JP5585291B2 - Method for producing hexafluoroacetone monohydrate - Google Patents

Description

  The present invention relates to a method for producing hexafluoroacetone monohydrate (1,1,1,3,3,3-hexafluoropropane-2-diol), and more particularly to solid hexafluoroacetone monohydrate. The present invention relates to a method for manufacturing a product.

  Hexafluoroacetone is an important compound as a pharmaceutical intermediate or various reaction raw materials. Hexafluoroacetone is industrially produced by epoxidation of hexafluoropropene followed by isomerization, hexachloroacetone obtained by chlorinating acetone with hydrogen fluoride using a chromium activated carbon supported catalyst, etc. Manufactured. Since hexafluoroacetone is a gas having a boiling point of −28 ° C. at atmospheric pressure, hexafluoroacetone trihydrate, which can be handled as a constant boiling point composition at 106 ° C., is used as a raw material for many reactions or used for storage. The However, hexafluoroacetone monohydrate may be required depending on reaction conditions, target product and other reasons. It has been reported that hexafluoroacetone monohydrate can introduce, for example, a hexafluoroisopropanol group into the 5-position of uracil (Non-patent Document 1).

  Hexafluoroacetone monohydrate is a crystal having a gem-diol structure with a melting point of 46 ° C. and decomposes simultaneously with melting to disproportionate to hexafluoroacetone and hexafluoroacetone trihydrate (Patent Document 1). It is a compound that is very difficult to handle because it deliquesces immediately with moisture in the air even at low temperatures.

US Pat. No. 3,544,633

Chemical Abstract 95: 151089 (All-Union Cancer Res. Cent., Moscow, USSR.Bioorganicheskaya Khimiya (1981), 7 (7), 1047-53.)

  Patent Document 1 describes that hexafluoroacetone monohydrate can be obtained by absorbing hexafluoroacetone in two stages into water charged in a container in two stages. It is also described that the solid contains a little hexafluoroacetone and water and is slightly moist, and its melting point is 40 ° C., which is lower than the literature value of 46 ° C.

  The solid hexafluoroacetone monohydrate obtained by this method reduces the stability of hexafluoroacetone monohydrate, which is inherently deliquescent, with water adhering to the solid surface, making it extremely difficult to use. ing.

  Therefore, the present invention provides a method for producing a hexafluoroacetone monohydrate solid that is easy to handle because it has low deliquescence and high stability.

  The present inventors have made hexafluoroacetone monohydrate (1,1,1,3,3) substantially free of water from aqueous solutions containing hydrates such as hexafluoroacetone or hexafluoroacetone trihydrate. , 3-hexafluoropropane-2-diol), the hexafluoroacetone monohydrate was precipitated as a solid when the molar ratio of hexafluoroacetone to water was adjusted in the presence of an organic solvent. By separating this from the liquid, it was found that hexafluoroacetone monohydrate without water adhering to the surface was obtained, and the present invention was achieved.

  The present invention is as follows.

[Invention 1]
A method for producing hexafluoroacetone monohydrate, comprising:
In a system in which water or hexafluoroacetone hydrate coexists with an organic solvent, the number of moles of water present in the system (the water generated when hexafluoroacetone hydrate is decomposed into hexafluoroacetone and water) The first step of introducing hexafluoroacetone so that the number of moles of free water and the number of moles of hexafluoroacetone are substantially equal;
A method for producing hexafluoroacetone monohydrate, which comprises a second step of obtaining solid hexafluoroacetone monohydrate from the contents formed in the system in the first step.

[Invention 2]
The method for producing hexafluoroacetone monohydrate according to invention 1, wherein the organic solvent is an aliphatic hydrocarbon or a halogenated aliphatic hydrocarbon.

[Invention 3]
Hexa of Invention 2 wherein the organic solvent is one or more organic solvents selected from n-pentane, n-hexane, n-heptane, cyclopentane, cyclohexane, carbon tetrachloride, chloroform, dichloromethane and 1,2-dichloroethane. Method for producing fluoroacetone monohydrate.

[Invention 4]
The hexafluoroacetone monohydrate according to inventions 1 to 3, wherein the second step includes a step of filtering and obtaining the solid hexafluoroacetone monohydrate contained in the contents formed in the system in the first step. Manufacturing method.

[Invention 5]
The method for producing hexafluoroacetone monohydrate according to inventions 1 to 4, wherein the second step includes a step of distilling off the organic solvent from the contents formed in the system in the first step.

  According to the production method of the present invention, solid hexafluoroacetone monohydrate can be obtained from a hydrate such as hexafluoroacetone trihydrate without using a special desiccant or dehydrating agent. Furthermore, since the obtained solid hexafluoroacetone monohydrate has substantially no water adhering to the surface, it has an effect of being easy to handle with little deliquescence.

  Hereinafter, the present invention will be described in detail.

  In the specification, hexafluoroacetone may be represented as “HFA”.

  In the specification, hexafluoroacetone monohydrate may be expressed as “HFA · W”.

  In the specification, hexafluoroacetone trihydrate may be expressed as “HFA · 3W”.

  In the specification, hexafluoroacetone hydrate is a general term for compounds obtained by hydration of hexafluoroacetone, and refers to a hydrate that does not limit the number of hydration or an aqueous solution thereof, including “HFA · 3W”. It is.

  The present invention introduces hexafluoroacetone into a system in which water or hexafluoroacetone hydrate coexists with an organic solvent so that the number of moles of water present in the system is substantially equal to the number of moles of hexafluoroacetone. Then, it is a manufacturing method of hexafluoroacetone monohydrate including the process of removing an organic solvent. Here, "the number of moles of water present in the system" refers to the total number of moles of water and free water produced when hexafluoroacetone hydrate is decomposed into hexafluoroacetone and water, “Free water” refers to water that is not contained in the molecule of hexafluoroacetone hydrate. A system in which water or hexafluoroacetone hydrate coexists with an organic solvent can be prepared by mixing an organic solvent and hexafluoroacetone or water and hexafluoroacetone hydrate. This system is liquid phase and may be homogeneous or heterogeneous. As the hexafluoroacetone hydrate, the hydration number is not particularly limited and may be an aqueous solution, but it is preferable to use hexafluoroacetone trihydrate. Hexafluoroacetone hydrate can also be used in combination with water.

Hexafluoroacetone trihydrate is a dihydrate of hexafluoroacetone monohydrate, which is a gem-diol produced by the reaction of hexafluoroacetone and water (herein the dihydrate 2 The water corresponding to is called “additional water”),

It is a stable liquid having the highest azeotropic composition (boiling point 106 ° C.).

On the other hand, hexafluoroacetone monohydrate is a solid with a melting point (46 ° C.), but decomposes above the melting point and disproportionates into anhydrous hexafluoroacetone and hexafluoroacetone trihydrate (patent) Reference 1).

  Examples of the organic solvent include aromatic compounds, ether compounds, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons (halogen-based solvents) that are liquid at room temperature (about 25 ° C.). The aromatic compound is not particularly limited and may be any of monocyclic, ring aggregate, and condensed polycyclic, but monocyclic benzene or a hydrogen atom of benzene is a halogen atom, an alkyl group, a fluoroalkyl group, or the like Compounds substituted with are preferred. Such compounds include benzene, toluene, xylene, ethylbenzene, chlorobenzene, benzotrifluoride, 2,4-dichlorobenzotrifluoride, o-, m- or p-bistrifluoromethylbenzene. Examples of the ether compound include chain ethers such as dimethyl ether, diethyl ether, isopropyl ether, ethyl isopropyl ether, butyl methyl ether, and ethyl butyl ether, and cyclic ethers such as tetrahydrofuran, pyran, and dioxane. Examples of the aliphatic hydrocarbon include n-pentane, n-hexane, n-heptane, n-octane, cyclopentane, cyclohexane, and cycloheptane. The halogen-based solvent is a compound in which a hydrogen atom of an aliphatic hydrocarbon is substituted with a halogen atom, an alkyl group, a fluoroalkyl group or the like, and carbon tetrachloride, chloroform, dichloromethane, 1,2-dichloroethane, cis-1,2 -Dichloroethylene, trans-1,2-dichloroethylene, 1,1,2-trichloroethane and the like. As the organic solvent, aliphatic hydrocarbons and halogenated aliphatic hydrocarbons are preferable. Specifically, aliphatic solvents such as aliphatic hydrocarbons such as n-pentane, n-hexane, n-heptane, cyclopentane, and cyclohexane, carbon tetrachloride, chloroform, dichloromethane, 1,2-dichloroethane, and the like are preferable organic solvents. As mentioned.

  The concentration of water or water in the system in which hexafluoroacetone hydrate coexists with the organic solvent may be determined arbitrarily, but usually hexafluoroacetone (assuming that hexafluoroacetone hydrate is decomposed into water and hexafluoroacetone) Hexafluoroacetone in a case.) It is 1-1000 mass parts of organic solvents with respect to 1 mass part, 5-100 mass parts is preferable, and 10-50 mass parts is more preferable. If the amount is less than 1 part by mass, the entire reaction system becomes a lump containing unreacted water, which is difficult to handle. If the amount exceeds 1000 parts by weight, the removal of the solvent is complicated and the throughput is not preferable.

  The hexafluoroacetone monohydrate according to the present invention is a mixture of an aqueous solution containing hexafluoroacetone hydrate, for example, hexafluoroacetone trihydrate or hexafluoroacetone and an organic solvent, with water in the system (additional water and Free water) and equimolar hexafluoroacetone can be added to obtain a solution dissolved in an organic solvent or precipitated.

  A system in which water or hexafluoroacetone hydrate coexists with an organic solvent is prepared, and the number of moles of water present in the system is substantially equal to the total number of moles of hexafluoroacetone and hexafluoroacetone hydrate. Hexafluoroacetone is introduced as follows. The hexafluoroacetone preferably has a molar ratio of hexafluoroacetone (hexafluoroacetone to be introduced) / water (total amount of added water and free water) of substantially 1, but is usually 1 to 1.2. That's fine. Considering operational loss, etc., a slight excess may be allowed. However, when hexafluoroacetone is excessive, it is not preferable because it will be unreacted to be washed away. Since the hydrate remains in the organic solvent solution, it is not preferable.

  When introducing hexafluoroacetone into the system, it is preferable that the liquid portion in the system is heated to 20 ° C. or higher and below the boiling temperature of the liquid. This is because a sufficient reaction rate cannot be obtained at a low temperature. When the temperature is not controlled, the temperature of the reaction system increases as the reaction proceeds and decreases with the completion of the reaction. Therefore, although the temperature in the system varies depending on the type of organic solvent, it is usually set to a boiling point (106 ° C.) or less of hexafluoroacetone trihydrate. In order to precipitate hexafluoroacetone monohydrate, it is necessary to carry out at a melting point (46 ° C.) or lower, so at least 46 ° C. or lower is required when separating a solid from an organic solvent. The lower limit temperature during the reaction is not particularly limited, but may be at least the melting point of the solvent, may be −40 ° C. or more, and is advantageously operation at 0 ° C. or more.

  According to the above, hexafluoroacetone monohydrate is formed in the system in which hexafluoroacetone is introduced, and the amount exceeding the solubility is precipitated as a solid. At this time, the temperature of the system can be cooled to promote precipitation, or the amount of precipitation can be increased. This solid can be recovered by filtration or decantation and dried. Drying is preferably performed at a melting point (46 ° C.) or lower, and for this purpose, it is preferably performed under reduced pressure. In addition, by reducing the pressure of the entire system in which hexafluoroacetone monohydrate was formed and distilling off the solvent, a portion of hexafluoroacetone monohydrate was precipitated and filtered and dried as described above. A solid can be obtained. Furthermore, the solid can also be recovered by distilling off all of the organic solvent from the reaction system to precipitate hexafluoroacetone monohydrate.

  When the solid hexafluoroacetone monohydrate thus obtained is obtained by contacting water and hexafluoroacetone at a ratio of 1: 1 without using a solvent, water adheres to the solid surface. In contrast, the surface has no water.

  Depending on the type of organic solvent used, hexafluoroacetone monohydrate may be dissolved in the remaining liquid (mother liquor) from which the solid has been separated by means such as filtration. Acetone hydrate and hexafluoroacetone can be introduced to precipitate hexafluoroacetone monohydrate.

  An example of the processing procedure of the present invention will be described. A predetermined amount of hexafluoroacetone trihydrate and an organic solvent are introduced into a closed reaction vessel equipped with a stirrer and a gas inlet. In the stationary state, the inside of the reaction vessel may be separated into two layers, but in that case, stirring is preferable.

  As the reaction proceeds rapidly, the temperature of the solution in the system rises, so stirring is performed while cooling from the outside, and the molar ratio of hexafluoroacetone (hexafluoroacetone to be introduced) and water (added water and free water) is 1: The amount of hexafluoroacetone that becomes 1 is gradually introduced from the gas inlet of the reaction vessel. At this time, care should be taken not to block the gas inlet due to the precipitation of hexafluoroacetone monohydrate regardless of whether the opening is a gas phase portion or a liquid phase portion. The reaction is completed when the introduction of a predetermined amount of hexafluoroacetone is completed and the reaction solution temperature is lowered and the pressure is lowered. A homogeneous solution or a solution in which a white solid is precipitated is obtained in the reaction vessel. The reaction solution may be cooled to promote precipitation. The contents of the reaction vessel are taken out, the precipitated solid is separated from the liquid phase, and then the solution is volatilized at a temperature below the melting point using a rotary evaporator or the like to obtain hexafluoroacetone monohydrate crystals. This treatment is preferably performed under reduced pressure.

  The reaction apparatus is not particularly limited, but a pressure vessel or a vessel provided with a condenser is preferable, and a stirrer is preferably provided. As the material of the apparatus, stainless steel, nickel alloy steel, glass, fluororesin, carbon, polyethylene, or a material lined or clad with these materials can be used.

  EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

[Example 1]
It is equipped with a stirrer, dry ice / acetone cooling reflux, thermometer, gas inlet, and the opening of the reflux is a glass 200 mL four-neck reactor closed with a balloon. Chloroform: 148 g, hexafluoroacetone Hydrate (HFA · 3W): 22 g (0.1 mol) is added, the outside is ice-cooled, and hexafluoroacetone (HFA): 32 g (0.2 mol) is kept at an internal temperature of 25 ° C. from the gas inlet. The reaction was terminated by introducing 1 hour. After completion of the reaction, crystals were collected from the slurry by filtration and dried under reduced pressure with an evaporator to obtain 21 g of white needle crystals (yield 32%).

The collected white needle-like crystals were measured by NMR ( ¹³ C, H, F) and FT-IR, and found to be hexafluoroacetone monohydrate (1,1,1,3,3,3-hexafluoropropane-2- Diol) and other components were not observed. Further, hexafluoroacetone contained in the crystal was measured by neutralization titration, and the water content was measured with a Karl Fischer moisture measuring device. As a result, the molar ratio of hexafluoroacetone to water was 1: 1.

[Example 2]
It is equipped with a stirrer, dry ice / acetone cooling reflux, thermometer, gas inlet, and the opening of the reflux is a 200 mL four-necked reactor with a balloon closed system. Chloroform: 200 g, normal hexane: 89 g Hexafluoroacetone trihydrate (HFA · 3W): 22 g (0.1 mol) was added, the outside was ice-cooled, and hexafluoroacetone (HFA): 32 g (0.2 mol) was added from the gas inlet. It was introduced over 1 hour while maintaining the temperature at 25 ° C. to complete the reaction. After completion of the reaction, crystals were collected from the slurry by filtration and dried under reduced pressure with an evaporator to obtain 31 g of white needle crystals (yield 55%).

The collected white needle-like crystals were measured by NMR ( ¹³ C, H, F) and FT-IR, and found to be hexafluoroacetone monohydrate (1,1,1,3,3,3-hexafluoropropane-2- Diol) and other components were not observed. Further, hexafluoroacetone contained in the crystal was measured by neutralization titration, and the water content was measured with a Karl Fischer moisture measuring device. As a result, the molar ratio of hexafluoroacetone to water was 1: 1.

[Example 3]
It is equipped with a stirrer, dry ice / acetone cooling reflux, thermometer, gas inlet, and the opening of the reflux is a 200 mL four-necked reactor made of a closed system with balloons. Normal hexane: 178 g, hexafluoroacetone Trihydrate (HFA · 3W): 22 g (0.1 mol) was added, the outside was ice-cooled, and hexafluoroacetone (HFA): 32 g (0.2 mol) was brought to an internal temperature of 25 ° C. from the gas inlet. It was introduced over 1 hour while maintaining the reaction to complete the reaction. After completion of the reaction, crystals were collected from the slurry by filtration and dried under reduced pressure with an evaporator to obtain 49 g of white needle crystals (yield 87%).

The collected white needle-like crystals were measured by NMR ( ¹³ C, H, F) and FT-IR, and found to be hexafluoroacetone monohydrate (1,1,1,3,3,3-hexafluoropropane-2- Diol) and other components were not observed. Further, hexafluoroacetone contained in the crystal was measured by neutralization titration, and the water content was measured with a Karl Fischer moisture measuring device. As a result, the molar ratio of hexafluoroacetone to water was 1: 1.

[Comparative Example 1]
It is equipped with a stirrer, dry ice / acetone cooled reflux, thermometer, gas inlet, and the opening of the reflux is a glass 200 ml four-neck reactor closed with a balloon. HFA · 3W): 44 g (0.2 mol) was added, and hexafluoroacetone (HFA): 66 g (0.4 mol) was slowly introduced from the gas inlet while the outside was ice-cooled. The internal temperature was kept at 25 ° C. At this time, HFA reflux was observed in the cooling reflux, and needle-like crystals were formed in the contents of the reactor, and then the whole became agglomerated and could not be stirred. Therefore, 50 g (0.3 mol) of HFA was introduced. Was stopped, the reactor was purged with unreacted HFA, the reactor was opened, and the solid content was removed. This solid was moist.

Claims (5)

A method for producing hexafluoroacetone monohydrate, comprising:
In a system in which water or hexafluoroacetone hydrate coexists with an organic solvent, the number of moles of water present in the system (the water generated when hexafluoroacetone hydrate is decomposed into hexafluoroacetone and water) The first step of introducing hexafluoroacetone so that the number of moles of free water and the number of moles of hexafluoroacetone are substantially equal;
A method for producing hexafluoroacetone monohydrate, which comprises a second step of obtaining solid hexafluoroacetone monohydrate from the contents formed in the system in the first step.   The method for producing hexafluoroacetone monohydrate according to claim 1, wherein the organic solvent is an aliphatic hydrocarbon or a halogenated aliphatic hydrocarbon.   The organic solvent is at least one organic solvent selected from n-pentane, n-hexane, n-heptane, cyclopentane, cyclohexane, carbon tetrachloride, chloroform, dichloromethane and 1,2-dichloroethane. The manufacturing method of the hexafluoroacetone monohydrate of description.   The second step includes the step of filtering and obtaining solid hexafluoroacetone monohydrate contained in the contents formed in the system in the first step. Process for the preparation of hexafluoroacetone monohydrate.   The method for producing hexafluoroacetone monohydrate according to any one of claims 1 to 4, wherein the second step includes a step of distilling off the organic solvent from the contents formed in the system in the first step. .