CN115286532A - Method for continuously synthesizing methyldopa intermediate DL-aminopropionitrile - Google Patents
Method for continuously synthesizing methyldopa intermediate DL-aminopropionitrile Download PDFInfo
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Abstract
The invention discloses a method for continuously synthesizing methyldopa intermediate DL-aminopropionitrile, which comprises the following steps: (1) Mixing and dissolving ammonium chloride, sodium cyanide and ammonia water to obtain an ammonia water solution containing sodium cyanide and ammonium chloride, which is a feed liquid A; dissolving veratone in an organic solvent D to obtain a feed liquid B; (2) Respectively inputting the feed liquid A and the feed liquid B into a first micro mixer at certain flow rates, mixing, and then entering a first tubular reactor for reaction to obtain a reaction liquid C containing a mixture of DL-aminopropionitrile and veratone; (3) Introducing the reaction liquid C and the organic solvent D into a second micro mixer, mixing, and directly entering a second tubular reactor for reaction to obtain a reaction liquid E containing DL-aminopropionitrile; (4) And continuously layering and continuously washing the reaction solution E to obtain an organic solution containing DL-aminopropionitrile. The method solves a series of problems of difficult feeding of solid sodium cyanide, more side reactions, more impurities, low production efficiency and the like in the existing production process.
Description
Technical Field
The invention relates to the technical field of fine chemical raw material synthesis, in particular to a method for continuously synthesizing a methyldopa intermediate DL-aminopropionitrile.
Background
Methyldopa is an antihypertensive drug, and can be used for treating moderate, severe or malignant hypertension, tranquilizing, and lowering intraocular pressure. It is especially suitable for treating renal hypertension and hypertension with renal hypofunction.
The synthesis of levomethyldopa generally follows the following route: 1) Synthesis of DL-3- (3, 4-dimethoxyphenyl) -2-amino-2-methylpropanenitrile comprising: adding ammonia, water, veratone, ammonium chloride and sodium cyanide into a reactor, stirring and heating to 35-80 ℃, keeping the temperature for reaction for 1-4 h, cooling to 0-25 ℃, and filtering to obtain a filter cake of DL-aminopropionitrile, wherein the filter liquor is the mother liquor synthesized by DL-aminopropionitrile; 2) The synthesis of L-3- (3, 4-dimethoxyphenyl) -2-amino-2-methylpropanenitrile (L-aminopropionitrile for short) hydrochloride comprises the following steps: adding water, hydrochloric acid and the DL-aminopropionitrile obtained in the step 1) into a reactor, stirring for dissolving, adding D-tartaric acid, separating out a solid from a system, cooling and filtering, wherein a filter cake is tartrate of the D-aminopropionitrile; adding a water-insoluble solvent into the filtrate, adjusting the pH value to be more than 6 by using alkali, layering, adding hydrochloric acid into an organic layer, separating out solids, filtering, wherein a filter cake is L-aminopropionitrile hydrochloride, and the filtrate is waste liquid obtained after the resolution of DL-aminopropionitrile; 3) Hydrolysis of L-3- (3, 4-dimethoxyphenyl) -2-amino-2-methylpropanenitrile hydrochloride to levomethyldopa comprises: adding concentrated hydrochloric acid and the L-aminopropionitrile hydrochloride obtained in the step 2) into a reactor, and hydrolyzing under the conditions of heating and a reducing agent to obtain the levomethyldopa.
DL-3- (3, 4-dimethoxyphenyl) -2-amino-2-methyl propionitrile is an important organic intermediate (hereinafter referred to as DL-amino propionitrile) for preparing methyldopa, and is mainly used for synthesizing levomethyldopa medicaments in the pharmaceutical industry. DL-aminopropionitrile having the formula C 12 H 16 N 2 O 2 The pure product is white or yellowish crystal, has a melting point of 85-87 ℃, is insoluble in water, and is easily soluble in organic solvents such as dichloromethane, methanol, acetone, diethyl ether, DMF and the like. The structural formula is as follows:
at present, the domestic method for preparing DL-aminopropionitrile mainly adopts Strecker reaction synthesis and is obtained by solid-liquid separation and water washing. For example, chinese patent publication No. CN104672105A discloses a method for synthesizing DL-3- (3, 4-dimethoxyphenyl) -2-amino-2-methylpropanenitrile, which comprises reacting veratone as a raw material with sodium cyanide and ammonium chloride in an aqueous ammonia solution, and then washing with a large amount of water by centrifugation (or filter pressing) to obtain DL-aminopropionitrile.
Because the method mainly adopts a kettle type intermittent production process, the reaction time period is long and is about 8-9 hours, the process control difficulty is high, the operation is complicated, and the waste water discharge is large.
Disclosure of Invention
The invention provides a method for continuously synthesizing a methyldopa intermediate DL-aminopropionitrile, and aims to solve a series of problems of difficult feeding of solid sodium cyanide, more side reactions, more impurities, low production efficiency and the like in a cyanidation reaction process in the conventional production process.
The technical scheme of the invention is as follows:
a method for continuously synthesizing methyldopa intermediate DL-aminopropionitrile comprises the following steps:
(1) Mixing and dissolving ammonium chloride, sodium cyanide and ammonia water to obtain an ammonia water solution containing sodium cyanide and ammonium chloride, which is a feed liquid A; dissolving veratone in an organic solvent D to obtain a feed liquid B;
(2) Respectively inputting the feed liquid A and the feed liquid B into a first micro mixer at certain flow rates, mixing, and then entering a first tubular reactor for reaction to obtain a reaction liquid C containing a mixture of DL-aminopropionitrile and veratone;
(3) Introducing the reaction liquid C and the organic solvent D into a second micro mixer, mixing, and directly entering a second tubular reactor for reaction to obtain a reaction liquid E containing DL-aminopropionitrile;
(4) And continuously layering and continuously washing the reaction solution E to obtain an organic solution containing DL-aminopropionitrile.
The method utilizes the micro mixer to rapidly and uniformly mix the veratone with the ammonia water solution of the ammonium chloride and the sodium cyanide, and then completes the reaction in the subsequent tubular reactor, thereby realizing accurate temperature control and effectively avoiding the generation of byproducts caused by insufficient material mixing and local overheating of the system. Meanwhile, in the second-stage low-temperature reaction process, an oil-water two-phase reaction system is adopted to prevent the separation of DL-aminopropionitrile, the utilization rate of reaction atoms is effectively improved, and reaction products can be extracted into an organic phase from a water phase in time to realize in-situ separation, so that the separation of solids is effectively avoided, and the occurrence of side reactions is reduced.
In the step (1), the concentration of ammonia water is 15-25%.
Preferably, in the feed liquid A, the mass fraction of ammonium chloride is 5-30 wt%, and the mass fraction of sodium cyanide is 10-50 wt%; in the feed liquid B, the mass fraction of the veratone is 30-80 wt%.
The organic solvent D is at least one of dichloromethane, dichloroethane and chloroform.
Preferably, during the reaction of step (2), the molar ratio of veratone to ammonium chloride to sodium cyanide is 1: (1.0-2.0): (1.0-2.0).
Preferably, in the step (3), the mass ratio of the reaction solution C to the organic solvent D is 1: (2.0-5.0), wherein the amount of the reaction liquid C is calculated by the mass of the veratone in the feed liquid A in the step (2).
Preferably, the first micromixer and the second micromixer are microchannel mixers, membrane dispersion mixers, or micromesh mixers.
Preferably, the reaction temperature of the first mixer and the first tubular reactor is 30-60 ℃, the residence time of the feed liquid A and the feed liquid B in the first mixer is 0.1-1 s, and the residence time in the first tubular reactor is 0.5-10 min.
Preferably, the reaction pressure in the first tubular reactor is 0.1 to 3MPa.
Preferably, the mixing temperature in the second micro mixer is 20-40 ℃; the mixing retention time is 0.5-10 min.
When the mixing residence time of the organic solvent D and the reaction liquid C in the second mixer is short, the organic solvent D and the reaction liquid C cannot be fully mixed, because the reaction liquid C is a two-phase mixture of a water-insoluble organic matter and an aqueous solution, the organic solvent D and the reaction liquid C need to be fully mixed in the second micro mixer and then enter the second tubular reactor. In the second micro mixer, certain mixing time is controlled, namely, the time is kept, so that sufficient mixing can be effectively carried out, and a foundation is laid for subsequent reaction. When the mixing residence time is too long, the production efficiency is affected, and the reaction is not greatly completed.
Preferably, the reaction temperature of the second tubular reactor is 20-40 ℃, and the residence time of the reaction liquid C and the organic solvent D in the second tubular reactor is 10-60 min.
Preferably, the reaction pressure in the second tubular reactor is 0.1 to 3MPa.
Preferably, the flow rate of the feed liquid A is 15-25 mL/min; the flow rate of the feed liquid B is 3-8mL/min; the flow rate of the organic solvent D is 5-10 mL/min.
The inner diameters of the first tubular reactor and the second tubular reactor are respectively and independently 2-5 mm. The first tubular reactor and the second tubular reactor are made of anticorrosive materials.
The outlet of the second tubular reactor is connected with a back pressure valve to regulate and control the system pressure so as to regulate the reaction residence time.
Compared with the prior art, the invention has the following beneficial effects:
the method solves a series of problems of difficult feeding of solid sodium cyanide, more side reactions, more impurities, low production efficiency and the like in the cyanidation reaction process, can improve the production efficiency, reduce the material leakage and the impurities in the reaction process and reduce the process risk by using the continuous production process, can be directly used for the next separation process by continuous extraction of an organic solvent without a solid-liquid separation step and simplifies the operation process.
In the invention, the micro mixer, the micro-channel continuous flow reaction and the continuous extraction are combined, so that the whole-process material pipeline transfer can be realized, and the overflow leakage of cyanide-containing materials and organic solvents is effectively avoided; the microchannel reactor has high-efficiency mass transfer and heat transfer performance, reduces the occurrence of side reactions and increases the reaction yield; the application of the process can realize continuous and automatic operation of a workshop, reduce field operators and improve the overall production efficiency.
Drawings
FIG. 1 is a schematic flow chart of the method for continuously synthesizing the intermediate DL-aminopropionitrile of methyldopa according to the invention.
Detailed Description
Example 1
Preparing feed liquid A: 35.85g of ammonium chloride is weighed, 300ml of 25% ammonia water is added, stirred and dissolved, 109.5 g of 30% sodium cyanide aqueous solution is added, stirred for 5 minutes, and then ammonia water is added to the solution until the volume is 500ml.
Preparing feed liquid B: 100g of veratone was weighed and added with dichloromethane (solvent D) to a volume of 125ml.
During the reaction, veratone: ammonium chloride: the molar ratio of sodium cyanide is 1.3.
Respectively conveying the feed liquid A and the feed liquid B to a No. 1 micro mixer by using a metering pump according to a set flow rate, quickly and uniformly mixing, then feeding the mixture into a No. 1 micro-channel reactor, wherein the temperature of the reactor is 50 ℃, the flow rate of the feed liquid A is 20mL/min, the flow rate of the feed liquid B is 5mL/min, a connected reaction coil is a stainless steel pipe with the outer diameter of 3mm and the inner diameter of 2mm, the residence time is 2.5min, the reaction temperature is 50 ℃, the reaction pressure is 0.5MPa, and the mixed feed liquid C obtained by reaction is directly introduced into a No. 2T-shaped micro-channel mixer (40 ℃). Meanwhile, the solvent D is conveyed to a No. 2T-shaped micro-channel mixer by using a metering pump, is quickly and uniformly mixed with the reaction liquid in the previous step, and then enters a No. 2 micro-channel reactor. The solvent flow is 8mL/min, the preheating temperature is 35 ℃, the connected reaction coil is a stainless steel pipe with the outer diameter of 4mm and the inner diameter of 3mm, the retention time is 30min, the system pressure is 0.3MPa, and the reaction liquid E containing DL-aminopropionitrile is obtained at the outlet of the pipeline. And continuously extracting and washing the reaction liquid E to obtain a DL-aminopropionitrile oil layer, and purifying to obtain 110.20g of DL-aminopropionitrile, wherein the purity is 97.5 percent, and the yield is 97.2 percent.
Example 2
Preparing feed liquid A: 30.34g of ammonium chloride is weighed, 300ml of 25% ammonia water is added, the mixture is stirred and dissolved, 126.29 g of 30% sodium cyanide aqueous solution is added, the mixture is stirred for 5 minutes, and then the volume is increased to 500ml by adding the ammonia water.
Preparing feed liquid B: 100g of veratone was weighed and added with dichloromethane (solvent D) to a volume of 125ml.
During the reaction, veratone: ammonium chloride: the molar ratio of sodium cyanide is 1.1.
Respectively conveying the feed liquid A and the feed liquid B to a No. 1 micro mixer by using a metering pump according to a set flow rate, quickly and uniformly mixing, then feeding the mixture into a No. 1 micro-channel reactor, wherein the temperature of the reactor is 50 ℃, the flow rate of the feed liquid A is 20mL/min, the flow rate of the feed liquid B is 5mL/min, a connected reaction coil is a stainless steel pipe with the outer diameter of 3mm and the inner diameter of 2mm, the residence time is 2.5min, the reaction temperature is 50 ℃, the reaction pressure is 0.5MPa, and the mixed feed liquid C obtained by reaction is directly introduced into a No. 2T-shaped micro-channel mixer (40 ℃). Meanwhile, a solvent D is conveyed to a No. 2T-shaped microchannel mixer by using a metering pump to be rapidly and uniformly mixed with the reaction liquid in the previous step and then enters the No. 2 microchannel mixer, the flow rate of the solvent is 8mL/min, the preheating temperature is 35 ℃, the connected reaction coil is a stainless steel pipe with the outer diameter of 4mm and the inner diameter of 3mm, the retention time is 30min, the system pressure is 0.3MPa, and the reaction liquid E containing DL-aminopropionitrile is obtained at the outlet of the pipeline. And continuously extracting and washing the reaction liquid E to obtain a DL-aminopropionitrile oil layer, and purifying to obtain 107.45g of DL-aminopropionitrile, wherein the purity is 95.2 percent and the yield is 94.8 percent.
Example 3
Preparing feed liquid A: 35.85g of ammonium chloride is weighed, 300ml of 25% ammonia water is added, the mixture is stirred and dissolved clearly, 109.5 g of 30% sodium cyanide aqueous solution is added, and after stirring for 5 minutes, the mixture is added with ammonia water to reach the volume of 500ml.
Preparing feed liquid B: 100g of veratone was weighed and added with dichloromethane (solvent D) to a volume of 125ml.
During the reaction process, the veratone: ammonium chloride: the molar ratio of sodium cyanide is 1.5.
Respectively conveying the feed liquid A and the feed liquid B to a No. 1 micro mixer by using a metering pump according to a set flow rate, quickly and uniformly mixing, then feeding the mixture into a No. 1 micro-channel reactor, wherein the temperature of the reactor is 50 ℃, the flow rate of the feed liquid A is 20mL/min, the flow rate of the feed liquid B is 5mL/min, a connected reaction coil is a stainless steel pipe with the outer diameter of 3mm and the inner diameter of 2mm, the residence time is 2.5min, the reaction temperature is 50 ℃, the reaction pressure is 0.5MPa, and the mixed feed liquid C obtained by reaction is directly introduced into a No. 2T-shaped micro-channel mixer (40 ℃). Meanwhile, a solvent D is conveyed to a No. 2T-shaped micro-channel mixer by using a metering pump and is rapidly and uniformly mixed with the reaction liquid in the previous step, and then the mixture enters a No. 2 micro-channel reactor, the flow rate of the solvent is 8mL/min, the preheating temperature is 35 ℃, the connected reaction coil is a stainless steel pipe with the outer diameter of 4mm and the inner diameter of 3mm, the retention time is 30min, the system pressure is 0.3MPa, and the reaction liquid E containing DL-aminopropionitrile is obtained at the outlet of a pipeline. The reaction solution E was continuously extracted and continuously washed with water to obtain an oil layer of DL-aminopropionitrile, 110.35g of DL-aminopropionitrile was obtained after purification, purity 97.5%, yield 97.3%.
Example 4
Preparing feed liquid A: 35.85g of ammonium chloride is weighed, 300ml of 25% ammonia water is added, the mixture is stirred and dissolved clearly, 109.5 g of 30% sodium cyanide aqueous solution is added, and after stirring for 5 minutes, the mixture is added with ammonia water to reach the volume of 500ml.
Preparing feed liquid B: 100g of veratone was weighed and added with dichloromethane (solvent D) to a volume of 125ml.
During the reaction, veratone: ammonium chloride: the molar ratio of sodium cyanide is 1.3.
Respectively conveying the feed liquid A and the feed liquid B to a No. 1 micro mixer by using a metering pump according to a set flow rate, quickly and uniformly mixing, then feeding the mixture into a No. 1 micro-channel reactor, wherein the temperature of the reactor is 55 ℃, the flow rate of the feed liquid A is 20mL/min, the flow rate of the feed liquid B is 5mL/min, a connected reaction coil is a stainless steel pipe with the outer diameter of 3mm and the inner diameter of 2mm, the residence time is 2.5min, the reaction temperature is 55 ℃, the reaction pressure is 0.5MPa, and the mixed feed liquid obtained by reaction is directly fed into a No. 3T-shaped micro-channel mixer (40 ℃). Meanwhile, a solvent D is conveyed to a No. 2T-shaped microchannel mixer by using a metering pump to be rapidly and uniformly mixed with the reaction liquid in the previous step and then enters the No. 2 microchannel mixer, the flow rate of the solvent is 8mL/min, the preheating temperature is 35 ℃, the connected reaction coil is a stainless steel pipe with the outer diameter of 4mm and the inner diameter of 3mm, the retention time is 30min, the system pressure is 0.3MPa, and the reaction liquid E containing DL-aminopropionitrile is obtained at the outlet of the pipeline. And (3) continuously extracting and washing the reaction liquid E to obtain a DL-aminopropionitrile oil layer, and purifying to obtain 108.20g of DL-aminopropionitrile, wherein the purity is 96.5 percent, and the yield is 95.4 percent.
Example 5
Preparing feed liquid A: 35.85g of ammonium chloride is weighed, 300ml of 25% ammonia water is added, stirred and dissolved, 109.5 g of 30% sodium cyanide aqueous solution is added, stirred for 5 minutes, and then ammonia water is added to the solution until the volume is 500ml.
Preparing feed liquid B: 100g of veratone was weighed and added with dichloromethane (solvent D) to a volume of 125ml.
During the reaction, veratone: ammonium chloride: the molar ratio of sodium cyanide is 1.3.
Respectively conveying the feed liquid A and the feed liquid B to a No. 1 micro mixer by using a metering pump according to a set flow rate, quickly and uniformly mixing, then feeding the mixture into a No. 1 micro-channel reactor, wherein the temperature of the reactor is 45 ℃, the flow rate of the feed liquid A is 20mL/min, the flow rate of the feed liquid B is 5mL/min, a connected reaction coil is a stainless steel pipe with the outer diameter of 3mm and the inner diameter of 2mm, the residence time is 2.5min, the reaction temperature is 45 ℃, the reaction pressure is 0.5MPa, and the mixed feed liquid C obtained by reaction is directly introduced into a No. 2T-shaped micro-channel mixer (40 ℃). Meanwhile, the solvent D is conveyed to a No. 2T-shaped microchannel mixer by using a metering pump to be rapidly and uniformly mixed with the reaction liquid in the previous step, and then enters a No. 2 microchannel reactor, the flow is 8mL/min, the preheating temperature is 30 ℃, the connected reaction coil is a stainless steel pipe with the outer diameter of 4mm and the inner diameter of 3mm, the retention time is 30min, the system pressure is 0.3MPa, and the reaction liquid E containing DL-aminopropionitrile is obtained at the outlet of the pipeline. The reaction solution E was continuously extracted and continuously washed with water to obtain a DL-aminopropionitrile oil layer, 108.0g of DL-aminopropionitrile was obtained on the basis of pure degree, purity 95.9%, yield 95.2%.
Example 6
Preparing feed liquid A: 35.85g of ammonium chloride is weighed, 300ml of 25% ammonia water is added, stirred and dissolved, 109.5 g of 30% sodium cyanide aqueous solution is added, stirred for 5 minutes, and then ammonia water is added to the solution until the volume is 500ml.
Preparing feed liquid B: 100g of veratone was weighed and added with dichloromethane (solvent D) to a volume of 125ml.
During the reaction, veratone: ammonium chloride: the molar ratio of sodium cyanide is 1.3.
Respectively conveying the feed liquid A and the feed liquid B to a No. 1 micro mixer by using metering pumps according to a set flow rate, quickly and uniformly mixing, then feeding the mixture into a No. 1 micro-channel reactor, wherein the temperature of the reactor is 50 ℃, the flow rate of the feed liquid A is 20mL/min, the flow rate of the feed liquid B is 5mL/min, a connected reaction coil is a stainless steel pipe with the outer diameter of 3mm and the inner diameter of 2mm, the retention time is 1.0min, the reaction temperature is 50 ℃, the reaction pressure is 0.5MPa, and the mixed feed liquid C obtained by reaction is directly introduced into a No. 2T type micro-channel mixer (40 ℃). Meanwhile, the solvent D is conveyed to a No. 2T-shaped microchannel mixer by using a metering pump to be rapidly and uniformly mixed with the reaction liquid in the previous step, and then enters a No. 2 microchannel reactor, the flow is 8mL/min, the preheating temperature is 35 ℃, the connected reaction coil is a stainless steel pipe with the outer diameter of 4mm and the inner diameter of 3mm, the retention time is 15min, the system pressure is 0.3MPa, and the reaction liquid E containing DL-aminopropionitrile is obtained at the outlet of the pipeline. The reaction solution E was continuously extracted and washed with water to obtain a DL-aminopropionitrile oil layer, 105.20g of DL-aminopropionitrile was obtained after purification, purity 92.1%, yield 92.8%.
Example 7
Preparing feed liquid A: 35.85g of ammonium chloride is weighed, 300ml of 25% ammonia water is added, the mixture is stirred and dissolved clearly, 109.5 g of 30% sodium cyanide aqueous solution is added, and after stirring for 5 minutes, the mixture is added with ammonia water to reach the volume of 500ml.
Preparing feed liquid B: 100g of veratone was weighed and added with dichloromethane (solvent D) to a volume of 125ml.
During the reaction, veratone: ammonium chloride: the molar ratio of sodium cyanide is 1.3.
Respectively conveying the feed liquid A and the feed liquid B to a No. 1 micro mixer by using a metering pump according to a set flow rate, quickly and uniformly mixing, then feeding the mixture into a No. 1 micro-channel reactor, wherein the temperature of the reactor is 50 ℃, the flow rate of the feed liquid A is 20mL/min, the flow rate of the feed liquid B is 5mL/min, a connected reaction coil is a stainless steel pipe with the outer diameter of 3mm and the inner diameter of 2mm, the retention time is 5.0min, the reaction temperature is 50 ℃, the reaction pressure is 0.5MPa, and the mixed feed liquid C obtained by reaction is directly introduced into a No. 2T-shaped micro-channel mixer (40 ℃). Meanwhile, a solvent D is conveyed to a No. 2T-shaped micro-channel mixer by using an advection pump to be rapidly and uniformly mixed with the reaction liquid in the previous step, and then the mixture enters a No. 2 micro-channel reactor, the flow is 8mL/min, the preheating temperature is 35 ℃, the connected reaction coil is a stainless steel pipe with the outer diameter of 4mm and the inner diameter of 3mm, the retention time is 60min, the system pressure is 0.3MPa, and the reaction liquid E containing DL-aminopropionitrile is obtained at the outlet of the pipeline. And (3) continuously extracting and washing the reaction liquid E to obtain a DL-aminopropionitrile oil layer, wherein the purity of the DL-aminopropionitrile is 109.60g, the purity is 97.0 percent, and the yield is 96.6 percent.
The experimental conditions and results of examples 1-7 are shown in Table 1.
TABLE 1
The above-mentioned embodiments are intended to illustrate the technical solutions and advantages of the present invention, and it should be understood that the above-mentioned embodiments are only specific embodiments of the present invention, and are not intended to limit the present invention, and any modifications, additions, equivalents, etc. made within the scope of the principles of the present invention should be included in the scope of the present invention.
Claims (10)
1. A method for continuously synthesizing a methyldopa intermediate DL-aminopropionitrile is characterized by comprising the following steps of:
(1) Mixing and dissolving ammonium chloride, sodium cyanide and ammonia water to obtain an ammonia water solution containing sodium cyanide and ammonium chloride, which is a feed liquid A; dissolving veratone in an organic solvent D to obtain a feed liquid B;
(2) Respectively inputting the feed liquid A and the feed liquid B into a first micro mixer at certain flow rates, mixing, and then entering a first tubular reactor for reaction to obtain a reaction liquid C containing a mixture of DL-aminopropionitrile and veratone;
(3) Introducing the reaction liquid C and an organic solvent D into a second micromixer, mixing, and directly introducing into a second tubular reactor for reaction to obtain a reaction liquid E containing DL-aminopropionitrile;
(4) And continuously layering and continuously washing the reaction solution E to obtain an organic solution containing DL-aminopropionitrile.
2. The method for continuously synthesizing methyldopa intermediate DL-aminopropionitrile of claim 1, wherein in feed liquid A, the mass fraction of ammonium chloride is 5-30 wt%, and the mass fraction of sodium cyanide is 10-50 wt%; in the feed liquid B, the mass fraction of the veratone is 30-80 wt%.
3. The method for continuously synthesizing methyldopa intermediate DL-aminopropionitrile according to claim 1, wherein during the reaction of step (2), the molar ratio of veratone, ammonium chloride and sodium cyanide is 1: (1.0-2.0): (1.0-2.0).
4. The method for continuously synthesizing methyldopa intermediate DL-aminopropionitrile according to claim 1, wherein in the step (3), the mass ratio of the reaction solution C to the organic solvent D is 1: (2.0-5.0), wherein the amount of the reaction liquid C is calculated by the mass of the veratone in the feed liquid A in the step (2).
5. The method for continuously synthesizing methyldopa intermediate DL-aminopropionitrile of claim 1, wherein the first micromixer and the second micromixer are microchannel mixers, membrane dispersion mixers, or micromesh mixers.
6. The method for continuously synthesizing the methyldopa intermediate DL-aminopropionitrile of claim 1, wherein the reaction temperature of the first mixer and the first tubular reactor is 30-60 ℃; the retention time of the feed liquid A and the feed liquid B in the first mixer is 0.1-1 s, and the retention time in the first tubular reactor is 0.5-10 min.
7. The method for continuously synthesizing the intermediate DL-aminopropionitrile of methyldopa according to claim 1, wherein the mixing temperature in the second micromixer is 20-40 ℃; the mixing retention time is 0.5-10 min.
8. The method for continuously synthesizing methyldopa intermediate DL-aminopropionitrile according to claim 1, wherein the reaction temperature of the second tubular reactor is 20-40 ℃, and the residence time of the reaction solution C and the organic solvent D in the second tubular reactor is 10-60 min.
9. The method for continuously synthesizing the methyldopa intermediate DL-aminopropionitrile according to claim 1, wherein the reaction pressure in the first tubular reactor and the reaction pressure in the second tubular reactor are respectively and independently 0.1-3 MPa.
10. The method for continuously synthesizing the methyldopa intermediate DL-aminopropionitrile according to claim 1, wherein the flow rate of the feed liquid A is 15-25 mL/min; the flow rate of the feed liquid B is 3-8mL/min; the flow rate of the organic solvent D is 5-10 mL/min.
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