Preparation method of N-hydroxyethyl-3, 4-methylenedioxy aniline
By performing condensation reaction and recrystallization purification in ether solvents, the problems of long preparation steps, serious pollution, and high cost in the preparation of N-hydroxyethyl-3,4-methylenedioxyaniline in the prior art have been solved, realizing a high-quality and low-cost preparation method that is suitable for large-scale production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- ZHEJIANG DINGLONG TECH
- Filing Date
- 2026-04-10
- Publication Date
- 2026-05-12
AI Technical Summary
Existing methods for preparing N-hydroxyethyl-3,4-methylenedioxyaniline suffer from problems such as lengthy steps, generation of large amounts of saline wastewater, and expensive and highly toxic raw materials, resulting in poor product quality and low yield.
Piperidine and ethylene carbonate were used as starting materials. The reaction was carried out in an ether solvent, followed by vacuum distillation and purification by recrystallization. Catalysts such as trifluoroacetic acid and methanesulfonic acid were used to control the reaction temperature and time. Diethylene glycol dimethyl ether was preferred as the solvent.
It has improved product quality, reduced environmental pollution, lowered costs, and is suitable for mass production, with product yield and purity reaching over 90%.
Smart Images
Figure CN122010895A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a method for preparing a chemical intermediate, and more particularly to a method for preparing N-hydroxyethyl-3,4-methylenedioxyaniline. Background Technology
[0002] N-Hydroxyethyl-3,4-methylenedioxyaniline is an important chemical and dye intermediate. As a coupling component of high-grade oxidizing agents, it is compounded with commonly used main intermediate components, and through oxidative coupling, it can produce a rich range of hair hues from deep yellow to olive. Oxidative dyes used for hair dyeing must meet many requirements besides achieving the desired intensity. For example, from a toxicological and dermatological perspective, the dye must be safe, and the resulting hair dye must have good lightfastness, permanent lightfastness, acid resistance, and rubbing fastness. Under any circumstances, such dyes must maintain stability for at least 4–6 weeks without the action of light, friction, and chemical reagents. Furthermore, it is necessary to combine appropriate developing agents and colorants to produce a wide range of subtle color variations. The methylenedioxy group in N-hydroxyethyl-3,4-methylenedioxyaniline enhances the stability of the conjugated system, while the hydroxyethyl group provides a water-soluble group and an anchor for subsequent derivatization reactions, significantly influencing the color and fastness after dyeing. It is one of the most promising varieties in the current international hair dyeing market.
[0003] There are few reports on the preparation methods of N-hydroxyethyl-3,4-methylenedioxyaniline. The current mainstream synthetic method is to use piperidine as a starting material, which is condensed with ethyl chloroformate, followed by cyclization and hydrolysis to prepare N-hydroxyethyl-3,4-methylenedioxyaniline. The route is as follows: This method is lengthy and generates a large amount of saline wastewater. Furthermore, the raw material, ethyl chloroformate, is expensive and highly toxic. Additionally, literature reports a one-step condensation method using piperine as a starting material with bromoethanol or chloroethanol to prepare the target compound. While this method is shorter, the bromoethanol or chloroethanol used is highly toxic, and the reaction selectivity is poor, resulting in poor product quality and an overall yield of only about 50%. Summary of the Invention
[0004] To overcome the shortcomings of existing technologies, this invention provides a green, safe, and low-cost method for preparing N-hydroxyethyl-3,4-methylenedioxyaniline.
[0005] To achieve the above-mentioned objectives, the technical solution adopted by this invention is as follows: A method for preparing N-hydroxyethyl-3,4-methylenedioxyaniline includes the following steps: (1) Condensation reaction: Piperidine and ethylene carbonate are used as starting materials for condensation reaction in ether solvent; (2) Distillation: The solvent of the reaction solution obtained in step (1) is recovered by vacuum distillation to obtain crude N-hydroxyethyl-3,4-methylenedioxyaniline; (3) Purification: The crude N-hydroxyethyl-3,4-methylenedioxyaniline was post-processed to obtain the refined N-hydroxyethyl-3,4-methylenedioxyaniline.
[0006] The ether solvent used in this invention is a high-boiling-point ether solvent with a boiling point ≥150℃. Preferably, in step (1), the ether solvent is diethylene glycol dimethyl ether.
[0007] The synthetic route of this invention is as follows: Preferably, in step (1), the reaction temperature is controlled at 120–170°C and the reaction time is controlled at 7–13 h. The reaction is incomplete if the temperature is below 120°C, and N,N-dihydroxyethyl byproducts may be generated if the temperature is above 170°C.
[0008] Preferably, the condensation reaction is carried out in the presence of a catalyst, with the amount of catalyst being 0.1 to 5% of the mass of piperidine.
[0009] Preferably, the catalyst is one or more of the following: trifluoroacetic acid, methanesulfonic acid, p-toluenesulfonic acid, phosphotungstic acid, and NaY molecular sieve.
[0010] Preferably, the molar ratio of piperidine to ethylene carbonate is 1:1.02–1.16. An excess of ethylene carbonate (0.02–0.16 mol) can promote the complete reaction of piperidine, but excessive excess will increase the difficulty of post-processing.
[0011] Preferably, in step (3), the post-processing is recrystallization.
[0012] Preferably, the solvent for recrystallization is an ethanol-water solution or a methanol-water solution.
[0013] Preferably, the amount of diethylene glycol dimethyl ether used is 5 to 15 times the mass of piperidine.
[0014] The beneficial effects of this invention are as follows: This invention improves product quality while reducing environmental pollution, and features green, low-cost, and simple operation. This invention makes product production cleaner, safer, and more environmentally friendly, making the product more suitable for mass production. Attached Figure Description
[0015] Figure 1 This is the hydrogen NMR spectrum of the product prepared in Example 1 of this invention. Detailed Implementation
[0016] The technical solutions of the present invention will be further described in detail below through embodiments. These embodiments are illustrative of the present invention and not intended to limit the present invention. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.
[0017] Unless otherwise specified, the experimental methods described in the embodiments are conventional methods; unless otherwise specified, the reagents and materials are commercially available.
[0018] Example 1 In a 250 ml four-necked flask equipped with a thermometer and stirrer, 13.71 g (0.10 mol) of piperidine, 9.68 g (0.11 mol) of ethylene carbonate, 0.30 g of NaY molecular sieve, and 80 ml of diethylene glycol dimethyl ether were added. The mixture was stirred and heated to 150 °C, and the reaction was maintained at this temperature for 10.0 h. The reaction solution was then distilled under reduced pressure to recover the solvent. After distillation, the mixture was cooled to obtain 18.9 g of crude N-hydroxyethyl-3,4-methylenedioxyaniline. This crude product was added to 100 ml of ethanol-water (v / v = 1:1) for recrystallization, yielding 16.4 g of purified N-hydroxyethyl-3,4-methylenedioxyaniline, with a yield of 90.61% and a purity of 99.63%. The 1H NMR spectrum of the prepared N-hydroxyethyl-3,4-methylenedioxyaniline is shown below. Figure 1 As shown.
[0019] Example 2 In a 250ml four-necked flask equipped with a thermometer and stirrer, 13.71g (0.10mol) of piperidine, 9.68g (0.11mol) of ethylene carbonate, 0.30g of trifluoroacetic acid, and 80ml of diethylene glycol dimethyl ether were added. The mixture was stirred and heated to 150℃ and kept at this temperature for 10.0h. The solvent was then recovered by vacuum distillation. After distillation, the mixture was cooled to obtain 17.1g of crude N-hydroxyethyl-3,4-methylenedioxyaniline. This crude product was added to 100ml of ethanol-water (v / v=1:1) for recrystallization to obtain 15.0g of purified N-hydroxyethyl-3,4-methylenedioxyaniline, with a yield of 82.87% and a purity of 99.55%.
[0020] Example 3 In a 250ml four-necked flask equipped with a thermometer and stirrer, 13.71g (0.10mol) of piperidine, 9.68g (0.11mol) of ethylene carbonate, 0.30g of methanesulfonic acid, and 80ml of diethylene glycol dimethyl ether were added. The mixture was stirred and heated to 150℃ and kept at this temperature for 10.0h. The solvent was then recovered by vacuum distillation. After distillation, the mixture was cooled to obtain 17.5g of crude N-hydroxyethyl-3,4-methylenedioxyaniline. This crude product was added to 100ml of ethanol-water (v / v=1:1) for recrystallization to obtain 15.5g of purified N-hydroxyethyl-3,4-methylenedioxyaniline, with a yield of 85.6% and a purity of 99.53%.
[0021] Example 4 In a 250ml four-necked flask equipped with a thermometer and stirrer, 13.71g (0.10mol) of piperidine, 9.68g (0.11mol) of ethylene carbonate, 0.30g of p-toluenesulfonic acid, and 80ml of diethylene glycol dimethyl ether were added. The mixture was stirred and heated to 150℃ and kept at this temperature for 10.0h. The solvent was then recovered by vacuum distillation. After distillation, the mixture was cooled to obtain 18.5g of crude N-hydroxyethyl-3,4-methylenedioxyaniline. This crude product was added to 100ml of ethanol-water (v / v=1:1) for recrystallization to obtain 15.8g of purified N-hydroxyethyl-3,4-methylenedioxyaniline, with a yield of 87.29% and a purity of 99.59%.
[0022] Example 5 In a 250ml four-necked flask equipped with a thermometer and stirrer, 13.71g (0.10mol) of piperidine, 9.68g (0.11mol) of ethylene carbonate, 0.30g of phosphotungstic acid, and 80ml of diethylene glycol dimethyl ether were added. The mixture was stirred and heated to 150℃ and kept at this temperature for 10.0h. The solvent was then recovered by vacuum distillation. After distillation, the mixture was cooled to obtain 15.9g of crude N-hydroxyethyl-3,4-methylenedioxyaniline. This crude product was added to 100ml of ethanol-water (v / v=1:1) for recrystallization to obtain 14.1g of purified N-hydroxyethyl-3,4-methylenedioxyaniline, with a yield of 77.90% and a purity of 99.25%.
[0023] Example 6 In a 250ml four-necked flask equipped with a thermometer and stirrer, 13.71g (0.10mol) of piperidine, 9.68g (0.11mol) of ethylene carbonate, 0.15g of p-toluenesulfonic acid, 0.15g of NaY molecular sieve, and 80ml of diethylene glycol dimethyl ether were added. The mixture was stirred and heated to 150℃ and maintained at this temperature for 10.0h. The reaction solution was then distilled under reduced pressure to recover the solvent. After distillation, the mixture was cooled to obtain 18.9g of crude N-hydroxyethyl-3,4-methylenedioxyaniline. This crude product was added to 100ml of ethanol-water (v / v=1:1) for recrystallization to obtain 16.1g of purified N-hydroxyethyl-3,4-methylenedioxyaniline, with a yield of 88.95% and a purity of 99.59%.
[0024] Example 7 A 1000L glass-lined reactor was purged with nitrogen three times and stirred at 20Hz. 320kg of diethylene glycol dimethyl ether was pumped into the reactor. After the solvent was pumped out, the feed port was opened, and 54.8kg of piperidine, 38.7kg of ethylene carbonate, and 0.6kg of NaY molecular sieve were added sequentially. After the materials were added, the feed port was sealed, and the reactor was purged with nitrogen three times. Stirring was continued at 40Hz, and steam heating was initiated to raise the temperature inside the reactor to 140~145℃. The reaction was maintained at 140~145℃ for 12.0h. A sample was taken for HPLC analysis to control the content of piperidine in the raw material to be <0.5%. After the reaction was deemed satisfactory, the reaction solution was transferred to another 1000L distillation vessel.
[0025] After the reaction solution was transferred, nitrogen was used to purge the solution three times. Then, reduced pressure distillation was started to recover the solvent. During the distillation process, the vacuum level inside the vessel was controlled to be less than 0.095 MPa and the temperature inside the vessel was less than 100°C. When the volume inside the vessel was about 100 L, the distillation was stopped. The jacket of the distillation vessel was circulated with circulating water to cool the temperature inside the vessel to 30~35°C. After cooling, 300 L of deionized water was pumped into the vessel. After the deionized water was pumped out, the temperature inside the vessel was cooled to 10~15°C and kept at this temperature for crystallization for 1.0 h. After crystallization, the product was centrifuged and filtered to obtain 74.5 kg of crude product.
[0026] The 1000L recrystallization reactor was purged with nitrogen three times. First, 200kg of deionized water was introduced, followed by another 200kg... After the solvent (95% ethanol) was completely removed, stirring was started, and 74.5 kg of crude product was added to the recrystallization reactor. After the crude product was added, the recrystallization reactor was purged with nitrogen three times. Steam was circulated through the jacket of the recrystallization reactor to raise the temperature inside the reactor to 70-75°C. The mixture was stirred for 15-20 minutes. After confirming that the material inside the reactor was completely dissolved, the temperature inside the recrystallization reactor was adjusted to 45-50°C and crystallized at 45-50°C for 2.0 hours. After crystallization, 7°C circulating water was circulated through the jacket of the recrystallization reactor to lower the temperature inside the reactor to 20-25°C. Crystallization was carried out at 20-25°C for 1.0 hour. After crystallization, the product was centrifuged and filtered. The refined wet product was vacuum dried at 55-60°C for 12 hours, controlling the product moisture content to be <0.2%. 66.1 kg of refined product was discharged, with a yield of 93.0% and a purity of 99.69%.
[0027] Comparative Example 1 In a 250ml four-necked flask equipped with a thermometer and stirrer, add 13.71g (0.10mol) of piperonidine, 7.95g (0.075mol) of sodium carbonate, and 60.0g of methanol. After the addition is complete, start stirring and adjust the system temperature to 20-25℃. Using a constant-pressure dropping funnel, add 17.04g (0.12mol) of ethyl chloroformate dropwise to the system, controlling the dropping time at 1.0-1.5h and the dropping temperature at 20-25℃. After the addition is complete, maintain the reaction temperature for 2.0h. After the reaction is complete, add 53.3g of [unspecified ingredient] dropwise to the system. After the 30% liquid alkali was added dropwise, the system was heated to 50-55℃ and kept at this temperature for 6.0 h. After the reaction was completed, the system was cooled to 10-15℃ and kept at this temperature for 1.0 h to crystallize. After filtration, 13.3 g of crude product was obtained. The crude product was recrystallized from 100 ml of ethanol to obtain 12.1 g of purified N-hydroxyethyl-3,4-methylenedioxyaniline, with a yield of 66.85% and a purity of 99.35%.
[0028] Comparative Example 2 In a 250ml four-necked flask equipped with a thermometer and stirrer, 13.71g (0.10mol) of piperidine, 7.95g (0.075mol) of sodium carbonate, and 60.0g of 95% ethanol were added. After the addition was complete, the stirrer was turned on, and the system temperature was adjusted to 40-45℃. 13.64g (0.11mol) of bromoethanol was added dropwise to the system using a constant pressure dropping funnel, controlling the dropping time at 2.0-2.5h and the dropping temperature at 40-45℃. After the addition was complete, the reaction was kept at this temperature for 1.0h. After the reaction was kept at this temperature, 60g of water was added dropwise to the system, and the system was cooled to 10-15℃ and kept at this temperature for 1.0h to crystallize. After filtration, 11.0g of crude product was obtained. The crude product was recrystallized from 80ml of ethanol to obtain 9.3g of purified N-hydroxyethyl-3,4-methylenedioxyaniline, with a yield of 51.41% and a purity of 99.07%.
[0029] Finally, it should be noted that the above examples are merely some specific embodiments of the present invention. Obviously, the present invention is not limited to the above embodiments and many variations are possible. All variations that can be directly derived or conceived by those skilled in the art from the disclosure of the present invention should be considered within the scope of protection of the present invention.
Claims
1. A method for preparing N-hydroxyethyl-3,4-methylenedioxyaniline, characterized in that, Includes the following steps: (1) Condensation reaction: Piperidine and ethylene carbonate are used as starting materials for condensation reaction in ether solvent; (2) Distillation: The solvent of the reaction solution obtained in step (1) is recovered by vacuum distillation to obtain crude N-hydroxyethyl-3,4-methylenedioxyaniline; (3) Purification: The crude N-hydroxyethyl-3,4-methylenedioxyaniline was post-processed to obtain the refined N-hydroxyethyl-3,4-methylenedioxyaniline.
2. The method for preparing N-hydroxyethyl-3,4-methylenedioxyaniline according to claim 1, characterized in that, In step (1), the ether solvent is diethylene glycol dimethyl ether.
3. The method for preparing N-hydroxyethyl-3,4-methylenedioxyaniline according to claim 1, characterized in that, In step (1), the reaction temperature is controlled at 120-170℃ and the reaction time is controlled at 7-13h.
4. The method for preparing N-hydroxyethyl-3,4-methylenedioxyaniline according to claim 1, characterized in that, The condensation reaction is carried out in the presence of a catalyst, with the amount of catalyst being 0.1–5% of the mass of piperidine.
5. The method for preparing N-hydroxyethyl-3,4-methylenedioxyaniline according to claim 4, characterized in that, The catalyst is one or more of the following: trifluoroacetic acid, methanesulfonic acid, p-toluenesulfonic acid, phosphotungstic acid, and NaY molecular sieve.
6. The method for preparing N-hydroxyethyl-3,4-methylenedioxyaniline according to claim 1, characterized in that, The molar ratio of piperidine to ethylene carbonate is 1:1.02 to 1.
16.
7. The method for preparing N-hydroxyethyl-3,4-methylenedioxyaniline according to claim 1, characterized in that, In step (3), the post-processing is recrystallization.
8. The method for preparing N-hydroxyethyl-3,4-methylenedioxyaniline according to claim 7, characterized in that, The solvent for recrystallization is an ethanol-water solution or a methanol-water solution.
9. The method for preparing N-hydroxyethyl-3,4-methylenedioxyaniline according to claim 2, characterized in that, The amount of diethylene glycol dimethyl ether used is 5 to 15 times the mass of piperidine.