CN112321628B - Preparation method of beta-dimethylphenyl silicon substituted organic nitrile compound - Google Patents

Abstract

The invention discloses a preparation method of beta-dimethylphenyl silicon substituted organic nitrile compound, which comprises the steps of firstly adding water into a chitosan loaded copper film material, and uniformly stirring at room temperature to obtain a mixed solution; adding alpha, beta-unsaturated carbonyl compound I and (dimethylbenzene silane group) boric acid pinacol ester into the mixed solution, and stirring at room temperature until the reaction is complete; after the reaction is finished, filtering, respectively washing precipitates obtained by filtering with tetrahydrofuran and acetone to obtain filtrate, and recycling the chitosan loaded copper film material; the filtrate is concentrated by rotary evaporation, and the residue is subjected to flash column chromatography by using ethyl acetate/petroleum ether mixed solvents with different proportions, and the organic nitrile compound II is obtained by separation and purification. The catalytic activity of the membrane material in the method is very high, and the higher conversion rate of the reactant can be realized only by using lower catalyst dosage.

Description

Preparation method of β-dimethylphenylsilane substituted organic nitrile compounds

Technical Field

The invention relates to the field of organic synthesis, and in particular to a method for preparing a beta-dimethylphenylsilane-substituted organic nitrile compound.

Background Art

Organic nitrile compounds are a class of important organic compounds containing cyano (-CN), which are useful intermediates in organic synthesis and important monomers in polymer synthesis. Due to their special properties, they are widely used in the fields of synthetic chemistry, materials and medicinal chemistry, especially in cutting-edge fields such as defense cutting-edge technology and aerospace special materials. Some nitriles can even be directly used as pesticides, fragrances, metal corrosion inhibitors or liquid crystal materials. Organic nitrile compounds can undergo a variety of chemical conversion reactions, such as conversion into carboxylic acids, aldehydes, ketones, esters, amides, amines, tetrazoles and other nitrogen heterocyclic compounds. There are many methods for the synthesis of organic nitrile compounds, among which the Rosenmund-von Braun reaction is the most traditional method, but it requires a certain amount of highly toxic CuCN, which will cause environmental pollution; the use of transition metal catalysis and safe cyanide sources can overcome this drawback. However, the production process of many nitrile compounds cannot avoid toxicity, the use of precious metals, harsh reaction conditions, and the generation of a large number of pollutants. These shortcomings hinder its more widespread application in organic synthesis. In the synthesis of β-silicon substituted nitrile compounds, cross-coupling is an important method and approach to construct C(sp ³ )-Si bonds. In recent years, the addition reaction of (dimethylphenylsilyl)boronic acid pinacol ester Ph ₂ MeSi-B(pin) to α,β-unsaturated nitrile compounds to prepare organic nitrile compounds has gradually become a hot research area.

At present, the literature generally requires the use of noble metals as catalysts, such as Pd, Rh, etc., and such methods are costly, polluting, and unsuitable for practical applications. In the case of using cheap metals, copper salts are generally used as catalysts in literature reports, but ligands or strong bases (such as sodium tert-butyl alcohol) need to be added, and the operation requirements are relatively strict, such as low temperature and anhydrous and oxygen-free operation. These problems greatly limit the large-scale application of such methods in actual production.

In 2008, the literature (Angewandte Chemie International Edition 2008, 47, 3818) reported that [Rh(cod) ₂ ]OTf was used as a catalyst, R-(+)-1,1'-binaphthyl-2,2'-bis(diphenylphosphine) was used as a ligand, 1,4-dioxane/H ₂ O (10:1) was used as a solvent, and the base Et ₃ N was added to react at 50°C. The β-silicon addition reaction of (dimethylphenylsilyl)boronic acid pinacol ester Me ₂ PhSi-Bpin to cyano-substituted alkenyl compounds was achieved for the first time to obtain β-dimethylphenylsilyl-substituted organic nitrile compounds. However, this method uses 5 mol% of noble metal catalysts and 10 mol% of toxic ligands, and the entire reaction system is a homogeneous catalytic system, the product is difficult to separate, and the residual metals, ligands and solvents will cause product and environmental pollution. In 2010, the document (Journal of the American Chemical Society 2010, 132, 2898) reported that 1 mol% CuCl was used as a catalyst, 2.2 mol% NaOt-Bu base was added, and the β-silicon addition reaction of (dimethylphenylsilyl) boric acid pinacol ester Me ₂ PhSi-Bpin to cyano-substituted alkenyl compounds was achieved at -78°C without the presence of a proton source, and β-dimethylphenylsilyl substituted organic nitrile compounds were obtained with enantioselectivity. This method uses a monovalent copper salt of metal and does not require a proton source, but requires the use of a strong base and expensive NHC ligands, and the post-processing is complicated and environmentally unfriendly. In 2015, the document (Journal of the American Chemical Society 2015, 137, 15422) reported the use of Cu(acac) ₂ and a specially prepared chiral bipyridine ligand, with H ₂ O as a solvent, at room temperature to catalyze the preparation of β-silicon substituted organic nitrile compounds. This method is currently the simplest route to prepare β-dimethylphenylsilane-substituted organic nitrile compounds, but due to the complex ligand preparation of this method, it has not been commercialized, which limits the reaction cost and is not conducive to actual production.

Therefore, it is urgent to develop a new method that is simple, easy to operate, has mild conditions, low cost, is green and environmentally friendly, and is suitable for large-scale production of β-dimethylphenylsilane-substituted organic nitrile compounds.

Summary of the invention

The present invention aims to provide a method for preparing β-dimethylphenylsilane-substituted organic nitrile compounds, which aims to overcome the following deficiencies in the prior art to at least a certain extent:

1) When precious metals are used as catalysts for synthesizing β-dimethylphenylsilane-substituted organic nitrile compounds as synthetic raw materials, the cost is high and industrialization is not possible;

2) When monovalent copper is used as a catalyst, the operation process is complicated and requires harsh conditions such as strong base (sodium tert-butoxide, etc.), low temperature, and strict anhydrous conditions, which also results in high production costs;

3) When divalent copper is used as a catalyst, a specially prepared chiral bipyridine ligand needs to be added. The preparation of the ligand is complicated, the cost is high, and it cannot be commercialized.

Therefore, the present invention aims to develop a new environmentally friendly method for efficiently preparing β-dimethylphenylsilane substituted organic nitrile compounds using low-cost chitosan-loaded copper film materials without adding any ligands.

In order to achieve the above-mentioned purpose, the present invention adopts the following technical measures:

A method for preparing β-dimethylphenylsilane-substituted organic nitrile compounds catalyzed by chitosan-supported copper film materials, the synthesis is as follows:

Wherein, R is any one of phenyl, p-methoxyphenyl, p-fluorophenyl, thiophene and methyl;

The synthesis steps are:

1) adding water to the chitosan-loaded copper film material (CP@Cu NPs), stirring evenly at room temperature to obtain a mixed solution;

2) adding the cyano-substituted alkenyl compound I and (dimethylphenylsilyl)boronic acid pinacol ester Ph ₂ MeSi-B(pin) to the mixed solution, and stirring at room temperature until the reaction is complete; wherein the molar ratio of the cyano-substituted alkenyl compound I to (dimethylphenylsilyl)boronic acid pinacol ester Ph ₂ MeSi-B(pin) is 1:1.2-2.0; and the amount of the chitosan-loaded copper film material is 25-80 mg per millimole (mmol) of the cyano-substituted alkenyl compound I;

3) After the reaction is completed, filtering is performed, and the precipitate obtained by filtering is washed with tetrahydrofuran and acetone respectively to obtain a filtrate, and the chitosan-loaded copper film material is recovered for reuse;

4) The filtrate was concentrated by rotary evaporation, and the residue was separated and purified by flash column chromatography using ethyl acetate/petroleum ether mixed solvents in different ratios to obtain organic nitrile compound II (the ratio of ethyl acetate/petroleum ether mixed solvent was selected according to the different polarities of the product, and the flash column chromatography used silica gel as the stationary phase).

Furthermore, R is any one of phenyl, p-fluorophenyl and thiophene;

Furthermore, in step 2), the molar ratio of the cyano-substituted alkenyl compound I to (dimethylphenylsilyl)boronic acid pinacol ester Ph ₂ MeSi-B(pin) is 1:1.2-1.6; and the amount of chitosan-loaded copper film material used is 30-70 mg per mmol of the cyano-substituted alkenyl compound I.

Furthermore, in the step 2), the stirring reaction time is 5-10 hours.

Furthermore, in step 3), the recovered chitosan-loaded copper film material is washed with distilled water, dried in an oven at 120° C. for 5 hours, and then used again in the above-mentioned preparation step of the organic nitrile compound.

Technical concept of the present invention:

The method of the present invention uses chitosan/polyvinyl alcohol supported nano copper composite film (Chitosan/PolyvinylAlcohol Support Nano Copper, CP@Cu NPs) as a catalyst, and the preparation method of chitosan/polyvinyl alcohol supported copper film catalyst material is carried out according to the reported method. (Dimethylphenylsilyl) boric acid pinacol ester Ph ₂ MeSi-B (pin) (Annaiji Chemical) is used as a reaction reagent, and water is used as a solvent. Under the catalysis of chitosan supported copper film material (CP@Cu NPs), the supported copper catalyst material and Ph ₂ MeSi-B (pin) are complexed, and addition is carried out with substrates containing different substituents to generate a silicon substitution reaction, thereby achieving the preparation of the target β-dimethylphenylsilane substituted organic nitrile compound. After the reaction is completed, the advantage of the membrane material catalyst being easy to separate and recycle is utilized, and the chitosan supported copper film material can be simply recovered by filtering, and the subsequent recycling of the catalyst is easy to achieve, thereby reducing costs, being more green and economical, and being environmentally friendly.

Beneficial effects of the present invention:

1. The present invention adopts chitosan-loaded copper film material for the first time, and provides a new method for the preparation of organic nitrile compounds in addition to the previously reported monovalent copper salt catalysis method, which has a completely different reaction mechanism and process.

2. The present invention does not need to add any toxic ligands, and also achieves efficient preparation of β-dimethylphenylsilane-substituted organic nitrile compounds, which not only reduces the cost but also reduces the difficulty of subsequent separation and purification;

3. The catalytic activity of the membrane material in the method of the present invention is very high, and only a relatively low amount of catalyst is required to achieve a high conversion rate of the reactants;

4. The method of the present invention has mild reaction conditions, uses pure water as solvent, and reacts at room temperature, which is simple and easy to operate;

5. The method of the present invention has a wide range of applications and can be used for various types of cyano-substituted alkenyl compounds, and successfully prepares the corresponding β-dimethylphenylsilane-substituted organic nitrile compounds.

6. In the method of the present invention, chitosan-loaded copper film material is used as a catalyst, and the entire reaction system is heterogeneous. The catalyst can be easily removed by filtering after the reaction is completed.

7. In the method of the present invention, the chitosan-loaded copper film material can be reused after simple post-treatment after recovery to carry out catalytic reactions without obvious activity loss. The recycling experimental data are shown below. Taking I-1 as the raw material to generate product II-1 as an example, after the reaction is completed, the chitosan-loaded copper film material is recovered by filtration and used for the next round of reaction after post-treatment. This step is repeated five times to obtain the target product with yields of 94%, 92%, 89%, 90%, and 91%, respectively, proving that the catalytic material can be recycled.

DETAILED DESCRIPTION

The present invention is further described in detail below in conjunction with specific embodiments so that those skilled in the art can understand.

Example 1

The preparation method of organic nitrile compound II-1 comprises the following steps:

1) Add 5 mg of chitosan-loaded copper film material (CP@Cu NPs) to a 2.5 mL reaction tube, add 2.0 mL of water, and stir at room temperature for 10 minutes to obtain a mixed solution;

2) Add cyano-substituted alkenyl compound I-1 (25.8 mg, 0.2 mmol) and (dimethylphenylsilyl)boronic acid pinacol ester Ph ₂ MeSi-B(pin) (62.9 mg, 0.24 mmol) to the mixed solution; stir and react at room temperature for 5 h;

3) After the reaction is completed, the entire reaction system is filtered, washed with 5 mL of tetrahydrofuran and 5 mL of acetone in sequence, and the chitosan-loaded copper film material is recovered;

4) The filtrate was concentrated by rotary evaporation, and the residue was separated and purified by column chromatography using a 6:1 ethyl acetate/petroleum ether mixed solvent to obtain an organic nitrile compound II-1, 47.8 mg, with a yield of 90%.

The H NMR spectrum and C NMR spectrum of the target product (organic nitrile compound II-1) are shown below:

¹ H NMR (600MHz); δ = 0.26 (s, 6H), 2.58-2.64 (m, 3H), 6.93 (d, J = 7.0Hz, 2H), 7.15-7.17 (m, 1H), 7.23-7.26 ( m,2H),7.35-7.40(m,5H).

¹³ C NMR (150MHz); δ = -5.6, -4.1, 18.8, 33.0, 119.6, 126.0, 127.4, 128.0, 128.5, 129.8, 134.0, 135.1, 139.6.

Example 2

The preparation method of organic nitrile compound II-2 comprises the following steps:

1) Add 8 mg of chitosan-loaded copper film material (CP@Cu NPs) to a 2.5 mL reaction tube, add 2.0 mL of water, and stir at room temperature for 10 minutes to obtain a mixed solution;

2) Add cyano-substituted alkenyl compound I-2 (31.8 mg, 0.2 mmol) and (dimethylphenylsilyl)boronic acid pinacol ester Ph ₂ MeSi-B(pin) (62.9 mg, 0.24 mmol) to the mixed solution; stir and react at room temperature for 8 h;

3) After the reaction is completed, the entire reaction system is filtered, washed with 5 mL of tetrahydrofuran and 5 mL of acetone in sequence, and the chitosan-loaded copper film material is recovered;

4) The filtrate was concentrated by rotary evaporation, and the residue was separated and purified by column chromatography using a 9:1 ethyl acetate/petroleum ether mixed solvent to obtain an organic nitrile compound II-2, 50.2 mg, with a yield of 85%.

The H NMR spectrum and C NMR spectrum of the target product (organic nitrile compound II-2) are shown below:

¹ H NMR (600MHz); δ=0.25 (d, J=2.7Hz, 6H), 2.50-2.60 (m, 3H), 3.77 (s, 3H), 6.78-6.86 (m, 4H), 7.34-7.39 ( m,5H);

¹³ C NMR (150MHz); δ = -5.5, -4.0, 19.2, 32.0, 55.2, 114.0, 119.7, 128.0, 128.4, 129.8, 131.6, 134.0, 135.4, 157.8.

Example 3

The preparation method of organic nitrile compound II-3 comprises the following steps:

1) Add 12 mg of chitosan-loaded copper film material (CP@Cu NPs) to a 2.5 mL reaction tube, add 2.0 mL of water, and stir at room temperature for 10 minutes to obtain a mixed solution;

2) Add cyano-substituted alkenyl compound I-3 (29.4 mg, 0.2 mmol) and (dimethylphenylsilyl)boronic acid pinacol ester Ph ₂ MeSi-B(pin) (104.9 mg, 0.4 mmol) to the mixed solution; stir and react at room temperature for 10 h;

3) After the reaction is completed, the entire reaction system is filtered, washed with 5 mL of tetrahydrofuran and 5 mL of acetone in sequence, and the chitosan-loaded copper film material is recovered;

4) The filtrate was concentrated by rotary evaporation, and the residue was separated and purified by column chromatography with a 9:1 ethyl acetate/petroleum ether mixed solvent to obtain 51.0 mg of organic nitrile compound II-3 with a yield of 90%. The H-NMR and C-NMR spectra of the target product (organic nitrile compound II-3) are shown below:

¹ H NMR (600MHz); δ=0.27 (d, J=3.4Hz, 6H), 2.56-2.63 (m, 3H), 6.87-6.96 (m, 4H), 7.35-7.40 (m, 5H);

¹³ C NMR (150MHz); δ = -5.5, -4.2, 19.1, 32.3, 115.4(d), 119.4, 128.1, 128.7(d), 130.0, 134.0, 134.8, 135.3, 162.1.

Example 4

The preparation method of organic nitrile compound II-4 comprises the following steps:

1) Add 16 mg of chitosan-loaded copper film material (CP@Cu NPs) to a 2.5 mL reaction tube, add 2.0 mL of water, and stir at room temperature for 10 minutes to obtain a mixed solution;

2) Add cyano-substituted alkenyl compound I-4 (23.8 mg, 0.2 mmol) and (dimethylphenylsilyl)boronic acid pinacol ester Ph ₂ MeSi-B(pin) (62.9 mg, 0.24 mmol) to the mixed solution; stir and react at room temperature for 10 h;

3) After the reaction is completed, the entire reaction system is filtered, washed with 5 mL of tetrahydrofuran and 5 mL of acetone in sequence, and the chitosan-loaded copper film material is recovered;

4) The filtrate was concentrated by rotary evaporation, and the residue was separated and purified by column chromatography with a 6:1 ethyl acetate/petroleum ether mixed solvent to obtain 48.5 mg of organic nitrile compound II-4 with a yield of 95%. The H-NMR and C-NMR spectra of the target product (organic nitrile compound II-4) are shown below:

¹ H NMR (600MHz); δ = 0.27 (s, 3H), 0.28 (s, 3H), 3.23 (dd, J = 3.7, 13.3Hz, 1H), 4.47 (dd, J = 3.9, 13.7Hz, 1H) ,4.80(t,J＝13.5Hz,1H),6.95(d,J＝7.2Hz,2H),7.12-7.15(m,1H),7.20-7.24(m,2H),7.35-7.43(m,5H );

¹³ C NMR (150MHz); δ = -5.5, -4.0, 36.1, 76.8, 126.1, 127.3, 128.2, 128.6, 130.0, 133.9, 134.8, 137.5.

Example 5

The preparation method of organic nitrile compound II-5 comprises the following steps:

1) Add 5 mg of chitosan-loaded copper film material (CP@Cu NPs) to a 2.5 mL reaction tube, add 2.0 mL of water, and stir at room temperature for 10 minutes to obtain a mixed solution;

2) Add cyano-substituted alkenyl compound I-5 (13.4 mg, 0.2 mmol) and (dimethylphenylsilyl)boronic acid pinacol ester Ph ₂ MeSi-B(pin) (62.9 mg, 0.24 mmol) to the mixed solution; stir and react at room temperature for 7 h;

3) After the reaction is completed, the entire reaction system is filtered, washed with 5 mL of tetrahydrofuran and 5 mL of acetone in sequence, and the chitosan-loaded copper film material is recovered;

4) The filtrate was concentrated by rotary evaporation, and the residue was separated and purified by column chromatography using a 9:1 ethyl acetate/petroleum ether mixed solvent to obtain an organic nitrile compound II-5, 36.2 mg, with a yield of 89%.

The H NMR spectrum and C NMR spectrum of the target product (organic nitrile compound II-5) are shown below:

¹ H NMR (600MHz); δ = 0.26 (s, 3H), 0.27 (s, 3H), 2.27 (s, 3H), 3.18 (dd, J = 3.8, 13.4Hz, 1H), 4.44-4.47 (m, 1H), 4.76 (t, J = 13.4Hz, 1H), 6.84 (d, J = 8.0Hz, 2H), 7.02 (d, J = 7.7Hz, 2H), 7.36-7.41 (m, 5H);

¹³ C NMR (150MHz); δ = -5.5, -3.9, 20.9, 35.6, 77.1, 127.2, 128.2, 129.3, 130.0, 133.9, 134.3, 135.1, 135.6.

Although the above embodiments have been described in detail, they are only a part of the embodiments of the present invention, not all of them. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all belong to the protection scope of the present invention.

Claims (5)

1. A method for preparing β-dimethylphenylsilane-substituted organic nitrile compounds catalyzed by chitosan-supported copper film material, characterized in that the synthesis is as follows:

Wherein, R is any one of phenyl, p-methoxyphenyl, p-fluorophenyl, thiophene and methyl; The synthesis steps are: 1) adding water to the chitosan-loaded copper film material, stirring evenly at room temperature to obtain a mixed solution; wherein the chitosan-loaded copper film material is prepared by the following steps: 200 mg of chitosan powder was added to 10 mL of acetic acid solution and stirred at room temperature for 5 h. 100 mg of polyvinyl alcohol was added to 10 mL of distilled water and stirred at 80 °C until completely dissolved. At room temperature, the chitosan solution and polyvinyl alcohol solution were mixed and stirred for half an hour until uniform, and then 80 μL of 25 w/w% glutaraldehyde solution was added dropwise while stirring. The mixed solution was then poured into a culture dish and dried in an oven at 40 °C for 24 h until all the water evaporated. The chitosan/polyvinyl alcohol film was peeled off from the culture dish, immersed in 100 mL of 0.1 mol/L sodium hydroxide solution for 5 minutes, and then washed with distilled water several times until the pH test paper detected it to be neutral, and then the CP film was dried in an oven at 40 °C for 24 h. The CP film was immersed in 25 mL of 0.2 mol/L CuCl ₂ ·2H ₂ O solution for 2.5 h, and then the CP@Cu ²⁺ film adsorbed with Cu ²⁺ ions was collected and placed in an oven at 40 °C for 24 h. The ²⁺ membrane was immersed in 100 mL of freshly prepared 50 mmol/L sodium borohydride solution for 15 minutes, then the membrane was taken out, washed several times with distilled water, and then placed in a 40 °C oven for drying for 24 h to obtain a CP membrane loaded with copper nanoparticles, namely, chitosan-loaded copper membrane material CP@Cu NPs; 2) adding the cyano-substituted alkenyl compound I and (dimethylphenylsilyl)boronic acid pinacol ester Ph ₂ MeSi-B(pin) to the mixed solution, and stirring at room temperature until the reaction is complete; wherein the molar ratio of the cyano-substituted alkenyl compound I to (dimethylphenylsilyl)boronic acid pinacol ester Ph ₂ MeSi-B(pin) is 1:1.2-2.0; and the amount of the chitosan-loaded copper film material is 25-80 mg per millimole of the cyano-substituted alkenyl compound I; 3) After the reaction is completed, filtering is performed, and the precipitate obtained by filtering is washed with tetrahydrofuran and acetone respectively to obtain a filtrate, and the chitosan-loaded copper film material is recovered for reuse; 4) The filtrate was concentrated by rotary evaporation, and the residue was separated and purified by flash column chromatography using a mixed solvent of ethyl acetate/petroleum ether in different ratios to obtain an organic nitrile compound II. 2. The method for preparing β-dimethylphenylsilane-substituted organic nitrile compounds catalyzed by chitosan-supported copper film material according to claim 1, characterized in that: the R is any one of phenyl, p-fluorophenyl and thiophene. 3. The method for preparing β-dimethylphenylsilyl substituted organic nitrile compounds catalyzed by chitosan-supported copper film material according to claim 1, characterized in that: in the step 2), the molar ratio of the cyano-substituted alkenyl compound I to (dimethylphenylsilyl) boric acid pinacol ester _Ph2MeSi -B(pin) is 1:1.2-1.6; and the amount of chitosan-supported copper film material used for each millimole of the cyano-substituted alkenyl compound I is 30-70 mg. 4. The method for preparing β-dimethylphenylsilane-substituted organic nitrile compounds catalyzed by chitosan-supported copper film material according to claim 1, characterized in that: in the step 2), the stirring reaction time is 5-10 hours. 5. The method for preparing β-dimethylphenylsilane-substituted organic nitrile compounds catalyzed by chitosan-loaded copper film material according to claim 1, characterized in that: in the step 3), the recovered chitosan-loaded copper film material is washed with distilled water, placed in an oven at 120° C. and dried for 5 hours, and then used again in the preparation step of the organic nitrile compounds.