Production of morpholine

Abstract

The present disclosure provides a method of producing morpholine. For embodiments, the method includes providing a ruthenium-based heterogeneous catalyst and converting 2-(2-aminoethoxy)ethanol in the presence of the ruthenium-based heterogeneous catalyst and hydrogen gas at a predetermined temperature for a predetermined time to produce morpholine.

Description

Technical Field

[0001] This disclosure generally relates to the production of morpholine. Background Technology

[0002] Morpholine is a heterocyclic organic compound characterized by a six-membered ring structure containing one oxygen (O) atom and one nitrogen (N) atom. Morpholine is an important compound due to its versatility and applications in various industries. For example, its cyclic structure and amine functionality make it a valuable intermediate in the production of pharmaceuticals, agrochemicals, and specialty chemicals, while also finding applications in the oil and gas industry and the polymer industry.

[0003] Morpholine can be synthesized using a variety of methods. For example, morpholine can be produced by reacting diethylene glycol with ammonia or by cyclizing N-(2-aminoethyl)ethanolamine, each reaction being carried out in the presence of a catalyst. Morpholine is also produced by reacting 2-(2-aminoethoxy)ethanol with ammonia in the presence of a hydrogenation dehydrogenation catalyst. As with many reactions, the production of morpholine, including those using the reactions described above, may generate undesirable byproducts, such as unwanted cyclic or acyclic products and amine and alcohol compounds. Therefore, there is a need in the art for methods of producing morpholine that reduce the amount of unwanted byproducts. Summary of the Invention

[0004] Embodiments of this disclosure provide a method for the selective formation of morpholine from 2-(2-aminoethoxy)ethanol (AEE) using a ruthenium-based heterogeneous catalyst, exhibiting improved selectivity relative to unwanted byproducts such as transamination dimers. The selective formation of morpholine from AEE (e.g., reductive amination products) relative to transamination dimers is challenging because catalysts typically used for amination reactions often favor transamination. However, the ruthenium-based heterogeneous catalyst of this disclosure exhibits AEE-specific selective formation of morpholine, as well as improved performance compared to other catalysts, leading to improved morpholine production.

[0005] Embodiments of this disclosure provide a method for producing morpholine. The method of this disclosure particularly includes providing a ruthenium (Ru)-based heterogeneous catalyst. For various embodiments, the ruthenium-based heterogeneous catalyst is formed by: mixing a cobalt metal precursor with 2-(2-aminoethoxy)ethanol (AEE) and potassium bis(trimethylsilyl)amino (KHMDS) to form a cobalt coordination compound in a suspension; mixing the ruthenium coordination compound on a heterogeneous solid support with the cobalt coordination compound in the suspension to form a pre-catalyst mixture; and reducing the pre-catalyst mixture under hydrogen at a predetermined temperature and a predetermined pressure to produce the ruthenium-based heterogeneous catalyst. The ruthenium-based heterogeneous catalyst can be used to convert AEE in the presence of the ruthenium-based heterogeneous catalyst and hydrogen at a predetermined temperature for a predetermined time to produce morpholine.

[0006] Further details regarding the method for producing morpholine according to this disclosure are provided below. For various embodiments, the ruthenium coordination compound may be selected from the group consisting of: RuOH x RuCl3 and combinations thereof, where x is 3 or 4. For various embodiments, the heterogeneous solid support can be selected from the group consisting of: γ-Al2O3, α-Al2O3, SiO2, TiO2, ZrO2, ZnO, and combinations thereof. For various embodiments, the cobalt metal precursor can be selected from the group consisting of: CoCl2, Co(NO3)2, CoSO4, Co2(CO)8, Co[N(SiMe3)2]2, and combinations thereof. For various embodiments, the ruthenium-based heterogeneous catalyst has a cobalt to ruthenium molar ratio of approximately 95:5. In another embodiment, the ruthenium-based heterogeneous catalyst can have a cobalt to ruthenium molar ratio in the range of 10:1 to 99:1. For various embodiments, hydrogen is at a pressure of 0 kPa to 20684 kPa during the AEE conversion. In an additional embodiment, hydrogen is at a pressure of 0 kPa to 6895 kPa during the AEE conversion. In one embodiment, hydrogen is at a pressure of 1724 kPa during the AEE conversion. For various embodiments, the predetermined temperature during the AEE conversion can be from 100°C to 200°C. In one embodiment, the predetermined temperature during the AEE conversion is preferably 180°C. For various embodiments, the predetermined time during the AEE conversion can be from 1 hour to 48 hours. In one embodiment, the predetermined time during the AEE conversion is preferably 24 hours. For various embodiments, the method may further include stirring the reaction mixture. For various embodiments, the method may further include recycling the ruthenium-based heterogeneous catalyst for subsequent AEE conversion to produce morpholine. Detailed Implementation

[0007] Embodiments of this disclosure provide a method for the selective formation of morpholine from 2-(2-aminoethoxy)ethanol (AEE) using a ruthenium-based heterogeneous catalyst, exhibiting improved selectivity relative to unwanted byproducts such as transamination dimers. The selective formation of morpholine from AEE (e.g., reductive amination products) relative to transamination dimers is challenging because catalysts typically used for amination reactions often favor transamination. However, the ruthenium-based heterogeneous catalyst of this disclosure exhibits AEE-specific selective formation of morpholine, as well as improved performance compared to other catalysts, leading to improved morpholine production.

[0008] For various embodiments, the ruthenium-based heterogeneous catalyst of this disclosure is used for the AEE-specific selective formation of morpholines. Specifically, the ruthenium-based heterogeneous catalyst of this disclosure comprises both ruthenium (Ru) and cobalt (Co), which allow for improved selectivity relative to the transammonimeric product. While various bimetallic heterogeneous catalysts for carrying out amination reactions may be known, no catalyst has been found that describes the AEE-specific selective formation of morpholines as described in this disclosure. More specifically, these reactions use more activated phenyl compounds or are carried out in the gas phase with ammonia. However, these types of reactions offer less desirable morpholine formation selectivity compared to this disclosure. In contrast, the ruthenium-based heterogeneous catalyst of this disclosure allows for higher selectivity, which can lead to less waste and lower costs in the production of morpholines.

[0009] As disclosed herein, embodiments of this disclosure provide a method for producing morpholine. The method of this disclosure particularly includes providing a ruthenium (Ru)-based heterogeneous catalyst. For various embodiments, the ruthenium-based heterogeneous catalyst comprises Ru and cobalt (Co) metal nanoparticles supported on a heterogeneous support material, these metal nanoparticles being catalytically active for the production of morpholine. The ruthenium-based heterogeneous catalyst is formed by mixing a cobalt metal precursor with 2-(2-aminoethoxy)ethanol (AEE) and potassium bis(trimethylsilyl)amino (KHMDS) to form a cobalt coordination compound in a suspension. For various embodiments, the suspension may contain 1 molar equivalent of the cobalt metal precursor, which is mixed with 10 to 100 molar equivalents of AEE and 1 to 10 molar equivalents of KHMDS to form the cobalt coordination compound in the suspension. Preferably, the cobalt metal precursor is mixed with 50 to 100 molar equivalents of AEE and 2 to 3 molar equivalents of KHMDS to form the cobalt coordination compound in the suspension. Optionally, a solvent may be used to form a suspension, wherein examples of suitable solvents include, but are not limited to, water, toluene, and mixtures thereof.

[0010] For various embodiments, the formation of the cobalt coordination compound in the suspension 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 formation of the cobalt coordination compound in the suspension can preferably be carried out under an inert atmosphere at the temperature and pressure described 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 suspension can be mixed for 1 hour to 48 hours at the predetermined temperature and pressure indicated above. Preferably, the resulting suspension is stirred for 24 hours at a predetermined temperature and pressure.

[0012] For various embodiments, the cobalt metal precursor can be selected from the group consisting of: CoCl2, Co(NO3)2, CoSO4, Co2(CO)8, Co[N(SiMe3)2]2, and combinations thereof. Preferably, the cobalt coordination compound is CoCl2. For various embodiments, the suspension can contain 1 molar equivalent of the cobalt metal precursor, which is mixed with 10 to 100 molar equivalents of AEE and 1 to 10 molar equivalents of KHMDS, as discussed herein. The suspension can be stirred for a predetermined time of 1 hour to 48 hours at the predetermined temperature and predetermined pressure described above. Preferably, the resulting suspension is stirred for 24 hours at the predetermined temperature and predetermined pressure. Examples of the formation of the cobalt coordination compound Co-AEE2 in the suspension are provided in the Examples section of this document.

[0013] For various embodiments, as discussed herein, the ruthenium-based heterogeneous catalyst formed from the suspension can have a cobalt to ruthenium molar ratio of approximately 95:5. In other embodiments, the ruthenium-based heterogeneous catalyst can have a cobalt to ruthenium molar ratio in the range of 10:1 to 99:1.

[0014] For various embodiments, forming a ruthenium-based heterogeneous catalyst further includes mixing a ruthenium coordination compound on a heterogeneous solid support with a cobalt coordination compound in a suspension to form a pre-catalyst mixture. For various embodiments, the ruthenium coordination compound may be selected from the group consisting of: RuOH x RuCl3 and combinations thereof, where x is 3 or 4. RuOH xThe preparation can be as described by Yamaguchi and Mizuno in “Supported Ruthenium Catalyst for the Heterogeneous Oxidation of Alcohols with Molecular Oxygen”, Angewandte Chemie International Edition; 2002, Vol. 41, pp. 4538-4542, 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 heterogeneous solid support can 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. For various embodiments, the amount of ruthenium coordination compound provided on the heterogeneous solid support can be from 1 wt% to 4 wt% based on the total weight (dry basis) of the heterogeneous solid support.

[0015] In forming the precatalyst mixture, a ruthenium coordination compound on a heterogeneous solid support is mixed with a cobalt coordination compound in a liquid suspension at a concentration of 5 parts per million parts by weight (ppmw) to 500 parts per million parts by weight of the solid support in the liquid suspension to form the precatalyst mixture. For various embodiments, the formation of the precatalyst mixture can preferably be carried out under an inert atmosphere at the temperature and pressure described above for forming the cobalt coordination compound in the suspension. 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 ruthenium coordination compound on the heterogeneous solid support can be mixed with the suspension for 1 hour to 48 hours at the predetermined temperature and pressure described above to form the precatalyst mixture. Preferably, the resulting precatalyst mixture is stirred for 24 hours at a predetermined temperature and pressure.

[0016] For various embodiments, the method further includes reducing the precatalyst mixture (e.g., activating a ruthenium-based heterogeneous catalyst) at a predetermined temperature and under hydrogen (H2) at a predetermined pressure to produce a ruthenium-based heterogeneous catalyst. For various embodiments, the chemical reduction of the precatalyst mixture can be carried out in situ under mixed conditions. For various embodiments, the predetermined hydrogen pressure is between 0 kPa and 20684 kPa (H2 gas pressure). In additional embodiments, 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 precatalyst mixture can be in the range of 100°C to 200°C. Preferably, the predetermined temperature for the chemical reduction of the precatalyst mixture can be in the range of 120°C to 200°C. Preferably, the predetermined temperature for the chemical reduction of the precatalyst mixture 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, with 18 hours being preferred. The ruthenium-based heterogeneous catalyst obtained according to the method herein has metal nanoparticles supported on a heterogeneous support material, which are catalytically active for the production of morpholine.

[0017] A ruthenium-based heterogeneous catalyst can be used to convert AEE to morpholine in the presence of a ruthenium-based heterogeneous catalyst and hydrogen at a predetermined temperature for a predetermined time. In the production of morpholine according to this disclosure, the ruthenium-based heterogeneous catalyst is mixed with AEE in a reactor. The headspace of the reactor is filled with hydrogen to a predetermined pressure, a predetermined temperature, and maintained for a predetermined time to produce morpholine. For various embodiments, in the conversion of AEE to morpholine, the hydrogen is at a predetermined pressure of H2 gas from 0 kPa to 20684 kPa. In an additional embodiment, in the conversion of AEE to morpholine, the hydrogen may be at a predetermined pressure of H2 gas from 0 kPa to 20684 kPa. Preferably, in the conversion of AEE to morpholine, the hydrogen may be at a predetermined pressure of H2 gas from 1724 kPa. For various embodiments, in the conversion of AEE to morpholine, the predetermined temperature may be in the range of 100°C to 200°C. Preferably, in the conversion of AEE to morpholine, the predetermined temperature can be in the range of 160°C to 200°C. Preferably, in the conversion of AEE to morpholine, the predetermined temperature is 180°C. For various embodiments, in the conversion of AEE to morpholine, 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, of which 18 hours is preferred. For various embodiments, the method may also include stirring the reaction mixture. Once the reaction is complete, the reactor is cooled, vented, and the product mixture is separated by filtering out the catalyst. For various embodiments, the method may also include recycling the ruthenium-based heterogeneous catalyst for subsequent AEE conversion to produce morpholine. Example

[0018] 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 mixture used to form the identified compound or mixture. Example Reaction

[0019] 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 “Rational Design of Selective Metal Catalysts for Alcohol Amination with Ammonia” by Wang T. et al., Nat. Catal., 2019, Vol. 2, pp. 773-779, which is incorporated herein by reference. Reductive amination was carried out using a HELDigiCAT high-pressure system (HEL, Ltd., UK) equipped with a 16 mL stainless steel (SS316) reaction vessel. Co(AEE)2

[0020] 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 the 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 a 150 mL medium-porosity glass filter to remove KCl. The solution was used as is without further purification (the [Co] concentration in the AEE was estimated to be 0.16 M). HRMS (m / z +H): Calculated value 286.0833 for those prepared by the methods disclosed in the literature; measured value 268.0895. CoRu@γ-Al2O3

[0021] 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.

[0022]

[0023] The following is a comparison of the catalyst performance of two AEE syntheses as described in co-pending application 63 / 631745 entitled “CATALYST FOR REDUCTIVE AMINATION,” which is incorporated herein by reference in its entirety. The silylamide synthesis is described below (b), which is identical to the AEE synthesis except that decahydronaphthalene is used instead of AEE 1-for-1. This results in CO(N(SiMe3)2)2 being a Co precursor, while the Co(AEE)2 substance is as described in co-pending application 63 / 631752 entitled “CATALYST FOR REDUCTIVE AMINATION,” which is incorporated herein by reference in its entirety, and the silylamide synthesis (referred to as decahydronaphthalene reduction). The specific values ​​used in these reactions are: (a) AEE synthesis: Co(AEE)₂ reduced in pure AEE over RuOHx@γ-Al₂O₃ at 180°C for 16 hours; (b) decahydronaphthalene reduction: Co(N(SiMe₃)₂)₂ reduced in decahydronaphthalene over RuOHx@γ-Al₂O₃ at 180°C for 16 hours. In this example, the catalyst synthesis procedure described above was followed, except that decahydronaphthalene was used instead of AEE. The catalyst was then recovered by evaporation and used in the following experiments.

[0024] The recyclability of the catalyst was tested by magnetic recovery in a glove box and washing with THF. Residual THF was removed by adding 2.0 mL of AEE and repeating the process three times, then 3.0 mL of fresh AEE was added to the catalyst and stirred in a glove box at room temperature for 2 hours. The recovered catalyst was then subjected to the same reaction as described above. The results are shown in Table 1.

[0025]

Claims

1. A method for producing morpholine, the method comprising: A ruthenium (Ru)-based heterogeneous catalyst is provided, wherein the ruthenium-based heterogeneous catalyst is formed by the following: The cobalt metal precursor was reacted with 2-(2-aminoethoxy)ethanol (AEE) and bis(trimethylsilyl)aminopotassium (KHMDS) mixed to form Cobalt coordination compounds in suspension; Ruthenium coordination compounds on heterogeneous solid supports and The cobalt coordination compounds in the suspension are mixed to form Precatalyst mixture; as well as At a predetermined temperature and under predetermined pressure in hydrogen gas The pre-catalyst mixture is reduced to produce the ruthenium-based heterogeneous phase. catalyst; as well as In the presence of the ruthenium-based heterogeneous catalyst and hydrogen, AEE is converted at a predetermined temperature for a predetermined time to produce morpholine.

2. The method according to claim 1, wherein the ruthenium coordination compound is selected from the group consisting of: RuOH x RuCl3 and their combinations, where x is 3 or 4.

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

5. The method according to claim 1, wherein the ruthenium-based heterogeneous catalyst has a cobalt to ruthenium molar ratio of about 95:

5.

6. The method of claim 1, wherein in the conversion of AEE, the hydrogen gas is at a pressure of 0 kPa to 20684 kPa.

7. The method according to claim 1, wherein the predetermined temperature during the conversion of AEE is 100°C to 200°C.

8. The method of claim 1, wherein the predetermined time in the conversion of AEE is from 1 hour to 48 hours.

9. The method according to claim 1, further comprising stirring the reaction mixture.

10. The method of claim 1, further comprising recycling the ruthenium-based heterogeneous catalyst for subsequent AEE conversion to produce morpholine.

Images