A process for the preparation of 3-bromopropylamine hydrobromide

Abstract

The application relates to the technical field of chemical synthesis, and particularly discloses a preparation method of 3-bromopropylamine hydrobromide, which comprises the following steps: S1, hydrogen bromide is divided into two parts; wherein the first part of hydrogen bromide accounts for 40-50% of the total amount of hydrogen bromide, and the second part is the remaining amount; S2, the first part of hydrogen bromide is mixed with 3-hydroxypropylamine to react, and then the dehydrated material is obtained through distillation and dehydration; S3, the second part of hydrogen bromide is added into the dehydrated material to mix and react, and then 3-bromopropylamine hydrobromide is obtained through azeotropic dehydration by using chlorobenzene. The product yield is greatly improved through the acid adding mode, and the waste acid treatment cost is reduced.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis technology, specifically to a method for preparing 3-bromopropylamine hydrobromide. Background Technology

[0002] 3-Bromopropylamine hydrobromide (CAS: 5003-71-4) is an important organic intermediate widely used in pharmaceuticals, pesticides, fine chemicals, and new materials. For example, it can be used to prepare low-odor inkjet printing inks, stain-resistant disc milling cutters for trenchers, and pharmaceutical intermediates such as high-taurine compounds. It also has applications in the preparation of passivation layers for perovskite solar cells. Furthermore, 3-Bromopropylamine hydrobromide can be used as a raw material to synthesize imidazolium quaternary ammonium salt compounds with antibacterial activity through reactions such as sulfonation-quaternization.

[0003] Currently, the conventional method for preparing 3-bromopropylamine hydrobromide involves a bromination reaction of 3-amino-1-propanol with hydrobromic acid. Existing technologies typically employ a one-step process, where 3-amino-1-propanol is mixed with a certain concentration of hydrobromic acid and reacted under reflux conditions. After the reaction, water and residual hydrobromic acid are removed from the reaction system by vacuum distillation or other methods to obtain the target product, 3-bromopropylamine hydrobromide. However, the aforementioned existing preparation methods have the following drawbacks: First, the yield is low. According to relevant literature, the yield of 3-bromopropylamine hydrobromide prepared by the one-step reaction of 3-amino-1-propanol with hydrobromic acid is only about 55%. This low yield not only increases raw material costs but also reduces production efficiency. Second, the utilization rate of hydrobromic acid is low. In the one-step process, hydrobromic acid is added to the reaction system all at once, and a large amount of hydrobromic acid is distilled off along with the water after the reaction, making effective recovery and utilization difficult, resulting in raw material waste and increased burden of waste acid treatment.

[0004] Therefore, there is an urgent need for a preparation method that can improve the yield of 3-bromopropylamine hydrobromide and increase the utilization rate of hydrobromic acid. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a method for preparing 3-bromopropylamine hydrobromide, which can solve the problems of low product yield, high cost, and raw material waste in existing technologies.

[0006] To address the above technical problems, this invention provides a method for preparing 3-bromopropylamine hydrobromide, comprising the following steps: S1. Divide hydrobromic acid into two portions; the first portion accounts for 40% to 50% of the total amount of hydrobromic acid used, and the second portion is the remaining amount. S2. The first part of hydrobromic acid is mixed and reacted with 3-hydroxypropylamine, and then distilled to dehydrate the material to obtain the dehydrated material. S3. Add the second part of hydrobromic acid to the dehydrated material for mixing and reaction, and then add chlorobenzene for azeotropic dehydration to obtain 3-bromopropylamine hydrobromide.

[0007] Furthermore, in S2, the distillation and dehydration temperature is 100–120°C.

[0008] Furthermore, in S3, the temperature for azeotropic dehydration is 125–135°C.

[0009] Furthermore, the mass ratio of chlorobenzene to 3-hydroxypropylamine is (2.0–3.5):1.

[0010] Furthermore, the total amount of hydrobromic acid used is in a molar ratio of (1.8 to 3.2):1 to 3.2.

[0011] Furthermore, in S1, the mass percentage concentration of the hydrobromic acid is 40%-48%.

[0012] Furthermore, in S3, the hydrobromic acid removed after azeotropic dehydration is recovered and recycled for use in step S1.

[0013] Compared with existing technologies, this solution has the following advantages: 1. Significantly improves product yield and purity. This invention employs a staged acid addition method, first reacting a portion of hydrobromic acid with 3-hydroxypropylamine to generate 3-hydroxypropylamine hydrobromide, which is then dehydrated by distillation before the remaining hydrobromic acid is added for bromination. This effectively avoids side reactions caused by the intense exothermic reaction and the presence of water in the traditional one-step method. Simultaneously, azeotropic dehydration with chlorobenzene at 125–135°C promptly removes the water generated in the reaction, shifting the reaction equilibrium towards the product.

[0014] 2. Significantly reduces hydrobromic acid consumption and saves raw material costs. This invention improves the effective utilization rate of hydrobromic acid through staged acid addition and distillation dehydration. The low-concentration hydrobromic acid (approximately 28%–30%) removed during the second azeotropic dehydration can be recovered and directly reused in the first acid addition step. The amount of fresh hydrobromic acid replenished can be reduced by 45%–50%, significantly reducing raw material costs and improving the economic efficiency of industrial production.

[0015] 3. Reduced wastewater discharge, environmentally friendly. The water removed during the first distillation and dehydration process of this invention contains almost no hydrogen bromide and can be directly discharged or simply treated; the low-concentration hydrobromic acid removed during the second process is recovered and reused, reducing waste acid emissions by more than 80%. Compared with the traditional one-step method that generates large amounts of acidic wastewater, the wastewater treatment difficulty and cost of this invention are significantly reduced, meeting the requirements of green chemistry and sustainable development.

[0016] 4. The process is simple to operate and easy to scale up for industrial production. This invention uses conventional equipment and operating conditions, requiring no special devices or harsh reaction conditions. Chlorobenzene can be recovered and reused after simple alkali washing, and low-concentration hydrobromic acid can be directly reused. The entire process is continuous and controllable, simple to operate, and suitable for large-scale industrial production. Detailed Implementation

[0017] The technical solutions in the embodiments of the present invention will be clearly and completely described below. 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.

[0018] Example 1 In a reaction flask equipped with a stirrer, thermometer, and condenser, 220 g of 48% hydrobromic acid, containing approximately 105.6 g of HBr (about 1.30 mol), was added. 75.1 g (1.0 mol) of 3-hydroxypropylamine was then added dropwise with stirring, controlling the dropping rate to keep the reaction temperature below 60°C. After the addition was complete, the temperature was raised to 100–120°C for distillation and dehydration, yielding 64.7 g of water. The hydrogen bromide content in the distillate was found to be below 0.5%.

[0019] Add 290g of residual hydrobromic acid (containing approximately 139.2g of HBr, or about 1.72mol) to the dehydrated material. Heat to 125–135°C, then add approximately 200mL of chlorobenzene (approximately 220g). The mass ratio of chlorobenzene to 3-hydroxypropylamine is approximately 2.93:1. Perform azeotropic reflux for water separation. During the reaction, products continuously precipitate until no more water evaporates from the separator. The total azeotropic water distillation is approximately 299.2g, and the low-concentration hydrobromic acid collected in the lower layer of the separator contains approximately 28.1%.

[0020] After the reaction was complete, the mixture was cooled to room temperature, filtered, and the filter cake was washed with a small amount of chlorobenzene. The crude product, with a wet weight of approximately 244 g, was dissolved in 150 mL of isopropanol at 77 °C, cooled to allow crystals to precipitate, filtered, and the wet product, approximately 220 g, was dried to give 183.3 g of a white to off-white solid. The yield was approximately 83.7% (based on 3-hydroxypropylamine), with an HPLC purity ≥99.5%. The mother liquor was distilled to recover isopropanol, and the residue was dissolved in 50 mL of tetrahydrofuran at approximately 60 °C. The mixture was then cooled to below 10 °C and stirred for 1 hour, filtered, washed with a small amount of tetrahydrofuran, and the wet product, 19 g, was dried to give 18.6 g of a second batch of product. The overall yield was approximately 92.2%.

[0021] Example 2 Take 294.5g of low-concentration hydrobromic acid (approximately 28.1%) obtained from azeotropic dehydration in Example 1 and add it to a reaction flask. Add approximately 52g of fresh 48% hydrobromic acid to bring the total acid content to meet the requirements for the first acid addition, containing approximately 1.33mol of HBr. Add 75.1g (1.0mol) of 3-hydroxypropylamine dropwise while stirring, controlling the temperature to not exceed 60°C. After the addition is complete, raise the temperature to 100–120°C for distillation dehydration, removing approximately 196.5g of water.

[0022] Add 300g of fresh 48% hydrobromic acid (containing approximately 144.0g of HBr, or about 1.78mol) to the dehydrated material. Heat to 125–135℃, then add 200mL (approximately 220g) of recovered chlorobenzene that has undergone alkali washing. Perform azeotropic reflux to separate the water until no more water is distilled off. The total azeotropic water distillate is approximately 266g. The low-concentration hydrobromic acid collected at the bottom of the separator contains approximately 29.8% and can be reused for the next batch.

[0023] After the reaction was completed, the mixture was cooled and filtered to obtain a crude product with a wet weight of 248 g. The crude product was slurried with 170 mL of tetrahydrofuran, then dissolved in 50 mL of isopropanol at 66 °C. After cooling, crystals were precipitated, filtered, and washed with an appropriate amount of tetrahydrofuran to obtain a wet product of 202 g. After drying, a white product of 184.5 g was obtained. The yield was approximately 84.3%, and the HPLC purity was ≥99.5%.

[0024] Example 3 260g of the recovered hydrobromic acid (29.8% purity) from Example 2 and 48g of fresh 48% hydrobromic acid were added to the reaction flask, totaling approximately 1.24mol of acid added initially (based on pure HBr). 75.1g (1.0mol) of 3-hydroxypropylamine was added dropwise with stirring, controlling the temperature to not exceed 60°C. After the addition was complete, the temperature was raised to 100–120°C for distillation and dehydration, removing approximately 170g of water.

[0025] Add 310g of fresh 48% hydrobromic acid to the dehydrated material, heat to 125-135℃, add approximately 200mL (about 220g) of recovered chlorobenzene, and after alkaline washing, perform azeotropic reflux separation until no more water is distilled off. The total azeotropic distillate is approximately 279g. The low-concentration hydrobromic acid collected in the lower layer of the separator contains approximately 30.15% and can be reused for the next batch.

[0026] After the reaction was complete, the mixture was cooled and filtered to obtain a crude product with a wet weight of 289 g. The crude product was dissolved in 150 mL of isopropanol at 74 °C. If not completely dissolved, a small amount of isopropanol could be added. The mixture was then cooled to allow crystals to precipitate, filtered, and washed with isopropanol to obtain a wet product of 240 g, which was dried to obtain the final product. The yield was approximately 83%–85%, and the HPLC purity was ≥99.5%. Comparative Example 1 (One-time acid addition) In a reaction flask equipped with a stirrer, thermometer, and condenser, 75.1 g (1.0 mol) of 3-hydroxypropylamine, 510 g of 48% hydrobromic acid (containing approximately 244.8 g of HBr, or about 3.02 mol), and 200 mL of chlorobenzene were added all at once. The mixture was heated to 125–135 °C and subjected to azeotropic reflux until no more water was distilled off. Approximately 350–380 g of water was distilled off via azeotropic reflux.

[0027] After the reaction is complete, the product is cooled, filtered, and the crude product is refined and dried to obtain the final product.

[0028] The yield is approximately 55%–60%, and the HPLC purity is approximately 95%–97%.

[0029] Comparative Example 2 (Toluene as an azeotropic dehydrating agent) The procedure is the same as in Example 1, except that the azeotropic dehydrating agent is replaced with toluene instead of chlorobenzene, and the amount used is approximately 200 mL. The toluene-water azeotropic temperature is around 85°C, and the reaction is carried out under azeotropic reflux at this temperature. Approximately 250–280 g of water is removed by azeotropic distillation.

[0030] After the reaction is complete, the mixture is cooled and filtered. The crude product is recrystallized from isopropanol and dried to obtain the final product.

[0031] The yield is approximately 60%–65%, and the HPLC purity is approximately 95%–97%.

[0032] The results of each embodiment and the comparative example are compared in Table 1 below: Table 1 Comparison of Results

[0033] Results Analysis 1. Yield Comparison The overall yield of Example 1 was as high as 92.2% (combined mother liquor recovery batches), which is about 32 percentage points higher than the single-step acid addition method of Comparative Example 1 (55%–60%). The reason for this is as follows: The staged addition of acid allows the first step of the salt formation reaction to proceed under relatively mild conditions, avoiding the side reactions caused by the violent exothermic reaction when 3-hydroxypropylamine is mixed with a large amount of hydrobromic acid at once. The first distillation and dehydration effectively removed the water generated in the reaction, reducing the water content in the system and creating favorable conditions for the subsequent bromination reaction. Chlorobenzene undergoes azeotropic dehydration at around 130°C, which effectively removes the water generated in the bromination reaction and shifts the reaction equilibrium toward the product.

[0034] Comparative Example 2 used toluene as an azeotropic dehydrating agent. Since the azeotropic temperature of toluene-water is only about 85°C, which is far below the activation temperature required for the bromination reaction, the reaction was not fully carried out, so the yield was only 60% to 65%.

[0035] 2. Dosage and Reduction Ratio of Hydrobromic Acid In Comparative Example 1, excess hydrobromic acid was distilled off with the water after the reaction, resulting in significant waste as it could not be effectively utilized. This method, through staged acid addition and distillation dehydration, allows hydrobromic acid to participate more fully in the reaction. In Example 2, the low-concentration hydrobromic acid removed during the second azeotropic dehydration is directly reused in the first acid addition of the next batch, reducing the amount of fresh hydrobromic acid required by approximately 45%–50%, significantly lowering raw material costs.

[0036] 3. Comparison of wastewater discharge In Comparative Example 1, the distilled water contained a large amount of hydrobromic acid (approximately 15%–25%), requiring neutralization or distillation before discharge, resulting in high treatment costs and a heavy environmental burden. In this scheme, the water removed by the first distillation contains almost no hydrogen bromide (<0.5%), allowing for direct discharge or simple treatment before discharge; the low-concentration hydrobromic acid removed by the second azeotropic dehydration is recovered and reused directly, reducing waste acid emissions by over 80%, achieving resource recycling, and significantly lowering wastewater treatment costs and environmental impact.

[0037] The above descriptions are merely embodiments of the present invention, and common knowledge regarding specific structures and characteristics is not elaborated upon here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the structure of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A method for preparing 3-bromopropylamine hydrobromide, characterized in that: Includes the following steps: S1. Divide hydrobromic acid into two portions; the first portion accounts for 40% to 50% of the total amount of hydrobromic acid used, and the second portion is the remaining amount. S2. The first part of hydrobromic acid is mixed and reacted with 3-hydroxypropylamine, and then distilled to dehydrate the material to obtain the dehydrated material. S3. Add the second part of hydrobromic acid to the dehydrated material for mixing and reaction, and then add chlorobenzene for azeotropic dehydration to obtain 3-bromopropylamine hydrobromide.

2. The method for preparing 3-bromopropylamine hydrobromide according to claim 1, characterized in that: In S2, the distillation and dehydration temperature is 100–120°C.

3. The method for preparing 3-bromopropylamine hydrobromide according to claim 1, characterized in that: In S3, the temperature for azeotropic dehydration is 125–135°C.

4. The method for preparing 3-bromopropylamine hydrobromide according to claim 1, characterized in that: The mass ratio of chlorobenzene to 3-hydroxypropylamine is (2.0–3.5):

1.

5. The method for preparing 3-bromopropylamine hydrobromide according to claim 1, characterized in that: The total amount of hydrobromic acid used is in a molar ratio of (1.8 to 3.2):1 to 3-hydroxypropylamine.

6. The method for preparing 3-bromopropylamine hydrobromide according to claim 1, characterized in that: In S1, the mass percentage concentration of the hydrobromic acid is 40%-48%.

7. The method for preparing 3-bromopropylamine hydrobromide according to claim 1, characterized in that: In step S3, the hydrobromic acid removed after azeotropic dehydration is recovered and recycled for use in step S1.

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