JP6677255B2 - Method for producing halogenated acrylate derivative - Google Patents

Description

  The present invention relates to a novel method for producing a halogenated acrylate derivative.

Α-Fluoroacrylates representing halogenated acrylate derivatives are useful as synthetic intermediates for drugs, polymers, optical materials, paints, semiconductor resist materials and the like, or as monomers of functional polymers.
As a method for producing an α-fluoroacrylic acid ester, 3-hydroxy-2-fluoropropionic acid ester is converted to 3-chloro-2-fluoropropionic acid ester using thionyl chloride, and hydrogen chloride is eliminated therefrom to remove 2-hydroxy-2-fluoropropionic acid ester. A method for producing a fluoroacrylate (Patent Document 1) is known.
Patent Document 2 discloses a method for producing an ethyl derivative of α-fluoroacrylic acid by deriving an ethylene derivative into a cyclopropane derivative using potassium t-butoxide and a large excess of chlorofluorocarbon, and decomposing the derivative.
As a method for synthesizing an ethylene derivative used in Patent Document 2, potassium 1,2-butoxide is allowed to act on 1,1-diethoxy-2-bromoethane, and hydrobromic acid is eliminated to form 1,1-diethoxyethene. A method for obtaining the same is known (Non-Patent Document 1).

Patent No. 5628305 European Patent Publication No. 0127920

Organic Synthesis, Coll.Vol.3, p.506 (1955); Vol.23, p.45 (1943)

The method of Patent Document 1 is disadvantageous in industrial economics in that it requires the use of thionyl chloride and generates highly corrosive hydrogen chloride. Further, it is industrially disadvantageous in that F ₂ (fluorine gas), which is difficult to handle, is used for preparing 3-hydroxy-2-fluoropropionate as a raw material.
The method of Patent Document 2 is disadvantageous in industrial economy because expensive potassium t-butoxide and a large excess of chlorofluorocarbon are used. Also, the method for producing an ethylene derivative (1,1-diethoxyethene or the like) as a raw material thereof is limited. For example, the method of Non-Patent Document 1 cannot use industrially economical production of an ethylene derivative because expensive potassium t-butoxide needs to be used and hydrogen bromide having high corrosiveness is generated.

  The present inventors have achieved a high conversion, a high selectivity, and a high yield, and have found a novel method for producing a halogenated acrylate derivative which is industrially and economically excellent, and an intermediate useful for the method. .

That is, the present invention includes the following inventions.
[1]
A compound represented by the following formula (1) and having a boiling point of 500 ° C. or lower is subjected to a de-R ³ OH reaction in the gas phase in the presence of a solid catalyst, A method for producing an ethene derivative represented by 2).

(Where
R ¹ and R ² each independently represent a hydrogen atom or a monovalent group that requires a carbon atom, or R ¹ and R ² together form a ring together with the carbon atom to which they are attached; May be
R ³ represents a monovalent group from which a group R ³ O can be eliminated by a de-R ³ OH reaction;
R ⁴ and R ⁵ each independently represent a hydrogen atom or a monovalent group essentially having a carbon atom. )

(In the formula, R ¹ , R ² , R ⁴ and R ⁵ are as described above.)
[2]
R ¹ and R ² are both hydrogen atoms, and R ³ , R ⁴ and R ⁵ each independently represent an alkyl group, a cycloalkyl group, an aryl group, an alkyl group having a substituent, The production method according to [1], which is a cycloalkyl group having the substituent or an aryl group having a substituent.
[3]
The production method according to [1] or [2], wherein the reaction temperature is 100 to 500 ° C.
[4]
The production method according to any one of [1] to [3], wherein the reaction is performed by flowing the vaporized compound represented by the formula (1) together with a carrier gas through the solid catalyst layer.
[5]
The production method according to [4], wherein the amount of the carrier gas used is more than 0 to 20 mol per 1 mol of the compound represented by the formula (1).
[6]
The production method according to any one of [1] to [5], wherein the solid catalyst is at least one solid catalyst selected from a metal catalyst and a metal oxide catalyst.
[7]
The production method according to any one of [1] to [5], wherein the solid catalyst is a metal oxide catalyst.
[8]
The production method according to any one of [1] to [5], wherein the solid catalyst is a catalyst containing at least one selected from the group consisting of zirconia, alumina, zeolite and zinc oxide.
[9]
The production method according to any one of [1] to [5], wherein the solid catalyst is a catalyst containing zinc oxide.
[10]
The solid catalyst is [1] to at least one solid catalyst selected from natural minerals, molecular sieves, carbon black, metal chlorides, metal fluorides, metal sulfates, metal sulfides, and metal phosphates. The production method according to any one of [5].

[11]
An ethene derivative represented by the formula (2) is obtained by the production method according to any one of [1] to [10], and the ethene derivative is converted into the following formula in the presence of a basic compound and a phase transfer catalyst. A method for producing a cyclopropane derivative represented by the following formula (4), characterized by reacting with a compound represented by the following (3).

(In the formula, X, Y, and Z each independently represent a halogen atom.)

(In the formula, R ¹ , R ² , R ⁴ and R ⁵ are as defined in [1], and X and Y are as defined above.)
[12]
The production method according to [11], wherein the basic compound is at least one selected from the group consisting of an alkali metal hydroxide, an alkali metal alkoxide, an alkali metal hydride and an alkyl lithium.
[13]
The production method according to [11] or [12], wherein the phase transfer catalyst is a quaternary ammonium salt.
[14]
The production method according to any one of [11] to [13], wherein X is a fluorine atom and Y is a chlorine atom or a fluorine atom.
[15]
The production method according to any one of [11] to [14], wherein the ethene derivative represented by the formula (2) is 1,1-dimethoxyethene.
[16]
The compound according to any one of [11] to [15], wherein the amount of the compound represented by the formula (3) is 1 to 5 mol per 1 mol of the ethene derivative represented by the formula (2). The manufacturing method as described.
[17]
The production method according to any one of [11] to [16], wherein the amount of the basic compound used is 1 to 10 mol per 1 mol of the compound represented by the formula (3).
[18]
The production method according to any one of [11] to [17], wherein the amount of the phase transfer catalyst used is 0.001 to 5% by mass relative to the mass of the ethene derivative represented by the formula (2). .

[19]
By obtaining the cyclopropane derivative represented by the formula (4) by the production method according to any one of [11] to [18], and heating the cyclopropane derivative in a liquid phase or a gas phase, A method for producing a halogenated acrylate derivative represented by the following formula (5), wherein the reaction is performed by removing R ⁴ Y.

(In the formula, R ¹ , R ² , R ⁴ and R ⁵ are as defined in [1], and X and Y are as defined in [11].)
[20]
The production method according to [19], wherein the temperature of the R ⁴ Y reaction is 80 to 400 ° C.

[21]
According to the production method described in any one of [11] to [18], a cyclopropane derivative represented by the formula (4) and a propene derivative represented by the following formula (8) are obtained. A method for producing a halogenated acrylate derivative represented by the following formula (5), comprising separating a propane derivative and the propene derivative, and then decomposing the separated propene derivative under acidic conditions. .

(In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are as defined in [1], and X is as defined in [11].)

(In the formula, R ¹ , R ² , R ⁵ and X are as described above.)
[22]
The production method according to any one of [19] to [21], wherein the production is performed in the presence of a polymerization inhibitor when producing the halogenated acrylate derivative represented by the formula (5).
[23]
The production method according to [22], wherein the amount of the polymerization inhibitor added is 10 ppm or more based on the halogenated acrylate derivative represented by the formula (5).

[24]
A compound represented by the following formula (6).

(In the formula, Me represents a methyl group, and Y ¹ represents a chlorine atom or a fluorine atom.)
[25]
A compound represented by the following formula (7).

(In the formula, Me represents a methyl group.)

  ADVANTAGE OF THE INVENTION According to this invention, a halogenated acrylate derivative can be manufactured with a high conversion, a high selectivity, and a high yield from a cheap and easily available raw material through a new and useful intermediate.

  Terms in this specification are defined as follows.

“Alkyl group” means a linear or branched monovalent saturated hydrocarbon group. The alkyl group has preferably 1 to 20 carbon atoms, more preferably 1 to 15 carbon atoms, further preferably 1 to 12 carbon atoms, and particularly preferably 1 to 6 carbon atoms. Examples of the alkyl group include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert -Pentyl, 1-ethylpropyl, n-hexyl, isohexyl, neohexyl and the like.
The “alkyl group” may be a monovalent saturated hydrocarbon group partially having a ring structure. For example, a cycloalkylalkyl group is exemplified.

  “Cycloalkyl group” means a cyclic monovalent saturated hydrocarbon group. The carbon number of the cycloalkyl group is preferably 3 to 20, more preferably 3 to 15, still more preferably 3 to 12, and particularly preferably 3 to 6. The number of ring structures in the cycloalkyl group may be one, or two or more. In the case of two or more, it has a condensed polycyclic structure, a bridged ring structure or a spiro ring structure. Examples of the cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and the like.

  The “alkenyl group” means a group in which an arbitrary carbon-carbon single bond of the above-mentioned alkyl group (excluding a methyl group) is replaced with a carbon-carbon double bond. The carbon number of the alkenyl group is preferably 2 to 20, more preferably 2 to 15, more preferably 2 to 12, and particularly preferably 2 to 6. Examples of the alkenyl group include ethenyl, 1-propenyl, 2-propenyl, 1-methyl-1-ethenyl, 1-butenyl, 2-butenyl, 3-butenyl, and 2-methyl-1-propenyl. Group, 2-methyl-2-propenyl group, 1-ethylethenyl group, 1-methyl-1-propenyl group, 1-methyl-2-propenyl group, 1-pentenyl group, 1-hexenyl group and the like.

  The “cycloalkenyl group” means a group in which an arbitrary carbon-carbon single bond of the cycloalkyl group is replaced with a carbon-carbon double bond. The number of ring structures in the cycloalkenyl group may be one, or two or more. In the case of two or more, it has a condensed polycyclic structure, a bridged ring structure or a spiro ring structure. The carbon number of the cycloalkenyl group is preferably 3 to 20, more preferably 3 to 15, still more preferably 3 to 12, and particularly preferably 3 to 6. Examples of the cycloalkenyl group include a 1-cyclopentenyl group, a 2-cyclopentenyl group, a 3-cyclopentenyl group, a 1-methyl-2-cyclopentenyl group, a 1-cyclohexenyl group, a 2-cyclohexenyl group, and a 3-cyclopentenyl group. And cyclohexenyl group.

  The term “alkynyl group” means that any carbon-carbon single bond of the alkyl group (excluding the methyl group) or any carbon-carbon single bond or carbon-carbon double bond of the alkenyl group is a carbon-carbon bond. It means a group replaced with a carbon triple bond. The alkynyl group preferably has 2 to 20 carbon atoms, more preferably has 2 to 15 carbon atoms, further preferably has 2 to 12 carbon atoms, and particularly preferably has 2 to 6 carbon atoms. Examples of the alkynyl group include an ethynyl group, a 1-propynyl group, a 2-propynyl group, a 1-butynyl group, a 2-butynyl group, a 3-butynyl group, a 1-methyl-2-propynyl group, a 1-pentynyl group, and a 1-pentynyl group. And a hexynyl group.

  “Alkoxy group” means a group in which the alkyl group is bonded to an etheric oxygen atom (—O—). The structure of the alkoxy group is preferably linear or branched. The carbon number of the alkoxy group is preferably 1 to 20, more preferably 1 to 15, further preferably 1 to 12, and particularly preferably 1 to 6. Examples of the alkoxy group include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, an n-pentyloxy group, and an n-hexyloxy group And the like.

  “Aryl group” means a monocyclic or bicyclic or higher aromatic hydrocarbon group. The carbon number of the aryl group is preferably 6 to 22, more preferably 6 to 18, more preferably 6 to 14, and particularly preferably 6 to 10. Examples of the aryl group include a phenyl group, an o-, p- or m-tolyl group, a naphthyl group, a phenanthrenyl group, an anthracenyl group, a fluorenyl group and the like.

  “Heteroaryl group” means an aromatic group having one or more heteroatoms. As the hetero atom, an oxygen atom, a sulfur atom, and a nitrogen atom are preferable. The carbon number of the heteroaryl group is preferably 3 to 21, more preferably 3 to 17, still more preferably 3 to 13, and particularly preferably 3 to 9. Examples of the heteroaryl group include a pyridyl group, a pyrimidinyl group, a pyridazinyl group, a pyrazinyl group, a thienyl group, a furyl group, a pyrrolyl group, a pyrazolyl group, a triazolyl group, an imidazolyl group, a thiazolyl group, an oxazolyl group, an indolyl group, and a quinolyl group. No.

  “Aryloxy group” means a group in which the aryl group is bonded to an etheric oxygen atom (—O—). The carbon number of the aryloxy group is preferably from 7 to 23, particularly preferably from 7 to 19, more preferably from 7 to 15, and even more preferably from 7 to 11. Examples of the aryloxy group include a phenoxy group.

  “Alkylthio group” means a group in which the alkyl group is bonded to —S—. The alkylthio group preferably has 1 to 20 carbon atoms, more preferably has 1 to 15 carbon atoms, further preferably has 1 to 12 carbon atoms, and particularly preferably has 1 to 6 carbon atoms. Examples of the alkylthio group include methanethio, ethanethio, n-propanethio, isopropanethio, n-butanethio, isobutanethio, s-butanethio, t-butanethio, n-pentanethio, and n-hexanethio. And the like.

“Monoalkylamino group” means a group in which one of the hydrogen atoms of an amino group (—NH ₂ ) is replaced with the above-mentioned alkyl group. “Dialkylamino group” means a group in which two hydrogen atoms of an amino group have been replaced with the above-mentioned alkyl group. The carbon number of the monoalkylamino group is preferably 1 to 20, more preferably 1 to 15, further preferably 1 to 12, and particularly preferably 1 to 8. The dialkylamino group preferably has 2 to 20 carbon atoms, more preferably has 2 to 15 carbon atoms, further preferably has 2 to 12 carbon atoms, and particularly preferably has 2 to 8 carbon atoms. Examples of the monoalkylamino group include a methylamino group, an ethylamino group, an n-propylamino group, an isopropylamino group, a t-butylamino group, an n-pentylamino group, and an n-hexylamino group. Examples of the dialkylamino group include an N, N-dimethylamino group and an N, N-diethylamino group.

  “Monoarylamino group” means a group in which one of the hydrogen atoms of an amino group has been replaced with the above-mentioned aryl group. “Diarylamino group” means a group in which two hydrogen atoms of an amino group have been replaced with the above-mentioned aryl group. The monoarylamino group preferably has 6 to 22 carbon atoms, more preferably has 6 to 18 carbon atoms, still more preferably has 6 to 14 carbon atoms, and particularly preferably has 6 to 10 carbon atoms. The carbon number of the diarylamino group is preferably 12 to 24, more preferably 12 to 20, and still more preferably 12 to 16. Examples of the monoarylamino group include a phenylamino group. Examples of the diarylamino group include a diphenylamino group.

  “Heterocyclyl group” means a saturated or unsaturated monovalent heterocyclic group having one or more heteroatoms. As the hetero atom, an oxygen atom, a sulfur atom, and a nitrogen atom are preferable. The carbon number of the heterocyclyl group is preferably 3 to 21, more preferably 3 to 17, still more preferably 3 to 13, and particularly preferably 3 to 9. Examples of the heterocyclyl group include an azepanyl group, a pyrrolidinyl group, a piperidinyl group, a piperazinyl group, a morpholinyl group, and a tetrahydrofuryl group.

  “Halogen atom” means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, and a fluorine atom or a chlorine atom is preferable.

  The aforementioned “alkyl group”, “cycloalkyl group”, “alkenyl group”, “cycloalkenyl group”, “alkynyl group”, “alkoxy group”, “aryl group”, “heteroaryl group”, “aryloxy group”, “Alkylthio group”, “monoalkylamino group”, “dialkylamino group”, “monoarylamino group”, “diarylamino group” and “heterocyclyl group” may be substituted with a substituent. The group substituted with the substituent is referred to as a group having a substituent. Examples of the substituent include an alkyl group, an alkenyl group, an alkoxy group, an aryl group, an alkylthio group, a nitro group, an amino group, a carboxyl group, a cycloalkyl group, a hydroxyl group, a halogen atom, a cyano group, a phenyl group, and a heterocyclyl group. Can be

  Next, the production method of the present invention will be described in more detail. The concept of the manufacturing process of the present invention is represented by the following equation.

(In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , X, Y and Z are as described above.)

[Step (i)]
In the step (i), a compound represented by the formula (1) and having a boiling point of 500 ° C. or lower (hereinafter also referred to as “orthocarboxylic acid ester (1)”) is vapor-phased. In this step, a de-R ³ OH reaction is performed in the presence of a solid catalyst to produce an ethene derivative represented by the formula (2) (hereinafter, also simply referred to as “ethene derivative (2)”).

In the orthocarboxylic acid ester (1), R ¹ and R ² are each independently a hydrogen atom or a monovalent group essentially having a carbon atom.
R ¹ and R ² each independently represent a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, a cycloalkenyl group, an alkynyl group, an alkoxy group, an aryl group, a heteroaryl group, an aryloxy group, an alkylthio group, a monoalkylamino Group, dialkylamino group, monoarylamino group, diarylamino group, heterocyclyl group, alkyl group having a substituent, cycloalkyl group having a substituent, alkenyl group having a substituent, substitution Cycloalkenyl group having a group, alkynyl group having a substituent, alkoxy group having a substituent, aryl group having a substituent, heteroaryl group having a substituent , An aryloxy group having a substituent, an alkylthio group having a substituent, a monoalkyl having a substituent Amino group, a dialkylamino group having a substituent, mono-arylamino group having a substituent, a diarylamino group has a substituent, or a heterocyclyl group having a substituent, are preferred.
Also, R ¹ and R ² may together form a ring with the carbon atom to which they are attached. Examples of the ring formed by R ¹ and R ² together with the carbon atom to which they are bonded include a cycloalkane such as cyclohexane or a cycloalkane having a substituent such as cyclohexane substituted with an alkyl group.
R ¹ and R ² each independently represent a hydrogen atom, an alkyl group, a cycloalkyl group, an alkoxy group, an aryl group, an aryloxy group, a substituted alkyl group, or a substituted cycloalkyl group. And an alkoxy group having a substituent, an aryl group having a substituent, and an aryloxy group having a substituent are more preferable.
Each of R ¹ and R ² is particularly preferably a hydrogen atom.

R ³ is a monovalent group from which a group R ³ O can be eliminated by a de-R ³ OH reaction. R ³ represents an alkyl group, a cycloalkyl group, an alkenyl group, a cycloalkenyl group, an alkynyl group, an aryl group, a heteroaryl group, a heterocyclyl group, an alkyl group having a substituent, a cycloalkyl group having a substituent, Group, alkenyl group having a substituent, cycloalkenyl group having a substituent, alkynyl group having a substituent, aryl group having a substituent, having a substituent A heteroaryl group or a substituted heterocyclyl group is preferred.
R ³ is more preferably an alkyl group, a cycloalkyl group, an aryl group, an alkyl group having a substituent, a cycloalkyl group having a substituent, or an aryl group having a substituent.
R ³ is more preferably an alkyl group, particularly preferably a methyl group.

R ⁴ and R ⁵ are each independently a hydrogen atom or a monovalent group essentially having a carbon atom, and specifically include a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, a cycloalkenyl group, and an alkynyl. Group, aryl group, heteroaryl group, heterocyclyl group, alkyl group having a substituent, cycloalkyl group having a substituent, alkenyl group having a substituent, having a substituent A cycloalkenyl group, an alkynyl group having a substituent, an aryl group having a substituent, a heteroaryl group having a substituent, or a heterocyclyl group having a substituent is preferable.
R ⁴ and R ⁵ each independently have an alkyl group, a cycloalkyl group, an aryl group, an alkyl group having a substituent, a cycloalkyl group having a substituent, or a substituent Aryl groups are more preferred.
R ⁴ and R ⁵ are each independently preferably an alkyl group, and particularly preferably a methyl group.

Suitable orthocarboxylic esters (1) include:
R ¹ and R ² are both hydrogen atoms, and R ³ , R ⁴ and R ⁵ each independently represent an alkyl group, a cycloalkyl group, an aryl group, an alkyl group having a substituent, A compound having a cycloalkyl group or an aryl group having a substituent.

More preferred orthocarboxylic acid esters (1) include
A compound wherein R ¹ and R ² are both hydrogen atoms, and R ³ , R ⁴ and R ⁵ are each independently an alkyl group.

Further preferred orthocarboxylic acid esters (1) include:
A compound wherein R ¹ and R ² are both hydrogen atoms, and R ³ , R ⁴ and R ⁵ are both methyl groups.

  The substituent in the orthocarboxylic acid ester (1) must be selected so that the boiling point of the orthocarboxylic acid ester (1) is 500 ° C. or less.

The orthocarboxylic acid ester (1) can be synthesized by a known method or a similar method thereof according to a conventional method of organic chemistry. A typical example is trimethyl orthoacetate, which is commercially available and very easily available.
Since the reaction in the step (i) is performed in a gas phase, the boiling point of the orthocarboxylic acid ester (1) is preferably a temperature at which the orthocarboxylic acid ester (1) is vaporized at the reaction temperature and the reaction pressure. The boiling point in the following refers to the boiling point at 1 atm (absolute pressure).
The boiling point of the orthocarboxylic acid ester (1) is 500 ° C. or lower, preferably 450 ° C. or lower, more preferably 400 ° C. or lower. Further, from the viewpoint of easy handling, the boiling point of the orthocarboxylic acid ester (1) is preferably 0 ° C. or higher, more preferably 20 ° C. or higher, even more preferably 50 ° C. or higher.

The solid catalyst used in the reaction of the step (i) is selected from catalysts that promote the de-R ³ OH reaction of the orthocarboxylic acid ester (1), and includes a solid catalyst having a solid acid amount that promotes the de-R ³ OH reaction. Preferably, it is selected.

  Examples of the solid catalyst include metal catalysts, metal oxide catalysts, natural minerals, molecular sieves, carbon black and the like. The natural mineral is preferably acid clay, kaolinite, bentonite, montmorillonite, talc, zirconium silicate, or zeolite. The carbon black is preferably amorphous carbon, charcoal, activated carbon, graphite or fullerenes. The solid catalyst is preferably at least one selected from a metal catalyst and a metal oxide catalyst, and more preferably a metal oxide catalyst.

  As the metal catalyst, a catalyst composed of a metal of Groups IVB and VIII of the periodic table is preferable, and molybdenum, tungsten, chromium, iron, cobalt, nickel, platinum, palladium, iridium, osmium, rhodium, rhenium, or ruthenium is preferable. .

  A metal oxide catalyst refers to a catalyst containing a metal oxide, such as silica, alumina, zirconia, titania, tungsten oxide, magnesium oxide (magnesia), vanadium oxide, chromium oxide, manganese oxide, iron oxide, nickel oxide, and cobalt oxide. Copper oxide, zinc oxide, molybdenum oxide, tin oxide, calcium oxide, boron oxide (boria), zeolites, or mixtures thereof are preferred. The metal oxide catalyst is used as a composite metal oxide such as silica-alumina, silica-magnesia, silica-boria, alumina-boria, silica-titania, silica-zirconia, zinc oxide-zirconia, and molecular sieve in an arbitrary molar ratio. May be.

  As the metal oxide catalyst, from the viewpoint of activity, a catalyst containing at least one selected from the group consisting of zirconia (zirconium oxide), alumina, zeolite and zinc oxide is more preferable, and a catalyst containing zinc oxide is particularly preferable. In this case, the content of at least one metal oxide selected from the group consisting of zirconia, alumina, zeolite and zinc oxide in the metal oxide catalyst is preferably 50% by mass or more based on the metal oxide catalyst, It is more preferably at least 70% by mass, even more preferably at least 70% by mass.

  Among the metal oxides, zeolites include A-type zeolites, L-type zeolites, X-type zeolites, Y-type zeolites, MFI zeolites represented by ZSM-5 type, MWW-type zeolites, β-type zeolites, mordenite, ferrierite, Or erionite is preferred.

Examples of the solid catalyst used in the reaction of the step (i) other than the above include metal chlorides such as aluminum chloride, metal fluorides such as aluminum fluoride and calcium fluoride, metal sulfates such as iron sulfate, and zinc sulfide. Examples include metal sulfides, metal phosphates such as zinc phosphate, solid catalysts such as metallosilicate catalysts, and solid catalysts in which a phosphorus compound, a boron compound, and the like are supported on an inert carrier.
As the solid catalyst used in the reaction of step (i), one type may be used alone, or two or more types may be used in combination.
The solid acid amount of the solid catalyst is preferably more than 0 to 5.0 mmol / g, more preferably more than 0 to 3.0 mmol / g, and even more preferably more than 0 to 1.0 mmol / g. When the amount of the solid acid of the solid catalyst is equal to or more than the lower limit, the conversion of the orthocarboxylic acid ester (1) is improved. When the amount of the solid acid of the solid catalyst is equal to or less than the upper limit, generation of by-products is easily suppressed.
The specific surface area of the solid catalyst is preferably 0.1~1000m ² / g, more preferably 0.5~500m ² / g, more preferably 1~350m ² / g. When the specific surface area of the solid catalyst is equal to or more than the lower limit, the conversion of the orthocarboxylic acid ester (1) is improved. When the specific surface area of the solid catalyst is equal to or less than the upper limit, generation of by-products is easily suppressed.

  The reaction of step (i) is performed in a gas phase. The reaction in the gas phase can be carried out by a conventional gas phase flow method. The gas phase flow method is a method in which a solid catalyst is filled in a reactor, and the vaporized orthocarboxylic acid ester (1) is allowed to flow through the solid catalyst layer to cause a reaction. Specific examples include reaction systems such as a fixed bed circulation system, a fixed bed circulation system, and a fluidized bed circulation system. In the present invention, any of these reaction systems can be applied.

  For example, in the gas-phase flow method, the vaporized orthocarboxylic acid ester (1) is passed through the solid catalyst layer. However, the orthocarboxylic acid ester (1) may be passed alone or with the carrier gas. Good. The carrier gas is not particularly limited, but is preferably an inert gas such as a nitrogen gas, a helium gas, or an argon gas, or a mixed gas thereof. When used together with the carrier gas, the amount of the carrier gas used is preferably more than 0 to 20 mol, more preferably more than 0 to 10 mol, per 1 mol of the orthocarboxylic acid ester (1). In general, when the amount of the carrier gas is large, the conversion rate of the orthocarboxylic acid ester (1) is reduced. When the amount of the carrier gas is small, by-products are generated. And so on. The optimum amount depends on the reaction temperature and the contact time.

The reaction pressure is not particularly limited, and may be pressurized, normal pressure or reduced pressure. From the viewpoint of easy operation, the reaction pressure is preferably from normal pressure to slight pressure.
If desired, a filler such as a static mixer or Raschig ring can be added.

  The method of heating the reactor is not particularly limited, but a method of heating using a heating medium oil, a molten salt, an electric heater, and sand is preferable. The reaction temperature in the step (i) is preferably from 100 to 500C, more preferably from 120 to 450C, even more preferably from 150 to 400C. In general, when the temperature is low, the conversion of the orthocarboxylic acid ester (1) decreases, when the temperature is high, by-products are formed, impurities such as carbides adhere to the surface of the solid catalyst, and the catalytic activity decreases. there is a possibility. The optimum reaction temperature also depends on the contact time.

  In addition, the reaction time of the step (i) corresponds to a time during which the orthocarboxylic acid ester (1) comes into contact with the solid catalyst (hereinafter, referred to as “contact time”). The contact time is preferably from 0.1 to 60 seconds, more preferably from 1 to 30 seconds. In general, if the contact time is short, the conversion of the orthocarboxylic acid ester (1) decreases, if the contact time is long, by-products are generated, impurities such as carbides adhere to the surface of the solid catalyst, and the catalytic activity decreases. There is. The optimal contact time depends on the reaction temperature. For example, if the contact time is extremely short at 100 ° C., the reaction may not substantially proceed. If the contact time is extremely long at 500 ° C., by-products may be generated or tar or oil may be generated. The reactor may become blocked.

  Step (i) is a step of using a solid catalyst to carry out the production of the ethene derivative (2), which was conventionally difficult, by a gas phase reaction which is extremely advantageous in handling, productivity and the like.

  Since the reaction in the step (i) is a gas phase reaction, the ethene derivative (2) can be continuously produced by, for example, a reaction system in which the orthocarboxylic acid ester (1) is passed through a tubular reactor, and the batch reaction can be performed. It is much better in productivity than the conventional manufacturing method which is a formula. Further, since the reaction is performed in the gas phase, separation of the product is extremely easy. Furthermore, in the step (i), highly corrosive hydrogen chloride or the like is not generated, the safety is high, and the restriction of the reactor is small, which is industrially extremely advantageous.

In the reaction according to the step (i) of the present invention, the ethene derivative (2) (1,1-dimethoxyethene) in which R ⁴ and R ⁵ are methyl, which was difficult to produce industrially and economically by the conventional method, is easily and easily obtained. Obtained in high yield.

  The ethene derivative (2) obtained in the step (i) is useful as a synthetic intermediate for various chemicals. In the present invention, it is preferable to perform the following step (ii) using the obtained ethene derivative (2) to obtain a target halogenated acrylate.

[Step (ii)]
In the step (ii), the ethene derivative (2) obtained in the step (i) is converted into a halogenated methane represented by the formula (3) in the presence of a basic compound and a phase transfer catalyst (hereinafter simply referred to as “halogenated”). This is a step of producing a cyclopropane derivative represented by the formula (4) (hereinafter, also simply referred to as “cyclopropane derivative (4)”) by reacting with methane (3).

  The ethene derivative (2) used in the reaction of the step (ii) may be used in the reaction of the step (ii) without purification, or the ethene derivative (2) obtained in the step (i) may be used in the reaction after purification. You may. Examples of the purification method include known methods such as extraction using a solvent, distillation, and crystallization. In the purification, it is also possible to separate the orthocarboxylic acid ester (1) which has been left unreacted in the product of the step (i) and reuse it in the step (i). Can be improved.

  In the reaction of step (ii), the halogenated methane (3) used is considered to generate a carbene by the action of a basic compound and to be inserted into the double bond of the ethene derivative (2).

As the halogenated methane (3), for example, chloroform, dichlorofluoromethane, chlorodifluoromethane, or trifluoromethane is preferable.
Halogenated methane (3) in which X is a fluorine atom and Y is a chlorine atom or a fluorine atom is more preferable, and dichlorofluoromethane, chlorodifluoromethane, and trifluoromethane are more preferable.
Halogenated methane (3) in which X is a fluorine atom and Y is a chlorine atom is more preferred, and specifically, dichlorofluoromethane and chlorodifluoromethane are more preferred.
The halogenated methane (3) may be reacted by gasification or may be reacted with a liquid. Further, the reaction solution may be simultaneously withdrawn and continuously performed, or may be performed in a batch system without simultaneously withdrawing the reaction solution. From the viewpoint of productivity, it is advantageous to carry out continuously.
The amount of the halogenated methane (3) to be used is preferably 1 mol or more, more preferably 1 to 5 mol, and still more preferably 1 to 2 mol, per 1 mol of the ethene derivative (2).

The basic compound used in the reaction of the step (ii) is a compound that promotes a reaction for producing a carbene from a halogenated methane (3).
Examples of the basic compound include hydroxides of alkaline earth or alkali metals such as sodium hydroxide and potassium hydroxide; alkali metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide; alkalis such as sodium hydride Metal hydrides; alkyl lithiums such as butyl lithium; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal hydrogen phosphates or alkalis such as sodium phosphate, potassium phosphate, sodium hydrogen phosphate, and potassium hydrogen phosphate Metal phosphates are preferred.
More preferred basic compounds are alkali metal hydroxides, alkali metal alkoxides, alkali metal hydrides or alkyllithiums. Further preferred basic compounds are alkali metal hydroxides. The most preferred basic compound is sodium hydroxide or potassium hydroxide. One basic compound may be used alone, or two or more basic compounds may be used in combination. These basic compounds may be used as an aqueous solution, or may be used by being mixed with an organic solvent. The concentration of the basic compound in the solvent is preferably 5 to 60% by weight, more preferably 10 to 60% by weight. If the concentration of the basic compound in the solution is low, the conversion of the ethene derivative (2) decreases, and if the concentration is high, the conversion of the ethene derivative (2) increases.

  The amount of the basic compound used in the reaction of the step (ii) is an amount capable of generating a carbene sufficient for the reaction with the ethene compound from the halogenated methane (3), 1 to 10 mol is preferable, 1 to 8 mol is more preferable, and 1 to 6 mol is more preferable for 1 mol.

The reaction of step (ii) is performed in the presence of a phase transfer catalyst together with a basic compound. Examples of the phase transfer catalyst include a compound represented by the general formula (R ^a ) ₄ M ⁺ A ⁻ (wherein ^Ra is independently a hydrogen atom or a C _1-25 hydrocarbon group, M is N or P, and A is OH, F, Br, Cl, I, HSO ₄ , CN, CH ₃ SO ₃ or PhCH ₂ CO ₂ (wherein Ph represents a phenyl group), or a crown ether is preferable. Specific examples include quaternary ammonium salts such as tetrabutylammonium salt, trioctylmethylammonium salt, and benzyldimethyloctadecylammonium salt. As the _C1-25 hydrocarbon group, a linear alkyl group having 1 to 25 carbon atoms is preferable, and a linear alkyl group having 1 to 20 carbon atoms is more preferable. As a preferable phase transfer catalyst, a quaternary ammonium salt such as tetrabutylammonium bromide and tetrabutylammonium chloride is preferable. These phase transfer catalysts may be used as an aqueous solution, or may be used by being mixed with an organic solvent.
The amount of the phase transfer catalyst to be used is preferably 0.001 to 5% by mass, more preferably 0.01 to 3% by mass, and still more preferably 0.05 to 2% by mass with respect to the mass of the ethene derivative (2).
Generally, the reaction can be promoted by using a phase transfer catalyst. Also, the use of a general-purpose phase transfer catalyst (such as a quaternary ammonium salt) is advantageous in terms of cost.

  The phase transfer catalyst may be used as a catalyst between an aqueous phase and an organic phase, or as a catalyst between two organic phases to be phase-separated, such as a chlorinated fluorinated hydrocarbon solvent and a hydrocarbon solvent. Is also good. In general, the use of a phase transfer catalyst can facilitate a reaction using two solvents that phase separate.

The reaction of the step (ii) is performed in a liquid phase, and is preferably performed in the presence of a solvent.
The solvent is preferably water, an aliphatic hydrocarbon, a halogenated aliphatic hydrocarbon, an aromatic hydrocarbon, or a halogenated aromatic hydrocarbon. Specific examples of the solvent include benzene, toluene, xylene, monochlorobenzene, dichlorobenzene, trichlorobenzene, petroleum ethers, pentane, hexane, cyclohexane, heptane, octane, nonane, decane, undecane, dodecane, tridecane, tetradecane, dichloromethane, Chloroform and carbon tetrachloride. One type of solvent may be used alone, or two or more types may be used in combination.
When water is used as a solvent, a synergistic effect can be obtained in combination with an organic solvent. For example, since the ethene derivative (2) and the halogenated methane (3) as raw materials and the cyclopropane derivative (4) as a product are present in the organic phase, the contact efficiency with water is reduced, so that the secondary The reaction can be suppressed. In addition, when a water-soluble basic compound is used, a uniform state is formed in the aqueous phase, so that local side reactions can be suppressed.
The use amount of the solvent is preferably from 10 to 1000% by volume, more preferably from 50 to 800% by volume, based on 100% by volume of the ethene derivative (2).

In the step (ii), the order of introducing the ethene derivative (2), the halogenated methane (3), the basic compound, and the phase transfer catalyst into the reaction vessel is not particularly limited. Good. Further, after mixing the basic compound and the phase transfer catalyst in the reactor, the ethene derivative (2) and the halogenated methane (3) may be added sequentially or simultaneously. Further, the halogenated methane (3) may be added last.
In general, when a reaction is performed, a solvent, a catalyst, and the like are mixed in advance, and then, raw materials and the like are sequentially or simultaneously charged. When the calorific value of the reaction is large, it is preferable to charge all or a part of the raw materials sequentially.

  The reaction temperature in the step (ii) is preferably from -20C to + 50C, more preferably from -10C to + 40C, and still more preferably from 0C to + 30C. The reaction pressure is not particularly limited, and the reaction can be carried out under any of pressurization, normal pressure or reduced pressure.

  The reaction of the step (ii) can be carried out continuously, and is extremely superior in productivity as compared with a conventional batch-type production method. Further, highly corrosive hydrogen chloride and the like are not generated, and the safety is high, and there are few restrictions on the reactor, which is industrially extremely advantageous.

When the ethene derivative (2) obtained in the step (i) is used in the step (ii) without purification, the ethene derivative (2) is added together with the cyclopropane derivative (4) due to R ³ OH generated in the step (i). A compound represented by the formula (8) (hereinafter, the compound is also referred to as “propene derivative (8)”) is produced.

(In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and X are as described above.)

  The propene derivative (8) can be converted into a halogenated acrylate derivative (5), which is a product of the step (iii) described below, by decomposing it under acidic conditions in the presence of a solvent. Therefore, the yield and productivity can be improved by recovering the propene derivative (8) and producing a halogenated acrylate.

  The decomposition reaction of the propene derivative (8) is preferably performed under acidic conditions, preferably at pH 0 to 7, and more preferably at pH 0 to 5. In order to achieve acidic conditions, it is preferable that an acid such as hydrochloric acid or sulfuric acid be present in the reaction system. The solvent used for the decomposition reaction is preferably an alcohol such as methanol or ethanol. The amount of the solvent used is preferably from 10 to 1000% by volume, more preferably from 20 to 800% by volume, based on 100% by volume of the propene derivative (8). The reaction temperature is preferably −20 to + 100 ° C., and more preferably −10 to + 80 ° C.

  Preferred propene derivatives (8) include, for example, compounds represented by the following formula (7).

(In the formula, Me represents a methyl group.)
The cyclopropane derivative (4) obtained in the step (ii) is useful as an intermediate for medicines, polymers and the like. Particularly, the cyclopropane derivative (4) in which X is a fluorine atom and Y is a chlorine atom or a fluorine atom in the formula (4) is useful.

  Further, the compound represented by the following formula (6) is a novel compound.

(In the formula, Me represents a methyl group, and Y ¹ represents a chlorine atom or a fluorine atom.)
Specific examples of the compound represented by the formula (6) include the following compounds.

(In the formula, Me represents a methyl group.)
For example, conventionally reported cyclopropane derivatives in which R ¹ and R ² are both hydrogen atoms, R ⁴ and R ⁵ are both ethyl groups, X is a fluorine atom, and Y is a chlorine atom ( Since 4) had a high boiling point, it was very difficult to carry out distillation purification at a low temperature in order to suppress decomposition. For example, when vacuum distillation is performed using a general vacuum distillation apparatus, when distillation and purification are performed at 50 ° C., which is the lowest temperature at which vacuum distillation is possible, the cyclopropane derivative (4) is decomposed by 20% or more. In comparison, the compound represented by the formula (6) of the present invention has a low boiling point, so that it can be purified by distillation at 20 ° C. or less using the same vacuum distillation apparatus, and its decomposition is less than 1%. Therefore, it is very useful industrially and economically.

[Step (iii)]
In the step (iii), the cyclopropane derivative (4) obtained in the step (ii) is heated in a liquid phase or a gaseous phase to cause a de-R ⁴ Y reaction, thereby obtaining a halogenated compound represented by the formula (5). This is a step of producing an acrylate derivative (hereinafter, also simply referred to as “halogenated acrylate derivative (5)”).

The cyclopropane derivative (4) used in the step (iii) may be used in the reaction of the step (iii) without purification of the compound obtained in the step (ii), or may be used after purification. . As a method for purifying the cyclopropane derivative (4), a known method such as extraction with a solvent, distillation, or crystallization can be used.
At the time of purification, the ethene derivative (2) and the halogenated methane (3) contained in the cyclopropane derivative (4) obtained in the step (ii), which are not reacted, are separated and subjected to the step (ii). It is also possible to return.

In the step (iii), the cyclopropane derivative (4) obtained in the step (ii) is heated in a reactor. The reaction of the step (iii) is an elimination reaction, and the compound represented by the formula R ⁴ Y is eliminated. The reaction of step (iii) may be performed in a gas phase or in a liquid phase. The reaction temperature in the step (iii) is preferably from 80 ° C to 400 ° C, more preferably from 100 ° C to 350 ° C, even more preferably from 120 ° C to 300 ° C. The reaction pressure is not particularly limited, and the reaction can be performed under any of pressurization, normal pressure or reduced pressure. In general, when the temperature is low, there is a possibility that the conversion of the cyclopropane derivative (4) is reduced, and when the temperature is high, by-products are generated, polymerization is accelerated, and the like. The optimal reaction temperature depends on the contact time.

  When the reaction is performed in a liquid phase or a gaseous phase, the raw materials may be introduced into a preheated reactor, or may be introduced before heating, and it is preferable to heat the reactor in advance. Further, the reaction solution or the reaction gas containing the halogenated acrylic acid ester derivative (5) may be extracted simultaneously and continuously, or may be batch-wise extracted without being extracted simultaneously. From the viewpoint of productivity, it is advantageous to carry out continuously.

  In the case where the reaction is continuously performed in the step (iii), the residence time in the reactor may be a time during which the cyclopropane derivative (4) is sufficiently converted, and is preferably 1 second or more, more preferably 10 seconds or more. Preferably, it is more preferably 30 seconds or more. Further, from the viewpoint of suppressing side reactions such as polymerization, the time is preferably within 5 hours, more preferably within 2 hours, further preferably within 1 hour. In general, if the contact time is short, there is a possibility that the conversion of the cyclopropane derivative (4) decreases, and if the contact time is long, a by-product is generated, and polymerization is accelerated.

When the step (iii) is carried out in a liquid phase, it can be carried out in the presence or absence of a solvent, and is preferably carried out in the presence of a solvent. When a solvent is used in step (iii), the solvent is stable to heating and is preferably an inert solvent in the reaction of step (iii). Examples of the solvent include aromatic hydrocarbon solvents such as benzene, toluene, and xylene; halogenated aromatic hydrocarbon solvents such as monochlorobenzene, dichlorobenzene, and trichlorobenzene; cyclohexane, heptane, octane, nonane, decane, undecane, dodecane; Preferred are hydrocarbon solvents such as tridecane and tetradecane; alcohol solvents such as methanol, ethanol and propanol; and halogenated hydrocarbon solvents such as chloroform and carbon tetrachloride.
The amount of the solvent used is preferably from 0 to 1000% by volume, more preferably from 0 to 800% by volume, based on 100% by volume of the cyclopropane derivative (4).

The halogenated acrylate derivative (5) obtained in the step (iii) can be purified by a known method such as extraction with a solvent, distillation, or crystallization.
The halogenated acrylate derivative (5) obtained in the step (iii) may be easily polymerized during the step (iii) or after isolation and purification to produce a polymer, depending on the structure. In this case, it is preferable to prevent polymerization during the step (iii) or after isolation and purification by adding a polymerization inhibitor.

Examples of the polymerization inhibitor include 2,2,6,6-tetramethylpiperidine N-oxyl, p-benzoquinone, hydroquinone, methoquinone, 2,6-di-tert-butyl-4-methylphenol (BHT), and 4-tert. -Butylcatechol, tert-butylhydroquinone, 2,5-di-tert-butylhydroquinone, 1,2,4-trihydroxybenzene, leucoquinizarin, chloranil, phenothiazine, Q-1300, Q-1301, tetraethyltyrium disulfide, sulfur And the like, and hydroquinone, 2,6-di-tert-butyl-4-methylphenol (BHT), and phenothiazine are more preferable. One type of polymerization inhibitor may be used alone, or two or more types may be used in combination.
The amount of the polymerization inhibitor to be used is preferably at least 10 ppm, particularly preferably from 20 to 50,000 ppm, based on the halogenated acrylate derivative (5) obtained in the step (iii). If the amount of the polymerization inhibitor is small, the effect of inhibiting the polymerization is low. If the amount is large, there is a possibility that the amount of waste increases and the cost is inferior.

  The method for adding the polymerization inhibitor is not particularly limited, and it is preferable that the polymerization inhibitor be present in a system in which the halogenated acrylate derivative (5) is present. Specifically, it is preferable that a polymerization inhibitor is present in the reaction system, in the kettle during distillation purification, and in the halogenated acrylate derivative (5) after distillation purification. In addition, by combining the polymerization inhibitor and aeration during distillation purification, self-polymerization of the halogenated acrylate derivative (5) in the gas phase can be effectively suppressed. The amount of oxygen introduced during aeration during distillation is not particularly limited, but may be any amount that does not induce explosion, including the entire distillation system.

  The reaction of the step (iii) can be carried out continuously, and is extremely superior in productivity as compared with a conventional batch-type production method. When the reaction is carried out in the gas phase, the separation of the product is extremely easy. Further, there is no generation of highly corrosive hydrogen chloride and the like, and the safety is high, and there are few restrictions on the reactor, which is extremely advantageous industrially.

The halogenated acrylate derivative (5) is useful as a raw material for pharmaceuticals, polymers, optical materials, paints, semiconductor resist materials and the like. In particular, α-fluoroacrylic acid ester derivatives are extremely useful for medical applications and as basic materials for polymers and optical materials.
That is, by polymerizing the halogenated acrylate derivative represented by the formula (5) obtained by the production method of the present invention, a method for producing a polymer containing a polymerized unit based on the halogenated acrylate derivative is achieved. Realized industrially and economically.

  Examples of such a halogenated acrylate derivative (5) include a compound represented by the following formula (9).

(In the formula, Me represents a methyl group.)
The above steps (i) to (iii) can be performed alone, but it is industrially advantageous to perform them continuously. For example, after performing step (i) in the gas phase, cooling the product, performing step (ii) in the liquid phase unpurified, and heating the product of step (ii) unpurified. Step (iii) can be carried out as a continuous process. As described above, a path that separates unreacted raw materials and returns to the previous step is further added to such a continuous flow, whereby a more productive process can be constructed.

  Each of the steps (i) to (iii) of the present invention is preferably performed using the following reaction substrate. The intermediate or the final product compound obtained in each step is a compound useful as an intermediate such as a drug or a polymer.

(In the formula, Me represents a methyl group.)

  Hereinafter, the present invention will be described specifically with reference to Examples, but the present invention is not limited to these Examples.

[Examples 1 to 3, Comparative Example 1]
<Preparation of Catalyst> Columnar zinc oxide having a diameter of 4.8 mm and a length of 9.8 mm (specific surface area 39 m ² / g, solid acid amount 0.1 mmol / g (in terms of NH ₃ ), “N748” manufactured by JGC Catalysts and Chemicals, Inc.) ) The catalyst was filled in a SUS316 reaction tube having an inner diameter of 15 mm and a length of 300 mm, and an electric heater was attached. The temperature of the catalyst layer was heated to 250 ° C., and nitrogen was passed for 3 hours to dry the catalyst.

<Step (i)> The reaction was carried out by heating with an electric heater so that the temperature of the catalyst layer became the temperature shown in Table 1, and flowing trimethyl orthoacetate as a raw material under the conditions shown in Table 1. The crude liquid at the outlet of the reactor was collected by a cold trap at 0 ° C. and analyzed by gas chromatography to analyze the composition of the reaction product. In addition, as a comparative example, a reaction was performed in the same operation as in Example 1 without using a solid catalyst. Table 1 shows the results.

Further, 1,1-dimethoxyethene is obtained as a colorless liquid by fractional distillation under atmospheric pressure using a packed column.
The ¹ H-NMR of 1,1-dimethoxyethene is shown below.
¹ H-NMR (400 MHz, CDCl ₃ ), δ ppm; 2.91 (s, 2H), 3.41 (s, 6H).

[Examples 4 to 6]
The reaction was carried out in the same manner as in Example 2 except that the catalyst was changed. Table 2 shows the results.

* Catalyst 1: Spherical α-alumina (specific surface area 3 m ² / g, solid acid amount 0.9 mmol / g (NH ₃ conversion), Nikkato “HD ball”)
* Catalyst 2: Columnar γ-alumina (specific surface area: 280 m ² / g, solid acid amount: 0.2 mmol / g (converted to NH ₃ ), “Selexsorb COS” manufactured by NE Chemcat)
* Catalyst 3: 5% zinc oxide-zirconium oxide (specific surface area 60 m ² / g, solid acid amount 0.06 mmol / g (NH ₃ equivalent), NE Chemcat)

[Examples 7 to 15]
The reaction was carried out in the same manner as in Example 2 except that the catalyst was changed. Table 3 shows the results.

[Example 16 (Step (ii))]
In a 300 ml flask, 20 g of 1,1-dimethoxyethene, 0.1 g of tetrabutylammonium bromide, 80 g of a 48% aqueous solution of potassium hydroxide, and 40 g of hexane were mixed, cooled to 5 ° C., and stirred, whereupon 32 g of dichlorofluoromethane was added. Was continuously fed so that the reaction temperature did not exceed 10 ° C. After the feed of dichlorofluoromethane was completed, the disappearance of 1,1-dimethoxyethene was confirmed by gas chromatography, and then 40 g of distilled water was added, and the organic layer was separated into two layers. The content of ¹ -chloro-1-fluoro-2,2-dimethoxycyclopropane contained in the obtained crude organic layer liquid was 29 g by ¹ H-NMR (quantification by an internal standard method). The yield was 83.6%.
1 H-NMR and ¹⁹ F-NMR of ¹ -chloro-1-fluoro-2,2-dimethoxycyclopropane are shown below.
¹ H-NMR (400 MHz, CDCl ₃ ), δ ppm; 1.51 (dd, 1H), 1.74 (dd, 1H), 3.47 (s, 3H), 3.49 (s, 3H).
¹⁹ F-NMR (400 MHz, CDCl ₃ ), δ ppm; -147.35 (dd, 1F).

Further, the content of 2-fluoro-3,3,3-trimethoxy-1-propene was 1.7 g by ¹ H-NMR (quantification by an internal standard method). Yield was 5.0%.
The ¹ H-NMR and ¹⁹ F-NMR of 2-fluoro-3,3,3-trimethoxy-1-propene are shown below.
¹ H-NMR (400 MHz, CDCl ₃ ), δ ppm; 3.22 (s, 9H), 5.22 (dd, 1H), 6.92 (dd, 1H).
¹⁹ F-NMR (400 MHz, CDCl ₃ ), δ ppm; -126.09 (dd, 1F).

In addition, when the organic layer crude liquid containing 1-chloro-1-fluoro-2,2-dimethoxycyclopropane produced in Example 16 was distilled by a reduced pressure distillation apparatus using a packed column, the bath temperature was 20 ° C. and the pressure was 20 ° C. Distillation was possible at 13 hPa. The obtained 1-chloro-1-fluoro-2,2-dimethoxycyclopropane is a colorless liquid, and the decomposition rate of 1-chloro-1-fluoro-2,2-dimethoxycyclopropane in distillation is less than 1%. there were.
On the other hand, using the same vacuum distillation apparatus, 1-chloro-1-fluoro-2, obtained in the same manner as in Example 16 except that 1,1-dimethoxyethene was changed to 1,1-diethoxyethene. When the organic layer crude liquid containing 2-diethoxycyclopropane was distilled, distillation was possible under the conditions of a bath temperature of 50 ° C. and a pressure of 10 hPa. However, the decomposition rate of 1-chloro-1-fluoro-2,2-diethoxycyclopropane in distillation was 24%.

[Examples 17 to 22]
The reaction was carried out in the same manner as in Example 16, except that the amounts of tetrabutylammonium bromide, 48% aqueous potassium hydroxide solution and dichlorofluoromethane were changed. Table 4 shows the results. In the table, TBAB indicates tetrabutylammonium bromide, KOH solution indicates a 48% aqueous potassium hydroxide solution, and CHCl ₂ F indicates dichlorofluoromethane.

[Example 23]
The reaction was carried out in the same manner as in Example 16, except that 32 g of dichlorofluoromethane was changed to 27 g of chlorodifluoromethane. The content of 1,1-difluoro-2,2-dimethoxycyclopropane contained in the obtained crude organic layer solution was 26 g by ¹ H-NMR (quantification by an internal standard method). The yield was 81.5%.
The ¹ H-NMR and ¹⁹ F-NMR of 1,1-difluoro-2,2-dimethoxycyclopropane are shown below.
¹ H-NMR (400 MHz, CDCl ₃ ), δ ppm; 1.55 (m, 2H), 3.30 (s, 6H).
¹⁹ F-NMR (400 MHz, CDCl ₃ ), δ ppm; -145.25 (m, 2F).

[Example 24 (Step (iii))]
A 100-ml three-necked flask connected to a receiver for reactive distillation (cooled to 0 ° C. and initially added with 0.5 g of 2,6-di-tert-butyl-4-methylphenol (BHT) as a polymerization inhibitor) was added. 0.5 g of 6-di-tert-butyl-4-methylphenol (BHT) and 100 ml of 1,2,4-trichlorobenzene were charged, and the pressure was reduced to 360 torr. When the mixture was heated to 145 ° C., the dropping of 45 g of the organic layer crude liquid produced in Example 16 was started, and the dropping was continued at such a rate that the internal temperature was maintained at 145 ° C. The formed α-methyl methyl fluoroacrylate accumulated in the distillation receiver. The content of methyl α-fluoroacrylate contained in the crude liquid collected in the distillation receiver was 10 g according to ¹ H-NMR (quantification by an internal standard method). The yield was 94.6%.

[Example 25]
The reaction was carried out in the same manner as in Example 24, except that the crude organic layer liquid produced in Example 16 was changed to the crude organic layer liquid produced in Example 23. The yield of α-methyl methyl acrylate contained in the crude liquid collected in the distillation receiver was 91.7% from ¹ H-NMR (quantification by an internal standard method).

  The method for producing a halogenated acrylic acid ester derivative according to the present invention is based on a method in which a readily available orthocarboxylic acid derivative is used as a raw material, and a high conversion rate, a high selectivity, and a high yield are obtained. It is a method of deriving and is extremely useful industrially. In addition, intermediates and compounds of final products produced by the method for producing a halogenated acrylate derivative according to the present invention are compounds useful as intermediates such as pharmaceuticals and polymers.

  The present application is based on Japanese Patent Application No. 2015-168339 filed on August 27, 2015 in Japan and Japanese Patent Application No. 2006-044724 filed on March 8, 2016, the contents of which are described in the present specification. Are all included.

Claims (19)

In the gas phase, a compound represented by the following formula (1) and having a boiling point of 500 ° C. or less is used as a metal oxide catalyst, a natural mineral, molecular sieve, carbon black, a metal chloride, and a metal fluoride. , metal sulfates, metal sulfides, and characterized de R ³ be OH reaction in the presence of at least one solid catalyst selected from metal phosphates, ethene derivative represented by the following formula (2) Manufacturing method.

(Where
R ¹ and R ² each independently represent a hydrogen atom or a monovalent group that requires a carbon atom, or R ¹ and R ² together form a ring together with the carbon atom to which they are attached; May be
R ³ represents a monovalent group from which a group R ³ O can be eliminated by a de-R ³ OH reaction;
R ⁴ and R ⁵ each independently represent a hydrogen atom or a monovalent group essentially having a carbon atom. )

(In the formula, R ¹ , R ² , R ⁴ and R ⁵ are as described above.) R ¹ and R ² are both hydrogen atoms, and R ³ , R ⁴ and R ⁵ each independently represent an alkyl group, a cycloalkyl group, an aryl group, an alkyl group having a substituent, The production method according to claim 1, wherein the production method is a cycloalkyl group having an aryl group or an aryl group having a substituent.   The method according to claim 1, wherein the reaction temperature is 100 to 500 ° C. 4.   The production method according to any one of claims 1 to 3, wherein the reaction is carried out by flowing the vaporized compound represented by the formula (1) through the solid catalyst layer together with a carrier gas. The production method according to any one of claims 1 to 4 , wherein the solid catalyst is a catalyst containing at least one selected from the group consisting of zirconia, alumina, zeolite, and zinc oxide. The method according to any one of claims 1 to 4 , wherein the solid catalyst is a catalyst containing zinc oxide. An ethene derivative represented by the formula (2) is obtained by the production method according to any one of claims 1 to 6 , and the ethene derivative is converted into the following formula (3) in the presence of a basic compound and a phase transfer catalyst. A method for producing a cyclopropane derivative represented by the following formula (4), characterized by reacting with a compound represented by the following formula:

(In the formula, X, Y, and Z each independently represent a halogen atom.)

(Wherein R ¹ , R ² , R ⁴ and R ⁵ are as defined in claim 1 and X and Y are as defined above) The production method according to claim 7 , wherein the basic compound is at least one selected from the group consisting of an alkali metal hydroxide, an alkali metal alkoxide, an alkali metal hydride and an alkyl lithium. The method according to claim 7 or 8 , wherein the phase transfer catalyst is a quaternary ammonium salt. The method according to any one of claims 7 to 9 , wherein X is a fluorine atom, and Y is a chlorine atom or a fluorine atom. The method according to any one of claims 7 to 10 , wherein the ethene derivative represented by the formula (2) is 1,1-dimethoxyethene. The compound according to any one of claims 7 to 11 , wherein the amount of the compound represented by the formula (3) is 1 to 5 mol per 1 mol of the ethene derivative represented by the formula (2). Production method. The production method according to any one of claims 7 to 12 , wherein the amount of the basic compound used is 1 to 10 mol per 1 mol of the compound represented by the formula (3). The production method according to any one of claims 7 to 13 , wherein the amount of the phase transfer catalyst used is 0.001 to 5% by mass based on the mass of the ethene derivative represented by the formula (2). The cyclopropane derivative represented by the formula (4) is obtained by the production method according to any one of claims 7 to 14 , and the cyclopropane derivative is heated in a liquid phase or a gas phase to remove R. ^{4. A} method for producing a halogenated acrylate derivative represented by the following formula (5), characterized by performing a Y reaction.

(Wherein R ¹ , R ² , R ⁴ and R ⁵ are as defined in claim 1, and X and Y are as defined in claim 7 ) Temperature of de ^{R 4} Y the reaction is a 80 to 400 ° C., the manufacturing method according to claim 15. A cyclopropane derivative represented by the formula (4) and a propene derivative represented by the following formula (8) are obtained by the production method according to any one of claims 7 to 14 , and then the cyclopropane derivative is obtained. And producing the halogenated acrylate derivative represented by the following formula (5), wherein the propene derivative is separated under an acidic condition.

(Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ are as defined in claim 1 and X is as defined in claim 7 )

(In the formula, R ¹ , R ² , R ⁵ and X are as described above.) The production method according to any one of claims 15 to 17 , wherein the production is performed in the presence of a polymerization inhibitor when producing the halogenated acrylate derivative represented by the formula (5). The method according to claim 18 , wherein the amount of the polymerization inhibitor added is 10 ppm or more based on the halogenated acrylate derivative represented by the formula (5).