CN112552187A - Purification method of N- (2-aminoethyl) -N-ethyl m-toluidine - Google Patents
Purification method of N- (2-aminoethyl) -N-ethyl m-toluidine Download PDFInfo
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- CN112552187A CN112552187A CN202011472041.2A CN202011472041A CN112552187A CN 112552187 A CN112552187 A CN 112552187A CN 202011472041 A CN202011472041 A CN 202011472041A CN 112552187 A CN112552187 A CN 112552187A
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- filter cake
- ethyl
- toluidine
- aminoethyl
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- FTMVEUXYYDLYFH-UHFFFAOYSA-N n'-ethyl-n'-(3-methylphenyl)ethane-1,2-diamine Chemical compound NCCN(CC)C1=CC=CC(C)=C1 FTMVEUXYYDLYFH-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 238000000034 method Methods 0.000 title claims abstract description 42
- 238000000746 purification Methods 0.000 title claims abstract description 15
- 239000012065 filter cake Substances 0.000 claims abstract description 89
- 239000000706 filtrate Substances 0.000 claims abstract description 58
- 238000002156 mixing Methods 0.000 claims abstract description 35
- 239000000203 mixture Substances 0.000 claims abstract description 33
- 239000000047 product Substances 0.000 claims abstract description 27
- 239000012043 crude product Substances 0.000 claims abstract description 23
- 238000003825 pressing Methods 0.000 claims abstract description 23
- 238000001035 drying Methods 0.000 claims abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 87
- 239000003960 organic solvent Substances 0.000 claims description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 34
- 238000011085 pressure filtration Methods 0.000 claims description 23
- 235000019476 oil-water mixture Nutrition 0.000 claims description 21
- 238000002390 rotary evaporation Methods 0.000 claims description 21
- 239000007787 solid Substances 0.000 claims description 15
- 238000001816 cooling Methods 0.000 abstract description 8
- 239000002904 solvent Substances 0.000 abstract description 5
- 238000010438 heat treatment Methods 0.000 abstract description 4
- 125000003916 ethylene diamine group Chemical class 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- GUYMMHOQXYZMJQ-UHFFFAOYSA-N n-ethyl-3-methylaniline Chemical compound CCNC1=CC=CC(C)=C1 GUYMMHOQXYZMJQ-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- WJAXXWSZNSFVNG-UHFFFAOYSA-N 2-bromoethanamine;hydron;bromide Chemical compound [Br-].[NH3+]CCBr WJAXXWSZNSFVNG-UHFFFAOYSA-N 0.000 description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000011403 purification operation Methods 0.000 description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical class NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000005826 halohydrocarbons Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/82—Purification; Separation; Stabilisation; Use of additives
- C07C209/84—Purification
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application relates to the technical field of purification of unsymmetrical substituted ethylene diamine, and particularly discloses a method for purifying N- (2-aminoethyl) -N-ethyl m-toluidine; the method comprises the following steps: adding a solvent into the crude product of the N- (2-aminoethyl) -N-ethyl m-toluidine, heating, cooling, and then carrying out filter pressing to obtain a first filter cake and a first filtrate; concentrating the first filtrate to obtain a first concentrated solution, performing filter pressing to obtain a second filter cake, and mixing the second filter cake with the first filter cake to obtain a mixed filter cake; adding a solvent into the mixed filter cake and heating to obtain a first mixture; adding a solvent into the mixture I to obtain a mixture II; carrying out filter pressing on the mixture II, cooling the obtained filtrate, and carrying out filter pressing again to obtain a fourth filter cake and a fourth filtrate; concentrating the fourth filtrate to obtain a second concentrated solution, cooling, and performing filter pressing to obtain a fifth filter cake; and mixing and drying the fifth filter cake and the fourth filter cake to obtain the refined product of the N- (2-aminoethyl) -N-ethyl m-toluidine. The purification method has the advantages of high yield and purity of the product and simple purification conditions.
Description
Technical Field
The application relates to the technical field of a purification method of asymmetric substituted ethylenediamine, in particular to a purification method of N- (2-aminoethyl) -N-ethyl m-toluidine.
Background
The molecular terminal of the N- (2-aminoethyl) -N-ethyl m-toluidine has amino group, contains lone pair electrons, is a good nucleophilic reagent, can react with halohydrocarbon, carboxylic acid, anhydride, acyl chloride and the like, and has important application in the fields of dye and medicine.
Under the conditions of normal temperature and normal pressure, the boiling point of N- (2-aminoethyl) -N-ethyl m-toluidine is near 300 ℃, the boiling point is high, in the related technology, the method is generally used for separating and purifying the N- (2-aminoethyl) -N-ethyl m-toluidine by adopting a reduced pressure distillation mode, but the method has high requirement on vacuum degree, further has high requirement on pressure resistance of equipment, and meanwhile, the yield of the product is low and is about 50 percent. Meanwhile, in order to ensure the purity of the product, the vacuum degree also needs to be kept stable in the separation process. And therefore the operating requirements are high.
In view of the above-mentioned related art, the inventors thought that there were disadvantages that the requirements for the equipment required for purification were high and the conditions required for purification were severe.
Disclosure of Invention
In order to improve the purification yield and purity of an N- (2-aminoethyl) -N-ethyl m-toluidine product and ensure the simplicity of purification operation conditions, the application provides a purification method of N- (2-aminoethyl) -N-ethyl m-toluidine.
The purification method of the N- (2-aminoethyl) -N-ethyl m-toluidine provided by the application adopts the following technical scheme:
a method for purifying N- (2-aminoethyl) -N-ethyl m-toluidine, which comprises the following steps:
(1) adding a first organic solvent into the crude product of the N- (2-aminoethyl) -N-ethyl m-toluidine, uniformly mixing, and keeping the temperature at 70-80 ℃ for 15-30 min to obtain an oil-water mixture;
(2) standing the oil-water mixture obtained in the step (1) for 10-15 hours at the temperature of 5-15 ℃ to separate out solids from the oil-water mixture, and then performing first pressure filtration for 1-2 hours under the vacuum degree of-0.09 to-0.06 MPa to obtain a first filter cake and a first filtrate;
(3) performing vacuum rotary evaporation on the first filtrate obtained in the step (2) until the mass is reduced by 25-30% to obtain a first concentrated solution;
controlling the vacuum degree to be-0.09 to-0.06 Mpa, the rotating speed to be 40r/min to 70r/min and the temperature to be 30 to 40 ℃ in the vacuum rotary evaporation process;
(4) standing the first concentrated solution in the step (3) for 5-10 h at the temperature of 5-15 ℃, then performing secondary filter pressing for 0.5-1 h under the vacuum degree of-0.09 to-0.06 MPa to obtain a second filter cake, and then mixing the second filter cake with the first filter cake obtained in the step (2) to obtain a mixed filter cake;
(5) adding a second organic solvent into the mixed filter cake obtained in the step (4), uniformly mixing, and keeping the temperature at 70-80 ℃ for 15-30 min to obtain a first mixture;
(6) adding a third organic solvent into the mixture I obtained in the step (5), and uniformly mixing the mixture for 5-10 min under the condition that the rotating speed is controlled to be 250-350 r/min to obtain a mixture II;
(7) performing third filter pressing on the mixture II obtained in the step (6) for 3-5 min under the condition that the vacuum degree is controlled to be-0.09 to-0.06 Mpa, standing the obtained filtrate for 10-15 h at the temperature of 5-15 ℃ to separate out solids from the filtrate, and performing fourth filter pressing for 5-10 min under the condition that the vacuum degree is controlled to be-0.09 to-0.06 Mpa to obtain a fourth filter cake and a fourth filtrate;
(8) performing vacuum rotary evaporation on the fourth filtrate obtained in the step (7) until the mass is reduced by 25-30% to obtain a second concentrated solution;
controlling the vacuum degree to be-0.09 to-0.06 Mpa, the rotating speed to be 40 to 70r/min and the temperature to be 30 to 40 ℃ in the vacuum rotary concentration process;
(9) standing the second concentrated solution in the step (8) for 5-10 h at the temperature of 5-15 ℃, and then performing fifth filter pressing for 5-10 min at the vacuum degree of-0.09 to-0.06 MPa to obtain a fifth filter cake and a fifth filtrate;
(10) mixing the fifth filter cake obtained in the step (9) with the fourth filter cake obtained in the step (7), and then drying for 5-8 h at the temperature of 50-60 ℃ to obtain a refined product of N- (2-aminoethyl) -N-ethyl m-toluidine;
the second organic solvent is ethanol;
the first organic solvent and the third organic solvent are both ethyl acetate.
By adopting the technical scheme, the ethyl acetate is poor solvent for the N- (2-aminoethyl) -N-ethyl m-toluidine, so that the addition of the ethyl acetate in the step (1) can promote the precipitation of the N- (2-aminoethyl) -N-ethyl m-toluidine, namely the recrystallization of the N- (2-aminoethyl) -N-ethyl m-toluidine and dissolve impurities in the crude product of the N- (2-aminoethyl) -N-ethyl m-toluidine into the ethyl acetate, thereby removing most impurities in the crude product of the N- (2-aminoethyl) -N-ethyl m-toluidine through pressure filtration.
And (4) concentrating, standing, cooling and filter-pressing the first filtrate to ensure that the N- (2-aminoethyl) -N-ethyl m-toluidine dissolved in the first filtrate can be separated out again, thereby improving the final yield of the refined N- (2-aminoethyl) -N-ethyl m-toluidine product.
And (8) concentrating, standing, cooling and filter-pressing the fourth filtrate in the step (9), so that the N- (2-aminoethyl) -N-ethyl m-toluidine dissolved in the fourth filtrate can be separated out, and the final yield of the refined N- (2-aminoethyl) -N-ethyl m-toluidine product can be further improved.
The ethanol is a good solvent for the N- (2-aminoethyl) -N-ethyl m-toluidine, the addition of the ethanol only is not beneficial to separating solid N- (2-aminoethyl) -N-ethyl m-toluidine from the mixture II in the step (5), the addition of the ethyl acetate can promote the mixture II to separate the N- (2-aminoethyl) -N-ethyl m-toluidine, and then impurities dissolved in the ethanol and the ethyl acetate in the mixture II are removed through pressure filtration, so that the N- (2-aminoethyl) -N-ethyl m-toluidine with higher purity can be obtained, and the operation can also improve the yield of the refined product of the N- (2-aminoethyl) -N-ethyl m-toluidine.
Preferably, in the step (1), the ratio of the crude product of N- (2-aminoethyl) -N-ethyl-m-toluidine to the first organic solvent is 1-1.8 g: 1ml, calculated by mass: volume.
By adopting the technical scheme, the purity of the final refined N- (2-aminoethyl) -N-ethyl m-toluidine product can reach 98.29-98.8%.
Preferably, in the step (1), the ratio of the N- (2-aminoethyl) -N-ethyl-m-toluidine crude product to the first organic solvent is 1.44-1.8 g: 1ml, calculated by mass: volume.
By adopting the technical scheme, the purity of the final N- (2-aminoethyl) -N-ethyl m-toluidine refined product can reach 98.36% -98.8%.
Preferably, the ratio of the dosage of the mixed filter cake to the second organic solvent in the step (4) is 1.5-2.5 g: 1ml in terms of mass: volume.
By adopting the technical scheme, the yield of the final refined N- (2-aminoethyl) -N-ethyl m-toluidine product can reach 80.8-82.2%.
Preferably, the ratio of the dosage of the mixed filter cake to the second organic solvent in the step (4) is 2.1-2.5 g: 1ml in terms of mass: volume.
By adopting the technical scheme, the purity of the final N- (2-aminoethyl) -N-ethyl m-toluidine refined product can reach 98.36% -98.8%.
Preferably, the ratio of the amount of the second organic solvent to the amount of the third organic solvent is 0.8-1.2: 1 by volume.
By adopting the technical scheme, the yield of the final refined N- (2-aminoethyl) -N-ethyl m-toluidine product can reach 80.8-82.2%.
Preferably, the ratio of the amount of the second organic solvent to the amount of the third organic solvent is 1-1.2: 1 by volume.
By adopting the technical scheme, the purity of the final N- (2-aminoethyl) -N-ethyl m-toluidine refined product can reach 98.36% -98.8%.
Preferably, the ratio of the amount of the second organic solvent to the amount of the third organic solvent is 1.2: 1 by volume.
By adopting the technical scheme, the yield of the final refined N- (2-aminoethyl) -N-ethyl m-toluidine product can reach 82.2%.
In summary, the present application has the following beneficial effects:
1. because the method adopts the modes of twice recrystallization, twice concentration and vacuum filter pressing, the difficulty of purification operation is reduced, and the yield can be obviously improved; the vacuum degree of vacuum filter pressing is only-0.09 to-0.06 Mpa, and the heating temperature is only 50 to 80 ℃, so the requirement on reaction equipment is low;
2. in the application, ethanol and ethyl acetate are preferably used as a mixed solvent for secondary recrystallization, so that the purity of the finally obtained refined N- (2-aminoethyl) -N-ethyl m-toluidine product reaches 98.29-98.8%, and the yield reaches 80.8-82.2%; in particular, when the ratio of the second organic solvent to the third organic solvent is 1.2: 1, the yield of the finally obtained purified N- (2-aminoethyl) -N-ethyl-m-toluidine can be increased to 82.2%.
Drawings
Fig. 1 is a flow chart of a method provided herein.
Detailed Description
The present application will be described in further detail with reference to the following drawings and examples.
In each example, the purity was determined by the following method: the product was tested by liquid chromatography (HPLC) and the HPLC purity of the product N- (2-aminoethyl) -N-ethyl-m-toluidine was determined by peak area normalization.
The yield of the refined N- (2-aminoethyl) -N-ethyl-m-toluidine product prepared in each example was calculated by the following equation: yield = mass of product/(molar mass charged of N-ethyl-m-toluidine × molar mass of N- (2-aminoethyl) -N-ethyl-m-toluidine) × 100%.
The raw material specifications and the manufacturer information used in the examples and comparative examples of the present application are commercially available unless otherwise specified;
n-ethyl m-toluidine, manufacturer: shanghai Aladdin Biotechnology Ltd.
The equipment model and the manufacturer information used in the embodiments of the present application are as follows:
magnetic stirrers, model: DF-101S heat collection type constant temperature heating magnetic stirrer; the manufacturer: consolidate City Prohua instruments, Inc.;
high performance liquid chromatograph: the model is as follows: alliance e 2695; the manufacturer: waters Corporation.
Preparation of a crude product of aminoethyl) -N-ethyl-m-toluidine
Preparation example 1
The preparation method comprises the following steps: in a 500mL three-necked flask equipped with a thermometer, a condenser and a magnetic stirrer, 0.2mol (27.04 g) of N-ethyl-m-toluidine, 0.26mol (53.27 g) of 2-bromoethylamine hydrobromide, 0.14mol (14.01 g) of calcium carbonate and 15mL of water were sequentially charged, and the contents of the flask were stirred at 350r/min, and the temperature was raised to 140 ℃ to conduct a reflux reaction for 4 hours, followed by natural cooling to room temperature to obtain 108.1g of a crude product having a purity of 92.14% of N- (2-aminoethyl) -N-ethyl-m-toluidine.
Preparation example 2
The preparation method comprises the following steps: in a 500mL three-necked flask equipped with a thermometer, a condenser and a magnetic stirrer, 0.2mol (27.04 g) of N-ethyl-m-toluidine, 0.26mol (53.27 g) of 2-bromoethylamine hydrobromide, 0.14mol (14.01 g) of calcium carbonate and 15mL of water were sequentially charged, and the contents of the flask were stirred at 350r/min, and the temperature was raised to 140 ℃ to conduct a reflux reaction for 4 hours, followed by natural cooling to room temperature to obtain 108.5g of a crude product having a purity of 90% of N- (2-aminoethyl) -N-ethyl-m-toluidine.
Preparation example 3
The preparation method comprises the following steps: a500 mL three-necked flask equipped with a thermometer, a condenser and a magnetic stirrer was charged with 0.2mol (27.04 g) of N-ethyl-m-toluidine, 0.26mol (53.27 g) of 2-bromoethylamine hydrobromide, 0.14mol (14.01 g) of calcium carbonate and 15mL of water in this order, and the contents of the flask were stirred at 350r/min, and the temperature was raised to 140 ℃ to conduct a reflux reaction for 4 hours, followed by natural cooling to room temperature to obtain 107.1g of a crude product having a purity of 93% of N- (2-aminoethyl) -N-ethyl-m-toluidine.
Examples
Example 1
A method for purifying N- (2-aminoethyl) -N-ethyl m-toluidine, which comprises the following steps:
(1) adding 75ml of ethyl acetate into a crude product of N- (2-aminoethyl) -N-ethyl m-toluidine with the purity of 92.14 percent and the mass of 108.1g, uniformly mixing, and keeping the temperature at 80 ℃ for 30min to obtain an oil-water mixture;
(2) standing the oil-water mixture obtained in the step (1) for 14 hours at the temperature of 8 ℃ to enable the oil-water mixture to separate out solids, and then performing first pressure filtration for 1.5 hours under the vacuum degree of-0.075 Mpa to obtain 47.7g of a first filter cake and 124.1g of a first filtrate;
(3) performing vacuum rotary evaporation on the first filtrate obtained in the step (2) until the mass is reduced by 28% to obtain a first concentrated solution;
controlling the vacuum degree to be-0.08 Mpa, the rotating speed to be 50r/min and the temperature to be 35 ℃ in the vacuum rotary evaporation process;
(4) standing the first concentrated solution in the step (3) for 8 hours at the temperature of 6 ℃, then performing secondary filter pressing for 0.7 hour under the vacuum degree of-0.08 Mpa to obtain 4.8g of a second filter cake, and then mixing the second filter cake with the first filter cake obtained in the step (2) to obtain 52.5g of a mixed filter cake;
(5) adding 25ml of ethanol into the mixed filter cake obtained in the step (4), uniformly mixing, and keeping the temperature at 80 ℃ for 30min to obtain a first mixture;
(6) adding 25ml of ethyl acetate into the mixture I obtained in the step (5), and uniformly mixing by stirring for 7min at the rotation speed of 300r/min to obtain a mixture II;
(7) performing third pressure filtration on the mixture II obtained in the step (6) for 5min under the condition that the vacuum degree is controlled to be-0.08 Mpa, standing the obtained filtrate for 12h under the condition that the temperature is controlled to be 5 ℃ so as to separate out solids from the filtrate, and performing fourth pressure filtration for 10min under the condition that the vacuum degree is controlled to be-0.08 Mpa to obtain a fourth filter cake and a fourth filtrate;
(8) performing vacuum rotary evaporation on the fourth filtrate obtained in the step (7) until the mass is reduced by 27% to obtain a second concentrated solution;
controlling the vacuum degree to be-0.08 Mpa, the rotating speed to be 50r/min and the temperature to be 35 ℃ in the vacuum rotary concentration process;
(9) standing the second concentrated solution in the step (8) for 7h at the temperature of 15 ℃, and then performing fifth pressure filtration for 10min at the vacuum degree of-0.08 Mpa to obtain a fifth filter cake and a fifth filtrate;
(10) and (3) mixing the fifth filter cake obtained in the step (9) with the fourth filter cake obtained in the step (7), and drying at the temperature of 60 ℃ for 7 hours to obtain a refined product of N- (2-aminoethyl) -N-ethyl-m-toluidine with the mass of 28.8g and the purity of 98.80%, wherein the yield is 80.8%.
In the step (1), the ratio of the crude product of N- (2-aminoethyl) -N-ethyl-m-toluidine to ethyl acetate is 1.44g to 1ml, calculated by mass: volume.
The ratio of the mixed filter cake in the step (4) to the ethanol in the step (5) is 2.1g to 1ml by mass to volume.
The ratio of the ethanol in the step (5) to the ethyl acetate in the step (6) is 1: 1 by volume.
Example 2
A method for purifying N- (2-aminoethyl) -N-ethyl m-toluidine, which comprises the following steps:
(1) adding 108.5ml of ethyl acetate into a crude product of N- (2-aminoethyl) -N-ethyl m-toluidine with the purity of 90 percent and the mass of 108.5g, uniformly mixing, and keeping the temperature at 70 ℃ for 15min to obtain an oil-water mixture;
(2) standing the oil-water mixture obtained in the step (1) for 10 hours at the temperature of 5 ℃ to enable the oil-water mixture to separate out solids, and then performing first pressure filtration for 1 hour under the vacuum degree of-0.06 Mpa to obtain 47.5g of a first filter cake and 153.2g of a first filtrate;
(3) performing vacuum rotary evaporation on the first filtrate obtained in the step (2) until the mass is reduced by 25% to obtain a first concentrated solution;
controlling the vacuum degree to be-0.06 Mpa, the rotating speed to be 40r/min and the temperature to be 30 ℃ in the vacuum rotary evaporation process;
(4) standing the first concentrated solution in the step (3) for 5 hours at the temperature of 5 ℃, then performing secondary filter pressing for 0.5 hour under the vacuum degree of-0.06 Mpa to obtain 3.5g of a second filter cake, and then mixing the second filter cake with the first filter cake obtained in the step (2) to obtain 51g of a mixed filter cake;
(5) adding 34ml of ethanol into the mixed filter cake obtained in the step (4), uniformly mixing, and keeping the temperature at 70 ℃ for 15min to obtain a first mixture;
(6) adding 42.5ml of ethyl acetate into the mixture I obtained in the step (5), and uniformly mixing by stirring for 5min at the rotation speed of 250r/min to obtain a mixture II;
(7) performing third pressure filtration on the mixture II obtained in the step (6) for 3min under the condition that the vacuum degree is controlled to be-0.06 Mpa, standing the obtained filtrate for 10h under the condition that the temperature is controlled to be 10 ℃ so as to separate out solids from the filtrate, and performing fourth pressure filtration for 5min under the condition that the vacuum degree is controlled to be-0.06 Mpa to obtain a fourth filter cake and a fourth filtrate;
(8) performing vacuum rotary evaporation on the fourth filtrate in the step (7) until the mass is reduced by 25% to obtain a second concentrated solution;
controlling the vacuum degree to be-0.06 Mpa, the rotating speed to be 40r/min and the temperature to be 30 ℃ in the vacuum rotary concentration process;
(9) standing the second concentrated solution in the step (8) for 5 hours at the temperature of 5 ℃, and then performing fifth filter pressing for 5 minutes at the vacuum degree of-0.06 Mpa to obtain a fifth filter cake and a fifth filtrate;
(10) and (3) mixing the fifth filter cake obtained in the step (9) with the fourth filter cake obtained in the step (7), and drying at 50 ℃ for 5 hours to obtain a refined product of N- (2-aminoethyl) -N-ethyl m-toluidine with the mass of 29.1g and the purity of 98.29%, wherein the yield is 81.6%.
In the step (1), the ratio of the N- (2-aminoethyl) -N-ethyl-m-toluidine crude product to ethyl acetate is 1g to 1ml by mass to volume.
The ratio of the mixed filter cake in the step (4) to the ethanol in the step (5) is 1.5g to 1ml by mass and volume.
The ratio of the ethanol in the step (5) to the ethyl acetate in the step (6) is 0.8: 1 by volume.
Example 3
A method for purifying N- (2-aminoethyl) -N-ethyl m-toluidine, which comprises the following steps:
(1) adding 59.5ml of ethyl acetate into a crude product of N- (2-aminoethyl) -N-ethyl m-toluidine with the purity of 93 percent and the mass of 107.1g, uniformly mixing, and keeping the temperature at 75 ℃ for 20min to obtain an oil-water mixture;
(2) standing the oil-water mixture obtained in the step (1) for 15 hours at the temperature of 15 ℃ to enable the oil-water mixture to separate out solids, and then performing first pressure filtration for 2 hours under the vacuum degree of-0.09 Mpa to obtain 49.2g of a first filter cake and 103.4g of a first filtrate;
(3) performing vacuum rotary evaporation on the first filtrate obtained in the step (2) until the mass is reduced by 30% to obtain a first concentrated solution;
controlling the vacuum degree to be-0.09 Mpa, the rotating speed to be 70r/min and the temperature to be 40 ℃ in the vacuum rotary evaporation process;
(4) standing the first concentrated solution in the step (3) for 10 hours at the temperature of 15 ℃, then performing secondary filter pressing for 1 hour under the vacuum degree of-0.09 Mpa to obtain 6.3g of a second filter cake, and then mixing the second filter cake with the first filter cake obtained in the step (2) to obtain 55.5g of a mixed filter cake;
(5) adding 22.2ml of ethanol into the mixed filter cake obtained in the step (4), uniformly mixing, and keeping the temperature at 75 ℃ for 25min to obtain a first mixture;
(6) adding 18.5ml of ethyl acetate into the mixture I obtained in the step (5), and uniformly mixing by stirring for 10min at the rotation speed of 350r/min to obtain a mixture II;
(7) performing third pressure filtration on the mixture II obtained in the step (6) for 4min under the condition that the vacuum degree is controlled to be-0.09 Mpa, standing the obtained filtrate for 15h under the condition that the temperature is controlled to be 15 ℃ so as to separate out solids from the filtrate, and performing fourth pressure filtration for 7.5min under the condition that the vacuum degree is controlled to be-0.09 Mpa to obtain a fourth filter cake and a fourth filtrate;
(8) performing vacuum rotary evaporation on the fourth filtrate obtained in the step (7) until the mass is reduced by 30% to obtain a second concentrated solution;
controlling the vacuum degree to be-0.09 Mpa, the rotating speed to be 70r/min and the temperature to be 40 ℃ in the vacuum rotary concentration process;
(9) standing the second concentrated solution in the step (8) for 10 hours at the temperature of 10 ℃, and then performing fifth pressure filtration for 8 minutes at the vacuum degree of-0.09 Mpa to obtain a fifth filter cake and a fifth filtrate;
(10) and (3) mixing the fifth filter cake obtained in the step (9) with the fourth filter cake obtained in the step (7), and drying at 55 ℃ for 8 hours to obtain a refined product of N- (2-aminoethyl) -N-ethyl-m-toluidine with the mass of 29.3g and the purity of 98.36%, wherein the yield is 82.2%.
In the step (1), the ratio of the N- (2-aminoethyl) -N-ethyl-m-toluidine crude product to ethyl acetate is 1.8g to 1ml, calculated by mass to volume.
The ratio of the mixed filter cake in the step (4) to the ethanol in the step (5) is 2.5g to 1ml by mass to volume.
The ratio of the ethanol in the step (5) to the ethyl acetate in the step (6) is 1.2: 1 by volume.
Comparative example
Comparative example 1
A method for purifying N- (2-aminoethyl) -N-ethyl m-toluidine, which comprises the following steps:
(1) adding 59.5ml of ethyl acetate into a crude product of N- (2-aminoethyl) -N-ethyl m-toluidine with the purity of 93 percent and the mass of 107.1g, uniformly mixing, and keeping the temperature at 75 ℃ for 20min to obtain an oil-water mixture;
(2) standing the oil-water mixture obtained in the step (1) for 15 hours at the temperature of 15 ℃ to enable the oil-water mixture to separate out solids, and then performing first pressure filtration for 2 hours under the vacuum degree of-0.09 Mpa to obtain 49.2g of a first filter cake and 103.4g of a first filtrate;
(3) performing vacuum rotary evaporation on the first filtrate obtained in the step (2) until the mass is reduced by 30% to obtain a first concentrated solution;
controlling the vacuum degree to be-0.09 Mpa, the rotating speed to be 70r/min and the temperature to be 40 ℃ in the vacuum rotary evaporation process;
(4) standing the first concentrated solution in the step (3) for 10 hours at the temperature of 15 ℃, then performing secondary filter pressing for 1 hour under the vacuum degree of-0.09 Mpa to obtain 6.3g of a second filter cake, and then mixing the second filter cake with the first filter cake obtained in the step (2) to obtain 55.5g of a mixed filter cake;
(5) adding 18.5ml of ethyl acetate into the mixed filter cake obtained in the step (4), and uniformly mixing by stirring for 10min at the rotation speed of 350r/min to obtain a mixture II;
(6) performing third pressure filtration on the mixture II obtained in the step (7) for 4min under the condition that the vacuum degree is controlled to be-0.09 Mpa, standing the obtained filtrate for 15h under the condition that the temperature is controlled to be 15 ℃ so as to separate out solids from the filtrate, and performing fourth pressure filtration for 7.5min under the condition that the vacuum degree is controlled to be-0.09 Mpa to obtain a fourth filter cake and a fourth filtrate;
(7) performing vacuum rotary evaporation on the fourth filtrate obtained in the step (6) until the mass is reduced by 30% to obtain a second concentrated solution;
controlling the vacuum degree to be-0.09 Mpa, the rotating speed to be 70r/min and the temperature to be 40 ℃ in the vacuum rotary concentration process;
(8) standing the second concentrated solution in the step (7) for 10 hours at the temperature of 10 ℃, and then performing fifth pressure filtration for 8 minutes at the vacuum degree of-0.09 Mpa to obtain a fifth filter cake and a fifth filtrate;
(9) and (3) mixing the fifth filter cake obtained in the step (8) with the fourth filter cake obtained in the step (6), and drying at the temperature of 55 ℃ for 8 hours to obtain a refined product of N- (2-aminoethyl) -N-ethyl-m-toluidine with the mass of 30.1g and the purity of 97.42%, wherein the yield is 84.4%.
In the step (1), the ratio of the N- (2-aminoethyl) -N-ethyl-m-toluidine crude product to ethyl acetate is 1.8g to 1ml, calculated by mass to volume.
Comparative example 2
A method for purifying N- (2-aminoethyl) -N-ethyl m-toluidine, which comprises the following steps:
(1) adding 59.5ml of ethyl acetate into a crude product of N- (2-aminoethyl) -N-ethyl m-toluidine with the purity of 93 percent and the mass of 107.1g, uniformly mixing, and keeping the temperature at 75 ℃ for 20min to obtain an oil-water mixture;
(2) standing the oil-water mixture obtained in the step (1) for 15 hours at the temperature of 15 ℃ to enable the oil-water mixture to separate out solids, and then performing first pressure filtration for 2 hours under the vacuum degree of-0.09 Mpa to obtain 49.2g of a first filter cake and 103.4g of a first filtrate;
(3) performing vacuum rotary evaporation on the first filtrate obtained in the step (2) until the mass is reduced by 30% to obtain a first concentrated solution;
controlling the vacuum degree to be-0.09 Mpa, the rotating speed to be 70r/min and the temperature to be 40 ℃ in the vacuum rotary evaporation process;
(4) standing the first concentrated solution in the step (3) for 10 hours at the temperature of 15 ℃, then performing secondary filter pressing for 1 hour under the vacuum degree of-0.09 Mpa to obtain 6.3g of a second filter cake, and then mixing the second filter cake with the first filter cake obtained in the step (2) to obtain 55.5g of a mixed filter cake;
(5) adding 40.7ml of ethyl acetate into the mixed filter cake obtained in the step (4), and uniformly mixing by stirring for 10min at the rotation speed of 350r/min to obtain a first mixture;
(6) performing third pressure filtration on the mixture I obtained in the step (5) for 4min under the condition that the vacuum degree is controlled to be-0.09 Mpa, standing the obtained filtrate for 15h under the condition that the temperature is controlled to be 15 ℃ so as to separate out solids from the filtrate, and performing fourth pressure filtration for 7.5min under the condition that the vacuum degree is controlled to be-0.09 Mpa to obtain a fourth filter cake and a fourth filtrate;
(7) performing vacuum rotary evaporation on the fourth filtrate obtained in the step (6) until the mass is reduced by 30% to obtain a second concentrated solution;
controlling the vacuum degree to be-0.09 Mpa, the rotating speed to be 70r/min and the temperature to be 40 ℃ in the vacuum rotary concentration process;
(8) standing the second concentrated solution in the step (7) for 10 hours at the temperature of 10 ℃, and then performing fifth pressure filtration for 8 minutes at the vacuum degree of-0.09 Mpa to obtain a fifth filter cake and a fifth filtrate;
(9) and (3) mixing the fifth filter cake obtained in the step (8) with the fourth filter cake obtained in the step (6), and drying at the temperature of 55 ℃ for 8 hours to obtain a refined product of N- (2-aminoethyl) -N-ethyl-m-toluidine with the mass of 29.7g and the purity of 96.98%, wherein the yield is 83.4%.
In the step (1), the ratio of the N- (2-aminoethyl) -N-ethyl-m-toluidine crude product to ethyl acetate is 1.8g to 1ml, calculated by mass to volume.
As can be seen by combining comparative example 1 with comparative example 2 and combining example 3, the purity of example 3 in which ethanol and ethyl acetate were added together to the mixed cake was higher than that of comparative example 1 and comparative example 2 in which only ethyl acetate was added, and it can be seen that the purity of refined N- (2-aminoethyl) -N-ethyl m-toluidine was improved by adding ethanol and ethyl acetate together to the mixed cake.
The present embodiment is only for explaining the present application, and it is not limited to the present application, and those skilled in the art can make modifications of the present embodiment without inventive contribution as needed after reading the present specification, but all of them are protected by patent law within the scope of the claims of the present application.
Claims (8)
1. A method for purifying N- (2-aminoethyl) -N-ethyl-m-toluidine, which comprises the following steps:
(1) adding a first organic solvent into the crude product of the N- (2-aminoethyl) -N-ethyl m-toluidine, uniformly mixing, and keeping the temperature at 70-80 ℃ for 15-30 min to obtain an oil-water mixture;
(2) standing the oil-water mixture obtained in the step (1) for 10-15 hours at the temperature of 5-15 ℃ to separate out solids from the oil-water mixture, and then performing first pressure filtration for 1-2 hours under the vacuum degree of-0.09 to-0.06 MPa to obtain a first filter cake and a first filtrate;
(3) performing vacuum rotary evaporation on the first filtrate obtained in the step (2) until the mass is reduced by 25-30% to obtain a first concentrated solution;
controlling the vacuum degree to be-0.09 to-0.06 Mpa, the rotating speed to be 40r/min to 70r/min and the temperature to be 30 to 40 ℃ in the vacuum rotary evaporation process;
(4) standing the first concentrated solution in the step (3) for 5-10 h at the temperature of 5-15 ℃, then performing secondary filter pressing for 0.5-1 h under the vacuum degree of-0.09 to-0.06 MPa to obtain a second filter cake, and then mixing the second filter cake with the first filter cake obtained in the step (2) to obtain a mixed filter cake;
(5) adding a second organic solvent into the mixed filter cake obtained in the step (4), uniformly mixing, and keeping the temperature at 70-80 ℃ for 15-30 min to obtain a first mixture;
(6) adding a third organic solvent into the mixture I obtained in the step (5), and uniformly mixing the mixture for 5-10 min under the condition that the rotating speed is controlled to be 250-350 r/min to obtain a mixture II;
(7) performing third filter pressing on the mixture II obtained in the step (6) for 3-5 min under the condition that the vacuum degree is controlled to be-0.09 to-0.06 Mpa, standing the obtained filtrate for 10-15 h at the temperature of 5-15 ℃ to separate out solids from the filtrate, and performing fourth filter pressing for 5-10 min under the condition that the vacuum degree is controlled to be-0.09 to-0.06 Mpa to obtain a fourth filter cake and a fourth filtrate;
(8) performing vacuum rotary evaporation on the fourth filtrate obtained in the step (7) until the mass is reduced by 25-30% to obtain a second concentrated solution;
controlling the vacuum degree to be-0.09 to-0.06 Mpa, the rotating speed to be 40 to 70r/min and the temperature to be 30 to 40 ℃ in the vacuum rotary concentration process;
(9) standing the second concentrated solution in the step (8) for 5-10 h at the temperature of 5-15 ℃, and then performing fifth filter pressing for 5-10 min at the vacuum degree of-0.09 to-0.06 MPa to obtain a fifth filter cake and a fifth filtrate;
(10) mixing the fifth filter cake obtained in the step (9) with the fourth filter cake obtained in the step (7), and then drying for 5-8 h at the temperature of 50-60 ℃ to obtain a refined product of N- (2-aminoethyl) -N-ethyl m-toluidine;
the second organic solvent is ethanol;
the first organic solvent and the third organic solvent are both ethyl acetate.
2. The method according to claim 1, wherein said N- (2-aminoethyl) -N-ethyl-m-toluidine comprises: the ratio of the N- (2-aminoethyl) -N-ethyl-m-toluidine crude product to the first organic solvent in the step (1) is 1-1.8 g: 1ml, calculated by mass: volume.
3. The method according to claim 2, wherein the purification step of N- (2-aminoethyl) -N-ethyl-m-toluidine comprises: the ratio of the N- (2-aminoethyl) -N-ethyl-m-toluidine crude product to the first organic solvent in the step (1) is 1.44-1.8 g: 1ml, calculated by mass: volume.
4. The method according to claim 1, wherein said N- (2-aminoethyl) -N-ethyl-m-toluidine comprises: the ratio of the dosage of the mixed filter cake and the second organic solvent in the step (4) is calculated according to the mass and the volume, and the ratio of the mixed filter cake to the second organic solvent is 1.5-2.5 g to 1 ml.
5. The method according to claim 4, wherein the purification step of N- (2-aminoethyl) -N-ethyl-m-toluidine comprises: the ratio of the dosage of the mixed filter cake and the second organic solvent in the step (4) is calculated according to the mass and the volume, and the ratio of the mixed filter cake to the second organic solvent is 2.1-2.5 g to 1 ml.
6. The method according to claim 1, wherein said N- (2-aminoethyl) -N-ethyl-m-toluidine comprises: the ratio of the second organic solvent to the third organic solvent is 0.8-1.2: 1 by volume.
7. The method according to claim 6, wherein the purification step of N- (2-aminoethyl) -N-ethyl-m-toluidine comprises: the ratio of the second organic solvent to the third organic solvent is 1-1.2: 1 by volume.
8. The method according to claim 7, wherein said N- (2-aminoethyl) -N-ethyl-m-toluidine comprises: the ratio of the dosage of the second organic solvent to the dosage of the third organic solvent is 1.2: 1 calculated by volume ratio.
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