A kind of synthesis method of trimethyl silyl nitrile

Abstract

The invention belongs to the technical field of organic synthesis, and specifically relates to a method for synthesizing trimethylsilyl nitrile, comprising the following steps: (1) synthesizing 1,1,1-trimethylsilylamine: reacting trimethylchlorosilane and ammonia to obtain oily 1,1,1-trimethylsilylamine; (2) synthesizing an intermediate diazonium salt: reacting the 1,1,1-trimethylsilylamine in step (1) with an acid and sodium nitrite; (3) synthesizing trimethylsilyl nitrile: adding a cyaniding agent to the reaction solution in step (2), reacting for 8 to 12 hours, and then extracting and rectifying to obtain the final product trimethylsilyl nitrile. Beneficial effects of the invention: the method for synthesizing trimethylsilyl nitrile uses potassium ferrocyanide or cuprous cyanide as a cyaniding agent, avoids the use of sodium cyanide, potassium cyanide and hydrogen cyanide to endanger the safety of workers, improves the safety of synthesizing trimethylsilyl nitrile, and thus the method for synthesizing trimethylsilyl nitrile is easy to carry out large-scale industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing trimethyl silylated nitrile. Background Art

[0002] Trimethylsilyl nitrile, also known as trimethylsilyl nitrile or trimethylsilyl cyanide, is a commonly used organic synthesis reagent. As a strong nucleophile, it is widely used in ring-opening reactions of cyclic nitrogen and epoxy compounds, addition of imines and aldehydes and ketones, multi-component reactions involving amines and aldehydes or ketones, coupling reactions, and cyanation addition reactions of alkynes and highly active carbon-carbon double bonds.

[0003] Patents US4328351A and US4570009A disclose a method for synthesizing trimethyl silyl nitrile, in which sodium cyanide is used in the synthesis. US4429145A also discloses a method for synthesizing trimethyl silyl nitrile, in which potassium cyanide is used in the synthesis. Both sodium cyanide and potassium cyanide are highly toxic substances, and the production operation risk is relatively high, which is not suitable for large-scale safe production. In addition, patent US5258534A uses hydrogen cyanide gas as a cyaniding reagent to synthesize trimethyl silyl nitrile, and its production risk is even higher. Therefore, how to design a method for synthesizing trimethyl silyl nitrile that can improve the safety of large-scale production while being simple to operate and easy to control has become a problem to be solved. Summary of the invention

[0004] In view of the above problems, the present invention provides a method for synthesizing trimethyl silylated nitrile.

[0005] The present invention relates to a method for synthesizing trimethyl silylated nitrile, comprising the following steps:

[0006] (1) Synthesis of 1,1,1-trimethylsilylamine:

[0007] Add trimethylsilyl chloride and solvent into a reaction vessel, start stirring, then slowly introduce ammonia gas, seal and react after the introduction is complete, add purified water for extraction and separation after the reaction is completed by gas chromatography, wash the organic phase with water, and concentrate the organic phase under reduced pressure to obtain oily 1,1,1-trimethylsilylamine;

[0008] (2) Synthesis of intermediate diazonium salt:

[0009] Add the 1,1,1-trimethylsilylamine and solvent in step (1) into a reaction vessel, start stirring, slowly add acid at 25°C, add sodium nitrite aqueous solution dropwise after cooling, and keep warm for 1 to 3 hours after the addition is complete;

[0010] (3) Synthesis of trimethylsilyl nitrile:

[0011] Slowly add the cyaniding reagent to the reaction solution of step (2), and after the addition is completed, keep the reaction warm. After the reaction is completed by gas chromatography, add dichloromethane for extraction and separation, wash the dichloromethane phase with water, and concentrate the dichloromethane phase under reduced pressure to obtain a crude trimethylsilyl nitrile, which is then distilled to obtain the final product trimethylsilyl nitrile.

[0012] Preferably, in step (1), the reaction is carried out in a sealed state at 20°C to 40°C for 4 to 6 hours.

[0013] Preferably, in step (1), the volume of the solvent is measured in milliliters, the mass of the trimethylchlorosilane is measured in grams, and the volume of the solvent is 0.5 to 5.0 times the mass of the trimethylchlorosilane; and the solvent is dichloromethane or ethyl acetate.

[0014] Preferably, in step (1), the molar ratio of trimethylsilyl chloride to ammonia is 1:1.5-3.0.

[0015] Preferably, in step (2), the reaction is carried out at a temperature between -10°C and 5°C.

[0016] Preferably, in step (2), the volume of the solvent is measured in milliliters, the mass of the 1,1,1-trimethylsilylamine is measured in grams, and the volume of the solvent is 0.5 to 5.0 times the mass of the 1,1,1-trimethylsilylamine; and the solvent is purified water.

[0017] Preferably, in step (2), the acid is concentrated hydrochloric acid, concentrated sulfuric acid or hydrobromic acid.

[0018] Preferably, in steps (2) and (3), the molar ratio of 1,1,1-trimethylsilylamine, sodium nitrite, acid and cyaniding agent is 1:1.0-1.3:2.0-3.0:1.0-2.0.

[0019] Preferably, in step (3), the cyaniding agent is potassium ferrocyanide or cuprous cyanide.

[0020] Preferably, in step (3), the temperature is lowered to -10°C to 5°C; and the reaction is kept at -10°C to 5°C for 8 to 12 hours.

[0021] Compared with the prior art, the advantages and positive effects of the present invention are:

[0022] (1) The synthesis method of trimethylsilyl nitrile uses potassium ferrocyanide or cuprous cyanide as a cyaniding agent, thereby avoiding the use of sodium cyanide, potassium cyanide and hydrogen cyanide to endanger the safety of workers, thereby improving the safety of synthesizing trimethylsilyl nitrile, so that the synthesis method of trimethylsilyl nitrile is easy to carry out large-scale industrial production;

[0023] (2) The synthesis method of trimethyl silylated nitrile has mild reaction conditions, so the reaction process is more stable, making the production process safer and easier to control, and the reaction performance will not be affected when it is scaled up to industrial production scale;

[0024] (3) The synthesis method of trimethylsilyl nitrile is simple to operate, reduces labor costs, and improves the stability and reliability of large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the technical solution of the embodiment of the present invention, the following briefly introduces the drawings required for describing the embodiment.

[0026] Figure 1 The synthetic route of the compound of the present invention is shown in FIG. DETAILED DESCRIPTION

[0027] In order to more clearly understand the above-mentioned objects, features and advantages of the present invention, the present invention is further described below in conjunction with embodiments.

[0028] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways than those described herein. Therefore, the present invention is not limited to the specific embodiments of the following disclosure.

[0029] Example 1

[0030] A method for synthesizing trimethyl silylated nitrile comprises the following steps:

[0031] (1) Synthesis of 1,1,1-trimethylsilylamine

[0032] 100 g (0.92 mol) of trimethylsilyl chloride and 300 ml of dichloromethane were added to a 1 L pressure-resistant reaction bottle, stirring was started, and then 31.35 g (1.84 mol) of ammonia gas was slowly introduced. After the introduction was completed, the reaction was sealed at 25 ° C for 5 hours. After the reaction was completed by gas chromatography, 500 ml of purified water was added for extraction and separation, and the dichloromethane phase was washed once with 300 ml of purified water. The dichloromethane phase was concentrated under reduced pressure to obtain 75.0 g of oily 1,1,1-trimethylsilylamine; the reaction yield was 91.33%, and the purity of 1,1,1-trimethylsilylamine was 98.5%.

[0033] (2) Synthesis of intermediate diazonium salts

[0034] 75.0 g (0.84 mol) of 1,1,1-trimethylsilylamine and 225 ml of purified water in step (1) were added to a 1 L three-necked reaction bottle, stirring was started, and 175.14 g (1.68 mol) of 35% concentrated hydrochloric acid was slowly added at 25°C. After stirring for 0.5 hours, the temperature was controlled at 0°C, and 200 ml of a 5.04 mol / L sodium nitrite aqueous solution was added dropwise. After the addition was completed, the mixture was kept at 0°C for 2 hours.

[0035] (3) Synthesis of trimethylsilyl nitrile

[0036] The temperature was controlled at 0°C, and 82.82 g (0.92 mol) of cuprous cyanide was slowly added in batches to the reaction solution of step (2). After the addition was completed, the reaction was kept warm for 10 hours. After the reaction was completed by gas chromatography, 200 ml of dichloromethane was added for extraction and separation. The dichloromethane phase was washed with 300 ml of purified water. The dichloromethane phase was concentrated under reduced pressure to obtain 78.5 g of crude trimethylsilyl nitrile, which was then distilled to obtain 70.6 g of the final product trimethylsilyl nitrile. The reaction yield was 84.6%, and the purity of the final product trimethylsilyl nitrile was 99.8%.

[0037] Example 2

[0038] A method for synthesizing trimethyl silylated nitrile comprises the following steps:

[0039] (1) Synthesis of 1,1,1-trimethylsilylamine

[0040] 100 g (0.92 mol) of trimethylsilyl chloride and 400 ml of ethyl acetate were added to a 1 L pressure-resistant reaction bottle, stirring was started, and then 34.08 g (2.0 mol) of ammonia gas was slowly introduced. After the introduction was completed, the reaction was sealed at 20°C for 4 hours. After the reaction was completed by gas chromatography, 500 ml of purified water was added for extraction and separation, and the dichloromethane phase was washed once with 400 ml of purified water. The dichloromethane phase was concentrated under reduced pressure to obtain 74.61 g of oily 1,1,1-trimethylsilylamine; the reaction yield was 90.85%, and the purity of 1,1,1-trimethylsilylamine was 99.2%.

[0041] (2) Synthesis of intermediate diazonium salts

[0042] 74.61 g (0.84 mol) of 1,1,1-trimethylsilylamine and 350 ml of purified water in step (1) were added to a 1 L three-necked reaction bottle, stirring was started, and 250 g (2.0 mol) of 98% concentrated sulfuric acid was slowly added at 25°C. After stirring for 0.5 hour, the temperature was controlled at -5°C, and 200 ml of a 6.0 mol / L sodium nitrite aqueous solution was added dropwise. After the addition was complete, the mixture was kept at -5°C for 1.5 hours.

[0043] (3) Synthesis of trimethylsilyl nitrile

[0044] The temperature was controlled at -5°C, and 368.52 g (1.0 mol) of potassium ferrocyanide was slowly added in batches to the reaction solution of step (2). After the addition was completed, the reaction was kept warm for 11 hours. After the reaction was completed by gas chromatography, 250 ml of dichloromethane was added for extraction and separation. The dichloromethane phase was washed with 350 ml of purified water. The dichloromethane phase was concentrated under reduced pressure to obtain 80.3 g of crude trimethylsilyl nitrile, which was then distilled to obtain 73.6 g of the final product trimethylsilyl nitrile; the reaction yield was 88.7%, and the purity of the final product trimethylsilyl nitrile was 99.5%.

[0045] The above description is only a preferred embodiment of the present invention and does not limit the present invention in other forms. Any technician familiar with the profession may use the technical content disclosed above to change or modify it into an equivalent embodiment with equivalent changes for application in other fields. However, any simple modification or equivalent change made to the above embodiment based on the technical essence of the present invention without departing from the content of the technical solution of the present invention still falls within the protection scope of the technical solution of the present invention.

Claims

1. A method for synthesizing trimethylsilyl nitrile, characterized in that: The following steps are involved: (1) Synthesis of 1,1,1-trimethylsilylamine: Add trimethylsilyl chloride and solvent into a reaction container, start stirring, then slowly introduce ammonia gas, seal and react after the introduction is complete, add purified water for extraction and separation after the reaction is completed by gas chromatography, wash the organic phase with water, and concentrate the organic phase under reduced pressure to obtain oily 1,1,1-trimethylsilylamine; the solvent is dichloromethane or ethyl acetate; (2) Synthesis of intermediate diazonium salt: Add the 1,1,1-trimethylsilylamine and solvent in step (1) into a reaction vessel, start stirring, slowly add acid at 25°C, add sodium nitrite aqueous solution dropwise after cooling, and keep warm for 1 to 3 hours after the addition is complete; the solvent is purified water; (3) Synthesis of trimethylsilyl nitrile: Slowly add the cyaniding agent to the reaction solution of step (2), and after the addition is completed, carry out the reaction at a heat preservation temperature. After the reaction is completed by gas chromatography, add dichloromethane to extract and separate the liquids, wash the dichloromethane phase with water, and concentrate the dichloromethane phase under reduced pressure to obtain a crude trimethylsilylnitrile, which is then distilled to obtain the final product trimethylsilylnitrile; the cyaniding agent is potassium ferrocyanide or cuprous cyanide.

2. The method for synthesizing trimethylsilyl nitrile according to claim 1, wherein In the step (1), the reaction is carried out in a sealed state at 20°C to 40°C for 4 to 6 hours.

3. The method for synthesizing trimethylsilyl nitrile according to claim 1, characterized in that: In the step (1), the volume of the solvent is measured in milliliters, the mass of the trimethylchlorosilane is measured in grams, and the volume of the solvent is 0.5 to 5.0 times the mass of the trimethylchlorosilane.

4. The method for synthesizing trimethylsilyl nitrile according to claim 1, characterized in that: In the step (1), the molar ratio of trimethylsilyl chloride to ammonia is 1:1.5-3.

0.

5. The method for synthesizing trimethylsilyl nitrile according to claim 1, characterized in that: In the step (2), the reaction is carried out at a temperature of -10°C to 5°C.

6. The method for synthesizing trimethyl silylation nitrile according to claim 1, characterized in that: In the step (2), the volume of the solvent is measured in milliliters, the mass of the 1,1,1-trimethylsilylamine is measured in grams, and the volume of the solvent is 0.5 to 5.0 times the mass of the 1,1,1-trimethylsilylamine.

7. The method for synthesizing trimethylsilyl nitrile according to claim 1, characterized in that: In the step (2), the acid is concentrated hydrochloric acid, concentrated sulfuric acid or hydrobromic acid.

8. The method for synthesizing trimethyl silylation nitrile according to claim 1, characterized in that: In the steps (2) and (3), the molar ratio of the 1,1,1-trimethylsilylamine, sodium nitrite, acid and cyaniding agent is 1:1.0-1.3:2.0-3.0:1.0-2.

0.

9. The method for synthesizing trimethylsilyl nitrile according to claim 1, characterized in that: In the step (3), the temperature is lowered to -10°C to 5°C; and the reaction is carried out at -10°C to 5°C for 8 to 12 hours.

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