A method for the synthesis of triarylantimony derivatives mediated by fluorides

Abstract

The application relates to the technical field of organic synthesis, and particularly discloses a synthesis method of triarylantimony derivatives mediated by fluoride, which does not use any transition metal catalyst, only uses inexpensive KF*2H2O as a promoter, and eliminates metal toxicity, catalyst cost, product metal residual pollution and other problems from the source, so that the synthesized triarylantimony compound has extremely high purity and can be directly applied to functional materials, electronic devices and biological medicine fields which are sensitive to metal impurities; the reaction temperature of the application is only 80-140 DEG C, which is much lower than the high temperature (more than 200 DEG C) required by a traditional reduction coupling method, the mild reaction condition not only reduces energy consumption and equipment requirement, but also improves the safety and operability of the reaction; in addition, the reaction is carried out in a conventional organic solvent (acetonitrile or ethyl acetate), and strict anhydrous conditions are not required, so that the operation is extremely simple.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and specifically to a method for synthesizing triarylantimony derivatives mediated by fluorides. Background Technology

[0002] Main group organo-antimony compounds, due to their unique electronic structure, tunable valence state, σ-hole interaction, and Pnictogen bond characteristics, have shown significant research value in organic synthesis, main group catalysis, supramolecular assembly, and functional materials. Triarylantimony, as the most representative organo-antimony structural unit, is not only an important ligand in catalysis and coordination chemistry but also a key functional monomer for constructing antimony-doped porous organic polymers. Its efficient and green synthesis has become an important research direction in organo-antimony chemistry. sp 2 The mild and highly selective construction of the )–Sb bond is a core scientific issue that determines the structural diversity and application range of triarylantimony products.

[0003] The synthesis of traditional triarylantimony mainly relies on nucleophilic substitution reactions between antimony trichloride and strongly basic organometallic reagents such as organolithium compounds and Grignard reagents. These methods require stringent reaction conditions, including strict anhydrous and oxygen-free environments and low-temperature control. They exhibit extremely poor functional group tolerance, are incompatible with sensitive groups such as hydroxyl, halogen, alkenyl, alkynyl, and carbonyl groups, and are prone to over-arylation, isomerization, and elimination of side reactions, making it difficult to achieve precise and highly selective triarylization transformations.

[0004] In recent years, transition metal catalytic coupling strategies such as nickel and palladium have been used for C( sp 2 The construction of the )–Sb bond provides a new approach, but such methods still require the prior synthesis of organic antimony chloride intermediates. They cannot directly react with inexpensive inorganic antimony trichloride as a raw material in one step. At the same time, they have inherent defects such as expensive catalysts, difficulty in removing heavy metal residues, cumbersome product purification, and poor environmental compatibility, which seriously limit their practical application in the fields of high-purity functional materials and pharmaceutical intermediates.

[0005] Currently, a synthetic strategy for the direct one-step preparation of triarylantimony from antimony trichloride without the involvement of transition metals, using arylboronic acid as a mild aryl source, has not yet been systematically developed. The key scientific bottlenecks lie in the high activation energy barrier of the Sb–Cl bond, the unclear synergistic mechanism between fluoride ions and water, and the difficulty in achieving a stepwise controllable triarylization process.

[0006] Therefore, developing a new method that is mild, efficient, free of metal residues, has broad substrate applicability, and can directly prepare triarylantimony derivatives from antimony trichloride, and overcomes the multiple limitations of traditional synthetic routes in terms of reagents, conditions, selectivity, and functional group compatibility, has become a key technical problem that urgently needs to be solved in the field of organoantimony synthesis methodology and functional material precursor preparation. Summary of the Invention

[0007] In view of the shortcomings of the prior art, the purpose of this invention is to provide a method for synthesizing triarylantimony derivatives mediated by fluorides.

[0008] To achieve the above objectives, the present invention adopts the following technical solution: A method for synthesizing triarylantimony derivatives mediated by fluoride, comprising the following steps: In an inert atmosphere, antimony trichloride and compound 1 were used as reactants, and fluoride was used as a promoter. The reaction was carried out in an organic solvent under heating. After the reaction was completed, the product was separated and purified to obtain triarylantimony derivative 2.

[0009] In the technical solution disclosed in this invention, R in compound 1 represents unsubstituted or substituted by one or more substituents.

[0010] The substituents are selected from one or more of hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen, amino, nitro, cyano, hydroxy, aldehyde, ester, amide, alkynyl, vinyl, trifluoromethyl, and acetyl.

[0011] In the technical solution disclosed in this invention, the molar ratio of antimony trichloride and compound 1 is 1:3-6. For example, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, and 1:6 can be selected, but are not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0012] In the technical solution disclosed in this invention, the fluoride is selected from KF·nH2O, where n=0-3.

[0013] In the technical solution disclosed in this invention, the organic solvent is selected from at least one of acetonitrile, ethyl acetate, toluene, xylene, 1,4-dioxane, tetrahydrofuran, N,N-dimethylformamide, or N-methylpyrrolidone.

[0014] In the technical solution disclosed in this invention, the heating reaction temperature is 80-140℃, for example, 80℃, 90℃, 100℃, 110℃, 120℃, 130℃, 140℃ can be selected; the heating reaction time is 8-24h, for example, 8h, 10h, 12h, 14h, 15h, 16h, 18h, 20h, 21h, 22h, 24h can be selected, but it is not limited to the listed values, and other unlisted values ​​within the range are also applicable.

[0015] In the technical solution disclosed in this invention, the inert atmosphere is a nitrogen atmosphere or an argon atmosphere.

[0016] Compared with the prior art, the present invention has the following beneficial effects: (1) The method provided by the present invention does not use any transition metal catalysts at all, but only uses inexpensive KF·2H2O as a promoter, which eliminates the problems of metal toxicity, catalyst cost and metal residue pollution in the product from the source. This advantage makes the triaryl antimony compound synthesized by the present invention have extremely high purity and can be directly applied to functional materials, electronic devices and biomedicine that are sensitive to metal impurities.

[0017] (2) The reaction temperature of the present invention is only 80-140℃, which is much lower than the high temperature of more than 200℃ required by the traditional reduction coupling method. The mild reaction conditions not only reduce energy consumption and equipment requirements, but also improve the safety and operability of the reaction. In addition, the reaction is carried out in a conventional organic solvent (acetonitrile or ethyl acetate), without the need for strict anhydrous conditions, and the operation is extremely simple.

[0018] (3) The method provided by this invention exhibits excellent tolerance to a variety of functional groups. The arylboronic acid substrate can carry a variety of substituents such as methyl, ethyl, isopropyl, methoxy, fluorine, chlorine, bromine, iodine, trifluoromethyl, aldehyde, ester, amide, amino, nitro, cyano, hydroxyl, alkynyl, vinyl, and trimethylsilyl. The substrate is applicable to electron donor substituents and electron acceptor substituents, as well as functional groups that can be further transformed.

[0019] (4) The KF·2H2O used in this invention is an inexpensive and readily available inorganic salt. Compared with expensive transition metal catalysts and their ligands, the synthesis cost is greatly reduced. At the same time, the method provided by this invention avoids the emission of metal waste, which meets the requirements of green chemistry and sustainable development. Detailed Implementation

[0020] The present invention will be further described in detail below through specific preferred embodiments, but the present invention is not limited to the following embodiments.

[0021] It should be noted that, unless otherwise specified, all chemical reagents involved in this invention were purchased through commercial channels.

[0022] Example 1 Synthesis of tri(p-tolyl)antimonane In a 10 mL dry Schlenk tube, a magnetic stir bar, antimony trichloride (SbCl3, 22.8 mg, 0.10 mmol), p-tolylboronic acid (2b, 61.2 mg, 0.45 mmol, 4.5 equiv), and potassium fluoride dihydrate (KF·2H2O, 42.3 mg, 0.45 mmol, 4.5 equiv) were added. The Schlenk tube was connected to a double-row tube, and the tube was evacuated and purged with nitrogen three times to ensure thorough deoxygenation and dehydration. Dry ethyl acetate (EA, 2 mL) was added to the tube using a syringe. After sealing, the Schlenk tube was immersed in an oil bath preheated to 120°C, and the reaction was carried out with magnetic stirring for 12 hours.

[0023] After the reaction was completed, the reaction mixture was cooled to room temperature, and n-tetane (20 μL) was added as an internal standard. The sample was taken for GC analysis to determine the yield. The solvent was removed by vacuum distillation, and the residue was dissolved in a small amount of dichloromethane and purified by neutral alumina column chromatography to obtain 37.4 mg of white solid product 5b, which is tris(p-tolyl)antimonane, with a yield of 94%.

[0024] Characterization data: ¹H NMR (400 MHz, CDCl3) δ = 7.36 (d, J = 7.3 Hz, 6H), 7.16 (d, J =7.4 Hz, 6H), 2.36 (s, 9H) ppm. ¹³C NMR (101 MHz, CDCl3) δ = 138.4, 136.3, 135.0, 129.8, 21.5 ppm. HRMS (m / z) [M+K]+ calculated for [C 21 H 21 KSb]+ 433.0313, found433.0313. Example 2 Synthesis of tris(4-ethynylphenyl)antimonane In a 100 mL dry Schlenk flask, add a magnetic stir bar, antimony trichloride (SbCl3, 456 mg, 2.0 mmol), 4-ethynylphenylboronic acid (1.35 g, 9.0 mmol, 4.5 equiv), high-purity potassium fluoride (KF, 99.99%, metal basis, 522 mg, 9.0 mmol, 4.5 equiv), and deionized water (320 μL). Connect the Schlenk flask to a double-row tube, evacuate and purge with nitrogen three times to ensure thorough deoxygenation and dehydration. Add dry ethyl acetate (EA, 20 mL) through a syringe. After sealing, immerse the Schlenk flask in an oil bath preheated to 120°C and react with magnetic stirring for 12 hours.

[0025] After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by vacuum distillation, and the residue was dissolved in a small amount of dichloromethane and purified by neutral alumina column chromatography (eluent: petroleum ether / dichloromethane = 2:1 → 1:2, v / v, gradient elution) to give 0.97 g of yellow solid product 5k, which is tris(4-ethynylphenyl)antimonane with a yield of 52%. The product is relatively stable in air and can be stored for a long time at -20℃.

[0026] Characterization data: ¹H NMR (400 MHz, CDCl3) δ = 7.45 (d, J = 7.7 Hz, 6H), 7.36 (d, J =7.6 Hz, 6H), 3.11 (s, 3H) ppm. ¹³C NMR (101 MHz, CDCl3) δ = 139.3, 136.2, 132.5, 122.8, 83.4, 78.4ppm. HRMS (m / z) [M+Na]+ calculated for [C 24 H 15 NaSb]+ 447.0104, found447.0102. Example 3 Synthesis of tris(4-bromophenyl)antimonane In a 100 mL dry Schlenk flask, add a magnetic stir bar, antimony trichloride (SbCl3, 456 mg, 2.0 mmol), 4-bromophenylboronic acid (1.81 g, 9.0 mmol, 4.5 equiv), high-purity potassium fluoride (KF, 99.99%, metalbasis, 522 mg, 9.0 mmol, 4.5 equiv), and deionized water (320 μL). Connect the Schlenk flask to a double-row tube and evacuate and purge with nitrogen three times to ensure thorough deoxygenation and dehydration. Add 20 mL of dry ethyl acetate (EA) using a syringe, seal the flask, and immerse it in an oil bath preheated to 120°C. React with magnetic stirring for 12 hours.

[0027] After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by vacuum distillation, the residue was dissolved in a small amount of dichloromethane, and then purified by neutral alumina column chromatography (eluent: petroleum ether / dichloromethane = 5:1, v / v) to give 0.88 g of white solid product 5p, which is tris(4-bromophenyl)antimonane, with a yield of 34%.

[0028] Characterization data: ¹H NMR (400 MHz, CDCl3) δ = 7.47 (d, J = 7.3 Hz, 6H), 7.24 (d, J =7.6 Hz, 6H) ppm. ¹³C NMR (101 MHz, CDCl3) δ = 137.7, 136.4, 132.4, 124.1 ppm. HRMS (m / z) [M+NH4]+ calculated for [C 18 H 16 Br3NSb]+ 603.7866, found603.7860. Comparative Example 1 Compared with Example 1, the reaction was carried out in the absence of KF·2H2O.

[0029] In a 10 mL dry Schlenk tube, a magnetic stir bar, antimony trichloride (SbCl3, 22.8 mg, 0.10 mmol), and p-tolylboronic acid (2b, 61.2 mg, 0.45 mmol, 4.5 equiv) were added. The Schlenk tube was connected to a double-row tube, and the tube was evacuated and purged with nitrogen three times to ensure thorough deoxygenation and dehydration. Dry ethyl acetate (EA, 2 mL) was added to the tube using a syringe, and the tube was sealed. The Schlenk tube was then immersed in an oil bath preheated to 120°C, and the reaction was carried out with magnetic stirring for 12 hours.

[0030] After the reaction was completed, the reaction mixture was cooled to room temperature, and n-tetane (20 μL) was added as an internal standard. Samples were taken for GC analysis to determine the yield was <5%, indicating that KF is crucial for promoting the metallization of borate.

[0031] This invention aims to obtain optimal conditions for the triarylation reaction of antimony trichloride with arylboronic acid. Using the model reaction of SbCl3 with p-tolylboronic acid as an example, parameters such as the type and amount of base, solvent, reaction temperature, and KF purity were systematically optimized. All optimization experiments were conducted in 10 mL dry Schlenk tubes, with n-tetane (20 μL) as an internal standard, and the yield was determined by GC.

[0032] Table 1. Effect of type of alkali As shown in Table 1, KF·2H2O yielded the highest amount of alkali (78%), significantly better than other alkalis. This may be because F... - It can effectively promote the boric acid to metallization process, while water molecules may participate in stabilizing the reaction intermediates.

[0033] Table 2 Effect of KF·2H2O dosage As can be seen from Table 2, the yield can reach up to 78% when the molar ratio of SbCl3:arylboronic acid:KF·2H2O is 1:4.5:4.5.

[0034] Table 3 Effect of Solvent Type As can be seen from Table 3, the yield can reach up to 78% when ethyl acetate is used as the solvent.

[0035] Table 4 Effect of Temperature As can be seen from the table, increasing the reaction temperature is beneficial to increasing the yield, and the yield can reach 94% at 120℃.

[0036] Table 5. Effect of KF Purity As shown in Table 5, when using high-purity KF (99.99%, metal basis) and adding 16 μL H2O / 0.10 mmol SbCl3, the reaction yield further increased from 85% to 90%. This indicates that trace metal ion impurities have an inhibitory effect on the reaction, while an appropriate amount of moisture is crucial for the efficient conduct of the reaction.

[0037] This invention also systematically investigated the substrate applicability of arylboronic acids, and the experimental results are shown in Table 6.

[0038] Table 6 Substrate Expansion for Arylboronic Acid Compounds a Reaction conditions: SbCl3 (0.10 mmol, 1.0 eq.), 2 (0.45 mmol, 4.5 eq.), KF·2H2O (0.45 mmol, 4.5 eq.), 120 °C, ethyl acetate (2 mL), reaction under N2 atmosphere for 12 h. b Separation yield. c The reaction scale was SbCl3 (1.0 g, 6.58 mmol).

[0039] As shown in the table, substrates with neutral or electron-donating substituents reacted smoothly, yielding the target product in stable, high yields. The reaction exhibited excellent tolerance to a variety of functional groups, including vinyl, ethynyl, and halogen substituents, with halogen substituents providing abundant synthetic sites for subsequent derivatization reactions. Electron-deficient substrates had relatively low yields but still possessed synthetic application value; heteroarylboronic acids showed good reactivity. Furthermore, vinylboronic acid also participated effectively in the reaction under standard conditions.

[0040] Finally, it should be noted that the above embodiments do not limit the present invention in any way. Those skilled in the art can make modifications and improvements based on the present invention. Therefore, any modifications or improvements made without departing from the spirit of the present invention are within the scope of protection claimed by the present invention.

Claims

1. A method for synthesizing triarylantimony derivatives mediated by fluoride, characterized in that, Includes the following steps: In an inert atmosphere, antimony trichloride and compound 1 were used as reactants, and fluoride was used as a promoter. The reaction was carried out in an organic solvent under heating. After the reaction was completed, the product was separated and purified to obtain triarylantimony derivative 2.

2. The synthesis method according to claim 1, characterized in that, In compound 1, R represents unsubstituted or substituted with one or more substituents, wherein the substituents are selected from one or more of hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen, amino, nitro, cyano, hydroxy, aldehyde, ester, amide, alkynyl, vinyl, trifluoromethyl, and acetyl.

3. The synthesis method according to claim 1, characterized in that, The molar ratio of antimony trichloride to compound 1 is 1:3-6.

4. The synthesis method according to claim 1, characterized in that, The molar ratio of antimony trichloride to fluoride is 1:3-6.

5. The synthesis method according to claim 1, characterized in that, The fluoride is selected from KF·nH2O, where n = 0-3.

6. The synthesis method according to claim 1, characterized in that, The organic solvent is selected from at least one of acetonitrile, ethyl acetate, toluene, xylene, 1,4-dioxane, tetrahydrofuran, N,N-dimethylformamide, or N-methylpyrrolidone.

7. The synthesis method according to claim 1, characterized in that, The heating reaction temperature is 80-140℃, and the heating reaction time is 8-24h.

8. The synthesis method according to claim 1, characterized in that, The inert atmosphere is a nitrogen atmosphere or an argon atmosphere.

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