JPH06219998A - Production of fluorinated organic quaternary ammonium salt - Google Patents

Abstract

PURPOSE:To easily obtain the subject compound in high yield and high purity and in a one step reaction at a low cost by allowing a halogenated organic quaternary ammonium salt to react with hydrofluoric acid anhydride. CONSTITUTION:A halogenated organic quaternary ammonium salt expressed by the formula R<1>R<2>R<3>R<4>NX (R<1>, R<2>, R<3> and R<4> are alkyl or aralkyl; X is chlorine, bromine or iodine) is allowed to react with hydrofluoric acid anhydride to produce a fluorinated organic quaternary ammonium salt expressed by the formula R<1>R<2>R<3>R<4>NF AH2O (A is >0 integer).

Description

Detailed Description of the Invention

FIELD OF THE INVENTION The present invention relates to a method for producing a fluorinated organic quaternary ammonium salt.

[0002]

PRIOR ART AND ITS PROBLEMS Fluorinated organic quaternary ammonium salts are used as phase transfer catalysts in the synthesis of organic compounds.
It is a compound that is extremely useful as a fluorinating agent and a releasing agent for the silyl group used as a protecting group, and its application to various fields has been studied in recent years.

Of these, tetra-n-butylammonium fluoride is most widely used among the fluorinated organic quaternary ammonium salts because of its reactivity and easy handling.

This method of synthesizing a fluorinated organic quaternary ammonium salt is generally carried out by using a so-called halogenated organic quaternary ammonium salt of quaternary ammonium bromide, chloride or iodide as a raw material (in this case, fluorine-free). (1) After reacting the organic halide quaternary ammonium salt with silver oxide in an aqueous solution to remove the silver halide as a precipitate and synthesize a quaternary ammonium hydroxide,
This is neutralized in an aqueous solution of hydrofluoric acid (J. Am. Che.
m. Soc. , 87, 3048 (1965), Bul
l. Chem. Soc. , Jpn. , 54, 3717
(See (1981)); (2) The above quaternary ammonium hydroxide is synthesized by an electrolysis method (see JP-A-63-109183); (3) Halogenated organic quaternary ammonium salt in an organic solvent. And potassium fluoride are reacted to perform halogen exchange (J. Org. Chem., 54, 4827 (19
89)); (4) A halogenated organic quaternary ammonium salt is reacted with sodium azide to synthesize a tetraalkyl azide, which is reacted with sulfuric acid, and then a halogen exchange reaction using potassium fluoride. (Synthesis,
27, 953 (1983), Synthetic Co.
mmunication, 17, 521 (1987)); and the like.

However, each of these methods has the following problems. That is, the reaction of (1) is not suitable for use in a large amount for industrial use because the price is high due to the use of expensive silver. The reaction of (2) is
Large dedicated equipment is required. In the reaction (3), the halogen element contained in the raw material easily remains in the product,
In addition, the reaction yield is better when an alcohol solvent (particularly methanol) is used, but in general, the alcohol solvent is likely to remain in the product, and the originally solid compound becomes jelly-like, or , The purity decreases.
The reaction of (4) complicates the process, and the sodium azide used is highly explosive and dangerous.

[0006]

DISCLOSURE OF THE INVENTION Problems to be Solved In the course of intensive studies on the method for producing a fluorinated organic quaternary ammonium salt in order to improve the above-mentioned problems, the present inventors have found that hydrogen fluoride is better than other hydrogen halides. Attention was paid to the fact that it has a much higher boiling point of 0 ° C or higher. And, (1) the halogen exchange, which has been performed only by the metal fluoride so far, is
It is also possible by reacting the compound represented by the general formula (I) with hydrofluoric acid anhydride, (2) At this time, in the conventional method,
It is possible to remove the halogen, which has been removed from the product as a poorly soluble metal salt, from the reaction system in the form of hydrogen halide (gas), and as a result, (3) surprisingly, the above general By the reaction of the halogenated organic quaternary ammonium salt represented by the formula (II) with hydrofluoric acid anhydride, the target product can be easily obtained in a high yield and high purity in a one-step reaction with a low production cost. This has led to the completion of the present invention.

[0007]

That is, the present invention includes: (1) General formula R ¹ R ² R ³ R ⁴ NF.AH ₂ O (I) (wherein R ¹ , R ² , R ³ , and R ⁴ are respectively A method for producing a fluorinated organic quaternary ammonium salt represented by the same or different alkyl group or aralkyl group, wherein A is an integer of 0 or more, and having the general formula R ¹ R ² R ³ R ⁴ NX (II) (Wherein R ¹ , R ² , R ³ and R ⁴ are the same as described above, and X is chlorine, bromine or iodine), and a halogenated organic quaternary ammonium salt is reacted with anhydrous hydrofluoric acid. (2) The method according to claim 1, wherein the amount of hydrofluoric anhydride used is based on the compound represented by the general formula (II):
3 times or more and 30 times or less moles; (3) The method according to claim 1, wherein the formula (I)
After the reaction of the compound shown in I) with hydrofluoric acid anhydride, excess hydrofluoric acid anhydride is removed by heating, reduced pressure, gas blowing or a combination thereof, and then residual hydrofluoric acid anhydride is removed by neutralization. (4) The method according to claim 1, wherein the general formula (I
In the reaction of the compound represented by I) with hydrofluoric anhydride,
A reaction temperature is −85 ° C. or higher and 150 ° C. or lower; (5) The method according to claim 1, wherein the compound is represented by the general formula (I):
The compound represented by the formula is tetra-n-butylammonium fluoride represented by the general formula (C ₄ H ₉ ) ₄ NF.AH ₂ O (III) (wherein A is the same as above). how to;
I will provide a.

[0008]

DETAILED DESCRIPTION OF THE INVENTION The method of the present invention will be described in more detail below. In the present invention, many kinds of the halogenated organic quaternary ammonium salt represented by the general formula (II) used as a raw material are industrially easily available, and many production methods thereof are also available. Has been reported (for example, JP-A-59-27854). In the present invention, any of halogenated organic quaternary ammonium salts which are commercially available or synthesized as required can be used. The alkyl group and aralkyl group contained in the ammonium salt are not particularly limited. When a part of these groups has a possibility of reacting with hydrofluoric acid, the corresponding part may be protected and used according to a conventional method.

The water content of the hydrofluoric acid used in the present invention may be such that it is generally used as hydrofluoric acid. It is preferably 3% by weight or less, more preferably 0.5% by weight or less. Hydrogen halide produced by the reaction is dissolved in water contained in hydrofluoric anhydride and remains as an impurity in the intended product,
The water content in the hydrofluoric acid used is preferably as low as possible.

The molar ratio of anhydrous hydrofluoric acid and the halogenated organic quaternary ammonium salt represented by the general formula (II) (hydrofluoric acid anhydride / halogenated organic quaternary ammonium salt) is preferably 3 to 30. . When the molar ratio is less than 3, the progress of the reaction is slow, and the amount of halogen as a raw material remaining in the product increases. When the molar ratio exceeds 30, there is no great difference as compared with the case where the molar ratio is less than 30, but labor is required to remove the excess hydrofluoric acid. The most preferable molar ratio is 7-
It is within the range of 15.

As the reaction solvent, it is preferable to use hydrofluoric acid itself. In this case, hydrofluoric anhydride has the effects of both a reactant and a solvent. If another solvent is used, it takes extra time to separate the solvent, and the hydrogen halide produced by the reaction tends to dissolve in the solvent and remain as an impurity.

The reaction mode of the hydrofluoric acid anhydride and the halogenated organic quaternary ammonium salt represented by the general formula (II) is not particularly limited. Usually, (1) hydrofluoric acid anhydride is dropped into the halogenated organic quaternary ammonium salt; (2) halogenated organic quaternary ammonium salt is added into the anhydrous hydrofluoric acid; (3) the container is cooled, A method such as mixing a halogenated organic quaternary ammonium salt and hydrofluoric acid anhydride and gradually heating the mixture can be used. Of these, the method (1) or (3), especially the method (1), is preferable. In the method (2), the halogenated organic quaternary ammonium salt reacts with the anhydrous hydrofluoric acid vapor that has volatilized in the container before it reacts with the liquid phase hydrofluoric acid anhydride, resulting in a jelly-like form, which makes addition difficult. This is because sometimes it becomes.

The reaction temperature is usually -80 ° C to 150 ° C, preferably 0 ° C to 60 ° C. The reaction temperature varies depending on the type of halogenated organic quaternary ammonium salt. Specifically, in the compound represented by the general formula (II), when X is chlorine, the boiling point of hydrogen chloride produced is −85 ° C., so that the temperature higher than that is the same as when X is bromine. In this case, the temperature is preferably −66.7 ° C., and when X is iodine, the temperature is preferably −35.4 ° C. or higher. Furthermore, many of the fluorinated organic quaternary ammonium salts produced by the reaction decompose at high temperatures, so it is preferable to carry out the reaction at or below the decomposition temperature. Specifically, in the compound represented by the general formula (I), R ¹ R ²
When synthesizing tetramethylammonium fluoride in which all R ³ R ⁴ are methyl groups, it is 30 ° C. or lower, and similarly, when synthesizing tetra-n-butylammonium fluoride represented by the general formula (III), 70 ° C. or lower. It is preferable to react with.

However, gas is blown into the reaction solution even if the reaction temperature is not higher than the boiling point of hydrogen halide.
Alternatively, it is possible to remove the hydrogen halide produced by performing an operation such as reducing the pressure in the reaction vessel. In this case, the gas to be blown may be any gas that does not react with the halogenated organic quaternary ammonium salt and anhydrous hydrofluoric acid, and specific examples thereof include argon, helium, nitrogen and air. Here, the amount of water in the gas to be blown is not particularly limited, but if water is present in the gas, the hydrogen halide produced will dissolve into the water and tend to remain in the product, so dehydrated as much as possible Is preferably used. In general, there is no problem if a commercially available cylinder is used as it is, or a tank dehydrated by passing through a sulfuric acid trap, a silica gel tube or the like is used.

Further, after the reaction between the halogenated organic quaternary ammonium salt represented by the general formula (II) and hydrofluoric acid anhydride,
Excess hydrofluoric acid is removed by heating, depressurizing, blowing gas, and combining them as in the case of removing hydrogen halide. In this case, since the hydrofluoric acid anhydride, which is generally present in excess, cannot be completely removed,
Then a neutralization reaction is required. This neutralization reaction is carried out by dissolving the reaction product in a suitable solvent and then adding an alkali. The solvent used here may be one that does not react with the reaction product and anhydrous hydrofluoric acid and dissolves the reaction product, and specific examples include water,
Tetrahydrofuran, acetonitrile, methanol and a mixed solution thereof and the like can be mentioned.

On the other hand, although the alkali required for neutralization is not particularly limited, it is generally difficult to neutralize the acidic fluorinated compound produced during the reaction with a compound having a weaker basicity than the fluorinated organic quaternary ammonium salt. . Specific examples of the neutralizing agent include potassium hydroxide, sodium hydroxide,
Sodium carbonate, sodium hydrogen carbonate, potassium carbonate,
Examples thereof include inorganic bases such as calcium hydroxide, calcium carbonate and zinc carbonate, and organic bases such as tetramethylammonium hydroxide. When water is used as the solvent used in the neutralization reaction, the neutralizing agent used is preferably one in which the resulting fluorinated salt such as calcium hydroxide or calcium carbonate is poorly soluble in water. This is because the produced fluoride salt can be easily separated by filtration.

On the other hand, when a fluoride salt by-produced by the reaction, such as potassium carbonate, uses a neutralizing agent which is easily soluble in water, it is generally mixed with water to separate it, and the fluoride is mixed. By mixing the salt with an organic solvent that does not dissolve it is possible to separate the fluoride salt as a precipitate. The neutralization point in this neutralization reaction must be adjusted accurately. If it remains acidic from the neutralization point, hydrogen fluoride and an acidic fluorinated compound remain in the product, and if it becomes basic, an organic quaternary ammonium hydroxide is produced. After the neutralization reaction, the fluorinated organic quaternary ammonium salt can be obtained by removing excess solvent or by crystallization of the desired product from the solvent.

Generally, this fluorinated organic quaternary ammonium salt is stable when it has water of crystallization, but when water is used as the solvent during the neutralization reaction, the water of crystallization is used as the solvent. Given from water. On the other hand, when an organic solvent is used during the neutralization reaction, water of crystallization is provided by adding an equal amount of water. Further, it is also possible to synthesize an anhydrous salt without using water or by dehydrating a crystalline water salt. The present invention will be specifically described below with reference to examples.

[0019]

EXAMPLE 1 Tetra-n-butylammonium bromide 16 was added to a 500 ml Teflon bottle equipped with a magnetic stirrer.
1.0 g (0.50 mol) was added, and under a nitrogen atmosphere, from a dropping funnel made of Teflon, 150.0 g (7.
5 mol) was added dropwise at room temperature over 30 minutes. After completion of the dropping, the mixture was stirred for 2 hours at the same temperature, then heated to 40 ° C. while blowing nitrogen gas into the reaction solution, and stirred for 3 hours. Then, this reaction liquid was poured into 500 ml of water, and then calcium carbonate was added to neutralize. After neutralization, the formed precipitate was separated by filtration, and the obtained filtrate was concentrated under reduced pressure to obtain 154.4 g of a white solid. The melting point of the obtained solid was 62 ° C. The amount of water of crystallization was calculated by measuring the water content of this solid with a Karl Fischer water content meter (Kyoto Electronics Industry Co., Ltd .: MKA-3P type). The product is (C ₄ H ₉ ) ₄ NF
It was 3H ₂ O (yield 98%). Further, the purity and the amount of residual bromine were measured by ion chromatography (Abe Shoji Co., Ltd .: Dionex 2000i type) F ⁻ ,
It was calculated by performing a quantitative analysis of Br ⁻ ions. The purity determined from the F ⁻ ion concentration was 97.5%. The amount of residual bromine was 18 ppm.

[0020]

Example 2 25.7 g (0.10 mol) of tetraethylammonium iodide was placed in a 100 ml stainless steel container equipped with a magnetic stirrer and having a Teflon coating inside. 20 g (1.0 mol) of hydrofluoric acid anhydride was added dropwise thereto at 10 ° C. over 20 minutes from a Teflon dropping funnel. After completion of the dropping, the mixture was stirred for 2 hours at the same temperature, and then the reaction vessel was depressurized while heating to 30 ° C. in a water bath to remove the produced hydrogen iodide and excess hydrofluoric acid. Then, the reaction solution was poured into 50 ml of water and neutralized with sodium hydrogen carbonate. Then, the aqueous solution was concentrated under reduced pressure to obtain tetrahydrofuran 300
Poured into ml. The produced sodium fluoride was filtered and then dried under reduced pressure to obtain 18.3 g (yield 99%) of a white solid of tetraethylammonium fluoride (C ₂ H ₅ ) ₄ NF.2H ₂ O.

[0021]

Example 3 A 100 ml Teflon bottle equipped with a magnetic stirrer was sufficiently cooled in advance with a dry ice-methanol bath, and 10.9 g of tetramethylammonium chloride was added.
(0.10 mol), 16.0 g (0.80) of anhydrous hydrofluoric acid
(mol) was added, and the mixture was gradually heated to 20 ° C. in 2 hours. Then, after stirring for 2 hours at that temperature while blowing dry air, the reaction solution was poured into 50 ml of water and neutralized with an aqueous solution of tetramethylammonium hydroxide 105. At this time, the amount of the tetramethylammonium hydroxide aqueous solution required for neutralization was 400.9 g. The aqueous solution was concentrated under reduced pressure to obtain 90.0 g of a white solid of tetramethylammonium fluoride (CH ₃ ) ₄ NF.4H ₂ O. (Melting point 41 ° C.) The reaction yield was 95%, excluding the amount of tetramethylammonium hydroxide used.

[0022]

Example 4 12.0 g (0.60 mol) of hydrofluoric acid anhydride was placed in the same device as in Example 3 sufficiently cooled with ice-water, and tetraoctyl ammonium bromide 5 was added while stirring.
4.7 g (0.10 mol) was added over 20 minutes.
After the addition was completed, the mixture was stirred at room temperature for 2 hours and then further stirred for 3 hours while warming to 60 ° C. After completion of stirring, the reaction solution was poured into tetrahydrofuran containing 10% water,
Neutralized with sodium carbonate. After neutralization, the formed sodium fluoride was removed by filtration, and the filtrate was concentrated under reduced pressure to give tetraoctyl ammonium fluoride (C ₈ H ₁₇ ) ₄ NF.3H ₂ O oily liquid 53.9 g.
Was obtained (yield 100%).

[0023]

[Embodiment 5] An apparatus similar to that of Embodiment 3 is used, in which a
liquat336 (Aldrich reagent) 40.40
g (0.10 mol) was added, and 24.0 g (1.20 mol) of hydrofluoric acid anhydride was added dropwise from a dropping funnel made of Teflon over 30 minutes at room temperature. After completion of dropping, the mixture was heated to 70 ° C. while being blown with dry air and stirred for 2 hours. After completion of stirring, the reaction solution was poured into water and neutralized with calcium hydroxide. After removing the produced calcium fluoride by filtration, the filtrate was concentrated under reduced pressure to give an oily liquid of monomethyltrioctyl ammonium fluoride (38.7 g).
Was obtained (yield 100%).

[0024]

Example 6 The same operation as in Example 5 was carried out except that 79.3 g (0.10 mol) of monomethyltrihexadecyl ammonium chloride was used as a raw material. 69.9 g of an oily liquid of monomethyltrihexadecyl ammonium fluoride was obtained (yield 96%).

Claims (5)

[Claims] 1. A compound represented by the general formula R ¹ R ² R ³ R ⁴ NF.AH ₂ O (I) (wherein R ¹ , R ² , R ³ and R ⁴ are the same or different alkyl groups or aralkyl groups, respectively). And A is an integer greater than or equal to 0), and a method for producing a fluorinated organic quaternary ammonium salt represented by the general formula R ¹ R ² R ³ R ⁴ NX (II) (wherein R ¹ , R ² , R ³ and R ⁴ are the same as above, and X is chlorine, bromine or iodine), and a hydrofluoric acid anhydride is reacted with the halogenated organic quaternary ammonium salt. 2. The method according to claim 1, wherein the amount of hydrofluoric anhydride used is 3 times or more and 30 times or less with respect to the compound represented by the general formula (II). And how to. 3. The method according to claim 1, wherein after the reaction of the compound represented by the general formula (II) with hydrofluoric acid anhydride, excess hydrofluoric acid anhydride is heated, decompressed, gas-blended or A method comprising removing by a combination, and then removing residual hydrofluoric acid by neutralization. 4. The method according to claim 1, wherein in the reaction of the compound represented by the general formula (II) with hydrofluoric acid anhydride, the reaction temperature is −85 ° C. or higher and 150 ° C. or lower. how to. 5. The method according to claim 1, wherein the compound represented by the general formula (I) is represented by the general formula (C ₄ H ₉ ) ₄ NF.AH ₂ O (III) (wherein A is The same as the above), which is tetra-n-butylammonium fluoride. [0001]