JP2002249479A - Method for producing sulfonic acid fluoride - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new method for producing a sulfonic acid fluoride. SOLUTION: The method of producing sulfonic acid fluoride comprises reacting a sulfonic acid or a sulfonic acid halide with a compound represented by general formula (1) [wherein, R1, R2, R3, and R4 are each a 1-6C alkyl group or an aryl group, and may be the same as or different from each other; R1 and R3 may combine with each other to form a 5 or 6-membered ring; R1 and R2 may combine with each other to form a ring or R2 and R4 may combine with each other to form a ring].

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing sulfonic acid fluoride.

[0002]

2. Description of the Related Art Development of new products using fluorine compounds has been carried out in various fields such as functional materials and physiologically active substances. Compounds and fluorinating agents are being developed.

[0003] Among them, sulfonic acid fluorides are one of the important compounds as intermediates for producing pharmaceuticals and agricultural chemicals. For example, methanesulfonic acid fluoride is a compound that is a raw material for producing trifluoromethanesulfonic acid, which is useful as a pharmaceutical and agricultural chemical intermediate. Trifluoromethanesulfonic acid is produced by the electrolytic fluorination of methanesulfonic acid fluoride. At this time, the use of methanesulfonic acid fluoride as a raw material has the advantage that the use of methanesulfonic acid fluoride has higher current efficiency, improves the yield, and suppresses the generation of chlorine.

A major conventional method for producing sulfonic acid fluorides is a method for producing sulfonic acid fluorides by subjecting a corresponding sulfonic acid chloride and a fluorinating agent to halogen exchange reaction. Here, as the fluorinating agent, an alkali metal salt of fluorine such as sodium fluoride or potassium fluoride is mainly used.

For example, methanesulfonic acid fluoride, benzenesulfonic acid fluoride, p-toluenesulfonic acid fluoride and the like are produced by subjecting the corresponding sulfonic acid chlorides to sodium fluoride by a halogen exchange reaction (J. Amer). Chem.Soc., 8
5,997-1000 (1963)). When sodium fluoride or potassium fluoride is used as the fluorinating agent, an example in which a crown ether is used in combination to improve the reactivity (J. Org. Chem., 42, 2031-
2 (1977)) and an example of using spray-dried potassium fluoride (Japanese Patent Publication No. 2002-33020). In addition, diethylaminosulfur trifluoride (hereinafter referred to as D
There is also known a method of producing sulfonic acid fluoride by subjecting sulfonic acid chlorides to halogen exchange reaction with AST (Synthesis, 12, 801-2).
(1975)).

However, in the above-mentioned method, it is necessary to prepare sulfonic acid chlorides as starting materials from sulfonic acids in advance. In this case, it is necessary to use thionyl chloride, phosphorus trichloride, phosphorus pentachloride or the like as a chlorinating agent, and this is not preferable from an environmental point of view, especially when a large amount is industrially used.

The above-mentioned DAST is a compound useful as a fluorinating agent for an oxygen-containing functional group such as a hydroxyl group, a carboxyl group and a carbonyl group (US Pat. No. 3,976,6).
No. 91). However, the production method of DAST is -78.
It is manufactured by reacting highly dangerous sulfur tetrafluoride with diethylaminotrimethylsilane at a low temperature of -60 ° C to -60 ° C, and requires special manufacturing equipment. In terms of safety, there was a report that there was an explosion in the production and use of DAST (J. FluorineChe).
m. , 42 137 (1989)). Therefore, it is a compound that cannot be said to be a fluorinating agent that can be easily used industrially.

As described above, there are several methods for producing sulfonic acid fluoride. However, in a situation where a method for producing sulfonic acid fluoride which can be industrially easily implemented has not been sufficiently developed. is there.

[0009]

Means for Solving the Problems Accordingly, the present inventors have
In order to solve these problems, intensive studies have been made on fluorinating agents that can be easily used industrially, and as a result, general formula (1)

[0010]

Embedded image (In the formula, R1, R2, R3, and R4 represent an alkyl group or an aryl group having 1 to 6 carbon atoms and may be the same or different. In the formula, R1 and R3 are bonded to form a 5-membered ring or 6 R1, R3 or R2, R2
And 4 may combine to form a ring. ) Is excellent as a selective novel fluorinating agent for an oxygen-containing functional group such as a hydroxyl group, a carboxyl group, a formyl group, or a carbonyl group. It has been found that it can be performed extremely safely and easily without the need for technology. Further, the fluorinating agent represented by the general formula (1) is recovered as a urea compound which is a raw material of the general formula (1) after the fluorination reaction,
It has also been found that it is economically advantageous because it can be reused (JP-A-2000-38370).

Further, they have found that the compound represented by the general formula (1) can be used for a conversion reaction of sulfonic acids and sulfonic acid halides to sulfonic acid fluoride, and completed the present invention. . In particular, the method of the present invention provides a useful industrial production method because sulfonic acid fluoride can be directly produced from sulfonic acid, unlike many conventional production methods.

That is, the present invention provides 1) a general formula (1)

[0013]

Embedded image (In the formula, R1, R2, R3, and R4 represent an alkyl group or an aryl group having 1 to 6 carbon atoms and may be the same or different. In the formula, R1 and R3 are bonded to form a 5-membered ring or 6 R1, R3 or R2, R2
And 4 may combine to form a ring. ) And a compound represented by the general formula (2)

[0014]

Embedded image (Wherein R5 represents a linear or branched alkyl group or a substituted or unsubstituted aryl group, and n represents an integer of 1 to 6). , A method for producing sulfonic acid fluoride, 2) General formula (1)

[0015]

Embedded image (Wherein R1, R2, R3 and R4 have the same meanings as described above) and a compound represented by the general formula (3)

[0016]

Embedded image (In the formula, R5 represents a linear or branched alkyl group or a substituted or unsubstituted aryl group, n represents an integer of 1 to 6, and X represents a chlorine, bromine or iodine atom.) A method for producing a sulfonic acid fluoride, characterized by reacting a sulfonic acid halide represented by the formula (3):

[0017]

Embedded image 1) The production method according to 1), which is 2,2-difluoro-1,3-dimethylimidazolidine represented by the formula: 4) The compound represented by the general formula (1) is represented by the formula (4):

[0018]

Embedded image 2. The production method according to 2), wherein the compound is 2,2-difluoro-1,3-dimethylimidazolidin.

[0019]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail.

R1 to R of the compound represented by the general formula (1)
4 is an alkyl group or an aryl group, preferably an alkyl group or an aryl group having 1 to 6 carbon atoms, and the alkyl group may be linear or branched. That is, methyl group, ethyl group, n-propyl group, isopropyl group, n
-Butyl group, n-hexyl group, phenyl group and the like, which may be the same or different.

Further, R1 and R3 may combine to form a hetero 5- or 6-membered ring containing two nitrogen atoms. Examples of such a ring include an imidazolidine ring, a pyrimidine ring and the like.

Furthermore, R1 and R2, and R3 and R4 may be bonded to each other to form a nitrogen-containing heterocyclic ring having 3 to 5 carbon atoms. Examples of such a ring include a pyrrolidine ring and a piperidine ring.

Specific examples of the compound represented by the general formula (1) include bis-dimethylamino-difluoromethane, bis-diethylamino-difluoromethane, bis-di (n
-Propyl) amino-difluoromethane, bis-diisopropylamino-difluoromethane, bis-di (n-butyl) amino-difluoromethane, bis-di (n-hexyl) amino-difluoromethane, 2,2-difluoro-1, 3-dimethyl imidazolidine, 2,2-difluoro-1,3-diethyl imidazolidine, 2,2-difluoro-1,3-di (n-propyl) imidazolidine,
2,2-difluoro-1,3-diisopropylimidazolidine, 2,2-difluoro-1,3-di (n-butyl) imidazolidine, N, N-dimethyl-N ′, N′-methyl, phenyl-1 , 1-difluoromethanediamine,
Bis (1-piperidyl) difluoromethane and the like can be mentioned. 2,2-Difluoro-1,3-dimethylimidazolidine is particularly preferred.

The compound represented by the general formula (1) is represented by the general formula (5)

[0025]

Embedded image (In the formula, R1, R2, R3, and R4 represent an alkyl group or an aryl group having 1 to 6 carbon atoms and may be the same or different. In the formula, R1 and R3 are bonded to form a 5-membered ring or 6 R1, R3 or R2, R2
And 4 may combine to form a ring. )) Can be safely and easily obtained by subjecting a tetraalkyl chloroformamidinium chloride and an alkali metal salt of fluorine to halogen exchange reaction in a solvent.

As the alkali metal salt of fluorine used in the halogen exchange reaction, sodium fluoride, potassium fluoride, cesium fluoride, rubidium fluoride and the like can be used. Preferably, spray-dried potassium fluoride for a fluorination reaction, which is advantageous in terms of economy and reaction efficiency, is preferred.

The amount of the alkali metal salt of fluorine used depends on the reaction substrate, but is preferably at least 2.5 equivalents, more preferably from 3 to 3 equivalents to the compound represented by the general formula (5). 4 equivalents. If the amount is less than 2.5 equivalents, the progress of the halogen exchange reaction may be insufficient, and the reaction result may not be significantly improved.

The reaction temperature of the halogen exchange reaction depends on the reaction substrate, but is preferably 50 to 100 ° C., more preferably 70 to 100, from the viewpoint of the reaction rate and the stability of the product.
90 ° C. range. The reaction time is preferably 5 to 15 hours, more preferably 6 to 10 hours.

The compound represented by the general formula (5) is a compound represented by the general formula (6)

[0030]

Embedded image (In the formula, R1, R2, R3, and R4 represent an alkyl group or an aryl group having 1 to 6 carbon atoms and may be the same or different. In the formula, R1 and R3 are bonded to form a 5-membered ring or 6 R1, R3 or R2, R2
And 4 may combine to form a ring. ) Can be easily obtained by reacting a chlorinating agent such as phosgene, trichloromethyl chloroformate, oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, and phosphorus oxychloride with the compound represented by the formula (1). Of these, phosgene is used in the urethane industry in large quantities at low cost and is economically advantageous.

For example, the production of 2-chloro-1,3-dimethylimidazolinium chloride is described in JP-A-59-253.
No. 75, it can be easily manufactured.

Next, the compound represented by the general formula (1) is reacted with the sulfonic acid represented by the general formula (2) and the sulfonic acid halide represented by the general formula (3) to convert the sulfonic acid fluoride. The manufacturing method will be described.

In the general formulas (2) and (3) used in the present invention, R5 represents a linear or branched alkyl group or a substituted or unsubstituted aryl group, and n represents 1 to
Indicates an integer of 6. X in the general formula (3) represents a chlorine, bromine or iodine atom.

Specific examples of the sulfonic acids represented by the general formula (2) include, for example, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, 3,4-dimethylbenzenesulfonic acid, , 5-diethylbenzenesulfonic acid, o-dichlorobenzene-4
Sulfonic acids such as -sulfonic acid, 2,6-dichlorotoluene-4-sulfonic acid, benzene-1,3-disulfonic acid, 1-naphthalenesulfonic acid, and 2-naphthalenesulfonic acid, but are not limited thereto. Not something.

Specific examples of the sulfonic acid halides represented by the general formula (3) include methanesulfonic acid chloride, ethanesulfonic acid chloride, 1-propanesulfonic acid chloride, 2-propanesulfonic acid chloride, and 1-propanesulfonic acid chloride. Sulfonic acid halides such as butanesulfonic acid chloride, benzenesulfonic acid chloride, p-toluenesulfonic acid chloride, 1,2-benzenedisulfonyl dichloride, 1-naphthalenesulfonic acid chloride, and 2-naphthalenesulfonic acid chloride are exemplified. However, the present invention is not limited to this.

The amount of the compound represented by the general formula (1) relative to the sulfonic acid and the sulfonic acid halide is at least stoichiometric, preferably 1.0 to 1.5 times, more preferably 1. It is 1 to 1.3 times.

The reaction solvent for producing a sulfonic acid fluoride by reacting a compound represented by the general formula (1) with a sulfonic acid and a sulfonic acid halide is represented by the general formula (1):
There is no particular limitation as long as the solvent does not react with the compound represented by the formula (1) and the sulfonic acid fluoride formed. For example, benzene, toluene, xylene, hydrocarbon solvents such as hexane, dichloromethane, chloroform, carbon tetrachloride, 1,
Halogenated hydrocarbon solvents such as 2-dichloroethane, chlorobenzene and dichlorobenzene, acetonitrile,
Examples include, but are not limited to, solvents such as 1,3-dimethyl-2-imidazolidinone.

The reaction temperature for producing a sulfonic acid fluoride by reacting a compound represented by the general formula (1) with a sulfonic acid and a sulfonic acid halide depends on a reaction substrate and a solvent. From the viewpoint of the stability of the compound represented by the general formula (1), preferably 0 to 12
0 ° C, more preferably room temperature to 90 ° C.

The sulfonic acid fluoride formed by the reaction can be easily removed from the reaction mixture by a conventional method such as distillation or crystallization.

After completion of the reaction, the compound represented by the general formula (1) is economically advantageous because it can be recovered and reused as urea represented by the general formula (6).

[0041]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the present invention is limited thereto.

Synthesis Example 1 2,2-Difluoro-1,3-dimethylimidazolidin
Preparation of (DFI) In a 1 L glass flask, 2-chloro-1,3-dimethylimidazolinium chloride (CDC) (99.74) was placed.
g, 0.590 mol), spray-dried potassium fluoride (102.84 g, 1.770 mol), DMi (3
29.14 g) and reacted at 80 ° C. for 6 hours under a nitrogen atmosphere. After the reaction, cool the reaction mixture to room temperature,
After filtering off the inorganic salt, the inorganic salt was washed with about 160 g of DMi. The DFI concentration in the obtained reaction solution was 15.1% (76.3 g of DFI, yield 95.0% / CDC).
72.5 g of DFI was obtained from the reaction solution by distillation under reduced pressure (purity: 99%, distillation yield: 95%).

Example 1 Preparation of methanesulfonic acid fluoride Methanesulfonic acid (1.42 g, 14.8 mmol),
2,2-Difluoro-1,3-dimethylimidazolidine (DFI) synthesized in Synthesis Example 1 (2.26 g, 16.6)
mmol) and acetonitrile (11.0 g) were charged into a glass reaction flask, and reacted at acetonitrile reflux temperature for 4 hours under a nitrogen atmosphere.

After the reaction, the result of gas chromatography analysis showed that the reaction yield of methanesulfonic acid fluoride was 85%.

Example 2 Preparation of methanesulfonic acid fluoride Methanesulfonic acid chloride (1.72 g, 15.0 mm)
ol), 2,2-difluoro-1,2 synthesized in Synthesis Example 1.
3-dimethylimidazolidine (DFI) (2.26 g,
16.6 mmol) and acetonitrile (11.0 g) were charged into a glass reaction flask, and reacted at acetonitrile reflux temperature for 4 hours under a nitrogen atmosphere.

After the reaction, the result of gas chromatography analysis showed that the reaction yield of methanesulfonic acid fluoride was 87%.

[0047]

According to the method of the present invention, compounds sulfonic acids or sulfonic acid fluorides, which are important as intermediates for the production of pharmaceuticals and agricultural chemicals, can be easily produced with a safe and easy-to-handle fluorinating agent.

 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Masahiko Kusumoto 30 Asamuta-cho, Omuta-shi, Fukuoka Mitsui Chemicals, Inc. F-term (reference) 4H006 AA02 AC30 BA51 BE61 4H039 CA51 CD10

Claims (4)

[Claims] 1. A compound of the general formula (1) (In the formula, R1, R2, R3, and R4 represent an alkyl group or an aryl group having 1 to 6 carbon atoms and may be the same or different. In the formula, R1 and R3 are bonded to form a 5-membered ring or 6 R1, R3 or R2, R2
And 4 may combine to form a ring. ) And a compound represented by the general formula (2): (Wherein R5 represents a linear or branched alkyl group or a substituted or unsubstituted aryl group, and n represents an integer of 1 to 6). , A method for producing sulfonic acid fluoride. 2. A compound of the general formula (1) (Wherein, R1, R2, R3, and R4 have the same meanings as described above) and a compound represented by the general formula (3): (In the formula, R5 represents a linear or branched alkyl group or a substituted or unsubstituted aryl group, n represents an integer of 1 to 6, and X represents a chlorine, bromine or iodine atom.) A method for producing sulfonic acid fluoride, which comprises reacting a sulfonic acid halide represented by the formula (I). 3. The compound represented by the general formula (1) is a compound represented by the formula (4): The production method according to claim 1, which is 2,2-difluoro-1,3-dimethylimidazolidine represented by the following formula: 4. The compound represented by the general formula (1) is a compound represented by the formula (4): The production method according to claim 2, which is 2,2-difluoro-1,3-dimethylimidazolidine represented by the following formula: