JP4364545B2 - Novel difluorotetrahydrothiophene 1,1-dioxide and process for producing the same - Google Patents

Description

【０００６】
【非特許文献１】
J.Fluorine Chem. 93 (1999) 27
【非特許文献２】
Zh. Org. Khim. 9[11] p2428-2429 (1973)
【非特許文献３】
J. Fluorine Chem. 36 (1987) 373
【特許文献１】
特開２００２−４７２８６号公報
【特許文献２】
特開２００２−１５５０７４号公報
【０００７】
【発明が解決しようとする課題】
本発明は、このような従来の製造方法による問題点を解決し、簡便な装置ないしは設備で、新規な３，３−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド（１）を製造する方法を提供することを目的とする。
【０００８】
【課題を解決するための手段】
本発明者らは、３，４−ジヒドロキシ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド（２）（別名、３，４−ジヒドロキシスルホラン）のフッ素化反応を鋭意検討していたところ、予期せずして３，３−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド（１）が、シス−３，４−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド（３）、トランス−３，４−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド（４）、３−フルオロ−２，３−ジヒドロチオフェン １，１−ジオキシド（５）、及び３，４−エポキシ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド（６）とともに生成することを発見した。
【０００９】
即ち、上記の３，４−ジヒドロキシ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドを原料に、４フッ化硫黄をフッ素化剤とするとともに、好ましくはフッ化水素存在下で反応させることにより、３，３−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドが効率良く得られることを見出した。
【００１０】
本発明の反応を下記スキーム５に示す。
【００１１】
【化４】

【００１２】
即ち、本発明は、下式［１］：
【００１３】
【化５】

【００１４】
で表される３，３−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド、および
下式［２］：
【００１５】
【化６】

【００１６】
で表される３，４−ジヒドロキシ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドを４フッ化硫黄と、好ましくはフッ化水素の存在下に反応させることにより、上記３，３−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドを製造する方法である。
【００１７】
より具体的には、３，４−ジヒドロキシ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドを、フッ化水素に溶解させ、これに４フッ化硫黄を反応させた後、有機溶媒に抽出し蒸留精製することで３，３−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドを製造するという方法である。
【００１８】
【発明の実施の形態】
以下、本発明について詳しく説明する。式（２）で示される３，４−ジヒドロキシ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドは、２，５−ジヒドロチオフェン １，１−ジオキシドを酢酸溶媒中で過酸化水素により酸化することで容易に得ることができる（J. Chem.Soc.,Perkin Trans.1(1972) 1335）。また、３，４−ジヒドロキシ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドは、フッ化水素溶媒に溶解して使用するのが望ましい。その使用量は、好ましくは原料１ｇに対し１〜２０ｍＬである。なお、無溶媒、あるいはジクロロメタンまたはクロロホルム等の塩素系溶媒を使用してもよく、その場合、溶媒の使用量は、好ましくは原料１ｇに対し０〜２０ｍＬである。
【００１９】
また、フッ素化剤である４フッ化硫黄の使用量は、好ましくは原料に対して２．０〜１５．０倍モル量である。
【００２０】
この反応は常圧下でも行えるが、加熱する場合は加圧下で行うのが望ましい。反応圧力は、０〜２０ＭＰａの範囲内で行うことができるが、好ましくは、０．５〜３．０ＭＰａである。また、反応温度は、−４０〜３２０℃の範囲内で行うことができるが、望ましくは、０〜１５０℃である。反応時間は、好ましくは２〜１５０時間である。反応終了後は、通常の後処理、精製を行うことにより、式（１）で示される３，３−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドを得ることができる。
【００２１】
【実施例】
以下、実施例により本発明を具体的に説明するが、本発明の新規化合物の製造方法はこれらの実施例に限定されるものではない。
実施例１（３，３−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドの製造）
１００ｍＬオートクレーブに、３，４−ジヒドロキシ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド（５ｇ，３２．９ｍｍｏｌ)を仕込み、オートクレーブ容器を−４０℃に冷却した。その後、フッ化水素（２６ｇ，１．３ｍｏｌ）をオートクレーブ容器に導入した。引き続いて、４フッ化硫黄（１８．４ｇ，１７０ｍｍｏｌ）を導入した。その後、オートクレーブ容器を密封し、攪拌機で撹拌させながら８０℃で５時間反応させた。反応終了後、低沸点化合物を放棄し、容器内部を充分窒素置換した後、濃褐色粘性液体状の反応混合物をジクロロメタン（４０ｍＬ）で抽出し、フッ化ナトリウムを加えて残存フッ化水素を除去した。抽出液をセライト濾過し溶媒を留去し、精製することで、３，３−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドを２４％の収率で得た。
【００２２】
その他の化合物として、シス−３，４−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド、トランス−３，４−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド、及び３−フルオロ−２，３−ジヒドロチオフェン １，１−ジオキシドをそれぞれ、４０％、６％及び９％の¹⁹Ｆ−ＮＭＲ収率で得た。また、３，４−エポキシ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドを１１％の収率で得た。
【００２３】
３，３−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドの構造は核磁気共鳴分析及び質量分析等で確認した。核磁気共鳴分析装置は、バリアンジャパン（株）製Varian Gemini 200 NMR Spectrometerを使用し、質量分析装置は（株）島津製作所製GCMS-QP5050Aを使用した。
【００２４】
そのスペクトルデータを次に示す。

実施例２
１００ｍＬオートクレーブに、３，４−ジヒドロキシ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド（５ｇ，３２．９ｍｍｏｌ）、引き続きジクロロメタン（３０ｍＬ）を仕込み、オートクレーブ容器を−４０℃に冷却した。次に、４フッ化硫黄（１１．２ｇ，１０４ｍｍｏｌ）を導入した。その後、オートクレーブ容器を密封し、攪拌機で撹拌させながら５５℃で３時間反応させた。反応終了後、低沸点化合物を放棄し、容器内部を充分窒素置換した後、濃褐色粘性液体状の反応混合物をジクロロメタン（４０ｍＬ）で抽出し、フッ化ナトリウムを加えて残存フッ化水素を除去した。抽出液をセライト濾過し溶媒を留去し、精製することで、３，３−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドを５％の収率で得た。
【００２５】
その他の化合物として、シス−３，４−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド、トランス−３，４−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド、及び３−フルオロ−２，３−ジヒドロチオフェン １，１−ジオキシドをそれぞれ、２３％、１５％及び１６％の¹⁹Ｆ ＮＭＲ収率で得た。また、３，４−エポキシ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドを１８％の収率で得た。
参考比較例１
撹拌子、温度計、ラバーセプタム、及び窒素シールを装備した１００ｍＬのガラス製三つ口フラスコに、３，４−ジヒドロキシ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシド（０．７６ｇ，５ｍｍｏｌ）を仕込み、引き続いてジクロロメタン（１０ｍＬ）を加えた。その後、反応容器を−７８℃まで冷却し、３フッ化ジエチルアミノ硫黄（１．６ｇ，１０ｍｍｏｌ）を反応液の中に徐々に加えた。その後、反応温度を−７８℃から室温まで昇温させながら反応を行った。反応混合物に２０ｍＬの水を加えて洗浄し、水相をジクロロメタンで抽出した。溶媒を減圧留去した後、粗生成物を精製すると、３，３−ジフルオロ−２，３，４，５−テトラヒドロチオフェン １，１−ジオキシドの生成は確認できなかったが、３−フルオロ−２，３−ジヒドロチオフェン １，１−ジオキシドを５９％の収率で得た。[0001]
BACKGROUND OF THE INVENTION
The present invention is expected to be used in various fields as a raw material for solvents and additives for lithium ion secondary batteries or lithium polymer secondary batteries, and further as a raw material for synthesizing various compounds such as pharmaceuticals, agricultural chemicals and functional polymer materials. 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide (also known as 3,3-difluorosulfolane), which is a very useful and important compound, and a process for producing the same .
[0002]
[Prior art]
Production of fluorine-containing tetrahydrothiophene 1,1-dioxide (also known as fluorine-containing sulfolane) is 2,5-dihydrothiophene 1,1-dioxide (7). The same applies hereinafter (the same applies hereinafter) (also known as sulfolene) and a method of reacting fluorine gas (Non-patent Document 1) (below, Scheme 1), tetrahydrothiophene 1,1-dioxide (8) (also known as sulfolane) ) And fluorine gas (Patent Document 1 and Patent Document 2) (hereinafter, Scheme 2) have been reported. In the former method, as a product, cis-3,4-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide (3) (also known as cis-3,4-difluorosulfolane), trans-3 , 4-Difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide (4) (also known as trans-3,4-difluorosulfolane), 3-fluoro-2,3-dihydrothiophene 1,1- Dioxide (5) and 3,4-epoxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide (6) (also known as 3,4-epoxysulfolane) were obtained with poor selectivity. In the case of the latter method, 2-fluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide (9) and 3-fluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide ( A mixture of 10) is obtained.
[0003]
However, in both of these reactions, 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide (1) which is the subject of the present application has not been obtained. Furthermore, these manufacturing methods use fluorine gas, which makes it difficult to control the reaction due to its very high reactivity, which is also a dangerous method.
[0004]
Therefore, studies have been made to use a fluorinating agent other than fluorine gas. Examples of the reaction include 3,4-epoxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide (6) and 4 Reaction with sulfur fluoride (Non-Patent Document 2) (Scheme 3 below), 3,4-epoxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide (6) and diethylaminosulfur trifluoride It was reported that cis-3,4-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide (3) was obtained by the reaction with (Non-patent Document 3) (Scheme 4 below). ing. However, the former method requires a long reaction time of 4 days, and the latter method uses a very expensive fluorinating agent. In any reaction, 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide (1) of the present invention was not obtained.
[0005]
[Chemical 3]

[0006]
[Non-Patent Document 1]
J. Fluorine Chem. 93 (1999) 27
[Non-Patent Document 2]
Zh. Org. Khim. 9 [11] p2428-2429 (1973)
[Non-Patent Document 3]
J. Fluorine Chem. 36 (1987) 373
[Patent Document 1]
Japanese Patent Laid-Open No. 2002-47286 [Patent Document 2]
Japanese Patent Laid-Open No. 2002-155074
[Problems to be solved by the invention]
The present invention solves the problems caused by the conventional production method, and uses a simple apparatus or facility to provide a novel 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide (1 ).
[0008]
[Means for Solving the Problems]
The present inventors have intensively studied the fluorination reaction of 3,4-dihydroxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide (2) (also known as 3,4-dihydroxysulfolane). However, unexpectedly, 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide (1) is converted to cis-3,4-difluoro-2,3,4,5-tetrahydro. Thiophene 1,1-dioxide (3), trans-3,4-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide (4), 3-fluoro-2,3-dihydrothiophene 1,1 It was found to form with -dioxide (5) and 3,4-epoxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide (6).
[0009]
That is, the above 3,4-dihydroxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide is used as a raw material, and sulfur tetrafluoride is used as a fluorinating agent, preferably in the presence of hydrogen fluoride. It has been found that 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide can be obtained efficiently by making it.
[0010]
The reaction of the present invention is shown in Scheme 5 below.
[0011]
[Formula 4]

[0012]
That is, the present invention provides the following formula [1]:
[0013]
[Chemical formula 5]

[0014]
3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide represented by the following formula [2]:
[0015]
[Chemical 6]

[0016]
By reacting 3,4-dihydroxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide represented by the following formula with sulfur tetrafluoride, preferably in the presence of hydrogen fluoride, -A process for producing difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide.
[0017]
More specifically, 3,4-dihydroxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide is dissolved in hydrogen fluoride and reacted with sulfur tetrafluoride. This is a method in which 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide is produced by extraction and distillation purification.
[0018]
DETAILED DESCRIPTION OF THE INVENTION
The present invention will be described in detail below. 3,4-dihydroxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide represented by the formula (2) is obtained by converting 2,5-dihydrothiophene 1,1-dioxide with hydrogen peroxide in an acetic acid solvent. It can be easily obtained by oxidation (J. Chem. Soc., Perkin Trans. 1 (1972) 1335). Further, 3,4-dihydroxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide is desirably used by dissolving in a hydrogen fluoride solvent. The amount used is preferably 1 to 20 mL per 1 g of raw material. In addition, you may use no solvent or chlorinated solvents, such as a dichloromethane or chloroform, In that case, the usage-amount of a solvent becomes like this. Preferably it is 0-20mL with respect to 1g of raw materials.
[0019]
Moreover, the usage-amount of sulfur tetrafluoride which is a fluorinating agent becomes like this. Preferably it is 2.0-15.0 times mole amount with respect to a raw material.
[0020]
Although this reaction can be carried out under normal pressure, it is desirable to carry out the reaction under pressure when heating. Although reaction pressure can be performed within the range of 0-20 MPa, Preferably, it is 0.5-3.0 MPa. Moreover, although reaction temperature can be performed within the range of -40-320 degreeC, It is 0-150 degreeC desirably. The reaction time is preferably 2 to 150 hours. After the completion of the reaction, 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide represented by the formula (1) can be obtained by performing usual post-treatment and purification.
[0021]
【Example】
EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, the manufacturing method of the novel compound of this invention is not limited to these Examples.
Example 1 (Production of 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide)
3,4-Dihydroxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide (5 g, 32.9 mmol) was charged into a 100 mL autoclave, and the autoclave vessel was cooled to -40 ° C. Thereafter, hydrogen fluoride (26 g, 1.3 mol) was introduced into the autoclave container. Subsequently, sulfur tetrafluoride (18.4 g, 170 mmol) was introduced. Then, the autoclave container was sealed and reacted at 80 ° C. for 5 hours while stirring with a stirrer. After completion of the reaction, the low boiling point compound was discarded, and the inside of the container was sufficiently purged with nitrogen. Then, the reaction mixture in the form of a dark brown viscous liquid was extracted with dichloromethane (40 mL), and sodium fluoride was added to remove residual hydrogen fluoride. . The extract was filtered through Celite, the solvent was distilled off, and purification was performed to obtain 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide in a yield of 24%.
[0022]
As other compounds, cis-3,4-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide, trans-3,4-difluoro-2,3,4,5-tetrahydrothiophene 1,1 -Dioxide and 3-fluoro-2,3-dihydrothiophene 1,1-dioxide were obtained in ¹⁹ F-NMR yields of 40%, 6% and 9%, respectively. In addition, 3,4-epoxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide was obtained in a yield of 11%.
[0023]
The structure of 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide was confirmed by nuclear magnetic resonance analysis and mass spectrometry. Varian Gemini 200 NMR Spectrometer manufactured by Varian Japan Co., Ltd. was used as the nuclear magnetic resonance analyzer, and GCMS-QP5050A manufactured by Shimadzu Corporation was used as the mass spectrometer.
[0024]
The spectrum data is shown below.

Example 2
A 100 mL autoclave was charged with 3,4-dihydroxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide (5 g, 32.9 mmol), followed by dichloromethane (30 mL), and the autoclave vessel was cooled to -40 ° C. . Next, sulfur tetrafluoride (11.2 g, 104 mmol) was introduced. Then, the autoclave container was sealed and reacted at 55 ° C. for 3 hours while stirring with a stirrer. After completion of the reaction, the low boiling point compound was discarded, and the inside of the container was sufficiently purged with nitrogen. Then, the reaction mixture in the form of a dark brown viscous liquid was extracted with dichloromethane (40 mL), and sodium fluoride was added to remove residual hydrogen fluoride. . The extract was filtered through Celite, the solvent was distilled off, and purification was performed to obtain 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide in a yield of 5%.
[0025]
As other compounds, cis-3,4-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide, trans-3,4-difluoro-2,3,4,5-tetrahydrothiophene 1,1 -Dioxide and 3-fluoro-2,3-dihydrothiophene 1,1-dioxide were obtained in ¹⁹ F NMR yields of 23%, 15% and 16%, respectively. In addition, 3,4-epoxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide was obtained in a yield of 18%.
Reference Comparative Example 1
To a 100 mL glass three-necked flask equipped with a stir bar, thermometer, rubber septum, and nitrogen seal was added 3,4-dihydroxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide (0.76 g). , 5 mmol), followed by the addition of dichloromethane (10 mL). Thereafter, the reaction vessel was cooled to −78 ° C., and diethylaminosulfur trifluoride (1.6 g, 10 mmol) was gradually added into the reaction solution. Thereafter, the reaction was carried out while raising the reaction temperature from −78 ° C. to room temperature. The reaction mixture was washed by adding 20 mL of water, and the aqueous phase was extracted with dichloromethane. When the crude product was purified after distilling off the solvent under reduced pressure, the formation of 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide could not be confirmed, but 3-fluoro-2 , 3-Dihydrothiophene 1,1-dioxide was obtained in 59% yield.

Claims (3)

The following formula [1]:

3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide represented by The following formula [2]:

The 3,3-difluoro-2,3 of claim 1 by reacting 3,4-dihydroxy-2,3,4,5-tetrahydrothiophene 1,1-dioxide represented by , 4,5-tetrahydrothiophene 1,1-dioxide The method for producing 3,3-difluoro-2,3,4,5-tetrahydrothiophene 1,1-dioxide according to claim 2, wherein the reaction is carried out in the presence of hydrogen fluoride.