Application of lanthanum ion-doped stable polyoxometallate in catalytic synthesis of quinazoline compound and preparation method of quinazoline compound

Abstract

The invention provides application of lanthanum ion doped stable polyoxometallate in catalytic synthesis of a quinazoline compound and a preparation method of the quinazoline compound, and belongs to the technical field of catalysts. According to the invention, phosphorous acid is taken as a template, three kinds of lanthanum-containing phosphomolybdic acid are synthesized, sodium ions are regulated and controlled in the synthesis process, lanthanum ion doped stable polyoxometallate with different three-dimensional configurations is obtained, and the lanthanum ion doped stable polyoxometallate comprises one of [CH3NH3] 6 {La (H2O) 3Na [Mo6O12 (OH) 3 (HPO3) 4] 2}. 10H2O, [CH3NH3] 2 {La (H2O) [Mo6O15 (HPO3) 4]}. 8H2O and [CH3NH3] 5 {La2 (H2O) 8Na [Mo6O12 (OH) 3 (HPO3) 3 (PO4) 2}. 16H2O. The three kinds of stable polyoxometallate doped with lanthanum ions have good stability under the alkaline condition, 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 particularly relates to the application of lanthanum ion-doped and stabilized polyoxometalates in the catalytic synthesis of quinazoline compounds and a preparation method of quinazoline compounds. Background Art

[0002] Quinazoline, as an important class of heterocyclic compounds, is a very important structural unit in natural products and the chemical industry. They are widely used in the fields of cosmetics and pesticides, especially in the pharmaceutical field. In the pharmaceutical field, quinazoline compounds exhibit significant anti-cancer and antibacterial properties. In recent years, significant progress has been made in the synthesis of quinazoline. Although classical synthesis methods can effectively prepare quinazoline, the cumbersome reaction steps and complex product separation processes pose challenges to these reaction modes. Therefore, developing 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 quinazoline. Compared with metal complexes, cluster catalysts have obvious advantages. Especially polyoxometalates (POMs), as a special class of metal oxide clusters, are constructed from MO x (x = 5 or 6; M = molybdenum (Mo), tungsten (W), vanadium (V), etc.), have more metal active sites and a relatively simple synthesis process, thus showing excellent catalytic activity. However, the main structure of polyoxometalates is usually formed by the acidification and condensation reaction of metal oxides, and its functional fragments generally have acid resistance but are unstable under alkaline conditions. And the reaction system for the formation of quinazoline by alcohol dehydrogenation coupling requires the addition of a base to catalyze the reaction. Therefore, the design and synthesis of alkali-resistant polyoxometalates (POMs) are still a challenge. Summary of the Invention

[0003] Aiming at the above technical problems, the present invention provides an application of lanthanum ion-doped and stabilized polyoxometalates in the catalytic synthesis of quinazoline compounds and a preparation method of quinazoline compounds.

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

[0005] One object of the present invention is to provide an application of lanthanum ion-doped and stabilized polyoxometalates in the catalytic generation of quinazoline compounds under alkaline conditions. The lanthanum ion-doped and stabilized 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 One of (OH)3(HPO3)3(PO4)]2}·16H2O.

[0006] Optionally, the preparation method of the lanthanum ion-doped and stabilized polyoxometalate includes the following steps: using hydrogen phosphite as a template, lanthanum ions as a doping element, cations and polymolybdates as raw materials, and under the action of a reducing agent, performing a hydrothermal reaction to obtain a lanthanum ion-doped and stabilized 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 and stabilized polyoxometalate is [CH3NH3]2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O.

[0011] Furthermore, the conditions of the hydrothermal reaction are to react at 80 °C for 48 h. If the reaction temperature is too high or too low, it will cause the product morphology to be incomplete and affect the later performance. Therefore, it is preferably to react at 80 °C for 48 h.

[0012] Furthermore, the specific preparation steps of [CH3NH3]6{La(H2O)3Na[Mo6O 12 (OH)3(HPO3)4]2}·10H2O include: according to the stoichiometric ratio, adding Na2MoO4·2H2O, LaCl3·6H2O and CH3NH2·HCl into water, stirring at room temperature, adjusting the pH of the obtained 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] Further, the dosage ratio of Na2MoO4·2H2O, LaCl3·6H2O, CH3NH2·HCl, NH2NH2·HCl and water is 0.4 g∶0.2 g∶0.8 g∶0.1 g∶40 mL; and / or,

[0014] The acidity refers to pH = 1.3.

[0015] Further, the specific preparation steps of [CH3NH3]2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O include: according to the stoichiometric ratio, adding (NH4)5[Mo7O 24 ·4H2O, LaCl3·6H2O and CH3NH2·HCl into water, stirring at room temperature, adjusting the pH of the obtained solution to acidity with H3PO3, then adding NH2NH2·HCl, heating and reacting to obtain brown needle-like crystals, namely [CH3NH3]2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O.

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

[0017] The acidity refers to pH = 1.3.

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

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

[0020] The acidity refers to pH = 1.3.

[0021] A second object of the present invention is to provide a method for preparing quinazoline compounds. Under alkaline conditions, the lanthanum ion-doped and stabilized polyoxometalate is used as a catalyst to catalyze the reaction of an alcohol with a benzonitrile derivative to form a 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 substrate alcohol and benzonitrile derivative are as follows:

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

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

[0024] Further, the temperature of the reaction 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 for the first time uses the hydrothermal method with phosphite as a 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). Their structures were comprehensively characterized, and it was found that the diverse coordination modes of lanthanum elements and the partial oxidation of phosphite to phosphate in Compound 3 created their unique structural features. At the same time, when the three compounds were used as catalysts for the reaction of alcohol with ketone to form quinazoline under alkaline conditions, they exhibited excellent catalytic performance and stability. The present invention not only enriches the family of hourglass-shaped polyoxometalates but also expands their catalytic applications under alkaline conditions, providing important value for the efficient synthesis of quinazoline compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The drawings constituting a part of the present invention are used to provide a further understanding of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation to the present invention. In the drawings:

[0028] Figure 1For the structures 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 For the structures of the {P4Mo6} unit in Example 2 (a), the coordination situation of one La 3+ ion (b), the coordination environment of {P4Mo6} (c), and the three-dimensional structure of Compound 2 (d);

[0030] Figure 3 For the differences in the {P4Mo6} units between Compound 1 and Compound 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 For the thermogravimetric analysis (TGA) curve of Compound 1;

[0032] Figure 5 For the thermogravimetric analysis (TGA) curve of Compound 2;

[0033] Figure 6 For the thermogravimetric analysis (TGA) curve of Compound 3;

[0034] Figure 7 For the proton-decoupled 31 P nuclear magnetic resonance spectra of Compound 1, Compound 2, Compound 3, phosphoric acid (H3PO4), and phosphorous acid (H3PO3) dissolved in heavy water (D2O);

[0035] Figure 8 For the PXRD patterns of Compound 1 under alkaline conditions at different concentrations;

[0036] Figure 9 For the PXRD patterns of Compound 2 under alkaline conditions at different concentrations;

[0037] Figure 10 For the PXRD patterns of Compound 3 under alkaline conditions at different concentrations;

[0038] Figure 11 For the conversion rate of Compound 2 cycled 5 times under the conditions of Application Example 1;

[0039] Figure 12 For the speculative mechanism of synthesizing phenylquinazoline. Detailed implementation manners

[0040] The various exemplary embodiments of the present invention will be described in detail. This detailed description should not be construed as a limitation on 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 used in the present invention are only for describing specific embodiments and are not intended to limit the present invention. Additionally, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0042] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention pertains. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation 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 related to the documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0043] Without departing from the scope or spirit of the present invention, various improvements and changes can be made to the specific embodiments of the present invention specification, which are obvious to those skilled in the art. Other embodiments obtained from the specification of the present invention are obvious to those skilled in the art. The specification and examples of the present invention are merely exemplary.

[0044] Regarding the use of "comprising", "including", "having", "containing", etc. herein, they are all open-ended terms, meaning including but not limited to.

[0045] Generally, phosphate / phosphite templates are used to regulate the structure of polyoxometalates (POMs). The researchers of the present invention explored the assembly of phosphites during the synthesis of molybdenum-based polyoxometalates. Through microwave-assisted synthesis, a sandglass-shaped {M[P4Mo6]2} structure was successfully developed. This structure is characterized by a central metal ion connecting two {P4Mo6} units. Due to the molybdenum atoms being in the +5 oxidation state, it has excellent redox activity and exhibits stability in heterogeneous catalysis, photocatalysis, biological applications, electrochemical processes, etc. Generally, the central metal ion between the two {P4Mo6} units is sodium ion (Na + )、potassium ion (K + )、aluminum ion (Al 3+) and so on, presenting a six - coordinate geometric configuration. In addition, the exposed oxygen atoms on the phosphorous acid in the hourglass - shaped {M[P4Mo6]2} structure can serve as potential connection sites for further connection with other metals (such as first - row transition metals), thus forming a multi - dimensional structure. Compared with first - row transition metals, lanthanide metals have more excellent catalytic activities, and due to their diverse coordination modes and strong oxygen - philicity, they can serve as excellent connectors for linking polyoxometalate units, and then form lanthanide - substituted polyoxometalates. However, there is no relevant report on using lanthanide metals to connect hourglass - shaped polyoxometalates. Therefore, the present invention provides a lanthanum - ion - doped stable polyoxometalate, its preparation method and application. Using hydrogen phosphite (HPO3 2- ) as a template, three kinds of lanthanum - ion - doped stable phosphomolybdic acids were synthesized, and their 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). Structure analysis shows that Compound 1 is connected through lanthanum ions (La 3+ ) to the hourglass - shaped {Na[P4Mo6O 27 2} unit to form a three - dimensional structure. Compound 2 has porous channels and forms a three - dimensional structure by the same {P4Mo6O 27} structural units. When the synthetic micro - environment is adjusted by changing the type of reducing agent, some hypophosphite groups in the structural units are oxidized, thus changing the structure and forming Compound 3. All three compounds have alkali resistance and are catalytically active for the reaction of converting 2 - aminobenzyl alcohol and benzonitrile into 2 - phenylquinazoline. Among them, the catalytic conversion rate of Compound 2 is the highest, reaching 91.7%, far superior to the classical Keggin - type {PMo 12} and inorganic CaMoO4, which indicates the synergistic catalytic effect of molybdenum (Mo) and lanthanum (La) centers. In addition, Compound 2 shows good activity and reliability in catalyzing the same type of reactions of different substrates.

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

[0047] The technical solutions of the present invention are further described below through examples.

[0048] In the following examples:

[0049] 1. Unless otherwise stated, all other reagents are of analytical grade and can be 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 with a scanning rate of 5° / min.

[0051] 3. Thermogravimetry-differential scanning calorimetry (TGA-DSC) was carried out on a TA Q600 instrument. Under flowing nitrogen, the temperature was set in the range of 30 °C to 800 °C, the heating rate was 10 °C / min, and the nitrogen flow rate was 25 mL / min.

[0052] 4. Fourier transform infrared spectroscopy (FT-IR) was collected on a Bruker Vertex 70 spectrometer by the KBr pellet method.

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

[0054] 6. Nuclear magnetic resonance (NMR) spectra were recorded on a Bruker Avance 400 MHz spectrometer using deuterated reagents with tetramethylsilane as the internal standard.

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

[0056] 8. Absorption corrections were performed using the multi-scan technique.

[0057] 9. The structure was solved by direct methods using the ShelXT structure solution program with the Olex2 software and refined by least-squares methods using the ShelXL refinement software package. The crystal 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 Synthesis: Add 0.4 g of Na2MoO4·2H2O, 0.2 g of LaCl3·6H2O, and 0.8 g of CH3NH2·HCl to 40 mL of water. Stir for 30 min at room temperature. Adjust the pH of the resulting solution to 1.3 using H3PO3. Then add 0.1 g of NH2NH2·HCl. Transfer the obtained mixed solution to a stainless-steel autoclave lined with polytetrafluoroethylene and react 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 is 73.2%. 31 PNMR (ppm): 3.15. FT-IR (KBr, cm -1 ) : 492 (strong peak), 572 (weak peak), 727 (medium-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: Measured value (calculated value) %, for Compound 1 (C6H 76 LaMo 12 N6NaO 67 P8), the carbon content is 2.45 (2.51); the hydrogen content is 2.61 (2.65); the nitrogen content is 2.90 (2.93).

[0060] Example 2

[0061] Synthesis of [CH3NH3]2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O: Add 0.4 g of (NH4)5[Mo7O 24 ·4H2O, 0.2 g of LaCl3·6H2O, and 0.8 g of CH3NH2·HCl to 40 mL of water. Stir for 30 min at room temperature. Adjust the pH of the resulting solution to 1.3 using H3PO3. Then add 0.1 g of NH2NH2·HCl. Transfer the obtained mixed solution to a stainless-steel autoclave lined with polytetrafluoroethylene and react at 80 °C for 48 h to obtain brown needle crystals, namely [CH3NH3]2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O (denoted as Compound 2). The yield based on molybdenum is 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: measured value (calculated value) %, 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] Synthesis of [CH3NH3]5{La2(H2O)8Na[Mo6O 12 (OH)3(HPO3)3(PO4)]2}·16H2O: Add 0.4 g of Na2MoO4·2H2O, 0.2 g of LaCl3·6H2O, and 0.8 g of CH3NH2·HCl to 40 mL of water, stir at room temperature for 30 min, adjust the pH of the resulting solution to 1.3 using H3PO3, then add 0.1 g of Na2S2O3, transfer the obtained mixed solution to a stainless-steel autoclave lined with polytetrafluoroethylene, react 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 is 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: measured value (calculated value) %, 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 1Structures of the {P4Mo6} unit (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) in Example 1. For clarity, some hydrogen atoms have been omitted. Single-crystal X-ray diffraction (SCXRD) analysis indicates that Compound 1 belongs to the hexagonal crystal system, with the space group 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 (bridging oxygen) atoms, six Ot (terminal oxygen) atoms, and three HPO3 2- anions. These octahedra are arranged around a phosphite ligand by sharing two oxygen atoms, forming a cyclic {P4Mo6} structure ((a) in Figure 1 ). The six Mo centers are in the same plane, with HPO3 2- on one side, while one Na + ion coordinates with three μ2-O ligands on the other side. The Na + ion also coordinates with three μ2-O ligands in the adjacent {P4Mo6} unit, forming an hourglass-shaped {Na[P4Mo6]2} dimer ((b) in Figure 1 ). In addition, the {P4Mo6} unit is connected to three La atoms through HPO3 2- ligands ((c) in Figure 1 ). This coordination mode forms a three-dimensional network structure in which the {Na[P4Mo6]2} dimers are interconnected by La 3+ ions ((d) in Figure 1 ).

[0065] Figure 2 Structures of the {P4Mo6} unit (a), the coordination of one La 3+ ion (b), the coordination environment of {P4Mo6} (c), and the three-dimensional structure of Compound 2 (d) in Example 2. For clarity, some hydrogen atoms have been omitted. The blue octahedra represent MoO6; the cyan polyhedra represent LaO9. Blue represents molybdenum (Mo); brown represents lanthanum (La); red represents oxygen (O); pink represents phosphorus (P); gray represents hydrogen (H). Single-crystal X-ray diffraction (SCXRD) analysis indicates that Compound 2 belongs to the hexagonal crystal system, with the space group P63 / m. Similar to Compound 1, the {P4Mo6} unit consists of six {MoO6} octahedra and four HPO3 2- anions. However, in the absence of Na + , three μ2-O atoms on one side of the Mo plane coordinate directly with La ((b) in Figure 2(a) in it. Since La 3+ has a larger atomic radius than the first transition series metals and more diverse coordination modes, it does not form a hourglass-like structure. Instead, La 3+ exhibits a seven-coordination mode, coordinating with three μ2-O atoms of a {P4Mo6} unit, one water molecule, and three oxygen atoms in the phosphite groups of three {P4Mo6} units ( Figure 2 (b) in it. Since La 3+ cannot fit well into the cavity in the structure, it crystallizes in a disordered mode, with each {P4Mo6} unit connected to four La 3+ atoms, one through μ2-O coordination and the other three through HPO3 2- anions ( Figure 2 (c) in it. This coordination mode forms a three-dimensional structure through the interaction between the {P4Mo6} unit and La 3+ ions ( Figure 2 (d) in it).

[0066] Figure 3 are the differences of the {P4Mo6} units in Compound 1 and Compound 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. The blue octahedra represent MoO6; the cyan polyhedra represent LaO9. Blue represents molybdenum (Mo); brown represents lanthanum (La); cyan represents sodium (Na); red represents oxygen (O); pink represents phosphorus (P); gray represents hydrogen (H). Single-crystal X-ray diffraction (SCXRD) analysis shows that when changing the reducing agent in the system, Compound 3 can be isolated, which belongs to the triclinic system with the space group P-1. Similar to Compound 1, Compound 3 contains a {Na[P4Mo6]2} dimer, and the Mo-Mo bond length and Na-O bond length are comparable to those in Compound 1. Due to the change in the microenvironment, the central ligand of the six Mo centers unexpectedly changes from HPO3 2- to PO4 3+ , while the remaining three ligands are still HPO3 2- ( Figure 3 (a) in it). It is worth noting that different from the C3 symmetry of Compound 1, the {P4Mo6} unit in Compound 3 exhibits Cs symmetry. This change is mainly attributed to the coordination of La with HPO3 2- and PO4 3+ ( Figure 3 (b) in it). This coordination mode causes the distortion of HPO3 2- , thus reducing the symmetry. The remaining two HPO32- Each ligand coordinates with two La atoms ( Figure 3 (c) in Figure 3 ). Different from Compound 2, Compound 3 forms a two-dimensional coordination network ( 3+ ). This oxidation process may be due to the oxidation by O2 in the air as an oxidant. Experiments show that when oxygen is excluded during the synthesis, a structure containing PO4

[0067] Figure 4 is not obtained. Figure 5 is the thermogravimetric analysis (TGA) curve of Compound 1, Figure 6 is the thermogravimetric analysis (TGA) curve of Compound 2, Figures 4 - 6 is the thermogravimetric analysis (TGA) curve of Compound 3. It can be seen from 12 that Compounds 1, 2, and 3 show similar weight loss stages. The first stage corresponds to the loss of crystal water. According to the thermogravimetric analysis results, the determined structural formulas are [CH3NH3]6{La(H2O)3Na[Mo6O 15 (OH)3(HPO3)4]2}·10H2O, [CH3NH3]2{La(H2O)[Mo6O 12 (HPO3)4]}·8H2O, and [CH3NH3]5{La2(H2O)8Na[Mo6O

[0068] Figure 7 are the proton-decoupled 31 31P nuclear magnetic resonance spectra of Compounds 1, 2, and 3, phosphoric acid (H3PO4), and phosphorous acid (H3PO3) dissolved in heavy water (D2O). As Figure 7 shown, the 31P nuclear magnetic resonance signals of phosphoric acid (H3PO4) and phosphorous acid (H3PO3) are located at -0.03 ppm and 4.69 ppm, respectively. In Compound 1, a single nuclear magnetic resonance peak is observed at 3.15 ppm, corresponding to HPO3 2- , and there is no sign of phosphonate groups, indicating that the peak shift is caused by the coordination of HPO3 2- with molybdenum and lanthanum. Similar results are also observed for Compound 2. However, in Compound 3, in addition to the peak of HPO3 2- at 3.25 ppm, an additional peak is detected at -0.07 ppm, corresponding to PO4 3+ . This confirms that during the synthesis, the [PO3] 3- part is partially oxidized to PO4 3+The differences in the positions of the nuclear magnetic resonance peaks in Compound 1, Compound 2, and Compound 3 are attributed to the different chemical coordination environments of the phosphorus atoms.

[0069] Application Example 1

[0070] Compound 1, Compound 2, or Compound 3 was used as a catalyst for the synthesis of quinazoline derivatives, and 2-aminobenzyl alcohol and benzonitrile were 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), and 6.6×10 -3 of Compound 2 were added to 2 mL of tert-butanol (t-BuOH), and the reaction was carried out at 95 °C for 24 hours to produce 2-phenylquinazoline with a conversion rate of 91.7%.

[0073] Application Examples 2 - 13

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

[0075] Table 1 Optimization of reaction conditions

[0076] Item Catalyst Base 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[Potassium carbonate]]> 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 Determined by nuclear magnetic resonance hydrogen spectrum ( 1 HNMR); DMF c is dimethylformamide; THF d is tetrahydrofuran; " / " indicates not added; "{PMo 12}" refers to [NH2(CH3)2]3[PMo 12 O 40 .

[0078] As can be seen from Table 1, although both Compound 2 and the base played a catalytic role during the reaction, the reaction could not be catalyzed without adding the base or Compound 2 (Application Examples 2 - 3). Replacing potassium tert - butoxide with potassium hydroxide (KOH), potassium carbonate (K2CO3), or sodium hydroxide (NaOH) led to a decrease in conversion rate (Application Examples 4 - 6), indicating that Compound 2 could only improve the catalytic efficiency when acting 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 confirmed that tert - butanol was the optimal solvent. In addition, in Application Example 1, after reacting at 95 °C for 10 hours, the reaction mixture was filtered and the catalyst was removed, and it was found that no further conversion occurred in the reaction, indicating that this 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 more excellent catalytic activity, indicating the influence of structural differences on catalytic efficiency. For comparison, lanthanum chloride (LaCl3) and {PMo 12} were also used as catalysts for evaluation (Application Examples 12 - 13). Both showed catalytic activity, indicating that lanthanum and molybdenum could each serve as catalytic centers. In Compound 2, their combination produced a synergistic catalytic effect, improving the overall catalytic activity. This was also the first time that polyoxometalates (POMs) were used as catalysts to convert aminobenzyl alcohol and benzonitrile into phenylquinazoline.

[0079] Application Example 14

[0080] To verify the stability of Compound 1 under different alkaline conditions, the specific steps were as follows: Dissolve 20 mg of Compound 1 in 10 mL of tert - butanol, and then use potassium tert - butoxide and HCl 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 the xrd before and after standing for 12 h to observe whether Compound 1 changes).

[0081] Application Example 15

[0082] To verify the stability of Compound 2 under different alkaline conditions, the specific steps were as follows: Dissolve 20 mg of Compound 2 in 10 mL of tert - butanol, and then use potassium tert - butoxide and HCl 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 the xrd before and after standing for 12 h to observe whether Compound 1 changes).

[0083] Application Example 16

[0084] Verify the stability of Compound 3 under different alkaline conditions. The specific steps are as follows: Dissolve 20 mg of Compound 3 in 10 mL of tert-butanol, and then use potassium tert-butoxide and HCl 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 (in the actual experiment, let it stand for 12 h, measure the XRD before and after the reaction, and observe whether Compound 1 changes).

[0085] Figure 8 is the PXRD pattern of Compound 1 under different concentrations of alkaline conditions, Figure 9 is the PXRD pattern of Compound 2 under different concentrations of alkaline conditions, Figure 10 is the PXRD pattern of Compound 3 under different concentrations of alkaline conditions. From Figures 8 - 10 it can be seen that Compound 1, Compound 2, and Compound 3 all remain stable after being stirred in tert-butanol solution containing different concentrations of potassium tert-butoxide for 24 hours. When the pK a value of the solution is higher than 13, Compound 3 becomes unstable. This is also because Compound 3 decomposes partially under alkaline conditions, resulting in a lower catalytic efficiency.

[0086] Perform 5 cycles of Compound 2 under the conditions of Application Example 1 to test the catalytic stability of Compound 2. Figure 11 is the conversion rate of Compound 2 after 5 cycles under the conditions of Application Example 1. It can be seen that Compound 2 still has high catalytic stability after 5 cycles.

[0087] Application Example 17

[0088] Use different substrates to test Compound 2. The experimental method is the same as that in Application Example 1. The reaction substrates, reaction general formula, and product structures are as follows:

[0089]

[0090] It can be seen that except for products c3 and c5 with lower yields due to the presence of electron-withdrawing groups and steric hindrance, the yields of other products all exceed 90%, indicating that Compound 2 has excellent catalytic effects on various catalytic substrates.

[0091] Furthermore, based on the control experiment, 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 the coordination mode of lanthanum plays an important role. In contrast, sodium chloride (NaCl) does not show catalytic activity, indicating that sodium ions (Na +) makes no contribution to this 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}. Then, the intermediate undergoes a β-elimination reaction to generate a carbonyl intermediate and regenerate compound 2. Meanwhile, the base promotes the hydration of benzonitrile, resulting in 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, in this invention, phosphorous acid was used as a template to synthesize three lanthanum-containing phosphomolybdic acids. By regulating sodium ions (Na + ) during the synthesis process, compounds 1 and 2 with different three-dimensional configurations were obtained. During the synthesis process, by changing the reducing ability of the reducing agent, compound 3 with partial characteristics of phosphorous acid was obtained. This provides a new synthesis method for synthesizing polyoxometalates (POMs) 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. This 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 synthesizing polyoxometalate-based catalysts with high efficiency and stability under alkaline conditions.

[0093] The above is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention should be covered by the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.

Claims

1. Use of a lanthanum ion-doped and stabilized polyoxometalate in the catalytic production of quinazoline compounds under alkaline conditions, characterized in that, The lanthanum ion-doped and stabilized polyoxometalate includes one of the following: [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.

2. Use of the lanthanum ion-doped and stabilized polyoxometalate in the catalytic production of quinazoline compounds under alkaline conditions, characterized in that, The preparation method of the lanthanum ion-doped and stabilized polyoxometalate comprises the following steps: using hydrogen phosphite as a template, lanthanum ions as doping elements, cations and polymolybdates as raw materials, and carrying out a hydrothermal reaction under the action of a reducing agent to obtain the lanthanum ion-doped and stabilized 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)5[Mo7O 24 ·4H2O.

3. Use of the lanthanide ion-doped and stabilized polyoxometalate according to claim 1 in the catalytic production of quinazoline compounds under alkaline conditions, characterized in that, the conditions of the hydrothermal reaction are reacting at 80 °C for 48 h.

4. Use of the lanthanide ion-doped and stabilized polyoxometalate according to claim 2 in the catalytic production of quinazoline compounds under alkaline conditions, characterized in that, The specific preparation steps of [[CH3NH3]]6{La(H2O)3Na[Mo6O 12 (OH)3(HPO3)4]2}·10H2O are as follows: According to the stoichiometric ratio, add Na2MoO4·2H2O, LaCl3·6H2O, and CH3NH2·HCl into water, stir at room temperature, adjust the pH of the obtained solution to acidic with H3PO3, then add NH2NH2·HCl, and carry out a hydrothermal reaction to obtain brown block crystals, namely [[CH3NH3]]6{La(H2O)3Na[Mo6O 12 (OH)3(HPO3)4]2}·10H2O.

5. Use of the lanthanum ion-doped and stabilized polyoxometalate in the catalytic production of quinazoline compounds under alkaline conditions, characterized in that, The specific preparation steps of [(CH3NH3)2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O] are as follows: According to the stoichiometric ratio, (NH4)5[Mo7O 24 ·4H2O, LaCl3·6H2O, and CH3NH2·HCl are added to water, stirred at room temperature, the pH of the resulting solution is adjusted to acidic with H3PO3, and then NH2NH2·HCl is added for hydrothermal reaction to obtain brown needle-like crystals, namely [(CH3NH3)2{La(H2O)[Mo6O 15 (HPO3)4]}·8H2O].

6. Use of the lanthanide ion-doped and stabilized polyoxometalate according to claim 2 in the catalytic production of quinazoline compounds under alkaline conditions, characterized in that, The specific preparation steps of [[CH3NH3]5{La2(H2O)8Na[Mo6O 12 (OH)3(HPO3)3(PO4)]2}·16H2O are as follows: According to the stoichiometric ratio, Na2MoO4·2H2O, LaCl3·6H2O and CH3NH2·HCl are added to water, stirred at room temperature, the pH of the resulting solution is adjusted to acidic with H3PO3, then Na2S2O3 is added, and a hydrothermal reaction is carried out to obtain brown block crystals, namely [[CH3NH3]5{La2(H2O)8Na[Mo6O 12 (OH)3(HPO3)3(PO4)]2}·16H2O.

7. The application of the lanthanum ion-doped and stabilized polyoxometalate according to any one of claims 4 to 6 in the catalytic generation of quinazoline compounds under alkaline conditions, characterized in that, Adjusting the pH of the obtained solution to acidic by using H3PO3 specifically means adjusting it to pH = 1.

3.

8. A method for preparing a quinazoline compound, characterized in that, Under alkaline conditions, using the lanthanum ion-doped and stabilized polyoxometalate in the application according to any one of claims 1-7 as a catalyst to catalyze the reaction of an alcohol and a benzonitrile derivative to generate a quinazoline compound.

9. The preparation method of the quinazoline compound according to claim 8, characterized in that, The molar ratio of the catalyst to the benzonitrile derivative is 1:

2.

10. The preparation method of the quinazoline compound according to claim 8, characterized in that, The temperature of the reaction is 95 °C and the reaction time is 24 h.

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