A general method for reduction using sodium borohydride

Abstract

The present invention relates to the field of compound reduction, in particular to a general method for reduction using sodium borohydride. Its technical solution includes weighing dichloromethane liquid, with the mass ratio of dichloromethane to the substrate being 3:1. Add the substrate into dichloromethane. Weigh ethanol liquid, with the molar ratio of ethanol to the substrate being 1:1. Add ethanol into the mixed solution of dichloromethane and the substrate, and stir until evenly mixed. Lower the reaction temperature to 4 - 6 °C. Weigh sodium borohydride, with the molar ratio of sodium borohydride to the substrate being 0.4:1. Add sodium borohydride into the reaction solution in batches, and track the reaction of the solution to keep the temperature at 4 - 6 °C when the raw materials are completely reacted. The present invention uses a mixed solvent of dichloromethane and ethanol as the reaction solvent, reducing the dosage of sodium borohydride, saving a large amount of costs. At the same time, the by-products after the quenching of sodium borohydride are also significantly reduced, reducing the workload of the post-treatment operation. The reaction is mild and controllable, without causing the accumulation of sodium borohydride and reducing the accident risk.

Description

Technical Field

[0001] The invention relates to the field of compound reduction, and in particular to a universal reduction method using sodium borohydride. Background Art

[0002] At present, when carbonyl compounds, silver nitrate, copper sulfate, etc. use sodium borohydride as a reducing agent, methanol or ethanol is generally used as a solvent. In order to ensure solubility and dispersion effect, the amount of solvent used is large, and methanol and ethanol will react chemically with sodium borohydride. Therefore, in the reaction process, sodium borohydride not only reacts with the substrate, but more sodium borohydride will be consumed in the reaction with the solvent. The molar amount of sodium borohydride that needs to be added is 3-4 times the molar amount of the substrate in order to make the raw material react completely, and the reaction is relatively violent. In order to ensure the safety of the reaction, it is often necessary to control the reaction speed at a lower temperature. However, if the temperature is controlled too low, sodium borohydride may sometimes accumulate, and violent reactions at a certain time point may cause accidents such as spraying.

[0003] There are also some carbonyl compounds that use sodium borohydride as a reducing agent and use aprotic solvents, such as THF. Since sodium borohydride is insoluble in aprotic solvents, the reaction is very slow and the temperature needs to be increased, which makes the selectivity of sodium borohydride worse, and the solvent recovery is difficult to reuse.

[0004] The existing quenching system generally uses water or dilute hydrochloric acid to quench sodium borohydride. The introduction of a large amount of water into the reaction system will cause the reaction system to become colloidal and make solid-liquid separation difficult. If the product is water-soluble, the product is difficult to extract, resulting in product loss.

[0005] In view of this, the present invention proposes a universal method for reduction using sodium borohydride. Summary of the invention

[0006] The object of the present invention is to provide a universal method for reduction using sodium borohydride to solve the problems raised in the above background technology.

[0007] To achieve the above object, the present invention provides the following technical solution: a general method for reduction using sodium borohydride, comprising the following steps:

[0008] S1, the substrate is dissolved in an organic solvent, and a reducing agent is added to carry out a reduction reaction;

[0009] S2, diluting concentrated sulfuric acid with ethanol to obtain a diluted sulfuric acid solution, adding the diluted sulfuric acid solution to the reaction solution for quenching, and then adding sodium hydroxide solution to adjust the pH value of the reaction solution to 8-9;

[0010] S3, filter out the solid, evaporate the filtrate, collect the solvent for recycling, and obtain the product by vacuum distillation of the concentrated solution;

[0011] Among them, the substrate described in step S1 is one of ethyl acetoacetate, ethyl 4-chloroacetoacetate, silver nitrate, and copper sulfate pentahydrate. The organic solvent is a mixed solvent of dichloromethane and ethanol. The reducing agent is sodium borohydride. In the reduction reaction, the mass ratio of the substrate to dichloromethane is 1:3, and the molar ratio of the substrate to ethanol and sodium borohydride is 1:1:0.4.

[0012] Furthermore, the specific steps of S1 include:

[0013] A1. Weigh the corresponding mass ratio of the substrate and dichloromethane, and completely dissolve the substrate in dichloromethane to obtain a first mixed solution;

[0014] A2. Weigh the corresponding molar ratio of ethanol according to the substrate, and add the ethanol to the first mixed solution, and stir until evenly mixed to obtain a second mixed solution;

[0015] A3. Weigh the corresponding molar ratio of sodium borohydride according to the substrate, add sodium borohydride to the reaction solution in batches, and perform a tracking reaction on the solution to obtain a third mixed solution.

[0016] Furthermore, the specific steps of S2 include:

[0017] B1. Dilute concentrated sulfuric acid with ethanol to obtain a sulfuric acid dilution solution, and slowly drip the sulfuric acid dilution solution into the third mixed solution until no bubbles emerge from the reaction solution to obtain a fourth mixed solution;

[0018] B2. Then add a sodium hydroxide solution to the fourth mixed solution and adjust the pH value of the reaction solution to 8-9.

[0019] Furthermore, the reaction temperature of sodium borohydride in step A3 is 4-6°C.

[0020] Furthermore, the temperature is maintained at 4-6°C after the raw materials have reacted, and then step B1 is carried out.

[0021] Furthermore, the sulfuric acid dilution solution is obtained by diluting concentrated sulfuric acid 5 times with ethanol.

[0022] Furthermore, in the sodium hydroxide solution, the mass of sodium hydroxide is 25% of the total mass of the sodium hydroxide solution.

[0023] Compared with the prior art, the beneficial effects of the present invention are:

[0024] 1. In the present invention, dichloromethane does not react with sodium borohydride. Dichloromethane can also play a role in dissolving and dispersing, and it basically does not react with the substrate. Compared with methanol, the reaction between ethanol and sodium borohydride is relatively mild. Therefore, using a mixed solvent of dichloromethane and ethanol as the reaction solvent can reduce the dosage of sodium borohydride, save a large amount of costs. At the same time, the by-products after the quenching of sodium borohydride are also significantly reduced, reducing the workload of the post-treatment operation. The reaction temperature of the mixed solvent of dichloromethane and ethanol as the reaction solvent is about 5 °C. Sodium borohydride is added in batches, and the reaction is mild and controllable, without causing the accumulation of sodium borohydride and reducing the accident risk.

[0025] 2. In the present invention, a quenching system of sulfuric acid + ethanol + 25% sodium hydroxide is used, without introducing other solvents, and the solvent can be recycled and reused after recovery. After adding a mixed solution of sulfuric acid and ethanol for quenching, the pH is adjusted to 8 - 9 with a 25% sodium hydroxide solution. Sodium sulfate in the quenched product has a water absorption effect, which is beneficial to reducing the water content in the recycled solvent. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 It is the gas chromatogram of ethyl 3 - hydroxybutyrate, the product obtained after the reduction of ethyl acetoacetate of the present invention;

[0027] Figure 2 It is the gas chromatogram of ethyl 4 - chloro - 3 - hydroxybutyrate, the product obtained after the reduction of ethyl 4 - chloroacetoacetate of the present invention;

[0028] Figure 3 It is the laser particle size diagram of micro - nano silver powder, the product obtained after the reduction of silver nitrate of the present invention;

[0029] Figure 4 It is the laser particle size diagram of micron - sized copper powder, the product obtained after the reduction of copper sulfate pentahydrate of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0030] The technical solutions of the present invention will be further described below with reference to the accompanying drawings and specific embodiments.

[0031] Example 1

[0032] As Figure 1 shown, Example 1 is the reduction of ethyl acetoacetate. 130.1 g of ethyl acetoacetate is taken and dissolved in 390 g of dichloromethane. 46.1 g of ethanol is added, and the mixture is stirred evenly. The temperature of the reaction system is lowered to 4 - 6 °C, and 15.1 g of sodium borohydride is added in batches. The reaction is tracked by TLC until the raw materials are completely reacted, and the temperature is maintained at 4 - 6 °C.

[0033] Dilute concentrated sulfuric acid 5 times with ethanol and slowly drop it into the reaction solution until no bubbles emerge from the reaction solution. Then adjust the pH to 8 - 9 with 25% sodium hydroxide solution. Filter off the solid by suction, rotary evaporate the filtrate, and collect the solvent for recycling. Distill the concentrated solution under reduced pressure to obtain 116.2 g of ethyl 3 - hydroxybutyrate, with a yield of 88% and a gas phase purity of 99%.

[0034] Comparative Experiment 1 - 1

[0035] Take 130.1 g of ethyl acetoacetate, dissolve it in 260 g of ethanol, stir and mix evenly. Cool the reaction system to 4 - 6 °C and add 43 g of sodium borohydride in batches. Monitor the reaction by TLC until the raw materials are completely reacted, and keep the temperature at 4 - 6 °C.

[0036] Dilute concentrated sulfuric acid 5 times with ethanol and slowly drop it into the reaction solution until no bubbles emerge from the reaction solution. Then adjust the pH to 8 - 9 with 25% sodium hydroxide solution. Filter off the solid by suction, rotary evaporate the filtrate, and collect the solvent for recycling. Distill the concentrated solution under reduced pressure to obtain 97.7 g of ethyl 3 - hydroxybutyrate, with a yield of 74% and a gas phase purity of 98.2%.

[0037] Compared with Example 1, in Comparative Experiment 1 - 1, ethanol was used as the solvent during the reduction reaction, and the quenching process was the same as that in Example 1.

[0038] Compared with Comparative Experiment 1 - 1, for reducing the same mass of ethyl acetoacetate in Example 1, the present invention requires less sodium borohydride, obtains a higher - quality product, and has higher yield and gas - phase purity.

[0039] Comparative Experiment 1 - 2

[0040] Take 130.1 g of ethyl acetoacetate, dissolve it in 390 g of dichloromethane, add 46.1 g of ethanol, stir and mix evenly. Cool the reaction system to 4 - 6 °C and add 15.1 g of sodium borohydride in batches. Monitor the reaction by TLC until the raw materials are completely reacted, and keep the temperature at 4 - 6 °C.

[0041] Slowly drop dilute hydrochloric acid into the reaction solution until no bubbles emerge from the reaction solution. Filter off the solid by suction, rotary evaporate the filtrate, and collect the solvent for recycling. Distill the concentrated solution under reduced pressure to obtain 113.4 g of ethyl 3 - hydroxybutyrate, with a yield of 81% and a gas phase purity of 98.6%.

[0042] Compared with Example 1, in Comparative Experiment 1 - 2, the reduction reaction process was the same as that in Example 1, and dilute hydrochloric acid was used for quenching.

[0043] Compared with Comparative Experiment 1 - 2, for reducing the same mass of ethyl acetoacetate in Example 1, the present invention obtains a higher - quality product, and has higher yield and gas - phase purity.

[0044] Example 2

[0045] As Figure 2 shown, Example 2 is the reduction of ethyl 4-chloroacetoacetate. 164.6 g of ethyl 4-chloroacetoacetate was taken and dissolved in 494 g of dichloromethane. 46.1 g of ethanol was added, and the mixture was stirred evenly. The reaction system was cooled to 4-6 °C, and 15.1 g of sodium borohydride was added in batches. The reaction was monitored by TLC until the raw materials were completely reacted, and the temperature was maintained at 4-6 °C.

[0046] Concentrated sulfuric acid was diluted 5 times with ethanol and slowly added dropwise to the reaction solution until no bubbles emerged from the reaction solution. Then, the pH was adjusted to 8-9 with 25% sodium hydroxide solution. The solid was filtered off by suction, the filtrate was rotary evaporated, and the solvent was collected for recycling. The concentrated solution was distilled under reduced pressure to obtain 148 g of the product ethyl 4-chloro-3-hydroxybutyrate, with a yield of 89% and a gas-phase purity of 99%.

[0047] Comparative Experiment 2-1

[0048] 164.6 g of ethyl 4-chloroacetoacetate was taken and dissolved in 330 g of ethanol. The mixture was stirred evenly. The reaction system was cooled to 4-6 °C, and 43 g of sodium borohydride was added in batches. The reaction was monitored by TLC until the raw materials were completely reacted, and the temperature was maintained at 4-6 °C.

[0049] Concentrated sulfuric acid was diluted 5 times with ethanol and slowly added dropwise to the reaction solution until no bubbles emerged from the reaction solution. Then, the pH was adjusted to 8-9 with 25% sodium hydroxide solution. The solid was filtered off by suction, the filtrate was rotary evaporated, and the solvent was collected for recycling. The concentrated solution was distilled under reduced pressure to obtain 131.2 g of the product ethyl 3-hydroxybutyrate, with a yield of 75% and a gas-phase purity of 98.4%.

[0050] Compared with Example 2, ethanol was used as the solvent during the reduction reaction in Comparative Experiment 2-1, and the quenching process was the same as that in Example 2.

[0051] Compared with Comparative Experiment 2-1, for the reduction of the same mass of ethyl 4-chloroacetoacetate in Example 2, the present invention requires less sodium borohydride, and the obtained product has higher quality, higher yield and higher gas-phase purity.

[0052] Comparative Experiment 2-2

[0053] 164.6 g of ethyl 4-chloroacetoacetate was taken and dissolved in 494 g of dichloromethane. 46.1 g of ethanol was added, and the mixture was stirred evenly. The reaction system was cooled to 4-6 °C, and 15.1 g of sodium borohydride was added in batches. The reaction was monitored by TLC until the raw materials were completely reacted, and the temperature was maintained at 4-6 °C.

[0054] Slowly drip dilute hydrochloric acid into the reaction solution until no bubbles emerge from the reaction solution. Filter off the solid by suction filtration, rotary evaporate the filtrate, and collect the solvent for recycling. Distill the concentrated solution under reduced pressure to obtain 145.4 g of ethyl 4-chloro-3-hydroxybutyrate with a yield of 82% and a gas-phase purity of 98.8%.

[0055] In comparative experiment 2-2, compared with Example 2, the reduction reaction process is the same as that in Example 2, and dilute hydrochloric acid is used for quenching.

[0056] Compared with comparative experiment 2-2, in Example 2, when reducing the same mass of ethyl 4-chloroacetoacetate, the product quality obtained by the present invention is higher, and the yield and gas-phase purity are higher.

[0057] Example 3

[0058] As Figure 3 shown, Example 3 is the reduction of silver nitrate. 169.9 g of silver nitrate is dissolved in 510 g of dichloromethane, 46.1 g of ethanol is added, and the mixture is stirred evenly. The temperature of the reaction system is lowered to 4-6 °C, and 15.1 g of sodium borohydride is added in batches. ICP-OES is used to track the silver ions until the reaction is completed, and the temperature of the raw materials is maintained at 4-6 °C after the reaction is completed.

[0059] Concentrated sulfuric acid is diluted 5 times with ethanol and slowly dripped into the reaction solution until no bubbles emerge from the reaction solution. Then, the pH is adjusted to 8-9 with 25% sodium hydroxide solution. After the quenching is completed, the solid is filtered off with a 200-mesh filter paper, the filtrate is settled, the powder is washed with water and ethanol, and then dried to obtain 101.3 g of micro-nano silver powder with a yield of 93.9%.

[0060] Comparative experiment 3-1

[0061] 169.9 g of silver nitrate is dissolved in 340 g of ethanol, and the mixture is stirred evenly. The temperature of the reaction system is lowered to 4-6 °C, and 43 g of sodium borohydride is added in batches. ICP-OES is used to track the silver ions until the reaction is completed, and the temperature of the raw materials is maintained at 4-6 °C after the reaction is completed.

[0062] Concentrated sulfuric acid is diluted 5 times with ethanol and slowly dripped into the reaction solution until no bubbles emerge from the reaction solution. Then, the pH is adjusted to 8-9 with 25% sodium hydroxide solution. After the quenching is completed, the solid is filtered off with a 200-mesh filter paper, the filtrate is settled, the powder is washed with water and ethanol, and then dried to obtain 87.2 g of micro-nano silver powder with a yield of 88.2%.

[0063] In comparative experiment 3-1, compared with Example 3, ethanol is used as the solvent in the reduction reaction process, and the quenching process is the same as that in Example 3.

[0064] Compared with comparative experiment 3-1, in Example 3, when reducing the same mass of silver nitrate, the present invention requires less sodium borohydride, and the obtained product has higher quality and higher yield.

[0065] Comparative Experiment 3-2

[0066] 169.9 g of silver nitrate was dissolved in 510 g of dichloromethane, 46.1 g of ethanol was added, and the mixture was stirred evenly. The reaction system was cooled to 4-6 °C, and 15.1 g of sodium borohydride was added in batches. ICP-OES was used to track the silver ions until the reaction was completed, and the temperature was maintained at 4-6 °C after the raw materials reacted completely.

[0067] Dilute hydrochloric acid was slowly dropped into the reaction solution until no bubbles emerged from the reaction solution. After the quenching was completed, the solid was filtered off with a 200-mesh filter paper, the filtrate was allowed to settle, the powder was washed with water and then with ethanol, and after drying, 99.6 g of micro-nano silver powder was obtained, with a yield of 85.7%.

[0068] Compared with Example 3, the reduction reaction process of Comparative Experiment 3-2 was the same as that of Example 3, and dilute hydrochloric acid was used for quenching.

[0069] Compared with Comparative Experiment 3-2, when reducing the same mass of silver nitrate, the product obtained by the present invention has a higher quality and a higher yield.

[0070] Example 4

[0071] As Figure 4 shown, Example 4 was the reduction of copper sulfate pentahydrate. 249.7 g of copper sulfate pentahydrate was dissolved in 750 g of dichloromethane, 46.1 g of ethanol was added, and the mixture was stirred evenly. The reaction system was cooled to 4-6 °C, and 15.1 g of sodium borohydride was added in batches. ICP-OES was used to track the silver ions until the reaction was completed, and the temperature was maintained at 4-6 °C after the raw materials reacted completely.

[0072] Concentrated sulfuric acid was diluted 5 times with ethanol and slowly dropped into the reaction solution until no bubbles emerged from the reaction solution, and then the pH was adjusted to 8-9 with 25% sodium hydroxide solution. After the quenching was completed, the solid was filtered off with a 200-mesh filter paper, the filtrate was allowed to settle, the powder was washed with water and then with ethanol, and after drying, 60.5 g of micron-sized copper powder was obtained, with a yield of 95.3%.

[0073] Comparative Experiment 4-1

[0074] 249.7 g of copper sulfate pentahydrate was dissolved in 750 g of dichloromethane, 46.1 g of ethanol was added, and the mixture was stirred evenly. The reaction system was cooled to 4-6 °C, and 15.1 g of sodium borohydride was added in batches. ICP-OES was used to track the silver ions until the reaction was completed, and the temperature was maintained at 4-6 °C after the raw materials reacted completely.

[0075] Concentrated sulfuric acid was diluted 5 times with ethanol and slowly added dropwise to the reaction solution until no bubbles emerged from the reaction solution, and then the pH was adjusted to 8-9 with 25% sodium hydroxide solution. After quenching, the solid was filtered off with a 200-mesh filter paper, the filtrate was allowed to settle, the powder was washed with water and ethanol, and after drying, 53.8 g of micron-sized copper powder was obtained with a yield of 89.6%.

[0076] In Comparative Experiment 4-1, compared with Example 4, ethanol was used as the solvent during the reduction reaction, and the quenching process was the same as that in Example 4.

[0077] Compared with Comparative Experiment 4-1, for reducing the same mass of copper sulfate pentahydrate in Example 4, less sodium borohydride was required in the present invention, and the product obtained had higher quality and higher yield.

[0078] Comparative Experiment 4-2

[0079] 249.7 g of copper sulfate pentahydrate was dissolved in 500 g of ethanol, stirred and mixed evenly, the reaction system was cooled to 4-6 °C, and 43 g of sodium borohydride was added in batches. ICP-OES was used to track the silver ions until the reaction was completed, and the temperature was maintained at 4-6 °C after the raw materials reacted completely.

[0080] Dilute hydrochloric acid was slowly added dropwise to the reaction solution until no bubbles emerged from the reaction solution. After quenching, the solid was filtered off with a 200-mesh filter paper, the filtrate was allowed to settle, the powder was washed with water and ethanol, and after drying, 59.4 g of micron-sized copper powder was obtained with a yield of 87.3%.

[0081] Compared with Comparative Experiment 4-2, for reducing the same mass of copper sulfate pentahydrate in Example 4, the product obtained in the present invention had higher quality and higher yield.

[0082] The above specific embodiments are merely several preferred embodiments of the present invention. Based on the technical solution of the present invention and the relevant inspirations of the above embodiments, those skilled in the art can make various alternative improvements and combinations to the above specific embodiments.

Claims

1. A general method for reduction using sodium borohydride, characterized in that, The method comprises the following steps: S1, the substrate is dissolved in an organic solvent, and a reducing agent is added to carry out a reduction reaction; S2, diluting concentrated sulfuric acid with ethanol to obtain a diluted sulfuric acid solution, adding the diluted sulfuric acid solution to the reaction solution for quenching, and then adding sodium hydroxide solution to adjust the pH value of the reaction solution to 8-9; S3, filter out the solid, evaporate the filtrate, collect the solvent for recycling, and obtain the product by vacuum distillation of the concentrated solution; Wherein, the substrate in step S1 is one of ethyl acetoacetate, ethyl 4-chloroacetoacetate, silver nitrate, and copper sulfate pentahydrate, the organic solvent is a mixed solvent of dichloromethane and ethanol, the reducing agent is sodium borohydride, and the mass ratio of the substrate to dichloromethane in the reduction reaction is 1:3, and the molar ratio of the substrate to ethanol and sodium borohydride is 1:1:0.

4.

2. A general method for reduction using sodium borohydride according to claim 1, characterized in that, The specific steps of S1 include: A1, weighing a substrate and dichloromethane in a corresponding mass ratio, and completely dissolving the substrate in the dichloromethane to obtain a first mixed solution; A2, weighing ethanol in a corresponding molar ratio according to the substrate, adding the ethanol to the first mixed solution, stirring until the mixture is uniform, and obtaining a second mixed solution; A3. Weigh sodium borohydride in a corresponding molar ratio according to the substrate, add the sodium borohydride to the reaction solution in batches, and perform a follow-up reaction on the solution to obtain a third mixed solution.

3. A general method for reduction using sodium borohydride according to claim 1, characterized in that, The specific steps of S2 include: B1. diluting concentrated sulfuric acid with ethanol to obtain a diluted sulfuric acid solution, and slowly dripping the diluted sulfuric acid solution into the third mixed solution until no bubbles emerge in the reaction solution to obtain a fourth mixed solution; B2. Add sodium hydroxide solution to the fourth mixed solution to adjust the pH value of the reaction solution to 8-9.

4. A general method for reduction using sodium borohydride according to claim 2, characterized in that, The reaction temperature of sodium borohydride in step A3 is 4-6°C.

5. A general method for reduction using sodium borohydride according to claim 3, characterized in that, After the raw materials have reacted, the temperature is maintained at 4-6°C, and then step B1 is performed.

6. A general method for reduction using sodium borohydride according to claim 3, characterized in that, The diluted sulfuric acid solution is obtained by diluting concentrated sulfuric acid 5 times with ethanol.

7. A general method for reduction using sodium borohydride according to claim 3, characterized in that, In the sodium hydroxide solution, the mass of sodium hydroxide is 25% of the total mass of the sodium hydroxide solution.

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