Synthesis method of aryl silicon compound
Through the room temperature reaction catalyzed by palladium acetate, the problems of harsh reaction conditions for the synthesis of aryl silicon compounds and limited application scope of substrates in the prior art are solved, and a synthesis method with mild conditions, low cost and wide application scope is realized.
Patent Information
- Application Number
- CN202411866750.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-18
- Publication Date
- 2025-04-11
AI Technical Summary
The existing methods for synthesizing aryl silicon compounds have problems such as harsh reaction conditions, high preparation costs and limited application scope of substrates.
Palladium acetate was used as a catalyst, and aryl halide was used as substrate to react with silane compounds at room temperature to construct C(sp2)-Si bonds to achieve the synthesis of aryl silicon compounds.
The synthesis of aryl silicon compounds with mild conditions and a wide range of substrate application has been achieved, which reduces the preparation cost and broadens the application range.
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Figure CN119798293A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic chemical synthesis and relates to a new method for synthesizing aryl silicon compounds. Background Art
[0002] Synthesis of aryl silicon compounds and construction of C(sp 2 )-Si bonds are of profound importance in the fields of chemistry and materials science. 2 )-Si bonds can enrich the types of organosilicon compounds and promote the development of organosilicon chemistry. These organosilicon compounds have broad application prospects in the fields of medicine, pesticides, dyes, and fragrances. For example, 2 )-Si bonded organosilicon materials have excellent high and low temperature resistance, oxidation resistance, electrical insulation and biocompatibility, and can be used to manufacture high-performance coatings, rubbers, plastics, etc.
[0003] There are many methods for synthesizing aryl silicon compounds. One of them is the organometallic reagent method. The following are two examples of the organometallic reagent method for synthesizing aryl silicon compounds:
[0004] 1. Reaction of organic lithium reagents with halogenated silanes: Organic lithium reagents have strong nucleophilicity and can undergo nucleophilic substitution reaction with halogenated silanes to construct C(sp 2 )-Si bond. For example, phenyllithium reacts with trimethylsilyl chloride to form a phenyl group. 2 The trimethylsilyl group is introduced on the carbon. However, the reaction conditions are relatively harsh and need to be carried out at low temperature, in the absence of water and oxygen to avoid the reaction of the organic lithium reagent with water and oxygen.
[0005] 2. Reaction of Grignard reagent with halogenated silane: Grignard reagent can also react with halogenated silane to construct C(sp 2 )-Si bond. For example, vinyl Grignard reagent reacts with chlorosilane to generate a C(sp 2 )-Si bond products. However, this reaction requires the preparation of Grignard reagents first, and attention must be paid to the dryness of the reaction system.
[0006] The second method is to construct C(sp) by transition metal-catalyzed cross-coupling reactions of aryl halides with disilanes as silicon sources. 2 )-Si bond. However, according to the reported work, the transition metal-catalyzed silylation reaction of aryl halides (I, Br) with triethoxysilane is only effective for electron-rich and neutral para-substituted aryl halides, while for electron-deficient aryl halides, the reaction efficiency is low or does not work because the presence of para-position electron-withdrawing groups (such as -NO2) on the aromatic ring interferes with the reaction.
[0007] Although the above methods have made some progress, there is still a great demand for the construction of C(sp 2 )-Si bonds are still in high demand. Therefore, it is necessary to develop a new method with better functional group compatibility that can achieve direct Si-based transfer to various aryl halides. Summary of the invention
[0008] In view of the above-mentioned technical status, especially the existing methods for synthesizing aryl silicon compounds, which mostly use organometallic reagents, have the defects of complex reactions, high preparation costs, and limited application range of substrates, the inventors of the present invention have conducted in-depth and extensive research on the construction of C(sp2)-Si bonds, studied the silylation reaction of aryl halides under palladium catalysis, thereby obtaining various aryl silane compounds, and constructed C(sp 2 )-Si bond. A method for preparing aryl silicon compounds with mild conditions, readily available raw materials and applicable to various aromatic hydrocarbons was determined.
[0009] Therefore, the purpose of the present invention is to provide a method for synthesizing aryl silicon compounds under mild conditions and with a wider range of synthetic substrates. Compared with the existing method using an organic metal reagent, the present invention uses palladium acetate as a catalyst and an aryl halide as a substrate to obtain an aryl silicon compound at room temperature, thereby constructing C(sp 2 )-Si bond. The aryl silane compounds of the present invention are of wide variety, and one side of the aryl structure can be various electron-withdrawing, electron-donating and neutral groups, and one side of the silane is not limited to a single structure, and can also be a chain alkane, an aromatic group or a chlorine or hydrogen atom. The silanization of aromatic hydrocarbons is achieved, which is of great significance for further development and application in the fields of functional materials, life and medical sciences, etc.
[0010] The technical solution for achieving the above-mentioned purpose of the present invention can be summarized as follows:
[0011] A method for synthesizing an aryl silicon compound, using palladium acetate as a catalyst and an aryl halide as a substrate, reacting with a silane compound in the presence of a solvent and an organic base; the aryl silicon compound has a structure shown in formula (III):
[0012]
[0013] In formula (III), R 1 is one of nitro, methoxy, cyano, ester, acetyl, trifluoromethyl, oxytrifluoromethyl, methyl, and hydrogen; R 2 , R 3 , R 4 are independently selected from at least one of alkyl, phenyl, chlorine and hydrogen, R 2 , R 3, R 4 Same or different.
[0014] According to the present invention, preferably, the alkyl group is a C2-C4 alkyl group, and more preferably a methyl group or an ethyl group.
[0015] According to the present invention, preferably, the aryl silane compound has the following structure:
[0016]
[0017] According to the present invention, preferably, the aryl halide has a structure shown in formula (I):
[0018]
[0019] In formula (I), X is one of chlorine, bromine and iodine.
[0020] R 1 The meanings are the same as in the structure of formula (III).
[0021] According to the present invention, preferably, the silane compound has a structure shown in formula (II):
[0022]
[0023] R 2 , R 3 , R 4 The meanings are the same as in the structure of formula (III).
[0024] According to the present invention, preferably, the molar ratio of the aryl halide to the silane compound is 1:(1-3), more preferably 1:(1.5-1.8), and most preferably 1:2.5.
[0025] According to the present invention, preferably, the amount of palladium acetate catalyst used is 1 mol%-10 mol% of the amount of aryl halide used, further preferably 3 mol%-8 mol%, and most preferably 4 mol%.
[0026] According to the present invention, preferably, the organic base is pyridine, DMAP or DIPEA, and pyridine is most preferred.
[0027] According to the present invention, preferably, the molar ratio of the aryl halide to the organic base is 1:(1-3), more preferably 1:(1.5-2.5); most preferably 1:2.4.
[0028] According to the present invention, preferably, the solvent is DMI (1,3-dimethyl-2-imidazolidinone), DMA (N,N-dimethylacetamide), DMF (N,N-dimethylformamide) or NMP (N-methylpyrrolidone), and DMI is most preferred.
[0029] According to the present invention, preferably, the reaction temperature is 10°C to 50°C, more preferably 15°C to 40°C, and most preferably 25°C.
[0030] According to the present invention, preferably, an additive is further added to the reaction system, and the additive is LiCl, NaCl, NaOAc, KOAc or LiBr; most preferably, the additive is LiCl.
[0031] According to the present invention, preferably, the molar ratio of the aryl halide to the additive is 1:(2-5), more preferably 1:(5.5-4.5); most preferably 1:4.
[0032] Beneficial effects of the present invention:
[0033] 1. The present invention reports a C(sp 2 )-Si bond construction strategy, and palladium-catalyzed synthesis strategy of aryl silane. By using cheap aryl halides to react with silane compounds, C(sp 2 )-Si bonds were efficiently constructed. This strategy achieved the silylation of aromatic hydrocarbons and successfully constructed C(sp 2 )-Si bond, which is of great significance for its further development and application in the fields of functional materials, life and medical sciences.
[0034] 2. The present invention is not limited to the synthesis of a single aromatic silane compound. The types of aromatic silane compounds that can be synthesized are relatively wide. One side of the aromatic structure can be various electron-withdrawing, electron-donating and neutral groups. One side of the silane is not limited to a single structure, but can also be a chain alkane, an aromatic group or a chlorine or hydrogen atom, which broadens the scope of application.
[0035] 3. The present invention is easy to operate, has a wide substrate adaptability, and has good universality, including aromatic halides substituted with various substituents, which can effectively realize C(sp 2 )-Si bonds were efficiently constructed, and structurally diverse aromatic silane compounds were prepared in good yields.
[0036] 4. The raw materials, organic bases and additives used in the present invention are commonly used commercial reagents, which are very stable and have the characteristics of low cost, high yield, simple process and less pollution.
[0037] 5. The post-processing of the present invention is simple and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS
[0038] Figure 1 The triethyl (4-nitrophenyl) silane prepared in Example 1 of the present invention is 1 H-NMR spectrum;
[0039] Figure 2 The triethyl (4-nitrophenyl) silane prepared in Example 1 of the present invention is 13 C-NMR spectrum. DETAILED DESCRIPTION
[0040] The present invention provides a method for synthesizing an aryl silicon compound. Compared with the existing method using an organic metal reagent, the present invention uses palladium acetate as a catalyst and an aryl halide as a substrate to obtain an aryl silicon compound at room temperature, thereby constructing C(sp 2 )-Si bond.
[0041] According to the present invention, a method for synthesizing an aryl silicon compound is provided, wherein palladium acetate is used as a catalyst, an aryl halide is used as a substrate, and a silane compound is reacted in the presence of a solvent and an organic base; the aryl silicon compound has a structure shown in formula (III):
[0042]
[0043] In formula (III), R 1 is one of nitro, methoxy, cyano, ester, acetyl, trifluoromethyl, oxytrifluoromethyl, methyl, and hydrogen; R 2 , R 3 , R 4 are independently selected from at least one of alkyl, phenyl, chlorine and hydrogen, R 2 , R 3 , R 4 Same or different.
[0044] In one or more preferred embodiments, the alkyl group is a C2-C4 alkyl group, more preferably a methyl group or an ethyl group.
[0045] In one or more preferred embodiments, the arylsilane compound has the following structure:
[0046]
[0047] In one or more preferred embodiments, the aryl halide has a structure shown in formula (I):
[0048]
[0049] In formula (I), X is one of chlorine, bromine and iodine.
[0050] R 1 The meanings are the same as in the structure of formula (III).
[0051] In one or more preferred embodiments, the silane compound has a structure shown in formula (II):
[0052]
[0053] R 2 , R 3 , R 4 The meanings are the same as in the structure of formula (III).
[0054] In one or more preferred embodiments, the molar ratio of the aryl halide to the silane compound is 1:(1-3), more preferably 1:(1.5-2.8), for example: 1:2.3, 1:2.5, 1:2.7, etc., and most preferably 1:2.5.
[0055] In one or more preferred embodiments, the amount of palladium acetate catalyst used is 1 mol%-10 mol% of the amount of aryl halide used, more preferably 3 mol%-8 mol%, most preferably 4 mol%.
[0056] In one or more preferred embodiments, the organic base is pyridine, DMAP or DIPEA, most preferably pyridine.
[0057] According to the present invention, preferably, the molar ratio of the aryl halide to the organic base is 1:(1-3), more preferably 1:(1.5-2.5); most preferably 1:2.4.
[0058] In one or more preferred embodiments, the solvent is DMI (1,3-dimethyl-2-imidazolidinone), DMA (N,N-dimethylacetamide), DMF (N,N-dimethylformamide) or NMP (N-methylpyrrolidone), most preferably DMI.
[0059] In one or more preferred embodiments, the reaction temperature is 10°C to 50°C, more preferably 15°C to 40°C, for example 18°C, 20°C, 23°C, 25°C, 28°C, 30°C, 35°C, etc., most preferably 25°C.
[0060] According to the present invention, an additive is further added to the reaction system. The additive further inhibits the generation of by-products, increases the yield, and can also improve the selectivity of the reaction.
[0061] According to the present invention, preferably, an additive is further added to the reaction system, and the additive is LiCl, NaCl, NaOAc, KOAc or LiBr; most preferably, the additive is LiCl.
[0062] According to the present invention, preferably, the molar ratio of the aryl halide to the additive is 1:(2-5), more preferably 1:(5.5-4.5); most preferably 1:4.
[0063] According to the present invention, a method for synthesizing an aryl silicon compound, a preferred embodiment, comprises the following steps:
[0064] Add aryl halide, additive and palladium acetate catalyst to a Schlenk tube equipped with a magnetic bar and a rubber stopper;
[0065] The Schlenk tube is evacuated with N2, and the solvent is added via a syringe, followed by the silane compound via a syringe; for solid organic bases, it is added together with the aryl halide; for liquid organic bases, it is added together with the silane compound;
[0066] After the reaction is completed, the aryl silane compound is obtained by purification.
[0067] In one or more preferred embodiments, the reaction progress is followed by TLC.
[0068] In one or more preferred embodiments, the purification method is as follows:
[0069] After the reaction is completed, 10 mL of water is added to the reaction system, and the organic phase is extracted with ethyl acetate. The obtained organic phase is concentrated and purified by silica gel chromatography (PE) to obtain an aryl silane compound.
[0070] According to the present invention, the arylsilane compound has received extensive attention in organic synthetic chemistry, material chemistry, medicinal chemistry, etc. and has shown good application prospects. It is an important type of synthetic intermediate in synthetic chemistry and has great research value and application prospects.
[0071] The technical route of the present invention is as follows:
[0072]
[0073] The present invention is further described below by means of specific examples, but is not limited thereto.
[0074] Example 1
[0075] A method for synthesizing an aryl silicon compound, wherein the aryl silane compound has the following structure:
[0076]
[0077] To a Schlenk tube equipped with a magnetic bar and a rubber stopper, 1-iodo-4-nitrobenzene (124.7 mg, 0.5 mmol), LiCl (87.4 mg, 2 mmol) and Pd(OAc)2 (4.5 mg, 0.02 mmol) were added.
[0078] The Schlenk tube was vented with N2, and DMI (2 ml) was added via a syringe. Pyridine (100 μL, 1.2 mmol) and Et3SiH (200 μL, 1.25 mmol) were added via a syringe. After the reaction was completed, 10 mL of water was added to the reaction system, and the organic phase was extracted with ethyl acetate. The resulting organic phase was concentrated and purified by silica gel chromatography (PE) to obtain triethyl (4-nitrophenyl) silane (73 mg, 63%).
[0079] 1 H NMR (500MHz, CDCl3) δ8.2(d,J=8.6Hz,2H),7.7(d,J=8.5Hz,2H),1.0–0.9(m,9H),0.9–0.8(m,6H);
[0080] 13 C NMR (126MHz, CDCl3) δ148.5,147.3,135.0,122.2,7.2,3.1.
[0081] Example 2
[0082] A method for synthesizing an aryl silicon compound, wherein the aryl silane compound has the following structure:
[0083]
[0084] To a Schlenk tube equipped with a magnetic bar and a rubber stopper, 1-iodo-4-nitrobenzene (124.7 mg, 0.5 mmol), LiCl (87.4 mg, 2 mmol) and Pd(OAc)2 (4.5 mg, 0.02 mmol) were added.
[0085] The Schlenk tube was ventilated with N2, and DMI (2 ml) was added via a syringe. Pyridine (100 μL, 1.2 mmol) and Ph3SiH (262.1 mg, 1 mmol) were added via a syringe. After the reaction was completed, 10 mL of water was added to the reaction system, and the organic phase was extracted with ethyl acetate. The resulting organic phase was concentrated and purified by silica gel chromatography (PE) to obtain (4-nitrophenyl)triphenylsilane (133.9 mg, 70%).
[0086] Example 3
[0087] A method for synthesizing an aryl silicon compound, wherein the aryl silane compound has the following structure:
[0088]
[0089] To a Schlenk tube equipped with a magnetic bar and a rubber stopper, 1-iodo-4-nitrobenzene (124.7 mg, 0.5 mmol), LiCl (87.4 mg, 2 mmol) and Pd(OAc)2 (4.5 mg, 0.02 mmol) were added.
[0090] The Schlenk tube was ventilated with N2, and DMI (2 ml) was added via a syringe. Pyridine (100 μL, 1.2 mmol) and PhMe2SiH (200 μl, 1.3 mmol) were added via a syringe. After the reaction was completed, 10 mL of water was added to the reaction system, and the organic phase was extracted with ethyl acetate. The resulting organic phase was concentrated and purified by silica gel chromatography (PE) to obtain (4-nitrophenyl)triphenylsilane (133.9 mg, 70%).
[0091] Example 4
[0092] A method for synthesizing an aryl silicon compound, wherein the aryl silane compound has the following structure:
[0093]
[0094] To a Schlenk tube equipped with a magnetic bar and a rubber stopper were added 4-iodobenzonitrile (115.9 mg, 0.5 mmol), LiCl (87.4 mg, 2 mmol) and Pd(OAc)2 (4.5 mg, 0.02 mmol).
[0095] The Schlenk tube was vented with N2, and DMI (2 ml) was added via a syringe. Pyridine (100 μL, 1.2 mmol) and Et3SiH (200 μL, 1.25 mmol) were added via a syringe. After the reaction was completed, 10 mL of water was added to the reaction system, and the organic phase was extracted with ethyl acetate. The resulting organic phase was concentrated and purified by silica gel chromatography (PE) to obtain 4-triethylsilylbenzonitrile (51 mg, 46%).
[0096] Example 5
[0097] A method for synthesizing an aryl silicon compound, wherein the aryl silane compound has the following structure:
[0098]
[0099] To a Schlenk tube equipped with a magnetic bar and a rubber stopper were added 4-iodobenzonitrile (115.9 mg, 0.5 mmol), LiCl (87.4 mg, 2 mmol) and Pd(OAc)2 (4.5 mg, 0.02 mmol).
[0100] The Schlenk tube was ventilated with N2, and DMI (2 ml) was added via a syringe. Pyridine (100 μL, 1.2 mmol) and Ph3SiH (262.1 mg, 1 mmol) were added via a syringe. After the reaction was completed, 10 mL of water was added to the reaction system, and the organic phase was extracted with ethyl acetate. The resulting organic phase was concentrated and purified by silica gel chromatography (PE) to obtain 4-triphenylsilylbenzonitrile (119 mg, 64%).
[0101] Example 6
[0102] A method for synthesizing an aryl silicon compound, wherein the aryl silane compound has the following structure:
[0103]
[0104] To a Schlenk tube equipped with a magnetic bar and a rubber stopper were added 4-iodoacetophenone (125.8 mg, 0.5 mmol), LiCl (87.4 mg, 2 mmol) and Pd(OAc)2 (4.5 mg, 0.02 mmol).
[0105] The Schlenk tube was vented with N2, and DMI (2 ml) was added via a syringe. Pyridine (100 μL, 1.2 mmol) and Et3SiH (200 μL, 1.25 mmol) were added via a syringe. After the reaction was completed, 10 mL of water was added to the reaction system, and the organic phase was extracted with ethyl acetate. The resulting organic phase was concentrated and purified by silica gel chromatography (PE), yielding 1-(4-triethylsilylphenyl)ethanone (46 mg, 38%).
[0106] Test Example 1
[0107] Using 1-iodo-4-nitrobenzene and triethylsilane as raw materials, the catalyst dosage was 4 mol%, the additive was LiCl, 1,3-dimethyl-2-imidazolidinone was the solvent, the solvent dosage was 2 mL, the base was pyridine, the base dosage was 2.4 equivalents, the reaction temperature was 25 ° C, the reaction time was 8 hours, and the effect of the type of catalyst on the reaction was investigated, as shown in Table 1.
[0108] Table 1 Effect of [Pd] on the reaction
[0109]
[0110]
[0111] From the experimental results in Table 1, it can be seen that Pd(OAc)2 is the best catalyst for this reaction.
[0112] Test Example 2
[0113] Using 1-iodo-4-nitrobenzene and triethylsilane as raw materials, Pd(OAc)2 as catalyst, the amount of catalyst is 4 mol%, LiCl as additive, the amount of solvent is 2 mL, the base is pyridine, the amount of base is 2.4 equivalents, the reaction temperature is 25 ° C, the reaction time is 8 hours, and the effect of solvent type on the reaction is investigated, as shown in Table 2.
[0114] Table 2 Effect of solvent on reaction
[0115]
[0116] From the experimental results in Table 2, it can be seen that DMI is the best solvent for this reaction.
[0117] Test Example 3
[0118] Using 1-iodo-4-nitrobenzene and triethylsilane as raw materials, Pd(OAc)2 as catalyst, the catalyst dosage is 4 mol%, LiCl as additive, 1,3-dimethyl-2-imidazolidinone as solvent, the solvent dosage is 2 mL, the base dosage is 2.4 equivalents, the reaction temperature is 25 ° C, the reaction time is 8 hours, and the effect of the type of base on the reaction is investigated, as shown in Table 3.
[0119] Table 3 Effect of alkali on the reaction
[0120]
[0121]
[0122] From the experimental results in Table 3, it can be seen that pyridine is the best base for this reaction.
[0123] Test Example 4
[0124] 1-iodo-4-nitrobenzene and triethylsilane were used as raw materials, the catalyst was Pd(OAc)2, the catalyst dosage was 4 mol%, the additive was LiCl, 1,3-dimethyl-2-imidazolidinone was used as solvent, the solvent dosage was 2 mL, the base was pyridine, the base dosage was 2.4 equivalents, the reaction was 1-12 h, and the effects of temperature and time on the reaction were investigated, as shown in Table 4.
[0125] Table 4 Effect of temperature and time on reaction
[0126]
[0127]
[0128] From the experimental results in Table 4, it can be seen that the optimal temperature and time for the reaction are 25°C and 8h.
Claims
1. A method for synthesizing an aryl silicon compound, characterized in that: The method uses palladium acetate as a catalyst and an aryl halide as a substrate to react with a silane compound in the presence of a solvent and an organic base; the aryl silicon compound has a structure shown in formula (III): In formula (III), R 1 is one of nitro, methoxy, cyano, ester, acetyl, trifluoromethyl, oxytrifluoromethyl, methyl, and hydrogen; R 2 , R 3 , R 4 are independently selected from at least one of alkyl, phenyl, chlorine and hydrogen, R 2 , R 3 , R 4 Same or different.
2. The method for synthesizing an aryl silicon compound according to claim 1, characterized in that: The alkyl group is a C2-C4 alkyl group.
3. The method for synthesizing an aryl silicon compound according to claim 1, characterized in that: The arylsilane compound has the following structure:
4. The method for synthesizing an aryl silicon compound according to claim 1, characterized in that: The aryl halide has a structure shown in formula (I): In formula (I), X is one of chlorine, bromine and iodine, and R 1 The meaning is the same as in the structure of formula (III); The silane compound has a structure shown in formula (II): R 2 , R 3 , R 4 The meanings are the same as in the structure of formula (III).
5. The method for synthesizing an aryl silicon compound according to claim 1, characterized in that: The molar ratio of the aryl halide compound to the silane compound is 1:(1-3).
6. The method for synthesizing an aryl silicon compound according to claim 1, characterized in that: The amount of palladium acetate catalyst used is 1 mol%-10 mol% of the amount of aryl halide used.
7. The method for synthesizing an aryl silicon compound according to claim 1, characterized in that: The organic base is pyridine, DMAP or DIPEA; Preferably, the solvent is 1,3-dimethyl-2-imidazolidinone, N,N-dimethylacetamide, N,N-dimethylformamide or N-methylpyrrolidone.
8. The method for synthesizing an aryl silicon compound according to claim 1, characterized in that: The molar ratio of the aryl halide to the organic base is 1:(1-3).
9. The method for synthesizing an aryl silicon compound according to claim 1, characterized in that: The reaction temperature is 10°C to 50°C.
10. The method for synthesizing an aryl silicon compound according to claim 1, characterized in that: An additive is further added to the reaction system, wherein the additive is LiCl, NaCl, NaOAc, KOAc or LiBr; Preferably, the molar ratio of the aryl halide to the additive is 1:(2-5).