A method for synthesizing secondary amines by substitution amination of alcohol compounds

Abstract

The present invention relates to the field of organic catalytic synthesis, and discloses a niobium (Nb)-based catalyst and a synthesis method for directly performing substitution amination of an alcohol compound with an organic amine to synthesize a corresponding secondary amine. Through the catalyst and method of the present invention, an alcohol compound and an organic amine can be used as raw materials to undergo a substitution amination reaction in a reaction device to obtain a secondary amine with a high yield. There are mainly three traditional methods for catalytic synthesis of secondary amines: 1) Through the method of borrowing hydrogen or reductive catalytic amination, secondary amines are synthesized through intermediate products aldehydes and ketones, and common catalysts are noble metal catalysts such as platinum, palladium, and ruthenium; 2) Through the substitution amination route, catalysts prepared using trifluoromethanesulfonates, etc., and secondary amines are synthesized under the action of an auxiliary agent, or secondary amines are obtained by reacting with homogeneous catalysts such as ferric chloride. Compared with the above three methods, the method of the present invention is a heterogeneous catalytic reaction, does not require the addition of an auxiliary agent, the product is easy to separate, the synthesis process is pollution-free, and compared with noble metal catalysts such as platinum, palladium, and ruthenium, the catalyst has low cost and good stability.

Description

Technical Field

[0001] The present invention relates to the field of organic catalytic synthesis, and particularly to a niobium (Nb)-based catalyst and a synthesis method for directly substituting aminating an alcohol compound with an organic amine to synthesize a corresponding secondary amine. Background Art

[0002] Organic amines are an important class of intermediates in synthetic chemistry. In industry, they are commonly used as components of functional materials, agrochemicals, or fine chemicals. Among them, secondary amines have a wide range of applications in the fields of surfactants, flotation agents, gasoline detergents, corrosion inhibitors, rubber processing aids, emulsifiers for herbicides, textile softeners, etc. Therefore, the development of new catalytic methods for synthesizing secondary amines has attracted much attention. Among them, synthetic routes based on classical nucleophilic substitution have been successively developed, such as the Buchwald−Hartwig amination reaction (F. Inoue, M. Kashihara, M. R. Yadav, Y. Nakao, Angew. Chem. Int. Ed. 2017, 56, 13307).

[0003] The synthesis of organic amines usually uses alkylating agents such as alkyl halides. However, due to the toxicity of halides and the generation of a large amount of inorganic salts, it is not environmentally friendly. In 2006, the Prim research group reported the use of a metal Lewis acid gold catalyst for the direct amination of benzyl alcohol. The catalyst used in this reaction is gold(III) chloride. Using dichloromethane as a solvent, sulfonamidation reactions can be carried out on a series of differently substituted benzyl alcohols. In this reaction, a weakly acidic amine source such as sulfonamide must be used. Subsequently, in 2012, Professor Xiag Chungu of Chinese scientists developed a method for catalyzing the direct amination of benzyl alcohol using a sulfonic acid ionic liquid. The sulfonamidation product of diphenylmethanol can be obtained when this reaction is carried out at 80 °C using 1,4-dioxane as a solvent. The above two synthesis methods both require a series of weakly acidic organic amines such as sulfonic acid amines and amides as amine sources, and these limiting conditions cannot meet the actual applications in chemical production. Therefore, it is very necessary to develop an alcohol amination reaction that is non-metal catalyzed and uses organic amine compounds as the amine source. Patent CN109053460B discloses a method for catalyzing the amination of alcohol compounds using a non-metal Lewis acid catalyst. In this method, a benzyl alcohol compound and an aniline compound are mixed, and a solvent and the catalyst tris(pentafluorophenyl)borane are added for reaction. Although amine compounds are also obtained by this method, the catalyst tris(pentafluorophenyl)borane used contains fluorine, is complex to prepare, and is easily affected by moisture. Therefore, there is an urgent need to develop a pollution-free and highly active heterogeneous catalytic system to achieve the green and efficient synthesis of organic secondary amine compounds. Summary of the Invention

[0004] In view of this, the object of the present invention is to provide a niobium-based catalyst and a synthesis method for directly aminating alcohol compounds by substitution to obtain secondary amines, so as to solve the problems of environmental unfriendliness, difficult catalyst separation or complex preparation in the prior art.

[0005] Based on the above object, the present invention provides a method for one-step substitution amination of alcohol compounds to synthesize secondary amines, and the method includes: using alcohol compounds as raw materials, and carrying out an amination reaction under the action of a heterogeneous niobium-based catalyst.

[0006] The catalyst includes one or more of niobium oxide, phosphorus-modified niobium oxide, nitrogen-modified niobium oxide, sulfur-modified niobium oxide, and carbon-modified niobium oxide catalyst, and phosphorus-modified niobium oxide is preferred. The niobium-based catalyst can be prepared by a hydrothermal crystallization method. The niobium source used for preparing the niobium-based catalyst is one or more of niobium oxalate, niobium acetate, and niobium tartrate, and niobium tartrate is preferred. The modifiers used in the preparation process of the modified niobium-based catalyst are: the phosphorus-containing reagent used for phosphorus modification is one or more of phosphate (A3PO4), hydrogen phosphate (A2HPO4), and dihydrogen phosphate (AH2PO4), and A can be one or more of K+, Na+, and NH4+; the nitrogen-containing reagent used for nitrogen modification is one or more of NH3, ammonia water, urea, and melamine; the sulfur-containing reagent used for sulfur modification is one or more of sulfate (B2SO4), bisulfate (BHSO4), sulfite (B2SO3), and bisulfite (BHSO3), and B can be one or more of K+, Na+, and NH4+; the carbon-containing reagent used for carbon modification is one or more of furfural, glucose, phenol, resorcinol, catechol, and hydroquinone.

[0007] In the amination reaction, the weight ratio of the alcohol compound to the catalyst is 1:0.1 - 1:0.5, the reaction temperature is 100 - 220 °C, the reaction time is 0.5 - 24 hours, the filled nitrogen pressure is 0.1 - 2 Mpa, and the reaction is carried out in an organic solvent. Among them, the alcohol compounds include one or several of alcohol compounds containing a benzene ring or alcohol compounds containing a double bond; the organic amines include one or several of amine compounds containing a benzene ring; the organic solvent can be one or several of methanol, ethanol, toluene, isopropanol, ethylene glycol dimethyl ether, tetrahydrofuran, and p-xylene, and the N source is amine compounds containing a benzene ring and their corresponding amine compounds. The weight ratio of the alcohol compound to the solvent is 1:5 - 1:50.

[0008] The reaction can be an intermittent reaction process or a continuous reaction process. The reactor for the intermittent reaction process is an intermittent reaction kettle; the reactor for the continuous reaction process is one of a fixed bed and a fluidized bed.

[0009] According to literature reports, catalytic reductive amination is a major method for synthesizing amines, which requires the use of noble metals such as Ru, Pd, Pt, or complexes of non-noble metals such as Co, Ni, etc. Through this method for amination reaction, the catalyst is prone to deactivation after reacting for a period of time, and this method will generate some Schiff base intermediates. The Schiff base is prone to hydrogenation to form stable by-products, resulting in a decrease in the yield of secondary amine products. There are also reports in the literature on the method of amination through substitution reaction. This method uses an acidic catalyst for dehydration to directly obtain the amination product, which can avoid the generation of by-products. However, its catalyst system usually contains additives or promoters, or uses homogeneous catalysts, and the separation is difficult. Or, there is also a reported substitution amination that obtains the final amination product through the formation of an ether intermediate and then substitution, and its reaction path is complex.

[0010] In the present invention, the niobium-based catalyst contains abundant acidic sites. The acidic sites can activate the hydroxyl groups in alcohol compounds, making the hydroxyl groups easily be directly substituted by nucleophilic substitution groups through the SN1 or SN2 type mechanism, and finally obtaining the required amination product.

[0011] Therefore, the method of the present invention has the following advantages: 1. The catalyst has high activity and can achieve the substitution amination of alcohol compounds to obtain high-value-added secondary amine products; 2. The used niobium-based catalyst is a solid material, which is easy to separate from the reaction solution and can be recycled, and has good industrial application prospects; 3. Compared with noble metal catalysts, the niobium-based catalyst is inexpensive and can effectively reduce the industrialization cost of secondary amine synthesis. Specific Embodiments

[0012] To make the objectives, technical solutions, and advantages of the present invention clearer, the following further elaborates on the present invention in detail with specific embodiments, but there are many other examples. After reading the present invention, those skilled in the art can make various equivalent forms of deformation or modification to the present invention, but these deformations or modifications all fall within the scope protected by the claims of this application.

[0013] The alcohol compounds used in the examples are mainly benzyl alcohol, and the amine compounds used are mainly aniline, but are not limited to the two substrates. The conversion rate of benzyl alcohol ranges from 40% to 100%, and the yield of N-benzylaniline ranges from 15% to 99%.

[0014] Using benzyl alcohol and aniline as raw materials, under the action of a niobium-based catalyst, substitution amination is carried out to prepare N-benzylaniline. The steps of the batch reactor are as follows: 0.4 g of benzyl alcohol, 0.5 g of aniline, 0.1 g of catalyst and 5 ml of solvent are added to a 50 ml batch reactor, and the reaction is carried out for 2 - 12 hours under the conditions of a nitrogen pressure of 0.5 - 2 MPa and a temperature of 100 °C - 200 °C. Qualitative analysis of the reaction product is carried out by gas chromatography-mass spectrometry (GC-MS Agilent 7890A-5975C), and quantitative analysis is carried out by gas chromatography (GC Agilent 7890A). The HP-5 chromatographic column is used, and the programmed temperature conditions of the chromatographic column are: maintaining at 50 °C for 10 mins, rising to 250 °C at a heating rate of 5 °C / min, and maintaining at 250 °C for 5 mins.

[0015] Examples 1 - 5

[0016] Comparing the performance of niobium-based catalysts prepared under different crystallization conditions in the reaction of preparing N-methylaniline from benzyl alcohol and aniline, including the following steps:

[0017] Hydrothermal method: Take 20 g of niobium tartrate, 1 g of ammonium dihydrogen phosphate and 20 ml of deionized water and add them to a beaker and stir to dissolve. Then transfer them to a 100 ml polytetrafluoroethylene container for crystallization. After filtration, washing, drying and calcination, a phosphorus-modified niobium oxide catalyst is obtained.

[0018] Among them, the performance evaluation conditions of the niobium-based catalysts with different crystallization conditions in Examples 1 - 5 are: 0.4 g of benzyl alcohol, 0.5 g of aniline, 0.1 g of niobium-based catalyst, 5 ml of p-xylene, a nitrogen pressure of 1 MPa, 140 °C, 6 h; the analysis results are shown in Table 1 (where the conversion rate refers to the conversion rate of benzyl alcohol, and the yield refers to the yield of N-benzylaniline).

[0019] .

[0020] Examples 6 - 8

[0021] Performance evaluation of niobium-based catalysts prepared from different niobium sources in the amination reaction:

[0022] Prepare different niobium-based catalysts according to the hydrothermal method in Examples 1 - 5. The crystallization conditions are the same as those in Example 2, except that niobium oxalate, niobium acetate and niobium citrate are used instead of niobium tartrate.

[0023] Performance evaluation conditions of niobium-based catalysts prepared with different niobium sources in Examples 6-8: 0.4 g of benzyl alcohol, 0.5 g of aniline, 0.1 g of niobium-based catalyst, 5 ml of p-xylene, 1 MPa nitrogen pressure, 140 °C, 6 h; the analysis results are shown in Table 2 (where the conversion rate refers to the conversion rate of benzyl alcohol, and the yield refers to the yield of N-benzylaniline).

[0024] .

[0025] Examples 9-11

[0026] Performance evaluation of niobium-based catalysts prepared with different modifiers in the amination reaction:

[0027] Niobium-based catalysts with different modifiers were prepared by the hydrothermal method in Examples 1-5. The crystallization conditions were the same as those in Example 2, except that NH3, potassium bisulfate, and glucose were used instead of ammonium dihydrogen phosphate.

[0028] Performance evaluation conditions of niobium-based catalysts prepared with different modifiers in Examples 9-11: 0.4 g of benzyl alcohol, 0.5 g of aniline, 0.1 g of niobium-based catalyst, 5 ml of p-xylene, 1 MPa nitrogen pressure, 140 °C, 6 h; the analysis results are shown in Table 3 (where the conversion rate refers to the conversion rate of benzyl alcohol, and the yield refers to the yield of N-benzylaniline).

[0029] .

[0030] Examples 12-33

[0031] Catalytic performance evaluation of niobium-based catalysts under different reaction conditions: The niobium-based catalyst used had the same preparation conditions as the catalyst in Example 2.

[0032] In Examples 12-33, 0.1 g of niobium-based catalyst was used for the amination reaction under different conditions, where the molar ratio of alcohol to amine was 1:1.5, the solvent was 5 ml, and the analysis results are shown in Table 4 (where the conversion rate refers to the conversion rate of alcohol, and the yield refers to the yield of secondary amine products).

[0033] .

[0034] Examples 34-41

[0035] Performance evaluation of niobium-based catalysts in the amination reaction in a fixed-bed reactor:

[0036] Niobium-based catalysts with different crystallization conditions were prepared by the hydrothermal method in Examples 1-5 under conditions of different crystallization times and crystallization temperatures.

[0037] Performance evaluation of niobium-based catalysts under different crystallization conditions in a continuous fixed-bed: 0.1 g catalyst, feed space velocity of benzyl alcohol is 30 h-1, nitrogen flow rate is 30 ml / h, nitrogen pressure is 1 MPa, temperature is 140 °C; the analysis results are shown in Table 5 (where the conversion rate refers to the conversion rate of benzyl alcohol, and the yield refers to the yield of N-benzylaniline).

[0038] 。

Claims

1. A method for synthesizing secondary amines by substituting amination of alcohol compounds, characterized in that, The method includes: using an alcohol and an organic amine compound as raw materials, carrying out an amination reaction under the action of a niobium-based catalyst in the presence of a solvent, with the conversion rate of the alcohol compound > 99%, and the yield of the corresponding secondary amine product formed by the amination reaction being 72%; the niobium-based catalyst is phosphorus-modified niobium oxide; the niobium-based catalyst can be prepared by a hydrothermal crystallization method, with the hydrothermal crystallization temperature being 150 - 180 °C; the crystallization time being 20 - 30 hours; the niobium source used for preparing the niobium-based catalyst being niobium tartrate; the alcohol compound includes one or more of alcohol compounds containing a benzene ring; the organic amine compound includes one or more of amine compounds containing a benzene ring.

2. The method according to claim 1, characterized in that, The phosphorus-containing modifier used in the preparation process of the modified niobium-based catalyst is one or more of phosphate (A3PO4), hydrogen phosphate (A2HPO4), and dihydrogen phosphate (AH2PO4), where A is K + , Na + , NH4 + or one or more of them.

3. The method according to claim 1, characterized in that, The weight ratio of the alcohol compound to the catalyst is 1:0.1 - 1:0.5; the reaction temperature of the alcohol compound and the organic amine compound is 120 - 180 °C, the reaction time is 2 - 20 hours, and the pressure of filled nitrogen is 0.5 - 1.2 MPa.

4. The method according to claim 1, characterized in that, The solvent is one or both of toluene and p-xylene; the weight ratio of the alcohol compound to the solvent is 1:10 - 1:

25.

5. The method according to claim 1, characterized in that, Among them, The reaction can be an intermittent reaction process or a continuous reaction process; the reactor for the intermittent reaction process is an intermittent reaction kettle; the reactor for the continuous reaction process is one of a fixed bed and a fluidized bed.