Synthesis method of diaryl compounds containing silicon atoms

Abstract

The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of diaryl compounds containing silicon atoms. Toluene as shown in a formula 1a, iodobenzene as shown in a formula 2a and vinyl silane as shown in a formula 3 are mixed to react in the presence of a catalytic amount of PdCl2 (dppf), phosphorus ligand 4, 6-di (diphenylphosphine) phenazine and alkali metals LiN (SiMe3) 2 and CsF, and the diaryl compound containing silicon atoms as shown in a formula 4 is synthesized through the reaction. According to the invention, the combination reaction of toluene, iodobenzene and vinyl silane is realized by adopting a catalytic amount of PdCl2 (dppf), and the palladium catalyst shows obvious catalytic performance.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, and specifically relates to a method for synthesizing diaryl compounds containing silicon atoms. Background Technology

[0002] Diarylmethane structural units are widely found in natural products and drug molecules, such as tolterodine, acrivastine, suprahistamine, desloratadine, latifolin, and terfenadine. These drugs typically exhibit a variety of biological activities, including antibacterial, antiviral, antitumor, and antioxidant effects. The introduction of silicon atoms can often optimize the properties and performance of these drugs. Therefore, developing novel silicon-containing diarylmethane synthesis strategies not only has significant theoretical importance but also holds enormous application potential. Summary of the Invention

[0003] This invention provides a palladium-catalyzed, alkali metal-mediated synthesis of various silicon-containing diaryl compounds from toluene, iodobenzene, and vinylsilane, possessing potential biological activity and pharmaceutical value. This synthetic method is mild, simple, convenient, and efficient. The specific scheme is as follows:

[0004]

[0005] A method for synthesizing a silicon-containing diaryl compound involves reacting toluene (Formula 1a), iodobenzene (Formula 2a), and vinylsilane (Formula 3) in the presence of a palladium catalyst, a phosphorus ligand, and an alkali metal to synthesize the silicon-containing diaryl compound shown in Formula 4.

[0006] Where R 1 Selected from phenyl, methyl, R 2 Selected from methyl, phenyl, R 3 Selected from phenyl.

[0007] The method of this invention achieves efficient synthesis of silicon-containing diaryl compounds under mild reaction conditions using alkali metals and a catalytic amount of palladium; the toluene, iodobenzene, and vinylsilane used in the synthesis method are inexpensive and readily available; R in this invention... 1 and R 2 It offers a variety of options and has wider applicability.

[0008] Preferably, the reaction is carried out under the protection of an inert gas, and preferably, the inert gas is nitrogen.

[0009] Preferably, the synthesis occurs in the presence of a transition metal catalyst, a phosphorus ligand, and an alkali metal.

[0010] Preferably, the transition metal catalyst is a palladium catalyst; the phosphorus ligand is 4,6-bis(diphenylphosphine)phenazine; and the alkali metal is LiN(SiMe3)2 and CsF.

[0011] Preferably, the palladium catalyst is PdCl2(dppf).

[0012] Preferably, the organic solvent is toluene.

[0013] Preferably, the ratio of iodobenzene shown in formula 2a, reaction formula 3, and palladium catalyst in the reaction is 1-2:1-2:0.05-0.2;

[0014] Preferably, the reaction temperature is 120-160℃.

[0015] Preferably, the method of the present invention can synthesize silicon-containing diaryl compounds with the following structures:

[0016]

[0017] A silicon-containing diaryl compound was synthesized by reacting toluene, iodobenzene, and vinylsilane in the presence of a catalytic amount of PdCl2 (dppf), an alkali metal, and the ligand 4,6-bis(diphenylphosphine)phenazine.

[0018] The technical solution of the present invention can achieve at least one of the following beneficial effects:

[0019] The raw materials used in the synthesis method of this invention are all inexpensive and readily available;

[0020] This invention uses inexpensive palladium as a catalyst, which has higher economic value compared to previously reported methods;

[0021] The operation steps required by this invention are relatively simple, requiring no extreme heating or cooling, and the reaction can be carried out under normal pressure, making it safe and convenient.

[0022] R in this invention 1 R 2 The substrates available can be varied, thus the present invention has a wider range of applicability and can synthesize various diaryl compounds containing silicon atoms;

[0023] Compared with traditional methods, the method of this invention has many advantages such as high yield, mild conditions, simple operation, and less pollution. Attached Figure Description

[0024] The attached figures are the proton and carbon NMR spectra of the products from each embodiment. The figure numbers correspond to the embodiment numbers. Figure 1AThe above is the proton NMR spectrum of the product obtained in Example 1. Figure 1B The carbon NMR spectrum of the product obtained in Example 1; Figure 2A The above is the proton NMR spectrum of the product obtained in Example 2. Figure 2B The carbon NMR spectrum of the product obtained in Example 2; Figure 3A The image shows the proton NMR spectrum of the product obtained in Example 3. Figure 3B The image shows the carbon NMR spectrum of the product obtained in Example 3. Specific Implementation

[0025] To facilitate understanding by those skilled in the art, the concept of the present invention will be further explained below with reference to embodiments. The specific descriptions of the following embodiments are not intended to limit the present invention, but are merely for the convenience of those skilled in the art to understand the technical solution. All raw materials mentioned in the specification were purchased from the market or synthesized through simple methods. Other pharmaceuticals were purchased from Amex, Bide, Leyan, Adamas, or J&K. The nuclear magnetic resonance spectrometer was a Bruker 400M.

[0026] Example 1

[0027] In a nitrogen-filled glove box, a pre-dried 10 mL microwave reaction tube (with a built-in magnetic stirrer) was sequentially loaded with PdCl2 (dppf) (16.3 mg, 0.02 mmol), Nixantphos (16.5 mg, 0.03 mmol), LiN(SiMe3)2 (100.4 mg, 0.6 mmol), CsF (91.1 mg, 0.6 mmol), toluene 1a (4 mL), iodobenzene 2a (0.2 mmol), and dimethylphenylvinylsilane 3a (0.4 mmol). The reaction tube was sealed and removed from the glove box, and the reaction was stirred at 140 °C for 15 hours. After the reaction was complete, the reaction tube was exposed to air and quenched with a drop of water. The reaction solution was filtered through a short silica gel column (coated with anhydrous sodium sulfate on top) and washed with ethyl acetate (3 mL). The combined organic phases were then concentrated under reduced pressure. The crude product was rapidly purified by chromatography using a 200-300 mesh silica gel column to obtain product 4a (48.3 mg, 73% yield) as a colorless oil. 1 H NMR (400MHz, CDCl3) δ: 7.57-754 (m, 2H), 7.44-7.42 (m, 3H), 7.37-7.32 (m, 4H), 7.29-7 .22(m, 6H), 3.93-3.88(m, 1H), 2.17-2.10(m, 2H), 0.85-0.80(m, 2H), 0.34(s, 6H)ppm.13 C{ 1 H} NMR (101MHz, CDCl3) δ: 145.1, 139.2, 133.7, 129.0, 128.5, 128.1, 127.9, 126.2, 54.8, 30.1, 14.4, -3.0ppm.

[0028] By changing the raw materials in Example 1, two sets of experimental examples were designed as follows, where the first set of experiments is Example 1, and the corresponding NMR spectrum of the product is shown in Figure 1. The NMR spectra of the other two sets of products are numbered according to the corresponding example numbers.

[0029] The table lists the structural formulas of the products in each of the 1-3 embodiments. The last column lists the yield of the products in each embodiment and indicates the specific implementation conditions of each embodiment. The specific meaning of the implementation conditions of each embodiment is shown below the table.

[0030]

[0031] Example 2

[0032] In a nitrogen-filled glove box, a pre-dried 10 mL microwave reaction tube (with a built-in magnetic stirrer) was sequentially loaded with PdCl2 (dppf) (16.3 mg, 0.02 mmol), Nixantphos (16.5 mg, 0.03 mmol), LiN(SiMe3)2 (100.4 mg, 0.6 mmol), CsF (91.1 mg, 0.6 mmol), toluene 1a (4 mL), iodobenzene 2a (0.2 mmol), and methyldiphenylvinylsilane 3b (0.4 mmol). The reaction tube was sealed and removed from the glove box, and the reaction was stirred at 140 °C for 15 hours. After the reaction was complete, the reaction tube was exposed to air and quenched with a drop of water. The reaction solution was filtered through a short silica gel column (coated with anhydrous sodium sulfate on top) and washed with ethyl acetate (3 mL). The combined organic phases were then concentrated under reduced pressure. The crude product was rapidly purified by chromatography using a 200-300 mesh silica gel column to obtain product 4b (55.7 mg, 71% yield) as a colorless oil. 1 H NMR (400MHz, CDCl3) δ: 7.57 (d, J=6.8Hz, 4H), 7.48-7.41 (m, 6H), 7.38-7.34 (m, 4H), 7.2 9-7.21(m, 6H), 3.98-3.94(m, 1H), 2.26-2.19(m, 2H), 1.19-114(m, 2H), 0.66(s, 3H)ppm. 13 C{ 1H} NMR (101MHz, CDCl3) δ: 145.0, 137.1, 134.6, 129.3, 128.5, 128.1, 127.9, 126.2, 54.8, 30.0, 12.8, -4.4ppm.

[0033] Example 3

[0034] In a nitrogen-filled glove box, a pre-dried 10 mL microwave reaction tube (with a built-in magnetic stirrer) was sequentially loaded with PdCl2 (dppf) (16.3 mg, 0.02 mmol), Nixantphos (16.5 mg, 0.03 mmol), LiN(SiMe3)2 (100.4 mg, 0.6 mmol), CsF (91.1 mg, 0.6 mmol), toluene 1a (4 mL), iodobenzene 2a (0.2 mmol), and triphenylvinylsilane 3c (0.4 mmol). The reaction tube was sealed and removed from the glove box, and the reaction was stirred at 140 °C for 15 hours. After the reaction was complete, the reaction tube was exposed to air and quenched with a drop of water. The reaction solution was filtered through a short silica gel column (coated with anhydrous sodium sulfate on top) and washed with ethyl acetate (3 mL). The combined organic phases were then concentrated under reduced pressure. The crude product was rapidly purified by chromatography using a 200-300 mesh silica gel column to obtain product 4c (61.8 mg, 68% yield) as a colorless oil. 1 H NMR (400MHz, CDCl3) δ: 7.72 (d, J=7.1Hz, 6H), 7.61-7.53 (m, 9H), 7.48-7.44 (m, 4H) , 7.40-7.34(m, 6H), 4.11(t, J=7.6Hz, 1H), 2.52-246(m, 2H), 1.63-1.59(m, 2H)ppm. 13 C{ 1 H} NMR (101MHz, CDCl3) δ: 145.0, 135.9, 135.2, 129.7, 128.7, 128.2, 128.1, 126.4, 55.0, 30.1, 12.0ppm.

Claims

1. A method for synthesizing a silicon-containing diaryl compound, characterized in that: Toluene (Formula 1a), iodobenzene (Formula 2a), and vinylsilane (Formula 3) were reacted in the presence of an alkali metal, a phosphorus ligand, and a palladium catalyst to synthesize a silicon-containing diaryl compound of Formula 4; the palladium catalyst was PdCl2(dppf); the phosphorus ligand was 4,6-bis(diphenylphosphine)phenazine; and the alkali metals were LiN(SiMe3)2 and CsF. Among them, R 1 Selected from phenyl, methyl, R 2 Selected from methyl, phenyl, R 3 Selected from phenyl.

2. The synthesis method according to claim 1, characterized in that, The reaction is carried out under the protection of an inert gas, namely nitrogen.

3. The synthesis method according to claim 1, characterized in that, The organic solvent is toluene.

4. The synthesis method according to claim 1, characterized in that, The ratio of iodobenzene (as shown in formula 2a), reaction formula 3, and palladium catalyst in the reaction is 1-2:1-2:0.05-0.2; the reaction temperature is 120-160℃.

5. The synthesis method according to claim 1, characterized in that, The toluene, iodobenzene, vinylsilane, and silicon-containing diaryl compounds mentioned are listed in one of the following tables:

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