WO2020073176A1

WO2020073176A1 - Applications of lithium anilide in catalyzing hydroboration reaction of imine and borane

Info

Publication number: WO2020073176A1
Application number: PCT/CN2018/109371
Authority: WO
Inventors: 薛明强; 颜丹丹; 徐晓娟; 朱章野; 武振杰; 沈琪
Original assignee: 南通纺织丝绸产业技术研究院; 苏州大学
Priority date: 2018-10-08
Filing date: 2018-10-08
Publication date: 2020-04-16

Abstract

The present invention relates to applications of a lithium anilide and specifically relates to applications of lithium anilide in catalyzing a hydroboration reaction of imine and borane. A catalyst, borane, and imine are sequentially stirred and mixed evenly, reacted for 1-2 hours, and exposed in air to terminate the reaction; the reaction solution is depressurized to remove a solvent, thus producing borates having different substituents. The lithium anilide disclosed provides high activity in catalyzing the hydroboration reaction of imine and borane at room temperature, the amount of catalyst used is 4-5 mol% of the molar volume of imine, the yield of the reaction is 90% or more, compared with the prior catalyst system, a simple lithium anilide is utilized, reaction conditions are moderate, and the yield of the borates having different substituents under optimized conditions is 99%.

Description

Application of Lithium Anilide in Catalytic Hydroboration of Imine and Borane

Technical field

The invention relates to the application of anilide lithium, in particular to the high-efficiency application of anilide lithium in the catalytic hydroboration reaction of imine and borane.

Background technique

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. The prior art has a hydroboration reaction of C = O bond. Since the hydroboration of carbonyl group is easy to occur, the hydroboration reaction of farbiamine easily occurs. Therefore, the prior art has very harsh conditions for the hydroboration reaction of C = N bond, so it has been developed. It is of great significance to modern industry and organic synthetic chemistry to produce a highly efficient catalytic system for the borohydride reaction of unsaturated C = N bonds.

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.

technical problem

The purpose of the invention of the present invention is to provide the application of lithium anilide, that is, the application of lithium anilide as a high-efficiency catalyst to catalyze the borohydride reaction of imine and borane.

Technical solution

In order to achieve the above object of the invention, the technical scheme adopted by the present invention is: the application of lithium anilide in the catalytic hydroboration reaction of imine and borane; the chemical formula of the lithium anilide is: PhNHLi.

The invention also discloses a method for the borohydride reaction of lithium anilide catalyzed imine and borane, which includes the following steps: adding an imine to a reaction bottle subjected to dehydration and deoxygenation in an inert gas atmosphere under an anhydrous and oxygen-free environment Add organic solvent, then borane, mix evenly, then add catalyst lithium anilide, react for 1h ~ 2h, and terminate the reaction by exposure to air to obtain the product.

The invention further discloses a method for preparing a boric acid ester by the borohydration reaction of lithium anilide catalyzed imine and borane. Add imine to the bottle, add organic solvent, then add borane, mix well, then add catalyst lithium anilide, react for 1h ~ 2h, and terminate the reaction by exposure to air to obtain the product.

In the above technical solution, the imine is selected from aldimine; the general chemical structure of the imine is as follows:

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.

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.

In the above technical solution, the reaction temperature is room temperature, and the reaction time is 1 to 2 hours.

In the above technical solution, the organic solvent is tetrahydrofuran.

The above technical solution can be expressed as follows:

Beneficial effect

Due to the application of the above technical solutions, the present invention has the following advantages compared with the prior art:

1. The present invention finds for the first time that a simple lithium anilide salt can efficiently catalyze the borohydride reaction between imine and borane, which is highly consistent with the economical synthesis of atoms.

2. The lithium anilide catalyzed by 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), the reaction conditions are mild (room temperature), and the reaction time is short (1h to 2h ), And the reaction yield is high, the post-treatment is simple, the reaction is simple and controllable, the reaction uses inexpensive THF as the solvent.

3. The catalyst disclosed in the present invention has good universality for imines with different substitution positions and different electronic effects.

Embodiments of the invention

The present invention will be further described in combination with the following embodiments:

Example One: Lithylanilide catalyzes the hydroboration reaction of benzylidene with pinacol borane

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 0.5 mmol (0.0726 mL) of borane and mix well, and finally add 43.4 ul of lithium anilide Of tetrahydrofuran solution (0.5759M) (5mol% dosage, the same below), after reaction for 2h, draw a drop into the nuclear magnetic tube with a dropper, 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).

Example 2: Lithylanilide catalyzes the hydroboration reaction of benzylidene aniline with pinacol borane

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 0.55 mmol (0.0798 mL) of borane and mix well, and finally add 43.4 ul of lithium anilide The solution of tetrahydrofuran (0.5759M) (5mol% dosage, the same below), after 2 hours of reaction, draw a drop into the nuclear magnetic tube with a dropper, add CDCl3 to make a solution. The calculated 1H spectrum yield was 95%. Nuclear magnetic data of the product: 1H NMR (CDCl3, 400MHz) δ: 7.29 ~ 7.12 (m, 9H), 6.88 ~ 6.84 (t, 1H), 4.69 (s, 2H), 1.29 (s, 12H).

Example 3: Lithylanilide catalyzes the hydroboration reaction of benzylidene and pinacol borane

Add 0.5mmol of bifuridine to the reaction flask after dehydration and deoxygenation treatment, add 100ul of THF, then use a pipette to add 0.6mmol (0.0871mL) of borane to mix well, and finally add 43.4ul of lithium anilide The solution of tetrahydrofuran (0.5759M) (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).

Substituting the lithium anilide with the lithium amido compound of formula I, the product cannot be obtained.

Example 4: Lithylanilide catalyzes the hydroboration reaction of benzylidene aniline with pinacol borane

Add 0.5mmol of bifuridine to the reaction flask after dehydration and deoxygenation treatment, add 100ul of THF, then use a pipette to add 0.6mmol (0.0871mL) of borane to mix well, and finally add 43.4ul of lithium anilide The solution of tetrahydrofuran (0.5759M) (5mol% dosage, the same below), after 1h of reaction, draw a drop into the nuclear magnetic tube with a dropper, add CDCl ^{3 to make a} solution. The calculated ¹ H spectrum yield was 93%. Nuclear magnetic data of the product: ¹ H NMR (CDCl3, 400 MHz) δ: 7.29-7.12 (m, 9H), 6.88-6.84 (t, 1H), 4.69 (s, 2H), 1.29 (s, 12H).

Example 5: Lithium anilide catalyzes the hydroboration reaction of benzylidene aniline with pinacol borane

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 34.8 ul of lithium anilide The solution of tetrahydrofuran (0.5759M) (4mol% dosage), after 2 hours of reaction, draw a drop into the nuclear magnetic tube with a dropper, 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).

Example 6: Lithylanilide catalyzed N- (p-methylbenzylidene) aniline and pinacol borane hydroboration reaction

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 43.4ul lithium anilide in tetrahydrofuran solution (0.5759M) (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).

Example 7: Lithanilide catalyzed N- (p-methoxybenzylidene) aniline and pinacol borane hydroboration reaction

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 The alkane was mixed evenly. Finally, 43.4 ul of lithium anilide in tetrahydrofuran solution (0.5759M) (5mol% dosage, the same below) was added. After the reaction for 2h, a drop was drawn into the nuclear magnetic tube with a dropper and CDCl _{3 was} added 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).

Example 8: Lithylanilide catalyzes the hydroboration of N- (4-fluorobenzylidene) aniline with pinacol borane

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 43.4ul of lithium anilide in tetrahydrofuran solution (0.5759M) (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: 7.22 ～ 7.15 (d, 6H), 6.98 ～ 6.94 (d, 3H), 4.66 (s, 2H), 1.30 (s, 12H).

Example 9: Lithylanilide catalyzes the hydroboration of N- (4-chlorobenzylidene) aniline with pinacol borane

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 43.4ul of lithium anilide in tetrahydrofuran solution (0.5759M) (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: 7.20 ～ 7.14 (d, 6H), 6.99 ～ 6.93 (d, 3H), 4.64 (s, 2H), 1.30 (s, 12H).

Example 10: Lithylanilide catalyzes the hydroboration of N- (4-bromobenzylidene) aniline with pinacol borane

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 43.4ul of lithium anilide in tetrahydrofuran solution (0.5759M) (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: 7.24 ～ 7.16 (d, 6H), 6.97 ～ 6.93 (d, 3H), 4.63 (s, 2H), 1.31 (s, 12H).

Example 11: Lithylanilide catalyzes the hydroboration reaction of benzylidene-p-toluidine with pinacol borane

In the reaction flask after dehydration and deoxygenation, add 0.5 mmol of benzylidene p-toluene under argon protection, 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 43.4 ul of aniline Lithium-based tetrahydrofuran solution (0.5759M) (4mol% 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).

Example 12: Lithylanilide catalyzed N- (benzylidene) -4-fluoroaniline and pinacol borane hydroboration reaction

In the reaction flask after dehydration and deoxygenation, add 0.5 mmol of benzylidene p-toluene under argon protection, 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 43.4 ul of aniline Lithium-based tetrahydrofuran solution (0.5759M) (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).

Example 13: Lithylanilide catalyzes the hydroboration of N- (benzylidene) -4-chloroaniline with pinacol borane

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 43.4ul lithium anilide in tetrahydrofuran solution (0.5759M) (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).

Example 14: Lithylanilide catalyzes the hydroboration of N- (benzylidene) -4-bromoaniline with pinacol borane

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 43.4ul lithium anilide in tetrahydrofuran solution (0.5759M) (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).

The reaction temperature of the above embodiment is room temperature; the present invention finds for the first time that simple anilide 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 possibilities for industrial applications.

Claims

The application of lithium anilide in the catalytic hydroboration of imine and borane.
The application according to claim 1, characterized in that the method for the borohydride reaction of lithium anilide catalyzed imine and borane includes the following steps: dehydrated and deoxidized in an inert gas atmosphere under an anhydrous and oxygen-free environment Add imine to the reaction bottle, add organic solvent, then add borane, mix well, then add catalyst lithium anilide, react at room temperature for 1 to 2 hours, and terminate the reaction by exposure to air to obtain the product.
The application according to claim 2, characterized in that the general chemical structure of the imine is as follows:

Wherein R1 or R2 is independently selected from halogen, methyl and methoxy; the borane is selected from pinacol borane; the organic solvent is tetrahydrofuran;

The dosage of the anilide lithium 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.
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, and then add the catalyst lithium anilide, the reaction to obtain the product borate.
The method according to claim 4, wherein the general chemical structure of the imine is as follows:

Wherein R1 or R2 is independently selected from halogen, methyl and methoxy; the borane is selected from pinacol borane.
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.
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.
The method according to claim 4, wherein the reaction temperature is room temperature and the reaction time is 1 to 2 hours.
The method according to claim 4, wherein the organic solvent is tetrahydrofuran.
The application of lithium anilide in the preparation of borate esters.