JPH0552839B2 - - Google Patents
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- Publication number
- JPH0552839B2 JPH0552839B2 JP268888A JP268888A JPH0552839B2 JP H0552839 B2 JPH0552839 B2 JP H0552839B2 JP 268888 A JP268888 A JP 268888A JP 268888 A JP268888 A JP 268888A JP H0552839 B2 JPH0552839 B2 JP H0552839B2
- Authority
- JP
- Japan
- Prior art keywords
- cyclic
- reaction
- present
- general formula
- compound
- 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.)
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- 125000004122 cyclic group Chemical group 0.000 claims description 7
- MTIQLOQTQUBOLK-UHFFFAOYSA-N silyl dihydrogen phosphite Chemical compound OP(O)O[SiH3] MTIQLOQTQUBOLK-UHFFFAOYSA-N 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 1
- -1 cyclic acetonyl phosphonates Chemical class 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000000034 method Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- ZWAJLVLEBYIOTI-UHFFFAOYSA-N cyclohexene oxide Chemical compound C1CCCC2OC21 ZWAJLVLEBYIOTI-UHFFFAOYSA-N 0.000 description 5
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohexene oxide Natural products O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- YCGFIYLHOXVFDN-UHFFFAOYSA-N (5,5-dimethyl-1,3,2-dioxaphosphinan-2-yl)oxy-trimethylsilane Chemical compound CC1(C)COP(O[Si](C)(C)C)OC1 YCGFIYLHOXVFDN-UHFFFAOYSA-N 0.000 description 2
- WEFSXBPMNKAUDL-UHFFFAOYSA-N 1-iodopropan-2-one Chemical compound CC(=O)CI WEFSXBPMNKAUDL-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- DYOVNLGWRVITHY-UHFFFAOYSA-N C[Si](C)(C)OP1OCCCO1 Chemical compound C[Si](C)(C)OP1OCCCO1 DYOVNLGWRVITHY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000003434 Perkow synthesis reaction Methods 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 230000002213 calciumantagonistic effect Effects 0.000 description 2
- 239000003218 coronary vasodilator agent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 230000001077 hypotensive effect Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- CUFUMXQZMOXRGC-UHFFFAOYSA-N 1-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)propan-2-one Chemical compound CC(=O)CP1(=O)OCCCO1 CUFUMXQZMOXRGC-UHFFFAOYSA-N 0.000 description 1
- UKUZWKGFVBSNHO-UHFFFAOYSA-N 1-(5,5-dimethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)propan-2-one Chemical compound CC(=O)CP1(=O)OCC(C)(C)CO1 UKUZWKGFVBSNHO-UHFFFAOYSA-N 0.000 description 1
- UONFDRFWKRFEDU-UHFFFAOYSA-N 2-hydroxy-1,3,2-dioxaphosphinane Chemical compound OP1OCCCO1 UONFDRFWKRFEDU-UHFFFAOYSA-N 0.000 description 1
- DVSHXLWNRCEDCW-UHFFFAOYSA-N 2-oxopropylphosphonic acid Chemical class CC(=O)CP(O)(O)=O DVSHXLWNRCEDCW-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 238000005654 Michaelis-Arbuzov synthesis reaction Methods 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000005600 alkyl phosphonate group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- HWSUUGHIDOOOOJ-UHFFFAOYSA-N dioxaphosphinane Chemical compound C1COOPC1 HWSUUGHIDOOOOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012156 elution solvent Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000003385 ring cleavage reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、強いカルシウム拮抗性の降圧作用と
冠血管拡張作用を有する１，４−ジヒドロピリジ
ン−５−環状ホスホネート誘導体を製造するため
の中間体として有用な化合物の製造法に関する。Detailed Description of the Invention (Industrial Application Field) The present invention provides an intermediate for producing a 1,4-dihydropyridine-5-cyclic phosphonate derivative having strong calcium antagonistic hypotensive action and coronary vasodilator action. This invention relates to a method for producing compounds useful as compounds.
更に詳しくは、本発明は、次の一般式〔〕
で表される環状シリルホスフアイト類と、次の一
般式〔〕
CH3COCH2X 〔〕
で表されるハロアセトン類とを、副生するトリア
ルキルシリタハライドのスカベンジヤーの共存下
に反応させることを特徴とする、次の一般式
〔〕
で表されるホスホネート誘導体の製造法に関す
る。 More specifically, the present invention relates to the following general formula [] A cyclic silyl phosphite represented by the formula [] and a haloacetone represented by the following general formula [] CH 3 COCH 2 The following general formula [] is characterized by The present invention relates to a method for producing a phosphonate derivative represented by:
式中、Ｒは低級アルキルを表す。Ａは、炭素数
２〜４のアルキレンを表し、当該炭素のうちのい
くつかは低級アルキルで置換されていてもよい。
Ｘは、ハロゲンを表す。 In the formula, R represents lower alkyl. A represents alkylene having 2 to 4 carbon atoms, and some of the carbon atoms may be substituted with lower alkyl.
X represents halogen.
本発明に係る化合物〔〕は、医薬品として有
用な１，４−ジヒドロピリジン−５−環状ホスホ
ネート誘導体〔特開昭59−161392号公報、
Chem、Pharm.Bull.35、3898（1987）〕及び、５
−環状ホスホネート誘導体〔特開昭60−248693号
公報。Chem.Pharm.Bull.354144（1987）。
Arzneim.Forsch.、36、1329、1336（1986）。〕に
誘導することができる。これら化合物は、強いカ
ルシウム拮抗性降圧作用と冠血管拡張作用を有
し、高血圧症、狭心症等の治療剤として有用であ
ることが判つている。 The compound [] according to the present invention is a 1,4-dihydropyridine-5-cyclic phosphonate derivative useful as a pharmaceutical [JP-A-59-161392,
Chem, Pharm. Bull. 35 , 3898 (1987)] and 5
-Cyclic phosphonate derivative [JP-A-60-248693. Chem.Pharm.Bull. 35 4144 (1987).
Arzneim.Forsch., 36 , 1329, 1336 (1986). ]. These compounds have strong calcium antagonistic hypotensive effects and coronary vasodilator effects, and are known to be useful as therapeutic agents for hypertension, angina pectoris, and the like.
従つて、本発明は医薬品として有用な化合物の
製造原料を従来法よりも極めて有利に提供するも
のである。 Therefore, the present invention provides raw materials for producing compounds useful as pharmaceuticals more advantageously than conventional methods.
（従来の技術）
従来、本発明に係る一般式〔〕で表されるア
セトニルホスホネート誘導体の製造法うとして、
トリアルキルホスフアイトとハロアセトンとのア
ルブゾフ（Arbuzov）反応による方法がよく知ら
れている〔Chem.Soc.、38、687（1906）。Chem.
Rev.、81、415（1981）〕。(Prior Art) Conventionally, a method for producing an acetonylphosphonate derivative represented by the general formula [] according to the present invention was
A well-known method is the Arbuzov reaction between a trialkyl phosphite and a haloacetone [Chem.Soc., 38 , 687 (1906). Chem.
Rev., 81 , 415 (1981)].
環状のアセトニルホスホネート類も同様の反応
で得られることも知られている（特開昭60−
248693号公報）。 It is also known that cyclic acetonyl phosphonates can be obtained by a similar reaction (Japanese Patent Application Laid-open No. 1989-1999).
248693).
しかしながら、環状のアセトニルホスホネート
類の製造においては、トリアルキルスフアイトの
場合の異なり、環の開裂や他の副反応（ペルコウ
（Perkow）反応）が起こり、環状のアセトニル
ホスホネート化合物の収率が低い。また、ペルコ
ウ反応成績体（エノールホスホネート類）及びア
ルキルホスホネート類が生成し、純度も悪いこと
が知られている。 However, in the production of cyclic acetonyl phosphonates, unlike the case of trialkyl sulfite, ring cleavage and other side reactions (Perkow reaction) occur, reducing the yield of cyclic acetonyl phosphonate compounds. low. It is also known that Perkow reaction products (enol phosphonates) and alkyl phosphonates are produced and the purity is poor.
（発明が解決しようとする問題点）
そこで本発明者らは上記欠点を克服する目的で
シリルホスフアイトを用いる方法を検討した。(Problems to be Solved by the Invention) Therefore, the present inventors investigated a method using silyl phosphite in order to overcome the above-mentioned drawbacks.
非環状のシリルホスフアイとハロアセトンとの
反応は知られているが〔J.Org.Chem.、46、2097
（1982）〕、副生するトリメチルシリルハライドに
よつてホスホネートエステルの結合が切断され、
シリルエステル体として単離されており、直接ア
ルキルエステル体を得る方法は未だなかつた。 Although the reaction between acyclic silyl phosphites and haloacetones is known [J.Org.Chem., 46 , 2097
(1982)], the bond of the phosphonate ester is cleaved by the by-produced trimethylsilyl halide, and
It was isolated as a silyl ester, and there was no method to directly obtain the alkyl ester.
環状のシリルホスフアイトから直接環状のアセ
トニルホスホネート化合物を得るためには、副生
するトリメチルシリルハライドは、生成後すぐに
失活させることが必要であつたのである。 In order to obtain a cyclic acetonyl phosphonate compound directly from a cyclic silyl phosphite, it was necessary to deactivate the by-product trimethylsilyl halide immediately after its formation.
（問題点を解決するための手段）
本発明者らは、上記の副生するトリメチルシリ
ルハライドを生成後すぐに失活させるために、ト
リメチルシリハライドとの反応性の高いオキシラ
ン化合物の共存下に反応させる方法を見出し、本
発明を完成させることができた。即ち、本発明の
要旨は、上記反応をプロピレンオキサイド又はシ
クロヘキセンオキサイド等の共存下に行うことに
ある。(Means for Solving the Problems) In order to deactivate the above-mentioned by-product trimethylsilyl halide immediately after its production, the present inventors conducted a reaction in the coexistence of an oxirane compound that is highly reactive with trimethylsilyl halide. We found a method to do this, and were able to complete the present invention. That is, the gist of the present invention is to carry out the above reaction in the coexistence of propylene oxide, cyclohexene oxide, or the like.
以下に本発明を詳細に説明する。 The present invention will be explained in detail below.
環状シリルホスフアイト類〔〕と、ハロアセ
トン類〔〕とを、オキシラン化合物の共存下に
有機溶媒中又は無溶媒で、冷却下又は加熱下に反
応させて、環状アセトニルホスホネート化合物
〔〕を製造する。 A cyclic acetonyl phosphonate compound [] is produced by reacting a cyclic silyl phosphite [] with a haloacetone [] in an organic solvent or without a solvent in the presence of an oxirane compound, under cooling or under heating. .
通常、化合物〔〕に対して〔〕を１〜1.2
倍当量用いるのがよい。オキシラン化合物は、ト
リアルキルシリルハライド（R3SiX）のスカベン
ジヤーとして用いるものであり、プロピレンオキ
サイド又はシクロヘキセンオキサイドが適してい
るが、シクロヘキセンオキサイドが最も収率のよ
い結果を与える。通常、〔〕１モルに対して３
〜20倍モル量の使用が好ましい。 Usually, [] is 1 to 1.2 for compound []
It is better to use double equivalents. The oxirane compound is used as a scavenger for trialkylsilyl halide (R 3 SiX), and propylene oxide or cyclohexene oxide are suitable, but cyclohexene oxide gives the best yield. Usually, 3 to 1 mole []
It is preferable to use a molar amount of ~20 times.
有機溶媒を用いる場合、非プロトン性の有機溶
媒を用いることができ、例えば、アセトニトリ
ル、ベンゼン、トルエン、キシレン、ジオキサ
ン、テトラヒドロフラン、酢酸エチル、クロロホ
ルム、アセトン等を挙げることができる。 When using an organic solvent, an aprotic organic solvent can be used, and examples thereof include acetonitrile, benzene, toluene, xylene, dioxane, tetrahydrofuran, ethyl acetate, chloroform, acetone, and the like.
反応温度は、−15〜100℃の範囲がよいが、加熱
下での反応が好ましい。 The reaction temperature is preferably in the range of -15 to 100°C, but reaction under heating is preferred.
反応時間は、出発原料、スカベンジヤー、溶媒
の種類やその量、及び反応温度によつて異なる
が、通常は10分〜20時間で完結する。 The reaction time varies depending on the starting materials, scavenger, type and amount of solvent, and reaction temperature, but is usually completed in 10 minutes to 20 hours.
本発明において目的化合物は、通常の分離精製
手段、例えば、抽出、濃縮、中和、濾過、再結
晶、カラムクロマトグラフイー等の方法によつて
単離精製することができる。 In the present invention, the target compound can be isolated and purified by conventional separation and purification methods, such as extraction, concentration, neutralization, filtration, recrystallization, column chromatography, and the like.
本発明の出発原料として用いる環状シリルホス
フアイト〔〕は、新規化合物であり、後に参考
例として詳述するが、例えば、次の方法により容
易に製造することができる。 The cyclic silyl phosphite used as a starting material in the present invention is a new compound, which will be described in detail later as a reference example, and can be easily produced, for example, by the following method.
通常のシリル化方法であるトリメチルシリルク
ロライド／トリエチルアミン系でのシリル化より
もヘキサメチレンジシラザン（HMDS：Ｒがメ
チルの場合）と触媒としてイミダゾールを用いる
方法が適しており、83〜85％の収率で環状のシリ
ルホスフアイトが得られる。 A method using hexamethylene disilazane (HMDS: when R is methyl) and imidazole as a catalyst is more suitable than the usual silylation method using trimethylsilyl chloride/triethylamine system, with a yield of 83-85%. A cyclic silyl phosphite is obtained.
トリアルキルシリル基のＲとしては、メチルが
好ましく、環状基のＡとしては、炭素数３のもの
が好ましい。 R of the trialkylsilyl group is preferably methyl, and A of the cyclic group is preferably one having 3 carbon atoms.
ハロアセトンのＸは、ヨウ素又は臭素が用いら
れ、特にヨウ素が最も適している。 Iodine or bromine is used as X in haloacetone, and iodine is particularly suitable.
（実施例）
以下に本発明に係る参考例及び実施例を掲げて
本発明を更に詳しく説明する。(Example) The present invention will be described in more detail below with reference to Reference Examples and Examples according to the present invention.
参考例
２−トリメチルシリルオキシ−１，３，２−ジ
オキサホスホリナン
２−ハイドロキシ−１，３，２−ジオキサホス
ホリナン24.4ｇとイミダゾール0.27ｇをアセトニ
トリル30mlの溶解し、40℃に加熱撹拌下、ヘキサ
メチルレンジシラザン（HMDS）32.2ｇをゆつ
くりと滴下する。滴下後２時間加熱還流し、反応
液を減圧下に濃縮して残留物を減圧蒸留し、目的
化合物32.7ｇを得た。沸点63〜65℃（６mmHg）。Reference Example 2-Trimethylsilyloxy-1,3,2-dioxaphosphorinane 24.4 g of 2-hydroxy-1,3,2-dioxaphosphorinane and 0.27 g of imidazole were dissolved in 30 ml of acetonitrile, and heated to 40°C with stirring. , 32.2 g of hexamethyldisilazane (HMDS) was slowly added dropwise. After the dropwise addition, the mixture was heated under reflux for 2 hours, the reaction solution was concentrated under reduced pressure, and the residue was distilled under reduced pressure to obtain 32.7 g of the target compound. Boiling point 63-65℃ (6mmHg).
同様にして、５，５−ジメチル−２−トリメチ
ルシリルオキシ−１，３，２−ジオキサホスホリ
ナン、沸点82〜83℃（15mmHg）を得た。 In the same manner, 5,5-dimethyl-2-trimethylsilyloxy-1,3,2-dioxaphosphorinane, boiling point 82-83°C (15 mmHg) was obtained.
実施例 １
２−アセトニル−２−オキソ−１，３，２−ジ
オキサホスホリナン
(a) アセトニトリル20mlに、２−トリメチルシリ
ルオキシ−１，３，２−ジオキサホスホリナン
3.88ｇとシクロヘキセンオキサイド9.82ｇを溶
解し、加熱還流下にヨードアセトン3.68ｇを適
下する。30分間還流後、反応液を冷却し、シリ
カゲルカラムクロマトグラフイーに付し精製
（シリカゲル150ｇ：溶出溶媒：酢酸エチル）し
て、目的化合物の1.78ｇを得た。沸点158〜160
℃（0.8mmHg）。Example 1 2-acetonyl-2-oxo-1,3,2-dioxaphosphorinane (a) 2-trimethylsilyloxy-1,3,2-dioxaphosphorinane in 20 ml of acetonitrile
Dissolve 3.88 g of cyclohexene oxide and 9.82 g of cyclohexene oxide, and drop 3.68 g of iodoacetone while heating under reflux. After refluxing for 30 minutes, the reaction solution was cooled and purified by silica gel column chromatography (150 g of silica gel: elution solvent: ethyl acetate) to obtain 1.78 g of the target compound. Boiling point 158-160
°C (0.8mmHg).
MSｍ／ｚ（％）：M+178（25.7）
元素分析値（C6H11O4P・1/2H2O）
計算値（％） Ｃ：38.50 Ｈ：6.46
実測値（％） Ｃ：38.67 Ｈ：6.59
IRνfiLm nax：cm-1：1710、1270、
NMR：（CDCl3）δ：1.96〜2.22（2H，ｍ）、
2.38（3H、ｓ）、3.21（2H、ｄ、Ｊ＝22Hz）、
4.26〜4.65（4H、ｍ）
(b) ２−トリメチルシリルオキシ−１，３，２−
ジオキサホスホリナン19.4ｇにプロピレンオキ
サイド87ｇを加え、−１℃に冷却撹拌下ヨード
アセトンを滴下する。滴下後室温に戻し、15時
間撹拌を続ける。反応液をシリカゲルカラムク
ロマトグラフイーに付して精製し、目的化合物
の7.3ｇを得た。MSm/z (%): M + 178 (25.7) Elemental analysis value (C 6 H 11 O 4 P・1/2H 2 O) Calculated value (%) C: 38.50 H: 6.46 Actual value (%) C: 38.67 H: 6.59 IRν fiLm nax : cm -1 : 1710, 1270, NMR: (CDCl 3 ) δ: 1.96 to 2.22 (2H, m),
2.38 (3H, s), 3.21 (2H, d, J=22Hz),
4.26-4.65 (4H, m) (b) 2-trimethylsilyloxy-1,3,2-
87 g of propylene oxide was added to 19.4 g of dioxaphosphorinane, and iodoacetone was added dropwise while stirring at -1°C. After dropping, return to room temperature and continue stirring for 15 hours. The reaction solution was purified by silica gel column chromatography to obtain 7.3 g of the target compound.
実施例 ２
２−アセトニル５，５−ジメチル−２−オキソ
−１，３，２−ジオキサホスホリナン
５，５−ジメチル−２−トリメチルシリルオキ
シ−１，３，２−ジオキサホスホリナン11.1ｇを
用い、実施例１の(a)と同様に反応と後処理をし
て、目的化合物4.4ｇを得た。Example 2 2-acetonyl 5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane 11.1 g of 5,5-dimethyl-2-trimethylsilyloxy-1,3,2-dioxaphosphorinane The reaction and post-treatment were carried out in the same manner as in Example 1 (a) to obtain 4.4 g of the target compound.
融点91〜92℃（エーテルから再結晶）。Melting point 91-92°C (recrystallized from ether).
元素分析値（C8H15O4P）
計算値（％） Ｃ：46.60 Ｈ：7.33
実施例（％） Ｃ：46.48 Ｈ：7.01
IRνKBr nax：cm-1：1705、1270、
（発明の効果）
本発明の方法の確立により、極めて高収率、高
純度で目的化合物を製造することができる。即
ち、従来より知られている２−アルコキシ環状ホ
スフアイト類とハロアセトンとの反応と比べて収
率が高く、副生物が少ないために純度も高く、精
製が容易で、工業的製造法としてし極めて有用で
ある。Elemental analysis value (C 8 H 15 O 4 P) Calculated value (%) C: 46.60 H: 7.33 Example (%) C: 46.48 H: 7.01 IRν KBr nax : cm -1 : 1705, 1270, (Effect of the invention ) By establishing the method of the present invention, the target compound can be produced with extremely high yield and high purity. That is, compared to the conventionally known reaction of 2-alkoxy cyclic phosphites and haloacetones, the yield is higher, the purity is higher due to fewer by-products, the purification is easier, and it is extremely useful as an industrial production method. It is.
Claims (1)
般式〔〕 CH3COCH2X 〔〕 で表されるハロアセトン類とを、副生するトリア
ルキルシリルハライドのスカベンジヤーの共存下
に反応させることを特徴とする、次の一般式
〔〕 で表されるホスホネート誘導体の製造法。 式中、Ｒは低級アルキルを表す。Ａは、炭素数
２〜４のアルキレンを表し、当該炭素のうちのい
くつかは低級アルキルで置換されていてもよい。
Ｘは、ハロゲンを表す。[Claims] First-order general formula [] Reacting a cyclic silyl phosphite represented by the formula [] with a haloacetone represented by the following general formula [] CH 3 COCH 2 The following general formula [ ], characterized by A method for producing a phosphonate derivative represented by In the formula, R represents lower alkyl. A represents alkylene having 2 to 4 carbon atoms, and some of the carbon atoms may be substituted with lower alkyl.
X represents halogen.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP268888A JPH01180891A (en) | 1988-01-08 | 1988-01-08 | Phosphonate derivative and production thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP268888A JPH01180891A (en) | 1988-01-08 | 1988-01-08 | Phosphonate derivative and production thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01180891A JPH01180891A (en) | 1989-07-18 |
| JPH0552839B2 true JPH0552839B2 (en) | 1993-08-06 |
Family
ID=11536224
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP268888A Granted JPH01180891A (en) | 1988-01-08 | 1988-01-08 | Phosphonate derivative and production thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01180891A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08271988A (en) * | 1995-03-31 | 1996-10-18 | Nec Corp | Screen for projector |
-
1988
- 1988-01-08 JP JP268888A patent/JPH01180891A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08271988A (en) * | 1995-03-31 | 1996-10-18 | Nec Corp | Screen for projector |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH01180891A (en) | 1989-07-18 |
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