Metallo-organic tetrahedral cage compounds, methods of making and using the same

Abstract

The application relates to a metal organic tetrahedral cage compound, a preparation method and application thereof, and belongs to the technical field of fine chemical industry. The metal organic tetrahedral cage compound is obtained by reacting a rare earth metal cerium salt with H4BPDS as a ligand 3+ As a node, H4BPDS is used as a ligand. The metal organic tetrahedral cage compound prepared by the application has low raw material price, high yield, stable chemical properties, and can efficiently catalyze the reaction of aryl iodide and aryl sulfinate to prepare diaryl sulfone derivatives under mild light and warm conditions. For the catalysis of the reactions of 4-bromo-iodobenzene and 4-methylphenyl sulfinate sodium to prepare 4-bromophenyl-4-methylphenyl sulfone, 3-bromo-iodobenzene and 4-methylphenyl sulfinate sodium to prepare 3-bromophenyl-4-methylphenyl sulfone, and 4-bromo-3-fluoro-iodobenzene and 4-methylphenyl sulfinate sodium to prepare 4-bromo-3-fluorophenyl-4-methylphenyl sulfone, the yield can reach 95% at the highest.

Description

TECHNICAL FIELD

[0001] The present application relates to a metal organic tetrahedral cage compound, a preparation method and application thereof, and belongs to the technical field of fine chemical industry. BACKGROUND

[0002] Sulfone compounds are common organic intermediates, which play an important role in organic chemistry and medicinal chemistry, and have good biological activity, and are widely used in chemical industry, medicine, pesticides, material science and other fields. In the field of medicine, the antibiotic sulfomycin, the antipsychotic drug amine sulfonyl, and the anti-migraine drug eletriptan all contain sulfone structural units. Sulfone compounds are also used as androgen inhibitors and protease inhibitors, etc. such as the non-steroidal anti-androgen drug caruamine and the anti-HIV drug protease inhibitor telaprevir. Sulfone derivatives have high antibacterial activity and are often used for insect and weed control, such as diacloden, an effective insecticide for aphids and leaf-eating pests, and mesotrione, a selective benzoylcyclohexanedione herbicide for corn crops. In addition, aryl sulfones with conjugated systems have special photophysical properties and have broad application prospects in organic light-emitting diode materials.

[0003] Among sulfone compounds, diaryl sulfone is an important small-molecule drug structure, such as sulfonamides used for treating leprosy. Current methods for synthesizing aryl sulfones include oxidation of sulfides / sulfoxides, Friedel-Crafts type sulfonylation of arenes, insertion of sulfur dioxide, addition of sulfinic acid salts to alkynes / alkenes, and cross-coupling of sulfinic acid salts with alkyl / aryl halides. These methods have significant drawbacks, such as the use of malodorous mercaptans and toxic sulfur dioxide gas, stoichiometric oxidants, highly air- and moisture-sensitive sulfonylating agents, harsh acidic treatments, and high reaction temperatures, which limit functional group tolerance and substrate scope. Transition metal photocatalytic systems are a mild and efficient platform for the synthesis of diaryl sulfone cross-coupling reactions, but usually require the use of toxic noble metal photosensitizers and structurally complex and difficult-to-synthesize photoactive ligands to achieve light conversion functions. In summary, the existing methods for synthesizing aryl sulfones have certain limitations for industrialization, such as harsh reaction conditions that can cause high damage and corrosion rates of equipment, high production input costs, and environmental unfriendliness, etc. SUMMARY

[0004] In order to overcome the deficiencies in the prior art, the present application aims to provide a metal organic tetrahedral cage compound and a preparation method and application thereof. The metal organic tetrahedral cage compound retains a 2,2'-bipyridine group, can be combined with transition metal copper (I) through coordination, and constructs an isolated copper (I) catalytic site. The spatial configuration of the metal organic tetrahedral cage compound can stabilize the copper (I) active center, avoid the deactivation of the intermolecular pathway, and make the copper (I) active center retain an accessible site for direct interaction with substrates and intermediates. The copper (I) photocatalyst is generated in situ by combining the metal organic tetrahedral cage compound with transition metal copper (I), and the C(sp 2 )-S cross-coupling of aryl iodide and aryl sulfinic acid salt is realized to prepare sulfone under normal temperature and light irradiation.

[0005] In order to achieve the above-mentioned application purposes and solve the problems existing in the prior art, the technical scheme adopted by the present application is as follows: a metal organic tetrahedral cage compound, taking trivalent cerium as a node and H4BPDS as a ligand to form a tetrahedral structure:

[0006]

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

[0008] Specifically, the metal organic tetrahedral cage compound has the following structure:

[0009]

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

[0011] A preparation method of a metal organic tetrahedral cage compound, taking Ce 3+ of a rare earth metal salt as a node and L as a ligand to react and obtain the metal organic tetrahedral cage compound, and the 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] The application discloses a preparation method of a specific metal organic tetrahedral cage compound, and the method comprises the following steps: adding a ligand H4BPDS, an alkali and a cerium salt into an organic solvent, and stirring and reacting at normal temperature to obtain the compound.

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

[0018] Specifically, the molar ratio of the ligand H4BPDS, the alkali and the cerium salt is 1:2:1-1.5.

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

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

[0021] The application discloses a preparation method of a specific metal organic tetrahedral cage compound.

[0022] Step 1: 5,5'-dimethyl-2,2'-bipyridine and potassium permanganate are added into 50-70 mL of water at a molar ratio of 1:6-7, and stirring is conducted at 110-120 DEG C for 2-3 hours; the mixture after reaction is cooled to room temperature, is filtered through diatomite, the filtrate is acidified with 8-10 mL of concentrated hydrochloric acid, white solid is precipitated, then filtration is conducted, and the filter cake is washed with 60-80 mL of water and is vacuum dried to obtain white solid;

[0023] Step 2: the white solid obtained in step 1 is added into 80-100 mL of anhydrous ethanol, 1-2 mL of concentrated sulfuric acid is slowly added dropwise, and stirring is conducted at 75-85 DEG C for 20-24 hours; the reaction mixture is cooled to room temperature, is neutralized to PH=6-7 with a saturated NaHCO3 solution, then 80-100 mL of water is added, and 150-200 mL of dichloromethane is used for extraction; the combined organic layer is dried with anhydrous Na2SO4, is vacuum filtered, the filtrate is reserved, the solvent is evaporated under vacuum, and white powder is obtained;

[0024] Step 3: the white powder obtained in step 2 and 5-10 mL of 80% hydrazine hydrate are added into 100-120 mL of ethanol, and stirring is conducted at 75-85 DEG C for 12-15 hours; the reaction mixture is cooled to room temperature, then filtration is conducted, and the filter cake is washed with 80-100 mL of ethanol and is vacuum dried to obtain white powder;

[0025] Step 4, the white powder obtained in step 3 and salicylaldehyde are added into 100-120 mL of methanol in a molar ratio of 1:2, then 1-3 drops of glacial acetic acid are added dropwise, and stirring is carried out at 75-85°C for 20-24 hours. The reaction mixture is cooled to room temperature, then filtered, and the filter cake is washed with 80-100 mL of methanol, and vacuum dried to obtain a white powder, which is ligand H4BPDS;

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

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

[0028] Some specific applications, the compound is used for catalyzing the reaction of iodobenzene containing substituents or not containing substituents and sodium benzenesulfinate containing substituents or not containing substituents to synthesize diphenyl sulfone derivatives.

[0029] Some specific applications, the substituents are each independently selected from F, Cl, Br, and alkyl with 1-5 carbon atoms.

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

[0031] The metal organic tetrahedral cage compound is used for catalyzing the reaction of 4-bromoiodobenzene and 4-methyl sodium benzenesulfinate to prepare 4-bromophenyl-4-methyl phenyl sulfone, 3-bromoiodobenzene and 4-methyl sodium benzenesulfinate to prepare 3-bromophenyl-4-methyl phenyl sulfone, and 4-bromo-3-fluoroiodobenzene and 4-methyl sodium benzenesulfinate to prepare 4-bromo-3-fluorophenyl-4-methyl phenyl sulfone.

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

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

[0034] The present application has the following beneficial effects: a preparation method and application of a metal organic tetrahedral cage compound, the metal organic tetrahedral cage compound is Ce 3+As a node, the metal organic tetrahedral cage compound is prepared by reacting H4BPDS as a ligand, the method has low raw material price and is easy to synthesize, the obtained compound can combine copper (I) under mild light and warm conditions to construct a stable copper (I) catalytic site, and 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 and 4-methylphenylsulfinate sodium to prepare 4-bromophenyl-4-methylphenyl sulfone, 3-bromoiodobenzene and 4-methylphenylsulfinate sodium to prepare 3-bromophenyl-4-methylphenyl sulfone, and 4-bromo-3-fluoroiodobenzene and 4-methylphenylsulfinate sodium to prepare 4-bromo-3-fluorophenyl-4-methylphenyl sulfone. BRIEF DESCRIPTION OF DRAWINGS

[0035] Figure 1 is the crystal structure diagram of the target compound Ce-BPDS of embodiment 1 of the present application.

[0036] Figure 2 is the high resolution mass spectrum of the solution of the target compound Ce-BPDS of embodiment 1 of the present application.

[0037] Figure 3 is the reaction yield-time curve diagram of the reaction of 4-bromoiodobenzene and 4-methylphenylsulfinate sodium to prepare 4-bromophenyl-4-methylphenyl sulfone under the catalysis of the compound Ce-BPDS of the present application under light irradiation. DETAILED DESCRIPTION

[0038] The present application will be further described below in combination with examples.

[0039] Example 1

[0040] 5,5'-dimethyl-2,2'-dipyridyl (1.47 g, 8 mmol) and potassium permanganate (8.22 g, 52 mmol) were added to 60 mL of water, and stirred under reflux at 115℃ for 2 hours. The reaction mixture was cooled to room temperature, filtered with diatomite, the filtrate was acidified with 10 mL of concentrated hydrochloric acid, and a white solid precipitated. Then, suction filtration was performed, the filter cake was washed with 80 mL of water, and vacuum drying was performed to obtain 1.81 g of white solid, with a yield of 93%. 1 H NMR (400 MHz, DMSO-d6): δ 13.53 (s, 2H), 9.21 (s, 2H), 8.59 (d, J = 8.0 Hz, 2H), 8.46 (d, J = 8.0 Hz, 2H).

[0041] White solid (1.71 g, 7 mmol) was added to 100 mL of absolute ethanol, 2 mL of concentrated sulfuric acid was added dropwise, and the mixture was stirred at 80 °C for 24 h. The reaction mixture was cooled to room temperature, neutralized to pH = 7 with saturated NaHC03solution. Then 100 mL of water was added, and extracted with 200 mL of dichloromethane. The combined organic layers were dried over anhydrous Na2S04, filtered under vacuum, and the filtrate was evaporated under vacuum to give white powder 1.81 g in 86% yield. 1 H NMR (400 MHz, CDC13): δ 9.29 (s, 2H), 8.58 (d, J = 8.4 Hz, 2H), 8.44 (d, J = 8.4 Hz, 2H), 4.45 (q, J = 3.2 Hz, 4H), 1.44 (t, J = 3.2 Hz, 6H).

[0042] White powder (1.80 g, 6 mmol) and 8 mL of 80% hydrazine hydrate were added to 100 mL of ethanol, and the mixture was stirred at 80 °C for 15 h. The reaction mixture was cooled to room temperature, then filtered under vacuum, and the filter cake was washed with 80 mL of ethanol and dried under vacuum to give white powder 1.39 g in 85% yield. 1 H NMR (600 MHz, DMSO-d6): δ 10.08 (s, 2H), 9.09 (s, 2H), 8.50 (d, J = 8.4 Hz, 2H), 8.34 (d, J = 8.4 Hz, 2H), 4.66 (s, 4H).

[0043] 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 3 drops of glacial acetic acid were added dropwise, and the mixture was stirred at 80 °C for 4 h. The reaction mixture was cooled to room temperature, then filtered under vacuum, and the filter cake was washed with 100 mL of methanol and dried under vacuum to give white powder, ligand H4BPDS 1.80 g in 75% yield. 1 H NMR (600 MHz, DMSO-d6): δ 12.35 (s, 2H), 11.14 (s, 2H), 9.25 (s, 2H), 8.70 (s, 2H), 8.63 (d, J = 8.4 Hz, 2H), 8.50 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 6.6 Hz, 2H), 7.33 (t, J = 7.8 Hz, 2H), 6.95 (dd, J = 12.0, 7.8 Hz, 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 of N,N-dimethylformamide. The resulting suspension was stirred at room temperature, followed by the addition of 0.5 mL of a methanolic solution of NaOH (8.0 mg, 0.2 mmol). To the resulting light red solution was added 1 mL of a methanolic solution of Ce(NO3)3·6H2O (52.1 mg, 0.12 mmol). The resulting black solution was stirred at room temperature for 2 h. After filtration, 3 mL of the filtrate was transferred to a 20 mL test tube, sealed with plastic wrap, and allowed to diffuse in ether for 5–7 days. Black square crystals precipitated from the solution, yielding 34.1 mg of the target compound, Ce–BPDS, in a 60% yield. The crystal structure of crystalline Ce–BPDS was determined using a Bruker SMART APEX single crystal X-ray diffractometer using a Mo-Kα source. Crystallographic data were collected using a CCD detector. The structure was solved using SHELXT by intrinsic phase and refined using SHELXL in OLEX2 by least squares minimization. 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 subjected to ESI-MS analysis using methanol as the mobile phase 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 into 10 mL of N,N- dimethylformamide, the resulting suspension was stirred at room temperature, then 0.5 mL of NaOH (8.0 mg, 0.2 mmol) in methanol was added, 1 mL of CeCl3-6H2O (31.7 mg, 0.12 mmol) in methanol was added to the resulting light red solution, the resulting black solution was continued to stir at room temperature for 2 h. After filtration, 3 mL of the filtrate was taken in a 20 mL test tube, sealed with plastic wrap, and black square crystals were precipitated in the solution after 5-7 days of diffusion in ether, thus obtaining the target compound Ce-BPDS 28.3 mg, yield 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 from 4-bromoiodobenzene and sodium 4-methylbenzenesulfinate using the compound Ce-BPDS prepared in Example 1 as catalyst

[0048] In a 20 mL photoreaction tube, Ce-BPDS (2 mg, 0.5 μmol), 200 μL of CuI in dimethyl sulfoxide (5 mmol / L), Cs2CO3(16.3 mg, 0.05 mmol), 4-bromoiodobenzene (14.1 mg, 0.05 mmol), sodium 4-methylbenzenesulfinate (89.1 mg, 0.5 mmol) were added, then 1.8 mL of dimethyl sulfoxide solvent was added, sealed with a plug, bubbled with argon for 10 minutes to remove air, and irradiated under a 395 nm wavelength lamp for 0-8 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 at different times. As shown in Figure 3 , the yield of 4-bromophenyl-4-methylphenyl sulfone after 8 h of reaction was 78%.

[0049] Example 4 Preparation of 3-bromophenyl-4-methylphenyl sulfone from 3-bromoiodobenzene and sodium 4-methylbenzenesulfinate using the compound Ce-BPDS prepared in Example 1 as catalyst

[0050] In a 20 mL photoreactor tube, Ce-BPDS (2 mg, 0.5 μmol), 200 μL of CuI in dimethyl sulfoxide (5 mmol / L), Cs2CO3(16.3 mg, 0.05 mmol), 3-bromoiodobenzene (14.1 mg, 0.05 mmol), sodium 4-methylbenzenesulfinate (89.1 mg, 0.5 mmol) were added, followed by 1.8 mL of dimethyl sulfoxide solvent, sealed with a stopper, purged with argon for 10 minutes to remove air, and irradiated under a 395 nm wavelength 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. The yield of 3-bromophenyl-4-methylphenyl sulfone was calculated to be 83%.

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

[0052] In a 20 mL photoreactor tube, Ce-BPDS (2 mg, 0.5 μmol), 200 μL of CuI in dimethyl sulfoxide (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, followed by 1.8 mL of dimethyl sulfoxide solvent, sealed with a stopper, purged with argon for 10 minutes to remove air, and irradiated under a 395 nm wavelength 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. The yield of 4-bromo-3-fluorophenyl-4-methylphenyl sulfone was calculated to be 95%.

Claims

1. A metal organic tetrahedral cage compound, characterized in that: With trivalent cerium as the node and H4BPDS as the ligand, they form a tetrahedral structure. The structure of the ligand H4BPDS is as follows: ； Each end of the ligand H4BPDS is coordinated to the cerium metal through two oxygens and a double-bonded nitrogen; The structure of the metal organic tetrahedral cage compound is as follows: 。 2. The method for preparing the compound according to claim 1, wherein The following steps are involved: The ligand H4BPDS, a base, and a cerium salt are reacted in an organic solvent at room temperature with stirring 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 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 1~2 h.

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

5. Use of the compound according to claim 1 in catalyzing the synthesis of diphenyl sulfone derivatives from iodobenzene containing or not containing substituents and sodium benzenesulfinate containing or not containing substituents; The compound cooperates with cuprous iodide to catalyze the reaction under light; The substituents are independently selected from F, Cl, Br, and an alkyl group having 1 to 5 carbon atoms.

6. The use according to claim 5, characterized in that The substituents are each independently selected from F, Cl, Br, methyl, and ethyl.

7. The use according to claim 6, 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.

8. The use according to claim 7, characterized in that The molar ratio of the compound to cuprous iodide is 1:2.

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