Background and overview[1][2]
N-methylphthalimide is an important organic chemical raw material with a wide range of uses. It is an important raw material for a series of fine chemicals. Since the H on the N-methyl methyl group is very active and has an aromatic hydrocarbon structure , can be used as an intermediate for the synthesis of drugs, dyes and pesticides, and is mainly used for the synthesis of resins and pharmaceutical products such as 4-amino-N-methylphthalimide. 4-Amino-N-methylphthalimide is an important intermediate for the synthesis of isoluminol derivatives. Its molecule has electron donating and accepting sites and is very sensitive to hydrogen bonding. It can be used in micelles, Study of biparental systems such as biofilms. In recent years, NMP has been used to synthesize chemiluminescent immunoassay reagents, which will have potential application prospects.
Synthesis method[1][2][3][4]
Synthesis method 1:
Using phthalimide as the starting material, react with potassium hydroxide in an anhydrous ethanol environment to prepare potassium salt. The potassium salt and dimethyl sulfate are alkylated in acetone or acetonitrile solvent. . The reaction equation is as follows. The specific process flow is: add the raw materials phthalimide, potassium hydroxide, and anhydrous ethanol into the reaction kettle, perform a reflux and stir reaction for 2-3 hours to cool, put it into a suction filter barrel, and remove the water ethanol, and then Use acetone to repeatedly pump out the unreacted raw materials, add the potassium imine salt into the methylation reactor, then add the solvent acetone and dimethyl sulfate to perform a reflux methylation reaction, and then fractionate acetone and unreacted sulfuric acid. Dimethyl ester is cooled and put into a crystallization tank for crystallization. The crystals are dried by a centrifuge and rinsed with a small amount of acetone. The crude NMP obtained is recrystallized in an acetone solvent.
Synthesis method 2:
Using phthalimide as the starting material, it reacts with formaldehyde in an aqueous solution to form a transition state quaternary ammonium base, and then reacts with hydrogen to form N-methyl phthalimide. The reaction equation is shown in the figure below. The specific steps are: add 200g (1.36mo1) phthalimide, 160g (1.97mol) industrial formaldehyde aqueous solution with a mass fraction of 37% and 200g deionized water into a 1L stainless steel magnetic stirring autoclave. Use 10% hydrochloric acid to adjust the pH to 5.5, seal the reaction kettle, replace the air in the kettle with nitrogen and start stirring to raise the temperature. When the temperature rises to 80°C, the gauge pressure is 0.015MPa. At this time, introduce hydrogen gas and ensure that the temperature in the kettle is between 80-85°C. After 45 minutes, the pressure in the kettle began to rise. Close the hydrogen gas inlet valve, and the gauge pressure in the kettle is 0.05MPa. Continue to keep warm and stir for 20 minutes. Cool the temperature to 40 degrees. After replacing the gas in the kettle with nitrogen, pour out the solid-liquid mixed reaction solution. The reaction solution was filtered with a Buchner funnel, and the filter cake was washed with 50 ml of water and dried to obtain 215 g of white fine needle-shaped crystalline powder, which is the product phthalimide.
Synthesis method 3: One-step synthesis of fatty amines
Using phthalic anhydride as the starting material, react with methylamine under heating conditions to prepare N-methylphthalimide. The reaction equation is shown in the figure below. The specific process flow is: put phthalic anhydride into the reaction vessel, control the temperature at 130℃-300℃ under the protection of inert gas, stirStir in methylamine gas and react for 1-4 hours. Add the reaction mixture to the water-soluble solvent to precipitate white crystals, filter and dry to obtain the finished product.
Synthesis method 4: Microwave radiation synthesis method
Under microwave radiation, N-methyl methyl phthalate can be directly synthesized by reacting phthalic anhydride and methylamine aqueous solution. The specific steps are: add ground 3.7g (25mmol) phthalic anhydride and 4.3mL (32.5mmol) methylamine aqueous solution into a 100mL Erlenmeyer flask, mix thoroughly, put it into a microwave oven, install an air condenser tube, and place it in a microwave oven. Reaction at 119W for 5 minutes. After cooling to room temperature, the crude product was taken out and recrystallized with absolute ethanol to obtain 3.35 g of colorless solid with a yield of 83.2%. The optimal conditions are: radiation power is 119W, radiation time is 4 minutes, and the material ratio of phthalic anhydride to methylamine is 1:1.3.
Application fields[5]
Synthesis of N-methyl-4-nitrophthalimide
N-Methylphthalamide is mainly used to synthesize N-methyl-4-nitrophthalimide (NMP) and N-methyl-4-aminophthalamide Imine and NMP are important intermediates for the synthesis of various monomeric dianhydrides of polyimide. N-methyl-4-aminophthalimide and its derivatives can be used for fluorescence and other labeling studies. It is also an important intermediate in the synthesis of isoluminol and its derivatives. Its molecular structure has electron donors and acceptors and is very sensitive to hydrogen bonding. It can be used in the study of amphiphilic systems such as micelles and biological membranes.
The synthesis of N-methyl-4-nitrophthalimide from N-methylphthalamide is mainly obtained through nitration reaction. The specific steps are as follows:
(1) First cool the fuming concentrated nitric acid to 5°C. According to the molar ratio of concentrated sulfuric acid to fuming concentrated nitric acid is 0.5:1.1, slowly add concentrated sulfuric acid dropwise, control the temperature at 10°C, and prepare a mixed acid. Backup;
(2) Control the temperature of the ice bath at 0°C, stir and mix N-methyl-phthalimide and concentrated sulfuric acid at a molar ratio of 1:1.8, and then mix N-methyl-phthalimide and concentrated sulfuric acid according to the molar ratio of 1:1.8. The molar ratio of formimide to mixed acid is 1:1.6. Add the prepared mixed acid dropwise into the mixed solution. After adding dropwise for 0.5 hours, react for 3 hours
(3) After the reaction is completed, use a mixed solution of ethyl acetate and chloroform to extract the nitrate produced by the reaction. The volume ratio of ethyl acetate to chloroform is 2:1, and the weight of the extractant is N- 1.2 times the weight of methyl-phthalimide;
(4) After extraction, separate layers to separate the upper organic phase and the lower sulfuric acid mother liquor
(5) Recover the upper organic phase to obtain N-methyl-4-nitrophthalimide, centrifuge, filter and dry to obtain
(6) The lower sulfuric acid mother liquor is used to remove water through the desiccant calcium sulfate, and is concentrated and used for the next batch of nitration reactions to prepare mixed acid. Formic anhydride is added when preparing mixed acid. The amount of formic anhydride is N-methyl- 1.5% by weight of phthalimide. The yield of N-methyl-4-nitrophthalimide prepared by this method is 96.3%, and the purity is 99.1%.
Main reference materials
[1] Qu Yuanyi, Preparation process of N-methylphthalimide, CN 200410053743, application date 2004-8-13
[2] Li Yalin, Su Yongqing, Zhang Zhixia. Research on the synthesis of N-methylphthalimide[J]. Academic Research of Shijiazhuang Vocational College of Science and Technology, 2017(Z1):28-33.
[3] Zou Congwei, Zhou Fen, Dai Jiukun, synthesis method of N-methylphthalimide, CN 201610474115, application date 2016-06-26
[4] Bian Yongjun, Zhou Zhongqiang. Synthesis of N-methylphthalimide by microwave radiation[J]. Chemical Reagents, 2007, 29(10):639-640.
[5] Min Jianghua, Huang Jianxiong, CN 201410225001, preparation method of N-methyl-4-nitrophthalimide, application date 2014-05-26
