阅读说明：本技术 一种光催化制备不对称亚胺或不对称仲胺类化合物的方法 (Method for preparing asymmetric imine or asymmetric secondary amine compound through photocatalysis ) 是由 乔玮 苏韧 李雅如 于 2021-10-18 设计创作，主要内容包括：本发明涉及一种光催化制备不对称亚胺或不对称仲胺类化合物的方法。该方法包括通过在光照、惰性气体条件下,选用不同类型助催化剂负载的光催化剂,可实现芳香醇化合物与芳香氨基化合物反应得到不对称亚胺类化合物或不对称仲胺类化合物。本发明的方法可以用于代替现有成熟的有机合成工艺,条件温和、选择性高、具有普适性、适合于工业化生产。(The invention relates to a method for preparing asymmetric imine or asymmetric secondary amine compounds by photocatalysis. The method comprises the step of selecting different types of cocatalyst-loaded photocatalysts under the conditions of illumination and inert gas to realize the reaction of aromatic alcohol compounds and aromatic amino compounds to obtain asymmetric imine compounds or asymmetric secondary amine compounds. The method can be used for replacing the existing mature organic synthesis process, has the advantages of mild condition, high selectivity and universality, and is suitable for industrial production.)

1. A method for preparing asymmetric imine compounds or secondary amine compounds through photocatalysis, wherein the method comprises the following steps:

reacting an aromatic alcohol compound with an aromatic amino compound by a metal-loaded photocatalyst under the conditions of illumination and inert gas to obtain an asymmetric imine compound shown as a formula I or an asymmetric secondary amine compound shown as a formula II,

in the formulae I and II, R¹And R²Independently of one another, are 1, 2, 3, 4 or 5 substituents bonded to the benzene ring, each substituent independently of one another being hydrogen, halogen, C₁-C₁₀Alkyl radical, C₂-C₁₀Alkenyl radical, C₂-C₁₀Alkynyl, C₆-C₂₀Aryl, -OR', -OCF₃Any one of-NHR ', -C (═ O) OR ', -NHC (═ O) R ', and-C (═ O) R ', wherein R ' is H, C₁-C₆Alkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Any one of alkynyl, phenyl and benzyl.

2. The method according to claim 1, wherein the aromatic alcohol compound has a general structural formula shown in formula iii:

R¹is 1, 2, 3, 4 or 5 substituents attached to the benzene ring, each substituent independently of the others is hydrogen, halogen, C₁-C₁₀Alkyl radical, C₂-C₁₀Alkenyl radical, C₂-C₁₀Alkynyl, C₆-C₂₀Aryl radicals、-OR’、-OCF₃Any one of-NHR ', -C (═ O) OR ', -NHC (═ O) R ', and-C (═ O) R ', wherein R ' is H, C₁-C₆Alkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Any one of alkynyl, phenyl and benzyl.

3. The method according to claim 1 or 2, wherein the aromatic amino compound has a general structural formula shown in formula IV:

R²is 1, 2, 3, 4 or 5 substituents attached to the benzene ring, each substituent independently of the others is hydrogen, halogen, C₁-C₁₀Alkyl radical, C₂-C₁₀Alkenyl radical, C₂-C₁₀Alkynyl, C₆-C₂₀Aryl, -OR', -OCF₃Any one of-NHR ', -C (═ O) OR ', -NHC (═ O) R ', and-C (═ O) R ', wherein R ' is H, C₁-C₆Alkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Any one of alkynyl, phenyl and benzyl.

4. The method of claim 1, wherein the method comprises the steps of:

mixing the aromatic alcohol compound and the aromatic amino compound according to a molar ratio of 1: (0.1-10), adding a metal-loaded photocatalyst for ultrasonic dispersion, wherein the ultrasonic working frequency is 10-100Hz, and the ultrasonic time is 0.1-3h, and finally obtaining a mixed solution;

under the protection of inert gas, the mixed solution is at 0.001-50W/cm²Stirring reaction is carried out under illumination, the stirring speed is maintained at 50-1500r/min, the reaction temperature is controlled at 0-100 ℃, and an organic phase is obtained;

and drying and concentrating the organic phase, and reacting to obtain the asymmetric imine compound or the asymmetric secondary amine compound.

5. The method of claim 1, the metal-supported photocatalyst supports a cocatalyst that is a combination of one or more of Pt, Au, Ag, Pd, Ir, Rh, Ni, and Fe;

preferably, when Rh, Pt, Cu, Ni and Ru are selected as promoters, the obtained product is asymmetric imine;

preferably, when Fe, Au, Pd and Ag are used as promoters, the obtained product is asymmetric secondary amine.

6. The method of claim 1 or 4, wherein the metal-supported photocatalyst is a semiconductor material having a bandwidth in the range of 1eV to 4 eV.

7. The method of claim 5, wherein the photocatalyst in the metal-supported photocatalyst is selected from the group consisting of one or more of a metal oxide semiconductor, a metal nitrogen compound semiconductor, a metal sulfide semiconductor, a metal selenide semiconductor, a perovskite semiconductor, a delafossite semiconductor, a carbon-based polymer semiconductor, and a nitrogen-based polymer semiconductor.

8. The method according to claim 7, wherein the metal oxide semiconductor is an oxide containing Ti, Zn, Zr, W, V, Cu, Fe, Ce, Ta, In, or Nb;

the metal sulfide semiconductor is a sulfur-containing compound of Cd, Zn, Cu, W or Bi; the metal selenide semiconductor is a selenium-containing compound of Cd, Zn, Cu, W or Bi;

the metal nitrogen compound semiconductor is a nitrogen-containing compound of C, Ti, Ga, Ge or Ta.

9. The method of claim 4, wherein the inert gas is He, Ar, N₂、CO₂CO or H₂。

10. The method according to claim 4, wherein the concentration ratio of the aromatic nitro compound and the metal-supported photocatalyst in the mixed solution is (1-100) mmol/L: (1-100) mg/mL.

Technical Field

The invention relates to a preparation method of an asymmetric imine compound and an asymmetric secondary amine compound, belonging to the technical field of organic synthesis.

Background

Amine compounds (imine, secondary amine, benzylamine and the like) widely exist in various active natural products in the nature, and meanwhile, the amine group is a key active group of most medicines and is an industrially important raw material. Therefore, the amine compound is widely applied to industries such as biomedicine, pesticide, fine chemicals and the like as an organic synthesis intermediate.

The traditional method for synthesizing imine includes hydrogenation coupling of nitro compound, amine oxidation coupling of benzylamine, amination reaction of halogenated aromatic hydrocarbon and the like. In order to synthesize secondary amines, it is generally necessary to further reduce the imine, and methods such as sodium borohydride reduction and lithium aluminum hydride reduction are included. The methods have the problems of high pollution, more byproducts, harsh reaction conditions, low atom utilization rate and the like, so that the green sustainable production is difficult to realize. It is known from the structure of imine (C ═ N) that the oxidative condensation reaction of alcohol and amine produces imine in one step, which is one of the more desirable methods, and this method is highly atom-economical, and enables the synthesis of asymmetric imine structures, thus greatly enriching the variety of imine synthesis. However, the method inevitably generates byproducts such as benzaldehyde and toluene in the reaction process, and has the problems of poor reaction selectivity and difficult product separation.

In recent years, the photocatalytic organic synthesis technology has the advantages of mild reaction conditions, no need of using an additional redox agent, controllable selectivity and the like, and provides a green and economic technical route for synthesizing various high-value-added chemicals. The direct imine synthesis route by coupling the photocatalytic aniline and the benzyl alcohol has the advantages of mild reaction conditions, high catalytic efficiency, low cost and the like. Importantly, through the design of the photocatalyst and the control of a reaction system, the selective synthesis of products can be realized.

Therefore, by utilizing the photocatalyst technology, the efficient, green and high atom economy alcohol-amine oxidative condensation synthesis of imine is realized, the one-step controllable synthesis of asymmetric imine and secondary amine and derivatives thereof is realized, and the method has very important research value.

Disclosure of Invention

In order to achieve the above technical objects, the present invention provides a method for preparing an asymmetric imine compound or a secondary amine compound by photocatalysis, the method comprising the steps of:

under the conditions of illumination and inert gas, different types of cocatalyst (metal) loaded photocatalysts are selected to realize the reaction of aromatic alcohol compounds and aromatic amino compounds to obtain asymmetric imine compounds shown in a formula I or asymmetric secondary amine compounds shown in a formula II,

wherein, in the formula I and the formula II, R¹And R²Independently of one another, are 1, 2, 3, 4 or 5 substituents bonded to the benzene ring, each substituent independently of one another being hydrogen, halogen, C₁-C₁₀Alkyl radical, C₂-C₁₀Alkenyl radical, C₂-C₁₀Alkynyl, C₆-C₂₀Aryl, -OR', -OCF₃Any one of-NHR ', -C (═ O) OR ', -NHC (═ O) R ', and-C (═ O) R ', R ' is H, C₁-C₆Alkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Any one of alkynyl, phenyl and benzyl.

In one embodiment of the present invention, the general structural formula of the aromatic alcohol compound is represented by formula iii:

R¹is 1, 2, 3, 4 or 5 substituents attached to the benzene ring, each substituent independently of the others is hydrogen, halogen, C₁-C₁₀Alkyl radical, C₂-C₁₀Alkenyl radical, C₂-C₁₀Alkynyl, C₆-C₂₀Aryl, -OR', -OCF₃Any one of-NHR ', -C (═ O) OR ', -NHC (═ O) R ', and-C (═ O) R ', wherein R ' is H, C₁-C₆Alkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Any one of alkynyl, phenyl and benzyl.

In one embodiment of the present invention, the structural general formula of the aromatic amino compound is represented by formula IV:

R²is 1, 2, 3, 4 or 5 substituents attached to the benzene ring, each substituent independently of the others is hydrogen, halogen, C₁-C₁₀Alkyl radical, C₂-C₁₀Alkenyl radical, C₂-C₁₀Alkynyl, C₆-C₂₀Aryl, -OR', -OCF₃Any one of-NHR ', -C (═ O) OR ', -NHC (═ O) R ', and-C (═ O) R ', R ' is H, C₁-C₆Alkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Any one of alkynyl, phenyl and benzyl.

In one embodiment of the present invention, the method comprises the steps of:

mixing an aromatic alcohol compound and an aromatic amino compound according to a molar ratio of 1: (0.1-10), adding a solvent (whether the solvent is added or not can be selected according to actual needs), and carrying out ultrasonic dispersion on the metal-loaded photocatalyst, wherein the ultrasonic working frequency is 10-100Hz, and the ultrasonic time is 0.1-3h, so as to obtain a mixed solution;

the mixed solution is protected by inert atmosphere at 0.001-50W/cm²Stirring reaction is carried out under illumination, the stirring speed is maintained at 50-1500r/min (revolutions per minute) and the reaction temperature is controlled at 0-100 ℃, so as to obtain an organic phase;

and drying and concentrating the organic phase to obtain the asymmetric imine compound or the asymmetric secondary amine compound.

In one embodiment of the present invention, the concentration ratio of the aromatic nitro compound and the metal-supported photocatalyst in the mixed solution is (1-100) mmol/L: (1-100) mg/mL.

Importantly, the metal-loaded photocatalyst is loaded with a cocatalyst which is one or a combination of more of Pt, Au, Ag, Pd, Ir, Rh, Ni and Fe; wherein, when Rh, Pt, Cu, Ni and Ru are selected as the promoters, the obtained product is asymmetric imine; when Fe, Au, Pd and Ag are selected as the promoters, the obtained product is asymmetric secondary amine.

Wherein the metal-supported photocatalyst is a semiconductor material with a bandwidth range of 1-4 eV; specifically, the photocatalyst employed in the metal-supported photocatalyst is selected from one or a combination of more of a metal oxide semiconductor, a metal nitrogen compound semiconductor, a metal sulfide semiconductor, a metal selenide semiconductor, a perovskite semiconductor, a delafossite semiconductor, a carbon-based polymer semiconductor, and a nitrogen-based polymer semiconductor. In a further embodiment of the present invention, the metal oxide semiconductor is an oxide containing Ti, Zn, Zr, W, V, Cu, Fe, Ce, Ta, In or Nb; the metal sulfide semiconductor is a sulfur-containing compound of Cd, Zn, Cu, W or Bi; the metal selenide semiconductor is a selenium-containing compound of Cd, Zn, Cu, W or Bi; the metal nitrogen compound semiconductor is a nitrogen-containing compound of C, Ti, Ga, Ge or Ta.

In one embodiment of the present invention, the solvent used is one or a combination of water, cyclohexane, N-hexane, methyl sulfoxide, acetonitrile, N-dimethylformamide and 1, 4-dioxane.

In one embodiment of the present invention, the inert gas is He, Ar, N₂、CO₂CO or H₂。

The method for preparing the asymmetric imine compound or the secondary amine compound by photocatalysis realizes the aim of obtaining the asymmetric imine compound or the secondary amine compound by reacting aromatic alcohol and aromatic amine in one step under the action of the metal-loaded photocatalyst, and has the advantages of high atom economy, mild conditions and high product selectivity. Can be used for replacing the existing mature organic synthesis process, has universality and is suitable for industrial production.

Drawings

FIG. 1 is a general reaction formula of the method for preparing asymmetric imine compounds or secondary amine compounds by photocatalysis.

FIG. 2 is a gas chromatogram and mass spectrum against a standard database of N-benzylidene-4-methylaniline of example 1.

FIG. 3 is a gas chromatogram and mass spectrum against a standard database of N-benzyl-4-methylaniline of example 2.

Detailed Description

Example 1

The embodiment provides a method for preparing an asymmetric imine compound by photocatalysis, which comprises the following steps:

(a) 10mg of 1 wt% Rh/TiO₂Uniformly mixing a photocatalyst, 20 mu mol of 4-methylaniline, 30 mu mol of benzyl alcohol and 2mL of cyclohexane solvent, and performing ultrasonic dispersion for 10min to obtain a suspension;

(b) stirring and reacting the dispersed suspension for 6 hours at room temperature under the irradiation of an LED lamp simulating sunlight and the protection of nitrogen;

(c) drying and concentrating the organic phase obtained in the step (b) to obtain the N-benzylidene-4-methylaniline

According to the test and analysis of a gas chromatograph, the conversion rate of the 4-methylaniline is 90%, the conversion rate of the benzyl alcohol is 92%, and the selectivity of the N-benzylidene-4-methylaniline is 98%. The results of the reaction stirred at room temperature for 12h were analyzed by gas chromatograph test, as shown in fig. 2, and as can be seen from fig. 2, the gas chromatogram in panel a shows a single product peak (22.5min) in addition to the solvent peak (1.5min), and in combination with mass spectrometry (fig. 2b) compared to the standard mass spectrum peak, the results show that the product structure is: n-benzylidene-4-methylaniline.

Example 2

This example provides a method for photocatalytic preparation of asymmetric imines and secondary amines, substantially in accordance with example 1, except that: in step (a), the catalyst used is Fe/TiO₂(ii) a The final result of step (c) is that the reaction can obtain N-benzyl-4-methylaniline by testing and analyzing through a gas chromatographIn particular, the method comprises the following steps of,the conversion of 4-methylaniline was 95%, the conversion of benzyl alcohol was 93%, and the selectivity of N-benzyl-4-methylaniline was 98%. The gas chromatogram of N-benzyl-4-methylaniline and the mass spectrum compared with the standard database in this example are shown in fig. 3, and as can be seen from fig. 3, the gas chromatogram in panel a shows that a stronger peak is present at 22.7min except the solvent peak (2.5min), and the result shows that the product structure is as follows by comparing the mass spectrum (fig. 2b) with the standard mass spectrum peak: n-benzyl-4-methylaniline.

Example 3

This example provides a method for preparing asymmetric imine compounds by photocatalysis, which is substantially the same as example 1, except that: in the step (b), 10 mu mol of 4-methoxyaniline and 30 mu mol of benzyl alcohol are used as reactants, and finally the N-benzylidene-4-methoxyaniline can be obtained after the reaction for 12h in the step (c)According to the test and analysis of a gas chromatograph, the conversion rate of the 4-methoxyaniline is 79%, the conversion rate of the benzyl alcohol is 80%, and the selectivity of the N-benzylidene-4-methoxyaniline is 89%.

Example 4

This example provides a method for preparing asymmetric imine compounds by photocatalysis, which is substantially the same as example 1, except that: in the step (a), the metal cocatalyst is Rh, and reactants are selected to be 10 mu mol of 4-methylaniline and 20 mu mol of 4-methylbenzyl alcohol; finally, the reaction is carried out in the step (c) to obtain 4-methyl-N- (4-methylbenzylidene) anilineAccording to the test and analysis of a gas chromatograph, the conversion rate of the 4-methylaniline is 80 percent, the conversion rate of the 4-methylbenzyl alcohol is 79 percent, and the selectivity of the 4-methyl-N- (4-methylbenzylidene) aniline is 98 percent.

Example 5

This example provides a method for preparing asymmetric secondary amines by photocatalysis, which is substantially the same as example 4 except that: in step (a), the catalyst used is Fe/CdS; the final step (c) is carried out for 8h to obtain 4-methyl-N-(4-methylbenzyl) anilineAccording to the test and analysis of a gas chromatograph, the conversion rate of the 4-methylaniline is 90%, the conversion rate of the 4-methylbenzyl alcohol is 92%, and the selectivity of the 4-methyl-N- (4-methylbenzyl) aniline is 99%.

Example 6

This example provides a method for preparing asymmetric imine compounds by photocatalysis, which is substantially the same as example 1, except that: in step (a), the photocatalyst used is Rh/CeO₂The reactants are 8 mu mol of 4-methylaniline and 40 mu mol of 4-ethyl benzyl alcohol; the solvent is acetonitrile. The final step (c) is carried out for 12 hours to obtain 4-methyl-N- (4-ethylbenzylidene) anilineAccording to the test and analysis of a gas chromatograph, the conversion rate of the 4-methylaniline is 89%, the conversion rate of the 4-ethylbenzenol is 60%, and the selectivity of the 4-methyl-N- (4-ethylbenzylidene) aniline is 88%.

Example 7

This example provides a method for preparing asymmetric imine compounds by photocatalysis, which is substantially the same as example 1, except that: in the step (a), the reactants are 20mmol of 3-chloroaniline and 25mmol of 4-methylbenzyl alcohol; in the step (b), the illumination intensity is 50W/cm²Controlling the reaction temperature to be 50 ℃, and obtaining the N- (4-methylbenzylidene) -3-chloroaniline after the reaction in the final step (c) for 48hAccording to the test and analysis of a gas chromatograph, the conversion rate of the 3-chloroaniline is 88 percent, the conversion rate of the 4-methylbenzene alcohol is 88 percent, and the selectivity of the N- (4-methylbenzylidene) -3-chloroaniline is 94 percent.

Example 8

This example provides a method for preparing asymmetric imine compounds by photocatalysis, which is substantially the same as example 1, except that: in step (a), 4mmol of 4-methoxyaniline and 6mmol of 4-methylbenzyl alcohol are used as reactants; solvent(s)Is methyl sulfoxide and acetonitrile according to the volume ratio of 1: 1; in the step (b), the illumination intensity is 10W/cm²(ii) a Finally, the reaction in the step (c) is carried out for 10 hours to obtain the N- (4-methylbenzylidene) -4-methoxyanilineAccording to the test and analysis of a gas chromatograph, the conversion rate of the 4-methoxyaniline is 88 percent, the conversion rate of the 4-methylbenzyl alcohol is 90 percent, and the selectivity of the N- (4-methylbenzylidene) -4-methoxyaniline is 86 percent.

Example 9

This example provides a method for the photocatalytic preparation of an asymmetric imine compound, substantially in accordance with example 1, except that: in step (a), the catalyst used is Ni/TiO₂The solvent is 1, 4-dioxane; the result of the final step (c) was a test analysis by gas chromatography, N-benzylidene-4-methylanilineAccording to the test and analysis of a gas chromatograph, the conversion rate of the 4-methylaniline is 93 percent, the conversion rate of the benzyl alcohol is 85 percent, and the selectivity of the N-benzylidene-4-methylaniline is 96 percent.

Example 10

This example provides a method for preparing asymmetric secondary amines by photocatalysis, which is substantially the same as example 1 except that: in the step (a), the photocatalyst used is Pd/ZnS; the reactants were used for 4-bromoaniline conversion and 4-methylbenzyl alcohol; finally obtaining the N- (4-methylbenzyl) -4-bromoaniline through the reaction of the step (c)According to the test and analysis of a gas chromatograph, the conversion rate of the 4-bromoaniline is 90%, the conversion rate of the 4-methylbenzyl alcohol is 88%, and the selectivity of the N- (4-methylbenzyl) -4-bromoaniline is 81%.

Example 11

This example provides a method for preparing asymmetric secondary amines by photocatalysis, which is substantially the same as example 1 except that: the photocatalyst used in step (a)Is Au/GaN; the final reaction in step (c) can obtain N- (4-ethylbenzyl) -4-bromoanilineAccording to the test and analysis of a gas chromatograph, the conversion rate of 4-bromoaniline is 80%, the conversion rate of 4-ethyl benzyl alcohol is 82%, and the selectivity of N- (4-ethyl benzyl) -4-bromoaniline is 87%; .

Example 12

This example provides a method for preparing asymmetric imine compounds by photocatalysis, which is substantially the same as example 1, except that: the raw materials used are 80 mu mol of 4-chlorobenzyl alcohol and 800 mu mol of 4-methoxyaniline, and the N- (4-chlorobenzylidene) -4-methoxyaniline can be obtained after the final reaction for 7 hours with stirring at room temperatureWherein the conversion rate of the 4-methoxyaniline is 90 percent, the conversion rate of the 4-chlorobenzol is 89 percent, and the selectivity of the N- (4-chlorobenzylidene) -4-methoxyaniline is 91 percent.

Comparative example 1

This comparative example is essentially identical to example 1, except that: asymmetric imine and secondary amine compounds cannot be obtained without using a photocatalyst.

Comparative example 2

This comparative example is essentially identical to example 1, except that: the photocatalyst used is ZrO₂(bandwidth 5eV), the result of the final step (c) is that asymmetric imines and secondary amines are not obtained.

Comparative example 3

This comparative example is essentially identical to example 1, except that: the cocatalyst used is Co, and the result of the final step (c) is: only 30% of the 4-methylaniline and benzyl alcohol were consumed and no asymmetric imines and secondary amines were obtained.

The above embodiments are merely illustrative of the technical ideas and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and not to limit the protection scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.