Purpurine-modified metal organic coordination compound as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of metal organic coordination compounds, and particularly relates to a viologen-modified metal organic coordination compound as well as a preparation method and application thereof. Two novel viologen-MOFs (Metal Organic Frameworks), namely a compound 1 and a compound 2, are constructed by adopting a hydrothermal method. On the basis, the compound 1 and the compound 2 are subjected to structural analysis and characterization, and the structural characteristics of the compound 1 and the compound 2 are researched through infrared, thermogravimetric, X-ray powder diffraction and ultraviolet reflection tests. Researches show that the two viologen-MOFs are formed by inserting viologen molecules into holes of an MOF framework, and the special electron transfer property of the viologen and the Lewis acid property of the MOF framework cooperate to catalyze a Knoevenagel condensation-Michael addition cyclization reaction.

Description

Technical Field

[0001] The invention belongs to the technical field of metal organic coordination compounds, and in particular relates to a viologen-modified metal organic coordination compound and a preparation method and application thereof. Background Art

[0002] In recent years, 4H-pyran derivatives have attracted much attention due to their anticonvulsant, antiviral, anticancer and antiallergic pharmacological effects, as well as their ability to treat Parkinson's disease and Alzheimer's disease. Many catalysts that can catalyze the synthesis of 4H-pyran derivatives have been reported. However, these catalysts also have their own disadvantages. Most of the reported catalysts are homogeneous catalysts or have more intense reaction conditions. Therefore, there is an urgent need to develop a recyclable and efficient heterogeneous catalyst. Summary of the invention

[0003] In view of this, the purpose of the present invention is to provide a viologen-modified metal organic coordination compound and a preparation method and application thereof in view of the problems existing in the prior art.

[0004] It should be noted that developing a recyclable and efficient heterogeneous catalyst is also an initiative to practice green chemistry. Among heterogeneous catalysts, metal organic frameworks (MOFs) have become promising heterogeneous catalysts for green chemistry due to their suitable porosity, recyclability, and adjustability of catalytic sites. Viologen has a unique electron-deficient structure, which enables it to act as an electron acceptor and form charge transfer with the surrounding negative charges under certain conditions (such as light, stirring, and voltage application). Viologen with the above properties has been maturely applied in the fields of photochromism and photocatalysis.

[0005] It has been reported that the presence of basic sites (O-carboxylic acid sites) in MOFs can improve catalytic performance. 2 -BDC can catalyze the synthesis of 4H-pyran, but it is difficult to achieve the desired effect. Therefore, the present invention introduces methyl viologen and ethyl viologen into Zn-NH 2 -BDC pores and explored its structural features as well as the catalytic properties of the Knoevenagel condensation-Michael addition cyclization reaction to prepare viologen MOF functionalized with viologen.

[0006] In order to achieve the above object, the present invention adopts the following technical solution:

[0007] A viologen-modified metal organic coordination compound, in which the viologen molecule is inserted into the Zn-NH 2 -BDC MOF framework, the general formula is {[Zn(MV)(NH 2 -BDC)]} n (1); {[Zn(EV)(NH 2-BDC)]·2DMF} n (2).

[0008] The second object of the present invention is to provide a method for preparing the viologen-modified metal organic coordination compound.

[0009] The method for preparing the viologen-modified metal organic coordination compound comprises the following steps:

[0010] Methyl viologen MV·2Cl (0.03 mmol), 2-aminoterephthalic acid (NH 2 -BDC) (0.1 mmol) and Zn(NO 3 ) 2 6H 2 O (0.05 mmol) was added to the autoclave, followed by 4 mL of DMF, 1 mL of methanol and 1 mL of water, and the sealed reactor was placed in an oven and heated at 80° C. for 48 hours. After cooling to room temperature, the obtained crystals were the metal organic coordination compound 1.

[0011] The method for preparing the viologen-modified metal organic coordination compound comprises the following steps:

[0012] Ethyl viologen EV·2Br (0.03 mmol), 2-aminoterephthalic acid (NH 2 -BDC) (0.1 mmol) and Zn(NO 3 ) 2 6H 2 O (0.05 mmol) was added to the autoclave, followed by 4 mL of DMF, 1 mL of methanol and 1 mL of water, and the sealed reactor was placed in an oven and heated at 80° C. for 48 hours. After cooling to room temperature, the obtained crystals were the metal organic coordination compound 2.

[0013] The third object of the present invention is to provide the application of the viologen-modified metal organic coordination compound in the synthesis of pharmaceutical intermediates.

[0014] Furthermore, the metal organic coordination compound is used as a heterogeneous catalyst to catalyze the synthesis of drug intermediates.

[0015] Furthermore, the metal organic coordination compound is used as a catalyst for catalyzing the synthesis of 4H-pyran derivatives.

[0016] Specifically, the metal organic coordination compound has an excellent catalytic effect on the one-pot synthesis of 4H-pyran.

[0017] Compared with the prior art, the present invention has the following excellent effects:

[0018] The present invention constructs two new viologen-MOFs by using a hydrothermal method, namely compound 1 and compound 2. On this basis, the structures of compound 1 and compound 2 are analyzed and characterized, and their structural characteristics are studied by infrared, thermogravimetric, X-ray powder diffraction and ultraviolet reflection tests. Studies have shown that both viologen-MOFs insert viologen molecules into the holes of the MOF framework, and the special electron transfer properties of viologen and the Lewis acid properties of the MOF framework synergistically catalyze the Knoevenagel condensation-Michael addition cyclization reaction. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.

[0020] Figure 1 For compound 1NH 2 -The coordination environment of BDC.

[0021] Figure 2 is the PXRD of compound 1.

[0022] Figure 3 is the coordination environment of zinc ion in compound 1.

[0023] Figure 4 It is the asymmetric unit of compound 1.

[0024] Figure 5 For compound 2NH 2 -The coordination environment of BDC.

[0025] Figure 6 This is the PXRD of compound 2.

[0026] Figure 7 This is the coordination environment of the zinc ion in compound 2.

[0027] Figure 8 It is the asymmetric unit of compound 2.

[0028] Fig. 9 It is compound 1TGA.

[0029] Fig.10 It is compound 2TGA.

[0030] Fig.11 PXRD of compound 1 treated with water, acid and base.

[0031] Fig.12PXRD of compound 2 treated with water, acid and base.

[0032] Fig.13 PXRD of compound 1 immersed in different solvents.

[0033] Fig.14 PXRD of compound 2 immersed in different solvents.

[0034] Fig.15 is the infrared spectrum of compound 1.

[0035] Fig.16 is the infrared spectrum of compound 2.

[0036] Fig.17 This is the H NMR spectrum of the reaction of benzaldehyde, malononitrile and 1,3-cyclohexanedione.

[0037] Fig.18 After catalytic reaction, MV-ZN-NH 2 -IR spectrum of BDC.

[0038] Fig.19 After catalytic reaction, MV-ZN-NH 2 -PXRD of BDC.

[0039] Fig. 20 This is a cyclic experiment of Knoevenagel condensation-Michael addition cyclization reaction. DETAILED DESCRIPTION

[0040] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0041] The word "embodiment" used here as an "exemplary" does not necessarily mean that any embodiment described is superior or better than other embodiments. Performance index tests in the embodiments of the present invention are performed using conventional test methods in the art unless otherwise specified. It should be understood that the terms described in the present invention are only used to describe specific implementation methods and are not used to limit the content disclosed in the present invention.

[0042] Unless otherwise specified, the technical and scientific terms used herein have the same meanings as commonly understood by ordinary technicians in the technical field to which the invention belongs; other experimental methods and technical means not specifically specified in the present invention refer to experimental methods and technical means commonly used by ordinary technicians in the field.

[0043] The terms "substantially" and "approximately" used herein are used to describe small fluctuations. For example, they can refer to less than or equal to ±5%, such as less than or equal to ±2%, such as less than or equal to ±1%, such as less than or equal to ±0.5%, such as less than or equal to ±0.2%, such as less than or equal to ±0.1%, such as less than or equal to ±0.05%. The numerical data represented or presented in the range format herein are used only for convenience and brevity, and should therefore be flexibly interpreted as including not only the values ​​clearly listed as the limits of the range, but also all independent values ​​or sub-ranges contained in the range. For example, the numerical range of "1-5%" should be interpreted as including not only the clearly listed values ​​of 1% to 5%, but also the independent values ​​and sub-ranges within the range shown. Therefore, independent values ​​such as 2%, 3.5% and 4% and sub-ranges such as 1%-3%, 2%-4% and 3%-5% are included in this numerical range. This principle also applies to the range of only one numerical value. In addition, such an interpretation applies regardless of the width of the range or the characteristics described.

[0044] In order to better illustrate the present invention, numerous specific details are provided in the specific examples below. It should be understood by those skilled in the art that the present invention can be implemented without certain specific details. In the embodiments, some methods, means, instruments, equipment, etc. well known to those skilled in the art are not described in detail in order to highlight the gist of the present invention.

[0045] Under the premise of no conflict, the technical features disclosed in the embodiments of the present invention may be arbitrarily combined, and the resulting technical solutions belong to the contents disclosed in the embodiments of the present invention.

[0046] Example 1-2

[0047] Two kinds of viologen-MOFs were prepared by hydrothermal method.

[0048] Compound 1: MV·2Cl (0.03 mmol), 2-aminoterephthalic acid (NH 2 -BDC) (0.1 mmol) and Zn(NO 3 ) 2 6H 2 O (0.05 mmol) was added into the autoclave, followed by 4 mL of DMF, 1 mL of methanol and 1 mL of water. The sealed reactor was placed in an oven and heated at 80 °C for 48 h. After cooling to room temperature, red square crystals, namely compound 1, were obtained.

[0049] Compound 2: EV·2Br (0.03mmol), 2-aminoterephthalic acid (NH 2 -BDC) (0.1 mmol) and Zn(NO 3 ) 2 6H 2O (0.05 mmol) was added into the autoclave, followed by 4 mL of DMF, 1 mL of methanol and 1 mL of water. The sealed reactor was placed in an oven and heated at 80 °C for 48 h. After cooling to room temperature, red square crystals, namely compound 2, were obtained.

[0050] In order to further demonstrate the beneficial effects of the present invention and to better understand the present invention, the properties and application performance of the viologen-modified metal organic coordination compound described in the present invention are further illustrated by the following measurement tests, but they should not be understood as limitations of the present invention. The product properties obtained by other measurement experiments conducted by technicians in this field based on the above-mentioned invention content and the applications based on the above-mentioned properties are also regarded as falling within the protection scope of the present invention.

[0051] Experimental Example 1

[0052] Crystal structure determination

[0053] At room temperature, compound crystals of appropriate size were observed and selected through a microscope, and then X-ray diffraction experiments were carried out at room temperature.

[0054] The X-ray powder diffraction (PXRD) data of the metal organic coordination compounds 1-2 were collected on an Oxford Diffraction Gemini R Ultra diffractometer using Cu-Kα radiation monochromatized by a graphite monochromator. At 296K Diffraction data were collected by the SADABS program. The diffraction data of some structures were absorption corrected using the direct method combined with the difference Fourier solution. All non-hydrogen atomic coordinates and anisotropic parameters were corrected by the full-matrix least squares method. The positions of CH atoms were determined by calculation according to the theoretical model. OH atoms were first found based on the difference Fourier. Then, their hydrogen atomic coordinates and isotropic parameters were corrected by the full-matrix least squares method and participated in the final structure refinement.

[0055] Single crystal X-ray diffraction analysis showed that the molecular structure of compound 1 is as follows Figure 1-4 Compound 1 crystallized in a monoclinic system with a space group of P21 / c. As shown in Tables 1 and 2, the asymmetric unit contains two Zn(II) cations, one MV ligand and two NH 2 -BDC unit. The Zn1 ion in this structure adopts a four-coordinate model with four NH 2 -BDC carboxyl (O2, O3, O2 iv 、O5 iii ) to form a tetrahedral configuration. The Zn-O bond length is Within the range, NH 2 -BDC2- The carboxyl group of the ligand coordinates to the Zn(II) ion via two coordination modes: bidentate and monodentate. On the other hand, methyl viologen exists in the Zn-NH 2 -BDC hole. In the Zn atomic coordination model diagram, two four-coordinated Zn 2+ The ion is divided into two NH 2 -BDC 2- The carboxyl groups of the ligands are bridged to form a chain. 2 -BDC 2- It is fixed between two chains to form a two-dimensional laminar network. The final three-dimensional structure is formed by an NH 2 -BDC is formed by connecting two hierarchical networks.

[0056] The molecular structure of compound 2 is as follows Figure 5-8 Compound 2 crystallized in a monoclinic system with a P21 / c space group. As shown in Tables 1 and 3, the asymmetric unit consists of four Zn(II) cations, one EV ligand, and three NH 2 -BDC units. The Zn2 ion in this structure uses a tetragonal coordination model with four NH 2 -BDC carboxyl (O3, O5, O7, O11 iii ) to form a tetrahedral configuration. Zn1 is a hexagonal octahedral configuration, which is coordinated with six NH 2 -BDC carboxyl oxygen-containing compound coordination. In the Zn-O bond length range, NH 2 -BDC 2 -ligands coordinate to Zn(II) ions via two coordination modes: bidentate and monodentate. On the other hand, ethyl viologen exists in Zn-NH 2 -BDC hole. In the Zn atomic coordination model diagram, two tetradentate Zn are connected through NH 2 -BDC 2- The oxygen of the ligand is connected to the hexagonal Zn via NH 2 -BDC 2- Finally, through NH 2 -BDC 2- Connect different planes to form a three-dimensional network.

[0057] Table 1 Crystallographic parameters of target compounds

[0058]

[0059]

[0060] Table 2 Selected bond lengths of compound 1 and bond angle (°)

[0061]

[0062] Symmetry codes: (iii)1.5-y,0.5+z; (iv)1-x,2-y,1-z

[0063] Table 3 Selected bond lengths of compound 2 and bond angle (°)

[0064]

[0065] Symmetry codes: (i)2-x,-y,1-z; (ii)2-x,0.5+y,0.5-z; (iii)x,-0.5-y,0.5+z

[0066] Experimental Example 2

[0067] TG

[0068] Thermogravimetric analysis (TGA) was performed on an SDT 2960 differential thermal analyzer at a speed of 10 °C / min in flowing N 2 Thermogravimetric analysis was performed.

[0069] The thermal stability of the samples was determined by thermogravimetric analysis (TGA) in the temperature range of 25-1000°C. Fig. 9 As shown, two water molecules of the solvent were destroyed between 25-250°C (calculated 4.6%; actual 4.2%). After 316°C, the entire crystal framework began to collapse, which indicated that the structure of compound 1 remained stable within 316°C.

[0070] The thermal stability of the samples was determined by thermogravimetric analysis (TGA) in the temperature range of 25-4000°C. Fig.10 As shown. 2 DMF and 3 water molecules of the solvent were destroyed between 25 and 1205°C (calculated 3.9%; actual 4.0%). After 2000°C, the entire crystal framework began to collapse, indicating that the structure of compound 2 remained stable at 2000°C.

[0071] Experimental Example 3

[0072] Powder X-ray Diffraction (PXRD)

[0073] Powder X-ray diffraction (PXRD) was carried out on a DX-2600 spectrometer.

[0074] The experimental results of the powder X-ray diffraction (PXRD) spectra of compounds 1 and 2 are basically consistent with the simulation results, indicating that the bulk products of compounds 1 and 2 have high phase purity. In order to prove that the two MOFs have good chemical stability, the PXRD patterns were recorded before and after they were immersed in different solvents (such as MeOH, MeCN, DMF, DMA, EtOH and water) for 2 weeks. Figure 11-14 As shown, both Compound 1 and Compound 2 show high stability in common solvents. At the same time, the frameworks of Compound 1 and Compound 2 can also be retained in an aqueous solution with a pH of 12-13 for at least 3 days, which fully proves that these two MOFs have good tolerance to solvents, acids and bases.

[0075] Experimental Example 4

[0076] Infrared performance analysis

[0077] Infrared spectra were obtained on a Varian 640 FT / IR spectrometer with KBr pellets at 400–4000 cm -1 Area. Fig.15 , 16 As shown in the infrared spectra of the two compounds, 3447 and 3463 cm -1 OH stretching vibration peaks belonging to methanol, 2917, 2960 cm -1 Stretching vibration peaks attributable to methyl and methylene, 1639, 1630 cm -1 The characteristic stretching peaks of carbonyl C=O are 1432 and 1360 cm -1 It is attributed to the asymmetric stretching vibration peak of carboxylic acid.

[0078] Experimental Example 5

[0079] NMR analysis

[0080] 1 H NMR spectra were recorded on a Varian (400 MHz) spectrometer. Fig.17 shown.

[0081] To evaluate the catalytic activity of viologen-MOF, malononitrile, aromatic aldehydes and 1,3-cyclohexanedione (acetylacetone) were synthesized in a one-pot method. Compound 1 was used as a catalyst, benzaldehyde and 1,3-cyclohexanedione were used as model compounds to optimize the synthesis of 4H-pyran. The synergistic environment of active metal centers (Lewis acid sites) and nucleophilic groups (Lewis base sites) in porous MOFs, as well as the unique electron transfer effect of viologen molecules, can greatly accelerate chemical synthesis reactions. Most of the reported ones are homogeneous catalysts, which are not conducive to recycling or using strong reaction conditions. (Table 4) In contrast, the present catalyst, as a heterogeneous catalyst, can improve the reaction yield under mild conditions.

[0082] Table 44H-Optimization of pyran reaction catalyst

[0083]

[0084] Table 54 Optimization of H-pyran reaction

[0085]

[0086] The effect of the catalyst on the experiment under different reaction conditions was studied, and the optimal reaction conditions were screened (Table 5). The catalytic experiment was carried out in a 10mL Shrek tube equipped with a magnetic stirrer at room temperature. The reaction process was monitored by thin layer chromatography (TLC). By using 1mmol benzaldehyde, 1mmol malononitrile and 2mmol 1,3-cyclohexanedione as model reactions in different solvents, the most suitable solvent system for the reaction was explored. The results are shown in Table 5, among which methanol is the most superior solvent system. The optimal catalyst dosage using methanol as a solvent was continued to be studied, increasing from 1mol% to 2mol% in a gradient, and it was found that a yield of 99% could be achieved at a catalyst dosage of 1.5mol%. Finally, the effect of different reaction times from 10 to 40 minutes on the activity of the catalyst was focused on. Surprisingly, when the reaction time reached 10min, solid matter gradually appeared in the tube, and stirring continued for about 20min, and the solid matter in the system basically stopped increasing. At this time, thin layer chromatography was used to show that the reactants had reacted almost completely, and NMR proved that the solid material was indeed a 4H-pyran compound with a yield of 99%.

[0087] After optimizing the reaction conditions, the generality of the catalyst application was considered. A series of experiments have been carried out on aldehyde derivatives with different substituents in the ortho, meta or para position of the aromatic ring. Substituting 1,3-cyclohexanedione with acetylacetone also reacts with different aldehydes (Scheme 1). The results are shown in Figure 18-19 It is worth noting that the electron-withdrawing groups (-Cl, -Br, -NO 2 ) benzaldehyde can be completely reacted in a shorter time. Some aldehydes with weaker electron donor ability (-CH 3 ) can also complete the reaction within the expected time. In contrast, -OCH 3 It is a strong electron donor group, and its conversion time is significantly prolonged, and the reaction yield is not ideal. In addition, some heterocyclic aldehydes can also be successfully converted into target products with high yields. However, the yield of 9-o-phthalaldehyde is low, which may be due to its large size and large steric hindrance. This makes it difficult for it to contact the effective catalytic sites of the catalyst, resulting in a hindered reaction. In addition, the results of acetylacetone are similar to those of 1,3-cyclohexanedione.

[0088] As a heterogeneous catalyst, viologen-MOF can be easily recovered by centrifugation and continued to the next catalytic experiment after washing and drying. Fig. 20 As shown in Figure 2, the catalyst still maintains good performance after 5 cycles. In addition, PXRD and FT-IR data show that the structures of the new catalyst and the recycled catalyst remain unchanged. This indicates that the catalyst is a stable compound.

[0089] The mechanism of the reaction was speculated, in which the methylene group of malononitrile can donate a proton to the aldehyde group, thereby generating an imine intermediate. In this process, the coordination of Zn to the carboxylic acid in the viologen-MOF structure and the electron transfer between methyl viologen and the carboxylic acid can activate the carbonyl and nitrogen groups. Therefore, 2-benzyl malononitrile is rapidly generated. Similarly, M···O can act as an active Lewis acidic catalytic site, which together with the electron transfer promotes the enol interconversion of the enol and further catalyzes the Michael addition reaction. The synergistic effect of these two sites promotes the cyclization of the enol addition cyanide group. Finally, 4H-pyran is formed through tautomerism.

[0090] In summary, the present invention prepared two catalysts composed of viologens and metal organic frameworks, and characterized them by XRD, TGA and FT-IR. Both catalysts showed excellent catalytic effects on the one-pot synthesis of 4H-pyran. The catalytic synthesis reaction can be carried out in a short time under very mild conditions with high product yield. As heterogeneous catalysts, both catalysts can be easily recovered and recycled without significant loss of activity. In addition, this is the first time that viologens have been combined with this metal organic framework to synergistically catalyze the synthesis of drug intermediates, which is also a novel aspect of this study. In the future, it is planned to prepare more such complexes and apply them to more comprehensive drug intermediate synthesis.

[0091] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A viologen-modified metal organic coordination compound, characterized in that: The viologen molecule was inserted into the MOF framework of Zn-NH2-BDC, with the general formula {[Zn(MV)(NH2-BDC)]} n (1);{[Zn(EV)(NH2-BDC)]·2DMF} n (2).

2. The method for preparing a viologen-modified metal organic coordination compound according to claim 1, characterized in that the steps include: Methyl viologen MV·2Cl (0.03 mmol), 2-aminoterephthalic acid (NH2-BDC) (0.1 mmol) and Zn(NO3)2·6H2O (0.05 mmol) were added to an autoclave, followed by 4 mL of DMF, 1 mL of methanol and 1 mL of water. The sealed reactor was placed in an oven and heated at 80°C for 48 hours. After cooling to room temperature, the obtained crystals were the metal organic coordination compound 1.

3. The method for preparing a viologen-modified metal organic coordination compound according to claim 1, characterized in that the steps include: Ethyl viologen EV·2Br (0.03 mmol), 2-aminoterephthalic acid (NH2-BDC) (0.1 mmol) and Zn(NO3)2·6H2O (0.05 mmol) were added to an autoclave, followed by 4 mL of DMF, 1 mL of methanol and 1 mL of water. The sealed reactor was placed in an oven and heated at 80°C for 48 hours. After cooling to room temperature, the resulting crystals were the metal organic coordination compound 2.

4. Use of the viologen-modified metal organic coordination compound as claimed in claim 1 in the synthesis of pharmaceutical intermediates.

5. The use of the viologen-modified metal organic coordination compound according to claim 4, characterized in that: The metal organic coordination compound is used as a heterogeneous catalyst to catalyze the synthesis of drug intermediates.

6. The use according to claim 5, characterized in that: The metal organic coordination compound is used as a catalyst for catalyzing the synthesis of 4H-pyran derivatives.

7. The use according to claim 6, characterized in that: The metal organic coordination compound has an excellent catalytic effect on the one-pot synthesis of 4H-pyran.

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