JPS6331474B2 - - Google Patents
Info
- Publication number
- JPS6331474B2 JPS6331474B2 JP9559079A JP9559079A JPS6331474B2 JP S6331474 B2 JPS6331474 B2 JP S6331474B2 JP 9559079 A JP9559079 A JP 9559079A JP 9559079 A JP9559079 A JP 9559079A JP S6331474 B2 JPS6331474 B2 JP S6331474B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- general formula
- same
- phosphoric acid
- group
- 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.)
- Expired
Links
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 23
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- 150000005690 diesters Chemical class 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 7
- XHZNCTFRBLUSQE-UHFFFAOYSA-N 2-(1,3-benzoxazol-2-yloxy)-1,3-benzoxazole Chemical class C1=CC=C2OC(OC=3OC4=CC=CC=C4N=3)=NC2=C1 XHZNCTFRBLUSQE-UHFFFAOYSA-N 0.000 claims description 6
- MHSVUSZEHNVFKW-UHFFFAOYSA-N bis-4-nitrophenyl phosphate Chemical compound C=1C=C([N+]([O-])=O)C=CC=1OP(=O)(O)OC1=CC=C([N+]([O-])=O)C=C1 MHSVUSZEHNVFKW-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 6
- -1 phosphoric acid diesters Chemical class 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- MCZDHTKJGDCTAE-UHFFFAOYSA-M tetrabutylazanium;acetate Chemical compound CC([O-])=O.CCCC[N+](CCCC)(CCCC)CCCC MCZDHTKJGDCTAE-UHFFFAOYSA-M 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- KMGIHQOHAZZJKL-UHFFFAOYSA-N (4-methoxy-2-phenylbutyl) dihydrogen phosphate Chemical compound COCCC(COP(=O)(O)O)C1=CC=CC=C1 KMGIHQOHAZZJKL-UHFFFAOYSA-N 0.000 description 1
- XTHFMPNFHXEUMI-UHFFFAOYSA-N 2-(2-phenylethoxy)-1,3-benzoxazole Chemical compound N=1C2=CC=CC=C2OC=1OCCC1=CC=CC=C1 XTHFMPNFHXEUMI-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- LXTKCTMGEWVPTB-UHFFFAOYSA-N butylazanium;acetate Chemical compound CC(O)=O.CCCCN LXTKCTMGEWVPTB-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- ZHCAAFJSYLFLPX-UHFFFAOYSA-N nitrocyclohexatriene Chemical group [O-][N+](=O)C1=CC=C=C[CH]1 ZHCAAFJSYLFLPX-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 150000005691 triesters Chemical class 0.000 description 1
Description
【発明の詳細な説明】
本発明はリン酸ジエステルの新規な製造法、特
に次の一般式（）
式中、R1及びR2はフエニル基又は低級アルコ
キシ基で置換されていてもよい直鎖低級アルキル
基、あるいは低級アルキニル基を示す。ただし、
R1≠R2である。
で表わされるリン酸混合ジエステルの製造法に関
する。
従来、リン酸混合ジエステルの製造法として
は、リン酸のハロゲン化物に１モルずつ異なつた
アルコールを順次反応させる方法が一般的に行わ
れていた。しかしながら、この方法においては望
みの混合ジエステル以外に、さらに反応が進行し
たトリエステルや同じアルコールのジエステル等
の副生物を生じることが避けられないため収率よ
くリン酸混合ジエステルは得られなかつた。ま
た、フツ化セシウム等の触媒の存在下にリン酸の
トリクロルエチルエステルにアルコールを順次反
応させる方法も報告されているが、この方法は従
来法よりは欠点を克服しているけれども、高価な
フツ化セシウムを大量に使用しなければならず、
必らずしも優れた方法とはいえない。
本発明者らは前記欠点を克服したリン酸混合ジ
エステルを見出すべく種々研究を重ねた結果、高
収率でリン酸混合ジエステルを製造する方法を見
出し、本発明を完成した。
従つて、本発明の目的は簡便な反応でしかも高
収率でリン酸混合ジエステルを製造する新規な方
法を提供せんとするにある。
本発明方法は次の反応式で示される。
（式中、R1およびR2は前記と同じ）
すなわち、本発明はリン酸ビス（ｐ−ニトロフ
エニル）エステル（）にベンゾオキサゾリルエ
ーテル類（）を反応せしめて（）の化合物と
なし、次いでこれを穏和な条件で加水分解して式
（）の化合物となし、次いでこれにベンゾオキ
サゾリルエーテル類（）を反応せしめて式
（）の化合物となし、つづいてこれを穏和な条
件で加水分解せしめてリン酸混合ジエステル
（）を製造する方法である。
本発明方法は次の如くして実施される。
リン酸ビス（ｐ−ニトロフエニル）エステル
（）とベンゾオキサゾリルエーテル類（）か
ら式（）の化合物を得る反応は、ベンゼン、ト
ルエン等の反応に関与しない有機溶媒中、好まし
くはアルゴン、窒素等の不活性ガス雰囲気中、室
温〜溶媒の沸点までの温度で行う。
式（）の化合物とベンゾオキサゾリルエーテ
ル類（）から式（）の化合物を得る反応も同
様にして行われる。
式（）の化合物を加水分解して式（）の化
合物を得る方法および式（）の化合物を加水分
解して式（）のリン酸混合ジエステルを得る方
法は穏和な条件下で、すなわち、テトラブチルア
ンモニウムアセテートで処理することにより、選
択的に加水分解される。テトラブチルアンモニウ
ムアセテートは、パラニトロフエニルエステルの
選択的な加水分解に特に有用である。
次に実施例を挙げて本発明を詳細に説明する。
実施例 １
２−（２−メトキシエトキシ）ベンゾオキサゾ
ール193mg、リン酸ビス（ｐ−ニトロフエニル）
エステル408mgおよびベンゼン10mlの混合物をア
ルゴン雰囲気下に３時間加熱還流した。冷後、エ
ーテルを加えて水にて３回洗浄し、過して不溶
物を除去し、減圧下に溶媒を留去した。残渣を減
圧下に五酸化リン上で乾燥し、テトラヒドロフラ
ン５mlに溶解した。これにテトラブチルアンモニ
ウムアセテート362mgをテトラヒドロフラン５ml
に溶解させた液を加え、室温にて10分間撹拌し
た。水40mlを加え、エーテルにて４回洗浄し、濃
縮してイオン交換樹脂（IR−120〔H+〕）のカラ
ムに通してテトラブチルアンモニウムイオンを交
換した。溶出液を減圧下に溶媒留去し、真空中で
乾燥して、エーテルから再結晶して融点79.5〜82
℃のリン酸２−メトキシエチルｐ−ニトロフエニ
ルの結晶229mg（収率83％）を得た。次いで、リ
ン酸２−メトキシエチルｐ−ニトロフエニル139
mg、２−フエネチルオキシベンゾオキサゾール
144mgおよびベンゼン５mlの混合物をアルゴン雰
囲気下に８時間加熱還流した。冷後、エーテルを
加えて水にて３回洗浄し、過して不溶物を除去
し、減圧下に溶媒を留去した。残渣を減圧下に五
酸化リン上で乾燥し、テトラヒドロフラン５mlに
溶解した。これにテトラブチルアンモニウムアセ
テート301mgをテトラヒドロフラン５mlに溶解さ
せた液を加え、室温にて７時間撹拌した。水40ml
を加え、エーテルにて４回洗浄し、濃縮してイオ
ン交換樹脂（IR−120〔H+〕）のカラムに通して、
テトラブチルアンモニウムイオンを交換した。溶
出液を減圧下に溶媒留去して、リン酸２−メトキ
シエチルフエネチルの無色油状物108mg（収率83
％）を得た。
実施例 ２
実施例１と同様な操作にて一般式（）におい
てR1およびR2が次表の化合物を得た。
【表】DETAILED DESCRIPTION OF THE INVENTION The present invention provides a novel method for producing phosphoric acid diesters, particularly the following general formula () In the formula, R 1 and R 2 represent a phenyl group, a linear lower alkyl group which may be substituted with a lower alkoxy group, or a lower alkynyl group. however,
R 1 ≠ R 2 . This invention relates to a method for producing a phosphoric acid mixed diester represented by: Conventionally, a method for producing mixed diesters of phosphoric acid has generally involved a method in which a halide of phosphoric acid is sequentially reacted with alcohols of different moles each. However, in this method, in addition to the desired mixed diester, it is inevitable that by-products such as a triester in which the reaction has proceeded and a diester of the same alcohol are produced, so that a phosphoric acid mixed diester cannot be obtained in a good yield. Additionally, a method has been reported in which alcohol is sequentially reacted with trichloroethyl ester of phosphoric acid in the presence of a catalyst such as cesium fluoride, but although this method overcomes the drawbacks of the conventional method, it requires expensive equipment. A large amount of cesium chloride must be used,
This is not necessarily a good method. The present inventors have conducted various studies to find a phosphoric acid mixed diester that overcomes the above-mentioned drawbacks, and as a result, have discovered a method for producing a phosphoric acid mixed diester in high yield, and have completed the present invention. Accordingly, an object of the present invention is to provide a new method for producing phosphoric acid mixed diesters with a simple reaction and high yield. The method of the present invention is shown by the following reaction formula. (In the formula, R 1 and R 2 are the same as above.) That is, the present invention reacts phosphoric acid bis(p-nitrophenyl) ester () with benzoxazolyl ethers () to form the compound (), and then This is hydrolyzed under mild conditions to form a compound of formula (), which is then reacted with benzoxazolyl ethers () to form a compound of formula (), which is then hydrolyzed under mild conditions. At least this is a method for producing phosphoric acid mixed diester (). The method of the present invention is carried out as follows. The reaction to obtain the compound of formula () from phosphoric acid bis(p-nitrophenyl) ester () and benzoxazolyl ethers () is carried out in an organic solvent that does not participate in the reaction, such as benzene or toluene, preferably in an atmosphere such as argon or nitrogen. The reaction is carried out in an inert gas atmosphere at a temperature ranging from room temperature to the boiling point of the solvent. The reaction to obtain the compound of formula () from the compound of formula () and benzoxazolyl ethers () is carried out in the same manner. The method of hydrolyzing the compound of formula () to obtain the compound of formula () and the method of hydrolyzing the compound of formula () to obtain the phosphoric acid mixed diester of formula () are carried out under mild conditions, i.e. It is selectively hydrolyzed by treatment with butylammonium acetate. Tetrabutylammonium acetate is particularly useful for selective hydrolysis of para-nitrophenyl esters. Next, the present invention will be explained in detail with reference to Examples. Example 1 2-(2-methoxyethoxy)benzoxazole 193 mg, bis(p-nitrophenyl) phosphate
A mixture of 408 mg of ester and 10 ml of benzene was heated under reflux for 3 hours under an argon atmosphere. After cooling, ether was added, the mixture was washed three times with water, filtered to remove insoluble matter, and the solvent was distilled off under reduced pressure. The residue was dried under reduced pressure over phosphorus pentoxide and dissolved in 5 ml of tetrahydrofuran. Add 362 mg of tetrabutylammonium acetate to this and 5 ml of tetrahydrofuran.
A solution dissolved in was added, and the mixture was stirred at room temperature for 10 minutes. 40 ml of water was added, washed four times with ether, concentrated, and passed through a column of ion exchange resin (IR-120 [H + ]) to exchange tetrabutylammonium ions. The eluate was evaporated under reduced pressure, dried in vacuo and recrystallized from ether, mp 79.5-82.
229 mg (yield: 83%) of crystals of 2-methoxyethyl p-nitrophenyl phosphate were obtained. Then, 2-methoxyethyl p-nitrophenyl phosphate139
mg, 2-phenethyloxybenzoxazole
A mixture of 144 mg and 5 ml of benzene was heated under reflux for 8 hours under an argon atmosphere. After cooling, ether was added, the mixture was washed three times with water, filtered to remove insoluble matter, and the solvent was distilled off under reduced pressure. The residue was dried under reduced pressure over phosphorus pentoxide and dissolved in 5 ml of tetrahydrofuran. A solution prepared by dissolving 301 mg of tetrabutylammonium acetate in 5 ml of tetrahydrofuran was added to this, and the mixture was stirred at room temperature for 7 hours. 40ml water
was added, washed four times with ether, concentrated, and passed through a column of ion exchange resin (IR-120 [H + ]).
Tetrabutylammonium ion was exchanged. The eluate was evaporated under reduced pressure to give 108 mg of a colorless oil of 2-methoxyethylphenethyl phosphate (yield: 83
%) was obtained. Example 2 In the same manner as in Example 1, compounds of the general formula () with R 1 and R 2 shown in the following table were obtained. 【table】
Claims (1)
に、一般式 （式中、R1はフエニル基又は低級アルコキシ基
で置換されていてもよい直鎖低級アルキル基、あ
るいは低級アルキニル基を示す） で表わされるベンゾオキサゾリルエーテル類を反
応せしめて一般式 （式中、R1は前記と同じ） で表わされる化合物となし、次いでこれを緩和な
条件で加水分解せしめて一般式 （式中、R1は前記と同じ） で表わされる化合物となし、次いでこれに一般式 （式中、R2はフエニル基又は低級アルコキシ基
で置換されていてもよい直鎖低級アルキル基、あ
るいは低級アルキニル基を示す。ただしR1≠R2
である） で表わされるベンゾオキサゾリルエーテル類を反
応せしめて一般式 （式中、R1及びR2は前記と同じ） で表わされる化合物となし、更にこれを緩和な条
件で加水分解せしめることを特徴とする、一般式 （式中、R1及びR2は前記と同じ） で表わされるリン酸混合ジエステルの製造法。[Claims] 1. Phosphate bis(p-nitrophenyl) ester has the general formula (In the formula, R 1 represents a straight chain lower alkyl group optionally substituted with a phenyl group or a lower alkoxy group, or a lower alkynyl group) by reacting benzoxazolyl ethers represented by the general formula (In the formula, R 1 is the same as above) This is then hydrolyzed under mild conditions to form a compound represented by the general formula (In the formula, R 1 is the same as above) and then add this to the general formula (In the formula, R 2 represents a phenyl group, a linear lower alkyl group which may be substituted with a lower alkoxy group, or a lower alkynyl group. However, R 1 ≠ R 2
) by reacting benzoxazolyl ethers represented by the general formula (wherein R 1 and R 2 are the same as above) and further hydrolyzed under mild conditions, (In the formula, R 1 and R 2 are the same as above.) A method for producing a phosphoric acid mixed diester represented by the following.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9559079A JPS5620594A (en) | 1979-07-28 | 1979-07-28 | Preparation of mixed diester of phosphoric acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9559079A JPS5620594A (en) | 1979-07-28 | 1979-07-28 | Preparation of mixed diester of phosphoric acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5620594A JPS5620594A (en) | 1981-02-26 |
| JPS6331474B2 true JPS6331474B2 (en) | 1988-06-23 |
Family
ID=14141787
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9559079A Granted JPS5620594A (en) | 1979-07-28 | 1979-07-28 | Preparation of mixed diester of phosphoric acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5620594A (en) |
-
1979
- 1979-07-28 JP JP9559079A patent/JPS5620594A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5620594A (en) | 1981-02-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4622180A (en) | Derivatives of glycerophosphocholine and glycerophosphoethanolamine, their preparation and their use | |
| JPS59227891A (en) | Manufacture of phosphorus-containing cyanhydrin derivative | |
| JPS6072899A (en) | Manufacture of nucleosidoalkyl-, aralkyl- and allyl-phosphonite and -phosphonate | |
| JPH09309891A (en) | Production of monoalkyl phosphonite | |
| US5110964A (en) | Process for producing ferrocenoyl derivatives | |
| JPS6331474B2 (en) | ||
| JP3452374B2 (en) | Method for producing benzylphosphonate derivative | |
| DE1104957B (en) | Process for the preparation of optionally substituted dialkylphosphine oxides | |
| JPH10500656A (en) | Bis (pentaerythritol phosphate alcohol) alkyl phosphonate | |
| EP0468258A1 (en) | Substituted pyrido-oxazines | |
| JPS6260387B2 (en) | ||
| US4182759A (en) | Arylalkyl and aryloxyalkyl phosphonates and use as antiviral agents | |
| US4217346A (en) | Arylalkyl and aryloxyalkyl phosphonates as antiviral agents | |
| Thompson | Enol and acyl phosphates as intermediates in the synthesis of nonrandom triglycerides | |
| DE2033361C3 (en) | Acylpropanediol- (13) -phosphoric acid choline ester and process for their preparation | |
| US4020110A (en) | Production of tertiary methylphosphine oxides | |
| JPS6312070B2 (en) | ||
| JPH03397B2 (en) | ||
| EP0021112A1 (en) | Process for the preparation of derivatives of 1,3-dibromo-2,2-dimethyl-propane-1,3-dicarboxylic acid, as well as the dichloride of 1,3-dibromo-2,2-dimethyl-propane-1,3-dicarboxylic acid and its monoesterchlorides as intermediary products | |
| JP3863956B2 (en) | Novel process for producing phosphonic acid diesters | |
| US3548039A (en) | Process for producing cyclic catechol esters of phosphonic acid | |
| JP3619275B2 (en) | Ascorbic acid phosphoramide derivative and method for producing the same | |
| DE19541276C1 (en) | Sec. aryl-phosphane oxide prepn. from alkyl aryl-phosphinite without disproportionation | |
| JPH0931086A (en) | Cyclic diphosphoric ester and its preparation | |
| US3769364A (en) | Carboxyphenyl esters of propenyl and propadienylphosphonic acids |