Preparation process and application of high-purity benzyl alcohol

Abstract

The invention discloses a preparation process and application of high-purity benzyl alcohol, and relates to the technical field of benzyl alcohol refinement, the preparation process specifically comprises the following steps: S1, mixing benzaldehyde, mesoporous zeolite powder and a sodium hydroxide aqueous solution, carrying out reflux primary reaction, extracting, separating liquid, and distilling to obtain a reaction liquid A; s2, mixing the reaction liquid A, an activating agent and deionized water, heating for secondary reaction, filtering to obtain filtrate, extracting, separating liquid, and distilling to obtain reaction liquid B; s3, mixing the reaction liquid B, zinc borohydride and tetrahydrofuran, performing reflux reaction for three times, distilling and purifying, extracting and washing, drying with anhydrous magnesium sulfate, and distilling to obtain crude benzyl alcohol; s4, carrying out primary vacuum distillation on the crude benzyl alcohol, continuously heating, carrying out secondary vacuum distillation, and collecting distillate, namely high-purity benzyl alcohol; the method can be applied to medicine injection.

Description

Technical Field

[0001] The invention relates to the technical field of benzyl alcohol refining, and specifically to a preparation process of high-purity benzyl alcohol and application thereof. Background Art

[0002] The chemical formula of benzyl alcohol is C 7 H 8 O is a colorless liquid with an aromatic smell. It is an important organic chemical product and intermediate with a wide range of uses. In the field of spices, benzaldehyde is used to make floral spices such as jasmine, lilac, plum blossom, and violet due to its unique aromatic smell; in the agricultural field, it is used as an intermediate for herbicides and plant growth regulators; in the food industry, benzaldehyde is used as a edible flavoring for the preparation of almond, cherry, peach and other flavors; in the pharmaceutical field, benzaldehyde is used to make a variety of pharmaceutical intermediates, such as sulfate of N-methyl-2-methylfuranamine, phenylaminoacetic acid, 2-phenylbenzimidazole, etc., which has extremely important application value.

[0003] Benzyl alcohol has bactericidal, antifungal, and antiparasitic pharmacological activities. It can be used as an important or auxiliary ingredient in the preparation of antibiotics, anticancer drugs, antimalarial drugs, and other drugs. It can also be used as a drug excipient to improve the taste and aroma of the drug and enhance the patient's medication experience. It can also be used as a stabilizer in some drugs. Benzyl alcohol will oxidize into benzaldehyde and benzoic acid when it comes into contact with air. Benzaldehyde is an organic compound with strong irritation and toxicity. Long-term contact or inhalation may cause harm to human health and may even cause cancer. Therefore, the 2020 edition of the "Chinese Pharmacopoeia" has restricted the benzaldehyde content in medicinal benzyl alcohol, requiring that the benzaldehyde content in benzyl alcohol for injection shall not exceed 0.05%.

[0004] In the prior art, the commonly used industrial preparation methods of benzyl alcohol are the benzyl chloride hydrolysis method and the benzaldehyde direct reduction method: benzyl alcohol is obtained by azeotropic hydrolysis of benzyl chloride and an aqueous solution of an alkali, which is simple to operate, but the yield is not high, and because of the presence of chlorine, the product may contain chlorine, which is difficult to use for benzyl alcohol for injection; the benzaldehyde direct reduction method is to use benzaldehyde and a reducing agent to reduce benzyl alcohol to benzyl alcohol, but it also has the problem of low yield, and because the raw material is benzaldehyde, the benzaldehyde content in the product is high and the purity is low, which cannot meet the injection requirements.

[0005] In summary, in order to solve the above problems, it is of great significance to provide a preparation process of benzyl alcohol with high conversion rate and high purity and its application. Summary of the invention

[0006] The object of the present invention is to provide a preparation process of high-purity benzyl alcohol and application thereof, so as to solve the problems raised in the prior art.

[0007] To achieve the above object, the present invention provides the following technical solutions: A preparation process of high-purity benzyl alcohol comprises the following steps: S1: under an inert gas atmosphere, benzaldehyde, mesoporous zeolite powder and sodium hydroxide aqueous solution are added to the reaction system in sequence; reflux once for reaction, cool to room temperature; extract with anhydrous ether, take the ether layer, and evaporate the ether to obtain reaction solution A; S2: Under an inert gas atmosphere, reaction solution A, deionized water, and an activator are sequentially added to the reaction system, heated for secondary reaction, and cooled to room temperature; the filtrate is filtered, extracted with anhydrous ether, the ether layer is taken, and the ether is evaporated to obtain reaction solution B; S3: Under an inert gas atmosphere, the reaction solution B and zinc borohydride are added to tetrahydrofuran in sequence, and the mixture is refluxed for three times for reaction; the tetrahydrofuran is evaporated and the mixture is cooled to room temperature; anhydrous ether is used for extraction, and the ether layer is taken, which is further washed with saturated sodium carbonate, dried over anhydrous magnesium sulfate, filtered, and the ether is evaporated to obtain crude benzyl alcohol; S4: subjecting the crude benzyl alcohol to a vacuum distillation, continuing to raise the temperature, subjecting it to a second vacuum distillation, and collecting the distillate to obtain high-purity benzyl alcohol.

[0008] Preferably, during step S4, during the first vacuum distillation, the vacuum degree is ≤-0.095Mpa, the temperature is 65~75°C, and the time is 50~70min; during the second vacuum distillation, the vacuum degree is ≤-0.095Mpa, the temperature is 80~140°C, and the time is 20~22h.

[0009] Preferably, during step S1, during the primary reflux reaction, the temperature is 170-180°C and the time is 40-50 min; during step S2, during the secondary heating reaction, the temperature is 80-90°C and the time is 25-28 h; during step S3, during the tertiary reflux reaction, the temperature is 60-70°C and the time is 1-1.5 h.

[0010] The specific surface area of ​​the mesoporous zeolite powder is 250-300 g / m 2 The mesoporous zeolite powder is pre-activated in a 10-15% sodium hydroxide solution at room temperature for 10-20 minutes.

[0011] Preferably, the reaction solution A comprises the following raw materials in parts by mass: 10-11 parts of benzaldehyde, 27-28 parts of a sodium hydroxide aqueous solution with a mass fraction of 23-24wt%, and 0.4-0.6 parts of mesoporous zeolite powder; the reaction solution B comprises the following raw materials in parts by mass: 12-15 parts of reaction solution A, 30-40 parts of deionized water, and 0.5-1 parts of activator A; the crude benzyl alcohol comprises the following raw materials in parts by mass: 10-12 parts of reaction solution B, 30-40 parts of tetrahydrofuran, and 1-2 parts of zinc borohydride.

[0012] Preferably, the preparation method of the activator comprises the following steps: (1) adding polyethylene glycol and N-(n-propyl)diethanolamine into a reaction kettle and mixing them evenly, adding a catalyst, heating and stirring at 155-165°C for 6-8 hours under a hydrogen atmosphere, adding water to dissolve, centrifuging, purifying, and drying to obtain modified polyethylene glycol; (2) preparing a mixed salt solution, a mixed alkali solution, and a modified polyethylene glycol solution respectively for use; (3) mixing the mixed salt solution, the mixed alkali solution, the modified polyethylene glycol solution, and deionized water, stirring at 85-90°C for 6-7 hours, filtering, washing, drying, and calcining at 600-650°C under an inert gas atmosphere to obtain an activator.

[0013] Wherein, the mixed salt solution includes magnesium chloride with a concentration of 26-30 g / L and aluminum chloride with a concentration of 13-15 g / L; the mixed alkali solution includes sodium carbonate with a concentration of 21-22 g / L and sodium hydroxide with a concentration of 25-26 g / L; and the modified polyethylene glycol solution has a concentration of 6-7 g / L.

[0014] Preferably, the modified polyethylene glycol comprises the following raw materials in parts by mass: 18 to 22 parts of polyethylene glycol, 0.1 to 0.15 parts of N-(n-propyl)diethanolamine, and 0.5 to 0.8 parts of a catalyst; the mass ratio of the mixed salt solution, the mixed alkali solution, the modified polyethylene glycol solution, and the deionized water is 1:1 to 1.2:1:1.

[0015] Wherein, the molecular weight of the polyethylene glycol is 800-2000; and the catalyst is a SNCAT series loaded nickel catalyst.

[0016] Preferably, the high-purity benzyl alcohol prepared by the present invention can be used for medical injection, specifically including the following aspects: (1) as a disinfectant and preservative: used for local analgesia and preparation preservation; (2) moisturizing effect: benzyl alcohol has a high volatility and can keep the skin moist to a certain extent; (3) promoting wound healing: it has a bactericidal effect and can be used to improve the discomfort symptoms caused by skin trauma, such as pain and swelling, and can promote wound healing after use; (4) auxiliary role in medical operations; (5) sedation: by inhibiting the activity of the central nervous system, reducing the excited state, and producing a sedative effect; (6) anesthesia and analgesia: it can reduce pain perception and provide a comfortable operating environment, and is widely used in clinical operations; at the same time, it has a certain local anesthetic effect, which can effectively reduce or eliminate the patient's pain; (7) local infiltration anesthesia: the nerve fibers in the local tissue temporarily lose their conduction function to achieve a painless state; (8) muscle relaxation: it can affect the transmission of neurotransmitters, resulting in weakened or stopped muscle contraction.

[0017] Compared with the prior art, the present invention has the following beneficial effects: (1) The present invention adopts a multi-step purification of benzyl alcohol to maximize the conversion rate of raw materials and the purity of benzyl alcohol. The present invention first adopts the Cannizzaro reaction, adds sodium hydroxide to make benzaldehyde undergo a disproportionation reaction to generate benzyl alcohol and sodium benzoate, extracts with anhydrous ether, removes the water layer, and obtains a reaction solution A, which mainly contains benzyl alcohol, unreacted benzaldehyde, and a small amount of benzoic acid, while sodium benzoate is removed along with the water layer, and then acidified and purified to obtain benzoic acid, which can be used as a by-product; then an activator is added to preliminarily purify the benzyl alcohol A, and the activator is a hydrotalcite-type magnesium-aluminum layered bimetallic oxide, which has sufficient alkalinity to promote the small amount of benzaldehyde contained in the system to continue to undergo the Cannizzaro reaction. At the same time, due to its layered flaky structure, the carboxyl groups produced by the reaction can be Intercalation adsorption fixes benzoic acid ions between the hydrotalcite layers, effectively promotes the separation of acid and alcohol, and increases the reaction rate in disguise to obtain reaction solution B, which mainly contains benzyl alcohol, a small amount of benzoic acid and a small amount of benzaldehyde. However, the benzaldehyde content at this time cannot meet the requirements, so zinc borohydride is used to reduce trace amounts of benzaldehyde and improve the purity of benzyl alcohol. At the same time, zinc borohydride can also reduce a small amount of benzoic acid contained in the solution into benzoic acid, thereby increasing the conversion rate of the raw materials and obtaining crude benzyl alcohol. Further vacuum distillation and purification are performed to obtain high-purity benzyl alcohol with a benzaldehyde content of less than 0.001%, which meets the requirements for injection.

[0018] (2) The present invention adopts a specific surface area of ​​250-300 g / m 2Mesoporous zeolite is used as a catalyst for the reaction of benzaldehyde and sodium hydroxide, and its porous structure is conducive to providing multiple active sites, thereby increasing the reaction speed. The present invention uses a mesoporous zeolite with a smaller pore size, and activates it with a dilute alkaline solution before use to expose the surface active sites, thereby increasing the reaction rate. The smaller pore size can also prevent the holes from collapsing quickly in an alkaline environment, resulting in a decrease in reaction efficiency. The activator prepared by the present invention uses polyethylene glycol as a template agent, combines with the hydroxyl group on the surface of the generated hydrotalcite through hydrogen bonding, and makes the grown hydrotalcite particles uniform through a steric hindrance effect, and increases the specific surface area. In addition, N-(n-propyl) diethanolamine and polyethylene glycol are used for grafting modification, and its branched structure can further improve its self-assembly effect, increase the specific surface area of ​​the activator, thereby improving the reaction efficiency of benzaldehyde and improving the raw material conversion rate.

[0019] (3) The last step of the present invention uses two vacuum distillations, first removing possible residual water and other low-boiling point substances at a lower temperature, and then extracting ultra-pure benzyl alcohol at a higher temperature. At the same time, the use of vacuum distillation helps to perform distillation and purification at a temperature lower than the normal boiling point of the solution, which can reduce the molecular decomposition caused by excessive local temperature due to uneven temperature, thereby reducing the purity of the product.

[0020] (4) The present invention firstly uses benzaldehyde and sodium hydroxide to react, so that most of the benzaldehyde can be reacted. Then, only a small amount of catalyst is needed to step-by-step treat the remaining unreacted benzaldehyde, so as to gradually improve the conversion rate of benzaldehyde and reduce the benzaldehyde content, thereby greatly reducing the cost and improving the purity of benzyl alcohol and the conversion rate of raw materials. DETAILED DESCRIPTION

[0021] Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in the field without making any creative work shall fall within the scope of protection of the present invention.

[0022] It should be noted that the raw materials involved in the present invention are purchased from manufacturers without any special restrictions, and exemplary examples include: mesoporous zeolite powder with a specific surface area of ​​250-300 g / m 2 ; Benzaldehyde, purity 99%, provided by Nanjing Zhongchun Biotechnology Co., Ltd.; Zinc borohydride, purity 99%, provided by Hubei Wonder Chemical Co., Ltd.; Polyethylene glycol: molecular weight 800~2000; N-(n-propyl)diethanolamine: cas: 6735-35-9; Supported nickel catalyst: SNCAT-6210P, provided by Shanghai Xunkai New Materials Technology Co., Ltd.

[0023] In the following examples, parts are by mass, and raw materials are all commercially available.

[0024] Embodiment 1:

[0025] Step 1: Preparation of activator: (1) 20 parts of polyethylene glycol and 0.1 parts of N-(n-propyl)diethanolamine were added to a reaction kettle and mixed evenly, 0.6 parts of a catalyst was added, and the mixture was heated and stirred at 160° C. for 7 h under a hydrogen atmosphere, and water was added to dissolve the mixture, and the mixture was centrifuged, purified, and dried to obtain modified polyethylene glycol; (2) Prepare a mixed salt solution of 28 g / L magnesium chloride and 14 g / L aluminum chloride, an alkaline solution of 21.5 g / L sodium carbonate and 25.5 g / L sodium hydroxide, and a modified polyethylene glycol solution of 6.5 g / L respectively for use; (3) mixing a salt solution, an alkaline solution, a modified polyethylene glycol solution, and deionized water in a mass ratio of 1:1.1:1:1, stirring at 85°C for 6.5 hours, filtering, washing, drying, and calcining at 650°C under an inert gas atmosphere to obtain an activator; Step 2: Preparation of high-purity benzyl alcohol: S1: Under an inert gas atmosphere, 10.5 parts of benzaldehyde were added to a reaction kettle, and 27.5 parts of a 23.5 wt% sodium hydroxide aqueous solution and 0.5 parts of mesoporous zeolite powder were added, and the mixture was refluxed at 175°C for 50 min, cooled to room temperature, extracted with anhydrous ether, and the ether layer was taken and the ether was evaporated to obtain a reaction solution A; S2: Under an inert gas atmosphere, 13 parts of reaction solution A were added to 35 parts of deionized water and stirred evenly, 0.75 parts of activator were added, and secondary reaction was carried out at 85°C for 26 hours. The filtrate was filtered to obtain the filtrate, and extracted with anhydrous ether. The ether layer was taken and the ether was evaporated to obtain reaction solution B; S3: Under an inert gas atmosphere, 11 parts of the reaction solution B were added to 35 parts of tetrahydrofuran, and 1.5 parts of zinc borohydride were added, and the mixture was refluxed at 67° C. for three times for 1 hour, and the tetrahydrofuran was evaporated, and the mixture was cooled to room temperature; anhydrous ether was used for extraction, and the ether layer was taken, and the mixture was further washed with saturated sodium carbonate, dried over anhydrous magnesium sulfate, filtered, and the ether was evaporated to obtain crude benzyl alcohol; S4: The crude benzyl alcohol is vacuum distilled at 70°C for 60 min at a vacuum degree of ≤-0.095 MPa, and then the temperature is raised to 110°C and vacuum distilled for a second time for 20 h to obtain high-purity benzyl alcohol.

[0026] Embodiment 2:

[0027] Step 1: Preparation of activator: (1) 20 parts of polyethylene glycol and 0.1 parts of N-(n-propyl)diethanolamine were added to a reaction kettle and mixed evenly, 0.6 parts of a catalyst was added, and the mixture was heated and stirred at 160° C. for 7 h under a hydrogen atmosphere, and water was added to dissolve the mixture, and the mixture was centrifuged, purified, and dried to obtain modified polyethylene glycol; (2) Prepare a mixed salt solution of 28 g / L magnesium chloride and 14 g / L aluminum chloride, an alkaline solution of 21.5 g / L sodium carbonate and 25.5 g / L sodium hydroxide, and a modified polyethylene glycol solution of 6.5 g / L respectively for use; (3) mixing a salt solution, an alkaline solution, a modified polyethylene glycol solution, and deionized water in a mass ratio of 1:1.1:1:1, stirring at 85°C for 6.5 hours, filtering, washing, drying, and calcining at 650°C under an inert gas atmosphere to obtain an activator; Step 2: Preparation of high-purity benzyl alcohol: S1: Under an inert gas atmosphere, 10 parts of benzaldehyde were added to a reaction kettle, 27 parts of a 23 wt% sodium hydroxide aqueous solution and 0.5 parts of mesoporous zeolite powder were added, and the mixture was refluxed at 175°C for 50 min, cooled to room temperature, extracted with anhydrous ether, the ether layer was taken, and the ether was evaporated to obtain a reaction solution A; S2: Under an inert gas atmosphere, 12 parts of reaction solution A were added to 30 parts of deionized water and stirred evenly, 0.5 parts of activator were added, and secondary reaction was carried out at 85°C for 25 hours. The filtrate was filtered and extracted with anhydrous ether. The ether layer was taken and the ether was evaporated to obtain reaction solution B; S3: Under an inert gas atmosphere, 10 parts of the reaction solution B were added to 30 parts of tetrahydrofuran, and 1 part of zinc borohydride was added, and the mixture was refluxed at 67° C. for three times for 1 hour, and the tetrahydrofuran was evaporated, and the mixture was cooled to room temperature; anhydrous ether was used for extraction, and the ether layer was taken, and the mixture was further washed with saturated sodium carbonate, dried over anhydrous magnesium sulfate, filtered, and the ether was evaporated to obtain crude benzyl alcohol; S4: The crude benzyl alcohol is vacuum distilled at 70° C. for 60 min at a vacuum degree of ≤-0.095 MPa, and then the temperature is raised to 100° C. and vacuum distilled for a second time for 20 h to obtain high-purity benzyl alcohol.

[0028] Embodiment 3:

[0029] Step 1: Preparation of activator: (1) 20 parts of polyethylene glycol and 0.1 parts of N-(n-propyl)diethanolamine were added to a reaction kettle and mixed evenly, 0.6 parts of a catalyst was added, and the mixture was heated and stirred at 160° C. for 7 h under a hydrogen atmosphere, and water was added to dissolve the mixture, and the mixture was centrifuged, purified, and dried to obtain modified polyethylene glycol; (2) Prepare a mixed salt solution of 28 g / L magnesium chloride and 14 g / L aluminum chloride, an alkaline solution of 21.5 g / L sodium carbonate and 25.5 g / L sodium hydroxide, and a modified polyethylene glycol solution of 6.5 g / L respectively for use; (3) mixing a salt solution, an alkaline solution, a modified polyethylene glycol solution, and deionized water in a mass ratio of 1:1.1:1:1, stirring at 85°C for 6.5 hours, filtering, washing, drying, and calcining at 650°C under an inert gas atmosphere to obtain an activator; Step 2: Preparation of high-purity benzyl alcohol: S1: Under an inert gas atmosphere, 11 parts of benzaldehyde were added to a reaction kettle, and 28 parts of a 24 wt% sodium hydroxide aqueous solution and 0.5 parts of mesoporous zeolite powder were added, and the mixture was refluxed at 175°C for 50 min, cooled to room temperature, extracted with anhydrous ether, and the ether layer was taken and the ether was evaporated to obtain a reaction solution A; S2: Under an inert gas atmosphere, 15 parts of reaction solution A were added to 40 parts of deionized water and stirred evenly, 1 part of activator was added, and secondary reaction was carried out at 85°C for 28 hours. The filtrate was filtered and extracted with anhydrous ether. The ether layer was taken and the ether was evaporated to obtain reaction solution B; S3: Under an inert gas atmosphere, 12 parts of the reaction solution B were added to 40 parts of tetrahydrofuran, and 2 parts of zinc borohydride were added, and the mixture was refluxed at 67° C. for three times for 1.5 h, and the tetrahydrofuran was evaporated, and the mixture was cooled to room temperature; anhydrous ether was used for extraction, and the ether layer was taken, and the mixture was further washed with saturated sodium carbonate, dried over anhydrous magnesium sulfate, filtered, and the ether was evaporated to obtain crude benzyl alcohol; S4: The crude benzyl alcohol is vacuum distilled at 70°C for 60 min at a vacuum degree of ≤-0.095 MPa, and then the temperature is raised to 120°C and vacuum distilled for a second time for 20 h to obtain high-purity benzyl alcohol.

[0030] Comparative Example 1: Based on Example 1, the mesoporous zeolite powder was replaced with an anti-explosion molecular sieve, and the other processes remained unchanged, as follows: Step 1: Preparation of activator: (1) 20 parts of polyethylene glycol and 0.1 parts of N-(n-propyl)diethanolamine were added to a reaction kettle and mixed evenly, 0.6 parts of a catalyst was added, and the mixture was heated and stirred at 160° C. for 7 h under a hydrogen atmosphere, and water was added to dissolve the mixture, and the mixture was centrifuged, purified, and dried to obtain modified polyethylene glycol; (2) Prepare a mixed salt solution of 28 g / L magnesium chloride and 14 g / L aluminum chloride, an alkaline solution of 21.5 g / L sodium carbonate and 25.5 g / L sodium hydroxide, and a modified polyethylene glycol solution of 6.5 g / L respectively for use; (3) mixing a salt solution, an alkaline solution, a modified polyethylene glycol solution, and deionized water in a mass ratio of 1:1.1:1:1, stirring at 85°C for 6.5 hours, filtering, washing, drying, and calcining at 650°C under an inert gas atmosphere to obtain an activator; Step 2: Preparation of high-purity benzyl alcohol: S1: Under an inert gas atmosphere, 10.5 parts of benzaldehyde were added to a reaction kettle, and 27.5 parts of a sodium hydroxide aqueous solution with a mass fraction of 23.5wt% and 0.5 parts of an explosion-proof molecular sieve were added, and the mixture was refluxed at 175°C for 50 minutes, cooled to room temperature, extracted with anhydrous ether, and the ether layer was taken, and the ether was evaporated to obtain a reaction solution A; S2: Under an inert gas atmosphere, 13 parts of reaction solution A were added to 35 parts of deionized water and stirred evenly, 0.75 parts of activator were added, and secondary reaction was carried out at 85°C for 26 hours. The filtrate was filtered to obtain the filtrate, and extracted with anhydrous ether. The ether layer was taken and the ether was evaporated to obtain reaction solution B; S3: Under an inert gas atmosphere, 11 parts of the reaction solution B were added to 35 parts of tetrahydrofuran, and 1.5 parts of zinc borohydride were added, and the mixture was refluxed at 67° C. for three times for 1 hour, and the tetrahydrofuran was evaporated, and the mixture was cooled to room temperature; anhydrous ether was used for extraction, and the ether layer was taken, and the mixture was further washed with saturated sodium carbonate, dried over anhydrous magnesium sulfate, filtered, and the ether was evaporated to obtain crude benzyl alcohol; S4: The crude benzyl alcohol is vacuum distilled at 70°C for 60 min at a vacuum degree of ≤-0.095 MPa, and then the temperature is raised to 110°C and vacuum distilled for a second time for 20 h to obtain high-purity benzyl alcohol.

[0031] Comparative Example 2: Based on Example 1, polyethylene glycol is not modified, and the other processes remain unchanged, as follows: Step 1: Preparation of activator: (1) Prepare a mixed salt solution of 28 g / L magnesium chloride and 14 g / L aluminum chloride, an alkaline solution of 21.5 g / L sodium carbonate and 25.5 g / L sodium hydroxide, and a polyethylene glycol solution of 6.5 g / L respectively for use; (2) mixing a salt solution, an alkaline solution, a polyethylene glycol solution, and deionized water in a mass ratio of 1:1.1:1:1, stirring at 85° C. for 6.5 h, filtering, washing, drying, and calcining at 650° C. under an inert gas atmosphere to obtain an activator; Step 2: Preparation of high-purity benzyl alcohol: S1: Under an inert gas atmosphere, 10.5 parts of benzaldehyde were added to a reaction kettle, and 27.5 parts of a 23.5 wt% sodium hydroxide aqueous solution and 0.5 parts of mesoporous zeolite powder were added, and the mixture was refluxed at 175°C for 50 min, cooled to room temperature, extracted with anhydrous ether, and the ether layer was taken and the ether was evaporated to obtain a reaction solution A; S2: Under an inert gas atmosphere, 13 parts of reaction solution A were added to 35 parts of deionized water and stirred evenly, 0.75 parts of activator were added, and secondary reaction was carried out at 85°C for 26 hours. The filtrate was filtered to obtain the filtrate, and extracted with anhydrous ether. The ether layer was taken and the ether was evaporated to obtain reaction solution B; S3: Under an inert gas atmosphere, 11 parts of the reaction solution B were added to 35 parts of tetrahydrofuran, and 1.5 parts of zinc borohydride were added, and the mixture was refluxed at 67° C. for three times for 1 hour, and the tetrahydrofuran was evaporated, and the mixture was cooled to room temperature; anhydrous ether was used for extraction, and the ether layer was taken, and the mixture was further washed with saturated sodium carbonate, dried over anhydrous magnesium sulfate, filtered, and the ether was evaporated to obtain crude benzyl alcohol; S4: The crude benzyl alcohol is vacuum distilled at 70°C for 60 min at a vacuum degree of ≤-0.095 MPa, and then the temperature is raised to 110°C and vacuum distilled for a second time for 20 h to obtain high-purity benzyl alcohol.

[0032] Comparative Example 3: Based on Example 1, step S2 uses purchased hydrotalcite as an activator (provided by Hubei Rishengchang New Material Technology Co., Ltd.), specifically as follows: Step 1: Preparation of high-purity benzyl alcohol: S1: Under an inert gas atmosphere, 10.5 parts of benzaldehyde were added to a reaction kettle, and 27.5 parts of a 23.5 wt% sodium hydroxide aqueous solution and 0.5 parts of mesoporous zeolite powder were added, and the mixture was refluxed at 175°C for 50 min, cooled to room temperature, extracted with anhydrous ether, and the ether layer was taken and the ether was evaporated to obtain a reaction solution A; S2: Under an inert gas atmosphere, 13 parts of reaction solution A were added to 35 parts of deionized water and stirred evenly, 0.75 parts of hydrotalcite were added, and a secondary reaction was carried out at 85°C for 26 hours. The filtrate was filtered to obtain a filtrate, and extracted with anhydrous ether. The ether layer was taken and the ether was evaporated to obtain a reaction solution B; S3: Under an inert gas atmosphere, 11 parts of the reaction solution B were added to 35 parts of tetrahydrofuran, and 1.5 parts of zinc borohydride were added, and the mixture was refluxed at 67° C. for three times for 1 hour, and the tetrahydrofuran was evaporated, and the mixture was cooled to room temperature; anhydrous ether was used for extraction, and the ether layer was taken, and the mixture was further washed with saturated sodium carbonate, dried over anhydrous magnesium sulfate, filtered, and the ether was evaporated to obtain crude benzyl alcohol; S4: The crude benzyl alcohol is vacuum distilled at 70°C for 60 min at a vacuum degree of ≤-0.095 MPa, and then the temperature is raised to 110°C and vacuum distilled for a second time for 20 h to obtain high-purity benzyl alcohol.

[0033] Comparative Example 4: Based on Example 1, step S2 is removed, and the remaining processes remain unchanged, as follows: Step 1: Preparation of high-purity benzyl alcohol: S1: Under an inert gas atmosphere, 10.5 parts of benzaldehyde were added to a reaction kettle, and 27.5 parts of a 23.5 wt% sodium hydroxide aqueous solution and 0.5 parts of mesoporous zeolite powder were added, and the mixture was refluxed at 175°C for 50 min, cooled to room temperature, extracted with anhydrous ether, and the ether layer was taken and the ether was evaporated to obtain a reaction solution A; S2: Under an inert gas atmosphere, 11 parts of the reaction solution A were added to 35 parts of tetrahydrofuran, and 1.5 parts of zinc borohydride were added, and the mixture was refluxed at 67° C. for three times for 1 hour, and the tetrahydrofuran was evaporated, and the mixture was cooled to room temperature; anhydrous ether was used for extraction, and the ether layer was taken, and the mixture was further washed with saturated sodium carbonate, dried over anhydrous magnesium sulfate, filtered, and the ether was evaporated to obtain crude benzyl alcohol; S3: The crude benzyl alcohol is vacuum distilled at 70°C for 60 min at a vacuum degree of ≤-0.095 MPa, and then the temperature is raised to 110°C and vacuum distilled for a second time for 20 h to obtain high-purity benzyl alcohol.

[0034] Performance test: (1) Measure the benzaldehyde standard solution and each example by gas chromatography, record the spectrum and measure the peak area, calculate the purity of benzyl alcohol in Example 1 and the yield of other examples, and the experimental data are shown in Table 1 and Table 2; (2) According to the gas chromatography test (General Rule 0521) in the Chinese Pharmacopoeia, calculate the content of benzaldehyde in Example 1 and other examples by area according to the external standard method, and the experimental data are shown in Table 1 and Table 2; Table 1

[0035] Table 2

[0036] Conclusion: It can be seen from Table 1 that the benzyl alcohol prepared by the high-purity benzyl alcohol preparation process provided by the present invention has a high yield, a benzaldehyde content of less than 0.001%, a high purity, and meets the requirements for injection; It can be seen from Table 2 that in step S1 of comparative example 1, an anti-explosion boiling molecular sieve is added to replace the mesoporous zeolite powder, the specific surface area is low, the reaction active sites are lacking, the efficiency of the disproportionation reaction is reduced, and the yield is reduced, but since step S2 further continues to react the unreacted benzaldehyde, the yield decreases slightly, and comparative example 4 removes step 2, the yield has been significantly reduced, and the benzaldehyde content increases; in comparative example 2, polyethylene glycol is not modified, the self-assembly effect of the template agent is deteriorated, the specific surface area of ​​the activator is reduced, the catalytic activity is reduced, and the yield is reduced; in comparative example 3, step S2 uses purchased hydrotalcite as an activator, the specific surface area is small, the carboxyl group generated by the disproportionation reaction cannot be effectively adsorbed and removed, and the reaction efficiency is reduced, and the yield is reduced.

[0037] In summary, the present invention adopts multi-step purification of benzyl alcohol, and uses zeolite powder with a specific specific surface area and a prepared large specific surface area activator to promote the reaction, thereby successfully providing a high-purity benzyl alcohol preparation process with high yield and extremely low benzaldehyde content.

[0038] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A process for preparing high-purity benzyl alcohol, characterized in that: The following steps are involved: S1: under an inert gas atmosphere, benzaldehyde, mesoporous zeolite powder and sodium hydroxide aqueous solution are added to the reaction system in sequence; reflux once for reaction, cool to room temperature; extract with anhydrous ether, take the ether layer, and evaporate the ether to obtain reaction solution A; S2: Under an inert gas atmosphere, reaction solution A, deionized water, and an activator are sequentially added to the reaction system, heated for secondary reaction, and cooled to room temperature; the filtrate is filtered, extracted with anhydrous ether, the ether layer is taken, and the ether is evaporated to obtain reaction solution B; S3: Under an inert gas atmosphere, the reaction solution B and zinc borohydride are added to tetrahydrofuran in sequence, and the mixture is refluxed for three times for reaction; the tetrahydrofuran is evaporated and the mixture is cooled to room temperature; anhydrous ether is used for extraction, and the ether layer is taken, which is further washed with saturated sodium carbonate, dried over anhydrous magnesium sulfate, filtered, and the ether is evaporated to obtain crude benzyl alcohol; S4: subjecting the crude benzyl alcohol to a vacuum distillation, continuing to raise the temperature, subjecting it to a second vacuum distillation, and collecting the distillate to obtain high-purity benzyl alcohol.

2. A process for preparing high-purity benzyl alcohol according to claim 1, characterized in that: During step S4, during the first vacuum distillation, the vacuum degree is ≤-0.095Mpa, the temperature is 65-75°C, and the time is 50-70min; during the second vacuum distillation, the vacuum degree is ≤-0.095Mpa, the temperature is 80-140°C, and the time is 20-22h.

3. A process for preparing high-purity benzyl alcohol according to claim 1, characterized in that: During step S1, during the primary reflux reaction, the temperature is 170-180°C and the time is 40-50 min; during step S2, during the secondary heating reaction, the temperature is 80-90°C and the time is 25-28 h; during step S3, during the tertiary reflux reaction, the temperature is 60-70°C and the time is 1-1.5 h.

4. A process for preparing high-purity benzyl alcohol according to claim 1, characterized in that: The specific surface area of ​​the mesoporous zeolite powder is 250-300 g / m 2 The mesoporous zeolite powder is pre-activated in a 10-15% sodium hydroxide solution at room temperature for 10-20 minutes.

5. A process for preparing high-purity benzyl alcohol according to claim 1, characterized in that: The reaction solution A comprises the following raw materials in parts by weight: 10-11 parts of benzaldehyde, 27-28 parts of a sodium hydroxide aqueous solution with a mass fraction of 23-24wt%, and 0.4-0.6 parts of mesoporous zeolite powder; the reaction solution B comprises the following raw materials in parts by weight: 12-15 parts of reaction solution A, 30-40 parts of deionized water, and 0.5-1 parts of activator A; the crude benzyl alcohol comprises the following raw materials in parts by weight: 10-12 parts of reaction solution B, 30-40 parts of tetrahydrofuran, and 1-2 parts of zinc borohydride.

6. A process for preparing high-purity benzyl alcohol according to claim 1, characterized in that: The preparation method of the activator comprises the following steps: (1) adding polyethylene glycol and N-(n-propyl)diethanolamine into a reaction kettle and mixing them evenly, adding a catalyst, heating and stirring at 155-165° C. for 6-8 hours under a hydrogen atmosphere, adding water to dissolve, centrifuging, purifying, and drying to obtain modified polyethylene glycol; (2) preparing a mixed salt solution, a mixed alkali solution, and a modified polyethylene glycol solution respectively for use; (3) mixing the mixed salt solution, the mixed alkali solution, the modified polyethylene glycol solution, and deionized water, stirring at 85-90° C. for 6-7 hours, filtering, washing, drying, and calcining at 600-650° C. under an inert gas atmosphere to obtain an activator.

7. A process for preparing high-purity benzyl alcohol according to claim 6, characterized in that: The mixed salt solution includes magnesium chloride with a concentration of 26-30 g / L and aluminum chloride with a concentration of 13-15 g / L; the mixed alkali solution includes sodium carbonate with a concentration of 21-22 g / L and sodium hydroxide with a concentration of 25-26 g / L; and the modified polyethylene glycol solution has a concentration of 6-7 g / L.

8. A process for preparing high-purity benzyl alcohol according to claim 6, characterized in that: The modified polyethylene glycol comprises the following raw materials in parts by weight: 18 to 22 parts of polyethylene glycol, 0.1 to 0.15 parts of N-(n-propyl)diethanolamine, and 0.5 to 0.8 parts of a catalyst; The mass ratio of the mixed salt solution, the mixed alkali solution, the modified polyethylene glycol solution and the deionized water is 1:1-1.2:1:

1.

9. An application of high-purity benzyl alcohol, characterized in that: The high-purity benzyl alcohol prepared by the preparation process of high-purity benzyl alcohol according to any one of claims 1 to 8 is used for medical injection.

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