Method for preparing 3-hydroxypropyl nitrate through continuous flow

Abstract

The invention discloses a method for preparing 3-hydroxypropyl nitrate by continuous flow, the 3-hydroxypropyl nitrate is continuously prepared by a three-step method of monoacetylation, nitration and hydrolysis, and the prepared compound can be confirmed by a 1H NMR (nuclear magnetic resonance) characterization method. Meanwhile, through a two-step continuous flow reaction technology and a two-step online continuous separation technology which are connected in series, continuous production is realized, and key reaction parameters such as material mixing, heating and retention time can be accurately controlled, so that the product quality is improved, impurities are controlled, the chemical reaction is allowed to react in a higher temperature range without temperature runaway, and the product quality is improved. The reaction speed can be increased in reaction thermodynamics, the production efficiency is improved, heat accumulation of kettle type reaction is avoided, and the reaction is safer; the post-treatment process of the flow chemistry is always online, so that the reaction is cleaner, automatic and online sample collection is convenient to realize, reaction parameters are convenient to change, optimal reaction conditions are convenient to find, and the process exploration and substrate screening efficiency is greatly improved.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly relates to a method for continuously preparing 3-hydroxypropyl nitrate. Background Art

[0002] The global temperature is rising, a process known as global warming or climate change. One of the main focuses in reducing this warming effect is to reduce the amount of greenhouse gases emitted into the atmosphere. The two sources with the greatest impact on greenhouse gas emissions are agriculture and the fossil fuel industry. In agriculture, ruminants, especially cattle, are a major factor in the formation of biogenic methane, and it is estimated that preventing methane formation from ruminants would stabilize the atmospheric methane concentration.

[0003] 3-Hydroxypropyl nitrate (3-NOP, also known as 3-nitrooxy-propan-1-ol or 1,3-propanediol mononitrate) is very effective in reducing methane formation in ruminants without affecting microbial fermentation in a manner adverse to the host animal. The mononitration of polyols is generally poorly selective and is not easily kinetically controlled and rapidly leads to the formation of dinitrated alcohols or polynitrated alcohols.

[0004] WO-2012 / 084629 discloses a method for preparing 3-hydroxypropyl nitrate by reacting 3-bromopropanol with silver nitrate in acetonitrile, but this method is not economical for industrial-scale production.

[0005] Zikas et al. (Bioorganic & Medicinal Chemistry, 13(2005)6485 - 6492) disclose a process for the mononitration of alkane diols with acetyl nitrate (generated from nitric acid, acetic acid, and acetic anhydride) in the presence of ethyl acetate at room temperature. In addition to the need for organic solvents, another disadvantage of this method is the use of acetyl nitrate, which, although an excellent nitrating agent, is explosive and thus not suitable for industrial-scale production.

[0006] WO-2004043898 discloses the batch mononitration of alkane diols with stable nitric acid in a water-immiscible chlorinated organic solvent at below room temperature. In addition to using chlorinated solvents that are highly undesirable in chemical production, a significant disadvantage of this method is the need for a high acid equivalent, which results in a high salt load. Moreover, this method uses a non-commercial nitric acid diluent. Also, the reaction requires low temperature (i.e., <RT) to control selectivity and avoid thermal runaway or even explosion.

[0007] The preparation method of 3-hydroxypropyl nitrate mentioned in WO2021 / 214146 EN 2021.10.28 uses a batch reaction apparatus, resulting in low synthesis efficiency and high safety risks due to the frequent handling of high-concentration nitric acid. Some patents mention the mononitration preparation process of polyols, which uses distillation and rectification equipment, leading to high energy consumption and high safety risks in the production process.

[0008] Therefore, the industry urgently needs a safe and efficient process for preparing 3-hydroxypropyl nitrate. Summary of the Invention

[0009] The purpose of this invention is to provide a continuous flow method for preparing 3-hydroxypropyl nitrate, which includes a two-step continuous flow reaction technology and a two-step online continuous separation technology. Its advantages are not only reflected in the safer and more efficient handling of nitration reactions and the recovery and reuse of solvents, but also in the stable and controllable process parameters that ensure product quality.

[0010] To achieve the above objectives, the technical solution of the present invention is as follows:

[0011] A method for preparing 3-hydroxypropyl nitrate in a continuous flow process includes the following steps;

[0012] S1,1,3-propanediol undergoes a monoacylation reaction with acetyl chloride in an inert solvent at room temperature and pressure to give the monoacylated product;

[0013] S2. The monoacylated product is fed into a nitration reactor in an inert organic solvent along with a nitric acid / sulfuric acid mixed solution for nitration reaction. The nitrated product is obtained after online separation and purification. The nitration reactor is a set of continuous flow microchannel reactors. The concentration of the monoacylated product in the inert solvent is 1.5M to 2.5M, and the mass fraction is 10% to 30%. In the nitric acid / sulfuric acid mixed solution, the mass fraction of nitric acid is 65%, and the mass fraction of concentrated sulfuric acid is 95% to 98%. The nitric acid solution and the concentrated sulfuric acid solution are mixed at a mass ratio of 1:2 to 1:3.

[0014] S3. The nitration product is hydrolyzed in a hydrolysis reactor and then separated and purified online to obtain 3-hydroxypropyl nitrate; the hydrolysis reactor is a set of continuous flow microchannel reactors.

[0015] Further, the monoacylation reaction in step S1 includes: adding 1.2 equivalents of sodium carbonate to the esterification reactor beforehand, adding a 2M ethanol solution of 1,3-propanediol to the esterification reactor via a peristaltic pump, and then adding acetyl chloride dropwise via a syringe pump to carry out the monoacylation reaction; the dropping rate of the acetyl chloride is 1 mL / min / mol to 2 mL / min / mol.

[0016] Furthermore, in the monoacylation reaction of step S1, the mass fraction of the monoacylation product in the inert solvent is preferably 10% to 15%.

[0017] Furthermore, in step S2 nitration reaction, liquid stream 1 entering the nitration reactor comes from monoacylation products, and liquid stream 2 is a nitric acid / concentrated sulfuric acid mixed solution. The two liquid streams enter the nitration reactor at a flow rate of 1:1 to 2:1.

[0018] Furthermore, after the nitration reaction in step S2, the nitration product from the nitration reactor is mixed with water and enters the membrane separator 1 for online separation and purification, with a flow ratio of 1:1 to 1:3, preferably 1:2.

[0019] Furthermore, the temperature of the nitration reactor is controlled between 0°C and 10°C, with a preferred temperature between 3°C and 6°C.

[0020] Furthermore, in step S3, the liquid stream 3 entering the hydrolysis reactor comes from the nitration product of the membrane separator 1, and the liquid stream 4 is a 3N to 4N NaOH aqueous solution. The two liquid streams enter the hydrolysis reactor at a flow rate ratio of 1:1 to 1:2. The nitration product is dissolved in an inert solvent methanol or ethanol solution, preferably at a concentration of 2M and a mass fraction of about 15%. The mass fraction of the NaOH aqueous solution is 10% to 15%.

[0021] Furthermore, after the hydrolysis reaction in step S3, the liquid stream flowing out of the hydrolysis reactor is mixed with the ethanol solution and enters the membrane separator 2 for online separation and purification.

[0022] Furthermore, the temperature of the hydrolysis reactor is controlled between 40°C and 70°C, with a preferred temperature range of 50°C to 60°C.

[0023] Furthermore, in the online separation and purification after nitration and hydrolysis, the extractant used is water or an aqueous solution of saturated sodium carbonate. When the extractant is an aqueous solution of saturated sodium carbonate, its mass fraction is 30%.

[0024] Furthermore, in the online separation and purification after nitration and hydrolysis, the back-extraction solvent used is methanol or ethanol, which is 5 times the volume of the reaction liquid.

[0025] Compared with the prior art, the technical effects of the present invention are as follows:

[0026] The present invention provides a continuous flow method for preparing 3-hydroxypropyl nitrate, which employs a three-step continuous process of monoacetylation → nitration → hydrolysis to prepare 3-hydroxypropyl nitrate. The compound can be obtained through... 1The results were confirmed by ¹H NMR characterization. Furthermore, this invention achieves continuous production through a two-step continuous flow reaction technology and a two-step online continuous separation technology. Its advantages include: precise control of key reaction parameters such as material mixing, heating, and residence time, thereby improving product quality and controlling impurities; enhanced heat transfer in continuous flow chemistry allows for reactions within a higher temperature range without runaway, increasing reaction rate thermodynamically and improving production efficiency; increased safety by transforming traditional batch reactions into small-scale continuous reactions, avoiding heat accumulation and enhancing safety; online post-processing in flow chemistry, such as online separation and extraction, results in cleaner reactions; and the ability to easily automate and collect samples online, facilitating parameter adjustments to find optimal reaction conditions, significantly improving process exploration and substrate screening efficiency. Based on online analysis data feedback, global control is achieved, ensuring stable and controllable processes and greatly reducing human intervention. In summary, the process proposed in this invention is safe, efficient, stable, and has simple post-processing methods, suitable for laboratory and scale-up production of 3-hydroxypropyl nitrate. Attached Figure Description

[0027] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in this invention. For those skilled in the art, other drawings can be obtained based on these drawings.

[0028] Figure 1 The flowchart illustrates the continuous flow method for preparing 3-hydroxypropyl nitrate provided by this invention.

[0029] Figure 2 The monoacylated product provided in Example 1 of this invention 1 H NMR spectrum.

[0030] Figure 3 The nitration product provided in Example 1 of this invention 1 H NMR spectrum.

[0031] Figure 4 The hydrolysis product provided in Example 1 of this invention 1 H NMR spectrum.

[0032] Figure 5 The monoacylated product provided in Example 2 of this invention 1 H NMR spectrum.

[0033] Figure 6 The nitration product provided in Example 2 of this invention1 H NMR spectrum.

[0034] Figure 7 The monoacylated product provided in Example 2 of this invention 1 H NMR spectrum. Detailed Implementation

[0035] To enable those skilled in the art to better understand the technical solutions of the present invention, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise specified, the experimental methods in the following embodiments are conventional methods. Unless otherwise specified, the experimental materials used in the following embodiments are all purchased from conventional biochemical reagent stores.

[0036] The method for preparing 3-hydroxypropyl nitrate using continuous flow provided by this invention, such as... Figure 1 As shown, it includes the following steps:

[0037] S1,1,3-propanediol undergoes a monoacylation reaction with acetyl chloride in an inert solvent at room temperature and pressure to yield the monoacylated product.

[0038] The monoacylation reaction in step S1 includes: adding 1.2 equivalents of sodium carbonate to the esterification reactor beforehand, adding a 2M ethanol solution of 1,3-propanediol to the esterification reactor via a peristaltic pump, starting the stirrer, controlling the temperature of the reactor jacket from 0°C to 15°C, with the optimized temperature range being 5°C to 10°C, and then slowly adding acetyl chloride dropwise via a syringe pump to carry out the monoacylation reaction until the addition is complete, restoring to room temperature, and continuing stirring for 1 h.

[0039] Extraction after monoacylation: Add 2 times the volume of saturated sodium carbonate aqueous solution to the reaction vessel using a peristaltic pump, stir for 0.5 h, and after settling and separation, the lower layer material is the monoacylation product, which is used to feed the nitration reactor, and the upper layer material is wastewater discharged.

[0040] The monoacetylation of 3-hydroxypropyl nitrate is carried out using acetyl chloride at room temperature. The reaction conditions are milder than those for high-temperature reactions, and the post-reaction treatment only requires water washing. Its advantages are low energy consumption, safety, and environmental friendliness.

[0041] The dropping rate of the acetyl chloride is from 1 mL / min / mol to 2 mL / min / mol, preferably 2 mL / min / mol. In the monoacylation reaction of step S1, the mass fraction of the monoacylation product in the inert solvent is preferably 10% to 15%.

[0042] S2. The monoacylated product is introduced into a nitration reactor in an inert organic solvent along with a nitric acid / sulfuric acid mixed solution for nitration reaction. The nitrated product is obtained by online separation and purification. The nitration reactor is a set of continuous flow microchannel reactors.

[0043] The nitration process of 3-hydroxypropyl nitrate adopts continuous flow production technology. Its advantages are that it can precisely control the reaction temperature, avoid the heat accumulation caused by batch reaction, and enhance heat and mass transfer, which is unmatched by batch production methods. As a result, the nitration reaction can be completed in tens of seconds, which greatly improves production efficiency and reduces production safety risks.

[0044] The concentration of the monoacylated product in the inert solvent is 1.5M to 2.5M, and the mass fraction is 10% to 30%; in the nitric acid / sulfuric acid mixed solution, the mass fraction of nitric acid is 65%, and the mass fraction of concentrated sulfuric acid is 95% to 98%, and the nitric acid solution and concentrated sulfuric acid solution are mixed at a mass ratio of 1:2 to 1:3.

[0045] In step S2, during the nitration reaction, liquid stream 1 entering the nitration reactor comes from the monoacylation product, and liquid stream 2 is a mixed solution of nitric acid and concentrated sulfuric acid. The two liquid streams enter the nitration reactor at a flow rate of 1:1 to 2:1, with a preferred flow rate ratio of 1.5:1. The temperature of the nitration reactor is controlled between 0°C and 10°C, with a preferred temperature of 3°C to 6°C. The preferred nitration reaction time is 2-4 minutes.

[0046] Post-nitration extraction: The nitration product from the nitration reactor is mixed with water (using a dynamic mixer) and enters membrane separator 1 for online separation and purification. The flow ratio is 1:1 to 1:3, preferably 1:2. Two liquid streams flow out of the membrane separator: one is an organic phase containing the nitration product monoacylated nitrate, which enters the material buffer bottle; the other is an aqueous phase, which is treated as waste liquid.

[0047] S3. After passing through a membrane separator, the organic phase of the nitration product enters a buffer bottle and is then pumped into a hydrolysis reactor. The nitration product undergoes hydrolysis in the hydrolysis reactor, and the hydrolysis product 3-hydroxypropyl nitrate is obtained through online separation and purification. The hydrolysis reactor is a set of continuous flow microchannel reactors.

[0048] The hydrolysis process of 3-hydroxypropyl nitrate is also completed using continuous flow technology. Due to the advantages of continuous flow technology in enhancing heat and mass transfer, the hydrolysis reaction can be completed within minutes, which greatly improves production efficiency compared to the several hours required for batch reaction.

[0049] In step S3, the liquid stream 3 entering the hydrolysis reactor comes from the nitration product of membrane separator 1, and the liquid stream 4 is a 3N to 4N NaOH aqueous solution. The two liquid streams enter the hydrolysis reactor at a flow rate ratio of 1:1 to 1:2. The nitration product is dissolved in an inert solvent, methanol or ethanol solution, preferably at a concentration of 2M and a mass fraction of approximately 15%. The mass fraction of the NaOH aqueous solution is 10% to 15%. The temperature of the hydrolysis reactor is controlled between 40°C and 70°C, preferably between 50°C and 60°C. The residence time of the hydrolysis reaction is 2 min to 5 min.

[0050] Extraction after hydrolysis: The liquid stream from the hydrolysis reactor is mixed with an ethanol solution at a ratio of 1:4 (dynamic mixer), with an optimized flow ratio of 1:5, and then enters membrane separator 2 for online separation and purification. After mixing by the dynamic stirrer, the extract flows through the membrane separator to separate the organic phase and the aqueous phase. The aqueous phase is treated as waste liquid, the organic phase enters a multi-stage evaporator for solvent recovery, and the product 3-hydroxypropyl nitrate enters a collection bottle.

[0051] In the online separation and purification after nitration and hydrolysis, the extractant used is water or an aqueous solution of saturated sodium carbonate. When the extractant is an aqueous solution of saturated sodium carbonate, its mass fraction is 30%.

[0052] The post-treatment process of nitration and hydrolysis of 3-hydroxypropyl nitrate uses online membrane separation technology, which can complete the washing, extraction and separation process online without material exposure. Compared with the traditional batch production method, it can greatly improve efficiency and obtain ideal results without operators having to come into contact with the material.

[0053] Mononitrate esters have high solubility in water, which leads to the product dissolving in the aqueous phase and mixing with the hydrolysis reagent NaOH. However, it also has a certain solubility in inert solvents. A large amount of inert solvent is used to back-extract the nitrate ester product, and the solvent is then recovered through multi-stage evaporation after back-extraction.

[0054] In the online separation and purification after nitration and hydrolysis, the back-extraction solvent used is methanol or ethanol, which is 5 times the volume of the reaction liquid.

[0055] Example 1

[0056] (1) Acylation:

[0057] according to Figure 1 The continuous flow synthesis route for 3-hydroxypropyl nitrate shown first involves monoesterification of the starting material 1,3-propanediol to protect one of its hydroxyl groups. Sodium carbonate is added to the esterification reactor, and 1,3-propanediol is pumped into the reactor. The 1,3-propanediol is diluted with DCE to a concentration of 2M, and stirring is initiated.

[0058] After 1,3-propanediol and sodium carbonate are thoroughly mixed, acetyl chloride is slowly added to the esterification reactor using a syringe pump at a dropping rate of 1 mL / min / mol. The reactor temperature is maintained at 10°C. Once the acetyl chloride addition is complete, the reaction mixture is stirred for another 1 hour.

[0059] A pre-prepared saturated sodium carbonate aqueous solution was pumped into the esterification reactor. The volume of the saturated sodium carbonate aqueous solution was twice that of the reaction liquid. High-speed stirring was started for 5 minutes, and the reaction liquid was allowed to stand for 20 minutes. The materials were then allowed to separate into layers.

[0060] Open the bottom valve of the esterification reactor and take a sample for analysis of the organic phase. The purity of the monoacylation product is 94% (NMR spectrum as shown). Figure 2 The organic phase of the esterification reaction requires no post-treatment. The organic phase solution is pumped into the nitration reactor via a constant flow pump through a valve at the bottom of the reactor, where it enters the nitration reactor together with the nitric acid / sulfuric acid mixed solution.

[0061] (2) Nitrification:

[0062] The flow rate ratio of the monoacylated product solution to the nitric acid / sulfuric acid mixed solution was 1:1.

[0063] The residence time of the nitration reaction in the plate reactor is 4 minutes, and the temperature of the nitration reactor is controlled at 5℃.

[0064] The effluent from the nitration reactor is mixed with 1.5 times its volume of water and fed into a dynamic stirrer. After thorough stirring, the aqueous and organic phases are separated by a membrane separator. The nitration products remain in the organic phase, while the remaining byproducts, impurities, and unreacted feedstock are carried away by the water.

[0065] After the nitration reaction solution was separated by a membrane separator, the organic phase was sampled and analyzed. The purity was 93% (NMR spectrum as shown). Figure 3 The majority of the byproducts are diesters generated in the previous acylation step, which were not produced during the nitration reaction.

[0066] The nitration yield was calculated to be 95%.

[0067] (3) Hydrolysis:

[0068] After membrane separation, the nitration reaction solution enters a solution buffer bottle for later use, and is then introduced into the hydrolysis reaction plate together with the 3N NaOH solution.

[0069] The flow rate ratio of the nitration product solution to the 3N NaOH solution in the previous step was 1:2. The hydrolysis reaction plate was kept at a temperature of 65°C and the reaction residence time was 3 minutes.

[0070] The reaction liquid flowing out of the hydrolysis reaction plate is mixed with 5 times the volume of DCE and then fed into a dynamic stirrer to back-extract the product.

[0071] After separation by a membrane separator, the organic phase is collected and fed into a multi-stage evaporator for vacuum evaporation and concentration to obtain the final product. The product purity is 98%, and the overall yield is 86% (NMR spectrum shown). Figure 4 ).

[0072] Example 2

[0073] (1) Acylation:

[0074] Following the continuous flow synthesis route for 3-hydroxypropyl nitrate, the starting material 1,3-propanediol was first modified by monoesterification to protect one of its hydroxyl groups. Sodium carbonate was added to the esterification reactor, and 1,3-propanediol was pumped into the reactor. The 1,3-propanediol was diluted with DCE to a concentration of 2M, and stirring was started.

[0075] After 1,3-propanediol and sodium carbonate are thoroughly mixed, acetyl chloride is slowly added to the esterification reactor using a syringe pump at a dropping rate of 2 mL / min / mol. The reactor temperature is maintained at 5°C. Once the acetyl chloride addition is complete, the reaction mixture is stirred for another 1 hour.

[0076] A pre-prepared saturated sodium carbonate aqueous solution was pumped into the esterification reactor. The volume of the saturated sodium carbonate aqueous solution was twice that of the reaction liquid. High-speed stirring was started for 5 minutes, and the reaction liquid was allowed to stand for 20 minutes. The materials were then allowed to separate into layers.

[0077] Open the bottom valve of the esterification reactor and take a sample to analyze the organic phase. The purity of the monoacylation product is 95% (NMR spectrum as shown). Figure 5 The organic phase of the esterification reaction requires no post-treatment. The organic phase solution is pumped into the nitration reactor via a constant flow pump through a valve at the bottom of the reactor, where it enters the nitration reactor together with the nitric acid / sulfuric acid mixed solution.

[0078] (2) Nitrification:

[0079] The flow rate ratio of the monoacylated product solution to the nitric acid / sulfuric acid mixed solution is 2:1, which is the optimal concentration of the acylation reaction solution.

[0080] The residence time of the nitration reaction in the plate reactor is 2 minutes, and the temperature of the nitration reactor is controlled at 10℃.

[0081] The effluent from the nitration reactor is mixed with three times its volume of water and fed into a dynamic stirrer. After thorough stirring, the aqueous and organic phases are separated by a membrane separator. The nitration products remain in the organic phase, while the remaining byproducts, impurities, and unreacted feedstock are carried away by the water.

[0082] After the nitration reaction solution was separated by a membrane separator, the organic phase was sampled and analyzed. The purity was 93%. Most of the byproducts were diesters generated in the previous acylation step, which were not produced in the nitration reaction.

[0083] The nitration yield was calculated to be 95% (NMR spectrum as shown). Figure 6 ).

[0084] (3) Hydrolysis:

[0085] After membrane separation, the nitration reaction solution enters a solution buffer bottle for later use, and is then introduced into the hydrolysis reaction plate together with 4N NaOH solution.

[0086] The flow rate ratio of the nitration product solution to the 4N NaOH solution in the previous step was 1:1. The hydrolysis reaction plate was kept at a temperature of 70°C, and the reaction residence time was 2 minutes.

[0087] The reaction liquid flowing out of the hydrolysis reaction plate is mixed with 5 times the volume of DCE and then fed into a dynamic stirrer to back-extract the product.

[0088] After separation by a membrane separator, the organic phase is collected and fed into a multi-stage evaporator for vacuum evaporation and concentration to obtain the final product. The product purity is 98%, and the overall yield is 88% (NMR spectrum shown). Figure 7 ).

[0089] The above description of the disclosed embodiments is intended to enable those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the above drawings and descriptions are illustrative in nature and should not be construed as limiting the scope of the claims of this invention.

Claims

1. A method for the continuous flow preparation of 3-hydroxypropyl nitrate, characterized in that, The method comprises the following steps: S1, 1, 3-propanediol is subjected to monoacylation reaction with acetyl chloride in an inert solvent at room temperature and normal pressure to obtain a monoacylated product; S2, the monoacylated product is subjected to nitration reaction in an inert organic solvent and a mixed solution of nitric acid / sulfuric acid in a nitration reactor, and the nitration product is obtained through online separation and purification; the nitration reactor adopts a set of continuous flow micro-channel reactors; wherein the concentration of the monoacylated product in the inert solvent is 1.5M to 2.5M, and the mass fraction is 10% to 30%; in the mixed solution of nitric acid / sulfuric acid, the mass fraction of nitric acid is 65%, the mass fraction of concentrated sulfuric acid is 95% to 98%, and the mixed solution of nitric acid and concentrated sulfuric acid is mixed according to the mass ratio of 1:2-1:3; S3, the nitration product is subjected to hydrolysis reaction in a hydrolysis reactor, and 3-hydroxypropyl nitrate is obtained through online separation and purification; the hydrolysis reactor adopts a set of continuous flow micro-channel reactors.

2. The method of claim 1, wherein the continuous flow preparation of 3-hydroxypropyl nitrate is characterized by, The monoacylation reaction of step S1 comprises: 1.2 equivalents of sodium carbonate are added in advance in an esterification reactor, a 2M 1, 3-propanediol ethanol solution is added into the esterification reactor through a peristaltic pump, and then acetyl chloride is added dropwise through a syringe pump to carry out monoacylation reaction; the dropwise adding speed of acetyl chloride is 1mL / min / mol to 2mL / min / mol.

3. The method of claim 1, wherein the continuous flow preparation of 3-hydroxypropyl nitrate is characterized by, In the nitration reaction of step S2, liquid stream 1 comes from the monoacylated product, liquid stream 2 is a mixed solution of nitric acid / concentrated sulfuric acid, and the two liquid streams enter the nitration reactor according to the flow rate ratio of 1:1 to 2:

1.

4. The method of claim 1, wherein the continuous flow preparation of 3-hydroxypropyl nitrate is characterized by, After the nitration reaction of step S2, the nitration product from the nitration reactor is mixed with water to enter the membrane separator 1 for online separation and purification, and the flow ratio is 1:1 to 1:

3.

5. The method of claim 1, wherein the continuous flow preparation of 3-hydroxypropyl nitrate is characterized by, The temperature of the nitration reactor is controlled at 0°C to 10°C.

6. The method of claim 1, wherein the continuous flow preparation of 3-hydroxypropyl nitrate is characterized by, In the hydrolysis reaction of step S3, liquid stream 3 comes from the nitration product of the membrane separator 1, liquid stream 4 is a 3N to 4N NaOH aqueous solution, and the two liquid streams enter the hydrolysis reactor according to the flow rate ratio of 1:1 to 1:2; the nitration product is dissolved in an inert solvent methanol or ethanol solution, the concentration is preferably 2M, and the mass fraction is preferably about 15%, and the mass fraction of the NaOH aqueous solution is 10% to 15%.

7. The method of claim 1, wherein the continuous flow preparation of 3-hydroxypropyl nitrate is characterized by, After the hydrolysis reaction of step S3, the liquid stream from the hydrolysis reactor is mixed with an ethanol solution to enter the membrane separator 2 for online separation and purification.

8. The method of claim 1, wherein the continuous flow production of 3-hydroxypropyl nitrate is characterized by, The temperature of the hydrolysis reactor is controlled at 40°C to 70°C.

9. The method of claim 1, wherein the continuous flow production of 3-hydroxypropyl nitrate is characterized by, In the online separation and purification after the nitration reaction and the hydrolysis reaction, the extraction liquid used is water or a saturated sodium carbonate aqueous solution, and when the extraction liquid is a saturated sodium carbonate aqueous solution, the mass fraction is 30%.

10. The method of claim 1, wherein the continuous flow preparation of 3- hydroxypropyl nitrate is characterized by, In the online separation and purification after the nitration reaction and the hydrolysis reaction, the back-extraction solvent used is 5 times the volume of the reaction liquid of methanol or ethanol solvent.

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