JP5004119B2 - 2-phthalimido-3-phosphonopropionic acid ester compound and method for producing the same - Google Patents
2-phthalimido-3-phosphonopropionic acid ester compound and method for producing the same Download PDFInfo
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Description
本発明は、２−フタルイミド−３−ホスホノプロピオン酸のエステル化合物及びその製造方法に関する。 The present invention relates to an ester compound of 2-phthalimido-3-phosphonopropionic acid and a method for producing the same.
２−アミノ−３−ホスホノプロピオン酸は、医薬、化粧品、除草剤、高分子材料の難燃剤、錯体触媒の配位子等、又はこれらの製造原料として有用な化合物である。そのため、非特許文献１−１２に見られるように、それら自身又はその前駆物質の合成法について広く研究が行われている。アミノプロピオラクトン化合物を用いる方法（非特許文献１、２）、βホスホノピルビン酸エステルを用いる方法（非特許文献３）、ホスホノアセトアルデヒドを用いる方法（非特許文献４）、β−ブロモエチルホスホン酸エステルを用いる方法（非特許文献５）、ヨードメチルホスホン酸エステルを用いる方法（非特許文献６）、２−アミノ−３−ヒドロキシプロピルホスホン酸エステルを用いる方法（非特許文献７）、α−アミド−β−ヨードプロピオン酸エステルを用いる方法（非特許文献８）等が知られている。しかしながら、これらの方法は、いずれも収率が低く、これらの出発物質の合成そのものに多段のステップを要する。また、非特許文献４の方法では有毒なシアン化ナトリウムを必要とする等の点で実用的に不利である。セリン又はセリン誘導体から出発する方法も知られており、原料的には有利であるが、収率面で満足できるものではない（非特許文献９−１１）。工業的に入手容易なアセトアミドアクリル酸エステルをホスファイトと反応させる方法も知られているが（非特許文献２、１２及び１３）、収率は一般的に低く、工業的に満足できるレベルではない。上記方法では、いずれも２−アミノ−３−ホスホノプロピオン酸を効率よく製造できるものではなく、２−アミノ−３−ホスホノプロピオン酸又はその前駆物質の工業的に有利な合成法の開発が切望されている。
本発明は、かかる従来技術の実情に鑑みてなされたものであり、２−アミノ−３−ホスホノプロピオン酸に容易に変換できる前駆体としての２−フタルイミド−３−ホスホノプロピオン酸エステル化合物、及び該化合物を簡便かつ収率よく製造する方法を提供することを課題とする。 The present invention has been made in view of the situation of such prior art, and 2-phthalimido-3-phosphonopropionic acid ester compound as a precursor that can be easily converted into 2-amino-3-phosphonopropionic acid, Another object of the present invention is to provide a method for producing the compound in a simple and high yield.
本発明者らは、上記課題を達成するために、フタルイミド基でα−置換されたアクリル酸エステル化合物が容易に合成可能であることから、α−フタルイミドアクリル酸エステル化合物にＨ−Ｐ（Ｏ）結合を有するリン化合物を付加させるという新規な方法について鋭意研究を重ねてきた。その結果、特定の塩基触媒の存在下に上記反応が容易にかつ効率よく進行することを見出し、この知見に基づいて本発明を完成するに至った。 In order to achieve the above-mentioned problems, the present inventors can easily synthesize an acrylate ester compound α-substituted with a phthalimide group, so that HP-P (O) is added to the α-phthalimide acrylate compound. Research has been conducted on a novel method of adding a phosphorus compound having a bond. As a result, it has been found that the above reaction proceeds easily and efficiently in the presence of a specific base catalyst, and the present invention has been completed based on this finding.
すなわち本発明は、以下の項に示す２−フタルイミド−３−ホスホノプロピオン酸エステル化合物及びその製造方法を提供する：
項１．一般式（１）
That is, the present invention provides 2-phthalimido-3-phosphonopropionic acid ester compounds and methods for producing the compounds shown in the following sections:
Item 1. General formula (1)
［式中、Ｒ１及びＲ２は、同一又は異なって、炭素数６以下のアルキル基、炭素数１０以下のアリール基、炭素数１２以下のアラルキル基、炭素数６以下のアルコキシ基、炭素数３〜６のシクロアルコキシ基、炭素数１２以下のアリーロキシ基、又は炭素数１２以下のアラルキロキシ基を表す。
前記アリール基、アラルキル基、アリーロキシ基及びアラルキロキシ基を構成する芳香環は、複素芳香環であってもよい。
Ｒ１及びＲ２から水素原子を１原子ずつ除いた残基が分子内で互いに結合してリン原子を含む環構造を形成しても良い。
Ｒ３は、水素、炭素数６以下のアルキル基、炭素数１０以下のアリール基、又は炭素数１２以下のアラルキル基を表す。
Ｒ４は、炭素数６以下のアルキル基、炭素数１０以下のアリール基、又は炭素数１２以下のアラルキル基を表す。］
で示される２−フタルイミド−３−ホスホノプロピオン酸エステル化合物。
[Wherein, R 1 and R 2 are the same or different and are an alkyl group having 6 or less carbon atoms, an aryl group having 10 or less carbon atoms, an aralkyl group having 12 or less carbon atoms, an alkoxy group having 6 or less carbon atoms, or a carbon number. It represents a 3-6 cycloalkoxy group, an aryloxy group having 12 or less carbon atoms, or an aralkyloxy group having 12 or less carbon atoms.
The aromatic ring constituting the aryl group, aralkyl group, aryloxy group and aralkyloxy group may be a heteroaromatic ring.
Residues obtained by removing one hydrogen atom from R 1 and R 2 may be bonded to each other in the molecule to form a ring structure containing a phosphorus atom.
R 3 represents hydrogen, an alkyl group having 6 or less carbon atoms, an aryl group having 10 or less carbon atoms, or an aralkyl group having 12 or less carbon atoms.
R 4 represents an alkyl group having 6 or less carbon atoms, an aryl group having 10 or less carbon atoms, or an aralkyl group having 12 or less carbon atoms. ]
2-phthalimido-3-phosphonopropionic ester compound represented by the formula:
項２．塩基触媒の存在下、一般式（２） Item 2. In the presence of a base catalyst, the general formula (2)
［式中、Ｒ１及びＲ２は、同一又は異なって、炭素数６以下のアルキル基、炭素数１０以下のアリール基、炭素数１２以下のアラルキル基、炭素数６以下のアルコキシ基、炭素数１２以下のアリーロキシ基、又は炭素数１２以下のアラルキロキシ基を表す。
前記アリール基、アラルキル基、アリーロキシ基及びアラルキロキシ基を構成する芳香環は、複素芳香環であってもよい。
Ｒ１及びＲ２から水素原子を１原子ずつ除いた残基が分子内で互いに結合してリン原子を含む環構造を形成しても良い。］
で示されるヒドロリン化合物を、一般式（３）
[Wherein, R 1 and R 2 are the same or different and are an alkyl group having 6 or less carbon atoms, an aryl group having 10 or less carbon atoms, an aralkyl group having 12 or less carbon atoms, an alkoxy group having 6 or less carbon atoms, or a carbon number. It represents an aryloxy group having 12 or less or an aralkyloxy group having 12 or less carbon atoms.
The aromatic ring constituting the aryl group, aralkyl group, aryloxy group and aralkyloxy group may be a heteroaromatic ring.
Residues obtained by removing one hydrogen atom from R 1 and R 2 may be bonded to each other in the molecule to form a ring structure containing a phosphorus atom. ]
The hydroline compound represented by the general formula (3)
［式中、Ｒ３は、水素、炭素数６以下のアルキル基、炭素数１０以下のアリール基、又は炭素数１２以下のアラルキル基を表す。
Ｒ４は、炭素数６以下のアルキル基、炭素数１０以下のアリール基、又は炭素数１２以下のアラルキル基を表す。］
で示されるα−フタルイミドアクリル酸エステル化合物に付加させることを特徴とする、一般式（１）
[Wherein, R 3 represents hydrogen, an alkyl group having 6 or less carbon atoms, an aryl group having 10 or less carbon atoms, or an aralkyl group having 12 or less carbon atoms.
R 4 represents an alkyl group having 6 or less carbon atoms, an aryl group having 10 or less carbon atoms, or an aralkyl group having 12 or less carbon atoms. ]
It is added to the α-phthalimidoacrylic acid ester compound represented by the general formula (1)
［式中Ｒ１、Ｒ２、Ｒ３及びＲ４は、前記と同じ意味を表す。］
で示される２−フタルイミド−３−ホスホノプロピオン酸エステル化合物の製造方法。
[Wherein R 1 , R 2 , R 3 and R 4 represent the same meaning as described above. ]
The manufacturing method of 2-phthalimido-3-phosphonopropionic acid ester compound shown by these.
項３．塩基触媒が、有機アミン、アルカリ金属アルコキシド、アルカリ金属炭酸塩及びアルカリ金属水素化物からなる群より選択される少なくとも１種であることを特徴とする項２に記載の製造方法。 Item 3. Item 3. The production method according to Item 2, wherein the base catalyst is at least one selected from the group consisting of organic amines, alkali metal alkoxides, alkali metal carbonates, and alkali metal hydrides.
項４．有機アミンが、ジアザビシクロウンデセンであることを特徴とする項３に記載の製造方法。 Item 4. Item 4. The method according to Item 3, wherein the organic amine is diazabicycloundecene.
項５．アルカリ金属アルコキシドが、ナトリウムメトキシド及びカリウムｔ−ブトキシドからなる群より選択される少なくとも１種であることを特徴とする項３に記載の製造方法。 Item 5. Item 4. The method according to Item 3, wherein the alkali metal alkoxide is at least one selected from the group consisting of sodium methoxide and potassium t-butoxide.
項６．アルカリ金属炭酸塩が、炭酸セシウムであることを特徴とする項３に記載の製造方法。 Item 6. Item 4. The method according to Item 3, wherein the alkali metal carbonate is cesium carbonate.
項７．アルカリ金属水素化物が、水素化ナトリウムであることを特徴とする項３に記載の製造方法。 Item 7. Item 4. The method according to Item 3, wherein the alkali metal hydride is sodium hydride.
本明細書において示される各基は、具体的には次の通りである。 Specifically, each group shown in this specification is as follows.
炭素数６以下のアルキル基としては、メチル基、エチル基、ｎ−プロピル基、イソプロピル基、ｎ−ブチル基、イソブチル基、ｓｅｃ−ブチル基、ｔ−ブチル基、ｎ−ペンチル基、イソペンチル基、ｔ−ペンチル基、ｎ−へキシル基、イソへキシル基等の炭素数１〜６の直鎖又は分枝鎖状のアルキル基を例示することができる。 Examples of the alkyl group having 6 or less carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, t-butyl group, n-pentyl group, isopentyl group, Examples thereof include straight-chain or branched alkyl groups having 1 to 6 carbon atoms such as t-pentyl group, n-hexyl group, isohexyl group and the like.
炭素数１０以下のアリール基としては、フェニル基、ｐ−トリル基、ナフチル基等の炭素数６〜１０のアリール基を例示することができる。 Examples of the aryl group having 10 or less carbon atoms include aryl groups having 6 to 10 carbon atoms such as a phenyl group, a p-tolyl group, and a naphthyl group.
炭素数１２以下のアラルキル基としては、フェニル低級アルキル基、ナフチル低級アルキル基等を例示することができる。 Examples of the aralkyl group having 12 or less carbon atoms include a phenyl lower alkyl group and a naphthyl lower alkyl group.
フェニル低級アルキルとしては、ベンジル基、１−フェニルエチル基、２−フェニルエチル基、３−フェニルプロピル基等のアルキル部分が炭素数１〜６の直鎖又は分枝鎖状アルキル基であるフェニルアルキル基を例示することができる。 As phenyl lower alkyl, phenylalkyl whose alkyl part such as benzyl group, 1-phenylethyl group, 2-phenylethyl group, 3-phenylpropyl group is a linear or branched alkyl group having 1 to 6 carbon atoms Groups can be exemplified.
ナフチル低級アルキルとしては、１−ナフチルメチル基、２−ナフチルメチル基等のアルキル部分がメチル基又はエチル基であるナフチルアルキル基を例示することができる。 Examples of the naphthyl lower alkyl include naphthylalkyl groups in which an alkyl moiety such as a 1-naphthylmethyl group and a 2-naphthylmethyl group is a methyl group or an ethyl group.
炭素数６以下のアルコキシ基としては、メトキシ基、エトキシ基、ｎ−プロポキシ基、イソプロポキシ基、ｎ−ブトキシ基、ｓｅｃ−ブトキシ基、ｔ−ブトキシ基、ｎ−ペンチルオキシ基、ｎ−へキシルオキシ基等の炭素数１〜６の直鎖又は分枝鎖状のアルコキシ基を例示することができる。 Examples of the alkoxy group having 6 or less carbon atoms include methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, sec-butoxy group, t-butoxy group, n-pentyloxy group, and n-hexyloxy. Examples thereof include straight-chain or branched alkoxy groups having 1 to 6 carbon atoms such as groups.
炭素数３〜６のシクロアルコキシ基としては、シクロペンチルオキシ基、シクロヘキシルオキシ基等の炭素数３〜６のシクロアルコキシ基を例示することができる。 Examples of the C3-C6 cycloalkoxy group include C3-C6 cycloalkoxy groups such as a cyclopentyloxy group and a cyclohexyloxy group.
炭素数１２以下のアリーロキシ基としては、フェノキシ基、ｐ−メチルフェノキシ基、ナフトキシ基等の炭素数６〜１２のアリーロキシ基を例示することができる。 Examples of the aryloxy group having 12 or less carbon atoms include aryloxy groups having 6 to 12 carbon atoms such as phenoxy group, p-methylphenoxy group, and naphthoxy group.
炭素数１２以下のアラルキロキシ基としては、フェニル低級アルコキシ基、ナフチル低級アルコキシ基等を例示することができる。 Examples of the aralkyloxy group having 12 or less carbon atoms include a phenyl lower alkoxy group and a naphthyl lower alkoxy group.
フェニル低級アルコキシ基としては、ベンジロキシ基等のアルコキシ部分が炭素数１〜６の直鎖又は分枝鎖状のアルコキシ基であるフェニルアルコキシ基を例示することができる。 Examples of the phenyl lower alkoxy group include a phenylalkoxy group in which an alkoxy moiety such as a benzyloxy group is a linear or branched alkoxy group having 1 to 6 carbon atoms.
ナフチル低級アルコキシ基としては、１−ナフチルメトキシ基、２−ナフチルメトキシ基等のアルコキシ部分がメトキシ基又はエトキシ基であるナフチルアルコキシ基を例示することができる。 Examples of the naphthyl lower alkoxy group include naphthylalkoxy groups in which an alkoxy moiety such as a 1-naphthylmethoxy group and a 2-naphthylmethoxy group is a methoxy group or an ethoxy group.
Ｒ１及びＲ２から水素原子を１原子ずつ除いた残基が分子内で互いに結合して形成されるリン原子を含む環構造としては、４，５−ジメチル−２−オキソ−１，３，２−ジオキサホスファシクロペンタン環、４，４，５，５−テトラメチル−２−オキソ−１，３，２−ジオキサホスファシクロペンタン環等が例示される。 The ring structure containing a phosphorus atom formed by bonding a residue obtained by removing one hydrogen atom from R 1 and R 2 to each other in the molecule includes 4,5-dimethyl-2-oxo-1,3, Examples include 2-dioxaphosphacyclopentane ring, 4,4,5,5-tetramethyl-2-oxo-1,3,2-dioxaphosphacyclopentane ring and the like.
上記アリール基、アラルキル基、アリーロキシ基及びアラルキロキシ基を構成する芳香環は、複素芳香環であってもよく、複素芳香環としては、フラン環、チオフェン環、ベンゾチオフェン環等を例示することができる。 The aromatic ring constituting the aryl group, aralkyl group, aryloxy group and aralkyloxy group may be a heteroaromatic ring, and examples of the heteroaromatic ring include a furan ring, a thiophene ring, and a benzothiophene ring. .
本発明化合物には、例えば、上記一般式（１）においてＲ１及びＲ２が、同一又は異なって、炭素数６以下のアルキル基、炭素数１０以下のアリール基又は炭素数６以下のアルコキシ基を示し、Ｒ３が水素、炭素数６以下のアルキル基又は炭素数１０以下のアリール基を示し、Ｒ４が炭素数６以下のアルキル基を示す、２−フタルイミド−３−ホスホノプロピオン酸エステル化合物が含まれる。 In the compound of the present invention, for example, in the general formula (1), R 1 and R 2 are the same or different, and an alkyl group having 6 or less carbon atoms, an aryl group having 10 or less carbon atoms, or an alkoxy group having 6 or less carbon atoms 2-phthalimido-3-phosphonopropionic acid ester wherein R 3 represents hydrogen, an alkyl group having 6 or less carbon atoms or an aryl group having 10 or less carbon atoms, and R 4 represents an alkyl group having 6 or less carbon atoms Compounds are included.
また、本発明化合物には、例えば、上記一般式（１）においてＲ１及びＲ２が、互いに結合して−ＯＣＨ（ＣＨ３）ＣＨ（ＣＨ３）Ｏ−又はＯＣ（ＣＨ３）２Ｃ（ＣＨ３）２Ｏ−を示し、Ｒ３が水素を示し、Ｒ４が炭素数６以下のアルキル基を示す、２−フタルイミド−３−ホスホノプロピオン酸エステル化合物が含まれる。 In the compound of the present invention, for example, in the above general formula (1), R 1 and R 2 are bonded to each other to form —OCH (CH 3 ) CH (CH 3 ) O— or OC (CH 3 ) 2 C ( 2-phthalimido-3-phosphonopropionic acid ester compounds in which CH 3 ) 2 O—, R 3 represents hydrogen, and R 4 represents an alkyl group having 6 or less carbon atoms are included.
以下、本発明の製造方法を詳細に説明する。 Hereinafter, the production method of the present invention will be described in detail.
本発明の化合物である一般式（１） General formula (1) which is a compound of the present invention
［式中Ｒ１、Ｒ２、Ｒ３及びＲ４は、前記と同じ意味を表す。］で示される２−フタルイミド−３−ホスホノプロピオン酸エステル化合物は、
塩基触媒の存在下、一般式（２）
[Wherein R 1 , R 2 , R 3 and R 4 represent the same meaning as described above. ] The 2-phthalimido-3-phosphonopropionic acid ester compound represented by
In the presence of a base catalyst, the general formula (2)
［式中、Ｒ１及びＲ２は前記と同じ意味を表す。］で示されるヒドロリン化合物を、一般式（３） [Wherein, R 1 and R 2 represent the same meaning as described above. The hydroline compound represented by the general formula (3)
［式中、Ｒ３及びＲ４は前記と同じ意味を表す。］で示されるα−フタルイミドアクリル酸エステル化合物に付加させることにより製造される。 [Wherein R 3 and R 4 represent the same meaning as described above. ] Is added to the α-phthalimidoacrylic acid ester compound represented by the formula:
一般式（２）で示されるヒドロリン化合物と一般式（３）で示されるα−フタルイミドアクリル酸エステル化合物との使用割合は、前者１モルに対して、後者が、通常０．５〜２．０モル、好ましくは０．８〜１．２モルである。 The use ratio of the hydroline compound represented by the general formula (2) and the α-phthalimidoacrylic acid ester compound represented by the general formula (3) is usually 0.5 to 2.0 with respect to 1 mole of the former. Mol, preferably 0.8 to 1.2 mol.
一般式（２）で示されるヒドロリン化合物は、公知の化合物であるか、又は公知の方法に準じて容易に製造される。 The hydroline compound represented by the general formula (2) is a known compound or can be easily produced according to a known method.
一般式（２）で示されるヒドロリン化合物の具体例としては、ホスホン酸ジメチル、ホスホン酸ジエチル、ホスホン酸ジフェニル、４，４，５，５−テトラメチル−２−オキソ−１，３，２−ジオキサホスファシクロペンタン、ジエチルホスフィンオキシド、ジフェニルホスフィンオキシド、フェニルホスフィン酸エチル、メチルホスフィン酸フェニル、９，１０−ジヒドロ−９−オキサー１０−ホスファフェナンスレン−１０−オキシド等を例示することができる。 Specific examples of the hydroline compound represented by the general formula (2) include dimethyl phosphonate, diethyl phosphonate, diphenyl phosphonate, 4,4,5,5-tetramethyl-2-oxo-1,3,2-di Examples include oxaphosphacyclopentane, diethylphosphine oxide, diphenylphosphine oxide, ethyl phenylphosphinate, phenyl methylphosphinate, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide, and the like. it can.
一般式（３）で示されるα−フタルイミドアクリル酸エステル化合物は、公知の化合物であるか、又は公知の方法に準じて容易に製造される。 The α-phthalimidoacrylic acid ester compound represented by the general formula (3) is a known compound or can be easily produced according to a known method.
本発明に用いる塩基触媒としては、アルカリ金属カチオン又はアルカリ土類金属カチオンをカチオン部分に有し、炭酸イオン、アルコキシドイオン、アミドイオン、ヒドリドイオン等をアニオン部分に有する化合物、有機アルカリ金属化合物、有機アミン等を用いることができる。これらの塩基触媒には、種々の無機塩基又は有機塩基が含まれる。 As the base catalyst used in the present invention, a compound having an alkali metal cation or an alkaline earth metal cation in the cation portion and a carbonate ion, an alkoxide ion, an amide ion, a hydride ion or the like in the anion portion, an organic alkali metal compound, an organic An amine or the like can be used. These base catalysts include various inorganic bases or organic bases.
例えば、無機塩基としては、アルカリ金属又はアルカリ土類金属の炭酸塩（炭酸リチウム、炭酸ナトリウム、炭酸セシウム等）、アルカリ金属又はアルカリ土類金属のアルコキシド（ナトリウムメトキシド、ナトリウムエトキシド、カリウムｔ−ブトキシド等）、アルカリ金属又はアルカリ土類金属のアミド（ナトリウムアミド、リチウムジイロプロピルアミド等）、アルカリ金属又はアルカリ土類金属の水素化物（水素化ナトリウム、水素化カリウム等）等を挙げることができる。 Examples of the inorganic base include alkali metal or alkaline earth metal carbonates (lithium carbonate, sodium carbonate, cesium carbonate, etc.), alkali metal or alkaline earth metal alkoxides (sodium methoxide, sodium ethoxide, potassium t- Butoxides), alkali metal or alkaline earth metal amides (sodium amide, lithium diisopropylpropylamide, etc.), alkali metal or alkaline earth metal hydrides (sodium hydride, potassium hydride, etc.), etc. it can.
有機塩基としては、有機アルカリ金属化合物（有機リチウム（例えば、ｔ−ブチルリチウム）等）、有機アミン（ｐ−ジメチルアミノピリジン、ジアザビシクロウンデセン、ジアザビシクロオクタン等）等を挙げることができる。 Examples of the organic base include organic alkali metal compounds (such as organic lithium (eg, t-butyllithium)) and organic amines (such as p-dimethylaminopyridine, diazabicycloundecene, diazabicyclooctane). .
なかでも、有機アミン、アルカリ金属アルコキシド、アルカリ金属炭酸塩及びアルカリ金属水素化物が好ましい。 Of these, organic amines, alkali metal alkoxides, alkali metal carbonates and alkali metal hydrides are preferred.
より具体的には、ジアザビシクロウンデセン、ナトリウムメトキシド、カリウムｔ−ブトキシド、炭酸セシウム及び水素化ナトリウムが好ましい。 More specifically, diazabicycloundecene, sodium methoxide, potassium t-butoxide, cesium carbonate and sodium hydride are preferred.
これらの塩基は、１種単独で又は２種以上混合して使用される。 These bases are used individually by 1 type or in mixture of 2 or more types.
これらの塩基の添加量は塩基の強さや反応温度にも依るが、反応の進行のためには多量であるほど好ましく、一般的には一般式（２）で示されるヒドロリン化合物に対して１〜１０００モル％の範囲から選択されるが、通常、５〜１００モル％で十分である。 The amount of these bases to be added depends on the strength of the base and the reaction temperature, but is preferably as large as possible for the progress of the reaction. Although selected from the range of 1000 mol%, 5 to 100 mol% is usually sufficient.
本発明の反応は塩基が液体の場合には特に溶媒を用いなくてもよいが、必要に応じて溶媒中で実施することもできる。溶媒としては、ｎ−ヘキサン、シクロヘキサン、ベンゼン、トルエン等の炭化水素系溶媒；ジエチルエーテル、ジイソプロピルエーテル、テトラヒドロフラン、ジメトキシエタン、ジオキサン、ジグライム、ジブチルエーテル、シクロペンチルメチルエーテル、アニソール等のエーテル系溶媒等種々のものが使用できる。また、これらは単独若しくは２種以上の混合物として使用される。 In the reaction of the present invention, when the base is liquid, it is not particularly necessary to use a solvent, but it can also be carried out in a solvent if necessary. Solvents include hydrocarbon solvents such as n-hexane, cyclohexane, benzene, and toluene; various ether solvents such as diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane, dioxane, diglyme, dibutyl ether, cyclopentyl methyl ether, and anisole. Can be used. Moreover, these are used individually or in mixture of 2 or more types.
上記反応は、冷却下、室温下及び加温下のいずれで行ってもよい。具体的には、反応温度は、通常０℃から２５０℃、好ましくは２０℃から１７０℃の範囲から選択される。 The above reaction may be carried out under cooling, at room temperature, or under heating. Specifically, the reaction temperature is usually selected from the range of 0 ° C. to 250 ° C., preferably 20 ° C. to 170 ° C.
反応時間は、通常数時間〜数十時間、好ましくは２〜１０時間である。 The reaction time is usually several hours to several tens of hours, preferably 2 to 10 hours.
反応混合物からの生成物の分離は、各種クロマトグラフィー、蒸留或いは再結晶等通常行われる精製法により容易に達成される。なお、フタルイミド部分のアミノ基への加水分解脱保護は例えばＪｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ、１９８０年、４５巻、ｐ．２１４５に記述されたＨＣｌ水溶液による方法等により容易に実施できる。 Separation of the product from the reaction mixture can be easily achieved by various purification methods such as chromatography, distillation or recrystallization. Hydrolysis deprotection of the phthalimide moiety to the amino group is described, for example, in Journal of Organic Chemistry, 1980, Vol. 45, p. 2145 can be easily carried out by a method using an aqueous HCl solution.
上記一般式（１）で表される本発明の２−フタルイミド−３−ホスホノプロピオン酸エステル化合物は、耐熱性に優れかつ非極性分子に対する相溶性が高いので、高分子材料の難燃剤として有用である。 The 2-phthalimide-3-phosphonopropionic acid ester compound of the present invention represented by the above general formula (1) is excellent in heat resistance and highly compatible with nonpolar molecules, and thus is useful as a flame retardant for polymer materials. It is.
上記一般式（１）で表される本発明の２−フタルイミド−３−ホスホノプロピオン酸エステル化合物は、医薬、化粧品、除草剤、錯体触媒の配位子等、又はこれらの製造原料としても有用な化合物である。 The 2-phthalimide-3-phosphonopropionic acid ester compound of the present invention represented by the general formula (1) is useful as a pharmaceutical, cosmetic, herbicide, complex catalyst ligand or the like, or a raw material for producing these compounds. Compound.
さらに、本発明の製造方法によれば、２−フタルイミド−３−ホスホノプロピオン酸エステル化合物を、α−フタルイミドアクリル酸エステル化合物及びヒドロリン化合物から容易にかつ高収率で製造することができる。 Furthermore, according to the production method of the present invention, the 2-phthalimido-3-phosphonopropionic acid ester compound can be easily produced in high yield from the α-phthalimidoacrylic acid ester compound and the hydroline compound.
２−フタルイミド−３−ホスホノプロピオン酸エステル化合物の単離精製も容易に行うことができるので、本発明の方法は、２−アミノ−３−ホスホノプロピオン酸を合成するための中間体製造方法として有用である。 Since the 2-phthalimido-3-phosphonopropionic acid ester compound can be easily isolated and purified, the method of the present invention is an intermediate production method for synthesizing 2-amino-3-phosphonopropionic acid. Useful as.
以下、実施例により本発明を更に具体的に説明するが、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。 EXAMPLES Hereinafter, although an Example demonstrates this invention further more concretely, this invention is not limited at all by these Examples.
以下の実施例において、Ｐｈは、フェニル基を示し、Ｍｅは、メチル基を示し、そしてＥｔは、エチル基を示す。 In the following examples, Ph represents a phenyl group, Me represents a methyl group, and Et represents an ethyl group.
実施例１ ２−フタルイミドアクリル酸エチルと４，４，５，５−テトラメチル−２−オキソ−１，３，２−ジオキサホスファシクロペンタンの反応
１０ｍＬの二口フラスコに、２−フタルイミドアクリル酸エチルを０．７１１ミリモル、４，４，５，５−テトラメチル−２−オキソ−１，３，２−ジオキサホスファシクロペンタンを０．７１１ミリモル及びトルエンを４ｍＬ加え、ジアザビシクロウンデセンを０．３５５ミリモル添加し、この混合物を室温で８時間攪拌した。反応液を濃縮し、ｐ−ジメトキシベンゼン５０ｍｇを内部標準として加え１H NMRで分析したところ、２−フタルイミド−３−（４，４，５，５−テトラメチル−２−オキソ−１，３，２−ジオキサホスファシクロペンタン−２−イル）プロピオン酸エチルが９８．３％の収率で生成していることが判明した。
Example 1 Reaction of ethyl 2-phthalimidoacrylate with 4,4,5,5-tetramethyl-2-oxo-1,3,2-dioxaphosphacyclopentane Into a 10 mL two-necked flask was added 2-phthalimidoacrylic. 0.711 mmol of ethyl acid, 0.711 mmol of 4,4,5,5-tetramethyl-2-oxo-1,3,2-dioxaphosphacyclopentane and 4 mL of toluene were added, and diazabicyclone was added. 0.355 mmol of decene was added and the mixture was stirred at room temperature for 8 hours. The reaction solution was concentrated, 50 mg of p-dimethoxybenzene was added as an internal standard and analyzed by 1 H NMR, and 2-phthalimide-3- (4,4,5,5-tetramethyl-2-oxo-1,3, It was found that ethyl 2-dioxaphosphacyclopentan-2-yl) propionate was produced in a yield of 98.3%.
本生成物は以下の構造を有する文献未収載の新規物質であり、その物性や分光学データは以下の通りであった。 This product is a novel substance not yet published in the literature having the following structure, and its physical properties and spectroscopic data were as follows.
融点１４０．７−１４１．４℃
1H NMR (CDCl3, 300 MHz) δ 7.87-7.90 (m, 2H, Ph), 7.74 - 7.76 (m, 2H, Ph), 5.38-5.43 (m, 1H, CHC(O)), 4.19-4.27 (m, 2H, OCH2), 2.87-2.96 (m, 2H, CH2), 1.44, 1.36, 1.32 (3s, 9H, CH3), 1.23 (t, J(HH) = 7.1 Hz, 3H, CH3), 1.17 (s, 3H, CH3)
13C NMR (CDCl3, 75 MHz): δ 168.2 (d, 3J(PC) = 18.6 Hz, C(O)OEt), 167.1 (s, NC(O)), 134.1 (s, Ph), 131.8 (s, Ph), 123.5 (s, Ph), 88.5, 88.2 (2s, CMe2), 62.5 (s, OCH2), 47.2 (d, 2J(PC) = 4.2 Hz, CHCOOEt), 27.9 (d, 1J(PC) = 135.9 Hz, CH2P(O)), 24.5 (d, 3J(PC)= 3.7 Hz, C(CH3)), 24.4 (d, 3J(PC) = 4.8 Hz, C(CH3)), 23.9 (d, 3J(PC)= 4.7 Hz, C(CH3)), 23.5 (d, 3J(PC)= 5.7 Hz, C(CH3)), 14.0 (s, CH2 CH3)
31P NMR (CDCl3, 162 MHz): δ 38.1
IR (KBr, cm-1): 2987, 2943, 2908, 1776, 1740, 1724, 1616, 1469, 1392, 1271, 1232, 1182, 1134, 1088, 1024, 958, 933, 881
元素分析 C19H24NO7Pとしての計算値: C, 55.74; H, 5.91; N, 3. 42. 実測値: C, 55.43; H, 5.78; N, 3.39。
Melting point 140.7-141.4 ° C
1 H NMR (CDCl 3 , 300 MHz) δ 7.87-7.90 (m, 2H, Ph), 7.74-7.76 (m, 2H, Ph), 5.38-5.43 (m, 1H, C H C (O)), 4.19 -4.27 (m, 2H, OCH 2 ), 2.87-2.96 (m, 2H, CH 2 ), 1.44, 1.36, 1.32 (3s, 9H, CH 3 ), 1.23 (t, J (HH) = 7.1 Hz, 3H , CH 3 ), 1.17 (s, 3H, CH 3 )
13 C NMR (CDCl 3 , 75 MHz): δ 168.2 (d, 3 J (PC) = 18.6 Hz, C (O) OEt), 167.1 (s, N C (O)), 134.1 (s, Ph), 131.8 (s, Ph), 123.5 (s, Ph), 88.5, 88.2 (2s, C Me 2 ), 62.5 (s, O C H 2 ), 47.2 (d, 2 J (PC) = 4.2 Hz, C HCOOEt ), 27.9 (d, 1 J (PC) = 135.9 Hz, CH 2 P (O)), 24.5 (d, 3 J (PC) = 3.7 Hz, C ( C H 3 )), 24.4 (d, 3 J (PC) = 4.8 Hz, C ( C H 3 )), 23.9 (d, 3 J (PC) = 4.7 Hz, C ( C H 3 )), 23.5 (d, 3 J (PC) = 5.7 Hz, C ( C H 3 )), 14.0 (s, CH 2 C H 3 )
31 P NMR (CDCl 3 , 162 MHz): δ 38.1
IR (KBr, cm -1 ): 2987, 2943, 2908, 1776, 1740, 1724, 1616, 1469, 1392, 1271, 1232, 1182, 1134, 1088, 1024, 958, 933, 881
Calculated for elemental analysis C 19 H 24 NO 7 P: C, 55.74; H, 5.91; N, 3. 42. Found: C, 55.43; H, 5.78 ; N, 3.39.
実施例２ ２−フタルイミドアクリル酸メチルと４，４，５，５−テトラメチル−２−オキソ−１，３，２−ジオキサホスファシクロペンタンの反応
２−フタルイミドアクリル酸エチルに代えて２−フタルイミドアクリル酸メチルを用い、実施例１と同様にして以下の化合物を合成した。反応液を濃縮し、ｎ−ヘキサン−酢酸エチル４：６の混合液を用いて濃縮物のシリカゲルカラムクロマトグラフィーを行うと、無色固体である２−フタルイミド−３−（４，４，５，５−テトラメチル−２−オキソ−１，３，２−ジオキサホスファシクロペンタン−２−イル）プロピオン酸メチルが８０．３％の収率で得られた。
Example 2 Reaction of methyl 2-phthalimidoacrylate with 4,4,5,5-tetramethyl-2-oxo-1,3,2-dioxaphosphacyclopentane 2- The following compounds were synthesized in the same manner as Example 1 using methyl phthalimide acrylate. The reaction solution was concentrated, and the concentrate was subjected to silica gel column chromatography using a mixed solution of n-hexane-ethyl acetate 4: 6 to give 2-phthalimide-3- (4, 4, 5, 5 which was a colorless solid. -Methyl tetramethyl-2-oxo-1,3,2-dioxaphosphacyclopentan-2-yl) propionate was obtained in a yield of 80.3%.
本生成物は以下の構造を有する文献未収載の新規物質であり、その物性や分光学データは以下の通りであった。 This product is a novel substance not yet published in the literature having the following structure, and its physical properties and spectroscopic data were as follows.
融点146.6-147.1℃
1H NMR (CDCl3, 300 MHz): δ 7.87-7.90 (m, 2H, Ph), 7.73-7.76 (m, 2H, Ph), 5.38-5.44 (m, 1H, CHC(O)), 3.76 (s, 3H, C(O)OCH3), 2.86-2.97 (m, 2H, P(O)CH2), 1.43, 1.36, 1.32, 1.17 (4s, 12H, CCH3)
13C NMR (CDCl3, 75 MHz): δ 168.8 (d, J = 18.7 Hz, C(O)OMe), 167.0 (s, NC(O)), 134.1 (s, Ph), 131.9 (s, Ph), 123.6 (s, Ph), 88.5, 88.3 (2s, CMe2), 53.2 (s, OCH3), 47.2 (d, J = 4.1 Hz, CHC(O)OMe)), 27.9 (d, J = 136.0 Hz, P(O)CH2), 24.6 (d, J = 3.7 Hz, CCH3), 24.5 (d, J = 6.1 Hz, CCH3), 23.9 (d, J = 5.0 Hz, CCH3), 23.5 (d, J = 5.5 Hz, CCH3)
31P NMR (CDCl3, 162 MHz): δ 38.0
IR (KBr, cm-1): 2983, 2935, 2907, 1779, 1751, 1721, 1469, 1455, 1384, 1251, 1176, 1100, 1049, 1025, 966
元素分析 C18H22NO7Pとしての計算値: C, 54.68; H, 5.61; N, 3.54, 実測値: C, 54.65; H, 5.61; N, 3.47。
Melting point 146.6-147.1 ℃
1 H NMR (CDCl 3 , 300 MHz): δ 7.87-7.90 (m, 2H, Ph), 7.73-7.76 (m, 2H, Ph), 5.38-5.44 (m, 1H, C H C (O)), 3.76 (s, 3H, C (O) OCH 3 ), 2.86-2.97 (m, 2H, P (O) CH 2 ), 1.43, 1.36, 1.32, 1.17 (4s, 12H, CCH 3 )
13 C NMR (CDCl 3 , 75 MHz): δ 168.8 (d, J = 18.7 Hz, C (O) OMe), 167.0 (s, N C (O)), 134.1 (s, Ph), 131.9 (s, Ph), 123.6 (s, Ph), 88.5, 88.3 (2s, C Me 2 ), 53.2 (s, OCH 3 ), 47.2 (d, J = 4.1 Hz, C HC (O) OMe)), 27.9 (d , J = 136.0 Hz, P (O) CH 2 ), 24.6 (d, J = 3.7 Hz, C C H 3 ), 24.5 (d, J = 6.1 Hz, C C H 3 ), 23.9 (d, J = 5.0 Hz, C C H 3 ), 23.5 (d, J = 5.5 Hz, C C H 3 )
31 P NMR (CDCl 3 , 162 MHz): δ 38.0
IR (KBr, cm -1 ): 2983, 2935, 2907, 1779, 1751, 1721, 1469, 1455, 1384, 1251, 1176, 1100, 1049, 1025, 966
Calculated for elemental analysis C 18 H 22 NO 7 P: C, 54.68; H, 5.61; N, 3.54, Found: C, 54.65; H, 5.61 ; N, 3.47.
実施例３ ２−フタルイミドアクリル酸メチルとホスホン酸ジエチルの反応
４，４，５，５−テトラメチル−２−オキソ−１，３，２−ジオキサホスファシクロペンタンに代えてホスホン酸ジエチルを用い、実施例２と同様に以下の化合物を合成した。反応液を濃縮し、ｐ−ジメトキシベンゼン５０ｍｇを内部標準として加え１H NMRで分析したところ、２−フタルイミド−３−ジエチルホスホリルプロピオン酸メチルが９０．６％の収率で生成していることが判明した。
Example 3 Reaction of methyl 2- phthalimidoacrylate with diethyl phosphonate Diethyl phosphonate was used in place of 4,4,5,5-tetramethyl-2-oxo-1,3,2-dioxaphosphacyclopentane. The following compounds were synthesized as in Example 2. The reaction solution was concentrated, 50 mg of p-dimethoxybenzene was added as an internal standard and analyzed by 1 H NMR. As a result, it was found that methyl 2-phthalimido-3-diethylphosphorylpropionate was produced in a yield of 90.6%. found.
本生成物は以下の構造を有する文献未収載の新規物質であり、その物性や分光学データは以下の通りであった。 This product is a novel substance not yet published in the literature having the following structure, and its physical properties and spectroscopic data were as follows.
1H NMR (CDCl3, 300 MHz): δ 7.86-7.90 m, 2H, Ph), 7.73-7.78 (m, 2H, Ph), 5.19-5.28 (m, 1H, CHC(O)), 3.94-4.06 (m, 4H, OCH2), 3.76 (s, 3H, OCH3), 2.84-2.97, 2.63-2.75 (2m, 2H, CH2), 1.21, 1.11 (2t, 共にJ(HH) = 7.1 Hz, 6H, CCH3)
13C NMR (CDCl3, 75 MHz): δ 168.9 (d, 3J(PC) = 20.4 Hz, C(O)OMe), 167.0 (s, NC(O)), 134.2 (s, Ph), 131.8 (s, Ph), 123.5 (s, Ph), 62.1 (d, 2J(PC) = 6.4 Hz, OCH2CH3), 61.8 (d, 2J(PC) = 6.5 Hz, P(O)OCH2), 53.2 (s, OCH3), 46.7 (d, 2J(PC) = 5.3 Hz, CHCOOEt), 24.9 (d, 1J(PC) = 145.7 Hz, CH2P(O)), 16.2 (d, 3J(PC) = 6.1 Hz, OCH2 CH3), 16.0 (d, 3J(PC)= 6.4 Hz, CH2 CH3)
31P NMR (CDCl3, 162 MHz): δ 26.3
IR (液膜, cm-1): 2985, 2937, 1774, 1749, 1720, 1614, 1468, 1439, 1392, 1252, 1178, 1097, 1051, 1026, 968
HRMS C16H20NO7Pとしての計算値: 369.0977, 実測値: 369.0981。
1 H NMR (CDCl 3 , 300 MHz): δ 7.86-7.90 m, 2H, Ph), 7.73-7.78 (m, 2H, Ph), 5.19-5.28 (m, 1H, C H C (O)), 3.94 -4.06 (m, 4H, OCH 2 ), 3.76 (s, 3H, OCH 3 ), 2.84-2.97, 2.63-2.75 (2m, 2H, CH 2 ), 1.21, 1.11 (2t, both J (HH) = 7.1 Hz, 6H, CCH 3 )
13 C NMR (CDCl 3 , 75 MHz): δ 168.9 (d, 3 J (PC) = 20.4 Hz, C (O) OMe), 167.0 (s, N C (O)), 134.2 (s, Ph), 131.8 (s, Ph), 123.5 (s, Ph), 62.1 (d, 2 J (PC) = 6.4 Hz, O C H 2 CH 3 ), 61.8 (d, 2 J (PC) = 6.5 Hz, P ( O) O C H 2 ), 53.2 (s, O C H 3 ), 46.7 (d, 2 J (PC) = 5.3 Hz, C HCOOEt), 24.9 (d, 1 J (PC) = 145.7 Hz, CH 2 P (O)), 16.2 (d, 3 J (PC) = 6.1 Hz, OCH 2 C H 3 ), 16.0 (d, 3 J (PC) = 6.4 Hz, CH 2 C H 3 )
31 P NMR (CDCl 3 , 162 MHz): δ 26.3
IR (Liquid film, cm -1 ): 2985, 2937, 1774, 1749, 1720, 1614, 1468, 1439, 1392, 1252, 1178, 1097, 1051, 1026, 968
Calculated as HRMS C 16 H 20 NO 7 P: 369.0977, found: 369.0981.
実施例４ ２−フタルイミドアクリル酸エチルとホスホン酸ジメチルの反応
２−フタルイミドアクリル酸メチルに代えて２−フタルイミドアクリル酸エチルを用い、４，４，５，５−テトラメチル−２−オキソ−１，３，２−ジオキサホスファシクロペンタンに代えてホスホン酸ジメチルを用いて、実施例２と同様に以下の化合物を合成した。反応液を濃縮し、ｎ−ヘキサン−酢酸エチル１：１の混合液を用いて濃縮物のシリカゲルカラムクロマトグラフィーを行うと、無色粘稠液体である２−フタルイミド−３−ジメチルホスホリルプロピオン酸エチルが７４．６％の収率で得られた。
Example 4 Reaction of ethyl 2-phthalimidoacrylate and dimethyl phosphonate Using ethyl 2-phthalimidoacrylate in place of methyl 2-phthalimidoacrylate, 4,4,5,5-tetramethyl-2-oxo-1, The following compounds were synthesized in the same manner as in Example 2 using dimethyl phosphonate instead of 3,2-dioxaphosphacyclopentane. The reaction solution was concentrated, and the concentrate was subjected to silica gel column chromatography using a mixture of n-hexane-ethyl acetate 1: 1, and ethyl 2-phthalimido-3-dimethylphosphorylpropionate, which was a colorless viscous liquid, was obtained. Obtained in a yield of 74.6%.
本生成物は以下の構造を有する文献未収載の新規物質であり、その物性や分光学データは以下の通りであった。 This product is a novel substance not yet published in the literature having the following structure, and its physical properties and spectroscopic data were as follows.
1H NMR (CDCl3, 300 MHz): δ 7.83-7.87 (m, 2H, Ph), 7.69-7.75, (m, 2H, Ph), 5.13-5.22 (m, 1H, CHC(O)), 4.14-4.23 (m, 2H, OCH2), 3.63 (d, J = 3.4 Hz, 3H, OCH3), 3.60 (d, J = 3.4 Hz, 3H, OCH3), 2.62-2.94 (m, 2H, CH2), 1.20 (t, J(HH)= 7.1 Hz, 3H, CH3)
13C NMR (CDCl3, 75 MHz): δ 168.1 (d,3J(PC) = 20.2 Hz, C(O)OEt), 167.0 (s, NC(O)), 134.1 (s, Ph), 131.7 (s, Ph), 123.5 (s, Ph), 62.5 (s, OCH2CH3), 52.8 (d, 2J(PC) = 6.5 Hz, OCH3), 52.3 (d, 2J(PC) = 6.6 Hz, OCH3), 46.6 (d, 2J(PC) = 5.1 Hz, CHCOOEt), 23.9 (d, 1J(PC) = 145.8 Hz, CH2P(O)), 13.9 (s, CCH3)
31P NMR (CDCl3, 162 MHz): δ 29.1
IR (液膜, cm-1): 2985, 2956, 1778, 1747, 1716, 1612, 1468, 1390, 1250, 1182, 1097, 1055, 1030
元素分析 C15H18NO7Pとしての計算値: C, 50.71; H, 5.11; N, 3.94, 実測値: C, 50.47; H, 5.32; N, 3.95。
1 H NMR (CDCl 3 , 300 MHz): δ 7.83-7.87 (m, 2H, Ph), 7.69-7.75, (m, 2H, Ph), 5.13-5.22 (m, 1H, C H C (O)) , 4.14-4.23 (m, 2H, OCH 2 ), 3.63 (d, J = 3.4 Hz, 3H, OCH 3 ), 3.60 (d, J = 3.4 Hz, 3H, OCH 3 ), 2.62-2.94 (m, 2H , CH 2 ), 1.20 (t, J (HH) = 7.1 Hz, 3H, CH 3 )
13 C NMR (CDCl 3 , 75 MHz): δ 168.1 (d, 3 J (PC) = 20.2 Hz, C (O) OEt), 167.0 (s, N C (O)), 134.1 (s, Ph), 131.7 (s, Ph), 123.5 (s, Ph), 62.5 (s, O C H 2 CH 3 ), 52.8 (d, 2 J (PC) = 6.5 Hz, OCH 3 ), 52.3 (d, 2 J ( PC) = 6.6 Hz, OCH 3 ), 46.6 (d, 2 J (PC) = 5.1 Hz, C HCOOEt), 23.9 (d, 1 J (PC) = 145.8 Hz, CH 2 P (O)), 13.9 ( s, C C H 3 )
31 P NMR (CDCl 3 , 162 MHz): δ 29.1
IR (Liquid film, cm -1 ): 2985, 2956, 1778, 1747, 1716, 1612, 1468, 1390, 1250, 1182, 1097, 1055, 1030
Calculated for elemental analysis C 15 H 18 NO 7 P: C, 50.71; H, 5.11; N, 3.94, Found: C, 50.47; H, 5.32 ; N, 3.95.
実施例５ ２−フタルイミドアクリル酸メチルとホスホン酸ジメチルの反応
４，４，５，５−テトラメチル−２−オキソ−１，３，２−ジオキサホスファシクロペンタンに代えてホスホン酸ジメチルを用い、実施例２と同様に以下の化合物を合成した。反応液を濃縮し、ｐ−ジメトキシベンゼン５０ｍｇを内部標準として加え１H NMRで分析したところ、２−フタルイミド−３−ジメチルホスホリルプロピオン酸メチルが９０．２％の収率で生成していることが判明した。
Example 5 Reaction of methyl 2- phthalimidoacrylate and dimethyl phosphonate Using dimethyl phosphonate instead of 4,4,5,5-tetramethyl-2-oxo-1,3,2-dioxaphosphacyclopentane The following compounds were synthesized as in Example 2. The reaction solution was concentrated, and 50 mg of p-dimethoxybenzene was added as an internal standard and analyzed by 1 H NMR. As a result, it was found that methyl 2-phthalimido-3-dimethylphosphorylpropionate was produced in a yield of 90.2%. found.
本生成物は以下の構造を有する文献未収載の新規物質であり、その物性や分光学データは以下の通りであった。 This product is a novel substance not yet published in the literature having the following structure, and its physical properties and spectroscopic data were as follows.
1H NMR (CDCl3, 300 MHz): δ 7.87-7.92 (m, 2H, Ph), 7.76-7.80 (m, 2H, Ph), 5.19-5.28 (m, 1H, CHC(O)), 3.77 (s, 3H, OCH3), 3.68 (d, J = 3.2 Hz, 3H, P(O)OCH3), 3.64 (d, J = 3.0 Hz, 3H, P(O)OCH3), 2.66-2.98 (m, 2H, CH2)
13C NMR (CDCl3, 75 MHz): δ 168.6 (d, J = 20.0 Hz, C(O)OMe), 166.9 (s, NC(O)), 134.1 (s, Ph), 131.6 (s, Ph), 123.5 (s, Ph), 53.2 (s, C(O)OCH3), 52.7 (d, J = 6.4 Hz, P(O)OCH3), 52.3 (d, J = 6.6 Hz, P(O)OCH3), 46.4 (d, J = 4.8 Hz, CHC(O)), 23.8 (d, J = 145.9 Hz, CH2)
31P NMR (CDCl3, 162 MHz): δ 29.2
IR (液膜, cm-1): 2956, 2852, 1776, 1747, 1716, 1614, 1468, 1390, 1252, 1180, 1097, 1053, 1030
HRMS C14H16NO7Pとしての計算値: 341.0664, 実測値: 341.0662。
1 H NMR (CDCl 3 , 300 MHz): δ 7.87-7.92 (m, 2H, Ph), 7.76-7.80 (m, 2H, Ph), 5.19-5.28 (m, 1H, C H C (O)), 3.77 (s, 3H, OCH 3 ), 3.68 (d, J = 3.2 Hz, 3H, P (O) OCH 3 ), 3.64 (d, J = 3.0 Hz, 3H, P (O) OCH 3 ), 2.66- 2.98 (m, 2H, CH 2 )
13 C NMR (CDCl 3 , 75 MHz): δ 168.6 (d, J = 20.0 Hz, C (O) OMe), 166.9 (s, NC (O)), 134.1 (s, Ph), 131.6 (s, Ph ), 123.5 (s, Ph), 53.2 (s, C (O) O C H 3 ), 52.7 (d, J = 6.4 Hz, P (O) O C H 3 ), 52.3 (d, J = 6.6 Hz , P (O) O C H 3 ), 46.4 (d, J = 4.8 Hz, C HC (O)), 23.8 (d, J = 145.9 Hz, CH 2 )
31 P NMR (CDCl 3 , 162 MHz): δ 29.2
IR (liquid film, cm -1 ): 2956, 2852, 1776, 1747, 1716, 1614, 1468, 1390, 1252, 1180, 1097, 1053, 1030
Calculated as HRMS C 14 H 16 NO 7 P: 341.0664, found: 341.0662.
実施例６ ２−フタルイミドアクリル酸エチルとフェニルホスフィン酸エチルの反応
４，４，５，５−テトラメチル−２−オキソ−１，３，２−ジオキサホスファシクロペンタンに代えてフェニルホスフィン酸エチルを用い、実施例１と同様に以下の化合物を合成した。ｐ−ジメトキシベンゼンを５０ｍｇ加えて内部標準とし１Ｈ ＮＭＲで分析したところ、２−フタルイミド−３−（フェニルエトキシホスフィニル）プロピオン酸エチル3aＣが９３．９％％収率で生成していることが判明した。本生成物は二つのジアステレオマー混合物であり、その比は５６：４４であった。反応液を濃縮し、ｎ−ヘキサン−酢酸エチル４：６の混合液を用いてシリカゲルカラムクロマトグラフィーを行うと、無色液体である２−フタルイミド−３−（フェニルエトキシホスフィニル）プロピオン酸エチルがジアステレオマー混合物として得られた。
Example 6 Reaction of ethyl 2-phthalimidoacrylate with ethyl phenylphosphinate Ethyl phenylphosphinate instead of 4,4,5,5-tetramethyl-2-oxo-1,3,2-dioxaphosphacyclopentane The following compounds were synthesized in the same manner as in Example 1. When 50 mg of p-dimethoxybenzene was added as an internal standard and analyzed by 1 H NMR, ethyl 2-phthalimido-3- (phenylethoxyphosphinyl) propionate 3aC was found to be produced at a yield of 93.9%. There was found. This product was a mixture of two diastereomers, the ratio of 56:44. When the reaction solution was concentrated and subjected to silica gel column chromatography using a mixed solution of n-hexane-ethyl acetate 4: 6, ethyl 2-phthalimido-3- (phenylethoxyphosphinyl) propionate, which was a colorless liquid, was obtained. Obtained as a diastereomeric mixture.
本生成物は以下の構造を有する文献未収載の新規物質であり、ジアステレオマー混合物としての物性や分光学データは以下の通りであった。 This product is a novel substance not yet described in the literature having the following structure, and physical properties and spectroscopic data as a diastereomer mixture were as follows.
1H NMR (CDCl3, 300 MHz): δ 7.84-7.89 (m, 1H, Ph), 7.62-7.77 (m, 5 H, Ph), 7.39-7.46 (m, 1H, Ph), 7.18-7.23 (m, 2H, Ph), 5.29-5.37, 5.14-5.22 (2m, 1H, CH(C(O)OEt), 4.13-4.21, 3.94-4.05, 3.69-3.84(3m, 4H, P(O)OCH 2CH3及びC(O)OCH 2CH3), 3.07-3.20及び2.72-2.93 (それぞれm, 2H, P(O)CH2), 1.13-1.28 (m, OCH2CH 3), 1.06 (t, J = 7.1 Hz, OCH2CH 3)
13C NMR (CDCl3, 75 MHz): δ 168.4及び168.2 (それぞれd, 共にJ = 2.1 Hz, C(O)OEt), 167.0, 166.8 (2s, NC(O)), 134.0, 133.8 (2s, Ar-C), 132.4 (s, Ar-C), 132.3, 131.9, 131.8, 131.6, 131.4 (m, Ph), 130.7, 129.1, 128.5, 128.4, 128.3, 128.2 (m, Ph), 123.4, Ph), 123.2, Ph), 62.3 (C(O)OCH2CH3), 60.7, 60.66, 60.0 (m, P(O)OCH2CH3), 46.4 (d, J = 2.9 Hz, CHC(O)), 46.1 (d, J = 3.2 Hz, CHC(O)), 29.1(d, J = 102.1 Hz, P(O)CH), 28.2 (d, J = 103.5 Hz, P(O)CH), 15.96, 16.0, 16.1, 16.2 ( 4 lines, P(O)OCH2 CH3), 13.9 (s, C(O)OCH2 CH3)
31P NMR (CDCl3, 162 MHz): δ 40.2 (44%), 39.7 (56%)
IR (液膜, cm-1): 3059, 2983, 2937, 2906, 1778, 1743, 1716, 1614, 1590, 1469, 1439, 1389, 1272, 1180, 1146, 1137, 1122, 1087, 1024, 955
HRMS C21H22NO6Pとしての計算値: 415.1184, 実測値: 415.1186。
1 H NMR (CDCl 3 , 300 MHz): δ 7.84-7.89 (m, 1H, Ph), 7.62-7.77 (m, 5 H, Ph), 7.39-7.46 (m, 1H, Ph), 7.18-7.23 ( m, 2H, Ph), 5.29-5.37, 5.14-5.22 (2m, 1H, C H (C (O) OEt), 4.13-4.21, 3.94-4.05, 3.69-3.84 (3m, 4H, P (O) OC H 2 CH 3 and C (O) OC H 2 CH 3 ), 3.07-3.20 and 2.72-2.93 (m, 2H, P (O) CH 2 ), 1.13-1.28 (m, OCH 2 C H 3 ), 1.06 (t, J = 7.1 Hz, OCH 2 C H 3 )
13 C NMR (CDCl 3 , 75 MHz): δ 168.4 and 168.2 (d, both J = 2.1 Hz, C (O) OEt), 167.0, 166.8 (2s, NC (O)), 134.0, 133.8 (2s, Ar- C ), 132.4 (s, Ar- C ), 132.3, 131.9, 131.8, 131.6, 131.4 (m, Ph), 130.7, 129.1, 128.5, 128.4, 128.3, 128.2 (m, Ph), 123.4, Ph) , 123.2, Ph), 62.3 (C (O) O C H 2 CH 3 ), 60.7, 60.66, 60.0 (m, P (O) O C H 2 CH 3 ), 46.4 (d, J = 2.9 Hz, C HC (O)), 46.1 (d, J = 3.2 Hz, C HC (O)), 29.1 (d, J = 102.1 Hz, P (O) C H), 28.2 (d, J = 103.5 Hz, P ( O) C H), 15.96, 16.0, 16.1, 16.2 (4 lines, P (O) OCH 2 C H 3 ), 13.9 (s, C (O) OCH 2 C H 3 )
31 P NMR (CDCl 3 , 162 MHz): δ 40.2 (44%), 39.7 (56%)
IR (Liquid film, cm -1 ): 3059, 2983, 2937, 2906, 1778, 1743, 1716, 1614, 1590, 1469, 1439, 1389, 1272, 1180, 1146, 1137, 1122, 1087, 1024, 955
Calculated for HRMS C 21 H 22 NO 6 P : 415.1184, Found: 415.1186.
実施例７ ２−フタルイミドアクリル酸エチルとジフェニルホスフィンオキシドの反応
４，４，５，５−テトラメチル−２−オキソ−１，３，２−ジオキサホスファシクロペンタンに代えてジフェニルホスフィンオキシドを用い、実施例１と同様に以下の化合物を合成した。反応液を濃縮し、ｐ−ジメトキシベンゼン５０ｍｇを内部標準として加え１H NMRで分析したところ、２−フタルイミド−３−（ジフェニルホスフィニル）プロピオン酸エチルが９５．３％の収率で生成していることが判明した。
Example 7 Reaction of ethyl 2-phthalimidoacrylate with diphenylphosphine oxide Diphenylphosphine oxide was used instead of 4,4,5,5-tetramethyl-2-oxo-1,3,2-dioxaphosphacyclopentane. The following compounds were synthesized as in Example 1. The reaction mixture was concentrated, 50 mg of p-dimethoxybenzene was added as an internal standard and analyzed by 1 H NMR. As a result, ethyl 2-phthalimido-3- (diphenylphosphinyl) propionate was produced in a yield of 95.3%. Turned out to be.
本生成物は以下の構造を有する文献未収載の新規物質であり、その物性や分光学データは以下の通りであった。 This product is a novel substance not yet published in the literature having the following structure, and its physical properties and spectroscopic data were as follows.
融点158.4-160.2℃。
1H NMR (CDCl3, 300 MHz): δ 7.73-7.80 (m, 2H, Ar-H), 7.58-7.68 (m, 6H, Ph), 7.45-7.53 (m, 3H, Ph), 7.03-7.15 (m, 3H, Ph), 5.39-5.47 (m, 1H, CHC(O)), 4.14-4.25 (m, 2H, OCH2), 3.45-3.56 (m, 1H, CHH), 3.18-3.28 (m, 1H, CHH), 1.20 (t, J(HH) = 7.1 Hz, 3H, CH3)
13C NMR (CDCl3, 75 MHz): δ 168.6 (d, 3J(PC) = 15.2 Hz, C(O)OEt), 166.8 (s, NC(O)), 133.7 (s, Ph), 132.6 (d, J(PC) = 70.6 Hz, P-Ph), 132.0 (d, J(PC) = 2.6 Hz, P-Ph), 131.5 (s, Ph), 131.2 (d, J(PC) = 69.0 Hz, P-Ph), 131.0 (d, J(PC) = 2.7 Hz, P-Ph), 130.7 (s, Ph), 130.5 (s, Ph), 130.4 (s, Ph), 128.8 (Ph), 128. 6 (Ph), 128.3 (Ph), 128.1 (Ph), 62.5, OCH2CH3), 45.9 (d, 2J(PC)= 3.8 Hz, CHCOOEt), 28.5 (d, 1J(PC)= 72.4 Hz, CH2P(O)), 14.0 (OCH2 CH3)
31P NMR (CDCl3, 162 MHz): δ 27.3
IR (KBr, cm-1): 3057, 2972, 2929, 1772, 1731, 1716, 1442, 1390, 1232, 1196, 1119, 1084, 928
HRMS C25H22NO5Pとしての計算値: 447.1236, 実測値: 447.1230。
Melting point 158.4-160.2 ° C.
1 H NMR (CDCl 3 , 300 MHz): δ 7.73-7.80 (m, 2H, Ar- H ), 7.58-7.68 (m, 6H, Ph), 7.45-7.53 (m, 3H, Ph), 7.03-7.15 (m, 3H, Ph), 5.39-5.47 (m, 1H, C H C (O)), 4.14-4.25 (m, 2H, OCH 2 ), 3.45-3.56 (m, 1H, C H H), 3.18 -3.28 (m, 1H, CH H ), 1.20 (t, J (HH) = 7.1 Hz, 3H, CH 3 )
13 C NMR (CDCl 3 , 75 MHz): δ 168.6 (d, 3 J (PC) = 15.2 Hz, C (O) OEt), 166.8 (s, N C (O)), 133.7 (s, Ph), 132.6 (d, J (PC) = 70.6 Hz, P-Ph), 132.0 (d, J (PC) = 2.6 Hz, P-Ph), 131.5 (s, Ph), 131.2 (d, J (PC) = 69.0 Hz, P-Ph), 131.0 (d, J (PC) = 2.7 Hz, P-Ph), 130.7 (s, Ph), 130.5 (s, Ph), 130.4 (s, Ph), 128.8 (Ph) , 128. 6 (Ph), 128.3 (Ph), 128.1 (Ph), 62.5, O C H 2 CH 3 ), 45.9 (d, 2 J (PC) = 3.8 Hz, C HCOOEt), 28.5 (d, 1 J (PC) = 72.4 Hz, CH 2 P (O)), 14.0 (OCH 2 C H 3 )
31 P NMR (CDCl 3 , 162 MHz): δ 27.3
IR (KBr, cm -1 ): 3057, 2972, 2929, 1772, 1731, 1716, 1442, 1390, 1232, 1196, 1119, 1084, 928
Calculated for HRMS C 25 H 22 NO 5 P : 447.1236, Found: 447.1230.
実施例８ ２−フタルイミド桂皮酸エチルとジフェニルホスフィンオキシドの反応
２−フタルイミドアクリル酸エチルに代えて２−フタルイミド桂皮酸エチルを用い、塩基としてジアザビシクロウンデセンに代えてカリウムｔ−ブトキシドを用いて、実施例７と同様に以下の化合物を合成した。反応液を濃縮し、１Ｈ ＮＭＲで分析したところ、２−フタルイミド−３−（ジフェニルホスフィニル）−３−フェニルプロピオン酸エチルの二つの異性体ｉ及びｉｉの混合物が４２：５８の比率、合計収率８０．１％で生成していることが判明した。ｎ−ヘキサン−酢酸エチル１：１の混合液を用いてシリカゲルカラムクロマトグラフィーを行うと、無色固体である二つの異性体の混合物が合計収率７７．２％で単離された。再度ｎ−ヘキサン−酢酸エチル１：１の混合液でシリカゲルカラムクロマトグラフィーを行い、細かく分画することにより、各異性体を分離することができた。
Example 8 Reaction of 2 -phthalimidoethyl cinnamate with diphenylphosphine oxide Using 2-phthalimidoethyl cinnamate instead of ethyl 2-phthalimidoacrylate and using potassium t-butoxide as a base instead of diazabicycloundecene The following compounds were synthesized as in Example 7. The reaction solution was concentrated and analyzed by 1 H NMR. As a result, a mixture of the two isomers i and ii of ethyl 2-phthalimido-3- (diphenylphosphinyl) -3-phenylpropionate was in a ratio of 42:58, The total yield was found to be 80.1%. When silica gel column chromatography was performed using a mixed solution of n-hexane-ethyl acetate 1: 1, a mixture of two isomers as a colorless solid was isolated in a total yield of 77.2%. Again, silica gel column chromatography was performed with a mixed solution of n-hexane-ethyl acetate 1: 1, and each isomer could be separated by fine fractionation.
本生成物は以下の構造を有する異性体混合物である。いずれの異性体も文献未収載の新規物質であり、その物性や分光学データは以下の通りであった。 This product is an isomer mixture having the following structure. All of the isomers are new substances not yet described in the literature, and their physical properties and spectroscopic data are as follows.
異性体ｉ: 融点172.8-175.3℃
1H NMR (CDCl3, 300 MHz): δ 8.06 (br, 2H, Ph), 7.43-7.65 (m, 9H, Ph), 7.16-7.27 (m, 5H, Ph), 6.90, 6.92 (2 br s, 3H, Ph), 5.86 (t, J = 10.3 Hz, 1H, CHC(O)), 5.18 (t, J = 7.9 Hz, 1H, PCH), 3.81-3.87 (m, 1H, OCH), 3.55-3.61 (m, 1H, OCH), 1.00 (t, J(HH)= 7.1 Hz, 3H, CH3)
13C NMR (CDCl3, 75 MHz): δ 167.7 (d, 3J(PC) = 2.1 Hz, C(O)OEt), 166.9, NC(O)), 133.9 (Ar-C), 133.1 (d, J(PC)= 48.6 Hz, P-Ph), 133.0 (d, J(PC) = 5.3 Hz, P-Ph), 131.8 (d, J(PC) = 54.6 Hz, P-Ph), 131.7 (d, J(PC) = 3.2 Hz, P-Ph), 131.3 (Ph), 131.2 (Ph), 131.1 (Ph), 131.0 (Ph), 130.4 (br, Ph), 128.6 (Ph), 128.5 (Ph), 128.0 (Ph), 127.9 (Ph), 127.7 (Ph), 127.2 (Ph), 123.3 (Ph), 61.9 OCH2CH3), 51.9 (d, 2J(PC)= 3.5 Hz, CHCOOEt), 45.2 (d, J(PC) = 65.4 Hz, P(O)CHPh), 13.7 (OCH2 CH3)
31P NMR (CDCl3, 162 MHz): δ 30.8
IR (KBr, cm-1): 3059, 2929, 1781, 1740, 1718, 1637, 1439, 1385, 1250, 1186, 1099, 1026
HRMS C31H26NO5Pとしての計算値: 523.1549, 実測値: 523.1545.
Isomer i: mp 172.8-175.3 ° C
1 H NMR (CDCl 3 , 300 MHz): δ 8.06 (br, 2H, Ph), 7.43-7.65 (m, 9H, Ph), 7.16-7.27 (m, 5H, Ph), 6.90, 6.92 (2 br s , 3H, Ph), 5.86 (t, J = 10.3 Hz, 1H, C H C (O)), 5.18 (t, J = 7.9 Hz, 1H, PCH), 3.81-3.87 (m, 1H, OCH), 3.55-3.61 (m, 1H, OCH), 1.00 (t, J (HH) = 7.1 Hz, 3H, CH 3 )
13 C NMR (CDCl 3 , 75 MHz): δ 167.7 (d, 3 J (PC) = 2.1 Hz, C (O) OEt), 166.9, N C (O)), 133.9 (Ar- C ), 133.1 ( d, J (PC) = 48.6 Hz, P-Ph), 133.0 (d, J (PC) = 5.3 Hz, P-Ph), 131.8 (d, J (PC) = 54.6 Hz, P-Ph), 131.7 (d, J (PC) = 3.2 Hz, P-Ph), 131.3 (Ph), 131.2 (Ph), 131.1 (Ph), 131.0 (Ph), 130.4 (br, Ph), 128.6 (Ph), 128.5 ( Ph), 128.0 (Ph), 127.9 (Ph), 127.7 (Ph), 127.2 (Ph), 123.3 (Ph), 61.9 O C H 2 CH 3 ), 51.9 (d, 2 J (PC) = 3.5 Hz, C HCOOEt), 45.2 (d, J (PC) = 65.4 Hz, P (O) C HPh), 13.7 (OCH 2 C H 3 )
31 P NMR (CDCl 3 , 162 MHz): δ 30.8
IR (KBr, cm -1 ): 3059, 2929, 1781, 1740, 1718, 1637, 1439, 1385, 1250, 1186, 1099, 1026
Calculated as HRMS C 31 H 26 NO 5 P: 523.1549, found: 523.1545.
異性体ｉｉ: 融点217.2- 221.8℃
1H NMR (CDCl3, 300 MHz): δ 7.45-7.76 (m, 9H, Ph), 6.90-7.23 (m, 10H, Ph), 5.88 (dd, J = 7.1, 11.2 Hz, 1H, CHC(O)), 4.97-5.02 (br 4 lines, 1H, PCH), 3.79-3.93 (m, 2H, CH2), 0.86 (t, J(HH) = 6.9 Hz, 3H, CH3)
13C NMR (CDCl3, 75 MHz): δ 167.4 (d, 3J(PC) = 6.0 Hz, C(O)OEt), 166.6 (s, NC(O)), 134.0 (d, J(PC) = 5.9 Hz, P-Ph), 133.6 (Ph), 132.4 (d, J(PC)= 7.3 Hz, P-Ph), 131.3 (Ph), 131.1 (Ph), 131.0 (d, J(PC) = 2.6 Hz, P-Ph), 130.73 (Ph), 130.7 (Ph), 130.62 (Ph), 130.6, (Ph), 128.0 (Ph), 127.94 (Ph), 127.92 (Ph), 127.8 (Ph), 127.3 (d, J(PC)= 2.2 Hz, P-Ph), 123.3 (Ph), 61.6 (C(O)OCH2CH3), 52.2 (CHCOOEt), 45.2 (d, 1J(PC)= 67.2 Hz, P(O)CH), 13.5 (CH3)
31P NMR (CDCl3, 162 MHz): δ 27.7
IR (KBr, cm-1): 3057, 2964, 2929, 1765, 1736, 1718, 1635, 1439, 1387, 1261, 1188, 1103, 1026
HRMS C31H26NO5Pとしての計算値: 523.1549, 実測値: 523.1540。
Isomer ii: melting point 217.2-221.8 ° C
1 H NMR (CDCl 3 , 300 MHz): δ 7.45-7.76 (m, 9H, Ph), 6.90-7.23 (m, 10H, Ph), 5.88 (dd, J = 7.1, 11.2 Hz, 1H, C H C (O)), 4.97-5.02 (br 4 lines, 1H, PCH), 3.79-3.93 (m, 2H, CH 2 ), 0.86 (t, J (HH) = 6.9 Hz, 3H, CH 3 )
13 C NMR (CDCl 3 , 75 MHz): δ 167.4 (d, 3 J (PC) = 6.0 Hz, C (O) OEt), 166.6 (s, N C (O)), 134.0 (d, J (PC ) = 5.9 Hz, P-Ph), 133.6 (Ph), 132.4 (d, J (PC) = 7.3 Hz, P-Ph), 131.3 (Ph), 131.1 (Ph), 131.0 (d, J (PC) = 2.6 Hz, P-Ph), 130.73 (Ph), 130.7 (Ph), 130.62 (Ph), 130.6, (Ph), 128.0 (Ph), 127.94 (Ph), 127.92 (Ph), 127.8 (Ph), 127.3 (d, J (PC) = 2.2 Hz, P-Ph), 123.3 (Ph), 61.6 (C (O) O C H2CH3), 52.2 ( C HCOOEt), 45.2 (d, 1 J (PC) = 67.2 Hz, P (O) C H), 13.5 ( C H 3 )
31 P NMR (CDCl 3 , 162 MHz): δ 27.7
IR (KBr, cm -1 ): 3057, 2964, 2929, 1765, 1736, 1718, 1635, 1439, 1387, 1261, 1188, 1103, 1026
Calculated as HRMS C 31 H 26 NO 5 P: 523.1549, found: 523.1540.
実施例９ ２−フタルイミド桂皮酸エチルとフェニルホスフィン酸エチルの反応
ジフェニルホスフィンオキシドに代えてフェニルホスフィン酸エチルを用い、実施例８と同様に以下の化合物を合成した。ｐ−ジメトキシベンゼンを５０ｍｇ加えて内部標準とし１Ｈ ＮＭＲで分析したところ、２−フタルイミド桂皮酸エチルの転化率は１９．８％であり、２−フタルイミド−３−（フェニルエトキシホスフィニル）−３−フェニルプロピオン酸エチルの収率は１６．４％であることが判明した。反応液を濃縮し、ｎ−ヘキサン−酢酸エチル１：１の混合液を用いてシリカゲルカラムクロマトグラフィーを行うと、無色液体である２−フタルイミド−３−（フェニルエトキシホスフィニル）−３−フェニルプロピオン酸エチルが１２．１％の収率で得られた。
Example 9 Reaction of ethyl 2-phthalimidocinnamate and ethyl phenylphosphinate The following compounds were synthesized in the same manner as in Example 8 using ethyl phenylphosphinate instead of diphenylphosphine oxide. When 50 mg of p-dimethoxybenzene was added as an internal standard and analyzed by 1 H NMR, the conversion of ethyl 2-phthalimidocinnamate was 19.8%, and 2-phthalimido-3- (phenylethoxyphosphinyl)- The yield of ethyl 3-phenylpropionate was found to be 16.4%. The reaction solution was concentrated and subjected to silica gel column chromatography using a mixed solution of n-hexane-ethyl acetate 1: 1 to give 2-phthalimide-3- (phenylethoxyphosphinyl) -3-phenylpropylene which is a colorless liquid. Ethyl onate was obtained in a yield of 12.1%.
本生成物は以下の構造を有する異性体混合物である。その物性や分光学データは以下の通りであった。 This product is an isomer mixture having the following structure. The physical properties and spectroscopic data were as follows.
ジアステレオマー混合物：1H NMR (CDCl3, 300 MHz): δ 6.91-7.80 (m, 14H, Ph), 5.72-5.80, (m, 1H, CHC(O)), 4.71-4.84, 4.54-4.63 (2m, 1H, CHPh), 4.18-4.29, 4.03-4.15, 3.90-3.99, 3.63-3.88 (それぞれm, 4H, P(O)OCH 2CH3及びC(O)OCH 2CH3), 1.35 (t, J = 6.1 Hz, OCH2CH3), 1.27 (t, J = 7.2 Hz, OCH2CH 3), 1.16 (2t, それぞれJ = 6.6 Hz, OCH2CH 3), 1.08 (t, J = 7.0 Hz, OCH2CH 3), 0.92 (t, J = 7.1 Hz, OCH2CH 3)
13C NMR (CDCl3, 75 MHz): δ 167.3 (d, J = 26.2 Hz, C(O)OEt), 167.1 (NC(O)), 166.8 (NC(O)), 134.3 (d, J = 7.6 Hz, Ph), 133.9 (Ph), 133.8 (Ph), 132.3 (Ph), 132.2 (Ph), 132.1 (Ph), 131.9 (Ph), 131.7 (d, Ph), 131.1(Ph), 130.2-130.0 (br), 128.8 (Ph), 128.3 (Ph), 128.2 (Ph), 128.1 (Ph), 128.0 (Ph), 127.9 (Ph), 127.8 (Ph), 127.7 (Ph), 127.2-127.4 (m, Ph), 123.4 (Ph), 123.3 (Ph), 62.1 (C(O)OCH2CH3), 61.7 (C(O)OCH2), 61.4 (d, J = 7.0 Hz, P(O)OCH2), 61.2 (d, J = 6.7 Hz, P(O)OCH2), 51.0 (CHC(O)OEt), 51.5 (CHC(O)), 51.9 (CHC(O)), 46.4 (d, J = 94.8 Hz, P(O)CHPh), 45.7 (d, J = 96.7 Hz, P(O)CHPh), 16.4 (P(O)OCH2 CH3), 16.3 (P(O)OCH2 CH3), 16.2 (P(O)OCH2 CH3), 16.1 (P(O)OCH2 CH3), 14.0 (C(O)OCH2 CH3), 13.9 (C(O)OCH2 CH3), 13.6 (C(O)OCH2 CH3)
31P NMR (CDCl3, 162 MHz): δ 41.2, 40.6, 38.5, 38.3
IR (液膜, cm-1): 3060, 2983, 2939, 1780, 1743, 1716, 1601, 1469, 1439, 1385, 1234, 1119, 1026, 953, 879
HRMS C27H26NO6Pとしての計算値: 491.1498, 実測値: 491.1491。
Diastereomeric mixture: 1 H NMR (CDCl 3 , 300 MHz): δ 6.91-7.80 (m, 14H, Ph), 5.72-5.80, (m, 1H, C H C (O)), 4.71-4.84, 4.54 -4.63 (2m, 1H, C H Ph), 4.18-4.29, 4.03-4.15, 3.90-3.99, 3.63-3.88 (m, 4H, P (O) OC H 2 CH 3 and C (O) OC H 2 respectively CH 3 ), 1.35 (t, J = 6.1 Hz, OCH 2 C H 3), 1.27 (t, J = 7.2 Hz, OCH 2 C H 3 ), 1.16 (2 t, J = 6.6 Hz, OCH 2 C H respectively 3 ), 1.08 (t, J = 7.0 Hz, OCH 2 C H 3 ), 0.92 (t, J = 7.1 Hz, OCH 2 C H 3 )
13 C NMR (CDCl 3 , 75 MHz): δ 167.3 (d, J = 26.2 Hz, C (O) OEt), 167.1 (NC (O)), 166.8 (NC (O)), 134.3 (d, J = 7.6 Hz, Ph), 133.9 (Ph), 133.8 (Ph), 132.3 (Ph), 132.2 (Ph), 132.1 (Ph), 131.9 (Ph), 131.7 (d, Ph), 131.1 (Ph), 130.2- 130.0 (br), 128.8 (Ph), 128.3 (Ph), 128.2 (Ph), 128.1 (Ph), 128.0 (Ph), 127.9 (Ph), 127.8 (Ph), 127.7 (Ph), 127.2-127.4 (m , Ph), 123.4 (Ph), 123.3 (Ph), 62.1 (C (O) O C H 2 CH 3 ), 61.7 (C (O) O C H 2 ), 61.4 (d, J = 7.0 Hz, P (O) O C H 2 ), 61.2 (d, J = 6.7 Hz, P (O) O C H 2 ), 51.0 ( C HC (O) OEt), 51.5 ( C HC (O)), 51.9 ( C HC (O)), 46.4 (d, J = 94.8 Hz, P (O) C HPh), 45.7 (d, J = 96.7 Hz, P (O) C HPh), 16.4 (P (O) OCH 2 C H 3 ), 16.3 (P (O) OCH 2 C H 3 ), 16.2 (P (O) OCH 2 C H 3 ), 16.1 (P (O) OCH 2 C H 3 ), 14.0 (C (O) OCH 2 C H 3 ), 13.9 (C (O) OCH 2 C H 3 ), 13.6 (C (O) OCH 2 C H 3 )
31 P NMR (CDCl 3 , 162 MHz): δ 41.2, 40.6, 38.5, 38.3
IR (liquid film, cm -1 ): 3060, 2983, 2939, 1780, 1743, 1716, 1601, 1469, 1439, 1385, 1234, 1119, 1026, 953, 879
Calculated as HRMS C 27 H 26 NO 6 P: 491.1498, found: 491.1491.
実施例１０ ２−フタルイミド−２−ヘキセン酸メチルとホスホン酸ジエチルの反応
２−フタルイミドアクリル酸メチルに代えて２−フタルイミド−２−ヘキセン酸メチルを用い、塩基としてジアザビシクロウンデセンに代えてカリウムｔ−ブトキシドを用いて、実施例３と同様に以下の化合物を合成した。反応液を濃縮し、ｐ−ジメトキシベンゼン５０ｍｇを内部標準として加え１H NMRで分析したところ、２−フタルイミド−３−ジエチルホスホリルヘキサン酸メチルが６３．５％の収率で生成していることが判明した。
Example 10 Reaction of methyl 2-phthalimido-2-hexenoate and diethyl phosphonate Using methyl 2-phthalimido-2-hexenoate instead of methyl 2-phthalimidoacrylate and using potassium instead of diazabicycloundecene as the base The following compounds were synthesized in the same manner as in Example 3 using t-butoxide. The reaction solution was concentrated, 50 mg of p-dimethoxybenzene was added as an internal standard and analyzed by 1 H NMR. As a result, methyl 2-phthalimido-3-diethylphosphorylhexanoate was produced in a yield of 63.5%. found.
本生成物は以下の構造を有する異性体混合物である。その物性や分光学データは以下の通りであった。 This product is an isomer mixture having the following structure. The physical properties and spectroscopic data were as follows.
1H NMR (CDCl3, 300 MHz): δ 7.85-7.89 (m, 2H, Ph), 7.72-7.78 (m, 2H, Ph), 5.37-5.43, (m, 1H, CHC(O)), 5.00-5.05 (m, 1H, CHC(O)), 4.07-4.15及び3.89-4.06 (それぞれm, 4H, OCH 2), 3.69-3.75 (m, 3H, OCH 3), 3.36-3.47及び2.63-3.20 (m, 1H, P(O)CH), 1.53-1.73 (br m, 2H, CH 2CH2CH3), 0.81-1.32 (m, 11H, CH2CH 2CH 3及びOCH2CH 3)
13C NMR (CDCl3, 75 MHz): δ 171.7 (d, J = 8.8 Hz) 168.4 (d, J = 18.5 Hz), 167.2, 166.9, 134.1, 134.0, 133.7, 131.8, 131.7, 131.5, 123.4, 123.2, 123.1, 122.9, 61.3-62.0 (m, P(O)OCH2), 52.71, 52.70, 50.92, 50.90, 37.0 (d, J(PC) = 140.8 Hz), 36.4, 35.0 (d, J(PC)= 140.3 Hz), 32.0 (d, J(PC) = 4.3 Hz), 30.2 (d, J(PC)= 5.2 Hz), 28.5 (d, J(PC) = 3.5 Hz), 22.4 (d, J(PC)= 11.4 Hz), 21.7 (d, J(PC) = 4.4 Hz), 20.9 (d, J(PC)= 3.0 Hz), 15.8-16.2 (m), 14.1, 14.0
31P NMR (CDCl3, 162 MHz): δ 29.4, 29.2, 28.8
IR (液膜, cm-1): 3060, 2962, 2908, 2873, 1776, 1751, 1718, 1612, 1467, 1389, 1242, 1172, 1049, 1022, 962
HRMS C19H26NO7Pとしての計算値: 411.1447, 実測値: 411.1444。
1 H NMR (CDCl 3 , 300 MHz): δ 7.85-7.89 (m, 2H, Ph), 7.72-7.78 (m, 2H, Ph), 5.37-5.43, (m, 1H, C H C (O)) , 5.00-5.05 (m, 1H, C H C (O)), 4.07-4.15 and 3.89-4.06 (m, 4H, OC H 2 ), 3.69-3.75 (m, 3H, OC H 3 ), 3.36- 3.47 and 2.63-3.20 (m, 1H, P (O) C H ), 1.53-1.73 (br m, 2H, C H 2 CH 2 CH 3 ), 0.81-1.32 (m, 11H, CH 2 C H 2 C H 3 and OCH 2 C H 3 )
13 C NMR (CDCl 3 , 75 MHz): δ 171.7 (d, J = 8.8 Hz) 168.4 (d, J = 18.5 Hz), 167.2, 166.9, 134.1, 134.0, 133.7, 131.8, 131.7, 131.5, 123.4, 123.2 , 123.1, 122.9, 61.3-62.0 (m, P (O) O C H 2 ), 52.71, 52.70, 50.92, 50.90, 37.0 (d, J (PC) = 140.8 Hz), 36.4, 35.0 (d, J ( PC) = 140.3 Hz), 32.0 (d, J (PC) = 4.3 Hz), 30.2 (d, J (PC) = 5.2 Hz), 28.5 (d, J (PC) = 3.5 Hz), 22.4 (d, J (PC) = 11.4 Hz), 21.7 (d, J (PC) = 4.4 Hz), 20.9 (d, J (PC) = 3.0 Hz), 15.8-16.2 (m), 14.1, 14.0
31 P NMR (CDCl 3 , 162 MHz): δ 29.4, 29.2, 28.8
IR (liquid film, cm -1 ): 3060, 2962, 2908, 2873, 1776, 1751, 1718, 1612, 1467, 1389, 1242, 1172, 1049, 1022, 962
Calculated as HRMS C 19 H 26 NO 7 P: 411.1447, found: 411.1444.
実施例１１ ２−フタルイミドアクリル酸エチルとホスホン酸ジエチルの反応
２−フタルイミドアクリル酸メチルに代えて２−フタルイミドアクリル酸エチルを用い、実施例３と同様に以下の化合物を合成した。内部標準としてｐ−ジメトキシベンゼンを５０ｍｇ加えて１Ｈ ＮＭＲで分析したところ、２−フタルイミド−３−ジエチルホスホリルプロピオン酸エチルが９５．８％の収率で生成していることが判明した。実施例３と同様にカラムクロマトグラフィーを行い、目的フラクションを濃縮し、クーゲルロールで蒸留（225 ℃/ 1.7 mmHg）することで、無色粘稠液体として単離された。
Example 11 Reaction of ethyl 2-phthalimidoacrylate and diethyl phosphonate The following compounds were synthesized in the same manner as in Example 3 except that ethyl 2-phthalimidoacrylate was used instead of methyl 2-phthalimidoacrylate. When 50 mg of p-dimethoxybenzene was added as an internal standard and analyzed by 1 H NMR, it was found that ethyl 2-phthalimido-3-diethylphosphorylpropionate was produced in a yield of 95.8%. Column chromatography was performed in the same manner as in Example 3, and the target fraction was concentrated and distilled as a Kugelrohr (225 ° C./1.7 mmHg) to be isolated as a colorless viscous liquid.
本生成物は以下の構造を有する文献未収載の新規物質であり、その物性や分光学データは以下の通りであった。 This product is a novel substance not yet published in the literature having the following structure, and its physical properties and spectroscopic data were as follows.
1H NMR (CDCl3, 300 MHz): δ 7.89-7.83 (m, 2H, Ph), 7.71-7.76 (m, 2H, Ph), 5.15-5.24 (m, 1H, CHC(O)), 4.17-4.22 (m, 2H, OCH2), 3.95-4.03 (m, 4H, OCH2), 2.62-2.97 (m, 2H, PCH2), 1.21 (t, J(HH)= 7.2 Hz, 3H, CH3), 1.19 (t, J(HH) = 7.1 Hz, 3H, CH3), 1.08 (t, J(HH) = 7.1 Hz, 3H, CH3)
13C NMR (CDCl3, 75 MHz): δ 168.2 (d, 3J(PC) = 20.3 Hz, C(O)OEt), 167.0 (NC(O)), 134.1 (Ph), 131.8 (Ph), 123.5 (Ph), 62.4 (C(O)OCH2CH3), 62.0 (d, 2J(PC) = 6.4 Hz, P(O)OCH2), 61.7 (d, 2J(PC)= 6.6 Hz, P(O)OCH2), 46.8 (d, 2J(PC) = 5.3 Hz, CHCOOEt), 24.9 (d, 1J(PC) = 145.6 Hz, CH2P(O)), 16.1 (d, 3J(PC) = 6.2 Hz, P(O)OCH2 CH3), 16.0 (d, 3J(PC) = 6.4 Hz, P(O)OCH2 CH3), 14.0 (s, C(O)OCH2 CH3)
31P NMR (CDCl3, 162 MHz): δ 26.5
IR (液膜, cm-1): 2983, 2937, 2908, 1778, 1747, 1720, 1612, 1469, 1390, 1248, 1180, 1097, 1051, 1024。
1 H NMR (CDCl 3 , 300 MHz): δ 7.89-7.83 (m, 2H, Ph), 7.71-7.76 (m, 2H, Ph), 5.15-5.24 (m, 1H, C H C (O)), 4.17-4.22 (m, 2H, OCH 2 ), 3.95-4.03 (m, 4H, OCH 2 ), 2.62-2.97 (m, 2H, PCH2), 1.21 (t, J (HH) = 7.2 Hz, 3H, CH 3 ), 1.19 (t, J (HH) = 7.1 Hz, 3H, CH 3 ), 1.08 (t, J (HH) = 7.1 Hz, 3H, CH 3 )
13 C NMR (CDCl 3 , 75 MHz): δ 168.2 (d, 3 J (PC) = 20.3 Hz, C (O) OEt), 167.0 (N C (O)), 134.1 (Ph), 131.8 (Ph) , 123.5 (Ph), 62.4 (C (O) O C H 2 CH 3 ), 62.0 (d, 2 J (PC) = 6.4 Hz, P (O) O C H 2 ), 61.7 (d, 2 J ( PC) = 6.6 Hz, P (O) O C H 2 ), 46.8 (d, 2 J (PC) = 5.3 Hz, C HCOOEt), 24.9 (d, 1 J (PC) = 145.6 Hz, CH 2 P ( O)), 16.1 (d, 3 J (PC) = 6.2 Hz, P (O) OCH 2 C H 3 ), 16.0 (d, 3 J (PC) = 6.4 Hz, P (O) OCH 2 C H 3 ), 14.0 (s, C (O) OCH 2 C H 3 )
31 P NMR (CDCl 3 , 162 MHz): δ 26.5
IR (liquid film, cm -1 ): 2983, 2937, 2908, 1778, 1747, 1720, 1612, 1469, 1390, 1248, 1180, 1097, 1051, 1024.
実施例１２ ２−フタルイミドアクリル酸エチルとホスホン酸ジエチルの反応
実施例１１と同様の反応を、塩基触媒としてのジアザビシクロウンデセンの使用量を１／５に減じ、反応温度を６５℃、反応時間を２４時間として実施した。反応溶液を濃縮後１Ｈ ＮＭＲで分析したところ、２−フタルイミド−３−ジエチルホスホリルプロピオン酸エチルが８１．３％の収率で生成していることが判明した。
ＮＭＲデータは、実施例１１で生成した化合物のものと一致した。
Example 12 Reaction of Ethyl 2-phthalimidoacrylate and Diethyl Phosphonate The same reaction as in Example 11 was carried out, the amount of diazabicycloundecene used as a base catalyst was reduced to 1/5, the reaction temperature was 65 ° C. The time was 24 hours. When the reaction solution was concentrated and analyzed by 1 H NMR, it was found that ethyl 2-phthalimido-3-diethylphosphorylpropionate was produced in a yield of 81.3%.
The NMR data was consistent with that of the compound produced in Example 11.
実施例１３ ２−フタルイミドアクリル酸エチルとホスホン酸ジエチルの反応
ジアザビシクロウンデセンに代えて炭酸セシウムを触媒として用い、反応時間を4時間として、実施例１１と同様に以下の化合物を合成した。１Ｈ ＮＭＲで分析したところ、２−フタルイミド−３−ジエチルホスホリルプロピオン酸エチルが８１．４％の収率で生成していることが判明した。
ＮＭＲデータは、実施例１１で生成した化合物のものと一致した。
Example 13 Reaction of ethyl 2-phthalimidoacrylate and diethyl phosphonate The following compounds were synthesized in the same manner as in Example 11 except that cesium carbonate was used as a catalyst instead of diazabicycloundecene and the reaction time was 4 hours. Analysis by 1 H NMR revealed that ethyl 2-phthalimido-3-diethylphosphorylpropionate was produced in a yield of 81.4%.
The NMR data was consistent with that of the compound produced in Example 11.
実施例１４ ２−フタルイミドアクリル酸エチルとホスホン酸ジエチルの反応
炭酸セシウムに代えてナトリウムメトキシドを触媒として用い、実施例１３と同様に以下の化合物を合成した。１Ｈ ＮＭＲで分析したところ、２−フタルイミド−３−ジエチルホスホリルプロピオン酸エチルが８１．７％の収率で生成していることが判明した。
ＮＭＲデータは、実施例１１で生成した化合物のものと一致した。
Example 14 Reaction of ethyl 2-phthalimidoacrylate and diethyl phosphonate The following compounds were synthesized in the same manner as in Example 13 using sodium methoxide as a catalyst instead of cesium carbonate. Analysis by 1 H NMR revealed that ethyl 2-phthalimido-3-diethylphosphorylpropionate was produced in a yield of 81.7%.
The NMR data was consistent with that of the compound produced in Example 11.
実施例１５ ２−フタルイミドアクリル酸エチルとホスホン酸ジエチルの反応
炭酸セシウムに代えてカリウムｔ−ブトキシドを触媒として用い、実施例１３と同様に以下の化合物を合成した。１Ｈ ＮＭＲで分析したところ、２−フタルイミド−３−ジエチルホスホリルプロピオン酸エチルが７７．４％の収率で生成していることが判明した。
ＮＭＲデータは、実施例１１で生成した化合物のものと一致した。
Example 15 Reaction of ethyl 2-phthalimidoacrylate and diethyl phosphonate The following compounds were synthesized in the same manner as in Example 13 using potassium t-butoxide as a catalyst instead of cesium carbonate. Analysis by 1 H NMR revealed that ethyl 2-phthalimido-3-diethylphosphorylpropionate was produced in a yield of 77.4%.
The NMR data was consistent with that of the compound produced in Example 11.
実施例１６ ２−フタルイミドアクリル酸エチルとホスホン酸ジエチルの反応
炭酸セシウムに代えて水素化ナトリウムを触媒とし、トルエンに代えてテトラヒドロフランを溶媒に用いて、実施例１３と同様に以下の化合物を合成した。１Ｈ ＮＭＲで分析したところ、２−フタルイミド−３−ジエチルホスホリルプロピオン酸エチルが７６．４％の収率で生成していることが判明した。
ＮＭＲデータは、実施例１１で生成した化合物のものと一致した。
Example 16 Reaction of ethyl 2-phthalimidoacrylate and diethyl phosphonate The following compounds were synthesized in the same manner as in Example 13 using sodium hydride as a catalyst instead of cesium carbonate and tetrahydrofuran as a solvent instead of toluene. . Analysis by 1 H NMR revealed that ethyl 2-phthalimido-3-diethylphosphorylpropionate was produced in a yield of 76.4%.
The NMR data was consistent with that of the compound produced in Example 11.
実施例１７ ２−フタルイミド桂皮酸エチルとホスホン酸ジメチルの反応
ジフェニルホスフィンオキシドに代えてホスホン酸ジメチルを用い、実施例８と同様に以下の化合物を合成した。ｐ−ジメトキシベンゼンを５０ｍｇ加えて内部標準とし１Ｈ ＮＭＲで分析したところ、２−フタルイミド桂皮酸エチルの転化率は９１％であり、２−フタルイミド−３−（ジメトキシホスホリル）−３−フェニルプロピオン酸エチルが異性体比４６：５４、収率８４．３％で生成していることが判明した。
反応液を濃縮し、ｎ−ヘキサン−酢酸エチル３：７の混合液を用いてシリカゲルカラムクロマトグラフィーを行うと、ジアステレオマーの関係にある二つの異性体をそれぞれ単離することができた。
Example 17 Reaction of ethyl 2-phthalimidocinnamate and dimethyl phosphonate The following compounds were synthesized in the same manner as in Example 8 using dimethyl phosphonate instead of diphenylphosphine oxide. When 50 mg of p-dimethoxybenzene was added as an internal standard and analyzed by 1 H NMR, the conversion of ethyl 2-phthalimidocinnamate was 91%, and 2-phthalimido-3- (dimethoxyphosphoryl) -3-phenylpropionic acid It was found that ethyl was produced with an isomer ratio of 46:54 and a yield of 84.3%.
When the reaction solution was concentrated and subjected to silica gel column chromatography using a mixed solution of n-hexane-ethyl acetate 3: 7, two isomers in a diastereomeric relationship could be isolated.
本生成物は以下の構造を有する異性体混合物である。いずれの異性体も文献未収載の新規物質であり、その物性や分光学データは以下の通りであった。 This product is an isomer mixture having the following structure. All of the isomers are new substances not yet described in the literature, and their physical properties and spectroscopic data are as follows.
異性体 i (マイナーな異性体): 極めて粘稠な無色液体
1H NMR (CDCl3, 300 MHz): δ 7.63-7.70 (m, 2H, Ph), 7.60-7.64 (m, 2H, Ph), 7.27-7.30 (m, 2H, Ph), 7.09-7.17 (m, 3H, Ph), 5.63 (dd, J = 13.1 Hz, J = 10.5 Hz, 1H, CHC(O)), 4.69 (dd, J = 21.2 Hz, J = 10.5 Hz, 1H, P(O)CH), 4.24 (qrt, J = 7.2 Hz, 2H, OCH 2CH3), 3.76 (d, J = 10.7 Hz, 3H, OCH3), 3.52 (d, J = 11.0 Hz, 3H, OCH3), 1.25 (t, J = 7.2 Hz, 3H, CH2CH 3)
13C NMR (CDCl3, 75 MHz): δ 167.6 (d, J = 1.7 Hz, C(O)OEt), 166.8 (s, NC(O)), 134.0 (Ph), 132.3 (d, J = 7.6 Hz, Ph), 131.0 (Ph), 130.0 (d, J = 6.4 Hz, Ph), 128.3 (d, J = 2.0 Hz, Ph), 127.7 (d, J = 2.5 Hz, Ph), 123.3 (Ph), 62.2 (C(O)OCH2), 53.6 (d, J = 6.9 Hz, OCH3), 53.0 (d, J = 7.3 Hz, OCH3), 51.9 (d, J = 4.0 Hz, CHC(O)), 43.3 (d, J = 138.0 Hz, P(O)CH), 14.0, CH2 CH3)
31P NMR (CDCl3, 162 MHz): δ 27.0
IR (液膜, cm-1): 3064, 2985, 2956, 1778, 1747, 1720, 1610, 1496, 1469, 1385, 1254, 1182, 1049, 1028, 918, 837
HRMS C21H22NO7Pとしての計算値: 431.1133, 実測値431.1127。
Isomer i (minor isomer): extremely viscous colorless liquid
1 H NMR (CDCl 3 , 300 MHz): δ 7.63-7.70 (m, 2H, Ph), 7.60-7.64 (m, 2H, Ph), 7.27-7.30 (m, 2H, Ph), 7.09-7.17 (m , 3H, Ph), 5.63 (dd, J = 13.1 Hz, J = 10.5 Hz, 1H, CHC (O)), 4.69 (dd, J = 21.2 Hz, J = 10.5 Hz, 1H, P (O) CH) , 4.24 (qrt, J = 7.2 Hz, 2H, OC H 2 CH 3 ), 3.76 (d, J = 10.7 Hz, 3H, OCH 3 ), 3.52 (d, J = 11.0 Hz, 3H, OCH 3 ), 1.25 (t, J = 7.2 Hz, 3H, CH 2 C H 3 )
13 C NMR (CDCl 3 , 75 MHz): δ 167.6 (d, J = 1.7 Hz, C (O) OEt), 166.8 (s, NC (O)), 134.0 (Ph), 132.3 (d, J = 7.6 Hz, Ph), 131.0 (Ph), 130.0 (d, J = 6.4 Hz, Ph), 128.3 (d, J = 2.0 Hz, Ph), 127.7 (d, J = 2.5 Hz, Ph), 123.3 (Ph) , 62.2 (C (O) O C H 2 ), 53.6 (d, J = 6.9 Hz, OCH 3 ), 53.0 (d, J = 7.3 Hz, OCH 3 ), 51.9 (d, J = 4.0 Hz, C HC (O)), 43.3 (d, J = 138.0 Hz, P (O) C H), 14.0, CH 2 C H 3 )
31 P NMR (CDCl 3 , 162 MHz): δ 27.0
IR (Liquid film, cm -1 ): 3064, 2985, 2956, 1778, 1747, 1720, 1610, 1496, 1469, 1385, 1254, 1182, 1049, 1028, 918, 837
Calculated for HRMS C 21 H 22 NO 7 P : 431.1133, Found 431.1127.
異性体 ii (メジャーな異性体):極めて粘稠な無色液体
1H NMR (CDCl3, 300 MHz): δ 7.92-7.95 (m, 2H, Ph), 7.75-7.78 (m, 2H, Ph), 7.53-7.56 (m, 2H, Ph), 7.33-7.41 (m, 3H, Ph), 5.55 (dd, J = 11.5 Hz, J = 5.2 Hz, 1H, CH(C(O)), 4.53 (dd, J = 20.1 Hz, J = 11.4 Hz, 1H, P(O)CH), 3.96-4.00 (m, 2H, CH 2CH3), 3.44 (d, J = 10.9 Hz, 3H, OCH3), 3.37 (d, J = 10.7 Hz, 3H, OCH3), 0.98 (t, J = 7.1 Hz, 3H, CH2CH 3)
13C NMR (CDCl3, 75 MHz): δ 167.2 (d, J = 20.5 Hz, C(O)OEt), 167.0 (NC(O)), 134.1 (Ph), 134.0 (d, J = 8.9 Hz, Ph), 131.9 (Ph), 129.6 (d, J = 6.2 Hz, Ph), 128.5 (d, J = 2.4 Hz, Ph), 127.7 (d, J = 3.1 Hz, Ph), 123.5 (Ph), 61.8 (C(O)OCH2), 53.5(d, J = 6.9 Hz, P(O)OCH3), 52.6 (d, J = 7.3 Hz, OCH3), 52.1 (d, J = 3.0 Hz, CHC(O)), 42.9 (d, J = 140.0 Hz, P(O)CH), 13.6 (s, CH2 CH3)
31P NMR (CDCl3, 162 MHz): δ 26.1
IR (液膜, cm-1): 3060, 2985, 2954, 1780, 1751, 1720, 1612, 1496, 1469, 1387, 1254, 1180, 1053, 1030, 879。
Isomer ii (major isomer): extremely viscous colorless liquid
1 H NMR (CDCl 3 , 300 MHz): δ 7.92-7.95 (m, 2H, Ph), 7.75-7.78 (m, 2H, Ph), 7.53-7.56 (m, 2H, Ph), 7.33-7.41 (m , 3H, Ph), 5.55 (dd, J = 11.5 Hz, J = 5.2 Hz, 1H, CH (C (O)), 4.53 (dd, J = 20.1 Hz, J = 11.4 Hz, 1H, P (O) CH), 3.96-4.00 (m, 2H, C H 2 CH 3 ), 3.44 (d, J = 10.9 Hz, 3H, OCH 3 ), 3.37 (d, J = 10.7 Hz, 3H, OCH 3 ), 0.98 ( t, J = 7.1 Hz, 3H, CH 2 C H 3 )
13 C NMR (CDCl 3 , 75 MHz): δ 167.2 (d, J = 20.5 Hz, C (O) OEt), 167.0 (NC (O)), 134.1 (Ph), 134.0 (d, J = 8.9 Hz, Ph), 131.9 (Ph), 129.6 (d, J = 6.2 Hz, Ph), 128.5 (d, J = 2.4 Hz, Ph), 127.7 (d, J = 3.1 Hz, Ph), 123.5 (Ph), 61.8 (C (O) O C H 2 ), 53.5 (d, J = 6.9 Hz, P (O) OCH 3 ), 52.6 (d, J = 7.3 Hz, OCH 3 ), 52.1 (d, J = 3.0 Hz, C HC (O)), 42.9 (d, J = 140.0 Hz, P (O) CH), 13.6 (s, CH 2 C H 3 )
31 P NMR (CDCl 3 , 162 MHz): δ 26.1
IR (liquid film, cm -1 ): 3060, 2985, 2954, 1780, 1751, 1720, 1612, 1496, 1469, 1387, 1254, 1180, 1053, 1030, 879.
Claims (7)
前記アリール基、アラルキル基、アリーロキシ基及びアラルキロキシ基を構成する芳香環は、複素芳香環であってもよい。
Ｒ１及びＲ２から水素原子を１原子ずつ除いた残基が分子内で互いに結合してリン原子を含む環構造を形成しても良い。
Ｒ３は、水素、炭素数６以下のアルキル基、炭素数１０以下のアリール基、又は炭素数１２以下のアラルキル基を表す。
Ｒ４は、炭素数６以下のアルキル基、炭素数１０以下のアリール基、又は炭素数１２以下のアラルキル基を表す。］
で示される２−フタルイミド−３−ホスホノプロピオン酸エステル化合物。 General formula (1)
The aromatic ring constituting the aryl group, aralkyl group, aryloxy group and aralkyloxy group may be a heteroaromatic ring.
Residues obtained by removing one hydrogen atom from R 1 and R 2 may be bonded to each other in the molecule to form a ring structure containing a phosphorus atom.
R 3 represents hydrogen, an alkyl group having 6 or less carbon atoms, an aryl group having 10 or less carbon atoms, or an aralkyl group having 12 or less carbon atoms.
R 4 represents an alkyl group having 6 or less carbon atoms, an aryl group having 10 or less carbon atoms, or an aralkyl group having 12 or less carbon atoms. ]
2-phthalimido-3-phosphonopropionic ester compound represented by the formula:
前記アリール基、アラルキル基、アリーロキシ基及びアラルキロキシ基を構成する芳香環は、複素芳香環であってもよい。
Ｒ１及びＲ２から水素原子を１原子ずつ除いた残基が分子内で互いに結合してリン原子を含む環構造を形成しても良い。］
で示されるヒドロリン化合物を、一般式（３）
Ｒ４は、炭素数６以下のアルキル基、炭素数１０以下のアリール基、又は炭素数１２以下のアラルキル基を表す。］
で示されるα−フタルイミドアクリル酸エステル化合物に付加させることを特徴とする、一般式（１）
で示される２−フタルイミド−３−ホスホノプロピオン酸エステル化合物の製造方法。 In the presence of a base catalyst, the general formula (2)
The aromatic ring constituting the aryl group, aralkyl group, aryloxy group and aralkyloxy group may be a heteroaromatic ring.
Residues obtained by removing one hydrogen atom from R 1 and R 2 may be bonded to each other in the molecule to form a ring structure containing a phosphorus atom. ]
The hydroline compound represented by the general formula (3)
R 4 represents an alkyl group having 6 or less carbon atoms, an aryl group having 10 or less carbon atoms, or an aralkyl group having 12 or less carbon atoms. ]
It is added to the α-phthalimidoacrylic acid ester compound represented by the general formula (1)
The manufacturing method of 2-phthalimido-3-phosphonopropionic acid ester compound shown by these.
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