Method for synthesizing Schiff base 2-aniline by using calcium carbide as mediating agent
The two-step synthesis of the Schiff base 2-aniline using calcium carbide as a mediator solves the problems of expensive catalysts and complex reaction systems in existing technologies, achieving low-cost, high-yield Schiff base synthesis that is suitable for large-scale production.
Patent Information
- Application Number
- CN202511842017.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-09
- Publication Date
- 2026-03-06
AI Technical Summary
Existing methods for synthesizing 2-((1-arylethyl)amino)aniline require expensive catalysts, complex reaction systems, and poor functional group tolerance, which limits their application in the synthesis of downstream compounds.
Schiff base 2-aniline was synthesized in two steps using calcium carbide as a mediator. Inexpensive maleic anhydride was used as a water trapping agent to replace expensive metal catalysts, simplifying reaction conditions, reducing costs and increasing yield.
The synthesis of Schiff base 2-aniline was achieved with low cost and high yield. The operation is simple and suitable for large-scale production, with a yield of over 70%.
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Figure CN121609642A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the fields of organic synthesis and fine chemical technology, and in particular to a method for synthesizing the Schiff base 2-aniline using calcium carbide as a mediator. Background Technology
[0002] Schiff bases are a class of organic compounds containing imine (-RC=N-) or methylimine (-HC=N-) functional groups. Since their discovery in 1864, they have been widely used in coordination chemistry, drug synthesis, functional materials, and analytical detection due to their unique chemical properties. Among them, 2-((1-arylethyl)amino)aniline, as a Schiff base containing an active amino group, exhibits significantly enhanced nucleophilicity and coordination ability due to the lone pair electrons of its amino nitrogen atom. This makes it an important precursor for the synthesis of various nitrogen heterocyclic compounds such as quinoxaline and benzimidazole. Furthermore, it plays a crucial intermediate role in the construction of metal-organic frameworks, the design of metal ion fluorescent probes, and the synthesis of bioactive molecules such as anticancer and antiviral agents. Currently, the methods reported in the literature for the synthesis of 2-((1-arylethyl)amino)aniline and its analogues mainly have the following limitations: Synthetic strategies often involve expensive catalysts, costly starting materials, complex reaction systems, and poor substrate functional group tolerance. The limited number of synthetic strategies significantly inhibits the possibility of 2-((1-arylethyl)amino)aniline serving as a suitable reaction intermediate in the synthesis of downstream compounds. Therefore, exploring more synthetic strategies for such compounds has significant practical and theoretical research value. Summary of the Invention
[0003] (a) Technical problems to be solved To address the shortcomings of existing technologies, this invention presents a novel method for synthesizing 2-((1-arylethyl)amino)aniline Schiff bases using calcium carbide (calcium carbide) as a key mediator, achieving the goals of low cost, high yield, simple operation, and good functional group tolerance.
[0004] (II) Technical Solution To achieve the above objectives, the present invention provides the following technical solution: a method for synthesizing the Schiff base 2-aniline using calcium carbide as a mediator, which involves a two-step reaction using aromatic ketones as starting materials: Step 1: Aromatic ketones react with p-toluenesulfonylhydrazine to synthesize aromatic ketone p-toluenesulfonylhydrazone; The first step reaction is shown in the following equation:
[0005] Step 2: The aromatic ketone p-methylbenzenesulfonylhydrazone reacts with p-o-phenylenediamine, sodium tert-butoxide, calcium carbide and maleic anhydride to synthesize the Schiff base 2-aniline; The second step reaction is shown in the following equation: .
[0006] As a preferred embodiment, in the first step, the molar ratio of aromatic ketone, p-toluenesulfonyl hydrazine, and anhydrous ethanol is 1:(1.0~1.5), with 20~50 mL of anhydrous ethanol corresponding to every 0.01 mol of aromatic ketone.
[0007] As a preferred option, the specific steps of the first step reaction are as follows: 0.01 mol of aromatic ketone and 0.12 mol of p-methylbenzenesulfonylhydrazine are dissolved in 30 mL of anhydrous ethanol and stirred at room temperature until the solid precipitate is completely precipitated; then the mixture is filtered and the obtained solid is dried to obtain aromatic ketone p-methylbenzenesulfonylhydrazone.
[0008] As a preferred embodiment, in the second step of the reaction, based on the amount of the aromatic ketone p-methylbenzenesulfonylhydrazone fed as 1 equivalent, the molar ratio of o-phenylenediamine, sodium tert-butoxide, calcium carbide and maleic anhydride is 1: (0.8~1.5):(1.2~2.0):(1.2~2.0):(2.0~4.0).
[0009] As a preferred option, the specific steps of the second reaction include: S1: Mix the aromatic ketone p-methylbenzenesulfonylhydrazone, sodium tert-butoxide, and DMSO solvent, and stir until homogeneous; S2: Heat the mixture obtained in S1 to 70±5℃ and stir at this temperature for 2~4 hours until no bubbles are generated in the system; S3: Add calcium carbide and maleic anhydride to the system after the reaction of S2; S4: Heat the mixture obtained in S3 to 90±5℃ and react at this temperature for 3~8 hours; S5: After the reaction is complete, the reaction mixture is post-processed and purified to obtain the target product, Schiff base 2-aniline.
[0010] As a preferred embodiment, step S5 specifically includes: S51. Thin-layer chromatography was used to track the reaction. After the reaction was completed, the mixture was cooled to room temperature and the solid residue was filtered out. S52. The mother liquor was washed with saturated brine (3×30 mL), extracted with ethyl acetate (3×30 mL), and the combined organic phases were dried over anhydrous sodium sulfate. S53. Reduced pressure filtration was used to remove the solvent. The residue was separated and purified by column chromatography (silica gel, 200-300 mesh) using petroleum ether / ethyl acetate (V:V=8:1) as the eluent to obtain the target product.
[0011] As a preferred option, in the second step of the reaction, the preferred molar ratio of the feed is: aromatic ketone p-methylbenzenesulfonylhydrazone: o-phenylenediamine: sodium tert-butoxide: calcium carbide: maleic anhydride = 1:1.0:1.5:1.5:3.0.
[0012] As a preferred option, the calcium carbide used in the second step reaction is in powder form with a particle size ranging from 50 mesh to 200 mesh.
[0013] (III) Beneficial Effects Compared with the prior art, the present invention provides a method for synthesizing the Schiff base 2-aniline using calcium carbide as a mediator, which has the following beneficial effects: I. This invention innovatively uses calcium carbide, a widely available and inexpensive industrial chemical, as a reaction mediator, and simultaneously uses inexpensive maleic anhydride as a highly efficient water scavenger, replacing expensive metal catalysts or special reagents, thus significantly reducing synthesis costs. Furthermore, the timely consumption of water, a byproduct of the reaction, by maleic anhydride effectively promotes the forward shift of the condensation reaction equilibrium. The mediating effect of calcium carbide promotes the generation and transformation of key intermediates, and the synergistic effect of both results in a separation yield of the target product that is typically above 70%.
[0014] II. The first step of the operation process of this invention is a room temperature reaction, and the highest temperature of the second step is only about 90°C. It does not require harsh conditions such as high pressure, anhydrous and oxygen-free environments, or special light sources, thus requiring minimal experimental equipment, having a simple process flow, and being easy to scale up for mass production. Attached Figure Description
[0015] Figure 1 This is a diagram illustrating the reaction mechanism of aldehydes and ketones decomposing with benzenesulfonylhydrazone to form alkenes according to the present invention. Detailed Implementation
[0016] To better understand the purpose, structure, and function of this invention, the following description, in conjunction with the accompanying drawings and specific embodiments, will further illustrate a method for synthesizing the Schiff base 2-aniline using calcium carbide as a mediator. Example 1
[0017] refer to Figure 1 This invention discloses a method for synthesizing the Schiff base 2-aniline using calcium carbide as a mediator, which synthesizes 2-((1-arylethyl)amino)aniline under standard conditions, comprising: Step 1: Synthesis of the aromatic ketone p-methylbenzenesulfonylhydrazone In a 250 mL single-necked round-bottom flask, add an aromatic ketone (e.g., acetophenone) (0.01 mol), p-toluenesulfonyl hydrazine (0.012 mol), and 30 mL of anhydrous ethanol.
[0018] The mixture was placed on a magnetic stirrer and stirred at room temperature. After about 1.5 hours, a large amount of white solid precipitated in the flask.
[0019] Continue stirring for 0.5 hours to ensure the reaction is complete. After the reaction is complete, filter through a Buchner funnel and collect the white solid.
[0020] The solid was washed twice with a small amount of ice-cold anhydrous ethanol (about 5 ml), and then placed in a vacuum drying oven and dried at 40 °C for 4 hours to obtain a white powdery product, the aromatic ketone p-methylbenzenesulfonylhydrazone, with a yield of 94%.
[0021] Step 2: Synthesis of Schiff base 2-((1-arylethyl)amino)aniline In a 100 mL three-necked flask, add sequentially the aromatic ketone p-methylbenzenesulfonylhydrazone (0.005 mol), sodium tert-butoxide (0.0075 mol), and dimethyl sulfoxide (DMSO) prepared in the previous step.
[0022] Install a thermometer and reflux condenser, place the reaction flask in an oil bath preheated to 70°C, turn on the magnetic stirrer to mix the system thoroughly, and maintain the reaction at a constant temperature of 70±2°C. At this point, small nitrogen bubbles will be continuously released from the system. Maintain this temperature and stir the reaction for 3 hours, until bubble formation essentially stops.
[0023] Subsequently, powdered calcium carbide (0.0075 mol, particle size 100-150 mesh) and maleic anhydride (0.015 mol) were added sequentially to the reaction system. The oil bath temperature was raised to 90±2℃, and the reaction was continued with stirring for 6 hours. During this period, the reaction progress was monitored by thin-layer chromatography (TLC) using petroleum ether / ethyl acetate (volume ratio 4:1) as the developing solvent.
[0024] After the reaction was complete, the reaction solution was cooled to room temperature. Insoluble solid residues were removed by filtration, and the filter cake was washed with a small amount of DMSO (approximately 5 mL). The combined filtrates were poured into a beaker containing 100 mL of ice water, stirred, and then transferred to a separatory funnel. The aqueous phase was washed three times with saturated brine (30 mL each time). The aqueous phase was then extracted three times with ethyl acetate (30 mL each time). All organic phases were combined, and the mixture was dried over an appropriate amount of anhydrous sodium sulfate for approximately 30 minutes. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure using a rotary evaporator to remove most of the solvent, yielding a brownish-yellow oily crude product.
[0025] The crude product was purified by silica gel column chromatography (silica gel size: 200-300 mesh). A mixed solvent of petroleum ether / ethyl acetate (v / v 8:1) was used as the eluent. The eluent containing the target product was collected, combined, and the solvent was removed by rotary evaporation to give the pale yellow oily liquid product 2-((1-arylethyl)amino)aniline, in 82% yield. Example 2
[0026] Adjusting the feed ratio to synthesize Schiff base 2-((1-arylethyl)amino)aniline Step 1: Synthesis of the aromatic ketone p-methylbenzenesulfonylhydrazone Following the method in step one of Example 1, an unsubstituted aromatic ketone (e.g., 4'-chloroacetophenone) (0.01 mol) was used to replace the unsubstituted aromatic ketone in a reaction with p-toluenesulfonylhydrazine (0.012 mol). A white solid product, the aromatic ketone p-toluenesulfonylhydrazone, was obtained in 95% yield.
[0027] Step 2: Synthesis of Schiff base 2-((1-arylethyl)amino)aniline Refer to the reaction apparatus and basic operation in step 2 of Example 1.
[0028] Feeding: Aromatic ketone p-methylbenzenesulfonylhydrazone (0.005 mol), o-phenylenediamine (0.0045 mol, 0.9 equivalent), sodium tert-butoxide (0.01 mol, 2.0 equivalent), powdered calcium carbide (0.01 mol, 2.0 equivalent), maleic anhydride (0.02 mol, 4.0 equivalent), DMSO 20 mL.
[0029] Reaction process: First, react at 70℃ for 3 hours (until no bubbles appear), then add calcium carbide and maleic anhydride, and heat to 90℃ for 8 hours.
[0030] The post-processing and purification procedures were the same as in Example 1. The final product, Schiff base 2-((1-arylethyl)amino)aniline, was obtained in 78% yield.
[0031] This example demonstrates that by appropriately adjusting the feed ratio (especially reducing the amount of o-phenylenediamine and increasing the amounts of alkali and calcium carbide) and extending the reaction time, the target product can still be obtained in good yield for aromatic ketone substrates containing specific substituents (such as electron-withdrawing groups).
[0032] It is understood that the present invention has been described through some embodiments, and those skilled in the art will recognize that various changes or equivalent substitutions can be made to these features and embodiments without departing from the spirit and scope of the invention. Furthermore, under the teachings of the present invention, these features and embodiments can be modified to adapt to specific situations and materials without departing from the spirit and scope of the invention. Therefore, the present invention is not limited to the specific embodiments disclosed herein, and all embodiments falling within the scope of the claims of this application are within the protection scope of the present invention.
Claims
1. A method for synthesis of Schiff base 2-aniline using calcium carbide as mediator, characterized by, The aromatic ketone is used as a starting material to synthesize a Schiff base 2-aniline through two-step reactions. In the first step, the aromatic ketone reacts with p-methyl benzene sulfonyl hydrazine to synthesize an aromatic ketone p-methyl benzene sulfonyl hydrazone. The first step reaction is shown in the following formula: In the second step, the aromatic ketone p-methyl benzene sulfonyl hydrazone reacts with p-phenylenediamine, sodium tert-butoxide, calcium carbide and maleic anhydride to synthesize the Schiff base 2-aniline. The second step reaction is shown in the following formula:
2. A method of synthesizing Schiff base 2-aniline using calcium carbide as a mediator according to claim 1, characterized by, In the first step, the molar ratio of the aromatic ketone, p-methyl benzene sulfonyl hydrazine and anhydrous ethanol is 1: (1.0-1.5), and 20-50 mL of anhydrous ethanol is used per 0.01 mol of the aromatic ketone.
3. A method of synthesizing Schiff base 2-aniline using calcium carbide as mediator according to claim 2, characterized by, The specific steps of the first step reaction are as follows: 0.01 mol of the aromatic ketone and 0.12 mol of p-methyl benzene sulfonyl hydrazine are dissolved in 30 mL of anhydrous ethanol, and stirred at room temperature until the solid precipitate is completely precipitated; then, the mixture is filtered, and the obtained solid is dried to obtain the aromatic ketone p-methyl benzene sulfonyl hydrazone.
4. A method of synthesizing Schiff base 2-aniline using calcium carbide as a mediator according to claim 1, characterized by, In the second step reaction, the molar ratio of p-phenylenediamine, sodium tert-butoxide, calcium carbide and maleic anhydride is 1: (0.8-1.5): (1.2-2.0): (1.2-2.0): (2.0-4.0) based on 1 equivalent of the aromatic ketone p-methyl benzene sulfonyl hydrazone.
5. A method of synthesizing Schiff base 2-aniline using calcium carbide as mediator according to claim 1, characterized by, The specific steps of the second step reaction include: S1: the aromatic ketone p-methyl benzene sulfonyl hydrazone, sodium tert-butoxide and DMSO solvent are mixed and stirred uniformly; S2: the mixture obtained in S1 is heated to 70±5℃, and stirred at the constant temperature for 2-4 hours until no bubbles are generated in the system; S3: calcium carbide and maleic anhydride are added to the system after S2 reaction; S4: the mixture obtained in S3 is heated to 90±5℃, and reacted at the constant temperature for 3-8 hours; S5: after the reaction is completed, the reaction mixture is treated and purified to obtain the target product Schiff base 2-aniline.
6. A method of synthesizing Schiff base 2-aniline using calcium carbide as mediator according to claim 5, characterized by, The step S5 specifically includes: S51: thin layer chromatography is used to track the reaction, and the mixture is filtered to remove the solid residue after the reaction is completed and cooled to room temperature; S52: the mother liquor is washed with saturated brine (3×30 mL), and extracted with ethyl acetate (3×30 mL), and the combined organic phase is dried with anhydrous sodium sulfate; S53: the solvent is removed by vacuum filtration, and the residue is separated and purified by column chromatography (silica gel, 200-300 mesh), and petroleum ether / ethyl acetate (V:V=8:1) is used as the eluent to obtain the target product.
7. A method of synthesizing Schiff base 2-aniline using calcium carbide as mediator according to claim 5, characterized by, In the second step reaction, the preferred molar ratio is: aromatic ketone p-methyl benzene sulfonyl hydrazone: p-phenylenediamine: sodium tert-butoxide: calcium carbide: maleic anhydride = 1:1.0:1.5:1.5:3.
0.
8. A method of synthesizing Schiff base 2-aniline using calcium carbide as a mediator according to claim 5, characterized by, In the second step reaction, the calcium carbide used is in powder form, and the particle size range is 50 mesh to 200 mesh.