Preparation process and system of N-benzyl hydroxylamine hydrochloride

Abstract

The invention provides a preparation process and system of N-benzyl hydroxylamine hydrochloride, and the preparation process utilizes a microchannel reactor and a film concentration device to realize synthesis of a target product through a two-step method. The method comprises the following steps: firstly, continuously pumping dibenzylamine, an auxiliary agent and hydrogen peroxide into a micro-channel reactor, and carrying out accurate temperature control and efficient mixing under a micro-scale to promote an oxidation reaction to be rapidly completed so as to generate a key nitrone intermediate; the step effectively avoids the dangerous thermal runaway phenomenon possibly occurring in a traditional reaction kettle, and the operation safety is improved. Then, introducing the nitrone intermediate and hydrochloric acid into a film concentration device; in the device, the nitrone intermediate is hydrolyzed under an acidic condition, and meanwhile, a reaction solution can be quickly evaporated by a film concentration technology, so that a solvent and byproducts generated along with the reaction are efficiently removed. The thin film concentration technology not only inhibits the occurrence of side reactions, but also ensures the high yield and high purity of the final product.

Description

Technical Field

[0001] This invention relates to the field of N-benzylhydroxylamine hydrochloride preparation technology, and further to a preparation process and system for N-benzylhydroxylamine hydrochloride. Background Technology

[0002] N-Benzylhydroxylamine hydrochloride plays an indispensable role in organic synthesis. It is not only an effective antioxidant and synthetic reagent, but its greater value lies in its ability to react with aldehydes and ketones to generate nitrones, and then efficiently construct isoxazoline heterocycles via 1,3-cycloaddition. Given that isoxazolines are the core structure of many important pharmaceutical intermediates, the market demand for N-benzylhydroxylamine hydrochloride is therefore considerable.

[0003] Currently, there are two main synthetic routes for N-benzylhydroxylamine hydrochloride, but both have significant shortcomings:

[0004] First synthetic route: Refer to patent CN104529814A, such as Figure 3 As shown, dibenzylamine was used as the starting material, and C-phenyl-N-benzylnitroketone was obtained by oxidation with hydrogen peroxide. This C-phenyl-N-benzylnitroketone was then reacted with hydroxylamine hydrochloride under alkaline conditions to obtain the target product. The overall yield of this route was approximately 60%, which is slightly low. More importantly, the second step requires an excess of hydroxylamine hydrochloride. This not only results in a high residual amount of hydroxylamine hydrochloride in the final product, increasing the difficulty of subsequent purification and making it difficult to obtain a high-purity product, but also the initial decomposition temperature of the aqueous hydroxylamine solution used is below 50°C. At slightly higher temperatures, it is highly susceptible to violent or even explosive decomposition, posing a serious safety hazard and limiting the large-scale application of this method.

[0005] First synthetic route: Refer to patent CN101429136A, such as Figure 4 As shown, benzaldehyde first reacts with hydroxylamine hydrochloride via an oxime reaction to generate benzaldehyde oxime, which is then reduced using expensive sodium cyanoborohydride to obtain N-benzylhydroxylamine, and finally converted to hydrochloride to obtain the target product. Although the route is feasible, this method is costly, mainly due to the use of expensive sodium cyanoborohydride as a reducing agent. Furthermore, the reduction reaction itself is a high-risk process, posing significant safety risks during operation. These two drawbacks together limit the practical application prospects of this method in industrial production. Summary of the Invention

[0006] To address the problems of poor safety and low product purity in existing N-benzylhydroxylamine hydrochloride synthesis routes, this invention provides the following technical solution:

[0007] A process for preparing N-benzylhydroxylamine hydrochloride, comprising the following steps:

[0008] S1. Dibenzylamine, auxiliaries and hydrogen peroxide are continuously fed into a microchannel reactor, and an oxidation reaction is carried out to generate a nitrone intermediate.

[0009] S2. The nitrone intermediate and hydrochloric acid are introduced into a thin-film concentration device. The nitrone intermediate is hydrolyzed under acidic conditions, and then the solvent and by-products generated in the reaction mixture are evaporated to obtain the N-benzylhydroxylamine hydrochloride.

[0010] In some embodiments, the additive includes a catalyst and an alcohol solvent, wherein the catalyst is sodium tungstate; and the alcohol solvent includes one or more of methanol, ethanol, and isopropanol.

[0011] In some embodiments, the reaction temperature in step S1 is 20–40°C.

[0012] In some embodiments, in step S1, the molar ratio of dibenzylamine to hydrogen peroxide is 1:(8-15).

[0013] In some embodiments, in step S2, the hydrochloric acid has a mass percentage concentration of 20%.

[0014] In some embodiments, the reaction temperature in step S2 is 40-80°C.

[0015] The present invention also provides a preparation system for N-benzylhydroxylamine hydrochloride, applicable to the above-mentioned preparation process of N-benzylhydroxylamine hydrochloride. The preparation system includes: a microchannel reactor, a thin-film concentration device, multiple material supply units, and multiple product storage devices. The material supply units include a raw material supply device, an oxidant supply device, a nitrone intermediate supply device, and a hydrochloric acid supply device. The raw material supply device and the oxidant supply device are respectively connected to the microchannel reactor to introduce the raw material and oxidant for synthesizing the nitrone intermediate into the microchannel reactor. The nitrone intermediate supply device and the hydrochloric acid supply device are respectively connected to the thin-film concentration device to introduce the nitrone intermediate for synthesizing N-benzylhydroxylamine hydrochloride and hydrochloric acid into the thin-film concentration device. The product storage devices include a product collection tank and a by-product collection tank. The product collection tank is connected to the product outlet of the thin-film concentration device to store N-benzylhydroxylamine hydrochloride, and the by-product collection tank is connected to the by-product outlet of the thin-film concentration device to collect and store by-products.

[0016] In some embodiments, the raw material supply device includes a first storage tank, a first conveying pipe, and a first metering pump disposed on the first conveying pipe. The first storage tank is used to store dibenzylamine and auxiliaries. The first storage tank is connected to the microchannel reactor through the first conveying pipe, and the first metering pump is used to pump the material in the first storage tank into the microchannel reactor. The oxidant supply device includes a second storage tank, a second conveying pipe, and a second metering pump disposed on the second conveying pipe. The second storage tank is used to store oxidant. The second storage tank is connected to the microchannel reactor through the second conveying pipe, and the second metering pump is used to pump the oxidant into the microchannel reactor. The nitrone intermediate supply device includes a third storage tank, a third conveying pipe, and a third metering pump disposed on the third conveying pipe. The third storage tank is used to store nitrone intermediate. The third storage tank is connected to the thin-film concentration device through the third conveying pipe, and the third metering pump pumps the nitrone intermediate into the thin-film concentration device.

[0017] In some embodiments, the thin-film concentration device is a scraped-film evaporator.

[0018] In some embodiments, the negative pressure of the scraped film evaporator is lower than -0.08 MPa, and the scraped film evaporator is heated by a water bath at a temperature of 40-80°C.

[0019] Compared with the prior art, the preparation process and system for N-benzylhydroxylamine hydrochloride provided by the present invention have the following beneficial effects:

[0020] This invention provides an innovative two-step process for the preparation of N-benzylhydroxylamine hydrochloride, utilizing a microchannel reactor and a scraped-film evaporator to achieve efficient and safe continuous production. First, dibenzylamine and hydrogen peroxide are precisely pumped into the microchannel reactor, achieving rapid mixing and precise temperature control at a microscale. This not only efficiently synthesizes the key nitrone intermediate but also effectively avoids the risk of thermal runaway that may occur in traditional batch reactions, thus minimizing potential explosion hazards. Subsequently, the nitrone intermediate and hydrochloric acid are passed into the scraped-film evaporator. In this device, the reaction solution resides in the heating zone for only a very short time, significantly suppressing side reactions and substantially improving the yield and purity of the target product. The synergistic effect of the microchannel reactor and the scraped-film evaporator together constructs a high-yield, high-purity, and safe continuous preparation process for N-benzylhydroxylamine hydrochloride. Attached Figure Description

[0021] Figure 1 This is a schematic diagram of the structure of the preparation system for N-benzylhydroxylamine hydrochloride provided by the present invention;

[0022] Figure 2 The synthetic route for N-benzylhydroxylamine hydrochloride provided by this invention;

[0023] Figure 3 This is the first synthetic route for N-benzylhydroxylamine hydrochloride in the prior art;

[0024] Figure 4 This is the second synthetic route for N-benzylhydroxylamine hydrochloride in the prior art.

[0025] Explanation of icon numbers:

[0026] 10—Microchannel reactor;

[0027] 20—Thin-film concentration unit;

[0028] 30—Raw material supply device; 301—First storage tank; 302—First conveying pipe; 303—First metering pump;

[0029] 40—Oxidizing agent supply device; 401—Second storage tank; 402—Second conveying pipe; 403—Second metering pump;

[0030] 50—Nitroketone intermediate supply unit; 501—Third storage tank; 502—Third conveying pipe; 503—Third metering pump;

[0031] 60—Hydrochloric acid supply unit; 601—Fourth storage tank; 602—Fourth delivery pipe; 603—Fourth metering pump;

[0032] 70—Product collection tank;

[0033] 80—Byproduct collection tank. Detailed Implementation

[0034] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the specific implementation methods of the present invention will be described below with reference to the accompanying drawings. Obviously, the drawings described below are merely some embodiments of the present invention. For those skilled in the art, other drawings and other implementation methods can be obtained based on these drawings without any creative effort.

[0035] To keep the drawings concise, each figure only schematically shows the parts relevant to the invention, and these do not represent the actual structure of the product. Furthermore, to facilitate understanding, in some figures, only one of components with the same structure or function is schematically depicted, or only one is labeled. In this document, "one" not only means "only one," but can also mean "more than one."

[0036] It should also be further understood that the term "and / or" as used in this specification and the appended claims refers to any combination of one or more of the associated listed items and all possible combinations, and includes such combinations.

[0037] In this document, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to fixed connections, detachable connections, or integral connections; they can refer to mechanical connections or electrical connections; they can refer to direct connections or indirect connections through an intermediate medium; and they can refer to the internal communication between two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0038] Furthermore, in the description of this invention, the terms "first," "second," etc., are used only for distinguishing descriptions and should not be construed as indicating or implying relative importance.

[0039] Example 1

[0040] This embodiment provides a preparation system for N-benzylhydroxylamine hydrochloride, including: a microchannel reactor 10, a thin-film concentration device 20, multiple material supply units, and multiple product storage devices. For example... Figure 1 As shown,

[0041] The aforementioned multiple material supply units include a raw material supply device 30, an oxidant supply device 40, a nitroketone intermediate supply device 50, and a hydrochloric acid supply device 60, wherein:

[0042] The raw material supply device 30 and the oxidant supply device 40 are respectively connected to the microchannel reactor 10 to introduce the raw materials and oxidant for synthesizing nitroketone intermediates into the microchannel reactor 10.

[0043] Specifically:

[0044] The raw material supply device 30 includes a first storage tank 301, a first conveying pipe 302, and a first metering pump 303 disposed on the first conveying pipe 302. The first storage tank 301 is used to store dibenzylamine and additives. The first storage tank 301 is connected to the microchannel reactor 10 through the first conveying pipe 302. The first metering pump 303 pumps the homogeneous mixture of dibenzylamine and additives into the microchannel reactor 10 for reaction.

[0045] The oxidant supply device 40 includes a second storage tank 401, a second delivery pipe 402, and a second metering pump 403 disposed on the second delivery pipe 402. The second storage tank 401 is used to store hydrogen peroxide. The second storage tank 401 is connected to the microchannel reactor 10 through the second delivery pipe 402. The second metering pump 403 pumps hydrogen peroxide into the microchannel reactor 10 for reaction.

[0046] The nitrone intermediate supply device 50 and the hydrochloric acid supply device 60 are respectively connected to the thin-film concentration device 20 to introduce the nitrone intermediate for the synthesis of N-benzylhydroxylamine hydrochloride and hydrochloric acid into the thin-film concentration device 20. Specifically:

[0047] The nitrone intermediate supply device 50 includes a third storage tank 501, a third delivery pipe 502, and a third metering pump 503 installed on the third delivery pipe 502. The third storage tank 501 is used to store the nitrone intermediate. The third storage tank 501 is connected to the membrane concentration device 20 through the third delivery pipe 502. The nitrone intermediate is pumped into the membrane concentration device 20 by the third metering pump 503 for reaction.

[0048] The hydrochloric acid supply device 60 includes a fourth storage tank 601, a fourth delivery pipe 602, and a fourth metering pump 603 installed on the fourth delivery pipe 602. The fourth storage tank 601 is used to store hydrochloric acid. The fourth storage tank 601 is connected to the thin film concentration device 20 through the fourth delivery pipe 602. The fourth metering pump 603 pumps the hydrochloric acid into the thin film concentration device 20 for reaction.

[0049] The aforementioned thin-film concentration device 20 is preferably a scraped-film evaporator, a highly adaptable continuous evaporation device consisting of a rotating scraper and a heating jacket. Heating steam or hot water is supplied to the heating jacket, and the rotating scraper maintains a minimal gap with the inner wall of the heating jacket. The preheated feed liquid enters tangentially from the top of the scraped-film evaporator and spreads into a uniform thin film under the action of the rotating scraper, spiraling downwards. Under negative pressure (vacuum), the feed liquid thin film rapidly completes concentration and evaporation. Light components such as solvent and byproducts vaporize and are extracted from the top, while the concentrated liquid is continuously discharged from the bottom.

[0050] The aforementioned multiple product storage devices include a product collection tank 70 and a by-product collection tank 80. The product collection tank 70 is connected to the product outlet of the membrane concentration device 20 to store N-benzylhydroxylamine hydrochloride, while the by-product collection tank 80 is connected to the by-product outlet of the membrane concentration device 20 to collect and store by-products.

[0051] For example, when the thin film concentration device 20 is a scraped thin film evaporator, the product collection tank 70 is connected to the concentrate outlet at the bottom of the scraped thin film evaporator to store N-benzylhydroxylamine hydrochloride, while the by-product collection tank 80 is connected to the evaporation outlet at the top of the scraped thin film evaporator to collect and store by-products such as benzaldehyde and hydrochloric acid.

[0052] Example 2

[0053] In this embodiment, the present invention provides a preparation process for N-benzylhydroxylamine hydrochloride. This preparation process employs a two-step method: starting with dibenzylamine as a starting material, it is oxidized with hydrogen peroxide to obtain C-phenyl-N-benzylnitroketone, which is then reacted with hydrochloric acid to obtain N-benzylhydroxylamine hydrochloride. The synthetic route is as follows: Figure 2 As shown, the specific steps include:

[0054] Step S1: Preparation of nitrone intermediate: Dibenzylamine, auxiliaries and hydrogen peroxide are continuously fed into microchannel reactor 10 through a multi-stream feeding system, and nitrone intermediate is generated through oxidation reaction.

[0055] In some embodiments, the reaction temperature in step S1 is 20–40°C.

[0056] In some embodiments, in step S1, the molar ratio of dibenzylamine to hydrogen peroxide is 1:(8-15).

[0057] In some embodiments, in step S1, the auxiliaries include a catalyst and an alcohol solvent, wherein the catalyst is sodium tungstate. The core function of sodium tungstate is to activate hydrogen peroxide to form a highly reactive peroxytungstate complex, thereby increasing the reaction rate. Moreover, the peroxytungstate complex can selectively oxidize the tertiary amine group of dibenzylamine, efficiently converting it into a nitrone structure, while inhibiting the formation of byproducts (such as N,N-dibenzylhydroxylamine).

[0058] The aforementioned alcohol solvents include one or more of low-carbon alcohol solvents such as methanol, ethanol, and isopropanol. Dibenzylamine and sodium tungstate have limited solubility in water; alcohol solvents can act as co-solvents to ensure a homogeneous reaction system, preventing excessively high local concentrations that could lead to hydrogen peroxide decomposition or side reactions. Secondly, alcohol solvents can form in-situ peroxides with hydrogen peroxide, reducing the activity of free hydrogen peroxide and preventing excessive oxidation of dibenzylamine. Furthermore, alcohol solvents can stabilize hydrogen peroxide through hydrogen bonding, reducing its decomposition and exothermic rate.

[0059] Using the preparation system provided in Example 1, the specific process of step S1 includes the following:

[0060] S10. Material preparation: Add the prepared dibenzylamine solution, sodium tungstate solution, and alcohol solvent to the first storage tank 301 and stir well for later use. At the same time, add hydrogen peroxide to the second storage tank 401 for later use.

[0061] S11. Control the temperature of the microchannel reactor 10 to be between 20 and 40°C, and pump the material in the first storage tank 301 into the microchannel reactor 10 through the first metering pump 303. The pumping flow rate of the first metering pump 303 is 10 L / min.

[0062] Meanwhile, hydrogen peroxide in the second storage tank 401 is pumped into the microchannel reactor 10 through the second metering pump 403, with a pumping flow rate of 3L / min.

[0063] After the reaction has proceeded for a period of time, the effluent is collected.

[0064] S12. The nitrone intermediate in the effluent is extracted with dichloromethane, and then the obtained nitrone intermediate is stored in the third storage tank 501 for later use. Since the nitrone intermediate will continue to undergo side reactions such as peroxidation and hydrolysis with residual hydrogen peroxide or acidic impurities in the aqueous phase, these side reactions can be terminated immediately after the nitrone intermediate is extracted with dichloromethane.

[0065] Step S1 uses a microchannel reactor 10 to prepare the nitroketone intermediate. Its primary advantage lies in safety. The microchannel reactor 10 features a high specific surface area (typically exceeding 10,000 m² / m³) and excellent heat transfer performance (reaching the kW / m²·K level), enabling precise control of the exothermic reaction temperature and effectively preventing the dangerous thermal runaway that can occur in traditional batch reactors. The reaction volume is compressed to the milliliter level, keeping the storage level of the critical hazardous chemical hydrogen peroxide far below the safety warning line, thus effectively controlling potential explosion risks. Secondly, the continuous process of the microchannel reactor 10 is another advantage. Metering pumps continuously and stably pump in the reactants, significantly reducing the production cycle and increasing efficiency by over 90% compared to traditional batch operations. Finally, product quality can be optimized. The microchannel reactor 10 can precisely control key parameters such as reaction time and temperature, which effectively suppresses the occurrence of side reactions such as incomplete oxidation or excessive hydrolysis. This not only significantly improves the yield and purity of the target product, but its highly automated characteristics also eliminate quality fluctuations that may be introduced by manual operation, ensuring the consistency and stability of products between batches.

[0066] S2. Preparation of N-benzylhydroxylamine hydrochloride: After introducing the nitrone intermediate and hydrochloric acid into the thin-film concentration device 20, the nitrone intermediate immediately undergoes hydrolysis under acidic conditions. At the same time, the thin-film concentration device 20 utilizes rapid evaporation to efficiently remove the solvent and generated byproducts from the reaction mixture, thereby obtaining N-benzylhydroxylamine hydrochloride.

[0067] In some embodiments, in step S2, the hydrochloric acid has a mass percentage concentration of 20%.

[0068] In some embodiments, the reaction temperature in step S2 is 40-80°C.

[0069] In conjunction with the preparation system provided in Example 1, the specific process of step S2 includes the following:

[0070] S20. Add the prepared hydrochloric acid solution to the fourth storage tank 601.

[0071] S21. The nitrone intermediate in the third storage tank 501 is pumped into the scraped film evaporator through the third metering pump 503. The pumping flow rate of the third metering pump 503 is 2L / min.

[0072] Meanwhile, the hydrochloric acid in the fourth storage tank 601 is pumped into the scraped film evaporator through the fourth metering pump 603, with a pumping flow rate of 4 L / min.

[0073] The negative pressure of the scraped thin film evaporator is set below -0.08MPa, and the heating jacket is heated by a water bath at a temperature of 60℃.

[0074] The distillate is collected in the by-product collection tank 80. The distilled materials are benzaldehyde and hydrochloric acid, which are recycled.

[0075] The concentrate containing crude N-benzylhydroxylamine hydrochloride was collected into product collection tank 70.

[0076] In step S2, replacing the traditional reaction vessel with a scraped-film evaporator brings several significant advantages. One of these advantages is that the scraped-film evaporator, with its highly efficient scraper design, achieves an extremely high heat transfer coefficient, enabling the evaporation rate of organic solvents and water to reach 150–300 kg / h·m. 2 This significantly reduces energy consumption during the production process. A second advantage is that the scraped-film evaporation process provides an ideal solution to the problem of N-benzylhydroxylamine hydrochloride undergoing oxidative decomposition (generating benzaldehyde oxime and further hydrolysis) under prolonged heating. The key lies in the extremely short residence time of the reaction liquid in the heating zone, typically only tens of seconds. This effectively suppresses the aforementioned side reactions, thereby significantly improving product yield and ensuring product purity, avoiding excessive impurities. A third advantage is that the scraped-film evaporator has a wide adaptability to material viscosity; the viscosity ratio of its inlet to outlet material can reach 1000 or even higher. This means it can handle various materials from low to high viscosity, and can even concentrate the solution until some product begins to precipitate and flow out with the material. A fourth advantage is that the scraped-film evaporator is easy to operate, runs stably, and has reliable performance. Its efficient and precise concentration capabilities, combined with the aforementioned microchannel reactor technology, together create a safer and more efficient preparation process for N-benzylhydroxylamine hydrochloride.

[0077] In some embodiments, the preparation process also includes a crude product purification step, namely step S3, stirring and cooling the concentrate to allow N-benzylhydroxylamine hydrochloride to precipitate in large quantities in crystal form, then separating the N-benzylhydroxylamine hydrochloride crystals from the concentrate by centrifugation, and then removing the small amount of solvent adsorbed on the surface of the N-benzylhydroxylamine hydrochloride crystals by vacuum drying to obtain the refined benzylhydroxylamine hydrochloride.

[0078] Based on Examples 1 and 2, the present invention also provides Test Examples 1-5 as examples of the preparation process to evaluate and demonstrate the actual effect of the preparation process.

[0079] Test Example 1

[0080] Step S1: Preparation of nitroketone intermediate:

[0081] 1.0 kg of sodium tungstate was dissolved in 100.0 kg of water to make a sodium tungstate solution, which was then added to the first storage tank 301. At the same time, 100.0 kg of dibenzylamine (507.3 mol, 1.0 eq) and 400.0 L of methanol were added to the first storage tank 301 and stirred evenly for later use.

[0082] Weigh 180.0 kg of 30% hydrogen peroxide (158.8 mol, 3.2 eq) and add it to the second storage tank 401.

[0083] The temperature of the microchannel reactor 10 is controlled at 30°C, and the material in the first storage tank 301 is pumped into the microchannel reactor 10 through the first metering pump 303 at a flow rate of 10 L / min.

[0084] Meanwhile, hydrogen peroxide in the second storage tank 401 is pumped into the microchannel reactor 10 through the second metering pump 403 at a flow rate of 3L / min.

[0085] After 5 minutes of oxidation reaction, the effluent was collected. The nitrone intermediate was extracted with 400 L of dichloromethane and stored in the third storage tank 501 for later use.

[0086] S2. Preparation of N-benzylhydroxylamine hydrochloride:

[0087] Add 1000 kg of 20% hydrochloric acid (5479.5 mol, 10.8 eq) to the fourth storage tank 601.

[0088] The nitrone intermediate in the third storage tank 501 is pumped into the scraped film evaporator through the third metering pump 503 at a flow rate of 2L / min.

[0089] The material in the fourth storage tank 601 is pumped into the scraped film evaporator through the fourth metering pump 603 at a flow rate of 4 L / min.

[0090] The negative pressure of the scraped thin film evaporator is set below -0.08 MPa, and the water bath temperature of the heating jacket is 60℃.

[0091] The distillate was collected in the by-product collection tank 80, and the concentrate containing crude N-benzylhydroxylamine hydrochloride was collected in the product collection tank 70. The concentrate was then stirred and cooled to 0-5°C, and the crude benzylhydroxylamine hydrochloride was centrifuged. After vacuum drying at 50°C, 73 kg of benzylhydroxylamine hydrochloride product was obtained. The yield of the two steps was 90.1%. The purity of the benzylhydroxylamine hydrochloride product was >99.0% after determination by high performance liquid chromatography (HPLC).

[0092] Test Example 2

[0093] The difference from Test Example 1 is that the reaction temperature of the microchannel reactor 10 in step S1 is 20°C. All other steps are the same. The yield of the two steps S1 and S2 is 90%, and the purity of the benzylhydroxylamine hydrochloride product determined by HPLC is >99.0%.

[0094] Test Example 3

[0095] The difference from Test Example 1 is that the reaction temperature of the microchannel reactor 10 in step S1 is 40°C. All other steps are the same. The yield of the two steps S1 and S2 is 90.8%, and the purity of the benzylhydroxylamine hydrochloride product determined by HPLC is >99.0%.

[0096] Test Example 4

[0097] The difference from Test Example 1 is that the reaction temperature in the scraped-film evaporator in step S2 was 40°C. All other steps were the same. The yield of the two steps S1 and S2 was 89.7%, and the purity of the benzylhydroxylamine hydrochloride product determined by HPLC was >99.0%.

[0098] Test Example 5

[0099] The difference from Test Example 1 is that the reaction temperature in the scraped-film evaporator in step S2 was 80°C. All other steps were the same. The yield of the two steps S1 and S2 was 91.0%, and the purity of the benzylhydroxylamine hydrochloride product determined by HPLC was >99.0%.

[0100] The above are merely preferred embodiments of the present invention. It should be noted that, for those with ordinary technical skills, the present invention is not necessarily the best suited for their own purposes.

[0101] For those skilled in the art, several improvements can be made without departing from the principles of this invention.

[0102] And refinements, these improvements and refinements should also be considered within the scope of protection of this invention.

Claims

1. A preparation process for N-benzylhydroxylamine hydrochloride, characterized by the following steps: include: S1. Dibenzylamine, auxiliaries and hydrogen peroxide are continuously fed into a microchannel reactor, and an oxidation reaction is carried out to generate a nitrone intermediate. S2. The nitrone intermediate and hydrochloric acid are introduced into a thin-film concentration device. The nitrone intermediate is hydrolyzed under acidic conditions, and then the solvent and by-products generated in the reaction mixture are evaporated to obtain the N-benzylhydroxylamine hydrochloride.

2. The preparation process of N-benzylhydroxylamine hydrochloride according to claim 1, characterized in that, The additive includes a catalyst and an alcohol solvent, wherein the catalyst is sodium tungstate; and the alcohol solvent includes one or more of methanol, ethanol, and isopropanol.

3. The preparation process of N-benzylhydroxylamine hydrochloride according to claim 1, characterized in that, In step S1, the reaction temperature is 20–40°C.

4. The preparation process of N-benzylhydroxylamine hydrochloride according to claim 1, characterized in that, In step S1, the molar ratio of dibenzylamine to hydrogen peroxide is 1:(8-15).

5. The preparation process of N-benzylhydroxylamine hydrochloride according to claim 1, characterized in that, In step S2, the hydrochloric acid has a mass percentage concentration of 20%.

6. The preparation process of N-benzylhydroxylamine hydrochloride according to claim 1, characterized in that, In step S2, the reaction temperature is 40-80℃.

7. A system for preparing N-benzylhydroxylamine hydrochloride, characterized in that, The preparation process of N-benzylhydroxylamine hydrochloride as described in any one of claims 1-6 is applicable, wherein the preparation system comprises: a microchannel reactor, a thin-film concentration device, multiple material supply units, and multiple product storage devices; The material supply unit includes a raw material supply device, an oxidant supply device, a nitroketone intermediate supply device, and a hydrochloric acid supply device. The raw material supply device and the oxidant supply device are respectively connected to the microchannel reactor to introduce the raw materials and oxidant for synthesizing the nitrone intermediate into the microchannel reactor; The nitrone intermediate supply device and the hydrochloric acid supply device are respectively connected to the thin film concentration device to introduce the nitrone intermediate for synthesizing the N-benzylhydroxylamine hydrochloride and hydrochloric acid into the thin film concentration device; The product storage device includes a product collection tank and a by-product collection tank. The product collection tank is connected to the product outlet of the membrane concentration device to store N-benzylhydroxylamine hydrochloride, while the by-product collection tank is connected to the by-product outlet of the membrane concentration device to collect and store by-products.

8. The preparation system for N-benzylhydroxylamine hydrochloride according to claim 7, characterized in that, The raw material supply device includes a first storage tank, a first conveying pipe, and a first metering pump disposed on the first conveying pipe. The first storage tank is used to store dibenzylamine and auxiliaries. The first storage tank is connected to the microchannel reactor through the first conveying pipe. The first metering pump is used to pump the material in the first storage tank into the microchannel reactor. The oxidant supply device includes a second storage tank, a second delivery pipe, and a second metering pump disposed on the second delivery pipe. The second storage tank is used to store oxidant, and the second storage tank is connected to the microchannel reactor through the second delivery pipe. The second metering pump is used to pump the oxidant into the microchannel reactor. The nitrone intermediate supply device includes a third storage tank, a third delivery pipe, and a third metering pump installed on the third delivery pipe. The third storage tank is used to store the nitrone intermediate. The third storage tank is connected to the thin film concentration device through the third delivery pipe, and the nitrone intermediate is pumped into the thin film concentration device by the third metering pump. The hydrochloric acid supply device includes a fourth storage tank, a fourth delivery pipe, and a fourth metering pump installed on the fourth delivery pipe. The fourth storage tank is used to store hydrochloric acid. The fourth storage tank is connected to the thin-film concentration device through the fourth delivery pipe, and the hydrochloric acid is pumped into the thin-film concentration device through the fourth metering pump.

9. The preparation system for N-benzylhydroxylamine hydrochloride according to claim 7, characterized in that, The thin-film concentration device is a scraped-plate thin-film evaporator.

10. The preparation system for N-benzylhydroxylamine hydrochloride according to claim 9, characterized in that, The negative pressure of the scraped film evaporator is less than -0.08 MPa, and the scraped film evaporator adopts water bath heating with a water bath heating temperature of 40-80℃.

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