Purification method of 4, 4 '-diaminodiphenylmethane

Abstract

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a purification method for preparing 4, 4 '-diaminodiphenylmethane, which comprises the following steps: placing a 4, 4'-diaminodiphenylmethane crude product at pH gt; the 4, 4 '-diaminodiphenylmethane purification method provided by the invention is high in yield (the yield is greater than or equal to 90%), high in purity (greater than or equal to 99.0%) and good in impurity removal effect, and is more suitable for industrial production.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical chemistry and discloses a purification method of 4,4'-diaminodiphenylmethane Background Art

[0002] 4,4'-Diaminodiphenylmethane is an important chemical intermediate, which can be mainly used for the production of diisocyanates, such as MDI and HMDI, and can also be widely used for the preparation of high-grade insulating materials, such as bismaleimide resin, polyimide (PI), polyesterimide (PEI), insulating materials, etc.; in addition, it can also be used as a chain extender for polyurethane elastomers and a curing agent for epoxy resins. The various products synthesized from MDA have excellent heat resistance, insulation properties, mechanical properties and wear resistance, etc. It is a fine chemical product with wide uses and excellent properties, and its structure is as follows:

[0003]

[0004] Chinese Patent CN101007767A reported a catalytic synthesis process of MDA, which uses aniline and formaldehyde as raw materials and is prepared by an intermittent one-step condensation reaction under the action of a solid acid catalyst

[0005] Chinese Patent CN105294448A provides a method for continuously preparing 4,4'-diaminodiphenylmethane derivatives by solid acid catalysis. The condensation reaction is carried out by solid acid catalysis in a one-stage or two-stage fixed-bed reactor to obtain 4,4'-diaminodiphenylmethane derivatives

[0006] Chinese Patent CN106986777B reported that the crude product of MDA was recrystallized with ethanol, filtered and dried to obtain MDA, with a molar yield of 87% and a purity of 99%

[0007] The methods reported above have room for improvement in terms of both yield and purity. Therefore, based on the defects of the existing technology, it is urgent to invent a refining method that does not require repeated refining and has excellent purification effects Summary of the Invention

[0008] Only some aspects of the present invention are briefly described below and are not limited thereto. When there are differences between the disclosure content of this specification and the cited literature, the disclosure content of this specification shall prevail

[0009] The purpose of the present invention is to provide a purification method of 4,4'-diaminodiphenylmethane

[0010] The technical solution adopted by the present invention is as follows

[0011] A purification method of 4,4'-diaminodiphenylmethane, comprising the following steps

[0012] Step (1): Place the crude 4,4'-diaminodiphenylmethane in an alkaline solution with pH > 7 for reaction, separate, wash, and dry.

[0013] Step (2): Add the crude product obtained in step (1) to an organic solvent, add water and stir to mix, and heat to dissolve.

[0014] Step (3): Cool for crystallization, filter, and dry to obtain the purified 4,4'-diaminodiphenylmethane.

[0015] Further, in step (1), the alkaline solution is any one or a combination of an inorganic base solution and an organic base solution, wherein the solvent constituting the alkaline solution is selected from any one or a combination of water and an organic solvent.

[0016] Further, the inorganic base is selected from any one or a combination of hydroxides and strong base weak acid salts.

[0017] Further, the hydroxide is selected from any one or a combination of sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, rubidium hydroxide, and cesium hydroxide; the strong base weak acid salt is selected from any one or a combination of sodium carbonate, potassium carbonate, lithium carbonate, rubidium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, cesium bicarbonate, sodium phosphate, potassium phosphate, lithium phosphate, rubidium phosphate, cesium phosphate, sodium sulfite, potassium sulfite, and lithium sulfite.

[0018] Further, the hydroxide is selected from one or more of sodium hydroxide and potassium hydroxide.

[0019] Further, in step (2), the organic solvent is one or more of ethanol, isopropanol, ether, toluene, and DMF, preferably an ethanol / isopropanol mixed solution.

[0020] Further, in step (2), the volume ratio of ethanol to isopropanol in the organic solvent is (1 - 5):1, preferably 2:1.

[0021] Further, in step (2), the mass (g) of the crude 4,4'-diaminodiphenylmethane to the volume (ml) of the organic solvent and water is 1:(0.5 - 5):(0.1 - 0.5), preferably 1:3:0.3.

[0022] Further, in step (2), heat to 60 - 70°C, preferably 65°C.

[0023] Further, in step (3), the cooling is gradient cooling. First, cool to 30 - 50°C and keep warm for crystallization for 1 - 2 hours; then cool to 15 - 25°C and keep warm for crystallization for 1 - 2 hours.

[0024] Further, in the step (3), the temperature reduction is a gradient temperature reduction. The temperature is first reduced to 35 °C and crystallization is carried out while maintaining the temperature for 1 to 2 hours; then the temperature is reduced to 20 °C and crystallization is carried out while maintaining the temperature for 1 to 2 hours.

[0025] Advantageous technical effects of the present invention

[0026] Compared with the prior art, the technical solution of the present invention has the following advantages:

[0027] 1. The purification method of 4,4'-diaminodiphenylmethane of the present invention has excellent impurity removal effect on the crude product of 4,4'-diaminodiphenylmethane. The purified product has high quality and good crystallinity. Due to the good purification effect, it does not need to be repeatedly refined many times, has high process yield, low production cost, and is more suitable for industrial production.

[0028] 2. The purification method of 4,4'-diaminodiphenylmethane of the present invention has simple operation steps. An ordinary reaction tank can meet the requirements. It has a wide application range, and has a significant purification effect on most impurities in the crude product of 4,4'-diaminodiphenylmethane, including various impurities that are extremely difficult to purify. The purity can be as high as 99.95%. In addition, the method of the present invention can obtain a relatively high yield on the basis of meeting the high quality of the product. Specific embodiments

[0029] Unless otherwise specified or there is an obvious conflict in the context, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention belongs. If there is a contradiction, the definition provided in this application shall prevail. When a trade name appears in this article, it is intended to refer to the corresponding commodity or its active ingredient. All patents, published patent applications and publications cited herein are incorporated herein by reference.

[0030] Example 1:

[0031] 1. Place the crude product of 4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separate, wash, and dry;

[0032] 2. Add the crude product obtained in step 1 to a mixed solvent of ethanol / isopropanol, add water and stir to mix. The mass ratio of the crude product (g) to the volume ratio of the mixed solvent to water (ml) is 1:3:0.3; the volume ratio of ethanol to isopropanol is 2:1, and the temperature is raised to 65 °C until the solution becomes clear;

[0033] 3. Reduce the temperature for crystallization. The temperature is first reduced to 35 °C and crystallization is carried out while maintaining the temperature for 1 to 2 hours. Then the temperature is reduced to 20 °C and crystallization is carried out while maintaining the temperature for 1 to 2 hours. Filter and dry to obtain the purified product of 4,4'-diaminodiphenylmethane, with a yield of 93% and a purity of 99.5%.

[0034] Example 2:

[0035] 1. Place the crude 4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separate, wash, and dry;

[0036] 2. Add the crude product obtained in step 1 to a mixed solvent of ethanol / isopropanol, add water and stir to mix, where the mass (g) of the crude product and the volume ratio of the mixed solvent to water is 1:0.5:0.1; the volume ratio of ethanol to isopropanol is 1:1, heat to 60 °C, and wait for the solution to become clear;

[0037] 3. Cool down for crystallization, first cool down to 30 °C, keep the temperature for crystallization for 1 - 2 hours, then cool down to 15 °C again, keep the temperature for crystallization for 1 - 2 hours, filter, and dry to obtain the purified 4,4'-diaminodiphenylmethane, with a yield of 92% and a purity of 98.9%.

[0038] Example 3:

[0039] 1. Place the crude 4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separate, wash, and dry;

[0040] 2. Add the crude product obtained in step 1 to a mixed solvent of ethanol / isopropanol, add water and stir to mix, where the mass (g) of the crude product and the volume ratio of the mixed solvent to water is 1:5:0.5; the volume ratio of ethanol to isopropanol is 5:1, heat to 70 °C, and wait for the solution to become clear;

[0041] 3. Cool down for crystallization, first cool down to 50 °C, keep the temperature for crystallization for 1 - 2 hours, then cool down to 25 °C again, keep the temperature for crystallization for 1 - 2 hours, filter, and dry to obtain the purified 4,4'-diaminodiphenylmethane, with a yield of 89% and a purity of 99.1%.

[0042] Example 4:

[0043] 1. Place the crude 4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separate, wash, and dry;

[0044] 2. Add the crude product obtained in step 1 to a mixed solvent of ethanol / isopropanol, stir to mix, where the mass (g) of the crude product and the volume ratio of the mixed solvent to water is 1:0.2:0.05; the volume ratio of ethanol to isopropanol is 0.5:1, heat to 55 °C, and wait for the solution to become clear;

[0045] 3. Cool down for crystallization, first cool down to 25 °C, keep the temperature for crystallization for 1 - 2 hours, then cool down to 10 °C again, keep the temperature for crystallization for 1 - 2 hours, filter, and dry to obtain the purified 4,4'-diaminodiphenylmethane, with a yield of 89% and a purity of 97.2%.

[0046] Example 5:

[0047] 1. Place the crude 4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separate, wash, and dry.

[0048] 2. Add the crude product obtained in step 1 to a mixed solvent of ethanol / isopropanol, add water and stir to mix. The ratio of the mass of the crude product (g) to the volume of the mixed solvent and water (ml) is 1:6:0.6; the volume ratio of ethanol to isopropanol is 8:1. Heat up to 75 °C and wait until the solution is clear.

[0049] 3. Cool down for crystallization. First cool down to 55 °C and keep the temperature for crystallization for 1 - 2 hours. Then cool down to 30 °C and keep the temperature for crystallization for 1 - 2 hours. Filter and dry to obtain the purified 4,4'-diaminodiphenylmethane. The yield is 80% and the purity is 98.7%.

[0050] Example 6:

[0051] 1. Place the crude 4,4'-diaminodiphenylmethane in a sodium hydroxide solution for reaction, separate, wash, and dry.

[0052] 2. Add the crude product obtained in step 1 to a mixed solvent of ethanol / isopropanol, add water and stir to mix. The ratio of the mass of the crude product (g) to the volume of the mixed solvent and water (ml) is 1:3:0.3; the volume ratio of ethanol to isopropanol is 2:1. Heat up to 65 °C and wait until the solution is clear.

[0053] 3. Cool down for crystallization. First cool down to 35 °C and keep the temperature for crystallization for 1 - 2 hours. Then cool down to 20 °C and keep the temperature for crystallization for 1 - 2 hours. Filter and dry to obtain the purified 4,4'-diaminodiphenylmethane. The yield is 91% and the purity is 99.2%.

[0054] Example 7:

[0055] 1. Add the crude 4,4'-diaminodiphenylmethane to ethanol. The ratio of the mass of the crude product (g) to the volume of ethanol (ml) is 1:3; stir to mix, heat up to 65 °C and wait until the solution is clear.

[0056] 2. Cool down for crystallization. Cool down to 25 °C and keep the temperature for crystallization for 1 - 2 hours. Filter and dry to obtain the purified 4,4'-diaminodiphenylmethane. The yield is 77% and the purity is 97.5%.

[0057] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above embodiments. What is described in the above embodiments and the specification is only to illustrate the principle of the present invention.

[0058] Without departing from the concept of the present invention, those skilled in the art will make various non-substantial changes and improvements to the present invention, and these all fall within the scope claimed by the present invention.

Claims

1. A method for purifying 4,4'-diaminodiphenylmethane, comprising the following steps: Step (1) placing the crude 4,4'-diaminodiphenylmethane in an alkaline solution with a pH value greater than 7 for reaction, separation, washing and drying; Step (2) adding the crude product obtained in step 1 to an organic solvent, adding water, stirring and mixing, and heating to dissolve; Step (3) cooling, crystallizing, filtering and drying to obtain a purified product of 4,4'-diaminodiphenylmethane.

2. The purification method according to claim 1, characterized in that The alkaline solution in step (1) is any one of an inorganic alkaline solution and an organic alkaline solution or a combination thereof, wherein the solvent constituting the alkaline solution is selected from any one of water and an organic solvent or a combination thereof.

3. The purification method according to claim 2, characterized in that The inorganic base is selected from any one of hydroxides, strong base and weak acid salts, or a combination thereof.

4. The purification method according to claim 2, characterized in that The hydroxide is selected from any one of sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, rubidium hydroxide, and cesium hydroxide, or a combination thereof; the strong base and weak acid salt is selected from any one of sodium carbonate, potassium carbonate, lithium carbonate, rubidium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, cesium bicarbonate, sodium phosphate, potassium phosphate, lithium phosphate, rubidium phosphate, cesium phosphate, sodium sulfite, potassium sulfite, and lithium sulfite, or a combination thereof.

5. The purification method according to claim 1, characterized in that The organic solvent in step (2) is one or more of ethanol, isopropanol, ether, toluene and DMF, preferably an ethanol / isopropanol mixed solution.

6. The purification method according to claim 5, characterized in that The volume ratio of ethanol to isopropanol is (1-5):1, and preferably the volume ratio of ethanol to isopropanol is 2:

1.

7. The purification method according to claim 1, characterized in that In the step (2), the ratio of the mass (g) of crude 4,4'-diaminodiphenylmethane to the volume (ml) of organic solvent and water is 1:(0.5-5):(0.1-0.5), and preferably the ratio of the mass (g) of crude 4,4'-diaminodiphenylmethane to the volume (ml) of organic solvent and water is 1:3:0.

3.

8. The purification method according to claim 1, characterized in that In the step (2), the temperature is raised to 60-70°C, preferably 65°C.

9. The purification method according to claim 1, characterized in that The cooling in step (3) is a gradient cooling, the first cooling is to 30-50°C, and the temperature is kept for crystallization for 1-2 hours; the second cooling is to 15-25°C, and the temperature is kept for crystallization for 1-2 hours.

10. The purification method according to claim 1, characterized in that: The cooling in step (3) is a gradient cooling, first cooling to 35°C and keeping warm for crystallization for 1 to 2 hours; then cooling again to 20°C and keeping warm for crystallization for 1 to 2 hours.

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