be set within the range of 0.05–1 MPa using a gauge.

[0052] In the above gas-phase reaction, acyl fluoride (R) is generated. A COF). Through this acyl fluoride (R) A An alcohol is added to COF to produce an ester compound as shown in formula (1). Additionally, hydrogen fluoride is produced as a byproduct in this reaction.

[0053] There are no particular restrictions on the types of alcohols mentioned above; for example, R... B OH(R) B The meaning of the compound shown in formula (1) is the same. As R B For example, alkyl groups having 1 to 4 carbon atoms are preferred, specifically methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, etc. R is particularly preferred. B R in OH BR of the compound shown in formula (2) used in manufacturing method 1-1 B The same. For example, in the compound shown in formula (2), R B When it is ethyl, R is preferred. B OH represents ethanol. R B OH can be used in combination with two or more different types.

[0054] When the ester compound is manufactured according to the above manufacturing method 1-1, the product contains the ester compound shown in formula (1) as the main product. In addition, the product also contains hydrogen fluoride. Therefore, when a SiO2-containing material is added to the product, the mixture of step A can be prepared. In addition, SiF4 gas is also generated in the reaction, but the SiF4 gas can be released through a condenser to a cleaning tower in which an aqueous HF solution is added, and recovered in the form of fluorosilicic acid.

[0055] In the above manufacturing method 1-1, R is the compound shown in formula (2). A and R B The combination of R is particularly preferred. A HCF2 and R B It is an alkyl group having 1 to 4 carbon atoms. This is because, under these conditions, the desired ester compound of formula (1) can be easily obtained with high purity, and the obtained ester compound of formula (1) is particularly useful as an intermediate for pharmaceuticals and pesticides. R in formula (2) A HCF2 and R B When the alkyl group has 1 to 4 carbon atoms, the resulting ester compound represented by formula (1) is a difluoroacetate.

[0056] In addition, in the above manufacturing method 1-1, after synthesizing the ester compound containing hydrogen fluoride as a byproduct, a SiO2-containing material is added. However, it is not limited to this. Alternatively, the ester compound containing hydrogen fluoride as a byproduct can be synthesized in the presence of the SiO2-containing material to prepare the mixture of step A.

[0057] For example, in manufacturing method 1-1, after generating the aforementioned acyl fluoride and before adding the alcohol, a SiO2-containing material can be added beforehand, and then the alcohol can be added to generate an ester compound. Hereinafter, this method of generating an ester compound by adding a SiO2-containing material beforehand will be referred to as "manufacturing method 2". In this manufacturing method 2, since hydrogen fluoride is generated as a byproduct, an ester compound containing hydrogen fluoride as a byproduct can also be obtained. Therefore, when manufacturing the ester compound shown in formula (1) according to the above manufacturing method 2, the product may contain hydrogen fluoride in addition to the ester compound as the main product. Furthermore, in this manufacturing method 2, since the SiO2 used in the reaction also remains in the product, the reactants obtained from the above manufacturing method 2 can be directly used as the mixture of step A.

[0058] Besides manufacturing method 1-1, as a method for manufacturing the ester compound shown in formula (1) above, one can be listed as making the compound shown in formula (2) above in a SiO2-containing material and R B OH(R) B The method of contacting an acid catalyst in the presence of (the meaning of which is the same as that of formula (1)). Hereinafter, this method will be referred to as "manufacturing method 1-2". In this manufacturing method 1-2, a crude product containing the ester compound shown in formula (1) and hydrogen fluoride can be obtained. In addition, the crude product also contains SiO2 used in the reaction.

[0059] In manufacturing methods 1-2, the manner and preferred manner of the ester compound shown in formula (1) and the manner and preferred manner of the compound shown in formula (2) are the same as in manufacturing method 1-1. Furthermore, in manufacturing method 1-2, the manner and preferred manner of the SiO2-containing material are the same as in manufacturing method 1-1. And, in manufacturing method 1-2, R... B OH(R) B The meaning of (1) is the same as that of the manufacturing method 1-1.

[0060] R B The amount of OH used is preferably about 0.03 to 1 mole of the compound shown in formula (2) used as a raw material, and more preferably about 0.3 to 0.6 moles.

[0061] The acid catalyst used in manufacturing methods 1-2 can be any substance that is active in the acid hydrolysis reaction; there are no particular limitations. Specific examples of such acid catalysts include sulfuric acid, p-toluenesulfonic acid, methanesulfonic acid, boron trifluoride, trifluoromethanesulfonic acid, trifluoroacetic acid, and difluoroacetic acid. Sulfuric acid is particularly preferred. Two or more different acid catalysts can be used in combination.

[0062] In manufacturing methods 1-2, the SiO2-containing material and R B In the presence of OH, there is no particular limitation on the method of contacting the compound shown in formula (2) with the acid catalyst; for example, it can be contacted according to known methods. Examples include the compound shown in formula (2), SiO2-containing materials, and R... B A method involving simultaneous contact of OH and an acid catalyst. More specifically, this method can be applied to compounds containing formula (2), SiO2-containing materials, and R. B Methods such as adding acid catalysts dropwise into the reaction vessel for OH.

[0063] Regarding the amount of acid catalyst used, relative to 1 mole of the compound shown in formula (2), it can be, for example, about 0.1 to 0.5 moles, preferably about 0.2 to 0.4 moles. By setting the amount of acid catalyst used within the above range, the reaction can proceed even at low reaction temperatures such as 20 to 60°C without using an excess of acid catalyst. Furthermore, by using the acid catalyst in the above-mentioned amount with R... B Using OH in combination, the ester compound shown in formula (1) can be obtained with high selectivity.

[0064] By using SiO2-containing materials and R B In the presence of OH, the compound shown in formula (2) is brought into contact with an acid catalyst to react.

[0065] The reaction temperature can be, for example, around 20 to 60°C, preferably 30 to 50°C. By setting such a low reaction temperature, the volatilization of the raw materials and byproducts can be suppressed, and the ester compound represented by formula (1) can be obtained in good yield.

[0066] There are no particular limitations on the atmosphere during the reaction, but it is preferable to carry out the reaction at atmospheric pressure, provided that the reaction is carried out in the presence of excess moisture. When carrying out the reaction at atmospheric pressure, it is preferable to carry out the reaction in dry air, or in an atmosphere of nitrogen or other inert gases.

[0067] There is no particular pressure limit during the reaction. Since the reaction system contains SiO2, SiF4 gas is produced as the reaction proceeds, which easily increases the pressure inside the container.

[0068] The reaction time is usually around 3 to 48 hours.

[0069] In the reactions of manufacturing methods 1-2, R can also be used. B OH is added to the reaction system in two separate steps, which improves the selectivity and yield of the ester compound represented by formula (1). In this method, it is preferable to use R at the start of the reaction. B The amount of OH relative to 1 mole of the compound shown in formula (2) is about 0.01 to 0.5 moles, preferably about 0.2 to 0.3 moles. After more than 30 minutes from the start of the reaction, preferably more than 1 hour, and even more preferably more than 3 hours, about 0.02 to 0.5 moles, preferably about 0.1 to 0.3 moles of R are added. B OH. Add R for the second time. B After OH, the reaction is allowed to continue for about 1 to 10 hours, preferably with an overall reaction time of about 3 to 48 hours. Using this method, there is no decrease in reaction rate, and the ester compound shown in formula (1) can be obtained with high selectivity and good yield.

[0070] In the reactions of manufacturing methods 1-2, in addition to the ester compound represented by formula (1) which is the target product, hydrogen fluoride is also generated as a byproduct. Therefore, by using the reactions of manufacturing methods 1-2, a crude product containing the above-mentioned ester compound and hydrogen fluoride can be obtained. Furthermore, the crude product may also contain various raw materials (i.e., unreacted raw materials) used in manufacturing methods 1-2.

[0071] Furthermore, since the reaction system contains SiO2, the HF generated from the hydrolysis of the compound shown in equation (2) can react with SiO2 within the system. This also generates SiF4 as a byproduct. However, the SiF4 generated here is a gas, so it can be easily removed from the system during or after the reaction. The SiF4 gas generated here can be released, for example, through a condenser into a cleaning tower containing an aqueous HF solution, thereby being recovered as fluorosilicic acid.

[0072] The ester compound is not limited to the manufacture methods 1-1, 1-2 and 2, but can also be an ester compound obtained by other methods.

[0073] As described above, the mixture of step A can be prepared, for example, by adding a SiO2-containing material to the product obtained by manufacturing method 1-1. Alternatively, the mixture of step A can also be prepared by implementing manufacturing method 2.

[0074] The content of organic compounds (e.g., ester compounds) in the mixture is not particularly limited. From the viewpoint of recovering organic compounds with higher purity, the lower limit of the content of organic compounds relative to the total amount of organic compounds, hydrogen fluoride, and SiO2 can be 10% by mass. More specifically, the content of organic compounds relative to the total amount of organic compounds, hydrogen fluoride, and SiO2 can be 10 to 90% by mass, preferably 20 to 80% by mass, and particularly preferably 30 to 70% by mass.

[0075] Furthermore, the content of SiO2-containing material in the mixture is not particularly limited. From the viewpoint of recovering organic compounds with higher purity, the lower limit of the SiO2 content relative to the total amount of organic compounds, hydrogen fluoride, and SiO2 can be 10% by mass. More specifically, the SiO2-containing material can be 10 to 50% by mass relative to the total amount of organic compounds, hydrogen fluoride, and SiO2-containing material, preferably 15 to 40% by mass.

[0076] Furthermore, the content of hydrogen fluoride in the mixture is not particularly limited. From the viewpoint of recovering organic compounds with higher purity, the lower limit of the hydrogen fluoride content relative to the total amount of organic compounds, hydrogen fluoride, and SiO2 can be 1% by mass. More specifically, the hydrogen fluoride content relative to the total amount of organic compounds, hydrogen fluoride, and SiO2-containing materials can be 1 to 30% by mass, preferably 5 to 20% by mass.

[0077] In step B, an alkali is added to a mixture containing an organic compound, hydrogen fluoride, and a SiO2-containing material. Through step B, hydrogen fluoride and SiO2 are removed from the mixture obtained from step A, and the organic compound represented by formula (1) is recovered.

[0078] The type of base is not particularly limited; it can be any kind of inorganic or organic compound. Specific examples of bases include inorganic compounds such as NaHCO3, KHCO3, Ca(OH)2, Mg(OH)2, NaOH, and KOH, as well as metal alkoxides such as NaOR and KOR (where R is, for example, an alkyl group having 1 to 4 carbon atoms). When these bases are used, metal fluorides are formed, making separation easier and thus facilitating the production of high-purity organic compounds. In particular, when the base is a metal alkoxide such as NaOR or KOR, no water is generated during neutralization using the base, suppressing unwanted hydrolysis, which is preferable. Furthermore, when the base is inorganic, NaHCO3 and KHCO3 are preferred from the viewpoint of suppressing hydrolysis during neutralization. In addition, two or more different bases can be used together.

[0079] When adding a base to the reaction mixture in step B, the base can be added in solid form, or it can be pre-dissolved in a solvent and added as a base solution. Regarding the solvent used to dissolve the base, for example, when the base is inorganic, it can be water, or a high-boiling-point organic solvent such as decane, or other organic solvents. In this case, the base can be either inorganic or organic.

[0080] There is no limit to the amount of alkali used. From the viewpoint of easily removing impurities such as hydrogen fluoride, it can be 0.01 to 0.2 moles relative to 1 mole of organic compound. Preferably, the amount of alkali used is 0.01 to 0.1 moles relative to 1 mole of organic compound.

[0081] As described above, the mixture contains organic compounds, hydrogen fluoride, and SiO2-containing materials. Furthermore, the SiO2 in the mixture reacts with hydrogen fluoride to generate SiF4 as a byproduct. Additionally, hydrogen fluoride reacts with SiO2 to further generate H2SiF6 as a byproduct, thus also forming such compounds as byproducts.

[0082] That is, in addition to the organic compounds, hydrogen fluoride and SiO2-containing materials mentioned above, the mixture may also contain compounds such as SiF4 and H2SiF6 as impurities.

[0083] When an alkali is added to such a mixture, neutralization occurs, and hydrogen fluoride, SiF4, H2SiF6, etc., are decomposed by the alkali and form M as a precipitate. a SiF6 and M b F. Here, M is an alkali metal derived from the above-mentioned base, such as Na, K, Ca, or Mg. When M is Na or K, a is 2 and b is 1; when M is Ca or Mg, a is 1 and b is 0.5.

[0084] M generated through the above neutralization a SiF6 and M b F is formed in the form of precipitates, and therefore can be easily removed from the mixture. As a result, organic compounds (such as the ester compounds shown in formula (1)) can be easily extracted from the mixture, and organic compounds can be obtained with high purity.

[0085] The base is preferably selected from at least one of metal bicarbonates and metal alkoxides. In this case, the above-mentioned neutralization reaction is easily carried out. Examples of metal bicarbonates include NaHCO3 and KHCO3, with NaHCO3 being preferred. Examples of metal alkoxides include sodium methoxide and sodium ethoxide. In particular, when the base is sodium alkoxide, HF can be removed by the following reaction.

[0086] RONa + HF → NaF + ROH (The meaning of R is the same as that of formula (1), and alkyl groups with 1 to 4 carbon atoms are particularly preferred).

[0087] Furthermore, the formation of water can be suppressed in this reaction, producing ROH (alcohol). This ROH is easier to separate than water through operations such as distillation, so HF can be removed more easily when the base is sodium alkoxide.

[0088] There are no particular limitations on the method for extracting organic compounds from a mixture treated with alkali. For example, the organic compound shown in formula (1) can be extracted by distillation, filtration, separation, etc. These treatments can be combined.

[0089] That is, in the purification method of this embodiment, after adding alkali in step B, a step C can be performed, which involves at least one treatment selected from distillation, filtration, and separation. Therefore, organic compounds can be extracted from the alkali-treated mixture with high purity using a simple method.

[0090] The distillation described above can be carried out under reduced pressure of approximately 1 kPa or at atmospheric pressure. From the viewpoint of minimizing yield reduction due to evaporation, the filtration described above is preferably carried out at atmospheric pressure or under pressure. The separation method described above is not particularly limited and can be carried out at a temperature of approximately 0–40°C and at atmospheric pressure. The organic solvent used in this separation is not particularly limited; for example, the same organic solvent described later can be used.

[0091] In the purification method of this embodiment, before step B, there may be a separation step in which an organic solvent is added to the mixture obtained in step A for extraction treatment, and then the layer containing the organic solvent of the mixture is taken out.

[0092] In the above-described separation process, by adding an organic solvent to the mixture, the mixture can be extracted into the organic solvent layer. The extracted mixture mainly contains organic compounds. Although other impurities such as hydrogen fluoride are also extracted into the organic solvent layer, the amount of impurities in the organic solvent layer is significantly reduced compared to before extraction.

[0093] After the above extraction process, the organic solvent layer is removed, and the other layers are discarded. The mixture contained in this organic solvent layer is then subjected to the same alkali treatment as described above, resulting in a neutralization reaction. The mixture is removed, and the organic compound is obtained with high purity. Similarly, after the alkali treatment, step C may be performed as needed.

[0094] By performing the above separation process, the amount of impurities such as hydrogen fluoride in the mixture is further reduced, thus resulting in the acquisition of the target organic compound with higher purity.

[0095] The type of organic solvent used in the separation process is not particularly limited. For example, when the organic solvent is an ester compound obtained by manufacturing method 1 or manufacturing method 2 described above, it is preferable to select at least one of straight-chain or branched alkanes with 8 to 16 carbon atoms and straight-chain or branched alkenes with 8 to 16 carbon atoms. In this case, the ester compound represented by formula (1) can be easily extracted into the organic solvent layer, and the ester compound can be obtained with higher yield and higher purity. Examples of such organic solvents include n-decane. In addition, when the organic compound is not an ester compound obtained by manufacturing method 1 or manufacturing method 2, it is preferable to use an organic solvent that has a boiling point difference of 50°C or more with the organic compound and is sparingly soluble or insoluble in water. Two or more different solvents can be used together.

[0096] Furthermore, in the purification method of this embodiment, the mixture can be distilled before step B. This distillation can be performed before or after the separation step. Alternatively, distillation can be performed only before step B without the separation step.

[0097] In the purification method of this embodiment, impurities can be thoroughly removed, and the target organic compound can be obtained with high purity. In particular, the purification method of this embodiment is advantageous in that hydrogen fluoride, which was previously difficult to remove, can be removed in a simpler way.

[0098] Furthermore, in the purification method of this embodiment, since SiO2-containing materials are present in the mixture containing alkali, some of the hydrogen fluoride reacts as described above. This reduces the amount of hydrogen fluoride in the mixture, thus reducing the amount of alkali used. As a result, the organic compound of the target is less prone to hydrolysis due to alkali, and the target ester compound can be obtained in high yield. In particular, since ester compounds may undergo hydrolysis due to alkali, the purification method of the present invention is especially effective when the organic compound is an ester compound.

[0099] Furthermore, since organic compounds are less likely to contain hydrogen fluoride as an impurity, problems such as reactor corrosion are less likely to occur even when the product is supplied to subsequent processes. Therefore, the purification method of this embodiment is suitable, for example, as a method for manufacturing difluoroester compounds such as ethyl difluoroacetate, which are useful as intermediates in pharmaceuticals and pesticides.

[0100] Furthermore, in existing methods such as distillation to remove hydrogen fluoride, even if the hydrogen fluoride is removed, byproducts such as fluorosilicic acid tend to remain as impurities. Therefore, for example, when continuously synthesizing ester compounds using manufacturing method 2, fluorosilicic acid and other byproducts tend to remain as impurities, and SiO2 generated from the decomposition of these impurities can accumulate in the cooling tubes, causing a decrease in thermal conductivity within the cooling tubes. However, in the purification method of this embodiment, by performing alkali treatment, the H2SiF6 present as an impurity forms a more stable salt (e.g., Na2SiF6), effectively preventing the accumulation of SiO2 in the cooling tubes. Therefore, by applying the purification method of this embodiment, a decrease in thermal conductivity within the cooling tubes is less likely, and a stable reaction can be maintained even when continuously using manufacturing method 2 to react the ester compound. As a result, the reduction in the recovery rate of the ester compound can be suppressed, and the ester compound can be manufactured with high yield and high purity for an extended period.

[0101] Based on the above viewpoints, the purification method of the present invention is preferably included in the method for manufacturing organic compounds; that is, the method for manufacturing organic compounds preferably includes a purification step that includes at least step A and step B. This allows for the production of organic compounds with higher purity. The purification method of this embodiment is particularly suitable when the organic compound is the ester compound described above.

[0102] Example The present invention will now be described in more detail with reference to embodiments, but the present invention is not limited to these embodiments.

[0103] (Example 1) 60 g of silica gel was added to a 500 mL autoclave made of heat-resistant and corrosion-resistant nickel-based alloy (Hastelloy) equipped with a condenser. Then, 300 g of ethyl difluoroacetate containing 20% ​​by mass of hydrogen fluoride (containing 3.0 mol of hydrogen fluoride and 1.93 mol of ethyl difluoroacetate) was slowly added dropwise at room temperature to prepare a mixture. The mixture in the autoclave was heated and stirred at 50 °C for 6 hours, and then cooled to room temperature.

[0104] After transferring the mixture to a fluoropolymer separatory funnel, the organic layer was recovered at room temperature. 50 g of a 5% NaHCO3 aqueous solution was added to the organic layer, followed by washing. The organic layer was then recovered. The recovered amount was 217 g (90.4%), and the fluoride ion concentration was 13 ppm. The fluoride ion concentration was determined using an ion meter and analyzed according to ASTM standard D-1179. The same procedure was followed in subsequent examples and comparative examples.

[0105] (Example 2) 60 g of silica gel was added to a 500 mL autoclave made of heat-resistant and corrosion-resistant nickel-based alloy and equipped with a condenser. Then, 300 g of ethyl difluoroacetate containing 20% ​​by mass of hydrogen fluoride (containing 3.0 mol of hydrogen fluoride and 1.93 mol of ethyl difluoroacetate) was slowly added dropwise at room temperature to prepare a mixture. The mixture in the autoclave was heated and stirred at 50 °C for 6 hours, and then cooled to room temperature.

[0106] After transferring the mixture to a fluoropolymer separatory funnel, the lower layer was separated at room temperature, and the organic layer was recovered. 50 g of a 5% NaHCO3 aqueous solution was added to this organic layer, followed by distillation at atmospheric pressure. The recovery rate of ethyl difluoroacetate was 197 g (82%), and the fluoride ion concentration was 14 ppm.

[0107] (Example 3) 60 g of silica gel was added to a 500 mL autoclave made of heat-resistant and corrosion-resistant nickel-based alloy and equipped with a condenser. Then, 300 g of ethyl difluoroacetate containing 20% ​​by mass of hydrogen fluoride (containing 3.0 mol of hydrogen fluoride and 1.93 mol of ethyl difluoroacetate) was slowly added dropwise at room temperature to prepare a mixture. The mixture in the autoclave was heated and stirred at 50 °C for 6 hours, and then cooled to room temperature.

[0108] After transferring the mixture to a fluoropolymer separatory funnel, the lower layer was separated at room temperature, and the organic layer was recovered. 5.0 g of sodium ethoxide was added to this organic layer, followed by distillation at atmospheric pressure. The recovery rate of ethyl difluoroacetate was 205 g (85%), and the fluoride ion concentration was 8 ppm.

[0109] (Example 4) In a 500 mL autoclave made of heat-resistant and corrosion-resistant nickel-based alloy and equipped with a condenser, 60 g of silica gel, 300 g of 1-ethoxy-1,1,2,2-tetrafluoroethane, and 19.0 g of ethanol were added, and the internal temperature was heated to 50 °C. Then, 100.8 g of 98% sulfuric acid was added dropwise. After heating and stirring the autoclave at 50 °C for 18 hours, 28.4 g of ethanol was added, and the mixture was heated and stirred at 50 °C for 5 hours. The resulting reaction mixture (crude product) was cooled to room temperature.

[0110] After transferring the reaction mixture to a fluoropolymer separatory funnel, 300g of n-decane was added for washing and separation, and the upper organic layer was recovered. 200g of a 5% NaHCO3 aqueous solution was added to this organic layer for washing (step B). The alkali-treated reaction mixture was then recovered and added to a 1L glass flask for distillation using a glass distillation column at atmospheric pressure. The fraction with a purity of 99.8% or higher was collected to give 185g of ethyl difluoroacetate (73% yield). The F ion concentration in ethyl difluoroacetate was 5ppm.

[0111] (Example 5) In step B, instead of 200g of 5% NaHCO3 aqueous solution, 15g of NaHCO3 was used. Otherwise, ethyl difluoroacetate (192g, yield 75%) was obtained according to the same method as in Example 4. The F ion concentration in ethyl difluoroacetate was 13ppm.

[0112] (Example 6) In step B, 15g of NaHCO3 was replaced with 5g of sodium ethoxide. Otherwise, ethyl difluoroacetate (198g, yield 78%) was obtained by following the same method as in Example 5. The F ion concentration in ethyl difluoroacetate was 11ppm.

[0113] (Example 7) In a 500 mL autoclave made of heat-resistant and corrosion-resistant nickel-based alloy and equipped with a condenser, 60 g of silica gel, 300 g of 1-ethoxy-1,1,2,2-tetrafluoroethane, and 19.0 g of ethanol were added, and the internal temperature was heated to 50 °C. Then, 100.8 g of 98% sulfuric acid was added dropwise over 1 hour. After heating and stirring the autoclave at 50 °C for 18 hours, 28.4 g of ethanol was added, and the mixture was heated and stirred at 50 °C for 5 hours. The resulting reaction mixture (crude product) was cooled to room temperature.

[0114] The reaction mixture was simply distilled to obtain 230 g of crude product containing acid and ethanol. This crude product was loaded into a stainless steel distillation column with a diameter of 2.5 cm × height of 30 cm and a still capacity of 1 L. 30 g of NaHCO3 was added, and the mixture was stirred at room temperature for 1 hour (step B). Distillation was then carried out at atmospheric pressure. The fraction with a purity of 99.8% or higher was collected to obtain 219 g of ethyl difluoroacetate (yield 86%). The F ion concentration in ethyl difluoroacetate was 8 ppm.

[0115] (Comparative Example 1) 60 g of silica gel was added to a 500 mL autoclave made of heat-resistant and corrosion-resistant nickel-based alloy and equipped with a condenser. Then, 300 g of ethyl difluoroacetate containing 20% ​​by mass of hydrogen fluoride (containing 3.0 mol of hydrogen fluoride and 1.93 mol of ethyl difluoroacetate) was slowly added dropwise at room temperature to prepare a mixture. The mixture in the autoclave was heated and stirred at 60 °C for 1 hour, and then cooled to room temperature.

[0116] After transferring the mixture to a fluoropolymer separatory funnel, the lower layer was separated at room temperature, and the organic layer was recovered. The amount of ethyl difluoroacetate recovered was 221 g (recovery rate 92%). The acid content, converted to hydrogen fluoride, was 0.16% (18 mmol). This acid content was determined by titration with neutralization using 0.1N-NaOH solution.

[0117] (Comparative Example 2) In a 500 mL autoclave made of heat-resistant and corrosion-resistant nickel-based alloy and equipped with a condenser, 60 g of silica gel, 300 g of 1-ethoxy-1,1,2,2-tetrafluoroethane, and 19.0 g of ethanol were added, and the internal temperature was heated to 50 °C. Then, 100.8 g of 98% sulfuric acid was added dropwise. After heating and stirring the autoclave at 50 °C for 18 hours, 28.4 g of ethanol was added, and the mixture was heated and stirred at 50 °C for 5 hours. The resulting reaction mixture (crude product) was cooled to room temperature.

[0118] The reaction mixture was simply distilled to obtain 230 g of crude product containing acid and ethanol. This crude product was charged into a stainless steel distillation column with a diameter of 2.5 cm and a height of 30 cm and a static capacity of 1 L, and distilled at atmospheric pressure. The fraction containing more than 99.8% of the target analyte was collected to obtain 213 g of ethyl difluoroethylene (83% yield). The F ion concentration in ethyl difluoroethylene was 140 ppm. Additionally, silica was observed adhering to the condenser in the reaction apparatus.

[0119] As can be seen from the results of the above examples and comparative examples, by performing a process of adding alkali to a mixture containing organic compounds (ester compounds), hydrogen fluoride and SiO2-containing materials, fluorine components such as hydrogen fluoride can be removed efficiently, thereby enabling the recovery of ester compounds such as ethyl difluoroacetate with high purity.

Claims

1. A method for purifying an organic compound, characterized by, having: a process A of preparing a mixture containing an organic compound, hydrogen fluoride, and a SiO2-containing material; a process of taking out a layer containing the organic solvent of the mixture after an extraction treatment is performed by adding an organic solvent to the mixture obtained in the process A; a process B of adding a base to a layer containing the mixture; and a process C of performing at least one treatment selected from distillation, filtration, and liquid separation after the base is added in the process B, the organic compound is an ester compound represented by the following general formula (1), R A COOR B (1) wherein R A and R B are organic radicals, R A and R B each can be the same as or different from one another, the base is at least one selected from metal bicarbonates and metal alcoholates, in the process B, 0.01 to 0.2 moles of the base is added per 1 mole of the organic compound.

2. The purification method of an organic compound according to claim 1, wherein: In the organic ester compound represented by the formula (1), R A and R B are an alkyl group, a halogenated alkyl group, an ether oxygen atom-containing alkyl group, or an ether oxygen atom-containing alkyl group substituted with one or more halogen atoms.

3. The purification method of an organic compound according to claim 2, wherein: In General Formula (1), R A is HCF2, and R B is an alkyl group having 1 to 4 carbon atoms.

4. The purification method of an organic compound according to claim 1 or 2, wherein: the SiO2-containing material is at least one selected from silica stone powder and silica gel.

5. The purification method of an organic compound according to claim 1 or 2, wherein: the mixture is prepared by adding a SiO2-containing material to a mixed solution containing an organic compound and hydrogen fluoride.

6. The purification method of an organic compound according to claim 1, wherein: the organic solvent is at least one selected from linear or branched alkanes having 8 to 16 carbon atoms and linear or branched alkenes having 8 to 16 carbon atoms.

7. A method of producing an organic compound, comprising a purification process including the process A, the process of taking out a layer, the process B, and the process C according to any one of claims 1 to 6. ​