Process and use of organoaluminum compounds for the selective catalysis of isocyanate borohydride

Abstract

The application discloses a catalyst for isocyanate borohydration reaction and a preparation and application method thereof. When the catalyst is used for catalyzing the borohydration reaction of isocyanate and borane to synthesize borate, the catalyst has high catalytic activity, mild reaction conditions (the reaction can be carried out at room temperature), short reaction time, high product yield (≥99%), and the reaction is simple, controllable, and simple in post-treatment.

Description

Technical Field

[0001] This invention relates to the technical field of catalytic borohydride reaction of isocyanates. Background Technology

[0002] Hydroboration is widely used in the reduction and coupling of unsaturated bonds, and the resulting organoboron compounds are important synthetic intermediates with advantages such as simple structure, stable properties, easy-to-control preparation process, high reactivity, good chemoselectivity, 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 via hydroboration. Organoboron compounds not only play an important role in organic synthesis, but also serve as initiators for polymerization reactions, antioxidants for kerosene, bactericides, anticancer drugs, and neutron trapping agents, playing a particularly important role 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. Aluminum, due to its abundant reserves, low price, and low toxicity, has gradually attracted attention. With the development of green chemistry, non-precious metal catalysts have become one of the research focuses.

[0004] The Nembenna group first achieved selective hydroboration of isocyanates using zinc hydride catalysts (Angew. Chem. Int. Ed. 2021, 60, 11991-12000). The organozinc required for this reaction is expensive and difficult to obtain. However, organoaluminum-catalyzed hydroboration of isocyanates has not been reported. The organoaluminum compounds of this invention undergo only the first step of the hydroboration reaction, exhibiting high chemoselectivity for this reaction.

[0005] Using low-cost catalysts and reducing reaction temperature are pressing problems that need to be solved in the hydroboration of isocyanates. Summary of the Invention

[0006] The purpose of this invention is to provide a highly efficient catalyst for the hydroboration reaction of isocyanates, its preparation method, and its application.

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

[0008] A catalyst for a hydroboration reaction, which is a crystal having the following structural formula, is provided in this invention by a method for preparing the catalyst, comprising:

[0009]

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

[0011] (2) The solution of the aluminum methyl compound stabilized by the fluorinated Schiff base ligand was concentrated and refrigerated for 24 hours to crystallize, resulting in a yellow crystalline compound.

[0012] 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 carried out at 0 to 20°C for 0.5 to 10 hours, and then at 20 to 30°C for 4 to 14 hours.

[0015] More preferably, the reaction in step (1) is first carried out at 0 to 20°C for 0.5 to 10 hours, and then at 20 to 30°C for 8 to 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 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 carried out 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 application of the above-described catalyst and / or the catalyst prepared according to the above preparation method in the hydroboration reaction of isocyanates and borohydrides.

[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 borohydride reaction is 25–40°C.

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

[0027] According to some preferred embodiments of the present invention, the borohydride is selected from pinacolborane.

[0028] According to some preferred embodiments of the present invention, the isocyanate is selected from one or more of ethyl isocyanate, isopropyl isocyanate, propylene 3-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) This invention is the first to discover that organoaluminum compounds can efficiently catalyze the hydroboration reaction of isocyanates, which meets the requirements of green chemistry and atom economy reaction;

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

[0032] (3) In some preferred embodiments, the catalyst preparation method of the present invention has a high yield and can obtain crystals that meet the requirements of single crystal testing after 24 hours, resulting in high production efficiency.

[0033] (4) The catalyst of the present invention has high catalytic activity, mild reaction conditions (can be reacted at room temperature), short reaction time, high product yield (≥99%) when catalyzing the hydroboration reaction of isocyanate and borane to synthesize boronic acid esters. The reaction is simple and controllable, and the post-processing is simple.

[0034] (5) The catalyst of the present invention is applicable to isocyanates with different substituents and different electronic effects when catalyzing the hydroboration reaction of isocyanates and boranes to synthesize boronic esters. It has a wide range of substrates and provides more feasible methods for the industrial synthesis of boronic esters, making it suitable for industrial production. Detailed Implementation

[0035] The present invention will be described in detail below with reference to embodiments. However, it should be understood that the embodiments are only used to illustrate the present invention and do not constitute any limitation on the scope of protection of the present invention. All reasonable modifications and combinations included within the scope of the inventive spirit of the present invention fall within the scope of protection of the present invention.

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

[0037] (1) The obtained asymmetric nitrogen-containing ligand and diisobutylaluminum hydride were reacted in an organic solvent at 20℃~30℃ for 10~14 hours to obtain an asymmetric nitrogen-containing ligand-stable butylaluminum organic compound solution.

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

[0039] Furthermore, a specific catalytic reaction process using the obtained catalyst includes:

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

[0041] Example 1

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

[0043] At 0°C, an organic solution of diisobutylaluminum hydride was added dropwise to an organic solvent of hexane containing an asymmetric nitrogen ligand. The reaction mixture was heated to 20–30°C and stirred for 10–14 hours. The mixture was then filtered to obtain a filtrate. The filtrate was concentrated to 5 ml and then refrigerated at -15–5°C for 24 hours to crystallize the yellow catalyst.

[0044] The yield of the obtained catalyst crystals was 76%. The structural characterization results by 1H NMR and 1C NMR are as follows:

[0045] 1H 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 inert gas protection, 1 mmol of ethyl isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction flask, followed by 5 mmol% of the obtained catalyst crystals. After reacting for 0.5–1 hour, 1 mL of anhydrous methanol was added, and the mixture was stirred for 30 minutes. The methanol was then removed under vacuum, and the oily substance was dissolved with CDCl3. Samples were taken and characterized by NMR. The NMR data of the obtained product are as follows:

[0049] 1 ¹H NMR (400MHz, CDCl₃): δ 8.62 (s, ¹H, NCHO), 3.36 (q, J = 7.2Hz, ²H, CH₂), 1.31 (s, ¹²H, CH₃), 1.09 (t, J = 7.3Hz, ³H, CH₃). Calculated products... 1 The H-NMR yield was 99%.

[0050] Example 3

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

[0052] Under inert gas protection, 1 mmol of isopropyl isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction flask, followed by 5 mmol% of the obtained catalyst crystals. After reacting for 0.5–1 hour, 1 mL of anhydrous methanol was added, and the mixture was stirred for 30 minutes. The methanol was then removed under vacuum, and the oily substance was dissolved with CDCl3. Samples were taken and characterized by NMR. The NMR data of the obtained product are as follows:

[0053] 1 ¹H NMR (400MHz, CDCl₃): δ 8.93 (s, ¹H, NCHO), 4.61–4.59 (m, ¹H, CH), 1.24 (d, J = 7.4 Hz, ⁶H, CH₃), 0.95 (s, ¹²H, CH₃). Calculated products... 1 The H-NMR yield was 99%.

[0054] Example 4

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

[0056] Under inert gas protection, 1 mmol of propylene 3-isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction flask, followed by 5 mmol% of the obtained catalyst crystals. After reacting for 0.5–1 hour, 1 mL of anhydrous methanol was added, and the mixture was stirred for 30 minutes. The methanol was then removed under vacuum, and the oily substance was dissolved with CDCl3. Samples were taken and characterized by NMR. The NMR data of the obtained product are as follows:

[0057] 1 ¹H NMR (400MHz, CDCl₃): δ 8.69 (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). Calculated products... 1 The H-NMR yield was 99%.

[0058] Example 5

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

[0060] Under inert gas protection, 1 mmol of p-toluene isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction flask, followed by 5 mmol% of the obtained catalyst crystals. After reacting for 0.5–1 hour, 1 mL of anhydrous methanol was added, and the mixture was stirred for 30 minutes. The methanol was then removed under vacuum, and the oily substance was dissolved with CDCl3. Samples were taken and characterized by NMR. The NMR data of the obtained product are as follows:

[0061] 1 ¹H NMR (400MHz, CDCl₃): δ 8.85 (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). Calculated products... 1 The H-NMR yield was 99%.

[0062] Example 6

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

[0064] Under inert gas protection, 1 mmol of o-toluene isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction flask, followed by 5 mmol% of the obtained catalyst crystals. After reacting for 0.5–1 hour, 1 mL of anhydrous methanol was added, and the mixture was stirred for 30 minutes. The methanol was then removed under vacuum, and the oily substance was dissolved with CDCl3. Samples were taken and characterized by NMR. The NMR data of the obtained product are as follows:

[0065] 1 ¹H NMR (400MHz, CDCl₃): δ 8.85 (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). Calculated products... 1 The H-NMR yield was 99%.

[0066] Example 7

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

[0068] Under inert gas protection, 1 mmol of p-fluorophenyl isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction flask, followed by 5 mmol% of the obtained catalyst crystals. After reacting for 0.5–1 hour, 1 mL of anhydrous methanol was added, and the mixture was stirred for 30 minutes. The methanol was then removed under vacuum, and the oily substance was dissolved with CDCl3. Samples were taken and characterized by NMR. The NMR data of the obtained product are as follows:

[0069] 1 ¹H NMR (400MHz, CDCl₃): δ 8.84 (s, ¹H, NCHO), 7.14–7.05 (m, ⁴H, ArH), 1.29 (s, ¹²H, CH₃). Calculated products... 1 The H-NMR yield was 99%.

[0070] Example 8

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

[0072] Under inert gas protection, 1 mmol of 3-nitrobenzene isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction flask, followed by 5 mmol% of the obtained catalyst crystals. After reacting for 0.5–1 hour, 1 mL of anhydrous methanol was added, and the mixture was stirred for 30 minutes. The methanol was then removed under vacuum, and the oily substance was dissolved with CDCl3. Samples were taken and characterized by NMR. The NMR data of the obtained product are as follows:

[0073] 1 ¹H NMR (400MHz, CDCl₃): δ 8.91 (s, ¹H, NCHO), 8.05–8.04 (m, ¹H, ArH), 7.59–7.55 (m, ³H, ArH), 1.33 (s, ¹²H, CH₃). Calculated products... 1 The H-NMR yield was 99%.

[0074] Example 9

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

[0076] Under inert gas protection, 1 mmol of benzyl isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction flask, followed by 5 mmol% of the obtained catalyst crystals. After reacting for 0.5–1 hour, 1 mL of anhydrous methanol was added, and the mixture was stirred for 30 minutes. The methanol was then removed under vacuum, and the oily substance was dissolved with CDCl3. Samples were taken and characterized by NMR. The NMR data of the obtained product are as follows:

[0077] 1 ¹H NMR (400MHz, CDCl₃): δ 8.70 (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). Calculated products... 1 The H-NMR yield was 99%.

[0078] Example 10

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

[0080] Under inert gas protection, 1 mmol of 1-naphthyl isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction flask, followed by 5 mmol% of the obtained catalyst crystals. After reacting for 0.5–1 hour, 1 mL of anhydrous methanol was added, and the mixture was stirred for 30 minutes. The methanol was then removed under vacuum, and the oily substance was dissolved with CDCl3. Samples were taken and characterized by NMR. The NMR data of the obtained product are as follows:

[0081] 1 ¹H NMR (400MHz, CDCl₃): δ 9.05 (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). Calculated products... 1 The H-NMR yield was 99%.

[0082] Example 11

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

[0084] Under inert gas protection, 1 mmol of p-toluene isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction flask, followed by 5 mmol% of the obtained catalyst crystals. After reacting for 0.5–1 hour, 1 mL of anhydrous methanol was added, and the mixture was stirred for 30 minutes. The methanol was then removed under vacuum, and the oily substance was dissolved with CDCl3. Samples were taken and characterized by NMR. The NMR data of the obtained product are as follows:

[0085] 1¹H NMR (400MHz, CDCl₃): δ 7.03 (d, J = 8.4Hz, 2H, ArH), 6.55 (d, J = 8.3Hz, 2H, CH₂), 2.82 (s, 3H, CH₃), 2.25 (s, 3H, 6H, CH₃). Calculated products... 1 The H-NMR yield was 99%.

[0086] Example 12

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

[0088] Under inert gas protection, 1 mmol of p-methoxyphenyl isocyanate and 1 mmol of pinacol borane were added to a 10 mL reaction flask, followed by 5 mmol% of the obtained catalyst crystals. After reacting for 0.5–1 hour, 1 mL of anhydrous methanol was added, and the mixture was stirred for 30 minutes. The methanol was then removed under vacuum, and the oily substance was dissolved with CDCl3. Samples were taken and characterized by NMR. The NMR data of the obtained product are as follows:

[0089] 1 ¹H NMR (400MHz, CDCl₃): δ 6.82 (d, J = 8.7Hz, 2H, ArH), 6.61 (d, 2H, J = 9.1Hz, ArH), 3.77 (s, 3H, CH₃), 2.81 (s, 3H, CH₃). Calculated products... 1 The H-NMR yield was 99%.

[0090] The above embodiments are merely preferred embodiments of the present invention, and the scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, improvements and modifications made without departing from the principles of the present invention should also be considered within the scope of protection of the present invention.

Claims

1. The application of an asymmetric nitrogen-containing ligand-stabilized butylaluminum catalyst in the hydroboration reaction of isocyanates and borohydrides, wherein the catalyst is prepared by the following method: Under an inert atmosphere, an asymmetric nitrogen-containing ligand was reacted with diisobutylaluminum hydride in n-hexane solvent at a molar ratio of 1:

1. The reaction was first carried out at 0–20 °C for 0.5–10 hours, followed by a reaction at 20–30 °C for 8–14 hours. After concentration, the reaction solution was crystallized at -15–-5 °C for 24 hours to obtain a yellow crystalline catalyst with the following structural formula. .

2. The application according to claim 1, characterized in that: The amount of catalyst used is 1% to 5% of the molar amount of isocyanate.

3. The application according to claim 1, characterized in that: The temperature of the borohydride reaction is 25–40°C, and the reaction time is 0.5–1 hour.

4. The application according to claim 1, characterized in that: The borohydride is pinacolborane; the isocyanate is selected from one or more of ethyl isocyanate, isopropyl isocyanate, 3-propenyl isocyanate, p-toluene isocyanate, o-toluene isocyanate, p-fluorophenyl isocyanate, 3-nitrobenzene isocyanate, benzyl isocyanate, 1-naphthyl isocyanate, and p-methoxyphenyl isocyanate.

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