• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    3-Amino-5-(t-butyl) isoxazole, in optimum yield, is prepared by reacting pivalyl acetonitrile with hydroxylamine under controlled conditions of pH. The compound is a useful intermediate for the preparation of isoxazole derivatives having utility as herbicides.
    公开号:SU1003757A3
    申请号:SU792734110
    申请日:1979-02-21
    公开日:1983-03-07
    发明作者:Вэйн Бероу Кеннет (Младший)；Фрэнк Эйзембер Ричард
    申请人:Эли Лилли Энд Компани (Фирма)；
    IPC主号:
    专利说明:

    (B METHOD OF OBTAINING 3-AMINO-5-TETT
    The invention relates to methods for the preparation of 3-amino-5-tert-butylisoxazole, which is used as an intermediate in the synthesis of isoxazole derivatives with herbicidal activity.
    A method of obtaining derivatives of 3-aminoisoxazole of the formula
    D
    (I)
    where r is. Al Kil, the interaction of the nitrile of the formula
    R is C 5 C-CN, (I I) where R has the indicated values, with hydrochloric acid hydroxylamine in a solvent, for example, aqueous ethanol, in the presence of an alkali metal hydroxide at room temperature.
    The yield of the target products is a concrete example on semi-BUTYL-ISOXAZOLE
    5-tert-butyl derivative of 3-aminoisoxazole is absent flj.
    The disadvantage of this method is that, as a source
    5, it uses acetylenic nitrile, which is a crucible-synthesized and expensive product.
    The aim of the invention is to simplify and cheapen the process.
    10 This objective is achieved by the method for the preparation of 3 amino-5-tert-butylisoxazole, which consists in the fact that pivaloyl acetonitrile is reacted with hydroxylamine hydrochloride in
    15 water-ethanolic medium in the presence of alkali at the boiling point of the reaction mixture under reflux at a pH of 6.0 to 7.0,
    20 Preferably, the process is carried out at a pH of from 6.2 to 6.5.
    As alkali is used lithium hydroxide or caustic soda.
    The reaction time at the reflux temperature of the reaction mixture varies from 1 to 24 hours, preferably from 7 to 22 hours, the latter region of varying the reaction time generally providing optimal yields of 3 amino-5 tert-butylisoxazole. Optimally, the solvent consists of ethanol and water in a proportion of 95: 5 to 42:58 (ethanol-water). When hydroxylamine hydrochloride is added to the reaction mixture, it is preferable to quickly add this compound. The best results are obtained by adding an aqueous solution of hydroxylamine hydroxylamine in alkaline plant pivaloyl acetonitrile, and then during the first 15–30 min; it is necessary to provide a pH value in the range from 6.0 to 7.0, in a preferred embodiment from 6.2 to 6.5. Such careful adjustment of the pH of the reaction mixture is important to obtain a maximum yield of 3 amO-5-tert-butylisoxazole, since the reaction is very sensitive to the pH value. At pH below 5.0, as a result the isoxazolone compound is obtained as the main product. At higher pH, i.e. at a pH above 8.0, unacceptably large amounts of 5 amino-3-tert-butylisoxazo are formed compared with the yield of the desired 3-amino-5- {tert-butyl): isoxazole. Starting with a pH, the ratio of the desired 3-amino compound to 5 amino compounds is not entirely favorable. Such careful adjustment in pH is carried out during the first 6 hours from the start of the reaction between hydroxylamine lactate and pivaloyl acetonitrile. The most effective method for the isolation of the desired product is the crystallization of the 3-aminoisomer, which remains after the solvent is removed under vacuum without using heat. Although an amino isomer can be obtained from the reaction mixture by changing the pH or causing crystallization by lower temperatures, or by adding sodium chloride; All these methods lead to the release of the desired 3-PM-5-tert-butylisoxazole in a less pure form. The starting pivaloyl acetonitrile is obtained by reacting a lower alkyl ester, for example. 57 methyl pivalate, with acetonitrile in the presence of a base, such as sodium hydride, in the presence of a solvent under a nitrogen atmosphere at the reflux temperature of the reaction mixture for a time sufficient to complete the reaction. Other bases that can be used in this reaction include sodium ethoxide. and sodium methoxide. To the corresponding solvent is m-ratio-i with tc tetrahydrofuran, ether, toluene, ethanol and methanol. The reaction is complete within about 7 hours, although longer reflux times can be used, for example, up to about 2k hours. In the final stage of completion of the reaction, the reaction mixture is concentrated under vacuum to remove the solvent, water is added and the mixture is acidified. using an aqueous solution of hydrochloric acid. The desired source pivaloyl acetonitrile precipitates from the acidic solution; the precipitate is filtered off and dried. Example 1. Getting source pivaloyl acetonitrile. In a 1 L flask in a dry nitrogen atmosphere, 26, k g of a 50% dispersion in sodium hydride oil are placed together with 2kQ ml of dry tetrahydrofuran. While the mixture is maintained at reflux temperature, drop by drop in 1 hour. blend 40.6 g of methylpivalate and 22.6 g of acetonitrile in kQ ml of dry tetrahydrofuran. After the addition is complete, the mixture is maintained at reflux temperature overnight. The reaction mixture is further processed under vacuum, a portion of the tetrahydrofuran is evaporated, and the remaining solution is dissolved in about 300 ml of water. The resulting aqueous mixture is acidified to a pH of about k using a concentrated aqueous solution of hydrochloric acid. The tetrahydrofuran residue is then removed using a rotary evaporator. Then, the solid residue that is formed in this way is isolated by filtration and converted into sludge in 150 ml of hexane in order to remove the mineral oil. The crystals are isolated by filtration and dried. The crystals have a melting point of about 57-59 ° C and are identified as pivaloyl acetonitrile. Pump 36.3 g (83%).
    Example 2. Obtaining 3-amino 5 (ret-butyl) -isoxazole.
    In a 3-liter, 3-liter, round-bottom flask with a capacity of 1 l, 30 g of pivaloyl acetone for the body, 13.5 g of lithium oxide hydrate, ZE of water and 281 ml of ethanol are placed. The mixture is heated to reflux temperature, and then 9 ml of an aqueous solution of 22.2 g of hydroxylamine hydrochloride acid is added to the mixture for 1Q min. After the addition is complete. is about 7.3. The pH is then adjusted to pH 6.7 using concentrated hydrochloric acid. After 30 min. PhD 6,1. After 1 hour, the pH is 6.3. Next, the pH is determined again after 2 and 3 hours after the last 20 minutes of addition, and the pH at these times is 6.6. Repeated determination of the pH after 5 and 6 hours showed that the pH is 6.7. The mixture is then refluxed overnight. 2S The next morning the pH is 6.8. The reaction mixture is cooled and ethanol is removed from the mixture on a rotary evaporator at room temperature. The solid: the residue is filtered by filtration and dried. Its weight is 18.65 g and, with vapor chromatography, it is found that the project contains 37% of the desired 3-amino-5-tert butylisoxazole and 1.6% 5 amino-3-tert-butylisoxazole. The yield of the desired isomer is 52%.
    Limer 3. Preparation of 3-amino-5-tert-butylisoxazole.
    In this example, sodium hydroxide is used as a base instead of lithium oxide hydrate.
    In a 3-necked round bottom flask, 30 g of pivaloyl acetonitrile, 12.8 g of sodium hydroxide, 39 g of water, and 281 ml of ethanol are placed. This mixture is heated to the reflux temperature, and then an aqueous solution of 22.2 g of hydroxylamine hydrochloride is added to it over about 10 minutes. The pH of the reaction mixture after the addition is complete is 6.4. Through pH is 6.5. After 1 and 1/2 hours, the pH is 6.8, and after 2 hours, 7.0. The pH is then adjusted to 6.2 by addition of a concentrated hydrochloric acid solution. After another 3 hours, the pH is 6.6. The reaction mixture is maintained at refluxing overnight and at the end of 22 hours of the reaction time pH 7.3. The reaction mixture is cooled, and ethanol is removed under vacuum. The solid is separated by filtration and dried. Its weight is 18.9 g, melting point 103105 ° C, as a result of a study using vapor phase chromatography, the product was found to contain 91.2% of 3-amino-5-tert-butylisoxazole and 5.2% of 5-amino-3- tert-butylisoxazole. The yield of the desired isomer is 5b%
    Example j. Preparation of 3-amino-5-tert-butylisoxazole
    In a 100 ml round bottom flask, 2 g of pivaloyl acetonitrile, 0.6 g of sodium hydroxide, 35 ml of water and 25 ml of ethanol are placed. The mixture is heated to reflux temperature, with a pH of 8.9. Then an aqueous solution of 1.0 g of hydroxylamine hydrochloride is added slowly. After the addition is complete, the pH is 6.3 °. The pH of the reaction mixture is then adjusted to 6.5. After 1 hour, the pH is 6.3, then the pH is again adjusted to 6.5. After 2 hours, a pO is determined, which is 7.0, again adjusted to 6.5. After 3 hours, the pH is 6.5. The reaction mixture is then defluorized overnight and the next morning the pH is 6.1. The ethanol is removed using a rotary evaporator, and the yellow solid material precipitates out. This solid material I is isolated by filtration and dried. Its weight is 1.1 g and using vapor-phase chromatography, it is established that it contains 9.2% of 3-amino-5-tert-butylisoxazole and 3.7% of 5-a B4Ho-3-tret-butylisoxazole. The product has a melting point of 103 105s. The yield of the desired isomer is 73.6%.
    Example 5. Obtaining 3-amino-5-tert-butylisoxazole.
    In a 100 ml round bottom flask, 2 g of pivaloyl acetonitrile, 0.6 g of sodium hydroxide, 35 ml of water and 25 ml of ethanol are placed. The mixture is heated to reflux temperature. The pH of the mixture is 8.6. 1.1 g of hydroxylamine hydrochloride in 15 ml of water are then added dropwise. At the end of the addition stage, the pH of the reaction mixture is 5, K. The pH of the reaction mixture is then adjusted to 7.0. After 1 hour, a pH is determined which is about 7.6; again the pH is adjusted to. 7 7.0. After 2 hours, a pH of 6.9 is determined; again the pH was adjusted to 7.0. After 3 hours, a pH of 7.5 was determined; again the pH was adjusted to 7.0. After a pH of 6.8 is determined; it is adjusted to 7.0. The reaction mixture is refluxed overnight and the next morning the pH is 6.3; the pH was adjusted to 7.0 again. The ethanol solvent is evaporated using a rotary evaporator, while a yellow solid precipitates out. The solid is recovered by filtration and dried. Its weight is 1.1 g, and the melting point is 101-10 Cc. Using vapor-phase chromatography, the product was found to contain 92.6% no-5 tert-butylisoxazole and k% no-3-tert-butylisoxazole. The yield of the desired isomer is 72.9%. Example 6. Preparation of 3 amino-5 tert-butylisoxazyl. In a 100 ml round bottom flask, 2.0 g of pivaloyl acetonitrile, 0.6 g of sodium hydroxide 17.5 ml of water and 12.5 ml of ethanol are placed. The ECU is heated to reflux and an aqueous solution of 1.1 g of hydroxylamine hydrochloride is added dropwise to it. After completion of the addition, the pH is 7.2. The pH is then adjusted to 6.3 with 10% aqueous hydrochloric acid. After 1 hour, the pH was 7.0, his dreams were adjusted to 6.5 with the aid of a 101% hydrochloric acid solution. After 2 hours, the pH is 6.8. After 3 hours, the pH is 6.9, after 3 and 1/2 hours, the pH is 6.5, the reaction mixture is further defluted overnight and the next morning the pH is 6.8, the reaction mixture is concentrated using a rotor the evaporator and the solid material precipitates, the precipitate is recovered and dried. Its weight is 1.3 g, melting point. Using vapor chromatography, the product was found to contain 90.68% 3 -amino-5 tert-butylisoxazole and 6.68 5-amino-3 tert-butylisoxazole. The yield of the desired isomer was Example 7, Preparation of 3 Amino-5-tert-bobylisoxazole, In a 100 ml round-bottomed round bottom flask, 2 g of pivaloyl acetonitrile, 25 ml of ethanol and 10 ml of water are placed. The mixture is heated to reflux temperature, with 7578 added with a solution of 0.89 g of lithium hydroxide and 1.5 g of hydroxylamine hydrochloride in 25 ml of water. After the addition step, the pH of the reaction mixture was 7.2, it was adjusted to about 6.8 with the aid of (a concentrated aqueous solution of hydrochloric acid. After 30 minutes the pH was 6.0; the pH was adjusted to 6.5 using aqueous lithium hydroxide solution solution. After 1 hour the pH is 6.2, it is again adjusted to 6.8 with an aqueous solution of lithium oxide hydroxide. After 1.5 hours the pH is equal to 6.6 sec. After 2 hours the pH is 6, 7. After 2 and 1/2 hours the pH is 6.8, After 3 hours the pH is 7.0, again the pH is adjusted to 6.5 with a concentrated aqueous solution of hydrochloric acid. After 20 hours the pH is 7.0, The reaction mixture is cooled and the ethanol is evaporated using a rotary evaporator. The solid precipitates out, is isolated by filtration and dried. Its weight is 1.4 g, melting point 105 10bc, Using a vapor phase chromatography. that the product contains 98.5% of 3 amino-5-tert-butylisoxazole and 1% 5 amino-3-tert-butylisoxazole. The yield of the desired isomer is 62.5%, for example, and for p. tert-butylisoxazole. In a 3 ml round-bottom flask with a capacity of 100 ml, 2 g of pivaloyl acetonitrile, 0.6 g of sodium oxide hydrate, 35 l of water and 12.5 ml of ethanol are placed. The mixture is heated to reflux temperature and an aqueous solution of 1.1 g of hydroxylamine hydrochloride is added to it. At the end of the addition stage, the pH is 6.0, after 1 hour the pH is 6.3, after 2 hours - 6.7 and 3 h - 6.5. The next morning, after refluxing the reaction mixture overnight, the pH is about 7.2, Ethanol is removed under vacuum using a rotary evaporator. The solid residue is separated by filtration and dried. Its melting point is 105- 1, 1.1 GO Using vapor-phase chromatography, it was determined that the product contains E2, E% 3 ami but-5-tert-butylisoxazole and, b7% 5-amino-3-tert-butylisoxazole. The yield of the desired isomer is 60.7% of Example 9 Preparation of 3 amino-5-tert-butylisoxazole,
    权利要求:
    Claims (3)
    [1]
    The claims are cooled and ethanol is evaporated using a rotary evaporator. The white solid was filtered off and dried. The weight of the solid: dogo material is 6.8 g; using vapor-phase chromatography, it was found that the product contains 91.9% 3-amino ~ 5-tert-butylisoxazole and 5.7% 5-amino-3-tert-butylisoxazole. : The yield of the desired isomer is 48%.
    Example 10. Obtaining 3 - amino-5 “tert-butylisoxazole.
    In a 3-necked flask: with a round bottom with a capacity of 100 ml, 2 g of pivaloylacetonitrile in 25 ml of ethanol are placed. The solution is quickly added to this mixture.
    1.1 g of hydroxylamine hydrochloride in 15 ml of water. The pH of the reaction mixture was adjusted to 7.0 with a 10% aqueous sodium bicarbonate solution, then the mixture was heated to reflux. After 1 h, the pH is 8.6, AT THIS pH, BEFORE df 7.0 with a concentrated solution of hydrochloric acid. After 2 hours, the pH is 8.5, again. The pH was adjusted to 7.0. After 3 hours, the pH is 8.0; The pH was adjusted to 6.7. The mixture is then refluxed overnight. The next morning the pH is 7.2, again
    1. A process for preparing 5-3Zmino _ -tert-butilizoksazola reacting gidrrksilaminom nitrile with hydrochloric acid in aqueous-ethanolic medium in the presence of alkali, characterized in that, in order to simplify and reduce the cost of the process, the nitrile used pivaloilatsetonitril and the process is carried out at the boiling temperature of the reaction mixtures under reflux at a pH of from 6.0 to 7.0.
    [2]
    2. The method of pop. ^ characterized in that the process is conducted at a pH of from 6.2 to 6.5.
    [3]
    3. The method of pop. 1, distinguishing with the fact that lithium hydroxide or caustic soda are used as alkali.
    Priority on points:
    02.22.78 “according to paragraphs 1-3, examples 1-8. 12/07/78 - according to paragraphs 1-3, examples 9 and 10.
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    同族专利:
    公开号 | 公开日
    CS203945B2|1981-03-31|
    JPS54125661A|1979-09-29|
    AU4424779A|1979-08-30|
    FI790549A|1979-08-23|
    IE47859B1|1984-07-11|
    PL213592A1|1979-11-05|
    IL56693D0|1979-05-31|
    DK75679A|1979-08-23|
    EP0004149A1|1979-09-19|
    ES477948A1|1980-04-01|
    AR219790A1|1980-09-15|
    AT365583B|1982-01-25|
    DE2964936D1|1983-04-07|
    NZ189700A|1981-05-01|
    LU80945A1|1979-06-18|
    GR70019B|1982-07-23|
    CA1115715A|1982-01-05|
    BG32848A3|1982-10-15|
    DD141672A5|1980-05-14|
    BR7901064A|1979-10-02|
    FR2418228A1|1979-09-21|
    CH637125A5|1983-07-15|
    AU523641B2|1982-08-05|
    GB2014992B|1982-07-07|
    US4259501A|1981-03-31|
    JPS631306B2|1988-01-12|
    GB2014992A|1979-09-05|
    PT69233A|1979-03-01|
    IE790538L|1979-08-22|
    EP0004149B1|1983-03-02|
    YU37879A|1982-10-31|
    EG14113A|1983-09-30|
    RO77032A|1981-08-30|
    ATA135479A|1981-06-15|
    PH16085A|1983-06-20|
    FR2418228B1|1981-06-26|
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    US3435047A|1964-09-14|1969-03-25|Sankyo Co|Process for preparing 3-aminoisoxazole derivatives|
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    US4493728A|1983-06-27|1985-01-15|Shell Oil Company|Plant growth inhibiting oxazolyl-substituted triazinone and oxadiazinone derivatives, compositions, and method of use|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US88026678A| true| 1978-02-22|1978-02-22|
    US05/967,342|US4259501A|1978-02-22|1978-12-07|Method for preparing 3-amino-5-isoxazole|
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