JP3593523B2 - New process for producing N, N-disubstituted amides - Google Patents

Description

で示される構造を基本骨格として有するＮ，Ｎ−ジ置換チオアミド類を過酸化水素と反応させることを特徴とする、式［２］
【化１０】

で示される構造を基本骨格として有するＮ，Ｎ−ジ置換アミド類の製造法に関する。
【０００６】
【発明の実施の形態】
本発明で用いられる、式［１］で示される構造を基本骨格として有するＮ，Ｎ−ジ置換チオアミド類としては、例えば下記一般式［３］
【化１１】

（式中、Ｒ^１及びＲ^２は、それぞれ独立して置換基を有していても良い炭化水素基を表し、Ｒ^３は水素原子又は置換基を有していても良い炭化水素基を表す。また、Ｒ^１，Ｒ^２及びＲ^３の何れか二つが互いに結合してそれらが結合しているＮ原子、或いはＮ原子及びＣ原子と一緒になって、環状構造を形成していてもよい。）で示される化合物が挙げられる。
この場合、得られる式［２］で示される構造を基本骨格として有するＮ，Ｎ−ジ置換アミド類は、下記一般式［４］
【化１２】

（式中、Ｒ^１，Ｒ^２及びＲ^３は前記と同じ。）
で示される。
【０００７】
本発明で用いられる、式［１］で示される構造を基本骨格として有するＮ，Ｎ−ジ置換チオアミド類の他の例としては、例えば下記一般式［５］
【化１３】

（式中、Ｒ^１，Ｒ^２及びＲ^４は、それぞれ独立して置換基を有していても良い炭化水素基を表す。また、Ｒ^１，Ｒ^２及びＲ^４の何れか二つが互いに結合してそれらが結合しているＮ原子、或いはＮ原子及びＣ原子と一緒になって、環状構造を形成していてもよい。）で示されるＮ，Ｎ−ジ置換−β−オキソチオアミド誘導体が挙げられる。
この場合、得られる式［２］で示される構造を基本骨格として有するＮ，Ｎ−ジ置換アミド類は、下記一般式［６］
【化１４】

（式中、Ｒ^１，Ｒ^２及びＲ^４は前記と同じ。）で示されるＮ，Ｎ−ジ置換−β−オキソアミド誘導体となる。
【０００８】
本発明で用いられる、式［１］で示される構造を基本骨格として有するＮ，Ｎ−ジ置換チオアミド類の更なる例としては、例えば下記一般式［７］
【化１５】

（式中、Ｒ^１は置換基を有していても良い炭化水素基を表し、Ｒ^５は置換基を有していても良い炭化水素基又は鎖中に酸素、硫黄、窒素等が介在する置換基を有していても良い炭化水素基を表す。また、Ｒ^１とＲ^５とが互いに結合してそれらが結合しているＮ原子と一緒になって、環状構造を形成していてもよい。）で示されるＮ−置換−β−オキソチオラクタム誘導体が挙げられる。
この場合、得られる式［２］で示される構造を基本骨格として有するＮ，Ｎ−ジ置換アミド類は、下記一般式［８］
【化１６】

（式中、Ｒ^１及びＲ^５は前記と同じ。）で示されるＮ−置換−β−オキソラクタム誘導体となる。
【０００９】
前記一般式［３］〜［８］のそれぞれにおいて、Ｒ^１，Ｒ^２，Ｒ^３及びＲ^４で表される置換基を有していても良い炭化水素基における炭化水素基は、脂肪族炭化水素基、脂環式炭化水素基、芳香族炭化水素基の何れでもよい。このような炭化水素基の例としては、例えば、アルキル基、シクロアルキル基、アルケニル基、シクロアルケニル基、アルキニル基、アリール基、アラルキル基等が挙げられる。
具体的には、アルキル基としては、例えば、炭素数が１〜２０、好ましくは１〜１０、より好ましくは１〜６の直鎖状又は分枝状のアルキル基が挙げられ、より具体的には、例えば、メチル基、エチル基、プロピル基、イソプロピル基、ブチル基、イソブチル基、第二級ブチル基、第三級ブチル基、ペンチル基、ヘキシル基などが挙げられるが、キレート剤等の用途に用いる場合には、アルキル鎖の長さはむしろある程度長い方がよいので、必要に応じて炭素数１〜２０のアルキル基の中から最適なものを適宜選択すればよい。
また、シクロアルキル基としては、例えば、炭素数３〜３０、好ましくは３〜２０、より好ましくは３〜１０の単環、多環又は縮合環式のシクロアルキル基が挙げられ、より具体的には、シクロプロピル基、シクロペンチル基、シクロヘキシル基、シクロオクチル基等が挙げられる。
アルケニル基としては、例えば、前記した炭素数２以上のアルキル基に１個以上の二重結合などの不飽和基を有するものが挙げられ、より具体的には、ビニル基、アリル基、１−プロペニル基、イソプロペニル基、２−ブテニル基、１，３−ブタジエニル基、２−ペンテニル基、２−ヘキセニル基等が挙げられる。
シクロアルケニル基としては、前記したシクロアルキル基に１個以上の二重結合などの不飽和基を有するものが挙げられ、より具体的には、シクロプロペニル基、シクロペンテニル基、シクロヘキセニル基等が挙げられる。
アルキニル基としては、例えば、前記した炭素数２以上のアルキル基に１個以上の三重結合などの不飽和基を有するものが挙げられ、より具体的には、エチニル基、１−プロピニル基、２−プロピニル基等が挙げられる。
アリール基としては、例えば、炭素数６〜３０、好ましくは６〜２０、より好ましくは６〜１４の単環、多環又は縮合環式の芳香族炭化水素基が挙げられ、より具体的には、例えば、フェニル基、トリル基、キシリル基、ナフチル基、メチルナフチル基、アントリル基、フェナントリル基、ビフェニル基等が挙げられる。
アラルキル基としては、例えば、炭素数７〜３０、好ましくは７〜２０、より好ましくは７〜１５の単環、多環又は縮合環式のアラルキル基が挙げられ、より具体的には、例えば、ベンジル基、フェネチル基、ナフチルメチル基、ナフチルエチル基等が挙げられる。
【００１０】
これら炭化水素基の置換基としては、本発明に係る反応に支障を来さないものであればどのような置換基でも良いが、例えばメトキシ基、エトキシ基等のアルコキシ基、塩素原子、臭素原子等のハロゲン原子、アミノ基、例えばメチルチオ基、エチルチオ基等のアルキルチオ基、例えばアセチル基、プロピオニル基、ベンゾイル基等のアシル基等が挙げられる。
【００１１】
前記一般式［３］及び［４］において、Ｒ^１，Ｒ^２及びＲ^３の何れか二つが互いに結合してそれらが結合しているＮ原子、或いはＮ原子及びＣ原子と一緒になって、環状構造を形成している場合、及び前記一般式［５］及び［６］において、Ｒ^１，Ｒ^２及びＲ^４の何れか二つが互いに結合してそれらが結合しているＮ原子、或いはＮ原子及びＣ原子と一緒になって、環状構造を形成している場合、並びに前記一般式［７］及び［８］において、Ｒ^１とＲ^５とが互いに結合してそれらが結合しているＮ原子と一緒になって、環状構造を形成している場合の環としては、環中に更に窒素原子、硫黄原子又は酸素原子を有していても良い、飽和又は不飽和の単環、多環又は縮合環式のものが挙げられ、具体例としては、例えば、ピリジン環、チアゾール環、ピペリジン環、ピペラジン環、ピロール環、モルホリン環、イミダゾール環、インドール環、キノリン環、ピリミジン環等の複素環が挙げられる。
【００１２】
以下、本発明の製造法について詳細に述べる。
先ず、前記式［１］で示される構造を基本骨格として有するＮ，Ｎ−ジ置換チオアミド類、例えば前記一般式［３］で示されるＮ，Ｎ−ジ置換チオアミド類や、前記一般式［５］で示されるＮ，Ｎ−ジ置換−β−オキソチオアミド誘導体、或いは前記一般式［７］で示されるＮ−置換−β−オキソチオラクタム誘導体を溶媒に溶解し、これに２倍モル乃至若干過剰量の過酸化水素を含有する過酸化水素水溶液を加え、撹拌下に反応を行う。
反応は通常、上記した如くＮ，Ｎ−ジ置換チオアミド類を溶媒に溶解して行うが、例えば、合成されるアミドが水との相溶性がよい場合には、必ずしも溶媒を使用する必要はなく、過酸化水素水と溶媒に溶かさない原料チオアミドを懸濁状態で攪拌すれば反応の進行に伴い次第に均一な水溶液なる。
反応は両者を混合するだけで速やかに進行するので、特に加熱する必要はなく、反応温度は室温から氷点まで自由に選んで良い。但し混合直後は発熱による副反応や過酸化水素の分解をふせぐため望ましくは氷水等で冷却しながら開始した後、徐々に室温に戻すのがよい。但し、既に反応の状況がわかっている場合にはどの様な温度過程をとっても良く、場合により加熱することもあり得る。
反応の終末は、チオアミドの残存量を例えばガスクロマトグラフ、高速液体クロマトグラフ等で示される一般的な定量法で分析し、残存が認められなければそこで終了であり、それまで激しく撹拌を続ける。
【００１３】
チオアミドを溶解する溶媒は過酸化水素水溶液と混合したときこれと反応することがない溶媒であって、過酸化水素水溶液と混合したときチオアミドが不溶化せず、且つ原料のチオアミド及び生成するアミドを溶解する能力を有するものであればいかなるものを用いても良いが、一般に、生成したアミドを回収する目的から、溶媒の沸点が生成するアミドの沸点と常圧下で３０℃以上離れているものを用いるのが好ましい。但し溶媒が蒸留以外の方法で除去できるようなものであるか、或いは生成物が蒸留以外の方法で容易に単離出来るものであれば、溶媒としては上記反応性の問題や溶解性の問題がクリアできればどのようなものでも利用できる。 一般には、ジクロロメタン、クロロホルム、ジクロロエタン、トリクロロエタン等の炭素数１乃至２のハロゲン化炭化水素が利用し易く、好ましく用いられるが、酸、塩基、或いは金属錯体などの触媒を用いない反応なので、溶媒はハロゲン化炭化水素以外のものでも勿論使用可能であり、これに限定されるものではない。
【００１４】
反応終結が確認された後、必要ならば残存過酸化水素を望ましくは無機の酸化剤、還元剤、触媒等で分解して除き、また、要すれば反応により生じた硫黄を濾過等により除去し、更に溶媒、水等を濃縮等により除いた後、残渣を蒸留等の通常行われる単離精製法により単離精製すれば目的のアミド体を得ることが出来る。 アミド体の分子量が大きいか、或いは沸点が特に高い場合は、古典的液体クロマトグラフ法、ドライカラムクロマトグラフ法、フラッシュクロマトグラフ法、高圧液体クロマトグラフ法、ゲルパーミエーションクロマトグラフ法、薄層クロマトグラフ法等のクロマトグラフ法或いは親和性による抽出法等の方法でアミドを回収することも出来るが、得られるアミドの物性を利用し他の回収方法を用いても良い。
【００１５】
本発明の方法によれば、既存の方法では容易に脱硫・酸素置換できなかったチオアミドを安全且つ容易に当該アミド体へと転化させることが可能となる。これにより、本発明者らが先に見出し特許出願している、Ｎ，Ｎ−ジ置換アミドの二炭素伸長・β−オキソ化反応（日本国特許第２７０５７５４号、同第２９６３９８３号、米国特許第５６７７４４４号、Ｃｈｅｍ．Ｃｏｍｍｕｎ．１９９６，１６２１）を複数回用いて、ポリ−β−オキソアミドを合成することが極めて容易となった。これらポリ−β−オキソアミドは、金属の配位子、特に重金属抽出剤として有効であり、また、使用済み核燃料の再処理剤としても期待されている。
【００１６】
【実施例】
次に、実施例により本発明を更に詳細に説明するが、本発明はこれら実施例により何ら限定されるものではない。
【００１７】
実施例１
２８７ｍｇ（３．２ｍｍｏｌ）のＮ、Ｎ−ジメチル−チオホルムアミドをジクロロメタン２ｍＬに溶解し、氷冷したものに、６．５ｍｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま１００分間撹拌した後、これを減圧下蒸留するとＮ、Ｎ−ジメチルホルムアミド１７１ｍｇ（単離収率７４％）が得られた。
【００１８】
実施例２
２００ｍｇ（１．７ｍｍｏｌ）のＮ、Ｎ−ジメチル−チオアセトアミドをジクロロメタン２ｍＬに溶解し、氷冷したものに、３．５ｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま１８時間撹拌した後、これを減圧下蒸留するとＮ、Ｎ−ジメチルアセトアミド１７０ｍｇ（単離収率８３％）が得られた。
【００１９】
実施例３
２００ｍｇ（１．７ｍｍｏｌ）のＮ、Ｎ−ジメチル−チオプロピオンアミドをジクロロメタン２ｍＬに溶解し、氷冷したものに、３．６ｍｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま２０時間撹拌した後、これを減圧下蒸留するとＮ、Ｎ−ジメチルプロピオンアミド１７０ｍｇ（単離収率９８％）が得られた。
【００２０】
実施例４
４４０ｍｇ（３．０ｍｍｏｌ）のＮ、Ｎ−ジメチル−３−オキソブタン酸チオアミドをジクロロメタン８ｍＬに溶解し、氷冷したものに、６．３ｍｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま４時間撹拌した後、減圧下蒸留するとＮ、Ｎ−ジメチル−３−オキソブタン酸アミド２７０ｍｇ（単離収率６９％）が得られた。
【００２１】
実施例５
５０ｍｇ（０．２９ｍｍｏｌ）のＮ−（テトラメチレン）−３−オキソブタン酸チオアミドをジクロロメタン１ｍＬに溶解し、氷冷したものに、０．７ｍｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま２０時間撹拌した後、減圧下蒸留するとＮ−（テトラメチレン）−３−オキソブタン酸アミド４０ｍｇ（単離収率６２％）が得られた。
【００２２】
実施例６
１６０ｍｇ（１．０ｍｍｏｌ）のＮ−メチル−３−オキソカプロチオラクタムをジクロロメタン２ｍＬに溶解し、氷冷したものに、２．１ｍｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま６時間撹拌した後、これを減圧下蒸留するとＮ−メチル−３−オキソカプロラクタム
【化１７】

８９ｍｇ（単離収率６２％）が得られた。
^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＣＤＣｌ_３）δ １．８４−１．８７（ｍ，２Ｈ），２．３８−２．４２（ｍ，２Ｈ），２．８３（ｓ，３Ｈ），３．３４−３．３８（ｍ，４Ｈ）。^１３Ｃ−ＮＭＲ（１２５ＭＨｚ，ＣＤＣｌ_３）δ ２４．０，３４．９，４１．４，４８．７，５１．９，１６６．７，２０３．０。
【００２３】
実施例７
１９０ｍｇ（１．０２ｍｍｏｌ）のＮ−（１−メチルエチル）−３−オキソカプロチオラクタムをジクロロメタン２ｍＬに溶解し、氷冷したものに、２．１ｍｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま４．５時間撹拌した後、これを減圧下蒸留するとＮ−（１−メチルエチル）−３−オキソカプロラクタム
【化１８】

１１６ｍｇ（単離収率６８％）が得られた。
^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＣＤＣｌ_３）δ １．０９（ｓ，３Ｈ），１．１０（ｓ，３Ｈ），１．９１−１．９９（ｍ，２Ｈ），２．５６（ｔ，２Ｈ，Ｊ＝７．３Ｈｚ），３．４３（ｔ，２Ｈ，Ｊ＝６．１Ｈｚ），３．４９（ｓ，２Ｈ），４．８０〜４．８５（ｍ，１Ｈ）。^１３Ｃ−ＮＭＲ（１２５ＭＨｚ，ＣＤＣｌ_３）δ ２０．１，２０．３，２６．９，３９．９，４１．３，４４．７，５２．８，１６６．８，２０３．５。
【００２４】
実施例８
２００ｍｇ（１．０ｍｍｏｌ）のＮ−ブチル−３−オキソカプロチオラクタムをジクロロメタン２ｍＬに溶解し、氷冷したものに、２．１ｍｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま７時間撹拌した後、これを減圧下蒸留するとＮ−２−ブチル−３−オキソカプロラクタム
【化１９】

１６０ｍｇ（単離収率８７％）が得られた。
^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＣＤＣｌ_３）δ ０．８８（ｔ，３Ｈ，Ｊ＝７．３Ｈｚ），１．２４−１．３１（ｍ，２Ｈ），１．４６−１．５２（ｍ，２Ｈ），１．９６−２．０１（ｍ，２Ｈ），２．５７（ｔ，２Ｈ，Ｊ＝７．０Ｈｚ），３．３７（ｔ，２Ｈ，Ｊ＝７．６Ｈｚ），３．５０（ｓ，２Ｈ），３．５２（ｔ，２Ｈ，Ｊ＝６．１Ｈｚ）。^１３Ｃ−ＮＭＲ（１２５ＭＨｚ，ＣＤＣｌ_３）δ １３．７，２０．０，２６．０，３０．２，４１．７，４７．０，４７．６，５２．４，１６６．６，２０３．４。
【００２５】
実施例９
６００ｍｇ（２．３４ｍｍｏｌ）のＮ−オクチル−３−オキソカプロチオラクタムをジクロロメタン２ｍＬに溶解し、氷冷したものに、４．７ｍｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま２４時間撹拌した後、これを減圧下蒸留するとＮ−オクチル−３−オキソカプロラクタム
【化２０】

３００ｍｇ（単離収率５４％）が得られた。
^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＣＤＣｌ_３）δ ０．７９（ｔ，３Ｈ，Ｊ＝５．８Ｈｚ），１．１６−１．２５（ｍ，１２Ｈ），１．４０−１．４７（ｍ，２Ｈ），２．５４（ｔ，２Ｈ，Ｊ＝７．０Ｈｚ），３．３３（ｔ，２Ｈ，Ｊ＝７．６Ｈｚ），３．４８（ｓ，２Ｈ），３．５０（ｔ，２Ｈ，Ｊ＝５．７Ｈｚ）。^１３Ｃ−ＮＭＲ（１２５ＭＨｚ，ＣＤＣｌ_３）δ １４．２，２２．８，２６．３，２７．１，２７．３，２８．５，２９．４，３１．９，４２．６，４７．４，４８．３，５２．６，６０．６，１６７．１，２０３．７。
【００２６】
実施例１０
１．０ｇ（４．１ｍｍｏｌ）の（６Ｒ，９Ｓ）１，６−ジメチル−１−アザ−９−（１−メチルエチル）−４−オキソシクロノナン−２−チオンをジクロロメタン２ｍＬに溶解し、氷冷したものに、８．５ｍｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま２４時間撹拌した後、これを減圧下蒸留するとクロマトグラフ及び分光学的に単一の生成物（６Ｒ，９Ｓ）１，６−ジメチル−１−アザ−９−（１−メチルエチル）シクロノナン−２，４−ジオン
【化２１】

のみが８２０ｍｇ（単離収率８８％）得られた。
^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＣＤＣｌ_３）δ ０．８１（ｄ，３Ｈ，Ｊ＝６．４Ｈｚ），０．９３（ｄ，３Ｈ，Ｊ＝６．４Ｈｚ），０．９８（ｄ，３Ｈ，Ｊ＝７．０Ｈｚ），１．２１−１．３３（ｍ，２Ｈ），１．４６−１．５３（ｍ，１Ｈ），１．６２−１．６９（ｍ，１Ｈ），１．７７−１．８３（ｍ，１Ｈ），２．１２−２．１７（ｍ，１Ｈ），２．３２（ｔ，１Ｈ，Ｊ＝１１．０Ｈｚ），２．６０−２．６３（ｍ，１Ｈ），２．６８（ｓ，３Ｈ），３．１１−３．１７（ｍ，１Ｈ），３．３２と３．６５（ＡＢｑ，２Ｈ，Ｊ＝１４．３Ｈｚ）。^１３Ｈ−ＮＭＲ（１２５ＭＨｚ，ＣＤＣｌ_３）δ １８．２，１９．９，２０．２，２４．２，２６．７，２９．６，２９．９，３１．６，４８．４，５４．３，６３．６，１６６．９，２０５．７。
【００２７】
実施例１１
１９０ｍｇ（１．０ｍｍｏｌ）の１−メチル−１−アザ−４−オキソシクロノナン−２−チオンをジクロロメタン２ｍＬに溶解し、氷冷したものに、２．１ｍｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま８時間撹拌した後、これを減圧下蒸留すると１−メチル−１−アザ−シクロノナン−２，４−ジオン
【化２２】

１４６ｍｇ（単離収率８５％）が得られた。
^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＣＤＣｌ_３）δ １．３８−１．４２（ｍ，２Ｈ），１．６１−１．９２（ｍ，４Ｈ），２．４０（ｔ，２Ｈ，Ｊ＝６．４Ｈｚ），２．８３（ｓ，３Ｈ），３．２９−３．３０（ｍ，２Ｈ），３．４５（ｓ，２Ｈ）。^１３Ｃ−ＮＭＲ（１２５ＭＨｚ，ＣＤＣｌ_３）δ ２３．６，２５．３，２６．２，３１．９，４１．９，４７．１，５３．９，１６６．０，２０８．６。
【００２８】
実施例１２
７００ｍｇ（３．５ｍｍｏｌ）の１−メチル−１−アザ−４−オキソシクロデカン−２−チオンをジクロロメタン１０ｍＬに溶解し、氷冷したものに、７．３ｍｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま２０時間撹拌した後、これを減圧下蒸留すると１−メチル−１−アザ−シクロデカン−２，４−ジオン
【化２３】

５３０ｍｇ（単離収率８２％）が得られた。
^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＣＤＣｌ_３）δ １．２１−１．２５（ｍ，２Ｈ），１．２８−１．３２（ｍ，２Ｈ），１．４９−１．５３（ｍ，２Ｈ），１．６２−１．６６（ｍ，２Ｈ），２．５０−２．５３（ｍ， ２Ｈ），２．８３（ｓ，３Ｈ），３．２８（ｔ，２Ｈ，Ｊ＝５．８Ｈｚ），３．４６（ｓ，２Ｈ）。^１３Ｃ−ＮＭＲ（１２５ＭＨｚ，ＣＤＣｌ_３）δ １９．０，２３．６，２４．３，２６．０，３１．８，３７．０，４７．２，５２．４，１６７．６，２０７．８。
元素分析、実測値 Ｃ：６５．２７％，Ｈ：９．２１％，Ｎ：７．４５％。計算値（Ｃ_１０Ｈ_１７ＮＯ_２として）Ｃ：６５．５４％，Ｈ：９．３５％，Ｎ：７．６４％。
【００２９】
実施例１３
４．０ｇ（１５．６ｍｍｏｌ）の１−ブチル−１−アザ−４−オキソシクロウンデカン−２−チオンをジクロロメタン２０ｍＬに溶解し、氷冷したものに、３１．３ｍｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま１０時間撹拌した後、これを減圧下蒸留すると１−ブチル−１−アザ−シクロウンデカン−２，４−ジオン
【化２４】

３．６ｇ（単離収率９６％）が得られた。
^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＣＤＣｌ_３）δ ０．８４（ｔ，３Ｈ，Ｊ＝７．４Ｈｚ），１．１０−１．６５（ｍ，１４Ｈ），１．８１−１．９８（ｍ，２Ｈ），２．８３−２．８８（ｍ，２Ｈ），３．３５と３．４７（ＡＢｑ，２Ｈ，Ｊ＝１１．３Ｈｚ），３．６０−３．６９（ｍ，１Ｈ），４．１８−４．２４（ｍ，１Ｈ）。^１３ＣＮＭＲ（１２５ＭＨｚ，ＣＤＣｌ_３）δ １３．５，１９．７，２２．５，２３．１，２３．７，２６．４，２７．７，２９．２，４２．７，４５．５，４８．８，５４．８，１７１．３，２０３．５。
【００３０】
実施例１４
２２７ｍｇ（１．０ｍｍｏｌ）の１−メチル−１−アザ−４，６−ジオキソシクロウンデカン−２−チオンをジクロロメタン４ｍＬに溶解し、氷冷したものに、２．１ｍｍｏｌの過酸化水素を含む３０％過酸化水素水溶液を静かに加えた。氷冷のまま１０時間撹拌した後、これを減圧下蒸留すると１−メチル−１−アザ−シクロウンデカン−２，４，６−トリオン
【化２５】

１６２ｍｇ（粗収率７７％）が得られた。更にこれをカラムクロマトグラフで精製し、精製品４４ｍｇ（単離収率２１％）を得た。
^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＣＤＣｌ_３）δ １．０８−１．１７（ｍ，１Ｈ），１．４７−１．５９（ｍ，１Ｈ），１．６２−１．６８（ｍ，４Ｈ），２．４０（ｔ，２Ｈ，Ｊ＝５．５Ｈｚ），２．９７−３．０１（ｍ，１Ｈ），３．０８（ｓ，３Ｈ），３．８５（ｓ，２Ｈ），４．１０（ｓ，２Ｈ），４．９１−４．９５（ｍ，１Ｈ）。^１３Ｃ−ＮＭＲ（１２５ＭＨｚ，ＣＤＣｌ_３）δ ２１．３９，２２．０９，２４．６９，４１．８６，４１．８９，５３．８１，５５．０５，５８．２０，１９４．１６，１９６．４０，２０２．２４。
【００３１】
【発明の効果】
本発明は、付加価値の高い溶媒として有機合成化学の分野において汎用されているＮ，Ｎ−ジ置換アミド類や、その誘導体であって、キレート剤等として有用なＮ，Ｎ−ジ置換−β−オキソアミド類、並びに医薬品、農薬等の原料として有用なＮ−置換−β−オキソラクタム類等を、それぞれ対応するＮ，Ｎ−ジ置換チオアミド類から容易に、安全に、且つ極めて収率良く製造する方法を提供するものであり、本発明の方法によれば、既存の方法では容易に脱硫・酸素置換できなかったチオアミド類を安全且つ容易に当該アミド類へと転化させることが出来る。 また、これにより、本発明者らが先に開発したＮ，Ｎ−ジ置換アミドの二炭素伸長・β−オキソ化反応を複数回用いて、ポリ−β−オキソアミドを合成することが極めて容易となった。これらポリ−β−オキソアミドは、金属の配位子、特に重金属抽出剤として有効であり、また、使用済み核燃料の再処理剤としても期待されていることからも、本発明は斯業に貢献するところ極めて大なる発明である。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to N, N-disubstituted amides and derivatives thereof widely used in the field of synthetic organic chemistry as solvents having high added value, and N, N-disubstituted-β useful as a chelating agent and the like. The present invention relates to a novel, simple and high-yield production method of -oxoamides and N-substituted-β-oxolactams useful as raw materials for pharmaceuticals, agricultural chemicals and the like.
[0002]
[Prior art]
N, N-disubstituted amides are solvents frequently used as high value-added solvents in the field of organic synthetic chemistry. In addition, the β-oxo derivatives, N, N-disubstituted-β-oxoamides, are known as chelating agents that specifically bind to transition metals such as copper and nickel.
On the other hand, the present inventors have previously found a method for selectively synthesizing β-oxothioamide from amide in high yield and have applied for a patent (Japanese Patent No. 2705754, a patent on October 9, 1997; No. 2,963,983, Aug. 13, 1999, US Pat. No. 5,677,444, Oct. 14, 1997.)
In general, it is easy to synthesize the corresponding thioamide from an amide, and Lawesson's reagent is a representative reagent for replacing oxygen with sulfur. On the other hand, in the case of the reverse reaction in which sulfur of thioamides is replaced with oxygen, if there is hydrogen on the nitrogen of thioamide, silver oxide or air alone can easily oxidatively desulfurize to the corresponding amide. However, such reactions do not readily occur without hydrogen on the nitrogen of the thioamide. Generally, this desulfurization / oxygenation reaction is carried out oxidatively, and has been carried out by oxidation with a peracid such as m-chloroperbenzoic acid or singlet oxygen.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to provide a novel, simple, and high-yield production method of N, N-disubstituted amides. It is an object of the present invention to provide a means for easily, safely and inexpensively converting N-disubstituted amides.
[0004]
[Means for Solving the Problems]
The present inventors have conducted intensive studies on a method for obtaining the N, N-disubstituted amides by desulfurization and oxygenation of the N, N-disubstituted thioamides. It can be converted to the corresponding N, N-disubstituted amides easily and in good yield by oxidation with hydrogen oxide, and this method is applicable to a wide range of compounds falling within the category of N, N-disubstituted thioamides. The inventors have found that the present invention has been completed.
[0005]
That is, the present invention relates to formula [1]
Embedded image

Wherein an N, N-disubstituted thioamide having a structure represented by the following formula as a basic skeleton is reacted with hydrogen peroxide:
Embedded image

The present invention relates to a method for producing N, N-disubstituted amides having a structure represented by the following formula:
[0006]
BEST MODE FOR CARRYING OUT THE INVENTION
The N, N-disubstituted thioamides having a structure represented by the formula [1] as a basic skeleton used in the present invention include, for example, the following general formula [3]
Embedded image

(Where R ¹ And R ² Each independently represents a hydrocarbon group which may have a substituent; ³ Represents a hydrogen atom or a hydrocarbon group which may have a substituent. Also, R ¹ , R ² And R ³ May be bonded to each other to form an annular structure together with an N atom to which they are bonded, or an N atom and a C atom. )).
In this case, the obtained N, N-disubstituted amide having a structure represented by the formula [2] as a basic skeleton is represented by the following general formula [4]
Embedded image

(Where R ¹ , R ² And R ³ Is the same as above. )
Indicated by
[0007]
Other examples of the N, N-disubstituted thioamides having a structure represented by the formula [1] as a basic skeleton used in the present invention include, for example, the following general formula [5]
Embedded image

(Where R ¹ , R ² And R ⁴ Represents a hydrocarbon group which may have a substituent independently of each other. Also, R ¹ , R ² And R ⁴ May be bonded to each other to form an annular structure together with an N atom to which they are bonded, or an N atom and a C atom. )), N, N-disubstituted-β-oxothioamide derivatives.
In this case, the obtained N, N-disubstituted amide having the structure represented by the formula [2] as a basic skeleton is represented by the following general formula [6]
Embedded image

(Where R ¹ , R ² And R ⁴ Is the same as above. )), Is obtained as the N, N-disubstituted-β-oxoamide derivative.
[0008]
Further examples of N, N-disubstituted thioamides having a structure represented by the formula [1] as a basic skeleton used in the present invention include, for example, the following general formula [7]
Embedded image

(Where R ¹ Represents a hydrocarbon group which may have a substituent; ⁵ Represents a hydrocarbon group which may have a substituent or a hydrocarbon group which may have a substituent in which oxygen, sulfur, nitrogen or the like is interposed in the chain. Also, R ¹ And R ⁵ May be bonded to each other and together with the N atom to which they are bonded, to form a cyclic structure. And N-substituted-β-oxothiolactam derivatives.
In this case, the obtained N, N-disubstituted amide having the structure represented by the formula [2] as a basic skeleton is represented by the following general formula [8]
Embedded image

(Where R ¹ And R ⁵ Is the same as above. )) Is obtained as the N-substituted-β-oxolactam derivative.
[0009]
In each of the general formulas [3] to [8], R ¹ , R ² , R ³ And R ⁴ The hydrocarbon group in the hydrocarbon group which may have a substituent may be any of an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, and an aromatic hydrocarbon group. Examples of such hydrocarbon groups include, for example, alkyl groups, cycloalkyl groups, alkenyl groups, cycloalkenyl groups, alkynyl groups, aryl groups, aralkyl groups, and the like.
Specifically, examples of the alkyl group include a linear or branched alkyl group having 1 to 20, preferably 1 to 10, and more preferably 1 to 6 carbon atoms. Examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a secondary butyl group, a tertiary butyl group, a pentyl group, and a hexyl group. In this case, it is better that the length of the alkyl chain is rather long, so that an optimum one may be appropriately selected from an alkyl group having 1 to 20 carbon atoms as necessary.
Examples of the cycloalkyl group include, for example, a monocyclic, polycyclic or condensed cyclic alkyl group having 3 to 30, preferably 3 to 20, and more preferably 3 to 10 carbon atoms. Is a cyclopropyl group, a cyclopentyl group, a cyclohexyl group, a cyclooctyl group, or the like.
Examples of the alkenyl group include those having an alkyl group having 2 or more carbon atoms and an unsaturated group such as one or more double bonds, and more specifically, a vinyl group, an allyl group, and 1- Examples include a propenyl group, an isopropenyl group, a 2-butenyl group, a 1,3-butadienyl group, a 2-pentenyl group, and a 2-hexenyl group.
Examples of the cycloalkenyl group include those having an unsaturated group such as one or more double bonds in the above cycloalkyl group, and more specifically, a cyclopropenyl group, a cyclopentenyl group, a cyclohexenyl group, and the like. No.
Examples of the alkynyl group include those having an alkyl group having 2 or more carbon atoms and an unsaturated group such as one or more triple bonds, and more specifically, an ethynyl group, a 1-propynyl group, -Propynyl group and the like.
Examples of the aryl group include a monocyclic, polycyclic or condensed-ring aromatic hydrocarbon group having 6 to 30, preferably 6 to 20, and more preferably 6 to 14 carbon atoms, and more specifically, Examples include phenyl, tolyl, xylyl, naphthyl, methylnaphthyl, anthryl, phenanthryl, biphenyl and the like.
Examples of the aralkyl group include a monocyclic, polycyclic or condensed aralkyl group having 7 to 30, preferably 7 to 20, and more preferably 7 to 15 carbon atoms. More specifically, for example, Examples include a benzyl group, a phenethyl group, a naphthylmethyl group, and a naphthylethyl group.
[0010]
As the substituent of these hydrocarbon groups, any substituent may be used as long as it does not hinder the reaction according to the present invention. Examples of the substituent include a methoxy group, an alkoxy group such as an ethoxy group, a chlorine atom, and a bromine atom. And an amino group, for example, an alkylthio group such as a methylthio group and an ethylthio group, and an acyl group such as an acetyl group, a propionyl group, and a benzoyl group.
[0011]
In the general formulas [3] and [4], R ¹ , R ² And R ³ Any two of which are bonded to each other to form a cyclic structure together with the N atom or the N atom and the C atom to which they are bonded, and the above general formulas [5] and [6] In, R ¹ , R ² And R ⁴ Is bonded to each other to form a cyclic structure together with the N atom or the N atom and the C atom to which they are bonded, and the above general formulas [7] and [8] In, R ¹ And R ⁵ Are bonded to each other to form a ring structure together with the N atom to which they are bonded, the ring further has a nitrogen atom, a sulfur atom or an oxygen atom in the ring. Saturated or unsaturated monocyclic, polycyclic or fused cyclic ones, and specific examples thereof include, for example, a pyridine ring, a thiazole ring, a piperidine ring, a piperazine ring, a pyrrole ring, a morpholine ring, and an imidazole ring. And heterocycles such as an indole ring, a quinoline ring and a pyrimidine ring.
[0012]
Hereinafter, the production method of the present invention will be described in detail.
First, N, N-disubstituted thioamides having the structure represented by the formula [1] as a basic skeleton, such as the N, N-disubstituted thioamides represented by the general formula [3] and the general formula [5] The N, N-disubstituted-β-oxothioamide derivative represented by the general formula [7] or the N-substituted-β-oxothiolactam derivative represented by the general formula [7] is dissolved in a solvent. An aqueous solution of hydrogen peroxide containing an excess amount of hydrogen peroxide is added and the reaction is carried out with stirring.
The reaction is usually carried out by dissolving the N, N-disubstituted thioamides in a solvent as described above. For example, when the amide to be synthesized has good compatibility with water, it is not necessary to use a solvent. If the aqueous hydrogen peroxide and the raw material thioamide insoluble in the solvent are stirred in a suspended state, the aqueous solution becomes gradually uniform as the reaction proceeds.
Since the reaction proceeds quickly only by mixing the two, there is no particular need for heating, and the reaction temperature may be freely selected from room temperature to the freezing point. However, immediately after mixing, it is preferable to start the reaction with cooling with ice water or the like and then gradually return to room temperature in order to prevent side reactions due to heat generation and decomposition of hydrogen peroxide. However, if the state of the reaction is already known, any temperature process may be used, and heating may be performed in some cases.
At the end of the reaction, the remaining amount of thioamide is analyzed by a general quantitative method such as gas chromatography, high-performance liquid chromatography, and the like. If no residual is observed, the reaction is terminated, and vigorous stirring is continued until then.
[0013]
The solvent that dissolves thioamide is a solvent that does not react when mixed with an aqueous hydrogen peroxide solution.When mixed with an aqueous hydrogen peroxide solution, the thioamide is not insolubilized and dissolves the raw material thioamide and the generated amide. Any material may be used as long as it has the ability to perform the reaction. Generally, for the purpose of recovering the generated amide, a solvent whose boiling point is separated from the boiling point of the amide to be formed by 30 ° C. or more under normal pressure is used. Is preferred. However, if the solvent is such that it can be removed by a method other than distillation, or if the product can be easily isolated by a method other than distillation, then the above-mentioned reactivity problem and solubility problem will occur as the solvent. Anything that can be used if it can be cleared. In general, halogenated hydrocarbons having 1 to 2 carbon atoms such as dichloromethane, chloroform, dichloroethane, and trichloroethane are easily used and preferably used.However, since the reaction does not use a catalyst such as an acid, a base, or a metal complex, a solvent is used. Of course, other than the halogenated hydrocarbon can be used, and the present invention is not limited to this.
[0014]
After the completion of the reaction is confirmed, if necessary, residual hydrogen peroxide is removed by decomposition with an inorganic oxidizing agent, a reducing agent, a catalyst, or the like, and, if necessary, sulfur generated by the reaction is removed by filtration or the like. Further, after removing the solvent, water and the like by concentration or the like, the target amide can be obtained by isolating and purifying the residue by a commonly used isolation and purification method such as distillation. If the molecular weight of the amide compound is large or the boiling point is particularly high, classic liquid chromatography, dry column chromatography, flash chromatography, high pressure liquid chromatography, gel permeation chromatography, thin layer chromatography The amide can be recovered by a method such as a chromatography method such as a graph method or an extraction method based on affinity, but other recovery methods may be used by utilizing the physical properties of the obtained amide.
[0015]
According to the method of the present invention, it is possible to safely and easily convert thioamide, which could not be easily desulfurized and replaced with oxygen by the existing method, to the amide. As a result, the present inventors have previously found and filed a patent application for a two-carbon elongation / β-oxo-forming reaction of N, N-disubstituted amides (Japanese Patent Nos. 2705754 and 296983, U.S. Pat. No. 5,677,444, Chem. 1996 , 1621) multiple times to synthesize poly-β-oxoamide. These poly-β-oxoamides are effective as metal ligands, especially as heavy metal extractants, and are also expected to be used as reprocessing agents for spent nuclear fuel.
[0016]
【Example】
Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.
[0017]
Example 1
287 mg (3.2 mmol) of N, N-dimethyl-thioformamide was dissolved in 2 mL of dichloromethane, and a 30% aqueous hydrogen peroxide solution containing 6.5 mmol of hydrogen peroxide was gently added to the solution cooled with ice. After stirring for 100 minutes with ice cooling, this was distilled under reduced pressure to obtain 171 mg of N, N-dimethylformamide (isolation yield: 74%).
[0018]
Example 2
200 mg (1.7 mmol) of N, N-dimethyl-thioacetamide was dissolved in 2 mL of dichloromethane, and a 30% aqueous hydrogen peroxide solution containing 3.5 mol of hydrogen peroxide was gently added to the solution cooled with ice. After stirring for 18 hours while cooling on ice, this was distilled under reduced pressure to obtain 170 mg of N, N-dimethylacetamide (83% isolated yield).
[0019]
Example 3
200 mg (1.7 mmol) of N, N-dimethyl-thiopropionamide was dissolved in 2 mL of dichloromethane, and a 30% aqueous hydrogen peroxide solution containing 3.6 mmol of hydrogen peroxide was gently added to the solution cooled with ice. After stirring for 20 hours while cooling on ice, this was distilled under reduced pressure to obtain 170 mg of N, N-dimethylpropionamide (98% isolated yield).
[0020]
Example 4
440 mg (3.0 mmol) of N, N-dimethyl-3-oxobutanoic acid thioamide was dissolved in 8 mL of dichloromethane, and chilled with a 30% aqueous hydrogen peroxide solution containing 6.3 mmol of hydrogen peroxide. Was. After stirring for 4 hours while cooling on ice, distillation under reduced pressure yielded 270 mg (69% isolated yield) of N, N-dimethyl-3-oxobutanoic acid amide.
[0021]
Example 5
Dissolve 50 mg (0.29 mmol) of N- (tetramethylene) -3-oxobutanoic acid thioamide in 1 mL of dichloromethane and gently add a 30% aqueous hydrogen peroxide solution containing 0.7 mmol of hydrogen peroxide to an ice-cooled mixture. added. After stirring for 20 hours with ice cooling, distillation under reduced pressure gave N- (tetramethylene) -3-oxobutanoic acid amide (40 mg, yield 62%).
[0022]
Example 6
160 mg (1.0 mmol) of N-methyl-3-oxocaprothiolactam was dissolved in 2 mL of dichloromethane, and to a solution cooled with ice, a 30% aqueous hydrogen peroxide solution containing 2.1 mmol of hydrogen peroxide was gently added. Was. After stirring for 6 hours with ice cooling, this was distilled under reduced pressure to obtain N-methyl-3-oxocaprolactam.
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89 mg (62% isolated yield) were obtained.
¹ H-NMR (500 MHz, CDCl ₃ ) Δ 1.84-1.87 (m, 2H), 2.38-2.42 (m, 2H), 2.83 (s, 3H), 3.34-3.38 (m, 4H). ^Thirteen C-NMR (125 MHz, CDCl ₃ ) Delta 24.0, 34.9, 41.4, 48.7, 51.9, 166.7, 203.0.
[0023]
Example 7
190 mg (1.02 mmol) of N- (1-methylethyl) -3-oxocaprothiolactam was dissolved in 2 mL of dichloromethane, and cooled to ice with 30% hydrogen peroxide containing 2.1 mmol of hydrogen peroxide. The aqueous solution was added gently. After stirring for 4.5 hours while cooling with ice, the mixture was distilled under reduced pressure to give N- (1-methylethyl) -3-oxocaprolactam.
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116 mg (68% isolated yield) were obtained.
¹ H-NMR (500 MHz, CDCl ₃ ) Δ 1.09 (s, 3H), 1.10 (s, 3H), 1.91-1.99 (m, 2H), 2.56 (t, 2H, J = 7.3 Hz), 3. 43 (t, 2H, J = 6.1 Hz), 3.49 (s, 2H), 4.80-4.85 (m, 1H). ^Thirteen C-NMR (125 MHz, CDCl ₃ ) Δ 20.1, 20.3, 26.9, 39.9, 41.3, 44.7, 52.8, 166.8, 203.5.
[0024]
Example 8
200 mg (1.0 mmol) of N-butyl-3-oxocaprothiolactam was dissolved in 2 mL of dichloromethane, and a 30% aqueous hydrogen peroxide solution containing 2.1 mmol of hydrogen peroxide was gently added to the solution cooled with ice. Was. After stirring for 7 hours while cooling on ice, the mixture was distilled under reduced pressure to give N-2-butyl-3-oxocaprolactam.
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160 mg (87% isolated yield) were obtained.
¹ H-NMR (500 MHz, CDCl ₃ ) Δ 0.88 (t, 3H, J = 7.3 Hz), 1.24-1.31 (m, 2H), 1.46-1.52 (m, 2H), 1.96-2.01 (M, 2H), 2.57 (t, 2H, J = 7.0 Hz), 3.37 (t, 2H, J = 7.6 Hz), 3.50 (s, 2H), 3.52 (t , 2H, J = 6.1 Hz). ^Thirteen C-NMR (125 MHz, CDCl ₃ ) Δ 13.7, 20.0, 26.0, 30.2, 41.7, 47.0, 47.6, 52.4, 166.6, 203.4.
[0025]
Example 9
600 mg (2.34 mmol) of N-octyl-3-oxocaprothiolactam was dissolved in 2 mL of dichloromethane, and a 30% aqueous hydrogen peroxide solution containing 4.7 mmol of hydrogen peroxide was gently added to the solution cooled with ice. Was. After stirring for 24 hours with ice cooling, this was distilled under reduced pressure to obtain N-octyl-3-oxocaprolactam.
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300 mg (54% isolated yield) were obtained.
¹ H-NMR (500 MHz, CDCl ₃ ) Δ 0.79 (t, 3H, J = 5.8 Hz), 1.16-1.25 (m, 12H), 1.40-1.47 (m, 2H), 2.54 (t, 2H) , J = 7.0 Hz), 3.33 (t, 2H, J = 7.6 Hz), 3.48 (s, 2H), 3.50 (t, 2H, J = 5.7 Hz). ^Thirteen C-NMR (125 MHz, CDCl ₃ ) Δ 14.2, 22.8, 26.3, 27.1, 27.3, 28.5, 29.4, 31.9, 42.6, 47.4, 48.3, 52.6. 60.6, 167.1, 203.7.
[0026]
Example 10
Dissolve 1.0 g (4.1 mmol) of (6R, 9S) 1,6-dimethyl-1-aza-9- (1-methylethyl) -4-oxocyclononane-2-thione in 2 mL of dichloromethane and add ice To the cooled one, a 30% aqueous hydrogen peroxide solution containing 8.5 mmol of hydrogen peroxide was gently added. After stirring for 24 hours while cooling on ice, the mixture was distilled under reduced pressure, and chromatographically and spectroscopically, a single product (6R, 9S) 1,6-dimethyl-1-aza-9- (1-methylethyl) was obtained. ) Cyclononane-2,4-dione
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Only 820 mg (88% isolated yield) was obtained.
¹ H-NMR (500 MHz, CDCl ₃ ) Δ 0.81 (d, 3H, J = 6.4 Hz), 0.93 (d, 3H, J = 6.4 Hz), 0.98 (d, 3H, J = 7.0 Hz), 1.21 -1.33 (m, 2H), 1.46-1.53 (m, 1H), 1.62-1.69 (m, 1H), 1.77-1.83 (m, 1H), 2 .12-2.17 (m, 1H), 2.32 (t, 1H, J = 11.0 Hz), 2.60-2.63 (m, 1H), 2.68 (s, 3H), 3 .11-3.17 (m, 1H), 3.32 and 3.65 (ABq, 2H, J = 14.3 Hz). ^Thirteen H-NMR (125 MHz, CDCl ₃ ) Δ 18.2, 19.9, 20.2, 24.2, 26.7, 29.6, 29.9, 31.6, 48.4, 54.3, 63.6, 166.9, 205.7.
[0027]
Example 11
190 mg (1.0 mmol) of 1-methyl-1-aza-4-oxocyclononane-2-thione was dissolved in 2 mL of dichloromethane, and cooled to ice with 30% peroxide containing 2.1 mmol of hydrogen peroxide. Hydrogen aqueous solution was gently added. After stirring for 8 hours while cooling on ice, the mixture was distilled under reduced pressure to give 1-methyl-1-aza-cyclononane-2,4-dione.
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146 mg (85% isolated yield) were obtained.
¹ H-NMR (500 MHz, CDCl ₃ ) Δ 1.38-1.42 (m, 2H), 1.61-1.92 (m, 4H), 2.40 (t, 2H, J = 6.4 Hz), 2.83 (s, 3H) ), 3.29-3.30 (m, 2H), 3.45 (s, 2H). ^Thirteen C-NMR (125 MHz, CDCl ₃ ) Δ 23.6, 25.3, 26.2, 31.9, 41.9, 47.1, 53.9, 166.0, 208.6.
[0028]
Example 12
700 mg (3.5 mmol) of 1-methyl-1-aza-4-oxocyclodecane-2-thione was dissolved in 10 mL of dichloromethane, and ice-cooled, 30% peroxide containing 7.3 mmol of hydrogen peroxide was added. Hydrogen aqueous solution was gently added. After stirring for 20 hours while cooling on ice, the mixture was distilled under reduced pressure to give 1-methyl-1-aza-cyclodecane-2,4-dione.
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530 mg (82% isolated yield) were obtained.
¹ H-NMR (500 MHz, CDCl ₃ ) Δ 1.21-1.25 (m, 2H), 1.28-1.32 (m, 2H), 1.49-1.53 (m, 2H), 1.62-1.66 (m , 2H), 2.50-2.53 (m, 2H), 2.83 (s, 3H), 3.28 (t, 2H, J = 5.8 Hz), 3.46 (s, 2H). ^Thirteen C-NMR (125 MHz, CDCl ₃ ) Δ 19.0, 23.6, 24.3, 26.0, 31.8, 37.0, 47.2, 52.4, 167.6, 207.8.
Elemental analysis, found C: 65.27%, H: 9.21%, N: 7.45%. Calculated value (C ₁₀ H ₁₇ NO ₂ C) 65.54%, H: 9.35%, N: 7.64%.
[0029]
Example 13
4.0 g (15.6 mmol) of 1-butyl-1-aza-4-oxocycloundecane-2-thione was dissolved in 20 mL of dichloromethane, and ice-cooled, containing 30% containing 31.3 mmol of hydrogen peroxide. An aqueous solution of hydrogen peroxide was gently added. After stirring for 10 hours while cooling with ice, the mixture was distilled under reduced pressure to give 1-butyl-1-aza-cycloundecane-2,4-dione.
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3.6 g (96% isolated yield) were obtained.
¹ H-NMR (500 MHz, CDCl ₃ ) [Delta] 0.84 (t, 3H, J = 7.4 Hz), 1.10-1.65 (m, 14H), 1.81-1.98 (m, 2H), 2.83-2.88 (M, 2H), 3.35 and 3.47 (ABq, 2H, J = 11.3 Hz), 3.60-3.69 (m, 1H), 4.18-4.24 (m, 1H) . ^Thirteen CNMR (125 MHz, CDCl ₃ ) Δ 13.5, 19.7, 22.5, 23.1, 23.7, 26.4, 27.7, 29.2, 42.7, 45.5, 48.8, 54.8, 171.3, 203.5.
[0030]
Example 14
227 mg (1.0 mmol) of 1-methyl-1-aza-4,6-dioxocycloundecane-2-thione was dissolved in 4 mL of dichloromethane, and ice-cooled, containing 2.1 mmol of hydrogen peroxide. % Aqueous hydrogen peroxide was gently added. After stirring for 10 hours while cooling with ice, the mixture was distilled under reduced pressure to give 1-methyl-1-aza-cycloundecane-2,4,6-trione.
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162 mg (77% crude yield) were obtained. This was further purified by column chromatography to obtain 44 mg of a purified product (isolation yield: 21%).
¹ H-NMR (500 MHz, CDCl ₃ ) Δ 1.08-1.17 (m, 1H), 1.47-1.59 (m, 1H), 1.62-1.68 (m, 4H), 2.40 (t, 2H, J) = 5.5 Hz), 2.97-3.01 (m, 1H), 3.08 (s, 3H), 3.85 (s, 2H), 4.10 (s, 2H), 4.91- 4.95 (m, 1H). ^Thirteen C-NMR (125 MHz, CDCl ₃ ) Δ 21.39, 22.09, 24.69, 41.86, 41.89, 53.81, 55.05, 58.20, 194.16, 196.40, 202.24.
[0031]
【The invention's effect】
The present invention relates to N, N-disubstituted amides and derivatives thereof, which are widely used in the field of organic synthetic chemistry as a high value-added solvent, and are useful as chelating agents and the like. -Oxoamides and N-substituted-β-oxolactams useful as raw materials for pharmaceuticals, agricultural chemicals, etc. can be produced easily, safely and in extremely high yield from the corresponding N, N-disubstituted thioamides. According to the method of the present invention, thioamides, which could not be easily desulfurized and replaced with oxygen by the existing method, can be safely and easily converted to the amides. In addition, this makes it extremely easy to synthesize poly-β-oxoamide using the two-carbon elongation / β-oxo-formation reaction of N, N-disubstituted amide developed earlier by the present inventors a plurality of times. became. The present invention contributes to the industry because these poly-β-oxoamides are effective as metal ligands, particularly as heavy metal extractants, and are also expected to be used as reprocessing agents for spent nuclear fuel. However, this is a very large invention.

Claims (6)

Equation [1]

Wherein an N, N-disubstituted thioamide having a structure represented by the following formula as a basic skeleton is reacted with hydrogen peroxide:

A method for producing an N, N-disubstituted amide having a structure represented by the following formula as a basic skeleton. N, N-disubstituted thioamides having the structure represented by the formula [1] as a basic skeleton are represented by the following general formula [3]

(Wherein, R ¹ and R ² each independently represent a hydrocarbon group which may have a substituent, and R ³ represents a hydrogen atom or a hydrocarbon group which may have a substituent. Further, any two of R ¹ , R ² and R ³ may be bonded to each other to form a cyclic structure together with the N atom or the N atom and the C atom to which they are bonded. ), The N, N-disubstituted amides obtained by the reaction are represented by the following general formula [4]:

(In the formula, R ¹ , R ² and R ³ are the same as described above.)
The production method according to claim 1, which is an N, N-disubstituted amide represented by the formula: N, N-disubstituted thioamides having a structure represented by the formula [1] as a basic skeleton are represented by the following general formula [5]

(Wherein, R ¹ , R ² and R ⁴ each independently represent a hydrocarbon group which may have a substituent. In addition, any two of R ¹ , R ² and R ⁴ are bonded to each other. May form a cyclic structure together with the N atom to which they are bonded, or the N atom and the C atom together with an N, N-disubstituted-β-oxothioamide derivative. The N, N-disubstituted amides obtained by the reaction are represented by the following general formula [6]

(Wherein R ¹ , R ² and R ⁴ are the same as described above), which is an N, N-disubstituted-β-oxoamide derivative represented by the formula: N, N-disubstituted thioamides having the structure represented by the formula [1] as a basic skeleton are represented by the following general formula [7]

(Wherein, R ¹ represents a hydrocarbon group which may have a substituent, and R ⁵ represents a hydrocarbon group which may have a substituent or oxygen, sulfur, nitrogen or the like is interposed in the chain. And represents a hydrocarbon group which may have a substituent, or a group in which R ¹ and R ⁵ are bonded to each other to form a cyclic structure together with the N atom to which they are bonded. N-substituted-β-oxothiolactam derivatives represented by the following general formula [8]:

(Wherein R ¹ and R ⁵ are the same as described above), and the N-substituted-β-oxolactam derivative is represented by the formula: The method according to any one of claims 1 to 4, wherein the reaction is carried out by dissolving the N, N-disubstituted thioamides in a solvent. The method according to claim 5, wherein the solvent is a halogenated hydrocarbon.