WO2018066146A1

WO2018066146A1 - Method for producing fluorinated compound

Info

Publication number: WO2018066146A1
Application number: PCT/JP2017/000996
Authority: WO
Inventors: 栗原一樹; 原田晃典; 中村裕
Original assignee: 関東電化工業株式会社
Priority date: 2016-10-05
Filing date: 2017-01-13
Publication date: 2018-04-12
Also published as: TW201825445A; JP2019214513A

Abstract

The present invention relates to a method for producing a fluorinated compound represented by formula (2): R²-F (where R² represents a group obtained by removing a hydroxy group from a hydroxy compound having six or more carbon atoms), the method being characterized by fluorinating a hydroxy compound having six or more carbon atoms by a fluorinating agent represented by formula (1): R¹SO₂F (where R¹ represents a methyl group, an ethyl group, or an aromatic group) in the presence of a base selected from the group consisting of amidine base and phosphazene base.

Description

Method for producing fluorinated compound

The present invention relates to a method for producing a fluorinated compound.
Background art

Fluorinated compounds such as fluorinated alkanes are used as media for plasma reaction gases, fluorine-containing pharmaceutical intermediates, refrigerants and heat transfer media. In particular, highly purified fluorinated alkanes are suitably used as plasma etching gases, chemical vapor deposition (CVD) gases, and the like in the field of manufacturing semiconductor devices using plasma reactions.

Conventionally, as a method for producing a fluorinated alkane, a method of reacting a corresponding alcohol with an alkylsulfonic acid fluoride as a fluorinating agent is known.
For example, Non-Patent Document 1 uses perfluorobutanesulfonic acid fluoride as a fluorinating agent and 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) as a base in a toluene solvent. An example in which the hydroxyl group of a steroid precursor is fluorinated is described.
Non-Patent Document 2 discloses a method in which a primary to tertiary alcohol is fluorinated in a ternary system of perfluorobutanesulfonic acid fluoride-trialkylamine hydrogen fluoride complex-trialkylamine in tetrahydrofuran or methylene chloride solvent. Are listed.
Non-Patent Document 3 describes an example in which various alcohols are fluorinated using nonafluorobutanesulfonic acid fluoride as a fluorinating agent and DBU as a base.
Patent Document 1 describes that a high molecular weight alcohol compound is fluorinated using fluorinated aliphatic sulfonic acid fluoride as a fluorinating agent and DBU as a base in a solvent such as toluene and diethylene glycol dimethyl ether. ing.
Patent Document 2 discloses that in an inert organic solvent such as toluene, nonafluorobutanesulfonic acid fluoride is used as a fluorinating agent, amidine base is used as a base, aliphatic alcohols, aromatic hydrocarbon compounds, and enol compounds are fluorinated. It is described that.

However, the fluorinating agent perfluoroalkanesulfonic acid fluoride used in these documents is expensive and not suitable for industrial use. In addition, perfluoroalkanesulfonic acid derivatives produced when these fluorinating agents are used have a concern about long-term toxicity and have safety problems.

On the other hand, among the fluorinated compounds, the following are known as methods for producing fluorinated alkanes having 3 to 5 carbon atoms.
In Patent Document 3, 2-butanol was contacted with N, N′-diethyl-3-oxo-methyltrifluoropropylamine as a fluorinating agent to obtain 2-fluorobutane in a yield of 46%. Is described.
However, the N, N′-diethyl-3-oxo-methyltrifluoropropylamine used is prepared from 4-chloro-3,4,4-trifluoro-2-butanone and 2 equivalents of diethylamine which are difficult to obtain industrially. Therefore, it can be said to be a very expensive fluorinating agent. Also, the yield of the target 2-fluorobutane is not satisfactory at 46%.
Patent Document 4 describes that 2-fluorobutane was obtained from 2-butanol in a yield of 68% using triethylammonium hexafluorocyclobutane as a fluorinating agent in the absence of a solvent.
However, the triethylammonium hexafluorocyclobutane used is manufactured using hexafluorocyclobutene which is industrially very expensive and highly toxic.
Patent Document 5 describes that sec-butyl fluoride was obtained by contacting sulfur hexafluoride with a sec-butyllithium cyclohexane-hexane solution.
However, the sec-butyllithium cyclohexane-hexane solution used is highly ignitable and has a handling problem. Further, since sulfur hexafluoride has a very long atmospheric life, there is a problem with safety.
Further, Patent Document 6 describes that 2-fluorobutane was obtained by hydrogenating 2-fluorobutadiene in the presence of a catalyst.
However, the method described in this document has a problem that it is difficult to obtain the raw material 2-fluorobutadiene.

As described above, the methods described in these documents are hardly preferred industrial production methods for fluorinated alkanes.
Prior art documents Patent documents

Patent Document 1: JP 2002-530356 A Patent Document 2: JP 9-507503 JP Patent Document 3: JP 59-46251 JP Patent Document 4: JP 9-48741 JP Patent Document 5: JP 2009-292749 A Patent Document 6: USP. 2,550,953
Non-patent literature

Non-Patent Document 1: Tetrahedron Letters, Vol. 36, 2614 (1995)
Non-Patent Document 2: Organic Letters, Vol. 6, 1465 (2004)
Non-Patent Document 3: Synthesis, No. 8, 1165 (2008)
Summary of the Invention Problems to be Solved by the Invention

The present invention has been made in view of the above-described prior art, and an object thereof is to provide a method for producing a fluorinated compound in an industrially advantageous manner.
Means for solving the problem

As a result of intensive studies to solve the above problems, the present inventors have found that a hydroxy compound having 6 or more carbon atoms is represented by the formula (1): R ¹ SO ₂ F (R ¹ is methyl) in the presence of an amidine base or the like. And a fluorinating agent represented by formula (2): R ² -F (R ² is a hydroxy compound having 6 or more carbon atoms removed from the hydroxy group). It has been found that a fluorinated compound represented by a group (hereinafter sometimes referred to as “fluorinated compound”) can be obtained safely, simply, economically and in a high yield.
And based on these knowledge, it came to complete this invention.

Thus, according to the present invention, the following methods for producing fluorinated compounds [1] to [11] are provided.
[1] A hydroxy compound having 6 or more carbon atoms in the presence of a base selected from the group consisting of an amidine base and a phosphazene base is represented by the formula (1): R ¹ SO ₂ F (R ¹ is a methyl group, an ethyl group or Fluorinated by a fluorinating agent represented by the formula (2): R ² -F (R ² is a group obtained by removing a hydroxy group from a hydroxy compound having 6 or more carbon atoms) A method for producing a fluorinated compound represented by:
[2] The method for producing a fluorinated compound according to [1], wherein the reaction is performed by adding the base to a mixture of the hydroxy compound and the fluorinating agent at 60 ° C. to 150 ° C.
[3] The method for producing a fluorinated compound according to [1] or [2], wherein the fluorinating agent is methanesulfonic acid fluoride.
[4] The base is represented by the following formula (3)

(Wherein n is 0 or 2), the method for producing a fluorinated compound according to any one of [1] to [3], which is an amidine base.
[5] The production of the fluorinated compound according to any one of [1] to [4], wherein the base is 1,8-diazabicyclo [5.4.0] undec-7-ene Method.
[6] The method for producing a fluorinated compound according to any one of [1] to [5], wherein the base is present as an acid salt with hydrogen fluoride.

[7] A hydroxy compound having 3 or more carbon atoms in the presence of an acid salt of hydrogen fluoride and a base selected from the group consisting of an amidine base and a phosphazene base is represented by the formula (1): R ¹ SO ₂ F (R ¹ represents a methyl group, an ethyl group or an aromatic group), and is fluorinated by a fluorinating agent represented by the formula (2): R ² -F (R ² is a compound having 3 or more carbon atoms) Represents a group obtained by removing a hydroxy group from a hydroxy compound.).
[8] The method for producing a fluorinated compound according to [7], wherein the reaction is performed by adding the base to a mixture of the hydroxy compound and the fluorinating agent at 60 ° C. to 150 ° C.
[9] The method for producing a fluorinated compound according to [7] or [8], wherein the fluorinating agent is methanesulfonic acid fluoride.
[10] The base is represented by the following formula (3)

(Wherein n is 0 or 2), the method for producing a fluorinated compound according to any one of [7] to [9], which is an amidine base.
[11] The production of the fluorinated compound according to any one of [7] to [10], wherein the base is 1,8-diazabicyclo [5.4.0] undec-7-ene Method.
The invention's effect

According to the present invention, using raw materials and a fluorinating agent that can be obtained industrially inexpensively, safely and simply, economically, and in high yield, suitable as a plasma etching gas, a CVD gas, etc. Fluorinated compounds can be produced.
BEST MODE FOR CARRYING OUT THE INVENTION

<Method for producing fluorinated compound>
In the present invention, a hydroxy compound having 6 or more carbon atoms is fluorinated with a fluorinating agent represented by the formula (1): R ¹ SO ₂ F in the presence of a base selected from the group consisting of an amidine base and a phosphazene base. This is a method for producing a fluorinated compound represented by the formula (2): R ² -F.

(Raw material hydroxy compound)
The production method of the present invention uses a hydroxy compound having 6 or more carbon atoms as a raw material. The hydroxy compound having 6 or more carbon atoms is preferably a compound having one or more hydroxyl groups, for example, alcoholic hydroxyl groups. The hydroxy compound having 6 or more carbon atoms is preferably a compound having one or two hydroxyl groups. What is necessary is just to select and use the hydroxy compound from which the target fluorinated compound is obtained. The hydroxy compound may have 30 or less carbon atoms, 25 or less carbon atoms, 20 or less carbon atoms, 18 or less carbon atoms, and 15 or less carbon atoms.

Examples of the hydroxy compound having 6 or more carbon atoms include the following.
(A) Alcohol having 6 or more carbon atoms (B) N-substituted hydroxypyrrolidine and derivatives thereof, which are compounds having 6 or more total carbon atoms (C) Hydroxycarboxylic acids having 6 or more carbon atoms and derivatives thereof Hydroxy having 6 or more carbon atoms The compound may have a functional group other than a hydroxyl group, such as a ketone, ether, amide, or amine. The compounds (A), (B), and (C) may also have a functional group other than a hydroxyl group.
That is, in the present invention, (A) alcohol having 6 or more carbon atoms, (B) N-substituted hydroxypyrrolidine and derivatives thereof having a total carbon number of 6 or more, and (C) hydroxycarbon having 6 or more carbon atoms. Hydroxy compounds selected from acids and derivatives thereof can be used.

As the alcohol having 6 or more carbon atoms in (A),
(A1) Monohydric alcohol having 6 or more carbon atoms (A2) Polyhydric alcohol having 6 or more carbon atoms may be mentioned.

Examples of the compound (A1) include saturated alcohols and unsaturated alcohols. Specifically, monovalent saturated alcohol having 6 to 30 carbon atoms, further 6 to 20 carbon atoms, and further 6 to 15 carbon atoms, 6 to 30 carbon atoms, further 6 to 20 carbon atoms, and further 6 to 15 carbon atoms. Examples thereof include alcohols selected from monounsaturated alcohols, monovalent aromatic alcohols, and monovalent aromatic alcohols having 6 to 30 carbon atoms in total. Examples of the monohydric alcohol having 6 or more carbon atoms include primary alcohol, secondary alcohol, and tertiary alcohol. The monohydric alcohol is preferably a secondary alcohol.
More specifically, examples of the monovalent saturated alcohol include saturated steroids such as 1-hexanol, 2-hexanol, 2-octanol and androsterone.
Examples of monounsaturated alcohols include 2-hexen-1-ol, 3-hexen-1-ol, 2-octen-1-ol, and geraniol.

Examples of the monovalent aromatic alcohol include aralkyl alcohol and further aralkyl alcohol having 6 to 30 carbon atoms in total. As monovalent aromatic alcohols, benzyl alcohol, 1-phenylethanol, 2-phenylethanol, 1-naphthylethanol, 4-fluoro-α-methylbenzyl alcohol, 4-chloro-α-methylbenzyl alcohol, 4-bromo-α -Methylbenzyl alcohol, 4-methyl-α-methylbenzyl alcohol, 4-methoxy-α-methylbenzyl alcohol, 4-amino-α-methylbenzyl alcohol and the like.
Examples of the aralkyl alcohol include a compound represented by the following formula.

[Wherein, R is a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms, preferably an alkyl group or an alkenyl group, and R ′ is a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms, preferably an alkyl group. Or it is an alkenyl group, a hydroxyl group, an amino group, or a halogen group. ]
R is preferably an alkyl or alkenyl group having 1 to 10 carbon atoms, more preferably 1 to 5 carbon atoms. R ′ is preferably a hydrogen atom, or an alkyl or alkenyl group having 1 to 10 carbon atoms, more preferably 1 to 5 carbon atoms, and more preferably a hydrogen atom. The hydrocarbon group for R or R ′ may have a ring structure. The ring structure may have a substituent.

The compound (A1) is preferably 2-octanol or 1-phenylethanol from the viewpoint of easy availability of raw materials.

Examples of the compound (A2) include alkylene glycol having a total carbon number of 6 or more and polyglycerin having a total carbon number of 6 or more. The alkylene glycol preferably has a total carbon number of 30 or less, and more preferably 20 or less. The polyglycerin preferably has a total carbon number of 30 or less, and more preferably 20 or less.
Specific examples include triethylene glycol, dipropylene glycol, and diglycerin.

As in the case of a polyhydric alcohol, a hydroxy compound having two or more hydroxyl groups preferably does not have a structure in which hydroxyl groups are bonded to two adjacent carbon atoms.

The (B) N-substituted hydroxypyrrolidine and derivatives thereof having a total carbon number of 6 or more preferably have a total carbon number of 6 to 30, more preferably 6 to 20. (B) Examples of N-substituted hydroxypyrrolidine and its derivatives having a total carbon number of 6 or more include N-alkyl-substituted hydroxypyrrolidine and N-aralkyl-substituted hydroxypyrrolidine. Examples of N-substituted hydroxypyrrolidine derivatives include N-alkyl-substituted hydroxypyrrolidine carboxylic acid, N-alkyl-substituted hydroxypyrrolidine carboxylic acid ester, N-aralkyl-substituted hydroxypyrrolidine carboxylic acid, and N-aralkyl-substituted hydroxypyrrolidine carboxylic acid ester. Can be mentioned. Examples of the compound (B) include compounds represented by the following formula.

[Wherein, R represents an alkyl group having 1 to 20 carbon atoms, an alkenyl group having 1 to 20 carbon atoms, an aryl group having 7 to 20 carbon atoms, an acyl group having 2 to 20 carbon atoms, or an alkoxy group having 2 to 20 carbon atoms. A carbonyl group or an aryloxycarbonyl group having 7 to 20 carbon atoms. R ′ is a hydrocarbon group having 1 to 20 carbon atoms, preferably an alkyl group or an alkenyl group. However, R and R ′ are selected so that the total number of carbon atoms in the compound is 6 or more, preferably 6 to 30, and more preferably 6 to 20. ]

Of R, the alkyl group having 1 to 20 carbon atoms is preferably an alkyl group having 1 to 15 carbon atoms, and more preferably a methyl group. The aryl group having 7 to 20 carbon atoms is preferably an aryl group having 7 to 15 carbon atoms, and more preferably a benzyl group (Bn). The acyl group having 2 to 20 carbon atoms is preferably an acyl group having 2 to 15 carbon atoms, more preferably an acetyl group (Ac) or a benzoyl group (Bz). The alkoxycarbonyl group having 2 to 20 carbon atoms is preferably an alkoxy group having 2 to 15 carbon atoms, and more preferably a tert-butoxycarbonyl group (Boc). The aryloxycarbonyl group having 7 to 20 carbon atoms is preferably an aryloxycarbonyl group having 7 to 15 carbon atoms, and more preferably a benzyloxycarbonyl group (Cbz group). R is preferably a benzyl group (Bn).
R ′ is preferably an alkyl group having 1 to 20 carbon atoms, more preferably an alkyl group having 1 to 15 carbon atoms, still more preferably an alkyl group having 1 to 10 carbon atoms, and still more preferably a methyl group.

(C) The hydroxycarboxylic acid having 6 or more carbon atoms may be a hydroxycarboxylic acid having 6 to 30 carbon atoms. Examples of the hydroxycarboxylic acid having 6 or more carbon atoms include α-hydroxycarboxylic acids, preferably α-hydroxycarboxylic acids having 6 to 30 carbon atoms. Examples of the derivative of a hydroxycarboxylic acid having 6 or more carbon atoms include salts of the carboxylic acid and esters of the carboxylic acid. (C) is preferably a hydroxycarboxylic acid ester having 6 or more carbon atoms. Examples of the compound (C) include compounds represented by the following formula.

[In the formula, R represents a hydrocarbon group having 1 to 20 carbon atoms, preferably an alkyl group having 1 to 20 carbon atoms, and further an alkyl group having 1 to 15 carbon atoms, or an alkenyl group having 1 to 20 carbon atoms and further 1 to 15 carbon atoms. , R ′ is a hydrocarbon group having 1 to 20 carbon atoms, preferably an alkyl group having 1 to 20 carbon atoms, more preferably an alkyl group having 1 to 15 carbon atoms, an alkenyl group having 1 to 20 carbon atoms, further an alkenyl group having 1 to 15 carbon atoms, or carbon. An aryl group having 6 to 20 carbon atoms and 6 to 15 carbon atoms. However, R and R ′ are selected so that the total number of carbon atoms in the compound is 6 or more, preferably 6 to 30, and more preferably 6 to 20. ]
In the above formula, the hydrocarbon group for R or R ′ may have a ring structure. The ring structure may have a substituent.

In addition, examples of the hydroxycarboxylic acid having 6 or more carbon atoms include saturated steroids having a hydroxyl group and a carboxyl group such as lithocholic acid.

The hydroxy compound having 6 or more carbon atoms is preferably N-benzyl-3-hydroxypyrrolidine, N-benzyl-4-hydroxyproline, or lactic acid ester having 6 or more carbon atoms from the viewpoint of easy availability of raw materials. The lactic acid ester is preferably an ester of lactic acid and an alcohol having 3 to 20 carbon atoms.

(Fluorinating agent)
In the present invention, a compound represented by the formula (1): R ¹ SO ₂ F is used as the fluorinating agent.
In formula (1), R ¹ represents a methyl group, an ethyl group, or an aromatic group. Examples of the aromatic group include a phenyl group, a 1-naphthyl group, and a 2-naphthyl group. These aromatic groups may have a substituent such as a methyl group or an ethyl group.

Specific examples of the compound represented by the formula (1) include aliphatic sulfonic acid fluorides such as methanesulfonic acid fluoride and ethanesulfonic acid fluoride; aromatic sulfonic acid fluorides such as benzenesulfonic acid fluoride and p-toluenesulfonic acid fluoride; Etc. Among these, methanesulfonic acid fluoride and ethanesulfonic acid fluoride are preferable, and methanesulfonic acid fluoride is more preferable from the viewpoint of economically high yield of the target product and ease of handling.

The compound shown by Formula (1) can be manufactured using a conventionally well-known method.
For example, aliphatic sulfonic acid fluoride is prepared by a method in which sulfonic acid chloride is brought into contact with an alkali metal fluoride such as sodium fluoride or potassium fluoride in an aqueous solvent (Japanese Patent Laid-Open No. 6-263715), It can be produced by a method of contacting with potassium hydrogen difluoride in an aqueous solvent (Journal of Chemical Society, 173 (1956)) or the like.

Aromatic sulfonic acid fluoride uses aromatic sulfonic acid chloride as a starting material, phase transfer catalyst in the presence of polyethylene glycol or 18-crown-6-ether, and potassium fluoride as a fluorinating agent. Method of fluorination (Chemistry
Letters, 283 (1978), Journal of Organic Chemistry, Vol. 42, 2031 (1977)) or the like.
In the present invention, an inexpensive and easily available fluorinating agent as described above is used.

The amount of the fluorinating agent used may be 1 equivalent or more with respect to the raw material hydroxy compound, preferably 1.0 to 5.0 equivalent, more preferably 1.1 to 2.0 equivalent. . If the amount of the fluorinating agent used is too small relative to the raw material hydroxy compound, the raw material is wasted, which is not preferable. On the other hand, if the fluorinating agent is used in excess, the fluorinating agent will not be consumed efficiently.

(base)
The base used in the present invention is a base selected from the group consisting of an amidine base and a phosphazene base.
An amidine base is a basic organic compound having a —N—C═N— skeleton. The amidine base may be an open-chain compound or an alicyclic ring, bicyclic ring and tricyclic ring containing 4 to 8, preferably 5 or 6, ring members. The amidine base used in the present invention is preferably a compound containing 4 to 20, more preferably 4 to 14, and still more preferably 4 to 10 carbon atoms.
Specific examples of amidine bases include 7-methyl-1,5,7-triazabicyclo [4.4.0] dec-5-ene (MTBD); diazabicyclo [4.3.0] non-5-ene. (DBN), 1,8-diazabicyclo [5.4.0] -undec-7-ene (DBU), and the like, but are not limited thereto.

A phosphazene base is a basic organic compound having a (—N—) ₃ P═N— skeleton in the molecule. Examples of the phosphazene base include t-butyliminotris (dimethylaminophosphorane) (abbreviation: P ₁ -t-Bu), 1-t-butyl-4,4,4-tris (dimethylamino) -2,2 -Bis [tris (dimethylamino) phosphoranylideneamino] -2Λ ⁵ , 4Λ ⁵ -catenadi (phosphazene) (abbreviation: P ₄ -t-Bu) and the like, but are not limited thereto.

Among these, an amidine base is preferable from the viewpoint of availability, and an amidine base having a skeleton represented by the following formula (3) is more preferable.

(N represents an integer of 0 or 2)
Specific examples of the compound having the skeleton include 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), 1,5-diazabicyclo [4.3.0] non-5-ene. (DBN), with DBU being particularly preferred.

The amount of the base used is preferably 1 to 10 equivalents, more preferably 1.1 to 5.0 equivalents with respect to the raw material hydroxy compound. If the amount of base used is too small, the yield will be unfavorable. On the other hand, when the amount used is too large, the viscosity of the reaction solution increases, and the treatment after the reaction ends becomes troublesome.

In the present invention, the base is preferably present as an acid salt with hydrogen fluoride from the viewpoint of improving the yield. In this case, the base is preferably the amidine base of the formula (3). Examples of the acid salt of the base with hydrogen fluoride include DBU-hydrogen trifluoride / acid salt. This is an acid salt of hydrogen equivalent of 3 equivalents to 1 equivalent of DBU. The acid salt may be a complex salt.

The amount of the acid salt of the base with hydrogen fluoride used is preferably from 0.1 to 5.0 equivalents, more preferably from 0.5 to 2.0 equivalents, based on the raw material hydroxy compound. It is preferable to use an acid salt of the base and hydrogen fluoride.

In the present invention, it is preferable to use both the base and an acid salt of hydrogen fluoride of the base. In that case, the molar ratio of (the base) / (acid salt of the base and hydrogen fluoride) is preferably 1 to 20, and more preferably 1 to 5.

(reaction)
In the present invention, the fluorination of a hydroxy compound having 6 or more carbon atoms can be carried out without a solvent or in an organic solvent.

Organic solvents include toluene, ethyl acetate, methylene chloride, acetonitrile and the like. The organic solvent is preferably toluene or acetonitrile.

When the raw material hydroxy compound is liquid at the reaction temperature and can be obtained at a low cost, fluorination can be performed in the absence of a solvent.

In the present invention, the base can be added to the reaction system to carry out the reaction.
In the present invention, the reaction can be performed by adding the base and an acid salt of the base and hydrogen fluoride to a reaction system.
About the usage-amount of each component used for the manufacturing method of this invention, you may calculate the said equivalent and molar ratio on the basis of preparation amount.

The mixing order of the raw material hydroxy compound, the base, and the fluorinating agent is not particularly limited, but from the viewpoint of obtaining the target product with good yield, the raw material hydroxy compound and the fluorinating agent are mixed, and the resulting mixture contains a base. Is preferably added (dropped). The base may be added all at once or in small portions.

The reaction temperature is usually 50 ° C. to 150 ° C., preferably 60 ° C. to 150 ° C., more preferably 60 ° C. to 100 ° C.
In the present invention, it is preferable that the mixture of the raw material hydroxy compound and the fluorinating agent is preliminarily set to a temperature within the above range, then a base is dropped, and the reaction is further allowed to proceed within the above temperature range after the dropping is completed.
That is, the reaction is preferably performed by adding the base to the mixture of the hydroxy compound and the fluorinating agent at 60 ° C. to 150 ° C.
If the reaction start temperature and the subsequent reaction temperature are lower than the above temperature range, there is a risk that problems such as a low raw material conversion rate and a very long reaction time may occur. On the other hand, when the reaction start temperature and the reaction temperature are higher than the above temperature range, depending on the type of raw material hydroxy compound used, the hydroxy compound distills together with the product fluorinated compound, leading to a decrease in yield. Cheap.

The reaction time is usually 1 to 48 hours, preferably 3 to 20 hours, although it depends on the raw material hydroxy compound used and the type of base or base acid salt. When the reaction time is too short, the conversion rate of the raw material hydroxy compound is lowered, and the yield of the target product is lowered. On the other hand, if the reaction time is too long, energy costs are wasted, which is not preferable.

There is no particular limitation on the post-treatment, but usually the reaction completion solution is poured into water or an aqueous solution of an alkali metal inorganic base (for example, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, etc.), and an organic solvent ( The crude product can be obtained by extraction with toluene, ethyl acetate, methylene chloride or the like. The target fluorinated compound can be further purified by distillation, recrystallization, activated carbon treatment, silica gel chromatography, or the like, if necessary.

(Fluorinated compounds)
As described above, a fluorinated compound represented by the formula (2): R ² -F (R ² represents a group obtained by removing a hydroxy group from a hydroxy compound having 6 or more carbon atoms) can be produced.
In formula (2), R ² represents a group obtained by removing a hydroxy group from a hydroxy compound having 6 or more carbon atoms.

Specific examples of the fluorinated compound represented by the formula (2) include 1-fluorohexane, 2-fluorohexane, 2-fluorooctane, benzyl fluoride, 1-phenyl-1-fluoroethane, 2-phenyl-1- Fluoroethane, 1-naphthyl-1-fluoroethane, 4-fluoro-α-methylbenzyl fluoride, 4-chloro-α-methylbenzyl fluoride, 4-bromo-α-methylbenzyl fluoride, 4-methyl-α -Methylbenzyl fluoride, 4-methoxy-α-methylbenzyl fluoride, 4-amino-α-methylbenzyl fluoride, N-benzyl-3-fluoropyrrolidine, N-benzyl-4-fluoroproline.
Among these, from the viewpoint of easily obtaining the effects of the present invention, 2-fluorooctane, 1-phenyl-1-fluoroethane, N-benzyl-3-fluoropyrrolidine, N-benzyl-4-fluoroproline, 2- Fluoropropionic acid esters are preferred. These fluorinated compounds can be produced using 2-octanol, 1-phenylethanol, N-benzyl-3-hydroxypyrrolidine, N-benzyl-4-hydroxyproline, and lactic acid ester as raw material hydroxy compounds.

As described above, according to the production method of the present invention, using a raw material and a fluorinating agent that can be obtained industrially at low cost, without using a solvent, it is possible to safely, easily, at low cost and with high yield. The fluorinated compound can be produced at a rate.

In the present invention, a hydroxy compound having 6 or more carbon atoms and a fluorinating agent represented by the formula (1): R ¹ SO ₂ F (R ¹ represents a methyl group, an ethyl group or an aromatic group) are mixed. Then, a base selected from the group consisting of an amidine base and a phosphazene base, or an acid salt of the base and hydrogen fluoride of the base is added to the mixture, and a fluorination reaction is performed. ^A method for producing a fluorinated compound is preferred which obtains a fluorinated compound represented by ^2- F (R ² represents a group obtained by removing a hydroxy group from a hydroxy compound having 6 or more carbon atoms).

(Manufacturing method according to another aspect of the present invention)
The present invention also provides a hydroxy compound having 3 or more carbon atoms in the presence of a base selected from the group consisting of an amidine base and a phosphazene base and an acid salt of hydrogen fluoride with the formula (1): R ¹ SO ₂ It is fluorinated with a fluorinating agent represented by F (R ¹ represents a methyl group, an ethyl group or an aromatic group). Formula (2): R ² -F (R ² is the number of carbon atoms) And represents a group obtained by removing a hydroxy group from three or more hydroxy compounds.).

Examples of the hydroxy compound having 3 or more carbon atoms include hydroxy compounds having 3 to 5 carbon atoms and hydroxy compounds having 6 or more carbon atoms. The hydroxy compound having 6 or more carbon atoms is as described above.
Examples of the hydroxy compound having 3 to 5 carbon atoms include alcohols having 3 to 5 carbon atoms. Examples of the alcohol having 3 to 5 carbon atoms include monohydric alcohols having 3 to 5 carbon atoms and polyhydric alcohols having 3 to 5 carbon atoms. Examples of the monohydric alcohol having 3 to 5 carbon atoms include monovalent saturated alcohols having 3 to 5 carbon atoms and monovalent unsaturated alcohols having 3 to 5 carbon atoms.
Examples of the alcohol having 3 to 5 carbon atoms include alcohols having 3 carbon atoms such as 1-propanol and 2-propanol; carbon numbers such as 1-butanol, 2-butanol, isobutanol, t-butanol, cyclobutanol, and methallyl alcohol. 4 monohydric alcohols; 1-pentanol, 2-pentanol, 3-pentanol, 3-methyl-1-butanol, 3-methyl-2-butanol, 2-methyl-1-butanol, 2-methyl-2 -Monohydric alcohols having 5 carbon atoms such as butanol, 2,2-dimethyl-1-propanol and cyclopentanol; polyhydric alcohols having 3 to 5 carbon atoms such as propylene glycol and the like.
Among these, in the present invention, monohydric alcohols having 4 or 5 carbon atoms are preferable from the viewpoint of ease of handling and usefulness of the fluorinated compound to be produced, and 2-pentanol, 3-pentanol, cyclopent Tanol, 1-butanol, 2-butanol, isobutanol, t-butanol, and methallyl alcohol are more preferable. A dihydric alcohol having 3 to 5 carbon atoms such as propylene glycol is also preferred.

Further, examples of the hydroxy compound having 3 to 5 carbon atoms include hydroxycarboxylic acid esters having 3 to 5 carbon atoms. As the hydroxycarboxylic acid ester having 3 to 5 carbon atoms, a lactic acid ester having 4 or 5 carbon atoms is preferable, and ethyl lactate is more preferable.

A hydroxy compound having 3 or more carbon atoms, for example, a hydroxy compound having 3 to 5 carbon atoms, may have a functional group other than a hydroxyl group such as a ketone, an ether, an amide, or an amine.

In this method, an acid salt of the base and hydrogen fluoride is used. Specific examples and use conditions of the acid salt of the base and hydrogen fluoride are as described above. Other compounds and conditions are also as described above.

In this method, a hydroxy compound having 3 or more carbon atoms and a fluorinating agent represented by the formula (1): R ¹ SO ₂ F (R ¹ represents a methyl group, an ethyl group or an aromatic group) are mixed. Then, an acid salt of hydrogen fluoride of a base selected from the group consisting of an amidine base and a phosphazene base is added to the mixture, and a fluorination reaction is carried out to obtain a formula (2): R ² -F (R ² is carbon A method for producing a fluorinated compound is preferred, which represents a group obtained by removing a hydroxy group from a hydroxy compound of several formulas or more).

(Aspect of the present invention)
The aspect of the manufacturing method of the fluorinated compound of this invention is shown below. The matters relating to the method for producing the fluorinated compound of the present invention described so far can be appropriately applied to these embodiments.
<1a>
A hydroxy compound having 6 or more carbon atoms in the presence of a base selected from the group consisting of an amidine base and a phosphazene base in an organic solvent is represented by the formula (1): R ¹ SO ₂ F (R ¹ is a methyl group or an ethyl group) Or represents an aromatic group.), Which is fluorinated by a fluorinating agent represented by the formula (2): R ² -F (R ² is a hydroxy compound having 6 or more carbon atoms, and the hydroxy group is removed) A method for producing a fluorinated compound represented by:

<1b>
The number of 6 or more hydroxy compounds of carbon, the absence of a solvent in the presence of a base in selected from the group consisting of amidine bases and phosphazene base of formula ^{(1): R 1 SO 2} F (R 1 is a methyl group, an ethyl group Or represents an aromatic group.), Which is fluorinated by a fluorinating agent represented by the formula (2): R ² -F (R ² is a hydroxy compound having 6 or more carbon atoms, and the hydroxy group is removed) A method for producing a fluorinated compound represented by:

<1c>
A hydroxy compound having 6 or more carbon atoms in the presence of a base selected from the group consisting of an amidine base and a phosphazene base and an acid salt with hydrogen fluoride of the base in an organic solvent, is represented by the formula (1): R ¹ SO _It is fluorinated with a fluorinating agent represented by ₂ F (R ¹ represents a methyl group, an ethyl group or an aromatic group). Formula (2): R ² -F (R ² is carbon This represents a group obtained by removing a hydroxy group from a hydroxy compound of formula 6 or more).

<1d>
In the presence of a base selected from the group consisting of an amidine base and a phosphazene base and an acid salt with hydrogen fluoride of the base in the absence of a solvent, the hydroxy compound having 6 or more carbon atoms is represented by the formula (1): R ¹ SO _It is fluorinated with a fluorinating agent represented by ₂ F (R ¹ represents a methyl group, an ethyl group or an aromatic group). Formula (2): R ² -F (R ² is carbon This represents a group obtained by removing a hydroxy group from a hydroxy compound of formula 6 or more).

<2a>
A hydroxy compound having 3 or more carbon atoms is added in the presence of an acid salt of a base selected from the group consisting of an amidine base and a phosphazene base and an acid salt of hydrogen fluoride in an organic solvent with the formula (1): R ¹ SO ₂ F ( R ¹ represents a methyl group, an ethyl group, or an aromatic group), and is fluorinated with a fluorinating agent represented by the formula (2): R ² -F (R ² is a carbon number of 3 or more) Represents a group in which a hydroxy group is removed from the hydroxy compound.).

<2b>
In the presence of an acid salt of a base selected from the group consisting of an amidine base and a phosphazene base and an acid salt of hydrogen fluoride with no solvent, the hydroxy compound having 3 or more carbon atoms is represented by the formula (1): R ¹ SO ₂ F ( R ¹ represents a methyl group, an ethyl group, or an aromatic group), and is fluorinated with a fluorinating agent represented by the formula (2): R ² -F (R ² is a carbon number of 3 or more) Represents a group in which a hydroxy group is removed from the hydroxy compound.).

<2c>
A hydroxy compound having 3 or more carbon atoms in the presence of an acid salt of a base and hydrogen fluoride selected from the group consisting of an amidine base and a phosphazene base in the presence of an organic solvent and the base is represented by the formula (1): R ¹ SO _It is fluorinated with a fluorinating agent represented by ₂ F (R ¹ represents a methyl group, an ethyl group or an aromatic group). Formula (2): R ² -F (R ² is carbon A group obtained by removing a hydroxy group from a hydroxy compound of formula 3 or more).

<2d>
A hydroxy compound having 3 or more carbon atoms is added in the presence of an acid salt of a base selected from the group consisting of an amidine base and a phosphazene base and hydrogen fluoride in the absence of a solvent and the base (1): R ¹ SO _It is fluorinated with a fluorinating agent represented by ₂ F (R ¹ represents a methyl group, an ethyl group or an aromatic group). Formula (2): R ² -F (R ² is carbon A group obtained by removing a hydroxy group from a hydroxy compound of formula 3 or more).

<2e>
A hydroxy compound having 3 to 5 carbon atoms is represented by the formula (1): R ¹ SO ₂ F in the presence of an acid salt of hydrogen fluoride and a base selected from the group consisting of an amidine base and a phosphazene base in an organic solvent. (R ¹ represents a methyl group, an ethyl group, or an aromatic group), and is fluorinated by a fluorinating agent represented by the formula (2): R ² -F (R ² has 3 carbon atoms) Represents a group obtained by removing a hydroxy group from the above hydroxy compound.).

<2f>
A hydroxy compound having 3 to 5 carbon atoms is represented by the formula (1): R ¹ SO ₂ F in the presence of an acid salt of hydrogen fluoride and a base selected from the group consisting of an amidine base and a phosphazene base in the absence of a solvent. (R ¹ represents a methyl group, an ethyl group, or an aromatic group), and is fluorinated by a fluorinating agent represented by the formula (2): R ² -F (R ² has 3 carbon atoms) Represents a group obtained by removing a hydroxy group from the above hydroxy compound.).

<2g>
In the presence of an acid salt of a base selected from the group consisting of an amidine base and a phosphazene base with an acid salt of hydrogen fluoride and the base in an organic solvent, the hydroxy compound having 3 to 5 carbon atoms is represented by the formula (1): R ¹ It is fluorinated by a fluorinating agent represented by SO ₂ F (R ¹ represents a methyl group, an ethyl group or an aromatic group). Formula (2): R ² -F (R ² is A group obtained by removing a hydroxy group from a hydroxy compound having 3 or more carbon atoms).

<2d>
A hydroxy compound having 3 to 5 carbon atoms is represented by the formula (1): R ^{1 in} the presence of an acid salt of hydrogen fluoride and a base selected from the group consisting of an amidine base and a phosphazene base in the absence of a solvent. It is fluorinated by a fluorinating agent represented by SO ₂ F (R ¹ represents a methyl group, an ethyl group or an aromatic group). Formula (2): R ² -F (R ² is A group obtained by removing a hydroxy group from a hydroxy compound having 3 or more carbon atoms).

<Method for separating and recovering amidine base>
The present invention also provides the following formula (4):

(In the formula, R ¹ represents a methyl group, an ethyl group or an aromatic group, and n is 0 or 2.)
From the amidine base-sulfonic acid complex represented by the following formula (3)

(Wherein n is 0 or 2), wherein the amidine base is separated and recovered,
A step (I) of adding an aqueous alkali solution to a solution obtained by dissolving an amidine base-sulfonic acid complex in an aromatic hydrocarbon to precipitate an alkali metal sulfonate;
Water is added to the solution in which the alkali metal sulfonate salt obtained in step (I) is precipitated to dissolve the alkali metal salt of sulfonate, and the aqueous layer in which the alkali metal salt of sulfonic acid is dissolved and an amidine base are included. Separating into a layer of an aromatic hydrocarbon solution and removing the aqueous layer in which the alkali metal sulfonate is dissolved, and (II)
Step (III) of distilling off aromatic hydrocarbons from the aromatic hydrocarbon solution containing the amidine base obtained in Step (II)
Have
The amidine base-sulfonic acid complex is a hydroxy compound having 6 or more carbon atoms represented by the following formula (3):

(Wherein n is 0 or 2), in the presence of an amidine base, the formula (1): R ¹ SO ₂ F (R ¹ represents a methyl group, an ethyl group or an aromatic group. ) Obtained from a reaction mixture in which a reaction for fluorination with a fluorinating agent represented by
A method for separating and recovering amidine bases is disclosed.

The amidine base-sulfonic acid complex used in the present invention is represented by the amidine base represented by the formula (4) and the formula: R ¹ —SO ₃ H (R ¹ represents the same meaning as described above). It is a salt composed of sulfonic acid. Specific examples include DBU-methanesulfonic acid complex, DBU-ethanesulfonic acid complex, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN) -methanesulfonic acid complex, DBN-ethanesulfonic acid. Aliphatic sulfonic acid complexes such as complexes; aromatic sulfonic acid complexes such as DBU-benzenesulfonic acid complexes, DBU-p-toluenesulfonic acid complexes, DBN-benzenesulfonic acid complexes, DBN-p-toluenesulfonic acid complexes; Can be mentioned.
Among these, an aliphatic sulfonic acid complex is preferable and a DBU-methanesulfonic acid complex is particularly preferable from the viewpoint that the effects of the present invention can be obtained more remarkably.

The amidine base-sulfonic acid complex used in the present invention is obtained from a reaction mixture obtained by performing a reaction of fluorinating a hydroxy compound having 6 or more carbon atoms with a fluorinating agent represented by the above formula (3). It is. The amidine base-sulfonic acid complex is preferably obtained by the method for producing a fluorinated compound of the present invention.

(Process (I))
In the present invention, step (I) is a step of dissolving an amidine base-sulfonic acid complex in an aromatic hydrocarbon and adding an aqueous alkali solution to the resulting solution to precipitate an alkali metal sulfonate. .

The aromatic hydrocarbon used in the present invention is preferably one that dissolves the amidine base-sulfonic acid complex to form an azeotropic mixture with water. Specific examples include alkyl-substituted benzenes such as benzene, toluene, xylene and ethylbenzene; halogen-substituted benzenes such as fluorobenzene, chlorobenzene and dichlorobenzene. Among these, alkyl-substituted benzenes are preferable, and toluene that can be distilled off at a relatively low temperature is more preferable.

The amount of aromatic hydrocarbon used is usually 0.7 to 1 ml per 1 g of amidine base-sulfonic acid complex, although it depends on the reaction scale and the like. If the amount of aromatic hydrocarbon used is too small, the extraction efficiency of the amidine base may be deteriorated. On the other hand, if the amount used is too large, it takes a lot of time to distill off the aromatic hydrocarbons in the subsequent step, resulting in poor productivity.

As the alkaline aqueous solution used in the present invention, when added to an aromatic hydrocarbon solution of an amidine base-sulfonic acid complex, the sulfonic acid salt is formed by forming a salt with the sulfonic acid constituting the amidine base-sulfonic acid complex. If it precipitates, there will be no restriction | limiting in particular.
Among these, from the viewpoint of excellent affinity with water, an aqueous solution of an alkali metal hydroxide such as sodium hydroxide, potassium hydroxide or cesium hydroxide is preferable, and an aqueous solution of potassium hydroxide or cesium hydroxide is more preferable and inexpensive. In particular, an aqueous solution of potassium hydroxide having a high solubility in water of the resulting sulfonate is particularly preferable.

Alkali metal hydroxides themselves usually exist as pellets or flaky solids, but are used as aqueous solutions from the viewpoint of industrial ease of handling.
The concentration of the aqueous alkaline solution used is not particularly limited, but is preferably about 10% to 50% by weight. If the concentration of the alkaline aqueous solution is too low, a large amount of alkaline aqueous solution is required to neutralize the sulfonic acid in the amidine base-sulfonic acid complex and liberate the amidine base. The effect becomes smaller and the recovery rate becomes worse. On the other hand, if the concentration of the aqueous alkaline solution is too high, there is a risk that the heat generated becomes large when the sulfonic acid of the amidine base-sulfonic acid complex is neutralized, resulting in danger.

The amount of alkali used in the alkaline aqueous solution is usually 0.9 to 1.5 equivalents relative to the amidine base-sulfonic acid complex. If the amount of alkali (alkaline aqueous solution) used is too small, the neutralization reaction with sulfonic acid will not be completed, and the recovery rate of amidine base will deteriorate. On the other hand, if the amount of alkali (alkaline aqueous solution) used is too large, the treatment of the waste liquid becomes troublesome.

As a method of adding an alkaline aqueous solution to an aromatic hydrocarbon solution of an amidine base-sulfonic acid complex, a solution temperature range from 0 ° C. to room temperature (25 ° C. ± 10 ° C., the same applies hereinafter) while stirring the solution. And the method of dripping alkaline aqueous solution is preferable. If the addition temperature is too low, the aromatic hydrocarbon solution of the amidine base-sulfonic acid complex becomes viscous and the neutralization reaction between the sulfonic acid and the alkali does not proceed smoothly. On the other hand, when the addition temperature is too high, the neutralization reaction between the sulfonic acid and the alkali proceeds rapidly, which may cause problems such as bumping.

While stirring an aromatic hydrocarbon solution of an amidine base-sulfonic acid complex, when an alkaline aqueous solution is added dropwise at 0 ° C. to room temperature, a neutralization reaction proceeds, and the amidine base is liberated. A salt precipitates out.

(Process (II))
In the present invention, in the step (II), water is added to the solution obtained by precipitation of the alkali metal sulfonate salt obtained in the step (I) to dissolve the alkali metal salt of sulfonic acid, This is a step of removing the aqueous layer in which is dissolved.
When water is added to the solution in which the alkali metal sulfonate salt is deposited, it is separated into two layers: an aqueous layer in which the alkali metal salt of sulfonic acid is dissolved and an aromatic hydrocarbon layer (organic layer) in which the liberated amidine base is dissolved. .
The amount of water to be added may be an amount necessary for dissolving the alkali metal sulfonate. If the amount of water to be added is too small, the alkali metal salt of the sulfonic acid will remain undissolved, making it difficult to separate the two layers from the organic layer in which the liberated amidine base is dissolved (extracted). On the other hand, when the amount of water to be added is too large, the effect of extracting the amidine base is reduced, resulting in problems such as poor recovery.

By removing the aqueous layer in which the alkali metal salt of the lower sulfonic acid is dissolved, an aromatic hydrocarbon solution containing the extracted amidine base can be obtained.
In addition, since the amidine base is water-soluble, in order to increase the extraction efficiency of the amidine base, an extraction operation may be performed by further adding an aromatic hydrocarbon to the aqueous layer in which the alkali metal salt of the sulfonic acid is dissolved. good.

(Step (III))
Step (III) of the present invention is a step of distilling off aromatic hydrocarbons from the aromatic hydrocarbon solution containing the amidine base obtained in step (II).
Although there is no restriction | limiting in particular as a method of distilling off aromatic hydrocarbon from the aromatic hydrocarbon solution containing an amidine base, For example, the method of using concentration apparatuses, such as a rotary evaporator, under reduced pressure is mentioned.
Thereby, the amidine base can be recovered.

In addition, the amidine bases thus recovered may contain a small amount of tar components and salts (alkali metal salt of sulfonic acid). It is preferable to provide a purification step such as vacuum distillation.

(Process (IV))
When the recovered amidine base is reused, the amidine base preferably contains no water. However, the amidine base aromatic hydrocarbon solution obtained in step (II) often contains moisture. Therefore, it is preferable to provide a step (IV) for removing moisture from the aromatic hydrocarbon solution containing the amidine base obtained in the step (II) after the step (II) and before the step (III).

As a method for removing moisture from an aromatic hydrocarbon solution containing an amidine base, a dehydrating agent such as molecular sieve, anhydrous magnesium sulfate, or anhydrous sodium sulfate is added to the aromatic hydrocarbon solution, and moisture is added to the dehydrating agent. Examples of the method include a method of separating and removing the dehydrating agent that has absorbed water after absorption, a method of removing water using a Dean-Stark water separator, and the latter method is preferred. According to the Dean-Stark water separation device, water and aromatic hydrocarbons are azeotroped by heating by utilizing the property that aromatic hydrocarbons azeotrope with water, and moisture can be efficiently removed.

The azeotropic temperature of aromatic hydrocarbon and water is, for example, as follows. Toluene: water = 80.1: 19.9 (weight ratio, the same applies hereinafter) (boiling point: 85 ° C.), o-xylene: water = 50.1: 49.9 (boiling point 93.5 ° C.), m- Xylene: water = 60.0: 40.0 (boiling point: 94.5 ° C.), ethylbenzene: water = 67.0: 33.0 (boiling point: 92 ° C.), chlorobenzene: water = 71.6: 28.4 ( (Boiling point: 90.2 ° C.) (both under atmospheric pressure) (Chemical Handbook revised 3rd edition, Basic II, edited by the Chemical Society of Japan).

For example, when toluene is used as the aromatic hydrocarbon, the azeotropic point is 85 ° C. when the weight ratio of toluene and water is 80.1: 19.9. Therefore, using a Dean-Stark water separator, the toluene solution in which the amidine base is dissolved is continuously heated at a temperature higher than 85 ° C., and water is removed by azeotropy with toluene. When no change is observed in the amount of distilled water, heating is stopped, and then step (III) may be performed.

In the method for separating and recovering amidine base described above, the amidine base-sulfonic acid complex is preferably a 1,8-diazabicyclo [5.4.0] undec-7-ene-methanesulfonic acid complex.
In the method for separating and recovering amidine base described above, the water contained in the aromatic hydrocarbon solution containing the amidine base obtained in step (II) after step (II) and before step (III). The step (IV) of removing can be included.
In the method for separating and recovering amidine base described above, the step (IV) uses a Dean-Stark water separator to remove the water contained in the aromatic hydrocarbon solution containing the amidine base obtained in step (II). It is preferable to use and remove.
In the method for separating and recovering amidine base described above, the amidine base is preferably 1,8-diazabicyclo [5.4.0] undec-7-ene.

According to the present invention, an amidine base can be easily and efficiently separated and recovered from an amidine base-sulfonic acid complex produced in a reaction in which a hydroxy compound is fluorinated with sulfonic acid fluoride in the presence of an amidine base. This reduces the load on the environment while reducing the amount of amidine base-sulfonic acid complex, which is a very viscous oil that is difficult to handle and difficult to dispose of, and improves handling. .

<How to use recovered amidine base>
In the present invention, a hydroxy compound having 6 or more carbon atoms is represented by the formula (1): R ¹ SO ₂ F (R ¹ represents a methyl group, an ethyl group, or an aromatic group) in the presence of a base. In a reaction for producing a fluorinated compound represented by the formula (2): R ² -F (R ² is a group obtained by removing a hydroxy group from a hydroxy compound having 6 or more carbon atoms) by fluorination with a fluorinating agent, Disclosed is a method of using the recovered amidine base using the amidine base separated and recovered by the method of the present invention as a base.

Specific examples and preferred embodiments of the hydroxy compound having 6 or more carbon atoms and the fluorinating agent of formula (1) used in this method of use, the amount of use, and the like are the same as in the method for producing the fluorinated compound of the present invention. . In addition, the reaction for producing the fluorinated compound can be carried out without a solvent or in an organic solvent.

The amount of the recovered amidine base used is preferably 1 to 3 equivalents, more preferably 1.1 to 2.0 equivalents, relative to the raw material hydroxy compound. If the amount of base used is too small, the yield will be unfavorable. On the other hand, when the amount used is too large, the viscosity of the reaction solution increases, and the treatment after the reaction ends becomes troublesome.

The order of mixing the hydroxy compound, the recovered amidine base, and the fluorinating agent is not particularly limited, but from the viewpoint of obtaining the target product with good yield, the raw material hydroxy compound and the fluorinating agent are mixed, and the resulting mixture is It is preferable to add (drop) a base. The base may be added all at once or in small portions.

The reaction temperature is usually 50 ° C. to 150 ° C., preferably 60 ° C. to 150 ° C., more preferably 60 ° C. to 100 ° C.
In the present invention, it is preferable that the mixture of the raw material hydroxy compound and the fluorinating agent is preliminarily set to a temperature within the above range, then a base is dropped, and the reaction is further allowed to proceed within the above temperature range after the dropping is completed.
If the reaction start temperature and the subsequent reaction temperature are lower than the above temperature range, there is a risk that problems such as a low raw material conversion rate and a very long reaction time may occur. On the other hand, when the reaction start temperature and the reaction temperature are higher than the above temperature range, depending on the type of raw material hydroxy compound used, the hydroxy compound distills together with the product fluorinated compound, leading to a decrease in yield. Cheap.

The reaction time is usually 1 to 48 hours, preferably 3 to 20 hours, although it depends on the raw material hydroxy compound and the type of base used. If the reaction time is too short, the conversion rate of the raw material hydroxy compound is lowered, resulting in a decrease in the yield of the desired product. On the other hand, if the reaction time is too long, energy costs are wasted, which is not preferable.

After completion of the reaction, if the product (target product) has a boiling point lower than the reaction temperature, it is connected to a reaction vessel connected to a reaction vessel and cooled with a refrigerant such as dry ice ethanol. Can be collected and recovered.
When the product (target product) has a boiling point higher than the reaction temperature, the product can be recovered in a receiver cooled with a refrigerant or the like under reduced pressure after the reaction is stopped. In this case, the recovered unreacted hydroxy compound can be reused as a raw material.

The fluorinated compound collected in the receiver can be further purified by distillation purification or the like as necessary.

As described above, a fluorinated compound represented by the formula (2): R ² -F (R ² represents a group obtained by removing a hydroxy group from a hydroxy compound having 6 or more carbon atoms) can be produced.
In formula (2), R ² represents a group obtained by removing a hydroxy group from a hydroxy compound having 6 or more carbon atoms.

Specific examples of the fluorinated compound represented by the formula (2) include 1-fluorohexane, 2-fluorohexane, 2-fluorooctane, benzyl fluoride, 1-phenyl-1-fluoroethane, 2-phenyl-1- Fluoroethane, 1-naphthyl-1-fluoroethane, 4-fluoro-α-methylbenzyl fluoride, 4-chloro-α-methylbenzyl fluoride, 4-bromo-α-methylbenzyl fluoride, 4-methyl-α -Methylbenzyl fluoride, 4-methoxy-α-methylbenzyl fluoride, 4-amino-α-methylbenzyl fluoride, N-benzyl-3-fluoropyrrolidine, N-benzyl-4-fluoroproline, 2-fluoropropion Examples include acid esters.
Among these, from the viewpoint of easily obtaining the effects of the present invention, 2-fluorooctane, 1-phenyl-1-fluoroethane, N-benzyl-3-fluoropyrrolidine, N-benzyl-4-fluoroproline, 2- Fluoropropionic acid esters are preferred. These fluorinated compounds can be produced using 2-octanol, 1-phenylethanol, N-benzyl-3-hydroxypyrrolidine, N-benzyl-4-hydroxyproline, and lactic acid ester as raw material hydroxy compounds.

Thus, according to the method of use of the present invention, a fluorinated compound can be produced simply and at low cost and in high yield using the recovered amidine base.
According to the present invention, the cost can be reduced by collecting and using a very expensive amidine base.
Example

Hereinafter, the embodiments of the present invention will be specifically described by way of examples. However, the present invention is not limited to these examples.

[Example 1]
In a glass reaction vessel,

2.60 g (20.00 mmol, 1.00 eq) of a hydroxy compound represented by formula (2), 20.0 mL of toluene, 3.92 g (40.00 mmol, 2.00 eq) of methanesulfonic acid fluoride as a fluorinating agent were added, and 30 at room temperature was added. Stir for minutes. 2.78 g (13.10 mmol, 0. 1) of DBU-hydrogen trifluoride / acid salt (acid salt obtained by reacting 1 equivalent of DBU and 3 equivalents of hydrogen fluoride, the same shall apply hereinafter) by heating the internal temperature to 60 ° C. 65 eq) and 8.67 g (56.95 mmol, 2.84 eq) of DBU were added dropwise and stirred for 24 hours. By adding 20.0 mL of water to the reaction completion liquid and separating the organic layer,

A crude product of a fluorinated compound represented by the formula (1) was obtained as a toluene solution. The conversion rate of the reaction was measured by gas chromatography and found to be 100%. The selectivity of the crude product was measured by gas chromatography and found to contain 2.25 g (17.01 mmol) of the fluorinated compound. It was. The yield was 85%.

[Example 2]
In a glass reaction vessel,

2.44 g (20.00 mmol, 1.00 eq) of a hydroxy compound represented by formula (2), 20.0 mL of toluene, and 3.92 g (40.00 mmol, 2.00 eq) of fluorinated methanesulfonic acid fluoride were added at room temperature. Stir for minutes. The internal temperature was heated to 60 ° C., and 2.78 g (13.10 mmol, 0.65 eq) of DBU-hydrogen trifluoride / acid salt and 8.67 g (56.95 mmol, 2.84 eq) of DBU were added dropwise and stirred for 24 hours. . By adding 20.0 mL of water to the reaction completion liquid and separating the organic layer,

A crude product of a fluorinated compound represented by the formula (1) was obtained as a toluene solution. The conversion rate of the reaction was measured by gas chromatography to be 100%, and the crude product was measured by ¹⁹ F-NMR and found to contain 1.32 g (10.60 mmol) of the fluorinated compound. The yield was 53%.

[Example 3]
In a glass reaction vessel,

2.36 g (20.00 mmol, 1.00 eq) of a hydroxy compound represented by formula (2) and 2.35 g (24.00 mmol, 1.20 eq) of methanesulfonic acid fluoride as a fluorinating agent were added, and the mixture was stirred at room temperature for 30 minutes. The internal temperature was heated to 60 ° C., and 2.78 g (13.10 mmol, 0.65 eq) of DBU-hydrogen trifluoride / acid salt and 8.67 g (56.95 mmol, 2.84 eq) of DBU were added dropwise and stirred for 24 hours. . By adding 20.0 mL of water to the reaction completion liquid and separating the organic layer,

A crude product of a fluorinated compound represented by When the crude product was measured by ¹⁹ F-NMR, it was found that 1.54 g (12.80 mmol) of the fluorinated compound was contained. The yield was 64%.

[Example 4]
In a glass reaction vessel,

And 0.35 g (2.00 mmol, 1.00 eq) of a hydroxy compound represented by formula (2), 2.0 mL of toluene, and 0.29 g (3.00 mmol, 1.50 eq) of methanesulfonic acid fluoride as a fluorinating agent were added at room temperature. Stir for minutes. The internal temperature was heated to 60 ° C., and 0.42 g (2.00 mmol, 1.00 eq) of DBU-hydrogen trifluoride / acid salt and 0.98 g (6.43 mmol, 3.21 eq) of DBU were added dropwise and stirred for 24 hours. . By adding 10.0 mL of 5% aqueous sodium hydrogen carbonate solution to the reaction completion liquid, separating the organic layer, and concentrating the recovered organic layer under reduced pressure,

A crude product of a fluorinated compound represented by When the crude product was measured by ¹⁹ F-NMR, it was found that 0.31 g (1.72 mmol) of the fluorinated compound was contained. The yield was 86%.

[Example 5]
In a glass reaction vessel,

And 0.49 g (2.00 mmol, 1.00 eq) of a hydroxy compound represented by the following formula: 2.0 mL of toluene, 0.29 g (3.00 mmol, 1.50 eq) of fluorinated methanesulfonic acid fluoride, and 30 at room temperature. Stir for minutes. The internal temperature was heated to 60 ° C., and 0.42 g (2.00 mmol, 1.00 eq) of DBU-hydrogen trifluoride / acid salt and 0.98 g (6.43 mmol, 3.21 eq) of DBU were added dropwise and stirred for 24 hours. . By adding 10.0 mL of 5% aqueous sodium hydrogen carbonate solution to the reaction completion liquid, separating the organic layer, and concentrating the recovered organic layer under reduced pressure,

A crude product of a fluorinated compound represented by When the crude product was measured by ¹⁹ F-NMR, it was found that 0.42 g (1.76 mmol) of the fluorinated compound was contained. The yield was 88%.

[Example 6]
In a glass reaction vessel,

1.44 g (20.00 mmol, 1.00 eq) of a hydroxy compound represented by formula (2), 20.0 mL of acetonitrile, and 2.35 g (24.00 mmol, 1.20 eq) of methanesulfonic acid fluoride as a fluorinating agent were added, and 30 at room temperature was added. Stir for minutes. The internal temperature was heated to 60 ° C., and 2.82 g (13.3 mmol, 0.67 eq) of DBU-hydrogen trifluoride / acid salt and 7.41 g (48.67 mmol, 2.43 eq) of DBU were added dropwise and stirred for 20 hours. . By adding water to the reaction solution and separating the organic layer

A crude product of a fluorinated compound represented by When the crude product was measured by ¹⁹ F-NMR, it was found that 1.13 g (15.2 mmol) of the fluorinated compound was contained. The yield was 76%.

[Example 7]
In a glass reaction vessel,

1.52 g (20.00 mmol, 1.00 eq), 20.0 mL of acetonitrile, and 4.91 g (50.00 mmol, 2.50 eq) of methanesulfonic acid fluoride as a fluorinating agent were added, and 30 at room temperature was added. Stir for minutes. The internal temperature was heated to 60 ° C., and 2.82 g (13.3 mmol, 0.67 eq) of DBU-hydrogen trifluoride / acid salt and 11.10 g (72.91 mmol, 3.65 eq) of DBU were added dropwise and stirred for 20 hours. . By adding water to the reaction completion liquid and separating the organic layer,

[Example 8]
In a glass reaction vessel,

0.45 g (2.00 mmol, 1.00 eq) of a hydroxy compound represented by the following formula: 2.0 ml of acetonitrile, 0.29 g (3.00 mmol, 1.50 eq) of methanesulfonic acid fluoride which is a fluorinating agent were added at room temperature. For 30 minutes. DBU.hydrogen trifluoride complex 0.28 g (1.32 mmol, 0.66 eq) and DBU 0.78 g (5.12 mmol, 2.84 eq) were added dropwise, the internal temperature was heated to 60 ° C., and the mixture was stirred for 24 hours. By adding 20.0 mL of water to the reaction completion liquid and extracting the organic layer with toluene,

A crude product of a fluorinated compound represented by When the crude product was measured by ¹⁹ F-NMR, it was found that 0.32 g (14.00 mmol) of the fluorinated compound was contained. The yield was 70%.

[Example 9]
In a glass reaction vessel,

0.36 g (2.00 mmol, 1.00 eq) of a hydroxy compound represented by the formula, 2.0 ml of acetonitrile, 0.29 g (3.00 mmol, 1.50 eq) of methanesulfonic acid fluoride which is a fluorinating agent were added, and room temperature was added. For 30 minutes. DBU.hydrogen trifluoride complex 0.28 g (1.32 mmol, 0.66 eq) and DBU 0.78 g (5.12 mmol, 2.84 eq) were added dropwise, the internal temperature was heated to 60 ° C., and the mixture was stirred for 24 hours. By adding 20.0 mL of water to the reaction completion liquid and extracting the organic layer with toluene,

A crude product of a fluorinated compound represented by When the crude product was measured by ¹⁹ F-NMR, it was found that 0.15 g (0.82 mmol) of the fluorinated compound was contained. The yield was 41%.

Claims

In the presence of a base selected from the group consisting of an amidine base and a phosphazene base, a hydroxy compound having 6 or more carbon atoms is represented by the formula (1): R 1 SO 2 F (R 1 is a methyl group, an ethyl group or an aromatic group) Wherein R 2 -F (R 2 represents a group obtained by removing a hydroxy group from a hydroxy compound having 6 or more carbon atoms, which is characterized by being fluorinated with a fluorinating agent represented by: The manufacturing method of the fluorinated compound shown by this.
The method for producing a fluorinated compound according to claim 1, wherein the reaction is carried out by adding the base to a mixture of the hydroxy compound and the fluorinating agent at 50 ° C to 150 ° C.
The method for producing a fluorinated compound according to claim 1 or 2, wherein the fluorinating agent is methanesulfonic acid fluoride.
The base is represented by the following formula (3)

The method for producing a fluorinated compound according to any one of claims 1 to 3, which is an amidine base represented by the formula: wherein n is 0 or 2.
The method for producing a fluorinated compound according to any one of claims 1 to 4, wherein the base is 1,8-diazabicyclo [5.4.0] undec-7-ene.
The method for producing a fluorinated compound according to any one of claims 1 to 5, wherein the base is present as an acid salt with hydrogen fluoride.
In the presence of an acid salt of hydrogen fluoride and a base selected from the group consisting of an amidine base and a phosphazene base, a hydroxy compound having 3 or more carbon atoms is represented by the formula (1): R 1 SO 2 F (R 1 is Fluorinated by a fluorinating agent represented by the formula (2): R 2 -F (R 2 represents a hydroxy compound having 3 or more carbon atoms) Represents a group excluding a hydroxy group.).
The method for producing a fluorinated compound according to claim 7, wherein the reaction is carried out by adding the base to the mixture of the hydroxy compound and the fluorinating agent at 50 ° C to 150 ° C.
The method for producing a fluorinated compound according to claim 7 or 8, wherein the fluorinating agent is methanesulfonic acid fluoride.
The base is represented by the following formula (3)

The method for producing a fluorinated compound according to any one of claims 7 to 9, which is an amidine base represented by the formula (wherein n is 0 or 2).
The method for producing a fluorinated compound according to any one of claims 7 to 10, wherein the base is 1,8-diazabicyclo [5.4.0] undec-7-ene.