Metal catalyst, method for preparing the same, and use thereof

Abstract

The application discloses a metal catalyst and a preparation method and application thereof. The preparation method comprises the following steps: carrying out a first reaction on a mixed reaction system at least comprising a metal salt, a promoter, and an organic solvent, and then adding an alkaline substance to carry out a second reaction, so as to obtain the metal catalyst. In the application, the catalyst precursor is a non-noble metal salt, the reaction condition is mild, the operation is simple, the prepared metal catalyst has a wide substrate application range and good functional group tolerance, and the requirement for equipment is low.

Description

Technical Field

[0001] This invention belongs to the field of catalysis and organic synthesis, and relates to a metal catalyst, its preparation method and application, particularly to a metal catalyst and its preparation method, and the application of the metal catalyst in the hydrogenation reduction of aryl compounds and / or heteroaryl compounds to prepare cycloalkanes and / or saturated heterocyclic compounds. Background Technology

[0002] Organic compounds containing cycloalkyl or heterocyclic structures are important raw materials for the synthesis of pharmaceuticals, pesticides, and materials, such as cyclohexanol, cyclohexane, 1,4-cyclohexanediethanol, and piperazine. Catalytic hydrogenation of benzene rings or heterocyclic rings is the most direct and efficient method for synthesizing compounds containing cycloalkyl or heterocyclic structures. However, catalytic hydrogenation of benzene rings and heterocyclic rings faces many challenges, mainly including: (1) Benzene rings and heterocyclic rings are aromatic, and catalytic dearomatization requires overcoming a very high energy barrier; (2) The heterocyclic atomic bonds of CO or CN in the compound are easily broken during catalytic hydrogenation, resulting in structural damage; (3) The stereoselectivity of hydrogenation reactions of polysubstituted (hetero)aromatic hydrocarbons.

[0003] In 1901, Sabatier and Senderens reported the first benzene hydrogenation reaction. Since then, various catalytic systems have been developed, mainly focusing on noble metal-based catalysts such as Ru, Rh, Pd, and Pt. For example, in 2024, Yu Zhixiang's research group published in *Organic Letters* that they achieved the hydrogenation of aromatic compounds to cyclohexane derivatives at room temperature and pressure using commercially available Rh / Pd and Rh / Pt catalytic systems. However, these catalytic processes often require noble metals as catalysts, which is too costly. Therefore, exploring and developing inexpensive and efficient catalysts is a future trend.

[0004] Compared to noble metals, the hydrogenation of benzene rings catalyzed by non-noble metals remains extremely challenging. In 2023, Anand Narani and Kishore Natte et al. reported the catalytic hydrogenation of benzene rings and their derivatives using nitrogen-doped carbon-supported Co3O4 nanoparticles; however, this required a large catalyst dosage and involved complex catalytic preparation. Therefore, developing a simple catalytic system capable of preparing (hetero)aromatic compounds with high selectivity, high activity, and a broad substrate applicability under mild reaction conditions is of significant scientific and industrial implications. Summary of the Invention

[0005] The main objective of this invention is to provide a metal catalyst, its preparation method, and its application, in order to overcome the shortcomings of the prior art.

[0006] To achieve the aforementioned objectives, the technical solution adopted by this invention includes:

[0007] This invention provides a method for preparing a metal catalyst, comprising: subjecting a mixed reaction system containing at least a metal salt, a co-catalyst, and an organic solvent to a first reaction, followed by adding an alkaline substance to conduct a second reaction, thereby obtaining a metal catalyst.

[0008] The present invention also provides a metal catalyst prepared by the aforementioned preparation method.

[0009] The present invention also provides the application of the aforementioned metal catalysts in catalytic hydrogenation reactions.

[0010] This invention also provides a method for the catalytic hydrogenation reduction of aryl compounds and / or heteroaryl compounds to prepare cycloalkane compounds and / or saturated heterocyclic compounds, comprising:

[0011] Metal catalysts were prepared using the aforementioned preparation method;

[0012] Furthermore, in a hydrogen atmosphere and under the action of the metal catalyst, aryl compounds and / or heteroaryl compounds are selectively hydrogenated to produce cycloalkane compounds and / or saturated heterocyclic compounds.

[0013] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0014] (1) This invention prepares inexpensive metal catalysts in situ, without the need for complex ligands or specific supports. The catalyst synthesis steps are simple, the preparation cost is low, the operation is convenient, and it is easy to scale up.

[0015] (2) The hydrogenation reaction conditions in this invention are mild and can achieve highly selective hydrogenation of aryl compounds and / or heteroaryl compounds at room temperature.

[0016] (3) The method provided by the present invention has a wide range of applications and can realize the preparation of a variety of cycloalkyl or saturated heterocyclic compounds with excellent industrial prospects. It has low equipment requirements and has the potential for industrialization. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0018] Figure 1 This is a gas chromatogram of the product in Example 1 of this application;

[0019] Figure 2 This is a gas chromatogram of the product in Example 51 of this application. Detailed Implementation

[0020] In view of the deficiencies of the prior art, the inventors of this case, through long-term research and extensive practice, have proposed the technical solution of this invention. The technical solution of this invention will be clearly and completely described below. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0021] Specifically, as one aspect of the technical solution of the present invention, a method for preparing a metal catalyst includes: subjecting a mixed reaction system containing at least a metal salt, a co-catalyst, and an organic solvent to a first reaction, and then adding an alkaline substance to conduct a second reaction to obtain a metal catalyst.

[0022] In some preferred embodiments, the metal salt includes any one or more combinations of anhydrous cobalt chloride, cobalt chloride hexahydrate, anhydrous cobalt bromide, cobalt bromide hexahydrate, cobalt fluoride, cobalt iodide, cobalt iodide dihydrate, anhydrous cobalt carbonate, cobalt carbonate monohydrate, anhydrous cobalt acetate, cobalt acetate tetrahydrate, cobalt nitrate hexahydrate, cobalt acetylacetonate, cobalt sulfate, cobalt sulfate monohydrate, cobalt sulfate heptahydrate, elemental cobalt, cobalt hydroxide, nickel acetylacetonate, bis(1,5-cyclooctadiene) nickel, nickel acetate, nickel chloride, nickel bromide, nickel dibromo(ethylene glycol dimethyl ether) and nickel trifluoromethanesulfonate, and is not limited thereto.

[0023] In some preferred embodiments, the cocatalyst comprises any one or more combinations of borane, sodium borohydride, lithium borohydride, potassium borohydride, sodium triethylborohydride, lithium triethylborohydride, lithium aluminum tetrahydrogen, trimethylaluminum, diisobutylaluminum hydride, and borane ammonia, and is not limited thereto.

[0024] In some preferred embodiments, the organic solvent includes any one or more combinations of tetrahydrofuran, methyl tert-butyl ether, dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, methanol, ethanol, isopropanol, tert-butanol, cyclohexane, n-hexane, heptane, and methylcyclohexane, and is not limited thereto.

[0025] In some preferred embodiments, the alkaline substance includes any one or more combinations of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, potassium methoxide, sodium methoxide, lithium methoxide, potassium ethoxide, sodium ethoxide, lithium ethoxide, and sodium hydride, and is not limited thereto.

[0026] In some preferred embodiments, the reaction temperature of the first reaction is 0–100°C and the reaction time is 0.1–24 h.

[0027] In some preferred embodiments, the reaction temperature of the second reaction is 0–100°C, and the reaction time is 0.1–24 h.

[0028] In some preferred embodiments, the molar ratio of the metal salt, co-catalyst, and alkaline substance is 1–0.3:0.1–5:0.1–10.

[0029] Another aspect of the present invention provides a metal catalyst prepared by the aforementioned preparation method.

[0030] The catalyst precursor used in this invention is a non-precious metal salt, the reaction conditions are mild, the operation is simple, the prepared metal catalyst has a wide range of substrate applicability and good functional group tolerance, and the equipment requirements are low.

[0031] Another aspect of the present invention provides the application of the aforementioned metal catalyst in catalytic hydrogenation reactions.

[0032] Furthermore, the applications include the use of metal catalysts in the catalytic hydrogenation reduction of aryl compounds and / or heteroaryl compounds to prepare cycloalkanes and / or saturated heterocyclic compounds.

[0033] Another aspect of the present invention provides a method for the catalytic hydrogenation reduction of aryl compounds and / or heteroaryl compounds to prepare cycloalkane compounds and / or saturated heterocyclic compounds, comprising:

[0034] Metal catalysts were prepared using the aforementioned preparation method;

[0035] Furthermore, in a hydrogen atmosphere and under the action of the metal catalyst, aryl compounds and / or heteroaryl compounds are selectively hydrogenated to produce cycloalkane compounds and / or saturated heterocyclic compounds.

[0036] In some preferred embodiments, the aryl compound and / or heteroaryl compound has a structure as shown in formula (I):

[0037]

[0038] Wherein, X is selected from C, N or O; R is selected from alkyl, ester, carboxylic acid, amino, amide, hydroxyl, alcohol, alkenyl, alkynyl, alkyl, benzene ring or nitrogen heterocycle with 1 to 20 monosubstituted or polysubstituted C atoms.

[0039] In some preferred embodiments, the method specifically includes: selectively hydrogenating aryl compounds and / or heteroaryl compounds under the action of a metal catalyst for 3 to 80 hours at a hydrogen pressure of 0.1 to 20 MPa and a temperature of 0 to 200°C to obtain cycloalkane compounds and / or saturated heterocyclic compounds.

[0040] Furthermore, the temperature is 0–120°C.

[0041] In some preferred embodiments, the molar ratio of the metal salt to the aryl compound and / or heteroaryl compound is 0.01 to 20:100.

[0042] In some preferred embodiments, the molar ratio of the co-catalyst to the aryl compound and / or heteroaryl compound is 0.01 to 40:100.

[0043] In some preferred embodiments, the molar ratio of the alkaline substance to the aryl compound and / or heteroaryl compound is 0.01 to 100:100.

[0044] In some more specific embodiments, the method for catalytic hydrogenation reduction of aryl compounds and / or heteroaryl compounds to prepare cycloalkanes and / or saturated heterocyclic compounds includes:

[0045] The metal salt and co-catalyst are reacted in an organic solvent in the first stage; then an alkaline substance is added to carry out the second stage reaction; finally, aryl compounds and / or heteroaryl compounds are added, and the aryl compounds and / or heteroaryl compounds are hydrogenated to the corresponding cycloalkane compounds and / or saturated heterocyclic compounds in a high-pressure reactor under certain pressure, temperature and time.

[0046] In some more specific embodiments, the method for catalytic hydrogenation reduction of aryl compounds and / or heteroaryl compounds to prepare cycloalkanes and / or saturated heterocyclic compounds includes:

[0047] A metal catalyst is prepared by first reacting a mixed reaction system containing at least a metal salt, a co-catalyst, and an organic solvent, followed by adding an alkaline substance to carry out a second reaction.

[0048] In a high-pressure reactor, aryl compounds and / or heteroaryl compounds are hydrogenated to corresponding cycloalkane compounds and / or saturated heterocyclic compounds using a metal catalyst under specific pressure, temperature, and reaction time.

[0049] Furthermore, the amount of organic solvent used is 1-100 equivalents of the molar amount of the aryl compound and / or heteroaryl compound.

[0050] The technical solution of the present invention will be further described in detail below with reference to several preferred embodiments and accompanying drawings. This embodiment is implemented on the premise of the technical solution of the invention, and provides detailed implementation methods and specific operation processes. However, the protection scope of the present invention is not limited to the following embodiments.

[0051] Unless otherwise specified, the experimental materials used in the examples below can be purchased from conventional biochemical reagent companies.

[0052] Example 1

[0053] This embodiment provides a method for preparing cycloalkanes or saturated heterocyclic compounds from aryl or heteroaryl compounds under metal catalysis at room temperature. The reaction process is as follows:

[0054]

[0055] CoCl2 (32 mg, 0.25 mmol), LiAlH4 (10 mg, 0.25 mmol), and dioxane (2 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, MeONa (46 mg, 0.85 mmol) and dioxane (2 mL) were added, and stirring was continued at room temperature for 1 h. Then, dimethyl terephthalate (970 mg, 5 mmol, compound 1) and dioxane (4 mL) were added. The reaction tube was then placed in a 300 mL reaction vessel, and the vessel was purged three times with 2.0 MPa H2. The reaction vessel was then purged with 5.0 MPa H2 and reacted at room temperature for 24 h to obtain compound 2. Trimethylbenzene was used as an internal standard, and the reaction solution was quantitatively analyzed by gas chromatography with internal standard method. The yield of dimethyl cyclohexanedicarboxylate 2 was 86%. The gas chromatogram of the product dimethyl cyclohexanedicarboxylate 2 is shown below. Figure 1 As shown.

[0056] Examples 2 to 9

[0057]

[0058] CoCl2 (0.025–0.05 mmol), BH3·THF (0.05–0.06 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOLi (0.075–0.17 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, dimethyl terephthalate (97 mg, 0.5 mmol, compound 1) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reaction vessel, and the vessel was purged three times with 2.0 MPa H2. The reaction vessel was then purged with 5.0 MPa H2 and placed in an oil bath to prepare compound 2. Trimethylbenzene was used as an internal standard, and the reaction solution was quantitatively analyzed by gas chromatography with internal standard method.

[0059] The difference between Example 2 and Example 9 lies in the different amounts of CoCl2, BH3·THF, and t-BuOLi used, as well as the different reaction temperatures and times. The specific reaction conditions for Examples 2–9 and the yields of dimethyl 1,4-cyclohexanedicarboxylate 2 are shown in Table 1.

[0060] Table 1 shows the specific reaction conditions and yields of dimethyl 1,4-cyclohexanedicarboxylate 2 for Examples 2-9.

[0061]

[0062]

[0063] Examples 10 to 15

[0064]

[0065] CoCl2 (3.2 mg, 0.025 mmol), co-catalyst (0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOLi (6.8 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, dimethyl terephthalate (97 mg, 0.5 mmol, compound 1) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reaction vessel, and the vessel was purged three times with 2.0 MPa H2. The vessel was then purged with 5.0 MPa H2 and reacted at room temperature for 24 h to obtain compound 2. Trimethylbenzene was used as an internal standard, and the reaction solution was quantitatively analyzed by gas chromatography with internal standard method.

[0066] The difference between Examples 10-15 lies in the different cocatalysts used. The specific reaction conditions for Examples 10-15 and the yield of dimethyl 1,4-cyclohexanedicarboxylate 2 are shown in Table 2.

[0067] Table 2 shows the specific reaction conditions and yield of dimethyl 1,4-cyclohexanedicarboxylate 2 for Example 10N15.

[0068] name Types and dosages of co-catalysts 2. Yield Example 10 <![CDATA[BH3·THF(50μL)]]> 64％ Example 11 <![CDATA[NaHBEt3(50μL)]]> 59％ Example 12 <![CDATA[NaBH4(1.9mg)]]> 53％ Example 13 <![CDATA[LiBH4(1.1mg)]]> 58％ Example 14 <![CDATA[LiAlH4(2.3mg)]]> 75％ Example 15 DIBAL-H (50μL) 62％

[0069] Examples 16 to 25

[0070]

[0071] Metal salt (0.025 mmol), LiAlH4 (0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOLi (6.8 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, dimethyl terephthalate (97 mg, 0.5 mmol, compound 1) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reaction vessel, and the vessel was purged three times with 2.0 MPa H2. The vessel was then purged with 5.0 MPa H2 and reacted at room temperature for 24 h to obtain compound 2. Trimethylbenzene was used as an internal standard, and the reaction solution was quantitatively analyzed by gas chromatography with internal standard method.

[0072] The difference between Examples 16-25 lies in the type of metal salt used. The specific reaction conditions for Examples 16-25 and the yield of dimethyl 1,4-cyclohexanedicarboxylate 2 are shown in Table 3.

[0073] Table 3 shows the specific reaction conditions and yields of dimethyl 1,4-cyclohexanedicarboxylate for Examples 16-25.

[0074] Group Types and dosages of metal salts 2. Yield Example 16 <![CDATA[Ni(acac)2(50μL)]]> 56％ Example 17 <![CDATA[Ni(COD)2(50μL)]]> 51％ Example 18 <![CDATA[NiOAc2(1.9mg)]]> 50％ Example 19 <![CDATA[NiCl2(1.1mg)]]> 50％ Example 20 <![CDATA[NiBr2·dme(2.3mg)]]> 51％ Example 21 <![CDATA[NiOTf2(50μL)]]> 60％ Example 22 <![CDATA[CoBr2(5.5mg)]]> 66％ Example 23 <![CDATA[CoOAc2(4.4mg)]]> 55％ Example 24 <![CDATA[Co(acac)3(8.9mg)]]> 70％ Example 25 <![CDATA[CoCl2·6H2O(5.9mg)]]> 72％

[0075] Examples 26 to 36

[0076]

[0077] CoCl2 (0.0125–0.025 mmol), LiAlH4 (0.0125–0.05 mmol), and solvent (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOLi (0.0425–0.085 mmol) and solvent (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, dimethyl terephthalate (97 mg, 0.5 mmol, compound 1) and solvent (1 mL) were added. The reaction was then... tube placement Compound 2 was prepared by purging the 300 mL reaction vessel three times with 2.0 MPa H2, then filling the vessel with H2 and reacting at room temperature for 24 h. Mestriol was used as an internal standard, and the reaction solution was quantitatively analyzed by gas chromatography with internal standard method.

[0078] The difference between Example 26N36 and Example 26N36 lies in the different amounts of CoCl2, LiAlH4, and t-BuOLi used, the different solvents used, and the different hydrogen pressures. The specific reaction conditions corresponding to Example 26N36 and the yield of dimethyl 1,4-cyclohexanedicarboxylate 2 are shown in Table 4.

[0079] Table 4 shows the specific reaction conditions and yields of dimethyl 1,4-cyclohexanedicarboxylate 2 for Examples 26-36.

[0080] name <![CDATA[Dosage of CoCl2]]> <![CDATA[Dosage of LiAlH4]]> t-BuOLi dosage solvent <![CDATA[H2 pressure]]> 2. Yield Example 26 3.2mg 1mg 6.8mg dioxane 5.0MPa 81％ Example 27 3.2mg 1mg 6.8mg THF 5.0MPa 60％ Example 28 3.2mg 0.5mg 6.8mg dioxane 5.0MPa 80％ Example 29 3.2mg 1mg 6mg dioxane 5.0MPa 78％ Example 30 3.2mg 1mg 4mg dioxane 5.0MPa 72％ Example 31 2.6mg 0.8mg 5.4mg dioxane 5.0MPa 72％ Example 32 1.6mg 0.5mg 3.4mg dioxane 5.0MPa 67％ Example 33 3.2mg 1mg 6.8mg dioxane 4.0MPa 78％ Example 34 3.2mg 1mg 6.8mg dioxane 3.0MPa 73％ Example 35 3.2mg 1mg 6.8mg dioxane 2.0MPa 67％ Example 36 3.2mg 1mg 6.8mg dioxane 1.0MPa 51％

[0081] Examples 37 to 42

[0082]

[0083] CoCl2 (3.2 mg, 0.025 mmol), LiAlH4 (1 mg, 0.025 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, alkali (0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, dimethyl terephthalate (97 mg, 0.5 mmol, compound 1) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reaction vessel, and the vessel was purged three times with 2.0 MPa H2. The vessel was then purged with 5.0 MPa H2 and reacted at room temperature for 24 h to obtain compound 2. Trimethylbenzene was used as an internal standard, and the reaction solution was quantitatively analyzed by gas chromatography with internal standard method.

[0084] The difference between Examples 37 to 42 lies in the type of alkali used. The specific reaction conditions for Examples 37 to 42 and the yield of dimethyl 1,4-cyclohexanedicarboxylate 2 are shown in Table 5.

[0085] Table 5 shows the specific reaction conditions and yields of dimethyl 1,4-cyclohexanedicarboxylate 2 corresponding to Examples 37-42.

[0086] Group Types and dosages of alkali 2. Yield Example 37 t-BuOK (9.5mg) 74％ Example 38 t-BuONa (8.2mg) 74％ Example 39 MeONa (4.6mg) 79％ Example 40 MeOK (6.0mg) 53％ Example 41 EtONa (5.8mg) 82％ Example 42 MeOLi (3.2mg) 54％

[0087] Example 43

[0088]

[0089] CoCl2 (3.2 mg, 0.025 mmol), NaBH4 (1.9 mg, 0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOLi (6.8 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, terephthalic acid (69 mg, 0.5 mmol, compound 3) and THF (1 mL) were added. The reaction tube was then placed in a 300 mL reaction vessel, and the vessel was purged three times with 2.0 MPa H2. The vessel was then charged with 5.0 MPa H2 and reacted in a 100 °C oil bath for 11 h to obtain compound 4. The reaction solution was quantitatively analyzed by gas chromatography with tricresylbenzene as an internal standard. The yield of 1,4-cyclohexanediethanol 4 was 57%.

[0090] Example 44

[0091] This embodiment provides a method for preparing heterocycloalkanes by metal-catalyzed hydrogenation of heteroaromatic hydrocarbons at room temperature. The reaction process is as follows:

[0092]

[0093] CoCl2 (3.2 mg, 0.025 mmol), BH3·THF (50 μL, 0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOLi (6.8 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, phenol (47 mg, 0.5 mmol, compound 5) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reactor, and the reactor was purged three times with 2.0 MPa H2. The reactor was then purged with 5.0 MPa H2 and reacted at room temperature for 24 h to obtain compound 6. The reaction solution was quantified by gas chromatography normalization, and the yield of 1-hydroxy-cyclohexane 6 was 88%.

[0094] Example 45

[0095] This embodiment provides a method for preparing heterocycloalkanes by metal-catalyzed hydrogenation of heteroaromatic hydrocarbons at room temperature. The reaction process is as follows:

[0096]

[0097] CoCl2 (3.2 mg, 0.025 mmol), BH3·THF (50 μL, 0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOLi (6.8 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, ethylbenzene (53 mg, 0.5 mmol, compound 7) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reaction vessel, and the vessel was purged three times with 2.0 MPa H2. The vessel was then purged with 5.0 MPa H2 and reacted at room temperature for 24 h to obtain compound 8. The reaction solution was quantified by gas chromatography normalization, and the yield of 1-ethyl-cyclohexane 8 was 91%.

[0098] Example 46

[0099] This embodiment provides a method for preparing heterocycloalkanes by metal-catalyzed hydrogenation of heteroaromatic hydrocarbons at room temperature. The reaction process is as follows:

[0100]

[0101] CoCl2 (3.2 mg, 0.025 mmol), BH3·THF (50 μL, 0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOLi (6.8 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, dibenzylamine (99 mg, 0.5 mmol, compound 9) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reaction vessel, and the vessel was purged three times with 2.0 MPa H2. The vessel was then purged with 5.0 MPa H2 and reacted at 150 °C for 12 h to obtain compound 10. The reaction solution was quantified by gas chromatography normalization, and the yield of di(cyclohexylmethyl)amine 10 was 98%.

[0102] Example 47

[0103] This embodiment provides a method for preparing heterocycloalkanes by metal-catalyzed hydrogenation of heteroaromatic hydrocarbons at room temperature. The reaction process is as follows:

[0104]

[0105] CoCl2 (3.2 mg, 0.025 mmol), BH3·THF (50 μL, 0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOLi (6.8 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, biphenyl (77.1 mg, 0.5 mmol, compound 11) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reaction vessel, and the vessel was purged three times with 2.0 MPa H2. The vessel was then purged with 5.0 MPa H2 and reacted at 150 °C for 12 h to obtain compound 12. The reaction solution was quantified by gas chromatography normalization, and the yield of cyclohexylbenzene 12 was 70%.

[0106] Example 48

[0107] This embodiment provides a method for preparing heterocycloalkanes by metal-catalyzed hydrogenation of heteroaromatic hydrocarbons at room temperature. The reaction process is as follows:

[0108]

[0109] CoCl2 (3.2 mg, 0.025 mmol), BH3·THF (50 μL, 0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOLi (6.8 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, aniline (46.5 mg, 0.5 mmol, compound 13) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reaction vessel, and the vessel was purged three times with 2.0 MPa H2. The vessel was then purged with 5.0 MPa H2 and reacted at 60 °C for 8 h to obtain compound 14. The reaction solution was quantified by gas chromatography normalization, and the yield of cyclohexylamine 14 was 23%.

[0110] Example 49

[0111] This embodiment provides a method for preparing heterocycloalkanes by metal-catalyzed hydrogenation of heteroaromatic hydrocarbons at room temperature. The reaction process is as follows:

[0112]

[0113] CoCl2 (3.2 mg, 0.025 mmol), BH3·THF (50 μL, 0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOLi (6.8 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, benzyl alcohol (54.1 mg, 0.5 mmol, compound 15) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reaction vessel, and the vessel was purged three times with 2.0 MPa H2. The vessel was then purged with 5.0 MPa H2 and reacted at 60 °C for 8 h to obtain compound 16. The reaction solution was quantified by gas chromatography normalization, and the yield of cyclohexylethanol 16 was 93%.

[0114] Example 50

[0115] This embodiment provides a method for preparing heterocycloalkanes by metal-catalyzed hydrogenation of heteroaromatic hydrocarbons at room temperature. The reaction process is as follows:

[0116]

[0117] CoCl2 (3.2 mg, 0.025 mmol), BH3·THF (50 μL, 0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOLi (6.8 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, quinoline (64.6 mg, 0.5 mmol, compound 17) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reaction vessel, and the vessel was purged three times with 2.0 MPa H2. The vessel was then purged with 5.0 MPa H2 and reacted at 150 °C for 12 h to obtain compound 18. The reaction solution was quantified by gas chromatography normalization, and the yield of decahydroquinoline 18 was 76%.

[0118] Example 51

[0119]

[0120] CoCl2 (3.2 mg, 0.025 mmol), BH3·THF (50 μL, 0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOLi (6.8 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, 2-methylquinoline (71.6 mg, 0.5 mmol, compound 19) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reactor, and the reactor was purged three times with 2.0 MPa H2. The reactor was then charged with 5.0 MPa H2 and reacted at 150 °C for 12 h to obtain compounds 20, 21, and 22. Using n-decane as an internal standard, the reaction solution was quantitatively analyzed by gas chromatography with internal standard method. The yields of decahydroquinoline 20 were 19%, 5,6,7,8-tetrahydro-2-methylquinoline 21 were 62%, and 1,2,3,4-tetrahydro-2-methylquinoline 22 were 18%. The gas chromatogram of product 1,2,3,4-tetrahydro-2-methylquinoline 22 is shown below. Figure 2 As shown.

[0121] Example 52

[0122]

[0123] CoCl2 (3.2 mg, 0.025 mmol), BH3·THF (50 μL, 0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOK (9.5 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, 2-methylquinoline (71.6 mg, 0.5 mmol, compound 19) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reactor, and the reactor was purged three times with 2.0 MPa H2. The reactor was then charged with 5.0 MPa H2 and reacted at 150 °C for 12 h to obtain compounds 20, 21, and 22. Using n-decane as an internal standard, the reaction solution was quantitatively analyzed by gas chromatography with internal standard method. The yield of decahydroquinoline 20 was 2%, the yield of 5,6,7,8-tetrahydro-2-methylquinoline 21 was 17%, and the yield of 1,2,3,4-tetrahydro-2-methylquinoline 22 was 80%.

[0124] Example 53

[0125]

[0126] CoCl2 (3.2 mg, 0.025 mmol), BH3·THF (50 μL, 0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOK (9.5 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, bipyridine (78.1 mg, 0.5 mmol, compound 23) and dioxane (1 mL) were added. The reaction tube was then placed in a 300 mL reaction vessel, and the vessel was purged three times with 2.0 MPa H2. The vessel was then charged with 5.0 MPa H2 and reacted at 150 °C for 12 h to obtain compound 24. The reaction solution was quantified by gas chromatography normalization, and the yield of 2,2-bispiperidine 24 was 98%.

[0127] Example 54

[0128]

[0129] CoCl2 (3.2 mg, 0.025 mmol), BH3·THF (50 μL, 0.05 mmol), and dioxane (0.5 mL) were placed in a reaction tube. After stirring at room temperature for 0.5 h, t-BuOK (9.5 mg, 0.085 mmol) and dioxane (0.5 mL) were added, and stirring was continued at room temperature for 1 h. Subsequently, benzofuran (59 mg, 0.5 mmol, compound 25) and dioxane (1 mL) were added. The reaction was then... tube placement In a 300 mL reactor, the reactor was purged three times with 2.0 MPa H2, then charged with 2.0 MPa H2 and reacted at 50 °C for 12 h to obtain compound 26. The reaction solution was quantified using gas chromatography-normalization, and the yield of benzodihydrofuran 26 was 98%.

[0130] In addition, the inventors of this case also conducted experiments with other raw materials, process operations, and process conditions described in this specification, referring to the aforementioned embodiments, and obtained relatively ideal results in all cases.

[0131] It should be understood that the technical solutions of the present invention are not limited to the specific embodiments described above. Any technical modifications made to the technical solutions of the present invention without departing from the spirit and scope of the claims are within the scope of protection of the present invention.

Claims

1. The application of a metal catalyst in the catalytic hydrogenation reduction of aryl compounds and / or heteroaryl compounds to prepare cycloalkanes and / or saturated heterocyclic compounds, characterized in that, The method for preparing the metal catalyst includes: subjecting a mixed reaction system containing at least a metal salt, a co-catalyst, and an organic solvent to a first reaction, followed by adding an alkaline substance to conduct a second reaction, thereby obtaining the metal catalyst; The metal salts include any one or more combinations of anhydrous cobalt chloride, cobalt chloride hexahydrate, anhydrous cobalt bromide, cobalt bromide hexahydrate, cobalt fluoride, cobalt iodide, cobalt iodide dihydrate, anhydrous cobalt carbonate, cobalt carbonate monohydrate, anhydrous cobalt acetate, cobalt acetate tetrahydrate, cobalt nitrate hexahydrate, cobalt acetylacetonate, cobalt sulfate, cobalt sulfate monohydrate, cobalt sulfate heptahydrate, nickel acetylacetonate, bis(1,5-cyclooctadiene) nickel, nickel acetate, nickel chloride, nickel bromide, nickel dibromo(ethylene glycol dimethyl ether) dibromo, and nickel trifluoromethanesulfonate. The cocatalyst comprises any one or more combinations of borane, sodium borohydride, lithium borohydride, potassium borohydride, sodium triethylborohydride, lithium triethylborohydride, lithium aluminum tetrahydrogen, trimethylaluminum, diisobutylaluminum hydride, and borane ammonia. The organic solvent includes any one or more combinations of tetrahydrofuran, methyl tert-butyl ether, dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, methanol, ethanol, isopropanol, tert-butanol, cyclohexane, n-hexane, heptane, and methylcyclohexane. The alkaline substance includes any one or more combinations of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, potassium methoxide, sodium methoxide, lithium methoxide, potassium ethanol, sodium ethanol, lithium ethanol, and sodium hydride. The reaction temperature of the first reaction is 0~100 ℃ and the reaction time is 0.1~24 h; the reaction temperature of the second reaction is 0~100 ℃ and the reaction time is 0.1~24 h. The molar ratio of the metal salt, co-catalyst, and alkaline substance is 1~0.3:0.1~5:0.1~10.

2. A method for preparing cycloalkane compounds and / or saturated heterocyclic compounds by catalytic hydrogenation reduction of aryl compounds and / or heteroaryl compounds, characterized in that, include: The metal catalyst described in claim 1 is used; Furthermore, in a hydrogen atmosphere and under the action of the metal catalyst, aryl compounds and / or heteroaryl compounds are selectively hydrogenated to produce cycloalkane compounds and / or saturated heterocyclic compounds. The aryl compound and / or heteroaryl compound have the structure shown in formula (I): ； Formula (I); Wherein, X is selected from C, N or O; R is selected from alkyl, ester, carboxylic acid, amino, amide, hydroxyl, alcohol, alkenyl, alkynyl, alkyl, benzene ring or nitrogen heterocycle with 1 to 20 monosubstituted or polysubstituted C atoms.

3. The method according to claim 2, characterized in that, Specifically, it includes: Aromatic compounds and / or heteroaryl compounds are selectively hydrogenated for 3-80 h under the action of a metal catalyst at a hydrogen pressure of 0.1-20 MPa and a temperature of 25-200 °C to obtain cycloalkanes and / or saturated heterocyclic compounds.

4. The method according to claim 2, characterized in that: The molar ratio of the metal salt to the aryl compound and / or heteroaryl compound is 0.01 to 20:

100.

5. The method according to claim 2, characterized in that: The molar ratio of the cocatalyst to the aryl compound and / or heteroaryl compound is 0.01 to 40:

100.

6. The method according to claim 2, characterized in that: The molar ratio of the alkaline substance to the aryl compound and / or heteroaryl compound is 0.01 to 100:100.

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