JP2000290267A - Production of oxadiazolone derivative - Google Patents
Production of oxadiazolone derivativeInfo
- Publication number
- JP2000290267A JP2000290267A JP11099587A JP9958799A JP2000290267A JP 2000290267 A JP2000290267 A JP 2000290267A JP 11099587 A JP11099587 A JP 11099587A JP 9958799 A JP9958799 A JP 9958799A JP 2000290267 A JP2000290267 A JP 2000290267A
- Authority
- JP
- Japan
- Prior art keywords
- resin
- oxadiazolone
- derivative
- formula
- acid
- 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.)
- Pending
Links
- ZVTQYRVARPYRRE-UHFFFAOYSA-N oxadiazol-4-one Chemical class O=C1CON=N1 ZVTQYRVARPYRRE-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 238000004519 manufacturing process Methods 0.000 title claims description 11
- 239000011347 resin Substances 0.000 claims abstract description 75
- 229920005989 resin Polymers 0.000 claims abstract description 75
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 17
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 4
- CHNUNORXWHYHNE-UHFFFAOYSA-N Oxadiazon Chemical compound C1=C(Cl)C(OC(C)C)=CC(N2C(OC(=N2)C(C)(C)C)=O)=C1Cl CHNUNORXWHYHNE-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- RHAWWZKCMRZMEQ-UHFFFAOYSA-N 2-[4-(2,4-dichloro-5-propan-2-yloxyphenyl)-5-oxo-1,3,4-oxadiazol-2-yl]-2-methylpropanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC(N2C(OC(=N2)C(C)(C)C(O)=O)=O)=C1Cl RHAWWZKCMRZMEQ-UHFFFAOYSA-N 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 6
- 230000003301 hydrolyzing effect Effects 0.000 abstract description 4
- IKWAJKKOBDGNLR-UHFFFAOYSA-N 1,1-dichloro-2-phenylhydrazine Chemical compound ClN(Cl)NC1=CC=CC=C1 IKWAJKKOBDGNLR-UHFFFAOYSA-N 0.000 abstract description 3
- 239000003905 agrochemical Substances 0.000 abstract description 3
- 240000007594 Oryza sativa Species 0.000 abstract description 2
- 235000007164 Oryza sativa Nutrition 0.000 abstract description 2
- 238000006482 condensation reaction Methods 0.000 abstract description 2
- 235000009566 rice Nutrition 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract 5
- 239000000126 substance Substances 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 6
- 239000002994 raw material Substances 0.000 description 5
- -1 5-ethoxy-2,4-dichlorophenylhydrazine Chemical compound 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- GWHQKTAGVTYTJX-UHFFFAOYSA-N (2,4-dichloro-5-propan-2-yloxyphenyl)hydrazine Chemical compound CC(C)OC1=CC(NN)=C(Cl)C=C1Cl GWHQKTAGVTYTJX-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- OREAFAJWWJHCOT-UHFFFAOYSA-N dimethylmalonic acid Chemical compound OC(=O)C(C)(C)C(O)=O OREAFAJWWJHCOT-UHFFFAOYSA-N 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000013076 target substance Substances 0.000 description 3
- 150000003512 tertiary amines Chemical class 0.000 description 3
- ZTPAUBJZUBGGEY-UHFFFAOYSA-N (2,4-dichlorophenyl)hydrazine Chemical compound NNC1=CC=C(Cl)C=C1Cl ZTPAUBJZUBGGEY-UHFFFAOYSA-N 0.000 description 2
- JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- KJOZJSGOIJQCGA-UHFFFAOYSA-N dichloromethane;2,2,2-trifluoroacetic acid Chemical compound ClCCl.OC(=O)C(F)(F)F KJOZJSGOIJQCGA-UHFFFAOYSA-N 0.000 description 2
- OQYZYQSFESQDHK-UHFFFAOYSA-N (2,4-dichloro-5-methoxyphenyl)hydrazine Chemical compound COC1=CC(NN)=C(Cl)C=C1Cl OQYZYQSFESQDHK-UHFFFAOYSA-N 0.000 description 1
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 1
- OBOHMJWDFPBPKD-UHFFFAOYSA-N 1-[chloro(diphenyl)methyl]-4-methoxybenzene Chemical compound C1=CC(OC)=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 OBOHMJWDFPBPKD-UHFFFAOYSA-N 0.000 description 1
- VUTZFAOGDXUYEJ-UHFFFAOYSA-N 1-[chloro(diphenyl)methyl]-4-methylbenzene Chemical compound C1=CC(C)=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 VUTZFAOGDXUYEJ-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- QGHDLJAZIIFENW-UHFFFAOYSA-N 4-[1,1,1,3,3,3-hexafluoro-2-(4-hydroxy-3-prop-2-enylphenyl)propan-2-yl]-2-prop-2-enylphenol Chemical group C1=C(CC=C)C(O)=CC=C1C(C(F)(F)F)(C(F)(F)F)C1=CC=C(O)C(CC=C)=C1 QGHDLJAZIIFENW-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 241000286819 Malo Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- DADSZOFTIIETSV-UHFFFAOYSA-N n,n-dichloroaniline Chemical class ClN(Cl)C1=CC=CC=C1 DADSZOFTIIETSV-UHFFFAOYSA-N 0.000 description 1
- NJTMPILFXWNYAH-UHFFFAOYSA-N n-carbamoyl-2,2-dimethylpropanamide Chemical class CC(C)(C)C(=O)NC(N)=O NJTMPILFXWNYAH-UHFFFAOYSA-N 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、稲作等の農薬とし
て広範に利用されているオキサジアゾロン誘導体の製造
方法に関するものである。更に本発明は、そのオキサジ
アゾロン誘導体を製造するための中間体の製造方法に関
するものである。TECHNICAL FIELD The present invention relates to a method for producing an oxadiazolone derivative widely used as an agricultural chemical for rice cultivation and the like. Furthermore, the present invention relates to a method for producing an intermediate for producing the oxadiazolone derivative.
【０００２】[0002]
【従来の技術】オキサジアゾロン誘導体の製造方法とし
ては、特公昭４２−８７９８号公報および特公昭４６−
３８１５３号公報などで提案されている方法が知られて
いる。しかしながら、前者においてはオキサジアゾロン
骨格の構築に酸塩化物を用いるため、また後者において
は、中間体として必要となるカルボキシル基を有するト
リメチルアセチル尿素誘導体の合成が困難なため、これ
らの方法は、いずれも分子内にカルボキシル基をもった
オキサジアゾンアシッド等の製造方法に応用することは
できない。また、オキサジアゾンアシッドそのものは単
離されてはいるが（例えば、食衛誌.33,548（199
2））、その合成方法については提案されていない。2. Description of the Related Art Methods for producing oxadiazolone derivatives are described in JP-B-42-8798 and JP-B-46-8798.
A method proposed in, for example, Japanese Patent No. 38153 is known. However, since the former uses an acid chloride for the construction of the oxadiazolone skeleton, and in the latter, it is difficult to synthesize a trimethylacetylurea derivative having a carboxyl group required as an intermediate. None of them can be applied to a method for producing oxadiazon acid having a carboxyl group in the molecule. Although oxadiazon acid itself has been isolated (see, for example, Gastronomy. 33,548 (199
2)), the synthesis method has not been proposed.
【０００３】また特公昭４２−８７９８号公報において
は、オキサジアゾロン骨格を構築するときにホスゲンが
用いられているが、その危険性のため、厳密な安全性を
備えた状態でしか製造できないという欠点があった。In Japanese Patent Publication No. 42-8798, phosgene is used when constructing the oxadiazolone skeleton. However, due to its danger, it can be produced only with strict safety. There were drawbacks.
【０００４】[0004]
【発明が解決しようとする課題】本発明者等は、従来技
術の欠点に鑑み鋭意研究した結果、それ自身は公知であ
る不溶性樹脂に原料を結合させ、その樹脂表面上でオキ
サジアゾロン骨格を構築し、最後に樹脂から目的物を解
離させることにより、また、オキサジアゾン骨格を構築
するのに安全で取り扱いが容易なトリホスゲンを用いる
ことにより、簡便かつ安全にオキサジアゾンアシッド等
を得ることができることを見いだし、本発明に到達し
た。The present inventors have conducted intensive studies in view of the drawbacks of the prior art, and as a result, bonded a raw material to an insoluble resin known per se, and formed an oxadiazolone skeleton on the resin surface. By constructing and finally dissociating the target substance from the resin, and by using triphosgene, which is safe and easy to handle for constructing the oxadiazone skeleton, it is found that oxadiazon acid and the like can be obtained easily and safely. Reached the present invention.
【０００５】本発明の目的は、化学的に、簡便かつ安全
にオキサジアゾロン誘導体を製造する方法を提供するこ
とにある。An object of the present invention is to provide a method for producing an oxadiazolone derivative chemically, simply and safely.
【０００６】また、本発明の他の目的は、オキサジアゾ
ロン誘導体を製造するために有用な中間体の製造方法を
提供することにある。It is another object of the present invention to provide a method for producing an intermediate useful for producing an oxadiazolone derivative.
【０００７】[0007]
【課題を解決するための手段】前記本発明の目的は、以
下の構成により達成できる。The object of the present invention can be achieved by the following constitution.
【０００８】すなわち、本発明の次式(Ｉ）That is, the following formula (I) of the present invention
【０００９】[0009]
【化７】 （式中、ＲはＨ、アルキル基またはアルコキシ基）で示
されるオキサジアゾロン誘導体は、次式(Ｖ）Embedded image (Wherein R is H, an alkyl group or an alkoxy group), the oxadiazolone derivative represented by the following formula (V)
【００１０】[0010]
【化８】 （式中、ＲはＨ、アルキル基またはアルコキシ基）で示
されるオキサジアゾロン誘導体−樹脂結合体を加水分解
して樹脂と解離させることによって得ることができる。Embedded image (Wherein, R is H, an alkyl group or an alkoxy group) and can be obtained by hydrolyzing an oxadiazolone derivative-resin conjugate represented by the following formula and dissociating it from the resin.
【００１１】また、中間体である次式(Ｖ）Further, the following intermediate (V)
【００１２】[0012]
【化９】 （式中、ＲはＨ、アルキル基またはアルコキシ基）で示
されるオキサジアゾロン誘導体−樹脂結合体は、次式
（IV）Embedded image (Where R is H, an alkyl group or an alkoxy group), the oxadiazolone derivative-resin conjugate represented by the following formula (IV)
【００１３】[0013]
【化１０】 （式中、ＲはＨ、アルキル基またはアルコキシ基）で示
されるヒドラジド-樹脂結合体に、トリホスゲンを作用
させてオキサジアゾロン環を形成させることによって得
ることができる。Embedded image (Wherein, R is H, an alkyl group or an alkoxy group), and the hydrazide-resin conjugate represented by the following formula is reacted with triphosgene to form an oxadiazolone ring.
【００１４】また、ここでは樹脂として、トリチル樹脂
が好ましく用いられる。Here, a trityl resin is preferably used as the resin.
【００１５】[0015]
【発明の実施の形態】本発明は、不溶性樹脂に原料を結
合させ、その樹脂担体上でオキサジアゾロン骨格を構築
し、最後に樹脂から目的物を解離させることにより、簡
便かつ安全にオキサジアゾンアシッド等を得るものであ
り、また、オキサジアゾロン骨格を構築する際に、安全
で取り扱いが容易なトリホスゲンを用いるものである。BEST MODE FOR CARRYING OUT THE INVENTION The present invention provides a simple and safe oxadiazon acid acid by binding a raw material to an insoluble resin, constructing an oxadiazolone skeleton on the resin carrier, and finally dissociating the target substance from the resin. And the like, and use triphosgene which is safe and easy to handle when constructing the oxadiazolone skeleton.
【００１６】本発明の次式（Ｉ）The following formula (I) of the present invention
【００１７】[0017]
【化１１】 （式中、ＲはＨ、アルキル基またはアルコキシ基）で示
されるオキサジアゾロン誘導体は、次式（Ｖ）Embedded image (Wherein R is H, an alkyl group or an alkoxy group), an oxadiazolone derivative represented by the following formula (V)
【００１８】[0018]
【化１２】 （式中、ＲはＨ、アルキル基またはアルコキシ基）で示
されるオキサジアゾロン誘導体−樹脂結合体を加水分解
し、樹脂と解離させることによって得ることができる。
具体的には、例えば、式（Ｖ）で示される樹脂との結合
体を、1%トリフルオロ酢酸/ジクロロメタン溶液で1〜3
時間処理することによって解離させることができる。そ
の際の温度は、15〜30℃が好ましい。また、その他の手
段として、酢酸/トリフルオロエタノール/ジクロロメタ
ンや0.5%トリフルオロ酢酸/ジクロロメタン、30%ヘキサ
フルオロイソプロパノール/ジクロロメタンで処理する
方法でも解離させることができる。Embedded image (Wherein, R is H, an alkyl group or an alkoxy group), by hydrolyzing the oxadiazolone derivative-resin conjugate represented by the following formula and dissociating it with the resin.
Specifically, for example, the conjugate with the resin represented by the formula (V) is treated with a 1% trifluoroacetic acid / dichloromethane solution for 1 to 3 times.
Dissociation can be achieved by time processing. The temperature at that time is preferably 15 to 30 ° C. Alternatively, dissociation can also be achieved by a method involving treatment with acetic acid / trifluoroethanol / dichloromethane, 0.5% trifluoroacetic acid / dichloromethane, or 30% hexafluoroisopropanol / dichloromethane.
【００１９】上記式（Ｉ）、式（Ｖ）で示される化合物
中、Ｒがアルキル基の場合、炭素数は1〜6が好ましく、
またアルコキシ基の場合は、炭素数は1〜6が好ましい。In the compounds represented by the above formulas (I) and (V), when R is an alkyl group, it preferably has 1 to 6 carbon atoms.
In the case of an alkoxy group, the number of carbon atoms is preferably 1 to 6.
【００２０】樹脂から切り離した後、樹脂をろ過で除
き、上澄み液を集めて溶媒を留去するだけで純度70％程
度の前記式（Ｉ）で示されるオキサジアゾロン誘導体が
得られるが、必要ならばＨＰＬＣで精製して99％以上の
純度のオキサジアゾロン誘導体（Ｉ）を得ることができ
る。After the resin is separated from the resin, the resin is removed by filtration, the supernatant is collected, and the solvent is distilled off to obtain the oxadiazolone derivative of the above formula (I) having a purity of about 70%. Then, it can be purified by HPLC to obtain the oxadiazolone derivative (I) having a purity of 99% or more.
【００２１】本発明で用いられる次式（Ｖ）The following formula (V) used in the present invention:
【００２２】[0022]
【化１３】 （式中、ＲはＨ、アルキル基またはアルコキシ基）で示
されるオキサジアゾロン誘導体−樹脂結合体は、次式
（IV）Embedded image (Where R is H, an alkyl group or an alkoxy group), the oxadiazolone derivative-resin conjugate represented by the following formula (IV)
【００２３】[0023]
【化１４】 （式中、ＲはＨ、アルキル基またはアルコキシ基）で示
されるヒドラジド-樹脂結合体を、トリホスゲンで環化
させることによって得ることができる。具体的には、例
えば、前記式（IV）で示されるヒドラジド-樹脂結合体
をテトラヒドロフラン中、トリホスゲンで処理すること
により得られる。その際の反応温度は、0〜50℃が好ま
しいが、更に好ましくは25℃〜40℃である。Embedded image (Wherein R is H, an alkyl group or an alkoxy group) and can be obtained by cyclizing a hydrazide-resin conjugate represented by triphosgene. Specifically, for example, it is obtained by treating the hydrazide-resin conjugate represented by the formula (IV) with triphosgene in tetrahydrofuran. The reaction temperature at that time is preferably 0 to 50 ° C, more preferably 25 to 40 ° C.
【００２４】また、トリホスゲンの使用量は、ヒドラジ
ド-樹脂結合体に対して2乃至3倍（当量）過剰に使用す
ることが好ましい。またこの反応は、1回だけでも、原
料の20〜50%程度が前記式（Ｖ）で示されるオキサジア
ゾロン誘導体−樹脂結合体に転化するが、転化率を向上
させるため反応を2回以上繰り返すことが好ましい。反
応を繰り返す際には、樹脂をテトラヒドロフランで十分
に洗浄し、前回の反応で生成した副生成物や、過剰の試
薬等を除いてから、次の反応を開始できるという特徴を
有する。The amount of triphosgene used is preferably 2 to 3 times (equivalent) excess with respect to the hydrazide-resin conjugate. In this reaction, about 20 to 50% of the raw material is converted to the oxadiazolone derivative-resin conjugate represented by the formula (V) even once, but the reaction is performed twice or more to improve the conversion. It is preferred to repeat. When the reaction is repeated, the resin is sufficiently washed with tetrahydrofuran to remove the by-products generated in the previous reaction, excess reagents, and the like, before starting the next reaction.
【００２５】本発明で用いられる次式（IV）で示される
ヒドラジド-樹脂結合体は、次式（III）The hydrazide-resin conjugate represented by the following formula (IV) used in the present invention is represented by the following formula (III)
【００２６】[0026]
【化１５】 で示されるジメチルマロン酸-樹脂結合体と、次式（V
I）Embedded image And a dimethylmalonic acid-resin conjugate represented by the following formula (V
I)
【００２７】[0027]
【化１６】 （式中、ＲはＨ、アルキル基またはアルコキシ基）で表
されるジクロロフェニルヒドラジンとを脱水縮合反応さ
せて得られる。Embedded image (Wherein R is H, an alkyl group or an alkoxy group) and is obtained by a dehydration condensation reaction with dichlorophenylhydrazine represented by the following formula:
【００２８】ジクロロフェニルヒドラジンとしては、5-
イソプロポキシ-2,4-ジクロロフェニルヒドラジン、5−
メトキシ-2,4-ジクロロフェニルヒドラジン、5-エトキ
シ-2,4-ジクロロフェニルヒドラジン、2,4-ジクロロフ
ェニルヒドラジン等が挙げられるが、5-イソプロポキシ
-2,4-ジクロロフェニルヒドラジンが好ましく用いられ
る。この5-イソプロポキシ-2,4-ジクロロフェニルヒド
ラジンは、米国特許第４,７０５,５５７号明細書に従
い、対応するジクロロアニリン誘導体をジアゾ化し、つ
いで塩化すずを用いて還元反応を行うことにより製造す
ることができる。Dichlorophenylhydrazine includes 5-
Isopropoxy-2,4-dichlorophenylhydrazine, 5-
Methoxy-2,4-dichlorophenylhydrazine, 5-ethoxy-2,4-dichlorophenylhydrazine, 2,4-dichlorophenylhydrazine and the like, but 5-isopropoxy
-2,4-Dichlorophenylhydrazine is preferably used. The 5-isopropoxy-2,4-dichlorophenylhydrazine is produced by diazotizing the corresponding dichloroaniline derivative and then performing a reduction reaction using tin chloride according to U.S. Pat. No. 4,705,557. be able to.
【００２９】反応に用いられる溶媒としては、ジメチル
ホルムアミド、テトラヒドロフラン、ジクロロメタン等
が用いられる。また、脱水剤としては、ジシクロヘキシ
ルカルボジイミド、１−エチル−３−（３’−ジメチル
アミノプロピル）カルボジイミド、ベンゾトリアゾール
-1-イル-オキシ-トリス（ジメチルアミノ）フォスフォ
ニウム ヘキサフルオロフォスフェート、カルボニルジ
イミダゾール、２−（1Ｈベンゾトリアゾール−１−イ
ル）−１，１,３，３−テトラメチルウロニウムヘキサ
フルオロフォスフェート、ベンゾトリアゾール−１−イ
ル−オキシ−トリス−ピロリジノ−フォフォニウム ヘ
キサフルオロフォスフェート等が挙げられる。また、塩
基としては、トリエチルアミンやジイソプロピルエチル
アミン等の3級アミンが好ましく用いられる。As a solvent used in the reaction, dimethylformamide, tetrahydrofuran, dichloromethane and the like are used. Examples of the dehydrating agent include dicyclohexylcarbodiimide, 1-ethyl-3- (3′-dimethylaminopropyl) carbodiimide, and benzotriazole.
-1-yl-oxy-tris (dimethylamino) phosphonium hexafluorophosphate, carbonyldiimidazole, 2- (1Hbenzotriazol-1-yl) -1,1,3,3-tetramethyluronium hexafluoro Phosphate, benzotriazol-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate and the like. As the base, a tertiary amine such as triethylamine or diisopropylethylamine is preferably used.
【００３０】本発明の前記式（III）で示されるジメチ
ルマロン酸-樹脂結合体は次式（II）The dimethylmalonic acid-resin conjugate represented by the above formula (III) of the present invention is represented by the following formula (II)
【００３１】[0031]
【化１７】 （式中、XはHまたはClを表す）で示されるトリチルクロ
リド樹脂とジメチルマロン酸を適当な第３級アミンの存
在下、テトラヒドロフラン中で反応させて得られる。そ
の際の反応温度は、10〜30℃が好ましく、また、ジメチ
ルマロン酸は2〜5当量使用するのが好ましく、第３級ア
ミンは1〜2当量使用することが好ましい。Embedded image (Wherein X represents H or Cl) obtained by reacting a trityl chloride resin represented by the following formula with dimethylmalonic acid in tetrahydrofuran in the presence of a suitable tertiary amine. The reaction temperature at that time is preferably 10 to 30 ° C., preferably 2 to 5 equivalents of dimethylmalonic acid, and 1 to 2 equivalents of the tertiary amine.
【００３２】本発明の前記式（II）〜（V）で示される
化合物で使用される樹脂としては、４−メチルトリチル
クロリド樹脂、４−メトキシトリチルクロリド樹脂、ジ
クロロトリチルアルコール樹脂等のトリチル樹脂が挙げ
られるが、本発明では、２−クロロトリチルクロリド樹
脂という名称で市販されている樹脂が好ましく用いら
れ、この樹脂は容易に入手できる。この樹脂の架橋度は
好ましくは1%〜2%、大きさは好ましくは100〜200メッシ
ュ、官能基の含有率は好ましくは0.1mmol/g以上、より
好ましくは0.5mmol/g以上の樹脂が好ましく用いられ
る。Examples of the resin used in the compounds represented by the above formulas (II) to (V) of the present invention include trityl resins such as 4-methyltrityl chloride resin, 4-methoxytrityl chloride resin, and dichlorotrityl alcohol resin. In the present invention, a resin commercially available under the name of 2-chlorotrityl chloride resin is preferably used, and this resin is easily available. The crosslinking degree of this resin is preferably 1% to 2%, the size is preferably 100 to 200 mesh, and the content of the functional group is preferably 0.1 mmol / g or more, more preferably 0.5 mmol / g or more. Used.
【００３３】本発明で得られる前記式（I）で示される
オキサジアゾロン誘導体は、農薬として使用され環境中
に散逸したオキサジアゾロンの代謝物を分析する際の標
品として好ましく用いられる。The oxadiazolone derivative represented by the above formula (I) obtained by the present invention is preferably used as a standard when analyzing metabolites of oxadiazolone which are used as agricultural chemicals and dissipated in the environment.
【００３４】[0034]
【実施例】以下、実施例を挙げて更に本発明を具体的に
説明する。EXAMPLES The present invention will be described more specifically below with reference to examples.
【００３５】［実施例１］ 式（III）のジメチルマロ
ン酸-樹脂結合物の製造 ジメチルマロン酸4.54gを乾燥テトラヒドロフランに溶
解し、これにジイソプロピルエチルアミン3.3mlを加え
た。この溶液をクロロトリチルクロリド樹脂12.55gに添
加し、室温で3時間振とうした。上清を除きテトラヒド
ロフランで5回洗浄し、減圧乾燥して式（III）のジメチ
ルマロン酸-樹脂結合物を得た。反応後の樹脂重量は15.
35g（2.8gの増加）であった。Example 1 Dimethyl malo of the formula (III)
Preparation of acid-resin conjugate 4.54 g of dimethylmalonic acid was dissolved in dry tetrahydrofuran, and 3.3 ml of diisopropylethylamine was added thereto. This solution was added to 12.55 g of chlorotrityl chloride resin and shaken at room temperature for 3 hours. The supernatant was removed, and the mixture was washed five times with tetrahydrofuran and dried under reduced pressure to obtain a dimethylmalonic acid-resin conjugate of the formula (III). Resin weight after reaction is 15.
35 g (2.8 g increase).
【００３６】［実施例２］ 式（IV）のヒドラジド-樹
脂結合体の製造 式(III）のジメチルマロン酸-樹脂結合物15.35gをジメ
チルホルムアミド80mlに膨潤させ、ベンゾトリアゾール
-1-イル-オキシ-トリス（ジメチルアミノ）フォスフォ
ニウム24.34ｇ、ジイソプロピルエチルアミン10.5ml、5
-イソプロポキシ-2,4-ジクロロヒドラジン12.13ｇを順
に加えた後、室温で一夜振とうした。反応終了後、樹脂
をジメチルホルムアミドで6回、テトラヒドロフランで3
回洗浄し、減圧乾燥し、式（IV）のヒドラジド-樹脂結
合体を得た。このヒドラジド-樹脂結合体を重クロロホ
ルム溶液に分散させ、高分解能溶液MASプローブを使用
した1H-NMR分析を行なった。測定結果を図１に示す。Example 2 Hydrazide Tree of Formula (IV)
Preparation of Fat Conjugate 15.35 g of dimethylmalonic acid-resin conjugate of formula (III) is swollen in 80 ml of dimethylformamide, and benzotriazole
1-yl-oxy-tris (dimethylamino) phosphonium 24.34 g, diisopropylethylamine 10.5 ml, 5
After 12.13 g of -isopropoxy-2,4-dichlorohydrazine was added in order, the mixture was shaken at room temperature overnight. After completion of the reaction, the resin was washed six times with dimethylformamide and three times with tetrahydrofuran.
After washing twice and drying under reduced pressure, a hydrazide-resin conjugate of the formula (IV) was obtained. This hydrazide-resin conjugate was dispersed in a heavy chloroform solution, and subjected to 1 H-NMR analysis using a high-resolution MAS probe. FIG. 1 shows the measurement results.
【００３７】［実施例３］ 式（Ｖ）のオキサジアゾン
誘導体−樹脂結合体の製造 式（IV）のヒドラジド-樹脂結合体12.55ｇをテトラヒド
ロフラン80mlに膨潤させ、ジイソプロピルエチルアミン
30.0mlを加え、氷浴で冷却した。そこに、トリホスゲン
5.10ｇをテトラヒドロフラン20mlに溶解した溶液をゆっ
くりと加えた。全量加えた後、室温で一夜振とうした。
反応終了後、上清を除きテトラヒドロフランで4回樹脂
を洗浄した。この段階で樹脂1mgを採取し、実施例４の
処方に従い1%トリフルオロ酢酸−ジクロロメタン溶液で
処理後、ＨＰＬＣ分析を行ったところ、原料が60%程度
残存していることが判明した。そのため1回目の反応と
同じ条件で2回目の反応を行った。2回目の反応終了後反
応の進行を同様にチェックしたところ原料が消失してい
たので、反応を終了とした。樹脂全量をテトラヒドロフ
ラン、水、テトラヒドロフラン、ジクロロメタンで3回
づつ順に洗浄し、式（Ｖ）のオキサジアゾン誘導体−樹
脂結合体を得た。Example 3 Oxadiazone of Formula (V)
Preparation of derivative-resin conjugate 12.55 g of the hydrazide- resin conjugate of the formula (IV) is swollen in 80 ml of tetrahydrofuran, and diisopropylethylamine is added.
30.0 ml was added and cooled in an ice bath. There, triphosgene
A solution of 5.10 g in 20 ml of tetrahydrofuran was slowly added. After adding the whole amount, the mixture was shaken at room temperature overnight.
After completion of the reaction, the supernatant was removed and the resin was washed four times with tetrahydrofuran. At this stage, 1 mg of the resin was collected, treated with a 1% trifluoroacetic acid-dichloromethane solution according to the recipe of Example 4, and then subjected to HPLC analysis. As a result, it was found that about 60% of the raw material remained. Therefore, a second reaction was performed under the same conditions as the first reaction. After the completion of the second reaction, the progress of the reaction was checked in the same manner. When the raw materials had disappeared, the reaction was terminated. The whole amount of the resin was washed with tetrahydrofuran, water, tetrahydrofuran, and dichloromethane three times in order to obtain an oxadiazone derivative-resin conjugate of the formula (V).
【００３８】［実施例４］ 式（VI）のオキサジアゾン
アシッドの製造 実施例３で得られた式（Ｖ）のオキサジアゾン誘導体−
樹脂結合体に1%トリフルオロ酢酸−ジクロロメタン溶液
を加え2時間振とうした。上清を濾別し、樹脂をテトラ
ヒドロフランで3回洗浄した。有機層を混合し、溶媒を
留去してオキサジアゾンアシッドの粗成物4.7gを得た。
粗成物を逆相ＨＰＬＣで精製し、オキサジアゾンアシッ
ド3.62gを得た。Example 4 Oxadiazone of Formula (VI)
Preparation of Acid Oxadiazone Derivative of Formula (V) Obtained in Example 3
A 1% trifluoroacetic acid-dichloromethane solution was added to the resin conjugate and shaken for 2 hours. The supernatant was filtered off and the resin was washed three times with tetrahydrofuran. The organic layers were mixed and the solvent was distilled off to obtain 4.7 g of a crude product of oxadiazon acid.
The crude product was purified by reverse phase HPLC to obtain 3.62 g of oxadiazon acid.
【００３９】［実施例５］実施例1に従って製造したジ
メチルマロン酸-樹脂結合物240mg及び２、４−ジクロロ
フェニルヒドラジン187mgを用いて、実施例２の方法に
準じて操作し、ヒドラジド-樹脂結合物を得た。ついで
このヒドラジド-樹脂結合物220mgを用い、実施例３及び
４の方法に準じて環化、ついで樹脂からオキサジアゾロ
ン誘導体の解離操作を実施し、108mgの粗成物を得た。
またHPLCで精製すると、32mgのオキサジアゾロン誘導体
（R=H)が得られた。Example 5 A hydrazide-resin conjugate was prepared using 240 mg of the dimethylmalonic acid-resin conjugate prepared according to Example 1 and 187 mg of 2,4-dichlorophenylhydrazine according to the method of Example 2. I got Then, using 220 mg of this hydrazide-resin conjugate, cyclization was carried out according to the methods of Examples 3 and 4, and then the dissociation operation of the oxadiazolone derivative from the resin was carried out to obtain 108 mg of a crude product.
Purification by HPLC yielded 32 mg of the oxadiazolone derivative (R = H).
【００４０】[0040]
【発明の効果】本発明によれば、固体樹脂表面上で、ヒ
ドラジドにトリホスゲンを作用させオキサジアゾロン骨
格を構築し、最後に樹脂から目的物を解離させることに
より、簡便かつ安全にオキサジアゾンアシッド等を製造
することがでる。According to the present invention, an oxadiazolone skeleton is constructed by reacting hydrazide with triphosgene on the surface of a solid resin, and finally, the target substance is dissociated from the resin, so that oxadiazon acid or the like can be easily and safely obtained. Can be manufactured.
【図１】 ヒドラジド-樹脂結合体のＮＭＲチャート。FIG. 1 is an NMR chart of a hydrazide-resin conjugate.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 小椋 征 神奈川県鎌倉市手広1111番地 株式会社東 レリサーチセンター内 Ｆターム(参考） 4C056 AA01 AB02 AC05 AC07 AD01 AE03 AF01 FA16 FA17 FB05 FC04 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor, Osamu Ogura, 1111 Tehiro, Kamakura-shi, Kanagawa F-term in East Research Center Co., Ltd. 4C056 AA01 AB02 AC05 AC07 AD01 AE03 AF01 FA16 FA17 FB05 FC04
Claims (5)
されるオキサジアゾロン誘導体−樹脂結合体を加水分解
して樹脂と解離させることを特徴とする次式(Ｉ） 【化２】 （式中、ＲはＨ、アルキル基またはアルコキシ基）で示
されるオキサジアゾロン誘導体の製造方法。1. The following formula (V): Wherein R is H, an alkyl group or an alkoxy group, wherein the oxadiazolone derivative-resin conjugate represented by the following formula (I) is dissociated from the resin by hydrolysis: (Wherein, R is H, an alkyl group or an alkoxy group) A method for producing an oxadiazolone derivative represented by the formula:
されるヒドラジド-樹脂結合体に、トリホスゲンを作用
させてオキサジアゾロン環を形成させて得られた次式
（Ｖ） 【化４】 （式中、ＲはＨ、アルキル基またはアルコキシ基）で示
されるオキサジアゾロン誘導体−樹脂結合体を用いるこ
とを特徴とする請求項１記載のオキサジアゾロン誘導体
の製造方法。2. The following formula (IV): (Wherein R is H, an alkyl group or an alkoxy group) and a hydrazide-resin conjugate represented by the following formula (V) obtained by reacting triphosgene to form an oxadiazolone ring: The method for producing an oxadiazolone derivative according to claim 1, wherein an oxadiazolone derivative-resin conjugate represented by the formula (wherein R is H, an alkyl group or an alkoxy group) is used.
導体が、オキサジアゾンアシッドである請求項１または
２記載のオキサジアゾロン誘導体の製造方法。3. The method for producing an oxadiazolone derivative according to claim 1, wherein the oxadiazolone derivative represented by the formula (I) is oxadiazone acid.
を特徴とする請求項１〜３のいずれかに記載のオキサジ
アゾロン誘導体の製造方法。4. The method for producing an oxadiazolone derivative according to claim 1, wherein a trityl resin is used as the resin.
されるヒドラジド-樹脂結合体に、トリホスゲンを作用
させてオキサジアゾロン環を形成させることを特徴とす
る次式（Ｖ） 【化６】 （式中、ＲはＨ、アルキル基またはアルコキシ基）で示
されるオキサジアゾロン誘導体−樹脂結合体の製造方
法。5. The following formula (IV): (Wherein R is H, an alkyl group or an alkoxy group), by reacting triphosgene on a hydrazide-resin conjugate represented by the following formula (V): (Wherein R is H, an alkyl group or an alkoxy group) A method for producing an oxadiazolone derivative-resin conjugate represented by the formula:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11099587A JP2000290267A (en) | 1999-04-07 | 1999-04-07 | Production of oxadiazolone derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11099587A JP2000290267A (en) | 1999-04-07 | 1999-04-07 | Production of oxadiazolone derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000290267A true JP2000290267A (en) | 2000-10-17 |
Family
ID=14251236
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11099587A Pending JP2000290267A (en) | 1999-04-07 | 1999-04-07 | Production of oxadiazolone derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2000290267A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1285750A2 (en) | 2001-08-21 | 2003-02-26 | Mitsubishi Heavy Industries, Ltd. | Plate-making type printing press, multi-color printing press and plate-making type printing method |
| CN102924323A (en) * | 2012-11-21 | 2013-02-13 | 合肥星宇化学有限责任公司 | Neutralization improvement method for production of oxadiazon |
-
1999
- 1999-04-07 JP JP11099587A patent/JP2000290267A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1285750A2 (en) | 2001-08-21 | 2003-02-26 | Mitsubishi Heavy Industries, Ltd. | Plate-making type printing press, multi-color printing press and plate-making type printing method |
| CN102924323A (en) * | 2012-11-21 | 2013-02-13 | 合肥星宇化学有限责任公司 | Neutralization improvement method for production of oxadiazon |
| CN102924323B (en) * | 2012-11-21 | 2015-04-01 | 合肥星宇化学有限责任公司 | Neutralization improvement method for production of oxadiazon |
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