Method for preparing p-aminophenylacetylene
By performing a coupling reaction between p-bromonitrobenzene and 2-methyl-3-butyn-2-ol under nitrogen protection, reduction in a reducing agent and electrolyte, and finally catalytically synthesizing p-amino group under strong alkali conditions Phenylacetylene solves the problems of high synthesis conditions and low yield in the existing technology, and realizes an efficient and low-cost synthesis process.
Patent Information
- Application Number
- CN202411497193.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-25
- Publication Date
- 2025-01-21
AI Technical Summary
When synthesising p-aminophenylacetylene in the prior art, the experimental conditions are high, the product yield is low, the reaction time is long, the production operation is complicated, and the post-processing is difficult.
Under nitrogen protection, p-bromonitrobenzene and 2-methyl-3-butyn-2-ol are coupled in the presence of organic solvents and catalysts to obtain 4-(4-nitrophenyl)-2- Methyl-3-butyn-2-ol is then subjected to a reduction reaction in a reducing agent and electrolyte, and finally a catalytic reaction is carried out in the presence of an organic solvent and a strong base to synthesize p-aminophenylacetylene.
It has achieved simple operation, mild response conditions, high chemical income, and low cost. It is suitable for industrialized production.
Smart Images
Figure FT_1 
Figure SMS_1
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic synthesis and relates to a method for preparing p-aminophenylacetylene. Background Art
[0002] p-Aminophenylacetylene is an important raw material for synthesizing high-grade resins and liquid crystal polymers and certain new drugs in the fields of aviation, aerospace, and military affairs. It is also an important intermediate for synthesizing homogeneous time-resolved fluorescent immunoassay reagents. At present, the synthesis of alkynes from aldehydes using the Wittig reaction is a classic method, but the experimental conditions are relatively high. The synthesis of p-aminophenylacetylene using the Vilsmeier reaction is also a classic method. Specifically, the readily available substituted acetophenone is used as a raw material, and the Vilsmeier reaction is used to construct a molecule containing a substituted olefin bond. The product can be obtained by hydrolysis and elimination reaction. This method also has high requirements for controlling experimental conditions. Other synthesis methods also have the disadvantages of low product yield, long reaction time, complex production operation, and difficult post-processing. Summary of the invention
[0003] The invention provides a method for preparing p-aminophenylacetylene, which has the advantages of simple operation, mild reaction conditions, high chemical yield, low cost and suitability for industrial production.
[0004] The technical solution of the present invention is achieved in this way: A method for preparing p-aminophenylacetylene comprises the following steps: A. Under nitrogen protection, a coupling reaction is carried out between p-bromonitrobenzene and 2-methyl-3-butyn-2-ol in a molar ratio of 1:1-3 in the presence of an organic solvent and a catalyst to synthesize 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol, wherein the reaction temperature is 60-80°C and the reaction time is 1-3h; B. subjecting the 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol obtained in step A to a reduction reaction in the presence of a reducing agent and an electrolyte to obtain 4-(4-aminophenyl)-2-methyl-3-butyn-2-ol; C. The 4-(4-aminophenyl)-2-methyl-3-butyn-2-ol obtained in step B is subjected to a catalytic reaction in the presence of an organic solvent and a strong base to synthesize p-aminophenylacetylene, wherein the strong base is sodium methoxide and sodium carbonate in a mass ratio of 4:0.7-1.3; the amount ratio of the 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol and the strong base is 3.1-3.5:1; the reaction temperature is 82-95° C.; and the reaction time is 6-10 h.
[0005] Specifically, the synthetic route is as follows: Preferably, the molar ratio of p-bromonitrobenzene to 2-methyl-3-butyn-2-ol is 1:1-2.5.
[0006] Preferably, the organic solvent in step A is one or two of pyridine, triethylamine, N,N-dimethylformamide and methylpyrrolidone.
[0007] Preferably, the catalyst described in step A is one or two of cuprous iodide, cuprous chloride, triphenylphosphine, triphenylphosphine palladium chloride and palladium on carbon.
[0008] Preferably, the catalyst described in step A is triphenylphosphine, cuprous iodide and triphenylphosphine palladium chloride in a mass ratio of 1.2:0.5:0.4-0.7.
[0009] Preferably, the amount of the catalyst in step A is 0.3-3% of the mass of p-bromonitrobenzene, and the amount of the organic solvent is 1.8-5 times the total mass of p-bromonitrobenzene and 2-methyl-3-butyn-2-ol.
[0010] Preferably, the amount of the catalyst in step A is 0.5-1% of the mass of p-bromonitrobenzene, and the amount of the organic solvent is 1.8-3 times the total mass of p-bromonitrobenzene and 2-methyl-3-butyn-2-ol.
[0011] Preferably, the reducing agent in step B is iron powder, sodium sulfide, sodium thiosulfate or zinc powder.
[0012] Preferably, the reducing agent in step B is iron powder.
[0013] Preferably, the electrolyte in step B is one or more of ammonium chloride, sodium chloride and ammonium sulfide.
[0014] Preferably, the electrolyte in step B is ammonium chloride.
[0015] Preferably, the amount of the reducing agent used in step B is 0.4-1 times the mass of 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol.
[0016] Preferably, the amount of the reducing agent used in step B is 0.6-0.9 times the mass of 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol.
[0017] Preferably, the electrolyte described in step B is 4-10% of the mass of 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol.
[0018] Preferably, the reaction temperature in step B is 50-75°C; and the reaction time is 3-6h.
[0019] Preferably, in step C, the amount of the organic solvent and 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol is in the ratio of 130-600 ml to 20.5-82 g.
[0020] Preferably, the organic solvent in step C is one or more of methanol, ethanol, isopropanol, ethylene glycol dimethyl ether and toluene.
[0021] Preferably, the organic solvent in step C is isopropanol and ethylene glycol dimethyl ether in a volume ratio of 2-4:1. Isopropanol and ethylene glycol dimethyl ether are selected as solvents. Compared with other solvents, they can better dissolve various substances in the reaction, provide a relatively stable reaction environment, and allow the reaction to proceed under relatively mild conditions, reduce the occurrence of side reactions, and improve the yield and purity of the target product p-aminophenylacetylene; the composite catalysts sodium methoxide and sodium carbonate show better solubility and stability in isopropanol and ethylene glycol dimethyl ether, which is conducive to the reaction.
[0022] The working principle and beneficial effects of the present invention are: 1. The method for preparing p-aminophenylacetylene provided by the present invention is carried out under the protection of inert gas. The whole preparation reaction process is carried out under the protection of inert gas. With p-bromonitrobenzene and 2-methyl-3-butyn-2-ol as raw materials, firstly, a coupling reaction is carried out in an organic solvent under the action of a catalyst to obtain 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol; then, a reduction reaction is carried out in a reducing agent and an electrolyte to obtain 4-(4-aminophenyl)-2-methyl-3-butyn-2-ol; and then, acetone is completely removed by a strong base to obtain p-aminophenylacetylene. The method has the advantages of simple synthesis route, mild reaction conditions, cheap and easy-to-obtain raw materials, high total yield, high product purity, low cost, etc., and is suitable for industrial production and has good application prospects.
[0023] 2. In the method provided by the present invention, p-bromonitrobenzene and 2-methyl-3-butyn-2-ol are used as raw materials, and first a coupling reaction is carried out in an organic solvent under the action of a catalyst to obtain 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol, wherein the palladium catalyst used has high catalytic activity and stability, the copper catalyst and the palladium catalyst synergistically promote the reaction, and triphenylphosphine serves as a ligand to stabilize the palladium catalyst, thereby improving the activity and stability of the catalyst; the three synergistically can improve the reaction rate and reaction yield; 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol is subjected to a reduction reaction in a reducing agent and an electrolyte to obtain 4-(4-aminophenyl)-2-methyl-3-butyn-2-ol, wherein the reducing agent used is preferably iron powder, and the iron powder reduction is carried out under relatively mild conditions, without the need for high temperature or high pressure, which is conducive to controlling the reaction process and reducing the occurrence of side reactions. At the same time, the cost is low, the operation is simple, and no complex equipment and strict operating steps are required, which is suitable for large-scale industrial production. The presence of the electrolyte increases the conductivity of the solution, accelerates the electrochemical corrosion of iron, and is conducive to the reduction reaction; 4-(4-aminophenyl)-2-methyl-3-butyn-2-ol is subjected to a catalytic reaction in the presence of an organic solvent and a strong base to synthesize p-aminophenylacetylene, wherein the combined use of sodium methoxide and sodium carbonate can significantly improve the selectivity of the reaction and the yield of the product; meanwhile, the presence of sodium carbonate can help the sodium methoxide to be better dispersed in the reaction system, reduce the situation of local over-alkalinity, thereby improving the uniformity and controllability of the reaction, and at the same time improving the safety and operability of the reaction, and reducing the cost to a certain extent. BRIEF DESCRIPTION OF THE DRAWINGS
[0024] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments.
[0025] Figure 1 The p-aminophenylacetylene prepared in Example 3 of the present invention 1 HNMR spectrum. DETAILED DESCRIPTION
[0026] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0027] Example 1 Under nitrogen protection, 650 ml of triethylamine, 145.44 g of p-bromonitrobenzene, 90.72 g of 2-methyl-3-butyn-2-ol, 0.24 g of triphenylphosphine, and 0.24 g of triphenylphosphine palladium chloride were respectively placed in a dry four-necked flask, the temperature was raised to 60°C, and stirred at 60°C for 2 h. After the reaction was completed, triethylamine was concentrated, and then 550 ml of ethyl acetate and 300 ml of water were added. After stirring for 1 h, the liquid was separated, and 300 ml of water was added to the upper liquid. 00ml, separate the liquid again, concentrate the ethyl acetate, add 200ml of methanol and 200ml of water, cool, crystallize, filter, wash the solid twice with methanol to obtain 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol, dry the wet material of 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol at 40°C under reduced pressure for 12h to obtain 140.23g of 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol; Add 82g 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol, 48.8g zinc powder, 4.1g sodium chloride and 480ml distilled water to a reaction bottle, heat to 55°C, stir at 55°C for 6h, filter after the reaction, add 600ml isopropanol, 20g sodium methoxide and 5g sodium carbonate, heat to 82°C, stir and react for 10h, cool, crystallize and filter after the reaction to obtain p-aminophenylacetylene. Dry the wet material under reduced pressure at 60°C for 12h to obtain 32.76g p-aminophenylacetylene with a purity of 99.72% and a yield of 70.00%.
[0028] Embodiment 2: Under nitrogen protection, 950 ml of triethylamine, 145.44 g of p-bromonitrobenzene, 169.34 g of 2-methyl-3-butyn-2-ol, 0.64 g of triphenylphosphine, 0.24 g of cuprous iodide, and 2.4 g of 10% palladium carbon (the mass of palladium metal accounts for 10% of the total mass of the catalyst) were respectively put into a dry four-necked flask, heated to 80°C, and reacted at 80°C for 3 hours. After the reaction was completed, triethylamine was concentrated, 500 ml of ethyl acetate, 250 ml of water, and 20 g of 25% ammonia water (NH3 content 25%) were added, and stirred for 30 minutes. in, separate the liquids, add 250 ml of water and 20 g of 25% ammonia water to the obtained organic phase, separate the liquids again, concentrate the ethyl acetate, add 150 ml of methanol and 150 ml of water, cool, crystallize, filter, and wash the solid twice with methanol to obtain 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol. Dry the wet 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol at 50°C under reduced pressure for 12 hours to obtain 138.34 g of 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol. Add 20.5g 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol, 16.8g iron powder, 1.64 ammonium sulfide and 180ml distilled water to a reaction bottle, heat to 75°C, stir at 75°C for 3h, filter while hot after the reaction, add 130ml toluene, 5g sodium methoxide and 1g sodium carbonate to the filtrate, heat to 95°C, stir and react for 6h, cool, crystallize and filter to obtain p-aminophenylacetylene, dry the wet material under reduced pressure at 50°C for 12h to obtain 8.11g p-aminophenylacetylene with a purity of 99.60% and a yield of 69.32%.
[0029] Embodiment 3: Under nitrogen protection, 1500ml of triethylamine, 305.42g of p-bromonitrobenzene, 296.86g of 2-methyl-3-butyn-2-ol, 1.2g of triphenylphosphine, 0.5g of cuprous iodide, and 0.5g of triphenylphosphine palladium chloride were respectively put into a dry four-necked flask, heated to 70°C, and reacted at 70°C for 2h. After the reaction was completed, triethylamine was concentrated, 1000ml of ethyl acetate, 550ml of water, and 40g of sodium ethylenediaminetetraacetate were added, and the mixture was stirred for 30min, and then the liquid was separated, and 500ml of water and 40 g of sodium ethylenediaminetetraacetate are added to the obtained organic phase, the liquid is separated again, ethyl acetate is concentrated, 300 ml of methanol and 300 ml of water are added, cooled, crystallized, filtered, and the solid is washed twice with methanol to obtain 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol. The wet 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol is dried under reduced pressure at 45°C for 12 h to obtain 297.17 g of 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol.
[0030] Add 41g 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol, 35g iron powder, 3.28g ammonium chloride and 200ml distilled water to the reaction bottle, heat to 65℃, stir at 65℃ for 4h, filter while hot after the reaction is over, add 70ml ethylene glycol dimethyl ether and 210ml isopropanol to the filtrate, stir for 30min, add 10g sodium methoxide and 2.5g sodium carbonate, heat to 85℃, stir and react for 8h, cool, crystallize and filter to obtain p-aminophenylacetylene, dry the wet material under reduced pressure at 55℃ for 12h to obtain 17.02g p-aminophenylacetylene with a purity of 99.68% and a yield of 72.74%. Figure 1 The product was confirmed to be p-aminophenylacetylene.
[0031] Example 4 Under nitrogen protection, 1500ml of triethylamine, 305.42g of p-bromonitrobenzene, 296.86g of 2-methyl-3-butyn-2-ol, 1.2g of triphenylphosphine, 0.5g of cuprous iodide, and 0.5g of triphenylphosphine palladium chloride were respectively put into a dry four-necked flask, heated to 70°C, and reacted at 70°C for 2h. After the reaction was completed, triethylamine was concentrated, 1000ml of ethyl acetate, 550ml of water, and 40g of sodium ethylenediaminetetraacetate were added, and the mixture was stirred for 30min, and then 5 00ml of water and 40g of sodium ethylenediaminetetraacetate are added to the obtained organic phase, the liquid is separated again, ethyl acetate is concentrated, 300ml of methanol and 300ml of water are added, cooled, crystallized, filtered, and the solid is washed twice with methanol to obtain 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol. The wet 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol is dried under reduced pressure at 45°C for 12h to obtain 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol.
[0032] Add 41g 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol, 35g iron powder, 3.28g ammonium chloride and 200ml distilled water to a reaction bottle, heat to 65°C, stir at 65°C for 4h. After the reaction is completed, filter while hot, add 280ml isopropanol to the filtrate, stir for 30min, then add 10g sodium methoxide and 2.5g sodium carbonate, heat to 85°C, stir and react for 8h. After the reaction is completed, cool, crystallize and filter to obtain p-aminophenylacetylene. The wet material is dried under reduced pressure at 55°C for 12h to obtain 16.19g p-aminophenylacetylene with a purity of 99.57% and a yield of 69.19%.
[0033] Example 5 Under nitrogen protection, 1500ml of triethylamine, 305.42g of p-bromonitrobenzene, 296.86g of 2-methyl-3-butyn-2-ol, 1.2g of triphenylphosphine, 0.5g of cuprous iodide, and 0.5g of triphenylphosphine palladium chloride were respectively put into a dry four-necked flask, heated to 70°C, and reacted at 70°C for 2h. After the reaction was completed, triethylamine was concentrated, 1000ml of ethyl acetate, 550ml of water, and 40g of sodium ethylenediaminetetraacetate were added, and the mixture was stirred for 30min, and then 5 00ml of water and 40g of sodium ethylenediaminetetraacetate are added to the obtained organic phase, the liquid is separated again, ethyl acetate is concentrated, 300ml of methanol and 300ml of water are added, cooled, crystallized, filtered, and the solid is washed twice with methanol to obtain 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol. The wet 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol is dried under reduced pressure at 45°C for 12h to obtain 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol.
[0034] Add 41g 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol, 35g iron powder, 3.28g ammonium chloride and 200ml distilled water to a reaction bottle, heat to 65°C, stir at 65°C for 4h. After the reaction is completed, filter while hot, add 280ml ethylene glycol dimethyl ether to the filtrate, stir for 30min, add 10g sodium methoxide and 2.5g sodium carbonate, heat to 85°C, stir and react for 8h. After the reaction is completed, cool, crystallize and filter to obtain p-aminophenylacetylene. The wet material is dried under reduced pressure at 55°C for 12h to obtain 15.78g p-aminophenylacetylene with a purity of 99.64% and a yield of 67.44%.
[0035] Comparative Example 1 Under nitrogen protection, 1500ml of triethylamine, 305.42g of p-bromonitrobenzene, 296.86g of 2-methyl-3-butyn-2-ol, 1.2g of triphenylphosphine, 0.5g of cuprous iodide, and 0.5g of triphenylphosphine palladium chloride were respectively put into a dry four-necked flask, heated to 70°C, and reacted at 70°C for 2h. After the reaction was completed, triethylamine was concentrated, 1000ml of ethyl acetate, 550ml of water, and 40g of sodium ethylenediaminetetraacetate were added, and the mixture was stirred for 30min, and then 5 00ml of water and 40g of sodium ethylenediaminetetraacetate are added to the obtained organic phase, the liquid is separated again, ethyl acetate is concentrated, 300ml of methanol and 300ml of water are added, cooled, crystallized, filtered, and the solid is washed twice with methanol to obtain 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol. The wet 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol is dried under reduced pressure at 45°C for 12h to obtain 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol.
[0036] Add 41g 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol, 35g iron powder, 3.28g ammonium chloride and 200ml distilled water to a reaction bottle, heat to 65°C, stir at 65°C for 4h. After the reaction is completed, filter while hot, add 70ml ethylene glycol dimethyl ether and 210ml isopropanol to the filtrate, stir for 30min, add 12.5g sodium methoxide, heat to 85°C, stir and react for 8h. After the reaction is completed, cool, crystallize and filter to obtain p-aminophenylacetylene. The wet material is dried under reduced pressure at 55°C for 12h to obtain 15.28g p-aminophenylacetylene with a yield of 65.30%.
[0037] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.
Claims
1. A method for preparing p-aminophenylacetylene, characterized in that: The following steps are involved: A. Under nitrogen protection, a coupling reaction is carried out between p-bromonitrobenzene and 2-methyl-3-butyn-2-ol in a molar ratio of 1:1-3 in the presence of an organic solvent and a catalyst to synthesize 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol, wherein the reaction temperature is 60-80°C; B. subjecting the 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol obtained in step A to a reduction reaction in the presence of a reducing agent and an electrolyte to obtain 4-(4-aminophenyl)-2-methyl-3-butyn-2-ol; C. The 4-(4-aminophenyl)-2-methyl-3-butyn-2-ol obtained in step B is subjected to a catalytic reaction in the presence of an organic solvent and a strong base to synthesize p-aminophenylacetylene, wherein the strong base is sodium methoxide and sodium carbonate in a mass ratio of 4:0.7-1.3; the amount ratio of the 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol and the strong base is 3.1-3.5:1; and the reaction temperature is 82-95°C.
2. A method for preparing p-aminophenylacetylene according to claim 1, characterized in that: The organic solvent described in step A is one or two of pyridine, triethylamine, N,N-dimethylformamide and methylpyrrolidone.
3. A method for preparing p-aminophenylacetylene according to claim 1, characterized in that: The catalyst described in step A is one or two of cuprous iodide, cuprous chloride, triphenylphosphine, triphenylphosphine palladium chloride and palladium carbon.
4. A method for preparing p-aminophenylacetylene according to claim 1, characterized in that: The catalyst described in step A is triphenylphosphine, cuprous iodide and triphenylphosphine palladium chloride in a mass ratio of 1.2:0.5:0.4-0.
7.
5. A method for preparing p-aminophenylacetylene according to claim 1, characterized in that: The amount of the catalyst in step A is 0.3-3% of the mass of p-bromonitrobenzene, and the amount of the organic solvent is 1.8-5 times the total mass of p-bromonitrobenzene and 2-methyl-3-butyn-2-ol.
6. A method for preparing p-aminophenylacetylene according to claim 1, characterized in that: The reducing agent described in step B is iron powder, sodium sulfide, sodium thiosulfate or zinc powder.
7. A method for preparing p-aminophenylacetylene according to claim 1, characterized in that: The electrolyte described in step B is one or more of ammonium chloride, sodium chloride, and ammonium sulfide.
8. A method for preparing p-aminophenylacetylene according to claim 1, characterized in that: The amount of the reducing agent used in step B is 0.4-1 times the mass of 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol.
9. A method for preparing p-aminophenylacetylene according to claim 1, characterized in that: The electrolyte described in step B is 4-10% of the mass of 4-(4-nitrophenyl)-2-methyl-3-butyn-2-ol.
10. A method for preparing p-aminophenylacetylene according to claim 1, characterized in that: The reaction temperature of step B is 50-75°C; the reaction time is 3-6h.