WO2020073178A1 - Application of lithium o-methylaniline in catalyzing hydroboration of imine with borane - Google Patents

Application of lithium o-methylaniline in catalyzing hydroboration of imine with borane Download PDF

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WO2020073178A1
WO2020073178A1 PCT/CN2018/109373 CN2018109373W WO2020073178A1 WO 2020073178 A1 WO2020073178 A1 WO 2020073178A1 CN 2018109373 W CN2018109373 W CN 2018109373W WO 2020073178 A1 WO2020073178 A1 WO 2020073178A1
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imine
borane
add
lithium
reaction
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PCT/CN2018/109373
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薛明强
颜丹丹
武振杰
徐晓娟
朱章野
沈琪
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南通纺织丝绸产业技术研究院
苏州大学
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Priority to PCT/CN2018/109373 priority Critical patent/WO2020073178A1/en
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/12—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
    • C07F5/02—Boron compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
    • C07F5/02—Boron compounds
    • C07F5/04—Esters of boric acids

Definitions

  • the borohydride reaction of imines has become a research hotspot in recent years.
  • the reported catalysts used in the borohydride reaction of imines mainly include the catalytic systems of main group elements: magnesium, calcium, sodium, rhenium, zinc, etc. (see Manna, K .; Ji, P .; Greene, FX; Lin, WJAm. Chem. Soc. 2016, 138, 7488-7491; Lin, YC .; Hatzakis, E .; McCarthy, SM; Reichl, KD; Lai, TY. ; Yennawar, HP; Radosevich, ATJAm. Chem. Soc. 2017, 139, 6008-6016).
  • the purpose of the invention of the present invention is to provide the application of lithium o-toluidine, that is, the application of lithium o-toluidine as a high-efficiency catalyst to catalyze the hydroboration reaction of imine and borane.
  • the technical scheme adopted by the present invention is: the application of lithium o-toluidine in the catalytic hydroboration reaction of imine and borane; the chemical formula of lithium o-toluidine is: 2-MePhNHLi.
  • the invention also discloses a method for catalyzing the hydroboration reaction of imine and borane with lithium o-toluidine, which includes the following steps:
  • the invention further discloses a method for preparing boric acid ester, which includes the following steps:
  • the imine is selected from aldimine; the general chemical structure of the imine is as follows:
  • R 1 or R 2 is one of an electron-withdrawing group or an electron-donating group, which may be selected from halogen, methyl, and methoxy; the borane is selected from pinacol borane.
  • the amount of the catalyst may be 4% to 5% of the number of moles of imine, and the molar ratio of imine to pinacol borane is 1: 1 to 1: 1.2.
  • the reaction temperature is room temperature
  • the reaction time is 1 to 2 hours.
  • the organic solvent is tetrahydrofuran.
  • the present invention has the following advantages compared with the prior art:
  • the present invention discloses for the first time that simple o-toluidine lithium can efficiently catalyze the borohydride reaction between imine and borane, which is highly consistent with the economical synthesis of atoms.
  • the lithium o-methylanilinyl catalyst disclosed in the present invention has a high catalytic activity for the hydroboration reaction of imine and borane (4% to 5% of the moles of catalyst used), mild reaction conditions (room temperature), and short reaction time 1h ⁇ 2h), and the reaction yield is high, the reaction is simple and controllable, the post-treatment is simple, the reaction uses inexpensive THF as the solvent.
  • the catalyst disclosed in the present invention has good universality for imines with different substitution positions and different electronic effects.
  • Example 1 Lithium o-toluidine catalyzes the hydroboration reaction of benzylidene and pinacol borane
  • Example 2 Lithium o-toluidine catalyzes the hydroboration reaction of benzylidene with pinacol borane
  • Example 3 Lithium o-toluidine catalyzes the hydroboration reaction of benzylidene aniline with pinacol borane
  • Example 4 Lithium o-methylanilinyl catalyzes the hydroboration reaction of benzylidene aniline with pinacol borane
  • Embodiment 5 Lithium o-methylanilinyl catalyzes the hydroboration reaction of N- (p-methylbenzylidene) aniline with pinacol borane
  • Example 6 Lithium o-toluidine catalyzes the hydroboration of N- (p-methoxybenzylidene) aniline with pinacol borane
  • Example 7 Lithium o-toluidine catalyzes the hydroboration of N- (4-fluorobenzylidene) aniline with pinacol borane
  • Example 8 Lithium o-toluidine catalyzes the hydroboration of N- (4-chlorobenzylidene) aniline with pinacol borane
  • Example 9 Lithium o-toluidine catalyzes the hydroboration of N- (4-bromobenzylidene) aniline with pinacol borane
  • Example 10 Lithium o-toluidine catalyzes the hydroboration of benzylidene-p-toluidine with pinacol borane
  • Example 11 Lithium o-toluidine catalyzes the hydroboration of N- (benzylidene) -4-fluoroaniline with pinacol borane
  • Example 12 Lithium o-toluidine catalyzes the hydroboration of N- (benzylidene) -4-chloroaniline with pinacol borane
  • Example 13 Lithium o-toluidine catalyzes the hydroboration of N- (benzylidene) -4-bromoaniline with pinacol borane
  • the reaction temperature of the above example is room temperature; the present invention discloses for the first time that the commercial reagent o-methylanilinyl lithium can catalyze the borohydride reaction of imine under mild reaction conditions, with a high yield and a wide range of substrate applications , Cheap catalysts and mild catalytic conditions provide the possibility for industrial applications.

Abstract

The present invention relates to an application of lithium o-methylaniline, and specifically relates to an application of lithium o-methylaniline in catalyzing hydroboration of imine with borane. A catalyst, borane, and imine are sequentially stirred and thoroughly combined, react for 1-2 hours, and are exposed to the air to terminate the reaction. The solvent in the reaction solution is removed under reduced pressure to obtain borates having different substituents. The disclosed lithium o-methylaniline can catalyze the hydroboration of imine with borane with high activity at room temperature. The amount of catalyst used is 4-5 mol% of the moles of imine, and the yield of the reaction can be 90% or more. When compared with existing catalytic systems, the present invention simply uses lithium o-methylaniline, has mild reaction conditions, and the yield of the borates having different substituents can reach 99% under optimized conditions.

Description

邻甲基苯胺基锂在催化亚胺和硼烷硼氢化反应中的应用Application of Lithium O-toluidine in Catalytic Hydroboration of Imine and Borane 技术领域Technical field
本发明涉及的邻甲基苯胺基锂的应用，具体涉及邻甲基苯胺基锂在催化亚胺与硼烷硼氢化反应中的高效应用。The application of lithium o-toluidine involved in the present invention, in particular to the high-efficiency application of lithium o-toluidine in catalyzing the hydroboration reaction of imine and borane.
背景技术Background technique
胺类化合物及其衍生物在自然界中普遍存在，尤其广泛地存在于生物界中，具有极重要的生理作用。它们是生物，化学，医药等领域中重要的有机化合物，很多药物含有胺的官能团即氨基，例如蛋白质，核酸，抗生素和生物碱中都存在氨基。胺类化合物具有多方面使用价值，应用范围十分广泛，常常被用于合成纺织品、染料、聚合物、色素和农药等。由于羰基的硼氢化反应远比亚胺的硼氢化反应容易发生，所以开发出针对不饱和C＝N键的硼氢化反应的高效催化体系，对现代工业和有机合成化学都具有重要的意义。Amine compounds and their derivatives are ubiquitous in nature, especially in the biological world, and have extremely important physiological functions. They are important organic compounds in the fields of biology, chemistry, medicine, etc. Many drugs contain amine functional groups, ie amino groups, such as proteins, nucleic acids, antibiotics and alkaloids. Amine compounds have many uses and have a wide range of applications. They are often used to synthesize textiles, dyes, polymers, pigments, and pesticides. Since the hydroboration of the carbonyl group is easy to occur, the development of a highly efficient catalytic system for the hydroboration of unsaturated C = N bonds is of great significance to modern industry and organic synthetic chemistry.
亚胺的硼氢化反应近几年已成为研究热点，报道的催化剂应用于亚胺的硼氢化反应主要包括，主族元素的催化体系：镁、钙、钠、铼、锌等(参见Manna,K.；Ji,P.；Greene,F.X.；Lin,W.J.Am.Chem.Soc.2016,138,7488-7491；Lin,Y-C.；Hatzakis,E.；McCarthy,S.M.；Reichl,K.D.；Lai,T-Y.；Yennawar,H.P.；Radosevich,A.T.J.Am.Chem.Soc.2017,139,6008-6016)。但是，目前所报道的催化体系，催化剂都相对昂贵或难以制备，或者反应时间较长且要在高温下反应，有些催化体系产率很低。所以，开发温和条件下高效催化亚胺的硼氢化反应的催化体系极其重要。The borohydride reaction of imines has become a research hotspot in recent years. The reported catalysts used in the borohydride reaction of imines mainly include the catalytic systems of main group elements: magnesium, calcium, sodium, rhenium, zinc, etc. (see Manna, K .; Ji, P .; Greene, FX; Lin, WJAm. Chem. Soc. 2016, 138, 7488-7491; Lin, YC .; Hatzakis, E .; McCarthy, SM; Reichl, KD; Lai, TY. ; Yennawar, HP; Radosevich, ATJAm. Chem. Soc. 2017, 139, 6008-6016). However, in the currently reported catalytic systems, the catalysts are relatively expensive or difficult to prepare, or the reaction time is long and the reaction needs to be carried out at high temperature, and some catalyst systems have low yields. Therefore, it is extremely important to develop a catalytic system that efficiently catalyzes the hydroboration of imine under mild conditions.
技术问题technical problem
本发明的发明目的是提供邻甲基苯胺基锂的应用，即以邻甲基苯胺基锂为高效催化剂催化亚胺与硼烷发生硼氢化反应的应用。The purpose of the invention of the present invention is to provide the application of lithium o-toluidine, that is, the application of lithium o-toluidine as a high-efficiency catalyst to catalyze the hydroboration reaction of imine and borane.
技术解决方案Technical solution
为达到上述发明目的，本发明采用的技术方案是：邻甲基苯胺基锂在催化亚胺与硼烷硼氢化反应中的应用；所述邻甲基苯胺基锂化学式为：2-MePhNHLi。In order to achieve the above-mentioned object of the invention, the technical scheme adopted by the present invention is: the application of lithium o-toluidine in the catalytic hydroboration reaction of imine and borane; the chemical formula of lithium o-toluidine is: 2-MePhNHLi.
本发明还公开了邻甲基苯胺基锂催化亚胺与硼烷发生硼氢化反应的方法，包括以下步骤：The invention also discloses a method for catalyzing the hydroboration reaction of imine and borane with lithium o-toluidine, which includes the following steps:
无水无氧环境下，惰性气体氛围下，在经过脱水脱氧处理的反应瓶中加入亚胺，加入有机溶剂，然后加入硼烷，混合均匀，再加入催化剂邻甲基苯胺基锂，反应1h～2h，暴露于空气中终止反应，得到产物。In an anhydrous and oxygen-free environment, under an inert gas atmosphere, add imine, organic solvent, and then borane to the reaction flask after dehydration and deoxygenation treatment, mix well, then add catalyst o-methylanilide lithium, react for 1h ~ 2h, the reaction was terminated by exposure to air to obtain the product.
本发明进一步的公开了一种硼酸酯的制备方法，包括以下步骤：The invention further discloses a method for preparing boric acid ester, which includes the following steps:
无水无氧环境下，惰性气体氛围下，在经过脱水脱氧处理的反应瓶中加入亚胺，加入有机溶剂，然后加入硼烷，混合均匀，再加入催化剂邻甲基苯胺基锂，反应1h～2h，暴露于空气中终止反应，得到产物。In an anhydrous and oxygen-free environment, under an inert gas atmosphere, add imine, organic solvent, and then borane to the reaction flask after dehydration and deoxygenation treatment, mix well, then add catalyst o-methylanilide lithium, react for 1h ~ 2h, the reaction was terminated by exposure to air to obtain the product.
上述技术方案中，所述亚胺选自醛亚胺；所述亚胺的化学结构通式如下：In the above technical solution, the imine is selected from aldimine; the general chemical structure of the imine is as follows:
Figure PCTCN2018109373-appb-000001
Figure PCTCN2018109373-appb-000001
其中R 1或R 2为吸电子基团或给电子基团中的一种，可选自卤素，甲基，甲氧基；所述硼烷选自频哪醇硼烷。 Wherein R 1 or R 2 is one of an electron-withdrawing group or an electron-donating group, which may be selected from halogen, methyl, and methoxy; the borane is selected from pinacol borane.
上述技术方案中，所述催化剂用量可为亚胺摩尔数的4％～5％，亚胺与频哪醇硼烷的摩尔比为1∶1～1∶1.2。In the above technical solution, the amount of the catalyst may be 4% to 5% of the number of moles of imine, and the molar ratio of imine to pinacol borane is 1: 1 to 1: 1.2.
上述技术方案中，反应温度为室温，反应时间为1～2h。In the above technical solution, the reaction temperature is room temperature, and the reaction time is 1 to 2 hours.
上述技术方案中，有机溶剂为四氢呋喃。In the above technical solution, the organic solvent is tetrahydrofuran.
上述技术方案可表示如下：The above technical solution can be expressed as follows:
Figure PCTCN2018109373-appb-000002
Figure PCTCN2018109373-appb-000002
有益效果Beneficial effect
由于上述技术方案的运用，本发明与现有技术相比有如下优点：Due to the application of the above technical solutions, the present invention has the following advantages compared with the prior art:
1.本发明首次公开简单的邻甲基苯胺基锂能高效的催化亚胺与硼烷发生硼氢化反应，高度符合原子经济合成。1. The present invention discloses for the first time that simple o-toluidine lithium can efficiently catalyze the borohydride reaction between imine and borane, which is highly consistent with the economical synthesis of atoms.
2.本发明公开的邻甲基苯胺基锂催化亚胺与硼烷发生硼氢化反应的催化活性高(催化剂用量摩尔数的4％～5％)，反应条件温和(室温)，反应时间短(1h～2h)，且反应产率高，反应简单可控，后处理简单，反应采用廉价的THF为溶剂。2. The lithium o-methylanilinyl catalyst disclosed in the present invention has a high catalytic activity for the hydroboration reaction of imine and borane (4% to 5% of the moles of catalyst used), mild reaction conditions (room temperature), and short reaction time 1h ~ 2h), and the reaction yield is high, the reaction is simple and controllable, the post-treatment is simple, the reaction uses inexpensive THF as the solvent.
3.本发明公开的催化剂对于不同取代位置、不同电子效应的亚胺有着较好的普适性。3. The catalyst disclosed in the present invention has good universality for imines with different substitution positions and different electronic effects.
本发明的实施方式Embodiments of the invention
下面结合实施例对本发明做进一步描述：The present invention will be further described in combination with the following embodiments:
实施例一：邻甲基苯胺基锂催化卞叉苯胺与频哪醇硼烷硼氢化反应Example 1: Lithium o-toluidine catalyzes the hydroboration reaction of benzylidene and pinacol borane
在经过脱水脱氧处理的反应瓶中，氩气保护下加入0.5mmol的卞叉苯胺，加入100ul THF，然后用移液枪加入0.5mmol(0.0726mL)硼烷混合均匀，最后加入30.6ul邻甲基苯胺基锂的四氢呋喃溶液(0.8162M)(5mol％用量，下同)，反应2h后，用滴管吸取一滴于核磁管中，加入CDCl 3配成溶液。经计算 1H谱产率为91％。产物的核磁数据： 1H NMR(CDCl 3,400MHz)δ:7.29～7.12(m,9H),6.88～6.84(t,1H),4.69(s,2H),1.29(s,12H)。 In the reaction flask after dehydration and deoxygenation treatment, add 0.5 mmol of benzidine under the protection of argon, add 100ul of THF, then use a pipette to add 0.5mmol (0.0726mL) of borane and mix well, and finally add 30.6ul of o-methyl A solution of lithium anilide in tetrahydrofuran (0.8162M) (5mol% dosage, the same below), after reaction for 2h, use a dropper to draw a drop into the nuclear magnetic tube, add CDCl 3 to make a solution. The calculated 1 H spectrum yield was 91%. Nuclear magnetic data of the product: 1 H NMR (CDCl 3 , 400 MHz) δ: 7.29-7.12 (m, 9H), 6.88-6.84 (t, 1H), 4.69 (s, 2H), 1.29 (s, 12H).
实施例二:邻甲基苯胺基锂催化卞叉苯胺与频哪醇硼烷硼氢化反应Example 2: Lithium o-toluidine catalyzes the hydroboration reaction of benzylidene with pinacol borane
在经过脱水脱氧处理的反应瓶中，氩气保护下加入0.5mmol的卞叉苯胺，加入100ul THF，然后用移液枪加入0.6mmol(0.0871mL)硼烷混合均匀，最后加入30.6ul邻甲基苯胺基锂的四氢呋喃溶液(0.8162M)(5mol％用量，下同)，反应1h后，用滴管吸取一滴于核磁管中，加入CDCl 3配成溶液。经计算 1H谱产率为96％。产物的核磁数据： 1H NMR(CDCl 3,400MHz)δ:7.29～7.12(m,9H),6.88～6.84(t,1H),4.69(s,1H),1.29(s,12H)。 In the reaction flask after dehydration and deoxygenation treatment, add 0.5 mmol of benzidine under the protection of argon, add 100 ul of THF, then use a pipette to add 0.6 mmol (0.0871 mL) of borane to mix well, and finally add 30.6 ul o-methyl A solution of lithium anilide in tetrahydrofuran (0.8162M) (5mol% dosage, the same below), after reaction for 1h, use a dropper to draw a drop into the nuclear magnetic tube, add CDCl 3 to make a solution. The calculated 1 H spectrum yield was 96%. Nuclear magnetic data of the product: 1 H NMR (CDCl 3 , 400 MHz) δ: 7.29-7.12 (m, 9H), 6.88-6.84 (t, 1H), 4.69 (s, 1H), 1.29 (s, 12H).
实施例三：邻甲基苯胺基锂催化卞叉苯胺与频哪醇硼烷硼氢化反应Example 3: Lithium o-toluidine catalyzes the hydroboration reaction of benzylidene aniline with pinacol borane
在经过脱水脱氧处理的反应瓶中，氩气保护下加入0.5mmol的卞叉苯胺，加入100ul THF，然后用移液枪加入0.6mmol(0.0871mL)硼烷混合均匀，最后加入30.6ul邻甲基苯胺基锂的四氢呋喃溶液(0.8162M)(5mol％用量)，反应2h后，用滴管吸取一滴于核磁管中，加入CDCl 3配成溶液。经计算 1H谱产率为99％。产物的核磁数据： 1H NMR(CDCl 3,400MHz)δ:7.29～7.12(m,9H),6.88～6.84(t,1H),4.69(s,2H),1.29(s,12H)。 In the reaction flask after dehydration and deoxygenation treatment, add 0.5 mmol of benzidine under the protection of argon, add 100 ul of THF, then use a pipette to add 0.6 mmol (0.0871 mL) of borane to mix well, and finally add 30.6 ul o-methyl A solution of lithium anilide in tetrahydrofuran (0.8162M) (5mol% dosage), after 2 hours of reaction, use a dropper to draw a drop into the nuclear magnetic tube, add CDCl 3 to make a solution. The calculated 1 H spectrum yield was 99%. Nuclear magnetic data of the product: 1 H NMR (CDCl 3 , 400 MHz) δ: 7.29-7.12 (m, 9H), 6.88-6.84 (t, 1H), 4.69 (s, 2H), 1.29 (s, 12H).
将邻甲基苯胺基锂替换为式Ⅰ的胺基锂化合物，无法得到产物。Substituting lithium o-toluidine with the lithium amido compound of formula I, the product cannot be obtained.
Figure PCTCN2018109373-appb-000003
Figure PCTCN2018109373-appb-000003
实施例四：邻甲基苯胺基锂催化卞叉苯胺与频哪醇硼烷硼氢化反应Example 4: Lithium o-methylanilinyl catalyzes the hydroboration reaction of benzylidene aniline with pinacol borane
在经过脱水脱氧处理的反应瓶中，氩气保护下加入0.5mmol的卞叉苯胺，加入100ul THF，然后用移液枪加入0.6mmol(0.0871mL)硼烷混合均匀，最后加入24.5ul邻甲基苯胺基锂的四氢呋喃溶液(0.8162M)(4mol％用量)，反应2h后，用滴管吸取一滴于核磁管中，加入CDCl 3配成溶液。经计算 1H谱产率为97％。产物的核磁数据： 1H NMR(CDCl 3,400MHz)δ:7.29～7.12(m,9H),6.88～6.84(t,1H),4.69(s,2H),1.29(s,12H)。 In the reaction flask after dehydration and deoxygenation treatment, add 0.5 mmol of benzidine under the protection of argon, add 100 ul of THF, then use a pipette to add 0.6 mmol (0.0871 mL) of borane to mix well, and finally add 24.5 ul of o-methyl A solution of lithium anilide in tetrahydrofuran (0.8162M) (4mol% dosage). After 2 hours of reaction, use a dropper to draw a drop into the nuclear magnetic tube and add CDCl 3 to make a solution. The calculated 1 H spectrum yield was 97%. Nuclear magnetic data of the product: 1 H NMR (CDCl 3 , 400 MHz) δ: 7.29-7.12 (m, 9H), 6.88-6.84 (t, 1H), 4.69 (s, 2H), 1.29 (s, 12H).
实施例五：邻甲基苯胺基锂催化N-(p-甲基苯亚甲基)苯胺与频哪醇硼烷硼氢化反应Embodiment 5: Lithium o-methylanilinyl catalyzes the hydroboration reaction of N- (p-methylbenzylidene) aniline with pinacol borane
在经过脱水脱氧处理的反应瓶中，氩气保护下加入0.5mmol的N-(p-甲基苯亚甲基)苯胺，加入100ul THF，然后用移液枪加入0.6mmol(0.0871mL)硼烷混合均匀，最后加入30.6ul邻甲基苯胺基锂的四氢呋喃溶液(0.8162M)(5mol％用量，下同)，反应2h后，用滴管吸取一滴于核磁管中，加入CDCl 3配成溶液。经计算 1H谱产率为99％。产物的核磁数据： 1H NMR(CDCl 3,400MHz)δ:7.23～7.08(m,8H),6.89～6.85(t,1H),4.66(s,2H),2.31(s,3H),1.30(s,12H)。 In the reaction flask after dehydration and deoxygenation, add 0.5 mmol of N- (p-methylbenzylidene) aniline under the protection of argon, add 100 ul of THF, and then add 0.6 mmol (0.0871 mL) of borane with a pipette Mix well, and finally add 30.6ul of o-methylanilide lithium tetrahydrofuran solution (0.8162M) (5mol% dosage, the same below), after 2 hours of reaction, use a dropper to draw a drop into the nuclear magnetic tube, add CDCl 3 to make a solution. The calculated 1 H spectrum yield was 99%. Nuclear magnetic data of the product: 1 H NMR (CDCl 3 , 400 MHz) δ: 7.23 ～ 7.08 (m, 8H), 6.89 ～ 6.85 (t, 1H), 4.66 (s, 2H), 2.31 (s, 3H), 1.30 ( s, 12H).
实施例六：邻甲基苯胺基锂催化N-(p-甲氧基苯亚甲基)苯胺与频哪醇硼烷硼氢化反应Example 6: Lithium o-toluidine catalyzes the hydroboration of N- (p-methoxybenzylidene) aniline with pinacol borane
在经过脱水脱氧处理的反应瓶中，氩气保护下加入0.5mmol的N-(p-甲氧基苯亚甲基)苯胺，加入100ul THF，然后用移液枪加入0.6mmol(0.0871mL)硼烷混合均匀，最后加入30.6ul邻甲基苯胺基锂的四氢呋喃溶液(0.8162M)(5mol％用量，下同)，反应2h后，用滴管吸取一滴于核磁管中，加入CDCl 3配成溶液。经计算 1H谱产率为99％。产物的核磁数据： 1H NMR(CDCl 3,400MHz)δ:7.22～7.13(d,6H),6.89～6.80(d,3H),4.63(s,2H),3.77(s,3H),1.30(s,12H)。 In the reaction flask after dehydration and deoxygenation, add 0.5 mmol of N- (p-methoxybenzylidene) aniline under the protection of argon, add 100 ul of THF, and then add 0.6 mmol (0.0871 mL) of boron with a pipette gun Mix the alkane evenly, and finally add 30.6ul of o-methylanilide lithium tetrahydrofuran solution (0.8162M) (5mol% dosage, the same below), after reaction for 2h, use a dropper to draw a drop into the nuclear magnetic tube, add CDCl 3 to make a solution . The calculated 1 H spectrum yield was 99%. Nuclear magnetic data of the product: 1 H NMR (CDCl 3 , 400 MHz) δ: 7.22 ～ 7.13 (d, 6H), 6.89 ～ 6.80 (d, 3H), 4.63 (s, 2H), 3.77 (s, 3H), 1.30 ( s, 12H).
实施例七：邻甲基苯胺基锂催化N-(4-氟苯亚甲基)苯胺与频哪醇硼烷硼氢化反应Example 7: Lithium o-toluidine catalyzes the hydroboration of N- (4-fluorobenzylidene) aniline with pinacol borane
在经过脱水脱氧处理的反应瓶中，氩气保护下加入0.5mmol的N-(4-氟苯亚甲基)苯胺，加入100ul THF，然后用移液枪加入0.6mmol(0.0871mL)硼烷混合均匀，最后加入30.6ul邻甲基苯胺基锂的四氢呋喃溶液(0.8162M)(5mol％用量，下同)，反应2h后，用滴管吸取一滴于核磁管中，加入CDCl 3配成溶液。经计算 1H谱产率为99％。产物的核磁数据： 1H NMR(CDCl 3,400MHz)δ:7.22～7.15(d,6H),6.98～6.94(d,3H),4.66(s,2H),1.30(s,12H)。 Add 0.5 mmol of N- (4-fluorobenzylidene) aniline under the protection of argon to 100 μL of THF, then add 0.6 mmol (0.0871 mL) of borane with a pipette Evenly, finally add 30.6ul of o-toluidine lithium tetrahydrofuran solution (0.8162M) (5mol% dosage, the same below), after reaction for 2h, use a dropper to draw a drop into the nuclear magnetic tube, add CDCl 3 to make a solution. The calculated 1 H spectrum yield was 99%. Nuclear magnetic data of the product: 1 H NMR (CDCl 3 , 400 MHz) δ: 7.22 ～ 7.15 (d, 6H), 6.98 ～ 6.94 (d, 3H), 4.66 (s, 2H), 1.30 (s, 12H).
实施例八：邻甲基苯胺基锂催化N-(4-氯苯亚甲基)苯胺与频哪醇硼烷硼氢化反应Example 8: Lithium o-toluidine catalyzes the hydroboration of N- (4-chlorobenzylidene) aniline with pinacol borane
在经过脱水脱氧处理的反应瓶中，氩气保护下加入0.5mmol的N-(4-氯苯亚甲基)苯胺，加入100ul THF，然后用移液枪加入0.6mmol(0.0871mL)硼烷混合均匀，最后加入30.6ul邻甲基苯胺基锂的四氢呋喃溶液(0.8162M)(5mol％用量，下同)，反应2h后，用滴管吸取一滴于核磁管中，加入CDCl 3配成溶液。经计算 1H谱产率为99％。产物的核磁数据： 1H NMR(CDCl 3,400MHz)δ:7.20～7.14(d,6H),6.99～6.93(d,3H),4.64(s,2H),1.30(s,12H)。 In the reaction flask after dehydration and deoxygenation treatment, add 0.5 mmol of N- (4-chlorobenzylidene) aniline under the protection of argon, add 100 ul of THF, then add 0.6 mmol (0.0871 mL) of borane with a pipette to mix Evenly, finally add 30.6ul of o-toluidine lithium tetrahydrofuran solution (0.8162M) (5mol% dosage, the same below), after reaction for 2h, use a dropper to draw a drop into the nuclear magnetic tube, add CDCl 3 to make a solution. The calculated 1 H spectrum yield was 99%. Nuclear magnetic data of the product: 1 H NMR (CDCl 3 , 400 MHz) δ: 7.20 ～ 7.14 (d, 6H), 6.99 ～ 6.93 (d, 3H), 4.64 (s, 2H), 1.30 (s, 12H).
实施例九：邻甲基苯胺基锂催化N-(4-溴苯亚甲基)苯胺与频哪醇硼烷硼氢化反应Example 9: Lithium o-toluidine catalyzes the hydroboration of N- (4-bromobenzylidene) aniline with pinacol borane
在经过脱水脱氧处理的反应瓶中，氩气保护下加入0.5mmol的N-(4-溴苯亚甲基)苯胺，加入100ul THF，然后用移液枪加入0.6mmol(0.0871mL)硼烷混合均匀，最后加入30.6ul邻甲基苯胺基锂的四氢呋喃溶液(0.8162M)(5mol％用量，下同)，反应2h后，用滴管吸取一滴于核磁管中，加入CDCl 3配成溶液。经计算 1H谱产率为99％。产物的核磁数据： 1H  NMR(CDCl 3,400MHz)δ:7.24～7.16(d,6H),6.97～6.93(d,3H),4.63(s,2H),1.31(s,12H)。 In the reaction flask after dehydration and deoxygenation treatment, 0.5 mmol of N- (4-bromobenzylidene) aniline was added under the protection of argon, 100 ul of THF was added, and then 0.6 mmol (0.0871 mL) of borane was added with a pipette to mix Evenly, finally add 30.6ul of o-toluidine lithium tetrahydrofuran solution (0.8162M) (5mol% dosage, the same below), after reaction for 2h, use a dropper to draw a drop into the nuclear magnetic tube, add CDCl 3 to make a solution. The calculated 1 H spectrum yield was 99%. Nuclear magnetic data of the product: 1 H NMR (CDCl 3 , 400 MHz) δ: 7.24 ～ 7.16 (d, 6H), 6.97 ～ 6.93 (d, 3H), 4.63 (s, 2H), 1.31 (s, 12H).
实施例十：邻甲基苯胺基锂催化亚苄基对甲苯胺与频哪醇硼烷硼氢化反应Example 10: Lithium o-toluidine catalyzes the hydroboration of benzylidene-p-toluidine with pinacol borane
在经过脱水脱氧处理的反应瓶中，氩气保护下加入0.5mmol的亚苄基对甲苯，加入100ul THF，然后用移液枪加入0.6mmol(0.0871mL)硼烷混合均匀，最后加入30.6ul邻甲基苯胺基锂的四氢呋喃溶液(0.8162M)(5mol％用量，下同)，反应2h后，用滴管吸取一滴于核磁管中，加入CDCl 3配成溶液。经计算 1H谱产率为99％。产物的核磁数据： 1H NMR(CDCl 3,400MHz)δ:7.32～7.28(d,5H),7.10～7.08(d,2H),6.64～6.60(d,2H),4.62(s,2H),1.31(s,12H)。 In the reaction flask after dehydration and deoxygenation treatment, add 0.5 mmol of benzylidene p-toluene under the protection of argon, add 100 ul of THF, then use a pipette to add 0.6 mmol (0.0871 mL) of borane to mix well, and finally add 30.6 ul ortho Tetrahydrofuran solution (0.8162M) of methylanilide lithium (5mol% dosage, the same below), after reaction for 2h, use a dropper to draw a drop into the nuclear magnetic tube, add CDCl 3 to make a solution. The calculated 1 H spectrum yield was 99%. Nuclear magnetic data of the product: 1 H NMR (CDCl 3 , 400MHz) δ: 7.32 ～ 7.28 (d, 5H), 7.10 ～ 7.08 (d, 2H), 6.64 ～ 6.60 (d, 2H), 4.62 (s, 2H), 1.31 (s, 12H).
实施例十一：邻甲基苯胺基锂催化N-(苯亚甲基)-4-氟苯胺与频哪醇硼烷硼氢化反应Example 11: Lithium o-toluidine catalyzes the hydroboration of N- (benzylidene) -4-fluoroaniline with pinacol borane
在经过脱水脱氧处理的反应瓶中，氩气保护下加入0.5mmol的亚苄基对甲苯，加入100ul THF，然后用移液枪加入0.6mmol(0.0871mL)硼烷混合均匀，最后加入30.6ul邻甲基苯胺基锂的四氢呋喃溶液(0.8162M)(5mol％用量，下同)，反应2h后，用滴管吸取一滴于核磁管中，加入CDCl 3配成溶液。经计算 1H谱产率为99％。产物的核磁数据： 1H NMR(CDCl 3,400MHz)δ:7.24～7.02(d,7H),6.75～6.70(d,2H),4.66(s,2H),1.32(s,12H)。 In the reaction flask after dehydration and deoxygenation treatment, add 0.5 mmol of benzylidene p-toluene under the protection of argon, add 100 ul of THF, then use a pipette to add 0.6 mmol (0.0871 mL) of borane to mix well, and finally add 30.6 ul ortho Tetrahydrofuran solution (0.8162M) of methylanilide lithium (5mol% dosage, the same below), after reaction for 2h, use a dropper to draw a drop into the nuclear magnetic tube, add CDCl 3 to make a solution. The calculated 1 H spectrum yield was 99%. Nuclear magnetic data of the product: 1 H NMR (CDCl 3 , 400 MHz) δ: 7.24 to 7.02 (d, 7H), 6.75 to 6.70 (d, 2H), 4.66 (s, 2H), 1.32 (s, 12H).
实施例十二：邻甲基苯胺基锂催化N-(苯亚甲基)-4-氯苯胺与频哪醇硼烷硼氢化反应Example 12: Lithium o-toluidine catalyzes the hydroboration of N- (benzylidene) -4-chloroaniline with pinacol borane
在经过脱水脱氧处理的反应瓶中，氩气保护下加入0.5mmol的N-(苯亚甲基)-4-氯苯胺，加入100ul THF，然后用移液枪加入0.6mmol(0.0871mL)硼烷混合均匀，最后加入30.6ul邻甲基苯胺基锂的四氢呋喃溶液(0.8162M)(5mol％用量，下同)，反应2h后，用滴管吸取一滴于核磁管中，加入CDCl 3配成溶液。经计算 1H谱产率为99％。产物的核磁数据： 1H NMR(CDCl 3,400MHz)δ:7.26～7.05(d,7H),6.74～6.69(d,2H),4.61(s,2H),1.30(s,12H)。 In the reaction flask after dehydration and deoxygenation treatment, add 0.5 mmol of N- (benzylidene) -4-chloroaniline under the protection of argon, add 100 ul of THF, and then add 0.6 mmol (0.0871 mL) of borane with a pipette Mix well, and finally add 30.6ul of o-methylanilide lithium tetrahydrofuran solution (0.8162M) (5mol% dosage, the same below), after 2 hours of reaction, use a dropper to draw a drop into the nuclear magnetic tube, add CDCl 3 to make a solution. The calculated 1 H spectrum yield was 99%. Nuclear magnetic data of the product: 1 H NMR (CDCl 3 , 400 MHz) δ: 7.26 ～ 7.05 (d, 7H), 6.74 ～ 6.69 (d, 2H), 4.61 (s, 2H), 1.30 (s, 12H).
实施例十三：邻甲基苯胺基锂催化N-(苯亚甲基)-4-溴苯胺与频哪醇硼烷硼氢化反应Example 13: Lithium o-toluidine catalyzes the hydroboration of N- (benzylidene) -4-bromoaniline with pinacol borane
在经过脱水脱氧处理的反应瓶中，氩气保护下加入0.5mmol的N-(苯亚甲基)-4-溴苯胺，加入100ul THF，然后用移液枪加入0.6mmol(0.0871mL)硼烷混合均匀，最后加入30.6ul邻甲基苯胺基锂的四氢呋喃溶液(0.8162M)(5mol％用量，下同)，反应2h后，用滴管吸取一滴于核磁管中，加入CDCl 3配成溶液。经计算 1H谱产率为99％。产物的核磁数据： 1H NMR(CDCl 3,400MHz)δ:7.27～7.03(d,7H),6.76～6.71(d,2H),4.62(s,2H),1.30(s,12H)。 In the reaction flask after dehydration and deoxygenation treatment, add 0.5 mmol of N- (benzylidene) -4-bromoaniline under the protection of argon, add 100 ul of THF, and then add 0.6 mmol (0.0871 mL) of borane with a pipette Mix well, and finally add 30.6ul of o-methylanilide lithium tetrahydrofuran solution (0.8162M) (5mol% dosage, the same below), after 2 hours of reaction, use a dropper to draw a drop into the nuclear magnetic tube, add CDCl 3 to make a solution. The calculated 1 H spectrum yield was 99%. Nuclear magnetic data of the product: 1 H NMR (CDCl 3 , 400 MHz) δ: 7.27 ～ 7.03 (d, 7H), 6.76 ～ 6.71 (d, 2H), 4.62 (s, 2H), 1.30 (s, 12H).
上述实施例的反应温度为室温；本发明首次公开商业化试剂邻甲基苯胺基锂能够在温和的反应条件催化亚胺的硼氢化反应，产率很高，具有着较广的底物适用范围，廉价的催化剂以及温和的催化条件，为工业化应用提供了可能。The reaction temperature of the above example is room temperature; the present invention discloses for the first time that the commercial reagent o-methylanilinyl lithium can catalyze the borohydride reaction of imine under mild reaction conditions, with a high yield and a wide range of substrate applications , Cheap catalysts and mild catalytic conditions provide the possibility for industrial applications.

Claims (10)

  1. 邻甲基苯胺基锂在催化亚胺与硼烷硼氢化反应中的应用。Application of Lithium o-toluidine in catalytic hydroboration of imine and borane.
  2. 根据权利要求1所述的应用，其特征在于，邻甲基苯胺基锂催化亚胺与硼烷发生硼氢化反应的方法包括以下步骤：无水无氧环境下，惰性气体氛围下，在经过脱水脱氧处理的反应瓶中加入亚胺，加入有机溶剂，然后加入硼烷，混合均匀，再加入催化剂邻甲基苯胺基锂，室温反应1～2h，暴露于空气中终止反应，得到产物。The application according to claim 1, characterized in that the method for the borohydride reaction of the o-toluidine lithium-catalyzed imine and borane includes the following steps: dehydrated under an inert gas atmosphere in an anhydrous and oxygen-free environment Add the imine to the deoxygenated reaction bottle, add the organic solvent, then add the borane, mix well, then add the catalyst o-toluidine lithium, react at room temperature for 1 to 2 hours, and terminate the reaction by exposure to air to obtain the product.
  3. 根据权利要求2所述的应用，其特征在于，所述亚胺的化学结构通式如下：The application according to claim 2, characterized in that the general chemical structure of the imine is as follows:
    Figure PCTCN2018109373-appb-100001
    Figure PCTCN2018109373-appb-100001
    其中R1或R2独立的选自卤素，甲基，甲氧基；所述硼烷选自频哪醇硼烷；所述有机溶剂为四氢呋喃；Wherein R1 or R2 is independently selected from halogen, methyl and methoxy; the borane is selected from pinacol borane; the organic solvent is tetrahydrofuran;
    所述邻甲基苯胺基锂的用量为亚胺摩尔数的4％～5％，亚胺与频哪醇硼烷的摩尔比为1∶1～1∶1.2。The amount of lithium o-toluidine is 4% to 5% of the mole number of imine, and the molar ratio of imine to pinacol borane is 1: 1 to 1: 1.2.
  4. 一种亚胺与硼烷发生硼氢化反应制备硼酸酯的方法，包括以下步骤：无水无氧环境下，惰性气体氛围中，在经过脱水脱氧处理的反应瓶中加入亚胺，加入有机溶剂，然后加入硼烷，混合均匀，再加入催化剂邻甲基苯胺基锂，反应得到产物硼酸酯。A method for preparing boric acid ester by borohydration reaction of imine and borane includes the following steps: in an anhydrous and oxygen-free environment, in an inert gas atmosphere, add imine to the reaction bottle after dehydration and deoxygenation treatment, add organic solvent Then, add borane, mix well, then add catalyst o-toluidine lithium, the reaction to obtain the product borate.
  5. 根据权利要求4所述的方法，其特征在于，所述亚胺的化学结构通式如下：The method according to claim 4, wherein the general chemical structure of the imine is as follows:
    Figure PCTCN2018109373-appb-100002
    Figure PCTCN2018109373-appb-100002
    其中R1或R2独立的选自卤素，甲基，甲氧基；所述硼烷选自频哪醇硼烷。Wherein R1 or R2 is independently selected from halogen, methyl and methoxy; the borane is selected from pinacol borane.
  6. 根据权利要求4所述的方法，其特征在于，所述催化剂用量为亚胺摩尔数的4％～5％，亚胺与频哪醇硼烷的摩尔比为1∶1～1∶1.2。The method according to claim 4, wherein the amount of the catalyst is 4% to 5% of the moles of imine, and the molar ratio of imine to pinacol borane is 1: 1 to 1: 1.2.
  7. 根据权利要求4所述的方法，其特征在于，所述催化剂用量为亚胺摩尔数的5％，亚胺与频哪醇硼烷的摩尔比为1∶1.2。The method according to claim 4, wherein the amount of the catalyst is 5% of the moles of imine, and the molar ratio of imine to pinacol borane is 1: 1.2.
  8. 根据权利要求4所述的方法，其特征在于，反应的温度为室温，反应的时间为1～2h。The method according to claim 4, wherein the reaction temperature is room temperature and the reaction time is 1 to 2 hours.
  9. 根据权利要求4所述的方法，其特征在于，有机溶剂为四氢呋喃。The method according to claim 4, wherein the organic solvent is tetrahydrofuran.
  10. 邻甲基苯胺基锂在制备硼酸酯中的应用。The application of lithium o-toluidine in the preparation of boric acid esters.
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006028977A2 (en) * 2004-09-02 2006-03-16 The Penn State Research Foundation Chiral spiro compounds and their use in asymmetric catalytic reactions
US20180044354A1 (en) * 2016-08-09 2018-02-15 Chevron Phillips Chemical Company Lp Olefin Hydroboration
CN108164555A (en) * 2016-06-30 2018-06-15 苏州大学 A kind of synthetic method of borate
CN109289914A (en) * 2018-09-27 2019-02-01 苏州大学张家港工业技术研究院 Application of the o-methyl-benzene amido lithium in catalysis imines and borine hydroboration

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006028977A2 (en) * 2004-09-02 2006-03-16 The Penn State Research Foundation Chiral spiro compounds and their use in asymmetric catalytic reactions
CN108164555A (en) * 2016-06-30 2018-06-15 苏州大学 A kind of synthetic method of borate
US20180044354A1 (en) * 2016-08-09 2018-02-15 Chevron Phillips Chemical Company Lp Olefin Hydroboration
CN109289914A (en) * 2018-09-27 2019-02-01 苏州大学张家港工业技术研究院 Application of the o-methyl-benzene amido lithium in catalysis imines and borine hydroboration

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