JP2014012644A - Fluorine-containing halosulfuric acid propyl derivative, method for producing the same, and the use thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing 2,2-difluoro-3-halopropionate ester, advantageous in cost.SOLUTION: The fluorine-containing halosulfuric acid propyl derivative is a compound represented by the formula (1) (in the formula, X represents a chlorine atom or a fluorine atom, Rand Reach represents a hydrogen atom or a fluorine atom, and Rand Rtogether forms an oxo group or each represents a hydrogen atom, and when Rand Reach is a hydrogen atom, Rand Rtogether forms an oxo group, and when Rand Reach is a fluorine atom, Rand Reach represents a hydrogen atom).

Description

  The present invention relates to a fluorine-containing propyl halosulfate derivative, its production, and its use.

α-Fluoroacrylic acid ester is a synthetic intermediate for pharmaceuticals (for example, antibiotics), a synthetic intermediate for optical fiber sheath materials, a synthetic intermediate for coating materials, a synthetic intermediate for semiconductor resist materials, and functionality. It is useful as a polymer monomer.
2,2-Difluoro-3-halopropionic acid ester is known as a synthetic intermediate of this α-fluoroacrylic acid ester (Patent Document 1).
Conventionally, this 2,2-difluoro-3-halopropionic ester has been obtained by a method such as treatment of 2,2,3,3-tetrafluorooxetane with sodium iodide.

JP 60-158137 A

However, the production method of α-fluoroacrylic acid ester using 2,2,3,3-tetrafluorooxetane as a raw material has the disadvantage of high cost.
Accordingly, an object of the present invention is to provide a cost-effective method for producing 2,2-difluoro-3-halopropionic acid ester that does not use 2,2,3,3-tetrafluorooxetane as a raw material. .

We have the formula (1):
[Where:
X represents a chlorine atom or a fluorine atom,
R ¹ and R ² each represent a hydrogen atom or a fluorine atom, and R ³ and R ⁴ together form an oxo group, or R ³ and R ⁴ each represent a hydrogen atom.
However,
When R ¹ and R ² are each a hydrogen atom, R ³ and R ⁴ together form an oxo group;
When R ¹ and R ² are each a fluorine atom, R ³ and R ⁴ are each a hydrogen atom. ]
It has been found that a method for producing 2,2-difluoro-3-halopropionic acid ester which is advantageous in terms of cost can be provided by the compound represented by formula (I) and a production method using the compound, and the present invention has been completed.

The present invention has the embodiments described in the following items.
Item 1.
Formula (1):
[Where:
X represents a chlorine atom or a fluorine atom,
R ¹ and R ² each represent a hydrogen atom or a fluorine atom, and R ³ and R ⁴ together form an oxo group, or R ³ and R ⁴ each represent a hydrogen atom.
However,
When R ¹ and R ² are each a hydrogen atom, R ³ and R ⁴ together form an oxo group;
When R ¹ and R ² are each a fluorine atom, R ³ and R ⁴ are each a hydrogen atom. ]
A compound represented by
Item 2.
Item 2. The compound according to Item 1, wherein R ¹ and R ² are each a hydrogen atom, and R ³ and R ⁴ together form an oxo group.
Item 3.
Item 3. The compound according to Item 2, wherein X is a chlorine atom.
Item 4.
Item 3. The compound according to Item 2, wherein X is a fluorine atom.
Item 5.
X is a fluorine atom,
Item 2. The compound according to Item 1, wherein R ¹ and R ² are each a fluorine atom, and R ³ and R ⁴ are each a hydrogen atom.
Item 6.
A method for producing the compound according to Item 1, comprising:
A production method comprising a step A in which tetrafluoroethylene is reacted with polyformaldehyde in the presence of halosulfuric acid to obtain a compound represented by the formula (1).
Item 7.
Item 6. The method according to Item 6, wherein the halosulfuric acid is chlorosulfuric acid, and the compound according to Item 3 is obtained.
Item 8.
Item 6. The production method according to Item 6, wherein the halosulfuric acid is fluorosulfuric acid, and the compound according to Item 4 and / or the compound according to Item 5 is obtained.
Item 9.
Formula (2):
[Where:
^Xb represents a halogen atom. ]
A process for producing a compound represented by
A production method comprising a step B-1 in which the compound according to item 3 is reacted with an alkali metal halide to obtain a compound represented by the formula (2).
Item 10.
Formula (3):
[Where:
X ^b represents a halogen atom,
R ⁵ represents an alkyl group. ]
A process for producing a compound represented by
The compound represented by the formula (2) obtained by the production method according to item 9 is represented by the formula (4):
R ⁵ —OH (4)
[The symbols in the formula are as defined above. ] The manufacturing method including the process B-2 which makes it react with the compound represented by this, and obtains the compound represented by Formula (3).

  According to the present invention, 2,2-difluoro-3-halopropionic acid ester can be produced at low cost.

In the present specification, examples of the “alkyl group” include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a neopentyl group, and a hexyl group. C1-6 alkyl groups such as
In the present specification, examples of “halo” or “halogen” include fluorine, chlorine, bromine and iodine.

1. Compound represented by Formula (1) Formula (1):
[Where:
X represents a chlorine atom or a fluorine atom,
R ¹ and R ² each represent a hydrogen atom or a fluorine atom, and R ³ and R ⁴ together form an oxo group, or R ³ and R ⁴ each represent a hydrogen atom.
However,
When R ¹ and R ² are each a hydrogen atom, R ³ and R ⁴ together form an oxo group;
When R ¹ and R ² are each a fluorine atom, R ³ and R ⁴ are each a hydrogen atom. ]
A compound represented by

The compound represented by Formula (1) has the following aspects.
[Aspect 1]
In equation (1),
X represents a chlorine atom or a fluorine atom,
R ¹ and R ² each represent a hydrogen atom or a fluorine atom, and R ³ and R ⁴ together form an oxo group, or R ³ and R ⁴ each represent a hydrogen atom.
However,
When R ¹ and R ² are each a hydrogen atom, R ³ and R ⁴ together form an oxo group;
A compound in which R ³ and R ⁴ are each a hydrogen atom when R ¹ and R ² are each a fluorine atom.

[Aspect 2]
In aspect 1,
A compound in which R ¹ and R ² are each a hydrogen atom, and R ³ and R ⁴ together form an oxo group.
[Aspect 3]
In embodiment 2, the compound wherein X is a chlorine atom.
[Aspect 4]
In embodiment 2, the compound wherein X is a fluorine atom.

[Aspect 5]
In aspect 1,
X is a fluorine atom,
A compound in which R ¹ and R ² are each a fluorine atom, and R ³ and R ⁴ are each a hydrogen atom.

2. Method for Producing Compound Represented by Formula (1) The compound represented by formula (1) can be produced, for example, by the following production method.
A production method comprising a step A in which tetrafluoroethylene is reacted with polyformaldehyde in the presence of halosulfuric acid to obtain a compound represented by the formula (1).

  In the present specification, polyformaldehyde means a polymer composed of two or more molecules of formaldehyde, which may be chain-like or cyclic. Examples thereof include polyoxymethylene and 1,3,5-trioxane. The number average polymerization degree of polyoxymethylene is preferably 2 to 100.

  The amount of trifluoroethylene (TFE) is usually 1 to 10 mol, preferably 2 to 5 mol, per 1 mol of polyformaldehyde.

  Examples of halosulfuric acid include chlorosulfuric acid and fluorosulfuric acid.

  When the halosulfuric acid is chlorosulfuric acid, the compound of Embodiment 3 is suitably obtained.

  When the halosulfuric acid is fluorosulfuric acid, the compound of aspect 4 and / or the compound of aspect 5 is suitably obtained.

  The amount of halosulfuric acid is usually 1 to 20 mol, preferably 6 to 10 mol, per 1 mol of polyformaldehyde.

  The reaction temperature of the reaction is usually 20 to 160 ° C, preferably 30 to 100 ° C.

  The reaction time of the reaction is usually 1 hour to 3 days, preferably 6 hours to 2 days. By adopting a higher reaction temperature, the reaction time can be shortened.

The reaction may be performed under an inert gas.
Examples of the inert gas include nitrogen and argon.
The reaction may be performed under reduced pressure.

  The obtained compound represented by the formula (1) can be purified by a known purification method such as solvent extraction, drying, filtration, concentration, and a combination thereof, if desired.

3. A method for producing a compound represented by formula (3): Formula (3), which is an α-fluoroacrylic acid ester:
[Where:
X ^b represents a halogen atom,
R ⁵ represents an alkyl group. The compound represented by formula (1) is, for example, a compound represented by the formula (1):
R ¹ and R ² are each a hydrogen atom,
R ³ and R ⁴ together form an oxo group,
A compound in which X is a chlorine atom, that is, the following formula (1 ′):
[Wherein X has the same meaning as in formula (1). ]
A method for producing a compound represented by the formula (2) using a compound represented by the formula (2), and a compound represented by the formula (3) using the compound represented by the formula (2) It can manufacture with the manufacturing method to manufacture.

Examples of the alkyl group represented by R ⁵ include a linear or branched alkyl group having 1 to 6 carbon atoms (for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl). Pentyl, isopentyl, neopentyl, hexyl).

  The production method for producing the compound represented by the formula (2) using the compound represented by the formula (1 ′) comprises reacting the compound represented by the formula (1 ′) with an alkali metal halide. Step B-1 to obtain a compound represented by the formula (2).

[Step B-1]
Examples of the alkali metal halide include lithium halide (for example, lithium fluoride, lithium chloride, lithium bromide, lithium iodide), sodium halide (for example, sodium fluoride, sodium chloride, sodium bromide, iodine). Sodium halide, etc.), potassium halide (eg, potassium fluoride, potassium chloride, potassium bromide, potassium iodide, etc.), cesium halide (eg, cesium fluoride, cesium chloride, cesium bromide, cesium iodide, etc.) Etc. Of these, lithium bromide is preferable.

  The amount of the alkali metal halide is usually 0.2 to 5 mol, preferably 1.0 to 2 mol, relative to 1 mol of the compound represented by the formula (4).

The reaction is performed in the presence or absence of a solvent.
Examples of the solvent used in the reaction include dimethyl sulfoxide, acetonitrile, dimethylformamide, acetamide and the like.

  The reaction temperature of the reaction is usually 30 to 200 ° C, preferably 70 to 130 ° C.

  The reaction time of the reaction is usually 1 hour to 18 hours, preferably 5 hours to 15 hours.

The manufacturing method which manufactures the compound represented by the said Formula (3) using the compound represented by the said Formula (2),
The compound represented by the formula (2) is represented by the formula (4):
R ⁵ —OH (4)
[Wherein, R ⁵ represents an alkyl group. The process B-2 which makes it react with the compound represented by this, and obtains the compound represented by Formula (3) is included.

[Step B-2]
The reaction is preferably performed in the presence of an acid catalyst.
Examples of the acid catalyst used in the reaction include concentrated sulfuric acid.

The amount of the acid catalyst is usually 1 to 10 mol, preferably 2 to 5 mol, per 1 mol of the compound represented by the formula (2).
The amount of the compound represented by the formula (4) is usually 1 mol to large excess with respect to 1 mol of the compound represented by the formula (2).

  The reaction is performed in the presence or absence of a solvent. The compound represented by the formula (2) may be used as a solvent in the reaction.

  The reaction temperature of the reaction is usually about 0 to about 200 ° C, preferably about 10 to about 100 ° C.

  The reaction time is usually about 1 hour to about 100 hours, preferably about 1 hour to about 50 hours.

  The obtained compound represented by the formula (1) can be purified by a known purification method such as solvent extraction, drying, filtration, concentration, and a combination thereof, if desired.

  EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited to this.

Example 1
In a 100 mL autoclave, 2.5 g (30 mmol) of 1,3,5-trioxane was added, N ₂ substitution was performed, and after evacuation, 25 g (250 mmol) of fluorosulfuric acid was added from a suction tube. After further evacuation, 8.3 g (83 mmol) of TFE was introduced and stirred at room temperature. After stirring for 28 hours, the internal volume in the autoclave was measured, and TFE was blown to complete the reaction. Compound A was obtained in a yield of 54% and compound B was obtained in a yield of 26% in terms of TFE. This reaction solution was distilled to remove fluorosulfuric acid, thereby obtaining 12.4 g of a brown distillation residue.
¹⁹ F NMR (CDCl ₃ ) Compound A δ -123.0 (s, 2F), -86.1 (s, 2F), 49.7 (s, 1F),
Compound B -113.7 (s, 2F), 37.2 (s, 1F)

Example 2
In a 100 mL autoclave, 2.5 g (30 mmol) of 1,3,5-trioxane was put, N ₂ substitution and evacuation were performed, and then 29.1 g (250 mmol) of chlorosulfuric acid was added from the suction tube. After further evacuation, 8.3 g (83 mmol) of TFE was introduced and stirred at room temperature. After stirring for 28 hours, the internal volume in the autoclave was measured, TFE was blown to terminate the reaction, and Compound C was obtained at 76% in terms of TFE. This reaction solution was distilled under reduced pressure to remove chlorosulfuric acid to obtain 14.2 g of a brown distillation residue.
¹⁹ F NMR (CDCl ₃ ) Compound C δ −107.4 (s, 2F)

Example 3
Synthesis of BrCH ₂ CF ₂ COOH In 0.5 ml of DMSO solvent, 0.3 g (1.3 mmol) of compound C and 0.11 g (1.3 mmol) of LiBr were added, stirred at 100 ° C. for 8 hours, and BrCH ₂ CF ₂ COOH. Got. (Yield 75%) (Raw material conversion 75%)

  According to the present invention, synthetic intermediates for pharmaceuticals (eg, antibiotics), synthetic intermediates for optical fiber sheath materials, synthetic intermediates for coating materials, synthetic intermediates for semiconductor resist materials, and functional polymers A synthetic intermediate of α-fluoroacrylic acid ester useful as a monomer or the like can be produced at low cost.

Claims (10)

Formula (1):
[Where:
X represents a chlorine atom or a fluorine atom,
R ¹ and R ² each represent a hydrogen atom or a fluorine atom, and R ³ and R ⁴ together form an oxo group, or R ³ and R ⁴ each represent a hydrogen atom.
However,
When R ¹ and R ² are each a hydrogen atom, R ³ and R ⁴ together form an oxo group;
When R ¹ and R ² are each a fluorine atom, R ³ and R ⁴ are each a hydrogen atom. ]
A compound represented by The compound according to claim 1, wherein R ¹ and R ² are each a hydrogen atom, and R ³ and R ⁴ together form an oxo group. The compound according to claim 2, wherein X is a chlorine atom. The compound according to claim 2, wherein X is a fluorine atom. X is a fluorine atom,
The compound according to claim 1, wherein R ¹ and R ² are each a fluorine atom, and R ³ and R ⁴ are each a hydrogen atom. It is a manufacturing method of the compound of Claim 1, Comprising:
A production method comprising a step A in which tetrafluoroethylene is reacted with polyformaldehyde in the presence of halosulfuric acid to obtain a compound represented by the formula (1). The production method according to claim 6, wherein the halosulfuric acid is chlorosulfuric acid, and the compound according to claim 3 is obtained. The production method according to claim 6, wherein the halosulfuric acid is fluorosulfuric acid, and the compound according to claim 4 and / or the compound according to claim 5 is obtained. Formula (2):
[Where:
^Xb represents a halogen atom. ]
A process for producing a compound represented by
The manufacturing method including the process B-1 which makes the compound of Claim 3 react with an alkali metal halide, and obtains the compound represented by the said Formula (2). Formula (3):
[Where:
X ^b represents a halogen atom,
R ⁵ represents an alkyl group. ]
A process for producing a compound represented by
The compound represented by the formula (2) obtained by the production method according to claim 9 is represented by the formula (4):
R ⁵ —OH (4)
[The symbols in the formula are as defined above. ] The manufacturing method including the process B-2 which makes it react with the compound represented by this, and obtains the compound represented by Formula (3).