Application of lanthanum ion-doped stable polyoxometalate in catalytic synthesis of quinazoline compounds and preparation method of quinazoline compounds

Abstract

The present invention provides an application of a lanthanum ion-doped stable polyoxometalate in the catalytic synthesis of quinazoline compounds and a method for preparing the quinazoline compounds, belonging to the field of catalyst technology. The present invention uses phosphorous acid as a template to synthesize three lanthanum-containing phosphomolybdic polyacids. By regulating sodium ions during the synthesis process, lanthanum ion-doped stable polyoxometalates with different three-dimensional structures are obtained. The lanthanum ion-doped stable polyoxometalates include: [CH3NH3]6{La(H2O)3Na[Mo6O 12 (OH)3(HPO3)4]2}·10H2O, [CH3NH3]2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O and [CH3NH3]5{La2(H2O)8Na[Mo6O 12 (OH)3(HPO3)3(PO4)]2}·16H2O. These three lanthanum ion-doped polyoxometalates have good stability under alkaline conditions and show excellent catalytic performance in the synthesis of quinazoline.

Description

Technical Field

[0001] The present invention belongs to the technical field of catalysts, and in particular relates to an application of a lanthanum ion-doped stable polyoxometalate in the catalytic synthesis of quinazoline compounds and a preparation method of the quinazoline compounds. Background Art

[0002] Quinazolines, as an important class of heterocyclic compounds, are extremely important structural units in natural products and the chemical industry. They are widely used in the fields of cosmetics and pesticides, especially in medicine. In the medical field, quinazoline compounds exhibit significant anti-cancer and antibacterial properties. In recent years, significant progress has been made in the synthesis of quinazolines. Although classical synthetic methods can effectively prepare quinazolines, the tedious reaction steps and complex product separation processes pose challenges to these reaction modes. Therefore, the development of simple and efficient catalytic methods using cheap and readily available starting materials has become a key research focus. Among these methods, the complex-catalyzed alcohol dehydrogenation functionalization reaction provides a green and efficient catalytic model for the synthesis of quinazolines. Compared with metal complexes, cluster catalysts have obvious advantages. In particular, polyoxometalates (POMs), as a special class of metal oxide clusters, are composed of MO x (x=5 or 6; M=molybdenum (Mo), tungsten (W), vanadium (V), etc.), have more metal active sites, and the synthesis process is relatively simple, thus showing excellent catalytic activity. However, the main structure of polyoxometalates is usually formed by the acidification condensation reaction of metal oxides, and their functional fragments are generally acid-resistant, but unstable under alkaline conditions. The reaction system of alcohol dehydrogenation coupling to form quinazoline requires the addition of a base to catalyze the reaction, so the design and synthesis of alkali-resistant polyoxometalates (POMs) remains a challenge. Summary of the Invention

[0003] In response to the above technical problems, the present invention proposes an application of a lanthanum ion-doped stable polyoxometalate in the catalytic synthesis of quinazoline compounds and a method for preparing the quinazoline compounds.

[0004] To achieve the above object, the present invention provides the following technical solutions:

[0005] One of the purposes of the present invention is to provide a lanthanum ion doped stable polyoxometalate for catalytic generation of quinazoline compounds under alkaline conditions, wherein the lanthanum ion doped stable polyoxometalate comprises: [CH3NH3]6{La(H2O)3Na[Mo6O 12 (OH)3(HPO3)4]2}·10H2O, [CH3NH3]2{La(H2O)[Mo6O 15(HPO3)4]}·8H2O and [CH3NH3]5{La2(H2O)8Na[Mo6O 12 One of (OH)3(HPO3)3(PO4)]2}·16H2O.

[0006] Optionally, the preparation method of the lanthanum ion-doped stable polyoxometalate comprises the following steps: using hydrogen phosphite as a template, lanthanum ions as a doping element, cations and polymolybdate as raw materials, and performing a hydrothermal reaction under the action of a reducing agent to obtain a lanthanum ion-doped stable polyoxometalate;

[0007] Wherein, the reducing agent is NH2NH2·HCl or Na2S2O3; and / or,

[0008] The cation is CH3NH2·HCl; and / or,

[0009] The polymolybdate is Na2MoO4·2H2O or (NH4)5[Mo7O 24 ]·4H2O or [CH3NH3]5{La2(H2O)8Na[Mo6O 12 (OH)3(HPO3)3(PO4)]2}·16H2O.

[0010] When the polymolybdate is (NH4)5[Mo7O 24 ]·4H2O, the lanthanum ion doped stable polyoxometalate is [CH3NH3]2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O.

[0011] Furthermore, the hydrothermal reaction is carried out at 80° C. for 48 hours. Too high or too low a reaction temperature will result in an incomplete product morphology and affect subsequent performance, so the reaction is preferably carried out at 80° C. for 48 hours.

[0012] Furthermore, the [CH3NH3]6{La(H2O)3Na[Mo6O 12 The specific preparation steps of [OH)3(HPO3)4]2}·10H2O include: adding Na2MoO4·2H2O, LaCl3·6H2O and CH3NH2·HCl into water according to the stoichiometric ratio, stirring at room temperature, adjusting the pH of the resulting solution to acidic with H3PO3, then adding NH2NH2·HCl, heating and reacting to obtain brown block crystals, namely [CH3NH3]6{La(H2O)3Na[Mo6O 12 (OH)3(HPO3)4]2}·10H2O.

[0013] Furthermore, the amount ratio of Na2MoO4·2H2O, LaCl3·6H2O, CH3NH2·HCl, NH2NH2·HCl and water is 0.4g:0.2g:0.8g:0.1g:40mL; and / or,

[0014] The acidic refers to pH=1.3.

[0015] Furthermore, the [CH3NH3]2{La(H2O)[Mo6O 15 The specific preparation steps of (HPO3)4]}·8H2O include: (NH4)5[Mo7O 24 ]·4H2O, LaCl3·6H2O and CH3NH2·HCl were added to water and stirred at room temperature. The pH of the resulting solution was adjusted to acidic with H3PO3, and then NH2NH2·HCl was added and heated to react to obtain brown needle-like crystals, namely [CH3NH3]2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O.

[0016] Furthermore, the (NH4)5[Mo7O 24 ]·4H2O, LaCl3·6H2O, CH3NH2·HCl, NH2NH2·HCl and water in a ratio of 0.4g:0.2g:0.8g:0.1g:40mL; and / or,

[0017] The acidic refers to pH=1.3.

[0018] Furthermore, the [CH3NH3]5{La2(H2O)8Na[Mo6O 12 The specific preparation steps of [OH)3(HPO3)3(PO4)]2}·16H2O include: adding Na2MoO4·2H2O, LaCl3·6H2O and CH3NH2·HCl into water according to the stoichiometric ratio, stirring at room temperature, adjusting the pH of the resulting solution to acidic with H3PO3, then adding Na2S2O3, heating and reacting to obtain brown block crystals, namely [CH3NH3]5{La2(H2O)8Na[Mo6O 12 (OH)3(HPO3)3(PO4)]2}·16H2O.

[0019] Furthermore, the (NH4)5[Mo7O 24 ]·4H2O, LaCl3·6H2O, CH3NH2·HCl, Na2S2O3 and water in a ratio of 0.4g:0.2g:0.8g:0.1g:40mL; and / or,

[0020] The acidic refers to pH=1.3.

[0021] A second object of the present invention is to provide a method for preparing a quinazoline compound. Under alkaline conditions, the lanthanum ion-doped, stabilized polyoxometalate is used as a catalyst to catalyze the reaction of an alcohol with a benzonitrile derivative to produce the quinazoline compound. In this reaction, the base used is potassium tert-butoxide, and the solvent used is tert-butanol. The general formulas a and b of the reaction substrates, the alcohol and the benzonitrile derivative, are as follows:

[0022] Wherein, R1 is H, CH3 or Br, and R2 is H, CH3 or Cl.

[0023] Furthermore, the molar ratio of the catalyst to the benzonitrile derivative is 1:2.

[0024] Furthermore, the reaction temperature is 95° C. and the reaction time is 24 h.

[0025] Compared with the prior art, the present invention has the following advantages and technical effects:

[0026] The present invention adopts the hydrothermal method for the first time and uses phosphite as template to synthesize three hourglass-shaped phosphomolybdic acids containing rare earth elements, namely [CH3NH3]6{La(H2O)3Na[Mo6O 12 (OH)3(HPO3)4]2}·10H2O (compound 1), [CH3NH3]2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O (compound 2) and [CH3NH3]5{La2(H2O)8Na[Mo6O 12 (OH)3(HPO3)3(PO4)]2}·16H2O (Compound 3). Comprehensive structural characterization revealed that the diverse coordination patterns of lanthanum and the partial oxidation of phosphorous acid to phosphoric acid in Compound 3 contribute to their unique structural characteristics. Furthermore, when used as catalysts for the reaction of alcohols and ketones to form quinazolines under alkaline conditions, the three compounds exhibited excellent catalytic performance and stability. This invention not only enriches the family of hourglass-shaped polyoxometalates but also expands their catalytic applications under alkaline conditions, providing significant value for the efficient synthesis of quinazoline compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The accompanying drawings, which constitute part of the present invention, are provided to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are provided to explain the present invention and do not constitute an undue limitation of the present invention. In the accompanying drawings:

[0028] Figure 1The structure of the {P4Mo6} unit in Example 1 (a), the three-dimensional structure of compound 1 (b), the structure of the La6Na{P4Mo6}2 unit (c), and the structure of the Na{P4Mo6}2 dimer (d);

[0029] Figure 2 The structure (a) of the {P4Mo6} unit in Example 2, a La 3+ Coordination of ions (b), coordination environment of {P4Mo6} (c), three-dimensional structure of compound 2 (d);

[0030] Figure 3 The difference between the {P4Mo6} units in compounds 1 and 3 (a), the two-dimensional structure of compound 3 (b), the {P4Mo6} unit coordinated with one La atom in compound 3 (c), and the {Na[P4Mo6]2} dimer coordinated with six La atoms in compound 3 (d);

[0031] Figure 4 is the thermogravimetric analysis (TGA) curve of compound 1;

[0032] Figure 5 is the thermogravimetric analysis (TGA) curve of compound 2;

[0033] Figure 6 is the thermogravimetric analysis (TGA) curve of compound 3;

[0034] Figure 7 Proton decoupling of compounds 1, 2, 3, phosphoric acid (H3PO4) and phosphorous acid (H3PO3) dissolved in heavy water (D2O) 31 P NMR spectrum;

[0035] Figure 8 is the PXRD pattern of compound 1 under alkaline conditions of different concentrations;

[0036] Figure 9 is the PXRD pattern of compound 2 under alkaline conditions of different concentrations;

[0037] Figure 10 is the PXRD pattern of compound 3 under alkaline conditions of different concentrations;

[0038] Figure 11 The conversion rate of compound 2 after 5 cycles under the conditions of Application Example 1;

[0039] Figure 12 This is the proposed mechanism for the synthesis of phenylquinazolines. DETAILED DESCRIPTION

[0040] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0041] It should be understood that the terms described herein are intended only to describe particular embodiments and are not intended to limit the present invention. In addition, for numerical ranges herein, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each smaller range between any intermediate value within a stated value or stated range and any other stated value or intermediate value within the stated range is also encompassed by the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the scope.

[0042] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of any conflict with any incorporated document, the contents of this specification shall prevail.

[0043] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from the description of the invention. The description and examples are intended to be illustrative only.

[0044] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0045] Generally speaking, phosphate / phosphite templates are used to regulate the structure of polyoxometalates POMs. In the process of synthesizing molybdenum-based polyoxometalates, the researchers of the present invention explored the assembly of phosphites. Through microwave-assisted synthesis, an hourglass-shaped {M[P4Mo6]2} structure was successfully developed. This structure is characterized by a central metal ion connecting two {P4Mo6} units. Since the molybdenum atom is in the +5 oxidation state, it has excellent redox activity and shows stability in heterogeneous catalysis, photocatalysis, biological applications, electrochemical processes, etc. Usually, the central metal ion between the two {P4Mo6} units is a sodium ion (Na + ), potassium ion (K + ), aluminum ions (Al 3+) and so on, presenting a hexacoordinate geometry. In addition, the oxygen atoms exposed on the phosphorous acid in the hourglass-shaped {M[P4Mo6]2} structure can be used as potential connection sites for further connection with other metals (such as the first transition series metals), thereby forming a multidimensional structure. Compared with the first transition series metals, lanthanide metals have more excellent catalytic activity, and due to their diverse coordination modes and strong oxygen affinity, they can be used as excellent linkers to connect polyoxometalate units, thereby forming lanthanide-substituted polyoxometalates. However, there are currently no reports on the use of lanthanide metals to connect hourglass-shaped polyoxometalates. Therefore, the present invention provides a lanthanum ion-doped stable polyoxometalate and its preparation method and application. With hydrogen phosphite (HPO3 2- ) as templates, three stable lanthanum ion-doped phosphomolybdic acid were synthesized, whose chemical formulas are [CH3NH3]6{La(H2O)3Na[Mo6O 12 (OH)3(HPO3)4]2}·10H2O (compound 1), [CH3NH3]2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O (compound 2) and [CH3NH3]5{La2(H2O)8Na[Mo6O 12 (OH)3(HPO3)3(PO4)]2}·16H2O (Compound 3). Structural analysis showed that compound 1 was formed by lanthanum ions (La 3+ ) and hourglass-shaped {Na[P4Mo6O 27 ]2} units are connected to form a three-dimensional structure. Compound 2 has porous channels and is composed of the same {P4Mo6O 27} structural units form a three-dimensional structure. When the synthetic microenvironment is adjusted by changing the type of reducing agent, some of the hypophosphites in the structural units are oxidized, thereby changing the structure and forming compound 3. All three compounds are alkali-resistant and have catalytic activity in the reaction of converting 2-aminobenzyl alcohol and benzonitrile to 2-phenylquinazoline. Among them, compound 2 has the highest catalytic conversion rate, reaching 91.7%, which is far superior to the classic Keggin-type {PMo 12} and inorganic CaMoO4, indicating the synergistic catalytic effect of molybdenum (Mo) and lanthanum (La) centers. In addition, compound 2 showed good activity and reliability in catalyzing the same reaction with different substrates.

[0046] Unless otherwise specified, the "room temperature" in the present invention refers to 20-30°C.

[0047] The technical solution of the present invention is further illustrated by the following examples.

[0048] In the following examples:

[0049] 1. Unless otherwise specified, all other reagents were of analytical grade and used directly without further purification.

[0050] 2. Powder X-ray diffraction (PXRD) analysis was performed on a Rigaku Mini Flex 600-C diffractometer using CuKα radiation. The scanning rate was 5° / min.

[0051] 3. Thermogravimetric-dissipative scanning calorimetry (TGA-DSC) was performed on a TA Q600 instrument under flowing nitrogen conditions with a temperature setting range of 30°C to 800°C, a heating rate of 10°C / min, and a nitrogen flow rate of 25 mL / min.

[0052] 4. Fourier transform infrared spectra (FT-IR) were collected on a Bruker Vertex 70 spectrometer using the potassium bromide pellet method.

[0053] 5. X-ray photoelectron spectroscopy (XPS) data were collected by a Thermo Fisher Nexsa spectrometer.

[0054] 6. Nuclear magnetic resonance (NMR) spectroscopy was performed on a Bruker Avance 400 MHz spectrometer using deuterated reagents and tetramethylsilane as the internal standard.

[0055] 7. Single crystal X-ray diffraction (SCXRD) analysis was performed on a Rigaku XtaLAB-Synergy-R diffractometer at 296 K using graphite monochromatized Mo Kα radiation.

[0056] 8. Use multi-scanning technology for absorption correction.

[0057] 9. The structure was solved by the direct method using the ShelXT structure solution program using Olex2 software and refined by the least-squares method using the ShelXL refinement package. Crystallographic data are listed in the Supporting Information.

[0058] Example 1

[0059] A lanthanum ion doped and stabilized polyoxometalate [CH3NH3]6{La(H2O)3Na[Mo6O 12[OH)3(HPO3)4]2}·10H2O was synthesized by adding 0.4 g of Na2MoO4·2H2O, 0.2 g of LaCl3·6H2O and 0.8 g of CH3NH2·HCl into 40 mL of water and stirring at room temperature for 30 min. The pH of the resulting solution was adjusted to 1.3 with H3PO3, and then 0.1 g of NH2NH2·HCl was added. The resulting mixed solution was transferred to a polytetrafluoroethylene-lined stainless steel autoclave and reacted at 80°C for 48 h to obtain brown block crystals, namely [CH3NH3]6{La(H2O)3Na[Mo6O 12 (OH)3(HPO3)4]2}·10H2O (denoted as Compound 1). The yield based on molybdenum was 73.2%. 31 PNMR (ppm): 3.15. FT-IR(KBr, cm -1 ): 492 (strong peak), 572 (weak peak), 727 (moderate intensity peak), 947 (weak peak), 966 (strong peak), 1009 (weak peak), 1079 (strong peak), 1145 (strong peak), 1470 (weak peak), 1478 (weak peak), 1506 (weak peak), 1630 (strong peak). Elemental analysis: Found (calculated)%, for compound 1 (C6H 76 LaMo 12 N6NaO 67 P8), carbon content is 2.45 (2.51); hydrogen content is 2.61 (2.65); nitrogen content is 2.90 (2.93).

[0060] Example 2

[0061] A [CH3NH3]2{La(H2O)[Mo6O 15 Synthesis of (HPO3)4]}·8H2O: 0.4g of (NH4)5[Mo7O 24 ]·4H2O, 0.2g of LaCl3·6H2O and 0.8g of CH3NH2·HCl were added to 40mL of water and stirred at room temperature for 30min. The pH of the resulting solution was adjusted to 1.3 with H3PO3, and then 0.1g of NH2NH2·HCl was added. The resulting mixed solution was transferred to a polytetrafluoroethylene-lined stainless steel autoclave and reacted at 80℃ for 48h to obtain brown needle-shaped crystals, namely [CH3NH3]2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O (denoted as compound 2). The yield based on molybdenum was 84.7%. 31 PNMR (ppm): 3.30. FT-IR(KBr, cm -1): 496 (strong peak), 572 (weak peak), 750 (strong peak), 947 (medium intensity peak), 971 (strong peak), 1018 (weak peak), 1074 (strong peak), 1117 (weak peak), 1399 (medium intensity peak), 1473 (weak peak), 1512 (weak peak), 1634 (strong peak). Elemental analysis: Found (calculated)%, for compound 2 (C2H 34 LaMo6N2O 36 P4), carbon content is 1.58 (1.60); hydrogen content is 2.20 (2.27); nitrogen content is 1.81 (1.87).

[0062] Example 3

[0063] A [CH3NH3]5{La2(H2O)8Na[Mo6O 12 Synthesis of (OH)3(HPO3)3(PO4)]2}·16H2O: 0.4 g of Na2MoO4·2H2O, 0.2 g of LaCl3·6H2O and 0.8 g of CH3NH2·HCl were added to 40 mL of water and stirred at room temperature for 30 min. The pH of the resulting solution was adjusted to 1.3 with H3PO3, and then 0.1 g of Na2S2O3 was added. The resulting mixed solution was transferred to a polytetrafluoroethylene-lined stainless steel autoclave and reacted at 80°C for 48 h to obtain brown block crystals, namely [CH3NH3]5{La2(H2O)8Na[Mo6O 12 (OH)3(HPO3)3(PO4)]2}·16H2O (denoted as compound 3). The yield based on molybdenum was 79.6%. 31 PNMR (ppm): 3.25, -0.07. FT-IR(KBr, cm -1 ): 492 (strong peak), 567 (medium intensity peak), 613 (weak peak), 736 (strong peak), 924 (medium intensity peak), 957 (strong peak), 1013 (strong peak), 1065 (strong peak), 1145 (strong peak), 1404 (weak peak), 1460 (weak peak), 1516 (weak peak), 1634 (strong peak). Elemental analysis: Found (calculated)%, for 3 (C5H 84 La2Mo6N5O 56 P5), carbon content is 2.88 (2.83); hydrogen content is 3.91 (3.96); nitrogen content is 3.33 (3.30).

[0064] Figure 1The structure of the {P4Mo6} unit in Example 1 (a), the three-dimensional structure of compound 1 (b), the structure of the La6Na{P4Mo6}2 unit (c), and the structure of the Na{P4Mo6}2 dimer (d). For clarity, some hydrogen atoms have been omitted. Single crystal X-ray diffraction (SCXRD) analysis shows that compound 1 belongs to the hexagonal system with a space group of P63 / mmc and is composed of La 3+ 、Na + and {P4Mo6} units. The {P4Mo6} unit consists of six {MoO6} octahedra formed by six Mo atoms, nine μ2-O (double-bridge oxygen) atoms, six Ot (terminal oxygen) atoms, and three HPO3 2- These octahedra are arranged around a phosphite ligand by sharing two oxygen atoms to form a cyclic {P4Mo6} structure ( Figure 1 (a) in the figure). The six Mo centers are located in the same plane, and HPO3 2- Located on one side, and a Na + The ion is coordinated with three μ2-O ligands on the other side. + The ion also coordinates with three μ2-O ligands in the adjacent {P4Mo6} unit to form an hourglass-shaped {Na[P4Mo6]2} dimer ( Figure 1 (b) in Figure 2). In addition, the {P4Mo6} unit is connected to the HPO3 2- The ligand is connected to three La atoms ( Figure 1 (c) in Figure 1). This coordination mode forms a three-dimensional network structure in which the {Na[P4Mo6]2} dimer is connected by La 3+ Ionic interconnection ( Figure 1 (d) in the above figure.

[0065] Figure 2 The structure (a) of the {P4Mo6} unit in Example 2, a La 3+ Coordination of ions (b), coordination environment of {P4Mo6} (c), three-dimensional structure of compound 2 (d). For clarity, some hydrogen atoms have been omitted. The blue octahedron represents MoO6; the turquoise polyhedron represents LaO9. Blue represents molybdenum (Mo); brown represents lanthanum (La); red represents oxygen (O); pink represents phosphorus (P); and gray represents hydrogen (H). Single crystal X-ray diffraction (SCXRD) analysis shows that compound 2 belongs to the hexagonal system with a space group of P63 / m. Similar to compound 1, the {P4Mo6} unit consists of six {MoO6} octahedra and four HPO3 2- However, in the absence of Na + In the case of the Mo plane, the three μ2-O atoms on one side directly coordinate with La ( Figure 2(a) in the above). Due to La 3+ The atomic radius of La is larger than that of the first transition metals, and the coordination mode is more diverse, and it does not form an hourglass structure. 3+ It exhibits a seven-coordinate mode, coordinated with three μ2-O atoms of one {P4Mo6} unit, one water molecule, and three oxygen atoms of the phosphite of three {P4Mo6} units ( Figure 2 (b) in the figure). Since La 3+ The cavity does not fit well in the structure and it crystallizes in a disordered pattern with each {P4Mo6} unit cell and four La 3+ One of them is coordinated by μ2-O, and the other three are coordinated by HPO3 2- Anion coordination ( Figure 2 (c) in Figure 1). This coordination mode is linked to La via the {P4Mo6} unit. 3+ The interactions between ions form a three-dimensional structure ( Figure 2 (d) in the above figure.

[0066] Figure 3 The differences between the {P4Mo6} units in compounds 1 and 3 (a), the two-dimensional structure of compound 3 (b), the {P4Mo6} unit coordinated with one La atom in compound 3 (c), and the {Na[P4Mo6]2} dimer coordinated with six La atoms in compound 3 (d). For clarity, some hydrogen atoms have been omitted. Blue octahedra represent MoO6; turquoise polyhedra represent LaO9. Blue represents molybdenum (Mo); tan represents lanthanum (La); turquoise represents sodium (Na); red represents oxygen (O); pink represents phosphorus (P); and gray represents hydrogen (H). Single crystal X-ray diffraction (SCXRD) analysis shows that compound 3 can be isolated by varying the reducing agent in the system. It crystallizes in the triclinic system with space group P-1. Similar to compound 1, compound 3 contains a {Na[P4Mo6]2} dimer, with Mo-Mo and Na-O bond lengths comparable to those in compound 1. Due to the change in the microenvironment, the central ligand of the six Mo centers unexpectedly shifted from HPO3 2- Converted to PO4 3+ , while the remaining three ligands are still HPO3 2- ( Figure 3 (a) in the figure). It is worth noting that, unlike the C3 symmetry of compound 1, the {P4Mo6} unit in compound 3 exhibits Cs symmetry. This change is mainly attributed to the interaction between La and HPO3 2- and PO4 3+ The coordination ( Figure 3 (b) in Figure 2). This coordination mode results in HPO3 2- The remaining two HPO32- The ligands are each coordinated to two La atoms ( Figure 3 (c) in the figure). Unlike compound 2, compound 3 forms a two-dimensional coordination network ( Figure 3 (d) in the figure). This oxidation process may be due to the oxidation of O2 in the air as an oxidant. Experiments have shown that when oxygen is excluded during the synthesis process, no PO4 3+ structure.

[0067] Figure 4 is the thermogravimetric analysis (TGA) curve of compound 1, Figure 5 is the thermogravimetric analysis (TGA) curve of compound 2, Figure 6 is the thermogravimetric analysis (TGA) curve of compound 3. Figure 4-6 It can be seen that compounds 1, 2, and 3 exhibit similar weight loss stages, with the first stage corresponding to the loss of crystalline water. According to the thermogravimetric analysis results, the structural formulas determined are [CH3NH3]6{La(H2O)3Na[Mo6O 12 (OH)3(HPO3)4]2}·10H2O, [CH3NH3]2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O and [CH3NH3]5{La2(H2O)8Na[Mo6O 12 (OH)3(HPO3)3(PO4)]2}·16H2O.

[0068] Figure 7 Proton decoupling of compounds 1, 2, 3, phosphoric acid (H3PO4) and phosphorous acid (H3PO3) dissolved in heavy water (D2O) 31 P NMR spectrum. Figure 7 As shown, the 31P NMR signals of phosphoric acid (H3PO4) and phosphorous acid (H3PO3) are located at -0.03ppm and 4.69ppm, respectively. In compound 1, a single NMR peak was observed at 3.15ppm, corresponding to HPO3 2- , there is no sign of phosphonic acid groups, indicating that the peak shift is caused by HPO3 2- The coordination with molybdenum and lanthanum is caused. Similar results are also observed for compound 2. However, in compound 3, in addition to HP O3 2- In addition to the peak at 3.25 ppm, an additional peak was detected at -0.07 ppm, corresponding to PO4 3+ This confirms that during the synthesis process, [PO3] 3- Partially oxidized to PO4 3+The differences in the NMR peak positions among compounds 1, 2, and 3 are attributed to the different chemical coordination environments of the phosphorus atoms.

[0069] Application Example 1

[0070] Quinazoline derivatives were synthesized using Compound 1, Compound 2, or Compound 3 as catalysts, with 2-aminobenzyl alcohol and benzonitrile selected as model substrates. As shown in Table 1, using Compound 2 and potassium tert-butoxide (t-BuOK) (base) as catalysts, 2-aminobenzyl alcohol and benzonitrile reacted in tert-butanol (t-BuOH) at 95°C for 24 hours to produce 2-phenylquinazoline. The reaction equation is as follows:

[0071]

[0072] The specific steps are as follows: 1 mmol of 2-aminobenzyl alcohol, 1 mmol of benzonitrile, 0.5 mmol of potassium tert-butoxide (t-BuOK), 6.6×10 -3 Compound 2 was added to 2 mL of tert-butanol (t-BuOH) and reacted at 95° C. for 24 hours to generate 2-phenylquinazoline with a conversion rate of 91.7%.

[0073] Application Example 2-13

[0074] Same as Application Example 1, with the differences shown in Table 1.

[0075] Table 1 Optimization of reaction conditions

[0076] entry catalyst alkali solvent <![CDATA[Conversion rate b > Application Example 1 2 t-BuOK t-BuOH 91.70％ Application Example 2 / t-BuOK t-BuOH 34.80％ Application Example 3 2 / t-BuOH trace Application Example 4 2 KOH t-BuOH 14.50％ Application Example 5 2 <![CDATA[K2CO3]]> t-BuOH trace Application Example 6 2 NaOH t-BuOH 13.30％ Application Example 7 2 t-BuOK Toluene 14.90％ Application Example 8 2 t-BuOK <![CDATA[DMF c ]]> trace Application Example 9 2 t-BuOK <![CDATA[THF d ]]> trace Application Example 10 1 t-BuOK t-BuOH 81.30％ Application Example 11 3 t-BuOK t-BuOH 68.60％ Application Example 12 <![CDATA[LaCl3]]> t-BuOK t-BuOH 40.30％ Application Example 13 <![CDATA[{PMo 12 }]]> t-BuOK t-BuOH 45.80％

[0077] Note: Conversion rate b By nuclear magnetic resonance spectroscopy ( 1 HNMR) determination; DMF c is dimethylformamide; THF d is tetrahydrofuran; “ / ” means not added; “{PMo 12}" refers to [NH2(CH3)2]3[PMo 12 O 40 ].

[0078] As can be seen from Table 1, although compound 2 and the base both play a catalytic role in the reaction process, if the base or compound 2 is not added, the reaction cannot be catalyzed (Application Examples 2-3). Replacing potassium tert-butoxide with potassium hydroxide (KOH), potassium carbonate (K2CO3) or sodium hydroxide (NaOH) will result in a decrease in conversion rate (Application Examples 4-6), indicating that compound 2 can only improve the catalytic efficiency when it works together with potassium tert-butoxide. Replacing tert-butanol with toluene, dimethylformamide and tetrahydrofuran was found to result in a decrease in conversion rate (Application Examples 7-9), which confirms that tert-butanol is the best solvent. In addition, after Application Example 1 reacted at 95°C for 10 hours, the reaction mixture was filtered and the catalyst was removed. It was found that no further conversion occurred in the reaction, indicating that the reaction was a heterogeneous catalytic process. Under the optimal reaction conditions, different catalysts were studied using this model reaction. As shown in Table 1 (Application Examples 10-11), compared with compounds 1 and 3, compound 2 exhibited better catalytic activity, which shows the influence of structural differences on catalytic efficiency. For comparison, lanthanum chloride (LaCl3) and {PMo 12} were also evaluated as catalysts (Application Examples 12-13). Both exhibited catalytic activity, indicating that lanthanum and molybdenum can each serve as catalytic centers. In compound 2, their combination produced a synergistic catalytic effect, enhancing the overall catalytic activity. This is also the first time that polyoxometalates (POMs) have been used as catalysts to convert aminobenzyl alcohol and benzonitrile to phenylquinazoline.

[0079] Application Example 14

[0080] The stability of compound 1 under different alkaline conditions was verified as follows: 20 mg of compound 1 was dissolved in 10 mL of tert-butanol, and then potassium tert-butoxide and HCl were used to adjust the acidity and alkalinity of the system to pK a =1, 3, 5, 7, 9, 11, 13, and let it stand for 12 h (measure xrd before and after the reaction to observe whether compound 1 changes).

[0081] Application Example 15

[0082] The stability of compound 2 under different alkaline conditions was verified as follows: 20 mg of compound 2 was dissolved in 10 mL of tert-butanol, and then potassium tert-butoxide and HCl were used to adjust the acidity and alkalinity of the system to pK a =1, 3, 5, 7, 9, 11, 13, and let it stand for 12 h (measure xrd before and after the reaction to observe whether compound 1 changes).

[0083] Application Example 16

[0084] The stability of compound 3 under different alkaline conditions was verified as follows: 20 mg of compound 3 was dissolved in 10 mL of tert-butanol, and then potassium tert-butoxide and HCl were used to adjust the acidity and alkalinity of the system to pK a =1, 3, 5, 7, 9, 11, 13, and let it stand for 12 h (the actual experiment is to measure xrd before and after the reaction for 12 h to observe whether compound 1 changes).

[0085] Figure 8 is the PXRD pattern of compound 1 under alkaline conditions of different concentrations, Figure 9 is the PXRD pattern of compound 2 under alkaline conditions of different concentrations, Figure 10 The PXRD patterns of compound 3 under different concentrations of alkaline conditions are shown in Figure 2. Figure 8-10 It can be seen that compound 1, compound 2 and compound 3 remain stable after being stirred in tert-butanol solutions containing different concentrations of potassium tert-butoxide for 24 hours. a When the value is higher than 13, compound 3 becomes unstable. This is also because compound 3 partially decomposes under alkaline conditions, resulting in low catalytic efficiency.

[0086] Compound 2 was subjected to 5 cycles under the conditions of Application Example 1 to test the catalytic stability of Compound 2. Figure 11 The figure shows the conversion rate of compound 2 after five cycles under the conditions of application example 1. It can be seen that compound 2 still has high catalytic stability after five cycles.

[0087] Application Example 17

[0088] Compound 2 was tested using different substrates. The experimental method was the same as that in Application Example 1. The reaction substrates, general reaction formula, and product structure are as follows:

[0089]

[0090] It can be seen that except for products C3 and C5, which have low yields due to the presence of electron-withdrawing groups and steric hindrance, the yields of other products are all over 90%, which indicates that compound 2 has excellent catalytic effect on various catalytic substrates.

[0091] Furthermore, based on the control experiments, the present invention proposes a catalytic mechanism (such as Figure 12 The catalytic efficiency of compound 2 exceeds that of compound 1 and compound 3, lanthanum chloride (LaCl3) and {PMo 12}, indicating that both lanthanum (La) and molybdenum (Mo) act as catalytic sites and that the coordination mode of lanthanum plays an important role. In contrast, sodium chloride (NaCl) showed no catalytic activity, suggesting that sodium ions (Na +) does not contribute to the reaction. Therefore, taking compound 2 as an example, the proposed mechanism mainly involves molybdenum and lanthanum as catalytic centers. Initially, aminobenzyl alcohol reacts with compound 2 in the presence of a base to form an intermediate. In compound 2, both molybdenum and lanthanum act as catalytic centers to activate aminobenzyl alcohol, which makes its catalytic activity higher than that of lanthanum chloride and {PMo 12} higher. This intermediate then undergoes a β-elimination reaction to form a carbonyl intermediate and regenerate compound 2. Simultaneously, the base promotes the hydration of benzonitrile, leading to the formation of an amide intermediate. Finally, the carbonyl intermediate and the amide intermediate undergo a condensation reaction to produce the product phenylquinazoline.

[0092] In summary, the present invention uses phosphorous acid as a template to synthesize three lanthanum-containing phosphomolybdic polyacids. + ), compounds 1 and compound 2 with different three-dimensional configurations were obtained. During the synthesis process, compound 3 with the characteristics of partial oxidation of phosphorous acid was obtained by changing the reducing ability of the reducing agent. This provides a new synthesis method for the synthesis of polyoxometalates (POM) using hypophosphite as a template. These three compounds have good stability under both acidic and alkaline conditions and exhibit excellent catalytic performance in the synthesis of quinazoline. Among the three polyoxometalates synthesized, compound 2 exhibits the highest catalytic activity due to its three-dimensional structure and the presence of more catalytic active sites. The present invention not only enriches the family of hourglass-shaped polyoxometalates, but also expands their potential applications in the field of catalytic synthesis, especially in the synthesis of quinazoline compounds. These findings provide a new approach for the synthesis of polyoxometalate-based catalysts with high efficiency and stability under alkaline conditions.

[0093] The above are merely preferred embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included in the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. A lanthanum ion-doped stable polyoxometalate for catalytic production of quinazoline compounds under alkaline conditions, characterized in that: The lanthanum ion doped stable polyoxometalate comprises: [CH3NH3]6{La(H2O)3Na[Mo6O 12 (OH)3(HPO3)4]2}·10H2O and [CH3NH3]5{La2(H2O)8Na[Mo6O 12 One of (OH)3(HPO3)3(PO4)]2}·16H2O.

2. The use of the lanthanum ion-doped stable polyoxometalate according to claim 1 in catalyzing the production of quinazoline compounds under alkaline conditions, characterized in that: The preparation method of the lanthanum ion-doped stable polyoxometalate comprises the following steps: using hydrogen phosphite as a template, lanthanum ions as a doping element, cations and polymolybdate as raw materials, and performing a hydrothermal reaction under the action of a reducing agent to obtain the lanthanum ion-doped stable polyoxometalate; Wherein, the reducing agent is NH2NH2·HCl or Na2S2O3; and / or, The cation is CH3NH2·HCl; and / or, The polymolybdate is Na2MoO4·2H2O or (NH4)6[Mo7O 24 ]·4H2O.

3. The use of the lanthanum ion-doped stable polyoxometalate according to claim 2 in catalyzing the production of quinazoline compounds under alkaline conditions, characterized in that: The hydrothermal reaction was carried out at 80° C. for 48 h.

4. The use of the lanthanum ion-doped stable polyoxometalate according to claim 2 in catalyzing the production of quinazoline compounds under alkaline conditions, characterized in that: The [CH3NH3]6{La(H2O)3Na[Mo6O 12 The specific preparation steps of [OH)3(HPO3)4]2}·10H2O include: adding Na2MoO4·2H2O, LaCl3·6H2O and CH3NH2·HCl into water according to the stoichiometric ratio, stirring at room temperature, adjusting the pH of the resulting solution to acidic with H3PO3, and then adding NH2NH2·HCl to carry out hydrothermal reaction to obtain brown block crystals, namely [CH3NH3]6{La(H2O)3Na[Mo6O 12 (OH)3(HPO3)4]2}·10H2O.

5. The use of the lanthanum ion-doped stable polyoxometalate according to claim 2 in catalyzing the production of quinazoline compounds under alkaline conditions, characterized in that: The [CH3NH3]5{La2(H2O)8Na[Mo6O 12 The specific preparation steps include: adding Na2MoO4·2H2O, LaCl3·6H2O and CH3NH2·HCl into water according to the stoichiometric ratio, stirring at room temperature, adjusting the pH of the resulting solution to acidic with H3PO3, and then adding Na2S2O3 to carry out hydrothermal reaction to obtain brown block crystals, namely [CH3NH3]5{La2(H2O)8Na[Mo6O 12 (OH)3(HPO3)3(PO4)]2}·16H2O.

6. Use of the lanthanum ion-doped stable polyoxometalate according to any one of claims 4 to 5 in catalyzing the production of quinazoline compounds under alkaline conditions, characterized in that: The pH of the resulting solution was adjusted to acidic, specifically to pH=1.3, using H3PO3.

7. A method for preparing a quinazoline compound, characterized in that: Under alkaline conditions, the lanthanum ion-doped stable polyoxometalate described in any one of claims 1 to 6 is used as a catalyst to catalyze the reaction of alcohol with a benzonitrile derivative to produce a quinazoline compound.

8. The method for preparing quinazoline compounds according to claim 7, wherein The molar ratio of the catalyst to the benzonitrile derivative is 1:

2.

9. The method for preparing a quinazoline compound according to claim 7, wherein The reaction temperature is 95° C. and the reaction time is 24 h.

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