A process for the preparation of 5-methyl-N-aryl-2-pyrrolidones

Abstract

The application discloses a preparation method of 5-methyl-N-aryl-2-pyrrolidone compounds, which comprises the following steps: taking biomass derivative acetylenic acid and nitroaromatic hydrocarbon as starting materials, taking formic acid as a hydrogen source, taking a non-noble metal multifunctional catalyst NiMnAl@NC as a catalyst, and adopting a one-pot reduction amination method to synthesize 5-methyl-N-aryl-2-pyrrolidone. The non-noble metal multifunctional catalyst NiMnAl@NC comprises a metal-organic framework material derived nitrogen-doped carbon-based carrier NC and metal Ni, Mn and Al embedded on the NC. The preparation method has the advantages of high yield of 5-methyl-N-aryl-2-pyrrolidone, environmental protection, simple operation, recyclable catalyst and obvious industrial production advantages.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical chemicals, and in particular relates to a method for preparing a 5-methyl-N-aryl-2-pyrrolidone compound. Background Art

[0002] N-aryl pyrrolidones are an important class of nitrogen heterocyclic compounds, widely used in the synthesis of pharmaceuticals, pesticides, and fine chemicals. Therefore, developing cost-effective, safe, environmentally friendly, and simple-to-operate synthesis technologies for N-aryl pyrrolidones is of great value.

[0003] With the increasing shortage of fossil resources and the deteriorating environment, biomass, as a green renewable resource, has received increasing attention both at home and abroad. Levulinic acid is an important biomass-based platform compound that can be obtained from lignocellulosic waste by simple acid hydrolysis. Therefore, using the biomass-derived platform molecule levulinic acid as a substrate and reductively aminating it with amine compounds to synthesize pyrrolidone is a green and sustainable process route. Amine compounds can usually be obtained from nitro compounds (especially nitroaromatics) by hydrogenation. Therefore, using nitroaromatic compounds and levulinic acid to synthesize pyrrolidone through a "one-pot" reductive amination is a more economical and attractive route.

[0004] Ir-PVP prepared by Chaudhari et al. can obtain 64-95% of the target product after the reaction of levulinic acid and nitroarene in methanol solvent under the conditions of H2(1 MPa) and 30℃ for 72h (Green Chemistry, 2020, 22(22):7760-7764). Pt / TiO2-NT prepared by Vidal et al. is used for the synthesis of 5-methyl-N-aryl-2-pyrrolidone, and the yield is 55-61% under the conditions of H2(1 MPa) and 120℃ for 48h (ChemSusChem, 2017, 10(1):119-128). Cophen@C-800-HCl catalyst is prepared by Gao et al. Aliphatic, aromatic and heterocyclic nitro compounds can selectively undergo one-pot reductive amination with levulinic acid on the catalyst, and the yield of the desired pyrrolidone is 80-97% (Chem Catalysis, 2022, 2(1):178-194). Chinese invention patent CN1764376A discloses a method for preparing 5-methyl-N-aryl-2-pyrrolidone compounds from levulinic acid and nitro compounds under the catalysis of a supported metal catalyst. However, the yield of the target product is not high. At present, noble metal catalysts are mainly used for the one-pot reductive amination of levulinic acid and nitro compounds to synthesize 5-methyl-N-aryl-2-pyrrolidone, and the production cost is high. In addition, hydrogen is mainly used as the hydrogen source, and the hydrogen pressure used is large, and the operation risk is large. SUMMARY

[0005] The present application aims to provide an environmentally friendly method for the one-pot reductive amination synthesis of 5-methyl-N-aryl-2-pyrrolidone compounds from biomass derivative levulinic acid and nitroarene as raw materials, formic acid as hydrogen source, and under the action of non-noble metal multifunctional catalyst NiMnAl@NC in a reaction solvent, which solves the problems of low yield of target product, high cost of using noble metal catalyst, and large operation risk of using hydrogen as hydrogen source in the existing production process.

[0006] To achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows:

[0007] A preparation method of 5-methyl-N-aryl-2-pyrrolidone compounds, specifically: levulinic acid and nitroarene shown in formula I and II are used as starting materials, formic acid is used as hydrogen source, and 5-methyl-N-aryl-2-pyrrolidone shown in formula III is prepared under the action of non-noble metal multifunctional catalyst at a temperature of 100-170℃ in a reaction solvent for 4-15h, and the reaction formula is as shown below:

[0008]

[0009] In the formula, H on the benzene ring is replaced by a substituent R or is not replaced, when replaced, the substituent R is an alkyl group, an alkoxy group or a halogen;

[0010] The non-noble metal multifunctional catalyst is NiMnAl@NC, comprising a metal-organic framework material derived nitrogen-doped carbon base carrier NC and metals Ni, Mn and Al embedded on the NC.

[0011] In the non-noble metal multifunctional catalyst NiMnAl@NC, Ni is the main hydrogenation active site of the catalyst; the introduction of metals Mn and Al can improve the dispersion of Ni, at the same time, provide suitable acid sites, which are more conducive to the occurrence of reductive amination reaction.

[0012] The nitrogen-doped carbon base carrier has a large specific surface area and pore volume, so that the metals can be uniformly dispersed on the carrier; at the same time, the surface of the nitrogen-doped carbon base carrier has abundant pores, which can promote the mass transfer and diffusion of reactants, and limit or anchor the effective active components of metals Ni, Mn and Al, thereby improving the activity and stability of the catalyst.

[0013] Further, the content of metal Ni in the NiMnAl@NC multifunctional catalyst is 5-15wt%, the content of metal Mn is 1-10wt%, and the content of metal Al is 5-30wt%.

[0014] The suitable metal content makes the catalyst have good catalytic performance. When the content of Ni is too low, the content of hydrogenation active component is low, resulting in low hydrogenation activity of the catalyst; when the content of Mn and Al is too low, the acidity is low, and the acid active sites on the catalyst are insufficient, which will affect the reaction speed.

[0015] Further, the preparation method of the NiMnAl@NC multifunctional catalyst comprises the following steps: dissolving Ni salt, Mn salt and Al salt in N,N-dimethylformamide to form solution A, dissolving 2-amino terephthalic acid in N,N-dimethylformamide to form solution B, mixing solution A and solution B, and stirring uniformly at room temperature, transferring to a hydrothermal synthesis kettle, heat treating at 100-150℃ for 12-24h, after cooling, filtering with a Buchner funnel, washing with N,N-dimethylformamide and methanol for several times, then drying at 100℃ for 6-12h after grinding to powder, to obtain a metal-organic framework material catalyst precursor, and finally calcining at 600-900℃ under nitrogen atmosphere for 1-6h, to prepare the non-noble metal multifunctional catalyst NiMnAl@NC.

[0016] During the high-temperature cracking process of the metal-organic framework catalyst precursor in an inert gas, the soluble salt of metal Ni decomposes at high temperature and is in situ reduced to metal Ni by carbon, forming small-sized active metal particles that are evenly distributed on the carrier. At the same time, Mn and Al are in the form of MnO x 2-Aminoterephthalic acid forms a nitrogen-doped carbon-based support, leaving a large number of pores in the support, thereby increasing the specific surface area of ​​the catalyst and improving the mass transfer efficiency of the reactants, thereby efficiently synthesizing 5-methyl-N-aryl-2-pyrrolidone.

[0017] Furthermore, the Ni salt is one of nickel nitrate, nickel acetate or nickel chloride, the Mn salt is one of manganese acetate, manganese nitrate or manganese chloride, and the Al salt is aluminum nitrate or aluminum chloride.

[0018] Furthermore, the molar ratio of Ni salt to 2-aminoterephthalic acid is 1:1-10, the molar ratio of Mn salt to 2-aminoterephthalic acid is 1:1-5, and the molar ratio of Al salt to 2-aminoterephthalic acid is 1:0.5-2.

[0019] Furthermore, the molar ratio of levulinic acid to nitroaromatic hydrocarbon is 1:1-2, and the mass ratio of levulinic acid to NiMnAl@NC multifunctional catalyst is 1:0.05-0.3.

[0020] Furthermore, the molar ratio of levulinic acid to formic acid is 1:1-16.

[0021] Furthermore, the solvent is water, ethanol, methanol, tetrahydrofuran or toluene, and the volume of the solvent used is 10-50 mL / g based on the mass of levulinic acid.

[0022] Furthermore, the reaction temperature is 100-170° C., and the reaction time is 4-15 h, preferably 140-160° C., and the reaction time is 8-12 h.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] 1) The non-precious metal multifunctional catalyst NiMnAl@NC provided by the present invention has excellent catalytic activity and stability, is simple to prepare, and has low preparation cost;

[0025] 2) The present invention uses formic acid as a hydrogen source, levulinic acid and nitroaromatic hydrocarbon in a reaction solvent in a one-pot process to prepare 5-methyl-N-aryl-2-pyrrolidone. The yield of 5-methyl-N-aryl-2-pyrrolidone can reach over 90%. The reaction conditions are mild, environmentally friendly, the product yield is high, and the process is simple.

[0026] 3) The non-precious metal multifunctional catalyst of the present invention has a small usage amount, can be recycled and reused, and has a low production cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is the XRD spectrum of the NiMnAl@NC-700 catalyst prepared in the present invention. DETAILED DESCRIPTION

[0028] The technical solutions of the present invention are described below with reference to specific embodiments, but the protection scope of the present invention is not limited thereto.

[0029] The preparation method of the 5-methyl-N-aryl-2-pyrrolidone compound of the present invention uses levulinic acid and nitroaromatic hydrocarbon as raw materials, formic acid as a hydrogen source, and uses a non-precious metal multifunctional catalyst to carry out a reductive amination reaction in a solvent using a "one-pot method" to prepare the 5-methyl-N-aryl-2-pyrrolidone;

[0030] The non-noble metal multifunctional catalyst used in the present invention is NiMnAl@NC, which comprises a nitrogen-doped carbon-based carrier NC derived from a metal-organic framework material and metals Ni, Mn and Al embedded in the NC.

[0031] The preparation method of the non-precious metal multifunctional catalyst NiMnAl@NC of the present invention is as follows: 0.4511 g (1.55 mmol) of nickel nitrate hexahydrate, 0.3797 g (1.55 mmol) of manganese acetate tetrahydrate and 1.6506 g (4.4 mmol) of aluminum nitrate nonahydrate are dissolved in 30 mL of N,N-dimethylformamide to form solution A; 1.35 g (7.5 mmol) of 2-aminoterephthalic acid is dissolved in 35 mL of Solution B was formed in N,N-dimethylformamide. Solution A and Solution B were mixed and stirred at room temperature. The mixture was then transferred to a hydrothermal synthesis reactor and heat treated at 120°C for 24 hours. After cooling, the mixture was filtered using a Buchner funnel and washed three times with N,N-dimethylformamide and methanol. The mixture was then dried at 100°C for 12 hours and ground into a powder to obtain a catalyst precursor material. Finally, the mixture was calcined at 700°C for 2 hours under a nitrogen atmosphere and naturally cooled to room temperature to obtain a black solid powder named NiMnAl@NC-700. ICP-OES analysis of the catalyst revealed a Ni content of 9.14wt%, a Mn content of 2.25wt%, and an Al content of 17.77wt%.

[0032] According to the same method as above, different non-precious metal multifunctional catalysts were prepared by changing the calcination temperature of the catalyst precursor material, and were named NiMnAl@NC-A.

[0033] The XRD spectrum of the catalyst prepared by the present invention is as follows: Figure 1The characteristic peaks of metallic Ni were observed at 2Q = 44.4°, 51.9° and 76.2°, and the diffraction peaks at 37.3°, 42.6° and 61.9° were attributed to NiO. The diffraction peaks at 2Q = 34.9°, 40.5°, 58.7° and 70.2° corresponded to the (111), (200), (220) and (311) planes of MnO, respectively, and the diffraction peaks at 42.6° and 66.5° corresponded to MnO2, which indicated the successful doping of Mn. No peaks of Al2O3 were detected in the XRD pattern, mainly because the aggregation and crystallization of Al2O3 were limited during calcination. In this catalyst, Al2O3 existed in an amorphous form.

[0034] The above-prepared catalyst was applied in the following examples.

[0035] Example 1:

[0036] Take 0.115 g (1 mmol) of levulinic acid, 0.160 g (1.3 mmol) of nitrobenzene, 0.560 g (12 mmol) of formic acid, 20 mg of NiMnAl@NC-700 catalyst and 4 mL of water into a 25 mL high-pressure reaction kettle. Seal the reaction kettle and purge it with nitrogen five times. The reaction temperature is 160°C, the reaction time is 8h, the conversion rate of levulinic acid is 100%, and the yield of 5-methyl-N-phenyl-2-pyrrolidone is 91.4%.

[0037] Example 2:

[0038] Take 0.115 g (1 mmol) of levulinic acid, 0.160 g (1.3 mmol) of nitrobenzene, 0.560 g (12 mmol) of formic acid, 20 mg of NiMnAl@NC-700 catalyst and 4 mL of water into a 25 mL high-pressure reaction kettle. Seal the reaction kettle and purge it with nitrogen five times. The reaction temperature is 160°C, the reaction time is 6h, the conversion rate of levulinic acid is 87.0%, and the yield of 5-methyl-N-phenyl-2-pyrrolidone is 78.7%.

[0039] Example 3:

[0040] Take 0.115 g (1 mmol) of levulinic acid, 0.160 g (1.3 mmol) of nitrobenzene, 0.373 g (8 mmol) of formic acid, 50 mg of NiMnAl@NC-600 catalyst and 4 mL of water into a 25 mL high-pressure reaction kettle. Seal the reaction kettle and purge it with nitrogen five times. The reaction temperature is 160°C, the reaction time is 8h, the conversion rate of levulinic acid is 82.7%, and the yield of 5-methyl-N-phenyl-2-pyrrolidone is 76.6%.

[0041] Example 4:

[0042] 0.115 g (1 mmol) of levulinic acid, 0.160 g (1.3 mmol) of nitrobenzene, 0.560 g (12 mmol) of formic acid, 50 mg of NiMnAl@NC-600 catalyst, and 4 mL of water were added to a 25 mL autoclave. The autoclave was sealed and purged with nitrogen five times. The reaction temperature was 160°C for 12 hours, resulting in a levulinic acid conversion of 89.4% and a 5-methyl-N-phenyl-2-pyrrolidone yield of 85.2%.

[0043] Example 5:

[0044] 0.115 g (1 mmol) of levulinic acid, 0.160 g (1.3 mmol) of nitrobenzene, 0.560 g (12 mmol) of formic acid, 20 mg of NiMnAl@NC-600 catalyst, and 4 mL of water were added to a 25 mL autoclave. The autoclave was sealed and purged with nitrogen five times. The reaction temperature was 160°C for 12 hours, resulting in a levulinic acid conversion of 68.0% and a 5-methyl-N-phenyl-2-pyrrolidone yield of 63.0%.

[0045] Example 6:

[0046] 0.115 g (1 mmol) of levulinic acid, 0.160 g (1.3 mmol) of nitrobenzene, 0.560 g (12 mmol) of formic acid, 20 mg of NiMnAl@NC-700 catalyst, and 4 mL of toluene were added to a 25 mL autoclave. The autoclave was sealed and purged with nitrogen five times. The reaction temperature was 160°C for 8 hours, resulting in a 62.7% conversion of levulinic acid and a 61.4% yield of 5-methyl-N-phenyl-2-pyrrolidone.

[0047] Example 7:

[0048] 0.115 g (1 mmol) of levulinic acid, 0.160 g (1.3 mmol) of nitrobenzene, 0.560 g (12 mmol) of formic acid, 20 mg of NiMnAl@NC-700 catalyst, and 4 mL of water were added to a 25 mL autoclave. The autoclave was sealed and purged with nitrogen five times. The reaction temperature was 160°C for 6 hours, resulting in a levulinic acid conversion of 87.0% and a 5-methyl-N-phenyl-2-pyrrolidone yield of 78.7%.

[0049] Example 8:

[0050] Take 0.115 g (1 mmol) of levulinic acid, 0.160 g (1.3 mmol) of nitrobenzene, 0.747 g (16 mmol) of formic acid, 20 mg of NiMnAl@NC-700 catalyst and 4 mL of water into a 25 mL high-pressure reaction kettle. Seal the reaction kettle and purge it with nitrogen five times. The reaction temperature is 160℃, the reaction time is 12 h, the conversion rate of levulinic acid is 98.2%, and the yield of 5-methyl-N-phenyl-2-pyrrolidone is 87.4%.

[0051] Examples 9-12:

[0052] Other operations are the same as in Example 1, and the reaction results are as follows (Table 1) by changing the molar ratio of levulinic acid and nitrobenzene:

[0053] Table 1 Summary of 5-methyl-N-phenyl-2-pyrrolidone yield under different molar ratios of levulinic acid and nitrobenzene

[0054]

[0055]

[0056] Examples 13-18:

[0057] Other operations are the same as in Example 7, and the following reaction results are shown in Table 2 by changing the number of times the catalyst is recycled (after each reaction, the reaction liquid is centrifuged, and the catalyst is recovered and reused):

[0058] Table 2 Summary of 5-methyl-N-phenyl-2-pyrrolidone yield under different numbers of catalyst recycling

[0059] Example Catalyst repetition times Levulinic acid conversion rate (%) Yield of 5-methyl-N-phenyl-2-pyrrolidone (%) 13 1 90.2 76.9 14 2 86.5 76.0 15 3 85.8 75.4 16 4 84.0 74.0 17 5 83.9 73.4 18 6 81.1 71.7

[0060] Examples 19-21:

[0061] Other operations are the same as in Example 1, and the following reaction results are shown in Table 3 by changing different nitroaromatics:

[0062] Table 3 Summary of reactions under different nitroaromatics

[0063]

[0064]

[0065] According to the above factors affecting the yield of the product, the appropriate reaction conditions can be obtained: the molar ratio of levulinic acid to nitroaromatic is 1:1.3, the molar ratio of levulinic acid to formic acid is 1:12, the reaction solvent is water, the reaction temperature is 160℃, and the reaction time is 8 h. At the same time, it can be seen from Table 2 that the catalyst has excellent reusability. It can be seen from Table 3 that the catalyst shows good substrate applicability.

Claims

1. A 5-methyl- N -A method for preparing an aryl-2-pyrrolidone compound, characterized in that: Using levulinic acid and nitroaromatic hydrocarbons as starting materials, formic acid as hydrogen source, and a non-precious metal multifunctional catalyst, a one-pot reductive amination reaction is carried out in a solvent to prepare 5-methyl- N -aryl-2-pyrrolidone; the reaction formula is as follows: ； In the formula, the H on the benzene ring is substituted by a substituent R or not. When substituted, the substituent R is an alkyl, alkoxy or halogen; The non-precious metal multifunctional catalyst is NiMnAl@NC, which includes a nitrogen-doped carbon-based support NC derived from a metal-organic framework material and metal Ni, Mn and Al embedded in the NC; The non-precious metal multifunctional catalyst NiMnAl@NC has a metal Ni content of 5-15 wt%, a metal Mn content of 1-10 wt%, and a metal Al content of 5-30 wt%. The preparation method of non-precious metal multifunctional catalyst NiMnAl@NC comprises the following steps: dissolving Ni salt, Mn salt and Al salt in N , N -dimethylformamide to form solution A, 2-aminoterephthalic acid is dissolved in N , N -dimethylformamide to form solution B, mix solution A and solution B, stir evenly at room temperature, transfer to a hydrothermal synthesis reactor, heat treat at 100~150℃ for 12-24h, cool down, filter with a Buchner funnel, and use N , N -dimethylformamide and methanol several times, then dried at 100 ° C for 6-12 h and ground into powder to obtain a metal-organic framework catalyst precursor, and finally calcined at 600-900 ° C in a nitrogen atmosphere for 1-6 h to prepare the non-precious metal multifunctional catalyst NiMnAl@NC.

2. A 5-methyl- N -A method for preparing an aryl-2-pyrrolidone compound, characterized in that: The Ni salt is one of nickel nitrate, nickel acetate or nickel chloride, the Mn salt is one of manganese acetate, manganese nitrate or manganese chloride, and the Al salt is aluminum nitrate or aluminum chloride.

3. A 5-methyl- N -A method for preparing an aryl-2-pyrrolidone compound, characterized in that: The molar ratio of Ni salt to 2-aminoterephthalic acid is 1:1-10, the molar ratio of Mn salt to 2-aminoterephthalic acid is 1:1-5, and the molar ratio of Al salt to 2-aminoterephthalic acid is 1:0.5-2.

4. A 5-methyl- N -A method for preparing an aryl-2-pyrrolidone compound, characterized in that: The molar ratio of levulinic acid to nitroaromatic hydrocarbon is 1:1-2, and the mass ratio of levulinic acid to NiMnAl@NC multifunctional catalyst is 1:0.05-0.

3.

5. A 5-methyl- N -A method for preparing an aryl-2-pyrrolidone compound, characterized in that: The molar ratio of levulinic acid to formic acid is 1:1-16.

6. A 5-methyl- N -A method for preparing an aryl-2-pyrrolidone compound, characterized in that: The solvent is water, ethanol, methanol, tetrahydrofuran or toluene, and the volume of the solvent is 10-50 mL / g based on the mass of the levulinic acid.

7. A 5-methyl- N -A method for preparing an aryl-2-pyrrolidone compound, characterized in that: The reaction temperature is 100-170 ℃, and the reaction time is 4-15 h.

8. A 5-methyl- N -A method for preparing an aryl-2-pyrrolidone compound, characterized in that: The reaction temperature is 140-160 ℃, and the reaction time is 8-12 h.

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