JP5223305B2 - Method for producing fluorine-containing keto alcohol and derivatives thereof - Google Patents

Description

  The present invention relates to a method for producing a fluorine-containing compound useful as a raw material for a monomer corresponding to a next-generation photoresist material.

  Fluorine-containing ketoalcohols are promising compounds as intermediate raw materials for monomers of next-generation resist materials, and their structural units are esters of 1,3-diol compounds that are carbonyl reductants and (meth) acrylic acids. It is known that the resist material is excellent in light transmission and surface adsorption.

  As a manufacturing method of fluorine-containing keto alcohol, the following are mentioned, for example.

  Patent Document 1 describes a method for producing fluorine-containing keto alcohols by heating acetone and hexafluoroacetone at 160 ° C. in a closed pressure vessel. However, in order to heat the reaction to 160 ° C., a high pressure of about 4 MPa is applied, and a reaction apparatus that can withstand this pressure is required. On the other hand, if this reaction is performed at a practical pressure, the reaction hardly proceeds even if the reaction is performed for a long time.

In Patent Document 2 and Non-Patent Document 1, acetone and 1,1,1,3,3,3-hexafluoroacetone are reacted with an aldol reaction in the presence of an acid catalyst such as non-catalyst or sulfuric acid or BF ₃ etherate. And a method for producing a fluorine-containing keto alcohol is described. However, according to this production method, it is necessary to add the acid catalyst to the reaction solution, and it is necessary to select a reactor that can withstand the reaction. Although it is possible to manufacture at a relatively low pressure as compared with Patent Document 1, it is still necessary to manufacture using a pressure vessel. Furthermore, if an excess amount of acetone is not used relative to 1,1,1,3,3,3-hexafluoroacetone, it is possible to produce a fluorine-containing ketoalcohol with good selectivity, and the excess acetone is reused. It had to be used or disposed of as waste. Another problem is that even if acetone is used in excess, a by-product in which two molecules of 1,1,1,3,3,3-hexafluoroacetone are added to acetone is obtained.
US Pat. No. 3,660,711 JP 2005-239710 A Journal of Fluorine Chemistry, 128 (2007) 902-909

  An object of the present invention is to provide a method capable of producing fluorinated keto alcohols in a high yield under simple and mild conditions applicable on an industrial scale without causing the above problems.

  As a result of intensive studies to solve the above-mentioned problems, the inventor reacted hexafluoroacetone with a predetermined enol ether compound and / or enesulfonamide compound in the absence of a catalyst, followed by solvolysis. By doing so, it was found that fluorine-containing keto alcohols were obtained.

  These methods can be carried out basically under catalyst-free conditions, under mild reaction temperatures and pressures, and since fluorine-containing keto alcohols can be produced in high yields, on an industrial scale. Is suitable. As a result of further research based on this knowledge, the present invention has been completed.

  That is, the present invention relates to a fluorine-containing keto alcohol represented by the general formula [3].

(In the formula, R and R ¹ are the same or different and are a hydrogen atom, an alkyl group having 1 to 7 carbon atoms which may have a substituent, or an aryl group which may have a substituent. Alternatively, R and R ¹ may be connected to form a ring, and further may have a substituent on the ring.)
A manufacturing method of
Hexafluoroacetone represented by the formula [1]

And an enol ether compound represented by the general formula [2]

(Wherein R ² is an optionally substituted alkyl group having 1 to 7 carbon atoms, an optionally substituted alkanoyl group having 1 to 7 carbon atoms, and an optionally substituted carbon. An alkoxycarbonyl group of 1 to 7; a benzyloxycarbonyl group which may have a substituent on the benzene ring; a benzyl group which may have a substituent on the benzene ring; or a trihydrocarbon group-substituted silyl group. And R and R ² may be linked to form a ring, R and R ¹ are the same as above), and / or
Ensulfonamide compounds represented by general formula [10]

(In the formula, R ⁴ is an optionally substituted alkyl group having 1 to 7 carbon atoms or an optionally substituted aryl group, and R ⁵ has a hydrogen atom and a substituent. An alkyl group having 1 to 7 carbon atoms or an aryl group which may have a substituent, and R and R ¹ are the same as above.)
And a solvolysis in the presence of an acid or a base, and a method for producing a fluorinated keto alcohol.

When the enol ether compound represented by the general formula [2] is used, it is preferable that R is a hydrogen atom, R ¹ is a methyl group, and R ² is a methyl group or an acetyl group. R and R ¹ are hydrogen atoms, and R ² is an alkyl group having 1 to 7 carbon atoms (for example, methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group) or acetyl group Are also preferred.

When the enesulfonamide compound represented by the general formula [10] is used, it is preferable that one of the R is a hydrogen atom, the other is a methyl group, and R ¹ is an aryl group. It is also preferred that R and R ¹ are methyl groups. R ⁵ is preferably a hydrogen atom. R ⁴ is preferably an aryl group.

  ADVANTAGE OF THE INVENTION According to this invention, the target fluorine-containing keto alcohol can be manufactured in high yield from mild conditions under a mild condition from an enol ether compound and / or an enesulfonamide compound. Therefore, the present invention is an excellent method for producing a fluorine-containing keto alcohol on an industrial scale. The obtained fluorine-containing keto alcohol can be efficiently converted to fluorine-containing 1,3-diol. Further, when the fluorine-containing 1,3-diol is reacted with an acrylic acid derivative, it can be easily derived into a fluorine-containing acrylic ester. The fluorine-containing acrylic ester is effectively used as a monomer for the resist material.

Hereinafter, the present invention will be described in detail.
(Step I)
In step I, 1,1,1,3,3,3-hexafluoroacetone represented by the formula [1], an enol ether compound represented by the general formula [2] and / or the general formula [10] After reacting the enesulfonamide compound, the resulting mixture is solvolyzed in the presence of acid or base.

The reaction with 1,1,1,3,3,3-hexafluoroacetone represented by the formula [1] is carried out by reacting an enol ether compound represented by the general formula [2] and an enesulfonamide represented by the general formula [10]. The compounds can be reacted alone, or both can be mixed and reacted. When both are mixed and reacted, R and R ¹ in the enol ether compound represented by the general formula [2] are the same as or different from R and R ¹ of the enesulfonamide compound represented by the general formula [10]. It may be.

  Hereinafter, each reaction of the enol ether compound represented by the general formula [2] and the enesulfonamide compound represented by the general formula [10] will be specifically described.

In the reaction step I of the enol ether compound [2], 1,1,1,3,3,3-hexafluoroacetone represented by the formula [1] is reacted with the enol ether compound represented by the general formula [2]. And the resulting mixture is solvolyzed.

(Wherein R ¹ , R ² and R are the same as above)
The alkyl group having 1 to 7 carbon atoms of the alkyl group having 1 to 7 carbon atoms which may have a substituent represented by R and R ¹ may be linear, branched or cyclic. Examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a hexyl group, a cyclohexyl group, and a heptyl group.

  Examples of the substituent on the alkyl group having 1 to 7 carbon atoms include an alkoxy group, an alkanoyl group, a carboxyl group, a hydroxyl group, a halogen atom, etc., and 1 to 3 of these are substituted on the alkyl group. May be.

Examples of the aryl group of the aryl group which may have a substituent represented by R and R ¹ include a phenyl group, a toluyl group, and a naphthyl group.

  Examples of the substituent on the aryl group include an alkoxy group (methoxy group, ethoxy group, etc.), a nitro group, an amino group, and a halogen atom, and 1 to 3 of these are substituted on the aryl group. Also good.

When two Rs or R and R ¹ are connected to form a ring, the carbon-carbon bond forming the ring may contain an unsaturated bond (such as a double bond). Examples of the substituent include a carboxyl group, a hydroxyl group, an alkoxy group, and an oxo group (═O). 1-3 of these may be substituted on the ring.

R is preferably a hydrogen atom or a methyl group, and R ¹ is preferably a hydrogen atom, a methyl group, an ethyl group or a cyclohexyl group.

The alkyl group having 1 to 7 carbon atoms which may have a substituent represented by R ² may be linear, branched or cyclic, for example, methyl group, ethyl group, propyl group, isopropyl group Butyl group, sec-butyl group, tert-butyl group, pentyl group, hexyl group, cyclohexyl group, heptyl group and the like. Preferred are methyl group, ethyl group, propyl group, isopropyl group, butyl group and tert-butyl group.

  Examples of the substituent on the alkyl group having 1 to 7 carbon atoms include an alkoxy group, an alkanoyl group, a carboxyl group, a hydroxyl group, a halogen atom, etc., and 1 to 3 of these are substituted on the alkyl group. May be.

The alkanoyl group of the alkanoyl group having 1 to 7 carbon atoms which may have a substituent represented by R ² may be linear, branched or cyclic, for example, formyl group, acetyl group, propionyl group , Butyryl group, isobutyryl group, valeryl group, bivaloyl group, benzoyl group and the like. Preferably, they are a formyl group, an acetyl group, and a benzoyl group.

The alkoxycarbonyl group having 1 to 7 carbon atoms which may have a substituent represented by R ² may be linear, branched or cyclic, for example, methoxycarbonyl group, propoxycarbonyl group, butoxycarbonyl Group, isobutoxycarbonyl group, t-butoxycarbonyl and the like. Preferably, it is a t-butoxycarbonyl group.

  Examples of the substituent on the alkanoyl group having 1 to 7 carbon atoms and the alkoxycarbonyl group include an alkoxy group, an alkanoyl group, a carboxyl group, a hydroxyl group, a halogen atom, etc., and 1 to 3 of these groups on the alkanoyl group. May be substituted.

Examples of the benzyloxycarbonyl group which may have a substituent on the benzene ring represented by R ² or the substituent of the benzyl group which may have a substituent on the benzene ring include a nitro group and a methoxy group. It is done.

In the trihydrocarbon group-substituted silyl group represented by R ² , the three hydrocarbon groups on silicon may be the same or different, for example, trimethylsilyl group, triethylsilyl group, tert-butyldimethylsilyl, triisopropylsilyl, etc. And a trialkylsilyl group, tert-butyldiphenylsilyl, and the like.

  Specific examples of the enol ether compound represented by the general formula [2] include, for example, 2-methoxypropene, 2-benzyloxypropene, ethyl vinyl ether, vinyl pivalate, butyl vinyl ether, tert-butyl vinyl ether, isopropenyl acetate, isopropenyl chloro. Examples include formate, vinyl propionate, vinyl acetate, and 2-methoxy-1-propenylbenzene. Moreover, the silyl enol ether compound which can be induced | guided | derived from ketones like 2-trimethylsiloxypropene, 2-triethylsiloxypropene, etc. can also be mentioned. As ketones, acetone, methyl ethyl ketone, methyl n-propyl ketone, isopropyl methyl ketone, methyl n-butyl ketone, methyl isobutyl ketone, pinacolone, diethyl ketone, di-n-propyl ketone, diisopropyl ketone, acetophenone, propiophenone, butyrophenone, valerophenone Etc.

A compound in which two Rs or R and R ¹ are connected to form a ring may contain an oxo group or a double bond on the ring. Examples of such a compound include 2,3 -Dihydro-5-methylfuran, 1,5-dimethoxy-1,4-cyclohexadiene, 1-cyclopent-1-yl acetate, 3-ethoxy-2-cyclohexenone, 6,7-dihydrocyclopentane-1,3 -Dioxin-5 (4H) -one, 1-methoxy-2-methyl-1,4-cyclohexadiene, 3-ethoxy-2-cyclopenten-1-one, 3-methoxy-2-cyclopenten-1-one, -Methoxy-1,4-cyclohexadiene and the like.

  Examples of cyclic ketones that can be used after being derived from a silyl enol ether compound include cyclopentanone, cyclohexanone, cycloheptanone, cyclooctanone, and indanone.

  These enol ether compounds represented by the general formula [2] can be synthesized by a known method and can be easily obtained as a reagent.

Of these, 2-methoxypropene or isopropenyl acetate is a particularly preferred example because the usefulness of the product is remarkable (R ¹ = methyl group or acetyl group, R = hydrogen atom). When the enol ether compound represented by the general formula [2] is 2-methoxypropene or isopropenyl acetate, 1,1-bis (trifluoromethyl) -1-hydroxybutane-3- ON is obtained. As described later, this is reduced by a reaction using a metal hydride compound or a catalytic hydrogenation reaction using hydrogen to obtain 1,1-bis (trifluoromethyl) -butane-1,3-diol.

  Also preferred are 2-trimethylsiloxypropene, 2-benzyloxypropene, ethyl vinyl ether, butyl vinyl ether, vinyl acetate, and 2-methoxy-1-propenylbenzene.

  This reaction can be carried out, for example, in a batch reactor. The reaction conditions will be described below, but this does not prevent changes in the reaction conditions that can be easily adjusted by those skilled in the art in each reaction apparatus.

  First, the reaction process of hexafluoroacetone and an enol ether compound will be described. In this step, hexafluoroacetone is reacted with an enol ether compound represented by the general formula [2].

  In this reaction, no additive is particularly required, and the reaction proceeds only by mixing hexafluoroacetone and enol ether compound. In addition, although an acid etc. may be used as an additive, there is almost no reaction promotion effect. In the case of using an acid, examples thereof include metal chlorides such as aluminum chloride, tin chloride, iron chloride and titanium chloride, inorganic acids such as sulfuric acid, and the like. When using an additive, the usage-amount is 1 mol or less with respect to 1 mol of hexafluoroacetone, Preferably it is 0.01-0.2 mol.

  The reaction temperature for this reaction is usually from -20 to 140 ° C, preferably from -10 to 100 ° C, more preferably from 0 to 60 ° C. If it is less than -20 degreeC, it is not economically preferable from a viewpoint of energy efficiency. Moreover, when it exceeds 140 degreeC, since the production | generation of a by-product and decomposition | disassembly of an enol ether compound are seen, it is unpreferable.

  The reaction pressure of this reaction is generally −0.1 to 0.8 MPa (G), preferably −0.1 to 0.4 MPa (G), more preferably −0.1 to 0.1 MPa (G). . Usually, the reaction is carried out under normal pressure. Further, the reaction can be carried out in a state where the inside of the reactor is in a vacuum state (760 Torr or less). In this way, the reaction proceeds under very mild conditions, and it is not necessary to add a catalyst during the addition reaction of the enol ether compound, thereby reducing the cost of the reaction equipment.

  The compounding quantity of an enol ether compound is 0.8-10.0 mol with respect to 1 mol of hexafluoroacetone, 0.9-2.0 mol is preferable and 1.0-1.1 mol is more preferable. If the amount of the enol ether compound is less than 0.8 mol per 1 mol of hexafluoroacetone, hexafluoroacetone is not involved in the reaction by 0.2 mol or more, so the yield of the target product is reduced and 10.0 mol is reduced. When it exceeds, the enol ether compound which does not participate in reaction will increase, and it is economically not preferable from the effort of disposal.

  Although it is not necessary to use a solvent in this reaction, when the enol ether compound is a solid, it is preferable to use a solvent in which the enol ether compound is soluble because the reaction proceeds particularly smoothly. There are no particular restrictions on the type of solvent that can be used, but examples include hydrocarbon compounds such as pentane, hexane, heptane, octane, and cyclohexane, ether solvents such as diethyl ether, methyl-t-butyl ether, diisopropyl ether, and tetrahydrofuran. These may be used alone or in combination with a plurality of solvents. Moreover, it is preferable to perform reaction of the 1st process on the conditions which water does not exist.

  The time required for the above reaction depends on the reaction temperature, the blending amount of raw materials, and the like. The reaction is preferably carried out while confirming the progress of the reaction by means such as gas chromatography or thin phase chromatography, as appropriate.

  In this reaction, it is preferable to react while adding (introducing) hexafluoroacetone to a mixture containing an enol ether compound and, if necessary, a solvent. This makes it easy to adjust the internal pressure of the reaction system and makes it easy to confirm the end point of the reaction. For example, while the reaction is in progress, the reaction conditions can be set so that the decrease in internal pressure due to consumption of hexafluoroacetone is compensated for by the addition of the compound so that a predetermined internal pressure is obtained. Since this is not done, the internal pressure in the reaction system rises. The end point of the reaction can be easily confirmed by the increase in the internal pressure.

  The reactor used in this reaction is preferably a glass, tetrafluoroethylene resin, chlorotrifluoroethylene resin, vinylidene fluoride resin, PFA resin or the like lined inside, a glass container or stainless steel.

In addition, the compound obtained by said reaction becomes a mixture normally, for example, when it reacts with an enol ether compound, it is usually mainly represented by the following general formula [7], general formula [8], and general formula [9]. A mixture of the compounds shown. Incidentally, an alkyl group of R ¹ is carbon atoms which may have a substituent 1 to 7, R ² is an alkyl group having 1 to 7 carbon atoms which may have a substituent group, the substituent on the aromatic ring In the case of a benzyl group or a trihydrocarbyl group-substituted silyl group which may have, it has been confirmed that a compound represented by the general formula [7] and / or the general formula [8] is given as a main product. . This is presumed to be a compound obtained by an ene reaction between hexafluoroacetone and an enol ether compound. In the case where R ¹ and R are a hydrogen atom or R ² is an optionally substituted alkanoyl group having 1 to 7 carbon atoms or an optionally substituted alkoxycarbonyl group having 1 to 7 carbon atoms. Has been confirmed to give the oxetane compound of general formula [9] as the main product. This is presumed to be a compound obtained by [2 + 2] cycloaddition reaction of hexafluoroacetone and an enol ether compound.

(In the formula, R ^{1 ′} is an optionally substituted alkylidene group having 1 to 7 carbon atoms, and any one or more of R ^{1 ′} , R and R ² are connected to form a ring. It may also have a substituent on the ring, and R ¹ , R ² and R are the same as above.)
Subsequently, the mixture obtained above is converted into a fluorinated ketoalcohol without any particular purification. As a method for conversion, a solvolysis method (for example, a hydrolysis method, alcoholysis or transesterification method) can be used in the presence of an acid or a base.

  Specifically, when a hydrolysis method is employed, inorganic acids such as hydrochloric acid; sulfonic acids such as methanesulfonic acid, paratoluenesulfonic acid and trifluoromethanesulfonic acid; hydroxide salts such as sodium hydroxide, carbonic acid Water, alcohols (methanol, ethanol, propanol etc.) etc. which added carbonates, such as sodium, etc. can be used.

  When employing an alcoholysis or transesterification method, an alcohol (methanol, ethanol, propanol, etc.) added with an inorganic acid such as hydrochloric acid; a sulfonic acid such as methanesulfonic acid, paratoluenesulfonic acid, trifluoromethanesulfonic acid, etc. Can be used.

  When the above mixture contains a trihydrocarbon group-substituted silyl group, fluoride ions should be present in the reaction system using cesium fluoride, potassium fluoride, sodium fluoride, tetrabutylammonium fluoride, etc. Can be disassembled.

  The amount of acid or base used in the solvolysis reaction is generally 0.005 to 10.0 mol, preferably 0.01 to 5.0 mol, per 1 mol of the raw material hexafluoroacetone. 0.1 to 2.0 mol is more preferable. If the amount used is less than 0.005 mol, the reaction rate decreases, and if it exceeds 10.0 mol, the amount of excess acid or base that does not participate in the reaction increases, which takes time for disposal and is not economically preferable.

  The reaction temperature for the solvolysis is usually from 0 to 140 ° C, preferably from 20 to 120 ° C, more preferably from 30 to 100 ° C. If it is less than 0 degreeC, it is economically not preferable from a viewpoint of energy efficiency, and progress of reaction will also become slow. Moreover, when it exceeds 140 degreeC, it is economically unpreferable from a viewpoint of energy efficiency.

  After completion of the reaction, the fluorine-containing keto alcohol represented by the general formula [3], which is the target product, is purified according to a conventional method. Examples of the purification method include column chromatography, distillation, recrystallization, crystallization and the like. In addition, it can also use for a 2nd process, without refine | purifying as needed.

As another method in the reaction step I of the ensulfonamide compound [10], 1,1,1,3,3,3-hexafluoroacetone represented by the formula [1] and represented by the general formula [10] After reacting the enesulfonamide compound, the resulting mixture is solvolyzed.

(In the formula, R ¹ , R ⁴ , R ⁵ and R are the same as above.)
R and R ¹ are synonymous with R and R ¹ in the reaction with the enol ether compound represented by the general formula [2].

R is preferably a hydrogen atom or an alkyl group having 1 to 5 carbon atoms (particularly a methyl group), more preferably one of the two Rs is a hydrogen atom and the other is a methyl group. R ¹ is preferably an alkoxy group or an aryl group optionally substituted with a halogen atom (particularly a phenyl group) or an alkyl group having 1 to 5 carbon atoms, more preferably a phenyl group or methoxy (particularly p-methoxy). A phenyl group, a chloro (particularly p-chloro) phenyl group, and an ethyl group;

The alkyl group having 1 to 7 carbon atoms of the alkyl group having 1 to 7 carbon atoms which may have a substituent represented by R ⁴ and R ⁵ may be linear, branched or cyclic. Methyl group, ethyl group, propyl group, isopropyl group, butyl group, sec-butyl group, tert-butyl group, pentyl group, hexyl group, cyclohexyl group, heptyl group and the like.

  Examples of the substituent on the alkyl group having 1 to 7 carbon atoms include an alkoxy group, an alkanoyl group, a carboxyl group, a hydroxyl group, a halogen atom, etc., and 1 to 3 of these are substituted on the alkyl group. May be.

Examples of the aryl group of the aryl group which may have a substituent represented by R ⁴ and R ⁵ include a phenyl group, a toluyl group, and a naphthyl group.

  Examples of the substituent on the aryl group include an alkoxy group (methoxy group, ethoxy group, etc.), a nitro group, an amino group, and a halogen atom, and 1 to 3 of these are substituted on the aryl group. Also good.

R ⁴ is preferably an aryl group, more preferably a phenyl group, a toluyl group, or a phenyl group.

R ⁵ is preferably a hydrogen atom.

  Specific examples of the enesulfonamide compound represented by the general formula [10] include, for example, N- (benzenesulfonyl)-(E) -1-phenylprop-1-en-1-amine, N- (benzenesulfonyl) -(Z) -1-phenylprop-1-en-1-amine, N-((p-methoxy) -benzenesulfonyl)-(E) -1-phenylprop-1-en-1-amine, N- ((p-methoxy) -benzenesulfonyl)-(Z) -1-phenylprop-1-en-1-amine, N-((p-chloro) -benzenesulfonyl)-(E) -1-phenylprop- 1-ene-1-amine, N-((p-chloro) -benzenesulfonyl)-(Z) -1-phenylprop-1-en-1-amine.

These enesulfonamide compounds represented by the general formula [10] can be synthesized by a known method (for example, Angelante Chemie International Edition, 2007, 46, 3047-50). Of these, N- (benzenesulfonyl)-(Z) -1-phenylprop-1-en-1-amine is a particularly preferred example because of the usefulness of the product (R ¹ = phenyl group, R = hydrogen). Atoms and methyl groups).

  When the enesulfonamide compound represented by the general formula [10] is N- (benzenesulfonyl)-(Z) -1-phenylprop-1-en-1-amine, 3-Bis (trifluoromethyl) -3-hydroxy-2-methyl-1-phenylpropan-1-one is obtained. This is reduced by a reaction using a metal hydride compound or a catalytic hydrogenation reaction using hydrogen to obtain 3,3-bis (trifluoromethyl) 2-methyl-1-phenylpropane-1,3-diol. I can do it.

  This reaction can be carried out, for example, in a batch reactor. The reaction conditions will be described below, but this does not prevent changes in the reaction conditions that can be easily adjusted by those skilled in the art in each reaction apparatus.

  A reaction process between hexafluoroacetone and an enesulfonamide compound will be described. In this step, hexafluoroacetone is reacted with an enesulfonamide compound represented by the general formula [10].

  In this reaction, no additive is particularly required, and the reaction proceeds only by mixing hexafluoroacetone and an enesulfonamide compound. In addition, although an acid etc. may be used as an additive, there is almost no reaction promotion effect. In the case of using an acid, examples thereof include metal chlorides such as aluminum chloride, tin chloride, iron chloride and titanium chloride, inorganic acids such as sulfuric acid, and the like. When using an additive, the usage-amount is 1 mol or less with respect to 1 mol of hexafluoroacetone, Preferably it is 0.01-0.2 mol.

  The reaction temperature for this reaction is usually from -20 to 140 ° C, preferably from -10 to 100 ° C, more preferably from 0 to 60 ° C. If it is less than -20 degreeC, it is not economically preferable from a viewpoint of energy efficiency. Moreover, when it exceeds 140 degreeC, since the production | generation of a by-product and decomposition | disassembly of an enesulfonamide compound are seen, it is unpreferable.

  The reaction pressure of this reaction is generally −0.1 to 0.8 MPa (G), preferably −0.1 to 0.4 MPa (G), more preferably −0.1 to 0.1 MPa (G). . Usually, the reaction is carried out under normal pressure. The reaction can also be carried out in a state where the pressure in the reactor is reduced (760 Torr or less). In this way, the reaction proceeds under very mild conditions, and it is not necessary to add a catalyst during the addition reaction of the enesulfonamide compound, thereby reducing the cost of the reaction equipment.

  The compounding amount of the enesulfonamide compound is 0.02 to 10.0 mol, preferably 0.05 to 2.0 mol, more preferably 0.05 to 1.1 mol, per 1 mol of hexafluoroacetone. .

  In this reaction, when the enesulfonamide compound is a solid, it is preferable to use a solvent in which the enesulfonamide compound is soluble because the reaction proceeds particularly smoothly. There are no particular limitations on the type of solvent that can be used, but for example, halogen compounds such as chloroform and dichloromethane, ether solvents such as diethyl ether, methyl-t-butyl ether, diisopropyl ether, and tetrahydrofuran are preferred, and these are used alone. A plurality of solvents may be used in combination. Moreover, it is preferable to perform reaction of the 1st process on the conditions which water does not exist.

  The time required for the above reaction depends on the reaction temperature, the blending amount of raw materials, and the like. The reaction is preferably carried out while confirming the progress of the reaction by means such as gas chromatography or thin phase chromatography, as appropriate.

  In this reaction, it is preferable to carry out the reaction while adding (introducing) hexafluoroacetone to a mixture containing an enesulfonamide compound and, if necessary, a solvent. This makes it easy to adjust the internal pressure of the reaction system and makes it easy to confirm the end point of the reaction. For example, while the reaction is in progress, the reaction conditions can be set so that the decrease in internal pressure due to consumption of hexafluoroacetone is compensated for by the addition of the compound so that a predetermined internal pressure is obtained. Since this is not done, the internal pressure in the reaction system rises. The end point of the reaction can be easily confirmed by the increase in the internal pressure.

  The reactor used in this reaction is preferably a glass, tetrafluoroethylene resin, chlorotrifluoroethylene resin, vinylidene fluoride resin, PFA resin or the like lined inside, a glass container or stainless steel.

  Subsequently, the mixture obtained above is converted into a fluorinated ketoalcohol without any particular purification. As a method for conversion, a solvolysis method (for example, a hydrolysis method, an alcoholysis method, etc.) can be used in the presence of an acid or a base.

  Specifically, when a hydrolysis method is employed, inorganic acids such as hydrochloric acid; sulfonic acids such as methanesulfonic acid, paratoluenesulfonic acid and trifluoromethanesulfonic acid; hydroxide salts such as sodium hydroxide, carbonic acid Water, alcohols (methanol, ethanol, propanol etc.) etc. which added carbonates, such as sodium, etc. can be used.

  When employing an alcoholysis or transesterification method, an alcohol (methanol, ethanol, propanol, etc.) added with an inorganic acid such as hydrochloric acid; a sulfonic acid such as methanesulfonic acid, paratoluenesulfonic acid, trifluoromethanesulfonic acid, etc. Can be used.

  The amount of acid or base used in the solvolysis reaction is generally 0.005 to 10.0 mol, preferably 0.01 to 5.0 mol, per 1 mol of the raw material hexafluoroacetone. 0.1 to 2.0 mol is more preferable. If the amount used is less than 0.005 mol, the reaction rate decreases, and if it exceeds 10.0 mol, the amount of excess acid or base that does not participate in the reaction increases, which takes time for disposal and is not economically preferable.

  The reaction temperature for the solvolysis is usually from 0 to 140 ° C, preferably from 20 to 120 ° C, more preferably from 30 to 100 ° C. If it is less than 0 degreeC, it is economically not preferable from a viewpoint of energy efficiency, and progress of reaction will also become slow. Moreover, when it exceeds 140 degreeC, it is economically unpreferable from a viewpoint of energy efficiency.

After completion of the reaction, the fluorine-containing keto alcohol represented by the general formula [3], which is the target product, is purified according to a conventional method. Examples of the purification method include column chromatography, distillation, recrystallization, crystallization and the like.
(Process II)
In Step II, the fluorine-containing keto alcohol represented by the general formula [3] is reduced to obtain a fluorine-containing 1,3-diol compound represented by the general formula [4]. As the fluorine-containing keto alcohol represented by the general formula [3], those produced by the step I of the present invention can be used.

(In the formula, R and R ¹ are the same as above.)
This step may be performed by a general means of reduction, but a method of reducing by catalytic hydrogenation using a metal hydride compound or hydrogen is usually employed. Moreover, it is also possible to use a fluorine-containing 1,3-diol compound while increasing the carbon by using a Grineer reagent or the like. Preferred methods and conditions are described below.

  First, a method for obtaining a fluorine-containing 1,3-diol compound represented by the general formula [4] by reducing the fluorine-containing keto alcohol represented by the general formula [3] using a metal hydride compound will be described. Examples of the metal hydride compound used include sodium borohydride, sodium cyanoborohydride, lithium triethylborohydride, lithium tri (sec-butyl) borohydride, potassium tri (sec-butyl) borohydride, Examples thereof include lithium borohydride, zinc borohydride, sodium acetoxyborohydride, lithium aluminum hydride, diisobutylaluminum hydride, diborane and the like.

  Of these, borohydride compounds are preferred because they are highly stable and easy to handle, and water can be used as a solvent. Further, sodium borohydride is preferable because it is easily available commercially and has high activity. In addition, it can also carry out by making multiple types of these metal hydride compounds coexist.

  The amount of the metal hydride compound used in this reaction is usually from 0.25 mol to 1.00 mol, and from 0.40 mol to 0 mol, relative to 1 mol of the fluorinated keto alcohol represented by the general formula [3]. .90 mol is preferred. When the amount of the metal hydride compound is less than the lower limit, the reaction is not completed. When the amount of the metal hydride compound is more than the upper limit, it is not preferable economically.

  In this reaction, it is preferable to use a solvent in order to make the reaction proceed smoothly. There are no particular restrictions on the type of solvent that can be used. For example, aromatic compounds such as benzene, toluene, xylene, mesitylene; diethyl ether, methyl-t-butyl ether, diisopropyl ether, tetrahydrofuran, ethylene glycol monomethyl ether, ethylene glycol Ether solvents such as dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, propylene glycol dimethyl ether; methanol, ethanol, propanol, 2-propanol, tert-butyl alcohol, trifluoroethanol, 1,1,1,3 Alcohol solvents such as 1,3,3-hexafluoro-2-propanol, ethylene glycol, propylene glycol; Water or the like is preferable, and these may be used alone or in combination with a plurality of solvents.

  The usage-amount of the solvent used for this reaction is 0.005-10g normally with respect to 1g of fluorine-containing keto alcohol represented by General formula [3], 0.01-6g is preferable, and 0.1-0.1 4 g is more preferable. If it exceeds 100 g, it is not economically preferable from the viewpoint of productivity.

  The reaction temperature of this reaction is usually −10 to 110 ° C., preferably 0 to 80 ° C., more preferably 10 ° C. to 50 ° C. If it is less than -10 degreeC, reaction rate is slow and it cannot become a practical manufacturing method. Further, heating to a temperature exceeding 110 ° C. is not economically preferable from the viewpoint of energy efficiency.

  Reactors that perform reduction using metal hydride are made of glass, tetrafluoroethylene resin, chlorotrifluoroethylene resin, vinylidene fluoride resin, PFA resin, etc. lined inside, glass containers, or stainless steel. Those are preferred.

  The time required for the reduction using the metal hydride depends on the reaction temperature, the type of the metal hydride compound, and the blending amount. The reaction is preferably carried out while confirming the progress of the reaction by means such as gas chromatography or thin phase chromatography, as appropriate.

  Next, a method for reducing the fluorine-containing keto alcohol represented by the general formula [3] with hydrogen in the presence of a catalyst to obtain a fluorine-containing 1,3-diol compound represented by the general formula [4] will be described. .

  A ruthenium catalyst, a rhodium catalyst, etc. can be used for the catalyst used.

Examples of the ruthenium catalyst include ruthenium metal, ruthenium supported on a support (activated carbon, alumina, silica, clay, etc.), ruthenium salt (for example, RuCl ₃ , RuBr ₃ , Ru (NO ₃ ) ₃ ), ruthenium, and the like. Complexes (for example, Ru (CO) ₅ , Ru (NO) ₅ , K ₄ [Ru (CN) ₆ ], Ru (phen) ₃ Cl ₃ (where phen represents phenanthroline)), ruthenium oxide and the like can be mentioned.

  Examples of the rhodium catalyst include rhodium salts, rhodium complexes, and the like in addition to rhodium metal or rhodium supported on a carrier (activated carbon, alumina, silica, clay, etc.).

  Although Patent Document 2 describes that a ruthenium catalyst is preferable, the reduction reaction proceeds well even when a rhodium catalyst is used.

  Among these, a solid-phase catalyst in which ruthenium or rhodium is supported on a carrier is preferable because it exhibits high activity, has high stability, and is easy to handle.

  Ru / C (ruthenium carbon catalyst), ruthenium-alumina catalyst, ruthenium-silica catalyst, Rh / C (rhodium carbon catalyst), rhodium-alumina catalyst, rhodium-silica catalyst, Pd / C (palladium carbon catalyst) are commercially available. It is preferable because it can be easily obtained. These are particularly easy to handle when using water-containing products (for example, products containing 50% by weight of water in the total weight of the catalyst). There is no particular limitation on the metal content in the solid components (components other than water) of these catalysts, but those of about 2 to 10% by weight (for example, 5% by weight) are easily available and stable. It is preferably used because of its high properties and easy handling.

  In addition, this reduction reaction can also be performed in the presence of a plurality of types of these metal catalysts. However, there are usually no special merits even if a plurality of types of metal catalysts coexist.

  The amount of the metal catalyst used is usually 0.0002 mol to 0.04 mol, 0.0004 mol to 0.02 mol in terms of metal atom, per mol of the fluorine-containing keto alcohol represented by the general formula [3]. Is preferable, and 0.001 mol to 0.01 mol is more preferable. When the metal catalyst is less than the above lower limit, the reaction rate decreases, and when it is more than the upper limit, it is not economically preferable.

  Hydrogen can be supplied at normal pressure (0.1 MPa) to 5 MPa, but it is preferable to supply hydrogen pressure under pressure because the reaction rate increases and the operation is simple. Specifically, 0.15 to 2 MPa is preferable, and 0.3 to 1.5 MPa is more preferable. Although the reaction can be carried out even at a pressure lower than normal pressure, there is no particular advantage because the reaction may be slow and the equipment becomes complicated.

  The metal catalyst used is highly stable and can be used in air, but in order to maintain higher activity, the reaction should be carried out after replacing the reactive groups with hydrogen gas and eliminating air (oxygen). Is particularly effective.

  In this reaction, it is preferable to use a solvent because the reaction proceeds smoothly. There are no particular restrictions on the type of solvent that can be used, but aromatic compounds such as benzene, toluene, xylene, and mesitylene; ether solvents such as diethyl ether, methyl-t-butyl ether, diisopropyl ether, and tetrahydrofuran; methanol, ethanol, Preferred are alcohol solvents such as propanol, 2-propanol, tert-butyl alcohol, trifluoroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, ethylene glycol, propylene glycol, and the like. It may be used alone or in combination with a plurality of solvents.

  The amount of the solvent used is 0.005 to 100 g, preferably 0.01 to 20 g, and more preferably 0.1 to 5 g with respect to 1 g of the fluorinated keto alcohol represented by the general formula [3]. If it exceeds 100 g, it is not economically preferable from the viewpoint of productivity.

  The reaction temperature is usually 0 to 150 ° C, preferably 30 to 120 ° C, more preferably 50 ° C to 110 ° C. If it is less than 0 degreeC, reaction rate will be very slow and will not become a practical manufacturing method. Moreover, even if it heats to the temperature exceeding 150 degreeC, there is no remarkable change in reaction rate, and it is economically unpreferable from a viewpoint of energy efficiency.

  The reactor for performing catalytic hydrogenation is preferably a reactor made of tetrafluoroethylene resin, chlorotrifluoroethylene resin, vinylidene fluoride resin, PFA resin, glass or the like, glass container, or stainless steel.

The time required for the catalytic hydrogenation reaction depends on the reaction temperature, the type of catalyst, the blending amount and the like. It is preferable to observe the state of consumption of H ₂ as needed from the pressure in the reaction group, etc., and to carry out the reaction at the stage where the consumption of H ₂ is virtually completed.

After completion of the reaction, the fluorine-containing diol represented by the general formula [4], which is the target product, is purified according to a conventional method. Examples of the purification method include column chromatography, distillation, recrystallization, crystallization and the like. In addition, it can also use for a III process, without refine | purifying as needed.
(Process III)
Next, the step III will be described. In the step III, the fluorine-containing 1,3-diol compound represented by the general formula [4] obtained in the step II is reacted with the acrylic acid derivative represented by the general formula [5], and the general formula [5] 6] is a step of producing a fluorine-containing acrylic acid ester represented by [6].

(In the formula, R ³ is a hydrogen atom, C _m H _{2m + 1} , or C _n F _{2n + 1} , and m and n are integers of 1 to 4. X is F, Cl, a hydroxyl group, or a general formula [5a]:

It is group shown by these. R and R ¹ are the same as above. )
Of C _m H _{2m + 1 represented} by R ³ , _m is preferably an integer of 1 to 2, and _n of C _n F _{2n + 1} is preferably an integer of 1 or 4. In particular, a hydrogen atom, a methyl group or a trifluoromethyl group is particularly preferable from the viewpoint of the usefulness of the product.

  This step may be performed by a general means of esterification, but preferable methods, conditions and the like are described below.

  When the acrylic acid derivative represented by the general formula [5] is an α-substituted acrylic acid halide, it is preferably carried out in the presence of a base. As the base, at least one selected from the group consisting of trimethylamine, triethylamine, pyridine, 2,6-dimethylpyridine, dimethylaminopyridine, sodium carbonate, potassium carbonate, sodium hydroxide, and potassium hydroxide is preferably used. . Of these, pyridine and 2,6-dimethylpyridine are particularly preferred.

  The amount of the base used is usually 0.2 to 2.0 mol, preferably 0.5 to 1.5, with respect to 1 mol of the fluorine-containing 1,3-diol compound represented by the general formula [4]. More preferably, it is 9 to 1.2 mol. If the amount of the base is less than 0.2 mol relative to 1 mol of the fluorine-containing 1,3-diol compound of the substrate, both the selectivity of the reaction and the yield of the target product are reduced, and if it exceeds 2.0 mol, the reaction is not involved. This is economically undesirable because the amount of base increases.

  The amount of the α-substituted acrylic acid halide to be used is 0.2 to 2.0 mol, preferably 0.5 to 1.5 mol, based on 1 mol of the fluorine-containing 1,3-diol compound. 9-1.2 mol is more preferable. When the amount of the α-substituted acrylate halide is less than 0.2 mol with respect to 1 mol of the fluorine-containing 1,3-diol compound, both the selectivity of the reaction and the yield of the target product are decreased. The α-substituted acrylic acid halide not involved in the reaction increases, which is economically undesirable from the time of disposal.

  In this reaction, a base hydrohalide (hydrofluoride, hydrochloride, etc.) is precipitated as a by-product. It is necessary to use a solvent to improve operability. There are no particular restrictions on the type of solvent that can be used, but aromatic compounds such as benzene, toluene, xylene, and mesitylene; ether solvents such as diethyl ether, methyl-t-butyl ether, diisopropyl ether, and tetrahydrofuran; methylene chloride, chloroform And halogen-based solvents such as carbon tetrachloride are preferable, and these may be used alone or in combination with a plurality of solvents.

  The amount of the solvent to be used is 0.5 to 100 g, preferably 1.0 to 20 g, and more preferably 2.0 to 10 g based on 1 g of the fluorine-containing 1,3-diol compound. When the amount of the solvent is less than 0.5 g relative to 1 g of the fluorine-containing 1,3-diol compound, the slurry concentration of the base hydrochloride precipitated during the reaction is too high, so that the operability is lowered. If it exceeds 100 g, it is not economically preferable from the viewpoint of productivity.

  The reaction temperature is -50 to 200 ° C, preferably -20 to 150 ° C, more preferably 0 ° C to 120 ° C. If it is less than −50 ° C., the reaction rate is very slow and it is not a practical production method. Moreover, when it exceeds 200 degreeC, since the fluorine-containing acrylic acid ester shown by the general formula [6] of the alpha-substituted acrylic acid halide or product of the raw material is not preferable.

  In this reaction, it may be carried out in the presence of a polymerization inhibitor for the purpose of preventing polymerization of the raw material α-substituted acrylate halide or the product fluorine-containing ester compound. Polymerization inhibitors used are 2,5-di-t-butylhydroquinone, 1,2,4-trihydroxybenzene, 2,5-bistetramethylbutylhydroquinone, leucoquinizarin, nonflex F, nonflex H, nonflex DCD. Nonflex MBP, Ozonon 35, Phenothiazine, Tetraethylthiuram disulfide, 1,1-diphenyl-2-picrylhydrazyl, 1,1-diphenyl-2-picrylhydrazine, Q-1300, Q-1301 It is a kind of compound. The above polymerization inhibitors are commercially available products and can be easily obtained.

  The amount of the polymerization inhibitor to be used is 0 to 0.1 mol, preferably 0.00001 to 0.05 mol, preferably 0.0001 to 0.001 mol per mol of the raw fluorine-containing 1,3-diol compound. 01 mol is more preferable. Even if the amount of the polymerization inhibitor exceeds 0.1 mol relative to 1 mol of the fluorine-containing 1,3-diol compound as a raw material, there is no significant difference in the ability to prevent polymerization, which is economically undesirable.

  The reactor for carrying out the reaction of the present invention is preferably a tetrafluoroethylene resin, chlorotrifluoroethylene resin, vinylidene fluoride resin, PFA resin, glass lined inside, glass container, or stainless steel. .

  Next, the case where the acrylic acid derivative represented by the general formula [4] is α-substituted acrylic acid will be described. The amount of α-substituted acrylic acid to be used is usually 0.5 to 5.0 mol with respect to 1.0 mol of the fluorine-containing 1,3-diol compound represented by the general formula [4]. 7-3.0 mol is preferable and 1.0-2.0 mol is more preferable. If the amount of α-substituted acrylic acid is less than 0.5 mol relative to 1.0 mol of the fluorine-containing 1,3-diol compound, the conversion rate of the reaction and the yield of the target product are not sufficient, and 5.0 mol If it exceeds, α-substituted acrylic acid which does not participate in the reaction increases, which is not economically preferable from the time of disposal.

  Additives can be added to promote the reaction. The additive used is selected from the group of inorganic acids such as organic sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid and trifluoromethanesulfonic acid, Lewis acids and sulfuric acid, for example. At least one acid is preferably used. The amount of the additive used in this reaction is 0.01 to 2.0 mol, preferably 0.02 to 1.8 mol, relative to 1.0 mol of the fluorine-containing 1,3-diol compound of the substrate. 05-1.5 mol is more preferable. If the amount of the additive is less than 0.01 mol with respect to 1.0 mol of the fluorine-containing 1,3-diol compound of the substrate, both the conversion rate of the reaction and the yield of the target product are reduced. This is economically undesirable because the amount of the additive not involved in the increase increases.

  When no additive is added, the reaction temperature is usually 80 to 200 ° C, preferably 100 to 180 ° C, more preferably 120 to 160 ° C. In this case, the reaction rate is extremely low at less than 80 ° C., and when it exceeds 200 ° C., the raw material α-substituted acrylic acid or the fluorine-containing acrylic acid ester represented by the general formula [6] may be polymerized. It is not preferable. When adding an additive, it implements at 0-160 degreeC, Preferably it is 30-140 degreeC, More preferably, it is 50-120 degreeC. In this case, if it is less than 0 ° C., the reaction rate is slow and it is not a practical production method. Moreover, when it exceeds 160 degreeC, a side reaction will advance easily and since the selectivity of the target fluorine-containing ester compound may fall, it is unpreferable. In the present invention, it is preferable to add an additive because sufficient reactivity is obtained at a low temperature and the selectivity is improved. That is, additives such as organic sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, and trifluoromethanesulfonic acid, inorganic acids such as Lewis acids, sulfuric acid, and the like are allowed to coexist in the system. Carrying out the reaction in the temperature range of 120 ° C. is a particularly preferred embodiment of this step.

  This reaction proceeds even in the absence of a solvent, but it is desirable to use a solvent in consideration of the uniformity of the reaction and the distillation of generated water. There are no particular restrictions on the type of solvent that can be used, but aromatic compounds such as benzene, toluene, xylene, mesitylene; ether solvents such as diethyl ether, methyl-t-butyl ether, diisopropyl ether, and tetrahydrofuran; methylene chloride, chloroform And halogen-based solvents such as carbon tetrachloride; hydrocarbon-based solvents such as cyclohexane and hexane are preferable. These may be used alone or in combination with a plurality of solvents.

  The amount of the solvent to be used is usually 0.1 to 100 g, preferably 0.5 to 50 g, more preferably 1.0 to 20 g based on 1 g of the fluorine-containing 1,3-diol compound. If the amount of the solvent is less than 0.1 g with respect to 1 g of the fluorine-containing 1,3-diol compound, the merit of using the solvent cannot be sufficiently extracted. If it exceeds 100 g, it is not economically preferable from the viewpoint of productivity.

  In this reaction, it is desirable to allow a polymerization inhibitor to coexist for the purpose of preventing the α-substituted acrylic acid or the product (fluorinated acrylate ester) from being polymerized. Examples of the polymerization inhibitor to be used include hydroquinone, methoquinone, 2,5-di-t-butylhydroquinone, 1,2,4-trihydroxybenzene, 2,5-bistetramethylbutylhydroquinone, leucoquinizarin, and nonflex F ( N, N′-di-2-naphthyl-p-phenylenediamine), nonflex H (N, N′-diphenyl-p-phenylenediamine), nonflex DCD (4,4′-dicumyl-diphenylamine), nonflex MBP (2,2′-methylene-bis (4-methyl-6-tert-butylphenol)), ozonone 35 (N- (1-methylheptyl) -N′-phenyl-p-phenylenediamine), phenothiazine, tetraethylthiuram Disulfide, 1,1-diphenyl-2-picrylhydrazyl, 1,1 Diphenyl-2-picryl hydrazine, Q-1300 (N-nitroso-phenylhydroxylamine) is at least one compound selected from Q-1301 (N-nitroso-phenylhydroxylamine aluminum salt). The above polymerization inhibitors are commercially available products and can be easily obtained.

  The amount of the polymerization inhibitor used is usually 0.0001 to 0.1 mol, preferably 0.0001 to 0.05 mol, relative to 1.0 mol of the fluorine-containing 1,3-diol compound as a raw material. 0.001-0.01 mol is more preferable. Even if the amount of the polymerization inhibitor exceeds 0.1 mol with respect to 1.0 mol of the fluorine-containing 1,3-diol compound as a raw material, there is no great difference in ability to prevent polymerization, which is economically undesirable.

  The reactor used in this reaction is made of tetrafluoroethylene resin, chloro-trifluoroethylene resin, vinylidene fluoride resin, PFA resin, glass lined inside, glass container, or stainless steel. preferable.

  Next, Step III of the present invention in the case where the acrylic acid derivative represented by the general formula [5] is an α-substituted acrylic anhydride, that is, a compound in which X is a group represented by the general formula [5a] Will be explained.

  The amount of the α-substituted acrylic anhydride to be used is usually 0.5 to 5.0 mol with respect to 1.0 mol of the fluorine-containing 1,3-diol compound represented by the general formula [4]. 0.7-3.0 mol is preferable, and 1.0-2.0 mol is more preferable. If the amount of the α-substituted acrylic anhydride is less than 0.5 mol with respect to 1.0 mol of the fluorinated 1,3-diol compound, both the conversion rate of the reaction and the yield of the target product are not sufficient. If it exceeds the mole, α-substituted acrylic anhydride that does not participate in the reaction increases, which is economically undesirable from the time of disposal.

  Additives can be added to promote the reaction. The additive used is at least one selected from the group of inorganic acids such as methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, organic sulfonic acids such as trifluoromethanesulfonic acid, Lewis acids, and sulfuric acid. An acid is preferably used. The amount of the additive used in this reaction is 0.01 to 2.0 mol, preferably 0.02 to 1.8 mol, relative to 1.0 mol of the fluorine-containing 1,3-diol compound of the substrate, 0.05 -1.5 mol is more preferable. If the amount of the additive is less than 0.01 mol with respect to 1.0 mol of the fluorine-containing 1,3-diol compound of the substrate, both the conversion rate of the reaction and the yield of the target product are reduced. This is economically undesirable because the amount of the additive not involved in the increase increases.

  When this reaction is carried out, the reaction temperature is usually 80 to 200 ° C., preferably 100 to 180 ° C., more preferably 120 to 160 ° C. when no additive is added. In this case, the reaction rate is very slow below 80 ° C., and when it exceeds 200 ° C., the raw material α-substituted acrylic acid anhydride or the product fluorine-containing ester compound represented by the general formula [6] may be polymerized. It is not preferable. When adding an additive, it is 0-80 degreeC, Preferably it is 10-70 degreeC, More preferably, it implements at 20-60 degreeC. In this case, if it is less than 0 ° C., the reaction rate is slow and it is not a practical production method. Moreover, when it exceeds 80 degreeC, a side reaction will advance easily and it is unpreferable since the selectivity of the target fluorine-containing ester compound may fall. In the present invention, it is preferable to add an additive because sufficient reactivity is obtained at a low temperature and the selectivity is improved. That is, an additive such as methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, trifluoromethanesulfonic acid, and an inorganic acid such as sulfuric acid coexist in the system at a temperature range of 20 to 60 ° C., Carrying out the reaction is a particularly preferred embodiment of this step.

  This reaction proceeds even without solvent, but it is desirable to use a solvent in consideration of the uniformity of the reaction and the operability after the reaction. There are no particular restrictions on the type of solvent that can be used, but aromatic compounds such as benzene, toluene, xylene, and mesitylene, ether solvents such as diethyl ether, methyl-t-butyl ether, diisopropyl ether, and tetrahydrofuran, methylene chloride, and chloroform And halogen-based solvents such as carbon tetrachloride are preferable, and these may be used alone or in combination with a plurality of solvents.

  The amount of the solvent used in this reaction is usually 0.1 to 100 g, preferably 0.5 to 50 g, and more preferably 1.0 to 20 g based on 1 g of the fluorine-containing 1,3-diol compound. If the amount of the solvent is less than 0.1 g relative to 1 g of the fluorine-containing 1,3-diol compound, the merit of using the solvent cannot be sufficiently extracted. If it exceeds 100 g, it is not economically preferable from the viewpoint of productivity.

  In this reaction, it may be carried out in the presence of a polymerization inhibitor for the purpose of preventing the polymerization of the α-substituted acrylic anhydride or the product (fluorinated ester compound). Usually, the polymerization inhibitor described above is used. Can be used.

  The amount of the polymerization inhibitor used in the present invention is usually 0.00001 to 0.1 mol, preferably 0.0001 to 0.05 mol, relative to 1.0 mol of the raw fluorine-containing 1,3-diol compound. 0.001-0.01 mol is more preferable. Even if the amount of the polymerization inhibitor exceeds 0.1 mol relative to 1.0 mol of the fluorine-containing 1,3-diol compound as a raw material, there is no significant difference in the ability to prevent polymerization, which is economically undesirable.

  The reactor used in this reaction is made of tetrafluoroethylene resin, chloro-trifluoroethylene resin, vinylidene fluoride resin, PFA resin, glass lined inside, glass container, or stainless steel. preferable.

  After completion of the reaction, the fluorine-containing ester compound represented by the general formula [6], which is the target product, is purified according to a conventional method. Examples of the purification method include column chromatography, distillation, recrystallization, crystallization and the like.

The fluorine-containing ester compound obtained by the above steps I to III is useful as a monomer corresponding to the next-generation photoresist material. In particular, a fluorine-containing ester compound in which R ³ is a hydrogen atom, a methyl group, or a trifluoromethyl group in General Formula [6], R is a hydrogen atom, and R ¹ is a hydrogen atom or a methyl group is preferable.

  Examples are given below to clarify the features of the present invention. The present invention is not limited to these examples.

  In the following Examples, NMR and measurement conditions used for evaluation of physical properties such as the content rate are as follows.

NMR: manufactured by BRUKER
¹ H-NMR measurement conditions: 300 MHz (tetramethylsilane = 0 ppm)
¹⁹ F-NMR measurement conditions: 282 MHz (trichlorofluoromethane = 0 ppm)
Here, “%” of the composition analysis value was obtained by collecting a part of the reaction mixture or extracting the organic component with diethyl ether or the like as necessary, and measuring this by gas chromatography. “Area%” of the component excluding the solvent component is represented.

GC / MS was measured using PerkinElmer's Claras 500 GC / MS (gas chromatograph mass spectrometer).
[Example 1]
Production of 1,1-bis (trifluoromethyl) -1-hydroxybutan-3-one
(1) A reaction stirrer of hexafluoroacetone and 2-methoxypropene , a pressure gauge, a thermometer, and 100.0 g (1.39 mol) of 2-methoxypropene were placed in a glass 500 mL reactor equipped with a gas introduction tube, With stirring, 217.9 g (1.31 mol) of hexafluoroacetone was introduced over 1 hour in the range of 0 ° C. to 20 ° C. After the introduction of hexafluoroacetone, the reaction was completed by stirring at 0 to 10 ° C. for 1 hour. The reaction solution was sampled and the composition was measured by gas chromatography. When excess 2-methoxypropene was removed, 1,1,1-trifluoro-4-methoxy-2-trifluoromethylpent-4-ene-2 -The abundance of the ol is 89.9%, the abundance of the peak considered to be 1,1,1-trifluoro-4-methoxy-2-trifluoromethylpent-3-en-2-ol is 6.2% The amount of the peak considered to be 2-methoxy-2-methyl-4,4-bis (trifluoromethyl) oxetane was 3.9%.

Spectral data for 1,1,1-trifluoro-4-methoxy-2-trifluoromethylpent-4-en-2-ol:
¹ H-NMR (solvent: CDCl ₃ , reference material: TMS); δ4.92 (s, 1H), 4.22-4.18 (m, 2H), 3.26 (s, 3H), 2.77 (s, 2H), ¹⁹ F-NMR (solvent: CDCl ₃ , reference material: CCl ₃ F); δ-77.7 (s, 6F)
1,1,1-trifluoro-4-methoxy-2-trifluoromethylpent-3-en-2-ol and 2-methoxy-2-methyl-4,4-bis (trifluoromethyl) oxetane are GC / Its existence was suggested from the measurement result of MS spectrum.
(2) Hydrolysis of the reaction mixture of hexafluoroacetone and 2-methoxypropene Add 165 g of 2N hydrochloric acid to 317.9 g of the reaction mixture obtained by the reaction of hexafluoroacetone and 2-methoxypropene, and add water for 2 hours at room temperature. Disassembled. The reaction solution was sampled and the composition was measured by gas chromatography. When acetone and methanol by-products were removed, 1,1,1-trifluoro-2-hydroxy-2- (trifluoromethyl) pentan-4-one The abundance of was 97.4%.

  This reaction solution was separated to obtain 298.6 g. Further, the aqueous layer was re-extracted with 40 g of diisopropyl ether to obtain 41.3 g of a diisopropyl ether solution layer.

339.9 g of the organic layer obtained here was distilled under reduced pressure and a fraction of 67 ° C. to 68 ° C./4.8 kPa (1.0 kPa = 7.5 Torr) was collected. 262.1 g of (trifluoromethyl) -1-hydroxybutan-3-one was obtained with a purity of 99.7%. The yield was 88.0%.
¹ H-NMR (solvent: CDCl ₃ , reference material: TMS); δ 6.74 (bs, 1H), 2.95 (s, 2H), 2.34 (s, 3H), ¹⁹ F-NMR (solvent: CDCl ₃ , reference material: CCl ₃ F); δ-78.9 (s, 6F)
[Example 2]
Production of 1,1-bis (trifluoromethyl) -1-hydroxybutan-3-one
(1) 10.0 g (0.10 mol) of isopropenyl acetate was placed in a 100 mL pressure-resistant reactor made of SUS316 equipped with a reaction stirrer, pressure gauge, thermometer, and gas introduction tube of hexafluoroacetone and isopropenyl acetate, and stirred. However, 15.7 g (0.095 mol) of hexafluoroacetone was introduced over 1 hour in the range of 50 ° C to 60 ° C. After the introduction of hexafluoroacetone, the reaction was terminated by stirring at 50-60 ° C. for 2 hours. At the end of the reaction, the pressure in the reactor was 0.02 MPa. The reaction solution was sampled and the composition was measured by gas chromatography. When excess isopropenyl acetate was removed, the amount of acetic acid 2-methyl-4,4-bistrifluoromethyloxeta-2-nyl ester was 83.9%. The amount of acetic acid 4,4,4, -trifluoro-3-hydroxy-1-methylene-3-trifluoromethylbutyl ester was 16.1%.

Spectral data of acetic acid 2-methyl-4,4-bistrifluoromethyloxeta-2-nyl ester:
¹ H-NMR (solvent: CDCl ₃ , reference material: TMS); δ3.52 (s, 2H), 2.20 (s, 3H), 2.19 (s, 3H), ¹⁹ F-NMR (solvent: CDCl ₃ , reference substance: CCl ₃ F); δ-74.7 (s, 6F)
Spectral data for acetic acid 4,4,4, -trifluoro-3-hydroxy-1-methylene-3-trifluoromethylbutyl ester:
¹ H-NMR (solvent: CDCl ₃ , reference material: TMS); δ 5.07 (dd, 1H), 4.67-4.65 (m, 1H), 2.86 (s, 2H), 2.14 (s, 3H), ¹⁹ F-NMR (solvent: CDCl ₃ , reference material: CCl ₃ F); δ-77.5 (s, 6F)
(2) Transesterification of the reaction mixture of hexafluoroacetone and isopropenyl acetate To 2 g of the reaction mixture obtained by the reaction of hexafluoroacetone and isopropenyl acetate, 0.1 g of methanol and 0.16 mol of concentrated sulfuric acid were added. 03 g (0.0003 mol) was added, and the mixture was heated to reflux for 8 hours. The reaction solution was sampled and the composition was measured by gas chromatography. When methyl acetate and methanol by-products were removed, 1,1,1-trifluoro-2-hydroxy-2- (trifluoromethyl) pentane-4- The abundance of ON was 98.6%.
[Example 3]
Production of 1,1-bis (trifluoromethyl) -1-hydroxybutan-3-one
(1) Reaction of hexafluoroacetone and 2-trimethylsiloxypropene 10.0 g (0.077 mol) of 2-trimethylsiloxypropene in a glass-made 100 mL reactor equipped with a stirrer, pressure gauge, thermometer and gas introduction tube While stirring, 14.5 g (0.087 mol) of hexafluoroacetone was introduced over 0.5 hours in the range of 0 ° C. to 20 ° C. After the introduction of hexafluoroacetone, the reaction was terminated by stirring at 10 to 20 ° C. for 0.5 hour. At the end of the reaction, the reaction solution was sampled and the composition was measured by GC / MS. As a result, a compound considered to have hexafluoroacetone added to three types of 2-trimethylsiloxypropene was observed. Although each compound could not be identified, 1,1,1-trifluoro-2-trifluoromethyl-4-trimethylsilanyloxypent-4-en-2-ol, trimethyl- (2-methyl -4,4-bistrifluoromethyloxeta-2-nyloxy) silane, 1,1,1-trifluoro-2-trifluoromethyl-4-trimethylsiloxen-3-en-2-ol it is conceivable that.
(2) Hydrolysis of the reaction mixture of hexafluoroacetone and 2-trimethylsiloxypropene 0.5 g of 2N hydrochloric acid was added to 0.5 g of the reaction mixture obtained by the reaction of hexafluoroacetone and 2-trimethylsiloxypropene. Hydrolyzed for 5 hours at room temperature. The reaction solution was sampled and the composition was measured by gas chromatography. As a result, 1,1,1-trifluoro-2-hydroxy-2- (trifluoromethyl) was removed except for acetone, trimethylsilanol and hexamethylsiloxane. The abundance of pentan-4-one was 59.9%.
(3) Decomposition reaction of the reaction mixture of hexafluoroacetone and 2-trimethylsiloxypropene using a fluoride ion source 25% to 0.5 g of the reaction mixture obtained by the reaction of hexafluoroacetone and 2-trimethylsiloxypropene 0.5 g of potassium fluoride aqueous solution was added and decomposed at 50 ° C. for 3 hours. The reaction solution was sampled and the composition was measured by gas chromatography. As a result, 1,1-bis (trifluoromethyl) -1-hydroxybutane was removed from acetone, fluorotrimethylsilane, trimethylsilanol and hexamethylsiloxane. The abundance of 3-one was 88.3%.
(4) Hydrolysis reaction of the reaction mixture of hexafluoroacetone and 2-trimethylsiloxypropene 0.5 g of water was added to 0.5 g of the reaction mixture obtained by the reaction of hexafluoroacetone and 2-trimethylsiloxypropene. Hydrolyzed at 50 ° C. for hours. The reaction solution was sampled and the composition was measured by gas chromatography. When acetone, trimethylsilanol and hexamethylsiloxane were by-produced, 1,1-bis (trifluoromethyl) -1-hydroxybutan-3-one was removed. The abundance was 45.4%.
[Example 4]
Preparation of 4,4,4-trifluoro-3-hydroxy-3-trifluoromethylbutyraldehyde
(1) Reaction of hexafluoroacetone and n -butyl vinyl ether 10.0 g (0.10) of n-butyl vinyl ether was added to a 100 mL glass reactor equipped with a stirrer, pressure gauge, thermometer and gas introduction tube. 15.5 g (0.093 mol) of hexafluoroacetone was introduced in the range of 0 ° C. to 20 ° C. with stirring over 1.0 hour. After the introduction of hexafluoroacetone, the reaction was completed by stirring at 20-30 ° C. for 2 hours. At the end of the reaction, the reaction solution was sampled and the composition was measured by gas chromatography. When the excess n-butyl vinyl ether was removed, the amount of 4-butoxy-2,2-bistrifluoromethyloxetane was 93.0%. there were.

Spectral data of 4-butoxy-2,2-bistrifluoromethyloxetane: ¹ H-NMR (solvent: CDCl ₃ , reference material: TMS); δ 5.56 (t, J = 5.5 Hz, 1H), 3.80 To 3.69 (m, 1H), 3.57 to 3.49 (m, 1H), 3.07 to 3.00 (m, 1H), 2.88 to 2.81 (m, 1H), 1 .64 to 1.56 (m, 2H), 1.44 to 1.31 (m, 2H), 0.92 (t, J = 8.1 Hz, 3H), ¹⁹ F-NMR (solvent: CDCl ₃ , Reference substance: CCl ₃ F); δ-79.4 to -79.5 (m, 6F)
(2) Hydrolysis of the reaction mixture of hexafluoroacetone and n-butyl vinyl ether 24.5 g of 2N hydrochloric acid and 25.0 g of diisopropyl ether were added to 24.5 g of the reaction mixture obtained by the reaction of hexafluoroacetone and n-butyl vinyl ether. Was added and hydrolyzed at room temperature for 6 hours. The reaction solution was sampled and the composition was measured by gas chromatography. As a result, 4,4,4-trifluoro-3-hydroxy-3-trifluoromethylbutyraldehyde was obtained except for diisopropyl ether used as a solvent and butanol as a by-product. The abundance of was 47%.

Spectral data of 4,4,4-trifluoro-3-hydroxy-3-trifluoromethylbutyraldehyde: ¹ H-NMR (solvent: CDCl ₃ , reference material: TMS); δ 9.85 (s, 1H), 5 .93 (bs, 1H), ¹⁹ F-NMR (solvent: CDCl ₃ , reference material: CCl ₃ F); δ-78.5 (s, 6F), GC / MS (M ⁺ = 210)
[Example 5]
Preparation of 1,1-bis (trifluoromethyl) butane-1,3-diol Sodium borohydride (1.75 g, 0.046 mol) was added to a mixture of diisopropyl ether (48.5 g) and IPA (9.8 g). ) 1,1-bis (trifluoromethyl) -1-hydroxybutan-3-one (19.5 g, 0.087 mol) was dissolved in diisopropyl ether (10.0 g) and added dropwise in about 10 minutes. The reaction was monitored by GC, and quenched with 2N hydrochloric acid (70.4 g) 5 hours after the starting material was exhausted.

  Next, the organic layer and the aqueous layer were separated, and diisopropyl ether (24.0 g) was added to the aqueous layer for re-extraction. The re-extracted diisopropyl ether solution and the previously separated organic layer were mixed, dried over magnesium sulfate (4.5 g), filtered and the solvent was distilled off. As a result, 22.4 g of a crude product was obtained.

The crude product obtained here was distilled under reduced pressure (20 mmHg) to give a ¹⁹ F-NMR purity of 94% (99 GC% for GC) and 15.4 g (yield: 78%) of 1,1-bis (Trifluoromethyl) butane-1,3-diol was obtained.
¹ H-NMR (solvent: CDCl ₃ , reference material: TMS); δ 6.62 (s, 1H), 4.48-4.42 (m, 1H), 2.79 (d, J = 3.9 Hz) , 1H), 2.06 to 2.03 (m, 2H), 1.31 (d, J = 6.0 Hz, 3H)
¹⁹ F-NMR (solvent: CDCl ₃ , reference material: CCl ₃ F); δ-76.2 (q, J = 9.9 Hz, 3F), −80.0 (q, J = 10.2 Hz, 3F)
[Example 6]
Production of 1,1-bistrifluoromethylbutane-1,3-diol Sodium borohydride (25.8 g, 0.68 mol) was added to water (750 g). 1,1-Bis (trifluoromethyl) -1-hydroxybutan-3-one (250 g, 1.12 mol) was added dropwise in about 30 minutes. The reaction was monitored by GC, and quenched with concentrated hydrochloric acid (165.4 g) 3 hours after the raw material was exhausted.

Next, the organic layer and the aqueous layer were separated, and diisopropyl ether (85 g) was added to the aqueous layer for re-extraction. The re-extracted diisopropyl ether solution and the previously separated organic layer were mixed and distilled under reduced pressure (20 mmHg) to obtain a purity of ¹⁹ F-NMR of 96% (99.9 GC% for GC), 191. 1,1-bistrifluoromethylbutane-1,3-diol was obtained in 1 g (yield: 75%).
[Example 7]
Production of 1,1-bistrifluoromethylbutane-1,3-diol 150 mL of diisopropyl ether, 1,1-bis (trifluoromethyl) -1 in a 1 L pressure-resistant reactor made of SUS316 equipped with a pressure gauge, a thermometer and a stirrer -300 g (1.34 mol) of hydroxybutan-3-one, 30.0 g of 5% Rh / C (50% water-containing product, manufactured by N.E. Chemcat) were added, the inside of the reactor was replaced with hydrogen, hydrogen The pressure was 1.2 MPa. It heated with the oil bath and the internal temperature was 110 degreeC. After 6 hours, the reaction was terminated by cooling to room temperature. The reaction solution was sampled and the composition was measured by gas chromatography. The amount of the desired 1,1-bistrifluoromethylbutane-1,3-diol was 95.1% excluding diisopropyl ether used as the solvent. Met. 5% Rh / C of the catalyst was filtered off, and this was distilled under reduced pressure to collect a fraction of 58 ° C. to 60 ° C./0.65 kPa (1.0 kPa = 7.5 Torr). 272 g of 1-bistrifluoromethylbutane-1,3-diol was obtained with a purity of 99.0%. The yield was 89.0%.
[Example 8]
Production of 1,1-bistrifluoromethylbutane-1,3-diol 150 mL of diisopropyl ether, 1,1-bis (trifluoromethyl) -1 in a 1 L pressure-resistant reactor made of SUS316 equipped with a pressure gauge, a thermometer and a stirrer -300 g (1.34 mol) of hydroxybutan-3-one, 30.0 g of 5% Ru / C (50% water-containing product, manufactured by N.E. Chemcat) were added, the inside of the reactor was replaced with hydrogen, hydrogen The pressure was 0.6 MPa. It heated with the oil bath and the internal temperature was 80 degreeC. After 9 hours, the reaction was terminated by cooling to room temperature. The reaction solution was sampled and the composition was measured by gas chromatography. The amount of the desired 1,1-bistrifluoromethylbutane-1,3-diol, excluding diisopropyl ether used as a solvent, was 98.8%. Met. 5% Ru / C of the catalyst was filtered off, and this was distilled under reduced pressure to collect a fraction of 58 ° C. to 60 ° C./0.65 kPa (1.0 kPa = 7.5 Torr). 264 g of 1-bistrifluoromethylbutane-1,3-diol was obtained with a purity of 99.2%. The yield was 86.3%.
[Example 9]
Preparation of 4,4,4-trifluoro-3-hydroxy-1-methyl-3- (trifluoromethyl) butyl 2-methyl acrylate Tetrafluoroethylene in a 1000 mL four-necked flask equipped with a thermometer and a reflux condenser Resin-coated stir bar and 1,1-bis (trifluoromethyl) butane-1,3-diol 191.1 g (0.85 mol), toluene 613 g, 2,6-dimethylpyridine 111.5 g (0. 91 mol), 131.1 g (1.25 mol) of methacrylic acid chloride and 0.5 g of hydroquinone were added, and the mixture was heated to an internal temperature of 90 to 100 ° C. with an oil bath while stirring with a stirrer. After 6 hours, the composition was measured by gas chromatography. The desired 4,4,4-trifluoro-3-hydroxy-1-methyl-3- (trifluoromethyl) butyl 2-methyl acrylate was found to be 87.5. %, The raw material 1,1-bis (trifluoromethyl) butane-1,3-diol was 2.9%, and the others were 9.6%.

  After cooling the reaction solution, 2,6-dimethylpyridine hydrochloride was removed by filtration, and the filtrate was washed with 100 g of 10% aqueous hydrochloric acid. The aqueous layer was extracted with 150 g of diisopropyl ether, and this was combined with the organic layer and washed twice with 150 g of 10% brine. To the obtained organic layer, 0.7 g of hydroquinone as a polymerization inhibitor was added and the solvent was distilled off. Then, distillation under reduced pressure (10 Torr = 1.33 kPa) was performed, and a fraction at 85 to 88 ° C. was collected. 0.0 g of 4,4,4-trifluoro-3-hydroxy-1-methyl-3- (trifluoromethyl) butyl 2-methyl acrylate was obtained.

When the composition was examined by gas chromatography, it was found that the desired product 4,4,4-trifluoro-3-hydroxy-1-methyl-3- (trifluoromethyl) butyl 2-methylacrylate was 98.0%. The 1,1-bis (trifluoromethyl) butane-1,3-diol was 0.8% and the others were 1.0%. The yield was 60.9%.
¹ H-NMR (solvent: CDCl ₃ , reference material: TMS); δ 6.17-6.15 (m, 1H), 5.96 (s, 1H), 5.68-5.65 (m, 1H ), 5.20-5.12 (m, 1H), 2.30-2.28 (m, 2H), 1.95-1.92 (m, 3H), 1.43 (d, J = 6 3 Hz, 3H), ¹⁹ F-NMR (solvent: CDCl ₃ , reference substance CCl ₃ F); δ-77.0 (q, J = 9.9 Hz, 3F), −79.4 (q, J = 9 .6Hz, 3F).
[Example 10]
4,4,4-trifluoro-3-hydroxy-1-methyl-3- (trifluoromethyl) butyl 2-methylacrylate 1000 mL four-neck equipped with thermometer, moisture meter and reflux condenser A stirrer coated with tetrafluoroethylene resin on a flask and 191.1 g (0.85 mol) of 1,1-bis (trifluoromethyl) butane-1,3-diol, 87.2 g (1.01) of methacrylic acid Mol), 160.8 g (0.85 mol) of p-toluenesulfonic acid, 613 g of toluene and 0.5 g of hydroquinone were added, and the mixture was heated to reflux at 120 ° C. with an oil bath while stirring with a stirrer. After 7 hours, about 30 mL of water produced by the reaction was separated in the moisture meter. The reaction solution was measured by gas chromatography. As a result, the target 4,4,4-trifluoro-3-hydroxy-1-methyl-3- (trifluoromethyl) butyl methacrylate was 91.0%, 1-bis (trifluoromethyl) butane-1,3-diol was 4.0%, and the others were 5.0%.

  After washing the reaction solution twice with 516 g of water, 0.78 g of hydroquinone as a polymerization inhibitor was added to the organic layer obtained by liquid separation and the solvent was distilled off, followed by distillation under reduced pressure (8 Torr = 1.07 kPa). And a fraction of 80-82 ° C. was collected and 127.6 g of 4,4,4-trifluoro-3-hydroxy-1-methyl-3- (trifluoromethyl) butyl 2-methyl acrylate, 1, 80. A mixture of 1-bis (trifluoromethyl) butane-1,3-diol and 4,4,4-trifluoro-3-hydroxy-1-methyl-3- (trifluoromethyl) butyl 2-methyl acrylate. 9 g was obtained.

The composition was examined by gas chromatography. As a result, 98.6% of 4,4,4-trifluoro-3-hydroxy-1-methyl-3- (trifluoromethyl) butyl 2-methylacrylate, which was the object, was a raw material. Of 1,1-bis (trifluoromethyl) butane-1,3-diol was 1.4%. The yield was 50.5%.
[Example 11]
4,4,4-trifluoro-3-hydroxy-1-methyl-3- (trifluoromethyl) butyl 2-methylacrylate 1000 mL four-neck equipped with thermometer, moisture meter and reflux condenser A stirrer coated with tetrafluoroethylene resin on a flask and 191.1 g (0.85 mol) of 1,1-bis (trifluoromethyl) butane-1,3-diol, 87.2 g (1.01) of methacrylic acid Mol), 15.5 g (0.16 mol) of concentrated sulfuric acid, 613 g of cyclohexane and 0.5 g of hydroquinone were added, and the mixture was heated to reflux at 100 ° C. with an oil bath while stirring with a stirrer. After 9 hours, about 20 mL of water produced by the reaction was separated in the moisture meter. When the reaction solution was measured by gas chromatography, the target 4,4,4-trifluoro-3-hydroxy-1-methyl-3- (trifluoromethyl) butyl methacrylate was 88.6%, and the others were 11. It was 4%.

  After washing the reaction solution with 191 g of water three times, 0.8 g of hydroquinone as a polymerization inhibitor was added to the organic layer obtained by liquid separation and the solvent was distilled off, followed by vacuum distillation (8 Torr = 1.07 kPa). And a fraction of 80-82 ° C. was collected and 200.4 g of 4,4,4-trifluoro-3-hydroxy-1-methyl-3- (trifluoromethyl) butyl 2-methyl acrylate was obtained. It was.

The composition was examined by gas chromatography. As a result, 98.9% of 4,4,4-trifluoro-3-hydroxy-1-methyl-3- (trifluoromethyl) butyl 2-methyl acrylate, which was the object, was a raw material. Of 1,1-bis (trifluoromethyl) butane-1,3-diol was 1.1%. The yield was 79.7%.
[Example 12]
Preparation of 4,4,4-trifluoro-3- (trifluoromethyl) -3-hydroxy-2-methyl-1-phenylbutan-1-one

  To a SUS autoclave (50 mL) equipped with a magnetic stirrer, thermometer and gas inlet tube, N- (benzenesulfonyl)-(Z) -1-phenylprop-1-en-1-amine (Angewandte Chemie International Edition, 2007) , 46, 3047-3050) (0.5 g (1.83 mmol)) and chloroform (3 ml) were added, and the mixture was cooled with dry ice-acetone and decompressed.

  Next, 5 g (30 mmol) of hexafluoroacetone was introduced in the range of 0 ° C. to 20 ° C. with stirring. After the introduction of hexafluoroacetone, the mixture was stirred at room temperature for 3 days. 20 g (40 mmol) of 2N hydrochloric acid was added to the reaction solution and hydrolyzed at room temperature for 2 hours. When the lower layer (chloroform layer) TLC (hexane-ethyl acetate = 4: 1 (v / v)) of the reaction solution was measured, the raw material enesulfonamide was lost.

The reaction solution was extracted with chloroform and washed with saturated brine. The organic layer was dried over magnesium sulfate, and the filtrate after filtration was concentrated under reduced pressure and purified by silica gel column chromatography (hexane-ethyl acetate = 4: 1 (v / v)) to obtain the desired 4,4,4- Trifluoro-3- (trifluoromethyl) -3-hydroxy-2-methyl-1-phenylbutan-1-one was obtained. Yield 0.37g (Yield 67.4%)
¹ H-NMR (solvent: CDCl ₃ , reference material: TMS); δ7.2-7.8 (5H, m, Ph), 3.43 (1H, q, J = 7.0 Hz, CH), 1.47 (3H, d, J = 7.0Hz, CH ₃ );
¹⁹ F-NMR (solvent: CDCl ₃ , reference material: CCl ₃ F); δ-74.8 (6F, s, 2 × CF ₃ )

Claims (14)

Fluorine-containing keto alcohol represented by the general formula [3]

(In the formula, R and R ¹ are the same or different and are a hydrogen atom, an alkyl group having 1 to 7 carbon atoms which may have a substituent, or an aryl group which may have a substituent. Alternatively, R and R ¹ may be connected to form a ring, and further may have a substituent on the ring.)
A manufacturing method of
Hexafluoroacetone represented by the formula [1]

And an enol ether compound represented by the general formula [2]

(Wherein R ² is an optionally substituted alkyl group having 1 to 7 carbon atoms, an optionally substituted alkanoyl group having 1 to 7 carbon atoms, and an optionally substituted carbon. An alkoxycarbonyl group of 1 to 7; a benzyloxycarbonyl group which may have a substituent on the benzene ring; or a benzyl group which may have a substituent on the benzene ring, and R and R ² are connected to each other. A ring may be formed, and R and R ¹ are the same as above.)
And a solvolysis in the presence of an acid or a base, and then a method for producing a fluorinated keto alcohol. The production method according to claim ¹ , wherein R is a hydrogen atom, and R ¹ is a methyl group. The production method according to claim 1, wherein R and R ¹ are hydrogen atoms. The production method according to claim 1, wherein R ² is a methyl group or an acetyl group. Fluorine-containing 1,3-diol compound represented by the general formula [4]

( Wherein R and R ¹ are the same or different and are a hydrogen atom, an alkyl group having 1 to 7 carbon atoms which may have a substituent, or an aryl group which may have a substituent. Alternatively, R and R ¹ may be connected to form a ring, and further may have a substituent on the ring.
A manufacturing method of
(I) Hexafluoroacetone represented by the formula [1]

And an enol ether compound represented by the general formula [2]

(Wherein R ² is an optionally substituted alkyl group having 1 to 7 carbon atoms, an optionally substituted alkanoyl group having 1 to 7 carbon atoms, and an optionally substituted carbon. An alkoxycarbonyl group of 1 to 7; a benzyloxycarbonyl group which may have a substituent on the benzene ring; or a benzyl group which may have a substituent on the benzene ring, and R and R ² are connected to each other. A ring may be formed, and R and R ¹ are the same as above.)
And then solvolysis in the presence of an acid or base to give a fluorinated keto alcohol represented by the general formula [3]

(In the formula, R and R ¹ are the same as above.)
A process of manufacturing
(II) a step of reducing the fluorine-containing keto alcohol represented by the general formula [3] ,
The manufacturing method characterized by including. Fluorine-containing ester compound represented by the general formula [6]

(In the formula, R ³ is a hydrogen atom, C _m H _{2m + 1} , or C _n F _{2n + 1} , and m and n are integers of 1 to 4. R and R ¹ are the same or different and each represents a hydrogen atom or a substituent. An optionally substituted alkyl group having 1 to 7 carbon atoms, or an aryl group optionally having a substituent, and two R or R and R ¹ may be connected to form a ring; You may have a substituent on the top.
A manufacturing method of
(I) Hexafluoroacetone represented by the formula [1]

And an enol ether compound represented by the general formula [2]

(Wherein R ² is an optionally substituted alkyl group having 1 to 7 carbon atoms, an optionally substituted alkanoyl group having 1 to 7 carbon atoms, and an optionally substituted carbon. An alkoxycarbonyl group of 1 to 7; a benzyloxycarbonyl group which may have a substituent on the benzene ring; or a benzyl group which may have a substituent on the benzene ring, and R and R ² are connected to each other. A ring may be formed, and R and R ¹ are the same as above.)
And then solvolysis in the presence of an acid or base to give a fluorinated keto alcohol represented by the general formula [3]

(In the formula, R and R ¹ are the same as above.)
Manufacturing process,
(II) A fluorine-containing 1,3-diol compound represented by the general formula [4] by reducing the fluorine-containing keto alcohol represented by the general formula [3].

(In the formula, R and R ¹ are the same as above.)
A process of manufacturing

(III) A fluorine-containing 1,3-diol compound represented by the general formula [4] is converted to an acrylic acid derivative represented by the general formula [5].

(In the formula, X is F, Cl, hydroxyl group, or general formula [5a]:

And R ³ is the same as defined above. And the step of reacting with
The manufacturing method characterized by including. Fluorine-containing keto alcohol represented by the general formula [3]

(In the formula, R and R ¹ are the same or different and are a hydrogen atom, an alkyl group having 1 to 7 carbon atoms which may have a substituent, or an aryl group which may have a substituent. Alternatively, R and R ¹ may be connected to form a ring, and further may have a substituent on the ring.)
A manufacturing method of
Hexafluoroacetone represented by the formula [1]

And an enesulfonamide compound represented by the general formula [10]

(In the formula, R ⁴ is an optionally substituted alkyl group having 1 to 7 carbon atoms or an optionally substituted aryl group, and R ⁵ has a hydrogen atom and a substituent. An alkyl group having 1 to 7 carbon atoms or an aryl group which may have a substituent, and R and R ¹ are the same as above.)
And a solvolysis in the presence of an acid or a base, and then a method for producing a fluorinated keto alcohol. The production method according to claim 7, wherein one of R is a hydrogen atom, the other is a methyl group, and R ¹ is an aryl group. The production method according to claim 7, wherein R and R ¹ are methyl groups. The production method according to claim 7, wherein R ⁵ is a hydrogen atom. The manufacturing method according to claim 7, wherein R ⁴ is an aryl group. Fluorine-containing 1,3-diol compound represented by the general formula [4]

(In the formula, R and R ¹ are the same or different and are a hydrogen atom, an alkyl group having 1 to 7 carbon atoms which may have a substituent, or an aryl group which may have a substituent. Alternatively, R and R ¹ may be connected to form a ring, and further may have a substituent on the ring.)
A manufacturing method of
(I) Hexafluoroacetone represented by the formula [1]

And an enesulfonamide compound represented by the general formula [10]

(In the formula, R ⁴ is an optionally substituted alkyl group having 1 to 7 carbon atoms or an optionally substituted aryl group, and R ⁵ has a hydrogen atom and a substituent. An alkyl group having 1 to 7 carbon atoms or an aryl group which may have a substituent, and R and R ¹ are the same as above.)
And then solvolysis in the presence of an acid or base to give a fluorinated keto alcohol represented by the general formula [3]

(In the formula, R and R ¹ are the same as above.)
And (II) a step of reducing the fluorine-containing ketoalcohol represented by the general formula [3]. Fluorine-containing ester compound represented by the general formula [6]

Wherein R ³ is a hydrogen atom, C _m H _{2m + 1} , or C _n F _{2n + 1} , and m and n are 1 to
It is an integer of 4. R and R ¹ are the same or different and each represents a hydrogen atom, an alkyl group having 1 to 7 carbon atoms which may have a substituent, or an aryl group which may have a substituent. ¹ may be connected to form a ring, and may further have a substituent on the ring. )
A manufacturing method of
(I) Hexafluoroacetone represented by the formula [1]

And an enesulfonamide compound represented by the general formula [10]

(In the formula, R ⁴ is an optionally substituted alkyl group having 1 to 7 carbon atoms or an optionally substituted aryl group, and R ⁵ has a hydrogen atom and a substituent. An alkyl group having 1 to 7 carbon atoms or an aryl group which may have a substituent, and R and R ¹ are the same as above.)
And then solvolysis in the presence of an acid or base to give a fluorinated keto alcohol represented by the general formula [3]

(In the formula, R and R ¹ are the same as above.)
Manufacturing process,
(II) A fluorine-containing 1,3-diol compound represented by the general formula [4] by reducing the fluorine-containing keto alcohol represented by the general formula [3].

(In the formula, R and R ¹ are the same as above.)
And (III) a fluorine-containing 1,3-diol compound represented by the general formula [4], an acrylic acid derivative represented by the general formula [5]

(In the formula, X is F, Cl, hydroxyl group, or general formula [5a]:

And R ³ is the same as defined above. )
The manufacturing method characterized by making it react with. The method for producing a fluorinated keto alcohol according to any one of claims 1 to 4, wherein the hexafluoroacetone and the enol ether compound are reacted without using a solvent.