A platinum-tin bimetallic catalyst for the reductive methylation of quinoline compounds, its preparation method and application

Abstract

The present invention discloses a platinum-tin bimetallic catalyst for the reductive methylation of quinoline compounds, a preparation method thereof, and an application thereof. The supported platinum-tin bimetallic catalyst prepared by the ultrasonic impregnation method is used in the present invention, and methanol, which is clean, safe, and widely sourced, is used as a green hydrogen source and methyl source. The activation dehydrogenation of methanol and the reductive methylation reaction of quinoline are coupled in multiple steps to synthesize N-methylated tetrahydroquinoline compounds by a one-pot method. The platinum-tin bimetallic catalytic reductive methylation reaction system provided by the present invention has the advantages of being clean, having simple steps, wide substrate applicability, high atom economy and step economy, etc. The platinum-based bimetallic catalyst is simple to prepare, has a high dispersion degree of active metals, high activity and selectivity, can be recycled and reused, has good stability, and has good industrial application prospects.

Description

Technical Field

[0001] The present invention belongs to the technical field of catalytic synthesis, and particularly relates to a platinum-tin bimetallic catalyst for the reductive methylation of quinoline compounds, a preparation method thereof, and an application thereof. Background Art

[0002] The N-methyl-1,2,3,4-tetrahydroquinoline skeleton structure is a key structural unit of many natural alkaloids and drugs, such as drugs like Angustureine, Galipeine, Galipinine, Cuspareine, etc. containing the N-methyl-1,2,3,4-tetrahydroquinoline structural unit. These drugs have excellent antiplasmodial and antiviral activities and can be used to treat diseases such as dyspepsia, dysentery, chronic diarrhea, fever, etc. At present, N-methyl-1,2,3,4-tetrahydroquinoline compounds are mainly obtained by the methylation reaction of 1,2,3,4-tetrahydroquinoline compounds, which are the hydrogenation products of quinoline, with methylation reagents such as methyl iodide, dimethyl sulfate, formaldehyde, etc. Most of the methylation reagents used are toxic and carcinogenic compounds, and a large amount of by-products are generated during the reaction process, which is not environmentally friendly and not conducive to sustainable industrial production. If the hydrogenation reduction and subsequent methylation reaction of quinoline compounds can be integrated and an environmentally friendly methylation reagent can be used, the economical and green synthesis of N-methyl-1,2,3,4-tetrahydroquinoline compounds may be achieved.

[0003] Currently, only a few catalytic systems have reported the synthesis of N-methyl-1,2,3,4-tetrahydroquinoline compounds through the direct reductive methylation tandem reaction of quinoline compounds. For example, the homogeneous ruthenium-phosphine complex catalyzed reductive methylation of quinoline with CO2 in a H2 atmosphere reported by Researcher Han Buxing et al. of the Institute of Chemistry, Chinese Academy of Sciences (Sci.China:Chem., 2017, 60, 927); the reductive methylation reaction of quinoline with CO2 catalyzed by aminopyrrole zinc using NaBH4 as a reducing agent disclosed in Chinese Patent CN 116239529 A; the reductive methylation reaction of quinoline with HCHO catalyzed by Pd / C reported by Researcher Shi Feng of the Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences in a H2 atmosphere (Chem.Commun., 2019, 55, 3915). Although these catalytic systems have improved the synthesis efficiency of N-methyl-1,2,3,4-tetrahydroquinoline compounds to a certain extent, there are still problems such as the difficulty in recycling and reuse of homogeneous catalysts such as ruthenium-phosphine complexes and aminopyrrole zinc, and high reaction system pressure (such as the ruthenium-phosphine catalytic system P CO2 is 2 MPa, P H2Problems such as the difficulty in recycling homogeneous catalysts, high reaction system pressure, waste generated after the reaction with reducing agents (such as NaBH4), and certain toxicity of methylation reagents (such as HCHO) exist. Developing a heterogeneous catalytic system with reusable catalysts, greener reducing agents, and methylation reagents for the reductive methylation of quinoline to prepare N-methyl-1,2,3,4-tetrahydroquinoline compounds still has great practical application value.

[0004] Methanol has been an ideal hydrogen source (ChemCatChem, 2022, 14, e202101794) and methylation reagent (Catal. Sci. Technol., 2021, 11, 3364) that has received much attention in recent years. Its hydrogen mass density is 12.5 wt%, and it has significant advantages such as low toxicity, wide sources, biodegradability, and safe and convenient storage and transportation. For the reductive methylation reaction of quinoline compounds, if a suitable multifunctional heterogeneous catalyst with catalytic activities of methanol dehydrogenation, quinoline hydrogen transfer hydrogenation, and tetrahydroquinoline methylation can be developed, a highly atom-economical and step-economical synthetic route for the one-step preparation of N-methyl-1,2,3,4-tetrahydroquinoline compounds using green methanol as both the hydrogen source and the methyl source can be achieved. Since there is currently no catalytic technology for quinoline-methanol reductive methylation, developing an efficient and clean catalytic system for methanol activation and conversion and multi-step coupling in the quinoline-methanol reaction has significant practical and economic value. Summary of the Invention

[0005] The purpose of this section is to outline some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section, as well as in the abstract and title of the present application, to avoid obscuring the purpose of this section, the abstract, and the title. However, such simplifications or omissions cannot be used to limit the scope of the present invention.

[0006] In view of the above and / or problems existing in the prior art, such as the difficulty in recycling homogeneous catalysts, high reaction system pressure, waste generated after the reaction with reducing agents, and certain toxicity of methylation reagents, the present invention is proposed.

[0007] One of the purposes of the present invention is to provide a platinum-tin bimetallic catalyst for the reductive methylation of quinoline compounds, which has high catalytic activity, good stability, can be recycled more than 5 times, and the reductive methylation reaction is clean, with high atom economy and step economy.

[0008] To solve the above technical problems, the present invention provides the following technical solution: a platinum-tin bimetallic catalyst for the reductive methylation of quinoline compounds, and the general formula of the platinum-tin bimetallic catalyst is xPtSn y / Support; wherein,

[0009] Pt is metallic platinum;

[0010] Sn is the metal promoter tin;

[0011] x is the loading amount of metal Pt, and its value is 0.5 - 2.0 wt%;

[0012] y is the molar ratio of Pt to Sn, and its value is 0.2 - 1.0;

[0013] Support is the catalyst support, including one of Al2O3, ZrO2, CeO2, ZnO, SiO2, and TiO2.

[0014] As a preferred embodiment of the platinum-tin bimetallic catalyst for the reductive methylation of quinoline compounds in the present invention, wherein: the value of x is 1 wt%; the value of y is 0.5; Support is Al2O3.

[0015] Another object of the present invention is to provide a preparation method of the platinum-tin bimetallic catalyst for the reductive methylation of quinoline compounds as described above, which has the advantages of simple catalyst preparation, high activity and selectivity, good stability, and reusability; the substrate of the reductive methylation system has wide practicability, mild and safe reaction conditions, and strong operability. The specific method includes,

[0016] The metal Pt precursor and the metal Sn precursor are sequentially added to anhydrous ethanol, the carrier is added under ultrasonic conditions, and ultrasonic oscillation is carried out under water bath heating conditions until it is evaporated to dryness and dried;

[0017] The dried solid is reduced in a H2 / Ar mixed atmosphere.

[0018] As a preferred embodiment of the preparation method of the platinum-tin bimetallic catalyst for the reductive methylation of quinoline compounds in the present invention, wherein: the metal Pt precursor includes one of hexachloroplatinic acid hexahydrate (H2PtCl6·6H2O), potassium hexachloroplatinate (K2PtCl6), dichlorodiammineplatinum (PtCl2(NH3)2), platinum tetrachloride (PtCl4), and platinum(II) acetylacetonate (C 10 H 14 O4Pt).

[0019] As a preferred embodiment of the preparation method of the platinum-tin bimetallic catalyst for the reductive methylation of quinoline compounds in the present invention, wherein: the metal Sn precursor includes one of tin tetrachloride (SnCl4), tin acetate (Sn(CH3CO2)2), and tin ethoxide (C4H 14 O2Sn).

[0020] As a preferred embodiment of the preparation method of the platinum-tin bimetallic catalyst for the reductive methylation of quinoline compounds in the present invention, wherein: for the reduction, the reduction temperature is 300-600°C and the reduction time is 0.5-2 h.

[0021] Another object of the present invention is to provide the application of the platinum-tin bimetallic catalyst as described above in the reductive methylation of quinoline compounds using methanol as a hydrocarbon source. This method has high atom economy and step economy; the reaction system is green, safe, and highly operable; the catalyst has high activity and selectivity, and good reusability. Specifically,

[0022] Using methanol as both a hydrogen source and a methyl source, and a platinum-tin bimetallic catalyst as a catalyst, N-methyl-1,2,3,4-tetrahydroquinoline compounds are prepared by a one-pot method of hydrogen transfer reduction and N-methylation reaction of quinoline compounds.

[0023] As a preferred embodiment of the application of the platinum-tin bimetallic catalyst of the present invention in the reductive methylation of quinoline compounds using methanol as a hydrocarbon source, wherein: the quinoline compound is one of quinoline, 2-methylquinoline, 4-methylquinoline, 7-methylquinoline, 8-methylquinoline, 3-methoxyquinoline, 5-methoxyquinoline, 3-chloroquinoline, methyl 3-quinolinecarboxylate, isoquinoline, quinoxaline, 7,8-benzoquinoline.

[0024] As a preferred embodiment of the application of the platinum-tin bimetallic catalyst of the present invention in the reductive methylation of quinoline compounds using methanol as a hydrocarbon source, wherein: the dosage of the quinoline compound is 0.07-0.33 mol / L.

[0025] As a preferred embodiment of the application of the platinum-tin bimetallic catalyst of the present invention in the reductive methylation of quinoline compounds using methanol as a hydrocarbon source, wherein: for the reaction, the reaction temperature is 120-130°C, the nitrogen pressure is 1-5 bar, and the reaction time is 5-12 h.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The present invention uses clean, safe, and widely sourced methanol as both a hydrogen source, a methyl source, and a solvent for the reductive methylation reaction of quinoline, avoiding the use of reducing agents such as hydrogen that are flammable, explosive, and inconvenient for storage and transportation, and at the same time replacing traditional methylation reagents with high toxicity and strong carcinogenicity, which is of great significance for realizing a clean, sustainable, highly atom-economic, and step-economic process for the reductive methylation of quinoline compounds. Description of the Drawings

[0028] To more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the following drawings are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on these drawings. Among them:

[0029] Figure 1 It is a scanning transmission electron micrograph of the platinum-tin bimetallic catalyst prepared in Example 1 of the present invention. Specific Embodiments

[0030] To make the above objects, features, and advantages of the present invention more obvious and understandable, the following will provide a detailed description of the specific embodiments of the present invention in combination with the embodiments of the specification.

[0031] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention can also be implemented in other ways different from those described herein. Those skilled in the art can make similar generalizations without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below.

[0032] Secondly, the so-called "one embodiment" or "embodiment" refers to specific features, structures, or characteristics that can be included in at least one implementation manner of the present invention. The phrase "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor is it a separate or alternative embodiment that excludes other embodiments.

[0033] Unless otherwise specified, the raw materials used in the embodiments are all commercially purchased.

[0034] Example 1

[0035] (1) Add 2.63 mL of chloroplatinic acid solution (3.8 mg / mL Pt) and 6 mg of SnCl2·2H2O to 10 mL of absolute ethanol. After ultrasonic oscillation for 5 min, add 1.0 g of γ-Al2O3, ZrO2, CeO2, ZnO, SiO2, or TiO2. After ultrasonic evaporation to dryness in a 75°C water bath, place it in an 80°C oven and dry for 5 h;

[0036] (2) Place the solid dried in step (1) in a 10 vol% H2 / Ar mixed atmosphere and reduce it at 300°C for 0.5 h. The obtained catalysts are named 1 wt% PtSn 0.5 / Al2O3, 1 wt% PtSn 0.5 / ZrO2, 1 wt% PtSn 0.5 / CeO2, 1 wt% PtSn 0.5 / ZnO, 1 wt% PtSn 0.5 / SiO2 and 1 wt% PtSn 0.5 / TiO2.

[0037] Figure 1 This is the scanning transmission electron microscopy image of the 1 wt% PtSn 0.5 / Al2O3 catalyst prepared in Example 1 of the present invention. It can be seen from Figure 1 this that the active metal is highly dispersed on the surface of alumina in the form of nano-clusters. The obtained PtSn catalyst was applied to the catalytic quinoline reductive methylation reaction using methanol as the hydrocarbon source. The specific method is as follows:

[0038] 0.5 mmol of quinoline, 5 mL of methanol and 195 mg of 1 wt% PtSn 0.5 catalyst were successively added to a 25 mL reaction kettle, and the reaction was carried out at 0.5 MPa N2 and 130 °C for 5 h; the conversion rate and yield were analyzed by gas chromatography, and the results are shown in Table 1:

[0039] Table 1

[0040] Catalyst Quinoline conversion rate (%) Yield of N-methyltetrahydroquinoline (%) <![CDATA[1 wt% PtSn 0.5 / Al2O3]]> 100 99 <![CDATA[1 wt% PtSn 0.5 / ZrO2]]> 72 70 <![CDATA[1 wt% PtSn 0.5 / TiO2]]> 78 46 <![CDATA[1 wt% PtSn 0.5 / CeO2]]> 60 52 <![CDATA[1 wt% PtSn 0.5 / SiO2]]> 18 14 <![CDATA[1 wt% PtSn 0.5 / ZnO]]> 17 15

[0041] It can be seen from Table 1 that the PtSn catalysts supported on different carriers have different activities in the reductive methylation reaction of quinoline and methanol. Among them, 1 wt% PtSn 0.5 / Al2O3 has the best catalytic performance, the conversion rate of quinoline is 100%, and the selectivity of the target product reaches 99%.

[0042] Example 2

[0043] (1) 2.63 mL of chloroplatinic acid solution (3.8 mg / mL Pt) and 3 mg, 6 mg, and 12 mg of SnCl2·2H2O were respectively added to 10 mL of absolute ethanol. After ultrasonic oscillation for 5 min, 1.0 g of γ-Al2O3 was added. After the mixture was ultrasonically evaporated to dryness in a 75 °C water bath, it was placed in an 80 °C oven and dried for 5 h;

[0044] (2) The solid dried in step (1) was placed in a 10 vol% H2 / Ar mixed atmosphere and reduced at 300 °C for 0.5 h. The obtained catalysts were respectively named 1 wt% PtSn 0.25 / Al2O3, 1 wt% PtSn 0.5 / Al2O3 and 1 wt% PtSn 1.0 / Al2O3.

[0045] (3) 0.5 mmol of quinoline, 5 mL of methanol and 195 mg of PtSn / Al2O3 catalysts with different Pt / Sn ratios were successively added into a 25 mL autoclave, and the reaction was carried out at 0.5 MPa N2 and 130 °C for 5 h; the conversion rate and yield were analyzed by gas chromatography, and the results are shown in Table 2:

[0046] Table 2

[0047] Catalyst Quinoline conversion rate (%) Yield of N-methyltetrahydroquinoline (%) <![CDATA[1 wt% PtSn 0.25 / Al2O3]]> 58 54 <![CDATA[1 wt% PtSn 0.5 / Al2O3]]> 100 99 <![CDATA[1 wt% PtSn 1.0 / Al2O3]]> 80 78

[0048] As can be seen from the results in Table 2, the Pt / Sn molar ratio has a great influence on the reductive methylation reaction. With the increase of the Pt / Sn molar ratio, the catalytic activity first increases and then decreases; when the Pt / Sn molar ratio is 0.5, the best catalytic activity and product yield are obtained. At this time, the conversion rate of quinoline is 100%, and the selectivity of the target product reaches 99%.

[0049] Example 3

[0050] (1) 1.32 mL, 2.63 mL and 5.26 mL of chloroplatinic acid solution (3.8 mg / mL Pt) and 6 mg of SnCl2·2H2O were respectively added into 10 mL of absolute ethanol. After ultrasonic oscillation for 5 min, 1.0 g of γ-Al2O3 was added. After the mixture was ultrasonically evaporated to dryness in a 75 °C water bath, it was placed in an 80 °C oven and dried for 5 h;

[0051] (2) The solid dried in step (1) was placed in a 10 vol% H2 / Ar mixed atmosphere and reduced at 300 °C for 0.5 h. The obtained catalysts were respectively named 0.5 wt% PtSn 0.5 / Al2O3, 1 wt% PtSn 0.5 / Al2O3 and 2 wt% PtSn 0.5 / Al2O3.

[0052] (3) 0.5 mmol of quinoline, 5 mL of methanol and 195 mg of PtSn 0.5 / Al2O3 catalysts with different Pt loadings were successively added into a 25 mL autoclave, and the reaction was carried out at 0.5 MPa N2 and 130 °C for 5 h; the conversion rate and yield were analyzed by gas chromatography, and the results are shown in Table 3:

[0053] Table 3

[0054] Catalyst Quinoline conversion rate (%) Yield of N-methyltetrahydroquinoline (%) <![CDATA[0.5 wt% PtSn 0.5 / Al2O3]]> 37 35 <![CDATA[1 wt% PtSn 0.5 / Al2O3]]> 100 99 <![CDATA[2 wt% PtSn 0.5 / Al2O3]]> 64 61

[0055] As can be seen from the results in Table 3, when the Pt loading is 0.5 wt%, the conversion rate of quinoline decreases significantly, from 100% to 37%; when the Pt loading increases to 2.0 wt%, due to the decrease in Pt dispersion, the conversion rate of quinoline may decrease.

[0056] Example 4

[0057] Activity evaluation of 1wt% PtSn 0.5 / Al2O3 catalyst under different methanol dosages.

[0058] Evaluation conditions: Using the 1wt% PtSn 0.5 / Al2O3 catalyst in Example 1, with 1 mmol of quinoline as the reactant. 1.5 mL, 3 mL, 5 mL, and 7 mL of methanol and 195 mg of 1wt% PtSn 0.5 / Al2O3 catalyst were successively added into a 25 mL autoclave, and the reaction was carried out at 0.5 MPa N2 and 120 °C for 5 h; the conversion rate and yield were analyzed by gas chromatography, and the results are shown in Table 4:

[0059] Table 4

[0060] Dosage of methanol (mL) Quinoline conversion rate (%) Yield of N-methyltetrahydroquinoline (%) 1.5 43 28 3 59 51 5 74 72 7 49 47

[0061] It can be seen from Table 4 that as the methanol dosage gradually increases, the conversion rate of quinoline first increases and then decreases. When the methanol dosage is 5 mL, the catalytic reaction has the best activity, and the yield of the target product reaches 72%.

[0062] Example 5

[0063] 1.0wt% PtSn 0.5 Reusability evaluation of / Al2O3 catalyst.

[0064] Evaluation conditions: Using the 1wt% PtSn 0.5 / Al2O3 catalyst in Example 1, 0.5 mmol of quinoline, 5 mL of methanol, and 195 mg of 1wt% PtSn 0.5 / Al2O3 were successively added into a 25 mL autoclave, and the reaction was carried out at 0.5 MPa N2 and 130 °C for 5 h.

[0065] Catalyst reuse method: After the reaction, the catalyst was filtered and the catalyst and filtrate were collected. The catalyst was washed three times with methanol and then three times with dichloromethane, and then dried in an oven at 80 °C for 5 h to obtain the catalyst after the first use. Before the next reaction, the catalyst after the first use was calcined in a muffle furnace at 400 °C for 30 min, and then reduced at 300 °C for 30 min in a 10vol% H2 / Ar atmosphere. The results are shown in Table 5:

[0066] Table 5

[0067] Number of cycles Quinoline conversion rate (%) Yield of N-methyltetrahydroquinoline (%) 1 100 99 2 100 97 3 100 96 4 100 96 5 100 95

[0068] It can be seen from Table 5 that the 1.0wt% PtSn 0.5After the / Al2O3 catalyst was reused 5 times, the activity and selectivity of the catalyst did not decrease significantly, indicating that the catalyst has good stability and reusability.

[0069] Example 6

[0070] 1.0wt% Pt-Sn 0.5 Evaluation of the substrate applicability of the / Al2O3-catalyzed reductive methylation reaction of quinoline compounds.

[0071] Evaluation conditions: The 1.0wt% PtSn 0.5 / Al2O3 catalyst prepared in Example 1 was applied to the reductive methylation reactions of different quinoline compounds. Among them, the amount of quinoline compounds used was 0.5 mmol each, the solvent was 5 mL of methanol, and the reaction was carried out at 0.5 MPa N2 and 120 - 130 °C for 5 - 12 h. The products and yields were analyzed by gas chromatography and gas chromatography-mass spectrometry. The specific results are shown in Table 6 as follows:

[0072] Table 6

[0073]

[0074]

[0075] As can be seen from Table 6, the 1.0wt% PtSn 0.5 / Al2O3 catalyst has good substrate generality and shows good reactivity in the reductive methylation reaction with methanol for quinoline compounds containing different functional groups; for quinoline containing halogen (Cl), no dehalogenation phenomenon occurred. It shows that the platinum-tin bimetallic-catalyzed reductive methylation of quinoline-methanol to prepare N-methyl-1,2,3,4-tetrahydroquinoline compounds disclosed in the present invention has good generality.

[0076] It should be noted that the above examples are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and they should all be covered within the scope of the claims of the present invention.

Claims

1. Application of a platinum-tin bimetallic catalyst in the reductive methylation of quinoline compounds using methanol as a hydrocarbon source, characterized in that: including, using methanol as both the hydrogen source and the methyl source, a platinum-tin bimetallic catalyst as the catalyst, and preparing N-methyl-1,2,3,4-tetrahydroquinoline compounds by a one-pot method of hydrogen transfer reduction and N-methylation reaction of quinoline compounds; Among them, the general formula of the platinum-tin bimetallic catalyst is xPtSn y / Support; where Pt is metallic platinum; Sn is metallic promoter tin; x is the loading amount of metallic Pt, and its value is 0.5-2.0 wt%; y is the molar ratio of Pt to Sn, and its value is 0.2-1.0; Support is the catalyst support, including one of Al2O3, ZrO2, CeO2, and TiO2.

2. The application according to claim 1, characterized in that: The quinoline compounds are one of quinoline, 2-methylquinoline, 4-methylquinoline, 7-methylquinoline, 8-methylquinoline, 3-methoxyquinoline, 5-methoxyquinoline, 3-chloroquinoline, methyl 3-quinolinecarboxylate, isoquinoline, quinoxaline, and 7,8-benzoquinoline.

3. The application according to claim 2, wherein: The dosage of the quinoline compounds is 0.07-0.33 mol / L.

4. The application according to any one of claims 1 to 3, characterized in that: For the reaction, the reaction temperature is 120-130 °C, the nitrogen pressure is 1-5 bar, and the reaction time is 5-12 h.

5. The application according to claim 1, characterized in that: The value of x is 1 wt%; the value of y is 0.5; Support is Al2O3.

6. The application according to claim 1, wherein: The preparation method of the shown platinum-tin bimetallic catalyst includes, successively adding a metallic Pt precursor and a metallic Sn precursor into absolute ethanol, adding the support under ultrasonic conditions, and ultrasonically oscillating and evaporating to dryness and drying under water bath heating conditions; placing the dried solid in a H2 / Ar mixed atmosphere for reduction.

7. The application according to claim 6, wherein: The metallic Pt precursor includes one of chloroplatinic acid hexahydrate, potassium chloroplatinate, dichlorodiammineplatinum, platinum chloride, and platinum(II) acetylacetonate.

8. The application according to claim 6, wherein: The metallic Sn precursor includes one of tin tetrachloride, tin acetate, and tin ethoxide.

9. The application according to claim 6, characterized in that: For the reduction, the reduction temperature is 300-600 °C, and the reduction time is 0.5-2 h.

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