JP5262623B2 - Method for producing sulfonamide compound - Google Patents

Description

  The present invention relates to a method for producing a sulfonamide compound, and more particularly to a technique for synthesizing a sulfonamide compound that can be used as a material for a solid polymer electrolyte membrane in a high yield.

The polymer electrolyte fuel cell has a membrane electrode assembly (MEA) as a basic unit, and the membrane electrode assembly is obtained by bonding electrodes to both surfaces of a solid polymer electrolyte membrane. The use of a sulfonamide compound as a material (monomer) for the solid polymer electrolyte membrane has been studied.
As a method for producing a sulfonamide compound, a compound containing a sulfonyl halide group (—SO ₂ X, X is halogen) is used as a starting material, and ammonia (NH ₃ , NH ₄ OH) or sodium azide (NaN ₃ ) is added thereto. A method of synthesizing them by reacting them is known.
In addition, various methods for producing sulfonamide compounds have been proposed. For example, Patent Documents 1 and 2 disclose a method of synthesizing a sulfonamide compound by using a compound containing a sulfonyl halide group as a starting material and reacting it with hexamethyldisilazane (HMDS, Hexamethyldisilazane). ing.
There are also reports of Patent Documents 3 to 5 as described later.

Y. L. Yagupol'skii et al., Z. Org. Farm. Khimii, 2003, 1 (3-4), 65. S. F. Britcher et al., J. Org. Chem., 1983, 48 (6), 763. R. Juschke et al., Z. Naturforsch. B, 1997, 52, 359. JP-A-10-168194 D. D. DesMateau et al., J. Fluorine Chem., 1995, 72, 203.

However, as a compound containing a sulfonyl halide group, XO ₂ S (CF ₂ ) _n SO ₂ X (where X is a halogen, n = 1, 2) is used as a starting material, and ammonia is used as described above. There is a report that only a cyclic compound is produced when it is used (see Patent Document 3). The reason is considered as follows. That is, when the number of carbon atoms is small (when n = 1, 2 as described above), the sulfonyl halide groups (—SO ₂ X) are close to each other, so that the sulfonyl halide groups in the same molecule react with each other. This is because a sulfonimide group is considered to be formed. Therefore, using XO ₂ S (CF ₂ ) _n SO ₂ X (where X is a halogen, n = 1, 2) as a starting material and reacting with ammonia, a “desired sulfonamide compound that is not a cyclic compound” For example, when a linear sulfonamide compound is to be synthesized, there is a problem that the cyclic compound becomes a by-product and the yield is poor. In such a case, since a process such as column purification is required, there is a problem that the cost is increased.

Further, in XO ₂ S (CF ₂ ) _n SO ₂ X (where X is a halogen), when n = 3, that is, even when XO ₂ S (CF ₂ ) ₃ SO ₂ X is reacted with ammonia, Although it has not been reported that a cyclic compound has been formed (see Patent Document 4), a synthesis method for reacting with ammonia in the case of n = 3 is not known. Accordingly, even in the case where n = 3 in XO ₂ S (CF ₂ ) _n SO ₂ X (where X is a halogen), that is, when XO ₂ S (CF ₂ ) ₃ SO ₂ X is used as a starting material, , N = 1, 2 are estimated to have the same problem.

Further, in XO ₂ S (CF ₂ ) _n SO ₂ X (where X is halogen), when n = 4, that is, using XO ₂ S (CF ₂ ) ₄ SO ₂ X as a starting material, ammonia It is known that a sulfonamide compound can be obtained in good yield without producing a cyclic compound even when allowed to act (see Patent Document 5).

  This invention is made | formed in view of the said situation, The objective is to provide the manufacturing method of the sulfonamide compound which can suppress the production | generation of a cyclic compound and can raise a yield. In addition, an object of the present invention is to provide a method for producing a sulfonamide compound capable of obtaining a sulfonamide compound at a low cost.

In order to solve the above-mentioned problem, the present inventors, as an organic compound having a sulfonyl halide group, for example, in XO ₂ S (CF ₂ ) _n SO ₂ X, n = 3, X = F (fluorine) and Using the FO ₂ S (CF ₂ ) ₃ SO ₂ F thus obtained as a starting material, a synthesis method for obtaining a sulfonamide compound in a high yield without generating a cyclic compound was intensively studied. In the course of the research, the present inventors made ammonia act on the starting material (that is, FO ₂ S (CF ₂ ) ₃ SO ₂ F) to synthesize a sulfonamide compound, and a cyclic compound was formed as a by-product. I confirmed that it was a thing.

On the other hand, the present inventors have made sulfonamide in a high yield without generating a cyclic compound when lithium hexamethyldisilazane is reacted with its starting material (ie, FO ₂ S (CF ₂ ) ₃ SO ₂ F). The knowledge that a compound can be obtained was acquired. As a result of further research based on this knowledge, the present inventors have obtained knowledge that a sulfonimide compound can be obtained by reacting an organic compound having a sulfonyl halide group with an alkali metal hexamethyldisilazane. It came to.
The present invention has been made based on such knowledge.

Method for producing a sulfonamide compound according to the present invention, e Bei two or more scan Ruhoniruharaido group, and comprises the step of reacting an alkali metal hexamethyldisilazane organic compounds carbon atoms is 1 to 3 and it shall be the gist.
In the case of this, it is desirable that the reaction temperature is -100 ° C. or higher 0 ℃ less.

  According to the method for producing a sulfonamide compound according to the present invention, an organic compound having a sulfonyl halide group is reacted with an alkali metal hexamethyldisilazane. Alkali metal hexamethyldisilazane is bulky and highly reactive. Therefore, the sulfonimide group production | generation reaction by the sulfonyl halide groups in the same molecule is suppressed, a cyclic compound and an oligomer are not produced | generated, and a sulfonamide compound is obtained with a high yield. Therefore, the purification process of the sulfonamide compound can be simplified and the production cost can be reduced.

According to the present invention, since alkali metal hexamethyldisilazane is used as a reagent, the organic compound having the sulfonyl halide group can be applied even if it has 1 to 3 carbon atoms. Alkali metal hexamethyldisilazane is bulky and highly reactive, so sulfonimide group formation reaction between sulfonyl halide groups in the same molecule is suppressed, and cyclic compounds and oligomers are not generated. This is because When conventionally known ammonia is used as a reagent, a cyclic compound is produced, but the present invention has a high utility value in that the production is suppressed.
In this case, the reaction temperature is desirably −100 ° C. or higher and 0 ° C. or lower. That is, temperature management is important, and reaction time management only needs to be focused on waiting until the end of the reaction. Therefore, if temperature control is performed appropriately, sulfonamide can be obtained in a high yield, and the present invention has a high utility value.

Hereinafter, an embodiment of the present invention will be described in detail.
The manufacturing method of the sulfonamide compound which concerns on one Embodiment of this invention is equipped with the process (refer (1) Formula of Chemical formula 1) which makes the alkali compound hexamethyldisilazane react with the organic compound provided with the sulfonyl halide group.

In one embodiment of the present invention, the “sulfonyl halide group” refers to a functional group represented by —SO ₂ X (X is halogen).
The “organic compound having a sulfonyl halide group” is a compound represented by the general formula: A- (SO ₂ X) _m (m is an arbitrary number of sulfonyl halide groups) and having a carbon atom as a basic skeleton of the structure. Say. Where A is
(1) a perfluoro compound containing a C—F bond and not containing a C—H bond,
(2) a fluorinated hydrocarbon compound obtained by substituting a part of fluorine of the perfluoro compound with hydrogen,
(3) Any hydrocarbon compound containing a C—H bond and no C—F bond may be used.
A may have a linear or branched aliphatic skeleton, or may have an aromatic skeleton.

Examples of the “perfluoro compound having a sulfonyl halide group” include those represented by the general formula: XO ₂ S (CF ₂ ) _n SO ₂ X (where X is halogen, n = 1 to 10). Specifically, FO ₂ S (CF ₂ ) ₃ SO ₂ F (hereinafter also simply referred to as “PPDSF”), FO ₂ S (CF ₂ ) ₄ SO ₂ F (hereinafter also simply referred to as “PBDSF”), FO ₂ S (CF ₂ ) ₈ SO ₂ F (hereinafter also simply referred to as “PODSF”), XO ₂ S (CF ₂ ) ₂ O (CF ₂ ) ₂ SO ₂ X (where X is a halogen), CF ₃ (CF ₂ ) ₃ SO ₂ X (where X is halogen), FC (SO ₂ X) ₃ (where X is halogen), CF ₂ (SO ₂ X) ₂ (where X is halogen), etc. .
Examples of the “fluorinated hydrocarbon compound having a sulfonyl halide group” include CHF (SO ₂ X) ₂ (where X is a halogen).
Furthermore, as “a hydrocarbon compound having a sulfonyl halide group”, BTSC having a benzene ring (see Formula (2) in Chemical Formula 2), CH ₂ (SO ₂ X) ₂ (where X is a halogen), CH ( SO ₂ X) ₃ (where X is halogen), XO ₂ S (CH ₂ ) _n SO ₂ X (where X is halogen, n = 1 to 10) and the like.

“Alkali metal hexamethyldisilazane” refers to a compound represented by the general formula: MN (SiMe ₃ ) ₂ (M: alkali metal, ie, Li, Na, K, Rb, Cs). Alkali metal hexamethyldisilazane is a reagent that is reacted with a starting material, and in particular, LiHMDS (lithium hexamethyldisilazane (LiN (SiMe ₃ ) ₂ )) is preferable, but all or part of Li is replaced with another alkali metal. It may be substituted with (Na, K). LiHMDS is generally dissolved in a tetrahydrofuran (THF) solution, but the concentration may be adjusted as appropriate.

Here, the number of carbon atoms of the “organic compound having a sulfonyl halide group” is preferably 1 or more and 3 or less. When the number of carbon atoms is 3 or less, a cyclic compound is generated when ammonia or the like is used as a reagent. On the other hand, when the number of carbon atoms is 4 or more, a cyclic compound is not generated even when ammonia is used as a reagent. This is because the utility value is particularly high when the carbon number is 1 or more and 3 or less.
That is, when alkali metal hexamethyldisilazane is used as a reagent as in the present invention, it is bulky and highly reactive. Therefore, even if the starting material has 1 to 3 carbon atoms, the desired cyclization reaction does not occur. A sulfonamide compound is obtained.

The reaction conditions are not particularly limited, but the reaction temperature is desirably −100 ° C. or higher and 0 ° C. or lower. The reason why −100 ° C. is set as the lower limit temperature is that when THF is used as a solvent, the freezing point is −108 ° C., and therefore −100 ° C. is the limit at which an ice bath can be produced. The reason why the upper temperature is set to 0 ° C. is that when the temperature exceeds 0 ° C., the reagent is decomposed.
When carrying out the method for producing a sulfonamide compound according to one embodiment of the present invention, the temperature is maintained at −100 ° C. or more and 0 ° C. or less until the reaction represented by the above formula (1) is completed, and then the temperature returns to room temperature Just wait. The reason for returning to room temperature is to purify the synthesized sulfonamide compound. This purification process is simpler than the conventional method due to the high yield of the synthesized sulfonamide compound, and the production cost is reduced.

The “sulfonamide compound” synthesized by carrying out the present invention refers to a compound represented by the general formula: A- (SO ₂ NH ₂ ) _m (m is an arbitrary number of sulfonyl halide groups). Here, a sulfonamide group _(-SO 2 NH ₂₎ is a synthetic conditions and post, all or part of the hydrogen is other group _(e.g., -SO 2 NHM (M: alkali metal), - SO ₂ It may be substituted with NHR (R = COCH ₃ , COCF ₃ , COPh, SO ₂ Ph, SO ₂ (CF ₂ ) ₃ CF ₃ ), etc. Details of “A” constituting the sulfonamide compound are described above. The explanation is omitted because it is as described above.
As specific examples of the “sulfonamide compound”, H ₂ NO ₂ S (CF ₂ ) ₃ SO ₂ NH ₂ (hereinafter also simply referred to as “PPDSA”) using the above PPDSF as a starting material, and H ₂ using the above PBDSF as a starting material. NO ₂ S (CF ₂ ) ₄ SO ₂ NH ₂ (hereinafter also simply referred to as “PBDSA”), H ₂ NO ₂ S (CF ₂ ) ₈ SO ₂ NH ₂ (hereinafter also simply referred to as “PODSA”) using the PODSF as a starting material. H ₂ NO ₂ S (CF ₂ ) ₂ O (CF ₂ ) ₂ SO ₂ NH ₂ , CF ₃ (CF ₂ ) ₃ SO ₂ NH ₂ , FHC (SO ₂ NH ₂ ) ₂ , CH ₂ ( _{SO 2 NH 2) 2, CH} (SO 2 NH 2) 3 , and the like, further, BTSA with a benzene ring to the BTSC as a starting material (formula 3 (3) reference) is given al That.

Examples of the present invention and comparative examples will be described below.
(Example 1) Synthesis of PPDSA using LiHMDS In a 100 ml reaction vessel, 66 ml (66 mmol) of LiHMDS 1M THF solution was placed in a nitrogen atmosphere, and 9.48 g (30 mmol) of PPDSF was slowly added at −80 ° C. with a syringe. Then, the mixture was stirred for 12 hours while gradually returning to room temperature (see the formula (4) in Chemical Formula 4). It became a light brown suspension. Volatiles were removed, 300 ml of 1N hydrochloric acid was added, and the mixture was extracted with 300 ml of diethyl ether. After drying over anhydrous magnesium sulfate and filtering, 20 g of activated carbon was added and stirred for about 20 minutes until the solution became colorless. The activated charcoal was filtered and the solution was distilled off to obtain 7.6 g of PPDSA (white powder, purity> 99%, yield 82%). Purity was confirmed by NMR. FIG. 1 shows the ¹⁹ F NMR spectrum (400 MHz in CD ₃ CN) of the reaction mixture. From the figure, it was confirmed that the production ratio of PPDSA and the cyclic compound was 98: 2.

(Example 2) Synthesis of PPDSA using LiHMDS PPDSA was synthesized in the same manner as in Example 1 except that PPDSF was slowly added with a syringe at -100 ° C. As a result, 7.4 g of PPDSA was obtained (white powder, purity 99%, yield 80%). Purity was confirmed by NMR. The production ratio of PPDSA and the cyclic compound was confirmed to be 99: 1.

(Example 3) Synthesis of PPDSA using LiHMDS PPDSA was synthesized in the same manner as in Example 1 except that PPDSF was slowly added with a syringe at -50 ° C. As a result, 6.9 g of PPDSA was obtained (white powder, purity 95%, yield 74%). Purity was confirmed by NMR. The production ratio of PPDSA and the cyclic compound was confirmed to be 90:10.

(Example 4) Synthesis of PPDSA using LiHMDS PPDSA was synthesized in the same manner as in Example 1 except that PPDSF was slowly added with a syringe at 0 ° C. As a result, 5.6 g of PPDSA was obtained (white powder, purity 85%, yield 60%). Purity was confirmed by NMR. The production ratio of PPDSA and the cyclic compound was confirmed to be 78:22.

(Example 5) Synthesis of PPDSA using LiHMDS PDSDF 0.12M THF solution was slowly added to the LiHMDS 1M THF solution with a dropping funnel and reacted at 0 ° C for 3 hours in the same manner as in Example 1. PPDSA was synthesized. As a result, 6.2 g of PPDSA was obtained (white powder, purity 90%, yield 68%). From the ¹⁹ F NMR spectrum of the reaction mixture, the production ratio of PPDSA and the cyclic compound was confirmed to be 85:15.

(Example 6) Synthesis of PPDSA using LiHMDS PPDSA was synthesized in the same manner as in Example 1 except that the reaction was performed at a temperature of 0 ° C for 3 hours. As a result, 5.5 g of PPDSA was obtained (white powder, purity 85%, yield 60%). From the ¹⁹ F NMR spectrum of the reaction mixture, the production ratio of PPDSA and the cyclic compound was confirmed to be 78:22.

Reference Example 7 Synthesis of BTSA using LiHMDS In a 300 ml reaction vessel, 100 ml of LiHMDS 1M THF solution was placed in a nitrogen atmosphere, and 1.12 g (3 mmol) of BTSC was slowly added with a syringe at −80 ° C. or less. After stirring for an hour, the mixture was stirred for 12 hours while gradually returning to room temperature. It became a light brown suspension. The volatile matter was removed, 1N hydrochloric acid was added, and the solid was filtered to obtain 718 mg of BTSA (white powder, purity> 99%, yield 76%). Purity was confirmed by NMR.

(Comparative example 1) Synthesis of PPDSA using NH ₃ PDSDF 300 g (0.949 mol) was dropped into 2.4 L of liquid ammonia in 2.4 L of liquid ammonia in a 5 L reaction vessel under an argon stream. Thereafter, the mixture was stirred at the same temperature for 4 hours, and then stirred for 16 hours while gradually returning to room temperature (see Formula (5) of Chemical Formula 5). To this was added 1 L of concentrated hydrochloric acid, and the mixture was stirred for 1 hour at room temperature and extracted with ethyl acetate. The solvent was distilled off, and silica gel column purification was performed at a ratio of 2: 1 of n-hexane: ethyl acetate to obtain 145 g of PPDSA (white powder, purity> 99%, yield 49%). Purity was confirmed by NMR. FIG. 2 shows the ¹⁹ F NMR spectrum (500 MHz in CD ₃ CN) of the reaction mixture. From the figure, it was confirmed that the production ratio of PPDSA and the cyclic compound was 1: 1.

(Comparative Example 2) Synthesis of PPDSA using HMDS The reaction was carried out in the same procedure as in Example 1 except that 1M HMDS THF solution was used instead of LiHMDS. From the ¹⁹ F NMR spectrum of the reaction mixture, the production ratio of PPDSA and the cyclic compound was confirmed to be 0: 100. That is, only a cyclic compound was confirmed.

(Comparative Example 3) Synthesis of PBDSA using NH _{3 In the same} manner as in Comparative Example 1, 250 ml of liquid ammonia and 14.6 g (40 mmol) of PBDSF were reacted in an argon stream, after which volatile components were removed, and 1N hydrochloric acid was added. The solid was filtered to give 14 g of PBDSA (white powder, purity> 99%, yield 97%). Purity was confirmed by NMR. From the ¹⁹ F NMR spectrum (400 MHz, in CD ₃ CN) of the reaction mixture, formation of a cyclic compound was not observed.

(Comparative Example 4) Synthesis of PODSA using NH _{3 In the same} manner as in Comparative Example 1, 225 ml of liquid ammonia and 47 g (83 mmol) of PODSF were reacted in an argon stream, and then volatile components were removed, and 1N hydrochloric acid was added to obtain a solid. Filtration gave 40 g of PODSA (white powder, purity> 99%, yield 86%). Purity was confirmed by NMR. From the ¹⁹ F NMR spectrum (400 MHz, in CD ₃ CN) of the reaction mixture, formation of a cyclic compound was not observed.

(Comparative Example 5) Synthesis of BTSA using NH _{3 As} in Comparative Example 1, 150 ml of liquid ammonia and 80 mL of THF solution of 7.48 g (20 mmol) of BTSC were reacted in an argon stream, and then volatile components were removed. By adding 1N hydrochloric acid and filtering the solid, 5.2 g of BTSA was obtained (white powder, purity> 99%, yield 83%). Purity was confirmed by NMR.

(Reaction temperature dependence)
FIG. 3 is a graph showing the reaction temperature dependence of the yield of PPDSA based on Examples 1-4. As shown in the figure, it was confirmed that a good yield was exhibited in the temperature range of −100 ° C. or more and 0 ° C. or less. In particular, since a cyclic compound is hardly formed at −80 ° C. or less, it was found that −80 ° C. or less is particularly preferable. In addition, since the freezing point of solvent THF is -108 degreeC, -100 degreeC is the minimum temperature of ice bath preparation. Moreover, when it exceeds 0 degreeC, a reagent (LiHMDS) will decompose | disassemble.

(Evaluation)
In Examples 1 to 6, by-products of the cyclic compound were suppressed, and the sulfonamide compound was obtained in high yield. Accordingly, from Examples 1 to 6, when an alkali metal hexamethyldisilazane is reacted with a perfluoro compound having a sulfonyl halide group, a sulfonamide compound (H ₂ NO ₂ S (CF ₂ ) _n SO ₂ NH ₂ ) ( It was found that any number of carbon atoms n) can be obtained in high yield. Similarly, in Reference Example 7 , the sulfonamide compound was obtained in high yield. Therefore, it was found from Reference Example 7 that a sulfonamide compound can be obtained in a high yield even when a hydrocarbon compound having a sulfonyl halide group is reacted with an alkali metal hexamethyldisilazane.

In particular, Examples 1 to 6 are obtained by reacting alkali metal hexamethyldisilazane with “perfluoro compound (carbon number: 3) having a sulfonyl halide group (SO ₂ F)” as a starting material. As in Comparative Examples 1 and 2 conventionally known, when liquid ammonia or HMDS is reacted with a “perfluoro compound (3 carbon atoms) having a sulfonyl halide group (SO ₂ F)”, a cyclic compound is generated, Considering that the yield was low, reacting the alkali metal hexamethyldisilazane as in Examples 1 to 6 can suppress the formation of the cyclic compound and obtain the target substance in a high yield. It turns out that utility value is high. Moreover, since the reagent (LiHMDS) of Example 1 is more reactive than the reagent (HMDS) used in Comparative Example 2, the reagent used for the reaction needs to have high reactivity like LiHMDS. I understood.

  Comparative Examples 3 and 4 are obtained by reacting liquid ammonia with a “perfluoro compound having a sulfonyl halide group (4 carbon atoms and 8 carbon atoms, respectively)” as a starting material. In the case of the above, it was found that a sulfonamide compound can be obtained with good yield even with liquid ammonia. From this, it was found that the utility value of the present invention is high particularly when a “perfluoro compound having a sulfonyl halide group” having 3 or less carbon atoms is used as a starting material.

  The reaction temperature dependency is as described above, but other reaction conditions will be discussed. Comparing Example 5 and Example 6, Example 6 produced less cyclic compound than Example 5, but the difference between Examples 5 and 6 was that the concentration of PPDSF used as the starting material was different. Only different. Therefore, according to this result, it is understood that lowering the concentration of PPDSF can suppress the formation of cyclic compounds. On the other hand, when Example 1 and Example 5 were compared, Example 1 had a higher yield than Example 5, but these differed in a plurality of conditions such as the concentration of starting materials, reaction temperature and reaction time. Yes. Therefore, it is judged that the formation of the cyclic compound can be suppressed by adjusting the reaction temperature and the reaction time according to the concentration of the starting material.

By the way, the present invention is also effective when a “hydrocarbon compound having a sulfonyl halide group” having 3 or more carbon atoms is used as a starting material. Comparing Reference Example 7 and Comparative Example 5, Reference Example 7 uses LiHMDS as a reagent, and Comparative Example 5 uses liquid ammonia as a reagent. This is because.

  Although the embodiments of the present invention have been described in detail above, the present invention is not limited to the above embodiments, and various modifications can be made without departing from the scope of the present invention.

  Since the method for producing a sulfonamide compound according to the present invention is suitable for producing a sulfonamide compound that can be applied as a material (monomer) of a solid polymer electrolyte membrane, it is extremely useful in various industries including fuel cell related industries and automobile industries. It is beneficial.

FIG. ¹⁹ shows the ¹⁹ F NMR spectrum (400 MHz in CD ₃ CN) of the reaction mixture of Example 1. FIG. ¹⁹ shows the ¹⁹ F NMR spectrum (400 MHz, in CD ₃ CN) of the reaction mixture of Comparative Example 1. It is a graph which shows the reaction temperature dependence of Example 1- Example 4. FIG.

Claims (3)

E Bei two or more sulfonyl halide groups, and method for producing a sulfonamide compound characterized by comprising the step of reacting an alkali metal hexamethyldisilazane organic compounds carbon atoms is 1 to 3 .   The organic compound is
XO ₂ S (CF ₂ ) _n SO ₂ X, FC (SO ₂ X) _Three Or CF ₂ (SO ₂ X) ₂ ,
CHF (SO ₂ X) ₂ Or
XO ₂ S (CH ₂ ) _n SO ₂ X, CH (SO ₂ X) _Three Or CH ₂ (SO ₂ X) ₂
(However, n = 1 to 3, X = halogen)
The method for producing a sulfonamide compound according to claim 1.   The method for producing a sulfonamide compound according to claim 1 or 2, wherein a reaction temperature in the step is from -100 ° C to 0 ° C.

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