Method for selectively catalyzing hydroboration of isocyanate by organic aluminum compound and application

Abstract

The invention discloses a catalyst for hydroboration of isocyanate as well as a preparation method and an application method of the catalyst. When the catalyst is used for catalyzing the hydroboration reaction of isocyanate and borane to synthesize boric acid ester, the catalytic activity is high, the reaction condition is mild (the reaction can be carried out at room temperature), the reaction time is short, the yield of the product is high (more than or equal to 99%), the reaction is simple and controllable, and the post-treatment is simple.

Description

Technical Field

[0001] The present invention relates to the technical field of catalytic boronation reaction of isocyanate. Background Art

[0002] Hydroboration is widely used in the reduction and coupling reactions of unsaturated bonds. The resulting organoboron compounds are important synthetic intermediates with the advantages of simple structure, stable properties, easy control of the preparation process, strong reactivity, good chemical selectivity and high yield. These compounds are widely used in the development of new transition metal-catalyzed reactions. For example, isocyanates can be reduced to borate esters by hydroboration. Organoboron compounds not only play an important role in organic synthesis, but can also be used as initiators for polymerization reactions, antioxidants for kerosene, bactericides, anticancer drugs and neutron capture agents, especially in the treatment of brain tumors.

[0003] In the past few decades, catalysts for hydroboration reactions have mostly been compounds containing transition metals and rare earth metals. These metals are expensive and have limited reserves, making it difficult to fully meet the needs of sustainable industrial production. Elemental aluminum has gradually attracted people's attention due to its abundant reserves, low price and low toxicity. With the development of green chemistry, non-precious metal catalysts have become one of the research focuses.

[0004] The Nembenna research group used zinc hydride catalyst to realize the selective hydroboration conversion of isocyanate for the first time (Angew.Chem.Int.Ed.2021,60,11991-12000). The organic zinc required for this reaction is expensive and difficult to obtain. However, the hydroboration reaction of organoaluminum-catalyzed isocyanate has not been reported. The organoaluminum compound of the present invention will only undergo the first step of hydroboration reaction, which has a high degree of chemical selectivity for this reaction.

[0005] Using catalysts with low preparation costs and lowering the reaction temperature are urgent problems to be solved in the isocyanate hydroboration reaction. Summary of the invention

[0006] The purpose of the present invention is to provide a high-efficiency catalyst for catalyzing the hydroboration reaction of isocyanate and a preparation method and application thereof.

[0007] The present invention first provides the following technical solution:

[0008] A catalyst for hydroboration reaction is a crystal having the following structural formula. The present invention provides a method for preparing the catalyst, which comprises:

[0009]

[0010] (1) Under an inert atmosphere, an asymmetric nitrogen-containing ligand and diisobutylaluminum hydride are reacted in an organic solvent, and the reaction mixture is heated and stirred overnight to obtain a butylaluminum compound solution stabilized by the asymmetric nitrogen-containing ligand.

[0011] (2) Concentrating the fluorine-containing Schiff base ligand-stabilized aluminum methyl compound solution and refrigerating it for 24 hours for crystallization to obtain a yellow crystalline compound.

[0012] Wherein, the structural formula of the asymmetric nitrogen-containing ligand is as follows.

[0013]

[0014] According to some preferred embodiments of the present invention, the reaction in step (1) is first carried out at 0-20°C for 0.5-10 hours, and then at 20-30°C for 4-14 hours.

[0015] More preferably, the reaction in step (1) is first carried out at 0-20°C for 0.5-10 hours, and then at 20-30°C for 8-14 hours.

[0016] According to some preferred embodiments of the present invention, in step (2), the crystallization temperature is -15 to -5°C.

[0017] More preferably, in the step (2), the crystallization temperature is -12 to -8°C.

[0018] According to some preferred embodiments of the present invention, the reaction process is always under an inert atmosphere.

[0019] According to some preferred embodiments of the present invention, the molar ratio of the asymmetric nitrogen-containing ligand to diisobutylaluminum hydride is 1:1.

[0020] According to some preferred embodiments of the present invention, the concentration of diisobutylaluminum hydride in the organic solution of diisobutylaluminum hydride is 0.5-1.5 mol / L.

[0021] According to some preferred embodiments of the present invention, the organic solvent is selected from n-hexane.

[0022] According to some preferred embodiments of the present invention, the ratio of the amount of the asymmetric nitrogen-containing ligand to the volume of the organic solvent is 0.1 to 0.3 mmol / mL.

[0023] The present invention further provides the use of the above catalyst and / or the catalyst prepared according to the above preparation method in the hydroboration reaction of isocyanate and a borohydride compound.

[0024] According to some preferred embodiments of the present invention, the molar amount of the catalyst is 1 to 5% of the molar amount of the isocyanate compound.

[0025] The temperature of the hydroboration reaction is 25-40°C.

[0026] According to some preferred embodiments of the present invention, the hydroboration reaction time is 0.5 to 1 hour.

[0027] According to some preferred embodiments of the present invention, the boron hydride compound is selected from pinacol borane.

[0028] According to some preferred embodiments of the present invention, the isocyanate is selected from one or more of ethyl isocyanate, isopropyl isocyanate, 3-propylene isocyanate, p-toluene isocyanate, o-toluene isocyanate, p-fluorophenyl isocyanate, 3-nitrobenzene isocyanate, benzyl isocyanate, and 1-naphthyl isocyanate.

[0029] The present invention has the following beneficial effects:

[0030] (1) The present invention first discovered that organoaluminum compounds can efficiently catalyze the hydroboration reaction of isocyanates, which meets the requirements of green chemistry and atom-economic reactions;

[0031] (2) The catalyst of the present invention does not contain transition metals, but uses main group metal aluminum, which is abundant, cheap and non-toxic, and has the prospect of large-scale industrial application;

[0032] (3) In some preferred embodiments, the preparation method of the catalyst of the present invention has a high yield, and crystals meeting the requirements of single crystal testing can be obtained after 24 hours, and the production efficiency is high;

[0033] (4) When the catalyst of the present invention catalyzes the hydroboration reaction of isocyanate and borane to synthesize boric ester, the catalytic activity is high, the reaction conditions are mild (the reaction can be carried out at room temperature), the reaction time is short, the product yield is high (≥99%), and the reaction is simple and controllable, and the post-treatment is simple;

[0034] (5) When the catalyst of the present invention catalyzes the hydroboration reaction of isocyanate and borane to synthesize boric ester, it is applicable to isocyanates with different substituents and different electronic effects. The applicable scope of the substrate is wide, which provides more feasible implementation methods for the industrial synthesis of boric ester and is suitable for industrial production. DETAILED DESCRIPTION

[0035] The present invention is described in detail below in conjunction with the embodiments, but it should be understood that the embodiments are only used to exemplify the present invention and do not constitute any limitation on the protection scope of the present invention. All reasonable changes and combinations included in the scope of the invention spirit of the present invention fall within the protection scope of the present invention.

[0036] According to the technical solution of the present invention, a specific method for preparing a catalyst for isocyanate hydroboration reaction comprises:

[0037] (1) The obtained asymmetric nitrogen-containing ligand and diisobutylaluminum hydride are reacted in an organic solvent at 20° C. to 30° C. for 10 to 14 hours to obtain a butylaluminum organic compound solution stabilized by the asymmetric nitrogen-containing ligand.

[0038] (2) The solution was concentrated to 5 mL and refrigerated at -15 to -5°C for 23 to 25 hours before crystallization to obtain the yellow catalyst.

[0039] Further, a specific catalytic reaction process carried out by the obtained catalyst includes:

[0040] The obtained catalyst (1) is added to a mixed system of isocyanate and boron hydride compound (HBpin), and reacted at a reaction temperature of 25 to 40° C. for 0.5 to 1 hour to obtain a borate ester compound. In the above process, the boron hydride compound is preferably pinacol borane.

[0041] Example 1

[0042] The catalyst is prepared by the following process:

[0043] At 0°C, an organic solution of diisobutylaluminum hydride is dropped into an organic solvent of n-hexane containing an asymmetric nitrogen-containing ligand, and the reaction mixture is heated to 20-30°C, stirred for 10-14 hours, and filtered to obtain a filtrate; the obtained filtrate is concentrated to 5 ml, and refrigerated at -15-5°C for 24 hours for crystallization to obtain the yellow catalyst;

[0044] After testing, the yield of the obtained catalyst crystals was 76%. The results of characterization of its structure by nuclear magnetic hydrogen spectrum and carbon spectrum are as follows:

[0045] H NMR spectrum: 1 H NMR (400MHz, CDCl3) δ7.16–7.07(m,6H,Ar-H),3.22(p,J=6.7Hz,4H,CH),2.36(t,J=6.3Hz,2H,CH2),2.02(t,J=6.5Hz,2H,CH2),1.77(s,3H,CH3),1.57(s ,2H,CH2),1.42(t,J=6.3Hz,2H,CH2),1.19(dd,J=11.2,6.8Hz,12H,CH3),1. 04(dd,J=20.6,6.7Hz,12H,CH3),0.75–0.43(m,12H,CH3),-0.33(s,4H,CH2).

[0046] Example 2

[0047] The catalytic reaction is carried out through the following process:

[0048] Under the protection of inert gas, 1 mmol of ethyl isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction bottle, and then 5 mmol% of the obtained catalyst crystals were added. After reacting for 0.5 to 1 hour, 1 mL of anhydrous methanol was added. After stirring for 30 minutes, the methanol was removed in vacuo, the oil was dissolved with CDCl3, and a sample was taken for NMR characterization. The NMR data of the obtained product are as follows:

[0049] 1 H NMR (400MHz, CDCl3): δ8.62 (s, 1H, NCHO), 3.36 (q, J = 7.2 Hz, 2H, CH2), 1.31 (s, 12H, CH3), 1.09 (t, J = 7.3 Hz, 3H, CH3). The product was calculated 1 The H-NMR yield was 99%.

[0050] Example 3

[0051] The catalytic reaction is carried out through the following process:

[0052] Under the protection of inert gas, 1 mmol of isopropyl isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction bottle, and then 5 mmol% of the obtained catalyst crystals were added. After reacting for 0.5 to 1 hour, 1 mL of anhydrous methanol was added. After stirring for 30 minutes, the methanol was removed in vacuo, the oil was dissolved with CDCl3, and a sample was taken for NMR characterization. The NMR data of the obtained product are as follows:

[0053] 1 H NMR (400MHz, CDCl3): δ8.93 (s, 1H, NCHO), 4.61-4.59 (m, 1H, CH), 1.24 (d, J = 7.4 Hz, 6H, CH3), 0.95 (s, 12H, CH3). The product was calculated 1 The H-NMR yield was 99%.

[0054] Example 4

[0055] The catalytic reaction is carried out through the following process:

[0056] Under the protection of inert gas, 1 mmol of 3-isocyanate propylene and 1 mmol of pinacol borane were added to a 10 mL reaction bottle, and then 5 mmol% of the obtained catalyst crystals were added. After reacting for 0.5 to 1 hour, 1 mL of anhydrous methanol was added. After stirring for 30 minutes, the methanol was removed in vacuo, the oil was dissolved with CDCl3, and a sample was taken for NMR characterization. The NMR data of the obtained product are as follows:

[0057] 1 H NMR (400MHz, CDCl3): δ8.69 (s, 1H, NCHO), 5.84-5.78 (m, 1H, CH), 5.13-5.06 (m, 2H, CH2), 3.91 (d, J=5.3, 2H, CH2), 1.31 (s, 12H, CH3). The product was calculated 1 The H-NMR yield was 99%.

[0058] Example 5

[0059] The catalytic reaction is carried out through the following process:

[0060] Under the protection of inert gas, 1 mmol of p-toluene isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction bottle, and then 5 mmol% of the obtained catalyst crystals were added. After reacting for 0.5 to 1 hour, 1 mL of anhydrous methanol was added. After stirring for 30 minutes, the methanol was removed in vacuo, the oil was dissolved with CDCl3, and a sample was taken for NMR characterization. The NMR data of the obtained product are as follows:

[0061] 1 H NMR (400MHz, CDCl3): δ8.85 (s, 1H, NCHO), 7.18 (d, J = 8.2, 2H, ArH), 7.03 (d, J = 8.3, 2H, ArH), 2.35 (s, 3H, CH3), 1.31 (s, 12H, CH3). The product was calculated 1 The H-NMR yield was 99%.

[0062] Example 6

[0063] The catalytic reaction is carried out through the following process:

[0064] Under the protection of inert gas, 1mmol o-toluene isocyanate and 1mmol pinacol borane were added to a 10mL reaction bottle, and then 5mmol% of the obtained catalyst crystals were added. After reacting for 0.5 to 1 hour, 1mL of anhydrous methanol was added. After stirring for 30 minutes, the methanol was removed in vacuo, the oil was dissolved with CDCl3, and a sample was taken for NMR characterization. The NMR data of the obtained product are as follows:

[0065] 1 H NMR (400MHz, CDCl3): δ8.85 (s, 1H, NCHO), 7.28-7.21 (m, 3H, ArH), 7.01-6.99 (m, 1H, ArH), 2.18 (s, 3H, CH3), 1.29 (s, 12H, CH3). The product was calculated 1 The H-NMR yield was 99%.

[0066] Example 7

[0067] The catalytic reaction is carried out through the following process:

[0068] Under the protection of inert gas, 1mmol of p-fluorophenyl isocyanate and 1mmol of pinacol borane were added to a 10mL reaction bottle, and then 5mmol% of the obtained catalyst crystals were added. After reacting for 0.5 to 1 hour, 1mL of anhydrous methanol was added. After stirring for 30 minutes, the methanol was removed in vacuo, the oil was dissolved with CDCl3, and a sample was taken for NMR characterization. The NMR data of the obtained product are as follows:

[0069] 1 H NMR (400MHz, CDCl3): δ8.84 (s, 1H, NCHO), 7.14-7.05 (m, 4H, ArH), 1.29 (s, 12H, CH3). The product was calculated 1 The H-NMR yield was 99%.

[0070] Example 8

[0071] The catalytic reaction is carried out through the following process:

[0072] Under the protection of inert gas, 1mmol 3-nitrobenzene isocyanate and 1mmol pinacol borane were added to a 10mL reaction bottle, and then 5mmol% of the obtained catalyst crystals were added. After reacting for 0.5 to 1 hour, 1mL of anhydrous methanol was added. After stirring for 30 minutes, the methanol was removed in vacuo, the oil was dissolved with CDCl3, and a sample was taken for NMR characterization. The NMR data of the obtained product are as follows:

[0073] 1 H NMR (400MHz, CDCl3): δ8.91 (s, 1H, NCHO), 8.05-8.04 (m, 1H, ArH), 7.59-7.55 (m, 3H, ArH), 1.33 (s, 12H, CH3). The product was calculated 1 The H-NMR yield was 99%.

[0074] Example 9

[0075] The catalytic reaction is carried out through the following process:

[0076] Under the protection of inert gas, 1 mmol of benzyl isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction bottle, and then 5 mmol% of the obtained catalyst crystals were added. After reacting for 0.5 to 1 hour, 1 mL of anhydrous methanol was added. After stirring for 30 minutes, the methanol was removed in vacuo, the oil was dissolved with CDCl3, and a sample was taken for NMR characterization. The NMR data of the obtained product are as follows:

[0077] 1 H NMR (400MHz, CDCl3): δ8.70 (s, 1H, NCHO), 7.31 (d, J = 7.6, 2H, ArH), 7.27 (d, J = 7.5, 2H, ArH), 7.25-7.18 (m, 1H, ArH), 4.46 (s, 2H, CH2), 1.26 (s, 12H, CH3). The product was calculated 1 The H-NMR yield was 99%.

[0078] Example 10

[0079] The catalytic reaction is carried out through the following process:

[0080] Under the protection of inert gas, 1 mmol 1-naphthyl isocyanate and 1 mmol pinacol borane were added to a 10 mL reaction bottle, and then 5 mmol% of the obtained catalyst crystals were added. After reacting for 0.5 to 1 hour, 1 mL of anhydrous methanol was added. After stirring for 30 minutes, the methanol was removed in vacuo, the oil was dissolved with CDCl3, and a sample was taken for NMR characterization. The NMR data of the obtained product are as follows:

[0081] 1 H NMR (400MHz, CDCl3): δ9.05 (s, 1H, NCHO), 7.84-7.76 (m, 2H, ArH), 7.67 (d, J=7.3, 2H, ArH), 7.48-7.45 (m, 3H, ArH), 7.23 (d, J=7.3, 1H, ArH), 1.28 (s, 6H, CH3), 1.24 (s, 6H, CH3). The product was calculated 1 The H-NMR yield was 99%.

[0082] Embodiment 11

[0083] The catalytic reaction is carried out through the following process:

[0084] Under the protection of inert gas, 1 mmol of p-toluene isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction bottle, and then 5 mmol% of the obtained catalyst crystals were added. After reacting for 0.5 to 1 hour, 1 mL of anhydrous methanol was added. After stirring for 30 minutes, the methanol was removed in vacuo, the oil was dissolved with CDCl3, and a sample was taken for NMR characterization. The NMR data of the obtained product are as follows:

[0085] 1H NMR (400MHz, CDCl3): δ7.03 (d, J = 8.4 Hz, 2H, ArH), 6.55 (d, J = 8.3 Hz, 2H, CH2), 2.82 (s, 3H, CH3), 2.25 (s, 3H,, 6H, CH3). The product was calculated 1 The H-NMR yield was 99%.

[0086] Example 12

[0087] The catalytic reaction is carried out through the following process:

[0088] Under the protection of inert gas, 1 mmol of p-methoxyphenyl isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction bottle, and then 5 mmol% of the obtained catalyst crystals were added. After reacting for 0.5 to 1 hour, 1 mL of anhydrous methanol was added. After stirring for 30 minutes, the methanol was removed in vacuo, the oil was dissolved with CDCl3, and a sample was taken for NMR characterization. The NMR data of the obtained product are as follows:

[0089] 1 H NMR (400MHz, CDCl3): δ6.82 (d, J = 8.7 Hz, 2H, ArH), 6.61 (d, 2H, J = 9.1 Hz, ArH), 3.77 (s, 3H, CH3), 2.81 (s, 3H, CH3). The product was calculated 1 The H-NMR yield was 99%.

[0090] The above embodiments are only preferred implementations of the present invention, and the protection scope of the present invention is not limited to the above embodiments. All technical solutions under the concept of the present invention belong to the protection scope of the present invention. It should be pointed out that for ordinary technicians in this technical field, improvements and modifications without departing from the principle of the present invention should also be regarded as the protection scope of the present invention.

Claims

1. A butyl aluminum catalyst stabilized by an asymmetric nitrogen-containing ligand, characterized in that: The catalyst is a crystal having the following structural formula:

2. The method for preparing the compound according to claim 1, characterized in that: It includes: (1) Under an inert atmosphere, an asymmetric nitrogen-containing ligand and diisobutylaluminum hydride are reacted in an organic solvent, and the reaction mixture is heated and stirred overnight to obtain a butylaluminum compound solution stabilized by an asymmetric nitrogen-containing ligand; (2) The butyl aluminum compound solution stabilized by the asymmetric nitrogen-containing ligand is concentrated and refrigerated for 24 hours for crystallization to obtain a yellow crystalline compound.

3. Wherein, the structural formula of the asymmetric nitrogen-containing ligand is as follows:

4. The preparation method according to claim 2, characterized in that: The reaction in step (1) should be carried out at 0-20°C for 0.5 to 10 hours, and then at 20-30°C for 8 to 14 hours; in step (2), the crystallization temperature is -15 to -5°C.

5. The preparation method according to claim 2, characterized in that: The reaction in step (1) is carried out under a nitrogen or argon atmosphere.

6. The preparation method according to claim 2, characterized in that: The molar ratio of the asymmetric nitrogen-containing ligand to the diisobutylaluminum hydride is 1:1; and / or the concentration of diisobutylaluminum hydride in the organic solution of diisobutylaluminum hydride is 0.5-1.5 mol / L.

7. The preparation method according to claim 2, characterized in that: The organic solvent is selected from n-hexane.

8. Use of the catalyst according to claim 1 and / or the catalyst prepared by the preparation method according to any one of claims 1 to 7 in the hydroboration reaction of isocyanate and a borohydride compound.

9. The use according to claim 8, characterized in that: The molar amount of the catalyst is 1 to 5% of the molar amount of the isocyanate compound.

10. The use according to claim 8, characterized in that: The temperature of the hydroboration reaction is 25 to 40° C., and / or the time of the hydroboration reaction is 0.5 to 1 hour.

11. The use according to claim 8, characterized in that: The boron hydride compound is selected from pinacol borane, and / or the isocyanate is selected from one or more of ethyl isocyanate, isopropyl isocyanate, 3-propylene isocyanate, p-toluene isocyanate, o-toluene isocyanate, p-fluorophenyl isocyanate, 3-nitrobenzene isocyanate, benzyl isocyanate, 1-naphthyl isocyanate, p-toluene isocyanate, and p-methoxyphenyl isocyanate.

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