JP3871191B2 - Method for electrolytic fluorination of aromatic nitrogen-containing heterocyclic compounds - Google Patents

Description

【０００５】
以下、本発明方法をより詳細に説明する。
本発明方法は、電子吸引基が結合した芳香族含窒素複素環化合物の部分フッ素化に有効で、条件設定を的確に行うと、つまり使用する電解質や溶媒の組み合わせの選定等により、モノフッ素化物、ジフッ素化物等のようにフッ素化の程度を調節したり、フッ素化される部位を選択したりすることができる。
芳香族含窒素複素環化合物に電子吸引基が結合しているので、フッ素化の収率は向上する。これは電子吸引基の存在により電子密度の低下した芳香族環の水素原子を原料のフッ素アニオンが攻撃して、芳香環を破壊せずに置換できるからであると推測できる。
【０００６】
この芳香族含窒素複素環化合物のフッ素化により生成される化合物の中には、新規で有用なものが多く、幾つかの化合物は、Diels−Alder反応に利用でき、また同一炭素上に２個のフッ素原子を有する化合物はgem-ジフッ素化体と称し、生理活性物質として有用である。
本発明により得られる芳香族含窒素複素環化合物の部分フッ素化生成物は、更に他の有用な含フッ素化合物の原料となり、この原料を基にする該含フッ素化合物の新規な合成ルートの確立に寄与できる。
本発明の出発原料である基質は、芳香族含窒素複素環化合物で目的とするフッ素化生成物の化学構造から導かれる。複素環を構成する窒素原子は遊離の水素を有しているとフッ素化反応より重合反応を受けやすくなる。出発原料は、Ｎ−アルキルピロール誘導体及びＮ−アリールピロール誘導体があり、例えば(化１)に示すピロール誘導体を好ましく使用できる。
【０００８】
フッ素原料はフッ素化の対象である基質をフッ素化できる化合物から選択され、単にフッ素化反応進行の機能だけでなく、所望部位のフッ素化の選択性等も考慮して決定することが望ましい。好ましいフッ素原料として、トリアルキルアミンポリフッ化水素塩化合物｛Ｒ₃Ｎ.ｎＨＦ（ｎ＝１〜10）｝又はテトラアルキルアンモニウムフロリドポリフッ化水素化合物｛Ｒ₄ＮＦ.ｎＨＦ（ｎ＝１〜10）｝があるが、これらには限定されない。
本発明方法に使用できる陽極としては、一般に酸化鉛、酸化錫、白金、ＤＳＡ、黒鉛、アモルファスカーボン（grassy carbon：ＧＣ）、導電性ダイアモンド等が使用され、還元を行う電極である陰極としては、一般に鉛、鉄、白金、チタン、カーボン等が使用される。電極基体として使用しうる材料は、寿命の長期化を達成しかつ処理表面の汚染を防止するために耐食性を有することが好ましく、電極への給電のための給電体は陽極用としてはチタン等の弁金属又はその合金の使用が望ましく、陽極触媒としては白金やイリジウム等の貴金属及びそれらの酸化物の使用が望ましい。前述した通り、ダイアモンドを金属集電体上に形成したものも好ましい。
【０００９】
集電体は導電性の材料であればその使用に問題はなく、チタン、ニオブ、タンタル、シリコン、カーボン、ニッケル、タングステンカーバイドなどを、板、打ち抜き板、金網、粉末焼結体、金属繊維焼結体の形状に加工して使用することが望ましい。
電解槽材料としては、有機化合物に対する耐久性、安定性の観点から、ガラスライニング材料、カーボン、耐食性の優れたチタン、ステンレス及びＰＴＦＥ樹脂などが好ましく使用できる。
電解条件は、温度が０〜60℃であることが好ましく、通常の電極を使用する場合の電流密度は0.1〜100Ａ／ｄｍ²であることが好ましい。
【００１０】
【発明の実施の形態】
次に本発明に係る含窒素複素環化合物の電解による部分フッ素化の実施例及び比較例を記載するが、これらは本発明を限定するものではない。
【００１１】
実施例１
陽極及び陰極として白金板（いずれも20mm×20mm）を収容した無隔膜電解槽を使用して含窒素複素環化合物のフッ素化を試みた。電解液として、フッ素原料としても機能するEt₃N・２HFを１Ｍ濃度になるようにアセトニトリル10mlに溶解したものを使用した。基質として２−シアノ−１−メチルピロール１ミリモルを前記電解液に溶解した。
この電解液を窒素雰囲気下、室温で攪拌しながら １Ａ／dm²、４Ｆ／モルの定電流電解を行った。反応終了後に溶媒を減圧濾過して除去し、残留物の分析をＮＭＲを用いて行った。
【００１２】
分析の結果、表１に示すように、５−フルオロ体（１）が20％、２−フルオロ−５−オキソ体（２）が痕跡量、２，２−ジフルオロ−５−オキソ体（３）が痕跡量、及び２，５，５−トリフルオロ体（４）が３２％得られた。
得られたフッ素化生成物のうち前記５−フルオロ体（１）が芳香族性を保持していることに注目すべきである。
【００１３】
実施例２
Et₃N・２HFの代わりにEt₃N・３HFを１Ｍ使用したこと以外は実施例１と同一条件で電解を行い、実施例１の場合と同様に得られるフッ素化生成物の分析を行ったところ、表１に示すように、５−フルオロ体（１）が５％、２−フルオロ−５−オキソ体（２）が２％、２，２−ジフルオロ−５−オキソ体（３）が３％、及び２，５，５−トリフルオロ体（４）が６５％得られた。
【００１４】
実施例３
Et₃N・２HFの代わりにEt₃N・５HFを１Ｍ使用したこと以外は実施例１と同一条件で電解を行い、実施例１の場合と同様に得られるフッ素化生成物の分析を行ったところ、表１に示すように、５−フルオロ体（１）が０％、２−フルオロ−５−オキソ体（２）が12％、２，２−ジフルオロ−５−オキソ体（３）が47％、及び２，５，５−トリフルオロ体（４）が６５％得られた。
【００１５】
実施例４
Et₃N・２HFの代わりにEt₄NＦ・４HFを１Ｍ使用したこと以外は実施例１と同一条件で電解を行い、実施例１の場合と同様に得られるフッ素化生成物の分析を行ったところ、表１に示すように、５−フルオロ体（１）が０％、２−フルオロ−５−オキソ体（２）が21％、２，２−ジフルオロ−５−オキソ体（３）が28％、及び２，５，５−トリフルオロ体（４）が６％得られた。
【００１６】
【表１】

【００１７】
実施例５
基質として、２−シアノ−１、５−ジメチルピロール１ミリモルを前記電解液に溶解したこと、フッ素源としてEt₃N・３HFを使用したこと、及び電流値を２Ｆ／モルとしたこと以外は実施例１と同一条件で電解を行い、得られたフッ素化生成物の分析を行った。
表２に示すように、５−メチル置換体（５）が33％、１−メチル置換体（６）が３％、５−メチル２置換体（７）が痕跡量得られた。
【００１８】
実施例６
溶媒をアセトニトリルの代わりにジメトキシエタン（ＤＭＥ）としたこと以外は実施例５と同一条件で電解を行い、得られたフッ素化生成物の分析を行った。表２に示すように、５−メチル置換体（５）が29％、１−メチル置換体（６）が７％、５−メチル２置換体（７）が３％得られた。
【００１９】
実施例７
溶媒をアセトニトリルの代わりにジクロロメタン（ＣＣＨ₂Ｃｌ₂）としたこと以外は実施例５と同一条件で電解を行い、得られたフッ素化生成物の分析を行った。
表２に示すように、５−メチル置換体（５）が21％、１−メチル置換体（６）が12％、５−メチル２置換体（７）が４％得られた。
【００２０】
【表２】

【００２１】
比較例１
基質として２−シアノ−１−メチルピロールの代わりに２−シアノピロール１ミリモルを使用し、電流量を４Ｆ／モルから２Ｆ／モルに減少させたこと以外は実施例１と同一条件で電解を行い、得られたフッ素化生成物の分析を行った。
フッ素化されたピロール誘導体は得られず、主としてポリピロールが生成した。
【００２２】
比較例２
基質として２−シアノピロールの代わりにピロール１ミリモルを使用したこと以外は比較例１と同一条件で電解を行い、得られたフッ素化生成物の分析を行った。
フッ素化されたピロールは得られず、主としてポリピロールが生成した。
【００２３】
比較例３
基質として２−シアノピロールの代わりにメチルピロール１ミリモルを使用したこと以外は比較例１と同一条件で電解を行い、得られたフッ素化生成物の分析を行った。
フッ素化されたピロールは得られず、主としてポリピロールが生成した。
【００２４】
実施例及び比較例の考察
基質として２−シアノ−１−メチルピロールを使用した実施例１〜４では、２位及び／又は５位の水素がフッ素で置換され、又条件に依っては５位がオキソ化され、かつ２−３位と４−５位の共役結合が解裂して芳香族性が失われた。逆に（１）の化合物では芳香族性が維持された。このようにピロール誘導体のフッ素化生成物が得られたのは、電子吸引基である２−シアノ基が芳香環の電子を吸引して環の電子を欠乏させ、フッ素イオンの近接を容易にしているからであると考えられる。
【００２５】
基質として２−シアノ−１、５−ジメチルピロールを使用した実施例５〜７では、芳香環に直接結合した水素原子は置換されず、１位又は５位のメチル基の水素原子がフッ素で置換された。これらの場合には全ての場合で芳香族性が保持された。これらも電子吸引基である２−シアノ基に関係していると考えられる。
更にこれらの実施例では、溶媒を変えるのみで得られるフッ素化生成物の割合が変化した。
前記実施例から明らかなように、被フッ素化材料である基質の化学構造、フッ素化源の種類、及び溶媒等の条件を変化させることによりフッ素置換部位の異なる複数のフッ素化生成物が異なった組成で得られることが分かった。
【００２６】
比較例１の２−シアノピロールでは電子吸引基を有するにもかかわらず、フッ素化が生ぜず、重合によるポリマー化が進行した。この理由は明確ではないが、ピロール環のＮ−位が保護されていないとフッ素化が起こらないものと推測できる。
ピロールを使用した比較例２及びメチルピロールを使用した比較例３でフッ素化が生じなかったのは、シアノ基の有する電子吸引性が存在しないからであると推測できる。
【００２７】
【発明の効果】
本発明は、Ｎ−アルキルピロール誘導体及びＮ−アリールピロール誘導体から選択されかつ（化１）で表される芳香族含窒素複素環化合物（ここでＲ ₁ は、ＣＮ、ＮＯ ₂ 、Ｆ、Ｃｌ、Ｂｒ、 I 、ＲＣＯ及びＲＣＯＯから成る群から選択される電子吸引基、Ｒ ₂ はアルキル基又はアリール基、Ｒ ₃ はＣＮ、ＮＯ ₂ 、Ｆ、Ｃｌ、Ｂｒ、 I 、ＲＣＯ及びＲＣＯＯから成る群から選択される電子吸引基、Ｈ又はメチル基）をフッ素化原料とともに溶媒に溶解して電解液を調製し、該電解液を電解槽中で電解して、前記含窒素複素環化合物の一部の水素をフッ素で置換することを特徴とする芳香族含窒素複素環化合物の電解フッ素化方法である。
この発明では、フッ素化原料や電解液用の溶媒を適切に選択すると、Ｎ−アルキルピロール誘導体及びＮ−アリールピロール誘導体である芳香族含窒素複素環化合物のフッ素化反応を進行させて有用なフッ素化生成物を得ることができる。
【００２８】
本発明における芳香族含窒素複素環化合物は（化１）の通りのピロール誘導体で、ここでＲ ₁ は、ＣＮ、ＮＯ₂、Ｆ、Ｃｌ、Ｂｒ、I、ＲＣＯ及びＲＣＯＯから成る群から選択される電子吸引基、Ｒ₂はアルキル基又はアリール基、Ｒ ₃ はＣＮ、ＮＯ ₂ 、Ｆ、Ｃｌ、Ｂｒ、 I 、ＲＣＯ及びＲＣＯＯから成る群から選択される電子吸引基又はＨである。芳香族含窒素複素環化合物に電子吸引基が結合しているので、フッ素化の収率は向上する。これは電子吸引基の存在により電子密度の低下した芳香族環の水素原子を原料のフッ素アニオンが攻撃して、芳香環を破壊せずに置換できるからであると推測できる。
（化１）のＲ₂ はアルキル基又はアリール基である、つまりピロールの窒素原子が遊離の水素を有しないと、モノマーの重合が抑制され、フッ素化反応が促進される。
フッ素化原料としては、トリアルキルアミンポリフッ化水素塩化合物又はテトラアルキルアンモニウムフロリドポリフッ化水素化合物が好ましく使用できる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing a partially fluorinated nitrogen-containing heterocyclic compound by electrolytic fluorination of an aromatic nitrogen-containing heterocyclic compound.
[0002]
[Prior art]
Electrolysis is a chemical synthesis method that uses clean electrical energy to perform chemistry without the use of reaction reagents. The reaction rate can be controlled by the current density, and the product can be controlled by regulating the potential. It has a feature that can be selected. In the field of electrolytic synthesis of organic compounds, many organic compound oxidation-reduction processes have been put to practical use by utilizing a non-aqueous solvent that is stable and promotes the reaction. The electrolysis method is not suitable for mass production because it is a heterogeneous phase reaction on the electrode surface, but since selective synthesis is possible, it is considered to produce a high added-value substance in a new electrosynthesis system. Has been.
For example, fluorine-containing organic sulfur compounds are chemical synthetic products important as pharmaceuticals and agricultural chemicals, and compounds having a wide variety of molecular structures have been developed in order to obtain desired effects. It is known that an electrolytic method is useful for selectively converting the molecular structure of a fluorine-containing sulfur compound or selectively fluorinating an organic compound to obtain a desired fluorine-containing organic sulfur compound. Details on the electrolysis of organic compounds are reported in the electrochemical handbook.
[0003]
[Problems to be solved by the invention]
Nitrogen-containing heterocyclic compounds, particularly partially fluorinated products of aromatic nitrogen-containing heterocyclic compounds are interesting compounds that can be expected to have physiological activity. However, there are very few cases where aromatic nitrogen-containing heterocyclic compounds are directly fluorinated, including electrolysis, and it has been found that, for example, ethyl isonicotinate having an electron-withdrawing group on the pyridine ring has been directly electrofluorinated. (Organic Electrochemistry, 4th edition, pp.1035-1050, Marcel Dekker, New York (2001)). However, this method has not been put into practical use because of insufficient points in terms of yield and selectivity.
Accordingly, an object of the present invention is to provide a method capable of performing a partial fluorination reaction of a nitrogen-containing heterocyclic compound with a relatively high yield and selectivity.
[0004]
[Means for Solving the Problems]
The method of the present invention is an aromatic nitrogen-containing heterocyclic compound selected from N-alkylpyrrole derivatives and N-arylpyrrole derivatives and represented by (Chemical Formula 1) (wherein R ₁ is CN, NO ₂ , F, Cl , Br, I , RCO and RCOO, R ₂ is an alkyl or aryl group, R ₃ is CN, NO ₂ , F, Cl, Br, I , RCO and RCOO A part of the nitrogen-containing heterocyclic compound prepared by dissolving an electron-withdrawing group, H or methyl group selected from The method of electrolytic fluorination of an aromatic nitrogen-containing heterocyclic compound, characterized by substituting hydrogen with fluorine.
[Chemical 1]

[0005]
Hereinafter, the method of the present invention will be described in more detail.
The present invention is effective in partially fluorinated electron withdrawing group is bonded Kaoru aromatic nitrogen-containing heterocyclic compounds, when the condition setting appropriately, i.e. by the selection or the like of a combination of electrolyte and solvent to be used, a mono- containing It is possible to adjust the degree of fluorination, such as fluoride, difluoride, etc., or to select the site to be fluorinated.
Since the electron-withdrawing group to an aromatic nitrogen-containing heterocyclic compound is attached, the yield of the fluorination improved. It can be presumed that this is because an aromatic ring hydrogen atom whose electron density has decreased due to the presence of an electron-withdrawing group can be substituted by the raw material fluorine anion to attack the aromatic ring without destroying it.
[0006]
Many of the compounds produced by fluorination of this aromatic nitrogen-containing heterocyclic compound are new and useful, and some compounds can be used for Diels-Alder reaction, and two compounds can be used on the same carbon. These compounds having fluorine atoms are called gem-difluorinated compounds and are useful as physiologically active substances.
The partially fluorinated product of the aromatic nitrogen-containing heterocyclic compound obtained by the present invention becomes a raw material for another useful fluorine-containing compound, and the establishment of a novel synthesis route for the fluorine-containing compound based on this raw material. Can contribute.
Substrate is a starting material of the present invention are derived from the chemical structure of the fluorinated products of interest by Kaoru aromatic nitrogen-containing heterocyclic compound. If the nitrogen atom constituting the heterocyclic ring has free hydrogen, it is more susceptible to polymerization reaction than fluorination reaction. The starting material, N - there are alkyl pyrrole derivatives and N- arylpyrrole derived include, for example (Formula 1) can be preferably used a pyrrole derivative represented by.
[0008]
The fluorine raw material is selected from compounds capable of fluorinating a substrate to be fluorinated, and is preferably determined in consideration of not only the function of progressing the fluorination reaction but also the selectivity of fluorination at a desired site. As a preferable fluorine raw material, a trialkylamine polyhydrofluoride compound {R ₃ N.nHF (n = 1 to 10)} or a tetraalkylammonium fluoride polyhydrofluoride compound {R ₄ NF.nHF (n = 1 to 10) }, But is not limited to these.
As the anode that can be used in the method of the present invention, lead oxide, tin oxide, platinum, DSA, graphite, amorphous carbon (grassy carbon: GC), conductive diamond, etc. are generally used. Generally, lead, iron, platinum, titanium, carbon, etc. are used. The material that can be used as the electrode substrate preferably has corrosion resistance in order to achieve a long life and prevent contamination of the treated surface, and the power supply for supplying power to the electrode is made of titanium or the like for the anode. It is desirable to use a valve metal or an alloy thereof, and it is desirable to use noble metals such as platinum and iridium and oxides thereof as the anode catalyst. As described above, it is also preferable that diamond is formed on a metal current collector.
[0009]
As long as the current collector is a conductive material, there is no problem in its use. Titanium, niobium, tantalum, silicon, carbon, nickel, tungsten carbide, etc. are used for the plate, punched plate, wire mesh, powder sintered body, and metal fiber firing. It is desirable to process and use it in the shape of a knot.
As the electrolytic cell material, glass lining material, carbon, titanium, stainless steel and PTFE resin having excellent corrosion resistance can be preferably used from the viewpoints of durability and stability against organic compounds.
As for electrolysis conditions, the temperature is preferably 0 to 60 ° C., and the current density when using a normal electrode is preferably 0.1 to 100 A / dm ² .
[0010]
DETAILED DESCRIPTION OF THE INVENTION
Next, although the Example and comparative example of partial fluorination by electrolysis of the nitrogen-containing heterocyclic compound concerning this invention are described, these do not limit this invention.
[0011]
Example 1
An attempt was made to fluorinate a nitrogen-containing heterocyclic compound using a diaphragmless electrolytic cell containing platinum plates (both 20 mm × 20 mm) as an anode and a cathode. As the electrolytic solution, Et ₃ N · 2HF, which also functions as a fluorine raw material, was dissolved in 10 ml of acetonitrile to a concentration of 1M was used. As a substrate, 1 mmol of 2-cyano-1-methylpyrrole was dissolved in the electrolytic solution.
The electrolyte was subjected to constant current electrolysis at 1 A / dm ² and 4 F / mol while stirring at room temperature in a nitrogen atmosphere. After completion of the reaction, the solvent was removed by filtration under reduced pressure, and the residue was analyzed using NMR.
[0012]
As a result of analysis, as shown in Table 1, the 5-fluoro product (1) was 20%, the 2-fluoro-5-oxo product (2) was a trace amount, and the 2,2-difluoro-5-oxo product (3). Was a trace amount, and 32% of 2,5,5-trifluoro compound (4) was obtained.
It should be noted that among the obtained fluorinated products, the 5-fluoro product (1) retains aromaticity.
[0013]
Example 2
Electrolysis was performed under the same conditions as in Example 1 except that 1M of Et ₃ N · 3HF was used instead of Et ₃ N · 2HF, and the fluorinated product obtained was analyzed in the same manner as in Example 1. However, as shown in Table 1, 5-fluoro compound (1) was 5%, 2-fluoro-5-oxo compound (2) was 2%, and 2,2-difluoro-5-oxo compound (3) was 3%. %, And 65% of 2,5,5-trifluoro compound (4) was obtained.
[0014]
Example 3
Electrolysis was performed under the same conditions as in Example 1 except that 1M Et ₃ N · 5HF was used instead of Et ₃ N · 2HF, and the fluorinated product obtained was analyzed in the same manner as in Example 1. However, as shown in Table 1, the 5-fluoro product (1) was 0%, the 2-fluoro-5-oxo product (2) was 12%, and the 2,2-difluoro-5-oxo product (3) was 47%. %, And 65% of 2,5,5-trifluoro compound (4) was obtained.
[0015]
Example 4
Electrolysis was carried out under the same conditions as in Example 1 except that 1M Et ₄ NF · 4HF was used instead of Et ₃ N · 2HF, and the fluorinated product obtained was analyzed in the same manner as in Example 1. However, as shown in Table 1, the 5-fluoro product (1) was 0%, the 2-fluoro-5-oxo product (2) was 21%, and the 2,2-difluoro-5-oxo product (3) was 28%. %, And 6% of 2,5,5-trifluoro compound (4) was obtained.
[0016]
[Table 1]

[0017]
Example 5
Except that 1 mmol of 2-cyano-1,5-dimethylpyrrole was dissolved in the electrolyte as a substrate, Et ₃ N · 3HF was used as a fluorine source, and the current value was 2 F / mol. Electrolysis was carried out under the same conditions as in Example 1, and the resulting fluorinated product was analyzed.
As shown in Table 2, 33% of 5-methyl substituted product (5), 3% of 1-methyl substituted product (6), and trace amount of 5-methyl 2-substituted product (7) were obtained.
[0018]
Example 6
Electrolysis was performed under the same conditions as in Example 5 except that the solvent was dimethoxyethane (DME) instead of acetonitrile, and the resulting fluorinated product was analyzed. As shown in Table 2, 29% of the 5-methyl substituted product (5), 7% of the 1-methyl substituted product (6), and 3% of the 5-methyl 2-substituted product (7) were obtained.
[0019]
Example 7
Electrolysis was performed under the same conditions as in Example 5 except that dichloromethane (CCH ₂ Cl ₂ ) was used instead of acetonitrile, and the resulting fluorinated product was analyzed.
As shown in Table 2, 21% of the 5-methyl substituted product (5), 12% of the 1-methyl substituted product (6), and 4% of the 5-methyl 2-substituted product (7) were obtained.
[0020]
[Table 2]

[0021]
Comparative Example 1
Electrolysis was carried out under the same conditions as in Example 1, except that 1 mmol of 2-cyanopyrrole was used instead of 2-cyano-1-methylpyrrole as a substrate, and the amount of current was reduced from 4 F / mol to 2 F / mol. The obtained fluorinated product was analyzed.
A fluorinated pyrrole derivative was not obtained, and polypyrrole was mainly produced.
[0022]
Comparative Example 2
Electrolysis was performed under the same conditions as in Comparative Example 1 except that 1 mmol of pyrrole was used instead of 2-cyanopyrrole as a substrate, and the resulting fluorinated product was analyzed.
Fluorinated pyrrole was not obtained, and polypyrrole was mainly produced.
[0023]
Comparative Example 3
Electrolysis was carried out under the same conditions as in Comparative Example 1 except that 1 mmol of methylpyrrole was used instead of 2-cyanopyrrole as a substrate, and the resulting fluorinated product was analyzed.
Fluorinated pyrrole was not obtained, and polypyrrole was mainly produced.
[0024]
Discussion of Examples and Comparative Examples In Examples 1 to 4, where 2-cyano-1-methylpyrrole was used as the substrate, hydrogen at the 2-position and / or 5-position was replaced with fluorine, and depending on the conditions, the 5-position Was oxidized and the conjugated bond at the 2-3 and 4-5 positions was cleaved to lose aromaticity. On the other hand, aromaticity was maintained in the compound (1). Thus, the fluorinated product of the pyrrole derivative was obtained because the 2-cyano group, which is an electron-withdrawing group, attracts electrons in the aromatic ring and depletes the electrons in the ring, facilitating the proximity of fluorine ions. It is thought that it is because it is.
[0025]
In Examples 5 to 7 using 2-cyano-1,5-dimethylpyrrole as a substrate, the hydrogen atom directly bonded to the aromatic ring is not substituted, and the hydrogen atom of the 1- or 5-position methyl group is substituted with fluorine. It was done. In these cases, aromaticity was maintained in all cases. These are also considered to be related to the 2-cyano group which is an electron withdrawing group.
Furthermore, in these examples, the ratio of the fluorinated product obtained by simply changing the solvent was changed.
As is clear from the above examples, the fluorinated products having different fluorine substitution sites differed by changing the chemical structure of the substrate that is the material to be fluorinated, the type of fluorination source, and the solvent. It was found to be obtained by composition.
[0026]
Although 2-cyanopyrrole of Comparative Example 1 had an electron withdrawing group, fluorination did not occur and polymerization by polymerization proceeded. The reason is not clear, but it can be assumed that fluorination does not occur unless the N-position of the pyrrole ring is protected.
It can be presumed that the fluorination did not occur in Comparative Example 2 using pyrrole and Comparative Example 3 using methylpyrrole because the electron-withdrawing property of the cyano group does not exist.
[0027]
【The invention's effect】
The present invention is an aromatic nitrogen-containing heterocyclic compound selected from N-alkylpyrrole derivatives and N-arylpyrrole derivatives and represented by (Chemical Formula 1) (wherein R ₁ is CN, NO ₂ , F, Cl, An electron withdrawing group selected from the group consisting of Br, I , RCO and RCOO; R ₂ is an alkyl or aryl group; R ₃ is CN, NO ₂ , F, Cl, Br, I , RCO and RCOO; A selected electron withdrawing group, H or methyl group) is dissolved in a solvent together with a fluorinated raw material to prepare an electrolytic solution, the electrolytic solution is electrolyzed in an electrolytic bath, and a part of the nitrogen-containing heterocyclic compound is prepared. A method for electrolytic fluorination of an aromatic nitrogen-containing heterocyclic compound, wherein hydrogen is substituted with fluorine.
In the present invention, when a fluorination raw material and a solvent for an electrolytic solution are appropriately selected, a useful fluorine can be obtained by advancing a fluorination reaction of an aromatic nitrogen-containing heterocyclic compound which is an N-alkylpyrrole derivative and an N-arylpyrrole derivative. The product can be obtained.
[0028]
The aromatic nitrogen-containing heterocyclic compound in the present invention is a pyrrole derivative as shown in (Formula 1), wherein R ₁ is selected from the group consisting of CN, NO ₂ , F, Cl, Br, I, RCO and RCOO. that the electron-withdrawing group, R ₂ is an alkyl group or an aryl group, R ₃ is _{CN, NO 2, F, Cl} , Br, I, an electron withdrawing group or H is selected from the group consisting of RCO and RCOO. Since the electron-withdrawing group to an aromatic nitrogen-containing heterocyclic compound is attached, the yield of the fluorination improved. It can be presumed that this is because an aromatic ring hydrogen atom whose electron density has decreased due to the presence of an electron-withdrawing group can be substituted by the raw material fluorine anion to attack the aromatic ring without destroying it.
R _{2 in} (Chemical Formula 1) is an alkyl group or an aryl group, that is, if the nitrogen atom of pyrrole does not have free hydrogen, polymerization of the monomer is suppressed and the fluorination reaction is promoted.
As the fluorination raw material, a trialkylamine polyhydrofluoride compound or a tetraalkylammonium fluoride polyhydrofluoride compound can be preferably used.

Claims (2)

An aromatic nitrogen-containing heterocyclic compound selected from N-alkylpyrrole derivatives and N-arylpyrrole derivatives and represented by (Chemical Formula 1) (wherein R ₁ is CN, NO ₂ , F, Cl, Br, I , An electron withdrawing group selected from the group consisting of RCO and RCOO, R ₂ is an alkyl or aryl group, R ₃ is an electron selected from the group consisting of CN, NO ₂ , F, Cl, Br, I , RCO and RCOO (Suction group, H or methyl group) is dissolved in a solvent together with a fluorinated raw material to prepare an electrolytic solution, the electrolytic solution is electrolyzed in an electrolytic bath, and a part of the nitrogen-containing heterocyclic compound is replaced with fluorine. A method for electrolytic fluorination of an aromatic nitrogen-containing heterocyclic compound, characterized by substituting.

Fluorinated raw material, electrolytic fluorination method of claim 1 trialkylamines poly hydrogen fluoride salt compound or tetraalkylammonium fluoride poly hydrogen fluoride compound.