N-methyl-4-aminophthalimide and preparation method thereof

Abstract

The invention provides N-methyl-4-amino phthalimide and a preparation method of the N-methyl-4-amino phthalimide. The preparation method comprises the following steps: a hydrogenation step: mixing N-methyl-4-nitrophthalimide, a catalyst and a first solvent, introducing hydrogen, and carrying out a reduction reaction to obtain a reduction product; a first solvent recovery step: cooling the reduction product, distilling and recovering the first solvent; a catalyst separation step: mixing the reduction product after recovery of the first solvent with a second solvent, and carrying out solid-liquid separation to obtain a filtrate and a solid catalyst; and a second solvent recovery step: carrying out reduced pressure distillation on the filtrate to recover the second solvent so as to obtain an N-methyl-4-aminophthalimide crude product. According to the preparation method disclosed by the invention, the original iron powder reduction process is replaced by hydrogenation catalytic reduction, so that the discharge of wastewater and waste residues in the preparation process is greatly reduced, the complete use of solvents in the reaction process is basically realized, and the atom economy of the reaction is improved.

Description

Technical Field

[0001] The invention relates to N-methyl-4-aminophthalimide and a preparation method thereof, and belongs to the field of organic synthesis. Background Art

[0002] N-methyl-4-aminophthalimide can be used as a dye intermediate, a photosensitizer, and can also be used as a dye-sensitized solar cell and a photocatalyst.

[0003] The existing production method of N-methyl-4-aminophthalimide mainly uses N-methyl-4-nitrophthalimide as a raw material, and uses an iron powder reduction scheme to reduce the nitro group to an amino group to obtain the N-methyl-4-aminophthalimide product. However, in the above method, the iron powder reduction process will produce a large amount of difficult-to-treat iron mud and high COD wastewater after reduction, and the iron mud and high COD wastewater are difficult to treat.

[0004] Therefore, researching a synthesis process that can reduce solid waste and wastewater emissions and meet national environmental protection requirements has become a technical problem that needs to be solved in product research and development and improvement. Summary of the invention

[0005] Problem that the invention aims to solve

[0006] In view of the technical problems existing in the prior art, the present invention provides a method for preparing N-methyl-4-aminophthalimide. Under the premise that the purity and yield of the N-methyl-4-aminophthalimide prepared by the method for preparing N-methyl-4-aminophthalimide meet the standards, the discharge of waste water and waste residue in the preparation process is greatly reduced, the full use of methanol and solvent in the reaction process is basically achieved, and the atom economy of the reaction is improved.

[0007] Furthermore, the preparation method of N-methyl-4-aminophthalimide of the present invention has more reasonable process and lower production cost, and is suitable for mass production.

[0008] Solutions for solving problems

[0009] The present invention provides a method for preparing N-methyl-4-aminophthalimide, which comprises the following steps:

[0010] A hydrogenation step: mixing N-methyl-4-nitrophthalimide, a catalyst and a first solvent, and introducing hydrogen to carry out a reduction reaction to obtain a reduction product;

[0011] The first solvent recovery step: cooling the reduction product, distilling it and recovering the first solvent;

[0012] Catalyst separation step: mixing the reduction product after recovering the first solvent with the second solvent and performing solid-liquid separation to obtain a filtrate and a solid catalyst;

[0013] The second solvent recovery step: the filtrate is subjected to reduced pressure distillation to recover the second solvent, thereby obtaining a crude product of N-methyl-4-aminophthalimide.

[0014] According to the preparation method of the present invention, in the hydrogenation step, the mass ratio of the N-methyl-4-nitrophthalimide to the first solvent is 1:4 to 1:9; the mass ratio of the N-methyl-4-nitrophthalimide to the catalyst is 40:1 to 80:1; the temperature of the reduction reaction is 80 to 100° C., and the pressure of the reduction reaction is 0.5 to 2.0 MPa.

[0015] According to the preparation method of the present invention, in the hydrogenation step, the catalyst includes a noble metal catalyst, preferably a palladium-carbon catalyst; and the first solvent includes an alcohol solvent.

[0016] According to the preparation method of the present invention, in the first solvent recovery step, the distillation temperature is 60-100°C; preferably, the mass of the distilled and recovered first solvent is 1 / 2-3 / 4 of the first solvent added in the hydrogenation step.

[0017] According to the preparation method of the present invention, in the catalyst separation step, the mass ratio of the N-methyl-4-nitrophthalimide to the second solvent is 1:4 to 1:9; the mass ratio of the second solvent to the first solvent added in the hydrogenation step is 0.5:1 to 1.2:1; and the temperature of the catalyst separation step is 30 to 70°C.

[0018] According to the preparation method of the present invention, in the second solvent recovery step, the temperature of the reduced pressure distillation is 120-130°C, and the vacuum degree of the reduced pressure distillation is -0.07MPa to -0.09MPa; preferably, the second solvent includes N,N-dimethylformamide and / or N,N-dimethylacetamide.

[0019] According to the preparation method of the present invention, the mass ratio of the second solvent to N-methyl-4-aminophthalimide in the crude N-methyl-4-aminophthalimide product is 1.5:1 to 3:1.

[0020] According to the preparation method of the present invention, after the second solvent recovery step, a dilution step using an inorganic solvent is further included; preferably, the mass ratio of the inorganic solvent to the N-methyl-4-nitrophthalimide is 2:1 to 3:1.

[0021] According to the preparation method of the present invention, the dilution temperature is 50-80°C, and the temperature is lowered to 0-30°C after dilution.

[0022] The present invention also provides N-methyl-4-aminophthalimide, which is prepared by the preparation method of the present invention.

[0023] Effects of the Invention

[0024] In the preparation method of the present invention, the original iron powder reduction process is replaced by hydrogenation catalytic reduction, which greatly reduces the discharge of waste water and waste residues in the preparation process, basically realizes the full use of the solvent in the reaction process, and improves the atomic economy of the reaction.

[0025] Furthermore, the preparation method of the present invention has more reasonable process and lower production cost, and is suitable for mass production. DETAILED DESCRIPTION

[0026] Various exemplary embodiments, features and aspects of the present invention will be described in detail below. The word "exemplary" used here means "used as an example, embodiment or illustrative". Any embodiment described here as "exemplary" is not necessarily interpreted as being superior or better than other embodiments.

[0027] In addition, in order to better illustrate the present invention, numerous specific details are provided in the following specific embodiments. It should be understood by those skilled in the art that the present invention can be implemented without certain specific details. In other examples, methods, means, equipment and steps well known to those skilled in the art are not described in detail in order to highlight the subject matter of the present invention.

[0028] Unless otherwise stated, the units used in this specification are all international standard units, and the numerical values ​​and numerical ranges appearing in the present invention should be understood to include the inevitable systematic errors in industrial production.

[0029] In this specification, the word "may" means both performing a certain process and not performing a certain process.

[0030] In this specification, the references to "some specific / preferred embodiments", "other specific / preferred embodiments", "embodiments", etc., mean that the specific elements (e.g., features, structures, properties and / or characteristics) described in connection with the embodiments are included in at least one embodiment described herein, and may or may not exist in other embodiments. In addition, it should be understood that the elements may be combined in various embodiments in any suitable manner.

[0031] In this specification, the numerical range expressed using "a numerical value A to a numerical value B" means a range including the endpoints numerical values ​​A and B.

[0032] In this specification, when "normal temperature" or "room temperature" is used, the temperature may be 15-25°C.

[0033] The present invention first provides a method for preparing N-methyl-4-aminophthalimide, which comprises the following steps:

[0034] A hydrogenation step: mixing N-methyl-4-nitrophthalimide, a catalyst and a first solvent, and introducing hydrogen to carry out a reduction reaction to obtain a reduction product;

[0035] The first solvent recovery step: cooling the reduction product, distilling it and recovering the first solvent;

[0036] Catalyst separation step: mixing the reduction product after recovering the first solvent with the second solvent and performing solid-liquid separation to obtain a filtrate and a solid catalyst;

[0037] The second solvent recovery step: the filtrate is subjected to reduced pressure distillation to recover the second solvent, thereby obtaining a crude product of N-methyl-4-aminophthalimide.

[0038] In the preparation method of the present invention, the original iron powder reduction process is replaced by hydrogenation catalytic reduction, which greatly reduces the discharge of waste water and waste residues in the preparation process, basically realizes the full use of the solvent in the reaction process, and improves the atomic economy of the reaction.

[0039] Hydrogenation step

[0040] In the hydrogenation step of the present invention, N-methyl-4-nitrophthalimide and a catalyst can be added to the first solvent, and then hydrogen is introduced to perform a reduction reaction to obtain a reduced product. Specifically, the reduction reaction can be performed in an autoclave.

[0041] In some specific embodiments, regarding the amount of solvent, in the hydrogenation step of the present invention, the mass ratio of the N-methyl-4-nitrophthalimide to the first solvent is 1:4 to 1:9, such as 1:5, 1:6, 1:7, 1:8, etc. When the mass ratio of N-methyl-4-nitrophthalimide to the methanol is 1:4 to 1:9, N-methyl-4-nitrophthalimide has good fluidity in the solvent and the reaction is sufficient.

[0042] Furthermore, the mass ratio of the N-methyl-4-nitrophthalimide to the catalyst is 40:1 to 80:1, such as 50:1, 60:1, 70:1, etc. When the mass ratio of the N-methyl-4-nitrophthalimide to the catalyst is 40:1 to 80:1, the hydrogenation reduction effect is better and the reaction is sufficient. Too much raw material relative to the catalyst will lead to insufficient reaction and too low reaction conversion rate.

[0043] In some specific embodiments, the temperature of the reduction reaction is 80-100°C, for example: 82°C, 85°C, 88°C, 90°C, 92°C, 95°C, 98°C, etc.; the pressure of the reduction reaction is 0.5-2.0MPa, for example: 0.8MPa, 1MPa, 1.2MPa, 1.5MPa, 1.8MPa, etc. When the temperature of the reduction reaction is 80-100°C and the pressure of the reduction reaction is 0.5-2.0MPa, the reaction can proceed smoothly. If the temperature of the reduction reaction is too low, the reaction time may be extended to 3 times the expected time and the reaction may not be able to proceed to the end point (the raw material reaction is completed and the product liquid phase purity is above 97%). Similarly, when the reaction pressure is too low, even if the reaction temperature is appropriate, the reaction will proceed slowly.

[0044] In the present invention, the specific operation method for the reaction pressure of the reduction reaction is as follows: the hydrogen pressure can be first increased to 2.0 MPa, the hydrogen inlet is closed, the reaction absorbs hydrogen, the hydrogen pressure is reduced to 0.5 MPa, and then the hydrogen inlet is opened, and the operation is repeated until the hydrogen pressure no longer changes, and the reaction is completed.

[0045] Further, in the present invention, in the hydrogenation step, the catalyst includes a noble metal catalyst, preferably a palladium carbon catalyst. The palladium carbon catalyst may be a commercially available palladium carbon catalyst having a content of 1 to 10%. Further, the first solvent includes an alcohol solvent, preferably methanol and / or ethanol. Considering the subsequent distillation recovery, methanol is preferably used.

[0046] In the present invention, the HPLC purity of the N-methyl-4-nitrophthalimide is 95-99%; the solid content of the N-methyl-4-nitrophthalimide is above 99%.

[0047] In the present invention, the reduction product prepared by the hydrogenation step contains N-methyl-4-nitrophthalimide, a catalyst and a first solvent. N-methyl-4-nitrophthalimide and the catalyst are mixed together and can be precipitated as a solid from the first solvent. Since the catalyst and N-methyl-4-nitrophthalimide are not easy to separate, the purity of N-methyl-4-nitrophthalimide in the reduction product is actually low.

[0048] During the in-process control test, N-methyl-4-nitrophthalimide and the catalyst are mixed together and tested using high performance liquid chromatography. During the test, N-methyl-4-nitrophthalimide can be dissolved in the solvent, while the catalyst is not soluble, so the test result is still high.

[0049] First solvent recovery step

[0050] In the first recovery step, the reduction product is cooled and then distilled to recover the first solvent; most of the first solvent can be recovered by distilling the reduction product.

[0051] In some specific embodiments, the distillation temperature is 60-100°C, for example: 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, etc. And the distillation can be carried out at normal pressure. The boiling point of methanol is 64.7°C, and the hydrogenation reaction will generate water. In the present invention, the temperature of distilling the first solvent from the methanol-water binary system at normal pressure can be 60-100°C.

[0052] Further, the mass of the first solvent recovered by distillation is 1 / 2 to 3 / 4 of the first solvent added in the hydrogenation step. In the present invention, the amount of distillation is related to the amount of solvent added in the subsequent catalyst separation step. N-methyl-4-nitrophthalimide and N-methyl-4-aminophthalimide have poor solubility in the first solvent. Therefore, when the mass of the first solvent is 1 / 2 to 3 / 4 of the first solvent added in the hydrogenation step, the reduction product can still maintain good fluidity, and the subsequent addition of solvent can dissolve the solids in the system except the catalyst, which is convenient for the subsequent catalyst separation operation. In addition, in the present invention, the mass concentration of the first solvent can be 98 to 99%.

[0053] Catalyst separation step

[0054] The reduction product after the first solvent is recovered is mixed with the second solvent and then subjected to solid-liquid separation to obtain a filtrate and a solid catalyst. Specifically, the reduction product after the first solvent is recovered is added to the second solvent for dissolution, and then subjected to solid-liquid separation to obtain a filtrate and a solid catalyst.

[0055] Specifically, in the catalyst separation step, the mass ratio of the N-methyl-4-nitrophthalimide to the second solvent is 1:4 to 1:9, for example, 1:5, 1:6, 1:7, 1:8, etc.; when the mass ratio of N-methyl-4-nitrophthalimide to the second solvent is 1:4 to 1:9, the solvent ratio is higher, the fluidity of the reaction system is better, the reaction is easier to proceed fully, and it is not easy for the product to wrap the raw material.

[0056] In some specific embodiments, the mass ratio of the second solvent to the first solvent added in the hydrogenation step is 0.5:1 to 1.2:1, for example: 0.6:1, 0.7:1, 0.8:1, 0.9:1, 1:1, 1.1:1, etc.; in the present invention, the amount of the second solvent used is related to the amount of residual methanol recovered in the previous step of methanol recovery. Increasing the dissolution temperature can speed up the dissolution rate of the material and reduce the time required for the process.

[0057] Furthermore, the temperature of the catalyst separation step is 30-70°C, for example, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, 65°C, etc. When the temperature of the catalyst separation step is 30-70°C, the catalyst can be separated more effectively.

[0058] Specifically, the second solvent includes dimethylformamide and / or dimethylacetamide. The mass concentration of the second solvent may be 98-99%.

[0059] Second solvent recovery step

[0060] The present invention obtains a crude N-methyl-4-aminophthalimide product by subjecting the filtrate to reduced pressure distillation to recover the second solvent. The N-methyl-4-aminophthalimide solution is subjected to reduced pressure distillation to recover most of the solvent, thereby obtaining a crude N-methyl-4-aminophthalimide product.

[0061] Specifically, in the present invention, in the second solvent recovery step, the temperature of the vacuum distillation is 120-130°C, for example, 122°C, 124°C, 128°C, 128°C, etc.; the vacuum degree of the vacuum distillation is -0.07MPa to -0.09MPa, for example, -0.08MPa, etc. The temperature of the vacuum distillation is related to the vacuum degree of the vacuum distillation. When the vacuum degree is low, a higher temperature is required to evaporate the solvent in the system. In order to reduce the heat source requirements during actual production, a vacuum degree of -0.07MPa to -0.09MPa is used for vacuum distillation.

[0062] Further, in the present invention, since the boiling point of the first solvent is low, after vacuum distillation, the first solvent is substantially no longer contained. Therefore, after the vacuum distillation removes most of the solvent, the mass ratio of the second solvent in the crude N-methyl-4-aminophthalimide product to the N-methyl-4-aminophthalimide is 1.5:1 to 3:1, for example: 1.8:1, 2:1, 2.2:1, 2.4:1, 2.6:1, 2.8:1, etc. When the mass of the second solvent remaining in the crude N-methyl-4-aminophthalimide product is too small, a large amount of solid material will be precipitated during the cooling process of the system, resulting in poor fluidity and even material hardening, and the system temperature is lower than that during vacuum distillation when diluting with water in order to prevent the initial water addition temperature from being too high, resulting in material explosion and impact.

[0063] Other steps

[0064] In some specific embodiments, after the second solvent recovery step, a dilution step using an inorganic solvent is also included. Since N-methyl-4-aminophthalimide has good solubility in the second solvent, dilution with water can destroy the solvent system and fully precipitate N-methyl-4-aminophthalimide.

[0065] Preferably, in the present invention, the mass ratio of the inorganic solvent to the N-methyl-4-nitrophthalimide is 2:1 to 3:1, for example, 2.2:1, 2.4:1, 2.6:1, 2.8:1, etc. When the mass ratio of the inorganic solvent to the N-methyl-4-nitrophthalimide is 2:1 to 3:1, the amount of the inorganic solvent added is sufficient to fully separate the N-methyl-4-nitrophthalimide from the solvent system. Specifically, in the present invention, the inorganic solvent may be water.

[0066] Furthermore, the dilution temperature is 50-80°C, for example, 55°C, 60°C, 65°C, 70°C, 75°C, etc., and the temperature is lowered to 0-30°C after dilution, for example, 5°C, 10°C, 15°C, 20°C, 25°C, etc. Lowering the temperature to 0-30°C after dilution is further conducive to fully precipitating N-methyl-4-nitrophthalimide from the solvent system.

[0067] The present invention also provides N-methyl-4-aminophthalimide, which is prepared by the preparation method of the present invention.

[0068] Example

[0069] The embodiments of the present invention will be described in detail below with reference to the examples, but those skilled in the art will appreciate that the following examples are only for

[0070] The present invention is described in detail and should not be construed as limiting the scope of the present invention. If no specific conditions are specified in the examples, the experiments were carried out under conventional conditions or conditions recommended by the manufacturer. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be obtained commercially.

[0071] The methanol used was industrial grade with a mass concentration of 99%; the palladium-carbon catalyst was purchased from Shanghai Linghan Scientific Instrument Co., Ltd. with a content of 5%; the solvent used was N,N-dimethylformamide (DMF) or dimethylacetamide (DMAC), industrial grade with a mass concentration of 99%.

[0072] Example 1

[0073] Hydrogenation step: add 360g methanol (content 99%) to a 1000mL autoclave with stirring, temperature control, and condensed water inner coil, put in 40g (purity 98%) N-methyl-4-nitrophthalimide (0.19mol), put in 1g palladium carbon catalyst (content 5%), start stirring, heat to 80°C, hydrogen replacement three times, pressure rises to 0.5-2.0MPa, react until hydrogen pressure is maintained for 30 minutes and no longer decreases, takes about 3 hours, keeps warm for 0.5 hours, and cools to 50°C to obtain a reduction product. The reduction product has good fluidity, and the reduction product is sampled and tested. The purity of the reduction product N-methyl-4-aminophthalimide is 99.12% in the solid liquid phase detection of the central control, and the raw material N-methyl-4-nitrophthalimide is not detected.

[0074] Methanol recovery step: transfer the reduction product to a 500 mL flask with stirring and a thermometer, raise the temperature to 90°C and recover methanol at normal pressure, a total of 208 g is recovered, and then cool down to 50°C until the remaining product in the flask can flow.

[0075] Catalyst separation step: Add 250 g of DMF (content 99%) solvent into the above flask, stir until the material is completely dissolved, and separate 0.8 g of catalyst by suction filtration to obtain a filtrate for standby use.

[0076] DMF recovery step: transfer the above filtrate to a 500 mL flask with stirring and a thermometer, heat to 125°C and distill under reduced pressure, with a vacuum degree of -0.09 MPa, and recover the solvent. A total of 315 g of solvent methanol and DMF are recovered to obtain a crude product of N-methyl-4-aminophthalimide.

[0077] Dilution step: remove the negative pressure, cool to 80 ° C, the crude N-methyl-4-aminophthalimide product can flow, slowly add 120 g of water, cool to 30 ° C after the dropwise addition, filter and wash the material, the product after drying is 32.09 g, the liquid phase detection product N-methyl-4-aminophthalimide purity is 98.22%, the raw material N-methyl-4-nitrophthalimide is not detected.

[0078] Example 2

[0079] Hydrogenation step: add 360g methanol (content 99%) to a 1000mL autoclave with stirring, temperature control, and condensed water inner coil, put in 40g (purity 98%) N-methyl-4-nitrophthalimide (0.19mol), put in 0.5g palladium carbon catalyst (content 5%), start stirring, heat to 100°C, and after hydrogen replacement three times, the pressure rises to 0.5-2.0MPa, react until the hydrogen pressure is maintained for 30 minutes and no longer decreases, which takes about 4 hours, and is kept warm for 0.5 hours, and cooled to 50°C to obtain a reduction product. The reduction product has good fluidity, and the reduction product is sampled and tested. The purity of the reduction product N-methyl-4-aminophthalimide is 98.77% in the solid and liquid phase detection of the central control, and the raw material N-methyl-4-nitrophthalimide is not detected.

[0080] Methanol recovery step: transfer the reduction product to a 500 mL flask with stirring and thermometer, raise the temperature to 90°C and recover methanol at normal pressure, a total of 260 g is recovered, and then cool down to 50°C until the remaining product in the flask can flow.

[0081] Catalyst separation step: Add 270 g of DMF solvent (content 99%) into the above flask, stir until the material is completely dissolved, filter and separate 0.4 g of catalyst to obtain a filtrate for standby use.

[0082] DMF recovery step: transfer the above filtrate to a 500 mL flask with stirring and a thermometer, heat to 125°C and distill under reduced pressure, with a vacuum degree of -0.09 MPa, and recover the solvent. A total of 290 g of solvent methanol and DMF are recovered to obtain a crude product of N-methyl-4-aminophthalimide.

[0083] Dilution step: remove the negative pressure, cool to 50 ° C, the crude N-methyl-4-aminophthalimide product can flow, slowly add 100 g of water, cool to 30 ° C after dropping, filter and wash the material, the product after drying is 31.14 g, the liquid phase detection product N-methyl-4-aminophthalimide purity is 97.45%, the raw material N-methyl-4-nitrophthalimide is not detected.

[0084] Example 3

[0085] Hydrogenation step: add 240g methanol (content 99%) to a 1000mL autoclave with stirring, temperature control, and condensed water inner coil, put in 40g (purity 98%) N-methyl-4-nitrophthalimide (0.19mol), put in 0.8g palladium carbon catalyst (content 5%), start stirring, heat to 100°C, and after hydrogen replacement three times, the pressure rises to 0.5-2.0MPa, react until the hydrogen pressure is maintained for 30 minutes and no longer decreases, which takes about 2 hours, and is kept warm for 0.5 hours, and cooled to 50°C to obtain a reduction product. The reduction product has good fluidity, and the reduction product is sampled and tested. The purity of the reduction product N-methyl-4-aminophthalimide is 98.33% in the solid and liquid phase detection of the central control, and the raw material N-methyl-4-nitrophthalimide is not detected.

[0086] Methanol recovery step: transfer the reduction product to a 500 mL flask with stirring and thermometer, raise the temperature to 90°C and recover methanol at normal pressure, recovering a total of 150 g, and cool down to 50°C until the remaining product in the flask can flow.

[0087] Catalyst separation step: Add 200 g of DMF (content 99%) solvent into the above flask, stir until the material is completely dissolved, filter and separate 0.6 g of catalyst to obtain a filtrate for standby use.

[0088] DMF recovery step: transfer the above filtrate to a 500 mL flask with stirring and a thermometer, heat to 125°C and distill under reduced pressure, with a vacuum degree of -0.09 MPa, and recover the solvent. A total of 200 g of solvent methanol and DMF are recovered to obtain a crude product of N-methyl-4-aminophthalimide.

[0089] Dilution step: remove the negative pressure, cool to 80 ° C, the crude N-methyl-4-aminophthalimide product can flow, slowly add 150 g of water, cool to 30 ° C after the drop, filter and wash the material, the product after drying is 31.26 g, the liquid phase detection product N-methyl-4-aminophthalimide purity is 98.10%, the raw material N-methyl-4-nitrophthalimide is not detected.

[0090] Example 4

[0091] Hydrogenation step: add 180g methanol (content 99%) to a 1000mL autoclave with stirring, temperature control, and condensed water inner coil, add 40g (purity 98%) N-methyl-4-nitrophthalimide (0.19mol), add 0.8g palladium carbon catalyst (content 5%), start stirring, heat to 100°C, and after hydrogen replacement three times, the pressure rises to 0.5-2.0MPa, react until the hydrogen pressure is maintained for 30 minutes and no longer decreases, which takes about 5 hours, keep warm for 0.5 hours, and cool to 50°C to obtain the reduction product. The reduction product has a high solid content and poor fluidity. The reduction product is sampled and tested. The purity of the reduction product N-methyl-4-aminophthalimide is 97.54% in the solid liquid phase detection of the central control, and the raw material N-methyl-4-nitrophthalimide is not detected.

[0092] Methanol recovery step: transfer the reduction product to a 500 mL flask with stirring and thermometer, raise the temperature to 90°C and recover methanol at normal pressure, a total of 100 g is recovered, and then cool down to 50°C until the remaining product in the flask can flow.

[0093] Catalyst separation step: Add 200 g of DMF (content 99%) solvent into the above flask, stir until the material is completely dissolved, filter and separate 0.6 g of catalyst to obtain a filtrate for standby use.

[0094] DMF recovery step: transfer the above filtrate to a 500 mL flask with stirring and a thermometer, heat to 125°C and distill under reduced pressure, with a vacuum degree of -0.09 MPa, and recover the solvent. A total of 190 g of solvent methanol and DMF are recovered to obtain a crude product of N-methyl-4-aminophthalimide.

[0095] Dilution step: remove the negative pressure, cool to 70 ° C, the crude N-methyl-4-aminophthalimide product can flow, slowly add 120 g of water, cool to 20 ° C after the drop, filter and wash the material, the product after drying is 31.54 g, the liquid phase detection product N-methyl-4-aminophthalimide purity is 97.12%, the raw material N-methyl-4-nitrophthalimide is not detected.

[0096] Example 5

[0097] Hydrogenation step: add 360g methanol (99%) to a 1000mL autoclave with stirring, temperature control, and condensed water inner coil, put in 40g (98% purity) N-methyl-4-nitrophthalimide (0.19mol), put in 0.8g palladium carbon catalyst (5% content), start stirring, heat to 100°C, and after hydrogen replacement three times, the pressure rises to 0.5-2.0MPa, react until the hydrogen pressure is maintained for 30 minutes and no longer decreases, which takes about 2 hours, and is kept warm for 0.5 hours, and cooled to 50°C to obtain a reduction product. The reduction product can flow, and the reduction product is sampled and tested. The purity of the reduction product N-methyl-4-aminophthalimide is 98.99% in the solid and liquid phase detection of the central control, and the raw material N-methyl-4-nitrophthalimide is not detected.

[0098] Methanol recovery step: transfer the reduction product to a 500 mL flask with stirring and thermometer, raise the temperature to 90°C and recover methanol at normal pressure, a total of 265 g is recovered, and then cool down to 50°C until the remaining product in the flask can flow.

[0099] Catalyst separation step: Add 200 g (content 99%) of DMAC solvent into the above flask, stir until the material is completely dissolved, and separate 0.6 g of catalyst by suction filtration to obtain a filtrate for standby use.

[0100] DMAC recovery step: The filtrate was transferred to a 500 mL flask with a stirrer and a thermometer, heated to 125°C and distilled under reduced pressure, with a vacuum degree of -0.09 MPa, to recover the solvent, and a total of 240 g of solvent methanol and DMAC were recovered to obtain a crude product of N-methyl-4-aminophthalimide.

[0101] Dilution step: remove the negative pressure, cool to 70 ° C, the crude N-methyl-4-aminophthalimide product can flow, slowly add 120 g of water, cool to 20 ° C after the drop, filter and wash the material, the product after drying is 32.11 g, the liquid phase detection product N-methyl-4-aminophthalimide purity is 98.07%, the raw material N-methyl-4-nitrophthalimide is not detected.

[0102] Example 6

[0103] Hydrogenation step: add 360g methanol (content 99%) to a 1000mL autoclave with stirring, temperature control, and condensed water inner coil, put in 40g (purity 98%) N-methyl-4-nitrophthalimide (0.19mol), put in 0.8g palladium carbon catalyst (content 5%), start stirring, heat to 100°C, and after hydrogen replacement three times, the pressure rises to 0.5-2.0MPa, react until the hydrogen pressure is maintained for 30 minutes and no longer decreases, which takes about 2 hours, and is kept warm for 0.5 hours, and cooled to 50°C to obtain a reduction product. The reduction product flows, and the reduction product is sampled and tested. The purity of the reduction product N-methyl-4-aminophthalimide is 99.10% by the central control solid liquid phase detection, and the raw material N-methyl-4-nitrophthalimide is not detected.

[0104] Methanol recovery step: transfer the reduction product to a 500 mL flask with stirring and thermometer, raise the temperature to 90°C and recover methanol at normal pressure, a total of 260 g is recovered, and then cool down to 50°C until the remaining product in the flask can flow.

[0105] Catalyst separation step: Add 180 g DMF (content 99%) into the above flask, stir until the material is completely dissolved, and separate 0.6 g of the catalyst by suction filtration to obtain a filtrate for standby use.

[0106] DMF recovery step: transfer the above filtrate to a 500 mL flask with stirring and a thermometer, heat to 125°C and distill under reduced pressure, with a vacuum degree of -0.09 MPa, and recover the solvent. A total of 210 g of solvent methanol and DMF are recovered to obtain a crude product of N-methyl-4-aminophthalimide.

[0107] Dilution step: remove the negative pressure, cool to 70 ° C, the crude N-methyl-4-aminophthalimide product can flow, slowly add 120 g of water, cool to 10 ° C after the drop, filter and wash the material, the product after drying is 31.87 g, the liquid phase detection product N-methyl-4-aminophthalimide purity is 98.32%, the raw material N-methyl-4-nitrophthalimide is not detected.

[0108] Example 7

[0109] Hydrogenation step: add 360g methanol (content 99%) to a 1000mL autoclave with stirring, temperature control, and condensed water inner coil, add 40g (purity 98%) N-methyl-4-nitrophthalimide (0.19mol), add 0.4g palladium carbon catalyst (content 5%), start stirring, heat to 90°C, and after hydrogen replacement three times, the pressure rises to 0.5-2.0MPa, react until the hydrogen pressure is maintained for 30 minutes and no longer decreases, which takes about 4 hours, keep warm for 0.5 hour, and cool to 50°C to obtain a primary reduction product. The primary reduction product can flow, and the primary reduction product is sampled and tested. The central control solid liquid phase test shows that the primary reduction product N-methyl-4-aminophthalimide has a purity of 88.43%, and the raw material N-methyl-4-nitrophthalimide is not detected. 0.1g of palladium carbon catalyst (content 5%) is added, the temperature is raised to 90°C, and the pressure is raised to 0.5-2.0MPa after hydrogen replacement three times. The reaction is maintained until the hydrogen pressure is maintained for 30 minutes and no longer decreases, which takes about 1.5 hours, and the temperature is kept for 0.5 hours, and the temperature is lowered to 50°C to obtain the secondary reduction product. The secondary reduction product is sampled and tested, and the solid liquid phase test shows that the secondary reduction product N-methyl-4-aminophthalimide has a purity of 98.50%, and the raw material N-methyl-4-nitrophthalimide is not detected.

[0110] Methanol recovery step: transfer the secondary reduction product to a 500 mL flask with stirring and a thermometer, raise the temperature to 90°C and recover methanol at normal pressure, recovering a total of 250 g, and cool down to 50°C until the remaining product in the flask can flow.

[0111] Catalyst separation step: Add 180 g DMF (content 99%) into the above flask, stir until the material is completely dissolved, and separate 0.4 g of the catalyst by suction filtration to obtain a filtrate for standby use.

[0112] DMF recovery step: the filtrate was transferred to a 500 mL flask with a stirrer and a thermometer, the temperature was raised to 125°C and the vacuum was distilled at -0.09 MPa to recover the solvent. A total of 240 g of solvent methanol and DMF were recovered to obtain a crude product of N-methyl-4-aminophthalimide.

[0113] Dilution step: remove the negative pressure, cool to 70 ° C, the crude N-methyl-4-aminophthalimide product can flow, slowly add 120 g of water, cool to 30 ° C after the drop, filter and wash the material, the product after drying is 31.44 g, the liquid phase detection product N-methyl-4-aminophthalimide purity is 98.01%, the raw material N-methyl-4-nitrophthalimide is not detected.

[0114] Example 8

[0115] Hydrogenation step: add 360g methanol (content 99%) to a 1000mL autoclave with stirring, temperature control, and condensed water inner coil, add 40g (purity 98%) N-methyl-4-nitrophthalimide (0.19mol), add 0.8g palladium carbon catalyst (content 5%), start stirring, heat to 70°C, and after hydrogen replacement three times, the pressure rises to 0.5-2.0MPa, react until the hydrogen pressure is maintained for 30 minutes and no longer decreases, which takes about 6 hours, keep warm for 0.5 hour, and cool to 50°C to obtain a primary reduction product. The primary reduction product can flow, and the primary reduction product is sampled and tested. The central control solid liquid phase test shows that the primary reduction product N-methyl-4-aminophthalimide has a purity of 91.43%, and the raw material N-methyl-4-nitrophthalimide is not detected. The temperature is raised to 90°C, and the pressure is raised to 0.5-2.0MPa after hydrogen replacement three times. The reaction is maintained until the hydrogen pressure is maintained for 30 minutes and no longer decreases, which takes about 1 hour. The temperature is kept for 0.5 hours, and the temperature is lowered to 50°C to obtain the secondary reduction product. The secondary reduction product is sampled and tested. The solid liquid phase test shows that the secondary reduction product N-methyl-4-aminophthalimide has a purity of 98.17%, and the raw material N-methyl-4-nitrophthalimide is not detected.

[0116] Methanol recovery step: transfer the secondary reduction product to a 500 mL flask with stirring and thermometer, raise the temperature to 90°C and recover methanol at normal pressure, a total of 260 g is recovered, and then cool down to 50°C until the remaining product in the flask can flow.

[0117] Catalyst separation step: Add 200 g of DMF (content 99%) solvent into the above flask, stir until the material is completely dissolved, filter and separate 0.6 g of catalyst to obtain a filtrate for standby use.

[0118] DMF recovery step: transfer the above filtrate to a 500 mL flask with stirring and a thermometer, heat to 125°C and distill under reduced pressure, with a vacuum degree of -0.09 MPa, and recover the solvent. A total of 245 g of solvent methanol and DMF are recovered to obtain a crude product of N-methyl-4-aminophthalimide.

[0119] Dilution step: remove the negative pressure, cool to 70 ° C, the crude N-methyl-4-aminophthalimide product can flow, slowly add 120 g of water, cool to 30 ° C after the dropwise addition, filter and wash the material, the product after drying is 31.20 g, the liquid phase detection product N-methyl-4-aminophthalimide purity is 97.55%, and the raw material N-methyl-4-nitrophthalimide is not detected.

[0120] Example 9

[0121] Hydrogenation step: add 360g methanol (content 99%) to a 1000mL autoclave with stirring, temperature control, and condensed water inner coil, put in 40g (purity 98%) N-methyl-4-nitrophthalimide (0.19mol), put in 0.8g catalyst (palladium carbon, content 5%), start stirring, heat up to 110°C, hydrogen replacement three times, pressure rises to 0.5-2.0MPa, react until hydrogen pressure is maintained for 30 minutes and no longer decreases, it takes about 1.5 hours (cooling water pressure is large when hydrogen is passed, heat is large in the initial stage of reaction, and temperature rises quickly), keep warm for 0.5 hours, cool to 50°C to obtain reduction product. The reduction product can flow, sample the reduction product for detection, the central control solid liquid phase detection reduction product N-methyl-4-aminophthalimide purity 98.22%, raw material N-methyl-4-nitrophthalimide is not detected.

[0122] Methanol recovery step: transfer the reduction product to a 500 mL flask with stirring and thermometer, raise the temperature to 90°C and recover methanol at normal pressure, recovering a total of 250 g, and cool down to 50°C until the remaining product in the flask can flow.

[0123] Catalyst separation step: Add 200 g of DMF (content 99%) solvent into the above flask, stir until the material is completely dissolved, filter and separate 0.6 g of catalyst to obtain a filtrate for standby use.

[0124] DMF recovery step: transfer the above filtrate to a 500 mL flask with stirring and a thermometer, heat to 125°C and distill under reduced pressure, with a vacuum degree of -0.09 MPa, to recover the solvent. A total of 245 g of solvent methanol and DMF were recovered to obtain a crude product of N-methyl-4-aminophthalimide.

[0125] Dilution step: remove the negative pressure, cool to 70 ° C, the crude N-methyl-4-aminophthalimide product can flow, slowly add 120 g of water, cool to 30 ° C after the dropwise addition, filter and wash the material, the product after drying is 31.23 g, the liquid phase detection product N-methyl-4-aminophthalimide purity is 97.66%, the raw material N-methyl-4-nitrophthalimide is not detected.

[0126] Performance Testing

[0127] Purity detection method: Purity detection was performed using HPLC high performance liquid chromatography according to the method in Q / RTR J02225-2021. The results are shown in Table 1.

[0128] Table 1 Raw material ratio and product performance test of Examples 1-9

[0129]

[0130] As can be seen from Table 1, the purity of the products in Examples 1-6 is relatively high, which shows that in the present invention, when the palladium-carbon catalyst is sufficient and the temperature and pressure are appropriate, there is no obvious difference in the reaction selectivity, and the hydrogenation product does not have any additional side reactions.

[0131] In Examples 1 and 2, different amounts of catalyst were used in the hydrogenation reaction, and the hydrogenation results did not show very large differences, but the hydrogenation time varied greatly (the hydrogenation reaction time of Example 2 with a small amount of catalyst was significantly longer), indicating that more catalyst can be added according to the situation to speed up the reaction rate.

[0132] In Examples 3, 4, and 5, different amounts of solvent were used in the hydrogenation reactions. The hydrogenation results did not show very significant differences, but the fluidity of the reduction products varied greatly. The fluidity of the reduction product in Example 4 was poor. Therefore, more solvent may be added as appropriate to ensure that the reduction product maintains better fluidity.

[0133] In Examples 5 and 6, different solvents (DMF, DMAC) were used in the catalyst separation step, which did not have a significant impact on the subsequent product separation and product purity.

[0134] In Examples 1-6, after the reduction reaction is completed, changes in the amount of recovered methanol, the amount of added solvent, the amount of recovered solvent, and the amount of added dilution water have no significant effect on the product yield and purity, indicating that after the main hydrogenation reaction is completed, the reaction will not produce a large number of side reactions when the amount of solvent or dilution water is adjusted within a certain range, the process stability is high, and the possibility of actual production is greater.

[0135] In Example 7, the amount of catalyst in the hydrogenation reaction was insufficient. After a long reaction time, the central control sampling still did not reach the reaction endpoint (the central control solid and liquid phase detection product N-methyl-4-aminophthalimide had a purity of 88.43%, and the raw material N-methyl-4-nitrophthalimide was not detected). The raw material was not detected because there would be more intermediates in the hydrogenation reaction. After the catalyst was added later, the purity of the product N-methyl-4-aminophthalimide was improved.

[0136] In Example 8, when the amount of catalyst is sufficient, but the reaction temperature is low and the reaction time is long, the central control sampling still does not reach the reaction endpoint (the central control solid and liquid phase detection product N-methyl-4-aminophthalimide has a purity of 91.43%, and the raw material N-methyl-4-nitrophthalimide is not detected). Similarly, the raw material is not detected because there are more intermediates in the hydrogenation reaction. After continuing to increase the reaction temperature, the reaction reaches the endpoint smoothly, indicating that at 70°C, the reaction activation energy for some intermediate products to be converted into products is not reachable, and after increasing the temperature, these intermediate products can be smoothly converted.

[0137] In Example 9, there is no significant difference in the reaction, but a too fast reaction will cause a greater pressure on the cooling water. Considering the pressure of the engineering cooling source, the reaction temperature should not be set too high.

[0138] It should be noted that, although the technical solution of the present invention is introduced with specific examples, those skilled in the art will appreciate that the present invention should not be limited thereto.

[0139] The embodiments of the present invention have been described above, and the above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The selection of terms used herein is intended to best explain the principles of the embodiments, practical applications, or technical improvements in the market, or to enable other persons of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. A method for preparing N-methyl-4-aminophthalimide, characterized in that: The following steps are involved: A hydrogenation step: mixing N-methyl-4-nitrophthalimide, a catalyst and a first solvent, and introducing hydrogen to carry out a reduction reaction to obtain a reduction product; The first solvent recovery step: cooling the reduction product, distilling it and recovering the first solvent; Catalyst separation step: mixing the reduction product after recovering the first solvent with the second solvent and performing solid-liquid separation to obtain a filtrate and a solid catalyst; The second solvent recovery step: the filtrate is subjected to reduced pressure distillation to recover the second solvent, thereby obtaining a crude product of N-methyl-4-aminophthalimide.

2. The preparation method according to claim 1, characterized in that: In the hydrogenation step, the mass ratio of the N-methyl-4-nitrophthalimide to the first solvent is 1:4 to 1:9; the mass ratio of the N-methyl-4-nitrophthalimide to the catalyst is 40:1 to 80:1; the temperature of the reduction reaction is 80 to 100° C., and the pressure of the reduction reaction is 0.5 to 2.0 MPa.

3. The preparation method according to claim 1 or 2, characterized in that: In the hydrogenation step, the catalyst includes a noble metal catalyst, preferably a palladium-carbon catalyst; and the first solvent includes an alcohol solvent.

4. The preparation method according to any one of claims 1 to 3, characterized in that In the first solvent recovery step, the distillation temperature is 60-100° C.; preferably, the mass of the first solvent distilled and recovered is 1 / 2-3 / 4 of the first solvent added in the hydrogenation step.

5. The preparation method according to any one of claims 1 to 4, characterized in that: In the catalyst separation step, the mass ratio of the N-methyl-4-nitrophthalimide to the second solvent is 1:4 to 1:9; the mass ratio of the second solvent to the first solvent added in the hydrogenation step is 0.5:1 to 1.2:1; and the temperature of the catalyst separation step is 30 to 70°C.

6. The preparation method according to any one of claims 1 to 5, characterized in that: In the second solvent recovery step, the temperature of the reduced pressure distillation is 120-130° C., and the vacuum degree of the reduced pressure distillation is -0.07 MPa to -0.09 MPa; preferably, the second solvent includes N,N-dimethylformamide and / or N,N-dimethylacetamide.

7. The preparation method according to any one of claims 1 to 6, characterized in that: The mass ratio of the second solvent to N-methyl-4-aminophthalimide in the crude N-methyl-4-aminophthalimide product is 1.5:1 to 3:

1.

8. The preparation method according to any one of claims 1 to 7, characterized in that: After the second solvent recovery step, the method further comprises a dilution step using an inorganic solvent; preferably, the mass ratio of the inorganic solvent to the N-methyl-4-nitrophthalimide is 2:1 to 3:

1.

9. The preparation method according to claim 8, characterized in that: The dilution temperature is 50-80°C, and the temperature is lowered to 0-30°C after dilution.

10. N-methyl-4-aminophthalimide, prepared by the preparation method according to any one of claims 1 to 9.

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