CN115872873A - Recrystallization purification method of bis (2-bromoethyl) amine hydrobromide - Google Patents
Recrystallization purification method of bis (2-bromoethyl) amine hydrobromide Download PDFInfo
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- bromoethyl
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- YHHKEXPNBPDPOW-UHFFFAOYSA-N 2-bromo-n-(2-bromoethyl)ethanamine;hydrobromide Chemical compound Br.BrCCNCCBr YHHKEXPNBPDPOW-UHFFFAOYSA-N 0.000 title claims abstract description 81
- 238000000746 purification Methods 0.000 title claims abstract description 44
- 238000001953 recrystallisation Methods 0.000 title claims abstract description 38
- 238000000034 method Methods 0.000 title claims abstract description 24
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims abstract description 115
- 239000012043 crude product Substances 0.000 claims abstract description 37
- 239000002904 solvent Substances 0.000 claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 22
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims abstract description 19
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000012065 filter cake Substances 0.000 claims description 32
- 238000001816 cooling Methods 0.000 claims description 16
- 238000010992 reflux Methods 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 230000000694 effects Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 239000005416 organic matter Substances 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 17
- 230000000052 comparative effect Effects 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 13
- 239000002994 raw material Substances 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 229940043237 diethanolamine Drugs 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 241000662429 Fenerbahce Species 0.000 description 8
- 238000001514 detection method Methods 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000005303 weighing Methods 0.000 description 6
- 230000007547 defect Effects 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- 239000005457 ice water Substances 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 208000012839 conversion disease Diseases 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- -1 arylamine compounds Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- ZQBVUULQVWCGDQ-UHFFFAOYSA-N propan-1-ol;propan-2-ol Chemical compound CCCO.CC(C)O ZQBVUULQVWCGDQ-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application relates to the field of organic matter synthesis, and particularly discloses a recrystallization purification method of bis (2-bromoethyl) amine hydrobromide, which comprises the following steps: and (3) taking tert-butyl alcohol as a solvent, and recrystallizing a crude product obtained by the reaction of diethanolamine and hydrobromic acid to obtain purified bis (2-bromoethyl) amine hydrobromide. The application has the effect of improving the purification efficiency of the bis (2-bromoethyl) amine hydrobromide.
Description
Technical Field
The application relates to the field of organic matter synthesis, in particular to a recrystallization purification method of bis (2-bromoethyl) amine hydrobromide.
Background
Bis (2-bromoethyl) amine hydrobromide is an important organic synthesis intermediate, and can be synthesized with arylamine compounds through N-alkylation reaction under alkaline conditions to obtain N-arylpiperazine compounds, wherein the structure of the compounds is widely existed in various drug molecules and other related bioactive molecules.
In the related technology, diethanol amine which is cheap and easy to obtain is mainly used as a raw material, and is brominated with hydrobromic acid aqueous solution with the concentration of 48% at the temperature of 160-180 ℃ to prepare bis (2-bromoethyl) amine hydrobromide, and the reaction equation is as follows:
the conversion rate of the raw material in the above reaction is only about 75%, and it is difficult to further improve the conversion rate. Thus, the crude product obtained after concentration of the solvent is a mixture of the starting material and the product. In the related art, excess hydrobromic acid is usually evaporated to dryness and then recrystallized from acetone. However, because the physical and chemical characteristics of diethanolamine and bis (2-bromoethyl) amine hydrobromide are similar, the purification difficulty is higher, and the purification efficiency is lower.
Disclosure of Invention
In order to overcome the defect of low purification efficiency of the bis (2-bromoethyl) amine hydrobromide, the application provides a recrystallization purification method of the bis (2-bromoethyl) amine hydrobromide.
The recrystallization purification method of bis (2-bromoethyl) amine hydrobromide provided by the application adopts the following technical scheme: a recrystallization purification method of bis (2-bromoethyl) amine hydrobromide is characterized in that tert-butyl alcohol is used as a solvent, and a crude product obtained by the reaction of diethanolamine and hydrobromic acid is recrystallized to obtain purified bis (2-bromoethyl) amine hydrobromide.
By adopting the technical scheme, the reaction conversion rate is limited, 25% of unreacted raw materials are contained in a crude product of bis (2-bromoethyl) amine hydrobromide prepared by diethanol amine, most solvent systems are difficult to realize recrystallization purification of the product with high purity and low loss due to low product purity, in the related technology, acetone is used for recrystallization of the crude product, after three times of recrystallization, the purity of the bis (2-bromoethyl) amine hydrobromide reaches 90%, but the loss in the process is large, and the product yield is influenced;
experiments show that when tert-butyl alcohol is used as a recrystallization solvent in the purification of bis (2-bromoethyl) amine hydrobromide, the bis (2-bromoethyl) amine hydrobromide can be efficiently obtained with an overall yield of 56.6% and a purity of 98%, and the defect of low purification efficiency of the bis (2-bromoethyl) amine hydrobromide is overcome.
Optionally, the recrystallization purification method of bis (2-bromoethyl) amine hydrobromide comprises the following steps:
s1, adding tert-butyl alcohol into a crude product prepared by reacting diethanolamine and hydrobromic acid, heating to 80-100 ℃, stirring, cooling to 30-50 ℃, and filtering to obtain a filter cake;
and S2, washing the filter cake obtained in the step S1 by using tert-butyl alcohol, and drying the filter cake to remove the solvent to obtain the purified bis (2-bromoethyl) amine hydrobromide.
By adopting the technical scheme, in the step S1, the crude product is fully dissolved in tertiary butanol by heating, and then the crude product is cooled to separate out bis (2-bromoethyl) amine hydrobromide, because the melting point of the tertiary butanol is about 25 ℃, the crude product is cooled to 30-50 ℃ to start filtering to obtain a filter cake with high purity of the bis (2-bromoethyl) amine hydrobromide in order to avoid the solidification of the tertiary butanol;
in the step S2, impurities in the filter cake are further removed by washing with tert-butyl alcohol, and bis (2-bromoethyl) amine hydrobromide with the purity of 98% is obtained after drying.
Optionally, in the step S1, the feed ratio of the crude product to the tert-butanol is 5g: (8-15) ml.
By adopting the technical scheme, under the mixture ratio, the tert-butyl alcohol can fully dissolve the crude product to obtain the bis (2-bromoethyl) amine hydrobromide with higher yield and purity, and if the feeding amount of the tert-butyl alcohol is continuously increased, although the dissolution of the crude product is facilitated, the separation of the bis (2-bromoethyl) amine hydrobromide is easily influenced, and the loss in the purification process is increased.
Optionally, in the step S1, reflux stirring is carried out for 1-3h at 80-100 ℃.
By adopting the technical scheme, the boiling point of the tertiary butanol is about 84 ℃, the temperature is kept at 80-100 ℃, and the system can be in a reflux state, so that the crude product is fully dissolved in the tertiary butanol, and the dissolving efficiency is improved.
Optionally, in the step S2, the filter cake obtained in step S1 is washed with tert-butanol with 30 ℃ temperature.
By adopting the technical scheme, the melting point of the tert-butyl alcohol is about 25 ℃, and the filter cake is washed by using the tert-butyl alcohol with the temperature of 30 ℃, so that the tert-butyl alcohol is not easy to solidify, and the solubility of the bis (2-bromoethyl) amine hydrobromide is lower at 30 ℃, thereby facilitating the further purification of the product.
Optionally, the feeding ratio of the crude product to the tertiary butanol used in the step S2 is 5g: (8-12) ml.
By adopting the technical scheme, under the mixture ratio, impurities in the filter cake are further removed by washing with tert-butyl alcohol, and the bis (2-bromoethyl) amine hydrobromide with higher yield and purity can be obtained, if the feeding amount of the tert-butyl alcohol is continuously increased, the yield of the bis (2-bromoethyl) amine hydrobromide is not obviously increased, and the resource waste and the cost increase are easily caused.
Optionally, the crude product is obtained by reacting diethanolamine with hydrobromic acid and then distilling water and hydrobromic acid.
By adopting the technical scheme, the conversion rate of raw materials for the reaction of the diethanolamine and the hydrobromic acid is about 75 percent, and the reaction is difficult to further improve, so that the reaction is stopped when the reaction conversion rate reaches 75 percent, the water and the hydrobromic acid in the system are evaporated to dryness, and the tertiary butanol is recrystallized and purified.
In summary, the present application includes at least one of the following beneficial technical effects:
1. experiments show that when tert-butyl alcohol is used as a recrystallization solvent in the purification of bis (2-bromoethyl) amine hydrobromide, the bis (2-bromoethyl) amine hydrobromide can be efficiently obtained with the total yield of 56.6% and the purity of 98%, and the defect of low purification efficiency of the bis (2-bromoethyl) amine hydrobromide is overcome;
2. heating to fully dissolve the crude product in tert-butyl alcohol, cooling to separate out bis (2-bromoethyl) amine hydrobromide, cooling to 30-50 ℃ to start filtering to obtain a filter cake with high bis (2-bromoethyl) amine hydrobromide purity due to the melting point of the tert-butyl alcohol being about 25 ℃, washing by the tert-butyl alcohol to further remove impurities in the filter cake, and drying to obtain the bis (2-bromoethyl) amine hydrobromide with the purity of up to 98%;
3. the melting point of the tert-butyl alcohol is about 25 ℃, and the filter cake is washed by using the tert-butyl alcohol with the temperature of 30 ℃, so that the tert-butyl alcohol is not easy to solidify, and the solubility of bis (2-bromoethyl) amine hydrobromide is low at 30 ℃, so that the product can be further purified conveniently.
Detailed Description
The synthesis of bis (2-bromoethyl) amine hydrobromide mainly adopts a method that cheap and easily available diethanolamine is used as a raw material, and the raw material and hydrobromic acid aqueous solution with the concentration of 48% are brominated at the temperature of 160-180 ℃. In the reaction process, water needs to be continuously distilled off, so that sufficient hydrogen bromide concentration in the reaction system is ensured, the bromination reaction can further occur, and the reaction conversion rate and the product yield are improved. However, even in this case, the conversion of the raw material in the reaction is only about 75%, and it is difficult to further increase the conversion by further prolonging the reaction time or by supplementing the aqueous hydrobromic acid solution.
Based on the above, the post-treatment can be selected only by stopping the reaction when the conversion of the raw material reaches 75%. The usual post-treatment method is to evaporate the excess hydrobromic acid to dryness and to recrystallize the crude product from acetone. However, the acetone purification effect is not ideal, and after three times of recrystallization, the purity of the bis (2-bromoethyl) amine hydrobromide reaches 90%, and the loss in the process is large, so that the product yield is influenced.
In view of the above-mentioned drawbacks, the applicant has conducted extensive studies on the recrystallization purification system of bis (2-bromoethyl) amine hydrobromide, and found for the first time that: the tert-butyl alcohol is used as a recrystallization solvent in the purification of the bis (2-bromoethyl) amine hydrobromide, the bis (2-bromoethyl) amine hydrobromide can be efficiently obtained with the total yield of 56.6% and the purity of 98%, and the defect of low purification efficiency of the bis (2-bromoethyl) amine hydrobromide is overcome.
The present application will be described in further detail with reference to examples and comparative examples.
Source of raw materials
Unless otherwise specified, the specifications and sources of the raw materials in the following examples and comparative examples are shown in Table 1 below.
TABLE 1 raw material specifications and sources
| Starting materials | Specification of | Source |
| Diethanolamine (DEA) | CAS：111-42-2 | Adamas reagent |
| Hydrobromic acid | The concentration is 48 percent | Great reagent |
| Anhydrous acetone | CAS：67-64-1 | Adamas reagent |
| Ethyl acetate | CAS：141-78-6 | Adamas reagent |
| Anhydrous methanol | CAS：67-56-1 | Adamas reagent |
| Anhydrous ethanol | CAS：64-17-5 | Adamas reagent |
| Isopropanol (I-propanol) | CAS：67-63-0 | Adamas reagent |
| Tert-butyl alcohol | CAS：75-65-0 | Adamas reagent |
| Anhydrous diethyl ether | CAS：60-29-7 | Adamas reagent |
Preparation example
Preparation example 1
Preparation of crude bis (2-bromoethyl) amine hydrobromide product
180g of diethanolamine is weighed and added into a 2L three-necked flask, the mixture is cooled to 0 ℃ in an ice water bath, stirring is started at the speed of 300r/min, 1.5L of hydrobromic acid with the concentration of 48 percent is added, and the dropping speed is controlled to ensure that the reaction temperature does not exceed 30 ℃. After the addition of hydrobromic acid was complete, the ice-water bath was maintained at 0 ℃ and stirring was continued at 300r/min for 15min, after which the three-necked flask was transferred to a 160 ℃ oil bath and refluxed with a condenser tube, kept stirring at 300r/min, equipped with a distillation apparatus, keeping the temperature of the reaction solution at 130 ℃. After 400ml of water was distilled off at atmospheric pressure, the distillation apparatus was removed and refluxed for 1 hour. After the reflux is finished, a distillation device is continuously arranged, 550ml of water is distilled out under normal pressure, and then the distillation device is removed again for reflux for 4 hours. And finally, preparing a distillation device again, distilling out the residual aqueous solution, cooling the reaction solution at 25 ℃, and obtaining a yellow solid after cooling.
The mass ratio of the raw materials to the product in the yellow solid was 0.25 as determined by Varian 400 NMR spectrometer, yielding 530g of crude product.
Examples and comparative examples
Example 1
A recrystallization purification method of bis (2-bromoethyl) amine hydrobromide comprises the following steps:
s1, weighing 5g of the crude product obtained in the preparation example 1, adding 10ml of tert-butyl alcohol, heating to 90 ℃, refluxing, stirring at the speed of 300r/min for 1h, then cooling to 40 ℃ in the environment of 25 ℃, and filtering to obtain a filter cake;
s2, washing the filter cake obtained in the step S1 by using 10ml of tert-butyl alcohol with the temperature kept at 30 ℃, and drying the filter cake to remove the solvent to obtain the purified bis (2-bromoethyl) amine hydrobromide.
Detection by a Varian 400 NMR spectrometer gave 3.0g of a white solid as 98% pure bis (2-bromoethyl) amine hydrobromide.
Comparative example 1
A recrystallization purification method of bis (2-bromoethyl) amine hydrobromide comprises the following steps:
s1, weighing 5g of the crude product obtained in the preparation example 1, adding 10ml of ethyl acetate, heating to 80 ℃, refluxing, stirring at the speed of 300r/min for 1h, then cooling at 25 ℃, and filtering to obtain a filter cake after cooling;
s2, washing the filter cake obtained in the step S1 by using 10ml of ethyl acetate, and drying the filter cake to remove the solvent to obtain the purified bis (2-bromoethyl) amine hydrobromide.
Detection by a Varian 400 NMR spectrometer gave 4.3g of the product as a white solid as bis (2-bromoethyl) amine hydrobromide having a purity of 79.4%.
Combining example 1 and comparative example 1, it can be seen that, when ethyl acetate was used as the recrystallization solvent, although the pigment in the crude product could be removed, the purity of the product was only 79.4%, which was not significantly improved compared to the crude product. And the purity of the bis (2-bromoethyl) amine hydrobromide is greatly improved by using tert-butyl alcohol as a recrystallization solvent.
Comparative example 2
A recrystallization purification method of bis (2-bromoethyl) amine hydrobromide comprises the following steps:
s1, weighing 5g of the crude product obtained in the preparation example 1, adding 10ml of anhydrous acetone, heating to 80 ℃, refluxing, stirring at the speed of 300r/min for 1h, then cooling at 25 ℃, and filtering to obtain a filter cake after cooling;
s2, washing the filter cake obtained in the step S1 by using 10ml of anhydrous acetone, and drying the filter cake to remove the solvent to obtain the purified bis (2-bromoethyl) amine hydrobromide.
Detection by a Varian 400 NMR spectrometer gave 3.0g of the product as a white solid as 86.2% pure bis (2-bromoethyl) amine hydrobromide.
When anhydrous acetone is used as a recrystallization solvent, the purity of bis (2-bromoethyl) amine hydrobromide can be improved to 86.2%, but the purification effect is inferior to that of tert-butanol, and if further purification is desired, the purification causes great loss, resulting in reduction of the yield of the product, as can be seen by combining example 1 and comparative example 2.
Comparative example 3
A recrystallization purification method of bis (2-bromoethyl) amine hydrobromide comprises the following steps:
5g of the crude product from preparation 1 are weighed, 10ml of absolute methanol are added, the temperature is raised to 80 ℃ and the reflux is carried out, the mixture is stirred for 1h at the speed of 300r/min, and then the mixture is cooled in the environment of 25 ℃ and filtered after the cooling is finished.
Detection shows that the crude product is completely dissolved in anhydrous methanol at 25 ℃, the temperature is reduced to 0 ℃ in an ice-water bath, and no product is separated out. Therefore, anhydrous methanol cannot be used as a recrystallization solvent for bis (2-bromoethyl) amine hydrobromide.
Comparative example 4
A recrystallization purification method of bis (2-bromoethyl) amine hydrobromide comprises the following steps:
5g of the crude product from preparation 1 are weighed, 10ml of absolute ethanol are added, the temperature is raised to 90 ℃ and the reflux is carried out, the mixture is stirred for 1h at the speed of 300r/min, and then the mixture is cooled in the environment of 25 ℃ and filtered after the cooling is finished.
Detection shows that the crude product is completely dissolved in absolute ethyl alcohol at 25 ℃, the temperature is reduced to 0 ℃ in an ice-water bath, and no product is separated out. Therefore, absolute ethanol cannot be used as a recrystallization solvent for bis (2-bromoethyl) amine hydrobromide.
Comparative example 5
A recrystallization purification method of bis (2-bromoethyl) amine hydrobromide comprises the following steps:
s1, weighing 5g of the crude product obtained in the preparation example 1, adding 10ml of isopropanol, heating to 90 ℃, refluxing, stirring at the speed of 300r/min for 1h, then cooling at 25 ℃, and filtering to obtain a filter cake after cooling;
s2, washing the filter cake obtained in the step S1 by using 10ml of isopropanol, and drying the filter cake to remove the solvent to obtain the purified bis (2-bromoethyl) amine hydrobromide.
Detection by Varian 400 NMR spectrometer gave 2.5g of the product as a white solid as 91.7% pure bis (2-bromoethyl) amine hydrobromide.
Combining example 1 and comparative example 5, it can be seen that when isopropanol is used as the recrystallization solvent, the purity of bis (2-bromoethyl) amine hydrobromide can be increased to 91.7%, but the purification effect is inferior to that of tert-butanol, and the yield is low, which causes great loss if further purification is desired, resulting in a decrease in the yield of the product.
Comparative example 6
A recrystallization purification method of bis (2-bromoethyl) amine hydrobromide comprises the following steps:
s1, weighing 5g of the crude product obtained in preparation example 1, adding a mixture of 10ml of anhydrous ethanol and anhydrous ether (the volume ratio of the anhydrous ethanol to the anhydrous ether is 1);
s2, washing a filter cake obtained in the S1 by using 10ml of a mixture of anhydrous ethanol and anhydrous ether, and drying the filter cake to remove the solvent to obtain purified bis (2-bromoethyl) amine hydrobromide.
Detection by Varian 400 NMR spectrometer gave 4.0g of the product as a white solid as 75% pure bis (2-bromoethyl) amine hydrobromide.
It can be seen by combining example 1 and comparative example 6 that, when a mixture of anhydrous ethanol and anhydrous diethyl ether was used as a recrystallization solvent, although pigments in the crude product could be removed, the purity of the product was only 75%, and there was no significant improvement compared to the crude product.
As can be seen by combining example 1 with comparative examples 1-6, t-butanol is the best recrystallization solvent for the purification of bis (2-bromoethyl) amine hydrobromide.
Example 2
A recrystallization purification method of bis (2-bromoethyl) amine hydrobromide comprises the following steps:
s1, weighing 500g of the crude product obtained in the preparation example 1, adding 1000ml of tert-butyl alcohol, heating to 90 ℃, refluxing, stirring at the speed of 300r/min for 1h, then cooling to 40 ℃ in the environment of 25 ℃, and filtering to obtain a filter cake;
s2, washing the filter cake obtained in the step S1 by using 1000ml of tert-butyl alcohol with the temperature kept at 30 ℃, and drying the filter cake to remove the solvent to obtain the purified bis (2-bromoethyl) amine hydrobromide.
295g of a white solid product, bis (2-bromoethyl) amine hydrobromide with a purity of 98%, was obtained in a calculated yield of 56.6% by detection with a Varian 400 NMR spectrometer.
As can be seen by combining examples 1-2 and comparative examples 1-6, when tert-butanol was used as a recrystallization solvent in the purification of bis (2-bromoethyl) amine hydrobromide, bis (2-bromoethyl) amine hydrobromide could be obtained with an overall yield of 56.6% and a purity of 98% at high efficiency, and the defect of low purification efficiency of bis (2-bromoethyl) amine hydrobromide was improved.
The above embodiments are preferred embodiments of the present application, and the protection scope of the present application is not limited by the above embodiments, so: all equivalent changes made according to the structure, shape and principle of the present application shall be covered by the protection scope of the present application.
Claims (7)
1. A recrystallization purification method of bis (2-bromoethyl) amine hydrobromide is characterized in that: and (3) taking tert-butyl alcohol as a solvent, and recrystallizing a crude product obtained by the reaction of diethanolamine and hydrobromic acid to obtain purified bis (2-bromoethyl) amine hydrobromide.
2. The recrystallization purification method of bis (2-bromoethyl) amine hydrobromide according to claim 1, comprising the following steps:
s1, adding tert-butyl alcohol into a crude product prepared by reacting diethanolamine and hydrobromic acid, heating to 80-100 ℃, stirring, cooling to 30-50 ℃, and filtering to obtain a filter cake;
and S2, washing the filter cake obtained in the step S1 by using tert-butyl alcohol, and drying the filter cake to remove the solvent to obtain the purified bis (2-bromoethyl) amine hydrobromide.
3. The recrystallization purification process of bis (2-bromoethyl) amine hydrobromide according to claim 2, characterized in that: in the step S1, the feeding ratio of the crude product to the tertiary butanol is 5g: (8-15) ml.
4. The recrystallization purification process of bis (2-bromoethyl) amine hydrobromide according to claim 2, characterized in that: in the step S1, reflux stirring is carried out for 1 to 3 hours at a temperature of between 80 and 100 ℃.
5. The recrystallization purification process of bis (2-bromoethyl) amine hydrobromide according to claim 2, characterized in that: and in the step S2, washing the filter cake obtained in the step S1 by using tert-butyl alcohol with the temperature being kept at 30 ℃.
6. The method for purifying bis (2-bromoethyl) amine hydrobromide according to claim 2, wherein: the feeding ratio of the crude product to the tertiary butanol used in the S2 step is 5g: (8-12) ml.
7. The method for purifying bis (2-bromoethyl) amine hydrobromide according to claim 1, wherein: the crude product is obtained by distilling water and hydrobromic acid after reaction of diethanolamine and hydrobromic acid.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211711546.9A CN115872873A (en) | 2022-12-29 | 2022-12-29 | Recrystallization purification method of bis (2-bromoethyl) amine hydrobromide |
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| CN202211711546.9A CN115872873A (en) | 2022-12-29 | 2022-12-29 | Recrystallization purification method of bis (2-bromoethyl) amine hydrobromide |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08119954A (en) * | 1994-10-26 | 1996-05-14 | Konika Chem:Kk | Production of phenylpiperazines |
| CA2376076A1 (en) * | 1999-06-07 | 2000-12-14 | Warner-Lambert Company | Tricyclic analgesics |
| US20030008850A1 (en) * | 1999-07-14 | 2003-01-09 | Borch Richard F. | Phosphoramide compounds |
| CN1616440A (en) * | 2004-09-30 | 2005-05-18 | 中国人民解放军军事医学科学院放射医学研究所 | Method for synthesizing 1-acetyl-4-(4-hydroxy pheny) piperazine |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08119954A (en) * | 1994-10-26 | 1996-05-14 | Konika Chem:Kk | Production of phenylpiperazines |
| CA2376076A1 (en) * | 1999-06-07 | 2000-12-14 | Warner-Lambert Company | Tricyclic analgesics |
| US20030008850A1 (en) * | 1999-07-14 | 2003-01-09 | Borch Richard F. | Phosphoramide compounds |
| CN1616440A (en) * | 2004-09-30 | 2005-05-18 | 中国人民解放军军事医学科学院放射医学研究所 | Method for synthesizing 1-acetyl-4-(4-hydroxy pheny) piperazine |
Non-Patent Citations (2)
| Title |
|---|
| CAROLEE FLADER: "Development of Novel Quinone Phosphorodiamidate Prodrugs Targeted to DT-Diaphorase", J. MED. CHEM., vol. 43, no. 16, 18 July 2000 (2000-07-18), pages 3157 - 3167, XP002149334, DOI: 10.1021/jm000179o * |
| MANN, FREDERICK G.: "Hofmann\'s ethylene bases. Synthesis of β, β\'-diaminodiethylamine", JOURNAL OF THE CHEMICAL SOCIETY, 1 January 1934 (1934-01-01), pages 461 - 466 * |
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