Catalyst for the reduction of amination

Abstract

The present disclosure provides a catalyst for reductive amination. The catalyst can be formed from steps comprising: mixing a cobalt complex compound with 2-(2-aminoethoxy)ethanol (AEE) and potassium bis(trimethylsilyl)amide (KHMDS) to form a metal solution; mixing the metal solution with a heterogeneous solid support to form a supported precatalyst, wherein the heterogeneous solid support comprises a ruthenium species; and chemically reducing the supported precatalyst under a predetermined hydrogen pressure and a predetermined temperature for a predetermined time to produce the catalyst for reductive amination.

Description

Technical Field

[0001] This disclosure relates generally to catalysts, and more specifically to catalysts for reductive amination. Background Technology

[0002] In the field of organic synthesis, particularly in the production of amines for pharmaceuticals, fine chemicals, and other applications, the selective catalysis of reductive amination relative to transamination is an important area of ​​interest. Developing techniques for synthesizing such catalysts is challenging, but research continues to strive to improve the catalytic performance and selectivity of reductive amination relative to transamination. Examples of catalysts using nickel or cobalt as the main metal for reductive amination exist. However, these single-metal catalysts do not produce the desired product with high selectivity. Examples of catalysts combining both metals exist in an attempt to achieve the desired higher selectivity. However, methods using both metal catalysts typically require increased pressure to force the equilibrium toward the desired product. Catalysts with higher selectivity would result in less waste or cheaper operations to produce the same material. Therefore, there remains a need in the art to produce catalysts that selectively catalyze reductive amination rather than transamination. Summary of the Invention

[0003] Embodiments of this disclosure provide a catalyst with improved selectivity for reductive amination reactions. The catalyst of this disclosure comprises metal nanoparticles supported on a heterogeneous support material, which are catalytically active for reductive amination chemistry. For various embodiments, the metal nanoparticles are formed from two different metals discussed herein and supported on an oxide surface of the heterogeneous support material. Specifically, the catalyst is formed using 2-(2-aminoethoxy)ethanol (AEE) to form an AEE precursor with cobalt (Co) and ruthenium (Ru) compounds, which is then reduced on a solid support to Co / Ru nanoparticles. For various embodiments, the catalyst is particularly suitable for carrying out reductive amination chemistry.

[0004] For various embodiments, the catalyst of this disclosure can be used for reductive amination. The catalyst can be in the form of metal nanoparticles supported on a heterogeneous support material, which are catalytically active for reductive amination chemistry. The catalyst of this disclosure is formed by: mixing a cobalt coordination compound with AEE and potassium bis(trimethylsilyl)amino to form a metal solution; mixing the metal solution with a heterogeneous solid support to form a supported precatalyst, wherein the heterogeneous solid support contains ruthenium; and chemically reducing the supported precatalyst at a predetermined hydrogen pressure and a predetermined temperature for a predetermined time to produce a catalyst for reductive amination. The metal nanoparticles supported on the heterogeneous support material are catalytically active for reductive amination, as discussed herein.

[0005] Further details regarding the catalysts of this disclosure are provided below. For various embodiments, the cobalt coordination compound may be selected from the group consisting of: CoCl2, Co(NO3)2, CoSO4, Co2(CO)8, Co[N(SiMe3)2]2, Co-AEE2, and combinations thereof. For various embodiments, the heterogeneous solid support may be selected from the group consisting of: γ-Al2O3, α-Al2O3, SiO2, TiO2, ZrO2, ZnO, and combinations thereof. For various embodiments, based on the total weight of the heterogeneous solid support, the heterogeneous solid support may contain 1% to 4% wt% ruthenium material. For these embodiments, the ruthenium material may be, for example, RuOH. x The catalyst is formed from RuCl3 and combinations thereof, where x is 3 or 4. For various embodiments, the supported precatalyst has a cobalt to ruthenium molar ratio of approximately 95:5. In another embodiment, the ruthenium-based heterogeneous catalyst may have a cobalt to ruthenium molar ratio in the range of 10:1 to 99:1. For various embodiments, the predetermined hydrogen pressure is between 0 kPa and 20684 kPa. In another embodiment, the predetermined hydrogen pressure is between 0 kPa and 6895 kPa. In one embodiment, the predetermined hydrogen pressure is preferably 1724 kPa. For various embodiments, the predetermined temperature is in the range of 100°C to 200°C. Preferably, the predetermined temperature is 180°C. For various embodiments, the predetermined time can be in the range of 1 hour to 48 hours. Preferably, the predetermined time can be preferably 24 hours. Attached Figure Description

[0006] Figure 1 The structure of a Co(AEE)2 mixture using extended X-ray absorption fine structure (EXAFS) according to this embodiment is provided.

[0007] Figure 2 EXAFS of the CoRu@γ-Al2O3 catalyst obtained after reacting at 180°C under hydrogen for 1 hour is provided.

[0008] Figure 3 EXAFS of the CoRu@γ-Al2O3 catalyst obtained after the reaction was completed at 15 hours are provided. Detailed Implementation

[0009] Embodiments of this disclosure provide a catalyst with improved selectivity for reductive amination reactions. The catalyst of this disclosure comprises metal nanoparticles supported on a heterogeneous support material, which are catalytically active for reductive amination chemistry. For various embodiments, the metal nanoparticles may be formed from two different metals discussed herein and supported on an oxide surface of the heterogeneous support material. Specifically, the catalyst is formed using 2-(2-aminoethoxy)ethanol (AEE) to form an AEE precursor with cobalt (Co) and ruthenium (Ru) compounds, which is then reduced on a solid support to Co / Ru nanoparticles. For various embodiments, the catalyst is particularly suitable for carrying out reductive amination chemistry.

[0010] For various embodiments, the catalysts disclosed herein can be used for reductive amination. As discussed herein, the catalysts for reductive amination can be in the form of metal nanoparticles supported on a heterogeneous support material, which are catalytically active for reductive amination chemistry. The catalysts for reductive amination are formed by mixing a cobalt coordination compound with AEE and potassium bis(trimethylsilyl)amino (KHMDS) to form a metal solution. For various embodiments, mixing the cobalt coordination compound with AEE and KHMDS to form a metal solution can occur at a predetermined temperature in the range of 10°C to 80°C and a predetermined pressure in the range of 101 kPa to 20,684 kPa. Preferably, the predetermined temperature can be in the range of 20°C to 50°C and the predetermined pressure is 101 kPa to 3,477 kPa. Preferably, the predetermined temperature is 23°C (room temperature) and the predetermined pressure is 101 kPa (standard atmospheric pressure).

[0011] For various embodiments, the cobalt coordination compound can be selected from the group consisting of: CoCl2, Co(NO3)2, CoSO4, Co2(CO)8, Co[N(SiMe3)2]2, Co-AEE2, and combinations thereof. Examples of forming Co-AEE2 are provided in the Examples section of this document. Preferably, the cobalt coordination compound is CoCl2.

[0012] For various embodiments, the metal solution may contain 1 molar equivalent of a cobalt coordination compound dissolved in 10 to 100 molar equivalents of AEE to form a mixture. A 1 to 10 molar equivalent of KHMDS relative to the cobalt coordination compound is added to this mixture to form a metal solution, which is then stirred at the predetermined temperature and pressure indicated above for a predetermined time of 1 to 48 hours. Preferably, the cobalt coordination compound is mixed with 50 to 100 molar equivalents of AEE and 2 to 3 molar equivalents of KHMDS (more preferably 2 molar equivalents of KHMDS) to form a metal solution, which is then stirred at the predetermined temperature and pressure indicated above for a predetermined time of 1 to 48 hours. Preferably, the resulting metal solution is stirred at the predetermined temperature and pressure for 24 hours. Filtration may be used to remove any precipitates (e.g., KCl) formed in the metal solution.

[0013] For various embodiments, forming the catalyst further includes mixing a metal solution with a heterogeneous solid support comprising ruthenium to form a supported precatalyst. For various embodiments, the heterogeneous solid support may be selected from the group consisting of γ-Al₂O₃, α-Al₂O₃, SiO₂, TiO₂, ZrO₂, ZnO, and combinations thereof. Preferably, the heterogeneous solid support is γ-Al₂O₃.

[0014] For various embodiments, the heterogeneous solid support further comprises ruthenium. For example, based on the total weight of the heterogeneous solid support (dry basis), the heterogeneous solid support may further comprise 1% to 4% wt% ruthenium. For various embodiments, the ruthenium may be derived from, for example, RuOH. x RuOH is formed from RuCl3 and combinations thereof, where x is 3 or 4. xThe preparation can be as described by Yamaguchi and Mizuno in "Supported Ruthenium Catalyst for the Heterogeneous Oxidation of Alcohols with Molecular Oxygen" in Angewandte Chemie International Edition, Vol. 41, pp. 4538-4542, 2002, which is incorporated herein by reference in its entirety. Briefly, RuOHx is prepared by mixing a high-surface-area γ-Al₂O₃ catalyst support in an aqueous solution of RuCl₃ at room temperature. The solid is filtered and washed with water, then dried under vacuum. The solid is then resuspended in water and made alkaline to a pH of 13.2 by adding an aqueous solution of NaOH. The solid is recovered again by filtration and washing with water, and dried under vacuum. For various embodiments, the supported precatalyst can have a cobalt:ruthenium molar ratio of approximately 95:5. In another embodiment, the supported precatalyst may have a cobalt to ruthenium molar ratio in the range of 10:1 to 99:1.

[0015] For various embodiments, the amount of metal solution mixed with the heterogeneous solid support to form the supported precatalyst can be determined based on the ratio of the mass of Co metal in the solution to the mass of the heterogeneous solid support plus the mass of Co. Preferably, the ratio is provided such that the weight % of Co in the solution is 12.4 wt% relative to the weight of the heterogeneous solid support plus the weight of Co. However, for various embodiments, the range can be from 1 wt% to 30 wt%. In other words, the ratio of the mass of the heterogeneous solid support to the mass of dissolved Co is in the range of 99:1 to 2.33:1, with a ratio of 7.06:1 being preferred. Preferably, the mixing of the metal solution and the heterogeneous solid support to form the supported precatalyst can be carried out under an inert atmosphere at the temperature and pressure as indicated above. For various embodiments, the inert atmosphere can be a nitrogen atmosphere or other atmospheres known in the art (such as argon and helium). For various embodiments, the metal solution and the heterogeneous solid support can be mixed for 1 hour to 24 hours at the predetermined temperature and pressure indicated above to form the supported precatalyst. Preferably, the metal solution and the heterogeneous solid support are mixed at a predetermined temperature and a predetermined pressure as indicated above for 1 to 4 hours to form a supported precatalyst.

[0016] For various embodiments, the supported precatalyst is then chemically reduced over Co-AEE2 at a predetermined hydrogen (H2) pressure and a predetermined temperature to produce a catalyst for reductive amination. For various embodiments, the chemical reduction of the supported precatalyst can be carried out under mixed conditions. For various embodiments, the predetermined hydrogen pressure is between 0 kPa and 20684 kPa (H2 gas pressure). In another embodiment, the predetermined hydrogen pressure is between 0 kPa and 6895 kPa (H2 gas pressure). In one embodiment, the predetermined hydrogen pressure is preferably 1724 kPa (H2 gas pressure). For various embodiments, the predetermined temperature for the chemical reduction of the supported precatalyst can be in the range of 100°C to 200°C. Preferably, the predetermined temperature for the chemical reduction of the supported precatalyst can be in the range of 160°C to 200°C. Preferably, the predetermined temperature for the chemical reduction of the supported precatalyst is 180°C. For various embodiments, the predetermined time is in the range of 1 hour to 48 hours. Preferably, the predetermined time is in the range of 1 hour to 24 hours. The catalyst for reductive amination obtained according to the method herein has metal nanoparticles supported on a heterogeneous support material, which are catalytically active for reductive amination as discussed herein.

[0017] Considering the foregoing discussion and by way of example, the method disclosed herein can therefore involve employing a metal precursor (such as, for example, CoCl2) and mixing it with AEE and KHMDS to produce a metal solution containing a metal moiety (e.g., Co) in the AEE. The metal solution is then mixed with a heterogeneous solid support (such as, for example, γ-Al₂O₃). For various embodiments, the heterogeneous solid support may contain the metal moiety (e.g., RuOH on γ-Al₂O₃). x The catalyst can then be activated by heating and reducing it in the presence of hydrogen gas (H2) at a predetermined pressure and a predetermined temperature (e.g., 1724 kPa H2 and 180 °C). If desired, the method can be carried out in situ (e.g., in a container). The reaction produces metal nanoparticles supported on a heterogeneous carrier material, which, after filtration and washing, exhibit catalytic activity for reductive amination.

[0018] Example

[0019] Unless otherwise specified, all components were purchased from commercial suppliers and used as is. Unless otherwise specified, all percentages are weight percentages (wt%) based on the total weight of the mixtures used to form the following examples and comparative examples.

[0020] Example reaction

[0021] Anhydrous CoCl2 (97% purity) was purchased from Alfa Aesar and stored in a glove box under an inert N2 atmosphere. Alumina (γ-Al2O3, purity >99%, 150-200 mesh) was purchased from Alfa Aesar, ground using a mortar and pestle to break down any large lumps, then dried in an oven at 200°C and stored in a glove box under an N2 atmosphere. 2-(2-aminoethoxy)ethanol (AEE, 98% purity) was purchased from Acros Organics, degassed by CaH2 distillation under vacuum, and stored under an inert N2 atmosphere. Bis(trimethylsilyl)aminopotassium (KHMDS, 95% purity) was purchased from Sigma Aldrich and stored in a glove box under an inert N2 atmosphere. RuOHx@γ-Al2O3 was prepared according to the paper "Rational Design of Selective Metal Catalysts for Alcohol Amination Utilization of Ammonia" by Wang T. et al., published in *Nature Catalysis*, Vol. 2, 2019, pp. 773-779, which is incorporated herein by reference. Reductive amination was carried out using a HELDigiCAT high-pressure system equipped with a 16 mL stainless steel (SS316) reaction vessel.

[0022] Co(AEE)2

[0023] In a nitrogen-atmospheric glove box, anhydrous CoCl2 (1.695 g, 13.05 mmol) was added to a 100 mL oven-dried Schlenk flask equipped with a Teflon cap and a stir bar. While stirring vigorously, AEE (80 mL, 798.9 mmol) was added to dissolve the CoCl2, which immediately changed from blue to purple upon dissolution in AEE. The solution was stirred at room temperature for 20 minutes. Then, KHMDS (5.205 g, 26.09 mmol) was slowly added in portions over 10 minutes, yielding a deep purple solution and a white suspension (KCl). After the addition of KHMDS was complete, the solution was stirred at room temperature (23 °C) for 24 hours. The solution was then filtered through 150 mL of medium-porosity frit glass to remove KCl, resulting in a Co(AEE)2 mixture. The Co(AEE)2 mixture was used as is without further purification (estimated [Co] content in AEE was 0.16 M). HRMS (m / z + H): calculated value 286.0833; measured value 268.0895.

[0024] CoRu@γ-Al2O3

[0025] In a nitrogen-atmospheric glove box, 200 mg of RuOHx@γ-Al2O3 was weighed into a 16 mL stainless steel container. While stirring, a solution of Co(AEE)2 (3.0 mL, 0.16 M) was slowly added to the RuOHx@γ-Al2O3 via a syringe. After the addition was complete, the reactor was sealed inside the glove box, and the heterogeneous mixture was stirred at room temperature for 1 hour. The reaction vessel was then removed from the glove box, placed in an aluminum heating block with a stirring rate of 700 rpm, and connected to a HELDigiCAT high-pressure system. To ensure the removal of all residual oxygen, the reactor was purged with 1724 kPa H2, then vented, and this process was repeated three times. After the last cycle, the reactor was maintained at a static pressure of 1724 kPa H2 and heated to 180 °C with a stirring rate of 700 rpm. After 16 hours, the reactor was cooled to room temperature and vented. To remove residual H2 and NH3 (generated during the reaction), the headspace was replaced with 689 kPa argon and vented three times. The reactor was then transferred back to a glove box, and CoRu@γ-Al2O3 was recovered by filtration through 15 mL of medium-porosity glass frit. The supported catalyst was washed with multiple fractions of tetrahydrofuran (THF, 3 × 10 mL), dried under vacuum to produce 260 mg of black powder, and stored in a glove box under an inert atmosphere. Analysis of the filtrate by GC-FID using tetraethylene glycol dimethyl ether as an internal standard provided a 99% AEE conversion and a 42% morpholine GC yield.

[0026] The structure of the Co(AEE)2 mixture obtained after filtration but before reduction in an H2 atmosphere was analyzed using extended X-ray absorption fine structure (EXAFS) to confirm the presence of the desired structure. Figure 1 The illustrated structure, in which Co atoms are coordinated by nitrogen (100) and oxygen (102) atoms, which are connected by two carbon (104) atoms, is similar to the structure of AEE. EXAFS K-edge measurements were performed at the Taiwan Photon Source.

[0027] Now for reference Figure 2 and Figure 3 Examples of a series of EXAFS performed on the CoRu@γ-Al2O3 catalyst formed as described above are illustrated. Figure 2 The EXAFS of the CoRu@γ-Al2O3 catalyst was obtained after reacting at 180°C under hydrogen for 1 hour, and Figure 3 This is the EXAFS of the CoRu@γ-Al2O3 catalyst obtained after the reaction was completed at 15 hours.

[0028] The K-side measurements were fitted to obtain estimates of bond lengths and coordination numbers (CNs), as outlined in Tables 1 and 2 below. The data in Table 1 support the view that Co exists as nanoparticles with Ru present as separated regions on the nanoparticle surface. The CNs of the Co-Co bonds are consistent with the nanoparticles and are <2 nm. The equal CNs of the Ru-Co and Ru-Ru bonds indicate phase segregation between Ru and Co. The partial oxidation of Ru, as demonstrated by the increased Ru-O bonds during the reaction, also supports the presence of Ru on the nanoparticle surface.

[0029]

[0030]

[0031] The resulting particles are catalytically active, as demonstrated in co-pending application 63 / 631,794, the entire contents of which are incorporated herein by reference.

Claims

1. A catalyst for reductive amination, said catalyst being formed by the following steps: Cobalt coordination compounds were mixed with 2-(2-aminoethoxy)ethanol (AEE) and bis(trimethylsilyl)aminopotassium (KHMDS) to form a metal solution; The metal solution is mixed with a heterogeneous solid support to form a supported precatalyst, wherein the heterogeneous solid support comprises ruthenium; and The supported precatalyst is chemically reduced at a predetermined hydrogen pressure and temperature for a predetermined time to produce the catalyst for reductive amination.

2. The method according to claim 1, wherein the cobalt coordination compound is selected from the group consisting of: CoCl2, Co(NO3)2, CoSO4, Co2(CO)8, Co[N(SiMe3)2]2, Co-AEE2, and combinations thereof.

3. The method according to claim 1, wherein the heterogeneous solid support is selected from the group consisting of γ-Al2O3, α-Al2O3, SiO2, TiO2, ZrO2, ZnO, and combinations thereof.

4. The catalyst according to any one of claims 1 to 3, wherein the heterogeneous solid support comprises 1% to 4% by weight of the ruthenium material based on the total weight of the heterogeneous solid support.

5. The catalyst according to any one of claims 1 to 4, wherein the ruthenium substance is RuOH. x It is formed by RuCl3 and their combinations, where x is 3 or 4.

6. The catalyst according to any one of claims 1 to 5, wherein the predetermined hydrogen pressure is from 0 kPa to 20684 kPa.

7. The catalyst according to any one of claims 1 to 6, wherein the predetermined temperature is in the range of 100°C to 200°C.

8. The catalyst according to any one of claims 1 to 7, wherein the predetermined time is in the range of 1 hour to 48 hours.

9. The catalyst according to any one of claims 1 to 8, wherein the supported precatalyst has a cobalt to ruthenium molar ratio of about 95:5.

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