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

Abstract

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a purification method of 3, 3 '-dimethyl-4, 4'-diaminodiphenylmethane, which comprises the following steps: placing a 3, 3 '-dimethyl-4, 4'-diaminodiphenylmethane crude product at pH gt; the preparation method comprises the following steps: reacting in an alkaline solution of 3, 3 '-dimethyl-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 '-dimethyl-4, 4'-diaminodiphenylmethane. The 3, 3 '-dimethyl-4, 4'-diaminodiphenylmethane purification method 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'-dimethyl-4,4'-diaminodiphenylmethane Background Art

[0002] 3,3'-Dimethyl-4,4'-diaminodiphenylmethane is an important chemical raw material. It is a white or off-white frond or needle-shaped body (mainly depending on the solvent used in the refining process). It is mainly used as an adhesive and curing agent for epoxy resins and polyurethane resins. It is characterized by heat resistance, chemical resistance, and excellent electrical properties. 3,3'-Dimethyl-4,4'-diaminodiphenylmethane is combined with maleic anhydride and then prepolymerized with diamine to obtain polyimide resin. Furthermore, 3,3'-Dimethyl-4,4'-diaminodiphenylmethane is condensed with pyromellitic anhydride to obtain polyimide resin. Products processed with the above materials have excellent heat resistance, insulation properties and stability to solvents, so they are mostly used in high-temperature varnishes, capacitor films, printed circuit boards, and aviation parts. In addition, 3,3'-dimethyl-4,4'-diaminodiphenylmethane is also commonly used as an epoxy resin crosslinker, circuit insulation coating, glass fiber lubricant, and epoxy resin curing agent. It can be seen that 3,3'-dimethyl-4,4'-diaminodiphenylmethane has a wide range of uses. Although the amount used is not large, it still needs to be imported into China at present, and the price is relatively high. Its structural formula is:

[0003]

[0004] The method reported by Scanlan et al. is to react o-toluidine, hydrochloric acid and formaldehyde solution, and under alkaline conditions, steam distills out the unreacted raw material o-toluidine, and the obtained reactant is recrystallized twice to obtain 3,3'-dimethyl-4,4'-diaminodiphenylmethane with a yield of 63% (J.Am.Chem.Soc., 1935, May: 887-892). This method has high reaction temperature, many by-products, complicated post-processing, low yield, multiple recrystallizations, high cost, and little prospect for industrialization.

[0005] Chinese patent CN106986777B reports that crude MDT is recrystallized through ethanol, filtered, and dried to obtain MDT with a molar yield of 86% and a purity of 99%.

[0006] Chinese patent CN103130654B uses DMF and ethanol as solvents, and obtains MDT by recrystallization at room temperature, with a yield of 79.1% and a purity of 98.7%.

[0007] Chinese patent CN1948267A reported that MDT was obtained by post-treatment using DMF and ethanol as solvents, with a yield of 77% and a purity of 99.3%.

[0008] Chinese patent CN102249931B reported that MDT was obtained by post-treatment using DMF and ethanol as solvents, with a yield of 85% and a purity of 97%.

[0009] 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

[0010] 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.

[0011] The object of the present invention is to provide a method for purifying 3,3'-dimethyl-4,4'-diaminodiphenylmethane.

[0012] The technical solution adopted by the present invention is:

[0013] A method for purifying 3,3'-dimethyl-4,4'-diaminodiphenylmethane comprises the following steps:

[0014] Step (1) placing the crude 3,3'-dimethyl-4,4'-diaminodiphenylmethane in an alkaline solution with a pH value greater than 7 for reaction, separation, washing and drying;

[0015] Step (2) adding the crude product obtained in step (1) into an organic solvent, stirring and mixing, and heating to dissolve;

[0016] Step (3) cooling, crystallizing, filtering and drying to obtain a purified product of 3,3'-dimethyl-4,4'-diaminodiphenylmethane.

[0017] 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.

[0018] Furthermore, the inorganic base is selected from any one of hydroxides, strong base and weak acid salts, or a combination thereof.

[0019] 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.

[0020] Furthermore, the hydroxide is selected from one or more of sodium hydroxide and potassium hydroxide.

[0021] Furthermore, the organic solvent in step (2) is one or more of ethanol, ether, ketone, toluene, and DMF, preferably an ethanol / toluene mixed solution.

[0022] Furthermore, in the step (2), the volume ratio of ethanol to toluene of the organic solvent is (1-8):1, and preferably the volume ratio of ethanol to toluene is 3:1.

[0023] Furthermore, in the step (2), the mass (g) / volume (ml) ratio of the crude 3,3'-dimethyl-4,4'-diaminodiphenylmethane to the organic solvent is 1:(0.5-5), preferably the mass (g) / volume (ml) ratio of the crude 3,3'-dimethyl-4,4'-diaminodiphenylmethane to the organic solvent is 1:3.

[0024] Furthermore, in step (2), the temperature is raised to 60-70°C, preferably 60-65°C.

[0025] 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.

[0026] Furthermore, the cooling in step (3) is a gradient cooling, the first cooling to 35-40°C, keeping warm for crystallization for 1-2 hours; the second cooling to 18-20°C, keeping warm for crystallization for 1-2 hours.

[0027] Beneficial technical effects of the present invention

[0028] Compared with the prior art, the technical solution of the present invention has the following advantages:

[0029] 1. The purification method of 3,3'-dimethyl-4,4'-diaminodiphenylmethane of the present invention has excellent impurity removal effect for crude 3,3'-dimethyl-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.

[0030] 2. The purification method of 3,3'-dimethyl-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'-dimethyl-4,4'-diaminodiphenylmethane, including a variety of impurities that are extremely difficult to purify, with a purity of up to 99.94%. In addition, the method of the present invention can achieve a higher yield while meeting the high product quality. DETAILED DESCRIPTION

[0031] 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.

[0032] Embodiment 1:

[0033] 1. Place the crude 3,3'-dimethyl-4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separation, washing and drying;

[0034] 2. Add the crude product obtained in step 1 to a mixed solvent of ethanol / toluene, wherein the mass (g) to volume (ml) ratio of the crude product to the mixed solvent is 1:3; the volume ratio of ethanol to toluene is 3:1, stir and mix, raise the temperature to 60-65°C, and wait for the solution to become clear;

[0035] 3. Cooling and crystallization: first cooling to 35-40°C, keeping warm for 1-2 hours, cooling again to 18-20°C, keeping warm for 1-2 hours, filtering and drying to obtain purified 3,3'-dimethyl-4,4'-diaminodiphenylmethane with a yield of 92% and a purity of 99.4%.

[0036] Embodiment 2:

[0037] 1. Place the crude 3,3'-dimethyl-4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separation, washing and drying;

[0038] 2. Add the crude product obtained in step 1 to a mixed solvent of ethanol / 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 ethanol to toluene is 1:1, stir and mix, raise the temperature to 60-65°C, and wait for the solution to become clear;

[0039] 3. Cool down and crystallize. First cool down to 30-34°C, keep warm and crystallize for 1-2 hours, then cool down to 15-17°C again, keep warm and crystallize for 1-2 hours, filter and dry to obtain purified 3,3'-dimethyl-4,4'-diaminodiphenylmethane with a yield of 90% and a purity of 99.1%.

[0040] Embodiment 3:

[0041] 1. Place the crude 3,3'-dimethyl-4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separation, washing and drying;

[0042] 2. Add the crude product obtained in step 1 to a mixed solvent of ethanol / toluene, wherein the mass (g) to volume (ml) ratio of the crude product to the mixed solvent is 1:5; the volume ratio of ethanol to toluene is 8:1, stir and mix, raise the temperature to 66-70°C, and wait for the solution to become clear;

[0043] 3. Cooling and crystallization: first cooling to 41-50°C, keeping warm for 1-2 hours, cooling again to 21-25°C, keeping warm for 1-2 hours, filtering and drying to obtain purified 3,3'-dimethyl-4,4'-diaminodiphenylmethane with a yield of 89% and a purity of 98.7%.

[0044] Embodiment 4:

[0045] 1. Place the crude 3,3'-dimethyl-4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separation, washing and drying;

[0046] 2. Add the crude product obtained in step 1 to a mixed solvent of ethanol / 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 ethanol to toluene is 0.5:1, stir and mix, raise the temperature to 55-59°C, and wait for the solution to become clear;

[0047] 3. Cooling and crystallization: first cooling to 25-29°C, keeping warm for 1-2 hours, cooling again to 10-14°C, keeping warm for 1-2 hours, filtering and drying to obtain purified 3,3'-dimethyl-4,4'-diaminodiphenylmethane with a yield of 82% and a purity of 97.2%.

[0048] Embodiment 5:

[0049] 1. Place the crude 3,3'-dimethyl-4,4'-diaminodiphenylmethane in a potassium hydroxide solution for reaction, separation, washing and drying;

[0050] 2. Add the crude product obtained in step 1 to a mixed solvent of ethanol / toluene, wherein the mass (g) to volume (ml) ratio of the crude product to the mixed solvent is 1:6; the volume ratio of ethanol to toluene is 9:1, stir and mix, raise the temperature to 71-73°C, and wait for the solution to become clear;

[0051] 3. Cooling and crystallization: first cooling to 53-55°C, keeping warm for 1-2 hours, cooling again to 27-30°C, keeping warm for 1-2 hours, filtering and drying to obtain purified 3,3'-dimethyl-4,4'-diaminodiphenylmethane with a yield of 80% and a purity of 98.1%.

[0052] Embodiment 6:

[0053] 1. Place the crude 3,3'-dimethyl-4,4'-diaminodiphenylmethane in a sodium hydroxide solution for reaction, separation, washing and drying;

[0054] 2. Add the crude product obtained in step 1 to a mixed solvent of ethanol / toluene, wherein the mass (g) to volume (ml) ratio of the crude product to the mixed solvent is 1:3; the volume ratio of ethanol to toluene is 3:1, stir and mix, raise the temperature to 60-65°C, and wait for the solution to become clear;

[0055] 3. Cooling and crystallization: first cooling to 35-40°C, keeping warm for 1-2 hours, cooling again to 18-20°C, keeping warm for 1-2 hours, filtering and drying to obtain purified 3,3'-dimethyl-4,4'-diaminodiphenylmethane with a yield of 91% and a purity of 99.3%.

[0056] Embodiment 7:

[0057] 1. Add crude 3,3'-dimethyl-4,4'-diaminodiphenylmethane to ethanol, where the ratio of crude mass (g) to ethanol volume (ml) is 1:3; stir to mix, raise the temperature to 60-65°C, and wait for the solution to become clear;

[0058] 2. Cool down and crystallize to 20-25°C, keep warm for 1-2 hours, filter and dry to obtain purified 3,3'-dimethyl-4,4'-diaminodiphenylmethane with a yield of 78% and a purity of 98.3%.

[0059] 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.

[0060] 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'-dimethyl-4,4'-diaminodiphenylmethane, comprising the following steps: Step (1) placing the crude 3,3'-dimethyl-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, crystallizing, filtering and drying to obtain a purified product of 3,3'-dimethyl-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, ether, ketone, toluene and DMF, preferably an ethanol / toluene mixed solution.

6. The purification method according to claim 1, characterized in that In the step (2), the volume ratio of ethanol to toluene of the organic solvent is (1-8):1, and preferably the volume ratio of ethanol 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'-dimethyl-4,4'-diaminodiphenylmethane to the organic solvent is 1:(0.5-5), preferably the mass (g) / volume (ml) ratio of the crude 3,3'-dimethyl-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 60-70°C, preferably 60-65°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, the first cooling is to 35-40°C, and the temperature is kept for crystallization for 1-2 hours; the second cooling is to 18-20°C, and the temperature is kept for crystallization for 1-2 hours.

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