CN111269131B - Process for preparing cyclopropyl ethyl amide by taking tri-n-propylamine as acid acceptor - Google Patents

Process for preparing cyclopropyl ethyl amide by taking tri-n-propylamine as acid acceptor Download PDF

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CN111269131B
CN111269131B CN202010169285.7A CN202010169285A CN111269131B CN 111269131 B CN111269131 B CN 111269131B CN 202010169285 A CN202010169285 A CN 202010169285A CN 111269131 B CN111269131 B CN 111269131B
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propylamine
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amide
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CN111269131A (en
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沈文光
潘文华
莫振翼
王保军
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Jiangsu Feiyu Medical Technology Co ltd
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    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/04Formation of amino groups in compounds containing carboxyl groups
    • C07C227/06Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/16Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups

Abstract

The invention discloses a process for preparing cyclopropylethyl amide by taking tri-n-propylamine as an acid acceptor, which comprises the following steps: carrying out condensation reaction on N, N-dimethylamino ethyl acrylate, 2, 4-dichloro-5-fluorobenzoyl chloride and tri-N-propylamine to obtain a first feed liquid; adding cyclopropylamine into the first feed liquid to carry out substitution reaction to obtain a second feed liquid; the second feed liquid contains cyclopropyl ethyl amide, tri-n-propylamine and dimethylamine hydrochloride; adding water into the second feed liquid for washing, standing for layering, and separating to obtain an aqueous phase dimethylamine hydrochloride solution and a third feed liquid; cooling and crystallizing the third material liquid, wherein the cyclopropylethyl amide in the third material liquid is crystallized into a crystallized material; adding ethanol into the crystallized material for rinsing, and centrifuging under a closed condition to obtain a wet product; and drying the wet product to obtain a finished product. The invention takes the tri-n-propylamine as the acid acceptor and the solvent carrier, thereby not only ensuring the operation environment of operators, but also improving the conversion rate of condensation reaction and substitution reaction and the total yield of products.

Description

Process for preparing cyclopropyl ethyl amide by taking tri-n-propylamine as acid acceptor
Technical Field
The invention relates to a process for preparing cyclopropyl ethyl amide by taking tri-n-propylamine as an acid acceptor.
Background
Cyclopropylethylamide, alias cyclopropylamide, chemical name: 2(2, 4-dichloro-5-fluorobenzoyl) -3-cyclopropylamino ethyl acrylate, which is mainly used for producing ciprofloxacin hydrochloride medicaments. The ciprofloxacin hydrochloride is a cheap and good traditional medicine which can not be replaced in quinolone antiviral medicines, can be used for a human body and an animal body, and has a broad spectrum. In recent years, the demand of ciprofloxacin hydrochloride medicaments is increased year by year, the global demand is about 5000 tons/year, China is a main production country of ciprofloxacin hydrochloride medicaments, and the production amount accounts for more than 80 percent of the world.
At normal temperature and pressure, the cyclopropylethyl amide is a white powdery solid, and HCl gas is also generated in the condensation reaction in the first step. Therefore, it is critical to select a suitable acid acceptor and a solvent as a carrier of the reaction product during the reaction. In the traditional production process, 2, 4-dichloro-5-fluorobenzoyl chloride and N, N-dimethylamino ethyl acrylate are used as initial raw materials, tri-N-butylamine listed in the national hazardous chemical hypertoxic catalogue is used as an acid acceptor, and the molecular formula of the tri-N-butylamine is C12H27N, the molecular weight is 185.35, and the tri-N-butylamine is hypertoxic; colorless liquid at normal temperature and pressure, ammonia-like smell, 216.5 deg.C boiling point, 86 deg.C flash point, and 0.78 relative specific gravity, is insoluble in water, and is soluble in alcohol and ether. Because the boiling point is as high as 216.5 ℃, the energy consumption in the separation and recovery process is larger, and the recovery and separation are difficult; because of the strong toxicity, the operation health environment of the operators is bad.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a process for preparing a cyclopropylethyl amide by taking tri-n-propylamine as an acid acceptor, which takes the tri-n-propylamine as the acid acceptor and a solvent carrier, thereby not only ensuring the operation environment of operators, but also improving the conversion rate of condensation reaction and substitution reaction and the total yield of products.
In order to solve the technical problems, the technical scheme of the invention is as follows: a process for preparing cyclopropyl ethyl amide by taking tri-n-propylamine as an acid acceptor comprises the following process steps:
carrying out condensation reaction on N, N-dimethylamino ethyl acrylate, 2, 4-dichloro-5-fluorobenzoyl chloride and tri-N-propylamine to obtain a first feed liquid;
adding cyclopropylamine into the first feed liquid to carry out substitution reaction to obtain a second feed liquid; wherein the second feed liquid contains cyclopropylethyl amide, tri-n-propylamine and dimethylamine hydrochloride;
adding water into the second feed liquid for washing, standing for layering, and separating to obtain an aqueous phase dimethylamine hydrochloride solution and a third feed liquid;
cooling and crystallizing the third material liquid, wherein the cyclopropylethyl amide in the third material liquid is crystallized into a crystallized material;
adding ethanol into the crystallized material for rinsing, and centrifuging under a closed condition to obtain a wet product;
and drying the wet product to obtain a finished product of the cyclopropyl ethyl amide.
Further, the mass ratio of the ethyl N, N-dimethylamino acrylate, the 2, 4-dichloro-5-fluorobenzoyl chloride and the tri-N-propylamine is 1: (1.3-1.8): (2.74-3);
and/or the mass of the water added into the second feed liquid is 4-6% of the mass of the second feed liquid.
Further, the reaction temperature of the condensation reaction is 40-60 ℃, and the reaction time of the condensation reaction is 4-6 h;
and/or the reaction temperature of the substitution reaction is 60-80 ℃, and the reaction time of the substitution reaction is 4-6 h;
and/or the temperature of the water added into the second feed liquid is 60-85 ℃.
Further, condensation reaction and substitution reaction are carried out in a reaction kettle;
and/or transferring the second feed liquid into a water washing crystallization kettle through a closed pipeline, adding water for washing, standing and layering;
and/or cooling and crystallizing the third feed liquid in a water washing crystallization kettle;
and/or the crystallized material enters a rinsing centrifuge in a closed centrifuge;
and/or the wet product is dried in an internal dryer.
And further adding ethanol into the third feed liquid before cooling and crystallizing the third feed liquid so as to better separate out and form crystals.
Further, in order to recycle the ethanol, the liquid obtained after the third feed liquid is cooled and crystallized to obtain a crystallized material and the liquid obtained after the crystallized material is rinsed and centrifuged to obtain a wet product are mixed to obtain a centrifugal mother liquid;
the process steps further comprise:
transferring the centrifugal mother liquor into an ethanol recovery tower, extracting ethanol from the top of the ethanol recovery tower, and returning the extracted ethanol to a cooling crystallization section and/or a rinsing section.
Further, in order to recycle tri-n-propylamine, after ethanol is adopted at the tower top of the ethanol recovery tower, the residual material in the ethanol recovery tower is the material in the first tower kettle;
the process steps further comprise:
transferring the material in the first tower kettle into an evaporator, extracting a mixed material from the top of the evaporator, and feeding the mixed material into a tri-n-propylamine recovery tower, wherein the mixed material comprises ethanol, tri-n-propylamine and water;
returning the material extracted from the tower top of the tri-n-propylamine recovery tower to the ethanol recovery tower, and returning the residual material in the tri-n-propylamine recovery tower to the condensation reaction section.
Further, in order to recover the residual cyclopropylethyl amide, after the mixed material is extracted from the top of the evaporator, the residual material in the evaporator is the material in the second tower kettle;
the process steps further comprise:
adding water into the material in the second tower kettle, and adjusting the pH value to 11-12 by using alkali liquor;
cooling at below 0 deg.c for crystallization;
and performing suction filtration to obtain a crude product, and returning the crude product to a cooling crystallization working section.
Further, in order to recycle water and residual tri-n-propylamine, the residual material after the crude product is filtered is filtrate;
the process steps further comprise:
standing and layering the filtrate to obtain a water phase and an organic phase, rectifying and recovering the water phase, returning the recovered water to a washing and layering working section, carrying out vacuum rectification on the organic phase, and returning the recovered tri-n-propylamine to a condensation reaction working section.
Further, adjusting the pH value of the material in the second tower kettle in the neutralization kettle, and opening the refrigerant in the neutralization kettle for cooling crystallization;
and/or carrying out suction filtration operation in a suction filter;
and/or layering the filtrate in a layering kettle;
and/or rectifying and recovering the water phase in a wastewater recovery kettle;
and/or the organic phase is rectified in vacuum in a mother liquor recovery kettle.
Further, the separated aqueous phase dimethylamine hydrochloride solution is used for preparing N, N-dimethylamino ethyl acrylate.
After the technical scheme is adopted, the production process adopts tri-n-propylamine as an acid acceptor and a solvent carrier of the product. Tri-n-propylamine of formula C9H21N, colorless liquid at normal temperature and normal pressure, ammonia-like smell, boiling point of 156 ℃, flash point of 32 ℃, specific gravity of 0.77, water insolubility, alcohol and ether solubility, low toxicity and no listed national hypertoxic catalogues. Compared with tri-n-butylamine, the tri-n-propylamine used as an acid absorbent and a solvent carrier has no strong toxicity and low boiling point, effectively avoids the defects of strong toxicity, large energy consumption in the separation and recovery process, difficult recovery and separation and the like of the tri-n-butylamine, greatly improves the yield of products in the reaction process, achieves the conversion rate of the condensation reaction and the substitution reaction of 97-99 percent, achieves the total yield of the products of 98 percent, and improves the yield by two percent compared with the traditional process.
Drawings
FIG. 1 is a process flow diagram of the present invention for preparing cyclopropylethyl amide using tri-n-propylamine as an acid acceptor.
Detailed Description
In order that the present invention may be more readily and clearly understood, a more particular description of the invention briefly described above will be rendered by reference to specific embodiments that are illustrated in the appended drawings.
As shown in fig. 1, a process for preparing cyclopropylethyl amide by using tri-n-propylamine as an acid acceptor comprises the following steps:
carrying out condensation reaction on N, N-dimethylamino ethyl acrylate, 2, 4-dichloro-5-fluorobenzoyl chloride and tri-N-propylamine to obtain a first feed liquid;
adding cyclopropylamine into the first feed liquid to carry out substitution reaction to obtain a second feed liquid; wherein the second feed liquid contains cyclopropylethyl amide, tri-n-propylamine and dimethylamine hydrochloride;
adding water into the second feed liquid for washing, standing for layering, and separating to obtain an aqueous phase dimethylamine hydrochloride solution and a third feed liquid;
cooling and crystallizing the third material liquid, wherein the cyclopropylethyl amide in the third material liquid is crystallized into a crystallized material;
adding ethanol into the crystallized material for rinsing, and centrifuging under a closed condition to obtain a wet product;
and drying the wet product to obtain a finished product of the cyclopropyl ethyl amide.
In this example, the mass ratio of ethyl N, N-dimethylaminoacrylate, 2, 4-dichloro-5-fluorobenzoyl chloride and tri-N-propylamine was 1: (1.3-1.8): (2.74-3);
and/or the mass of the water added into the second feed liquid is 4-6% of the mass of the second feed liquid.
In the embodiment, the reaction temperature of the condensation reaction is 40-60 ℃, and the reaction time of the condensation reaction is 4-6 h;
and/or the reaction temperature of the substitution reaction is 60-80 ℃, and the reaction time of the substitution reaction is 4-6 h;
and/or the temperature of the water added into the second feed liquid is 60-85 ℃.
In this example, the condensation reaction and the substitution reaction were carried out in a reaction vessel;
and/or transferring the second feed liquid into a water washing crystallization kettle through a closed pipeline, adding water for washing, standing and layering;
and/or cooling and crystallizing the third feed liquid in water washing crystallization;
and/or the crystallized material enters a rinsing centrifuge in a closed centrifuge;
and/or the wet product is dried in an internal dryer.
In this example, ethanol was added to the third feed liquid before cooling and crystallizing the third feed liquid in order to precipitate and form crystals better.
As shown in fig. 1, in order to recycle ethanol, the liquid after the third feed liquid is cooled and crystallized to obtain a crystallized material and the liquid after the crystallized material is rinsed and centrifuged to obtain a wet product are mixed to obtain a centrifugal mother liquid;
the process steps further comprise:
transferring the centrifugal mother liquor into an ethanol recovery tower, extracting ethanol from the top of the ethanol recovery tower, and returning the extracted ethanol to a cooling crystallization section and/or a rinsing section.
As shown in fig. 1, in order to recycle tri-n-propylamine, after ethanol is used at the top of the ethanol recovery tower, the material left in the ethanol recovery tower is the material in the first tower kettle;
the process steps further comprise:
transferring the material in the first tower kettle into an evaporator, extracting a mixed material from the top of the evaporator, and feeding the mixed material into a tri-n-propylamine recovery tower, wherein the mixed material comprises ethanol, tri-n-propylamine and water;
returning the material extracted from the tower top of the tri-n-propylamine recovery tower to the ethanol recovery tower, and returning the residual material in the tri-n-propylamine recovery tower to the condensation reaction section.
As shown in fig. 1, after the mixed material is extracted from the top of the evaporator, the remaining material in the evaporator is the material in the second tower kettle in order to recover the residual cyclopropylethyl amide;
the process steps further comprise:
adding water into the material in the second tower kettle, and adjusting the pH value to 11-12 by using alkali liquor;
cooling at below 0 deg.c for crystallization;
and performing suction filtration to obtain a crude product, and returning the crude product to a cooling crystallization working section.
As shown in fig. 1, in order to recycle water and residual tri-n-propylamine, the residual material after the crude product is filtered is filtrate;
the process steps further comprise:
standing and layering the filtrate to obtain a water phase and an organic phase, rectifying and recovering the water phase, returning the recovered water to a washing and layering working section, carrying out vacuum rectification on the organic phase, and returning the recovered tri-n-propylamine to a condensation reaction working section.
In this embodiment, the PH of the material in the second column is adjusted in the neutralization kettle, and the refrigerant in the neutralization kettle is started for cooling crystallization;
and/or carrying out suction filtration operation in a suction filter;
and/or layering the filtrate in a layering kettle;
and/or rectifying and recovering the water phase in a wastewater recovery kettle;
and/or the organic phase is rectified in vacuum in a mother liquor recovery kettle.
In this example, the aqueous phase dimethylamine hydrochloride solution obtained by separation was used for the preparation of N, N-dimethylaminoethyl acrylate.
Example one
1. Preparing the final product
(1) Condensation reaction
292kg of N, N-dimethylamino ethyl acrylate, 461kg of 2, 4-dichloro-5-fluorobenzoyl chloride and 800kg of tri-N-propylamine are pumped into a reaction kettle, the temperature is slowly increased to 40 ℃ for condensation reaction, and the temperature is kept for reaction for 4 hours.
(2) Substitution reaction
113kg of cyclopropylamine from a cyclopropylamine tank in the intermediate tank area is metered by a flowmeter and pumped into a reaction kettle, the temperature is slowly raised to 60 ℃, and the reaction is carried out for 4 hours under the condition of heat preservation.
(3) Washing with water and layering
Transferring the feed liquid of the reaction kettle into a water-washing crystallization kettle through a closed pipeline, metering and adding industrial water preheated to 60 ℃, standing and layering, separating out an aqueous phase dimethylamine hydrochloride solution, and using the separated aqueous phase dimethylamine hydrochloride solution for producing N, N-dimethylamino ethyl acrylate products, wherein the industrial water amount is about 4% of the mass of the oil phase feed liquid.
The net weight of dimethylamine hydrochloride separated in this step was 210 kg.
(4) Cooling crystallization
After water washing and layering are finished, pumping ethanol into a water washing crystallization kettle, cooling and crystallizing, and adding ethanol mainly for better separating out and forming crystals.
(5) Rinsing and centrifuging
Transferring the kettle material after crystallization into a closed centrifuge, pumping 350kg of ethanol for rinsing and carrying out closed centrifugation to obtain a wet product and a centrifugal mother solution.
(6) Drying and packaging
And (3) putting the wet product obtained by centrifugation into a closed drier for drying, controlling the temperature to be not more than 60 ℃, cooling and packaging after drying to obtain 640kg of cyclopropyl ethyl amide.
2. Material recovery
(1) Recovery of ethanol
Pumping the centrifugal mother liquor into an ethanol recovery tower through a mechanical pump, and returning ethanol (containing a small amount of water) extracted from the tower top to a cooling crystallization working section or a centrifugal rinsing working section;
the tower bottom material in the ethanol recovery tower enters an evaporator for further rectification and recovery, the mixture material extracted from the tower top mainly comprises ethanol, tri-n-propylamine and water, the mixture material enters a tri-n-propylamine recovery tower, and the tower bottom material in the evaporator enters a neutralization kettle.
Returning the material extracted from the tower top of the tri-n-propylamine recovery tower to the ethanol recovery tower, and returning the tower kettle material (tri-n-propylamine and water) of the tri-n-propylamine recovery tower to the condensation reaction section.
(2) Recovering the crude product
The bottoms from the evaporator were pumped into a neutralizer, water was added in the appropriate amount, and adjusted to pH 11 with 30% liquid caustic.
Opening a refrigerant to cool to below 0 ℃, cooling and crystallizing, pumping into a filter press by a pump for filter pressing, returning a crude product obtained by filter pressing to a cooling and crystallizing working section, transferring a filtrate into a layering kettle, standing and layering, allowing a water phase obtained by layering to enter a wastewater recovery kettle, and allowing an organic phase to enter a mother liquor recovery kettle.
(3) Recovering water
Pumping the water phase obtained in the layering process into a wastewater recovery kettle for rectification recovery, and recycling the recovered water for a water washing and layering working section.
(4) Recovery of tri-n-propylamine
And pumping the organic phase into a mother liquor recovery kettle for vacuum rectification, and recycling the recovered tri-n-propylamine for the condensation reaction working section.
Example two
1. Preparing the final product
(1) Condensation reaction
290kg of N, N-dimethylamino ethyl acrylate, 458kg of 2, 4-dichloro-5-fluorobenzoyl chloride and 800kg of tri-N-propylamine are pumped into a reaction kettle, the temperature is slowly increased to 50 ℃ for condensation reaction, and the temperature is kept for reaction for 5 hours.
(2) Substitution reaction
112kg of cyclopropylamine from a cyclopropylamine tank in the intermediate tank area is metered by a flowmeter and pumped into a reaction kettle, the temperature is slowly raised to 70 ℃, and the reaction is carried out for 5 hours under the condition of heat preservation.
(3) Washing with water and layering
Transferring the feed liquid of the reaction kettle into a water-washing crystallization kettle through a closed pipeline, metering and adding industrial water preheated to 70 ℃, standing and layering, separating out an aqueous phase dimethylamine hydrochloride solution, and using the separated aqueous phase dimethylamine hydrochloride solution for producing N, N-dimethylamino ethyl acrylate products, wherein the industrial water amount is about 5% of the mass of the oil phase feed liquid.
The net weight of dimethylamine hydrochloride isolated in this step was 209 kg.
(4) Cooling crystallization
After water washing and layering are finished, pumping ethanol into a water washing crystallization kettle, cooling and crystallizing, and adding ethanol mainly for better separating out and forming crystals.
(5) Rinsing and centrifuging
Transferring the kettle material after crystallization into a sealed centrifuge, pumping 425kg of ethanol for rinsing and sealed centrifugation to obtain a wet product and a centrifugal mother solution.
(6) Drying and packaging
And (3) putting the wet product obtained by centrifugation into a closed drier for drying, controlling the temperature to be not more than 60 ℃, cooling and packaging after drying to obtain 634kg of cyclopropyl ethyl amide.
2. Material recovery
(1) Recovery of ethanol
Pumping the centrifugal mother liquor into an ethanol recovery tower through a mechanical pump, and returning ethanol (containing a small amount of water) extracted from the tower top to a cooling crystallization working section or a centrifugal rinsing working section;
the tower bottom material in the ethanol recovery tower enters an evaporator for further rectification and recovery, the mixture material extracted from the tower top mainly comprises ethanol, tri-n-propylamine and water, the mixture material enters a tri-n-propylamine recovery tower, and the tower bottom material in the evaporator enters a neutralization kettle.
Returning the material extracted from the tower top of the tri-n-propylamine recovery tower to the ethanol recovery tower, and returning the tower kettle material (tri-n-propylamine and water) of the tri-n-propylamine recovery tower to the condensation reaction section.
(2) Recovering the crude product
The bottoms from the evaporator were pumped into a neutralizer, water was added in the appropriate amount, and adjusted to pH 12 with 30% liquid caustic.
Opening a refrigerant to cool to below 0 ℃, cooling and crystallizing, pumping into a filter press by a pump for filter pressing, returning a crude product obtained by filter pressing to a cooling and crystallizing working section, transferring a filtrate into a layering kettle, standing and layering, allowing a water phase obtained by layering to enter a wastewater recovery kettle, and allowing an organic phase to enter a mother liquor recovery kettle.
(3) Recovering water
Pumping the water phase obtained in the layering process into a wastewater recovery kettle for rectification recovery, and recycling the recovered water for a water washing and layering working section.
(4) Recovery of tri-n-propylamine
And pumping the organic phase into a mother liquor recovery kettle for vacuum rectification, and recycling the recovered tri-n-propylamine for the condensation reaction working section.
EXAMPLE III
1. Preparing the final product
(1) Condensation reaction
291kg of N, N-dimethylamino ethyl acrylate, 459kg of 2, 4-dichloro-5-fluorobenzoyl chloride and 800kg of tri-N-propylamine are pumped into a reaction kettle, the temperature is slowly increased to 60 ℃ for condensation reaction, and the temperature is kept for reaction for 6 hours.
(2) Substitution reaction
113kg of cyclopropylamine from a cyclopropylamine tank in the intermediate tank area is metered by a flowmeter and pumped into a reaction kettle, the temperature is slowly raised to 80 ℃, and the reaction is carried out for 6 hours under the condition of heat preservation.
(3) Washing with water and layering
Transferring the feed liquid of the reaction kettle into a water-washing crystallization kettle through a closed pipeline, metering and adding industrial water preheated to 85 ℃, standing and layering, separating out an aqueous phase dimethylamine hydrochloride solution, and using the separated aqueous phase dimethylamine hydrochloride solution for producing N, N-dimethylamino ethyl acrylate products, wherein the industrial water amount is about 6% of the mass of the oil phase feed liquid.
The net weight of dimethylamine hydrochloride separated in this step was 210 kg.
(4) Cooling crystallization
After water washing and layering are finished, pumping ethanol into a water washing crystallization kettle, cooling and crystallizing, and adding ethanol mainly for better separating out and forming crystals.
(5) Rinsing and centrifuging
Transferring the kettle material after crystallization into a closed centrifuge, pumping 500kg of ethanol for rinsing and carrying out closed centrifugation to obtain a wet product and a centrifugal mother solution.
(6) Drying and packaging
And (3) putting the wet product obtained by centrifugation into a closed drier for drying, controlling the temperature to be not more than 60 ℃, cooling and packaging after drying to obtain 635kg of cyclopropyl ethyl amide.
2. Material recovery
(1) Recovery of ethanol
Pumping the centrifugal mother liquor into an ethanol recovery tower through a mechanical pump, and returning ethanol (containing a small amount of water) extracted from the tower top to a cooling crystallization working section or a centrifugal rinsing working section;
the tower bottom material in the ethanol recovery tower enters an evaporator for further rectification and recovery, the mixture material extracted from the tower top mainly comprises ethanol, tri-n-propylamine and water, the mixture material enters a tri-n-propylamine recovery tower, and the tower bottom material in the evaporator enters a neutralization kettle.
Returning the material extracted from the tower top of the tri-n-propylamine recovery tower to the ethanol recovery tower, and returning the tower kettle material (tri-n-propylamine and water) of the tri-n-propylamine recovery tower to the condensation reaction section.
(2) Recovering the crude product
The bottoms from the evaporator were pumped into a neutralizer, water was added in the appropriate amount, and adjusted to pH 12 with 30% liquid caustic.
Opening a refrigerant to cool to below 0 ℃, cooling and crystallizing, pumping into a filter press by a pump for filter pressing, returning a crude product obtained by filter pressing to a cooling and crystallizing working section, transferring a filtrate into a layering kettle, standing and layering, allowing a water phase obtained by layering to enter a wastewater recovery kettle, and allowing an organic phase to enter a mother liquor recovery kettle.
(3) Recovering water
Pumping the water phase obtained in the layering process into a wastewater recovery kettle for rectification recovery, and recycling the recovered water for a water washing and layering working section.
(4) Recovery of tri-n-propylamine
And pumping the organic phase into a mother liquor recovery kettle for vacuum rectification, and recycling the recovered tri-n-propylamine for the condensation reaction working section.
The reaction principle of the condensation reaction and the substitution reaction is as follows:
1. condensation reaction
(1) Main reaction
Figure BDA0002408599810000091
(2) Side reactions
Figure BDA0002408599810000092
2. Substitution reaction
Figure BDA0002408599810000101
In the three examples, the conversion rates of the condensation reaction and the substitution reaction are both 97-99%.
In the first example, the total yield of the product is 98.15%; in example two, the overall product yield was 98%; in the third example, the total yield of the product is 97.91%; wherein, the calculation mode of the total yield of the product is as follows:
the total yield of the product was 100% (weight of cyclopropylethyl amide + weight of dimethylamine hydrochloride)/(weight of N, N-dimethylaminoethyl acrylate + weight of 2, 4-dichloro-5-fluorobenzoyl chloride + weight of cyclopropylamine).
The production process adopts tri-n-propylamine as an acid acceptor and a solvent carrier of the product. Tri-n-propylamine of formula C9H21N, colorless liquid at normal temperature and normal pressure, ammonia-like smell, boiling point of 156 ℃, flash point of 32 ℃, specific gravity of 0.77, water insolubility, alcohol and ether solubility, low toxicity and no listed national hypertoxic catalogues. Compared with tri-n-butylamine, the tri-n-propylamine used as an acid absorbent and a solvent carrier has no strong toxicity and low boiling point, thereby not only effectively avoiding the defects of strong toxicity, large energy consumption in the separation and recovery process, difficult recovery and separation and the like of the tri-n-butylamine, but also greatly improving the yield of products in the reaction process, and compared with the traditional process, the conversion rates of condensation reaction and substitution reaction reach 97-99%, the total yield of the products reaches 98%, and the yield is improved by two percentage points.
The above embodiments are described in further detail to solve the technical problems, technical solutions and advantages of the present invention, and it should be understood that the above embodiments are only examples of the present invention and are not intended to limit the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. A process for preparing cyclopropyl amine compound by using tri-n-propylamine as acid acceptor,
the process steps comprise:
carrying out condensation reaction in the formula (1) on N, N-dimethylamino ethyl acrylate, 2, 4-dichloro-5-fluorobenzoyl chloride and tri-N-propylamine to obtain a first feed liquid;
Figure FDA0003363404480000011
adding cyclopropylamine into the first feed liquid to perform the substitution reaction in the formula (2) to obtain a second feed liquid; wherein the second feed liquid contains cyclopropylethyl amide, tri-n-propylamine and dimethylamine hydrochloride;
Figure FDA0003363404480000012
adding water into the second feed liquid for washing, standing for layering, and separating to obtain an aqueous phase dimethylamine hydrochloride solution and a third feed liquid;
cooling and crystallizing the third material liquid, wherein the cyclopropylethyl amide in the third material liquid is crystallized into a crystallized material;
adding ethanol into the crystallized material for rinsing, and centrifuging under a closed condition to obtain a wet product;
and drying the wet product to obtain a finished product of the cyclopropyl ethyl amide.
2. The process for preparing cyclopropylethyl amide, according to claim 1, wherein the acid acceptor is tri-n-propylamine,
the mass ratio of the N, N-dimethylamino ethyl acrylate to the 2, 4-dichloro-5-fluorobenzoyl chloride to the tri-N-propylamine is 1: (1.3-1.8): (2.74-3);
and/or the mass of the water added into the second feed liquid is 4-6% of the mass of the second feed liquid.
3. The process for preparing cyclopropylethyl amide, according to claim 1, wherein the acid acceptor is tri-n-propylamine,
the reaction temperature of the condensation reaction is 40-60 ℃, and the reaction time of the condensation reaction is 4-6 h;
and/or the reaction temperature of the substitution reaction is 60-80 ℃, and the reaction time of the substitution reaction is 4-6 h;
and/or the temperature of the water added into the second feed liquid is 60-85 ℃.
4. The process for preparing cyclopropylethyl amide, according to claim 1, wherein the acid acceptor is tri-n-propylamine,
the condensation reaction and the substitution reaction are carried out in a reaction kettle;
and/or transferring the second feed liquid into a water washing crystallization kettle through a closed pipeline, adding water for washing, standing and layering;
and/or cooling and crystallizing the third feed liquid in a water washing crystallization kettle;
and/or the crystallized material enters a rinsing centrifuge in a closed centrifuge;
and/or the wet product is dried in an internal dryer.
5. The process for preparing cyclopropylethyl amide, according to claim 1, wherein the acid acceptor is tri-n-propylamine,
the liquid after the third feed liquid is cooled and crystallized to obtain a crystallized material and the liquid after the crystallized material is rinsed and a wet product is centrifuged to obtain a centrifugal mother liquid;
the process steps further comprise:
transferring the centrifugal mother liquor into an ethanol recovery tower, extracting ethanol from the top of the ethanol recovery tower, and returning the extracted ethanol to a cooling crystallization section and/or a rinsing section.
6. The process for preparing cyclopropylethyl amide, according to claim 5, wherein,
after ethanol is adopted at the tower top of the ethanol recovery tower, the residual material in the ethanol recovery tower is the material in the first tower kettle;
the process steps further comprise:
transferring the material in the first tower kettle into an evaporator, extracting a mixed material from the top of the evaporator, and feeding the mixed material into a tri-n-propylamine recovery tower, wherein the mixed material comprises ethanol, tri-n-propylamine and water;
returning the material extracted from the tower top of the tri-n-propylamine recovery tower to the ethanol recovery tower, and returning the residual material in the tri-n-propylamine recovery tower to the condensation reaction section.
7. The process of claim 6 for preparing cyclopropylethyl amide using tri-n-propylamine as an acid acceptor,
after the mixed material is extracted from the top of the evaporator, the residual material in the evaporator is the material in the second tower kettle;
the process steps further comprise:
adding water into the material in the second tower kettle, and adjusting the pH value to 11-12 by using alkali liquor;
cooling at below 0 deg.c for crystallization;
and performing suction filtration to obtain a crude product, and returning the crude product to a cooling crystallization working section.
8. The process for preparing cyclopropylethyl amide, according to claim 7, wherein,
filtering the crude product to obtain the residual material as filtrate;
the process steps further comprise:
standing and layering the filtrate to obtain a water phase and an organic phase, rectifying and recovering the water phase, returning the recovered water to a washing and layering working section, carrying out vacuum rectification on the organic phase, and returning the recovered tri-n-propylamine to a condensation reaction working section.
9. The process of claim 8 for preparing cyclopropylethyl amide using tri-n-propylamine as an acid acceptor,
adjusting the pH value of the material in the second tower kettle in the neutralization kettle, and opening the refrigerant in the neutralization kettle for cooling crystallization;
and/or carrying out suction filtration operation in a suction filter;
and/or layering the filtrate in a layering kettle;
and/or rectifying and recovering the water phase in a wastewater recovery kettle;
and/or the organic phase is rectified in vacuum in a mother liquor recovery kettle.
10. The process for preparing cyclopropylethyl amide, according to claim 1, wherein the acid acceptor is tri-n-propylamine,
the separated aqueous phase dimethylamine hydrochloride solution is used for preparing N, N-dimethylamino ethyl acrylate.
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