A kind of preparation method of 2-methyl-4-methoxydiphenylamine

Abstract

The invention belongs to the technical field of organic synthesis, and in particular to a method for preparing 2-methyl-4-methoxydiphenylamine. Steps: (1) adding o-nitrotoluene, a metal catalyst, methanol and sulfuric acid to a reaction kettle, maintaining a hydrogen pressure of 0.03-0.05 MPa, obtaining a crude 2-methyl-4-methoxyaniline product, and separating a solid 3-methyl-4-aminophenol product; (2) adding 3-methyl-4-aminophenol to a reactor, adding a NaOH solution, adding DMAC and pure water, adding dimethyl carbonate dropwise, and washing with alkali to obtain a crude 2-methyl-4-methoxyaniline product; (3) adding solvent pure water, Na2CO3 and o-chlorobenzoic acid to the reactor, the crude 2-methyl-4-methoxyaniline product is put into the reactor, adding a dispersant and a catalyst ligand, and adding a CuCl catalyst at the same time, acid precipitation, filtering to obtain an MMD intermediate; (4) mixing the obtained intermediate with an organic solvent, decarboxylating, and purifying to obtain 2-methyl-4-methoxydiphenylamine. The by-products can be recovered, and the yield is increased by 6-7% compared with the original process, which reduces the requirements for process conditions.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, in particular to a method for preparing 2-methyl-4-methoxydiphenylamine. Background Art

[0002] Methyl-4-methoxydiphenylamine (MMDPA) is an important organic intermediate widely used in dyes, medicines, rubber, pesticides and other industries. It is mainly used in the synthesis of fluorane thermal and pressure-sensitive dyes. The synthesis technologies of 2-methyl-4-methoxydiphenylamine suitable for industrialization reported in the literature are mainly: The condensation method of 2-methyl-4-methoxyaniline and phenol, adding cyclohexanone, Pd / C and NaOH solution, uses a noble metal catalyst, catalyst poisoning occurs from time to time, and the catalyst needs to be applied multiple times; 2-Methyl-4-methoxyaniline is synthesized by formylation and condensation and hydrolysis with bromobenzene. This method has a long reaction time, complicated steps and high energy consumption. 2-methyl-4-methoxybromobenzene and phenylacetamide method, the synthesis of 2-methyl-4-methoxybromobenzene in this process is complex, bromine cannot be recovered, multiple steam distillations are required, the cost is high, the process is complicated, and the time is long. It has been replaced by 2-methyl-4-methoxyaniline and halogenated benzoic acid method, which uses 2-methyl-4-methoxyaniline and halogenated benzoic acid to add carbonate to toluene to produce a target product intermediate, and then decarboxylates and undergoes subsequent separation and purification steps to obtain the product 2-methyl-4-methoxydiphenylamine. Under this process, 2-methyl-4-methoxyaniline is synthesized by Bamberger rearrangement reaction, in which a noble metal catalyst is used, and its catalytic effect determines the selectivity of the reaction, the requirements for the catalyst are very strict, the frequency of catalyst replacement is high, and the side reaction synthesized 3-methyl-4-aminophenol cannot be treated as waste. These existing defects greatly increase the cost, which is one of the main reasons restricting large-scale industrial production. Summary of the invention

[0003] The invention provides a method for preparing 2-methyl-4-methoxydiphenylamine, wherein 3-methyl-4-aminophenol, one of the main byproducts of the reaction under the existing process, is recovered through a formylation reaction, so that the overall reaction yield is increased by 6-7% compared with the original process, and the requirements for a catalyst and the process conditions for industrial production are reduced.

[0004] The present invention solves the above technical problems through the following technical solutions: A method for preparing 2-methyl-4-methoxydiphenylamine, comprising the following steps: (1) adding o-nitrotoluene, metal catalyst, methanol and sulfuric acid into a reaction kettle, and after nitrogen replacement, maintaining the hydrogen pressure at 0.03-0.05 MPa, reacting at 35-45°C for 3-8 hours, distilling methanol, and washing with alkali to obtain crude 2-methyl-4-methoxyaniline, washing with alkali and adjusting the acidity of the aqueous phase to separate 3-methyl-4-aminophenol solid material; (2) Add 3-methyl-4-aminophenol in step (1) into a reaction kettle, add NaOH solution, and after complete dissolution, add DMAC and pure water, stir thoroughly, then drop dimethyl carbonate, react at 50-60° C. for 2 hours, and wash with alkali to obtain a crude product of 2-methyl-4-methoxyaniline; (3) Adding solvent pure water, Na2CO3, and o-chlorobenzoic acid to the reaction kettle, heating and stirring thoroughly, adding the crude 2-methyl-4-methoxyaniline obtained in (1) and (2) into the reaction kettle, adding a dispersant, adding the ligand in batches, and adding CuCl catalyst at the same time, the reaction temperature is 85-90°C, reacting for 20-30 hours, acid precipitation, and filtering to obtain the MMD intermediate; (4) The obtained intermediate is mixed with an organic solvent, decarboxylated at elevated temperature, and purified by vacuum distillation to obtain 2-methyl-4-methoxydiphenylamine.

[0005] In the above-mentioned method for preparing 2-methyl-4-methoxydiphenylamine, the metal catalyst in step (1) is one or more of Pt and Pd.

[0006] In the above-mentioned method for preparing 2-methyl-4-methoxydiphenylamine, the metal catalyst loading is 1% to 2%.

[0007] In the above-mentioned method for preparing 2-methyl-4-methoxydiphenylamine, the (2) methyl etherification agent is one or more of dimethyl carbonate, dimethyl sulfate, iodomethane, dichloromethyl methyl ether and diazomethane.

[0008] In the above-mentioned method for preparing 2-methyl-4-methoxydiphenylamine, the mass of the solvent pure water in step (3) is 1.2 to 2 times that of MMA.

[0009] In the preparation method of the above 2-methyl-4-methoxydiphenylamine, the dispersant comprises one or more of MF, NNO and lignin sulfonate.

[0010] In the above-mentioned method for preparing 2-methyl-4-methoxydiphenylamine, the mass of the dispersant is 1 / 300 to 1 / 450 of that of MMA.

[0011] The invention discloses a method for preparing 2-methyl-4-methoxydiphenylamine, wherein the ligand comprises oxalic acid diamide and related amide ligands.

[0012] Compared with the prior art, the present invention realizes the recovery of 3-methyl-4-aminophenol, one of the main by-products, through a formylation reaction, and generates an intermediate product through a reaction of the by-product, thereby increasing the overall reaction yield by 6-7% compared with the original process. At the same time, since the by-product can be recovered and then generates an intermediate product, the requirements for the catalyst and the process conditions in industrial production are reduced, thereby saving production costs.

[0013] In step (3), pure water is used as the solvent, thereby reducing the use of traditional solvents such as toluene and DMAC. The purity of the finished product is improved. The addition of a dispersant and an amide ligand lowers the condensation reaction temperature, makes the reaction milder, and reduces the occurrence of side reactions. The present invention has low requirements for the noble metal catalyst, recyclable by-products, and a high yield of 2-methyl-4-methoxydiphenylamine in the overall process.

[0014] The actual yield of 2-methyl-4-methoxyaniline in the present invention is greater than 70%, and the purity is greater than 99.8%; the overall yield from the initial raw material o-nitrotoluene to 2-methyl-4-methoxydiphenylamine is greater than 63%. DETAILED DESCRIPTION

[0015] The specific implementation methods of the present invention are further described in detail below in conjunction with the examples. The following examples are used to illustrate the present invention.

[0016] The following reaction equation is used to illustrate the overall process of the present invention, wherein MMA is 2-methyl-4-methoxyaniline and MMD is 2-methyl-4-methoxydiphenylamine.

[0017] Example 1

[0018] (1) Add 55g (0.4mol) of o-nitrotoluene, 50g (0.5mol) of concentrated industrial sulfuric acid, and 320g (10mol) of methanol, start stirring, add 5g of 2% loaded Pt / C catalyst into the reactor, replace the nitrogen three times, then introduce hydrogen to a pressure of 0.05MPa, heat to 45°C, adjust the speed to start the reaction, and after 3h of reaction, the system temperature does not rise significantly, the hydrogen pressure drops significantly, and the reaction is complete. After the reaction is completed, methanol is separated by distillation, and water is added to adjust the pH. The aqueous phase is separated, washed with alkali, and distilled to obtain 2-methyl-4-methoxyaniline. 44.53g of 2-methyl-4-methoxyaniline is obtained, with a content of 99.89% and a yield of 63.23%.

[0019] (2) Add 38.89 g (0.3 mol) of 3-methyl-4-aminophenol, 16 g (0.4 mol) of NaOH, 50 mL of pure water, and 500 ml of DMAC. Heat to 60°C under nitrogen protection. Stir for 50 min and then drop 63 g (0.7 mol) of DMC. The dropping time is controlled to 2 hours. Keep warm for 1 hour after the reaction. Cool to 40°C after the reaction, wash with alkali, wash with water twice, and dry to remove water. Then, 30.88 g of 2-methyl-4-methoxyaniline is obtained with a content of 94.9% and a yield of 81.83%.

[0020] (3) 233 g (11.1 mol) of water was used as a solvent, 106 g (1 mol) of sodium carbonate solid and 156 g (1 mol) of o-chlorobenzoic acid were added, and after sufficient stirring, 116.45 g (0.85 mol) of 2-methyl-4-methoxyaniline mixed with 0.39 g of dispersant was added to the reactor, and the temperature was raised to 90°C for reaction. 2 g of catalyst ligand and 5 g of CuCl powder catalyst were added twice, and the reaction was stirred for 30 hours. After the reaction was completed, 500 g of pure water was added to fully dissolve the materials. The condensed materials were added dropwise to a low-concentration acidic system with an acid amount of 1.1 times the equivalent of MMA. The condensation product 2-(2-methyl-4-methoxyanilino)-benzoic acid 215.13 g was obtained by filtration and washing, with a yield of 98.38% and an intermediate purity of 97%. 22.99 g of o-chlorobenzoic acid that was not completely reacted was recovered with a purity of 70.33% and a recovery rate of 90%.

[0021] (4) The intermediate 257.27 g (1 mol) was heated and decarboxylated in an N-methylpyrrolidone system to obtain the target product. After distillation, separation and purification, 192.81 g of 2-methyl-4-methoxydiphenylamine was obtained, with a main content of 99.5% and a yield of 90.52%. Example 2

[0022] (1) Add 55g (0.4mol) of o-nitrotoluene, 50g (0.5mol) of concentrated industrial sulfuric acid, and 320g (10mol) of methanol, start stirring, add 5g of 1% loaded Pt / C catalyst into the reactor, replace the nitrogen three times, then introduce hydrogen to a pressure of 0.03MPa, heat to 35°C, adjust the speed to start the reaction, and after 8h of reaction, the system temperature does not rise significantly, the hydrogen pressure drops significantly, and the reaction is complete. After the reaction is completed, methanol is separated by distillation, and water is added to adjust the pH. After the aqueous phase is separated, washed with alkali, and distilled, 2-methyl-4-methoxyaniline can be obtained. 45.32% of 2-methyl-4-methoxyaniline is obtained, the content is 99.82%, and the yield is 64.23%.

[0023] (2) Add 38.89 g (0.3 mol) of 3-methyl-4-aminophenol, 16 g (0.4 mol) of NaOH, 50 mL of pure water, and 500 ml of DMAC. Heat to 50°C under nitrogen protection. Stir for 50 min and then drop 63 g (0.7 mol) of DMC. The dropping time is 2 hours. Keep the temperature for 1 hour after the reaction. Cool to 40°C after the reaction, wash with alkali, wash with water twice, and dry to remove water. Then, 30.95 g of 2-methyl-4-methoxyaniline is obtained, with a content of 95.4% and a yield of 82.1%.

[0024] (3) 140 g (11.1 mol) of water was used as a solvent, 106 g (1 mol) of sodium carbonate solid and 156 g (1 mol) of o-chlorobenzoic acid were added, and after sufficient stirring, 116.45 g (0.85 mol) of 2-methyl-4-methoxyaniline mixed with 0.26 g of dispersant was added to the reactor, and the temperature was raised to 85°C for reaction. 2 g of catalyst ligand and 5 g of CuCl powder catalyst were added in batches, and the reaction was stirred for 30 hours. After the reaction was completed, 500 g of pure water was added to fully dissolve the materials. The condensed materials were added dropwise to a low-concentration acidic system with an acid amount of 1.1 times the equivalent of MMA. The condensation product 2-(2-methyl-4-methoxyanilino)-benzoic acid was obtained by filtration and washing, with a yield of 87.23% and an intermediate content of 95%. 36.70 g of o-chlorobenzoic acid that was not completely reacted was recovered with a purity of 72% and a recovery rate of 91%.

[0025] (4) The intermediate 257.27 g (1 mol) was heated and decarboxylated in an N-methylpyrrolidone system to obtain the target product. After distillation, separation and purification, 192.72 g of 2-methyl-4-methoxydiphenylamine was obtained with a content of 99.63% and a yield of 90.48%. Example 3

[0026] (1) Add 55g (0.4mol) of o-nitrotoluene, 50g (0.5mol) of concentrated industrial sulfuric acid, and 320g (10mol) of methanol, start stirring, add 5g of 1% loaded Pt / C catalyst into the reactor, replace the nitrogen three times, then introduce hydrogen to a pressure of 0.04MPa, raise the temperature to 43°C, adjust the speed to start the reaction, and after 7h of reaction, the system temperature does not rise significantly, the hydrogen pressure drops significantly, and the reaction is complete. After the reaction is completed, methanol is separated by distillation, and water is added to adjust the pH. The aqueous phase is separated, washed with alkali, and distilled to obtain 2-methyl-4-methoxyaniline. 45.20g of 2-methyl-4-methoxyaniline is obtained, with a content of 99.85% and a yield of 64.19%.

[0027] (2) Add 38.89 g (0.3 mol) of 3-methyl-4-aminophenol, 18 g (0.45 mol) of NaOH, 50 mL of pure water, and 500 ml of DMAC. Heat to 55 °C under nitrogen protection. Stir for 50 min and then drop 63 g (0.7 mol) of DMC. The dropping time is controlled within 2 hours. Keep warm for 1 hour after the reaction. Cool to 40 °C after the reaction. Wash with alkali and water twice, and dry to remove water. Then, 28.69 g of 2-methyl-4-methoxyaniline is obtained, with a content of 88.13% and a yield of 83.25%.

[0028] (3) 200 g (11.1 mol) of water was used as a solvent, 106 g (1 mol) of solid sodium carbonate and 156 g (1 mol) of o-chlorobenzoic acid were added, and after sufficient stirring, 116.45 g (0.85 mol) of 2-methyl-4-methoxyaniline mixed with 0.3 g of dispersant was added to the reactor, and the temperature was raised to 87°C for reaction. 2 g of catalyst ligand and 5 g of CuCl powder catalyst were added in batches, and the reaction was stirred for 27 hours. After the reaction was completed, 500 g of pure water was added to fully dissolve the materials. The condensed materials were added dropwise to a low-concentration acidic system with an acid amount of 1.1 times the equivalent of MMA. The condensation product 2-(2-methyl-4-methoxyanilino)-benzoic acid 217.50 g was obtained by filtration and washing, with a yield of 99.46% and an intermediate purity of 97%. 24.69 g of o-chlorobenzoic acid that was not completely reacted was recovered with a content of 73.4% and a recovery rate of 91.2%.

[0029] (4) The intermediate 257.27 g (1 mol) was heated and decarboxylated in an N-methylpyrrolidone system to obtain the target product. After distillation, separation and purification, 193.40 g of 2-methyl-4-methoxydiphenylamine was obtained with a content of 99.63% and a yield of 90.8%.

[0030] Comparative Example 1 (1) Add 137 g (1 mol) of 2-methyl-4-methoxyaniline and 90 ml of 85% formic acid, keep the mixture at 100°C for 1 hour, and then evaporate the water and excess formic acid. Add the system to 500 ml of the effluent water, cool it, filter and separate the precipitate, and dry it to obtain 153.45 g of N-formyl-2-methyl-4-methoxyaniline, with a content of 99.6% and a yield of 93%. (2) Add 148g (0.9mol) of N-formyl-2-methyl-4-methoxyaniline and 157g (1mol) of bromobenzene, heat to 110°C and stir until N-formyl-2-methyl-4-methoxyaniline is completely dissolved, add 68g of potassium carbonate, 2g of copper powder, and 2g of iodine, and heat to 200°C under 0.1MPa nitrogen protection. Keep the temperature for 2h, then evaporate the excess bromobenzene, extract with acetone to remove the copper powder and inorganic salts. After distilling off the acetone, add 1300ml of water and 90g (2.25mol) of sodium hydroxide, hydrolyze at 180°C for 5h, cool and collect the solid, recrystallize with ethanol, and dry to obtain 164g (0.77mol) of 2-methyl-4-methoxydiphenylamine, with a content of 99.82% and a yield of 85.6%.

[0031] Comparative Example 2 (1) Add 32.4 g (0.5 mol) of m-methylphenol, then add 500 ml of DMAC and 40.98 g (0.32 mol) of DMS, and heat to 140°C under nitrogen protection. The reaction is controlled for 5 hours. After the reaction is completed, cool to 40°C, wash with alkali, wash with water twice, and separate 52.46 g of 2-methylanisole by distillation. The content is 93.66% and the yield is 86.1%.

[0032] (2) Add 147 g (1.36 mol) of 2-methylanisole, 300 ml of ethanol, and 84 g (1.5 mol) of potassium hydroxide. The reaction temperature is 60°C, and monobromomethane is introduced. The reaction is carried out for 5 hours. After distillation and separation, 134 g of 2-methyl-4-methoxybromobenzene is obtained. The content of the 2-methyl-4-methoxybromobenzene is 98.2%, and the yield is 81%.

[0033] (3) Add 60.3 g (0.3 mol) of 2-methyl-4-methoxybromobenzene and 13.5 g (0.1 mol) of benzylacetamide, 0.8 g of copper powder, 13.8 g (0.1 mol) of potassium carbonate, and 0.1 g of iodine, raise the temperature to 210°C, and react for 10 hours. After the reaction is completed, add 5.6 g (0.1 mol) of potassium hydroxide and 88 g of isoamyl alcohol to reflux, evaporate the isoamyl alcohol, extract with toluene, and distill and recover the toluene to obtain 18.96 g of 2-methyl-4-methoxydiphenylamine with a content of 95.22% and a yield of 89%.

[0034] The invention starts with cheap raw material o-nitrotoluene, and synthesizes MMA, one of the raw materials, through Bamberger rearrangement reaction. After the reaction is completed, 3-methyl-4-aminophenol, one of the main byproducts of the reaction under the original process, is separated by post-treatment alkali washing. The byproduct is used as a waste and becomes solid waste after water treatment, acid adjustment and separation. By selecting a suitable reagent dimethyl carbonate and optimizing the formylation reaction conditions, the byproduct is recovered, so that the overall yield of the reaction is increased by 6-7% compared with the original process, while reducing the requirements for the catalyst and the process conditions of industrial production, achieving a mild reaction at 40°C and a hydrogen pressure of 0.05MP, and reducing the consumption of public works.

[0035] In step (3), the traditional toluene and DMAC are replaced with pure water to avoid agglomeration in the system, thereby affecting the reaction. The addition of dispersants and amide ligands lowers the condensation reaction temperature, makes the reaction milder, reduces the occurrence of side reactions, and achieves the preparation of 2-methyl-4-methoxydiphenylamine with low requirements for precious metal catalysts, recoverable by-products, and high yield of the overall process. Low requirements for precious metal catalysts, recoverable by-products, and high yield of the overall process.

[0036] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing 2-methyl-4-methoxydiphenylamine, characterized in that: The reaction steps include: (1) adding o-nitrotoluene, metal catalyst, methanol and sulfuric acid into a reaction kettle, and after nitrogen replacement, maintaining the hydrogen pressure at 0.03-0.05 MPa, reacting at 35-45°C for 3-8 hours, distilling methanol, and washing with alkali to obtain crude 2-methyl-4-methoxyaniline, washing with alkali and adjusting the acidity of the aqueous phase to separate 3-methyl-4-aminophenol solid material; (2) Add 3-methyl-4-aminophenol in step (1) into a reaction kettle, add NaOH solution, add DMAC and pure water after complete dissolution, stir thoroughly, add dimethyl carbonate dropwise, react at 50-60° C. for 2 hours, and wash with alkali to obtain a crude product of 2-methyl-4-methoxyaniline; (3) Adding solvent pure water, Na2CO3, and o-chlorobenzoic acid to the reaction kettle, heating and stirring thoroughly, adding the crude 2-methyl-4-methoxyaniline obtained in (1) and (2) into the reaction kettle, adding a dispersant, adding the ligand in batches, and adding CuCl catalyst at the same time, the reaction temperature is 85-90°C, reacting for 20-30 hours, acid precipitation, and filtering to obtain the MMD intermediate; (4) The obtained intermediate is mixed with an organic solvent, decarboxylated at elevated temperature, and purified by vacuum distillation to obtain 2-methyl-4-methoxydiphenylamine.

2. The method for preparing 2-methyl-4-methoxydiphenylamine according to claim 1, characterized in that: The metal catalyst in step (1) is one or more of Pt and Pd.

3. The method for preparing 2-methyl-4-methoxydiphenylamine according to claim 1, characterized in that: The metal catalyst loading is 1% to 2%.

4. The method for preparing 2-methyl-4-methoxydiphenylamine according to claim 1, characterized in that: The (2) methyl etherification agent is one or more of dimethyl carbonate, dimethyl sulfate, methyl iodide, dichloromethyl methyl ether, and diazomethane.

5. The method for preparing 2-methyl-4-methoxydiphenylamine according to claim 1, characterized in that: The mass of the solvent pure water in step (3) is 1.2 to 2 times that of MMA.

6. The method for preparing 2-methyl-4-methoxydiphenylamine according to claim 1, characterized in that: The dispersant includes one or more of MF, NNO and lignin sulfonate.

7. The method for preparing 2-methyl-4-methoxydiphenylamine according to claim 1, characterized in that: The mass of the dispersant is 1 / 300 to 1 / 450 of that of the MMA.

8. The method for preparing 2-methyl-4-methoxydiphenylamine according to claim 1, characterized in that: The ligands include oxalic acid diamide and related amide ligands.

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