JP2004269414A

JP2004269414A - Organic ionic liquid having amino acid as constituting ion

Info

Publication number: JP2004269414A
Application number: JP2003061534A
Authority: JP
Inventors: Hiroyuki Ono; 弘幸大野; Masahiro Yoshizawa; 正博吉沢; Kenta Fukumoto; 健太福元; Takashi Inagaki; 隆司稲垣
Original assignee: KATAYAMA SEIYAKUSHIYO KK
Current assignee: KATAYAMA SEIYAKUSHIYO KK
Priority date: 2003-03-07
Filing date: 2003-03-07
Publication date: 2004-09-30
Anticipated expiration: 2023-03-07
Also published as: JP4261223B2

Abstract

<P>PROBLEM TO BE SOLVED: To provide a chiral derivative of a low environmental load type which can be simply obtained at a low cost, and an ionic liquid as a new solvent. <P>SOLUTION: The organic ionic liquid is a quaternary nitrogen compound represented by formula I [wherein the cation part AN<SP>+</SP>is (R)<SB>4</SB>N<SP>+</SP>(wherein R is a nonsubstituted or substituted lower alkyl group), a cation in which one proton or one alkyl group is bonded to the nitrogen atom of a nonsubstituted or substituted heterocycle having at least one nitrogen atom as the ring member or another cation and the anion part is an amino acid anion of H<SB>2</SB>N-Y-C(=O)-O<SP>-</SP>(wherein Y is a constituting part of an amino acid whose amino group and carboxylic group are eliminated)]. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

【０００１】
【発明の属する技術分野】
本発明は一般式Ｉで示される第４級窒素化合物である有機イオン性液体に関する。
【０００２】
【従来の技術および発明が解決しようとする課題】
イオン性液体とは融点が１００℃程度以下の塩の総称であり、最近、水、有機溶媒に次ぐ第三の溶媒として注目を集めている（例えば、非特許文献１）。イオン性液体はイオン性液体形成に有利なカチオンとアニオンを組合せて合成される。これまで用いられてきたカチオンにはイミダゾリウムカチオン、ピリジニウムカチオン、アルキルアンモニウムカチオンなどがあり、アニオンとしては、ＢＦ_４ ⁻、ＰＦ_６ ⁻、トリフレートアニオン（ＣＦＳＯ_３ ⁻）、イミドアニオン（ＴＦＳＩ⁻）、ＣＨＣＯＯ⁻、ＣＦ_３ＨＣＯＯ⁻、ＮＯ_３ ⁻、（ＣＮ）_２Ｎ⁻などがある。
【０００３】
それらイオン性液体の特徴として、液体状態を保つ温度範囲が極めて広いこと、液体でありながら蒸気圧がほぼゼロであるため不揮発性・不燃性であること、イオンのみからなる液体であるため極めて高いイオン伝導度を有すること、種々の無機・有機化合物に対して高い溶解性を有すること、イオンの組み合わせに依存するが水や汎用の有機溶媒と混ざらない液相を提供できることなどが挙げられる。これらの特徴に基づき、イオン性液体は各種合成溶媒、分離・抽出溶媒としての応用はもちろんのこと、バッテリーなどの電解質材料（例えば、特許文献１）としても精力的に研究されている。
【０００４】
これらの応用の中でも、各種合成溶媒としての報告は群を抜く。イオン性液体の特徴は、生活環境への拡散を最小限にとどめる上で有用であり、繰り返し利用する上でも優れているため、地球環境に優しい溶媒として、また従来の溶媒の代替材料として適切と考えられてきている。これまでに、Ｆｒｉｅｄｅｌ−Ｃｒａｆｔｓ反応、Ｄｉｅｌｓ−Ａｌｄｅｒ反応、Ｈｅｃｋ反応、Ｂｉｇｉｎｅｌｌｉ反応、Ｂｅｃｋｍａｎｎ転移反応などに関して報告がなされている（例えば、特許文献２）。これらはほんの一例に過ぎず、極めて多くの反応に検討が及んでいる。いずれもイオン性液体が反応用の溶媒として繰り返し利用できること、反応によっては従来の溶媒よりも優れた収率や選択性が得られることが明らかとなっている。
【０００５】
これら有機合成の中で最も重要な反応の一つは不斉合成である。不斉合成は有機化学分野にとどまらず、生化学、薬理学の分野においても極めて重要な位置を占める。これまで、不斉誘導体としては、光学活性な試薬やキラル触媒が用いられてきたが、キラルイオン性液体の合成もすでに検討されている。Ｄｉｅｌｓ−Ａｌｄｅｒ反応にキラルイオン性液体を用いた場合、反応時間の短縮、収率の向上、反応位置の選択性向上など顕著な結果が得られている。しかし、現在までに報告されているキラルイオン性液体にも改善すべき点は多い。
【０００６】
従来のイオン性液体の欠点としては、（１）イミダゾリウムカチオンやアンモニウムカチオンのようなカチオン構造にキラル部位を有する系は、合成手順が煩雑で高純度物を得るのは容易ではない；（２）キラルな塩を用いたイオン性液体の合成は従来の系と同様にアニオン交換反応により合成するため出発物質が高価である；（３）キラル部位が２カ所あるため、不斉触媒反応の妨げになる；（４）光学純度が１００％でない；融点が室温よりも高い系が多い（熱処理を必要とするためラセミ化や熱変性するなどの欠点がある）などが挙げられる。
【０００７】
これまでに天然アミノ酸を出発物質とするキラルイオン性液体の合成を試みた報告はある（例えば、非特許文献２）が、目的物質の合成に多段階の操作を経る必要があること、前駆体の合成時に官能基がカルボキシル基からアルコールに置換されること、イミダゾリウムカチオンの側鎖に嵩高いアミノ酸誘導体が導入されるため、得られた塩の融点が比較的高くなり、イオン性液体とはいえなかった。
【０００８】
【特許文献１】特開２０００−１１０４７２号公報
【特許文献２】特開２００２−２７５１１８号公報
【非特許文献１】大野弘幸、「有機イオン性液体−蒸発しない極性液体−」、未来材料、２００２年、第２巻第９号６〜１１頁
【非特許文献２】ＷｅｌｉａｎｇＢａｏ，ＺｈｉｍｉａｎｇＷａｎｇａｎｄＹｕｘｉａＬｉ，ＪｏｕｒｎａｌｏｆＯｒｇａｎｉｃＣｈｅｍｉｓｔｒｙ，２００３，６８（２），５９１−５９３
【０００９】
【課題を解決するための手段】
本発明は、一般式Ｉ：
【化２】

［式中、カチオン部ＡＮ^＋は、（Ｒ）_４Ｎ^＋（ここで、Ｒは、非置換もしくは置換された低級アルキル基）であるか、または１もしくはそれ以上の窒素原子を環員とする非置換もしくは置換されたヘテロ環の窒素原子にプロトンが１個付加したカチオンであり、アニオン部Ｈ_２Ｎ−Ｙ−Ｃ（＝Ｏ）−Ｏ⁻（ここで、Ｙは、アミノ酸のアミノ基およびカルボキシ基を除いた構成部分）のアニオンは、Ｄ−またはＬ−アミノ酸アニオンである］で示される第４級窒素化合物である有機イオン性液体を提供する。
【００１０】
低級アルキル基のカチオン（Ｒ）_４Ｎ^＋の例としては、低級アルキルアンモニウムが挙げられ、ヘテロ環のカチオンの例としては、ピロリウム、イミダゾリウム、２Ｈ−ピロリウム、ピラゾリウム、ピリジニウム、ピラジニウム、ピリミジウム、ピリダジニウム、インドリジニウム、インドリウム、３Ｈ−インドリウム、１Ｈ−インダゾリウム、イソインドリウム、プリニウム、４Ｈ−キノリジニウム、イソキノリニウム、キノリニウム、フタラジニウム、ナフチリジニウム、キノキサリニウム、キナゾリニウム、シノリニウム、プテリジニウム、４ａＨ−カルバゾリウム、カルバゾリウム、β−カルボリニウム、フェナンスリジニウム、アクリジニウム、ペリミジニウム、フェナンスロリニウム、フェナジニウムを挙げることができるが、好ましくは、イミダゾリウム、ピリジニウム、ピロリジニウムであり、より好ましくは、イミダゾリウムである。
【００１１】
アニオンは、Ｄ−またはＬ−のアミノ酸のアニオンであり、好ましくは天然のα−アミノ酸であり、より好ましくは、Ｌ−ロイシン、Ｌ−フェニルアラニン、Ｌ−イソロイシン、グリシン、Ｌ−グルタミン酸、Ｌ−バリン、Ｌ−アスパラギン酸、Ｌ−トリプトファン、Ｌ−アラニン、Ｌ−アルギニン、Ｌ−アスパラギン、Ｌ−システイン、Ｌ−グルタミン、Ｌ−ヒスチジン、Ｌ−リジン、Ｌ−メチオニン、Ｌ−プロリン、Ｌ−セリン、Ｌ−トレオニンまたはＬ−チロシンから選ばれるアミノ酸のアニオンである。
【００１２】
【発明の実施の形態】
この明細書で用いられる低級アルキル基としては、飽和の直鎖または分枝状の、炭素原子１〜１２個、好ましくは２〜６個、より好ましくは２〜４個を含む炭化水素残基をいう。例えばメチル、エチル、プロピル、イソプロピル、ブチル、ｓ−ブチル、ｔ−ブチル、ペンチル、ヘキシルなどを挙げることができ、好ましくは、エチル、プロピル、イソプロピル、ブチル、ペンチル、ヘキシルであり、より好ましくは、エチルおよびブチルである。
【００１３】
式ＩのＲおよびヘテロ環の置換基としては、炭素原子１〜１２、好ましくは、炭素原子１〜６、より好ましくは、炭素原子１〜４の低級アルキル基であり、好ましくは、メチルおよびエチルを挙げることができる。
【００１４】
本発明の第４級窒素化合物の一般的製造方法
カチオン部のＡＮ^＋のハライド、好ましくはブロミド、１重量部を水性溶媒に溶解させ、適当な処理、例えば、陰イオン交換樹脂を通し、ヒドロキシ化合物に変換し、これに、アニオン部Ｈ_２Ｎ−Ｙ−Ｃ（＝Ｏ）−Ｏ⁻となるアミノ酸約１〜１．１重量部、好ましくは、約１．０重量部を添加し、得られた混合溶液を氷冷下攪拌し、溶媒を減圧留去し、残渣から適当な方法によって未反応のアミノ酸を除去し、所望のイオン性液体としての第４級窒素化合物を得る。
【００１５】
【実施例】
以下、実施例によってこの発明を具体的に説明するが本発明はこれに限定されるものではない。なお、これらの実施例における１，３−ジアルキルイミダゾリウム水酸化物とアミノ酸の中和反応の進行は、^１Ｈ−ＮＭＲ測定および元素分析によって行い確認された。
【００１６】
実施例１
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−ロイシン０．８ｇを水１００ｍｌに加え、均一溶液にしたものに、ＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のロイシン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムロイシン塩１．０ｇ（収率８０％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は図１に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。元素分析の結果は理論値に一致した。
元素分析（％）Ｃ_１２Ｈ_２３Ｎ_３О_２・４Ｈ_２О
Ｃ４４．６６％，Ｈ９．６１％，Ｎ１２．８１％
【００１７】
実施例２
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−フェニルアラニン１．０ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のフェニルアラニン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムフェニルアラニン塩１．２ｇ（収率８３％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は図２に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。
【００１８】
実施例３
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−イソロイシン１．０ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のイソロイシン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムイソロイシン塩１．０ｇ（収率８２％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は図３に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。
【００１９】
実施例４
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。グリシン０．５ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のグリシン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムグリシン塩０．８ｇ（収率８２％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は図４に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。元素分析の結果は理論値通りであった。
元素分析Ｃ_８Ｈ_１５Ｎ_３О_２・０．５Ｈ_２О
Ｃ４９．１８％，Ｈ８．２５％，Ｎ２１．１７％
【００２０】
実施例５
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−グルタミン酸０．９ｇを水１００ｍｌに加えたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のグルタミン酸）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムグルタミン酸塩１．１ｇ（収率８０％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は図５に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。
【００２１】
実施例６
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−バリン０．７ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のバリン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムバリン塩０．９ｇ（収率７９％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は図６に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。
【００２２】
実施例７
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−アスパラギン酸０．９ｇを水１００ｍｌに加えたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のアスパラギン酸）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムアスパラギン酸塩１．１ｇ（収率８９％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は図７に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。
【００２３】
実施例８
１−エチル−３−メチルイミダゾリウムブロミド１．５ｇに水１０ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−トリプトファン１．８ｇを水１００ｍｌに加えたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のトリプトファン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムトリプトファン塩１．０ｇ（収率８２％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は図８に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。
【００２４】
実施例９
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−アラニン０．７ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のアラニン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムアラニン塩０．９ｇ（収率８６％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は以下に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。元素分析の結果は理論値通りであった。
【化３】

^１Ｈ−ＮＭＲ（ＤＭＳＯ， δ／ｐｐｍＴＭＳ基準）：０．９６（ｄ，３Ｈ，Ｊ＝３．５Ｈｚ，（ｈ）），１．３５（ｔ，３Ｈ，Ｊ＝７Ｈｚ），２．８０（ｑ，１Ｈ，１０．３），３．８３（ｓ，３Ｈ），４．１７（ｑ，２Ｈ，Ｊ＝１１．３Ｈｚ），７．７２（ｓ，１Ｈ），７．８１（ｓ，１Ｈ），９．８３（ｓ，１Ｈ）
元素分析Ｃ_９Ｈ_１７Ｎ_３О_２・２Ｈ_２О
Ｃ４５．９２％，Ｈ８．７４％，Ｎ１７．４０％
【００２５】
実施例１０
１−エチル−３−メチルイミダゾリウムブロミド１．５ｇに水１０ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−アルギニン１．６ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これを温度を０℃に維持しながら２４時間冷却し、その後、濾過により析出した結晶（過剰に加えた未反応のアルギニン）を除去することで１−エチル−３−メチルイミダゾリウムアルギニン塩１．６ｇ（収率７４％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は以下に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。
【化４】

^１Ｈ−ＮＭＲ（ＤＭＳＯ， δ／ｐｐｍＴＭＳ基準）：１．２３（ｍ，２Ｈ，Ｊ＝１５Ｈｚ，（ｉ）），１．３５（ｔ，３Ｈ，Ｊ＝７Ｈｚ），１．４４（ｍ，２Ｈ，（ｈ）），２．７９（ｔ，１Ｈ，Ｊ＝６．５．（ｇ）），２．８５（ｔ，２Ｈ，Ｊ＝９Ｈｚ，（ｊ）），３．８１（ｓ，３Ｈ），４．１６（ｑ，２Ｈ，Ｊ＝１１Ｈｚ），７．６８（ｄ，１Ｈ，Ｊ＝１Ｈｚ），７．７７（ｄ，１Ｈ，Ｊ＝０．７５Ｈｚ）
【００２６】
実施例１１
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−アスパラギン０．８ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のアスパラギン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムアスパラギン塩１．１ｇ（収率８３％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は以下に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。
【化５】

^１Ｈ−ＮＭＲ（ＤＭＳＯ， δ／ｐｐｍＴＭＳ基準）：１．３６（ｔ，３Ｈ，Ｊ＝７．５Ｈｚ），１．９３（ｑ，１Ｈ，Ｊ＝１１．８Ｈｚ，（ｈ）），２．３５（ｑ，１Ｈ，Ｊ＝９．５Ｈｚ，（ｈ）），３．０６（ｑ，１Ｈ，Ｊ＝６．３Ｈｚ），３．８２（ｓ，３Ｈ），４．１６（ｑ，２Ｈ，Ｊ＝１０．８），６．５８（ｓ，１Ｈ，（ｉ）），７．７０（ｔ，１Ｈ，Ｊ＝２Ｈｚ），７．７８（ｔ，１Ｈ，Ｊ＝１．５Ｈｚ），７．９９（ｓ，１Ｈ，（ｉ）），９．５９（ｓ，１Ｈ）
【００２７】
実施例１２
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。窒素雰囲気下でＬ−システイン０．８ｇを脱気した水１００ｍｌに加えたものに脱気したＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のシステイン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムシステイン塩０．９ｇ（収率７７％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は以下に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。
【化６】

^１Ｈ−ＮＭＲ（ＤＭＳＯ， δ／ｐｐｍＴＭＳ基準）：１．３６（ｔ，３Ｈ，Ｊ＝７．５Ｈｚ），２．４５（ｄ，１Ｈ，Ｊ＝１０．３Ｈｚ，（ｈ）），２．６７（ｄ，１Ｈ，Ｊ＝８．５Ｈｚ，（ｈ）），２．９３（ｔ，１Ｈ，Ｊ＝５．５Ｈｚ），３．８２（ｓ，３Ｈ），４．１７（ｑ，２Ｈ，Ｊ＝１０．８Ｈｚ），７．７０（ｓ，１Ｈ），７．７８（ｓ，１Ｈ），９．５１（ｓ，１Ｈ）
【００２８】
実施例１３
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−グルタミン０．８ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のグルタミン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムグルタミン塩０．９ｇ（収率６６％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は以下に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。
【化７】

^１Ｈ−ＮＭＲ（ＤＭＳＯ， δ／ｐｐｍＴＭＳ基準）：１．３５（ｔ，３Ｈ，Ｊ＝７Ｈｚ），１．４３（ｍ，１Ｈ，Ｊ＝１８Ｈｚ（ｈ）），１．６６（ｍ，１Ｈ，Ｊ＝１３Ｈｚ，（ｈ）），２．０１（ｍ，２Ｈ，Ｊ＝２３．８Ｈｚ，（ｉ）），２．７７（ｔ，１Ｈ，Ｊ＝６．３Ｈｚ），３．８２（ｓ，３Ｈ），４．１７（ｑ，２Ｈ，Ｊ＝１０．８Ｈｚ），６．５５（ｓ，１Ｈ，（ｊ）），７．６１（ｓ，１Ｈ，（ｊ）），７．７１（ｓ，１Ｈ），７．７９（ｓ，１Ｈ），９．６７（ｓ，１Ｈ）
【００２９】
実施例１４
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−ヒスチジン１．０ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のヒスチジン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムヒスチジン塩１．１ｇ（収率７８％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は以下に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。
【化８】

^１Ｈ−ＮＭＲ（ＤＭＳＯ， δ／ｐｐｍＴＭＳ基準）：１．３４（ｔ，３Ｈ，Ｊ＝７Ｈｚ），２．３６（ｑ，１Ｈ，Ｊ＝１１Ｈｚ，（ｈ）），２．８２（ｑ，１Ｈ，Ｊ＝９．３Ｈｚ，（ｈ）），２．９９（ｔ，１Ｈ，Ｊ＝６Ｈｚ），３．８０（ｓ，３Ｈ），４．１４（ｑ，２Ｈ，Ｊ＝１０．８Ｈｚ），６．５８（ｓ，１Ｈ，（ｉ）），７．３５（ｓ，１Ｈ，（ｊ）），７．６８（ｓ，１Ｈ），７．７６（ｓ，１Ｈ），９．５３（ｓ，１Ｈ）
【００３０】
実施例１５
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−リジン０．９ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のリジン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムリジン塩１．０ｇ（収率７８％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は以下に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。元素分析の結果は理論値通りであった。
【化９】

^１Ｈ−ＮＭＲ（ＤＭＳＯ， δ／ｐｐｍＴＭＳ基準）：１．２２（ｍ，５Ｈ，Ｊ＝１３．５Ｈｚ，（ｉ）（ｊ）（ｈ）），１．３６（ｔ，３Ｈ，Ｊ＝７．５），１．４８（ｍ，１Ｈ，Ｊ＝１３Ｈｚ，（ｈ）），２．４２（ｄ，２Ｈ，Ｊ＝６．５Ｈｚ，（ｋ）），２．７３（ｔ，１Ｈ，Ｊ＝７．０Ｈｚ），３．８２（ｓ，３Ｈ），４．１７（ｑ，２Ｈ，Ｊ＝１１．３Ｈｚ），７．７０（ｔ，１Ｈ，Ｊ＝１．５Ｈｚ），７．７９（ｔ，１Ｈ，Ｊ＝１．５Ｈｚ），９．６７（ｓ，１Ｈ）
元素分析Ｃ_１２Ｈ_２４Ｎ_４О_２・Ｈ_２О
Ｃ５８．３６％，Ｈ８．０１％，Ｎ１３．５８％
【００３１】
実施例１６
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−メチオニン０．９ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のメチオニン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムメチオニン塩１．１ｇ（収率７８％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は以下に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。元素分析の結果は理論値通りであった。
【化１０】

^１Ｈ−ＮＭＲ（ＤＭＳＯ， δ／ｐｐｍＴＭＳ基準）：１．３６（ｔ，３Ｈ，Ｊ＝７．５Ｈｚ），１．４２（ｍ，１Ｈ，Ｊ＝２４．５Ｈｚ，（ｈ）），１．７４（ｍ，１Ｈ，Ｊ＝１６．５Ｈｚ，（ｈ）），１．９４（ｓ，１Ｈ），２．４２（ｔ，２Ｈ，Ｊ＝８．５Ｈｚ，（ｉ）），２．８２（ｑ，１Ｈ，Ｊ＝５．７５Ｈｚ），３．８２（ｓ，３Ｈ），４．１７（ｑ，２Ｈ，Ｊ＝１１．３Ｈｚ），７．７１（ｓ，１Ｈ），７．８０（ｓ，１Ｈ），９．６９（ｓ，１Ｈ）
元素分析Ｃ_１１Ｈ_２１Ｎ_３О_２Ｓ・２．２Ｈ_２О
Ｃ４３．８７％，Ｈ８．５１％，Ｎ１３．８６％
【００３２】
実施例１７
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−プロリン１．０ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のプロリン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムプロリン塩１．１ｇ（収率８３％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は以下に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。元素分析の結果は理論値通りであった。
【化１１】

^１Ｈ−ＮＭＲ（ＤＭＳＯ， δ／ｐｐｍＴＭＳ基準）：１．３６（ｔ，３Ｈ，Ｊ＝７．５Ｈｚ），１．４２（ｍ，１Ｈ，Ｊ＝１７Ｈｚ），１．５１（ｍ，１Ｈ，Ｊ＝１９Ｈｚ），１．６２（ｂｒｏａｄ，１Ｈ），１．７７（ｍ，１Ｈ，Ｊ＝１７．８Ｈｚ），２．６０（ｂｒｏａｄ，１Ｈ），２，９２（ｍ，１Ｈ，Ｊ＝１１．３Ｈｚ），３．１８（ｂｒｏａｄ，１Ｈ），３．８２（ｓ，３Ｈ），４．１６（ｑ，２Ｈ，Ｊ＝１１．３Ｈｚ），７．７０（ｓ，１Ｈ），７．７９（ｓ，１Ｈ），９．５３（ｓ，１Ｈ）
元素分析Ｃ_１１Ｈ_１９Ｎ_３О_２・２Ｈ_２О
Ｃ５０．１６％，Ｈ８．８５％，Ｎ１５．３２％
【００３３】
実施例１８
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−セリン０．７ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のセリン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムセリン塩０．９ｇ（収率７９％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は以下に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。元素分析の結果は理論値通りであった。
【化１２】

^１Ｈ−ＮＭＲ（ＤＭＳＯ， δ／ｐｐｍＴＭＳ基準）：１．３６（ｔ，３Ｈ，Ｊ＝７Ｈｚ），２．８３（ｔ，１Ｈ，Ｊ＝７Ｈｚ），３．２３（ｍ，２Ｈ，Ｊ＝１５．５Ｈｚ，（ｈ）），３．８１（ｓ，３Ｈ），４．１６（ｑ，２Ｈ，Ｊ＝１１Ｈｚ），７．６９（ｓ，１Ｈ），７．７８（ｓ，１Ｈ），９．４７（ｓ，１Ｈ）
元素分析Ｃ_８Ｈ_１７Ｎ_３О_３・Ｈ_２О
Ｃ４６．３７％，Ｈ８．２２％，Ｎ１７．７１％
【００３４】
実施例１９
１−エチル−３−メチルイミダゾリウムブロミド１．０ｇに水５ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−トレオニン０．７ｇを水１００ｍｌに加え、均一溶液にしたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のトレオニン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムトレオニン塩１．０ｇ（収率８４％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は以下に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。
【化１３】

^１Ｈ−ＮＭＲ（ＤＭＳＯ， δ／ｐｐｍＴＭＳ基準）：０．８６（ｄ，３Ｈ，Ｊ＝３Ｈｚ，（ｉ）），１．３６（ｔ，３Ｈ，Ｊ＝７Ｈｚ），２．８２（ｄ，１Ｈ，Ｊ＝２．５Ｈｚ），３．４４（ｍ，１Ｈ，Ｊ＝１２Ｈｚ，（ｈ）），３．８２（ｓ，３Ｈ），４．１７（ｑ，２Ｈ，Ｊ＝１０．８Ｈｚ），７．７０（ｓ，１Ｈ），７．７９（ｓ，１Ｈ），９．５２（ｓ，１Ｈ）
【００３５】
実施例２０
１−エチル−３−メチルイミダゾリウムブロミド２．０ｇに水１０ｍｌを加え、均一溶解させたのちこれを陰イオン交換樹脂に通し、１−エチル−３−メチルイミダゾリウムヒドロキシド水溶液（以下、ＥＭＩｍＯＨ水溶液と記す）を得た。Ｌ−チロシン２．２ｇを水１００ｍｌに加えたものにＥＭＩｍＯＨ水溶液をゆっくり滴下して、氷冷し、温度を０℃に維持しながら１２時間攪拌したのち、減圧乾燥して余分な水を除去した。これにアセトニトリル４０ｍｌとメチルアルコール１０ｍｌを加え、温度を０℃に維持しながら３０分攪拌した。その後、濾過により析出した結晶（過剰に加えた未反応のチロシン）を除去した。濾液を減圧加熱乾燥してアセトニトリルとメチルアルコールを除去し、１−エチル−３−メチルイミダゾリウムチロシン塩２．１ｇ（収率７０％）を得た。本品の^１Ｈ−ＮＭＲ測定を行った結果は以下に示したとおりであり、プロトンの化学シフトと積分強度から反応の進行が確認された。
【化１４】

^１Ｈ−ＮＭＲ（ＤＭＳＯ， δ／ｐｐｍＴＭＳ基準）：１．３４（ｔ，３Ｈ，Ｊ＝７Ｈｚ），２．１１（ｔ，１Ｈ，Ｊ＝１１．５Ｈｚ），２．８０（ｍ，２Ｈ，Ｊ＝２５．７Ｈｚ，（ｈ）），３．７８（ｓ，３Ｈ），４．１３（ｑ，２Ｈ，Ｊ＝１０．８Ｈｚ），６．３８（ｄ，２Ｈ，Ｊ＝４．３Ｈｚ，（ｉ）），６．７０（ｄ，２Ｈ，Ｊ＝４．３Ｈ，（ｊ）），７．６５（ｓ，１Ｈ），７．７４（ｓ，１Ｈ），９．４８（ｓ，１Ｈ）
【００３６】
【発明の効果】
本発明は安価で容易に入手できる天然アミノ酸を構成イオンとする第４級窒素化合物である有機イオン性液体を提供するものである。本発明によって、従来は合成が困難であった光学活性な環境を安価かつ容易に入手できる。すなわち、本発明によって、天然アミノ酸などを用いて適切なカチオンと共に塩とすることで、光学純度が１００％で、氷点下から２００℃を超す広い温度範囲において液体状態を保ち、アミノ酸反応前駆体としての可能性をもつキラルなイオン性液体を提供するものである。このイオン性液体は、通常のイオン性液体と同等の特性をより安価に得ることができ、通常のイオン性液体の応用分野全てに用いることができ、しかもアミノ酸の反応前駆体として各種機能分子の創製に利用できる可能性も併せ持つ。
【図面の簡単な説明】
【図１】１−エチル−３−メチルイミダゾリウムロイシン塩（実施例１）の^１Ｈ−ＮＭＲチャートである。
【図２】１−エチル−３−メチルイミダゾリウムフェニルアラニン塩（実施例２）の^１Ｈ−ＮＭＲチャートである。
【図３】１−エチル−３−メチルイミダゾリウムイソロイシン塩（実施例３）の^１Ｈ−ＮＭＲチャートである。
【図４】１−エチル−３−メチルイミダゾリウムグリシン塩（実施例４）の^１Ｈ−ＮＭＲチャートである。
【図５】１−エチル−３−メチルイミダゾリウムグルタミン酸塩（実施例５）の^１Ｈ−ＮＭＲチャートである。
【図６】１−エチル−３−メチルイミダゾリウムバリン塩（実施例６）の^１Ｈ−ＮＭＲチャートである。
【図７】１−エチル−３−メチルイミダゾリウムアスパラギン酸塩（実施例７）の^１Ｈ−ＮＭＲチャートである。
【図８】１−エチル−３−メチルイミダゾリウムトリプトファン塩（実施例８）の^１Ｈ−ＮＭＲチャートである。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to organic ionic liquids which are quaternary nitrogen compounds of the general formula I.
[0002]
2. Description of the Related Art
An ionic liquid is a general term for salts having a melting point of about 100 ° C. or less, and has recently been receiving attention as a third solvent next to water and organic solvents (for example, Non-Patent Document 1). Ionic liquids are synthesized by combining cations and anions that favor ionic liquid formation. The cations used so far include imidazolium cation, pyridinium cation, alkylammonium cation and the like.₄ ⁻, PF₆ ⁻, Triflate anion (CFSO₃ ⁻), Imide anion (TFSI⁻), CHCOO⁻, CF₃HCOO⁻, NO₃ ⁻, (CN)₂N⁻and so on.
[0003]
The characteristics of these ionic liquids are that the temperature range in which the liquid state is maintained is extremely wide, that the liquid is non-volatile and non-flammable because its vapor pressure is almost zero, and that it is extremely high because it is a liquid containing only ions It has ionic conductivity, has high solubility in various inorganic and organic compounds, and can provide a liquid phase which depends on the combination of ions but is not mixed with water or a general-purpose organic solvent. Based on these features, ionic liquids have been energetically studied as electrolyte materials for batteries and the like (for example, Patent Document 1) as well as applications as various synthesis solvents and separation / extraction solvents.
[0004]
Among these applications, reports as various synthetic solvents are outstanding. The characteristics of ionic liquids are useful for minimizing diffusion into the living environment and are also excellent for repeated use, making them suitable as environmentally friendly solvents and alternatives to conventional solvents. It has been considered. There have been reports on the Friedel-Crafts reaction, the Diels-Alder reaction, the Heck reaction, the Biginelli reaction, the Beckmann rearrangement reaction, and the like (for example, Patent Document 2). These are just a few examples, and numerous reactions have been studied. In any case, it is clear that the ionic liquid can be repeatedly used as a solvent for the reaction, and that depending on the reaction, a higher yield and selectivity than conventional solvents can be obtained.
[0005]
One of the most important reactions in these organic syntheses is asymmetric synthesis. Asymmetric synthesis occupies a very important position not only in the field of organic chemistry but also in the fields of biochemistry and pharmacology. Until now, optically active reagents and chiral catalysts have been used as asymmetric derivatives, but synthesis of chiral ionic liquids has already been studied. When a chiral ionic liquid is used in the Diels-Alder reaction, remarkable results such as a reduction in reaction time, an improvement in yield, and an improvement in selectivity of a reaction position have been obtained. However, there are many points to be improved in the chiral ionic liquids reported to date.
[0006]
Disadvantages of conventional ionic liquids include (1) systems having chiral sites in the cation structure, such as imidazolium cations and ammonium cations, are complicated in the synthesis procedure and it is not easy to obtain high-purity products; (2) ) The synthesis of an ionic liquid using a chiral salt is expensive as starting materials because it is synthesized by an anion exchange reaction as in the conventional system; (3) Since there are two chiral sites, the asymmetric catalytic reaction is hindered. (4) The optical purity is not 100%; there are many systems having a melting point higher than room temperature (there are drawbacks such as racemization and thermal denaturation due to the need for heat treatment).
[0007]
There have been reports of attempts to synthesize chiral ionic liquids using natural amino acids as starting materials (for example, Non-Patent Document 2), but it is necessary to go through multi-step operations to synthesize target substances, Since the functional group is substituted with an alcohol from a carboxyl group during the synthesis of the compound, and a bulky amino acid derivative is introduced into the side chain of the imidazolium cation, the melting point of the obtained salt becomes relatively high, and the ionic liquid I couldn't say it.
[0008]
[Patent Document 1] JP-A-2000-110472
[Patent Document 2] JP-A-2002-275118
[Non-Patent Document 1] Hiroyuki Ohno, "Organic Ionic Liquid-Polar Liquid That Does Not Evaporate-", Future Materials, 2002, Vol. 2, No. 9, pp. 6-11.
[Non-Patent Document 2] Weliang Bao, Zhimiang Wang and Yuxia Li, Journal of Organic Chemistry, 2003, 68 (2), 591-593.
[0009]
[Means for Solving the Problems]
The present invention provides compounds of the general formula I:
Embedded image

[Wherein the cation moiety AN⁺Is (R)₄N⁺(Where R is an unsubstituted or substituted lower alkyl group) or one proton is added to a nitrogen atom of an unsubstituted or substituted heterocyclic ring having one or more nitrogen atoms as ring members. An anion moiety H₂NYC (= O) -O⁻(Where Y is a constituent part excluding the amino group and the carboxy group of the amino acid), wherein the anion is a D- or L-amino acid anion]. I do.
[0010]
Cation (R) of lower alkyl group₄N⁺Examples of lower alkyl ammonium include; examples of heterocyclic cations include pyrrolium, imidazolium, 2H-pyrrolium, pyrazolium, pyridinium, pyrazinium, pyrimidium, pyridazinium, indolizinium, indolium, and 3H-india. Lium, 1H-indazolium, isoindolinium, prinium, 4H-quinolidinium, isoquinolinium, quinolinium, phthalazinium, naphthyridinium, quinoxalinium, quinazolinium, sinolinium, pteridinium, 4aH-carbazolium, carbazolium, β-carbolinium, phenanthridinium, diclinium , Phenanthrolinium, phenazinium, but preferably imidazolium, pyridini Arm, a pyrrolidinium, more preferably imidazolium.
[0011]
The anion is an anion of a D- or L-amino acid, preferably a natural α-amino acid, and more preferably L-leucine, L-phenylalanine, L-isoleucine, glycine, L-glutamic acid, L-valine. , L-aspartic acid, L-tryptophan, L-alanine, L-arginine, L-asparagine, L-cysteine, L-glutamine, L-histidine, L-lysine, L-methionine, L-proline, L-serine, An anion of an amino acid selected from L-threonine and L-tyrosine.
[0012]
BEST MODE FOR CARRYING OUT THE INVENTION
As the lower alkyl group used in this specification, a saturated linear or branched hydrocarbon residue containing 1 to 12, preferably 2 to 6, more preferably 2 to 4 carbon atoms is used. Say. For example, methyl, ethyl, propyl, isopropyl, butyl, s-butyl, t-butyl, pentyl, hexyl and the like, preferably, ethyl, propyl, isopropyl, butyl, pentyl, hexyl, more preferably, Ethyl and butyl.
[0013]
Substituents for R and the heterocycle in Formula I are lower alkyl groups of 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, preferably methyl and ethyl. Can be mentioned.
[0014]
General method for producing a quaternary nitrogen compound of the present invention
AN of cation part⁺Of a halide, preferably bromide, is dissolved in an aqueous solvent and converted into a hydroxy compound by a suitable treatment, for example, by passing through an anion exchange resin.₂NYC (= O) -O⁻About 1 to 1.1 parts by weight of an amino acid, preferably about 1.0 part by weight, is added, and the resulting mixed solution is stirred under ice-cooling, the solvent is distilled off under reduced pressure, and the residue is subjected to an appropriate method Unreacted amino acids are removed to obtain a quaternary nitrogen compound as a desired ionic liquid.
[0015]
【Example】
Hereinafter, the present invention will be described specifically with reference to Examples, but the present invention is not limited thereto. In these examples, the progress of the neutralization reaction between the 1,3-dialkylimidazolium hydroxide and the amino acid was as follows:¹Confirmed by H-NMR measurement and elemental analysis.
[0016]
Example 1
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). 0.8 g of L-leucine was added to 100 ml of water, and a homogeneous solution was slowly added dropwise with an aqueous solution of EMImOH. The mixture was cooled on ice, stirred for 12 hours while maintaining the temperature at 0 ° C., and dried under reduced pressure to remove excess. Water was removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (excess unreacted leucine) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol to obtain 1.0 g (80% yield) of 1-ethyl-3-methylimidazolium leucine salt. This product¹The result of the H-NMR measurement was as shown in FIG. 1, and the progress of the reaction was confirmed from the chemical shift of proton and the integrated intensity. The results of elemental analysis were consistent with the theoretical values.
Elemental analysis (%) C₁₂H₂₃N₃О₂・ 4H₂О
C 44.66%, H 9.61%, N 12.81%
[0017]
Example 2
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). L-Phenylalanine (1.0 g) was added to water (100 ml), and a uniform solution was slowly added with an aqueous solution of EMImOH. The mixture was cooled on ice, stirred at 0 ° C. for 12 hours, dried under reduced pressure, and dried under reduced pressure. The water was removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (unreacted phenylalanine added in excess) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol, to obtain 1.2 g of 1-ethyl-3-methylimidazolium phenylalanine salt (83% yield). This product¹The result of the H-NMR measurement was as shown in FIG. 2, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity.
[0018]
Example 3
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). 1.0 g of L-isoleucine was added to 100 ml of water, and a homogeneous solution was slowly added dropwise with an aqueous solution of EMImOH. The mixture was cooled on ice, stirred for 12 hours while maintaining the temperature at 0 ° C., and dried under reduced pressure to remove excess. The water was removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Then, the precipitated crystals (excess unreacted isoleucine) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol, to obtain 1.0 g of 1-ethyl-3-methylimidazolium isoleucine salt (82% yield). This product¹The result of the H-NMR measurement was as shown in FIG. 3, and the progress of the reaction was confirmed from the chemical shift of proton and the integrated intensity.
[0019]
Example 4
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). 0.5 g of glycine was added to 100 ml of water, and an EMImOH aqueous solution was slowly added dropwise to a homogeneous solution. The mixture was cooled on ice, stirred for 12 hours while maintaining the temperature at 0 ° C., and dried under reduced pressure to remove excess water. Removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (unreacted glycine added in excess) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol, to obtain 0.8 g (82% yield) of 1-ethyl-3-methylimidazolium glycine salt. This product¹The result of the H-NMR measurement is as shown in FIG. 4, and the progress of the reaction was confirmed from the chemical shift of proton and the integrated intensity. The results of elemental analysis were as expected.
Elemental analysis C₈H_FifteenN₃О₂・ 0.5H₂О
C 49.18%, H 8.25%, N 21.17%
[0020]
Example 5
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an anion exchange resin. To write). An aqueous solution of EMImOH was slowly dropped into 0.9 g of L-glutamic acid added to 100 ml of water, cooled with ice, stirred for 12 hours while maintaining the temperature at 0 ° C., and dried under reduced pressure to remove excess water. . 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (unreacted glutamic acid added in excess) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol, to obtain 1.1 g of 1-ethyl-3-methylimidazolium glutamate (80% yield). This product¹The result of the H-NMR measurement was as shown in FIG. 5, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity.
[0021]
Example 6
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an anion exchange resin. To write). 0.7 g of L-valine was added to 100 ml of water, and an aqueous solution of EMImOH was slowly added dropwise to a homogeneous solution. The mixture was cooled on ice, stirred for 12 hours while maintaining the temperature at 0 ° C., and dried under reduced pressure to remove excess. The water was removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (unreacted valine added in excess) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol, to obtain 0.9 g of 1-ethyl-3-methylimidazolium valine salt (yield 79%). This product¹The result of the H-NMR measurement was as shown in FIG. 6, and the progress of the reaction was confirmed from the chemical shift of proton and the integrated intensity.
[0022]
Example 7
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). An aqueous solution of EMImOH was slowly added dropwise to a mixture of 0.9 g of L-aspartic acid in 100 ml of water, cooled with ice, stirred for 12 hours while maintaining the temperature at 0 ° C., and dried under reduced pressure to remove excess water. did. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (excess unreacted aspartic acid added) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol to obtain 1.1 g of 1-ethyl-3-methylimidazolium aspartate (89% yield). This product¹The result of the H-NMR measurement is as shown in FIG. 7, and the progress of the reaction was confirmed from the chemical shift of proton and the integrated intensity.
[0023]
Example 8
10 ml of water was added to 1.5 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). An EMImOH aqueous solution was slowly added dropwise to 1.8 ml of L-tryptophan added to 100 ml of water, cooled with ice, stirred for 12 hours while maintaining the temperature at 0 ° C., and dried under reduced pressure to remove excess water. . 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (excessively added unreacted tryptophan) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol to obtain 1.0 g of 1-ethyl-3-methylimidazolium tryptophan salt (yield: 82%). This product¹The result of the H-NMR measurement was as shown in FIG. 8, and the progress of the reaction was confirmed from the chemical shift of proton and the integrated intensity.
[0024]
Example 9
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). 0.7 g of L-alanine was added to 100 ml of water, and a homogeneous solution was slowly added dropwise with an aqueous solution of EMImOH. The mixture was cooled on ice, stirred for 12 hours while maintaining the temperature at 0 ° C., and dried under reduced pressure to remove excess. The water was removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (unreacted alanine added in excess) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol to obtain 0.9 g of 1-ethyl-3-methylimidazolium alanine salt (yield 86%). This product¹The result of the H-NMR measurement was as shown below, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity. The results of elemental analysis were as expected.
Embedded image

¹H-NMR (DMSO, δ / ppm TMS standard): 0.96 (d, 3H, J = 3.5 Hz, (h)), 1.35 (t, 3H, J = 7 Hz), 2.80 (q , 1H, 10.3), 3.83 (s, 3H), 4.17 (q, 2H, J = 11.3 Hz), 7.72 (s, 1H), 7.81 (s, 1H), 9.83 (s, 1H)
Elemental analysis C₉H₁₇N₃О₂・ 2H₂О
C 45.92%, H 8.74%, N 17.40%
[0025]
Example 10
10 ml of water was added to 1.5 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). 1.6 g of L-arginine was added to 100 ml of water, and an aqueous solution of EMImOH was slowly added dropwise to a homogeneous solution. The mixture was cooled on ice, stirred for 12 hours while maintaining the temperature at 0 ° C., and dried under reduced pressure to remove excess. The water was removed. This was cooled for 24 hours while maintaining the temperature at 0 ° C., and then the precipitated crystals (excess unreacted arginine) were removed by filtration to remove 1-ethyl-3-methylimidazolium arginine salt. 6 g (yield 74%) was obtained. This product¹The result of the H-NMR measurement was as shown below, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity.
Embedded image

¹H-NMR (DMSO, δ / ppm TMS standard): 1.23 (m, 2H, J = 15 Hz, (i)), 1.35 (t, 3H, J = 7 Hz), 1.44 (m, 2H) , (H)), 2.79 (t, 1H, J = 6.5. (G)), 2.85 (t, 2H, J = 9 Hz, (j)), 3.81 (s, 3H) , 4.16 (q, 2H, J = 11 Hz), 7.68 (d, 1H, J = 1 Hz), 7.77 (d, 1H, J = 0.75 Hz)
[0026]
Example 11
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). 0.8 g of L-asparagine was added to 100 ml of water, and an aqueous solution of EMImOH was slowly added dropwise to a homogeneous solution. The water was removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Then, the precipitated crystals (excess unreacted asparagine added) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol, to obtain 1.1 g of 1-ethyl-3-methylimidazolium asparagine salt (83% yield). This product¹The result of the H-NMR measurement was as shown below, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity.
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¹H-NMR (DMSO, δ / ppm based on TMS): 1.36 (t, 3H, J = 7.5 Hz), 1.93 (q, 1H, J = 11.8 Hz, (h)), 2.35 (Q, 1H, J = 9.5 Hz, (h)), 3.06 (q, 1H, J = 6.3 Hz), 3.82 (s, 3H), 4.16 (q, 2H, J = 10.8), 6.58 (s, 1H, (i)), 7.70 (t, 1H, J = 2 Hz), 7.78 (t, 1H, J = 1.5 Hz), 7.99 ( s, 1H, (i)), 9.59 (s, 1H)
[0027]
Example 12
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). Under a nitrogen atmosphere, 0.8 g of L-cysteine was added to 100 ml of degassed water, a degassed EMImOH aqueous solution was slowly dropped, and the mixture was cooled on ice and stirred for 12 hours while maintaining the temperature at 0 ° C. Excess water was removed by drying under reduced pressure. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (excessly added unreacted cysteine) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol, to obtain 0.9 g of 1-ethyl-3-methylimidazolium cysteine salt (77% yield). This product¹The result of the H-NMR measurement was as shown below, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity.
Embedded image

¹H-NMR (DMSO, δ / ppm based on TMS): 1.36 (t, 3H, J = 7.5 Hz), 2.45 (d, 1H, J = 10.3 Hz, (h)), 2.67 (D, 1H, J = 8.5 Hz, (h)), 2.93 (t, 1H, J = 5.5 Hz), 3.82 (s, 3H), 4.17 (q, 2H, J = 10.8 Hz), 7.70 (s, 1H), 7.78 (s, 1H), 9.51 (s, 1H)
[0028]
Example 13
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). 0.8 g of L-glutamine was added to 100 ml of water, and an aqueous solution of EMImOH was slowly dropped into a homogeneous solution. The mixture was cooled on ice, stirred for 12 hours while maintaining the temperature at 0 ° C., and dried under reduced pressure to remove excess The water was removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (unreacted glutamine added in excess) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol to obtain 0.9 g of 1-ethyl-3-methylimidazolium glutamine salt (66% yield). This product¹The result of the H-NMR measurement was as shown below, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity.
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¹H-NMR (DMSO, δ / ppm TMS standard): 1.35 (t, 3H, J = 7 Hz), 1.43 (m, 1H, J = 18 Hz (h)), 1.66 (m, 1H, J = 13 Hz, (h)), 2.01 (m, 2H, J = 23.8 Hz, (i)), 2.77 (t, 1H, J = 6.3 Hz), 3.82 (s, 3H) ), 4.17 (q, 2H, J = 10.8 Hz), 6.55 (s, 1H, (j)), 7.61 (s, 1H, (j)), 7.71 (s, 1H) ), 7.79 (s, 1H), 9.67 (s, 1H)
[0029]
Example 14
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). L-Histidine (1.0 g) was added to water (100 ml), and a uniform solution was slowly added with an EMImOH aqueous solution. The water was removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (unreacted histidine added in excess) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol, thereby obtaining 1.1 g of 1-ethyl-3-methylimidazolium histidine salt (78% yield). This product¹The result of the H-NMR measurement was as shown below, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity.
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¹H-NMR (DMSO, δ / ppm TMS standard): 1.34 (t, 3H, J = 7 Hz), 2.36 (q, 1H, J = 11 Hz, (h)), 2.82 (q, 1H) , J = 9.3 Hz, (h)), 2.99 (t, 1H, J = 6 Hz), 3.80 (s, 3H), 4.14 (q, 2H, J = 10.8 Hz), 6 .58 (s, 1H, (i)), 7.35 (s, 1H, (j)), 7.68 (s, 1H), 7.76 (s, 1H), 9.53 (s, 1H) )
[0030]
Example 15
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). 0.9 g of L-lysine was added to 100 ml of water, and an aqueous solution of EMImOH was slowly added dropwise to a homogeneous solution. The water was removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (unreacted lysine added in excess) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol, to obtain 1.0 g of 1-ethyl-3-methylimidazolium lysine salt (yield 78%). This product¹The result of the H-NMR measurement was as shown below, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity. The results of elemental analysis were as expected.
Embedded image

¹H-NMR (DMSO, δ / ppm TMS standard): 1.22 (m, 5H, J = 13.5 Hz, (i) (j) (h)), 1.36 (t, 3H, J = 7. 5), 1.48 (m, 1H, J = 13 Hz, (h)), 2.42 (d, 2H, J = 6.5 Hz, (k)), 2.73 (t, 1H, J = 7) 2.0 Hz), 3.82 (s, 3H), 4.17 (q, 2H, J = 11.3 Hz), 7.70 (t, 1H, J = 1.5 Hz), 7.79 (t, 1H) , J = 1.5 Hz), 9.67 (s, 1H)
Elemental analysis C₁₂H₂₄N₄О₂・ H₂О
C 58.36%, H 8.01%, N 13.58%
[0031]
Example 16
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). 0.9 g of L-methionine was added to 100 ml of water, and an aqueous solution of EMImOH was slowly dropped into a homogeneous solution. The mixture was cooled on ice, stirred for 12 hours while maintaining the temperature at 0 ° C., and dried under reduced pressure to remove excess The water was removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (unreacted methionine added in excess) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol, to obtain 1.1 g of 1-ethyl-3-methylimidazolium methionine salt (yield 78%). This product¹The result of the H-NMR measurement was as shown below, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity. The results of elemental analysis were as expected.
Embedded image

¹H-NMR (DMSO, δ / ppm TMS standard): 1.36 (t, 3H, J = 7.5 Hz), 1.42 (m, 1H, J = 24.5 Hz, (h)), 1.74 (M, 1H, J = 16.5 Hz, (h)), 1.94 (s, 1H), 2.42 (t, 2H, J = 8.5 Hz, (i)), 2.82 (q, 1H, J = 5.75 Hz), 3.82 (s, 3H), 4.17 (q, 2H, J = 11.3 Hz), 7.71 (s, 1H), 7.80 (s, 1H) , 9.69 (s, 1H)
Elemental analysis C₁₁H₂₁N₃О₂S ・ 2.2H₂О
C 43.87%, H 8.51%, N 13.86%
[0032]
Example 17
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). 1.0 g of L-proline was added to 100 ml of water, and an aqueous EMImOH solution was slowly added dropwise to a homogeneous solution. The mixture was cooled on ice, stirred for 12 hours while maintaining the temperature at 0 ° C., and dried under reduced pressure to remove excess The water was removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (unreacted proline added in excess) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol, thereby obtaining 1.1 g (83% yield) of 1-ethyl-3-methylimidazolium proline salt. This product¹The result of the H-NMR measurement was as shown below, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity. The results of elemental analysis were as expected.
Embedded image

¹H-NMR (DMSO, δ / ppm TMS standard): 1.36 (t, 3H, J = 7.5 Hz), 1.42 (m, 1H, J = 17 Hz), 1.51 (m, 1H, J = 19 Hz), 1.62 (broad, 1H), 1.77 (m, 1H, J = 17.8 Hz), 2.60 (broad, 1H), 2,92 (m, 1H, J = 11.3 Hz) ), 3.18 (broad, 1H), 3.82 (s, 3H), 4.16 (q, 2H, J = 11.3 Hz), 7.70 (s, 1H), 7.79 (s, 1H), 9.53 (s, 1H)
Elemental analysis C₁₁H₁₉N₃О₂・ 2H₂О
C 50.16%, H 8.85%, N 15.32%
[0033]
Example 18
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). 0.7 g of L-serine was added to 100 ml of water, and an aqueous solution of EMImOH was slowly added dropwise to a homogeneous solution. The water was removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (excessively added unreacted serine) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol, to obtain 0.9 g of 1-ethyl-3-methylimidazolium serine salt (79% yield). This product¹The result of the H-NMR measurement was as shown below, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity. The results of elemental analysis were as expected.
Embedded image

¹H-NMR (DMSO, δ / ppm TMS standard): 1.36 (t, 3H, J = 7 Hz), 2.83 (t, 1H, J = 7 Hz), 3.23 (m, 2H, J = 15) 5.5 Hz, (h)), 3.81 (s, 3H), 4.16 (q, 2H, J = 11 Hz), 7.69 (s, 1H), 7.78 (s, 1H), 9. 47 (s, 1H)
Elemental analysis C₈H₁₇N₃О₃・ H₂О
C 46.37%, H 8.22%, N 17.71%
[0034]
Example 19
5 ml of water was added to 1.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was uniformly dissolved. The solution was passed through an anion exchange resin, and then passed through an aqueous solution of 1-ethyl-3-methylimidazolium hydroxide (hereinafter referred to as EMImOH aqueous solution). To write). 0.7 g of L-threonine was added to 100 ml of water, and an aqueous solution of EMImOH was slowly added dropwise to a homogeneous solution. The water was removed. 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (excessively added unreacted threonine) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol to obtain 1.0 g of 1-ethyl-3-methylimidazolium threonine salt (yield 84%). This product¹The result of the H-NMR measurement was as shown below, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity.
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¹H-NMR (DMSO, δ / ppm TMS standard): 0.86 (d, 3H, J = 3 Hz, (i)), 1.36 (t, 3H, J = 7 Hz), 2.82 (d, 1H) , J = 2.5 Hz), 3.44 (m, 1H, J = 12 Hz, (h)), 3.82 (s, 3H), 4.17 (q, 2H, J = 10.8 Hz), 7 .70 (s, 1H), 7.79 (s, 1H), 9.52 (s, 1H)
[0035]
Example 20
10 ml of water was added to 2.0 g of 1-ethyl-3-methylimidazolium bromide, and the mixture was dissolved uniformly. To write). An aqueous solution of EMImOH was slowly added dropwise to a mixture of 2.2 g of L-tyrosine in 100 ml of water, cooled with ice, stirred for 12 hours while maintaining the temperature at 0 ° C., and dried under reduced pressure to remove excess water. . 40 ml of acetonitrile and 10 ml of methyl alcohol were added thereto, and the mixture was stirred for 30 minutes while maintaining the temperature at 0 ° C. Thereafter, the precipitated crystals (unreacted tyrosine added in excess) were removed by filtration. The filtrate was dried by heating under reduced pressure to remove acetonitrile and methyl alcohol to obtain 2.1 g of 1-ethyl-3-methylimidazolium tyrosine salt (yield 70%). This product¹The result of the H-NMR measurement was as shown below, and the progress of the reaction was confirmed from the chemical shift of the proton and the integrated intensity.
Embedded image

¹H-NMR (DMSO, δ / ppm TMS standard): 1.34 (t, 3H, J = 7 Hz), 2.11 (t, 1H, J = 11.5 Hz), 2.80 (m, 2H, J) = 25.7 Hz, (h)), 3.78 (s, 3H), 4.13 (q, 2H, J = 10.8 Hz), 6.38 (d, 2H, J = 4.3 Hz, (i )), 6.70 (d, 2H, J = 4.3H, (j)), 7.65 (s, 1H), 7.74 (s, 1H), 9.48 (s, 1H)
[0036]
【The invention's effect】
The present invention provides an organic ionic liquid, which is a quaternary nitrogen compound having a natural amino acid as a constituent ion, which is easily available at low cost. According to the present invention, an optically active environment, which was conventionally difficult to synthesize, can be easily obtained at low cost. That is, according to the present invention, a salt is formed with a suitable cation using a natural amino acid or the like to maintain a liquid state in a wide temperature range from below freezing point to over 200 ° C. with an optical purity of 100%, It provides a potential chiral ionic liquid. This ionic liquid can obtain the same properties as ordinary ionic liquids at a lower cost, can be used in all application fields of ordinary ionic liquids, and furthermore, various functional molecules can be used as reaction precursors of amino acids. It also has the potential to be used for creation.
[Brief description of the drawings]
FIG. 1 shows the 1-ethyl-3-methylimidazolium leucine salt (Example 1).¹It is an H-NMR chart.
FIG. 2 shows the 1-ethyl-3-methylimidazolium phenylalanine salt (Example 2).¹It is an H-NMR chart.
FIG. 3 shows the 1-ethyl-3-methylimidazolium isoleucine salt (Example 3).¹It is an H-NMR chart.
FIG. 4 shows the 1-ethyl-3-methylimidazolium glycine salt (Example 4).¹It is an H-NMR chart.
FIG. 5: Comparison of 1-ethyl-3-methylimidazolium glutamate (Example 5)¹It is an H-NMR chart.
FIG. 6: 1-Ethyl-3-methylimidazolium valine salt (Example 6)¹It is an H-NMR chart.
FIG. 7: 1-Ethyl-3-methylimidazolium aspartate (Example 7)¹It is an H-NMR chart.
FIG. 8: 1-Ethyl-3-methylimidazolium tryptophan salt (Example 8)¹It is an H-NMR chart.

Claims

General formula I:

[Wherein the cation moiety AN ⁺ is (R) ₄ N ⁺ (where R is an unsubstituted or substituted lower alkyl group) or one or more nitrogen atoms are ring members. A cation in which one proton or an alkyl group is bonded to a nitrogen atom of an unsubstituted or substituted hetero ring and other cations, and an anion moiety of H ₂ N—Y—C (＝ O) —O ⁻ (where Y Is an amino acid anion of the amino acid except the amino group and the carboxy group of the amino acid).

The quaternary nitrogen compound according to claim 1, wherein the amino acid is not limited to an α-amino acid.

The quaternary nitrogen compound according to claim 1, wherein the cation is selected from the group consisting of imidazolium, pyridinium, and pyrrolidinium.

The quaternary nitrogen compound according to claim 3, wherein the cation is imidazolium.

The quaternary nitrogen compound according to any one of claims 1 to 4, wherein the anion is a natural α-amino acid anion.

The above anion is L-leucine, L-phenylalanine, L-isoleucine, glycine, L-glutamic acid, L-valine, L-aspartic acid, L-tryptophan, L-alanine, L-arginine, L-asparagine, L-cysteine The anion of an amino acid selected from the group consisting of L-glutamine, L-histidine, L-lysine, L-methionine, L-proline, L-serine, L-threonine and L-tyrosine. The quaternary nitrogen compound according to any one of the preceding claims.