Purification method of 3, 3 '-dichloro-4, 4'-diaminodiphenylmethane

Abstract

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a purification method of 3, 3 '-dichloro-4, 4'-diaminodiphenylmethane, which comprises the following steps: placing a 3, 3 '-dichloro-4, 4'-diaminodiphenylmethane crude product at pH gt; the invention discloses a method for purifying 3, 3 '-dichloro-4, 4'-diaminodiphenylmethane, which comprises the following steps: reacting 3, 3 '-dichloro-4, 4'-diaminodiphenylmethane in an alkaline solution containing 3, 3 '-dichloro-4, 4'-diaminodiphenylmethane, separating, washing, drying, adding into an organic solvent, stirring and mixing, heating for dissolving, and cooling for devitrification to obtain a purified product of 3, 3 '-dichloro-4, 4'-diaminodiphenylmethane, The method for purifying 3, 3 '-dichloro-4, 4'-diaminodiphenylmethane provided by the invention has the advantages of high yield (the yield is greater than or equal to 90%), high purity (greater than or equal to 99.0%) and good impurity removal effect, and is more suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the field of pharmaceutical chemistry and discloses a method for purifying 3,3'-dichloro-4,4'-diaminodiphenylmethane Background Art

[0002] 3,3'-Dichloro-4,4'-diaminodiphenylmethane (commonly known as MOCA, molecular formula: C 13 H 12 N2C l2 , molecular weight: 267.16, white or light yellow crystals at room temperature, relative density of 1.44 at 25°C, melting point of 110°C, decomposition temperature of 296°C). 3,3'-dichloro-4,4'-diaminodiphenylmethane is insoluble in water, but soluble in organic solvents such as isopropanol, acetone, toluene, chlorobenzene, dimethyl sulfoxide (DMSO), dimethylformamide (DMF), and tetrahydrofuran (THF). When heated at high temperatures or for a long time, 3,3'-dichloro-4,4'-diaminodiphenylmethane will oxidize and the color will become darker. 3,3'-Dichloro-4,4'-diaminodiphenylmethane is mainly used as a chain extender and curing agent for toluene diisocyanate (TDI)-based prepolymers. It is widely used in the machinery industry, automobile and aircraft manufacturing industries, mining industries, sports facilities and various light manufacturing industries. It can also be used as a crosslinker for polyurethane (PU) coatings and adhesives, a curing agent for epoxy resins, and high electrical resistance products. Its structure is as follows:

[0003]

[0004] Chinese patent CN103936594A provides a method for preparing 3,3'-dichloro-4,4'-diaminodiphenylmethane by adding o-chloroaniline, cation exchange resin and distilled water into a reaction container, stirring evenly and then adding formaldehyde aqueous solution.

[0005] Chinese patent CN105294448A provides a method for continuously preparing 3,3'-dichloro-4,4'-diaminodiphenylmethane derivatives with solid acid catalysis, wherein a condensation reaction is carried out with solid acid catalysis in a one-stage or two-stage fixed bed reactor to obtain 3,3'-dichloro-4,4'-diaminodiphenylmethane derivatives.

[0006] Chinese patent CN106986777B provides a method for preparing 3,3'-dichloro-4,4'-diaminodiphenylmethane derivatives using a microreactor, with a yield of 85% and a purity of 99%.

[0007] The yield and purity of the method used in the above report need to be improved. Therefore, based on the defects of the existing technology, it is urgent to invent a purification method that does not require repeated purification and has excellent purification effect. Summary of the invention

[0008] The following is a summary of some aspects of the present invention, but is not intended to limit the present invention. When there is a discrepancy between the disclosure of this specification and the referenced document, the disclosure of this specification shall prevail.

[0009] The object of the present invention is to provide a method for purifying 3,3'-dichloro-4,4'-diaminodiphenylmethane.

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

[0011] A method for purifying 3,3'-dichloro-4,4'-diaminodiphenylmethane comprises the following steps:

[0012] Step (1) placing the crude 3,3'-dichloro-4,4'-diaminodiphenylmethane in an alkaline solution with a pH value greater than 7 for reaction, separation, washing and drying;

[0013] Step (2) adding the crude product obtained in step (1) into an organic solvent, stirring and mixing, and heating to dissolve;

[0014] Step (3) cooling and crystallizing, filtering and drying to obtain a purified product of 3,3'-dichloro-4,4'-diaminodiphenylmethane.

[0015] Furthermore, 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.

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

[0017] Furthermore, 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.

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

[0019] Furthermore, in the step (2), the organic solvent is one or more of ethanol, acetone, butanone, toluene, and chlorobenzene, preferably an acetone / toluene mixed solution.

[0020] Furthermore, in the step (2), the volume ratio of acetone to toluene of the organic solvent is (1-5):1, and preferably the volume ratio of acetone to toluene is 3:1.

[0021] Furthermore, in the step (2), the mass (g) / volume (ml) ratio of the crude 3,3'-dichloro-4,4'-diaminodiphenylmethane to the organic solvent is 1:(0.5-5), preferably the mass (g) / volume (ml) ratio of the crude 3,3'-dichloro-4,4'-diaminodiphenylmethane to the organic solvent is 1:3.

[0022] Furthermore, in the step (2), the temperature is raised to 50-70°C, preferably 60°C.

[0023] Furthermore, the cooling in step (3) is a gradient cooling, wherein the temperature is first lowered to 30-50°C and kept warm for crystallization for 1-2 hours; and then the temperature is lowered to 15-25°C and kept warm for crystallization for 1-2 hours.

[0024] Furthermore, the cooling in step (3) is a gradient cooling, the first cooling to 35°C, keeping the temperature for crystallization for 1 to 2 hours; the second cooling to 20°C, keeping the temperature for crystallization for 1 to 2 hours.

[0025] Beneficial 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 3,3'-dichloro-4,4'-diaminodiphenylmethane of the present invention has excellent impurity removal effect for crude 3,3'-dichloro-4,4'-diaminodiphenylmethane, and the purified product has high quality and good crystallinity. Due to the good purification effect, repeated refining is not required, the process yield is high, the production cost is low, and it is more suitable for industrial production.

[0028] 2. The purification method of 3,3'-dichloro-4,4'-diaminodiphenylmethane of the present invention has simple operation steps, and an ordinary reaction tank can meet the requirements. It has a wide range of applications and has a significant purification effect on most impurities in crude 3,3'-dichloro-4,4'-diaminodiphenylmethane, including a variety of impurities that are extremely difficult to purify, with a purity of up to 99.93%. In addition, the method of the present invention can obtain a higher yield on the basis of meeting the high product quality. DETAILED DESCRIPTION

[0029] Unless otherwise indicated or there is an obvious conflict in the context, all technical and scientific terms used herein have the same meaning as those generally understood by those of ordinary skill in the art to which the invention belongs. If there is a conflict, the definitions provided in the 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] Embodiment 1:

[0031] 1. Place the crude 3,3'-dichloro-4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separation, washing and drying;

[0032] 2. Add the crude product obtained in step 1 to a mixed solvent of acetone / toluene, wherein the mass (g) to volume (ml) ratio of the crude product to the mixed solvent is 1:3; the volume ratio of acetone to toluene is 3:1, stir and mix, raise the temperature to 60°C, and wait for the solution to become clear;

[0033] 3. Cool down and crystallize. First cool down to 35°C and keep warm for 1 to 2 hours. Then cool down to 20°C and keep warm for 1 to 2 hours. Then filter and dry to obtain purified 3,3'-dichloro-4,4'-diaminodiphenylmethane with a yield of 92% and a purity of 99.3%.

[0034] Embodiment 2:

[0035] 1. Place the crude 3,3'-dichloro-4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separation, washing and drying;

[0036] 2. Add the crude product obtained in step 1 to a mixed solvent of acetone / toluene, wherein the mass (g) to volume (ml) ratio of the crude product to the mixed solvent is 1:0.5; the volume ratio of acetone to toluene is 1:1, stir and mix, heat to 50°C, and wait for the solution to become clear;

[0037] 3. Cool down and crystallize. First cool down to 30°C and keep warm for 1 to 2 hours. Then cool down to 15°C and keep warm for 1 to 2 hours. Then filter and dry to obtain purified 3,3'-dichloro-4,4'-diaminodiphenylmethane with a yield of 91% and a purity of 99.0%.

[0038] Embodiment 3:

[0039] 1. Place the crude 3,3'-dichloro-4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separation, washing and drying;

[0040] 2. Add the crude product obtained in step 1 to a mixed solvent of acetone / toluene, wherein the mass (g) to volume (ml) ratio of the crude product to the mixed solvent is 1:5; the volume ratio of acetone to toluene is 5:1, stir and mix, raise the temperature to 70°C, and wait for the solution to become clear;

[0041] 3. Cool down and crystallize. First, cool down to 50°C and keep warm for 1 to 2 hours. Then cool down to 25°C and keep warm for 1 to 2 hours. Then filter and dry to obtain purified 3,3'-dichloro-4,4'-diaminodiphenylmethane with a yield of 88% and a purity of 98.9%.

[0042] Embodiment 4:

[0043] 1. Place the crude 3,3'-dichloro-4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separation, washing and drying;

[0044] 2. Add the crude product obtained in step 1 to a mixed solvent of acetone / toluene, wherein the mass (g) to volume (ml) ratio of the crude product to the mixed solvent is 1:0.2; the volume ratio of acetone to toluene is 0.5:1, stir and mix, heat to 45°C, and wait for the solution to become clear;

[0045] 3. Cool down and crystallize. First cool down to 25°C and keep warm for 1 to 2 hours. Then cool down to 10°C and keep warm for 1 to 2 hours. Then filter and dry to obtain purified 3,3'-dichloro-4,4'-diaminodiphenylmethane with a yield of 89% and a purity of 97.8%.

[0046] Embodiment 5:

[0047] 1. Place the crude 3,3'-dichloro-4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separation, washing and drying;

[0048] 2. Add the crude product obtained in step 1 to a mixed solvent of acetone / toluene, wherein the mass (g) to volume (ml) ratio of the crude product to the mixed solvent is 1:6; the volume ratio of acetone to toluene is 6:1, stir and mix, raise the temperature to 75°C, and wait for the solution to become clear;

[0049] 3. Cool down and crystallize. First cool down to 55°C and keep warm for 1 to 2 hours. Then cool down to 30°C and keep warm for 1 to 2 hours. Then filter and dry to obtain purified 3,3'-dichloro-4,4'-diaminodiphenylmethane with a yield of 82% and a purity of 98.3%.

[0050] Embodiment 6:

[0051] 1. Place the crude 3,3'-dichloro-4,4'-diaminodiphenylmethane in a sodium hydroxide solution for reaction, separation, washing and drying;

[0052] 2. Add the crude product obtained in step 1 to a mixed solvent of acetone / toluene, wherein the mass (g) to volume (ml) ratio of the crude product to the mixed solvent is 1:3; the volume ratio of acetone to toluene is 3:1, stir and mix, raise the temperature to 60°C, and wait for the solution to become clear;

[0053] 3. Cool down and crystallize. First cool down to 35°C and keep warm for 1 to 2 hours. Then cool down to 20°C and keep warm for 1 to 2 hours. Then filter and dry to obtain purified 3,3'-dichloro-4,4'-diaminodiphenylmethane with a yield of 92% and a purity of 99.1%.

[0054] Embodiment 7:

[0055] 1. Add crude 3,3'-dichloro-4,4'-diaminodiphenylmethane to acetone, where the ratio of crude mass (g) to acetone volume (ml) is 1:3; stir to mix, heat to 60°C, and wait for the solution to become clear;

[0056] 2. Cool down and crystallize, cool to 20°C, keep warm for 1 to 2 hours, filter and dry to obtain purified 3,3'-dichloro-4,4'-diaminodiphenylmethane with a yield of 78% and a purity of 98.4%.

[0057] The above is a description of a specific embodiment of the present invention. It should be understood that the present invention is not limited to the above embodiment, and the above embodiment and description are only for illustrating the principle of the present invention.

[0058] Those skilled in the art may make various non-substantial changes and improvements to the present invention without departing from the concept of the present invention, all of which fall within the scope of protection claimed by the present invention.

Claims

1. A method for purifying 3,3'-dichloro-4,4'-diaminodiphenylmethane, comprising the following steps: Step (1) placing the crude 3,3'-dichloro-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, stirring and mixing, and heating to dissolve; Step (3) cooling and crystallizing, filtering and drying to obtain a purified product of 3,3'-dichloro-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, acetone, butanone, toluene and chlorobenzene, preferably an acetone / toluene mixed solution.

6. The purification method according to claim 1, characterized in that In the step (2), the volume ratio of acetone to toluene of the organic solvent is (1-5):1, and preferably the volume ratio of acetone to toluene is 3:

1.

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

3.

8. The purification method according to claim 1, characterized in that In the step (2), the temperature is raised to 50-70°C, preferably 60°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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