JPH01213272A - Production of isoxazolidine - Google Patents
Production of isoxazolidineInfo
- Publication number
- JPH01213272A JPH01213272A JP3745788A JP3745788A JPH01213272A JP H01213272 A JPH01213272 A JP H01213272A JP 3745788 A JP3745788 A JP 3745788A JP 3745788 A JP3745788 A JP 3745788A JP H01213272 A JPH01213272 A JP H01213272A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- reaction
- hydrolysis
- isoxazolidine
- 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 22
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 35
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 5
- 125000005843 halogen group Chemical group 0.000 claims abstract 2
- 239000000126 substance Substances 0.000 claims description 10
- 150000002546 isoxazolidines Chemical class 0.000 claims description 9
- 150000002240 furans Chemical class 0.000 claims description 2
- 150000002790 naphthalenes Chemical class 0.000 claims description 2
- 150000003577 thiophenes Chemical class 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 150000003222 pyridines Chemical class 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 21
- 239000002253 acid Substances 0.000 abstract description 15
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 11
- 230000007062 hydrolysis Effects 0.000 abstract description 9
- 229910052500 inorganic mineral Inorganic materials 0.000 abstract description 7
- 239000011707 mineral Substances 0.000 abstract description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 abstract description 6
- 238000004880 explosion Methods 0.000 abstract description 5
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical class BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 abstract description 3
- 125000003118 aryl group Chemical group 0.000 abstract description 3
- 239000003905 agrochemical Substances 0.000 abstract description 2
- 125000003342 alkenyl group Chemical group 0.000 abstract description 2
- 125000003710 aryl alkyl group Chemical group 0.000 abstract description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract description 2
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract 3
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 abstract 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 abstract 2
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract 1
- 229930192474 thiophene Natural products 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000009835 boiling Methods 0.000 description 8
- PGPQZSDFRTWCCZ-UHFFFAOYSA-N ethyl 1,2-oxazolidine-2-carboxylate Chemical compound CCOC(=O)N1CCCO1 PGPQZSDFRTWCCZ-UHFFFAOYSA-N 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- -1 after hydrolysis Substances 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 235000010755 mineral Nutrition 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- HPIVVOQIZYNVJE-UHFFFAOYSA-N 1,2-oxazolidin-2-ium;chloride Chemical compound Cl.C1CNOC1 HPIVVOQIZYNVJE-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 235000011007 phosphoric acid Nutrition 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 235000011118 potassium hydroxide Nutrition 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- VGEWEGHHYWGXGG-UHFFFAOYSA-N ethyl n-hydroxycarbamate Chemical compound CCOC(=O)NO VGEWEGHHYWGXGG-UHFFFAOYSA-N 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- ZRUBRZSVKDGKBQ-UHFFFAOYSA-N 1,2-oxazolidin-2-yl(phenyl)methanone Chemical compound C=1C=CC=CC=1C(=O)N1CCCO1 ZRUBRZSVKDGKBQ-UHFFFAOYSA-N 0.000 description 1
- ARITXYXYCOZKMU-UHFFFAOYSA-N 2,2-dibromopropane Chemical class CC(C)(Br)Br ARITXYXYCOZKMU-UHFFFAOYSA-N 0.000 description 1
- QHOINBKBMJLHPY-UHFFFAOYSA-N 2-chloroethyl formate Chemical compound ClCCOC=O QHOINBKBMJLHPY-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- NLPZOYIVSMAHLA-UHFFFAOYSA-N n-hydroxy-3-methylpyridine-2-carboxamide Chemical compound CC1=CC=CN=C1C(=O)NO NLPZOYIVSMAHLA-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- WQDUMFSSJAZKTM-UHFFFAOYSA-N sodium methoxide Substances [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- UTLZBWAGLRNNAY-UHFFFAOYSA-J thorium(4+);dicarbonate Chemical compound [Th+4].[O-]C([O-])=O.[O-]C([O-])=O UTLZBWAGLRNNAY-UHFFFAOYSA-J 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、イソオキサゾリジン類の新規な製造方法に関
する。DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a novel method for producing isoxazolidines.
イソオキサゾリジン類は、医薬、農薬などの生理活性物
質合成のための中間体として、また安定剤１機能性物質
あるいはその合成中間体などの化成品として広範に利用
できる。従って、化学工業分野で有用である。Isoxazolidines can be widely used as intermediates for the synthesis of physiologically active substances such as medicines and agricultural chemicals, and as chemical products such as stabilizer monofunctional substances or synthetic intermediates thereof. Therefore, it is useful in the chemical industry.
（従来の技術）
従来、イソオキサゾリジンの製法としては、ジャーナル
オブ ケミカル ソサイエティ１９４２年第４３２頁
に２Ｍ料としてエトキシヵルボニルイソオキサゾリジン
（ｍ）を用い、この塩酸による加水分解により、イソオ
キサゾリジン塩酸塩（ｍＶ）が得られたと記載されてい
るのみで（ＩＩＩ） （ｒｖ）しかし
ながら、本発明にみるような、後記−数式（Ｉ）で示さ
れるアシルイソオキサゾリジン話導体を加水分解して、
後記−数式（ＩＩ）で示されるイソオキサゾリジンを製
造する方法に関しては、全く文献に記載がない。(Prior art) Conventionally, as a method for producing isoxazolidine, as described in Journal of Chemical Society, 1942, p. 432, ethoxycarbonyl isoxazolidine (m) is used as a 2M material, and isoxazolidine hydrochloride ( (III) (rv) However, as seen in the present invention, by hydrolyzing an acylisoxazolidine conductor represented by formula (I) below,
There is no description in the literature regarding the method for producing the isoxazolidine represented by the following formula (II).
（発明が解決しようとする課題）
前述した文献に記載の方法、すなわち、エトキシカルボ
ニルイソオキサゾリジン（ｍ）を加水分解してイソオキ
サゾリジン塩酸塩（１７）を得ようとすると、この反応
では、用いたエトキシカルボニルイソオキサゾリジン（
ｍ）と等モルの炭酸ガスが発生する。大量の炭酸ガスの
発生は、反応装置の爆発を起こすことがある。特に中に
含まれている不純物の触媒作用あるいは反応容器の局部
的加熱などにより１反応か連鎖的に起こった場合は、爆
発による大事故につながる危険性がある。(Problems to be Solved by the Invention) When trying to obtain isoxazolidine hydrochloride (17) by the method described in the above-mentioned literature, that is, by hydrolyzing ethoxycarbonyl isoxazolidine (m), in this reaction, the Ethoxycarbonyl isoxazolidine (
Equimolar carbon dioxide gas is generated. The generation of large amounts of carbon dioxide gas may cause an explosion of the reactor. In particular, if a single reaction or a chain reaction occurs due to the catalytic action of impurities contained therein or local heating of the reaction vessel, there is a risk of a major accident due to explosion.
そのため、工業的な製法としては好ましくない。Therefore, it is not preferred as an industrial manufacturing method.
一方、これまでイソオキサゾリジン（ＩＶ）の前駆体で
あるエトキシカルボニルイソオキサゾリジン（ｍ）を得
るには、Ｎ−ヒドロキシウレタンと１．３−ジブロモプ
ロパンとの反応によって得られる（前記ジャーナル オ
ブ ケミカル ソサイエテイ １９４２年第４３２頁）
、ところか、原料のＮ−ヒドロキシウレタンを得るには
、ホスゲンとエタノールとの反応によって得られる、毒
性の高いクロルエチルホルメートとヒドロキシルアミン
との反応によらなければならない。そのため、従来のエ
トキシカルボニルイソオキサゾリジンを使用する反応経
路では、人畜毒性の極めて高いホスゲンの使用が不可避
であり、工業的な製造方法としては問題かある。On the other hand, until now, ethoxycarbonyl isoxazolidine (m), which is a precursor of isoxazolidine (IV), can be obtained by reacting N-hydroxyurethane with 1,3-dibromopropane (Journal of Chemical Society 1942). p. 432)
However, in order to obtain the raw material N-hydroxyurethane, it is necessary to react with hydroxylamine and highly toxic chloroethyl formate, which is obtained by reacting phosgene with ethanol. Therefore, in the conventional reaction route using ethoxycarbonyl isoxazolidine, the use of phosgene, which is extremely toxic to humans and animals, is unavoidable, which is problematic as an industrial production method.
こうした事情に鑑み、本発明は、爆発の危険性がなく、
また人畜毒性のない原料を使用し、工業的規模の製造に
適したイソオキサゾリジン類の新しい製法を確立するこ
とを目的とするものである。In view of these circumstances, the present invention has no danger of explosion,
The aim is also to establish a new method for producing isoxazolidines that is suitable for industrial scale production and uses raw materials that are non-toxic to humans and animals.
帽１を解決するための手段）
本発明者らは、上記課題を達成するため、数多くの反応
について鋭意検討した。その結果、下記の一般式（Ｉ）
〔式中、Ｒ１は、アルキル基、アルケニル基。Means for Solving Problem 1) In order to achieve the above object, the present inventors have intensively studied numerous reactions. As a result, the following general formula (I) [wherein R1 is an alkyl group or an alkenyl group].
シクロアルキル基、シクロアルキルアルキル基、アリー
ル基またはアリールアルキル基（ただし、アリールとは
、ベンゼン核、ナフタレン核、とりジン核、チオフェン
核またはフラン核を意味し、これらの核は、３個までの
同一または相異なるハロゲン原子、低級アルキル基、低
級ハロアルキル基、低級アルコキシ基およびニトロ基で
置換されでもよい）を示し、Ｒ２は低級アルキル基を示
し、ｎはθ〜３の整数を示し、Ａは一〇−基または−Ｓ
−基を示す〕で表される化合物を出発原料とじ４これを
加水分解することにより、−数式〔式中、Ｒ２は、低級
アルキル基を示し、ｎはθ〜３の整数を示す〕て表され
るイソオキサゾリジン類を収率よくしかも安全で、有利
に製造できることを見出した。Cycloalkyl group, cycloalkylalkyl group, aryl group or arylalkyl group (Aryl means benzene nucleus, naphthalene nucleus, toridine nucleus, thiophene nucleus or furan nucleus, and up to 3 of these nuclei R2 represents a lower alkyl group, n represents an integer of θ to 3, and A represents 10-group or -S
By hydrolyzing the starting material, a compound represented by the formula [wherein, R2 represents a lower alkyl group, and n represents an integer from θ to 3] is prepared as a starting material. We have discovered that it is possible to advantageously produce isoxazolidines with good yield and safety.
本発明の加水分解反応を実施するには、（Ｉ）式化合物
に単に水を入れ、これを加温することによっても行なわ
れるが１通常は反応を速めるため、さらに酸または塩基
を使用して加水分解するのかよい、この場合、（ｒ）式
化合物を加水分解した後（■）式化合物を酸の塩として
取扱うことか操作上便利であることから、酸での加水分
解か好ましい。本反応で使用しつる酸類としては、塩酸
、硫酸および燐酸などの鉱酸類が好ましく、また使用し
うる塩基として、力性ソーダ、カ性カリあるいは炭酸壬
トリウムなどがあげられる。The hydrolysis reaction of the present invention can be carried out by simply adding water to the compound of formula (I) and heating it; however, in order to speed up the reaction, an acid or base is usually used. In this case, it is preferable to hydrolyze the compound of formula (r) and then treat the compound of formula (■) as an acid salt because it is convenient in operation. The phosphoric acids used in this reaction are preferably mineral acids such as hydrochloric acid, sulfuric acid, and phosphoric acid, and the bases that can be used include sodium hydroxide, caustic potash, and thorium carbonate.
酸類を使用して加水分解を行う場合は、（Ｉ）式化合物
に対して１当量モル以上、好ましくは１．５〜３当量モ
ルの酸を含む水溶液を（Ｉ）式化合物と混合し、加温す
ればよい０反応温度は室温から水の沸点まで自由に選べ
るか、通常は室温より沸点まで加温し１反応を完結させ
る０反応終了後、鉱酸が塩酸でＲが低分子量の場合、水
と共に酸残基を留去することにより（ｎ）式化合物の塩
酸塩が得られ、このものをアルコール中、アルコキシド
、力性ソーダあるいは力性カリなどで遊離化し、塩類を
除いた後アルコールを留去することにより、（ＩＩ）式
化合物が得られる。またＲが低分子量でなく鉱酸か塩酸
の場合は、加水分解後、酸残基をトルエン、テトラヒド
ロフランあるいはクロロホルムなどで抽出して除いた後
、水を留去することにより、（■）式化合物の塩酸塩が
得られる。鉱酸が塩酸以外の場合１通常は加水分解後、
過剰の鉱酸を力性ソーダ、力性カリ、あるいは炭酸ナト
リウムなどで中和し、Ｒが低分子の場合はそのまま、そ
れ以外の場合は酸残基を抽出後、水を留去すると、（Ｉ
Ｉ）式化合物と無機塩の混合物が得られ、アルコール中
で遊離化することにより、（ｎ）式化合物が得られる。When hydrolysis is carried out using acids, an aqueous solution containing 1 equivalent mole or more, preferably 1.5 to 3 equivalent moles of acid based on the compound of formula (I) is mixed with the compound of formula (I), and the hydrolysis is carried out by mixing the compound with formula (I). The reaction temperature can be freely selected from room temperature to the boiling point of water, or it is usually heated from room temperature to the boiling point to complete one reaction.After the reaction is complete, if the mineral acid is hydrochloric acid and R is low molecular weight, By distilling off the acid residue together with water, the hydrochloride of the compound of formula (n) is obtained, which is liberated in alcohol, alkoxide, sodium hydroxide, sodium hydroxide, potassium hydroxide, etc. After removing the salts, the alcohol is removed. By distilling off, a compound of formula (II) is obtained. In addition, if R is not a low molecular weight mineral acid or hydrochloric acid, after hydrolysis, acid residues are removed by extraction with toluene, tetrahydrofuran, chloroform, etc., and water is distilled off to form a compound of formula (■). of hydrochloride is obtained. When the mineral acid is other than hydrochloric acid 1 Usually after hydrolysis,
Excess mineral acid is neutralized with hydric soda, hydric potassium, or sodium carbonate, etc. If R is a low molecular weight, leave it as is; otherwise, after extracting the acid residue, water is distilled off. I
A mixture of a compound of formula I) and an inorganic salt is obtained, and by liberating it in alcohol, a compound of formula (n) is obtained.
塩基を使用して加水分解を行う場合は、（Ｉ）式化合物
に対して１当量モル以上、好ましくは１〜２当量モルの
アルカリを含む水溶液と（Ｉ）式化合物を混合すること
によって行なわれる。加温は水の沸点まで選択できるが
１通常は５０℃〜６０℃で十分な場合が多い０反応終了
後は、水を留去すれば（ＩＩ）式化合物が得られる。ま
た場合によっては、得られた反応液に塩酸、硫酸および
燐酸などの鉱酸類を加えて塩となし、前記酸分解の場合
と同様に処理することにより、（ＩＩ）式化合物を得る
ことができる。When hydrolysis is carried out using a base, it is carried out by mixing the compound of formula (I) with an aqueous solution containing an alkali of 1 equivalent mole or more, preferably 1 to 2 equivalent moles, based on the compound of formula (I). . Heating can be selected up to the boiling point of water, but usually 50°C to 60°C is often sufficient. After the reaction is complete, the compound of formula (II) can be obtained by distilling off water. In some cases, the compound of formula (II) can be obtained by adding mineral acids such as hydrochloric acid, sulfuric acid, and phosphoric acid to the obtained reaction solution to form a salt, and treating it in the same manner as in the case of acid decomposition. .
なお、原料である（Ｉ）式化合物は、例えば、ジャーナ
ル オブ オルガニック ケミストリー第３６巻第２８
４頁（１９７１年）に記載の方法またはこれに類似する
方法、すなわち、アシルヒドロキシルアミン類と１．３
−ジブロモプロパン誘導体と反応させることにより得ら
れる。In addition, the compound of formula (I) which is a raw material is described in, for example, Journal of Organic Chemistry, Vol. 36, No. 28.
4 (1971) or a method similar thereto, that is, acylhydroxylamines and 1.3
-obtained by reaction with dibromopropane derivatives.
本発明の製造方法による（■）式化合物の製造例を実施
例１〜５に示した。そして（Ｉ）式化合物の製造例を参
考製造例１〜３に示した。また第１表には、本発明で使
用した（Ｉ）式化合物およびそれらを用いた（ＩＩ）式
化合物の製造例をまとめて示した。Examples 1 to 5 show examples of manufacturing compounds of formula (■) according to the manufacturing method of the present invention. Production examples of the compound of formula (I) are shown in Reference Production Examples 1 to 3. Furthermore, Table 1 summarizes the formula (I) compounds used in the present invention and production examples of the formula (II) compounds using them.
ｎ−ヘキサノイル−３−メチルイソオキサゾリジン １
８．５ｇ、４Ｎ−塩酸 ５０ｍＭの混合物を加温し、１
０分還流した。冷却後、４Ｎ−力性ソーダ ２５ｒｎＪ
ｌを加え、減圧で水を留去した。残渣にテトラヒドロフ
ラン １００ ｍ ｌを加え、結晶を濾過により分取し
た。風乾後結晶を１００ｍ１のＩＮ−ナトリウムメトキ
シド溶液に入れ、結晶な濾別後、減圧にてメタノールを
留去した。残渣を減圧蒸留すると、標記化合物が沸点５
８−５９°Ｃ／２１ｍｍＨｇを示す無色油状物として、
７．１ｇ得られた。n-hexanoyl-3-methylisoxazolidine 1
A mixture of 8.5g and 4N hydrochloric acid 50mM was heated, and 1
Refluxed for 0 minutes. After cooling, 4N-hydrocarbon soda 25rnJ
1 was added, and water was distilled off under reduced pressure. 100 ml of tetrahydrofuran was added to the residue, and the crystals were collected by filtration. After air-drying, the crystals were placed in 100 ml of IN-sodium methoxide solution, the crystals were filtered off, and methanol was distilled off under reduced pressure. Distillation of the residue under reduced pressure yields the title compound with a boiling point of 5.
As a colorless oil exhibiting 8-59°C/21mmHg,
7.1g was obtained.
−←ＩＬＬ！Ω−イソオキサゾリジン（反応Ｎｏ９）ベ
ンゾイルイソオキサゾリジン １７．７ｇを使用し、実
施例１と同様に反応させ、処理し、蒸留すると、標記化
合物が沸点 ７０−７２℃／４０ ｍ ｍ Ｈｇを示す
無色油状物として、１４．７ｇ得られた。-←ILL! Ω-Isoxazolidine (Reaction No. 9) Using 17.7 g of benzoyl isoxazolidine, the reaction was carried out in the same manner as in Example 1, and the treatment and distillation yielded the title compound as a colorless oil having a boiling point of 70-72°C/40 mm Hg. As a product, 14.7g was obtained.
一←Ｗ−イソオキサゾリジン（反・Ｎｏ Ｉｓ）の製造
４−メトキシフェニルスルホニルイソオキサゾリジン
２４．３ｇ、ＩＮ−力性ソーダ １２０ｍ文の混合物を
６０°Ｃで３０分攪拌した。冷却後、ＩＮ−塩酸２０
ｍ ｌを加えた後減圧にて水を留去した。残渣にテトラ
ヒドロフラン １００ｍ文を加え結晶を濾別後、残液を
無水硫酸ナトリウムで乾燥した。減圧にて溶媒を留去後
、残液を減圧蒸留すると、標記化合物が沸点７０−７２
℃／４０ｍｍＨｇを示す無色油状物として、５．９ｇ得
られた。1←Production of W-isoxazolidine (anti-No Is) 4-methoxyphenylsulfonylisoxazolidine
A mixture of 24.3 g and 120 m of IN-strength soda was stirred at 60°C for 30 minutes. After cooling, IN-hydrochloric acid 20
After adding ml of water, water was distilled off under reduced pressure. After adding 100 m of tetrahydrofuran to the residue and filtering off the crystals, the remaining liquid was dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the remaining liquid was distilled under reduced pressure to obtain the title compound with a boiling point of 70-72.
5.9 g of a colorless oil having a temperature of 0.degree. C./40 mmHg was obtained.
（４５−メチルイソオキサゾリジン
α−ナフチルスルホニル−５−メチルイソオキサゾリジ
ン ２６．３ｇを使用し、実施例１と同様に反応させ、
処理し、蒸留すると、標記化合物が沸点 ７０−７２°
Ｃ／３１ｍｍＨｇを示す無色油状物として、７．０ｇ得
られた。(Using 26.3 g of 45-methylisoxazolidine α-naphthylsulfonyl-5-methylisoxazolidine, the reaction was carried out in the same manner as in Example 1,
When treated and distilled, the title compound has a boiling point of 70-72°
7.0 g of a colorless oil having a C/31 mmHg was obtained.
ベンジルスルホニル−３−エチルイソオキサゾリジン
２１．９ｇを使用し、実施例１と同様に反応させ、処理
し、蒸留すると、標記化合物が沸点 ６４−６５℃／
２２ ｍ ｍ Ｈｇを示す無色油状物として、８．５ｇ
得られた。Benzylsulfonyl-3-ethyl isoxazolidine
Using 21.9 g, the reaction, treatment and distillation were carried out in the same manner as in Example 1, resulting in the title compound having a boiling point of 64-65°C/
8.5 g as a colorless oil exhibiting 22 mm Hg
Obtained.
ペンズヒトロキザム９ １３．７ｇ、ｌ−ブロモ−３−
クロロプロパン １５．８ｇ、無水炭酸カリウム ２９
．０ｇおよびジメチルホルムアミド ２００ｍ文の混合
物を８０℃で１時間攪拌した。冷却後、塩を濾別し、濾
液を減圧にて濃縮した。残渣にクロロホルムを加え、水
洗後、無水硫酸ナトリウムで乾燥した。減圧にて溶媒を
留去すると標記化合物が淡黄色油状物として１６．８ｇ
得られた。シリカゲルカラムクロマトグラフィーで精製
すると無色油状物となり、 ｎｏ３＝ １．４４３４
を示した。Penzhitroxam 9 13.7g, l-bromo-3-
Chloropropane 15.8g, anhydrous potassium carbonate 29
．． A mixture of 0 g and 200 m of dimethylformamide was stirred at 80°C for 1 hour. After cooling, the salts were filtered off and the filtrate was concentrated under reduced pressure. Chloroform was added to the residue, washed with water, and then dried over anhydrous sodium sulfate. When the solvent was distilled off under reduced pressure, 16.8 g of the title compound was obtained as a pale yellow oil.
Obtained. When purified by silica gel column chromatography, it becomes a colorless oil, no. 3 = 1.4434
showed that.
パラトルエンスルホニルイソオキサゾリジン１８．７ｇ
、ｌ−ブロモ−３−クロロプロパン１５．８ｇ、水酸化
カリウム １１．５ｇおよびエタノール ２００ｍＪｌ
の混合物を５０℃で３時間攪拌した、冷却後、テトラヒ
ドロフラン、トルエンおよび水を加えて有機層を分取し
、水洗後無水硫酸ナトリウムで乾燥した。減圧にて溶媒
を留去すると、標記化合物が淡褐色結晶として１９．１
ｇ得られた。ヘキサン−酢酸エチル混合溶媒で再結晶す
ると白色結晶となり、融点 ９３−９４．５℃を示した
。Para-toluenesulfonylisoxazolidine 18.7g
, l-bromo-3-chloropropane 15.8g, potassium hydroxide 11.5g and ethanol 200mJl
The mixture was stirred at 50° C. for 3 hours, and after cooling, tetrahydrofuran, toluene and water were added to separate the organic layer, washed with water and dried over anhydrous sodium sulfate. When the solvent was distilled off under reduced pressure, the title compound was obtained as pale brown crystals with 19.1
g was obtained. Recrystallization from a hexane-ethyl acetate mixed solvent gave white crystals with a melting point of 93-94.5°C.
３−メチル−２−ピリジルカルボニルヒドロキシルアミ
ン １５．２ｇ、１．３−ジブロモプロパン ２０．２
ｇ、水酸化ナトリウム ８．８ｇおよびエタノール ２
００ｍＪｌを使用し、参考製造例１と同様に反応および
処理をすると、標記化合物が淡褐色油状物として１５．
５ｇ得られた。3-Methyl-2-pyridylcarbonylhydroxylamine 15.2g, 1,3-dibromopropane 20.2
g, sodium hydroxide 8.8g and ethanol 2
When the reaction and treatment were carried out in the same manner as in Reference Production Example 1 using 00 mJl, the title compound was obtained as a light brown oil with 15.0 mJl.
5g was obtained.
シリカゲルカラムクロマトグラフィーで精製すると無色
油状物となり、％３．＝１．４６８３を示した。Purification by silica gel column chromatography yields a colorless oil with a percentage of 3. =1.4683.
（発明の効果）
本発明の製造方法を実施したときには、従来のエトキシ
カルボニルイソオキサゾリジンの加水分解法による場合
に比べて、加水分解反応に伴なうガスの発生がなく、反
応は円滑に進むため爆発の危険性がない、そのため、目
的とするイソオキサゾリジン類を安全にかつ高収率で得
ることができる。(Effect of the invention) When the production method of the present invention is carried out, compared to the conventional hydrolysis method of ethoxycarbonyl isoxazolidine, there is no generation of gas accompanying the hydrolysis reaction, and the reaction proceeds smoothly. There is no danger of explosion, so the desired isoxazolidines can be obtained safely and in high yield.
また１本発明の製造方法によれば、これまで知られたイ
ソオキサゾリジンのみならず、これに各種の置換基を有
した種々のイソオキサゾリジンの製造にも応用しつる。Furthermore, the production method of the present invention can be applied not only to the production of hitherto known isoxazolidines but also to the production of various isoxazolidines having various substituents.
また１本発明の製造方法によれば、原料であるアシルイ
ソオキサゾリジン類も、従来の原料のエトキシカルボニ
ルイソオキサゾリジンを使用する場合と異なり、ホスゲ
ンな使用することなく安全にしかも容易に得られる。Furthermore, according to the production method of the present invention, the raw material acylisoxazolidine can be obtained safely and easily without using phosgene, unlike the case of using the conventional raw material ethoxycarbonyl isoxazolidine.
したがって１本発明の製造方法によれば、目的物を安全
にかつ高収率で得ることができるので、工業的なイソオ
キサゾリジン類の製造方法とじて有用である。Therefore, according to the production method of the present invention, the desired product can be obtained safely and in high yield, and therefore it is useful as an industrial method for producing isoxazolidines.
特許出願人 北興化学工業株式会社手続補正書 平成１年 を月１２日Patent Applicant: Hokuko Chemical Industry Co., Ltd. Procedural Amendment 1999 month 12th
Claims (1)
アルキル基、シクロアルキルアルキル基、アリール基ま
たはアリールアルキル基（ただし、アリールとは、ベン
ゼン核、ナフタレン核、ピリジン核、チオフェン核また
はフラン核を意味し、これらの核は、３個までの同一ま
たは相異なるハロゲン原子、低級アルキル基、低級ハロ
アルキル基、低級アルコキシ基およびニトロ基で置換さ
れてもよい）を示し、Ｒ＿２は、低級アルキル基を示し
、ｎは０〜３の整数を示し、Ａは▲数式、化学式、表等
があります▼基または▲数式、化学式、表等があります
▼基を示す）で表される化合物を加水分解することによ
る 一般式 ▲数式、化学式、表等があります▼ （式中、Ｒ＿２は低級アルキル基を示し、ｎは０〜３の
整数を示す〕で表されるイソオキサゾリジン類の製造方
法。[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. ▼ means a benzene nucleus, a naphthalene nucleus, a pyridine nucleus, a thiophene nucleus or a furan nucleus, which can contain up to three identical or different halogen atoms, lower alkyl groups, lower haloalkyl groups, lower alkoxy groups and nitro R_2 represents a lower alkyl group, n represents an integer from 0 to 3, and A represents a ▲ mathematical formula, chemical formula, table, etc. ▼ group or ▲ mathematical formula, chemical formula, table, etc. General formulas obtained by hydrolyzing compounds represented by ▼ groups) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_2 represents a lower alkyl group, and n is an integer from 0 to 3. A method for producing isoxazolidines represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63037457A JP2640822B2 (en) | 1988-02-22 | 1988-02-22 | Method for producing isoxazolidines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63037457A JP2640822B2 (en) | 1988-02-22 | 1988-02-22 | Method for producing isoxazolidines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01213272A true JPH01213272A (en) | 1989-08-28 |
| JP2640822B2 JP2640822B2 (en) | 1997-08-13 |
Family
ID=12498051
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63037457A Expired - Fee Related JP2640822B2 (en) | 1988-02-22 | 1988-02-22 | Method for producing isoxazolidines |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2640822B2 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5953474A (en) * | 1982-09-21 | 1984-03-28 | Hokko Chem Ind Co Ltd | 2-(substituted phenoxy)propionic acid derivative and herbicide containing said derivative as active component |
| JPS61286352A (en) * | 1985-06-10 | 1986-12-16 | ロレアル | Nitro-m-phenylenediamine halogenated in position 6 |
-
1988
- 1988-02-22 JP JP63037457A patent/JP2640822B2/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5953474A (en) * | 1982-09-21 | 1984-03-28 | Hokko Chem Ind Co Ltd | 2-(substituted phenoxy)propionic acid derivative and herbicide containing said derivative as active component |
| JPS61286352A (en) * | 1985-06-10 | 1986-12-16 | ロレアル | Nitro-m-phenylenediamine halogenated in position 6 |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2640822B2 (en) | 1997-08-13 |
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