JP2018131437A - Stereoselective production method for disubstituted halogenated epoxide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for stereoselectively producing a disubstituted halogenated epoxide under industrially practicable conditions.SOLUTION: A disubstituted halogenoolefin represented by general formula in the figure, where Rrepresents a C1-10 linear or C3-10 branched fluoroalkyl group having one or more fluorine atoms and Xrepresents a halogen atom, is reacted with hypohalous acid or a salt thereof so as to produce a disubstituted halogenated epoxide represented by general formula in the figure, where Rand Xare the same as the Rand Xabove and the symbol * represents an asymmetric carbon.SELECTED DRAWING: None

Description

  The present invention relates to a method for producing a stereoselective disubstituted halogenated epoxide.

  As a method for producing a disubstituted halogenated epoxide, Non-Patent Document 1 discloses that 1,3,3,3-tetrafluoroethyl 1,3,3,3-tetrafluoroacetate is obtained by starting with ethyl 1,3,3,3-tetrafluoroacetoacetate and undergoing a multi-step process. Methods for obtaining propene oxide are known.

  In addition, as a method for synthesizing epoxides having fluorinated alkyl groups, Patent Document 1 discloses the production of corresponding epoxides by subjecting substituted olefins having fluoroalkyl groups to an oxidation reaction using hypofluoric acid (HOF). An example is known.

  Patent Document 2 discloses an oxidation reaction using sodium hypochlorite (NaClO) for perfluoropropene.

[Wherein TOMAC represents “trioctylmethylammonium chloride”. ]
The following formula:

A mixture of trans isomers of 1,3,3,3-tetrafluoropropene oxide represented by the formula:

No production example is known about a mixture of cis-isomers of 1,3,3,3-tetrafluoropropene oxide represented by

International Publication No. 1991/005778 Japanese Patent Laid-Open No. 58-134086

E. T.A. McBee. et al, J. et al. Am. Chem. Soc. 1953, 75, 4091-4092.

  Since the method described in Non-Patent Document 1 can obtain a disubstituted halogenated epoxide in a high yield, it is preferable as a seemingly preferable method. However, in this method, the fluorine atom bonded to the carbon atom at position 1 of the epoxide and the trifluoromethyl group bonded to the carbon atom at position 2 were not stereoselective to each other. In addition, since the target product was synthesized from ethyl 1,3,3,3-tetrafluoroacetoacetate through three steps in order to synthesize this epoxide, it was difficult to adopt as a simple method.

  On the other hand, the method described in Patent Document 2 is regulated by the Montreal Convention of R-113 (1,1,2-trichloro-1,2,2-trifluoroethane; also referred to as “CFC-113”) as a reaction solvent. The use of benzene, a toxic solvent such as benzene, and sodium hypochlorite, which is an oxidizing compound, and diisopropyl ether. Since it may occur, it could not be said to be an industrially adopted method.

  Thus, the process for producing disubstituted halogenated epoxides has not been fully satisfactory as that on an industrial scale.

  An object of the present invention is to provide a method for producing a stereoselective disubstituted halogenated epoxide under industrially feasible conditions.

  Therefore, the present inventors have made extensive studies in view of the above-mentioned problems, and as a result, hypofluoric acid (HOF), alkali metal hypochlorite, alkaline earth metal hypochlorous acid as an oxidant. It has been found that a disubstituted halogenated epoxide can be obtained stereoselectively by reacting a hypohalous acid such as a salt or a salt thereof, and the present invention has been completed.

That is, the present invention provides the inventions described in [Invention 1]-[Invention 8] below.
[Invention 1]
General formula [1]:

[Wherein, R _f represents a linear or branched C 1-10 fluoroalkyl group having one or more fluorine atoms, and X ¹ represents a halogen atom. ]
Is reacted with a hypohalous acid or a salt thereof to give a general formula [2]:

Wherein, R _f and X ¹ are the same as R _f and X ¹ in the general formula [1]. * Represents an asymmetric carbon. ] The method of manufacturing the disubstituted halogenated epoxide represented by these.
[Invention 2]
The disubstituted halogenated epoxide is represented by the general formula [2a] or the general formula [2aa]:

[In Formula [2a] and Formula [2aa], R _f and X ¹ are the same as R _f and X ^{1 in} General Formula [1], respectively. ]
A trans-disubstituted halogenated epoxide represented by:
Or
General formula [2b] or general formula [2bb]:

[In Formula [2b] and Formula [2bb], R _f and X ¹ are the same as R _f and X ^{1 in} General Formula [1], respectively. ]
A cis-disubstituted halogenated epoxide represented by:
A process according to invention 1, obtained as:
[Invention 3]
As the disubstituted halogenoolefin, the general formula [1a]:

When a trans-disubstituted halogenoolefin represented by the following formula is used as a starting material, a trans-disubstituted halogenated epoxide represented by the general formula [2a] or the general formula [2aa] is selectively produced,
General formula [1b]:

When a cis-disubstituted halogenoolefin represented by general formula [2b] or general formula [2bb] is used as a starting material, a cis-disubstituted halogenated epoxide represented by general formula [2bb] is selectively produced.
The method according to the invention 1 or 2.
[Invention 4]
General formula [3]:

[Wherein, X ¹ represents a halogen atom. ]
By reacting trans-1-halogeno-3,3,3-trifluoropropene represented by general formula [4a] or general formula [4aa]:

[In Formula [4a] and Formula [4aa], X ¹ is the same as X ^{1 in} General Formula [3]. ]
A process for producing trans-1-halogeno-3,3,3-trifluoropropene oxide represented by the formula:
[Invention 5]
General formula [5]:

[Wherein, X ¹ represents a halogen atom. ]
By reacting hypohalous acid or a salt thereof with cis-1-halogeno-3,3,3-trifluoropropene represented by general formula [6b] or general formula [6bb]:

[In Formula [6b] and Formula [6bb], X ¹ is the same as X ^{1 in} General Formula [3]. ]
A process for producing cis-1-halogeno-3,3,3-trifluoropropene oxide represented by the formula:
[Invention 6]
The method according to any one of Inventions 1 to 3, wherein R _f is a trifluoromethyl group, a pentafluoroethyl group, a heptafluoropropyl group, or a nonafluorobutyl group.
[Invention 7]
The method according to any one of Inventions 1 to 6, wherein X ¹ is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
[Invention 8]
The method according to any one of inventions 1 to 7, wherein the hypohalous acid or a salt thereof is hypofluoric acid, an alkali metal hypochlorite or an alkaline earth metal hypochlorite.

  The present invention has an effect that a disubstituted halogenated epoxide can be produced stereoselectively in an industrially feasible form.

  Hereinafter, the present invention will be described in detail. Hereinafter, embodiments of the present invention will be described. However, the present invention is not limited to the following embodiments, and may be appropriately implemented based on ordinary knowledge of a person skilled in the art without departing from the spirit of the present invention. can do.

  The present invention is a method for producing a disubstituted halogenated epoxide represented by the general formula [2] by reacting a hypohalogenous acid or a salt thereof with the disubstituted halogenoolefin represented by the general formula [1]. is there.

R _{f of the} disubstituted halogenoolefin represented by the general formula [1] is a linear or branched C 1-10 fluoroalkyl group having at least one fluorine atom. Specifically, trifluoromethyl group, pentafluoroethyl group, heptafluoropropyl group, heptafluoroisopropyl group, hexafluoroisopropyl group, nonafluorobutyl group, 2,2,2-trifluoroethyl group, 3, 3, 3 -Trifluoropropyl group, 4,4,4-trifluorobutyl group, difluoromethyl group, 1,1-difluoroethyl group, 2,2-difluoroethyl group, 1,1-difluoropropyl group, 2,2-difluoro Propyl group, 3,3-difluoropropyl group, 1,1-difluorobutyl group, 2,2-difluorobutyl group, 3,3-difluorobutyl group, 4,4-difluorobutyl group, fluoromethyl group, 1-fluoro Ethyl group, 2-fluoroethyl group, 1-fluoropropyl group, 2-fluoropropyl group, 3-fluoro Examples include propyl group, 1-fluorobutyl group, 2-fluorobutyl group, 3-fluorobutyl group, and 4-fluorobutyl group. Among them, trifluoromethyl group, pentafluoroethyl group, heptafluoropropyl group, nonafluoro A butyl group is preferred, and a trifluoromethyl group is particularly preferred.

X ^{1 of the} disubstituted halogenoolefin represented by the general formula [1] is a halogen atom and represents a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
Of these disubstituted halogenoolefins, those in which R _f is a trifluoromethyl group and X ¹ is a fluorine atom or a chlorine atom are particularly preferred. Specifically, 1,3,3,3-tetrafluoropropene and 1-chloro-3,3,3-trifluoropropene.

The disubstituted halogenoolefin represented by the general formula [1] can take a trans position or a cis position with R _f and X ^{1 being} centered on a double bond (trans isomer, The cis isomer) and the present invention can be used as starting materials regardless of whether the cis isomer and the trans isomer are used alone or as a mixture.

  In this invention, it carries out by making hypohalogenous acid or its salt react with a disubstituted halogeno olefin. Hypohalous acid or a salt thereof functions as an oxidizing agent (in this specification, hypohalous acid or a salt thereof is sometimes referred to as “oxidizing agent”), which oxidizes a double bond and generates a corresponding epoxide skeleton ( Or an oxirane skeleton).

Specific examples of hypohalous acid or a salt thereof include hypofluoric acid, alkali metal hypochlorite, alkaline earth metal hypochlorite, and the like. Specific examples of alkali metal hypochlorite and alkaline earth metal hypochlorite include lithium hypochlorite, sodium hypochlorite, potassium hypochlorite, rubidium hypochlorite, hypochlorous acid. Examples include cesium chlorate, magnesium hypochlorite, and calcium hypochlorite.
Of these oxidants, hypofluorite, lithium hypochlorite, sodium hypochlorite, potassium hypochlorite, and calcium hypochlorite are preferred. Hypofluorite, sodium hypochlorite, Calcium chlorite is particularly preferred.

Here, it describes about the preparation method of hypofluoric acid among oxidizing agents.
Hypochlorous acid used in the oxidation reaction of the present invention can be generated by reacting water and fluorine gas in a nitrile solvent, and the generated solution can be used for the reaction. Specific examples of the nitrile solvent to be used include acetonitrile, propane nitrile, butane nitrile, and pentane nitrile. Acetonitrile and propane nitrile are preferable, and acetonitrile is particularly preferable.

  The fluorine gas used is preferably diluted to 1 to 40%. The gas for diluting the fluorine gas is not particularly limited, but may be any gas that does not easily react with the fluorine gas. Specific examples include nitrogen, helium, neon, argon, and krypton.

  The temperature at the time of generating hypofluoric acid should just be 10 degrees C or less, -70 to +5 degreeC is preferable, and -40 to 0 degreeC is especially preferable.

  There is no particular restriction on the form of hypochlorous acid generated, but hypofluoric acid may be generated in the reactor by introducing fluorine gas into a normal reactor with a dip tube, such as a microreactor. It may be generated continuously by employing an apparatus.

  Regarding the method of generating hypofluoric acid, not only those described in the above-mentioned methods and examples, but also Patent Document 1 and Ming. H. Hung. et al, J. et al. Org. Chem. 1991, 56, 3187-3189. The method described in the above may be used as a reference.

  Alkali metal hypochlorite or alkaline earth metal hypochlorite can be used as a hydrate, and in the present invention, an alkali metal adjusted to have a concentration range of approximately 21% by mass or more. It is preferable to use an aqueous solution of hypochlorite or alkaline earth metal hypochlorite (a commercially available one may be used, and the aqueous solution is adjusted so that this concentration is within the reactor. However, the latter method is convenient).

This concentration range will be described. As used herein, “21% by mass or more of an aqueous solution of alkali metal hypochlorite or alkaline earth metal hypochlorite” means an alkali metal hypochlorite or alkaline earth as a component in a solid or liquid, respectively. It shows that a metal group hypochlorite is contained. As an example of the mass percentage, NaClO · 5H ₂ O is 45% by mass from “molecular weight of NaClO (74.4) ÷ molecular weight of NaClO · 5H ₂ O (164.5) × 100”. Ca (ClO) ₂ · H ₂ O, Ca (ClO) ₂ · 2H ₂ O, Ca (ClO) ₂ · 3H ₂ O and Ca (ClO) ₂ · CaCl ₂ · 2H ₂ O [CaCl (ClO) · H ₂ O] is 89 wt%, 80 wt%, 73 wt%, and 49 wt%, respectively, from the same calculation. The content of alkali metal hypochlorite and alkaline earth metal hypochlorite is intentionally added with additives that do not substantially affect the oxidation reaction itself (or have no oxidation activity). Even if the reaction is carried out with an apparent content of the oxidizer of less than 21 wt%, it is treated as being included in the claims of the present invention.

  The amount of the oxidizing agent used is usually 0.5 mol or more, preferably 0.75 to 20 mol, preferably 1 mol to 1 mol of the disubstituted halogenoolefin represented by the general formula [1]. 10 moles are particularly preferred.

  The reaction temperature may be + 150 ° C. or lower, preferably −50 ° C. to + 120 ° C., particularly preferably −40 ° C. to + 100 ° C.

  In the present invention, a solvent can be used for the reaction. The solvent only needs to be a solvent that does not easily react with the fluorinated olefin and the oxidizing agent. Water, nitrile solvent, hydrocarbon solvent, aromatic hydrocarbon solvent, halogenated hydrocarbon solvent, halogenated aromatic hydrocarbon A solvent is mentioned. Specifically, water, acetonitrile, propionitrile, hexane, peptane, nonane, dencan, cyclopropane, methylcyclopropane, benzene, dichloromethane, chloroform, tetrachloromethane, fluorobenzene, chlorobenzene, benzotrifluoride, 2-chloro- Benzotrifluoride, 2,4-dichloro-benzotrifluoride, 2,6-dichloro-benzotrifluoride and the like, water, acetonitrile, heptane, benzene, dichloromethane, chloroform, chlorobenzene, benzotrifluoride are preferred, water, Acetonitrile, dichloromethane, chloroform, and benzotrifluoride are particularly preferred. These solvents may be used alone or in combination.

  When hypochlorous acid is used as the oxidizing agent, it is possible to replace the solvent of the present invention with the used water and nitrile solvent when generating hypofluoric acid as described above. It is not always necessary to use the above solvent separately.

  In the reaction in the present invention, when the solution is separated into two layers, it is a particularly preferable embodiment to add a phase transfer catalyst into the reaction system. Examples of the phase transfer catalyst include halogenated quaternary ammonium salts and halogenated quaternary phosphonium salts. Specifically, tetramethylammonium fluoride, tetramethylammonium chloride, tetramethylammonium bromide, tetramethylammonium iodide, tetraethylammonium fluoride, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetrapropylammonium fluoride, Tetrapropylammonium chloride, tetrapropylammonium bromide, tetrapropylammonium iodide, tetrabutylammonium fluoride, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetraheptylammonium fluoride, tetraheptylammonium chloride, tetra Heptylammoni Mubromide, tetraheptylammonium iodide, tetrahexylammonium fluoride, tetrahexylammonium chloride, tetrahexylammonium bromide, tetrahexylammonium iodide, tetraoctylammonium fluoride, tetraoctylammonium chloride, tetraoctylammonium bromide, tetraoctylammonium iodide , Tetradecylammonium fluoride, tetradecylammonium chloride, tetradecylammonium bromide, tetradecylammonium iodide, benzyltrimethylammonium fluoride, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, benzyltrimethylammonium iodide, benzyltriethylammonium Umum fluoride, benzyltriethylammonium chloride, benzyltriethylammonium bromide, benzyltriethylammonium iodide, benzyldodecyldimethylammonium fluoride, benzyldodecyldimethylammonium chloride, benzyldodecyldimethylammonium bromide, benzyldodecyldimethylammonium iodide, trioctylmethylammonium fluoride , Trioctylmethylammonium chloride, trioctylmethylammonium bromide, trioctylmethylammonium iodide, octyltrimethylammonium fluoride, octyltrimethylammonium chloride, octyltrimethylammonium bromide, octyltrimethylammonium iodide, tetrabutylphosphonium Umum fluoride, tetrabutylphosphonium chloride, tetrabutylphosphonium bromide, tetrabutylphosphonium iodide, tetraoctylphosphonium fluoride, tetraoctylphosphonium chloride, tetraoctylphosphonium bromide, tetraoctylphosphonium iodide, tetraphenylphosphonium fluoride, tetraphenylphosphonium Chloride, tetraphenylphosphonium bromide, tetraphenylphosphonium iodide, benzyltriphenylphosphonium fluoride, benzyltriphenylphosphonium chloride, benzyltriphenylphosphonium bromide, benzyltriphenylphosphonium iodide, tetraethylammonium chloride, tetraethylammonium bromide Tetrapurpi Ammonium chloride, tetrapropylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium bromide, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, trioctylmethylammonium chloride, trioctylmethylammonium bromide, octyltrimethylammonium chloride, octyltrimethylammonium Preferred are bromide, tetrabutylphosphonium chloride, tetrabutylphosphonium bromide, tetraoctylphosphonium chloride, tetraoctylphosphonium bromide, particularly preferred are tetrabutylammonium chloride, tetrabutylammonium bromide, trioctylmethylammonium chloride, and trioctylammonium bromide. .

  The amount of the phase transfer catalyst used may be 0.00001 mol to 1 mol, preferably 0.0001 mol to 0.75 mol, preferably 0.001 mol to 1 mol with respect to 1 mol of the disubstituted halogenoolefin represented by the general formula [1]. 0.5 mol is particularly preferred.

  Furthermore, in the present invention, a basic compound may be added to the reaction system. Examples of basic compounds include alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates, alkaline earth metal carbonates, alkali metal hydrogen carbonates, alkaline earth metal hydrogen carbonates, and alkali metals. Hydroxides, alkaline earth metal hydroxides, and alkali metal carbonates are preferable, and alkali metal hydroxides and alkaline earth metal hydroxides are particularly preferable. Specifically, lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, magnesium hydroxide, calcium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, rubidium carbonate, cesium carbonate, magnesium carbonate, Calcium carbonate, lithium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, rubidium hydrogen carbonate, cesium hydrogen carbonate, magnesium hydrogen carbonate, calcium hydrogen carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, Cesium hydroxide, magnesium hydroxide, calcium hydroxide, lithium carbonate, sodium carbonate, and potassium carbonate are preferable, and lithium hydroxide, sodium hydroxide, potassium hydroxide, and calcium hydroxide are particularly preferable.

  In addition, as shown in the Example mentioned later, when using an alkali metal hypochlorite and an alkaline-earth metal hypochlorite as an oxidizing agent, adding a basic compound makes reaction progress efficiently. Are particularly preferably used.

The reactor used for the reaction may if made of a material having heat resistance and corrosion resistance, stainless steel, Hastelloy ^TM, Monel ^TM, nickel, or metal containers, such as platinum, tetrafluoroethylene resin, chlorotrifluoroethylene A reactor capable of performing a sufficient reaction under normal pressure or pressure, such as a resin, vinylidene fluoride resin, PFA resin, polypropylene resin, polyethylene resin, or a glass-lined resin inside can be used.

  The reaction end point is not particularly limited. Usually, after the introduction of the disubstituted halogenoolefin is completed, the reaction conversion rate is a predetermined value by means of a nuclear magnetic resonance apparatus (NMR), gas chromatography, liquid chromatography or the like. It is preferable to set the end point when the value reaches or when the amount of the product no longer changes.

  The post-treatment after the reaction is carried out by adopting a general procedure in organic synthesis to convert a disubstituted halogenated epoxide represented by the general formula [2], particularly in the present invention, a cis isomer or a trans isomer of the epoxide. It is possible to manufacture selectively.

The crude product can be purified to a high purity by activated carbon treatment, fractional distillation, column chromatography or the like, if necessary.
[Example]
EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited to these Examples. Here, “%” of the composition analysis value means “area” of the composition obtained by measuring the reaction mixture by nuclear magnetic resonance spectrum (NMR) or gas chromatography (the detector is FID unless otherwise specified). % ".

10 ml of water and 100 ml of acetonitrile were placed in a PFA reaction vessel to prepare an acetonitrile aqueous solution, and then a 20% fluorine gas diluted with nitrogen was introduced at a flow rate of 50 sccm for about 180 minutes using a mass flow controller. The temperature at this time was -10 ° C to -9 ° C. After the introduction of the diluted fluorine gas was completed, nitrogen gas was introduced at a flow rate of 50 sccm for about 10 minutes. 2.6 g (20 mmol) of cis-1-chloro-3,3,3-trifluoropropene was introduced into the hypofluoric acid-containing solution obtained here, and then reacted for 3 hours. The internal temperature at this time was −8.6 ° C. to 15 ° C. After completion of the reaction, an internal standard substance was added to the reaction solution and quantified by ¹⁹ F-NMR. As a result, 13.4 mmol (yield 67%) of cis-1-chloro-3,3,3-trifluoropropene oxide was contained. It was. At this time, isomer trans-1-chloro-3,3,3-trifluoropropene oxide could not be confirmed by ¹⁹ F-NMR.
[Physical data]
¹ H-NMR of cis-1-chloro-3,3,3-trifluoropropene oxide (heavy solvent: CDCl ₃ , reference substance: tetramethylsilane), δ ppm: 3.57 (m, 1H), 5.20 (Sext, 1H), ¹⁹ F-NMR (deuterated solvent: CDCl ₃ , reference material: hexafluorobenzene: set to −162.2 ppm), δ ppm: −66.6 (d, 3F)

A hypofluorite-containing solution was prepared in the same manner as in the method described in Example 1. To the obtained solution, 2.3 g (20 mmol) of cis-1,3,3,3-tetrafluoropropene was introduced, and then reacted for 3 hours. The internal temperature at this time was −11.9 ° C. to −8.7 ° C. After completion of the reaction, an internal standard substance was added to the reaction solution and quantified by ¹⁹ F-NMR. As a result, 19.1 mmol (yield 95%) of cis-1,3,3,3-tetrafluoropropene oxide was contained. . At this time, isomer trans-1,3,3,3-tetrafluoropropene oxide could not be confirmed by ¹⁹ F-NMR.

After preparing 10 mL of water and 100 ml of acetonitrile in a PFA reaction vessel to prepare an acetonitrile aqueous solution, 20% fluorine gas diluted with nitrogen was introduced at a flow rate of 60 sccm for about 370 minutes using a mass flow controller. The temperature at this time was -15 ° C to -10 ° C. When the introduction of the diluted fluorine gas was completed, nitrogen gas was introduced at a flow rate of 50 sccm for about 10 minutes.
To the obtained hypofluorite-containing solution, 5.8 g (50.9 mmol) of cis-1,3,3,3-tetrafluoropropene was introduced and then reacted for 3 hours. The internal temperature at this time was −13.7 ° C. to −8.7 ° C. After completion of the reaction, an internal standard substance was added to the reaction solution and quantitatively determined by ¹⁹ F-NMR. As a result, 43.1 mmol (yield 85%) of cis-1,3,3,3-tetrafluoropropene oxide was contained. . At this time, isomer trans-1-chloro-3,3,3-trifluoropropene oxide could not be confirmed by ¹⁹ F-NMR.

  Next, 100 g of 6% aqueous sodium hydrogen carbonate solution was added to the resulting reaction liquid containing cis-1,3,3,3-tetrafluoropropene oxide, and sodium hydrogen carbonate was further added directly until pH 7 was reached. Next, potassium sulfite was added until the peroxide content was below the lower limit of detection (0.5 ppm) using a semi-quantitative test paper for hydrogen peroxide, and this solution was separated into two layers. This solution contained 41.1 mmol of the target product.

  The same operation as described above was performed twice, and the obtained three solutions were mixed, dehydrated with sodium sulfate, and filtered. The filtrate contained 111 mmol of the desired product (cis-1,3,3,3-tetrafluoropropene oxide).

The obtained filtrate was subjected to precision distillation (rectification). The rectification was carried out with an instrument in which a manual reflux was attached to a packed tower packed with 25 cm × 2 cm of Helipak No2. Distillation kettle: 61.5 ° C to 62.4 ° C, tower top: 30.8 ° C to 39.7 ° C, degree of vacuum: 60.2 to 59.7 hPa, fraction 11.8 g (target product content 92.3% ) Next, the distillation kettle: 62.2 ° C. to 62.4 ° C., column top: 39.9 ° C. to 47.5 ° C., degree of vacuum: 58.9 to 59.7 hPa, fraction 3.8 g (target product content 94 .7 wt%).
[Physical data]
¹ H-NMR of cis-1,3,3,3-tetrafluoropropene oxide (deuterated solvent: CDCl ₃ , reference material: tetramethylsilane), δ ppm: 3.31 (m), 5.64 (dq), ¹⁹ F-NMR (deuterated solvent: CDCl ₃ , reference substance: hexafluorobenzene: set to −162.2 ppm), δ ppm: −68.9 (d), −164.9 (dq)

A hypofluorite-containing solution was prepared in the same manner as in the method described in Example 1. To the resulting solution, 2.0 g (17.6 mmol) of trans-1,3,3,3-tetrafluoropropene was introduced, followed by reaction for 3 hours. The internal temperature at this time was −15.6 ° C. to −6.2 ° C. After completion of the reaction, an internal standard substance was added to the reaction solution and quantitatively determined by ¹⁹ F-NMR. As a result, 11.5 mmol (yield 65%) of trans-1,3,3,3-tetrafluoropropene oxide was contained. . At this time, cis-1,3,3,3-tetrafluoropropene oxide which is an isomer could not be confirmed by ¹⁹ F-NMR.

In a stainless steel autoclave, sodium hypochlorite pentahydrate 378 g (2.31 mol, 6 equivalents), sodium hydroxide 46.2 g (1.15 mol, 3 equivalents), trioctylmethylammonium chloride 5.9 g (14.6 mmol) 3.86 mol%), 320 g of water, and 193 ml of benzotrifluoride were charged, the reactor was sealed, and the internal temperature was cooled to around 1 ° C. At this time, the concentration of sodium hypochlorite in the aqueous solution was 23 wt%. When cooled, the internal pressure was reduced to 0.01 MPa with a vacuum pump. Next, 43.9 g (0.385 mol) of cis-1,3,3,3-tetrafluoropropene was charged. The raw materials were charged and reacted for 3 hours. The internal temperature at this time was 1.3-4.1 degreeC. As a result of analyzing the reaction solution after completion of the reaction, 0.244 mol (yield: 63.5%) of the target product, cis-1,3,3,3-tetrafluoropropene oxide was contained. At this time, isomer trans-1,3,3,3-tetrafluoropropene oxide could not be confirmed by ¹⁹ F-NMR.

In a stainless steel autoclave, sodium hypochlorite pentahydrate 363.6 g (2.21 mol, 6 equivalents), sodium hydroxide 44.2 g (1.11 mol, 3 equivalents), trioctylmethylammonium chloride 5.4 g (13 4 mmol, 3.6 mol%), 292 g of water, and 183 ml of benzotrifluoride were charged, the reactor was sealed, and the internal temperature was cooled to around 1 ° C. At this time, the concentration of sodium hypochlorite in the aqueous solution was 24 wt%. When cooled, the internal pressure was reduced to 0.01 MPa with a vacuum pump. Next, 42.0 g (0.368 mol) of trans-1,3,3,3-tetrafluoropropene was charged. The raw materials were charged and reacted for 3 hours. The internal temperature at this time was 3.5 to 5.0 ° C. As a result of analyzing the reaction solution after completion of the reaction, 0.223 mol (yield: 60.4%) of the target product, trans-1,3,3,3-tetrafluoropropene oxide was contained. At this time, cis-1,3,3,3-tetrafluoropropene oxide which is an isomer could not be confirmed by ¹⁹ F-NMR.
[Physical data]
¹ H-NMR of trans-1,3,3,3-tetrafluoropropene oxide (heavy solvent: CDCl ₃ , reference substance: tetramethylsilane), δ ppm: 3.67 (m), 5.66 (d), ¹⁹ F-NMR (deuterated solvent: CDCl ₃ , reference substance: hexafluorobenzene: set to −162.2 ppm), δ ppm: −73.5 (d), −156.2 (d)

  With reference to Example 5, the experiment was conducted under the same conditions such as equivalent amount and the amount of solvent used, and cis-1,3,3,3-tetrafluoropropene was reacted to give the target product, cis-1,3. Thus, a solution containing 0.264 mol (yield 65.9%) of 3,3-tetrafluoropropene oxide was obtained.

The solution obtained in this example and the solution obtained in Example 5 were mixed, and 100 g of 10% aqueous potassium sulfite solution was added and stirred while cooling with ice water. When it was confirmed that the solution did not color potassium iodide starch paper, two layers were separated. Next, the obtained organic layer was rectified. The rectification was carried out with an instrument in which a manual reflux was attached to a packed tower packed with 25 cm × 2 cm of Helipak No2. Distillation conditions: distillation kettle: 72.9 ° C to 77.4 ° C, tower top: 35.5 ° C to 39.0 ° C, degree of vacuum: 0.045 MPa to 0.056 MPa, fraction of 38.5 g ( ¹⁹ F-NMR Purity: 99.9%).

  With reference to Example 6, the experiment was conducted under the same conditions such as the equivalent amount and the amount of solvent used, and 44.3 g (0.388 mol) of trans-1,3,3,3-tetrafluoropropene was reacted, A solution containing 0.252 mol (yield 65%) of trans-1,3,3,3-tetrafluoropropene oxide as a product was obtained.

The solution obtained in this example and the solution obtained in Example 6 were mixed, and 100 g of 10% aqueous potassium sulfite solution was added and stirred while cooling with ice water. When it was confirmed that the solution did not color potassium iodide starch paper, two layers were separated. The obtained organic layer was rectified by the same distillation apparatus as in Example 7. Distillation conditions: distillation kettle: 71.4 ° C. to 91.6 ° C., column top: 23.9 ° C. to 24.3 ° C., 29.8 g of a fraction at normal pressure (purity: 199.5% by ¹⁹ F-NMR) Got.
[Comparative Example 1]
A stainless steel autoclave was charged with 6.9 g (30 mmol) of m-chloroperbenzoic acid and 20 ml of dichloromethane, and the reactor was sealed and cooled with ice water. When cooled, the internal pressure was reduced to 0.05 MPa with a vacuum pump. Next, 2.5 g (22 mmol) of cis-1,3,3,3-tetrafluoropropene was charged. After charging the raw materials, they were reacted for 24 hours. The jacket temperature at this time was 0 degreeC-21 degreeC. After completion of the reaction, the reaction solution was analyzed by ¹⁹ F-NMR. As a result, the target product, cis-1,3,3,3-tetrafluoropropene oxide, could not be confirmed.
[Comparative Example 2]
A stainless steel autoclave was charged with 4.6 g (30 mmol) of sodium perborate tetrahydrate and 20 ml of acetic acid, and the reactor was sealed and cooled with ice water. When cooled, the internal pressure was reduced to 0.01 MPa with a vacuum pump. Next, 2.3 g (21 mmol) of cis-1,3,3,3-tetrafluoropropene was charged. After charging the raw materials, the reaction was carried out for 20 hours. The jacket temperature at this time was 0 degreeC-21 degreeC. After completion of the reaction, the reaction solution was analyzed by ¹⁹ F-NMR. As a result, the target product, cis-1,3,3,3-tetrafluoropropene oxide, could not be confirmed.
[Comparative Example 3]
A hypofluorite-containing solution was prepared in the same manner as in Example 1. To the resulting solution, 2.7 g (23.8 mmol) of 2,3,3,3-tetrafluoropropene was introduced and reacted for 3 hours. The internal temperature at this time was −12.2 ° C. to −6.0 ° C. As a result of analyzing the reaction solution after completion of the reaction, the corresponding 2,3,3,3-tetrafluoropropene epoxide was not obtained. As a result of adding an internal standard substance to the reaction liquid and quantifying by ¹⁹ F-NMR, 6.0 mmol of 2,3,3,3-tetrafluoropropene as a raw material and 10.7 mmol in total of two unidentified compounds are contained. It was.
[Comparative Example 4]
In a stainless steel autoclave reactor, sodium hypochlorite pentahydrate 86.6 g (526 mmol, 5.7 equivalents), sodium hydroxide 10.7 g (268 mmol, 2.9 equivalents), trioctylmethylammonium chloride 1.3 g (3.2 mmol, 3.5 mol%), 70 g of water and 44 ml of benzotrifluoride were charged, the reactor was sealed and cooled with ice water. When cooled, the internal pressure was reduced to 0.01 MPa with a vacuum pump. Next, 10.5 g (92 mmol) of 2,3,3,3-tetrafluoropropene was charged. The raw materials were charged and reacted for 3 hours. At this time, the reactor was cooled with ice water. As a result of analyzing the reaction solution after the reaction was completed, the reaction did not proceed and the raw material was recovered.

[Comparative Example 5]
A glass reactor equipped with a thermometer protection tube and a stopcock was charged with acetonitrile (7.7 ml) and 2.6 g (15.3 mmol) of m-chloroperbenzoic acid. Next, 1.0 g (7.7 mmol) of cis-1-chloro-3,3,3-trifluoropropene was added and reacted at room temperature for 15 hours. As a result of analyzing the solution after completion of the reaction, the target epoxide was not confirmed.

[Comparative Example 6]
Referring to Comparative Example 5, acetic acid (20 ml), sodium perborate tetrahydrate 4.6 g (30 mmol) and cis-1-chloro-3,3,3-trifluoropropene 2.6 g (20 mmol) were added at room temperature. The reaction was performed for 16 hours. As a result of analyzing the solution after completion of the reaction, the target epoxide was confirmed by ¹⁹ F-NMR to 0.2%.

  The disubstituted halogenated epoxide, which is the target compound of the present invention, can be used as an intermediate in pharmaceuticals and agricultural chemicals.

Claims (8)

General formula [1]:

[Wherein, R _f represents a linear or branched C 1-10 fluoroalkyl group having one or more fluorine atoms, and X ¹ represents a halogen atom. ]
Is reacted with a hypohalous acid or a salt thereof to give a general formula [2]:

Wherein, R _f and X ¹ are the same as R _f and X ¹ in the general formula [1]. * Represents an asymmetric carbon. ] The method of manufacturing the disubstituted halogenated epoxide represented by these. The disubstituted halogenated epoxide is represented by the general formula [2a] or the general formula [2aa]:

[In Formula [2a] and Formula [2aa], R _f and X ¹ are the same as R _f and X ^{1 in} General Formula [1], respectively. ]
A trans-disubstituted halogenated epoxide represented by:
Or
General formula [2b] or general formula [2bb]:

[In Formula [2b] and Formula [2bb], R _f and X ¹ are the same as R _f and X ^{1 in} General Formula [1], respectively. ]
A cis-disubstituted halogenated epoxide represented by:
The method of claim 1 obtained as As the disubstituted halogenoolefin, the general formula [1a]:

When a trans-disubstituted halogenoolefin represented by the following formula is used as a starting material, a trans-disubstituted halogenated epoxide represented by the general formula [2a] or the general formula [2aa] is selectively produced,
General formula [1b]:

When a cis-disubstituted halogenoolefin represented by general formula [2b] or general formula [2bb] is used as a starting material, a cis-disubstituted halogenated epoxide represented by general formula [2bb] is selectively produced.
The method according to claim 1 or 2. General formula [3]:

[Wherein, X ¹ represents a halogen atom. ]
By reacting trans-1-halogeno-3,3,3-trifluoropropene represented by general formula [4a] or general formula [4aa]:

[In Formula [4a] and Formula [4aa], X ¹ is the same as X ^{1 in} General Formula [3]. ]
A process for producing trans-1-halogeno-3,3,3-trifluoropropene oxide represented by the formula: General formula [5]:

[Wherein, X ¹ represents a halogen atom. ]
By reacting hypohalous acid or a salt thereof with cis-1-halogeno-3,3,3-trifluoropropene represented by general formula [6b] or general formula [6bb]:

[In Formula [6b] and Formula [6bb], X ¹ is the same as X ^{1 in} General Formula [3]. ]
A process for producing cis-1-halogeno-3,3,3-trifluoropropene oxide represented by the formula: The method according to any one of claims 1 to 3, wherein R _f is a trifluoromethyl group, a pentafluoroethyl group, a heptafluoropropyl group, or a nonafluorobutyl group. The method according to any one of claims 1 to 6, wherein X ¹ is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. The method according to any one of claims 1 to 7, wherein the hypohalous acid or a salt thereof is hypofluoric acid, an alkali metal hypochlorite or an alkaline earth metal hypochlorite.