CN111848433B - Process for preparing 4-aminophenylacetamide - Google Patents
Process for preparing 4-aminophenylacetamide Download PDFInfo
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- CN111848433B CN111848433B CN202010676355.8A CN202010676355A CN111848433B CN 111848433 B CN111848433 B CN 111848433B CN 202010676355 A CN202010676355 A CN 202010676355A CN 111848433 B CN111848433 B CN 111848433B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
Abstract
The invention discloses a preparation method of 4-aminophenylacetamide, which comprises the following steps: adding 1 part of para-aminophenylacetic acid and 4 parts of methanol into a reaction vessel, uniformly stirring, adding concentrated sulfuric acid for reaction, and recovering excessive methanol in the reaction vessel after the reaction is finished; after the recovery of methanol is finished, adding 5-6 parts of crystallization solution into a reaction container, uniformly stirring, then dropwise adding 10 parts of ammonia water under stirring, and controlling the dropwise adding time of the ammonia water to be 9-11 hours; after the ammonia water is added dropwise, preserving heat for 13 hours, cooling the reaction vessel to 7-9 ℃, continuously stirring until a large number of crystals appear in the kettle, and continuously stirring for 2 hours to obtain feed liquid; the method overcomes the defects of the prior art, the method has no residue of solvent, the yield of the 4-aminophenylacetamide can reach more than 89 percent, and the waste liquid is relatively environment-friendly and safe without discharge.
Description
Technical Field
The invention relates to the technical field of 4-aminophenylacetamides, and in particular belongs to a preparation method of 4-aminophenylacetamides.
Background
Aromatic amine compounds are important organic intermediates in the field of fine chemical industry, and are widely applied to industries such as medicines, pesticides, dyes, surfactants, chelating agents, textile assistants, high polymer materials, food additives and the like. The corresponding aromatic amines are prepared industrially mainly by reduction of the corresponding aromatic nitro compounds. There are various methods for reducing aromatic nitro compounds to aromatic amines, including metal reduction, alkali sulfide reduction, metal hydride reduction, electrochemical reduction, photochemical reduction, catalytic hydrogenation, and the like. The 4-aminophenylacetamide is mainly applied to synthesizing medicines, dyes and food additives, so that the method has very practical significance for synthesizing and researching the 4-aminophenylacetamide.
The cooling agent has large demand in the perfume industry, but the cooling agent has various synthesis routes, the raw materials required by each process method are different, 4-aminophenylacetamide is the main raw material of a novel cooling agent, 4-aminophenylacetamide is mixed acid for nitration to generate p-nitroacetanilide in the prior synthesis technology, then reduction is carried out, reaction liquid is neutralized, crystallized and dried to obtain a finished product, the synthesis process adopts a hydrogenation dangerous process, has high equipment requirement and poor applicability, the yield in unit time is low, the subsequent purification and separation difficulty is high, partial byproducts must be removed through a distillation process, the process steps are excessively complicated, the loss of solvent and feed liquid is large, the primary crystallization rate is low, repeated extraction and crystallization are carried out, excessive waste liquid is caused, the cost is gradually increased, the profit space is reduced, and the current environmental protection and economic harmony development are not facilitated.
Disclosure of Invention
The invention aims to provide an environment-friendly and safe preparation method of 4-aminophenylacetamide, which shortens the preparation time of 4-aminophenylacetamide, reduces byproducts and improves the purity of 4-aminophenylacetamide.
In order to solve the problems, the technical scheme adopted by the invention is as follows:
the preparation method of the 4-aminophenylacetamide comprises the following steps:
s1, adding 1 part of para-aminophenylacetic acid and 4 parts of methanol into a reaction container, uniformly stirring, adding concentrated sulfuric acid, heating to 50-55 ℃, reacting at constant temperature for 4 hours, and recovering excessive methanol in the reaction container after the reaction is finished;
s2, after the recovery of methanol is finished, adding 5-6 parts of crystallization solution into a reaction container, uniformly stirring, then stirring and dropwise adding 10 parts of ammonia water, and controlling the dropwise adding time of the ammonia water to be 9-11 hours;
s3, after the ammonia water is added dropwise, preserving heat for 13 hours, cooling the reaction vessel to 7-9 ℃, continuously stirring until a large number of crystals appear in the kettle, and continuously stirring for 2 hours to obtain feed liquid;
s4, separating crystals in the feed liquid to obtain a crystal wet material, and drying the crystal wet material to obtain the 4-aminophenylacetamide.
Preferably, the amount of concentrated sulfuric acid added in step S1 is 3 times that of para-aminophenylacetic acid.
Preferably, the concentrated sulfuric acid is added in the step S1 by dripping, and the temperature in the reaction vessel is controlled to be 10-28 ℃ during dripping.
Preferably, 1.4 to 1.65 parts of methanol is recovered in step S1, and the temperature in the reaction vessel during recovery is 71 to 75 ℃.
Preferably, the temperature in the reaction vessel at the time of adding 5 to 6 parts of the crystallization solution to the reaction vessel in step S2 is 30 ℃.
Preferably, the crystallization solution in the step S2 is one of sodium chloride, calcium chloride, zinc chloride and magnesium chloride aqueous solution.
Preferably, the solute content of the crystallization solution is 30-40wt%.
Preferably, the temperature in the reaction vessel during the stirring and dropwise addition of 10 parts of ammonia water in step S2 is 27 ℃.
According to the invention, the sulfating raw material is formed by integrating sulfating, methanol and sulfuric acid in one step, then sodium chloride aqueous solution is added, and the process operation of dropwise adding concentrated ammonia water is performed to synthesize the crude 4-aminophenylacetamide, so that the reaction time is short, byproducts are avoided, the raw material utilization rate is high, the subsequent purification is unnecessary, the distillation process is not needed, the energy consumption is reduced, no organic solvent is adopted any more, the aqueous solution of the reaction sodium chloride is added at one time, meanwhile, the aqueous solution is also used as a crystallization solvent, the aqueous solution is heated and then added into a crystallization kettle through a filtering device, the crystallization can be achieved, the crystallization time is short, the mother solution can be directly recycled after part of water is removed through evaporation, the complete crystallization temperature is controlled at 7 ℃, the aqueous solution is particularly easy to dry, the solvent is free from residue after drying, the cost is well reduced, the profit space is controlled, the primary yield of the 4-aminophenylacetamide with the purity of 99% can reach 89% or more, the waste solution is free from emission, and the method is relatively environment-friendly and safe.
Compared with the prior art, the invention has the following implementation effects:
1. the invention has the advantages of simple raw materials, short reaction time, no byproducts, mild control conditions and one-step completion of esterification and acidification.
2. The invention only needs to adopt common raw materials, avoids hydrogenation dangerous process, adopts one-pot reaction, has short steps, adopts water as solvent for crystallization, and is economical and environment-friendly.
3. The invention can obtain the finished product after one crystallization, has short crystallization time, lower content of 4-aminophenylacetamide in the mother liquor, lighter color of the mother liquor, direct recycling, no need of distillation or ion exchange treatment, greatly improved yield of the finished product, unchanged product quality, simple operation, one-pot reaction and crystallization, and good economy.
4. In the operation aspect of the process method, the 4-aminophenylacetamide product with higher purity is easy to obtain, an organic solvent is not used, the danger of industrial production is reduced, and the economic and environmental protection dual significance is realized.
Detailed Description
The following description of the technical solutions in the embodiments of the present invention will be clear and complete, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
Firstly, weighing 20kg of para-aminophenylacetic acid and 80kg of methanol in a reaction kettle, starting stirring, and starting circulating water to enable the temperature in the reaction kettle to reach 22 ℃; pumping 60kg of concentrated sulfuric acid into the overhead tank, dropwise adding sulfuric acid, keeping the temperature in the reaction kettle at 26 ℃ in the dropwise adding process, extruding cooling water after the sulfuric acid is completely added, heating by steam, controlling the heating temperature at 55 ℃, and heating for 4 hours; starting water jet vacuum, keeping the vacuum at-0.08 Mpa, recovering 32kg of methanol, recycling the recovered methanol, and keeping the temperature in the reaction kettle at 73 ℃; after recycling, starting circulating water to cool the reaction kettle to 30 ℃, adding 37kg of sodium chloride and 70kg of water into the reaction kettle, and stirring for 30min; then pumping 200kg of ammonia water into the overhead tank, starting dripping, and controlling the temperature in the reaction kettle to be 27 ℃ for 10.5 hours in the dripping process; after the dripping is finished, preserving the heat for 13 hours, starting chilled water after the heat preservation is finished, controlling the temperature in the reaction kettle to be 7 ℃, stirring until a large number of crystals appear in the reaction kettle, and then continuing stirring for 2 hours to obtain feed liquid; transferring the feed liquid into a centrifuge, starting centrifugal material throwing to obtain 23.2kg of crystal wet material, wherein the mother liquid is yellowish, and recycling part of water recovered from the mother liquid; drying the centrifuged wet crystal material in an oven at 50 ℃ under reduced pressure for 2 hours to obtain the 4-aminophenylacetamide, wherein the purity reaches 99.1%, the dried crystal material is white crystal, the weight is 18.6kg, and the yield reaches 93%.
Example 2
Firstly, weighing 20kg of para-aminophenylacetic acid and 80kg of methanol in a reaction kettle, starting stirring, and starting circulating water to enable the temperature in the reaction kettle to reach 10 ℃; pumping 60kg of concentrated sulfuric acid into the overhead tank, dropwise adding sulfuric acid, keeping the temperature in the reaction kettle at 20 ℃ in the dropwise adding process, extruding cooling water after the sulfuric acid is completely added, heating by steam, controlling the heating temperature at 51 ℃, and heating for 4 hours; starting water jet vacuum, keeping the vacuum at-0.08 Mpa, recovering 31kg of methanol, recycling the recovered methanol for the next time, and keeping the temperature in the reaction kettle at 75 ℃; after recycling, starting circulating water to cool the reaction kettle to 30 ℃, adding 37kg of sodium chloride and 70kg of water into the reaction kettle, and stirring for 30min; then pumping 200kg of ammonia water into the overhead tank, starting dripping, and controlling the temperature in the reaction kettle to be 27 ℃ for 9 hours in the dripping process; after the dripping is finished, preserving the heat for 13 hours, starting chilled water after the heat preservation is finished, controlling the temperature in the reaction kettle to be 7 ℃, stirring until a large number of crystals appear in the reaction kettle, and then continuing stirring for 2 hours to obtain feed liquid; transferring the feed liquid into a centrifuge, starting centrifugal material throwing to obtain 24.7kg of crystal wet material, wherein the mother liquid is yellowish, and recycling part of water recovered from the mother liquid; drying the centrifuged wet crystal material in an oven at 50 ℃ under reduced pressure for 2 hours to obtain the 4-aminophenylacetamide, wherein the purity reaches 99.4%, the dried crystal material is white crystal, the weight is 18.9kg, and the yield reaches 94.5%.
Example 3
Firstly, weighing 20kg of para-aminophenylacetic acid and 80kg of methanol in a reaction kettle, starting stirring, and starting circulating water to enable the temperature in the reaction kettle to reach 17 ℃; pumping 60kg of concentrated sulfuric acid into the overhead tank, dropwise adding sulfuric acid, keeping the temperature in the reaction kettle at 28 ℃ in the dropwise adding process, extruding cooling water after the sulfuric acid is completely added, heating by steam, controlling the heating temperature at 51 ℃, and heating for 4 hours; opening water jet vacuum, keeping the vacuum at-0.08 Mpa, recovering 29.7kg of methanol, recycling the recovered methanol for the next time, and keeping the temperature in the reaction kettle at 71 ℃; after recycling, starting circulating water to cool the reaction kettle to 30 ℃, adding 40kg of calcium chloride and 70kg of water into the reaction kettle, and stirring for 30min; then pumping 200kg of ammonia water into the overhead tank, starting dripping, and controlling the temperature in the reaction kettle to be 27 ℃ for 9 hours in the dripping process; after the dripping is finished, preserving the heat for 13 hours, starting chilled water after the heat preservation is finished, controlling the temperature in the reaction kettle to be 9 ℃, stirring until a large number of crystals appear in the reaction kettle, and then continuing stirring for 2 hours to obtain feed liquid; transferring the feed liquid into a centrifuge, starting centrifugal material throwing to obtain 21.2kg of crystal wet material, wherein the mother liquid is yellowish, and recycling part of water recovered from the mother liquid; drying the centrifuged wet crystal material in an oven at 50 ℃ under reduced pressure for 2 hours to obtain the 4-aminophenylacetamide, wherein the purity reaches 99.7%, the dried crystal material is white crystal, the weight is 17.9kg, and the yield reaches 89.5%.
Example 4
Firstly, weighing 20kg of para-aminophenylacetic acid and 80kg of methanol in a reaction kettle, starting stirring, and starting circulating water to enable the temperature in the reaction kettle to reach 4 ℃; pumping 60kg of concentrated sulfuric acid into the overhead tank, dropwise adding sulfuric acid, keeping the temperature in the reaction kettle at 10 ℃ in the dropwise adding process, extruding cooling water after the sulfuric acid is completely added, heating by steam, controlling the heating temperature at 54 ℃, and heating for 4 hours; starting water jet vacuum, keeping the vacuum at-0.08 Mpa, recovering 32.1kg of methanol, recycling the recovered methanol for the next time, and keeping the temperature in the reaction kettle at 75 ℃; after recycling, starting circulating water to cool the reaction kettle to 30 ℃, adding 35kg of magnesium chloride and 70kg of water into the reaction kettle, and stirring for 30min; then pumping 200kg of ammonia water into the overhead tank, starting dripping, and controlling the temperature in the reaction kettle to be 27 ℃ for 10.5 hours in the dripping process; after the dripping is finished, preserving the heat for 13 hours, starting chilled water after the heat preservation is finished, controlling the temperature in the reaction kettle to be 7 ℃, stirring until a large number of crystals appear in the reaction kettle, and then continuing stirring for 2 hours to obtain feed liquid; transferring the feed liquid into a centrifuge, starting centrifugal material throwing to obtain 25.7kg of crystal wet material, wherein the mother liquid is yellowish, and recycling part of water recovered from the mother liquid; drying the centrifuged wet crystal material in an oven at 50 ℃ under reduced pressure for 2 hours to obtain the 4-aminophenylacetamide, wherein the purity reaches 99.6%, the dried crystal material is white crystal, the weight is 19.1kg, and the yield reaches 95.5%.
Example 5
Firstly, weighing 20kg of para-aminophenylacetic acid and 80kg of methanol in a reaction kettle, starting stirring, and starting circulating water to enable the temperature in the reaction kettle to reach 5 ℃; pumping 60kg of concentrated sulfuric acid into the overhead tank, dropwise adding sulfuric acid, keeping the temperature in the reaction kettle at 15 ℃ in the dropwise adding process, extruding cooling water after the sulfuric acid is completely added, heating by steam, controlling the heating temperature at 50 ℃, and heating for 4 hours; starting water jet vacuum, keeping the vacuum at-0.08 Mpa, recovering 32.1kg of methanol, recycling the recovered methanol for the next time, and keeping the temperature in the reaction kettle at 75 ℃; after recycling, starting circulating water to cool the reaction kettle to 30 ℃, adding 35kg of zinc chloride and 70kg of water into the reaction kettle, and stirring for 30min; then pumping 200kg of ammonia water into the overhead tank, starting dripping, and controlling the temperature in the reaction kettle to be 27 ℃ during dripping for 11 hours; after the dripping is finished, preserving the heat for 13 hours, starting chilled water after the heat preservation is finished, controlling the temperature in the reaction kettle to be 7 ℃, stirring until a large number of crystals appear in the reaction kettle, and then continuing stirring for 2 hours to obtain feed liquid; transferring the feed liquid into a centrifuge, starting centrifugal material throwing to obtain 23.4kg of crystal wet material, wherein the mother liquid is yellowish, and recycling part of water recovered from the mother liquid; drying the centrifuged wet crystal material in an oven at 50 ℃ under reduced pressure for 2 hours to obtain the 4-aminophenylacetamide, wherein the purity reaches 99.7%, the dried crystal material is white crystal, the weight is 18.5kg, and the yield reaches 92.5%.
Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (7)
- The preparation method of the 4-aminophenylacetamide is characterized by comprising the following steps:s1, adding 1 part of para-aminophenylacetic acid and 4 parts of methanol into a reaction container, uniformly stirring, adding concentrated sulfuric acid, heating to 50-55 ℃, reacting at constant temperature for 4 hours, and recovering excessive methanol in the reaction container after the reaction is finished;s2, after the recovery of methanol is finished, adding 5-6 parts of crystallization solution into a reaction container, uniformly stirring, then stirring and dropwise adding 10 parts of ammonia water, and controlling the dropwise adding time of the ammonia water to be 9-11 hours;s3, after the ammonia water is added dropwise, preserving heat for 13 hours, cooling the reaction vessel to 7-9 ℃, continuously stirring until a large number of crystals appear in the kettle, and continuously stirring for 2 hours to obtain feed liquid;s4, separating crystals in the feed liquid to obtain a crystal wet material, and drying the crystal wet material to obtain 4-aminophenylacetamide;the crystallization solution in the step S2 is one of sodium chloride, calcium chloride, zinc chloride and magnesium chloride aqueous solution.
- 2. The process for producing 4-aminophenylacetamide according to claim 1, characterized in that: the amount of concentrated sulfuric acid added in step S1 is 3 times that of p-aminophenylacetic acid.
- 3. The process for producing 4-aminophenylacetamide according to claim 1, characterized in that: in the step S1, concentrated sulfuric acid is added dropwise, and the temperature in the reaction vessel is controlled to be 10-28 ℃ during the dropwise addition.
- 4. The process for producing 4-aminophenylacetamide according to claim 1, characterized in that: 1.4 to 1.65 parts of methanol is recovered in the step S1, and the temperature in the reaction vessel is 71 to 75 ℃ in the recovery process.
- 5. The process for producing 4-aminophenylacetamide according to claim 1, characterized in that: in step S2, the temperature in the reaction vessel was 30℃when 5 to 6 parts of the crystallization solution was added to the reaction vessel.
- 6. The process for producing 4-aminophenylacetamide according to claim 1, characterized in that: the content of solute in the crystallization solution is 30-40wt%.
- 7. The process for producing 4-aminophenylacetamide according to claim 1, characterized in that: the temperature in the reaction vessel during the stirring and dropwise addition of 10 parts of ammonia water in step S2 was 27 ℃.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003051909A2 (en) * | 2001-12-19 | 2003-06-26 | Astrazeneca Ab | Process for the manufacture of pharmaceutically acceptable salts of a compound |
| CN1617881A (en) * | 2000-07-22 | 2005-05-18 | 阿斯特拉曾尼卡有限公司 | Chemical process |
| US20100272655A1 (en) * | 2009-04-27 | 2010-10-28 | Kathryn Anne Bardsley | Menthylcarboxamides and Their Use as Cooling Agents |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1617881A (en) * | 2000-07-22 | 2005-05-18 | 阿斯特拉曾尼卡有限公司 | Chemical process |
| WO2003051909A2 (en) * | 2001-12-19 | 2003-06-26 | Astrazeneca Ab | Process for the manufacture of pharmaceutically acceptable salts of a compound |
| US20100272655A1 (en) * | 2009-04-27 | 2010-10-28 | Kathryn Anne Bardsley | Menthylcarboxamides and Their Use as Cooling Agents |
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