Preparation method of 2-((2, 5-dimethoxyphenyl) amino) ethane-1-alcohol

Abstract

The invention discloses a preparation method of 2-((2, 5-dimethoxyphenyl) amino) ethane-1-alcohol, which comprises the following steps: providing a solid base catalyst; 2, 5-dimethoxyaniline and 2-bromoethanol are used as initial raw materials in a reaction device, the solid alkali is used as a catalyst, water is used as a solvent, a surfactant is used as an additive, and heating is performed to realize an aminoalkylation reaction; cooling and filtering, and recovering the solid base catalyst; extracting the filtrate with ethyl acetate, concentrating under reduced pressure, and separating by column chromatography to obtain 2-((2, 5-dimethoxyphenyl) amino) ethane-1-ol; the solid base catalyst can be recycled, the recycled solid base can be repeatedly used, and compared with CaCO3, the process does not generate solid waste and alkaline wastewater and is suitable for large-scale production.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemicals, and specifically relates to a method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol. Background Art

[0002] 6-Hydroxybenzomorpholine has many important physical and chemical properties. It has very important application value in the field of fine chemicals. It is an indispensable chemical raw material and is widely used in dyeing, pigments, dyes, hair dyes, pharmaceutical chemicals and other fields.

[0003] In the preparation process of 6-hydroxybenzomorpholine, 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol is often used as an important synthetic intermediate, and its demethylation cyclization is achieved by acid catalysis to synthesize 6-hydroxybenzomorpholine. The traditional process generally reacts 2,5-dimethoxyaniline and 2-bromoethanol in an aqueous phase under the action of CaCO3 to obtain the intermediate - 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol.

[0004] However, in the traditional process, the base catalyst CaCO3 cannot be recycled, and the aminoalkylation yield is only 41%, which limits its large-scale industrial production. Given the important uses of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol in the fields of fine chemicals and hair dye preparation technology, finding an economical, efficient, environmentally friendly, and catalyst-recyclable synthesis route has become an urgent problem to be solved. Summary of the invention

[0005] The purpose of this section is to summarize some aspects of embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the specification abstract and the invention title of this application to avoid blurring the purpose of this section, the specification abstract and the invention title, and such simplifications or omissions cannot be used to limit the scope of the present invention.

[0006] In view of the above problems and / or the problems existing in the prior art, the present invention is proposed.

[0007] Therefore, the object of the present invention is to overcome the deficiencies in the prior art and provide a method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol.

[0008] In order to solve the above technical problems, the present invention provides the following technical solution: a method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol, comprising:

[0009] The 2,5-dimethoxyaniline represented by formula I and the 2-bromoethanol represented by formula II are subjected to an aminoalkylation reaction in a solvent in the presence of a solid base catalyst, a surfactant and heating conditions;

[0010]

[0011]

[0012] The solid base catalyst was recovered by cooling and filtering; the filtrate was extracted with ethyl acetate, concentrated under reduced pressure, and separated by column chromatography to obtain the 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol compound represented by formula III.

[0013] As a preferred embodiment of the method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol of the present invention, the method for preparing the solid base catalyst comprises:

[0014] Prepare 500 mL of 1-1.2 mol / L NaOH solution, take 6.0-8.0 g of NaY molecular sieve, soak it in the NaOH solution for 6-8 hours, heat under reflux for 2-4 hours, and filter;

[0015] The molecular sieve was baked in an oven at 120°C for 4 h, calcined in a muffle furnace at 400°C for 4-6 h, and stored in a desiccator after cooling for later use.

[0016] As a preferred embodiment of the method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol of the present invention, the solid base catalyst and 2,5-dimethoxyaniline are added in a molar ratio of 0.25 to 1:1.

[0017] As a preferred embodiment of the method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol of the present invention, the 2,5-dimethoxyaniline and 2-bromoethanol are added in a molar ratio of 1:0.8-1.

[0018] As a preferred embodiment of the method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol of the present invention, the additive is one or more of sodium dodecylbenzenesulfonate and sodium dodecyl sulfate, and the 2,5-dimethoxyaniline and the additive are added in a molar ratio of 1:0.1 to 0.2.

[0019] As a preferred embodiment of the method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol of the present invention, the heating temperature is 80 to 100° C. and the reaction time is 24 to 30 hours.

[0020] As a preferred embodiment of the method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol of the present invention, the reaction time of the aminoalkylation reaction is 24 to 30 hours.

[0021] As a preferred embodiment of the method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol of the present invention, the reaction is carried out under a nitrogen atmosphere.

[0022] Another object of the present invention is to overcome the deficiencies in the prior art and provide a use of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol in the fields of dyeing, pigments, dyes, hair dyes and pharmaceutical chemicals.

[0023] Beneficial effects of the present invention:

[0024] 1. The solid base catalyst of the present invention is recyclable, and the solid base can be reused after recovery. Compared with the use of CaCO3 as an alkaline catalyst, this process does not produce waste alkali and solid waste, and is suitable for mass production.

[0025] 2. The yield of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol prepared by the present invention can be as high as 60%. Compared with the prior art, the yield of the product is increased by about 50%, which is suitable for large-scale and industrial production.

[0026] 3. After the solid base catalyst of the present invention is recovered, 59% of the target product is obtained in one experiment. After it is recovered again and tested again, 58% of the target product can still be obtained. Within the experimental error range, multiple recovery and reuse meet the requirements of industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative labor. Among them:

[0028] Figure 1 This is the hydrogen NMR spectrum of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol prepared in Example 1 of the present invention.

[0029] Figure 2 This is the infrared spectrum of the activated solid base in Example 7 of the present invention. DETAILED DESCRIPTION

[0030] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0031] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein, and those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0032] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The term "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive with other embodiments.

[0033] Sources of raw materials used in the embodiments of the present invention:

[0034]

[0035]

[0036] Instruments used in the embodiments of the present invention:

[0037]

[0038] Example 1

[0039] 1. Preparation of solid base catalyst

[0040] Prepare 500 mL of 1 mol / L NaOH solution, take 6.0 g of commercially available NaY molecular sieve, soak it in the NaOH solution for 6 h, heat to reflux for 2 h, filter, bake the molecular sieve in an oven at 120 °C for 4 h, calcine at 400 °C in a muffle furnace for 4 h, cool and store in a desiccator for later use.

[0041] 2. Preparation of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol

[0042] In a 100 mL round-bottom flask, 1.0 g (50% wt) of alkali-treated NaY molecular sieve, 2.0 g of 2,5-dimethoxyaniline, 1.64 g of 2-bromoethanol, 0.91 g (20 mol%) of sodium dodecylbenzenesulfonate (SDBS), and 25 mL of water were added. The mixture was reacted at 80° C. for 24 hours under a nitrogen atmosphere. After the reaction was completed, the mixture was cooled and filtered to recover the solid base catalyst. The aqueous phase was extracted twice with ethyl acetate, the combined organic phases were washed once with saturated brine, and the organic phase was concentrated under reduced pressure. The crude product was separated by column chromatography to obtain 1.55 g of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol with a yield of 60%. The NMR hydrogen spectrum of the prepared 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol is as follows: Figure 1 shown.

[0043] Example 2

[0044] 1. Preparation of solid base catalyst

[0045] Prepare 500 mL of 1 mol / L NaOH solution, take 6.0 g of commercially available NaY molecular sieve, soak it in the NaOH solution for 6 h, heat it under reflux for 2 h, filter it, bake the molecular sieve in an oven at 120 ° C for 4 h, calcine it in a muffle furnace at 400 ° C for 4 h, cool it and store it in a desiccator for later use;

[0046] 2. Preparation of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol

[0047] In a 100 mL round-bottom flask, 0.50 g (25% wt) of alkali-treated NaY molecular sieve, 2.0 g of 2,5-dimethoxyaniline, 1.64 g of 2-bromoethanol, 0.91 g (20 mol%) of sodium dodecylbenzenesulfonate (SDBS), and 25 mL of water were added. The mixture was reacted at 80° C. for 24 hours under a nitrogen atmosphere. After the reaction was completed, the mixture was cooled and filtered to recover the solid base catalyst. The aqueous phase was extracted twice with ethyl acetate, the combined organic phases were washed once with saturated brine, and the organic phase was concentrated under reduced pressure. The crude product was separated by column chromatography to obtain 1.36 g of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol with a yield of 53%.

[0048] Example 3

[0049] 1. Preparation of solid base catalyst

[0050] Prepare 500 mL of 1 mol / L NaOH solution, take 6.0 g of commercially available NaY molecular sieve, soak it in the NaOH solution for 6 h, heat to reflux for 2 h, filter, bake the molecular sieve in an oven at 120 °C for 4 h, calcine at 400 °C in a muffle furnace for 4 h, cool and store in a desiccator for later use.

[0051] 2. Preparation of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol

[0052] In a 100 mL round-bottom flask, 2.0 g (100% wt) alkali-treated NaY molecular sieve, 2.0 g 2,5-dimethoxyaniline, 1.64 g 2-bromoethanol, 0.91 g (20 mol%) sodium dodecylbenzenesulfonate (SDBS), 25 mL water were added and reacted at 80° C. in a nitrogen atmosphere for 24 hours. After the reaction was completed, the reaction was cooled and filtered to recover the solid base catalyst. The aqueous phase was extracted twice with ethyl acetate, the combined organic phases were washed once with saturated brine, and the organic phase was concentrated under reduced pressure. The crude product was separated by column chromatography to obtain 1.18 g of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol with a yield of 46%.

[0053] Example 4

[0054] 1. Preparation of solid base catalyst

[0055] Prepare 500 mL of 1 mol / L NaOH solution, take 6.0 g of commercially available NaY molecular sieve, soak it in the NaOH solution for 6 h, heat to reflux for 2 h, filter, bake the molecular sieve in an oven at 120 °C for 4 h, calcine at 400 °C in a muffle furnace for 4 h, cool and store in a desiccator for later use.

[0056] 2. Preparation of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol

[0057] In a 100 mL round-bottom flask, 1.0 g (50% wt) alkali-treated NaY molecular sieve, 2.0 g 2,5-dimethoxyaniline, 1.64 g 2-bromoethanol, 0.45 g (10 mol%) sodium dodecylbenzenesulfonate (SDBS), 25 mL water were added and reacted at 80° C. for 24 hours under a nitrogen atmosphere. After the reaction was completed, the reaction was cooled and filtered to recover the solid base catalyst. The aqueous phase was extracted twice with ethyl acetate, the combined organic phases were washed once with saturated brine, and the organic phase was concentrated under reduced pressure. The crude product was separated by column chromatography to obtain 1.16 g of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol with a yield of 45%.

[0058] Example 5

[0059] 1. Preparation of solid base catalyst

[0060] Prepare 500 mL of 1 mol / L NaOH solution, take 6.0 g of commercially available NaY molecular sieve, soak it in the NaOH solution for 6 h, heat to reflux for 2 h, filter, bake the molecular sieve in an oven at 120 °C for 4 h, calcine at 400 °C in a muffle furnace for 4 h, cool and store in a desiccator for later use.

[0061] 2. Preparation of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol

[0062] In a 100 mL round-bottom flask, 1.0 g (50% wt) alkali-treated NaY molecular sieve, 2.0 g 2,5-dimethoxyaniline, 1.64 g 2-bromoethanol, 0.75 g (20 mol%) sodium dodecyl sulfate (SDS), 25 mL water were added and reacted at 80° C. for 24 hours in a nitrogen atmosphere. After the reaction was completed, the reaction was cooled and filtered to recover the solid base catalyst. The aqueous phase was extracted twice with ethyl acetate, the combined organic phases were washed once with saturated brine, and the organic phase was concentrated under reduced pressure. The crude product was separated by column chromatography to obtain 1.26 g of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol, with a yield of 49%.

[0063] Example 6 Recycling of solid alkali

[0064] According to the 15mmol feeding experiment, the catalyst used was recovered, and the specific recovery steps were as follows: the reaction solution after the reaction was filtered under reduced pressure, and the precipitate obtained on the filter paper was washed with ethyl acetate until the ethyl acetate flowing down was colorless and transparent; then a small amount of ethanol was used to wash the precipitate on the filter paper again until the ethanol flowing down was colorless and transparent, and the filter paper and the precipitate were removed and placed in an oven at 105°C for 2 hours for drying. After drying, the weight was weighed to calculate the recovery rate of the solid base.

[0065] The 1.1 g of solid alkali used in the above experiment was recovered to obtain 1.05 g, and the recovery rate reached 95.5%.

[0066] Two rounds of repeated recovery experiments were conducted on the recovered solid base. 2,5-dimethoxyaniline (0.5mmol, 76.59mg), 2-bromoethanol (0.5mmol, 62.48mg), the recovered solid base (380mg), 20mol% sodium dodecylbenzenesulfonate (SDBS), and solvent H2O (2mL) were added to the reaction tube and filled with nitrogen, and reacted at 80°C for 24 hours. The first round of experiments obtained 59% of the target product. After the solid base was recovered, it was fed again. The second round of experiments obtained 58% of the target product. Compared with the 60% yield obtained when the catalyst was first used, it was within the experimental error range, indicating that the prepared solid base molecular sieve can be recovered and reused many times, which meets the requirements of industrial production.

[0067] Example 7 Characterization and alkalinity determination of solid base

[0068] The Hammett indicator method was used to detect the surface alkalinity strength of the synthesized solid base. The indicator used was phenolphthalein. The indicator is colorless in an acidic environment and purple-red in an alkaline environment. The color change range is pK BH+ ≥9.8.

[0069] The determination process is as follows: accurately weigh 25 mg of solid base, add 1 mL of 1% phenolphthalein-ethanol solution, ultrasonically vibrate for 2 hours and observe the color development.

[0070] The color observed by this method is light pink-purple, and it can be inferred that the basicity of the prepared solid base is approximately pK BH+ It is 9.8.

[0071] Figure 2 is the infrared spectrum of the activated solid base, where 514 cm -1 The peak at 775 cm is the bending vibration peak of Si-O bond. -1 The peak at 1020cm is the Si-O tetrahedral symmetric stretching vibration peak. -1 、1125cm -1The peak at 3447cm is the asymmetric stretching vibration peak of Si-O tetrahedron inside and outside. -1 The peak at is the stretching vibration peak of -OH after alkalization.

[0072] Comparative Example 1

[0073] 1. Preparation of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol

[0074] In a 100 mL round-bottom flask, 4.4 g K2CO3, 2.0 g 2,5-dimethoxyaniline, 1.64 g 2-bromoethanol, 0.91 g (20 mol%) sodium dodecylbenzenesulfonate (SDBS), and 25 mL water were added. The mixture was reacted at 80°C for 24 hours in a nitrogen atmosphere. The aqueous phase was extracted twice with ethyl acetate, and the combined organic phases were washed once with saturated brine. The organic phase was concentrated under reduced pressure, and the crude product was separated by column chromatography to obtain 1.55 g of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol with a yield of 52%. However, the inorganic base catalyst could not be recovered.

[0075] Comparative Example 2

[0076] 1. Preparation of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol

[0077] In a 100 mL round-bottom flask, 3.05 g Na2CO3, 2.0 g 2,5-dimethoxyaniline, 1.64 g 2-bromoethanol, 0.91 g (20 mol%) sodium dodecylbenzenesulfonate (SDBS), and 25 mL water were added. The mixture was reacted at 80°C for 24 hours in a nitrogen atmosphere. The aqueous phase was extracted twice with ethyl acetate, and the combined organic phases were washed once with saturated brine. The organic phase was concentrated under reduced pressure, and the crude product was separated by column chromatography to obtain 1.55 g of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol with a yield of 43%. However, the inorganic base catalyst could not be recovered.

[0078] Comparative Example 3

[0079] 1. Preparation of solid base catalyst

[0080] Prepare 500 mL of 1 mol / L NaOH solution, take 6.0 g of commercially available NaY molecular sieve, soak it in the NaOH solution for 6 hours, heat to reflux for 2 hours, filter, bake the molecular sieve in an oven at 120°C for 4 hours, roast it in a muffle furnace at 400°C for 6 hours, cool it and store it in a desiccator for later use.

[0081] 2. Preparation of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol

[0082] In a 100 mL round-bottom flask, 1.0 g (50% wt) of alkali-treated NaY molecular sieve, 2.0 g of 2,5-dimethoxyaniline, 1.64 g of 2-bromoethanol, 0.91 g (20 mol%) of sodium dodecylbenzenesulfonate (SDBS), and 25 mL of water were added. The mixture was reacted at 80° C. for 24 hours under a nitrogen atmosphere. After the reaction was completed, the mixture was cooled and filtered to recover the solid base catalyst. The aqueous phase was extracted twice with ethyl acetate, the combined organic phases were washed once with saturated brine, and the organic phase was concentrated under reduced pressure. The crude product was separated by column chromatography to obtain 1.42 g of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol with a yield of 55%.

[0083] Comparative Example 4

[0084] 1. Preparation of solid base catalyst

[0085] Prepare 500 mL of 1 mol / L NaOH solution and take commercially available 6.0 g of type zeolite was soaked in NaOH solution for 6 h, heated under reflux for 2 h, filtered, and the molecular sieve was baked in an oven at 120 ° C for 4 h, calcined in a muffle furnace at 400 ° C for 4 h, and stored in a desiccator after cooling for later use.

[0086] 2. Preparation of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol

[0087] In a 100 mL round-bottom flask, 1.0 g (50% wt) of alkali-treated Type molecular sieve, 2.0g 2,5-dimethoxyaniline, 1.64g 2-bromoethanol, 0.91g (20mol%) sodium dodecylbenzenesulfonate (SDBS), 25mL water, nitrogen atmosphere, react at 80°C for 24 hours; after the reaction, cool and filter to recover the solid base catalyst; the aqueous phase is extracted twice with ethyl acetate, the combined organic phases are washed once with saturated brine, the organic phase is concentrated under reduced pressure, and the crude product is separated by column chromatography to obtain 0.95g of 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol, with a yield of 37%.

[0088] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention can be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the present invention.

Claims

1. A method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol, characterized in that: The method comprises: subjecting 2,5-dimethoxyaniline represented by formula I and 2-bromoethanol represented by formula II to an aminoalkylation reaction in a solvent in the presence of a solid base catalyst, a surfactant and heating conditions; The solid base catalyst was recovered by cooling and filtering; the filtrate was extracted with ethyl acetate, concentrated under reduced pressure, and separated by column chromatography to obtain the 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol compound represented by formula III.

2. The method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol according to claim 1, characterized in that: The preparation method of the solid base catalyst, include, Prepare 500 mL of 1-1.2 mol / L NaOH solution, take 6.0-8.0 g of NaY molecular sieve, soak it in the NaOH solution for 6-8 hours, heat under reflux for 2-4 hours, and filter; The molecular sieve is baked in an oven at 120°C for 4 h, calcined in a muffle furnace at 400°C for 4-6 h, and stored in a desiccator after cooling for later use.

3. The method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol according to claim 1, characterized in that: The solid base catalyst and 2,5-dimethoxyaniline are added in a molar ratio of 0.25 to 1:

1.

4. The method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol according to claim 1, characterized in that: The 2,5-dimethoxyaniline and 2-bromoethanol are added in a molar ratio of 1:0.8-1.

5. The method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol according to claim 1, characterized in that: The additive is one or more of sodium dodecylbenzene sulfonate and sodium dodecyl sulfate, and the 2,5-dimethoxyaniline and the additive are added in a molar ratio of 1:0.1-0.

2.

6. The method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol according to claim 1, characterized in that: The heating temperature is 80-100°C.

7. The method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol according to claim 1, characterized in that: The reaction time of the aminoalkylation reaction is 24 to 30 hours.

8. The method for preparing 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol according to claim 1, 6 or 7, characterized in that: The reaction was carried out under nitrogen atmosphere.

9. 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol obtained by the method according to any one of claims 1 to 8.

10. Use of the 2-((2,5-dimethoxyphenyl)amino)ethane-1-ol according to claim 9 in the fields of dyeing, pigments, dyes, hair dyes and pharmaceutical chemicals.

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