Metal organic tetrahedral cage compound and preparation method and application thereof

Abstract

The invention discloses a metal organic tetrahedron cage compound and a preparation method and application thereof, and belongs to the technical field of fine chemical engineering. The metal organic tetrahedron caged compound is obtained by taking Ce < 3 + > in rare earth metal cerium salt as a node and H4BPDS as a ligand through reaction. The prepared metal organic tetrahedron cage-shaped compound is low in raw material price and high in yield, the obtained compound is stable in chemical property, and aryl iodide and aryl sulfinate can be efficiently catalyzed to react to prepare the diaryl sulfone derivative under the condition of mild illumination. When the catalyst is used for catalyzing the reaction of preparing 4-bromophenyl-4-methyl phenyl sulfone from 4-bromo iodobenzene and 4-methyl benzene sulfinic acid sodium salt, preparing 3-bromophenyl-4-methyl phenyl sulfone from 3-bromo iodobenzene and 4-methyl benzene sulfinic acid sodium salt, and preparing 4-bromo-3-fluorophenyl-4-methyl phenyl sulfone from 4-bromo-3-fluoroiodobenzene and 4-methyl benzene sulfinic acid sodium salt, the highest yield can reach 95%.

Description

Technical Field

[0001] The invention relates to a metal organic tetrahedral cage compound and a preparation method and application thereof, belonging to the technical field of fine chemical industry. Background Art

[0002] Sulfone compounds are common organic intermediates that play an important role in organic chemistry and medicinal chemistry. They have good biological activity and are widely used in chemical engineering, pharmaceutical pesticides, materials science and other fields. In terms of drugs, the antibiotic thiamphenicol, the antipsychotic drug amisulpride, and the anti-migraine drug eletriptan all contain sulfone structural units. Sulfone compounds are also used as androgen inhibitors and protease inhibitors, such as the non-steroidal anti-androgen drug carlutamide and the protein inhibitor anti-HIV drug tipranavir. Sulfone derivatives have high antibacterial activity and are often used in insect control and weed control. For example, aldicarb is an insecticide effective against aphids and leaf-feeding pests, and mesotrione is a benzoylcyclohexanedione herbicide that is selective for corn crops. In addition, the conjugated aryl sulfone has special photophysical properties and has broad application prospects in organic light-emitting diode materials.

[0003] Among sulfone compounds, diaryl sulfones are important small molecule structures for drugs, such as dapsone for the treatment of leprosy. Current methods for the synthesis of aryl sulfones include oxidation of sulfides / sulfoxides, Friedel-Crafts-type sulfonylation of aromatics, insertion of sulfur dioxide, addition of sulfinates to alkynes / olefins, and cross-coupling of sulfinates with alkyl / aryl halides. These methods have significant disadvantages, such as the use of odorous thiols and toxic sulfur dioxide, stoichiometric oxidants, sulfonylating agents that are highly sensitive to air and moisture, harsh acidic treatments, and high reaction temperatures, which limit functional group tolerance and substrate scope. Transition metal photocatalytic systems are a mild and effective platform for the synthesis of diaryl sulfone cross-coupling reactions, but they usually require the use of toxic noble metal photosensitizers and complex and difficult-to-synthesize photoactive ligands to achieve photoconversion functions. In summary, the existing methods for synthesizing aromatic sulfones have certain limitations in industrialization, such as harsh reaction conditions that cause high damage and corrosion rates to equipment, high production input costs, and environmental unfriendliness. Summary of the invention

[0004] In order to overcome the deficiencies in the prior art, the present invention aims to provide a metal organic tetrahedral cage compound and a preparation method and application thereof. The metal organic tetrahedral cage compound retains the 2,2'-bipyridine group and can construct an isolated copper (I) catalytic site by coordinating with transition metal copper (I). The spatial configuration of the metal organic tetrahedral cage compound can stabilize the copper (I) active center, avoid inactivation of the intermolecular pathway, and allow the copper (I) active center to retain accessible sites for direct interaction with substrates and intermediates. The metal organic tetrahedral cage compound is combined with transition metal copper (I) to generate a copper (I) photocatalyst in situ, and the aryl iodide and aryl sulfinate are reacted through C(sp 2 )-S cross-coupling to prepare sulfone.

[0005] In order to achieve the above-mentioned invention purpose and solve the problems existing in the prior art, the technical solution adopted by the present invention is: a metal organic tetrahedral cage compound, with trivalent cerium as a node and H4BPDS as a ligand coordinated into a tetrahedral structure:

[0006]

[0007] Each end of the ligand H4BPDS is coordinated to the metal cerium through two oxygens and one double-bonded nitrogen.

[0008] Specifically, the structure of the metal organic tetrahedral cage compound is as follows:

[0009]

[0010] Among them, trivalent cerium is located at the four vertices of the tetrahedron, and each edge in the tetrahedron structure represents a ligand H4BPDS. The two ends of the ligand H4BPDS are coordinated with the metal cerium through two oxygens and a double-bonded nitrogen respectively.

[0011] A method for preparing a metal organic tetrahedral cage compound using Ce in a rare earth metal cerium salt 3+ As a node, L is used as a ligand to react to prepare a metal organic tetrahedral cage compound, and its synthesis route is as follows:

[0012] Ce 3+ +L→Ce-L.

[0013] The rare earth metal salt is selected from cerium chloride heptahydrate or cerium nitrate hexahydrate;

[0014] The ligand L (H4BPDS) has the following molecular structure,

[0015]

[0016] A specific method for preparing a metal organic tetrahedral cage compound comprises reacting a ligand H4BPDS, a base and a cerium salt in an organic solvent under stirring at room temperature to obtain the compound.

[0017] Specifically, the base is selected from at least one of sodium hydroxide, potassium hydroxide, sodium carbonate, triethylamine, and 2,6-lutidine.

[0018] Specifically, the molar ratio of the ligand H4BPDS, the base and the cerium salt is 1:2:1 to 1.5;

[0019] Specifically, the organic solvent is a mixed solvent of methanol and N,N-dimethylformamide or N,N-dimethylacetamide in a volume ratio of 1 to 2:10; the reaction time is 1 to 2 hours.

[0020] Specifically, after the reaction is completed, the filtrate is filtered, and the filtrate is divided into containers sealed with plastic wrap, and diffused in an ether environment for 5 to 7 days to precipitate square crystals to obtain the compound.

[0021] A specific method for preparing a metal organic tetrahedral cage compound comprises the following steps:

[0022] Step 1, add 5,5'-dimethyl-2,2'-bipyridine and potassium permanganate in a molar ratio of 1:6-7 to 50-70 mL of water, and stir at 110-120° C. for 2-3 hours. Cool the reaction mixture to room temperature, filter it with diatomaceous earth, acidify the filtrate with 8-10 mL of concentrated hydrochloric acid, and a white solid precipitate appears. Then, filter it with suction, wash the filter cake with 60-80 mL of water, and vacuum dry it to obtain a white solid;

[0023] Step 2: Add the white solid obtained in step 1 to 80-100 mL of anhydrous ethanol, slowly drop 1-2 mL of concentrated sulfuric acid, and reflux and stir at 75-85°C for 20-24 hours. Cool the reaction mixture to room temperature and neutralize it with saturated NaHCO3 solution to pH = 6-7. Then add 80-100 mL of water and extract with 150-200 mL of dichloromethane. Dry the combined organic layer with anhydrous Na2SO4, vacuum filter, retain the filtrate, and evaporate the solvent in vacuo to obtain a white powder;

[0024] Step 3: Add the white powder obtained in step 2 and 5-10 mL of 80% hydrazine hydrate to 100-120 mL of ethanol, and reflux and stir at 75-85° C. for 12-15 hours. Cool the reaction mixture to room temperature, then filter, wash the filter cake with 80-100 mL of ethanol, and vacuum dry to obtain a white powder;

[0025] Step 4: Add the white powder obtained in step 3 and salicylaldehyde in a molar ratio of 1:2 to 100-120 mL of methanol, then add 1-3 drops of glacial acetic acid, and reflux at 75-85° C. with stirring for 20-24 hours. Cool the reaction mixture to room temperature, then filter, wash the filter cake with 80-100 mL of methanol, and vacuum dry to obtain a white powder, i.e., the ligand H4BPDS;

[0026] Step 5. The ligand H4BPDS obtained in step 4, sodium hydroxide and rare earth metal cerium salt are added in a molar ratio of 1:2:1 to 1.5 to a mixed solvent of methanol and N,N-dimethylformamide in a volume ratio of 1 to 2:10, stirred at room temperature for 1 to 2 hours, filtered, and the filtrate is divided into test tubes and sealed with plastic wrap. After diffusion in an ether environment for 5 to 7 days, black square crystals are precipitated in the solution to obtain the target compound Ce-BPDS.

[0027] The compound is used in catalyzing the reaction of aryl iodide and aryl sulfinate to prepare diaryl sulfone derivatives.

[0028] Some specific applications include the use of the compound in catalyzing the synthesis of diphenyl sulfone derivatives from iodobenzene with or without substitution and sodium benzenesulfinate with or without substitution;

[0029] In some specific applications, the substituents are independently selected from F, Cl, Br, and an alkyl group having 1 to 5 carbon atoms.

[0030] In some specific applications, the substituents are independently selected from F, Cl, Br, methyl, and ethyl.

[0031] The metal organic tetrahedral cage compound is used in catalyzing 4-bromoiodobenzene and sodium 4-methylbenzenesulfinate to prepare 4-bromophenyl-4-methylphenyl sulfone, 3-bromoiodobenzene and sodium 4-methylbenzenesulfinate to prepare 3-bromophenyl-4-methylphenyl sulfone, and 4-bromo-3-fluoroiodobenzene and sodium 4-methylbenzenesulfinate to prepare 4-bromo-3-fluorophenyl-4-methylphenyl sulfone.

[0032] In some specific applications, the compound is combined with cuprous iodide to catalyze the reaction under light.

[0033] In some specific applications, the molar ratio of the compound to cuprous iodide is 1:2.

[0034] The invention has the beneficial effects of: a preparation method and application of a metal organic tetrahedral cage compound, wherein the metal organic tetrahedral cage compound is Ce in a rare earth metal salt. 3+As a node, H4BPDS is used as a ligand to react to prepare a metal organic tetrahedral cage compound. The method has low raw material price and is easy to synthesize. The obtained compound can be combined with transition metal copper (I) under mild light conditions to construct a stable copper (I) catalytic site, which can catalyze the reaction of aryl iodide and aryl sulfinate to prepare diaryl sulfone derivatives, especially for the catalysis of the reaction of 4-bromoiodobenzene with sodium 4-methylbenzenesulfinate to prepare 4-bromophenyl-4-methylphenyl sulfone, 3-bromoiodobenzene with sodium 4-methylbenzenesulfinate to prepare 3-bromophenyl-4-methylphenyl sulfone, and 4-bromo-3-fluoroiodobenzene with sodium 4-methylbenzenesulfinate to prepare 4-bromo-3-fluorophenyl-4-methylphenyl sulfone. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 It is a crystal structure diagram of the target compound Ce-BPDS in Example 1 of the present invention.

[0036] Figure 2 This is a high-resolution mass spectrum of the target compound Ce-BPDS solution in Example 1 of the present invention.

[0037] Figure 3 It is a curve diagram showing the change in yield over time of the reaction of 4-bromoiodobenzene and sodium 4-methylbenzenesulfinate to 4-bromophenyl-4-methylphenyl sulfone catalyzed by the compound Ce-BPDS of the present invention under light conditions. DETAILED DESCRIPTION

[0038] The present invention will be further described below in conjunction with the embodiments.

[0039] Example 1

[0040] 5,5'-dimethyl-2,2'-bipyridine (1.47 g, 8 mmol) and potassium permanganate (8.22 g, 52 mmol) were added to 60 mL of water and stirred at 115°C for 2 hours. The reaction mixture was cooled to room temperature and filtered through diatomaceous earth. The filtrate was acidified with 10 mL of concentrated hydrochloric acid to produce a white solid precipitate. Then, the filter cake was washed with 80 mL of water and vacuum dried to obtain 1.81 g of a white solid with a yield of 93%. 1 H NMR (400MHz, DMSO-d6): δ13.53(s,2H),9.21(s,2H),8.59(d,J=8.0Hz,2H),8.46(d,J=8.0Hz,2H).

[0041] The white solid (1.71 g, 7 mmol) was added to 100 mL of anhydrous ethanol, and 2 mL of concentrated sulfuric acid was slowly added dropwise, and the mixture was refluxed at 80 ° C for 24 hours. The reaction mixture was cooled to room temperature and neutralized to pH = 7 with saturated NaHCO3 solution. Then 100 mL of water was added and extracted with 200 mL of dichloromethane. The combined organic layer was dried with anhydrous Na2SO4, vacuum filtered, and the filtrate was retained. The solvent was evaporated in vacuo to obtain 1.81 g of white powder with a yield of 86%. 1 H NMR (400MHz, CDCl3): δ9.29 (s, 2H), 8.58 (d, J = 8.4Hz, 2H), 8.44 (d, J = 8.4Hz, 2H), 4.45 (q, J = 3.2Hz, 4H), 1.44 (t, J = 3.2Hz, 6H).

[0042] White powder (1.80 g, 6 mmol) and 8 mL of 80% hydrazine hydrate were added to 100 mL of ethanol and refluxed at 80° C. for 15 hours. The reaction mixture was cooled to room temperature, then filtered, and the filter cake was washed with 80 mL of ethanol and dried in vacuo to obtain 1.39 g of white powder with a yield of 85%. 1 H NMR (600MHz, DMSO-d6): δ10.08 (s, 2H), 9.09 (s, 2H), 8.50 (d, J = 8.4Hz, 2H), 8.34 (d, J = 8.4Hz, 2H), 4.66 (s, 4H).

[0043] The white powder (1.36 g, 5 mmol) obtained in the previous step and salicylaldehyde (1.22 g, 10 mmol) were added to 120 mL of methanol, and then 3 drops of glacial acetic acid were added, and the mixture was refluxed and stirred at 80° C. for 4 hours. The reaction mixture was cooled to room temperature, then filtered, and the filter cake was washed with 100 mL of methanol and dried in vacuo to obtain a white powder, i.e., 1.80 g of the ligand H4BPDS, with a yield of 75%. 1 H NMR (600MHz, DMSO-d6): δ12.35(s,2H),11.14(s,2H),9.25(s,2H),8.70(s,2H),8.63(d,J=8.4Hz,2H ), 8.50 (d, J = 8.4Hz, 2H), 7.62 (d, J = 6.6Hz, 2H), 7.33 (t, J = 7.8Hz, 2H), 6.95 (dd, J = 12.0, 7.8Hz, 4H). 13C NMR (101 MHz, DMSO-d6): δ 161.6, 157.9, 157.2, 149.3, 149.0, 137.4, 132.2, 129.7, 129.6, 121.3, 119.9, 119.2, 116.9. Electrospray ionization mass spectrometry (ESI-MS): accurate molecular weight 480.1546, actual peak 479.1473 [MH] – .

[0044] The ligand H4BPDS (48.0 mg, 0.1 mmol) was weighed and added to 10 mL N,N-dimethylformamide. The resulting suspension was stirred at room temperature, and then 0.5 mL NaOH (8.0 mg, 0.2 mmol) in methanol was added. 1 mL Ce(NO3)3·6H2O (52.1 mg, 0.12 mmol) in methanol was added to the resulting light red solution. The resulting black solution was stirred at room temperature for 2 h. After filtration, 3 mL of the filtrate was placed in a 20 mL test tube, sealed with plastic wrap, and diffused in an ether environment for 5 to 7 days. Black square crystals precipitated from the solution, and the target compound Ce-BPDS 34.1 mg was obtained with a yield of 60%. The crystal structure of crystalline Ce-BPDS was tested using a Bruker SMART APEX single crystal X-ray diffractometer, using a Mo-Kα ray source. The crystal data were collected with a CCD detector. The structure was solved by intrinsic phase using SHELXT and refined by least squares minimization using SHELXL in OLEX2. Non-H atoms were refined using anisotropic displacement parameters. The crystal structure is shown in Figure 1. Figure 1 The collected Ce-BPDS crystals were prepared into a 0.1 mM N,N-dimethylformamide / methanol (v:v, 1:1) solution, and methanol was used as the mobile phase for ESI-MS testing on an Agilent 6224 HPLC-TOF mass spectrometer. The ESI-MS result was, m / z: 857.6121 [Ce4(H2BPDS)6] 4+ ,1143.1476[Ce4(H2BPDS)5(HBPDS)] 3+ ,like Figure 2 shown.

[0045] Example 2

[0046] The ligand H4BPDS (48.0 mg, 0.1 mmol) was weighed and added to 10 mL N,N-dimethylformamide. The resulting suspension was stirred at room temperature, and then 0.5 mL NaOH (8.0 mg, 0.2 mmol) in methanol was added. 1 mL CeCl3·6H2O (31.7 mg, 0.12 mmol) in methanol was added to the resulting light red solution. The resulting black solution was stirred at room temperature for 2 h. After filtration, 3 mL of the filtrate was placed in a 20 mL test tube, sealed with plastic wrap, and diffused in an ether environment for 5 to 7 days. Black square crystals precipitated from the solution, and the target compound Ce-BPDS 28.3 mg was obtained with a yield of 50%. The ESI-MS result was m / z: 1143.1641 [Ce4(H2BPDS)5(HBPDS)] 3+ .

[0047] Example 3 Preparation of 4-bromophenyl-4-methylphenyl sulfone by catalyzing 4-bromoiodobenzene with sodium 4-methylbenzenesulfinate using the compound Ce-BPDS prepared in Example 1

[0048] In a 20mL photoreaction tube, add Ce-BPDS (2mg, 0.5μmol), 200μL CuI dimethyl sulfoxide solution (5mmol / L), Cs2CO3 (16.3mg, 0.05mmol), 4-bromoiodobenzene (14.1mg, 0.05mmol), sodium 4-methylbenzenesulfinate (89.1mg, 0.5mmol), then add 1.8mL dimethyl sulfoxide solvent, seal with a sealing stopper, bubble argon for 10 minutes to exclude air, and illuminate under a 395nm band lamp for 0 to 8 hours. After the reaction is completed, add 1,3,5-trimethoxybenzene (8.4mg, 0.05mmol) as an internal standard to calculate the yield at different times. Figure 3 As shown, the yield of 4-bromophenyl-4-methylphenyl sulfone was 78% after 8 hours of reaction.

[0049] Example 4 Preparation of 3-bromophenyl-4-methylphenyl sulfone by catalyzing 3-bromoiodobenzene with sodium 4-methylbenzenesulfinate using the compound Ce-BPDS prepared in Example 1

[0050] In a 20mL photoreaction tube, Ce-BPDS (2mg, 0.5μmol), 200μL CuI dimethyl sulfoxide solution (5mmol / L), Cs2CO3 (16.3mg, 0.05mmol), 3-bromoiodobenzene (14.1mg, 0.05mmol), sodium 4-methylbenzenesulfinate (89.1mg, 0.5mmol) were added, and then 1.8mL of dimethyl sulfoxide solvent was added. The tube was sealed with a sealing stopper, and argon was bubbled for 10 minutes to exclude air. The tube was illuminated under a 395nm band lamp for 6 hours. After the reaction was completed, 1,3,5-trimethoxybenzene (8.4mg, 0.05mmol) was added as an internal standard to calculate the yield. By calculation, the yield of 3-bromophenyl-4-methylphenyl sulfone was 83%.

[0051] Example 5: Preparation of 4-bromo-3-fluorophenyl-4-methylphenyl sulfone by catalyzing 4-bromo-3-fluoroiodobenzene with sodium 4-methylbenzenesulfinate using the compound Ce-BPDS prepared in Example 1

[0052] Ce-BPDS (2 mg, 0.5 μmol), 200 μL CuI dimethyl sulfoxide solution (5 mmol / L), Cs2CO3 (16.3 mg, 0.05 mmol), 1-bromo-2-fluoro-4-iodobenzene (15.0 mg, 0.05 mmol), sodium 4-methylbenzenesulfinate (89.1 mg, 0.5 mmol) were added to a 20 mL photoreaction tube, and then 1.8 mL of dimethyl sulfoxide solvent was added. The tube was sealed with a sealing stopper, and argon was bubbled for 10 minutes to exclude air. The tube was illuminated under a 395 nm band lamp for 6 hours. After the reaction was completed, 1,3,5-trimethoxybenzene (8.4 mg, 0.05 mmol) was added as an internal standard to calculate the yield. By calculation, the yield of 4-bromo-3-fluorophenyl-4-methylphenyl sulfone was 95%.

Claims

1. A metal organic tetrahedral cage compound, characterized in that: With trivalent cerium as the node and H4BPDS as the ligand, a tetrahedral structure is formed. The structure of the ligand H4BPDS is as follows: Each end of the ligand H4BPDS is coordinated to the metal cerium through two oxygens and a double-bonded nitrogen.

2. The method for preparing the compound according to claim 1, characterized in that: The following steps are involved: The ligand H4BPDS, a base and a cerium salt are reacted in an organic solvent under stirring at room temperature to obtain the compound; The base is selected from at least one of sodium hydroxide, potassium hydroxide, sodium carbonate, triethylamine, and 2,6-lutidine; The cerium salt is cerium chloride heptahydrate or cerium nitrate hexahydrate.

3. The preparation method according to claim 2, characterized in that: The molar ratio of the ligand H4BPDS, sodium hydroxide and cerium salt is 1:2:1-1.5; The organic solvent is a mixed solvent of methanol and N,N-dimethylformamide or N,N-dimethylacetamide in a volume ratio of 1 to 2:10; The reaction time is 1 to 2 hours.

4. The preparation method according to claim 2, characterized in that: After the reaction is completed, the reaction mixture is filtered, and the filtrate is divided into containers sealed with plastic wrap, and diffused in an ether environment for 5 to 7 days to precipitate square crystals to obtain the compound.

5. Use of the compound according to claim 1 in catalyzing the reaction of aryl iodide and aryl sulfinate to prepare diaryl sulfone derivatives.

6. The use according to claim 5, wherein the compound is used in catalyzing the synthesis of diphenyl sulfone derivatives from iodobenzene with or without substitution and sodium benzenesulfinate with or without substitution; The substituents are independently selected from F, Cl, Br, and an alkyl group having 1 to 5 carbon atoms.

7. The use according to claim 6, characterized in that: The substituents are each independently selected from F, Cl, Br, methyl, and ethyl.

8. The use according to claim 7, characterized in that: The compound catalyzes the reaction of 4-bromoiodobenzene with sodium 4-methylbenzenesulfinate to prepare 4-bromophenyl-4-methylphenyl sulfone, the reaction of 3-bromoiodobenzene with sodium 4-methylbenzenesulfinate to prepare 3-bromophenyl-4-methylphenyl sulfone, and the reaction of 4-bromo-3-fluoroiodobenzene with sodium 4-methylbenzenesulfinate to prepare 4-bromo-3-fluorophenyl-4-methylphenyl sulfone.

9. The use according to any one of claims 5 to 8, characterized in that: The compound cooperates with cuprous iodide to catalyze the reaction under light.

10. The use according to claim 9, characterized in that: The molar ratio of the compound to cuprous iodide is 1:2.

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