Application of decanuclear 3d-4f supramolecular nanocage materials in catalysis of three-component aza-darzens reaction

Abstract

The application belongs to the technical field of homogeneous catalysis, and provides application of a ten-core 3d-4f supramolecular nanocage material in catalyzing a three-component aza-Darzens reaction. The application comprises the following steps: mixing an aldehyde compound, an amino benzene compound, ethyl diazoacetate, the ten-core 3d-4f supramolecular nanocage material and an organic solvent, and then performing a reaction to obtain a reaction product, namely completing the three-component aza-Darzens reaction. The ten-core 3d-4f supramolecular nanocage material is used as a catalyst to catalyze the three-component aza-Darzens reaction to realize synthesis of a drug precursor with biological activity, and the catalyst has high catalytic efficiency, the operation steps are simple, and the yield of the target product is also high.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of homogeneous catalysis, and particularly relates to application of a ten-core 3d-4f supramolecular nanocage material in catalyzing a three-component aza-Darzens reaction. BACKGROUND

[0002] As a kind of Darzens reaction, aza-Darzens reaction has been applied to biological drug synthesis of various biologically active minimum saturated nitrogen heterocyclic compounds. The minimum saturated nitrogen heterocyclic compounds are also useful precursors of other nitrogen-containing compounds, although there are various synthesis methods that can effectively prepare the minimum saturated nitrogen heterocyclic compounds, most of which have the problems of expensive starting materials and complex synthesis steps. At present, the research on three-component aza-Darzens reaction is relatively few, and only tetrahedral Ga(III) nanoreactor, octahedral Er(III) nanoreactor and Zr-MOF are used as different types of heterogeneous catalysts in such reactions, which have proved that the three-component aza-Darzens reaction is an effective method for synthesizing aziridine derivatives. However, these three-component aza-Darzens reactions based on different types of catalysts require a long reaction time, a high catalyst loading or an additional additive K3PO4.

[0003] Many high-nuclear supramolecular cages, such as common tetrahedral and octahedral cages, have been applied in the related catalytic field, but the metal cage as an artificial enzyme in the homogeneous catalytic field is still a great challenge. The main influencing factors are that the small cavity leads to the difficulty of substrate entering and exiting, and the differences in metal ion species and coordination number, mode and stereochemistry often lead to the metal site as an active center being ignored. Therefore, how to develop a ten-core 3d-4f supramolecular nanocage material with high catalytic activity as an artificial enzyme to promote the multi-component catalytic activity has become a problem to be solved by those skilled in the art. SUMMARY

[0004] Therefore, the present application provides application of a ten-core 3d-4f supramolecular nanocage material in catalyzing a three-component aza-Darzens reaction, which aims to solve the problems of long reaction time and high catalyst loading of existing different complex catalysts in catalyzing a three-component aza-Darzens reaction.

[0005] In order to achieve the above purpose, the technical scheme adopted by the present application is as follows:

[0006] The present application provides application of a ten-core 3d-4f supramolecular nanocage material in catalyzing a three-component aza-Darzens reaction, which includes the following steps:

[0007] The aldehyde compound, the amino benzene compound, the ethyl diazoacetate, the ten-core 3d-4f supramolecular nanocage material and the organic solvent are mixed to react to obtain a reaction product, that is, a three-component aza-Darzens reaction is completed.

[0008] The reaction product has a structural formula of any one of the following formulas 1-20.

[0009]

[0010]

[0011] Further, the ten-core 3d-4f supramolecular nanocage material is used in an amount of 0.2-0.6 mol% of the total reactants.

[0012] Further, the molar volume ratio of the aldehyde compound, the amino benzene compound, the ethyl diazoacetate and the organic solvent is 1 mmol: 1-2 mmol: 1-2 mmol: 4-6 mL.

[0013] Further, the aldehyde compound includes formaldehyde or propyl aldehyde.

[0014] Further, the amino benzene compound includes any one of aniline, p-toluidine, p-aminophenyl ether, p-aminophenyl methyl ether, p-ethyl aniline, p-isopropyl aniline, p-tert-butyl aniline, p-chloroaniline, p-iodoaniline, p-bromoaniline, p-fluoroaniline, m-toluidine, m-tert-butyl aniline, m-ethyl aniline, o-isopropyl aniline, m-fluoroaniline, o-tert-butyl aniline, p-aminobenzoic acid and p-nitroaniline.

[0015] Further, the reaction temperature is 20-30 DEG C, and the reaction time is 0.5-3 h.

[0016] Further, the organic solvent includes any one of acetonitrile, methanol, dichloromethane and ethanol.

[0017] According to the above technical solution, compared with the prior art, the present application has the following advantages:

[0018] The ten-core 3d-4f supramolecular nanocage material used in the present application has a clear geometric structure, a large window is conducive to the entry and exit of substrate and product molecules, a large number of Lewis acid sites accelerate the conversion of the substrate and have excellent stability to realize a kilogram reaction.

[0019] Compared with other homogeneous catalysts, the preparation method of the ten-core 3d-4f supramolecular nanocage material is simple, the yield is high, and industrialized preparation can be realized; the structure is stable in solution, and exists in the form of molecular cage; three-component aza-Darzens reaction can be realized, and gram-scale production can be realized. The operation steps are simple, the catalytic activity is high, the required reaction conditions are mild, the total reaction time is short, and industrialized production can be realized. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 Fig. 1 is a ball-and-stick diagram of a ten-core 3d-4f supramolecular nanocage material, wherein the blue ball is zinc, the purple ball is a rare earth element, the red ball is oxygen, the green ball is chlorine, the blue ball is nitrogen, and the gray ball is carbon;

[0021] Figure 2 Fig. 2 is a yield nuclear magnetic resonance spectrum of Example 1;

[0022] Figure 3 Fig. 3 is a hydrogen spectrum of the target product of Example 1;

[0023] Figure 4 Fig. 4 is a carbon spectrum of the target product of Example 1;

[0024] Figure 5 Fig. 5 is a high-resolution mass spectrum of the target product of Example 1. DETAILED DESCRIPTION

[0025] The application provides an application of a ten-core 3d-4f supramolecular nanocage material in catalyzing a three-component aza-Darzens reaction, which comprises the following steps:

[0026] The aldehyde compound, the amino benzene compound, the ethyl diazoacetate, the ten-core 3d-4f supramolecular nanocage material, and the organic solvent are mixed and then reacted to obtain a reaction product, that is, the three-component aza-Darzens reaction is completed;

[0027] The reaction product has a structural formula as shown in any one of formulae 1-20:

[0028]

[0029]

[0030] In the application, the amount of the ten-core 3d-4f supramolecular nanocage material is 0.2-0.6 mol %, preferably 0.3-0.5 mol %, and more preferably 0.4 mol % of the total reactants.

[0031] The preparation of the ten-core 3d-4f supramolecular nanocage material comprises the following steps:

[0032] (1) 3-aminopropanoic acid methyl ester, triethylamine, dichloromethane, oxalyl chloride monoethyl ester dichloromethane solution, to obtain intermediate product a after reaction;

[0033] (2) intermediate product a, ethanol and hydrazine hydrate solution, to obtain intermediate product b after reaction;

[0034] (3) intermediate product b, 3,5-di-tert-butylsalicylaldehyde and ethanol, to obtain asymmetric semi-rigid ligand after reaction;

[0035] (4) asymmetric semi-rigid ligand, zinc salt, rare earth salt, triethylamine and methanol, to obtain ten-core 3d-4f supramolecular nanocage material after reaction.

[0036] In the step (1) of the present application, the molar ratio of 3-aminopropanoic acid methyl ester, triethylamine and oxalyl chloride monoethyl ester is preferably 1:1-5:0.9-6, further preferably 1:2-4:1.2-5.4, and more preferably 1:3:2.6-3.2; the concentration of oxalyl chloride monoethyl ester dichloromethane solution is preferably 0.8-6 mol / L, further preferably 1.2-4.7 mol / L, and more preferably 2.6-3.3 mol / L; and the volume ratio of dichloromethane to oxalyl chloride monoethyl ester dichloromethane solution is preferably 4-6:1, further preferably 4.5-5.5:1, and more preferably 5:1.

[0037] In the step (1) of the present application, the reaction is preferably carried out under a protective atmosphere, and the protective atmosphere is preferably argon; the reaction temperature is preferably 0-5℃, further preferably 1-4℃, and more preferably 2-3℃; and the reaction time is preferably 12-24 h, further preferably 16-22 h, and more preferably 18-20 h.

[0038] In the step (1) of the present application, the reaction product after reaction is preferably sequentially quenched, extracted, dried and purified; the quenching is preferably carried out by using sodium bicarbonate; the extraction agent for extraction is preferably dichloromethane; and the drying is preferably carried out by using anhydrous calcium sulfate.

[0039] In the step (2) of the present application, the mass fraction of hydrazine hydrate solution is preferably 75-85 wt%, further preferably 78-82 wt%, and more preferably 80 wt%; the hydrazine hydrate solution is preferably an aqueous hydrazine hydrate solution; and the molar volume ratio of intermediate product a, ethanol and hydrazine hydrate is preferably 1 mol:4.1-4.2 L:2-6 mol, further preferably 1 mol:4.1-4.2 L:3-5 mol, and more preferably 1 mol:4.15 L:4 mol.

[0040] In step (2) of the present application, the reaction temperature is preferably 68-80℃, further preferably 70-78℃, and more preferably 72-76℃, and the reaction time is preferably 12-24h, further preferably 14-20h, and more preferably 16-18h.

[0041] In step (2) of the present application, the reaction product is preferably sequentially cooled, filtered, washed, and dried after the reaction; the cooling temperature is preferably 23-30℃, further preferably 25-28℃, and more preferably 26-27℃, the washing is preferably performed using ethanol, the washing frequency is preferably 3-6 times, further preferably 4-5 times, and the drying is preferably performed using anhydrous calcium sulfate.

[0042] In step (3) of the present application, the molar volume ratio of intermediate product b, 3,5-di-tert-butylsalicylaldehyde, and ethanol is preferably 1mol:2-6mol:4.8-5.2L, further preferably 1mol:3-5mol:5L, and more preferably 1mol:4mol:5L, the reaction is preferably a reflux reaction, the reflux reaction temperature is preferably 76-80℃, further preferably 77-79℃, and more preferably 78℃, and the reflux reaction time is preferably 10-14h, further preferably 11-13h, and more preferably 12h.

[0043] In step (3) of the present application, the reaction product is preferably sequentially cooled, filtered, washed, and dried after the reaction; the cooling temperature is preferably 23-30℃, further preferably 25-28℃, and more preferably 26-27℃, the washing is preferably performed using ethanol, the washing frequency is preferably 3-6 times, further preferably 4-5 times, and the drying is preferably performed using anhydrous calcium sulfate.

[0044] In step (3) of the present application, the asymmetric semi-rigid ligand has the following structural formula:

[0045]

[0046] In the present application, the reaction equation of the asymmetric semi-rigid ligand is as follows:

[0047]

[0048] In step (4) of the present application, the molar volume ratio of the asymmetric semi-rigid ligand, the zinc salt, the rare earth salt, the triethylamine and the methanol is preferably 1 mmol: 1-2 mmol: 1-2 mmol: 2 mmol: 75-85 mL, further preferably 1 mmol: 1-2 mmol: 1-1.5 mmol: 2 mmol: 76-82 mL, and more preferably 1 mmol: 1.5 mmol: 1-1.2 mmol: 2 mmol: 80 mL.

[0049] In step (4) of the present application, the zinc salt is preferably zinc perchlorate or zinc chloride, and the rare earth salt is preferably lanthanum chloride, cerium chloride, praseodymium chloride, neodymium chloride, samarium chloride, europium chloride, gadolinium chloride, terbium chloride, dysprosium chloride, holmium chloride, erbium chloride, yttrium chloride, lutetium chloride or erbium perchlorate.

[0050] In step (4) of the present application, the reaction temperature is preferably 23-35°C, further preferably 26-32°C, and more preferably 28-30°C, and the reaction time is preferably 1-5 days, further preferably 2-4 days, and more preferably 3 days.

[0051] In step (4) of the present application, the reaction is preferably followed by filtration, washing and drying in this order; the washing is preferably performed using diethyl ether, and the washing is preferably performed 3-6 times, further preferably 4-5 times; and the drying is preferably performed using vacuum drying.

[0052] In the present application, the molar volume ratio of the aldehyde compound, the amino benzene compound, ethyl diazoacetate and the organic solvent is 1 mmol: 1-2 mmol: 1-2 mmol: 4-6 mL, preferably 1 mmol: 1.2-1.8 mmol: 1.2-1.8 mmol: 4.5-5.5 mL, and further preferably 1 mmol: 1.4-1.6 mmol: 1.4-1.6 mmol: 5.0 mL.

[0053] In the present application, the aldehyde compound includes formaldehyde or propyl aldehyde, and is preferably formaldehyde.

[0054] Further, the amino benzene compound includes any one of aniline, p-toluidine, p- amino phenyl ether, p-amino anisole, p-ethyl aniline, p-isopropyl aniline, p-tert-butyl aniline, p-chloroaniline, p-iodoaniline, p-bromoaniline, p-fluoroaniline, m-toluidine, m-tert-butyl aniline, m-ethyl aniline, o-isopropyl aniline, m-fluoroaniline, o-tert-butyl aniline, p-aminobenzoic acid, p-nitroaniline, preferably any one of aniline, p-toluidine, p-amino phenyl ether, p-amino anisole, p-ethyl aniline, p-isopropyl aniline, p-tert-butyl aniline, p-chloroaniline, p-iodoaniline, p-bromoaniline, p-fluoroaniline, m-toluidine, m-tert-butyl aniline, m-ethyl aniline, o-isopropyl aniline, m-fluoroaniline, o-tert-butyl aniline, further preferably any one of aniline, p-toluidine, p-amino phenyl ether, p-amino anisole, p-ethyl aniline, p-isopropyl aniline, p-tert-butyl aniline, p-chloroaniline, p-iodoaniline, p-bromoaniline, p-fluoroaniline, m-toluidine, m-tert-butyl aniline, m-ethyl aniline.

[0055] In the present application, the temperature of the reaction is 20-30℃, preferably 22-28℃, further preferably 24-26℃; the time of the reaction is 0.5-3h, preferably 1.0-2.5h, further preferably 1.5-2.0h.

[0056] In the present application, the yield of the reaction product is measured using internal standard sample of nuclear magnetic resonance, preferably using 1,1,2,2-tetrachloroethane as internal standard of reaction.

[0057] In the present application, the organic solvent includes any one of acetonitrile, methanol, dichloromethane and ethanol, preferably acetonitrile, methanol or ethanol, further preferably acetonitrile.

[0058] The technical solutions provided by the present application are described in detail below in combination with examples, but they should not be understood as limitations to the scope of protection of the present application.

[0059] The preparation of the ten-core 3d-4f supramolecular nanocage material used in the following examples and the asymmetric semi-rigid ligand used in the comparative examples includes the following steps:

[0060] Take 0.022 mol of 3-aminopropionic acid methyl ester, 0.065 mol of triethylamine and 100 mL of dichloromethane to obtain a colorless transparent mixed solution, add 20 mL of oxalyl chloride monomethyl ester solution in dichloromethane with a concentration of 1 mol / L at a rate of 30 drops / min into the mixed solution, stir at 0℃ for 13h after the completion of the dropwise addition to obtain a light yellow solution, take 150 mL of saturated sodium bicarbonate solution to quench the reaction, then separate the yellow organic phase by extraction with dichloromethane, dry the organic phase with anhydrous calcium sulfate to obtain the intermediate product a;

[0061] Take 0.012 mol of intermediate product a, 3.75 mL of 80 wt% hydrazine hydrate aqueous solution and 50 mL of ethanol, mix and heat to 78°C for 13 h, then cool to 25°C, filter the cooled product and wash with ethanol solution 5 times, dry with anhydrous calcium sulfate to obtain intermediate product b;

[0062] Take 0.01 mol of intermediate product b, 0.05 mol of 3,5-di-tert-butylsalicylaldehyde and 50 mL of ethanol, mix and heat to 78°C for 13 h, then cool to 25°C, filter the cooled product and wash with ethanol solution 5 times, dry with anhydrous calcium sulfate to obtain asymmetric semi-rigid ligand;

[0063] Take 0.05 mmol of asymmetric semi-rigid ligand, 0.05 mmol of zinc perchlorate, 0.05 mmol of erbium chloride, 0.1 mmol of triethylamine and 4 mL of methanol, mix and stir at 25°C for 36 h, filter the product after the reaction is complete, evaporate and crystallize, wash the crystals with ether 5 times, and dry the washed product under vacuum to obtain a ten-core 3d-4f supramolecular nanocage material. The yield of the obtained ten-core 3d-4f supramolecular nanocage material is 45% by calculation.

[0064] Example 1

[0065] The structural formula of the target product prepared in this example is as follows:

[0066]

[0067] A three-component aza-Darzens reaction was carried out using 0.5 mmol of formaldehyde, 0.6 mmol of aniline and 0.7 mmol of ethyl diazoacetate as model substrates, 3 mL of acetonitrile was added as the reaction solvent, and 0.4 mol% of the ten-core 3d-4f supramolecular nanocage material was added as the catalyst. The reaction was carried out at 25°C for 0.5 h to obtain the target product, and the yield of the target product was 88% using internal standard addition in NMR.

[0068] Figure 1 The yield of this example was calculated by integrating the 2H using 1,1,2,2-tetrachloroethane as the internal standard, and the yield was calculated by integrating the H on the three-membered ring.

[0069] Example 2

[0070] The structural formula of the target product prepared in this example is as follows:

[0071]

[0072] Three-component aza-Darzens reaction with 0.5 mmol of formaldehyde, 0.8 mmol of p-toluidine and 0.8 mmol of ethyl diazoacetate as model substrates, 3 mL of acetonitrile was added as the reaction solvent, and 0.2 mol% of the tenuclear 3d-4f supramolecular nanocage material was added as the catalyst. The reaction was carried out at 25°C for 2 hours to obtain the target product, and the yield of the target product was 88% by internal standard sample of nuclear magnetic resonance.

[0073] Example 3

[0074] The structural formula of the target product prepared in this example is as follows:

[0075]

[0076] Three-component aza-Darzens reaction with 0.5 mmol of formaldehyde, 0.9 mmol of p- aminoanisole and 1.0 mmol of ethyl diazoacetate as model substrates, 3 mL of acetonitrile was added as the reaction solvent, and 0.3 mol% of the tenuclear 3d-4f supramolecular nanocage material was added as the catalyst. The reaction was carried out at 25°C for 1 hour to obtain the target product, and the yield of the target product was 81% by internal standard sample of nuclear magnetic resonance.

[0077] Example 4

[0078] The structural formula of the target product prepared in this example is as follows:

[0079]

[0080] Three-component aza-Darzens reaction with 0.5 mmol of formaldehyde, 1.0 mmol of p- aminoanisole and 0.8 mmol of ethyl diazoacetate as model substrates, 3 mL of acetonitrile was added as the reaction solvent, and 0.5 mol% of the tenuclear 3d-4f supramolecular nanocage material was added as the catalyst. The reaction was carried out at 25°C for 3 hours to obtain the target product, and the yield of the target product was 65% by internal standard sample of nuclear magnetic resonance.

[0081] Example 5

[0082] The structural formula of the target product prepared in this example is as follows:

[0083]

[0084] Three-component aza-Darzens reaction with 0.5 mmol formaldehyde, 1.0 mmol p- ethylaniline and 0.9 mmol ethyl diazoacetate as model substrates, 3 mL acetonitrile as reaction solvent, 0.6 mol% of ten-nuclear 3d-4f supramolecular nanocage material as catalyst was added. The reaction was carried out at 25°C for 2.5 hours to obtain the target product, and the yield of the target product was 82% by using internal standard sample of nuclear magnetic resonance.

[0085] Example 6

[0086] The structural formula of the target product prepared in this example is as follows:

[0087]

[0088] The p-isopropylaniline was used to replace the aniline in Example 1, and the remaining steps and parameters were the same as those in Example 1. The yield of the target product was 84% by using internal standard sample of nuclear magnetic resonance.

[0089] Example 7

[0090] The structural formula of the target product prepared in this example is as follows:

[0091]

[0092] The p-tert-butylaniline was used to replace the aniline in Example 1, and the remaining steps and parameters were the same as those in Example 1. The yield of the target product was 83% by using internal standard sample of nuclear magnetic resonance.

[0093] Example 8

[0094] The structural formula of the target product prepared in this example is as follows:

[0095]

[0096] The p-chloroaniline was used to replace the aniline in Example 1, and the remaining steps and parameters were the same as those in Example 1. The yield of the target product was 60% by using internal standard sample of nuclear magnetic resonance.

[0097] Example 9

[0098] The structural formula of the target product prepared in this example is as follows:

[0099]

[0100] The p-iodoaniline was used to replace the aniline in Example 1, and the remaining steps and parameters were the same as those in Example 1. The yield of the target product was 64% by using internal standard sample of nuclear magnetic resonance.

[0101] Example 10

[0102] The structural formula of the target product prepared in this example is as follows:

[0103]

[0104] The aniline in Example 1 was replaced with p-bromoaniline, and the remaining steps and parameters were the same as in Example 1. The yield of the target product was 56% using internal NMR standards.

[0105] Example 11

[0106] The structure of the target product prepared in this example is as follows:

[0107]

[0108] The aniline in Example 1 was replaced with p-fluoroaniline, and the remaining steps and parameters were the same as in Example 1. The yield of the target product was 76% using internal NMR standards.

[0109] Example 12

[0110] The structure of the target product prepared in this example is as follows:

[0111]

[0112] The aniline in Example 1 was replaced with m-toluidine, and the remaining steps and parameters were the same as in Example 1. The yield of the target product was 85% using internal NMR standards.

[0113] Example 13

[0114] The structure of the target product prepared in this example is as follows:

[0115]

[0116] The aniline in Example 1 was replaced with m-tert-butyl aniline, and the remaining steps and parameters were the same as in Example 1. The yield of the target product was 88% using internal NMR standards.

[0117] Example 14

[0118] The structure of the target product prepared in this example is as follows:

[0119]

[0120] The aniline in Example 1 was replaced with m-ethyl aniline, and the remaining steps and parameters were the same as in Example 1. The yield of the target product was 86% using internal NMR standards.

[0121] Example 15

[0122] The structure of the target product prepared in this example is as follows:

[0123]

[0124] Example 1 using NMR internal standard. The yield of the target product was 87%.

[0125] Example 16

[0126] The structure of the target product prepared in this example is as follows:

[0127]

[0128] Example 1 using NMR internal standard. The yield of the target product was 55%.

[0129] Example 17

[0130] The structure of the target product prepared in this example is as follows:

[0131]

[0132] Example 1 using NMR internal standard. The yield of the target product was 83%.

[0133] Example 18

[0134] The structure of the target product prepared in this example is as follows:

[0135]

[0136] Example 1 using NMR internal standard. The yield of the target product was 10%.

[0137] Example 19

[0138] The structure of the target product prepared in this example is as follows:

[0139]

[0140] Example 1 using NMR internal standard. The yield of the target product was 11%.

[0141] Example 20

[0142] The structure of the target product prepared in this example is as follows:

[0143]

[0144] The formaldehyde in Example 1 is replaced with propionaldehyde, and the remaining steps and parameters are the same as in Example 1. The yield of the target product is 86% as obtained by internal standard addition in nuclear magnetic resonance.

[0145] Comparative Example 1

[0146] The ten-core 3d-4f supramolecular nanocage material in Example 1 is replaced with an asymmetric semi-rigid ligand, and the reaction is carried out for 3h. The remaining steps and parameters are the same as in Example 1. The target product is not obtained.

[0147] Comparative Example 2

[0148] The ten-core 3d-4f supramolecular nanocage material in Example 1 is replaced with ZnCl2, and the reaction is carried out for 3h. The remaining steps and parameters are the same as in Example 1. The target product is not obtained.

[0149] Comparative Example 3

[0150] The ten-core 3d-4f supramolecular nanocage material in Example 1 is replaced with Er(NO3)3·5H2O, and the reaction is carried out for 3h. The remaining steps and parameters are the same as in Example 1. The yield of the target product is 13% as obtained by internal standard addition in nuclear magnetic resonance.

[0151] Comparative Example 4

[0152] The ten-core 3d-4f supramolecular nanocage material in Example 1 is replaced with 0.4mol% Er(NO3)3·5H2O+0.4mol% ZnCl2 as a mixed catalyst, and the reaction is carried out for 3h. The remaining steps and parameters are the same as in Example 1. The yield of the target product is 9% as obtained by internal standard addition in nuclear magnetic resonance.

[0153] As can be seen from Examples 1-20, the ten-core 3d-4f supramolecular nanocage material can be used as a catalyst to catalyze a three-component aza-Darzens reaction to synthesize a drug precursor with biological activity. The catalyst has high catalytic efficiency, simple operation steps, and high yield of the target product.

[0154] As can be seen from Examples 1 and Comparative Examples 1-4, compared with other homogeneous catalysts, the ten-core 3d-4f supramolecular nanocage material as a catalyst has stable structure in solution, exists in the form of a molecular cage, has higher catalytic activity in a homogeneous three-component aza-Darzens reaction, has short reaction time, and can realize production at a kilogram level.

[0155] The above only describes preferred embodiments of the present application. It should be noted that those skilled in the art can make several improvements and refinements without departing from the principles of the present application, and these improvements and refinements should also be considered as falling within the protection scope of the present application.

Claims

1. Use of a decanuclear 3d-4f supramolecular nanocage material in catalyzing a three-component aza-Darzens reaction, characterized in that, The method comprises the following steps: The aldehyde compound, the amino benzene compound, the diazo acetic acid ethyl ester, the ten-core 3d-4f supramolecular nanocage material and the organic solvent are mixed to react to obtain a reaction product, that is, a three-component aza-Darzens reaction is completed; The reaction product has a structural formula as shown in any one of the following formulas 1-20: Formula 1 Formula 2 Formula 3 Formula 4 Formula 5 Formula 6 Formula 7 Formula 8 Formula 9 Formula 10 Formula 11 Formula 12 Formula 13 Formula 14 Formula 15 Formula 16 Formula 17 Formula 18 Formula 19 Formula 20. The aldehyde compound is formaldehyde or propyl aldehyde. The amino benzene compound is any one of aniline, p-toluidine, p-aminophenyl ether, p-aminophenyl methyl ether, p-ethyl aniline, p-isopropyl aniline, p-tert-butyl aniline, p-chloroaniline, p-iodoaniline, p-bromoaniline, p-fluoroaniline, m-toluidine, m-tert-butyl aniline, m-ethyl aniline, o-isopropyl aniline, m-fluoroaniline, o-tert-butyl aniline, p-aminobenzoic acid and p-nitroaniline. The preparation method of the ten-core 3d-4f supramolecular nanocage material comprises the following steps: 0.022 mol of 3-aminopropionic acid methyl ester, 0.065 mol of triethylamine and 100 mL of dichloromethane are mixed to obtain a colorless transparent mixed solution, 20 mL of oxalyl chloride monoisopropyl ester dichloromethane solution with a concentration of 1 mol / L is added dropwise into the mixed solution at a rate of 30 drops / min, after the dropwise addition is completed, the mixture is stirred at 0℃ for 13 h to obtain a light yellow solution, 150 mL of saturated sodium bicarbonate solution is taken to quench the reaction, and then dichloromethane is used for extraction and separation to obtain a yellow organic phase, the organic phase is dried by using anhydrous calcium sulfate to obtain an intermediate product a; 0.012 mol of the intermediate product a, 3.75 mL of 80wt% of a hydrazine hydrate aqueous solution and 50 mL of ethanol are mixed, then heated to 78℃ for reaction for 13 h, and then cooled to 25℃, the cooled product is filtered, washed with an ethanol solution for 5 times, dried by using anhydrous calcium sulfate to obtain an intermediate product b; 0.01 mol of the intermediate product b, 0.05 mol of 3,5-di-tert-butyl salicylaldehyde and 50 mL of ethanol are mixed, then heated to 78℃ for reaction for 13 h, and then cooled to 25℃, the cooled product is filtered, washed with an ethanol solution for 5 times, dried by using anhydrous calcium sulfate to obtain an asymmetric semi-rigid ligand; 0.05 mmol of the asymmetric semi-rigid ligand, 0.05 mmol of zinc perchlorate, 0.05 mmol of erbium chloride, 0.1 mmol of triethylamine and 4 mL of methanol are mixed, and stirred at 25℃ for 36 h, after the reaction is completed, the product is filtered, evaporated and crystallized, the crystals are washed with ether for 5 times, and then the washed product is dried in vacuum to obtain the ten-core 3d-4f supramolecular nanocage material.

2. Use according to claim 1, characterized in that, The amount of the ten-core 3d-4f supramolecular nanocage material is 0.2-0.6 mol% of the total reactants.

3. Use according to claim 2, characterized in that, The molar volume ratio of the aldehyde compound, the amino benzene compound, the diazo acetic acid ethyl ester and the organic solvent is 1 mmol:1-2 mmol:1-2 mmol:4-6 mL.

4. The use according to any one of claims 1 to 3, characterized in that, The reaction temperature is 20-30℃, and the reaction time is 0.5-3 h.

5. Use according to claim 4, characterized in that, The organic solvent is any one of acetonitrile, methanol, dichloromethane and ethanol. The organic solvent is any one of acetonitrile, methanol, dichloromethane and ethanol.

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