CN114605360B - Preparation method of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine - Google Patents
Preparation method of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine Download PDFInfo
- Publication number
- CN114605360B CN114605360B CN202210221659.4A CN202210221659A CN114605360B CN 114605360 B CN114605360 B CN 114605360B CN 202210221659 A CN202210221659 A CN 202210221659A CN 114605360 B CN114605360 B CN 114605360B
- Authority
- CN
- China
- Prior art keywords
- methyl
- condensation reaction
- furfuryl alcohol
- distillation
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- 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
- Y02P20/584—Recycling of catalysts
Abstract
The invention provides a preparation method of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine, and relates to the technical field of chemical synthesis. Furfuryl alcohol, a transition metal catalyst, cysteamine and an alkane solvent are mixed, and condensation reaction is carried out in the atmosphere of dimethylamine and formaldehyde, so as to obtain crude product liquid; the obtained crude product liquid is distilled and purified to obtain 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine. The preparation method provided by the invention adopts the transition metal catalyst to carry out catalytic reaction, adopts cysteamine to replace traditional cysteamine hydrochloride as a preparation raw material, avoids the generation of sodium chloride byproducts in the condensation reaction process, and has the advantages of high yield of more than 92.1%, and high purity. In addition, the preparation method provided by the invention can complete the purification process through distillation without alkalization and organic solvent extraction, and has the advantages of simple post-treatment steps and low organic solvent consumption.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a preparation method of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine.
Background
2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine is also called aminoethyl thioether, is a medical intermediate, and is mainly used as an intermediate for synthesizing the gastric drug ranitidine hydrochloride. Chinese patent CN106986847a discloses a process for preparing 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine, mixing dimethylamine hydrochloride alcohol solution, paraformaldehyde and quaternary ammonium salt, heating to 50-70 ℃, adding furfuryl alcohol into the reaction system, and carrying out the first condensation reaction to obtain an intermediate; mixing the intermediate with cysteamine hydrochloride, concentrated hydrochloric acid and perchloric acid, keeping the temperature of the system at 15-25 ℃, and performing a second condensation reaction to obtain a mixed solution containing 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine hydrochloride; alkalizing the mixed solution, extracting with dichloromethane, and distilling the obtained extract to obtain 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine, wherein the yield is 86-88%, and the purity is 98.7-99%. However, the preparation of 1000kg of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine by the above method yielded about 700kg of by-product sodium chloride, yielding a large amount of by-product sodium chloride.
Disclosure of Invention
In view of the above, the present invention aims to provide a method for preparing 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine, which does not produce sodium chloride as a byproduct.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a preparation method of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine, which is characterized by comprising the following steps:
furfuryl alcohol, a transition metal catalyst, cysteamine and an alkane solvent are mixed, and condensation reaction is carried out in the atmosphere of dimethylamine and formaldehyde, so as to obtain crude product liquid;
the obtained crude product liquid is distilled and purified to obtain 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine.
2. The method of claim 1, wherein the molar ratio of furfuryl alcohol to cysteamine is 1: 0.98-1.05.
Preferably, the transition metal catalyst comprises nanoscale copper;
the mass ratio of the furfuryl alcohol to the transition metal catalyst is 1:0.01 to 0.05.
Preferably, the molar ratio of furfuryl alcohol to dimethylamine is 1: 0.98-1.05.
Preferably, the molar ratio of dimethylamine to formaldehyde is 0.98-1.05: 0.98-1.05.
Preferably, the alkane solvent comprises cyclohexane.
Preferably, the temperature of the condensation reaction is 75-95 ℃ and the time is 5-11 h.
Preferably, the distillative purification comprises sequentially performing a first distillation and a second distillation;
the pressure of the first distillation is-0.09 MPa, and the temperature is 20-120 ℃;
the pressure of the second distillation is 50-150 Pa, and the temperature is 121-145 ℃.
The invention provides a preparation method of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine, which comprises the following steps: furfuryl alcohol, a transition metal catalyst, cysteamine and an alkane solvent are mixed, and condensation reaction is carried out in the atmosphere of dimethylamine and formaldehyde, so as to obtain crude product liquid; the obtained crude product liquid is distilled and purified to obtain 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine. According to the preparation method provided by the invention, the transition metal catalyst is adopted for catalytic reaction, cysteamine is adopted to replace traditional cysteamine hydrochloride as a preparation raw material, so that sodium chloride byproducts are avoided in the condensation reaction process, and the product yield is high. In addition, the preparation method provided by the invention can complete the purification process through distillation without alkalization and organic solvent extraction, and has the advantages of simple post-treatment steps and low organic solvent consumption. As shown in the test results of examples, the total yield of the 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine obtained by the preparation method provided by the invention is more than 92.1%, and the purity is more than 99.1%.
Detailed Description
The invention provides a preparation method of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine, which comprises the following steps:
furfuryl alcohol, a transition metal catalyst, cysteamine and an alkane solvent are mixed, and condensation reaction is carried out in the atmosphere of dimethylamine and formaldehyde, so as to obtain crude product liquid;
the obtained crude product liquid is distilled and purified to obtain 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine.
In the present invention, all raw material components are commercially available products well known to those skilled in the art unless specified otherwise.
Furfuryl alcohol, transition metal catalyst, cysteamine and alkane solvent are mixed and condensation reaction is carried out in dimethylamine and formaldehyde atmosphere to obtain crude product liquid.
In the present invention, the molar ratio of furfuryl alcohol to cysteamine is preferably 1:0.98 to 1.05, more preferably 1:1 to 1.04, more preferably 1:1.02 to 1.03.
In the present invention, the transition metal catalyst preferably includes nano-sized copper; the particle diameter of the transition metal catalyst is preferably 5 to 20nm, more preferably 5 to 10nm. In the present invention, the mass ratio of furfuryl alcohol to transition metal catalyst is preferably 1:0.01 to 0.05, more preferably 1:0.02 to 0.04, more preferably 1:0.02 to 0.03.
In the present invention, the molar ratio of furfuryl alcohol to dimethylamine is preferably 1:0.98 to 1.05, more preferably 1:1 to 1.04, more preferably 1:1.02 to 1.03. In the present invention, the dimethylamine is preferably subjected to a drying treatment before use, and the drying treatment is not particularly limited, and a drying operation of dimethylamine known to those skilled in the art may be employed.
In the present invention, the molar ratio of dimethylamine to formaldehyde is preferably 0.98 to 1.05:0.98 to 1.05, more preferably 1 to 1.04:1 to 1.04, more preferably 1.02 to 1.03:1.02 to 1.03. In the present invention, the formaldehyde is preferably subjected to a drying treatment before use, and the drying treatment is not particularly limited, and a drying operation of formaldehyde known to those skilled in the art may be employed.
In the present invention, the alkane solvent preferably includes cyclohexane. In the present invention, the mass ratio of furfuryl alcohol to alkane solvent is preferably 1:1 to 3, more preferably 1:1 to 2.5, more preferably 1:1 to 2.
In the present invention, the temperature of the condensation reaction is 75 to 95℃for a period of time of preferably 5 to 10 hours, the pressure is preferably 0 to 0.15MPa, more preferably 0.01 to 0.12MPa, and still more preferably 0.05 to 0.1MPa. In the present invention, the condensation reaction preferably includes sequentially performing a first condensation reaction at a temperature of preferably 75 to 85 ℃, more preferably 78 to 84 ℃ for a time of preferably 4 to 8 hours, more preferably 5 to 6 hours, and a second condensation reaction. In the present invention, the temperature of the second condensation reaction is preferably 90 to 95 ℃, and the time is preferably 1 to 3 hours, more preferably 1.5 to 2 hours. In the present invention, the water produced during the condensation reaction is removed to ensure that the water content in the system is not more than 0.2wt%, more preferably not more than 0.1wt%; the condensation reaction is preferably carried out in a closed reaction water collecting kettle (water separator); the dimethylamine and formaldehyde are preferably introduced into a closed reaction water collecting kettle through a dryer pipeline; the method is not particularly limited to the inflow flow rate of the dimethylamine and the formaldehyde, and can ensure that the pressure of the closed reaction water collecting kettle is 0-0.15 MPa. In the present invention, the reaction occurring during the condensation reaction is represented by formula (1):
in a specific embodiment of the present invention, the furfuryl alcohol, the transition metal catalyst, cysteamine and the alkane solvent are mixed, and the condensation reaction is preferably performed in an atmosphere of dimethylamine and formaldehyde: first mixing furfuryl alcohol with an alkane solvent to obtain furfuryl alcohol solution; the furfuryl alcohol solution is mixed with a transition metal catalyst for the second time, the obtained furfuryl alcohol-catalyst mixed solution is heated to the first temperature for the first time, and then mixed gas of dimethylamine and formaldehyde is introduced for the first condensation reaction, so that a reaction system is obtained; and (3) raising the temperature of the reaction system to a second temperature, and then dropwise adding cysteamine to perform a second condensation reaction. In the present invention, the first and second mixing modes are preferably stirring and mixing, and the speed and time of stirring and mixing are not particularly limited, and the raw materials may be uniformly mixed. In the present invention, the temperature rise rate of the first temperature rise is preferably 15 to 25 ℃/h, more preferably 20 to 22 ℃/h; the first temperature is preferably 75 to 85 ℃, more preferably 78 to 84 ℃. In the present invention, the water produced during the first condensation reaction is removed to ensure that the water content in the system is less than or equal to 0.2wt%. In the present invention, the temperature rise rate of the second temperature rise is preferably 15 to 25 ℃/h, more preferably 20 to 22 ℃/h; the second temperature is preferably 85 to 95 ℃, more preferably 90 to 95 ℃. In the present invention, the time for dropping cysteamine is preferably 2 to 4 hours, more preferably 3 to 4 hours. In the present invention, the water produced during the second condensation reaction is removed to ensure that the water content in the system is less than or equal to 0.2wt%
After the condensation reaction, the invention preferably further comprises the step of carrying out solid-liquid separation on the reaction liquid obtained by the condensation reaction to obtain a solid component and a liquid component; washing the solid component with an alkane solvent to obtain a washing liquid; combining the washing liquid with the liquid component to obtain a crude product liquid. In the present invention, the temperature of the solid-liquid separation is preferably 85 to 95 ℃, more preferably 90 to 95 ℃; the solid-liquid separation mode is not particularly limited, and can be a solid-liquid separation mode well known to those skilled in the art, such as filtration; the purpose of the solid-liquid separation is to recover the transition metal catalyst. In the present invention, the alkane solvent preferably includes cyclohexane; the mass ratio of the furfuryl alcohol to the organic solvent is preferably 1:0.01 to 0.2, more preferably 1:0.05 to 0.1.
After the crude product liquid is obtained, the obtained crude product liquid is distilled and purified to obtain the 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine.
In the present invention, the distillative purification includes sequentially performing a first distillation and a second distillation. In the present invention, the pressure of the first distillation is preferably-0.09 to 0.09MPa, more preferably-0.09 to 0MPa, still more preferably-0.09 to-0.05 MPa; the temperature of the first distillation is preferably 20 to 120 ℃, more preferably 50 to 120 ℃; the fraction I from the first distillation comprises the alkane solvent and unreacted starting materials (e.g., furfuryl alcohol and formaldehyde). In the present invention, the pressure of the second distillation is preferably 50 to 150Pa, more preferably 80 to 130Pa, still more preferably 90 to 100Pa; the temperature of the second distillation is preferably 121 to 145 ℃, more preferably 130 to 145 ℃; the fraction obtained by the second distillation is 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine. In the present invention, the distillation is preferably performed in a distillation still.
The technical solutions of the present invention will be clearly and completely described in the following in connection with the embodiments of the present invention. It will be apparent that the described embodiments are only some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
Adding 98.1kg of furfuryl alcohol and 120kg of cyclohexane into a 300L closed reaction water collecting kettle, stirring and mixing uniformly, adding 2kg of copper powder with the particle size of 10nm, stirring and mixing uniformly, heating to 81 ℃ at the heating rate of 20 ℃/h, introducing dimethylamine and formaldehyde gas through a dryer pipeline, and pre-reacting for 6 hours at the temperature of 79 ℃ and the pressure of 0.07MPa to obtain a pre-reaction system; 46kg of dimethylamine gas and 30.5kg of formaldehyde gas are added up, and water generated in the reaction process is removed to keep the water content in the reaction system to be 0.07wt%.
Heating the closed reaction water collecting kettle to 95 ℃ at a heating rate of 20 ℃/h, dropwise adding 78.5kg of cysteamine, carrying out heat preservation condensation reaction for 2h after the dropwise adding is finished, filtering at the temperature of 95 ℃ to obtain a liquid component and a solid component, washing the solid component with 5kg of cyclohexane, and combining the obtained washing liquid with the liquid component to obtain a crude product liquid; wherein, the dripping time of cysteamine is 4.5h, 18.1kg of water is adopted in the condensation reaction process, and the water content in the reaction system is kept to be 0.07wt%; 3.8kg of wet catalyst was recovered.
Feeding the crude product liquid into a 300L distillation kettle, starting a vacuum pump to control the vacuum degree of the distillation kettle to be minus 0.09MPa, and then starting heating, wherein a fraction I is collected in the first distillation process, and heating and collecting are stopped when the temperature of the distillation kettle is raised to 120 ℃ to obtain a fraction I (121.6 kg, wherein the cyclohexane content is 99.5wt%, the furfuryl alcohol content is 0.15wt% and the formaldehyde content is 0.09 wt%); vacuum degree is controlled to 1000Pa by a vacuum pump, vacuum pumping is continued until the vacuum degree is stable to 65Pa after the vacuum degree is stable, heating is started to collect 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine, and distillation is stopped when the temperature of a distillation still is raised to 142 ℃ to obtain 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine (205.3 kg, purity is 99.1%, and total yield is 95.8%).
Example 2
Adding 98.1kg of furfuryl alcohol and 100kg of cyclohexane into a 300L closed reaction water collecting kettle, stirring and mixing uniformly, adding 3kg of copper powder with the particle size of 10nm, stirring and mixing uniformly, heating to 83 ℃ at the heating rate of 22 ℃/h, introducing dimethylamine and formaldehyde gas through a dryer pipeline, and pre-reacting for 5.5 hours at the temperature of 83 ℃ and the pressure of 0.09MPa to obtain a pre-reaction system; 45kg of dimethylamine gas and 30kg of formaldehyde gas are added up, 16.9kg of water is adopted in the reaction process, and the water content in the reaction system is kept to be 0.08wt%.
Heating a closed reaction water collecting kettle to 90 ℃ at a heating rate of 20 ℃/h, dropwise adding 77.1kg of cysteamine, carrying out heat preservation condensation reaction for 2h after the dropwise adding is finished, filtering at 90 ℃ to obtain a liquid component and a solid component, washing the solid component with 5kg of cyclohexane, and combining the obtained washing liquid with the liquid component to obtain a crude product liquid; wherein, the dripping time of cysteamine is 4.3 hours, and the water generated in the reaction process is removed to keep the water content in the reaction system to be 0.08wt%; 5.5kg of wet catalyst was recovered.
Feeding the crude product liquid into a 300L distillation kettle, starting a vacuum pump to control the vacuum degree of the distillation kettle to be minus 0.09MPa, and then starting heating, wherein a fraction I is collected in the first distillation process, and heating and collecting are stopped when the temperature of the distillation kettle is raised to 120 ℃ to obtain a fraction I (100.9 kg, wherein the cyclohexane content is 99.4wt%, the furfuryl alcohol content is 0.17wt% and the formaldehyde content is 0.02 wt%); vacuum degree is controlled to 1000Pa by a vacuum pump, vacuum pumping is continued until vacuum degree is stabilized to 110Pa after vacuum degree is stabilized, heating is started to collect 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine, distillation is stopped when temperature of a distillation still is raised to 143 ℃, and 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine (197.4 kg, purity is 99.4%, and total yield is 92.11%).
Example 3
Adding 98.1kg of furfuryl alcohol and 140kg of cyclohexane into a 300L closed reaction water collecting kettle, stirring and mixing uniformly, adding 4kg of copper powder with the particle size of 5nm, stirring and mixing uniformly, heating to 80 ℃ at the heating rate of 20 ℃/h, introducing dimethylamine and formaldehyde gas through a dryer pipeline, and pre-reacting for 6 hours at the temperature of 80 ℃ and the pressure of 0.08MPa to obtain a pre-reaction system; 44.1kg of dimethylamine gas and 29.5kg of formaldehyde gas are added together, and water generated in the reaction process is removed to maintain the water content of the reaction system to be 0.09wt%.
Heating the closed reaction water collecting kettle to 95 ℃ at a heating rate of 20 ℃/h, dropwise adding 77.1kg of cysteamine, carrying out heat preservation condensation reaction for 2h after the dropwise adding is finished, filtering at 90 ℃ to obtain a liquid component and a solid component, washing the solid component with 5kg of cyclohexane, and combining the obtained washing liquid with the liquid component to obtain a crude product liquid; wherein, the dripping time of cysteamine is 4.3 hours, 18.4kg of water is adopted in the condensation reaction process, and the water content in the reaction system is kept to be 0.07wt%; 6kg of wet catalyst was recovered.
Feeding the crude product liquid into a 300L distillation kettle, starting a vacuum pump to control the vacuum degree of the distillation kettle to be minus 0.09MPa, and then starting heating, wherein a fraction I is collected in the first distillation process, and heating and collecting are stopped when the temperature of the distillation kettle is raised to 120 ℃ to obtain a fraction I (142.1 kg, wherein the cyclohexane content is 99.0wt%, the furfuryl alcohol content is 0.72wt%, and the formaldehyde content is 0.01 wt%); vacuum degree is controlled to 1000Pa by a vacuum pump, vacuum pumping is continued until vacuum degree is stabilized to 110Pa after vacuum degree is stabilized, heating is started to collect 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine, distillation is stopped when the temperature of a distillation still is raised to 142 ℃, and 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine (195.6 kg, purity is 99.2%, and total yield is 92.17%).
Comparative example 1
Adding 98.1kg of furfuryl alcohol and 50kg of cyclohexane into a 300L closed reaction water collecting kettle, stirring and mixing uniformly, adding 4kg of copper powder with the particle size of 10nm, stirring and mixing uniformly, heating to 80 ℃ at the heating rate of 20 ℃/h, introducing dimethylamine and formaldehyde gas through a dryer pipeline, and pre-reacting for 3 hours at the temperature of 80 ℃ and the pressure of 0.04MPa to obtain a pre-reaction system; 44.3kg of dimethylamine gas and 29.7kg of formaldehyde gas are added together, and the water produced in the reaction process is removed to maintain the water content of the reaction system to be 0.09wt%.
Heating the closed reaction water collecting kettle to 85 ℃ at a heating rate of 20 ℃/h, then dropwise adding 77.1kg of cysteamine, carrying out heat preservation condensation reaction for 2h after the dropwise adding is finished, then filtering at 90 ℃ to obtain a liquid component and a solid component, washing the solid component with 5kg of cyclohexane, and combining the obtained washing liquid with the liquid component to obtain a crude product liquid; wherein, the dripping time of cysteamine is 4.3 hours, 18.4kg of water is adopted in the condensation reaction process, and the water content in the reaction system is kept to be 0.08wt%; 6.5kg of wet catalyst was recovered.
Feeding the crude product liquid into a 300L distillation kettle, starting a vacuum pump to control the vacuum degree of the distillation kettle to be minus 0.09MPa, and then starting heating, wherein a fraction I is collected in the first distillation process, and heating and collecting are stopped when the temperature of the distillation kettle is raised to 120 ℃ to obtain a fraction I (39.8 kg, the cyclohexane content is 98.2wt%, the furfuryl alcohol content is 1.72wt%, and the formaldehyde content is 0.08 wt%); vacuum degree is controlled to 1000Pa by a vacuum pump, vacuum pumping is continued until the vacuum degree is stable to 75Pa after the vacuum degree is stable, heating is started to collect 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine, and distillation is stopped when the temperature of a distillation still is raised to 142 ℃ to obtain 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine (148.5 kg, purity is 99.1%, and total yield is 69.9%).
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (8)
1. A process for the preparation of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine comprising the steps of:
furfuryl alcohol, a transition metal catalyst, cysteamine and an alkane solvent are mixed, and condensation reaction is carried out in the atmosphere of dimethylamine and formaldehyde, so as to obtain crude product liquid; the condensation reaction is as follows: first mixing furfuryl alcohol with an alkane solvent to obtain furfuryl alcohol solution; the furfuryl alcohol solution is mixed with a transition metal catalyst for the second time, the obtained furfuryl alcohol-catalyst mixed solution is heated to the first temperature for the first time, and then mixed gas of dimethylamine and formaldehyde is introduced for the first condensation reaction, so that a reaction system is obtained; heating the reaction system to a second temperature, and then dropwise adding cysteamine to perform a second condensation reaction; the time of the first condensation reaction is 4-8 hours; the second condensation reaction time is 1-3 h;
the obtained crude product liquid is distilled and purified to obtain 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine.
2. The method of claim 1, wherein the molar ratio of furfuryl alcohol to cysteamine is 1:0.98 to 1.05.
3. The method of preparation of claim 1, wherein the transition metal catalyst comprises nanoscale copper;
the mass ratio of the furfuryl alcohol to the transition metal catalyst is 1:0.01 to 0.05.
4. The method of claim 1, wherein the molar ratio of furfuryl alcohol to dimethylamine is 1:0.98 to 1.05.
5. The preparation method of claim 1, wherein the molar ratio of dimethylamine to formaldehyde is 0.98-1.05: 0.98 to 1.05.
6. The method of claim 1, wherein the alkane solvent comprises cyclohexane.
7. The method according to any one of claims 1 to 6, wherein the temperature of the condensation reaction is 75 to 95 ℃.
8. The method of claim 1, wherein the distillative purification comprises performing a first distillation and a second distillation in sequence;
the pressure of the first distillation is-0.09 MPa, and the temperature is 20-120 ℃;
the pressure of the second distillation is 50-150 Pa, and the temperature is 121-145 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210221659.4A CN114605360B (en) | 2022-03-09 | 2022-03-09 | Preparation method of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210221659.4A CN114605360B (en) | 2022-03-09 | 2022-03-09 | Preparation method of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114605360A CN114605360A (en) | 2022-06-10 |
| CN114605360B true CN114605360B (en) | 2023-05-05 |
Family
ID=81860885
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210221659.4A Active CN114605360B (en) | 2022-03-09 | 2022-03-09 | Preparation method of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114605360B (en) |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1565966A (en) * | 1976-08-04 | 1980-04-23 | Allen & Hanburys Ltd | Aminoalkyl furan derivatives |
| NO811501L (en) * | 1980-05-13 | 1981-11-16 | Crc Ricerca Chim | PROCEDURE FOR THE PREPARATION OF ETHENDIAMINE DERIVATIVES, AND INTERMEDIATES FOR THESE |
| JPS5988458A (en) * | 1982-11-12 | 1984-05-22 | Toyama Chem Co Ltd | Amine derivative and its salt |
| JPH0725745B2 (en) * | 1986-11-11 | 1995-03-22 | 株式会社日本触媒 | Method for producing amine compound |
| DD298100A5 (en) * | 1990-09-24 | 1992-02-06 | Allen U. Hanburys Limited,Gb | AMINOALKYLFURANDERIVATE, METHOD FOR THE PRODUCTION THEREOF AND MEDICINES CONTAINING SUCH COMPOUNDS |
| CN1793120A (en) * | 2005-12-12 | 2006-06-28 | 北京大学 | Thiourea kind compund with inhibiting virus capsid protain activity and its preparation process and application thereof |
| CN103804388B (en) * | 2014-01-29 | 2016-03-23 | 中国医学科学院药用植物研究所 | 4 β-nitrogen substituted furan tertiary amines podophyllotoxin derivative and preparation method thereof and application |
-
2022
- 2022-03-09 CN CN202210221659.4A patent/CN114605360B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN114605360A (en) | 2022-06-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111004212A (en) | Method for preparing nicotine | |
| CN105061224B (en) | Synthetic method of L-2-aminobutanol | |
| AU2005257478B2 (en) | Method for producing (Z)-1-phenyl-1-diethylaminocarbonyl-2-aminomethyl cyclopropane hydrochloride | |
| CN102408559A (en) | Preparation process of amine terminated polyether | |
| CN114605360B (en) | Preparation method of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine | |
| CN102746161A (en) | Method for synthesizing 1,8-terpene diamine | |
| CN113105379A (en) | Method and device for preparing selenocysteine by using sodium formaldehyde sulfoxylate as reducing agent | |
| CN110437056B (en) | Method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid | |
| CN112812059A (en) | Preparation method of 2-aminosulfonyl-N, N-dimethylnicotinamide | |
| CN114369033B (en) | Green preparation method of N, N-dimethylamino ethyl acrylate | |
| CN105237412A (en) | N-methyl diisopropanolamine preparation method | |
| CN113999194A (en) | Process for the preparation of furan ammonium salts | |
| CN110590580B (en) | Preparation method of monoethanolamine and diethanolamine | |
| CN115466255B (en) | Tropine and synthetic method thereof | |
| CN105017064A (en) | Synthetic method for isopropyl hydrazine | |
| CN110835296A (en) | Preparation process of 2,2, 4-trimethyl-3-hydroxypentanoic acid | |
| CN109438210B (en) | Preparation method of pivalic aldehyde | |
| CN113072449B (en) | Synthesis method of 4,4, 4-trifluoroacetylacetic acid ethyl ester | |
| CN111087315A (en) | Synthetic method of eltrombopag intermediate and synthetic method of eltrombopag | |
| CN113173866B (en) | Method for treating heavy residual liquid in ketoxime production | |
| CN114315619B (en) | Synthesis method of dimethoxy dopa | |
| CN110981823B (en) | Method for preparing 3-mercapto-5-methyl-1, 2, 4-triazole from triazine ring | |
| CN108840791B (en) | Cyclopropanoyl acetone and its synthesis method | |
| CN106349083A (en) | Preparation method of 2,4,6-trifluorobenzylamine | |
| CN110590579B (en) | Method for synthesizing monoethanolamine and diethanolamine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: 052165 Jinsha Road, economic and Technological Development Zone, Shijiazhuang City, Hebei Province Applicant after: Hebei Haili Hengyuan New Material Co.,Ltd. Address before: 052165 No. 2 Jinsha Road, economic and Technological Development Zone, Shijiazhuang City, Hebei Province Applicant before: HEBEI HAILI FRAGRANCES CO.,LTD. |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |