JP2007119355A - Method for producing perfluoroalkanesulfonic acid ester - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a means for simply producing a perfluoroalkanesulfonic acid ester useful as an intermediate for medicines or agrochemicals, a reagent for introducing a fluorine-containing group or an organic solvent more inexpensively than conventional means under mild conditions. <P>SOLUTION: A perfluoroalkanesulfonyl halide is reacted with a cyclic hydroxy compound in the presence of a base to produce the perfluoroalkanesulfonic acid ester. In the process, water is made to coexist as a solvent without using the organic solvent. The reaction temperature is especially preferably ≥-5 to ≤40°C and the amount of the water is especially preferably ≥1 to ≤5 g based on 1 g of the cyclic hydroxy compound. The perfluoroalkanesulfonic acid ester can simply be produced under the mild conditions in higher yield than that of the conventional methods and toxic wastes are hardly discharged according to the method. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method for producing perfluoroalkanesulfonic acid esters useful as intermediates for pharmaceuticals and agricultural chemicals, fluorine-containing group introduction reagents, and organic solvents.

  Perfluoroalkanesulfonic acid esters obtained by perfluoroalkanesulfonylation of cyclic hydroxyl compounds are useful as intermediates for pharmaceuticals and agricultural chemicals, reagents for introducing fluorine-containing groups, and organic solvents. In particular, aryl triflates and cyclic vinyl triflates are widely used as precursors for various conversion reactions as described in Non-Patent Document 1, and are also elements constituting important pharmaceuticals.

  Numerous literatures have been reported on methods for producing these compounds. For example, Patent Document 1 reports an example of trifluoromethanesulfonylation (triflate) using 2-hydroxypyridines and Non-Patent Document 2 using phenols and the like using trifluoromethanesulfonic anhydride. Thus, most of the examples known so far for perfluoroalkanesulfonate formation of cyclic hydroxyl compounds are triflating. As the triflating agent, trifluoromethanesulfonic anhydride is mainly used.

  As an example of using a triflating agent other than trifluoromethanesulfonic anhydride, an example using N-phenyl-bis (trifluoromethanesulfonimide) is reported in Non-Patent Document 3, etc., and 4-nitrophenyl triflate An example of using is reported in Non-Patent Document 4. In addition, examples using imidazole triflate (Non-Patent Document 5), examples using N-phenyl-bis (trifluoromethanesulfonimide) derivatives supported on a polymer (Non-Patent Document 6), and the like are known. Furthermore, the present applicant has reported an example of triflating 2,2′-binaphthol using trifluoromethanesulfonyl fluoride in Patent Document 2.

  As perfluoroalkanesulfonate formation other than triflate formation, an example of nonafluorobutanesulfonate formation (nonaflatification) using nonafluorobutanesulfonyl fluoride is reported in Non-Patent Document 7 and the like.

By the way, in the methods described in these documents described above, an organic solvent such as methylene chloride or N, N-dimethylformamide (DMF) is used as a solvent in order to improve the selectivity. Non-Patent Document 8 reports an example in which trifluoromethanesulfonic acid anhydride is used and triflating is performed in a two-layer system using water and toluene as a solvent.
International Publication No. 04/078727 JP 2001-122844 A Synthesis, 735-762, 1993 (Germany) Journal of the American Chemical Society, 109, 5478-5486, 1987 (USA) Journal of Organic Chemistry, 65, 2368-2378, 2000 (USA) Tetrahedron Letters, 38, 1181-1182, 1997 (Netherlands) Tetrahedron Letters, 11, 3947-3948, 1970 (Netherlands) Organic Letters, 2, 477-480, 2000 (USA) Synthesis, pp. 481-485, 1984 (Germany) Organic Letters, 4, 4717-4718, 2002 (USA)

  The various methods for producing perfluoroalkanesulfonic acid esters by perfluoroalkanesulfonylation of the above-mentioned cyclic hydroxyl compounds are excellent methods for small-scale production in laboratories and the like. There are several problems in manufacturing.

  First, there is an economic problem. In general, trifluoromethanesulfonic anhydride (Patent Document 1 and Non-Patent Document 2) used as a perfluoroalkanesulfonylating agent is very expensive. In addition, although trifluoromethanesulfonic anhydride has two trifluoromethanesulfonyl groups, only one is involved in the reaction, which is not only economically wasteful but also increases waste. There are many problems in adopting it for mass synthesis. Further, N-phenyl-bis (trifluoromethanesulfonimide) (Non-patent document 3), 4-nitrophenyl triflate (Non-patent document 4), imidazole triflate (Non-patent document 5), N-phenyl-supported on a polymer Since most of the triflating agents such as bis (trifluoromethanesulfonimide) derivatives (Non-patent Document 6) are produced using expensive trifluoromethanesulfonic anhydride, trifluoromethanesulfonic anhydride is used. It is much more expensive and the economic problems are great.

  Generally, trifluoromethanesulfonic anhydride is produced by a method as shown in Scheme 1 below.

Thus, trifluoromethanesulfonic acid anhydride is produced from two molecules of trifluoromethanesulfonic acid (CF ₃ SO ₃ H), whereas trifluoromethanesulfonyl chloride (CF ₃ SO ₂ Cl) is produced from one molecule. Therefore, it is inexpensive. Furthermore, since trifluoromethanesulfonyl fluoride (CF ₃ SO ₂ F) is a raw material for trifluoromethanesulfonic acid (CF ₃ SO ₃ H), it is cheaper. Therefore, from an economical viewpoint, it is preferable to use trifluoromethanesulfonyl chloride (CF ₃ SO ₂ Cl) or trifluoromethanesulfonyl fluoride (CF ₃ SO ₂ F) rather than trifluoromethanesulfonic anhydride. From such a viewpoint, the method of Patent Document 2 is useful. However, relatively few examples are known in which good reactivity is obtained using trifluoroalkanesulfonyl halide as a perfluoroalkanesulfonylating agent.

  On the other hand, there are also environmental problems such as the waste problem. In the perfluoroalkanesulfonic acid ester production methods known so far, in most cases, methylene chloride, benzene, DMF and the like are used in large quantities as suitable solvents, and these organic solvents (especially methylene chloride) are used. It is reported that the desired product can be produced with high selectivity by suppressing the formation of by-products when used under high cooling conditions or at around -50 ° C. However, these organic solvents have a great impact on the environment. In particular, halogen-based hydrocarbons such as methylene chloride are compounds that are regulated by various laws as harmful substances, and must be used in a closed system, which imposes a burden on industrial use. In addition, the reaction at a low temperature condition of −50 ° C. is burdensome for implementation on a large scale.

  Although the methods of Patent Document 2 and Non-Patent Document 7 use inexpensive trifluoromethanesulfonyl fluoride or nonafluorobutanesulfonyl fluoride, they are reacted in DMF, methylene chloride, ether or DME (dimethoxyethane). There is concern about being. Further, although the method of Non-Patent Document 8 uses water as a solvent, there is a concern that toluene is coexistent and expensive trifluoromethanesulfonic anhydride is used.

  Thus, in order to industrially produce perfluoroalkanesulfonic acid esters by perfluoroalkanesulfonylation of cyclic hydroxyl compounds, an inexpensive and easy-to-handle perfluoroalkanesulfonylating agent is used, and it is environmentally friendly. It has been desired to establish a method that can be carried out more efficiently by using a less expensive solvent under mild conditions and without by-products.

  In order to solve such problems, the present inventors diligently studied a method for easily producing a perfluoroalkanesulfonic acid ester industrially by perfluoroalkanesulfonylation of a cyclic hydroxyl compound. As a result, the perfluoroalkanesulfonyl halide represented by the formula [1] has an acid dissociation constant (pKa) in the range of 4 to 13, and the cyclic hydroxyl compound represented by the formula [2]

(Where [A] represents a monovalent alicyclic group, aromatic ring group, or a heterocyclic group or aromatic heterocyclic group having a heteroatom selected from nitrogen, oxygen and sulfur in the ring), Perfluoroalkanesulfonic acid ester represented by the formula [3] by reacting in the presence of a base

When the reaction is carried out in the presence of water as a solvent and in the absence of an organic solvent, the desired product can be obtained in a short time and with a high selectivity under mild conditions. It has been found that the production of the product can be effectively suppressed.

In general, perfluoroalkanesulfonyl halide has a property of rapidly hydrolyzing in the presence of water and a base. For example, it is known that when water is dropped into a mixture of a fluorinated sulfonyl fluoride and a tertiary amine, a corresponding sulfonic acid is immediately formed (Japanese Patent Laid-Open No. 8-245546). Further, it is also known that CF ₃ CH ₂ SO ₂ Cl is hydrolyzed in water and converted to CF ₃ CH ₂ SO ₃ H (J. Org. Chem., 1981, 46, P. 3335-3336). For this reason, the present inventors initially used perfluoroalkanesulfonyl halide represented by the formula [1] as a raw material when water was used as a solvent, and reacted with water instead of a cyclic alcohol. It was predicted that it would be difficult to obtain the object.

  However, when the present inventors react the perfluoroalkanesulfonyl halide represented by the formula [1] with the cyclic hydroxyl compound represented by the formula [2] in the presence of a base, A unique finding was obtained that the perfluoroalkanesulfonyl halide preferentially reacts with the cyclic hydroxyl compound without hydrolysis.

  Under the conditions where water coexists in the system and the organic solvent is not used, each reagent not only dissolves well, but the target perfluoroalkanesulfonic acid ester has a higher selectivity than the reaction using the organic solvent. It turned out to be obtained. That is, the reaction targeted by the present invention includes, as a side reaction, “cyclic halide (compound in which the hydroxyl group of the cyclic hydroxyl compound as a starting material is substituted with Cl or F: [A] -X)”. Production conflicts. In the conventional method using an organic solvent and the solventless method, it is difficult to control this side reaction, resulting in a decrease in yield and an increase in the burden of a subsequent purification step.

  In comparison, the present invention is characterized in that water is used as a solvent and no other organic solvent is used. By adopting this condition, the side reaction was drastically reduced, and it was found that “the formation of cyclic halides can be minimized.

  Furthermore, depending on the type of cyclic hydroxyl compound used, the perfluoroalkanesulfonic acid ester produced is insoluble in water. Therefore, the cyclic hydroxyl compound is dissolved in water in advance, and the perfluoroalkanesulfonyl halide is sequentially added. It has also been found that the desired perfluoroalkanesulfonic acid ester (non-water-soluble) can be precipitated by adding it in water, and the target product can be purified simply by filtration after the reaction.

  As a result of these findings, an inexpensive perfluoroalkanesulfonylating agent can be used to synthesize the target product in a higher yield than conventional techniques under mild conditions that are easy to implement industrially, and no organic solvent is used. Therefore, the environment is not burdened, waste liquid processing becomes easy, and processing costs can be reduced. According to the present invention, the target perfluoroalkanesulfonic acid ester can be produced at a much lower cost and with higher productivity.

  The present inventors have further found that the above-mentioned perfluoroalkanesulfonic acid ester formation reaction in the presence of water proceeds particularly advantageously under specific conditions (water amount, temperature, presence of a surfactant), The present invention has been completed.

That is, the present invention is a method for producing 4,4,4-trifluorobutenoic acids based on the following [Invention 1] to [Invention 8].
[Invention 1]
Perfluoroalkanesulfonyl halide C _n F _{(2n + 1)} SO ₂ X [1] represented by the formula [1]
(In the formula, X represents F or Cl. N represents an integer of 1 to 4.)
And a cyclic hydroxyl compound represented by the formula [2] having an acid dissociation constant (pKa) in the range of 4 to 13

(Here, [A] represents a monovalent alicyclic group, aromatic ring group, or heterocyclic group or aromatic heterocyclic group having a heteroatom selected from nitrogen, oxygen and sulfur in the ring). And a perfluoroalkanesulfonic acid ester represented by the formula [3] in the presence of a base.

(In the formula, the meanings of n and [A] are the same as above.)
A process for producing a perfluoroalkanesulfonic acid ester, characterized in that the reaction is carried out in the presence of water as a solvent and in the absence of an organic solvent.
[Invention 2]
The perfluoroalkanesulfonyl halide is a trifluoromethanesulfonyl halide CF ₃ SO ₂ X [1a] represented by the formula [1a].
(In the formula, X means F or Cl.)
The method according to invention 1, characterized in that:
[Invention 3]
The method according to Invention 1 or Invention 2, wherein a phase transfer catalyst is allowed to coexist.
[Invention 4]
The method according to invention 3, characterized in that the phase transfer catalyst is a quaternary ammonium salt.
[Invention 5]
5. The method according to any one of inventions 1 to 4, wherein the reaction temperature is −5 ° C. or more and 40 ° C. or less.
[Invention 6]
6. The method according to any one of Inventions 1 to 5, wherein the amount of water is 1 g or more and 10 g or less per 1 g of the cyclic hydroxyl compound.
[Invention 7]
The phenolic compound in which the cyclic hydroxyl compound is represented by the formula [4]

(In the formula [4], R _{1 to} R ₅ are each independently a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, a methoxy group, a trifluoromethyl group, a trifluoromethoxy group, a cyano group, Or represents a nitro group.)
The method for producing a perfluoroalkanesulfonic acid ester according to any one of Inventions 1 to 6, wherein
[Invention 8]
Trifluoromethanesulfonyl halide CF ₃ SO ₂ X represented by formula [1a] [1a]
(In the formula, X means F or Cl.)
And phenols represented by the formula [4] having an acid dissociation constant (pKa) of 4 to 13

(In the formula [4], R _{1 to} R ₅ are each independently a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, a methoxy group, a trifluoromethyl group, a trifluoromethoxy group, a cyano group, Or represents a nitro group.)
Perfluoroalkanesulfonic acid ester represented by the formula [3a]

(In the formula [3a], R _{1 to} R ₅ are each independently a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, a methoxy group, a trifluoromethyl group, a trifluoromethoxy group, a cyano group, Or represents a nitro group.)
Wherein the reaction is carried out at a temperature of -5 ° C. or higher and 40 ° C. or lower in the presence of 1 to 10 g of water per 1 g of the phenol and without the presence of an organic solvent. A method for producing a perfluoroalkanesulfonic acid ester.

  The present invention provides a means for conveniently and efficiently producing perfluoroalkanesulfonic acid esters useful as pharmaceutical / agrochemical intermediates, fluorine-containing group introduction reagents, and organic solvents. According to the method of the present invention, an inexpensive perfluoroalkanesulfonylating agent is used, a halogenated hydrocarbon as a by-product is hardly generated, an organic solvent is not used, productivity is good, and methylene chloride, which is a harmful substance, is used. This is a particularly useful method for producing the target product because wastes such as halogenated hydrocarbons can be reduced.

  Hereinafter, the present invention will be described in more detail. The perfluoroalkanesulfonyl halide represented by the formula [1], which is a starting material of the present invention, has a perfluoroalkyl group having 1 to 4 carbon atoms and a sulfonyl group, and an F atom or Cl atom is bonded to the terminal. Acid halide compound. Specifically, the perfluoroalkanesulfonyl halide represented by the formula [1] is trifluoromethanesulfonyl chloride, trifluoromethanesulfonyl fluoride, pentafluoroethanesulfonyl chloride, pentafluoroethanesulfonyl fluoride, heptafluoropropanesulfonyl chloride, hepta. Examples thereof include fluoropropanesulfonyl fluoride, nonafluorobutanesulfonyl chloride, and nonafluorobutanesulfonyl fluoride.

  Of these, trifluoromethanesulfonyl chloride and trifluoromethanesulfonyl fluoride are preferred because the economic viewpoint, the usefulness of the product, and the effect of improving productivity by coexisting water are particularly remarkable. Sulfonyl fluoride is particularly preferred.

  The cyclic hydroxyl compound as a starting material of the present invention is not particularly limited in its structure as long as the acid dissociation constant (pKa) indicated by the hydroxyl group is in the range of 4 to 13. It may be an alicyclic compound having a hydroxyl group, an aromatic compound having a hydroxyl group, a heterocyclic compound having a hydroxyl group, or an aromatic heterocyclic compound. These may be monocyclic, condensed polycyclic, bridged cyclic, or spirocyclic. In addition, even a compound generally expressed in a ketone form, which can be perfluoroalkanesulfonylated via an enol form, is included in the object of the present invention. Among these, a cyclic hydroxyl compound having a pKa in the range of 6 to 11 is particularly preferable because the reactivity of the reaction targeted by the present invention is high.

  Specific examples of these cyclic hydroxyl compounds include the following compounds. First, examples of the alicyclic compound include dimedone, 2-methyl dimedone, and 2-acetyl dimedone. Examples of aromatic compounds include 2-acetylphenol, 3-acetylphenol, 4-acetylphenol, 2-bromophenol, 3-bromophenol, 4-bromophenol, catechol, 2-chlorophenol, 3-chlorophenol, 4- Chlorophenol, 2-cresol, 3-cresol, 4-cresol, 2-cyanophenol, 3-cyanophenol, 4-cyanophenol, 2,5-dichlorohydroquinone, 2,3-dichlorophenol, 2,4-dichlorophenol 2,5-dichlorophenol, 2,3-difluorophenol, 2,4-difluorophenol, 2,5-difluorophenol, 2,6-difluorophenol, 3,4-difluorophenol, 3,5-difluorophenol, 2,6-dimethyl-4 Cyanophenol, 3,5-dimethyl-4-cyanophenol, 2,3-dimethylphenol, 2,4-dimethylphenol, 2,5-dimethylphenol, 3,4-dimethylphenol, 3,5-dimethylphenol, eugenol 2-fluorophenol, 3-fluorophenol, 4-fluorophenol, 2-hydroxybenzaldehyde, 3-hydroxybenzaldehyde, 4-hydroxybenzaldehyde, hydroquinone, 2'-hydroxyacetophenone, 3'-hydroxyacetophenone, 4'-hydroxyacetophenone 2-phenylphenol, 3-phenylphenol, 4-phenylphenol, 4-indanol, 5-indanol, 2-iodophenol, 3-iodophenol, 4-iodophenol, -Methoxyphenol, 3-methoxyphenol, 4-methoxyphenol, 2-nitrophenol, 3-nitrophenol, 4-nitrophenol, 1-naphthol, 2-naphthol, phenol, pyrogallol, resorcinol, salicylamide, methylhydroquinone, 2 , 4,6-trimethylphenol, 2- (trifluoromethyl) phenol, 3- (trifluoromethyl) phenol, 4- (trifluoromethyl) phenol, 2,3-bis (trifluoromethyl) phenol, 2,4 -Bis (trifluoromethyl) phenol, 2,5-bis (trifluoromethyl) phenol, 2,6-bis (trifluoromethyl) phenol, 3,4-bis (trifluoromethyl) phenol, 3,5-bis (Trifluoromethyl) pheno 2- (trifluoromethoxy) phenol, 3- (trifluoromethoxy) phenol, 4- (trifluoromethoxy) phenol, 2,3-bis (trifluoromethoxy) phenol, 2,4-bis (trifluoromethoxy) ) Phenol, 2,5-bis (trifluoromethoxy) phenol, 2,6-bis (trifluoromethoxy) phenol, 3,4-bis (trifluoromethoxy) phenol, 3,5-bis (trifluoromethoxy) phenol Etc. Examples of the heterocyclic compound or the aromatic heterocyclic compound include 5,5-dimethylhydantoin, 3,6-dihydroxypyridazine, 1,2-dihydro-1-methyl-3,6-pyridazinedione, 1,2-dihydro. -1- (1-methylethyl) -3,6-pyridazinedione, 5-hydroxyuracil, 1-methyluracil, maleimide, 1-methylxanthine, 3-methylxanthine, 7-methylxanthine, 9-methylxanthine, 1 -(1-methylethyl) xanthine, 3- (1-methylethyl) xanthine, 7- (1-methylethyl) xanthine, 9- (1-methylethyl) xanthine, phthalimide, saccharin, succinimide, barbital, xanthine, etc. For example, but not limited to.

  There is no particular limitation on the mixing ratio of the perfluoroalkanesulfonyl halide represented by the formula [1] and the cyclic hydroxyl compound, but the reaction is performed at a molar ratio of 1: 1. 1) It is preferable to mix before and after. However, if one of them is significantly more expensive than the other, it is possible to use an excessive amount of an inexpensive compound in order to completely consume the expensive reagent in the reaction. Specifically, the perfluoroalkanesulfonyl halide is usually 0.5 to 5 mol, preferably 0.9 to 3 mol, and particularly preferably 1 to 2 mol with respect to 1 mol of the cyclic hydroxyl compound.

  In the reaction of the present invention, the amount of water is usually in the range of 0.1 g to 100 g with respect to 1 g of the cyclic hydroxyl compound. However, in the case of 0 ° C. or lower (particularly lower than −10 ° C.), if a large amount of water is used, water solidification may occur, and productivity is reduced. It is preferable to use within a range. Among these, the amount of water per 1 g of the cyclic hydroxyl compound is preferably in the range of 0.5 to 20 g, particularly preferably in the range of 1 to 10 g.

  From the above, in the present invention, it is particularly preferable to add 1 to 10 g of water at a temperature of −5 ° C. to 40 ° C. and 1 g of the cyclic hydroxyl compound.

  One feature of the present invention is that no organic solvent is allowed to coexist in the reaction. Here, the “organic solvent” means an inert organic compound that does not directly participate in the reaction (esterification reaction) of the present invention. Specifically, benzene, toluene, xylene, pentane, hexane, acetonitrile, carbon tetrachloride, chloroform, methylene chloride, 1,2-dichloroethane, ethylbenzene, mesitylene, dioxane, dimethyl ether, diethyl ether, dibutyl ether, dipentyl ether, naphthalene. , Ethyl acetate, propyl acetate, butyl acetate, tetrahydrofuran and the like, which are available as organic solvents. “Do not allow organic solvents to coexist” means that these organic solvents are not substantially present in the system, and specifically, 5% by weight or less, preferably 1% with respect to the cyclic hydroxyl compound. An amount of less than or equal to weight percent (more preferably less than or equal to 0.1 weight) As long as the reaction is carried out without positively adding these substances into the system, it is easy to achieve the condition of “no organic solvent coexist”. By using “water” as a solvent without the presence of the “organic solvent”, the target product can be synthesized with high selectivity and yield, as shown in Examples described later.

As the base to be used, a base having a strength that gives a pH of 8 or more when dissolved in water at a concentration of 1 mol · dm ⁻³ is preferable. Examples of the base include ammonia, sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, potassium carbonate, potassium hydrogen carbonate, potassium hydroxide and other inorganic bases, trimethylamine, triethylamine, tripropylamine, tributylamine and other tertiary amines, diethylamine, Examples thereof include organic bases such as secondary amines such as dipropylamine, and primary amines such as propylamine and butylamine.

  As the base, either an inorganic base or an organic base can be used. When an organic base is used as the base, specifically, a tertiary amine such as trimethylamine, triethylamine, tripropylamine or tributylamine, a secondary amine such as diethylamine or dipropylamine, or a primary amine such as propylamine or butylamine. Examples include amines, but the reaction proceeds particularly smoothly when a tertiary amine such as triethylamine is used.

  When an inorganic base is used as the base, specifically, ammonia, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate and the like can be used. Of these, sodium carbonate or potassium carbonate is particularly preferred because the reaction proceeds smoothly. Since one of the features of the present invention is that the burden on the environment is small, it is preferable to use an inorganic base rather than an organic base in terms of waste.

  Although there is no special restriction | limiting in the quantity of a base, It is 0.9-10 mol normally with respect to 1 mol of perfluoroalkane sulfonyl halides, It is preferable that it is 1-5 mol, It is 1-2 mol Is more preferable. If the base is less than 0.9 mol, the selectivity is not greatly affected, but the reaction conversion rate is low, leading to a decrease in yield. Conversely, if the base is more than 10 mol, it is economically disadvantageous. Therefore, neither is preferable.

  The reaction temperature (temperature of the internal liquid) can be in the range of −20 ° C. to + 90 ° C., but −10 ° C. to + 50 ° C. is preferable because the cooling load is not applied and temperature control is easy. Among these, it is a particularly preferable embodiment of the present invention to perform the reaction in the range of −5 ° C. to 40 ° C. When the temperature is lower than -20 ° C, it is not preferable because a large amount of water may be added to the reaction system to solidify and it is difficult to take advantage of the present invention that the reaction proceeds under mild conditions. On the other hand, if it exceeds 90 ° C., the reaction mixture is likely to be colored and by-products are likely to be generated, which is not preferable.

  The reaction of the present invention suitably proceeds even in the absence of a phase transfer catalyst, but the reaction may be promoted in the presence of a phase transfer catalyst. There are no particular restrictions on the type of phase transfer catalyst that can be used, but 15-crown-5, 18-crown-6, dicyclohexyl-18-crown-6, dicyclohexyl-24-crown-8, dibenzo-18-crown- 6, crown ethers such as dibenzo-24-crown-8, diaza-15-crown, diaza-18-crown, tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydroxide, tri Quaternary ammonium salts such as caprylylmethylammonium chloride, trioctamethylammonium chloride, benzyltriethylammonium bromide, tetraphenylphosphonium chloride, triphenylmethylphosphonium iodide, tetrabutylphosphonium Quaternary phosphonium salts are preferred, such as Mukurorido, they may be used in combination more of it is used alone. Among these, halogenated quaternary ammonium salts such as tetrabutylammonium bromide and tetrapropylammonium bromide are particularly preferable because they are inexpensive.

  When using a phase transfer catalyst, 0.001-1 mol can be used with respect to 1 mol of the cyclic hydroxyl compound, but 0.01-0.5 mol is preferably used from the viewpoint of economy.

  In the reaction, it is preferable to add the perfluoroalkanesulfonyl halide continuously or sequentially after mixing the cyclic hydroxyl compound, the base and the phase transfer catalyst in the presence of an aqueous solvent so that the reaction temperature can be easily controlled.

  The reaction time is not particularly limited, and the optimum reaction time varies depending on the conditions. Therefore, the reaction is carried out while measuring the composition of the reaction mixture by a method such as thin layer chromatography or gas chromatography, and the raw cyclic hydroxyl compound is used. It is desirable to end the process after confirming that the value is sufficiently reduced. There is no particular limitation on the reaction pressure, and the reaction can be carried out at normal pressure or under pressure.

  This reaction can be performed in air or in an inert gas such as nitrogen, helium, or argon. Since there is almost no difference in behavior such as reactivity and coloring due to the coexistence of these gases, it is usually performed in air. The reaction proceeds without stirring, but stirring is preferred.

  When the target perfluoroalkanesulfonic acid ester is a solid, the target product precipitates in an aqueous solvent as the reaction proceeds. In the case of a liquid, after completion of the reaction, the target layer and the aqueous solvent layer are separated into two layers. Therefore, when the perfluoroalkanesulfonyl halide is excessively used or the cyclic hydroxyl compound as a raw material is almost completely consumed by performing the reaction for a long time or the like (reaction conversion rate is approximately 95% or more), When the target product is a solid, it is easily recovered by filtration, and when it is a liquid, it is easily recovered by a liquid separation operation. When an inorganic base is used as the base, the organic matter is hardly contained in the water separated as the filtrate or the aqueous layer and can be easily discarded. As described above, one of the major features of the present invention is that the target product can be easily collected and no harmful and difficult-to-treat waste is produced.

The recovered perfluoroalkanesulfonic acid ester can be used as it is, but it can be further purified by performing purification operations such as distillation and recrystallization as necessary.
[Example]
The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

Preparation of phenyl trifluoromethanesulfonate Charge 5.0 g (0.053 mol) of phenol, 11.3 g (0.106 mol) of sodium carbonate and 40.0 g of water into an autoclave equipped with a stirrer, pressure gauge, thermocouple and dip tube. Cooled with stirring. After the internal temperature of the mixture reached 6 ° C, 10.7 g (0.070 mol) of trifluoromethanesulfonyl fluoride was added over 2.5 hours (while maintaining the internal temperature of the reaction solution at 6-30 ° C). ). Thereafter, stirring was continued for 2 hours at an internal temperature of the reaction solution of 30 ° C. to complete the reaction. As a result of analysis by gas chromatography after completion of the reaction, the composition of the reaction solution was 11% of the raw material phenol and 89% of phenyltrifluoromethanesulfonate, and no cyclic halide was detected. The aqueous layer and the crude phenyltrifluoromethanesulfonate phase were then separated. The organic layer was washed twice with water (10 g) to obtain 6.2 g of the desired product (yield 52%).

Preparation of phenyl trifluoromethanesulfonate Charge 5.0 g (0.053 mol) of phenol, 11.3 g (0.106 mol) of sodium carbonate and 40.0 g of water into an autoclave equipped with a stirrer, pressure gauge, thermocouple and dip tube. Cooled with stirring. After the internal temperature of the mixture reached 6 ° C, 10.9 g (0.072 mol) of trifluoromethanesulfonyl fluoride was added over 2.5 hours (while maintaining the internal temperature of the reaction solution at 6-30 ° C). ). Thereafter, stirring was continued for 3 hours at an internal temperature of the reaction solution of 30 ° C. to complete the reaction. As a result of analysis by gas chromatography after completion of the reaction, the composition of the reaction solution was 3% of the raw material phenol and 97% of phenyltrifluoromethanesulfonate, and no cyclic halide was detected. The aqueous layer and the crude phenyltrifluoromethanesulfonate phase were then separated. The organic layer was washed twice with water (10 g) to obtain 9.8 g of the desired product (yield 82%).

Production of 3,5-bis (trifluoromethyl) phenyl trifluoromethanesulfonate 10.1 g (0.044 mol) of 3,5-bis (trifluoromethyl) phenol was added to an autoclave equipped with a stirrer, a pressure gauge, a thermocouple, and a dip tube. ), 9.41 g (0.088 mol) of sodium carbonate and 80.0 g of water were added and cooled with stirring. When the internal temperature of the mixture reached 6 ° C., 13.4 g (0.088 mol) of trifluoromethanesulfonyl fluoride was added over 10 minutes (while maintaining the internal temperature of the reaction solution at 6 to 20 ° C.). Thereafter, stirring was continued for 3.5 hours at an internal temperature of the reaction solution of 28 ° C. to complete the reaction. As a result of analysis by gas chromatography after completion of the reaction, the composition of the reaction solution was 15% of 3,5-bis (trifluoromethyl) phenol as a raw material, and 3,5-bis (trifluoromethyl) phenyl trifluoromethanesulfonate. Was 85%, and no cyclic halide was detected. The aqueous layer and crude 3,5-bis (trifluoromethyl) phenyl trifluoromethanesulfonate phase were then separated. The organic layer was washed twice with water (20 g) to obtain 11.7 g of the desired product (yield 73%).

Preparation of 4- (trifluoromethoxy) phenyl trifluoromethanesulfonate In an autoclave equipped with a stirrer, pressure gauge, thermocouple, dip tube, 10.1 g (0.056 mol) of 4- (trifluoromethoxy) phenol, sodium carbonate 11. 9 g (0.112 mol) and 80.0 g of water were added and cooled with stirring. When the internal temperature of the mixture reached 6 ° C., 17.0 g (0.112 mol) of trifluoromethanesulfonyl fluoride was added over 10 minutes (while maintaining the internal temperature of the reaction solution at 6-25 ° C.). Thereafter, stirring was continued for 3.5 hours at an internal temperature of the reaction solution of 30 ° C. to complete the reaction. As a result of analysis by gas chromatography after completion of the reaction, the composition of the reaction solution was 11% of 4- (trifluoromethoxy) phenol as a raw material, and 89% of 4- (trifluoromethoxy) phenyl trifluoromethanesulfonate. No cyclic halide was detected. The aqueous layer and crude 4- (trifluoromethoxy) phenyl trifluoromethanesulfonate phase were then separated. The organic layer was washed twice with water (20 g) to obtain 12.4 g of the desired product (yield 71%).

  According to the method of the present invention, perfluoroalkanesulfonic acid ester can be produced in a higher yield than before, and harmful waste is hardly discharged.

Claims (8)

Perfluoroalkanesulfonyl halide C _n F _{(2n + 1)} SO ₂ X [1] represented by the formula [1]
(In the formula, X represents F or Cl. N represents an integer of 1 to 4.)
And a cyclic hydroxyl compound represented by the formula [2] having an acid dissociation constant (pKa) in the range of 4 to 13

(Here, [A] represents a monovalent alicyclic group, aromatic ring group, or heterocyclic group or aromatic heterocyclic group having a heteroatom selected from nitrogen, oxygen and sulfur in the ring). And a perfluoroalkanesulfonic acid ester represented by the formula [3] in the presence of a base.

(In the formula, the meanings of n and [A] are the same as above.)
A process for producing a perfluoroalkanesulfonic acid ester, characterized in that the reaction is carried out in the presence of water as a solvent and in the absence of an organic solvent. The perfluoroalkanesulfonyl halide is a trifluoromethanesulfonyl halide CF ₃ SO ₂ X [1a] represented by the formula [1a].
(In the formula, X means F or Cl.)
The method of claim 1, wherein: The method according to claim 1, wherein a phase transfer catalyst is allowed to coexist. The process according to claim 3, characterized in that the phase transfer catalyst is a quaternary ammonium salt. The method according to any one of claims 1 to 4, wherein the reaction temperature is -5 ° C or higher and 40 ° C or lower. 6. The method according to claim 1, wherein the amount of water is 1 g or more and 10 g or less per 1 g of the cyclic hydroxyl compound. The phenolic compound in which the cyclic hydroxyl compound is represented by the formula [4]

(In the formula [4], R _{1 to} R ₅ are each independently a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, a methoxy group, a trifluoromethyl group, a trifluoromethoxy group, a cyano group, Or represents a nitro group.)
The method for producing a perfluoroalkanesulfonic acid ester according to any one of claims 1 to 6, wherein Trifluoromethanesulfonyl halide CF ₃ SO ₂ X represented by formula [1a] [1a]
(In the formula, X means F or Cl.)
And phenols represented by the formula [4] having an acid dissociation constant (pKa) of 4 to 13

(In the formula [4], R _{1 to} R ₅ are each independently a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, a methoxy group, a trifluoromethyl group, a trifluoromethoxy group, a cyano group, Or represents a nitro group.)
Perfluoroalkanesulfonic acid ester represented by the formula [3a]

(In the formula [3a], R _{1 to} R ₅ are each independently a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, a methoxy group, a trifluoromethyl group, a trifluoromethoxy group, a cyano group, Or represents a nitro group.)
Wherein the reaction is carried out at a temperature of -5 ° C. or higher and 40 ° C. or lower in the presence of 1 to 10 g of water per 1 g of the phenol and without the presence of an organic solvent. A method for producing a perfluoroalkanesulfonic acid ester.