A Ureido Covalent Organic Framework Material, Preparation Method Thereof and Application Thereof

Abstract

The present invention relates to a urea-based covalent organic framework material, a preparation method thereof and an application thereof, belonging to the technical field of covalent organic framework materials. This material has a high specific surface area and one-dimensional nanochannels, and urea groups are uniformly distributed in the one-dimensional nanochannels, enabling rapid mass transfer and high accessibility of urea groups as effective chiral hydrogen bond donor catalysts. At the same time, combining with the excellent ability of porphyrin to generate singlet oxygen, this urea-based covalent organic framework material can achieve the photocatalytic semi-synthesis of artemisinin with high conversion rate and yield without adding acid. This material is obtained by condensing aldehyde porphyrin and 1,3-bis(4-aminophenyl)urea.

Description

Technical Field

[0001] The present invention relates to a urea-based covalent organic framework material, a preparation method thereof and an application thereof, belonging to the technical field of covalent organic framework materials. Background Art

[0002] Malaria is a parasitic disease caused by Plasmodium infection and has long been one of the serious public health problems of global concern. Artemisinin is currently the most effective drug for treating malaria parasites, and the World Health Organization has recommended artemisinin-based combination therapies as first-line drugs. At present, artemisinin is mainly extracted from Artemisia annua. However, the unstable supply of plants has led to large fluctuations in the price of artemisinin. The artificial synthesis of artemisinin provides an alternative method with stable production to meet market demand. However, the total synthesis of artemisinin is very laborious and expensive. The photochemical semi-synthesis of artemisinin using the abundant biosynthetic precursor dihydroartemisinin is a promising strategy. The photochemical conversion of dihydroartemisinin to artemisinin has been shown to involve the formation of a peroxide intermediate through a singlet oxygen-induced ene reaction, followed by an acid-catalyzed Hook cleavage and cyclization reaction. So far, a series of multifunctional composite catalysts have been developed by integrating excellent singlet oxygen-generating photosensitizers (i.e., porphyrin, 9,10-dicyanoanthracene, and ruthenium(III) tris(2,2'-bipyridyl) dichloride) and acids (i.e., benzenesulfonic acid, trifluoroacetic acid, sulfuric acid), and the photocatalytic synthesis of artemisinin has been successfully achieved. For example, in the article "Applying green chemistry to the photochemical route to artemisinin", ruthenium(III) tris(2,2'-bipyridyl) dichloride (photosensitizer) and trifluoroacetic acid (acid catalyst) were used to photocatalytically synthesize artemisinin in a mixed solvent system of tetrahydrofuran and water. In the article "Porphyrinic Metal−Organic Frameworks Installed with Brønsted Acid Sites for Efficient Tandem Semisynthesis of Artemisinin", Brønsted acid sites (sulfuric acid) were installed into a series of porphyrinic metal-organic frameworks (MOFs) for bifunctional solid acid / photocatalyst-catalyzed tandem semi-synthesis of artemisinin from dihydroartemisinin. However, for the above-reported photocatalytic synthesis of artemisinin, strong acids are necessary for catalyzing the Hook cleavage, which leads to difficulties in catalyst recovery and waste acid treatment. In addition, the strong acidic conditions may cause the decomposition of artemisinin, resulting in a decrease in productivity. Therefore, it is very urgent to develop environmentally friendly and effective catalysts for the photocatalytic synthesis of artemisinin. Summary of the Invention

[0003] In view of this, the purpose of the present invention is to provide a urea-based covalent organic framework material, a preparation method thereof and an application thereof. This material has a high specific surface area and one-dimensional nanochannels, and the urea groups are uniformly distributed in the one-dimensional nanochannels, which can achieve rapid mass transfer and high accessibility of the urea groups as effective chiral hydrogen bond donors (HBD) catalysts. At the same time, combined with the excellent ability of porphyrin to generate singlet oxygen, the urea-based covalent organic framework material can achieve the photocatalytic semi-synthesis of artemisinin with high conversion rate and yield without adding acid. This material is obtained by condensing aldehyde-based porphyrin and 1,3-bis(4-aminophenyl)urea.

[0004] To achieve the above purpose, the technical solution of the present invention is as follows.

[0005] A urea-based covalent organic framework material, the structural formula of the material is:

[0006] ;

[0007] Among them, M is 2H or a transition metal element in the fourth period.

[0008] Preferably, the transition metal element in the fourth period is Fe, Co, Ni, Cu or Zn.

[0009] Preferably, M is 2H, Cu or Zn.

[0010] A preparation method of the urea-based covalent organic framework material of the present invention, the method steps include:

[0011] (1) Disperse aldehyde-based porphyrin and 1,3-bis(4-aminophenyl)urea evenly in a mixed solvent, then add a catalyst, disperse evenly, freeze with liquid nitrogen and degas under vacuum; react at 60-100 °C for more than 72 hours, cool to obtain a crude product;

[0012] (2) Purify and dry the crude product to obtain a urea-based covalent organic framework material;

[0013] Among them, the structural formula of the aldehyde-based porphyrin is: , M is 2H or a transition metal element in the fourth period;

[0014] The structural formula of 1,3-bis(4-aminophenyl)urea is: .

[0015] Preferably, in step (1), the molar ratio of the aldehyde-based porphyrin to 1,3-bis(4-aminophenyl)urea is 1:2 to 1:2.5.

[0016] Preferably, in step (1), the mixed solvent is o-dichlorobenzene and alcohol in a volume ratio, and the alcohol is ethanol or n-butanol. More preferably, the volume ratio of o-dichlorobenzene to alcohol is 1:1 to 1:9; the molar ratio of aldehyde porphyrin to the mixed solvent is 1:200 to 1:1000.

[0017] Preferably, in step (1), the catalyst is acetic acid or trifluoroacetic acid. More preferably, the concentration of acetic acid is 5 to 7 mol / L, the concentration of trifluoroacetic acid is 2 to 4 mol / L, and the molar ratio of aldehyde porphyrin to the catalyst is 1:20 to 1:100.

[0018] Preferably, in step (2), the crude product is subjected to Soxhlet extraction with tetrahydrofuran and acetone respectively, and then vacuum dried at 60 to 70 °C.

[0019] An application of the urea-based covalent organic framework material of the present invention. Under an oxygen atmosphere, dihydroartemisinin and the urea-based covalent organic framework material are dispersed evenly in a solvent, and stirred and reacted for 6 to 12 hours at -10 to 10 °C under light conditions. After the reaction is completed, it is filtered, washed, dried, concentrated, and recrystallized to obtain artemisinin.

[0020] Preferably, the dosage of the urea-based covalent organic framework material is 0.5 mol% to 10 mol% of dihydroartemisinin.

[0021] Preferably, the solvent is dichloromethane or toluene.

[0022] Beneficial effects

[0023] The present invention provides a urea-based covalent organic framework material, a preparation method and an application thereof. The material has a high specific surface area and one-dimensional nanochannels, and the urea groups are evenly distributed in the one-dimensional nanochannels, which can achieve rapid mass transfer and improve the catalytic efficiency. When this material is used for the photocatalytic semi-synthesis of artemisinin, there is an obvious hydrogen bond interaction between the urea-based covalent organic framework material and dihydroartemisinin. The urea groups can effectively activate the reaction substrate and reduce the reaction energy barrier. It can catalyze the hook cleavage reaction without using strong acids. At the same time, the urea groups are evenly distributed in the one-dimensional nanochannels, which can avoid the self-quenching phenomenon; the synergistic effect between the urea groups and the porphyrin structure enables the urea-based covalent organic framework material to achieve the photocatalytic semi-synthesis of artemisinin with high conversion rate and yield without adding acid. This material is prepared by the condensation of aldehyde porphyrin and 1,3-bis(4-aminophenyl)urea, and has a periodic cyclic structure. The preparation method is simple in operation, and the reaction equation is as follows:

[0024] 。 Description of the drawings

[0025] Figure 1Fourier transform infrared (FT-IR) spectra of the urea-based covalent organic framework material, 5,10,15,20-tetra(4-carboxyphenyl)-21H,23H-porphyrin, and 1,3-bis(4-aminophenyl)urea in Example 1.

[0026] Figure 2 Solid state 13 C cross-polarization / magic angle spinning nuclear magnetic resonance spectrum of the urea-based covalent organic framework material in Example 1.

[0027] Figure 3 Powder X-ray diffraction pattern of the urea-based covalent organic framework material in Example 1.

[0028] Figure 4 Nitrogen adsorption-desorption isotherm curve of the urea-based covalent organic framework material in Example 1.

[0029] Figure 5 1H nuclear magnetic resonance spectrum of the photocatalytic synthesis of artemisinin using the urea-based covalent organic framework material in Example 3. Detailed implementation manners

[0030] The present invention will be further described in detail below in conjunction with specific examples.

[0031] Example 1

[0032] Step 1: Weigh 0.02 mmol (14.5 mg) of 5,10,15,20-tetra(4-carboxyphenyl)-21H,23H-porphyrin and 0.04 mmol (9.7 mg) of 1,3-bis(4-aminophenyl)urea and place them in a pyrex tube (one end sealed, 20 cm long, 0.8 cm inner diameter, 1.2 cm outer diameter). Add 0.5 mL of o-dichlorobenzene and 0.5 mL of n-butanol solvent thereto, and place the pyrex tube in an ultrasonic generator for ultrasonic treatment for 15 minutes.

[0033] Step 2: Take out the pyrex tube, add 0.1 mL of 6 mol / L acetic acid solution thereto, and then place the pyrex tube in an ultrasonic generator for ultrasonic treatment for 15 minutes to form a uniformly dispersed system.

[0034] Step 3: Take out the pyrex tube and place it in a Dewar flask containing liquid nitrogen for rapid freezing. Then connect the pyrex tube to a vacuum pump for degassing, take it out, thaw it, and freeze and degas it again. Repeat this three times.

[0035] Step 4: Under vacuum conditions, use an alcohol burner flame to melt and seal the pyrex tube, and the sealed tube length is 12 cm.

[0036] Step 5: After the pyrex tube returns to room temperature, place it in an oven at 100 °C for 72 hours to produce a brown precipitate. Take out the pyrex tube and cool it to room temperature;

[0037] Step 6: Break the pyrex tube, filter to obtain a brown fluffy precipitate, wash it three times with N,N-dimethylformamide and tetrahydrofuran respectively, then wrap the precipitate with filter paper and place it in a Soxhlet extractor, and extract it in tetrahydrofuran and acetone for 24 hours respectively;

[0038] Step 7: After the Soxhlet extraction is completed, take out the brown precipitate and vacuum dry it at 60 °C for 24 hours to obtain 19.7 mg of a ureido covalent organic framework material, with a yield of 86.4%.

[0039] As Figure 1 shown, in the Fourier transform infrared (FT-IR) spectrum, the characteristic vibration peak of the C=N double bond at 1622 cm -1 was observed. At the same time, the stretching vibration peak of the C=O double bond at 1700 cm -1 in 5,10,15,20-tetra(4-carboxyphenyl)-21H,23H-porphyrin and the N-H stretching peak in 1,3-bis(4-aminophenyl)urea at 3298 - 3403 cm -1 weakened, indicating that the aldehyde group of 5,10,15,20-tetra(4-carboxyphenyl)-21H,23H-porphyrin was successfully connected to the amino group of 1,3-bis(4-aminophenyl)urea. Similarly, in the solid-state 13 13C cross-polarization / magic angle spinning nuclear magnetic resonance spectrum, a signal caused by the imine bond carbon at 157 ppm was observed, further proving the formation of the imine bond, as Figure 2 shown.

[0040] Through powder X-ray diffraction (PXRD) testing, a series of sharp peaks were found in the ureido covalent organic framework material at 2.78°, 5.58°, 8.38°, 11.20° and 21.10°, indicating its high crystallinity, as Figure 3 shown.

[0041] Record the nitrogen adsorption-desorption isotherm data of the ureido covalent organic framework material at 77K. It can be observed from Figure 4 that this material shows a typical type IV adsorption curve, with a specific surface area of 1732 m 2 g -1 . Through non-local density functional theory (NLDFT) analysis, the average pore size of this material is 3.1 nm, which is consistent with the theoretical value.

[0042] It was determined by testing that the structural formula of the ureido covalent organic framework material is:

[0043] , M is 2H.

[0044] The urea-based covalent organic framework material was soaked in dihydroartemisinin acid solution and then subjected to Fourier transform infrared spectroscopy. The soaked urea-based covalent organic framework material showed a C-H stretching vibration peak of dihydroartemisinin acid at 2980 - 2830 cm -1 . In addition, compared with the urea-based covalent organic framework material before soaking, the soaked urea-based covalent organic framework material showed a significant change in the N-H stretching vibration of the urea group towards a lower frequency, and a new peak appeared at 1669 cm -1 . This peak was attributed to the characteristic signal of protonated imine C=NH + , and at the same time, the disappearance of the C=N stretching vibration at 1623 cm -1 was observed. The results showed that there was an obvious hydrogen bond interaction between the urea-based covalent organic framework material and dihydroartemisinin acid, indicating that the urea group could effectively activate the reaction substrate, reduce the reaction energy barrier, and catalyze the hook cleavage reaction without using strong acid.

[0045] Example 2

[0046] In this example, 5,10,15,20-tetra(4-carboxyphenyl)-21H,23H-porphyrin was replaced with 5,10,15,20-tetra(4-carboxyphenyl)-iron-porphyrin, 5,10,15,20-tetra(4-carboxyphenyl)-cobalt-porphyrin, 5,10,15,20-tetra(4-carboxyphenyl)-nickel-porphyrin, 5,10,15,20-tetra(4-carboxyphenyl)-copper-porphyrin or 5,10,15,20-tetra(4-carboxyphenyl)-zinc-porphyrin, and the rest was the same as in Example 1.

[0047] After testing, the structural formula of the urea-based covalent organic framework material was:

[0048] , M is Fe, Co, Ni, Cu or Zn.

[0049] The urea-based covalent organic framework material was soaked in dihydroartemisinin acid solution and then subjected to Fourier transform infrared spectroscopy. The results showed that there was an obvious hydrogen bond interaction between the urea-based covalent organic framework material and dihydroartemisinin acid.

[0050] Example 3

[0051] Step 1: Weigh 0.1 mmol (23.6 mg) of dihydroartemisinin acid and 5 mg of the urea-based covalent organic framework material prepared in Example 1 and place them in a 25 mL test tube. Add 5 mL of dichloromethane to the test tube;

[0052] Step 2: Place the test tube in an ice bath and slowly bubble oxygen into it for 10 minutes to saturate the solution with oxygen, then seal the test tube with a latex stopper.

[0053] Step 3: Place the test tube in a photoreactor, set the environmental temperature to 5 °C, and turn on the light source (the light source is a 420 - 650 nm LED light source, 200 mW cm -2 ) and irradiate for 12 hours.

[0054] Step 4: After the light irradiation is completed, take out the test tube, rotary evaporate the dichloromethane under reduced pressure and low temperature, and then add 0.1 mmol (15.4 mg) of biphenyl (internal standard) to it. Add 0.5 mL of deuterated chloroform to it for nuclear magnetic resonance hydrogen spectrum test. As Figure 5 shown, the conversion rate and yield of the photocatalytic synthesis of artemisinin from dihydroartemisinin using the urea-based covalent organic framework material in Example 1 are 99% and 73% respectively.

[0055] To obtain pure artemisinin, the reaction solution in the test tube after the light irradiation can be filtered, washed with dichloromethane, the filtrate is collected, dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product is recrystallized from ethanol and n-hexane to obtain the artemisinin product.

[0056] Example 4

[0057] Replace the urea-based covalent organic framework material in Example 3 with the urea-based covalent organic framework material in Example 2, and the rest is the same as in Example 3.

[0058] When M is nickel, the conversion rate and yield of the photocatalytic synthesis of artemisinin from dihydroartemisinin using the urea-based covalent organic framework material are 75% and 26% respectively.

[0059] When M is copper, the conversion rate and yield of the photocatalytic synthesis of artemisinin from dihydroartemisinin using the urea-based covalent organic framework material are 99% and 47% respectively.

[0060] When M is zinc, the conversion rate and yield of the photocatalytic synthesis of artemisinin from dihydroartemisinin using the urea-based covalent organic framework material are 99% and 54% respectively.

[0061] Comparative Example 1

[0062] Step 1: Weigh 0.1 mmol (23.6 mg) of dihydroartemisinin, 0.005 mmol (3.60 mg) of 5,10,15,20-tetra(4-carboxyphenyl)porphyrin, and 0.01 mmol (2.4 mg) of 1,3-bis(4-aminophenyl)urea and place them in a 25 mL test tube. Add 5 mL of dichloromethane to the test tube.

[0063] Step 2: Place the test tube in an ice bath and slowly bubble oxygen into it for 10 minutes to saturate the solution with oxygen, and then seal the test tube with a rubber stopper.

[0064] Step 3: Place the test tube in a photoreactor, set the environmental temperature to 5 °C, and turn on the light source (the light source is a 420 - 650 nm LED light source, 200 mW cm -2 ) for 12 hours of illumination.

[0065] Step 4: After the illumination is completed, take out the test tube, rotary evaporate dichloromethane under reduced pressure and low temperature, and then add 0.1 mmol (15.4 mg) of biphenyl (internal standard) to it. Add 0.5 mL of deuterated chloroform to it for nuclear magnetic resonance hydrogen spectrum testing. The conversion rate and yield of the photocatalytic synthesis of artemisinin from dihydroartemisinin are 99% and 15% respectively.

[0066] In summary, the invention includes but is not limited to the above embodiments. Any equivalent replacement or partial improvement made under the spirit and principle of the present invention will be regarded as being within the protection scope of the present invention.

Claims

1. An application of a urea-based covalent organic framework material, characterized in that: Under an oxygen atmosphere, dihydroartemisinic acid and urea-based covalent organic framework materials are uniformly dispersed in a solvent, stirred and reacted for 6 to 12 hours at -10 to 10°C under light conditions, and after the reaction, filtered, washed, dried, concentrated, and recrystallized to obtain artemisinin; The structural formula of the urea-based covalent organic framework material is: ； Wherein, M is 2H or a fourth period transition metal element.

2. The use of a urea-based covalent organic framework material as claimed in claim 1, characterized in that: The fourth period transition metal element is Fe, Co, Ni, Cu or Zn.

3. The use of a urea-based covalent organic framework material as claimed in claim 1, characterized in that: M is 2H, Cu or Zn.

4. The use of a urea-based covalent organic framework material as claimed in claim 1, characterized in that: The urea-based covalent organic framework material is prepared by the following method, which comprises the following steps: (1) Dispersing aldehyde porphyrin and 1,3-bis(4-aminophenyl)urea uniformly in a mixed solvent, then adding a catalyst, and after being uniformly dispersed, freezing with liquid nitrogen and vacuum degassing; reacting at 60-100° C. for more than 72 hours, cooling, and obtaining a crude product; (2) purifying and drying the crude product to obtain a urea-based covalent organic framework material; Among them, the structural formula of aldehyde porphyrin is: , M is 2H or a fourth period transition metal element; The structural formula of 1,3-bis(4-aminophenyl)urea is: .

5. The use of a urea-based covalent organic framework material as claimed in claim 4, characterized in that: In step (1), the molar ratio of the aldehyde porphyrin to 1,3-bis(4-aminophenyl)urea is 1:2 to 1:2.

5.

6. The use of a urea-based covalent organic framework material as claimed in claim 4, characterized in that: In step (1), the mixed solvent is o-phthalic acid dichloride and alcohol, and the alcohol is ethanol or n-butanol; the volume ratio of o-phthalic acid dichloride to alcohol is 1:1-1:9; and the molar ratio of aldehyde porphyrin to the mixed solvent is 1:200-1:1000.

7. The use of a urea-based covalent organic framework material as claimed in claim 4, characterized in that: In step (1), the catalyst is acetic acid or trifluoroacetic acid; the concentration of acetic acid is 5-7 mol / L, the concentration of trifluoroacetic acid is 2-4 mol / L, and the molar ratio of aldehyde porphyrin to catalyst is 1:20-1:

100.

8. The use of a urea-based covalent organic framework material as claimed in claim 4, characterized in that: In step (2), the crude product is subjected to Soxhlet extraction with tetrahydrofuran and acetone, respectively, and then dried in vacuum at 60-70°C.

9. The use of a urea-based covalent organic framework material as claimed in claim 1, characterized in that: The amount of the urea-based covalent organic framework material is 0.5 mol% to 10 mol% of dihydroartemisinic acid; the solvent is dichloromethane or toluene.

Images