JPS62207281A - Production of alpha,beta-epoxyphosphine derivative - Google Patents
Production of alpha,beta-epoxyphosphine derivativeInfo
- Publication number
- JPS62207281A JPS62207281A JP4741386A JP4741386A JPS62207281A JP S62207281 A JPS62207281 A JP S62207281A JP 4741386 A JP4741386 A JP 4741386A JP 4741386 A JP4741386 A JP 4741386A JP S62207281 A JPS62207281 A JP S62207281A
- Authority
- JP
- Japan
- Prior art keywords
- epoxyphosphine
- producing
- alkenylphosphine
- hydrogen peroxide
- derivative according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 43
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 38
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000003960 organic solvent Substances 0.000 claims abstract description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 12
- XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 10
- 238000010992 reflux Methods 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 239000002798 polar solvent Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 22
- 239000000126 substance Substances 0.000 abstract description 5
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 abstract description 4
- 239000007864 aqueous solution Substances 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 238000007086 side reaction Methods 0.000 abstract description 3
- 230000003115 biocidal effect Effects 0.000 abstract description 2
- 150000002118 epoxides Chemical class 0.000 description 12
- 238000006735 epoxidation reaction Methods 0.000 description 10
- 239000000758 substrate Substances 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 7
- -1 fosfomycin Chemical class 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 5
- 230000002194 synthesizing effect Effects 0.000 description 5
- QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000004593 Epoxy Substances 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- YMDXZJFXQJVXBF-STHAYSLISA-L (1R,2S)-epoxypropylphosphonate(2-) Chemical compound C[C@@H]1O[C@@H]1P([O-])([O-])=O YMDXZJFXQJVXBF-STHAYSLISA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229960000308 fosfomycin Drugs 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 150000003003 phosphines Chemical class 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 235000010259 potassium hydrogen sulphite Nutrition 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ONLFBNDNPYLPCT-UHFFFAOYSA-N 1-phosphorosoethene Chemical compound C=CP=O ONLFBNDNPYLPCT-UHFFFAOYSA-N 0.000 description 1
- GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 description 1
- ZYGNEXRUJCDSEG-UHFFFAOYSA-N 2-diphenylphosphoryl-2-ethyl-3-methyloxirane Chemical compound C=1C=CC=CC=1P(=O)(C=1C=CC=CC=1)C1(CC)OC1C ZYGNEXRUJCDSEG-UHFFFAOYSA-N 0.000 description 1
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 1
- BGUGKYYWOBECPJ-UHFFFAOYSA-N C(=C)[PH2]=O Chemical class C(=C)[PH2]=O BGUGKYYWOBECPJ-UHFFFAOYSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000007805 chemical reaction reactant Substances 0.000 description 1
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 125000003700 epoxy group Chemical group 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000005389 magnetism Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 150000002903 organophosphorus compounds Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 150000003008 phosphonic acid esters Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- DJEHXEMURTVAOE-UHFFFAOYSA-M potassium bisulfite Chemical compound [K+].OS([O-])=O DJEHXEMURTVAOE-UHFFFAOYSA-M 0.000 description 1
- 229940099427 potassium bisulfite Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、有機リン化合物の合成法、特に１−アルケニ
ルホスフィンオキシド類からα、β−エポキシホスフィ
ン誘導体を合成する方法に関する。DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a method for synthesizing organophosphorus compounds, particularly to a method for synthesizing α,β-epoxyphosphine derivatives from 1-alkenylphosphine oxides.
（従来の技術）
ホスホン酸系抗生物質として知られているホスホマイシ
ン等、リンのα、β−エポキシ化合物は、それ自身重要
な化合物であり、更に又α、β−エボキンホスフィン誘
導体は種々の有用な化合物を合成するための重要な合成
中間体である。(Prior art) Phosphorus α,β-epoxy compounds such as fosfomycin, which is known as a phosphonic acid antibiotic, are themselves important compounds, and α,β-evoquine phosphine derivatives have various useful properties. It is an important synthetic intermediate for synthesizing various compounds.
従来、１−アルケニルホスフィンオキシド類そのものの
エポキシド合成については提案された例がない。それに
関連した化合物として、ビニルホスフィンオキシト類の
エポキシドの合成法については、α−ケトトシラートへ
のリン化合物の付加並びにトシル酸、すなわちｐ−）ル
エンスルホン酸の脱離による方法が例えばシンセシス（
Ｓｙｎｔｈｅｓｉｓ）１９８５年第１号、第６５頁、お
よびジャーナル・オブ・オーガーツク・ケミストリ（Ｊ
、 Ｏｒｇ、 Ｃｈｅｍ、 ）第２６巻、第６５９頁（
１９６１年）等によって知られているが、これらを１−
アルケニルホスフィンオキシド類のエポキシ化に適用し
ても、反応が満足に進行しない。また、一般に行われて
いる過酢酸、過安息香酸、過フタル酸などの過酸により
、オレフィン二重結合に酸素を付加してエポキシドを合
成する方法も同様の理由で、ｌ−アルケニルホスフィン
オキシド類のエポキシ化には応用できない。Hitherto, there has been no proposal for epoxide synthesis of 1-alkenylphosphine oxides themselves. Regarding the synthesis of epoxides of vinylphosphine oxides as related compounds, for example, synthesis (
Synthesis) 1985, issue 1, page 65, and Journal of Augertsk Chemistry (J
, Org, Chem, ) Volume 26, Page 659 (
(1961), etc., but these are 1-
Even when applied to the epoxidation of alkenylphosphine oxides, the reaction does not proceed satisfactorily. In addition, for the same reason, the commonly used method of synthesizing epoxides by adding oxygen to olefin double bonds with peracids such as peracetic acid, perbenzoic acid, and perphthalic acid produces l-alkenylphosphine oxides. It cannot be applied to epoxidation of
更に、１−アルケンホスホン酸ジエステルなどのホスホ
ン酸エステル誘導体に対し、無水トリフルオロ酢酸と高
濃度過酸化水素、例えば９０％過酸化水素とを用いて酸
化しエポキシ化する方法が、ヘミ７７ 工’ ヘリヒテ
（Ｃｈｅｍ、Ｂｅｒ、 ）第１０１巻、３５３０頁（１
９６８年）およびケミカル・アガストラクツ（Ｃ。Furthermore, there is a method of oxidizing and epoxidizing a phosphonic acid ester derivative such as a 1-alkenephosphonic acid diester using trifluoroacetic anhydride and high concentration hydrogen peroxide, for example, 90% hydrogen peroxide. Chem, Ber, Vol. 101, p. 3530 (1)
968) and chemical agastrics (C.
Ａ）第１０３巻、２２６５４Ｐ、 に報告されている
が、かかる方法は、９０％の過酸化水素という高濃度過
酸化物を使用するために頗る危険である点や、かかる高
濃度過酸化水素が市販されておらず入手困難である点、
またこのエポキシド合成法においては、リン酸す） Ｉ
Ｊウム緩衡液を使用しなければならない点、及び生成し
たエポキシドの更なる開環反応等がエポキシ化反応に引
続いて進行し、副反応生成物の副生を伴うなどの欠点ま
たは問題点があり、従って、従来１−アルケニルホスフ
ィンオキシド類からそのエポキシドを簡便、容易且つ選
択的に合成する方法はなかった。A) Volume 103, 22654P, this method is very dangerous because it uses a high concentration of 90% hydrogen peroxide, and the high concentration of hydrogen peroxide is It is not commercially available and difficult to obtain,
In addition, in this epoxide synthesis method, phosphoric acid) I
Disadvantages or problems, such as the need to use a Jium buffer solution, and the fact that further ring-opening reactions of the generated epoxide proceed after the epoxidation reaction, resulting in the production of side reaction products. Therefore, there has been no conventional method for easily, easily and selectively synthesizing epoxides from 1-alkenylphosphine oxides.
（発明が解決しようとする問題点）
上述のような従来技術の問題点に鑑み、本発明の目的は
、現今汎用されているエポキシド合成法では合成するこ
とのできなかった１−アルケニルホスフィンオキシド類
のエポキシドを、入手容易な試薬を以って、安全、容易
且つ選択的に高収率で取得せんとするにある。(Problems to be Solved by the Invention) In view of the problems of the prior art as described above, the purpose of the present invention is to solve 1-alkenylphosphine oxides that cannot be synthesized by the currently widely used epoxide synthesis method. The objective is to obtain epoxides safely, easily and selectively in high yields using easily available reagents.
（問題点を解決するための手段）
上記目的を達成するための本発明方法の特徴は、無水ト
リフルオロ酢酸と約２５〜約３５％過酸化水素との反応
により生成したトリフルオロ過酢酸を、１−アルケニル
ホスフィン類に有機溶媒中で還流下に作用せしめてエポ
キシ化することにある。(Means for solving the problems) The feature of the method of the present invention for achieving the above object is that trifluoroperacetic acid produced by the reaction of trifluoroacetic anhydride and about 25 to about 35% hydrogen peroxide, The method involves epoxidizing 1-alkenylphosphine by reacting it in an organic solvent under reflux.
本発明方法を適用する１−アルケニルホスフィン類の主
要なものとしては、
１−アルケニルホスフィンオキシド、
１−アルケニルホスホン酸エステル、
１−アルケニルホスフィン酸エステル、等の１−アルケ
ニルリン酸化合物が含まれこれらのエポキシ化反応出発
物質は単独、若しくは複数の混合物として使用し得る。The main 1-alkenylphosphines to which the method of the present invention is applied include 1-alkenylphosphoric acid compounds such as 1-alkenylphosphine oxide, 1-alkenylphosphonic acid ester, and 1-alkenylphosphinic acid ester. The epoxidation reaction starting materials may be used alone or as a mixture of two or more.
またα、β−位以外の位置にオレフィン二重結合を有す
るアルケンのリン酸化合物にも本発明を適用することが
できる。The present invention can also be applied to alkene phosphoric acid compounds having an olefinic double bond at positions other than the α and β-positions.
本発明方法により上記１−アルケニルホスフィン類より
取得される生成物は、
α、β−エポキシホスフィンオキシド誘導体、α、β−
エポキシホスホン酸エステル誘導体、α、β−エポキシ
ホスフィン酸エステル誘導体、等のα、β−エポキシホ
スフィン誘導体であり、またα、β−位以外の位置にエ
ポキシ基を有するホスフィン誘導体を生成することも可
能である。The products obtained from the above 1-alkenylphosphine by the method of the present invention are α,β-epoxyphosphine oxide derivatives, α,β-
α, β-epoxyphosphine derivatives such as epoxyphosphonic acid ester derivatives, α, β-epoxyphosphinic acid ester derivatives, etc. It is also possible to produce phosphine derivatives having epoxy groups at positions other than α, β-positions. It is.
これら誘導体の中で特に重要なものとしては、ホスホマ
イシンが挙げられる。Particularly important among these derivatives is fosfomycin.
本発明方法において酸化作用を司り、アルケニル化合物
のオレフィンニ重結合に酸素を付加してエポキシ化する
ためには、特にトリフルオロ過酢酸の作用を必須とする
が、かかるトリフルオロ過酢酸は無水トリフルオロ酢酸
より、例えば次の手順により合成することができる。In the method of the present invention, the action of trifluoroperacetic acid is particularly essential in order to control the oxidation action and add oxygen to the olefin double bond of the alkenyl compound for epoxidation. It can be synthesized from fluoroacetic acid, for example, by the following procedure.
即ち水冷下、適量の有機液媒、例えば塩化メチレンに市
販の約２５〜約３５％、好ましくは約３０〜約３５％過
酸化水素水を添加し、約０℃で攪拌し、それに更に無水
トリフルオロ酢酸を攪拌しながら加え、約３０分後に室
温まで温度を上昇させればトリフルオロ過酢酸が塩化メ
チレン液媒中に効率よく生成する。That is, under cooling with water, a commercially available hydrogen peroxide solution of about 25% to about 35%, preferably about 30% to about 35%, is added to an appropriate amount of an organic liquid medium, such as methylene chloride, and the mixture is stirred at about 0°C. If fluoroacetic acid is added with stirring and the temperature is raised to room temperature after about 30 minutes, trifluoroperacetic acid is efficiently produced in the methylene chloride liquid medium.
上述のトリフルオロ過酢酸の生成反応は室温あるいは約
４０℃程度迄の昇温下においても可能であるが、温度の
上昇に伴い無水トリフルオロ酢酸の過剰量を必要とする
うえに収率が著しく低下するため、０℃乃至室温の範囲
の可及的低温域で前記手順を踏むことが好ましい。The above-mentioned reaction for producing trifluoroperacetic acid is possible at room temperature or at an elevated temperature of about 40°C, but as the temperature rises, an excessive amount of trifluoroacetic anhydride is required and the yield is significantly reduced. Therefore, it is preferable to carry out the above procedure at the lowest possible temperature in the range of 0° C. to room temperature.
かくして合成したトリフルオロ過酢酸に基質である１−
アルケニルホスフィン類の有機溶媒溶液、例えば１−ア
ルケニルホスフィンオキシドの塩化メチレン溶液を滴下
した後、前記有機溶媒の沸点、ＣＨ２Ｃｌ□の場合は約
４０℃、で還流下に約８〜１４時間、好ましくは約１０
〜１２時間攪拌してエポキシ化反応を行う。The substrate 1-
After dropping a solution of an alkenylphosphine in an organic solvent, for example, a solution of 1-alkenylphosphine oxide in methylene chloride, the organic solvent is heated under reflux at the boiling point of the organic solvent, which is about 40°C in the case of CH2Cl□, for about 8 to 14 hours, preferably. about 10
The epoxidation reaction is carried out by stirring for ~12 hours.
ここに用いられる有機溶媒は基質に対する溶剤であるこ
と、溶媒自体および系内の反応物質に対して不活性、非
反応性であること、比較的低沸点（沸点約１００℃以下
、好ましくは約８０℃以下）であること、および前記ト
リフルオロ過酢酸の合成に用いた有機液媒と相溶性を有
すること、好ましくは同一のものであること、の諸条件
を満足するものの中から選ばれる。適用可能なものとし
ては、例えば塩化メチレン、クロロホルム、酢酸エチル
、四塩化炭素、ジエチルエーテノペテトラヒドロフラン
、ベンゼン、ジオキサン等が挙げられるが、本反応では
基質の磁性が比較的大きく、溶解度が小さいために、塩
化メチレン、クロロホルム、酢酸エチル等、低沸点の極
性溶媒が好ましく、就中、塩化メチレンが最適である。The organic solvent used here must be a solvent for the substrate, be inert and non-reactive with respect to the solvent itself and the reactants in the system, and have a relatively low boiling point (boiling point of about 100°C or less, preferably about 80°C). C) or below) and be compatible with, preferably the same as, the organic liquid medium used in the synthesis of trifluoroperacetic acid. Applicable substances include, for example, methylene chloride, chloroform, ethyl acetate, carbon tetrachloride, diethylethenotetrahydrofuran, benzene, and dioxane, but in this reaction, the substrate has relatively high magnetism and low solubility. For this purpose, low-boiling polar solvents such as methylene chloride, chloroform, and ethyl acetate are preferred, with methylene chloride being most suitable.
これら溶媒は単独または混合して用い得る。These solvents may be used alone or in combination.
上述のエポキシ化反応は、次の一般式（Ｉ）を以って表
され、また、基質即ちエポキシ化反応の出発物質である
ジフェニル（１−エチル−１−プロペニル）−ホスフィ
ンオキシトをエポキシ化して、ジフェニル−（１，２−
エポキシ−１−エチルプロピル）−ホスフィンオキシト
を得る場合の例は式（Ｉ［）で示す通りである。The above-mentioned epoxidation reaction is represented by the following general formula (I), and the substrate, that is, the starting material of the epoxidation reaction, diphenyl(1-ethyl-1-propenyl)-phosphine oxide, is epoxidized. , diphenyl-(1,2-
An example of obtaining epoxy-1-ethylpropyl)-phosphine oxyto is as shown in formula (I[).
上記反応において、基質と無水トリフルオロ酢酸と過酸
化水素とのモル比については、過酸化水素は基質に対し
て少なくとも等モルを必要とし、また無水トリフルオロ
酢酸は低沸点であるため、反応中に蒸発して気相に移行
する量を補うために少なくとも２モノペ好ましくは少な
くとも３モルを反応初期に存在せしめることが良い。最
適モル比は約１：３：３である。In the above reaction, regarding the molar ratio of the substrate, trifluoroacetic anhydride, and hydrogen peroxide, hydrogen peroxide needs to be at least equimolar to the substrate, and trifluoroacetic anhydride has a low boiling point, so during the reaction In order to compensate for the amount that evaporates and transfers to the gas phase, it is preferred that at least 2 moles, preferably at least 3 moles, be present at the initial stage of the reaction. The optimum molar ratio is about 1:3:3.
かくしてエポキシ化反応が完結した反応混合物は冷却後
、分液ロートに移し、有機層を亜硫酸水素カリウム水溶
液、炭酸水素ナトリウム水溶液、更に水を以って相次い
で洗浄し、乾燥後、溶媒を減圧下に留去することにより
、１−アルケニルホスフィンオキシドのエポキシドが取
得される。After the reaction mixture in which the epoxidation reaction was completed was cooled, it was transferred to a separating funnel, and the organic layer was washed successively with an aqueous solution of potassium bisulfite, an aqueous solution of sodium bicarbonate, and then water. After drying, the solvent was removed under reduced pressure. Epoxide of 1-alkenylphosphine oxide is obtained by distilling it off.
以下、本発明方法を実施例について説明する。Hereinafter, the method of the present invention will be explained with reference to Examples.
（実施例１）
水浴上で塩化メチレン１０ｍ１に３０％過酸化水素水１
．２ｍｌを、約０℃で攪拌しながら加え、それに無水ト
リフルオロ酢酸２．９ｇを攪拌下僚々に添加した。全部
添加し了えてから温浴上に移し、３０℃にて３０分間攪
拌した後、室温とした。生成したトリフルオロ過酢酸に
基質ジフェニル−（１−エチル−１−プロペニル）−ホ
スフィンオキシト１．２３ｇの塩化メチレン１０ｍ！溶
液を滴下し、１２時間約４０℃で加熱還流下に攪拌した
。室温に冷却後、反応混合液を分岐ロートに移し、塩化
メチレン３０ｆｆｌβを加え、亜硫酸水素カリウム水溶
液、炭酸水素ナトリウム水溶液及び水で相次いで洗浄し
た。無水硫酸ナトリウムで乾燥後、減圧下、塩化メチレ
ンを留去して、１．２４ｇのジフェニル−（１，２−エ
ポキシ−１〜エチルプロピル）−ホスフィンオキシトを
得た。この場合の収率は９５％であり、得られた化合物
の融点は１５４〜１５６℃であった。(Example 1) 10 ml of methylene chloride and 1 part of 30% hydrogen peroxide solution on a water bath.
．． 2 ml was added with stirring at about 0°C, to which 2.9 g of trifluoroacetic anhydride was added under stirring. After all additions were completed, the mixture was transferred to a hot bath, stirred at 30°C for 30 minutes, and then cooled to room temperature. To the trifluoroperacetic acid produced was added 1.23 g of the substrate diphenyl-(1-ethyl-1-propenyl)-phosphine oxide and 10 m of methylene chloride! The solution was added dropwise and stirred under heating and reflux at about 40° C. for 12 hours. After cooling to room temperature, the reaction mixture was transferred to a branch funnel, 30 fflβ of methylene chloride was added, and the mixture was washed successively with an aqueous potassium bisulfite solution, an aqueous sodium bicarbonate solution, and water. After drying over anhydrous sodium sulfate, methylene chloride was distilled off under reduced pressure to obtain 1.24 g of diphenyl-(1,2-epoxy-1-ethylpropyl)-phosphine oxide. The yield in this case was 95%, and the melting point of the obtained compound was 154-156°C.
゛ （実施例２〜５）
前記式（ｎ）のＲ１，Ｒ２を種々に変えた４種類の１−
アルケニルジフェニルホスフィンオキシトを基質とし、
トリフルオロ過酢酸によるエポキシ化反応を前記実施例
１の方法に準じて塩化メチレン溶媒還流下１２時間反応
せしめた。この場合基質と、トリフルオロ過酢酸の生成
に用いた無水トリフルオロ酢酸と、過酸化水素との量比
をモル比で１：３：３とした。゛ (Examples 2 to 5) Four types of 1- in which R1 and R2 of the formula (n) were variously changed.
alkenyldiphenylphosphine oxyto as a substrate,
Epoxidation reaction using trifluoroperacetic acid was carried out for 12 hours under refluxing methylene chloride solvent according to the method of Example 1 above. In this case, the molar ratio of the substrate, trifluoroacetic anhydride used to produce trifluoroperacetic acid, and hydrogen peroxide was 1:3:3.
生成したα、β−エポキシホスフィン誘導体の収率、融
点及び質量分析値を次表に示す。The yield, melting point, and mass spectrometry values of the produced α,β-epoxyphosphine derivative are shown in the following table.
上述の実施例から明らかな通り、本発明方法によれば、
各種の１−アルケニルホスフィン類から対応するα、β
−エポキシホスフィン誘導体が極めて高収率で得られる
。As is clear from the above examples, according to the method of the present invention,
Corresponding α and β from various 1-alkenylphosphines
- Epoxyphosphine derivatives are obtained in extremely high yields.
（発明の効果） 本発明方法の効果を列挙すると次の通りである。(Effect of the invention) The effects of the method of the present invention are listed below.
１）従来法では合成至難であった１−アルケニルホスフ
ィンオキシド類のエポキシドを本発明方法により頗る安
全、簡便且つ高収率を以って合成することができる。1) Epoxides of 1-alkenylphosphine oxides, which have been extremely difficult to synthesize using conventional methods, can be synthesized in an extremely safe, simple and high yield by the method of the present invention.
２）α−ケトトシラートを経る従来のビニルホスフィン
オキシトのエポキシド合成よりも操作が著しく簡単であ
る。2) It is significantly simpler to operate than the conventional epoxide synthesis of vinylphosphine oxide via α-ketotosylate.
３）９０％過酸化水素を用いるエポキシホスホン酸エス
テル合成法に比して、本発明方法に適用する試薬は、布
中で容易に入手可能な約２５〜３５％過酸化水素を用い
て合成され（９０％過酸化水素水は市販されていないが
２５〜３５％のものは市販されている）、従って安全性
が高く、爆発等の危険性が少ないため、装置並びに操作
が至極簡単である。3) Compared to the epoxyphosphonic acid ester synthesis method that uses 90% hydrogen peroxide, the reagents applied to the method of the present invention are synthesized using about 25-35% hydrogen peroxide, which is easily available in cloth. (Although 90% hydrogen peroxide solution is not commercially available, 25-35% hydrogen peroxide solution is commercially available.) Therefore, it is highly safe and has little risk of explosion, etc., and the equipment and operation are extremely simple.
４）上述の高濃度過酸化水素を用いる方法に比し、副反
応や二次反応が無いために目的物質であるリン化合物の
α、β−エポキシ誘導体生成の選択性が高く、高純度且
つ高収率で目的物を取得することができる。4) Compared to the above-mentioned method using high-concentration hydrogen peroxide, there is no side reaction or secondary reaction, so the selectivity for producing α, β-epoxy derivatives of the target phosphorus compound is high, and the process is highly pure and The target product can be obtained in high yield.
５）本発明方法は、その技術思想の範囲内で、α。5) The method of the present invention, within the scope of its technical idea, α.
β−エポキシ誘導体のみならず、種々のエポキシド合成
に改変、応用し得ると思われ、広い応用範囲が期待され
る。It is thought that it can be modified and applied not only to β-epoxy derivatives but also to the synthesis of various epoxides, and a wide range of applications is expected.
Claims (1)
素水との反応により生成したトリフルオロ過酢酸を、１
−アルケニルホスフィン類に有機溶媒中で還流下に作用
せしめてエポキシ化することを特徴とするα，β−エポ
キシホスフィン誘導体の製造法。 ２、１−アルケニルホスフィン類が１−アルケニルホス
フィンオキシド、１−アルケニルホスホン酸エステルお
よび１−アルケニルホスフィン酸エステルよりなる群か
ら選ばれた少なくとも１種の１−アルケニルリン酸化合
物である特許請求の範囲第１項記載のα，β−エポキシ
ホスフィン誘導体の製造法。 ３、前記無水トリフルオロ酢酸と過酸化水素水との反応
が有機液媒中で行われる特許請求の範囲第１項または第
２項記載のα，β−エポキシホスフィン誘導体の製造法
。 ４、前記有機液媒と有機溶媒とが互いに相溶性を有する
ものである特許請求の範囲第３項記載のα，β−エポキ
シホスフィン誘導体の製造法。 ５、前記有機溶媒が、それ自体非反応性であり且つ低沸
点の極性溶媒である前記特許請求の範囲各項の何れかに
記載のα，β−エポキシホスフィン誘導体の製造法。 ６、前記有機溶媒が塩化メチレン、クロロホルム、酢酸
エチルより選ばれる少なくとも１種の極性溶媒である特
許請求の範囲第５項記載のα，β−エポキシホスフィン
誘導体の製造法。 ７、前記有機溶媒と有機液媒とが共に塩化メチレンであ
る特許請求の範囲第６項記載のα，β−エポキシホスフ
ィン誘導体の製造法。 ８、前記無水トリフルオロ酢酸と過酸化水素との反応が
約０℃乃至室温において行われる前記特許請求の範囲各
項の何れかに記載のα，β−エポキシホスフィン誘導体
の製造法。 ９、前記１−アルケニルホスフィン類と無水トリフルオ
ロ酢酸と過酸化水素とをモル比で約１：（２以上）：（
１以上）反応初期に存在せしめる前記特許請求の範囲各
項の何れかに記載のα，β−エポキシホスフィン誘導体
の製造法。 １０、前記モル比が約１：３：３である特許請求の範囲
第９項記載のα，β−エポキシホスフィン誘導体の製造
法。[Scope of Claims] 1. Trifluoroperacetic acid produced by the reaction of trifluoroacetic anhydride and about 25 to about 35% hydrogen peroxide solution,
- A method for producing an α,β-epoxyphosphine derivative, which comprises epoxidizing an alkenylphosphine in an organic solvent under reflux. Claims in which the 2,1-alkenylphosphine is at least one 1-alkenylphosphoric acid compound selected from the group consisting of 1-alkenylphosphine oxide, 1-alkenylphosphonic acid ester, and 1-alkenylphosphinic acid ester. 2. A method for producing an α,β-epoxyphosphine derivative according to item 1. 3. The method for producing an α,β-epoxyphosphine derivative according to claim 1 or 2, wherein the reaction between the trifluoroacetic anhydride and the hydrogen peroxide solution is carried out in an organic liquid medium. 4. The method for producing an α,β-epoxyphosphine derivative according to claim 3, wherein the organic liquid medium and the organic solvent are compatible with each other. 5. The method for producing an α,β-epoxyphosphine derivative according to any one of the claims, wherein the organic solvent is a polar solvent that is non-reactive in itself and has a low boiling point. 6. The method for producing an α,β-epoxyphosphine derivative according to claim 5, wherein the organic solvent is at least one polar solvent selected from methylene chloride, chloroform, and ethyl acetate. 7. The method for producing an α,β-epoxyphosphine derivative according to claim 6, wherein both the organic solvent and the organic liquid medium are methylene chloride. 8. The method for producing an α,β-epoxyphosphine derivative according to any one of the claims, wherein the reaction between the trifluoroacetic anhydride and hydrogen peroxide is carried out at about 0°C to room temperature. 9. The 1-alkenylphosphine, trifluoroacetic anhydride, and hydrogen peroxide in a molar ratio of about 1: (2 or more): (
1 or more) A method for producing an α,β-epoxyphosphine derivative according to any one of the claims, wherein the α,β-epoxyphosphine derivative is present at the initial stage of the reaction. 10. The method for producing an α,β-epoxyphosphine derivative according to claim 9, wherein the molar ratio is about 1:3:3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4741386A JPS62207281A (en) | 1986-03-06 | 1986-03-06 | Production of alpha,beta-epoxyphosphine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4741386A JPS62207281A (en) | 1986-03-06 | 1986-03-06 | Production of alpha,beta-epoxyphosphine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62207281A true JPS62207281A (en) | 1987-09-11 |
| JPH0471918B2 JPH0471918B2 (en) | 1992-11-16 |
Family
ID=12774453
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4741386A Granted JPS62207281A (en) | 1986-03-06 | 1986-03-06 | Production of alpha,beta-epoxyphosphine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62207281A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103588693A (en) * | 2013-10-14 | 2014-02-19 | 青岛文创科技有限公司 | Preparation method of trifluoroperacetic acid |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5231032A (en) * | 1975-08-29 | 1977-03-09 | Italchemi Spa | Process for manufacturing epoxyalkylphosphone acids |
| JPS5414925A (en) * | 1977-07-01 | 1979-02-03 | Kanebo Ltd | Preparation of epoxy compounds |
-
1986
- 1986-03-06 JP JP4741386A patent/JPS62207281A/en active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5231032A (en) * | 1975-08-29 | 1977-03-09 | Italchemi Spa | Process for manufacturing epoxyalkylphosphone acids |
| JPS5414925A (en) * | 1977-07-01 | 1979-02-03 | Kanebo Ltd | Preparation of epoxy compounds |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103588693A (en) * | 2013-10-14 | 2014-02-19 | 青岛文创科技有限公司 | Preparation method of trifluoroperacetic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0471918B2 (en) | 1992-11-16 |
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