A method and device for recovering and refining high-purity acetonitrile in peptide synthesis

Abstract

The present invention relates to a method and device for recovering and refining high-purity acetonitrile in polypeptide synthesis, and belongs to the field of high-purity solvent recovery. Steps: transporting the acetonitrile waste liquid generated in polypeptide synthesis to a conditioning tank to adjust the pH; transporting the neutralized acetonitrile waste liquid to a first distillation tower for distillation and concentration; sending the obtained acetonitrile distillate as feed to a pervaporation membrane separation unit for separation to obtain crude acetonitrile, and the water and a small amount of acetonitrile in the feed liquid side solution pass through the pervaporation membrane in the form of steam to obtain a permeate, and the permeate is condensed and returned to the conditioning tank to recover the acetonitrile therein again; sending the dehydrated low-water-content acetonitrile to a third distillation tower for further impurity removal to obtain a crude acetonitrile; sending the obtained crude acetonitrile to an oxidation tank for oxidation, and after the oxidation is completed, sending the acetonitrile oxidation liquid to an adsorption tower for adsorption and removal of impurities; sending the obtained acetonitrile after adsorption to a second distillation tower for refining to obtain a finished acetonitrile.

Description

Technical Field

[0001] The invention relates to a method and a device for recovering and refining high-purity acetonitrile in polypeptide synthesis, belonging to the field of high-purity solvent recovery. Background Art

[0002] Peptides generally refer to compounds composed of less than one hundred amino acids spliced ​​together through peptide bonds. As drugs, they have the advantages of strong activity, good specificity, and strong penetration. They have significant therapeutic effects in the treatment of tumors, diabetes, cardiovascular diseases, immune diseases, and antiviral and antibacterial effects. With the increasing maturity of peptide synthesis technology, more and more peptide drugs have begun to be put into actual production. Among them, as a purification solvent for peptide products, the demand for high-purity acetonitrile is also increasing. The acetonitrile mother liquor is separated and refined to obtain high-quality indicators of high-purity acetonitrile, which is then recycled as a purification solvent, which can significantly reduce the production of finished products and environmental protection costs. In the production process, acetonitrile is inevitably mixed with water and other impurities, generating a large amount of acetonitrile waste liquid. Acetonitrile will form an azeotrope with water (the water content of the acetonitrile-water azeotrope under normal pressure is about 16 wt.%). The conventional distillation method cannot directly separate and purify the acetonitrile waste liquid into a high-purity acetonitrile solvent that can be reused (content ≥99.9%, water ≤0.05wt.%, 200nm ≥90%, 210nm ≥94%, 220nm ≥96%, 240nm ≥98%, 250nm ≥99%). At the same time, if only conventional processes (extractive distillation, pressure swing distillation or membrane dehydration technology) are used, the acetonitrile waste liquid can only be recovered into industrial-grade acetonitrile with good quality, which cannot meet the requirements of recycling in production. As a purification solvent, the quality of high-purity recovered acetonitrile has a decisive influence on the quality of polypeptide products.

[0003] The existing technology for preparing high-purity acetonitrile includes one or more of oxidation, adsorption, drying and distillation processes. For example, Chinese patent CN104058994A "High-purity acetonitrile and its preparation method and device" describes that industrial acetonitrile is subjected to adsorption, oxidation and distillation to obtain high-purity acetonitrile; Chinese patent CN104072388A "A method for preparing gradient-grade high-purity acetonitrile" describes that industrial acetonitrile is subjected to adsorption, drying and distillation to obtain high-purity acetonitrile. The raw materials for preparing high-purity acetonitrile are limited to qualified industrial-grade acetonitrile on the market, the preparation cost is high, and the range of raw material sources is narrow. In addition, Chinese patents CN107382775A "Method for Recovering Acetonitrile-Containing Waste Liquid Produced by Chemical Synthesis Drugs" and CN107445863A "Method for Recovering Acetonitrile-Containing Waste Liquid Produced by Biopharmaceuticals" describe the recovery of high-purity acetonitrile through neutralization, dichloromethane extraction, fractionation, rectification and other steps, which can meet the requirements for acetonitrile application in chemical synthesis drugs or biopharmaceuticals. However, the process requires the use of dichloromethane as an extractant during implementation, which has the following problems: adding dichloromethane as the third component may cause trace amounts of dichloromethane to exist in acetonitrile; light components such as methanol and acetone in acetonitrile waste liquid will be enriched in dichloromethane, and it is difficult to completely separate light components such as acetone and methanol from dichloromethane, which affects the extraction efficiency after long-term operation; a large amount of dichloromethane volatilizes, leading to VOC emission problems. Summary of the invention

[0004] The purpose of the present invention is to provide a method and device for recovering and refining high-purity acetonitrile in peptide synthesis. The method has the advantages of simple process, no addition of third components, high acetonitrile purity, stable product quality, and is suitable for acetonitrile waste liquid of different peptide synthesis processes, high recovery rate, simple and efficient process, and low operating energy consumption.

[0005] A method for recovering and refining high-purity acetonitrile for peptide synthesis comprises the following steps:

[0006] Step 1, the acetonitrile waste liquid generated by elution during peptide synthesis is subjected to pH neutralization treatment;

[0007] Step 2, subjecting the neutralized acetonitrile waste liquid in step 1 to a first distillation treatment to remove heavy components;

[0008] Step 3, sending the acetonitrile distillate obtained in step 2 to a pervaporation membrane separation unit for dehydration, allowing water to pass through the membrane to obtain crude acetonitrile;

[0009] Step 4, sending the crude acetonitrile obtained in step 3 into an adsorption tower for adsorption and removal of impurities;

[0010] In step 5, the acetonitrile obtained after adsorption in step 4 is subjected to a second distillation treatment to remove light component impurities and heavy component impurities to obtain finished product acetonitrile.

[0011] In one embodiment, the crude acetonitrile obtained in step 3 is subjected to a third distillation treatment to remove light components to obtain a crude acetonitrile after light components are removed, and the crude acetonitrile after light components are removed is then fed to an adsorption tower.

[0012] In one embodiment, the light components obtained in the third distillation are returned to the feed of the third distillation process to recover the acetonitrile therein.

[0013] In one embodiment, in the step 5, light component impurities and heavy component impurities are removed by segmented distillation, and the middle distillate is taken; the front fraction of the second distillation and the refined acetonitrile kettle liquid are returned to the third distillation to recover the acetonitrile therein again.

[0014] In one embodiment, the third distillation is intermittently operated with an operating pressure of -70 to 50 kPa (gauge pressure), the acetonitrile distillate is withdrawn in stages, qualified fractions are collected, and the reflux ratio is controlled at 5 to 10, and the optimal ratio is 7; the transmittance of the collected qualified fractions at a wavelength of 200 to 220 nm is ≥50%, the acetonitrile purity is ≥99%, and the water content is 0.02 to 0.1 wt.%.

[0015] In one embodiment, the light components extracted from the third distillation need to be returned to the third distillation treatment step for distillation again to enrich the impurities in the light-depleted liquid, and the purity of acetonitrile in the light components of the second light-depletion needs to be ≤70%.

[0016] In one embodiment, the acetonitrile desorption liquid produced during the adsorption process in step 4 is returned to the third distillation step to recover the acetonitrile therein.

[0017] In one embodiment, the fore fraction of the second distillation tower and the kettle liquid in step 5 need to be returned to the third distillation in step 4 to recover the acetonitrile therein again.

[0018] In one embodiment, the permeate of the pervaporation membrane separation unit in step 3 is condensed and then returned to step 1 for pH neutralization treatment to recover the acetonitrile therein.

[0019] In one embodiment, in the fourth step, the crude acetonitrile is first subjected to oxidation treatment and then fed into the adsorption tower.

[0020] In one embodiment, in the fourth step, the acetonitrile desorption liquid generated during the adsorption process is returned to the third distillation tower to recover the acetonitrile therein.

[0021] In one embodiment, the acetonitrile waste liquid generated by elution during the polypeptide synthesis in the first step has a water content of 40 to 95 wt.%, a pH range of 1 to 4, and contains other organic impurities, which include one or more of methanol, ethanol, isopropanol, acetone, ethyl acetate, trifluoroacetic acid, and ammonia, and the content of organic impurities accounts for 1 to 15 wt.% of the total amount of organic matter.

[0022] In one embodiment, the conditioning solution for pH neutralization treatment in step 1 may be one or more of sodium hydroxide, sodium carbonate, and sodium bicarbonate solutions, and the end point pH of the conditioning is 6-9.

[0023] In one embodiment, the water content of the crude acetonitrile in step 3 is controlled at 0.05-5 wt.%, preferably 0.5-1.5 wt.%.

[0024] In one embodiment, the oxidant required for oxidation in step 4 can be a metal inorganic salt, such as potassium permanganate, potassium dichromate, silver nitrate, etc.; it can also be an inorganic acid, such as concentrated sulfuric acid, fuming sulfuric acid, concentrated nitric acid, etc.; it can also be a peroxide, such as sodium peroxide, hydrogen peroxide, etc.; preferably, it can be a mixture of two or three thereof, such as concentrated sulfuric acid and potassium permanganate, concentrated sulfuric acid, sodium peroxide and potassium permanganate.

[0025] In one embodiment, the adsorbent in step 4 is 3A molecular sieve, 4A molecular sieve, 13X molecular sieve, coal-based activated carbon, sepiolite, coconut shell activated carbon, carbon fiber, preferably a mixture of two or three thereof; the ratio of the adsorption column height to the inner diameter is 100:3, and the column loading is 70-90% of the column height.

[0026] In one embodiment, the ultraviolet transmittance index of the finished acetonitrile fraction in step 5 is 200nm≥90%, 210nm≥94%, 220nm≥96%, 240nm≥98%, 250nm≥99%, acetonitrile content is ≥99.9%, and water content is ≤0.05wt.%.

[0027] In one embodiment, the acetonitrile distillate obtained in step 2 is subjected to adsorption pretreatment before entering the pervaporation membrane unit; the adsorption is carried out using coal-based activated carbon, coconut shell activated carbon, carbon fiber, sepiolite or ion exchange resin, preferably a mixture of two or three thereof.

[0028] A device for recovering and refining high-purity acetonitrile in peptide synthesis, comprising:

[0029] Conditioning tank, used for neutralizing acetonitrile waste liquid;

[0030] The first distillation tower is connected to the conditioning tank and is used to distill and remove heavy components from the acetonitrile waste liquid after the neutralization treatment;

[0031] an evaporator connected to the top of the first distillation tower and used for heating the distillate of the first distillation tower;

[0032] A pervaporation separation unit, connected to the evaporator, is used to perform pervaporation dehydration treatment on the distillate;

[0033] An adsorption tower, connected to the interception side of the pervaporation separation unit, is used for adsorption treatment of dehydrated acetonitrile;

[0034] The second distillation tower is connected to the adsorption tower and is used to remove light components and heavy components from the acetonitrile obtained from the adsorption tower to obtain acetonitrile finished product.

[0035] In one embodiment, the method further comprises: a third distillation tower connected to the interception side of the pervaporation separation unit for distilling the dehydrated acetonitrile to remove light components; and the top of the third distillation tower is connected to the adsorption tower.

[0036] In one embodiment, it also includes an oxidation tank connected to the interception side of the pervaporation separation unit, which is used to oxidize the dehydrated acetonitrile; the liquid outlet of the oxidation tank is connected to an adsorption tower, and the adsorption tower is used to adsorb and remove impurities from the de-light acetonitrile crude product after the oxidation treatment.

[0037] In one embodiment, the permeate side of the pervaporation separation unit is connected to the conditioning tank via a permeate condenser.

[0038] In one embodiment, the adsorption tower is filled with an adsorbent.

[0039] In one embodiment, the adsorbent is 3A molecular sieve, 4A molecular sieve, 13X molecular sieve, coal-based activated carbon, sepiolite, coconut shell activated carbon or carbon fiber.

[0040] In one embodiment, the oxidation tank is filled with an oxidant.

[0041] In one embodiment, the oxidant is a metal inorganic salt oxidant, an inorganic acid oxidant or an oxide oxidant.

[0042] The above-mentioned recovery and purification device is used for recovering and refining waste acetonitrile used in polypeptide synthesis.

[0043] The above-mentioned pervaporation membrane separation unit is used for recovering waste acetonitrile for refining polypeptide synthesis.

[0044] Beneficial Effects

[0045] Compared with the existing high-purity acetonitrile preparation and recovery process, the method of the present invention has the following characteristics:

[0046] 1. The present invention uses acetonitrile waste liquid in polypeptide synthesis as the initial raw material, is not limited by the raw material, and is recycled to prepare high-purity acetonitrile;

[0047] 2. The present invention uses a pervaporation membrane separation unit for dehydration to concentrate the components in the acetonitrile waste liquid, which can effectively promote the oxidation effect of the oxidant and make the purity of the final acetonitrile product better;

[0048] 3. The present invention adopts a light component removal process to remove light components in the acetonitrile waste liquid, and the product quality is not affected by the change of impurity content in the acetonitrile waste liquid;

[0049] 4. The present invention returns the front fraction and the bottom liquid in the refining process to the light removal process for recycling, thereby reducing the amount of waste liquid discharged from acetonitrile and improving the comprehensive recovery rate of acetonitrile;

[0050] 5. The acetonitrile purification method provided by the present invention has high acetonitrile single-pass and comprehensive yields, stable product quality, and can reduce operating energy consumption by 20%. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 It is a structural diagram of the refining device of the present invention.

[0052] Among them, 1 is a conditioning tank, 2 is the first distillation tower, 3 is an evaporator, 4 is a pervaporation separation unit, 5 is a permeate condenser, 6 is the third distillation tower, 7 is an oxidation tank, 8 is an adsorption tower, and 9 is a second distillation tower. DETAILED DESCRIPTION

[0053] The present invention is further described in detail below by specific embodiments. However, it will be appreciated by those skilled in the art that the following examples are only used to illustrate the present invention and should not be considered as limiting the scope of the present invention. If specific techniques or conditions are not specified in the examples, they are carried out according to the techniques or conditions described in the literature in this area or according to the product instructions. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be obtained commercially.

[0054] Values ​​expressed in the form of ranges should be understood in a flexible manner to include not only the values ​​explicitly listed as range limits, but also all individual values ​​or subranges contained within the range, as if each value and subrange were explicitly listed. For example, a concentration range of "about 0.1% to about 5%" should be understood to include not only the explicitly listed concentrations of about 0.1% to about 5%, but also individual concentrations (e.g., 1%, 2%, 3% and 4%) and subranges (e.g., 0.1% to 0.5%, 1% to 2.2%, 3.3% to 4.4%) within the indicated range. The percentages described in the present invention refer to weight percentages unless otherwise specified.

[0055] The "one embodiment", "another embodiment", "implementation method" and the like mentioned in this specification refer to the specific features, structures described in conjunction with the embodiment or included in at least one embodiment generally described in this application. The same expression appearing in multiple places in the specification does not necessarily refer to the same embodiment. Furthermore, when a specific feature, structure or characteristic is described in conjunction with any embodiment, it is claimed that the realization of such feature, structure or characteristic in conjunction with other embodiments also falls within the scope of protection of this application.

[0056] The crude polypeptide is purified by a high performance liquid phase system, specifically using an HPLC preparative column as an adsorption carrier, and high-purity acetonitrile and high-purity water as a separation system. The crude polypeptide is eluted at a certain flow rate and gradient. The composition of the acetonitrile mother liquor produced at this time is: acetonitrile dry purity 85-99%, water content 40-95wt.%.

[0057] The indicators for recovered acetonitrile are 200nm≥90%, 210nm≥94%, 220nm≥96%, 240nm≥98%, 250nm≥99%, acetonitrile content≥99.9%, water content≤0.05wt.%.

[0058] The preparation process of high-purity acetonitrile of the present invention is as follows:

[0059] Step 1: transport the acetonitrile waste liquid generated in the peptide synthesis to a conditioning tank to adjust the pH; the purpose of this step is to adjust the pH of the acetonitrile waste liquid to neutral to reduce the impact on subsequent processes; here, it can be mainly achieved by adding alkaline substances, and the added conditioning solution can be one or more of sodium hydroxide, sodium carbonate, and sodium bicarbonate solution. The end point pH of the conditioning is 6 to 9. The acetonitrile mother liquor entering the conditioning tank in the first step has a water content of 40 to 95 wt.%, a pH range of 1 to 4, and other organic impurities include one or more of methanol, ethanol, isopropanol, acetone, ethyl acetate, trifluoroacetic acid, amino acids, and ammonia. The content of organic impurities accounts for 1 to 15% of the total amount of organic matter.

[0060] Step 2: The neutralized acetonitrile waste liquid in step 1 is transported to a first distillation tower for distillation and concentration; the purpose of the first distillation is to remove a portion of heavy components in the acetonitrile waste liquid, such as amino acids, by-products generated by the reaction, and excess water, which can improve the purity of the recovered acetonitrile on the one hand, and remove a portion of water on the other hand, reducing the workload of the pervaporation membrane;

[0061] In the third step, the acetonitrile distillate obtained in the second step is fed as a feed to a pervaporation membrane separation unit for separation to obtain crude acetonitrile. Water and a small amount of acetonitrile in the solution on the feed liquid side pass through the pervaporation membrane in the form of steam to obtain a permeate. The permeate is condensed and returned to the conditioning tank to recover the acetonitrile therein again. The purpose of pervaporation is to concentrate the recovered acetonitrile. Due to the subsequent oxidation treatment, when the system contains more water, it is easy to cause a low concentration, which affects the oxidation efficiency and causes the acetonitrile recovered to be of low purity. In addition, the present invention uses a pervaporation membrane separation unit for dehydration, which is not limited by azeotropic factors, has a simple process, a high safety factor, does not introduce a third component, and reduces unnecessary impurity residues. In the third step, the water content of the low-water-content acetonitrile is controlled at 0.05-5 wt.%, and the optimal is 0.5-1.5 wt.%; the feed liquid side pressure is 0.1-0.3 MPa (gauge pressure), and the permeate side pressure is controlled at 1000-3000 Pa. The acetonitrile distillate vapor is further superheated to 70-180°C and then sent to the pervaporation membrane separation unit. The pervaporation unit uses a NaA molecular sieve membrane.

[0062] Step 4: The crude acetonitrile obtained in step 3 is sent to an oxidation tank for oxidation. After the oxidation, the acetonitrile oxidation liquid is sent to an adsorption tower for adsorption and impurity removal. The acetonitrile desorption liquid generated during the adsorption process is returned to the third distillation tower to recover the acetonitrile therein. The purpose of this step is to oxidize some components in the acetonitrile into small molecules, such as amino acid residues. Since the present invention is to treat acetonitrile waste liquid in polypeptide synthesis, the amino acid residues, synthetic by-products and decomposition products contained in the eluent are not easy to be separated from the acetonitrile, which affects the recovery quality. Since the amino acid is oxidized and deaminated to keto acid, it can continue to be oxidized, and the products are carbon dioxide and water. The decarboxylation product of the amino acid is an organic amine, which can also continue to be oxidized, and the products are ammonia and carbon dioxide. After being effectively decomposed into small molecules, it is more suitable for the adsorption range of the 4A molecular sieve (its adsorption range is adsorption of water, methanol, ethanol, hydrogen sulfide, sulfur dioxide, carbon dioxide, ethylene, and propylene), so that the oxidation and adsorption operations cooperate with each other, thereby improving the recovery purity of acetonitrile. The oxidant required for oxidation in the fifth step can be a metal inorganic salt, such as potassium permanganate, potassium dichromate, silver nitrate, etc.; it can also be an inorganic acid, such as concentrated sulfuric acid, fuming sulfuric acid, concentrated nitric acid, etc.; it can also be a peroxide, such as sodium peroxide, hydrogen peroxide, etc.; preferably, it can be a mixture of two or three of them, such as concentrated sulfuric acid and potassium permanganate, concentrated sulfuric acid, sodium peroxide and potassium permanganate; in the adsorption process, some small molecular impurities that are easily adsorbed are removed by the adsorbent; in the fifth step, the adsorbent uses 3A molecular sieve, 4A molecular sieve, 13X molecular sieve, coal-based activated carbon, coconut shell activated carbon, carbon fiber, preferably two or three of them are mixed. The ratio of the height to the inner diameter of the adsorption column is 100:3, and the column loading is 70% to 90% of the column height; if the transmittance of the crude acetonitrile before entering the oxidation tank at a wavelength of 200nm is ≥70%, the oxidation section can be skipped and the adsorption tower can be directly entered for adsorption. As an improvement, the acetonitrile desorption liquid produced in the adsorption process in the fifth step needs to be returned to the third distillation tower to recover the acetonitrile therein; the present invention also provides the use of the above-mentioned adsorbent in the process of adsorption and impurity removal of crude acetonitrile.

[0063] In step 5, the acetonitrile obtained after adsorption in step 4 is sent to the second distillation tower for refining to obtain the finished acetonitrile, and the fore fraction distilled from the second distillation tower and the refined acetonitrile kettle liquid are returned to the third distillation tower to recycle the acetonitrile therein. Preferably, the ultraviolet transmittance index of the qualified acetonitrile fraction in step 5 is 200nm≥90%, 210nm≥94%, 220nm≥96%, 240nm≥98%, 250nm≥99%, acetonitrile content≥99.9%, and water content≤0.05wt.%. In step 5, the fore fraction and kettle liquid of the second distillation tower need to be returned to the third distillation tower in step 3 to recycle the acetonitrile therein.

[0064] In one embodiment, the dehydrated low-water acetonitrile obtained in step 3 is sent to the third distillation tower for further impurity removal to obtain a crude acetonitrile, wherein the light-removed liquid obtained by distillation can be returned to the third distillation tower and the acetonitrile therein can be recovered again to enrich the impurities and improve the acetonitrile yield; this step is to purify the acetonitrile by means of segmented distillation, first distilling out the low-boiling impurities, then distilling out the acetonitrile, and finally leaving the heavy component impurities in the bottom liquid of the kettle. The light-removed liquid extracted from the third distillation tower needs to be returned to the third distillation tower for distillation again to enrich the impurities in the light-removed liquid, and after the secondary light-removed liquid is treated again, the purity of acetonitrile needs to be ≤70% when the waste liquid is discharged for treatment; the third distillation tower adopts intermittent operation, the operating pressure is -70~50kPa(G), the acetonitrile distillate is extracted in stages, and the qualified fraction is collected, and the reflux ratio is controlled at 5~10, and the optimal is 7. The qualified fractions collected had a transmittance of ≥50% at a wavelength of 200-220 nm, an acetonitrile purity of ≥99%, and a water content of 0.02-0.1 wt.%;

[0065] In addition, since the present invention processes acetonitrile, the eluent in peptide synthesis, acetonitrile containing trifluoroacetic acid is usually used as the eluent. In order to eliminate the influence of trifluoroacetic acid on the separation factor of acetonitrile / water of the pervaporation membrane, the acetonitrile distillate obtained by the first distillation can be adsorbed using a sepiolite adsorbent modified with a surface sulfonic acid group. The preparation method of the sepiolite adsorbent modified with a surface sulfonic acid group used here is mainly to first graft a mercaptosilane coupling agent onto the surface of the sepiolite, and then convert the mercapto group into a sulfonic acid group by oxidation. After the adsorption treatment, the separation factor of the pervaporation membrane for acetonitrile / water in the treatment of acetonitrile liquid can be effectively improved. The present invention also provides the use of the above-mentioned adsorbent in the process of adsorption and impurity removal of acetonitrile distillate.

[0066] Based on the above method, the recovery and refining device provided by the present invention is as follows Figure 1 As shown, including:

[0067] Conditioning tank 1, used for neutralizing acetonitrile waste liquid;

[0068] The first distillation tower 2 is connected to the conditioning tank 1 and is used to distill and remove heavy components from the acetonitrile waste liquid after the neutralization treatment;

[0069] an evaporator 3 connected to the top of the first distillation tower 2 and used for heating the distillate of the first distillation tower 2;

[0070] The pervaporation separation unit 4 is connected to the evaporator 3 and is used for performing pervaporation dehydration treatment on the distillate;

[0071] The third distillation tower 6 is connected to the interception side of the pervaporation separation unit 4 and is used to distill the dehydrated acetonitrile to remove light components;

[0072] The adsorption tower 8 is connected to the top of the third distillation tower 6 and is used for adsorbing the crude acetonitrile obtained from the third distillation tower 6;

[0073] The second distillation tower 9 is connected to the adsorption tower 8 and is used to remove light components and heavy components from the acetonitrile obtained from the adsorption tower 8 to obtain acetonitrile product.

[0074] In one embodiment, it also includes an oxidation tank 7, which is connected to the top of the third distillation tower 6 and is used to oxidize the crude acetonitrile de-lightened obtained by the third distillation tower 6; the liquid outlet of the oxidation tank 7 is connected to the adsorption tower 8, and the adsorption tower 8 is used to adsorb and remove impurities from the crude acetonitrile de-lightened after the oxidation treatment.

[0075] In one embodiment, the permeate side of the pervaporation separation unit 4 is connected to the conditioning tank 1 via a permeate condenser 5 .

[0076] In one embodiment, the adsorption tower 8 is filled with an adsorbent.

[0077] In one embodiment, the adsorbent is 3A molecular sieve, 4A molecular sieve, 13X molecular sieve, coal-based activated carbon, coconut shell activated carbon or carbon fiber.

[0078] In one embodiment, the oxidation tank 7 is filled with an oxidant.

[0079] In one embodiment, the oxidant is a metal inorganic salt oxidant, an inorganic acid oxidant or an oxide oxidant.

[0080] The waste acetonitrile used in the following examples is the acetonitrile waste liquid obtained in the process of synthesizing bivalirudin by solid phase method. The main synthesis steps are: 1. Soak the resin in DMF for 2 hours to activate the resin. 2. According to the principle of Fmoc-solid phase peptide synthesis, dichlororesin is used as a solid phase carrier, DIEA is used as a catalyst, and DCM is used as a solvent to connect the first amino acid to the resin in a solid phase peptide synthesizer. 3. After washing, add 20% piperidine in DMF solution to remove the Fmoc. group, free the amino group of the first amino acid, and restore the reaction activity. 4. Take a small amount of resin from the reactor and put it in a dry and clean test tube, add 5% ninhydrin in anhydrous ethanol solution (W / V), heat in a boiling water bath for 5 minutes, and the color reaction is positive. 5. After washing, use HOBT\TBTU\DIEA as a catalyst, DMF as a solvent and cleaning agent, and connect the second amino acid in a solid phase peptide synthesizer. 6. Connect other amino acids in the same way. After connecting each amino acid, it is necessary to test with 5% ninhydrin in anhydrous ethanol solution. Only when the result is negative can the next step of reaction be carried out. 7. After connecting all amino acids, wash and blow dry the resin with nitrogen. 8. Use a cleavage reagent to cut the peptide from the resin. The cleavage reagent formula is as follows (TFA 9ml, phenol 0.759, EDT 0.25ml, Thioanisole0.25ml, H2O 0.5m1). 9. The cut peptide is precipitated in cold ether, washed and centrifuged. 10. Freeze-dry in a freeze dryer to obtain a crude product. Use an HPLC chromatography purification system with a chromatography acetonitrile solution containing 0.1% trifluoroacetic acid to obtain an acetonitrile eluent.

[0081] The acetonitrile waste liquid to be treated by the present invention is not limited to the waste liquid obtained from the above-mentioned polypeptide synthesis, but can be acetonitrile elution waste liquid obtained from other synthetic routes using solid phase method, such as immune octapeptide, sleep nonapeptide, etc.

[0082] The percentages described in the present invention are percentages by mass unless otherwise specified.

[0083] Example 1

[0084] Method for recovering and refining high-purity acetonitrile in peptide synthesis, using a device such as Figure 1As shown, the operation process includes the following steps: sending the acetonitrile mother liquor (water content of about 80wt.%, acetonitrile dry purity of about 90%) into the conditioning tank 1 for neutralization, and then sending it into the first distillation tower 2 for concentration after neutralization, and the organic salt and part of the water are discharged from the bottom of the tower. The acetonitrile distillate is transported to the evaporator 3, heated and vaporized to 110°C, and enters the NaA pervaporation membrane separation unit 4 for dehydration to obtain low-water acetonitrile; the feed liquid side pressure is 0.2MPa (gauge pressure), the permeate side pressure is controlled at 1500Pa, and the permeate is condensed by the permeate condenser 5 and returned to the conditioning tank 1 to recover a small amount of acetonitrile therein. The water content of the low-water acetonitrile obtained after the pervaporation separation unit is ≤0.5 wt.%. After the low-water acetonitrile enters the third distillation tower 6, it is treated with light and heavy removal. The operating pressure is 20kPa (G), and the bottom temperature of the third distillation tower is 90°C. It is first operated under the condition of reflux ratio of 18:1 to remove light components, and then the reflux ratio is adjusted to 6:1 to obtain acetonitrile, and ensure that the transmittance of the qualified fraction at a wavelength of 200-220nm is ≥50%, the purity of acetonitrile is ≥99%, and the water content is 0.02-0.1wt.%, to obtain crude acetonitrile. The obtained crude acetonitrile is sent to the oxidation tank 7, and 10% concentrated sulfuric acid and 1% potassium permanganate are added at room temperature for solid oxidation for 4h. The acetonitrile oxidation liquid evaporated after oxidation is sent to the adsorption tower 8 equipped with 4A molecular sieve for adsorption, and the acetonitrile desorption liquid is returned to the third distillation tower 6 to recover the acetonitrile therein. The acetonitrile adsorbed liquid enters the second distillation tower 9 for refining, and the acetonitrile fraction is collected in sections). The bottom temperature of the second distillation tower is 85°C. It is first operated under the condition of reflux ratio of 20:1 to remove light components, and then the reflux ratio is adjusted to 7:1 to obtain acetonitrile. The former components and acetonitrile kettle liquid are returned to the third distillation tower 6 to recover the acetonitrile therein.

[0085] Example 2

[0086] Method for recovering and refining high-purity acetonitrile in peptide synthesis, using a device such as Figure 1As shown, the operation process includes the following steps: sending the acetonitrile mother liquor (water content of about 85wt.%, acetonitrile dry purity of about 92%) into the conditioning tank 1 for neutralization, and then sending it into the first distillation tower 2 for concentration after neutralization, and the organic salt and part of the water are discharged from the bottom of the tower. The acetonitrile distillate is transported to the evaporator 3, heated and vaporized to 120°C, and enters the NaA pervaporation membrane separation unit 4 for dehydration to obtain low-water acetonitrile; the feed liquid side pressure is 0.2MPa (gauge pressure), the permeate side pressure is controlled at 1500Pa, and the permeate is condensed by the permeate condenser 5 and returned to the conditioning tank 1 to recover a small amount of acetonitrile therein. The water content of the low-water acetonitrile obtained after the pervaporation separation unit is ≤0.5 wt.%. After the low-water acetonitrile enters the third distillation tower 6, it is treated with light and heavy removal. The operating pressure is 30 kPa (G), and the bottom temperature of the third distillation tower is 92 ° C. It is first operated under the condition of a reflux ratio of 16:1 to remove the light components, and then the reflux ratio is adjusted to 5:1 to obtain acetonitrile, and ensure that the transmittance of the qualified fraction at a wavelength of 200-220 nm is ≥50%, the purity of acetonitrile is ≥99%, and the water content is 0.02-0.1wt.%, to obtain crude acetonitrile. The obtained crude acetonitrile is sent to the oxidation tank 7, and 12% concentrated sulfuric acid and 1.5% potassium permanganate are added at room temperature for solid oxidation for 3h. The acetonitrile oxidation liquid evaporated after oxidation is sent to the adsorption tower 8 equipped with 4A molecular sieve for adsorption, and the acetonitrile desorption liquid is returned to the third distillation tower 6 to recover the acetonitrile therein. The acetonitrile adsorbed liquid enters the second distillation tower 9 for refining, and the acetonitrile fraction is collected in sections). The bottom temperature of the second distillation tower is 85°C. It is first operated under the condition of reflux ratio of 18:1 to remove light components, and then the reflux ratio is adjusted to 6:1 to obtain acetonitrile. The former components and acetonitrile kettle liquid are returned to the third distillation tower 6 to recover the acetonitrile therein.

[0087] Example 3

[0088] Method for recovering and refining high-purity acetonitrile in peptide synthesis, using a device such as Figure 1As shown, the operation process includes the following steps: sending acetonitrile mother liquor (water content of about 80wt.%, acetonitrile dry purity of about 90%) to the conditioning tank 1 for neutralization, and then sending it to the first distillation tower 2 for concentration after neutralization, and the organic salt and part of the water are discharged from the bottom of the tower. The acetonitrile distillate is transported to the adsorption tower containing sepiolite for adsorption treatment, and then the acetonitrile after adsorption treatment is sent to the evaporator 3 for heating and vaporization to 110°C and enters the NaA pervaporation membrane separation unit 4 for dehydration to obtain low-water acetonitrile; the feed liquid side pressure is 0.2MPa (gauge pressure), the permeate side pressure is controlled at 1500Pa, and the permeate is condensed by the permeate condenser 5 and returned to the conditioning tank 1 to recover a small amount of acetonitrile therein. The water content of the low-water acetonitrile obtained after the pervaporation separation unit is ≤0.5 wt.%. After the low-water acetonitrile enters the third distillation tower 6, it is treated with light and heavy removal. The operating pressure is 20 kPa (G), and the bottom temperature of the third distillation tower is 90 ° C. It is first operated under the condition of reflux ratio of 18:1 to remove light components, and then the reflux ratio is adjusted to 6:1 to obtain acetonitrile, and ensure that the transmittance of the qualified fraction at a wavelength of 200-220 nm is ≥50%, the purity of acetonitrile is ≥99%, and the water content is 0.02-0.1 wt.%, to obtain crude acetonitrile. The obtained crude acetonitrile is sent to the oxidation tank 7, and 10% concentrated sulfuric acid and 1% potassium permanganate are added for solid oxidation for 4 hours at room temperature. The acetonitrile oxidation liquid evaporated after oxidation is sent to the adsorption tower 8 equipped with 4A molecular sieve for adsorption, and the acetonitrile desorption liquid is returned to the third distillation tower 6 to recover the acetonitrile therein. The acetonitrile adsorbed liquid enters the second distillation tower 9 for refining, and the acetonitrile fraction is collected in sections). The bottom temperature of the second distillation tower is 85°C. It is first operated under the condition of reflux ratio of 20:1 to remove light components, and then the reflux ratio is adjusted to 7:1 to obtain acetonitrile. The former components and acetonitrile kettle liquid are returned to the third distillation tower 6 to recover the acetonitrile therein.

[0089] Example 4

[0090] Method for recovering and refining high-purity acetonitrile in peptide synthesis, using a device such as Figure 1As shown, the operation process includes the following steps: sending acetonitrile mother liquor (water content of about 80wt.%, acetonitrile dry purity of about 90%) to the conditioning tank 1 for neutralization, and then sending it to the first distillation tower 2 for concentration, and the organic salt and part of the water are discharged from the bottom of the tower. The acetonitrile distillate is transported to an adsorption tower containing a surface sulfonic acid group-modified sepiolite adsorbent for adsorption treatment. The preparation method of the adsorbent is as follows: the sepiolite is activated at 150°C for 30 minutes, and then ethanol containing 0.15 mol / L (3-mercaptopropyl) trimethoxysilane and 0.02 mol / L lemon is added for grafting reaction. The reaction temperature is 40°C and the reaction time is 12 hours. The product is filtered out and washed with deionized water. The product is then immersed in 10% hydrogen peroxide at 25°C for oxidation for 5 hours to obtain the adsorbent, which is then washed and dried. The acetonitrile after adsorption treatment is then sent to an evaporator 3 for heating and vaporization to 110°C and enters a NaA pervaporation membrane separation unit 4 for dehydration to obtain acetonitrile with low water content. The pressure on the feed liquid side is 0.2 MPa (gauge pressure), and the pressure on the permeate side is controlled at 1500 Pa. After the permeate is condensed by a permeate condenser 5, it is returned to the conditioning tank 1 to recover a small amount of acetonitrile therein. The water content of the low-water acetonitrile obtained after the pervaporation separation unit is ≤0.5 wt.%. The low-water acetonitrile enters the third distillation tower 6 for light and heavy removal treatment, with an operating pressure of 20 kPa (G) and a bottom temperature of 90 ° C in the third distillation tower. It is first operated under a reflux ratio of 18:1 to remove light components, and then the reflux ratio is adjusted to 6:1 to obtain acetonitrile, and ensure that the transmittance of the qualified fraction at a wavelength of 200-220 nm is ≥50%, the purity of acetonitrile is ≥99%, and the water content is 0.02-0.1 wt.%, to obtain crude acetonitrile. The obtained crude acetonitrile is sent to the oxidation tank 7, and 10% concentrated sulfuric acid and 1% potassium permanganate are added for solid oxidation for 4 hours at room temperature. The acetonitrile oxidation liquid evaporated after oxidation is sent to the adsorption tower 8 equipped with 4A molecular sieve for adsorption, and the acetonitrile desorption liquid is returned to the third distillation tower 6 to recover the acetonitrile therein. The acetonitrile adsorbed liquid enters the second distillation tower 9 for refining, and the acetonitrile fraction is collected in sections). The bottom temperature of the second distillation tower is 85°C. It is first operated under the condition of reflux ratio of 20:1 to remove light components, and then the reflux ratio is adjusted to 7:1 to obtain acetonitrile. The former components and acetonitrile kettle liquid are returned to the third distillation tower 6 to recover the acetonitrile therein.

[0091] Example 5

[0092] The difference from Example 1 is: the acetonitrile light component is not subjected to oxidation treatment.

[0093] Method for recovering and refining high-purity acetonitrile in peptide synthesis, using a device such as Figure 1As shown, the operation process includes the following steps: sending the acetonitrile mother liquor (water content of about 80wt.%, acetonitrile dry purity of about 90%) into the conditioning tank 1 for neutralization, and then sending it into the first distillation tower 2 for concentration after neutralization, and the organic salt and part of the water are discharged from the bottom of the tower. The acetonitrile distillate is transported to the evaporator 3, heated and vaporized to 110°C, and enters the NaA pervaporation membrane separation unit 4 for dehydration to obtain low-water acetonitrile; the feed liquid side pressure is 0.2MPa (gauge pressure), the permeate side pressure is controlled at 1500Pa, and the permeate is condensed by the permeate condenser 5 and returned to the conditioning tank 1 to recover a small amount of acetonitrile therein. The water content of the low-water acetonitrile obtained after the pervaporation separation unit is ≤0.5 wt.%. After the low-water acetonitrile enters the third distillation tower 6, it is subjected to light and heavy removal treatment, with an operating pressure of 20 kPa (G), a kettle bottom temperature of 90 ° C in the third distillation tower, and first operates under the condition of a reflux ratio of 18: 1 to remove light components, and then adjusts the reflux ratio to 6: 1 to obtain acetonitrile, and ensures that the transmittance of the qualified fraction at a wavelength of 200 to 220 nm is ≥ 50%, the purity of acetonitrile is ≥ 99%, and the water content is 0.02 to 0.1 wt.%, to obtain acetonitrile crude product. The obtained acetonitrile crude product is sent to an adsorption tower 8 equipped with a 4A molecular sieve for adsorption, and the acetonitrile desorption liquid is returned to the third distillation tower 6 to recover the acetonitrile therein. The acetonitrile adsorption liquid enters the second distillation tower 9 for refining, and the acetonitrile fraction is collected in sections), the kettle bottom temperature in the second distillation tower is 85 ° C, first operates under the condition of a reflux ratio of 20: 1 to remove light components, and then adjusts the reflux ratio to 7: 1 to obtain acetonitrile. The front component and the acetonitrile kettle liquid are returned to the third distillation tower 6 to recover the acetonitrile therein.

[0094] Example 6

[0095] The difference from Example 1 is that the dehydrated acetonitrile obtained by the pervaporation membrane is not subjected to the third distillation treatment.

[0096] Method for recovering and refining high-purity acetonitrile in peptide synthesis, using a device such as Figure 1As shown, the operation process includes the following steps: the acetonitrile mother liquor (water content of about 80wt.%, acetonitrile dry purity of about 90%) is sent to the conditioning tank 1 for neutralization, and then sent to the first distillation tower 2 for concentration after neutralization, and the organic salt and part of the water are discharged from the bottom of the tower. The acetonitrile distillate is transported to the evaporator 3, heated and vaporized to 110°C, and enters the NaA pervaporation membrane separation unit 4 for dehydration to obtain low-water acetonitrile; the feed liquid side pressure is 0.2MPa (gauge pressure), the permeate side pressure is controlled at 1500Pa, and the permeate is condensed by the permeate condenser 5 and returned to the conditioning tank 1 to recover a small amount of acetonitrile. The low-water acetonitrile obtained after the pervaporation separation unit has a water content of ≤0.5 wt.%. The low-water acetonitrile enters the oxidation tank 7, and 10% concentrated sulfuric acid and 1% potassium permanganate solid are added at room temperature for oxidation for 4h. The acetonitrile oxidation liquid evaporated after oxidation is sent to the adsorption tower 8 equipped with 4A molecular sieve for adsorption. The acetonitrile adsorbent enters the second distillation tower 9 for refining, and the acetonitrile fraction is collected in sections). The bottom temperature of the second distillation tower is 85°C. It is first operated under a reflux ratio of 20:1 to remove light components, and then the reflux ratio is adjusted to 7:1 to obtain acetonitrile.

[0097] Comparative Example 1

[0098] The difference from Example 1 is that the light components of the first distillation are not treated by pervaporation membrane dehydration.

[0099] Method for recovering and refining high-purity acetonitrile in peptide synthesis, using a device such as Figure 1 As shown, the operation process includes the following steps: sending the acetonitrile mother liquor (water content of about 80wt.%, acetonitrile dry purity of about 90%) into the conditioning tank 1 for neutralization, and then sending it into the first distillation tower 2 for concentration after neutralization, and the organic salt and part of the water are discharged from the bottom of the tower. The acetonitrile distillate is transported to the third distillation tower 6 for light and heavy removal treatment, the operating pressure is 20kPa (G), the bottom temperature of the third distillation tower is 90℃, and it is first operated under the condition of reflux ratio of 18:1 to remove the light components, and then the reflux ratio is adjusted to 6:1 to obtain acetonitrile, and ensure that the transmittance of the qualified fraction at a wavelength of 200-220nm is ≥50%, the acetonitrile purity is ≥99%, and the water content is 0.02-0.1 wt.%, to obtain the crude acetonitrile. The obtained crude acetonitrile is sent to the oxidation tank 7, and 10% concentrated sulfuric acid and 1% potassium permanganate solid are added for oxidation for 4h at room temperature. The acetonitrile oxidation liquid evaporated after oxidation is sent to the adsorption tower 8 equipped with 4A molecular sieve for adsorption, and the acetonitrile desorption liquid is returned to the third distillation tower 6 to recover the acetonitrile therein. The acetonitrile adsorption liquid enters the second distillation tower 9 for refining, and the acetonitrile fraction is collected in stages). The bottom temperature of the second distillation tower is 85°C. It is first operated under the condition of reflux ratio of 20:1 to remove light components, and then the reflux ratio is adjusted to 7:1 to obtain acetonitrile. The former component and acetonitrile kettle liquid are returned to the third distillation tower 6 to recover the acetonitrile therein.

[0100] Comparative Example 2

[0101] The difference from Example 1 is that the oxidation step is placed after the adsorption step.

[0102] Method for recovering and refining high-purity acetonitrile in peptide synthesis, using a device such as Figure 1 As shown, the operation process includes the following steps: sending the acetonitrile mother liquor (water content of about 80wt.%, acetonitrile dry purity of about 90%) into the conditioning tank 1 for neutralization, and then sending it into the first distillation tower 2 for concentration after neutralization, and the organic salt and part of the water are discharged from the bottom of the tower. The acetonitrile distillate is transported to the evaporator 3, heated and vaporized to 110°C, and enters the NaA pervaporation membrane separation unit 4 for dehydration to obtain low-water acetonitrile; the feed liquid side pressure is 0.2MPa (gauge pressure), the permeate side pressure is controlled at 1500Pa, and the permeate is condensed by the permeate condenser 5 and returned to the conditioning tank 1 to recover a small amount of acetonitrile therein. The water content of the low-water acetonitrile obtained after the pervaporation separation unit is ≤0.5 wt.%. After the low-water-content acetonitrile enters the third distillation tower 6, it is subjected to light and heavy removal treatment, with an operating pressure of 20 kPa (G), a kettle bottom temperature of 90°C in the third distillation tower, and first operates under a reflux ratio of 18:1 to remove light components, and then adjusts the reflux ratio to 6:1 to obtain acetonitrile, and ensures that the transmittance of the qualified fraction at a wavelength of 200-220 nm is ≥50%, the acetonitrile purity is ≥99%, and the water content is 0.02-0.1wt.%, to obtain crude acetonitrile. The obtained crude acetonitrile is sent to an adsorption tower 8 equipped with a 4A molecular sieve for adsorption, and the adsorbed acetonitrile is sent to an oxidation tank 7, and 10% concentrated sulfuric acid and 1% potassium permanganate are added at room temperature for solid oxidation for 4 hours. The acetonitrile evaporated after oxidation enters the second distillation tower 9 for refining, and the acetonitrile fraction is collected in stages. The kettle bottom temperature in the second distillation tower is 85°C, and first operates under a reflux ratio of 20:1 to remove light components, and then adjusts the reflux ratio to 7:1 to obtain acetonitrile. The front component and the acetonitrile kettle liquid are returned to the third distillation tower 6 to recover the acetonitrile therein.

[0103] The technical indicators of the high-purity acetonitrile recovered from Examples 1-6 and Comparative Examples 1-2 are shown in Table 1:

[0104]

[0105] As can be seen from the above table, the acetonitrile obtained by the present invention has a very high purity. From the comparison between Example 1 and Example 5, it can be seen that for acetonitrile waste liquid in polypeptide synthesis, if the purity requirements meet the regulations, the oxidation process can be omitted. In order to make the purity higher, adding an oxidation step can improve the purity; from the comparison between Example 1 and Example 6, it can be seen that for some acetonitrile waste liquid in polypeptide synthesis, it can also be directly entered into the oxidation process without distillation and dehydration after pervaporation dehydration, and acetonitrile of a certain purity can be obtained after subsequent steps, but the purity of the final product acetonitrile can be improved after dehydration; from the comparison between Example 1 and Reference Example 1, it can be seen that after the pervaporation treatment in the present invention, the concentration in acetonitrile can be effectively increased, which can be more conducive to the treatment effect of the oxidant in the oxidation process and improve the purity of the product. From the comparison between Example 1 and Reference Example 2, it can be seen that the use of oxidation to treat the polypeptide acetonitrile eluate can effectively decompose the amino acids therein into small molecular substances, which is conducive to molecular sieve adsorption and improves the purity of the product. By comparing Example 1 with Examples 3 and 4, it can be seen that the treatment with sulfonic acid-modified sepiolite can effectively remove the components in the first distillation and prevent them from affecting the separation factor in the pervaporation operation process.

Claims

1. A method for recovering and refining high-purity acetonitrile for peptide synthesis, characterized in that: The steps include: Step 1, subjecting the acetonitrile waste liquid generated by elution during peptide synthesis to pH neutralization treatment; the acetonitrile waste liquid generated by elution during peptide synthesis has a water content of 40 to 95 wt.%, a pH range of 1 to 4, and contains other organic impurities, the other organic impurities include one or more of methanol, ethanol, isopropanol, acetone, ethyl acetate, trifluoroacetic acid, and ammonia water, and the organic impurity content accounts for 1 to 15 wt.% of the total organic matter; the conditioning solution for pH neutralization treatment is one or more of sodium hydroxide, sodium carbonate, and sodium bicarbonate solution, and the end point pH of pH neutralization treatment is 6 to 9; Step 2, subjecting the neutralized acetonitrile waste liquid in step 1 to a first distillation treatment to remove heavy components; Step 3, the acetonitrile distillate obtained in step 2 is sent into a pervaporation membrane separation unit for dehydration, so that water passes through the membrane to obtain crude acetonitrile; In the fourth step, the crude acetonitrile obtained in the third step is subjected to a third distillation treatment to remove light components and obtain a crude acetonitrile de-lightened product. The crude acetonitrile de-lightened product is first subjected to an oxidation treatment and then sent to an adsorption tower for adsorption and removal of impurities; the third distillation is performed intermittently, and the operating pressure is a gauge pressure of -70 to 50 kPa. The acetonitrile distillate is extracted in stages, and qualified fractions are collected, and the reflux ratio is controlled at 5 to 10; the light transmittance of the collected qualified fractions at a wavelength of 200 to 220 nm is ≥50%, the acetonitrile purity is ≥99%, and the water content is 0.02 to 0.1 wt.%; the oxidant required for oxidation is potassium permanganate, potassium dichromate, silver nitrate, concentrated sulfuric acid, concentrated nitric acid, sodium peroxide or hydrogen peroxide; the adsorbent is 3A molecular sieve, 4A molecular sieve, 13X molecular sieve, coal-based activated carbon, sepiolite, coconut shell activated carbon or carbon fiber; In step 5, the acetonitrile obtained after adsorption in step 4 is subjected to a second distillation treatment to remove light component impurities and heavy component impurities to obtain finished acetonitrile; in step 5, the light component impurities and heavy component impurities are removed by segmented distillation to obtain a middle distillate.

2. The method for recovering and refining high-purity acetonitrile for peptide synthesis according to claim 1, characterized in that: The light components obtained in the third distillation are returned to the feed of the third distillation process to recover the acetonitrile therein again; the front fraction of the second distillation and the refined acetonitrile kettle liquid are returned to the third distillation to recover the acetonitrile therein again.

3. The method for recovering and refining high-purity acetonitrile for peptide synthesis according to claim 2, characterized in that: The light components extracted from the third distillation need to be returned to the third distillation treatment step for distillation again to enrich the impurities in the light-desorbed liquid; the acetonitrile desorption liquid produced during the adsorption process in the fourth step is returned to the third distillation step to recover the acetonitrile therein; the front fraction of the second distillation and the kettle liquid in the fifth step need to be returned to the third distillation in the fourth step to recover the acetonitrile therein again.

4. The method for recovering and refining high-purity acetonitrile for peptide synthesis according to claim 1, characterized in that: In step 3, the permeate of the pervaporation membrane separation unit is condensed and returned to step 1 for pH neutralization treatment to recover the acetonitrile therein.

5. The method for recovering and refining high-purity acetonitrile for peptide synthesis according to claim 1, characterized in that: The water content of the crude acetonitrile in the step 3 is controlled at 0.05-5 wt.%; the ultraviolet transmittance index of the finished acetonitrile fraction in the step 5 is 200nm≥90%, 210nm≥94%, 220nm≥96%, 240nm≥98%, 250nm≥99%, acetonitrile content is ≥99.9%, and water content is ≤0.05wt.%.

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