JP6341040B2 - Process for producing 1,1,1,5,5,5-hexafluoroacetylacetone - Google Patents

Description

  The present invention relates to an industrial production method of 1,1,1,5,5,5-hexafluoroacetylacetone.

  1,1,1,5,5,5-hexafluoroacetylacetone has the formula [4]:

It is an important compound as an intermediate between medical pesticides and electronic materials.

  As a typical production method of 1,1,1,5,5,5-hexafluoroacetylacetone, a method of reacting trifluoroacetone and trifluoroacetate ester (Non-patent Document 1), trifluoroacetoacetate ester, A method of reacting trifluoroacetic anhydride (Patent Document 1) can be mentioned.

On the other hand, reactions between 3,3,3-trifluoropropynyl metal (for example, CF ₃ C≡CLi) and various electrophiles have been reported (Non-patent Documents 2 to 5).

Chinese Patent Application No. 102260151

J. et al. Am. Chem. Soc. (USA), 1956, vol. 78, p. 2790-2792 J. et al. Fluorine Chem. (Netherlands), 1990, 47, p. 45-57 J. et al. Chem. Soc. Perkin Trans. 1 (UK), 1992, p. 2485-2494 J. et al. Fluorine Chem. (Netherlands), 1993, Vol. 62, p. 39-49 J. et al. Org. Chem. (USA), 1995, Vol. 60, p. 6046-6056

  The method for producing 1,1,1,5,5,5-hexafluoroacetylacetone of Non-Patent Document 1 requires the use of an expensive raw material substrate (specifically, trifluoroacetone), and the availability of the raw material substrate is easy. From the viewpoint of, it was difficult to adopt industrially.

  In the production method of Patent Document 1, since trifluoroacetone is not used as a raw material substrate, cost competitiveness is improved as compared with the method of Non-Patent Document 1. However, there is a strong demand for a manufacturing method that can be easily employed industrially.

  Accordingly, an object of the present invention is to provide an industrially easy production method for 1,1,1,5,5,5-hexafluoroacetylacetone.

The present inventors have intensively studied based on the above problems. As a result, a method for producing a hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] including at least the following first to fifth steps,
First step:
A 1,3,3-trifluoropropynyl metal represented by the general formula [1] and a trifluoroacetic acid ester represented by the general formula [2] are reacted in the presence of a reaction solvent to obtain 1,1,1 , 5,5,5-hexafluoro-3-pent-2-one or a first reaction mixture containing an equivalent thereof,
Second step:
A hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] is obtained by bringing the first reaction mixture obtained in the first step into contact with water in the presence of an acid. Obtaining a second reaction mixture comprising
Third step:
Concentrating the second reaction mixture obtained in the second step as it is by distillation, or separating the second reaction mixture into an aqueous layer and an organic layer and concentrating the organic layer by distillation;
Fourth step:
Recovering part or all of the organic solvent distilled off in the third step, and recovering the reaction solvent from the contact liquid obtained by contacting with at least one basic compound;
5th step:
Reusing the reaction solvent recovered in the fourth step as at least a part of the reaction solvent in the first step, or reusing it as an extraction solvent for the second reaction mixture or the aqueous layer separated therefrom, A process for producing 1,1,1,5,5,5-hexafluoroacetylacetone having an industrially advantageous process in which the reaction solvent can be easily reused has been found, and the present invention has been completed.

［式中、ｎは正の整数を表す。］
で示される１，１，１，５，５，５−ヘキサフルオロアセチルアセトンの水和物を製造する方法。
第１工程：
一般式［１］：

［式中、Ｍはリチウム原子またはハロゲン化マグネシウム基（ＭｇＸ）を表し、Ｘは塩素原子、臭素原子またはヨウ素原子を表す。］
で示される３，３，３−トリフルオロプロピニル金属と、一般式［２］：

［式中、Ｒはアルキル基を表す。］
で示されるトリフルオロ酢酸エステルとを、反応溶媒の存在下で反応させて、１，１，１，５，５，５−ヘキサフルオロ−３−ペンチ−２−ノンまたはその等価体を含む第１反応混合液を得る工程、
第２工程：
第１工程で得た第１反応混合液を酸の存在下で水と接触させて、一般式［３］で示される１，１，１，５，５，５−ヘキサフルオロアセチルアセトンの水和物を含む第２反応混合液を得る工程、
第３工程：
第２工程で得られた第２反応混合液をそのまま蒸留により濃縮する、または、第２反応混合液を水層と有機層とに分離して該有機層を蒸留により濃縮する工程、
第４工程：
第３工程で留去された有機溶媒の一部又は全部を回収して、少なくとも１種の塩基性化合物と接触させて得られた接触液から反応溶媒を回収する工程、
第５工程：
第４工程で回収した反応溶媒を、第１工程の反応溶媒の少なくとも一部として再利用するか、または第２反応混合液もしくはそれから分離された水層の抽出溶媒として再利用する工程。
［発明２］
以下の第６工程をさらに含む、発明１の方法。
第６工程：
第３工程で濃縮された第２反応混合液の残渣から、精製用溶媒を用いて一般式［３］で示される１，１，１，５，５，５−ヘキサフルオロアセチルアセトンの水和物を精製する工程。
［発明３］
以下の第７工程をさらに含む、発明２の方法。
第７工程：
第４工程で回収した反応溶媒を、第６工程の精製用溶媒の少なくとも一部として再利用する工程。
［発明４］
第４工程の塩基性化合物が、アルカリ金属の水酸化物、炭酸塩および炭酸水素塩、アルカリ土類金属の水酸化物および炭酸塩、塩基性金属酸化物、水酸化テトラアルキルアンモニウム、トリアルキルアミンならびに含窒素複素環式化合物からなる群から選ばれる少なくとも１種である、発明１乃至発明３のいずれか一つの方法。
［発明５］
第４工程の塩基性化合物が、水酸化ナトリウム、水酸化カルシウム、水酸化マグネシウム、水酸化バリウム・８水和物、炭酸水素ナトリウム、炭酸セシウム、炭酸カリウム、炭酸カルシウム、塩基性アルミナおよびトリブチルアミンからなる群から選ばれる少なくとも１種である、発明１乃至発明４のいずれか一つの方法。
［発明６］
第４工程の塩基性化合物が、水酸化バリウム・８水和物、炭酸カルシウムおよびトリブチルアミンからなる群から選ばれる少なくとも１種である、発明１乃至発明５のいずれか一つの方法。
［発明７］
反応溶媒が、エーテル系溶媒、芳香族炭化水素系溶媒および脂肪族炭化水素系溶媒からなる群から選ばれる少なくとも１種である、発明１乃至発明６のいずれか一つの方法。
［発明８］
反応溶媒が、ｎ−ヘプタンを主成分とする脂肪族炭化水素系溶媒および、ｔｅｒｔ−ブチルメチルエーテルからなる群から選ばれる少なくとも１種である、発明１乃至発明７のいずれか一つの方法。
［発明９］
発明１乃至発明８のいずれか一つの方法により一般式［３］で示される１，１，１，５，５，５−ヘキサフルオロアセチルアセトンの水和物を製造し、次いで、得られた該水和物を脱水することにより、１，１，１，５，５，５−ヘキサフルオロアセチルアセトンを製造する方法。 That is, the present invention includes inventions 1 to 9.
[Invention 1]
General formula [3] including at least the following first to fifth steps:

[Wherein n represents a positive integer. ]
A process for producing a hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the formula:
First step:
General formula [1]:

[Wherein, M represents a lithium atom or a magnesium halide group (MgX), and X represents a chlorine atom, a bromine atom or an iodine atom. ]
A 3,3,3-trifluoropropynyl metal represented by the general formula [2]:

[Wherein, R represents an alkyl group. ]
And 1,1,1,5,5,5-hexafluoro-3-pent-2-one or an equivalent thereof. Obtaining a reaction mixture,
Second step:
A hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] is obtained by bringing the first reaction mixture obtained in the first step into contact with water in the presence of an acid. Obtaining a second reaction mixture comprising
Third step:
Concentrating the second reaction mixture obtained in the second step as it is by distillation, or separating the second reaction mixture into an aqueous layer and an organic layer and concentrating the organic layer by distillation;
Fourth step:
Recovering part or all of the organic solvent distilled off in the third step, and recovering the reaction solvent from the contact liquid obtained by contacting with at least one basic compound;
5th step:
Reusing the reaction solvent recovered in the fourth step as at least part of the reaction solvent in the first step, or reusing it as an extraction solvent for the second reaction mixture or the aqueous layer separated therefrom.
[Invention 2]
The method of Invention 1, further comprising the following sixth step.
Step 6:
From the residue of the second reaction mixture concentrated in the third step, a hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] is used using a purification solvent. The process to refine.
[Invention 3]
The method of the invention 2, further comprising the following seventh step.
Step 7:
A step of reusing the reaction solvent recovered in the fourth step as at least part of the purification solvent in the sixth step.
[Invention 4]
The basic compound of the fourth step is an alkali metal hydroxide, carbonate and bicarbonate, alkaline earth metal hydroxide and carbonate, basic metal oxide, tetraalkylammonium hydroxide, trialkylamine And the method according to any one of Inventions 1 to 3, which is at least one selected from the group consisting of nitrogen-containing heterocyclic compounds.
[Invention 5]
The basic compound of the fourth step is sodium hydroxide, calcium hydroxide, magnesium hydroxide, barium hydroxide octahydrate, sodium bicarbonate, cesium carbonate, potassium carbonate, calcium carbonate, basic alumina and tributylamine. The method according to any one of Inventions 1 to 4, wherein the method is at least one selected from the group consisting of:
[Invention 6]
The method according to any one of Inventions 1 to 5, wherein the basic compound in the fourth step is at least one selected from the group consisting of barium hydroxide octahydrate, calcium carbonate, and tributylamine.
[Invention 7]
The method according to any one of Inventions 1 to 6, wherein the reaction solvent is at least one selected from the group consisting of ether solvents, aromatic hydrocarbon solvents, and aliphatic hydrocarbon solvents.
[Invention 8]
The method according to any one of Inventions 1 to 7, wherein the reaction solvent is at least one selected from the group consisting of an aliphatic hydrocarbon solvent mainly composed of n-heptane and tert-butyl methyl ether.
[Invention 9]
A hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] is produced by the method of any one of Inventions 1 to 8, and then the water obtained A method for producing 1,1,1,5,5,5-hexafluoroacetylacetone by dehydrating a Japanese product.

By reacting a 3,3,3-trifluoropropynyl metal with an ester as an electrophile, an inone having a trifluoromethyl group (CF ₃ C≡CCOR ¹ ; R ¹ represents an alkyl group, an aryl group, or the like) )) Or an equivalent thereof is not reported in good yield. For example, 3,3,3-trifluoropropynyllithium reacts well with aldehydes and ketones to give the desired product in high yield, while esters only give a complex mixture (non- Patent Document 5). Naturally, no reaction using the trifluoroacetate ester disclosed in the present invention as an electrophile has been reported. Furthermore, in the present invention, the triple bond of 1,1,1,5,5,5-hexafluoro- _3- pent-2-one (CF ₃ C≡CCOCF ₃ ) or its equivalent is hydrated. However, it was also unclear whether the hydroxyl group could be introduced at the desired 4-position. For example, Non-Patent Document 4, Non-Patent Document 6 [J. Org. Chem. (USA), 1986, 51, p. 4082-4083] and Non-Patent Document 7 [J. Org. Chem. (USA), 1992, Vol. 57, p. 5530-5532], a carbon-carbon multiple bond compound having a trifluoromethyl group [CF ₃ C≡CCH (OAc) Me, CF ₃ C≡CCOPh, (CF ₃ ) ₂ C═CHCO ₂ Et; Ac is an acetyl group , Me represents a methyl group, Ph represents a phenyl group, and Et represents an ethyl group. ] And various nucleophiles have been reported, but a conjugated adduct having a trifluoromethyl group as an electron withdrawing group has been obtained as a main product, and the desired regioselectivity in the present invention can be obtained. Is the opposite.

［式中、ｎは正の整数を表す。］
で示される１，１，１，５，５，５−ヘキサフルオロアセチルアセトンの水和物を製造し（第２工程）、さらに、該水和物を脱水することで、１，１，１，５，５，５−ヘキサフルオロアセチルアセトンを製造できることを見出し、特許出願した（特願２０１４−０６５４５０号）。より具体的には、一般式［３］で示される１，１，１，５，５，５−ヘキサフルオロアセチルアセトンの水和物の製造方法は、以下の第１工程と第２工程を少なくとも含む。
第１工程：
一般式［１］：

［式中、Ｍはリチウム原子またはハロゲン化マグネシウム基（ＭｇＸ）を表し、Ｘは塩素原子、臭素原子またはヨウ素原子を表す。］
で示される３，３，３−トリフルオロプロピニル金属と、一般式［２］：

［式中、Ｒはアルキル基を表す。］
で示されるトリフルオロ酢酸エステルを反応させて１，１，１，５，５，５−ヘキサフルオロ−３−ペンチ−２−ノンまたはその等価体を少なくとも含む反応混合物（Ａ）を得る工程。
第２工程：
第１工程で得た反応混合物（Ａ）を酸の存在下で水と接触させることにより、一般式［３］で示される１，１，１，５，５，５−ヘキサフルオロアセチルアセトンの水和物を得る工程。 In addition, as a manufacturing method of 1,1,1,5,5,5-hexafluoroacetylacetone, which is easily adopted industrially, the present inventors used 3,3,3-trifluoropropynyl metal and trifluoroacetic acid ester. Reaction is performed to obtain a reaction mixture containing at least 1,1,1,5,5,5-hexafluoro-3-pent-2-one or an equivalent thereof (first step), and then the reaction mixture is treated with acid. By contacting with water in the presence of general formula [3]:

[Wherein n represents a positive integer. ]
1,1,1,5,5,5-hexafluoroacetylacetone hydrate is produced (second step), and the hydrate is further dehydrated to obtain 1,1,1,5 , 5,5-hexafluoroacetylacetone was found and a patent application was filed (Japanese Patent Application No. 2014-0665450). More specifically, the method for producing a hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] includes at least the following first step and second step. .
First step:
General formula [1]:

[Wherein, M represents a lithium atom or a magnesium halide group (MgX), and X represents a chlorine atom, a bromine atom or an iodine atom. ]
A 3,3,3-trifluoropropynyl metal represented by the general formula [2]:

[Wherein, R represents an alkyl group. ]
To obtain a reaction mixture (A) containing at least 1,1,1,5,5,5-hexafluoro-3-pent-2-one or an equivalent thereof.
Second step:
By bringing the reaction mixture (A) obtained in the first step into contact with water in the presence of an acid, hydration of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] The process of obtaining things.

  Japanese Patent Application No. 2014-0665450 also provides an industrially easy production method for 1,1,1,5,5,5-hexafluoroacetylacetone. In the present invention, the reaction solvent can be easily reused. Therefore, it is possible to provide a method for producing 1,1,1,5,5,5-hexafluoroacetylacetone by a more efficient industrial process.

  According to the present invention, 1,1,1,5,5,5-hexafluoroacetylacetone can be produced industrially advantageously.

  The method for producing 1,1,1,5,5,5-hexafluoroacetylacetone according to the present invention will be described in detail. The scope of the present invention is not limited to these descriptions, and other than the following examples, the scope of the present invention can be appropriately changed and implemented without departing from the spirit of the present invention. Also, all publications cited herein are hereby incorporated by reference.

  In the present invention, the 3,3,3-trifluoropropynyl metal represented by the general formula [1] and the trifluoroacetic acid ester represented by the general formula [2] are reacted in the presence of a reaction solvent to obtain the first. By obtaining a reaction mixture (first step), and then contacting the obtained first reaction mixture with water in the presence of an acid, 1,1,1,5 represented by the general formula [3] A second reaction mixture containing hydrate of 5,5-hexafluoroacetylacetone is obtained (second step). By dehydrating this hydrate (dehydration step), 1,1,1,5,5,5-hexafluoroacetylacetone represented by the formula [4] can be produced.

  Here, in the first reaction mixture obtained in the first step, in addition to the reaction solvent, 1,1,1,5,5,5-hexafluoro-3-pent-2-one or an equivalent thereof At least as a component. The equivalent of 1,1,1,5,5,5-hexafluoro-3-pent-2-one is represented by the general formula [3] in the second step (contact with water in the presence of an acid) described later. If it can give the hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone shown by, it will not specifically limit. Examples of the equivalent include metal hemiketals of 1,1,1,5,5,5-hexafluoro-3-pent-2-one represented by general formula [5], and 1 represented by general formula [6]. , 1,1,5,5,5-hexafluoro-3-pent-2-one hydrate or alkyl hemiketal, but is not limited thereto. These are very important equivalents of 1,1,1,5,5,5-hexafluoro-3-pent-2-one, and moreover, 1,1,1,5,5,5-hexa It becomes a very important precursor of fluoroacetylacetone or its hydrate.

  In addition to the hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3], the second reaction mixture obtained in the second step contains the first reaction mixture. The reaction solvent used in the process is included. The reaction solvent is recovered by collecting a part or all of the organic solvent distilled off by concentrating the second reaction mixture by distillation (third step) and then subjecting the organic solvent to a predetermined treatment. (4th process). The recovered reaction solvent can be reused as at least part of the reaction solvent in the first step and / or as the extraction solvent for the second reaction mixture (fifth step). In order to obtain a reusable reaction solvent, it is important that the organic solvent distilled off from the second reaction mixture is subjected to a predetermined base treatment and then distilled and purified in the fourth step. . By this series of treatments and operations, it is possible to recover a reusable high-purity reaction solvent. By circulating this reaction solvent, 1,1,1,5,5,5-hexafluoroacetylacetone can be produced efficiently.

  In the present invention, 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] is used from the residue of the second reaction mixture concentrated in the third step using a purification solvent. It is possible and preferably to purify the hydrate of (Sixth step). Furthermore, in the present invention, it is possible to reuse the reaction solvent distilled and purified in the aforementioned fourth step (seventh step) as at least a part of the purification solvent, and it is preferable to do so. .

  Hereinafter, the first to seventh steps will be described in detail.

[First step]
In the first step according to the present invention, the 3,3,3-trifluoropropynyl metal represented by the general formula [1] and the trifluoroacetic acid ester represented by the general formula [2] are present in the presence of a reaction solvent. Reaction is performed to obtain a first reaction mixture containing 1,1,1,5,5,5-hexafluoro-3-pent-2-one or its equivalent.

  M of the 3,3,3-trifluoropropynyl metal represented by the general formula [1] represents a lithium atom or a magnesium halide group (MgX), and X represents a chlorine atom, a bromine atom or an iodine atom. Among these, in order to smoothly advance the desired reaction in the first step, a lithium atom, a magnesium chloride group (MgCl) and a magnesium bromide group (MgBr) are preferable, and a lithium atom is particularly preferable.

  The 3,3,3-trifluoropropynyl metal represented by the general formula [1] is disclosed in Non-Patent Documents 2 to 4 and Russian Journal of Organic Chemistry (Russia), 1993, Vol. 29, p. It can be derived from 3,3,3-trifluoropropyne with reference to 1445-1449 and the like. Specifically, 3,3,3-trifluoropropyne and general formula [7]:

[Wherein R ³ represents a linear or branched alkyl group having 1 to 8 carbon atoms, or a cyclic alkyl group having 3 to 8 carbon atoms, and M represents a lithium atom or a magnesium halide group. (MgX) is represented, and X represents a chlorine atom, a bromine atom or an iodine atom. ]
3,3,3-trifluoropropynyl represented by the general formula [1] by reacting the organolithium reagent or Grignard reagent represented by the formula (1) in a preparation solvent described later at −150 to + 50 ° C. within 12 hours. The metal can be prepared with good yield. In this preparation, it is convenient to use various solutions of commercially available organic lithium reagent or Grignard reagent whose concentration is adjusted. The amount of 3,3,3-trifluoropropyne used may be 0.7 mol or more per mol of the organic lithium reagent or Grignard reagent, preferably 0.8 to 1.6 mol, 0.9 to 1.3 mol is particularly preferred. Moreover, what is necessary is just to consider the content described in the usage-amount of the reaction solvent in the below-mentioned 1st process for the usage-amount of a preparation solvent. In addition, the 3,3,3-trifluoropropynyl metal represented by the general formula [1] is disclosed in Non-Patent Document 5 and Chem. Commun. (UK), 2002, p. It can also be derived from 2-bromo-3,3,3-trifluoropropene or 1,1,1,3,3-pentafluoropropane with reference to 2420-2421 and the like. Of course, the method for preparing the 3,3,3-trifluoropropynyl metal represented by the general formula [1] is not limited to the above methods.

The method for obtaining the above-mentioned 3,3,3-trifluoropropyne is not particularly limited. For example, if a manufacturing method disclosed in International Publication No. 2008/132964 or the like is adopted, acquisition on a large scale is easy. Thus, 3,3,3-trifluoropropyne is 1,1,1,5,5,5-hexafluoro-nucleophile in the manufacture of acetylacetone ^- as _(CF 3 COCH ₂ equivalents), it was conventionally used Compared to trifluoroacetone and trifluoroacetoacetate, it is easy to adopt industrially. Therefore, it is a preferred embodiment in the present invention that the 3,3,3-trifluoropropyne metal represented by the general formula [1] is derived from 3,3,3-trifluoropropyne.

  The 3,3,3-trifluoropropynyl metal represented by the general formula [1] used in the first step may contain impurities as long as it does not inhibit the reaction in the first step and the second step described later. What was obtained by what kind of circumstances may be used. This 3,3,3-trifluoropropynyl metal may be subjected to a reaction, but it is unstable to heat, moisture, oxygen, etc., so that this 3,3,3-trifluoro metal is the product. A solution containing propynyl metal (prepared solution) may be directly subjected to the reaction. As the solvent (preparation solvent) of this solution, it is preferable to use the reaction solvent used in the first step.

  In addition, depending on the method for preparing the reaction raw material 3,3,3-trifluoropropynyl metal, lithium hydride, lithium halide (fluoride, chloride, bromide or iodide), magnesium halide (fluoride) , Chloride, bromide or iodide), methane, ethane, propane, n-butane, benzene, diisopropylamine, hexamethyldisilazane or 2,2,6,6-tetramethylpiperidine, etc. However, it is not necessary to remove it intentionally, and the reaction of the first step can be performed in the presence of these. Of course, the reaction can be carried out by intentionally adding a compound mixed in these systems.

The 3,3,3-trifluoropropynyl metal represented by the general formula [1] according to the present invention includes an aggregate of itself (CF ₃ C≡CM), a compound mixed in a preparation solution or a complex with a solvent, In addition, aggregates of the complex and the like are also included.

  R of the trifluoroacetate ester represented by the general formula [2] in the first step represents an alkyl group. The alkyl group is a linear or branched chain alkyl group having 1 to 12 carbon atoms or a cyclic alkyl group having 3 to 12 carbon atoms. Among them, an alkyl group having 1 to 4 carbon atoms is preferable, and a methyl group and an ethyl group are particularly preferable. The alkyl group may have a substituent that does not substantially affect the desired reaction, and such a substituted alkyl group is generally described in the claims of the present invention. Treated as being contained in R of the trifluoroacetate ester represented by the formula [2]. Examples of such a substituent include halogen atoms such as a fluorine atom and a chlorine atom, and alkoxy groups having 1 to 6 carbon atoms such as a methoxy group and an ethoxy group.

  The amount of the trifluoroacetate ester represented by the general formula [2] may be 0.7 mol or more relative to 1 mol of the 3,3,3-trifluoropropynyl metal represented by the general formula [1]. 0.8-5 mol is preferable and 0.9-3 mol is particularly preferable.

  In the first step, the reaction between the 3,3,3-trifluoropropynyl metal represented by the general formula [1] and the trifluoroacetate ester represented by the general formula [2] is performed by reacting zinc halide (fluoride, chloride). , Bromide or iodide), diethyl ether complex of boron trifluoride, 12-crown-4, polyethylene glycol, hexamethylphosphoric triamide (abbreviation: HMPA) and N, N, N ′, N′-tetramethylethylenediamine ( By adding an additive such as abbreviation (TMEDA), a desired reaction may proceed smoothly. Of course, by employing the preferred reaction conditions of the present invention, it is not necessary to add additives.

  Further, the first step can be performed not only by a batch type reaction but also by a flow type reaction. Of course, the process from the preparation of the 3,3,3-trifluoropropynyl metal represented by the general formula [1] to the reaction with the trifluoroacetate ester represented by the general formula [2] may be continuously performed by a flow type reaction. it can.

  As the reaction solvent in the first step, an aliphatic hydrocarbon solvent, an aromatic hydrocarbon solvent, an ether solvent, an amide solvent, dimethyl sulfoxide, or the like can be used. Among these, aliphatic hydrocarbon solvents, aromatic hydrocarbon solvents and ether solvents are preferable, and aliphatic hydrocarbon solvents and ether solvents are particularly preferable. These reaction solvents can be used alone or in combination.

  Examples of the aliphatic hydrocarbon solvent include, but are not limited to, n-pentane, n-hexane, cyclohexane, n-heptane, and the like. Among these, a linear alkane, branched alkane, or cycloalkane having a boiling point of 90 to 110 ° C. and having 6 to 8 carbon atoms is preferable as a main component, and n-heptane is a main component. Are particularly preferred, and these may be a single component or a mixture containing other aliphatic hydrocarbon solvents as subcomponents.

  Examples of the aromatic hydrocarbon solvent include, but are not limited to, benzene, toluene, xylene, cumene, mesitylene and the like.

  Examples of ether solvents include diethyl ether, tert-butyl methyl ether (abbreviation: MTBE), tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, 2-methyltetrahydrofuran, diethoxymethane, diisopropyl ether, diethylene glycol dimethyl ether, Anisole, di-n-butyl ether, diethylene glycol dibutyl ether and the like can be mentioned, but not limited thereto.

  Examples of amide solvents include, but are not limited to, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone and 1,3-dimethyl-2-imidazolidinone.

  The reaction solvent in the first step is more preferably at least one selected from the group consisting of an aliphatic hydrocarbon solvent mainly composed of n-heptane and tert-butyl methyl ether (abbreviation: MTBE). is there.

  The amount of the reaction solvent used in the first step is 0.05 L (L represents liter, the same shall apply hereinafter) or more with respect to 1 mol of the 3,3,3-trifluoropropynyl metal represented by the general formula [1]. The upper limit is not particularly limited. Especially, 0.1-30L is preferable and 0.2-20L is especially preferable. The amount used includes the amount of solvent accompanying the preparation solution of the 3,3,3-trifluoropropynyl metal represented by the general formula [1].

  The reaction temperature in the first step may be + 75 ° C. or less, preferably +50 to −100 ° C., particularly preferably +25 to −75 ° C., and extremely preferably 0 to −50 ° C. This reaction temperature is not the preparation temperature of 3,3,3-trifluoropropynyl metal, but the reaction temperature with the trifluoroacetic acid ester represented by the general formula [2].

  The reaction time in the first step may be within 48 hours, and varies depending on the raw material substrate and reaction conditions. Therefore, the progress of the reaction is traced by analysis means such as gas chromatography, liquid chromatography, nuclear magnetic resonance, The end point may be the time when almost no decrease in the raw material substrate is recognized.

For the post-treatment of the reaction in the first step, a general operation in organic synthesis can be adopted. By this post-treatment, the first reaction mixture according to the present invention can be obtained. In this first reaction mixture, 1,1,1,5,5,5-hexafluoro- _3- pent-2-onone (CF ₃ C≡CCOCF ₃ ), which is an intermediate, together with the reaction solvent as components. Alternatively, at least an equivalent of 1,1,1,5,5,5-hexafluoro-3-pent-2-one is included. Specific examples of the equivalent include metal hemiketals, hydrates, and alkyl hemiketals. In addition, a by-product (for example, corresponding metal alkoxide: ROM) of the reaction in the first step, unreacted raw material, and the like may be included.

  The structural formula of 1,1,1,5,5,5-hexafluoro-3-pent-2-one has the following formula:

Indicated by

  As a specific example of an equivalent of 1,1,1,5,5,5-hexafluoro-3-pent-2-one, the general formula [5]:

[Wherein, M represents a lithium atom or a halogenated magnesium group (MgX), X represents a chlorine atom, a bromine atom or an iodine atom, and R represents an alkyl group. M and R are derived from M of the 3,3,3-trifluoropropynyl metal represented by the general formula [1] and R of the trifluoroacetate ester represented by the general formula [2], respectively, and the same metal and alkyl group Take. ]
There is a metal hemiketal of 1,1,1,5,5,5-hexafluoro-3-pent-2-one represented by For example, as described later in Reference Example 1, a reaction mixture obtained by reacting 3,3,3-trifluoropropynyllithium with ethyl trifluoroacetate is directly reacted with trimethylsilyl chloride to obtain the following formula. :

[In the formula, Me represents a methyl group, and Et represents an ethyl group. ]
1,1,1,5,5,5-hexafluoro-3-pent-2-one trimethylsilylethyl ketal can be obtained in good yield. From this, the metal hemiketal of 1,1,1,5,5,5-hexafluoro-3-pent-2-one represented by the general formula [5] (M: lithium atom, R: ethyl group) It is proved to be present in the reaction mixture.

  Here, M in the metal hemiketal of 1,1,1,5,5,5-hexafluoro-3-pent-2-one represented by the general formula [5] is a lithium atom or a magnesium halide group (MgX). X represents a chlorine atom, a bromine atom or an iodine atom.

  Moreover, R of the metal hemiketal of 1,1,1,5,5,5-hexafluoro-3-pent-2-one represented by the general formula [5] represents an alkyl group. The alkyl group is derived from R of the trifluoroacetate ester represented by the general formula [2] and takes the same alkyl group.

  The equivalent of 1,1,1,5,5,5-hexafluoro-3-pent-2-one contained as a component in the first reaction mixture is 1,1,1 represented by the general formula [5]. The metal hemiketal of 1,5,5,5-hexafluoro-3-pent-2-one is not limited to the metal hemiketal, and after passing through the second step (contact with water in the presence of an acid), the general formula [ 3] as long as it gives a hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone. As an equivalent of such 1,1,1,5,5,5-hexafluoro-3-pent-2-one, general formula [6]:

[Wherein R ² represents a hydrogen atom or an alkyl group. When this R ² is an alkyl group, it is derived from R of the trifluoroacetate ester represented by the general formula [2] and takes the same alkyl group. ]
The hydrate or alkylhemiketal of 1,1,1,5,5,5-hexafluoro-3-pent-2-one represented by

Here, the general formula [6] ^{1,1,1,5,5,5-hexafluoro-3-pentyl-2-R 2} non hydrate or alkyl hemi ketal represented by a hydrogen atom or an alkyl Represents a group. The alkyl group is derived from R of the trifluoroacetate ester represented by the general formula [2] and takes the same alkyl group.

[Second step]
In the second step according to the present invention, the first reaction mixture obtained in the first step is brought into contact with water in the presence of an acid, and 1,1,1,5,5 represented by the general formula [3] A second reaction mixture containing 5-hexafluoroacetylacetone hydrate is obtained.

  The second step is the first step, and the reaction is completed by the reaction of the 3,3,3-trifluoropropynyl metal represented by the general formula [1] and the trifluoroacetate ester represented by the general formula [2]. It is simple and industrial to carry out the solution as it is without any treatment.

  There is no restriction | limiting in particular as a kind of acid in a 2nd process. For example, hydrogen chloride, hydrogen bromide, hydrogen iodide, perchloric acid, sulfuric acid, nitric acid and fluorosulfonic acid and other inorganic acids, methanesulfonic acid, trifluoromethanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid and paratoluenesulfonic acid Organic acids such as these can be used. Among these, inorganic acid is preferable, and sulfuric acid is particularly preferable in order to smoothly advance the contact with water in the second step.

  There is no restriction | limiting in particular in the usage-amount of the acid in a 2nd process, What is necessary is just to use 0.01-200 mol with respect to 1 mol of 3,3,3- trifluoropropynyl metals normally shown by General formula [1].

  The amount of water used in the second step may be 0.03 L or more with respect to 1 mol of the 3,3,3-trifluoropropynyl metal represented by the general formula [1], preferably 0.04 to 30 L, 0.05 to 15 L is particularly preferable.

  When performing this process with respect to the 1st reaction liquid mixture obtained at the 1st process, contact with water may become a two phase system. Such two-phase contacts can be made of tetramethylammonium chloride, tetramethylammonium bromide, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, benzyltriethylammonium chloride, methyltri-n-octylammonium chloride, etc. In the presence of a phase transfer catalyst such as quaternary ammonium salts and quaternary phosphonium salts such as tetra-n-butylphosphonium chloride, tetra-n-butylphosphonium bromide and methyltriphenylphosphonium chloride, In some cases, the contact may proceed smoothly. Of course, by employing the preferred reaction conditions of the present invention, it is not necessary to add a phase transfer catalyst.

  In the second step, the first reaction mixture obtained in the first step can be directly brought into contact with water in the presence of an acid. However, a new solvent (in order to distinguish from the reaction solvent in the first step, “contact May also be used. The type of contact solvent used here is preferably selected from reaction solvents that can be used in the first step, but other solvents can also be selected. Other solvents include, for example, halogen systems such as methylene chloride, chloroform and 1,2-dichloroethane, alcohol systems such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, and acetonitrile, propio Examples include nitriles such as nitrile and benzonitrile. Among these and the reaction solvent that can be used in the first step, aliphatic hydrocarbons, aromatic hydrocarbons, ethers and alcohols are preferred, aliphatic hydrocarbons and ethers are particularly preferred as contact solvents. Can be used. The solvents mentioned here can be used alone or in combination.

  The amount of contact solvent used in the second step (the total amount used when the solvent in the first step is included) is 1 mol of the 3,3,3-trifluoropropynyl metal represented by the general formula [1]. 0.05 L or more may be used, and the upper limit is not particularly limited. Especially, 0.1-30L is preferable and 0.2-20L is especially preferable.

  In the second step, the contact temperature when the first reaction mixture is brought into contact with water in the presence of an acid may be 150 ° C. or less, preferably 125 to 10 ° C., particularly preferably 100 to 20 ° C., 75 ˜30 ° C. is very preferred.

  In the second step, the contact time for bringing the first reaction mixture into contact with water in the presence of an acid is usually within 48 hours, and the intermediate (1,1,1,5,5,5- Hexafluoro-3-pent-2-one or its equivalent) and the contact conditions, the progress of the contact reaction is traced by analytical means such as gas chromatography, liquid chromatography, nuclear magnetic resonance, etc. The end point may be the point when almost no body loss is recognized.

  The method of the post-treatment in the second step is not particularly limited, and 1, 1, 1, 5 represented by the general formula [3], which is the target product, by adopting a general operation in organic synthesis. , 5,5-hexafluoroacetylacetone hydrate can be obtained. General operations in such organic synthesis include various methods such as crystallization, extraction, and distillation. For example, when the contact end solution (second reaction mixture) does not separate into two phases, the contact end solution is concentrated by distillation until a predetermined target product concentration is obtained, and a poor solvent (purification solvent) is added to the residue. An example is an operation of cooling and collecting the precipitated crystals by filtration and drying. When the contact-terminated liquid (second reaction mixture) undergoes two-phase separation, the organic layer is recovered and concentrated by distillation until a predetermined target product concentration is obtained, and a poor solvent (purification solvent) is added to the residue. The operation of cooling and collecting the precipitated crystals by filtration and drying can be mentioned as an example (see the third and sixth steps described later). The poor solvent (purification solvent) contained in the filtrate after the precipitated crystals are collected by filtration can be reused as the aforementioned poor solvent (purification solvent). At this time, the filtrate can be reused as it is, but it is preferred that the above-mentioned poor solvent (purification solvent) is purified by distillation from the filtrate and then reused. When the contact-terminated liquid (second reaction mixture) undergoes two-phase separation, the two-phase separated aqueous layer contains 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3]. Hydrates may be included. Therefore, it can be extracted and part or all of the extract can be added to the organic layer described above, and it is preferred to do so. Thereby, the fall of the yield of the target object by refinement | purification operation can be suppressed.

  As the solvent (extraction solvent) used for this extraction, the type exemplified as the reaction solvent in the first step can be used, and it is preferable to use the same type as the reaction solvent used in the first step. In addition, the hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] is an ether-based extraction solvent in spite of having a gem-diol group. Since it can collect | recover efficiently from a layer, using the ether type reaction solvent illustrated at the 1st process as an extraction solvent is mentioned as one of the preferable aspects.

  As a kind of the above-mentioned poor solvent (purification solvent), a poor solvent generally employed in organic synthesis can be used. For example, the aliphatic hydrocarbon solvent and aromatic hydrocarbon solvent described in the first step can be used. Examples of the aliphatic hydrocarbon solvent include, but are not limited to, n-pentane, n-hexane, cyclohexane, and n-heptane. Among these, a linear alkane, branched alkane, or cycloalkane having a boiling point of 90 to 110 ° C. and having 6 to 8 carbon atoms is preferable as a main component, and n-heptane is a main component. Are particularly preferred, and these may be a single component or a mixture containing other aliphatic hydrocarbon solvents as subcomponents. Moreover, examples of the aromatic hydrocarbon solvent include, but are not limited to, benzene, toluene, xylene, cumene, mesitylene and the like. These poor solvents (purification solvents) can be used alone or in combination.

  As will be described later, the reaction solvent used in the first step is purified by distillation from the organic solvent distilled off by concentration of the second reaction mixture (organic layer) by a predetermined method (fourth step) and recovered. The obtained reaction solvent can be reused as the reaction solvent in the first step and / or the extraction solvent described above. Similarly, it can be reused as a poor solvent (purification solvent) added to the above-mentioned residue.

  Here, n in the hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] represents a positive integer, and the upper limit is not particularly set. When n is 1, it represents a monohydrate and has the following formula:

And when n is 2, it represents a dihydrate and has the following formula:

Indicated by When n is 3 or more, it means that one or more water molecules are present in the dihydrate via a hydrogen bond or the like, and when n is an extremely large positive integer, the dihydrate Is present in the form of an aqueous solution. Of course, even if one or both carbonyl groups remain (corresponding to monohydrate and anhydride, respectively) and coexist with one water molecule, they are treated as dihydrate and monohydrate, respectively. . Among them, hydrates with n of 1 and 2 are preferable, and hydrates with n of 2 are particularly preferable.

  Water of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] contained in the residue of the second reaction mixture (organic layer) concentrated by distillation in the third step described later The Japanese product can be purified to a high purity through simple operations such as purification with a purification solvent (sixth step) and fractional distillation. When purifying by fractional distillation, purification by activated carbon treatment, recrystallization, column chromatography or the like may be combined as necessary. By performing such purification, 1,1,1,5,5,5-hexafluoroacetylacetone dihydrate can be isolated as a solid (crystal). Thereafter, high purity 1,1,1,5,5,5-hexafluoroacetylacetone (anhydride) can be obtained through a dehydration step described later (see JP-A-2001-187760).

  In addition, trimethylsilylethyl ketal of 1,1,1,5,5,5-hexafluoro-3-pent-2-one described above is also brought into contact with water in the presence of an acid to give a general formula [3]. 1,1,1,5,5,5-hexafluoroacetylacetone hydrate can be obtained in good yield (see Reference Example 1). As a component in the first reaction mixture of the present invention, 1,1,1,5,5,5-hexafluoro-3-pent-2-one obtained in the first step or 1,1,1,5 , 5,5-hexafluoro-3-pent-2-onone equivalents may be included in this way. There is no restriction | limiting in particular in the kind of this derivative, Protective Groups in Organic Synthesis, Third Edition, 1999, John Wiley & Sons, Inc. Among the protecting groups for hydroxyl groups described in the above, derivatives protected with protecting groups that can be deprotected by contact with water in the presence of an acid are preferred, and acyl protecting groups such as formyl group, acetyl group and benzoyl group And derivatives protected with silyl protecting groups such as trimethylsilyl, triethylsilyl and dimethyl-tert-butylsilyl groups are particularly preferred.

[Third step]
In the third step, the second reaction mixture obtained in the second step is converted into 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] in the second reaction mixture. This is a step of concentrating by distillation until the hydrate becomes a predetermined concentration. By this concentration, the organic solvent contained in the second reaction mixture is distilled off. This organic solvent includes the reaction solvent used in the first step.

  In the third step, the concentration of 1,1,1,5,5,5-hexafluoroacetylacetone hydrate represented by the general formula [3] is 1 to 100% by mass, preferably 5 to 100% by mass. Concentrate the second reaction mixture to such an extent. This concentration can be performed as it is without subjecting the second reaction mixture obtained in the second step to a special treatment. At this time, when the second reaction mixture obtained in the second step is separated into an aqueous layer and an organic layer, the organic layer obtained by separation is preferably subjected to concentration, It is preferable to concentrate to such an extent. The aspect of concentrating the organic layer is also included as one of the aspects of “concentrating the second reaction mixture by distillation” according to the third step.

  At this time, the separated aqueous layer may contain a hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3]. Part or all of the extract can be added to this organic layer and it is preferred to do so. As the solvent (extraction solvent) used for this extraction, those described above in the post-treatment in the second step can be employed.

  The concentrated second reaction mixture (or the organic layer thereof) is subjected to the sixth step described later, or 1, 1, 1, 5 represented by the general formula [3] by other purification methods. The hydrate of 5,5-hexafluoroacetylacetone is purified.

  In the present invention, a part or all of the organic solvent distilled off in the concentration step is subjected to a fourth step described later, and then as at least a part of the reaction solvent in the first step and / or the second reaction mixture. Or it reuses as an extraction solvent of the water layer obtained by isolate | separating from it. Furthermore, it can be reused as a purification solvent in the sixth step described later, and it is preferable to do so.

[Fourth step]
In the reaction of the 3,3,3-trifluoropropynyl metal represented by the general formula [1] and the trifluoroacetic acid ester represented by the general formula [2], 1,1,1,5,5,5-hexafluoro In addition to -3-pent-2-one or its equivalent, various fluorine-containing compounds may be by-produced as by-products. This fluorine-containing compound can be easily identified depending on the type, and can be easily separated from a solvent (such as a reaction solvent) or a target product in a reaction process or a purification process. However, among these fluorine-containing compounds, one or a plurality of fluorine-containing compounds that may not be easily identified (sometimes referred to as “fluorine-containing compound group”), or separation is easy even if they are easily identified. Difficult things (these may be collectively referred to as “fluorine atom-containing impurities”) may be included. Depending on the type of reaction raw material, separation from the solvent may be difficult. When such fluorine atom-containing impurities and solvents containing reaction raw materials (reaction solvent, extraction solvent, etc.) are circulated, fluorine atom-containing impurities and reaction raw materials are gradually accumulated in the reaction system and are continuously operated as they are. If this is the case, the balance of the proportion of the reaction raw material in the reaction system may be lost, and the yield of the target product may be reduced. Therefore, in order to reduce or suppress the increase of fluorine atom-containing impurities contained in the solvent used for circulation, as described above, it is necessary to perform a predetermined treatment on the organic solvent distilled off in the third step. Specifically, a part or all of the organic solvent distilled off in the third step is recovered and brought into contact with a predetermined basic compound. Although the recovered organic solvent may contain a reaction raw material as an impurity, the reaction raw material may be removed by contact with the basic compound described above.

  In this step, a prescribed treatment is applied for the purpose of reducing or suppressing the increase of fluorine atom-containing impurities contained in the solvent used for circulation. Among these fluorine atom-containing impurities, the fluorine-containing compound group is reduced. It is preferable to suppress or prevent the increase.

  Examples of the basic compound according to the present invention include alkali metal hydroxides, carbonates and hydrogen carbonates, alkaline earth metal hydroxides and carbonates, basic metal oxides, tetraalkylammonium hydroxide, and trialkyls. Examples include amines and nitrogen-containing heterocyclic compounds. These basic compounds may be used alone or in combination of two or more. Examples of the alkali metal hydroxide include lithium hydroxide, sodium hydroxide, potassium hydroxide, and cesium hydroxide. Examples of the alkali metal carbonate include lithium carbonate, sodium carbonate, potassium carbonate, and cesium carbonate. Examples of the alkali metal hydrogen carbonate include sodium hydrogen carbonate. Examples of the alkaline earth metal hydroxide include magnesium hydroxide, calcium hydroxide, barium hydroxide, barium hydroxide octahydrate, and the like. Examples of the alkaline earth metal carbonate include magnesium carbonate, carbonic acid carbonate. Examples include calcium and barium carbonate. Examples of the basic metal oxide include basic alumina and calcium oxide. Examples of the tetraalkylammonium hydroxide include tetramethylammonium hydroxide, tetraethylammonium hydroxide, tetra-n-propylammonium hydroxide, and tetra-n-butylammonium hydroxide. Examples of the trialkylamine include triethylamine, tri-n-propylamine, tri-n-butylamine, and diisopropylethylamine. Examples of the nitrogen-containing heterocyclic compound include pyridine, 2,6-dimethylpyridine, pyrazine, 4-dimethylaminopyridine, 1,8-diazabicyclo [5.4.0] undec-7-ene and the like. Among these, sodium hydroxide, calcium hydroxide, magnesium hydroxide, barium hydroxide octahydrate, sodium hydrogen carbonate, cesium carbonate, potassium carbonate, calcium carbonate, basic alumina, and tributylamine are preferable. Barium hydroxide -Especially preferred are octahydrate, calcium carbonate and tributylamine. In addition, the basic compound according to the present invention can be used as an aqueous solution for contact with the recovered organic solvent.

  The basic compound according to the present invention is used in the amount of 1,1,1,5,5,5-hexafluoroacetylacetone hydrate, trifluoroacetic acid ester contained in the organic solvent distilled off in the third step. (Reaction raw material) and 0.001 molar equivalent or more with respect to the total number of moles of trifluoroacetic acid (byproduct) may be used, preferably 0.005 to 50 molar equivalent, and 0.1 to 10 molar equivalent Particularly preferred.

  The contact temperature between the organic solvent and the basic compound may be usually + 150 ° C. or less, preferably +125 to −50 ° C., particularly preferably +100 to −25 ° C.

  The contact time between the organic solvent and the basic compound is usually 48 hours or less, and varies depending on the contact conditions. Therefore, the progress of the contact is traced by an analytical means such as gas chromatography, liquid chromatography, or nuclear magnetic resonance. 1,1,1,5,5,5-hexafluoroacetylacetone hydrate, trifluoroacetic acid ester, and the point at which almost no decrease in trifluoroacetic acid is observed is preferably used as the end point.

  The method for bringing the organic solvent into contact with the basic compound is not particularly limited, but in order to maximize the effects of the present invention, the recovered organic solvent and the basic compound are brought into contact with each other using a stirrer. Is preferred. Moreover, when making a basic compound contact as aqueous solution, the density | concentration of the basic compound in this aqueous solution should just be 0.01-99.99 mass%, and 1.0-99.99 mass% is preferable.

  When precipitation of crystals is observed in the solution after contact (contact liquid), it is preferable to remove this by filtration or the like.

  Subsequently, by subjecting the obtained contact liquid to distillation purification, a reusable high-purity solvent (reaction solvent, extraction solvent) can be recovered.

  The conditions for the distillation purification are not particularly limited, and the distillation purification may be performed using one or a plurality of distillation columns. The distillation column can be refluxed to increase purification efficiency. The number of theoretical plates is 1 to 100, preferably 5 to 100. The distillation purification conditions such as the reflux ratio, tower top temperature, tower bottom temperature, and pressure are preferably adjusted appropriately according to the type of reaction solvent to be purified and the purification state. The tower top temperature is preferably 20 to 140 ° C., and the pressure is preferably 1 to 760 mmHg.

  Further, the material constituting the wetted part of the distillation column is not particularly limited, and metals such as aluminum, copper, seven-three brass, titanium, cast iron, carbon steel, and stainless steel, ceramic, plastic, carbon, etc. are used. be able to. Among these, it is preferable to use at least one selected from the group consisting of metals, ceramics, plastics, and carbons that are difficult to elute metal components, and at least one selected from the group consisting of ceramics, plastics, and carbons is particularly preferable. When distillation purification is performed using a metal distillation column from which a metal component can be eluted as a material constituting the liquid contact portion, the distillate may turn red. Although details of the cause of this discoloration are not clear, a hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3], which may be contained in the contact liquid, It is presumed that it is complexed with a metal compound derived from the material (metal component) of the wetted part. Inorganic Chemistry (USA), 1992, Vol. 31, p. According to 4436-8, the following formula:

Is reported, but the metal complex compound corresponding to only the hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] and the metal compound It was unclear whether this would form. Actually, the distillate containing the hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] was changed to a distillation column made of stainless steel. When fractional distillation is performed, the solution may turn red (see Reference Example 2).

  In order to increase the purification efficiency, the distillation column may be provided with a packing. The material of the filler is not particularly limited, and metals such as aluminum, copper, seven-three brass, titanium, cast iron, carbon steel and stainless steel, ceramic, plastic, carbon, etc. can be used. From the viewpoint of preventing discoloration of the distillate, it is preferable to use at least one selected from the group consisting of metals, ceramics, plastics and carbons from which the metal component is not easily eluted, and selected from the group consisting of ceramics, plastics and carbons. At least one is particularly preferred.

  The reaction solvent recovered by distillation purification can be used for the fifth step as it is, or if necessary, the reaction solvent can be subjected to a dehydration treatment and then used for the fifth step.

[Fifth step]
In the fifth step according to the present invention, the reaction solvent recovered in the aforementioned fourth step is reused as at least part of the reaction solvent in the first step, and / or the second reaction mixture or separated therefrom. It is the process of reusing as an extraction solvent of the obtained water layer, or reusing as both.

[Sixth step]
In the sixth step according to the present invention, 1,1,1,5,5 represented by the general formula [3] is obtained from the residue of the second reaction mixture concentrated in the third step using a purification solvent. , 5-Hexafluoroacetylacetone hydrate purification step.

  Specifically, referring to JP-A-2001-187760, a method of dispersing the residue of the second reaction mixture concentrated in the above-mentioned third step in a purification solvent, followed by filtration / separation, and filtration device The method of spraying the purification solvent on the hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] held on the filter in FIG. By doing so, the hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] can be purified. As the purification solvent, the poor solvent (purification solvent) mentioned in the second step can be used. Further, after these operations, it is usually dried, but drying is not necessarily required. Moreover, the poor solvent (purification solvent) contained in the filtrate produced by these filtration operations can be reused as the purification solvent in this step. At this time, the filtrate can be reused as it is, but it is preferable to reuse the above-mentioned poor solvent (purification solvent) after purification from the filtrate by distillation.

[Seventh step]
The seventh step according to the present invention is a step of reusing the reaction solvent recovered in the aforementioned fourth step as at least a part of the purification solvent in the aforementioned sixth step.

  From the hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] produced by the above-described method, through a subsequent dehydration step, 1,1,1,5,5 5,5-Hexafluoroacetylacetone can be produced.

[Dehydration process]
A step of producing 1,1,1,5,5,5-hexafluoroacetylacetone by dehydrating 1,1,1,5,5,5-hexafluoroacetylacetone hydrate represented by the general formula [3] Will be described.

  The hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] obtained by the above method can be suitably used in this step. 1,5,5,5-hexafluoroacetylacetone can be obtained with high selectivity and high yield. Specific operations in this step are described in JP-A-2001-187760, JP-A-2001-261607, JP-A-2001-354610, JP-A-2004-2466, and references cited therein (J. Inorganic). and Nuclear Chemistry, 1956, Vol. 2, p. 11-31 and Non-Patent Document 1, etc.) and the like. For example, Japanese Patent Application Laid-Open No. 2001-187760 describes a method of dehydrating 1,1,1,5,5,5-hexafluoroacetylacetone dihydrate using concentrated sulfuric acid as a dehydrating agent.

  The method for dehydration is not particularly limited, and examples thereof include a thermal decomposition method, an azeotropic dehydration method, and a method using a dehydrating agent. Among these, a method using a dehydrating agent is preferable.

  The dehydrating agent is acetic anhydride, diphosphorus pentoxide, soda lime, calcium chloride, anhydrous zinc chloride, anhydrous sodium sulfate, anhydrous magnesium sulfate, anhydrous sulfuric acid in addition to the concentrated sulfuric acid used in the above-mentioned JP-A-2001-187760. Calcium, alumina, silica gel, synthetic zeolite and the like can be used.

  Embodiments of the present invention will be specifically described by way of examples, but the present invention is not limited to these examples.

[Preparation Example]
To 36 kg of tert-butyl methyl ether (abbreviation: MTBE), 6.5 kg (69 mol, 1.0 eq) of 3,3,3-trifluoropropyne was added at −98 to −44 ° C., and n-butyllithium n- A heptane solution (25 wt%) 17 kg (66 mol, 1.0 eq) was added at −103 to −28 ° C., and the mixture was stirred at −30 ° C. for 30 minutes. Furthermore, 9.5 kg (67 mol, 1.0 eq) of ethyl trifluoroacetate was added at −38 to −33 ° C., and the mixture was stirred at −30 ° C. for 2 hours (reaction completed solution). The operation so far was performed in a nitrogen gas atmosphere. Next, this reaction-terminated liquid was added to 64 kg [prepared from concentrated sulfuric acid 16 kg (160 mol, 2.4 eq) and water 48 kg] at 3 ° C. and stirred at 5 ° C. for 30 minutes (two-phase system). After stirring, two phases were separated, and an aqueous layer and an organic layer were recovered. ^It was quantified by an internal standard method (internal standard substance; α, α, α-trifluorotoluene) by ¹⁹ F-NMR analysis.

37 mol of ethyl hemiketal of 1,1,1,5,5,5-hexafluoro-3-pent-2-one represented by the following formula:

29 mol of 1,1,1,5,5,5-hexafluoro-3-pent-2-one represented by the following formula was contained. The combined yield of the equivalents was quantitative. ¹⁹ F-NMR of ethyl hemiketal and hydrate of 1,1,1,5,5,5-hexafluoro-3-pent-2-one are shown below.
¹⁹ F-NMR (reference material; CFCl ₃ , heavy solvent; not used, measured in the recovered organic layer)
Ethyl hemiketal / δ ppm; −85.05 (3F), −52.52 (3F).
Hydrate / δ ppm; −86.37 (3F), −52.52 (3F).

To the recovered organic layer thus obtained, 29 kg of sulfuric acid aqueous solution [prepared from concentrated sulfuric acid 0.29 kg (3.0 mol, 0.045 eq) and water 29 kg] was added and stirred at 52 ° C. for 10 hours (two-phase system). This was separated into two phases, and an aqueous layer and an organic layer were recovered. ^When determined by an internal standard method (internal standard substance; α, α, α-trifluorotoluene) by ¹⁹ F-NMR analysis, this recovered organic layer has the following formula:

58 mol of 1,1,1,5,5,5-hexafluoroacetylacetone dihydrate represented by The yield of the desired product was 88%. The recovered organic layer was washed with 40 kg of water and then concentrated under reduced pressure (oil bath temperature to 29 ° C./vacuum degree to 6.2 kPa) to obtain a distillate. 30 kg of n-heptane was added to the residue after the distillate was removed, and the mixture was again concentrated under reduced pressure (oil bath temperature to 33 ° C./vacuum degree to 5.5 kPa) to obtain a distillate. After removing this distillate, 45 kg of n-heptane was added to the residue, followed by stirring at 4 ° C. for 2 hours. After stirring, the precipitated crystals are filtered and dried under reduced pressure to give a hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone (dihydrate: 1 hydrate = 92: 8) 13 kg was obtained. The total yield was 82%.

[Examples 1-7]
<Purification of MTBE contained in distillate>
Purification of 61 g of the distillate obtained in the preparation example was performed.
^When quantified by an internal standard method (internal standard substance: α, α, α-trifluorotoluene) by ¹⁹ F-NMR analysis, this distillate contained 1,1,1,5,5 in addition to MTBE. , 5-hexafluoroacetylacetone hydrate 0.5 mmol, ethyl trifluoroacetate 0.8 mmol, trifluoroacetic acid 0.5 mmol, and other fluorine-containing compound group 0.3 mmol were contained. Further, as a result of moisture analysis, the distillate contained 0.1 g of water.

The basic compound shown in Table 1 was added to 61 g of this distillate, and the mixture was stirred at a hot water bath temperature of 50 to 60 ° C. for 1 hour. Ethyl trifluoroacetate and other fluorine-containing compounds contained in the solution after stirring were quantified by ¹⁹ F-NMR analysis by an internal standard method (internal standard substance: α, α, α-trifluorotoluene). Table 1 shows the added basic compound and the quantitative results.

[Example 8]
<Purification of MTBE contained in distillate (basic compound: barium hydroxide octahydrate)>
Purification of 2075.7 g of the distillate obtained in the preparation example was performed. ^When quantified by an internal standard method (internal standard substance: α, α, α-trifluorotoluene) by ¹⁹ F-NMR analysis, this distillate contained 1,1,1,5,5 in addition to MTBE. , 17-mmol of hexafluoroacetylacetone, 27 mmol of ethyl trifluoroacetate, 10 mmol of trifluoroacetic acid, and 10 mmol of other fluorine-containing compounds. As a result of moisture analysis, this distillate contained 4.8 g of water.

19.7 g (62 mmol) of barium hydroxide octahydrate was added to 2075.7 g of this distillate, and the mixture was stirred at 54 to 56 ° C. for 45 minutes. The solution was then cooled to room temperature and then stirred for 15 hours. After stirring, the crystals precipitated in the solution were filtered. The obtained filtered solution was fractionally distilled in a distillation column (wetted part: made of glass, filler: made of glass) [theoretical plate number: 15 stage, kettle temperature: 59-103 ° C., tower top temperature: 53-100 ° C., reflux] Ratio (open: closed) 1: 20-3: 1], MTBE1207.9 g and n-heptane 334.5 g were obtained as colorless and transparent liquids, respectively. The gas chromatography purity of this MTBE was 99.3%, and the gas chromatography purity of n-heptane was 99.6%. MTBE after fractional distillation was quantified by ¹⁹ F-NMR analysis by an internal standard method (internal standard substance: α, α, α-trifluorotoluene), and contained 2 mmol of other fluorine-containing compounds. When n-heptane was quantified by ¹⁹ F-NMR analysis by an internal standard method (internal standard substance: α, α, α-trifluorotoluene), it contained 2 mmol of other fluorine-containing compounds. Since the moisture content of this MTBE was high (water content: 1.1%), it was dehydrated using molecular sieves 5A (0.13 g used for 1.0 g of MTBE) (water content after dehydration: 0.0%).

<Reuse of purified MTBE>
To 150 mL of MTBE after the above dehydration, 20.0 g (213 mmol, 1.07 eq) of 3,3,3-trifluoropropyne was added at −62 to −56 ° C., and an n-heptane solution of n-butyllithium (25 wt% ) 51.2 g (200 mmol, 1.0 eq) was added at −64 to −34 ° C. and stirred at −30 ° C. for 30 minutes. Furthermore, 28.4 g (200 mmol, 1.0 eq) of ethyl trifluoroacetate was added at −44 to −38 ° C. and stirred at −30 ° C. for 2 hours (reaction completed solution). The operation so far was performed in a nitrogen gas atmosphere. The reaction-terminated liquid was added to 157 g of sulfuric acid aqueous solution [prepared from 39 g (400 mmol, 2.0 eq) of concentrated sulfuric acid and 118 g of water] at 3 ° C. and stirred at 3 ° C. for 30 minutes (two-phase system). After stirring, two phases were separated, and an aqueous layer and an organic layer were recovered. The recovered organic layer was quantified by ¹⁹ F-NMR analysis by an internal standard method (internal standard substance; α, α, α-trifluorotoluene).

72 mmol of 1,1,1,5,5,5-hexafluoro-3-pent-2-one ethylhemiketal represented by the following formula:

The hydrate of 1,1,1,5,5,5-hexafluoro-3-pent-2-one represented by formula (1) was contained. The combined yield of the equivalents was 95%. ¹⁹ F-NMR of ethyl hemiketal and hydrate of 1,1,1,5,5,5-hexafluoro-3-pent-2-one are shown below.
¹⁹ F-NMR (reference material; CFCl ₃ , heavy solvent; not used, measured in the recovered organic layer)
Ethyl hemiketal / δ ppm; −85.05 (3F), −52.52 (3F).
Hydrate / δ ppm; −86.37 (3F), −52.52 (3F).

To the recovered organic layer thus obtained, 98 g of a sulfuric acid aqueous solution [prepared from concentrated sulfuric acid 1.0 g (10 mmol, 0.05 eq) and water 97 g] was added and stirred at 50 ° C. for 17 hours (two-phase system). This was separated into two phases, and an aqueous layer and an organic layer were recovered. ^When determined by an internal standard method (internal standard substance; α, α, α-trifluorotoluene) by ¹⁹ F-NMR analysis, this recovered organic layer has the following formula:

163 mol of 1,1,1,5,5,5-hexafluoroacetylacetone dihydrate represented by The yield of the desired product was 82%.

[Example 9]
<Purification of MTBE contained in distillate (basic compound: tributylamine)>
614.0 g of the distillate obtained in the preparation example was purified.
^When determined by an internal standard method (internal standard substance: α, α, α-trifluorotoluene) from ¹⁹ F-NMR analysis, 1,1,1,5,5,5-hexafluoroacetylacetone was found in the distillate. Hydrate 5 mmol, ethyl trifluoroacetate 8 mmol, trifluoroacetic acid 5 mmol, and other fluorine-containing compound group 3 mmol. Further, from the water analysis, the distillate contained 1.4 g of water.

To 614.0 g of this distillate, 4.1 g (22 mmol) of tributylamine was added, and fractional distillation was performed in a distillation column (wetted part: made of glass, filler: made of glass) [theoretical plate number: 15 plates, kettle temperature: 59 to 98]. C., tower top temperature of 54 to 95 ° C., reflux ratio (open: closed) 1: 2] to obtain 424.1 g of colorless and transparent MTBE. The gas chromatographic purity of MTBE after fractional distillation was 98.7%. Moreover, when MTBE after fractional distillation was quantified by ¹⁹ F-NMR analysis by an internal standard method (internal standard substance: α, α, α-trifluorotoluene), 8 mmol of ethyl trifluoroacetate and other fluorine-containing compounds group Contained 1 mmol.

[Example 10] (Reuse of recovered n-heptane)
To 157 g of pure MTBE, 27.0 g (287 mmol, 1.1 eq) of 3,3,3-trifluoropropyne was added at −55 to −30 ° C., and n-heptane solution (24 wt%) 70 of n-butyllithium was added. 0.1 g (261 mmol, 1.0 eq) was added at −55 to −25 ° C., and the mixture was stirred at −30 ° C. for 30 minutes. Furthermore, 38.8 g (273 mmol, 1.05 eq) of ethyl trifluoroacetate was added at −45 to −35 ° C. and stirred at −30 ° C. for 2 hours (reaction completed solution). The operation so far was performed in a nitrogen gas atmosphere. To 216 g of sulfuric acid aqueous solution [prepared from concentrated sulfuric acid 54 g (549 mmol, 2.1 eq) and water 162 g], the reaction completed solution was added at 3 ° C., pure MTBE 70 g was added, and the mixture was stirred at 5 ° C. for 15 minutes (two-phase system) . Two-phase separation and ¹⁹ F-NMR analysis of the recovered organic layer were quantified by an internal standard method (internal standard substance: α, α, α-trifluorotoluene).

74 mmol of ethyl hemiketal of 1,1,1,5,5,5-hexafluoro-3-pent-2-one represented by the following formula:

As a result, an organic layer containing 180 mmol of 1,1,1,5,5,5-hexafluoro-3-pent-2-one hydrate represented by formula (1) was obtained. The combined yield of the equivalents was 97%.

To this organic layer, 134 g of a sulfuric acid aqueous solution [prepared from 1.3 g of concentrated sulfuric acid (13 mmol, 0.05 eq) and 133 g of water] was added and stirred at 50 ° C. for 17 hours (two-phase system). Two-phase separation was performed, and the amount was determined by internal standard method (internal standard substance: α, α, α-trifluorotoluene) from ¹⁹ F-NMR analysis of the recovered organic layer.

222 mol of 1,1,1,5,5,5-hexafluoroacetylacetone dihydrate represented by the formula: The yield of the desired product was 85%. The recovered organic layer was washed with 167 g of water and concentrated under reduced pressure (degree of vacuum: ˜14 kPa). To the residue after concentration under reduced pressure, n-heptane (referred to as “recovered n-heptane”) obtained by carrying out the same purification as in Example 3 on the distillate obtained by the same operation as in the preparation example. 107 g) was added, and the mixture was concentrated again under reduced pressure (degree of vacuum: ˜7.3 kPa). Thereafter, 161 g of recovered n-heptane was added, and the precipitated crystals were filtered. The crystals were washed with recovered n-heptane and dried under reduced pressure to give a hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone (dihydrate: 1 hydrate = 97: 3). ) 47.6g was obtained. The total yield was 75%.

[Example 11]
<Purification of MTBE contained in distillate (basic compound: sodium hydroxide)>
2109.0 g of distillate obtained by the same operation as in the preparation example was purified. ^When determined by an internal standard method (internal standard substance: α, α, α-trifluorotoluene) from ¹⁹ F-NMR analysis, 1,1,1,5,5,5-hexafluoroacetylacetone was found in the distillate. Hydrate 105 mmol, ethyl trifluoroacetate 33 mmol, trifluoroacetic acid 21 mmol, and other fluorine-containing compound group 134 mmol.

To 29.09.0 g of this distillate was added 26.4 g of 33% aqueous sodium hydroxide solution (prepared from 8.8 g (220 mmol) of sodium hydroxide and 17.6 g of water), and the mixture was stirred at room temperature for 30 minutes (two-phase system). ). After stirring, two phases were separated, and an aqueous layer and an organic layer were recovered. When this recovered organic layer was quantified by ¹⁹ F-NMR analysis by an internal standard method (internal standard substance: α, α, α-trifluorotoluene), it contained 200 mmol of other fluorine-containing compounds. This recovered organic layer is subjected to fractional distillation (theoretical number of plates: 10) in a distillation column (wetted part: glass, filler: glass) to give colorless and transparent MTBE [distillation temperature to 62 ° C., atmospheric pressure]. 887.6 g and 726.9 g of n-heptane [distillation temperature to 99 ° C., atmospheric pressure] were recovered. When MTBE after fractional distillation was quantified by ¹⁹ F-NMR analysis by an internal standard method (internal standard substance; α, α, α-trifluorotoluene), it contained 60 mmol of other fluorine-containing compounds. The moisture content of this MTBE was 0.0%. Further, n-heptane after fractional distillation was quantified by ¹⁹ F-NMR analysis by an internal standard method (internal standard substance; α, α, α-trifluorotoluene), and contained 21 mmol of other fluorine-containing compounds. .

<Reuse of purified MTBE>
To 120 mL of the above MTBE, 16.0 g (170 mmol, 1.1 eq) of 3,3,3-trifluoropropyne was added at −51 to −38 ° C., and n-heptane solution (25 wt%) in n-butyllithium was added. 0 g (160 mmol, 1.0 eq) was added at −51 to −29 ° C., and the mixture was stirred at −30 ° C. for 30 minutes. Furthermore, 23.9 g (168 mmol, 1.1 eq) of ethyl trifluoroacetate was added at −42 to −39 ° C. and stirred at −30 ° C. for 2 hours (reaction completed solution). The operation so far was performed in a nitrogen gas atmosphere. The reaction-terminated liquid was added to 157.2 g of sulfuric acid aqueous solution [prepared from 39.2 g (400 mmol, 2.5 eq) of concentrated sulfuric acid and 118 g of water] at 3 ° C. and stirred at 5 ° C. for 10 minutes (two-phase system). Two-phase separation was performed, and the amount was determined by internal standard method (internal standard substance: α, α, α-trifluorotoluene) from ¹⁹ F-NMR analysis of the recovered organic layer.

55 mmol of 1,1,1,5,5,5-hexafluoro-3-pent-2-one ethylhemiketal represented by the following formula:

70 mmol of 1,1,1,5,5,5-hexafluoro-3-pent-2-one hydrate represented by the formula (1) was contained. The combined yield of the equivalents was 79%.

[Example 12]
<Purification of MTBE contained in distillate (basic compound: basic alumina)>
Purification of 1000.0 g of the distillate obtained in the preparation example was performed.
^When determined by an internal standard method (internal standard substance: α, α, α-trifluorotoluene) from ¹⁹ F-NMR analysis, 1,1,1,5,5,5-hexafluoroacetylacetone was found in the distillate. Hydrate 8 mmol, ethyl trifluoroacetate 13 mmol, trifluoroacetic acid 8 mmol, and other fluorine-containing compound group 5 mmol. From the moisture analysis, the distillate contained 2.3 g of water.

Purification was carried out by column chromatography (distillation rate 0.5 g / sec) in which 1000.0 g of this distillate was packed with 100.0 g of basic alumina, and the colorless and transparent first half fraction 546.6 g, second half fraction 396.9 g was obtained. The obtained first half fraction was quantified by ¹⁹ F-NMR analysis by an internal standard method (internal standard substance: α, α, α-trifluorotoluene). As a result, 1 mmol of ethyl trifluoroacetate and 4 mmol of other fluorine-containing compounds were obtained. Was included. Moreover, when the obtained latter half fraction was quantified by ¹⁹ F-NMR analysis by an internal standard method (internal standard substance; α, α, α-trifluorotoluene), 1,1,1,5,5,5- It contained 2 mmol of hexafluoroacetylacetone hydrate, 3 mmol of ethyl trifluoroacetate, and 7 mmol of other fluorine-containing compounds.

[Comparative Example 1]
<Purification of MTBE contained in distillate (basic compound: not used)>
Purification of 1067 g of distillate obtained by the same operation as in the preparation example was performed.
^When determined by an internal standard method (internal standard substance: α, α, α-trifluorotoluene) from ¹⁹ F-NMR analysis, 1,1,1,5,5,5-hexafluoroacetylacetone was found in the distillate. Hydrate 52 mmol, ethyl trifluoroacetate 17 mmol, trifluoroacetic acid 11 mmol and other fluorine-containing compound group 66 mmol. Further, from the moisture analysis, the distillate contained 2.1 g of water.

This distillate is fractionally distilled in a distillation column (wetted part: made of glass, filler: made of glass) [theoretical plate number: 15 plates, kettle temperature: 69-101 ° C., column top temperature: 54-100 ° C., reflux ratio (open : Closed) 1: 5 to 1: 2] to obtain 569.4 g of colorless and transparent MTBE and 312.2 g of n-heptane. MTBE after fractional distillation was quantified by ¹⁹ F-NMR analysis by an internal standard method (internal standard substance: α, α, α-trifluorotoluene). 1,1,1,5,5,5-hexafluoroacetylacetone 1 mmol, 46 mmol of trifluoroacetic acid, 32 mmol of 1,1,1,5,5,5-hexafluoroacetylacetone, and 35 mmol of other fluorine-containing compounds. When n-heptane after fractional distillation was quantified by ¹⁹ F-NMR analysis by an internal standard method (internal standard substance: α, α, α-trifluorotoluene), it contained 16 mmol of other fluorine-containing compounds.

  As shown in Examples 1 to 9 and Examples 11 to 12 described above, the distillate containing a fluorine-containing compound group, ethyl trifluoroacetate and trifluoroacetic acid was brought into contact with a basic compound to thereby produce the distillate. The total amount of the fluorine-containing compound group, ethyl trifluoroacetate and trifluoroacetic acid contained in the effluent can be reduced. On the other hand, as shown in Comparative Example 1, when the basic compound was not used, an increase in the total amount of the fluorine-containing compound group, ethyl trifluoroacetate and trifluoroacetic acid contained in the distillate was observed.

  In addition, as shown in Examples 1, 2, 8 and 9, the distillate containing the fluorine-containing compound group is brought into contact with a specific basic compound to suppress the increase in the fluorine-containing compound group. Can do. As a result, when MTBE in which an increase in the number of fluorine-containing compounds was suppressed was reused (Example 8), 1,1,1,5,5,5-hexafluoro-3-pentyl which is a reaction intermediate. The combined yield of 2-nonone equivalents was good.

[Reference Example 1]
To 40 mL of tetrahydrofuran was added 7.1 g (50 mmol, 1.9 eq) of ethyl trifluoroacetate, and the mixture was cooled to −78 ° C. with stirring to give a liquid I. On the other hand, 2.5 g (27 mmol, 1.0 eq) of 3,3,3-trifluoropropyne was added to 60 mL of tetrahydrofuran at 0 ° C., and 16 mL (26 mmol, n-butyllithium solution in n-hexane (1.6 M) was added. 1.0 eq) was added at −78 ° C., and the mixture was stirred at the same temperature for 30 minutes to obtain a liquid II. Liquid II was added to liquid I and stirred at -78 ° C for 1 hour (reaction mixture). The operation so far was performed in a nitrogen gas atmosphere. The reaction mixture was added to 21 g of a trimethylsilyl chloride tetrahydrofuran solution [prepared from 3.0 g (28 mmol, 1.1 eq) of trimethylsilyl chloride and 18 g of tetrahydrofuran] at 0 ° C. and stirred at room temperature for 3 days (reaction completed solution). When determined by internal standard method (internal standard substance; α, α, α-trifluorotoluene) from ¹⁹ F-NMR analysis of this reaction completed solution, the following formula:

20 mmol of trimethylsilylethyl ketal of 1,1,1,5,5,5-hexafluoro-3-pent-2-one represented by the formula: The yield of the equivalent was 77%. The reaction-terminated liquid was directly concentrated under reduced pressure (40 ° C./200 hPa), the precipitated lithium chloride was removed by decantation, and distilled under reduced pressure (46 to 65 ° C./˜2.8 kPa) to obtain 1,1,1,5. , 5,5-hexafluoro-3-pent-2-one, 4.2 g of trimethylsilylethyl ketal was obtained. The total yield was 54%. The gas chromatography purity was 97.4%. ¹ H-NMR, ¹³ C-NMR and ¹⁹ F-NMR of trimethylsilylethyl ketal of 1,1,1,5,5,5-hexafluoro-3-pent-2- ^one are shown below.
¹ H-NMR [reference material; (CH ₃ ) ₄ Si, deuterated solvent; CDCl ₃ ]
δ ppm; 0.26 (9H), 1.29 (3H), 3.78 (2H).
¹³ C-NMR [reference material; (CH ₃ ) ₄ Si, deuterated solvent; CDCl ₃ ]
δ ppm; 0.82, 14.78, 61.37, 73.89, 79.53, 91.02, 113.42, 120.57.
¹⁹ F-NMR (reference material; C ₆ F ₆ , deuterated solvent; CDCl ₃ )
δ ppm; 78.09, 109.95.

To 0.15 g (0.49 mmol, 1 eq) of trimethylsilylethyl ketal of 1,1,1,5,5,5-hexafluoro-3-pent-2-one obtained, 2.0 mL of tetrahydrofuran and aqueous sulfuric acid solution 1. 3 g [prepared from 0.30 g (3.1 mmol, 6.3 eq) of concentrated sulfuric acid and 1.0 g of water] was added, and the mixture was stirred at 40 ° C. for 3 hours and 30 minutes, and further stirred at 50 ° C. for 4 hours and 30 minutes (uniform solution) ). From the ¹⁹ F-NMR analysis of the reaction completed solution, the following formula:

The conversion of 1,1,1,5,5,5-hexafluoroacetylacetone to dihydrate represented by the formula was 93%.

[Reference Example 2]
<Purification of MTBE contained in distillate>
Purification of 54 g of distillate obtained by the same operation as in the preparation example was performed. ^When determined by an internal standard method (internal standard substance; α, α, α-trifluorotoluene) from ¹⁹ F-NMR analysis, the mixed solution contains 1,1,1,5,5,5-hexafluoroacetylacetone. It contained 3 mmol of hydrate, 1 mmol of ethyl trifluoroacetate, 1 mmol of trifluoroacetic acid and 3 mmol of other fluorine-containing compounds. From the moisture analysis, the mixed solution contained 0.1 g of water.

  When this distillate is fractionally distilled in a distillation column (wetted part: made of stainless steel, filler: made of stainless steel) [theoretical plate number: 10 plates, internal temperature: 67 to 70 ° C., oil bath temperature: 90 ° C.] The solution was colored red after 1-2 hours.

Claims (9)

General formula [3] including at least the following first to fifth steps:

[Wherein n represents a positive integer. ]
A process for producing a hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the formula:
First step:
General formula [1]:

[Wherein, M represents a lithium atom or a magnesium halide group (MgX), and X represents a chlorine atom, a bromine atom or an iodine atom. ]
A 3,3,3-trifluoropropynyl metal represented by the general formula [2]:

[Wherein, R represents an alkyl group. ]
And 1,1,1,5,5,5-hexafluoro-3-pent-2-one , represented by the general formula [5]:

[Wherein, M represents a lithium atom or a halogenated magnesium group (MgX), X represents a chlorine atom, a bromine atom or an iodine atom, and R represents an alkyl group. M and R are derived from M of the 3,3,3-trifluoropropynyl metal represented by the general formula [1] and R of the trifluoroacetate ester represented by the general formula [2], respectively, and the same metal and alkyl group Take. ]
1,1,1,5,5,5-hexafluoro-3-pent-2-one metal hemiketal represented by
as well as
General formula [6]:

[Wherein R ² represents a hydrogen atom or an alkyl group. When R ² is an alkyl group, it is derived from R of the trifluoroacetate ester represented by the general formula [2] and takes the same alkyl group. ]
1,1,1,5,5,5-Hexafluoro-3-pent-2-one hydrate or alkylhemiketal represented by
Obtaining a first reaction mixture containing at least one selected from the group consisting of :
Second step:
A hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] is obtained by bringing the first reaction mixture obtained in the first step into contact with water in the presence of an acid. Obtaining a second reaction mixture comprising
Third step:
Concentrating the second reaction mixture obtained in the second step as it is by distillation, or separating the second reaction mixture into an aqueous layer and an organic layer and concentrating the organic layer by distillation;
Fourth step:
Recovering part or all of the organic solvent distilled off in the third step, and recovering the reaction solvent from the contact liquid obtained by contacting with at least one basic compound;
5th step:
Reusing the reaction solvent recovered in the fourth step as at least part of the reaction solvent in the first step, or reusing it as an extraction solvent for the second reaction mixture or the aqueous layer separated therefrom.
The method according to claim 1, further comprising the following sixth step.
Step 6:
From the residue of the second reaction mixture concentrated in the third step, a hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] is used using a purification solvent. The process to refine. The method according to claim 2, further comprising the following seventh step.
Step 7:
A step of reusing the reaction solvent recovered in the fourth step as at least part of the purification solvent in the sixth step.   The basic compound of the fourth step is an alkali metal hydroxide, carbonate and bicarbonate, alkaline earth metal hydroxide and carbonate, basic metal oxide, tetraalkylammonium hydroxide, trialkylamine The method according to any one of claims 1 to 3, which is at least one selected from the group consisting of a nitrogen-containing heterocyclic compound.   The basic compound of the fourth step is sodium hydroxide, calcium hydroxide, magnesium hydroxide, barium hydroxide octahydrate, sodium bicarbonate, cesium carbonate, potassium carbonate, calcium carbonate, basic alumina and tributylamine. The method according to any one of claims 1 to 4, wherein the method is at least one selected from the group consisting of:   The basic compound in the fourth step is at least one selected from the group consisting of barium hydroxide octahydrate, calcium carbonate, and tributylamine, according to any one of claims 1 to 5. Method.   The method according to any one of claims 1 to 6, wherein the reaction solvent is at least one selected from the group consisting of an ether solvent, an aromatic hydrocarbon solvent, and an aliphatic hydrocarbon solvent.   The reaction solvent according to any one of claims 1 to 7, wherein the reaction solvent is at least one selected from the group consisting of an aliphatic hydrocarbon solvent mainly composed of n-heptane and tert-butyl methyl ether. The method described. A hydrate of 1,1,1,5,5,5-hexafluoroacetylacetone represented by the general formula [3] is produced by the method according to any one of claims 1 to 8, A method for producing 1,1,1,5,5,5-hexafluoroacetylacetone by dehydrating the obtained hydrate.