Morpholine production

Abstract

The present disclosure provides for a method of producing morpholine. For the 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 at a predetermined temperature over a predetermined time to produce morpholine.

Description

[0001] MORPHOLINE PRODUCTION

[0002] Technical Field

[0003] The present disclosure relates generally to the production of morpholine.

[0004] Background

[0005] Morpholine is a heterocyclic organic compound characterized by a six-membered ring structure containing one oxygen (O) and one nitrogen (N) atom in the ring. 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, along with uses in the oil and gas, and polymer industries.

[0006] Morpholine can be synthesized using a variety of processes. For example, morpholine can be produced by reacting diethylene glycol with ammonia or through the cyclization of N-(2- aminoethyl)ethanolamine, each in the presence of a catalyst. Morpholine has also been 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 above reactions, can produce unwanted side products, such as undesired cyclic or acyclic products along with amine and alcohol compounds. As such, there is a need in the art for processes to produce morpholine that reduce the amount of unwanted side products.

[0007] Summary

[0008] Embodiments of the present disclosure provide a method for selectively forming morpholine from 2-(2-aminoethoxy)ethanol (AEE) using a ruthenium based heterogeneous catalyst that shows improved selectivity over unwanted side products, such as transamination dimers. Selectively forming morpholine from AEE (e.g., the reductive amination product) over transamination dimers is challenging as the transamination reaction is often favored by catalysts generally used for amination reactions. The ruthenium based heterogeneous catalyst of the present disclosure, however, exhibit specific selective formation of morpholine from AEE along with improved performance compared to other catalysts, which results in improvements in morpholine production. Embodiments of the present disclosure provide a method of producing morpholine. The method of the present disclosure includes, among other things, providing a ruthenium (Ru) based heterogeneous catalyst. For the 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)amide (KHMDS) to form a cobalt coordination compound in a suspension; mixing a ruthenium coordination compound on a heterogeneous solid support with the cobalt coordination compound in the suspension to form a precatalyst mixture; and reducing the precatalyst mixture at a predetermined temperature under hydrogen at a predetermined pressure to produce the ruthenium based heterogeneous catalyst. The ruthenium based heterogeneous catalyst can be used in converting AEE in the presence of the ruthenium based heterogeneous catalyst and hydrogen at a predetermined temperature over a predetermined time to produce morpholine.

[0009] The following provides further details on the method of producing morpholine according to the present disclosure. For the various embodiments, the ruthenium coordination compound can be selected from the group consisting of RuOHx, RUCI3 and combinations thereof, wherein x is 3 or 4. For the various embodiments, the heterogeneous solid support can be selected from the group consisting of Y-AI2O3, 01-AI2O3, SiO2, TiC>2, ZrO2, ZnO and combinations thereof. For the various embodiments, the cobalt metal precursor can be selected from the group consisting of C0CI2, Co(NC>3)2, COSO4, Co2(CO)g, Co[N(SiMe3)2]2 and combinations thereof. For the various embodiments, the ruthenium based heterogeneous catalyst has a cobalt to ruthenium molar- ratio of about 95:5. In an additional embodiment, the ruthenium based heterogeneous catalyst can have a cobalt to ruthenium molar ratio of in a range of 10: 1 to 99: 1. For the various embodiments, in converting AEE the hydrogen is at a pressure of 0 to 20684 kPa. In additional embodiments, in converting AEE the hydrogen is at a pressure of 0 to 6895 kPa. In one embodiment, in converting AEE the hydrogen is at a pressure of 1724 kPa. For the various embodiments, in converting AEE the predetermined temperature can be from 100 to 200 °C. In one embodiment, in converting AEE the predetermined temperature is preferably 180 °C. For the various embodiments, in converting AEE the predetermined time can be 1 to 48 hours. In one embodiment, in converting AEE the predetermined time is, preferably, 24 hours. For the various embodiments, the method can further include stirring the reaction mixture. For the various embodiments, the method can further include recycling the ruthenium based heterogeneous catalyst for use in a subsequent conversion of AEE to produce morpholine.

[0010] Detailed Description

[0011] Embodiments of the present disclosure provide a method for selectively forming morpholine from 2- (2- aminoethoxy )ethanol (AEE) using a ruthenium based heterogeneous catalyst that shows improved selectivity over unwanted side products, such as transamination dimers. Selectively forming morpholine from AEE (e.g., the reductive amination product) over transamination dimers is challenging as the transamination reaction is often favored by catalysts generally used for amination reactions. The ruthenium based heterogeneous catalyst of the present disclosure, however, exhibit specific selective formation of morpholine from AEE along with improved performance compared to other catalysts, which results in improvements in morpholine production.

[0012] For the various embodiments, the ruthenium based heterogeneous catalyst of the present disclosure is used for the specific selective formation of morpholine from AEE. Specifically, the ruthenium based heterogeneous catalyst of the present disclosure include both ruthenium (Ru) and cobalt (Co) that allow for improved selectivity over transamination dimer products. While various bimetallic heterogeneous catalysts used to perform amination reactions might be known, none have been found that describe the specific selective formation of morpholine from AEE as is done in the present disclosure. More specifically, these reactions use either more activated phenyl species or run in the gas phase with ammonia. These types of reactions, however, provide less desirable selectivities for morpholine formation as compared to the present disclosure. The ruthenium based heterogeneous catalyst of the present disclosure, in contrast, allows for higher selectivity that can result in lower waste and cost in producing morpholine.

[0013] As discussed herein, embodiments of the present disclosure provide a method of producing morpholine. The method of the present disclosure includes, among other things, providing a ruthenium (Ru) based heterogeneous catalyst. For the various embodiments, the ruthenium based heterogeneous catalyst includes metal nanoparticles of Ru and cobalt (Co) supported on a heterogeneous support material that is 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)amide (KHMDS) to form a cobalt coordination compound in a suspension. For the various embodiments, the suspension can include 1 molar equivalents 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 can be used in forming the suspension, where examples of suitable solvents include, but are not limited to, water, toluene and mixtures thereof.

[0014] For the various embodiments, forming the cobalt coordination compound in the suspension can occur at a predetermined temperature in the range of 10 to 80 °C and at a predetermined pressure of 101 to 20,684 kPa. Preferably, the predetermined temperature can be in the range of 20 to 50 °C and at a predetermined pressure of 101 to 3,477 kPa. Preferably, the predetermined temperature is 23 °C (room temperature) and the predetermined pressure is 101 kPa (standard atmospheric pressure).

[0015] For the various embodiments, forming the cobalt coordination compound in the suspension can be done, preferably, under an inert atmosphere at a temperature and pressure as noted above. For the various embodiments, the inert atmosphere can be a nitrogen atmosphere or others as are known in the art, such as argon and helium among others. For the various embodiments, the suspension can be mixed at the predetermined temperature and pressure noted above for a time of 1 to 48 hours. Preferably, the resulting suspension is stirred at the predetermined temperature and predetermined pressure for 24 hours.

[0016] For the various embodiments, the cobalt metal precursor can be selected from the group consisting of C0CI2, Co(NO3)2, CoSOq, Co2(CO)g, Co[N(SiMe3)2]2and combinations thereof. Preferably, the cobalt coordination compound is C0CI2. For the various embodiments, the suspension can include 1 molar equivalents of the cobalt metal precursor 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 at the predetermined temperature and predetermined pressure noted above for a predetermined time of 1 to 48 hours. Preferably, the resulting suspension is stirred at the predetermined temperature and predetermined pressure for 24 hours. An example of forming the cobalt coordination compound, C0-AEE2 , in the suspension is provided in the Examples section herein.

[0017] For the various embodiments, the ruthenium based heterogeneous catalyst formed from the suspension, as discussed herein, can have a cobalt to ruthenium molar ratio of about 95:5. In an additional embodiment, the ruthenium based heterogeneous catalyst can have a cobalt to ruthenium molar ratio of in a range of 10:1 to 99: 1.

[0018] For the various embodiments, forming the ruthenium based heterogeneous catalyst next includes mixing a ruthenium coordination compound on a heterogeneous solid support with the cobalt coordination compound in the suspension to form a precatalyst mixture. For the various embodiments, the ruthenium coordination compound can be selected from the group consisting of RuOHx, RUCI3 and combinations thereof, where x is 3 or 4. The RuOHxcan be prepared as described in “Supported Ruthenium Catalyst for the Heterogeneous Oxidation of Alcohols with Molecular Oxygen” Yamaguchi & Mizuno; Angewandte Chemie International Edition; 2002, 41, 4538-4542, which is incorporated herein by reference in its entirety. Briefly, the RuOHx is prepared by mixing a high surface area y- A12O3 catalyst support in an aqueous solution of RUCI3 at room temperature. The solid is filtered and washed with water then dried under vacuum. The solid is then resuspended in water and made basic by addition of aqueous NaOH to a pH of 13.2. The solid is again recovered by filtration and washing with water and dried under vacuum. For the various embodiments, the heterogeneous solid support can be selected from the group consisting of Y-AI2O3, 01-AI2O3, SiO2, TiO2, ZrO2, ZnO and combinations thereof. Preferably, the heterogeneous solid support is 7-AI2O3. For the various embodiments, the resulting amount of ruthenium coordination compound provided on the heterogeneous solid support can be from I to 4 weight percent of the ruthenium coordination compound based on a total weight of the heterogeneous solid support (dry basis).

[0019] In forming the precatalyst mixture, the ruthenium coordination compound on the heterogeneous solid support is mixed with the cobalt coordination compound in the liquid suspension at concentration of 5 - 500 parts per million by weight (ppmw) solid support in liquid suspension to form the precatalyst mixture. For the various embodiments, forming the precatalyst mixture can be done, preferably, under an inert atmosphere at a temperature and pressure as noted above in forming the cobalt coordination compound in the suspension. For the various embodiments, the inert atmosphere can be a nitrogen atmosphere or others as are known in the art, such as argon and helium among others. For the various embodiments, the ruthenium coordination compound on the heterogeneous solid support can be mixed with the suspension to form the precatalyst mixture at the predetermined temperature and predetermined pressure noted above in forming the cobalt coordination compound in the suspension for a time of 1 to 48 hours. Preferably, the resulting precatalyst mixture is stirred at the predetermined temperature and predetermined pressure for 24 hours.

[0020] For the various embodiments, the method further includes reducing the precatalyst mixture (e.g., activating the ruthenium based heterogeneous catalyst) at a predetermined temperature under hydrogen (H2) at a predetermined pressure to produce the ruthenium based heterogeneous catalyst. For the various embodiments, chemically reducing the precatalyst mixture can occur in situ under mixing conditions. For the various embodiments, the predetermined pressure of hydrogen is at a pressure of 0 to 20684 kPa of H2 gas. In additional embodiments, the predetermined pressure of hydrogen is at a pressure of 0 to 6895 kPa of H2 gas. In one embodiment, the predetermined pressure of hydrogen is, preferably, 1724 kPa of H2 gas. For the various embodiments, the predetermined temperature for chemically reducing the precatalyst mixture can be in the range of 100 to 200 °C. Preferably, the predetermined temperature for chemically reducing the precatalyst mixture can be in the range of 120 to 200 °C. Preferably, the predetermined temperature for chemically reducing the precatalyst mixture is 180 °C. For the various embodiments, the predetermined time is in a range of 1 to 48 hours. Preferably, the predetermined time is in a range of 1 to 24 hours, where 18 hours is preferred. The resulting ruthenium based heterogeneous catalyst formed according to the method herein has metal nanoparticles supported on the heterogeneous support material that are catalytically active for producing morpholine.

[0021] The ruthenium based heterogeneous catalyst can be used in converting AEE in the presence of the ruthenium based heterogeneous catalyst and hydrogen at a predetermined temperature over a predetermined time to produce morpholine. In producing morpholine according to the present 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, predetermined temperature for the predetermined time to produce morpholine. For the various embodiments, in converting AEE to morpholine, the hydrogen is at a predetermined pressure of 0 to 20684 kPa of H2 gas. In additional embodiments, in converting the AEE to morpholine the hydrogen can be at a predetermined pressure of 0 to 20684 kPa of H2 gas. Preferably, in converting the AEE to morpholine the hydrogen can be at a predetermined pressure of 1724 kPa of H2 gas. For the various embodiments, in converting the AEE to morpholine the predetermined temperature can be in the range of 100 to 200 °C. Preferably, in converting the AEE to morpholine the predetermined temperature can be in the range of 120 to 200 °C. Preferably, in converting the AEE to morpholine the predetermined temperature is 180 °C. For the various embodiments, in converting the AEE to morpholine the predetermined time is in a range of 1 to 48 hours. Preferably, the predetermined time is in a range of 1 to 24 hours, where 18 hours is preferred. For the various embodiments, the method can further include stirring the reaction mixture. Once the reaction is complete, the reactor is cooled, vented, and the product mixture separated by filtering out the catalyst. For the various embodiments, the method can further include recycling the ruthenium based heterogeneous catalyst for use in a subsequent conversion of AEE to produce morpholine.

[0022] Examples

[0023] All components purchased from commercial vendors and used as received unless otherwise noted. All percentages are weight percentages (wt.%) based on the total weight of the mixture used to form the identified compound or mixture, unless otherwise noted.

[0024] Example Reactions

[0025] Anhydrous C0CI2 (97% purity) was purchased from Alfa Aesar and stored in a glove box under an inert N2 atmosphere. Aluminum oxide (y-A12O3, >99% purity, 150-200 mesh) was purchased from Alfa Aesar, ground using a mortar and pestle to break down any large pieces, then dried in an oven at 200 °C and stored under a N2 atmosphere in a glove box. 2-(2- aminoethoxy)ethanol (AEE, 98% purity) was purchased from Acros Organics, distilled over C H2 under vacuum, degassed, and stored under an inert N2 atmosphere. Potassium bis(trimethylsilyl)amide) (KHMDS, 95% purity) was purchased from Sigma Aldrich and stored under an inert N2 atmosphere in a glove box. RuOHx@y-A12O3 was prepared according to “Rational Design of Selective Metal Catalysts for Alcohol Amination with Ammonia”, Wang T., et al. Nat. Catal. 2, 773-779 (2019), which is incorporated herein by reference. Reductive aminations were performed using an H.E.L. DigiCAT high-pressure system (H.E.L., Ltd., U.K.) equipped with 16 mL stainless steel (SS316) reactor vessels.

[0026] CO(AEE)2

[0027] In a nitrogen atmosphere glove box anhydrous C0O2 (1.695 g, 13.05 mmol) was added to a 100 mL oven-dried Schlenk flask equipped with a Teflon cap and stir-bar. While vigorously stirring, AEE (80 mL, 798.9 mmol) was added to dissolve C0CI2 which immediately turned from blue to purple upon dissolution in AEE. This solution was stirred for 20 minutes at room temperature. KHMDS (5.205g, 26.09 mmol) was then added slowly in portions over 10 minutes, resulting in a dark purple solution and a white suspension (KC1). After complete addition of KHMDS the solution was stirred at room temperature (23 °C) for 24 hours. The solution was then filtered over a 150 mL medium porosity frit to remove KC1. The solution was used as is without further purification (est. 0.16 M [Co] in AEE). HRMS (m / z +H): calc. 286.0833; found 268.0895.

[0028] CORU@Y-A12C>3

[0029] In a nitrogen atmosphere glove box, 200 mg of RuOHx@y-A12O3 was weighed into a 16 mL stainless steel vessel. A solution of Co(AEE)2 (3.0 mL, 0.16 M) was slowly added via syringe over RuOHx@y-A12O3 while stirring. After complete addition the reactor was sealed inside the glovebox and the heterogeneous mixture was stirred at room temperature for 1 hour. The reactor vessel was then removed from the glovebox, placed in an aluminum heating block with a stir rate of 700 rpm and connected to the H.E.L DigiCAT high-pressure system. To ensure the removal of all residual oxygen, the reactor was charged with 1724 kPa H2, then vented and this process was repeated three times. After the final cycle, the reactor was held under a static pressure of 1724 kPa H2 and heated to 180 °C with a stir rate of 700 rpm. After 16 hours, the reactor was cooled to room temperature and vented. To remove residual H2 and NH3 (produced during the reaction), the headspace was replaced with 689 pKa argon and vented three times. The reactor was then transferred back into the glove box and CoRu@y-A12O3 was recovered by filtering over a 15 mL medium porosity frit. The supported catalyst was washed with portions of tetrahydrofuran (THF, 3 x 10 mL), dried under vacuum to yield 260 mg black powder, and stored under an inert atmosphere inside the glovebox. The filtrate was analyzed by GC-FID using tetraglyme as an internal standard, providing 99% conversion of AEE and 42% GC yield of morpholine.

[0030] 0.16M Co-AEE solution

[0031] RuOH@y-AI2O3morpholine TA

[0032] Neat TA-morpholine 180 C AEE-Et 16 h 250 psig H2

[0033] Desired product, Transamination side product Transamination side product alcohol amination

[0034] The following is a comparison of catalyst performance using both the AEE synthesis 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 in (b), below, which is identical to the AEE synthesis except decaline is used in place of AEE 1-for-l. This results in CO(N(SiMe3)2)2 being the Co precursor vs. the CO(AEE)2 species 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 (called decalin reduction). Specific values used in these reactions are: (a) AEE synthesis: reduced Co(AEE)2 over RuOHx@y-A12O3 in neat AEE 180 °C for 16 hrs; (b) Decalin reduction: reduced Co(N(SiMe3)2)2 over RuOHx@y-A12O3 in decalin at 180 °C for 16 hrs. In this example, it follows the above catalyst synthesis procedure except decaline is used instead of AEE. The catalyst was then recovered by evaporation and used in the following experiments. The catalyst was tested for recyclability by recovering in a glovebox by magnet and washing with THF. Residual THF was removed by adding and removing 2.0 mL AEE 3x, then 3.0 mL fresh AEE was added to catalyst and stirred for 2 hours at room temperature in glovebox. The recovered catalyst was then subject to the same reaction described above. Results are shown in Table 1.

[0035] Table 1

Claims

What is Claimed is:

1. A method of producing morpholine, comprising: providing a ruthenium (Ru) based heterogeneous catalyst, wherein the ruthenium based heterogeneous catalyst is formed by: mixing a cobalt metal precursor with 2-(2-aminoethoxy)ethanol (AEE) and potassium bis(trimethylsilyl)amide (KHMDS) to form a cobalt coordination compound in a suspension; mixing a ruthenium coordination compound on a heterogeneous solid support with the cobalt coordination compound in the suspension to form a precatalyst mixture; and reducing the precatalyst mixture at a predetermined temperature under hydrogen at a predetermined pressure to produce the ruthenium based heterogeneous catalyst; and converting AEE in the presence of the ruthenium based heterogeneous catalyst and hydrogen at a predetermined temperature over a predetermined time to produce morphol inc.

2. The method of claim 1, wherein the ruthenium coordination compound is selected from the group consisting of RuOHx, RuClg and combinations thereof, wherein x is 3 or 4.

3. The method of claim 1, wherein the heterogeneous solid support is selected from the group consisting of Y-AI2O3, 01-AI2O3, SiO2, TiC>2, ZrC>2, ZnO and combinations thereof.

4. The method of claim 1, wherein the cobalt metal precursor is selected from the group consisting of C0CI2, Co(NO3)2, C0S04, Co2(CO)g, Co[N(SiMe3)2]2 and combinations thereof.

5. The method of 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 converting AEE the hydrogen is at a pressure of 0 to 20684 kPa.

7. The method of claim 1, wherein in converting AEE the predetermined temperature is 100 to 200 °C.

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

9. The method of claim 1, further including stirring the reaction mixture.

10. The method of claim 1 , further including recycling the ruthenium based heterogeneous catalyst for use in a subsequent conversion of AEE to produce morpholine.

Images