阅读说明：本技术 一种n-苯甲基苯甲胺的制备方法 (Preparation method of N-benzyl benzylamine ) 是由 陶朝富 常亚林 谢雅 王爱萍 余焓 于 2021-01-08 设计创作，主要内容包括：本发明涉及一种N-苯甲基苯甲胺的制备方法,其特征在于,该方法为：以多金属氧酸盐为催化剂,放进反应容器中,将有机溶剂、苄铵和苯甲酸依次加入容器,最后加入添加剂,加热搅拌反应,分离得到N-苯甲基苯甲胺。反应完成后,可以回收催化剂循环利用,直接将反应结束后的体系进行过滤,多金属氧酸盐可以直接滤出,处理后进行回收,将回收的多酸再用于对制备N-苯甲基苯甲胺。与现有技术相比,本发明具有可以将苄铵和苯甲酸反应制得N-苯甲基苯甲胺,具有高活性和高选择性,反应条件温和、绿色和环保,催化剂可以回收利用,具有极大的工业化生产潜力等优点。(The invention relates to a preparation method of N-benzyl benzylamine, which is characterized by comprising the following steps: the polyoxometallate is used as a catalyst and is put into a reaction container, an organic solvent, benzylammonium and benzoic acid are sequentially added into the container, finally, an additive is added, heating and stirring reaction are carried out, and separation is carried out to obtain the N-benzyl benzylamine. After the reaction is finished, the catalyst can be recycled, the system after the reaction is finished is directly filtered, the polyoxometallate can be directly filtered out, the polyoxometallate is recycled after treatment, and the recycled polyacid is reused for preparing the N-benzyl benzylamine. Compared with the prior art, the method has the advantages that the N-benzyl benzylamine can be prepared by reacting the benzylammonium with the benzoic acid, the method has high activity and high selectivity, the reaction condition is mild, green and environment-friendly, the catalyst can be recycled, and the method has great industrial production potential.)

1. A preparation method of N-benzyl benzylamine is characterized by comprising the following steps: the polyoxometallate is used as a catalyst and is put into a reaction container, an organic solvent, benzylammonium and benzoic acid are sequentially added into the container, finally, an additive is added, heating and stirring reaction are carried out, and separation is carried out to obtain the N-benzyl benzylamine.

2. The method of claim 1, wherein the polyoxometallate is Keggin, Dawson, Silverton, Waugh, Lindquist or Anderson.

3. The method of claim 1, wherein the catalyst is an Anderson polyoxometalate centered on Fe, Al, Cr, Ni, Mn, Cu, or Co.

4. The method of claim 1, wherein the catalyst is added in an amount of 0.1 to 2.0 mol%.

5. The method of claim 4, wherein the catalyst is added in an amount of 0.5 mol%.

6. The method of claim 1, wherein the additive is phenylsilane, and the amount of phenylsilane is 2.0 to 6.0 equivalents.

7. The method of claim 6, wherein the amount of phenylsilane is 3.0 equivalents.

8. The method of claim 1, wherein the organic solvent comprises N, N-dimethylformamide, toluene, 1, 4-dioxane, or benzene.

9. The method for preparing N-benzylbenzylamine according to claim 1, wherein the heating temperature is 80-120 ℃, and the reaction time is 12-48 h.

10. The method for preparing N-benzylbenzylamine according to claim 1, wherein the heating temperature is 120 ℃, and the reaction time is 18 h.

Technical Field

The invention relates to the technical field of catalysis, and particularly relates to a preparation method of N-benzyl benzylamine.

Background

The amine and the derivatives thereof widely exist in basic and commercially important molecules, are important structural units of a plurality of bioactive molecules, and widely exist in chemical drugs, natural products and functional materials, so that the development of a simple and efficient method for constructing the C-N bond is always the focus of attention in the industry and academia. There are many methods to date by which carbon-nitrogen bonds can be constructed, such as N-alkylation, Ullmann coupling, Buchwald-Hartwig coupling, Goldberg coupling reactions, and hydroamination.

The C-N bond is one of the most important structural motifs in nature, is present in natural products, proteins and therapeutic drugs, and has important significance in organic chemistry and biochemistry. In addition, it is counted that about 25% of the drugs on the global market contain at least one C-N group, including some drugs having important biological activities such as antitumor, antiviral, antihypertensive, lipid-lowering, etc., for example, Valsartan (which can effectively inhibit angiotensin-II receptor), Atorvastatin (which is the most effective cholesterol-lowering drug sold worldwide), Lisinopril (which is an effective angiotensin converting enzyme inhibitor), dialezem (which can be used as a calcium channel blocker to treat angina and hypertension), etc., and thus the development of a green, effective and inexpensive method for forming C-N bond has become an important research issue.

The traditional method has high toxicity of C-N bond reagent, and some reactions can also generate stoichiometric metal salt waste or waste acid to aggravate the problems of environmental pollution and the like. In the last two decades, metal organic catalysts have made great progress in selective oxidation and coupling reaction, but in the catalytic oxidation process, the metal organic catalysts have the problems of metal residue, difficult recycling, environmental unfriendliness and the like, so that the metal organic catalysts are difficult to reach the industrial level.

Disclosure of Invention

The invention aims to overcome the defects in the prior art and provide the method for preparing the N-benzyl benzylamine, which can prepare the N-benzyl benzylamine by reacting the benzylammonium with the benzoic acid, has the advantages of high activity and high selectivity, mild, green and environment-friendly reaction conditions, recyclable catalyst and great industrial production potential.

The purpose of the invention can be realized by the following technical scheme:

the inventors have appreciated that polyoxometallate is a very advantageous catalyst with unique redox properties, strong durability to oxidizing agents and environmental compatibility. Polyoxometallate (polyacid) is a novel high-efficiency multifunctional catalyst, has acid catalytic performance, redox catalytic performance and good stability, can be used for homogeneous reaction, heterogeneous reaction and even phase transfer catalyst, is a green and environment-friendly catalyst with a very promising prospect, and is widely applied to the fields of catalysis, analysis, medicine, electrochemistry, photochemistry, petrochemical industry and the like. Has the advantages of high activity, high selectivity, high stability and recycling, and then the following specific scheme is proposed:

a preparation method of N-benzyl benzylamine comprises the following steps: the method comprises the following steps of putting polyoxometallate serving as a catalyst into a reaction container, sequentially adding an organic solvent, benzylammonium and benzoic acid into the container, finally adding an additive, heating, stirring, reacting, and separating to obtain the N-benzyl benzylamine, wherein the reaction formula is as follows:

after the reaction is finished, the catalyst can be recycled, the system after the reaction is finished is directly filtered, the polyoxometallate can be directly filtered out, the polyoxometallate is recycled after treatment, and the recycled polyacid is reused for preparing the N-benzyl benzylamine.

Further, the polyoxometallate is Keggin type, Dawson type, Silverton type, Waugh type, Lindquist type or Anderson type.

Furthermore, the catalyst is Anderson type polyoxometallate taking Fe, Al, Cr, Ni, Mn, Cu or Co as the center.

Further, the amount of the catalyst added is 0.1 to 2.0 mol%, where mol% is compared to that of benzylammonium, e.g. 1mmol of benzylammonium and 1mmol of benzoic acid are added in an amount of 0.001 to 0.02mmol of catalyst.

Further, the amount of the catalyst added was 0.5 mol%.

Further, the additive is phenylsilane, and the amount of the phenylsilane is 2.0 to 6.0 equivalents. Equivalent means an amount corresponding to a particular or trivial value, where equivalent is relative to the amount of benzylammonium species, e.g. 1mmol of benzylammonium and 1mmol of benzoic acid requires the addition of 2-6mmol of phenylsilane.

Further, the amount of said phenylsilane was 3.0 equivalents.

Further, the organic solvent is N, N-dimethylformamide, toluene, 1, 4-dioxane or benzene, preferably toluene.

Further, the heating temperature is 80-120 ℃, and the reaction time is 12-48 h.

Further, the heating temperature is 120 ℃, and the reaction time is 18 h.

Further, when toluene is used as the solvent, the temperature is most effective at 120 ℃.

Compared with the prior art, the method has the characteristics of simple preparation, high product yield, no three wastes, low production cost and the like, and is an environment-friendly method for preparing the N-benzyl benzylamine with high atom economy. The catalyst is a novel catalyst, namely polyoxometallate (polyacid), can be recycled for multiple times after simple treatment, does not need to add acid in the reaction process, and is very beneficial to industrial production, so the method has potential application prospect.

Drawings

FIG. 1 is the NMR spectrum of N-benzylbenzylamine obtained by the present invention¹³C NMR(CDCl₃)；

FIG. 2 is the NMR spectrum of N-benzylbenzylamine obtained by the present invention¹H NMR(CDCl₃)。

Detailed Description

The invention is described in detail below with reference to the figures and specific embodiments. For further details of the present invention, several embodiments are given below, which mainly take the example of the Anderson-type polyoxometalate catalyst with different metal atoms as the center. However, the present invention is not limited to these examples.

Example 1

0.1072g of benzylammonium, 0.1222g of benzoic acid, 0.1-2.0 mol% of Anderson type polyoxometallate taking Ni as a central metal, 2.0-6.0equiv of phenyl silane and 2.0-6.0mL of solvent toluene are put into a dry reaction tube, an air ball is sleeved on the reaction tube, the reaction temperature is controlled to be 80-120 ℃, the reaction is stopped after 18 hours of heat preservation reaction, the reaction is cooled to room temperature, a sample is prepared and is subjected to GC-MS detection, and the GC-MS result shows that the conversion rate of a reaction substrate is 96%. And performing nuclear magnetic test after separation and purification, and verifying that the product is N-benzyl benzylamine by using the obtained hydrogen spectrum and carbon spectrum data.

Example 2

0.1072g of benzylammonium, 0.1222g of benzoic acid, 0.1-2.0 mol% of Anderson type polyoxometallate taking Al as a central metal, 2.0-6.0equiv of phenyl silane and 2.0-6.0mL of solvent toluene are put into a dry reaction tube, an air ball is sleeved on the reaction tube, the reaction temperature is controlled to be 80-120 ℃, the reaction is stopped after 18 hours of heat preservation reaction, the reaction is cooled to room temperature, a sample is prepared and is subjected to GC-MS detection, and the GC-MS result shows that the conversion rate of a reaction substrate is 83%. And performing nuclear magnetic test after separation and purification, and verifying that the product is N-benzyl benzylamine by using the obtained hydrogen spectrum and carbon spectrum data.

Example 3

0.1072g of benzylammonium, 0.1222g of benzoic acid, 0.1-2.0 mol% of Anderson type polyoxometallate taking Cr as a central metal, 2.0-6.0equiv of phenyl silane and 2.0-6.0mL of solvent toluene are put into a dry reaction tube, an air ball is sleeved on the reaction tube, the reaction temperature is controlled to be 80-120 ℃, the reaction is stopped after 18 hours of heat preservation reaction, the reaction is cooled to room temperature, a sample is prepared and is subjected to GC-MS detection, and the GC-MS result shows that the conversion rate of a reaction substrate is 91%. And performing nuclear magnetic test after separation and purification, and verifying that the product is N-benzyl benzylamine by using the obtained hydrogen spectrum and carbon spectrum data.

Example 4

0.1072g of benzylammonium, 0.1222g of benzoic acid, 0.1-2.0 mol% of Anderson type polyoxometallate taking Fe as a central metal, 2.0-6.0equiv of phenyl silane and 2.0-6.0mL of solvent toluene are put into a dry reaction tube, an air ball is sleeved on the reaction tube, the reaction temperature is controlled to be 80-120 ℃, the reaction is stopped after 18 hours of heat preservation reaction, the reaction is cooled to room temperature, a sample is prepared and is subjected to GC-MS detection, and the GC-MS result shows that the conversion rate of a reaction substrate is 86%. And performing nuclear magnetic test after separation and purification, and verifying that the product is N-benzyl benzylamine by using the obtained hydrogen spectrum and carbon spectrum data.

Example 5

0.1072g of benzylammonium, 0.1222g of benzoic acid, 0.1-2.0 mol% of Anderson type polyoxometallate taking Mn as a central metal, 2.0-6.0equiv of phenyl silane and 2.0-6.0mL of solvent toluene are put into a dry reaction tube, an air ball is sleeved on the reaction tube, the reaction temperature is controlled to be 80-120 ℃, the reaction is stopped after 18 hours of heat preservation reaction, the reaction is cooled to room temperature, a sample is prepared and is subjected to GC-MS detection, and the GC-MS result shows that the conversion rate of a reaction substrate is 92%. And performing nuclear magnetic test after separation and purification, and verifying that the product is N-benzyl benzylamine by using the obtained hydrogen spectrum and carbon spectrum data.

Example 6

0.1072g of benzylammonium, 0.1222g of benzoic acid, 0.1-2.0 mol% of Anderson type polyoxometallate taking Co as a central metal, 2.0-6.0equiv of phenyl silane and 2.0-6.0mL of solvent toluene are put into a dry reaction tube, an air ball is sleeved on the reaction tube, the reaction temperature is controlled to be 80-120 ℃, the reaction is stopped after 18 hours of heat preservation reaction, the reaction is cooled to room temperature, a sample is prepared and is subjected to GC-MS detection, and the GC-MS result shows that the conversion rate of a reaction substrate is 91%. And performing nuclear magnetic test after separation and purification, and verifying that the product is N-benzyl benzylamine by using the obtained hydrogen spectrum and carbon spectrum data.

Example 7

0.1072g of benzylammonium, 0.1222g of benzoic acid, 0.1-2.0 mol% of Anderson type polyoxometallate taking Cu as a central metal, 2.0-6.0equiv of phenyl silane and 2.0-6.0L of toluene solvent are put into a dry reaction tube, an air ball is sleeved on the reaction tube, the reaction temperature is controlled to be 80-120 ℃, the reaction is stopped after 18 hours of heat preservation reaction, the reaction is cooled to room temperature, a sample is prepared and is subjected to GC-MS detection, and the GC-MS result shows that the conversion rate of a reaction substrate is 80%. And performing nuclear magnetic test after separation and purification, and verifying that the product is N-benzyl benzylamine by using the obtained hydrogen spectrum and carbon spectrum data. And (4) treating and recycling the catalyst after reaction.

Example 8

The reaction procedure is the same as example 1, but the difference is that the catalyst is recovered and used for the 1 st time, the GC-MS analysis shows that the conversion rate of the reaction substrate is more than 94%, the product is obtained by separation and purification, and the nuclear magnetism is confirmed to be N-benzyl benzylamine.

Example 9

The reaction procedure is the same as example 1, but the difference is that the catalyst is recovered and used for the 2 nd time, the GC-MS analysis shows that the conversion rate of the reaction substrate is more than 93%, the product is obtained by separation and purification, and the nuclear magnetism is confirmed to be N-benzyl benzylamine.

Example 10

The reaction procedure was the same as in example 1, except that the catalyst was recovered and used 3 rd time, the conversion of the reaction substrate was 92% by GC-MS analysis, and the product was isolated and purified and confirmed to be N-benzylbenzylamine by nuclear magnetic resonance.

Example 11

The reaction procedure was the same as in example 1, except that the catalyst was used 4 th time after recovery, the conversion of the reaction substrate was 90% by GC-MS analysis, and the product was isolated and purified and confirmed to be N-benzylbenzylamine by nuclear magnetic resonance.

Example 12

The reaction procedure was the same as in example 1, except that 4.8g (0.5 mol%) of 4-butylammonium bromide was added to the reaction, the conversion of the reaction substrate was less than 90% by GC-MS analysis, the catalyst solid was obtained by filtration, washed and dried, collected for reuse, and the filtrate was separated and purified to obtain a pale yellow product which was confirmed to be N-benzylbenzylamine by nuclear magnetic resonance.

The foregoing is directed to preferred embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow. However, any simple modification, equivalent change and modification of the above embodiments according to the technical essence of the present invention are within the protection scope of the technical solution of the present invention.