CN113501796B - Aminoethylated piperazine and preparation method thereof - Google Patents

Aminoethylated piperazine and preparation method thereof Download PDF

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CN113501796B
CN113501796B CN202110799928.0A CN202110799928A CN113501796B CN 113501796 B CN113501796 B CN 113501796B CN 202110799928 A CN202110799928 A CN 202110799928A CN 113501796 B CN113501796 B CN 113501796B
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piperazine
hydrochloride
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amine
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CN113501796A (en
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陈绍云
刘安华
吕小兵
张永春
刘家旭
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Dalian University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • 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
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    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/151—Reduction of greenhouse gas [GHG] emissions, e.g. CO2

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Abstract

The invention provides a preparation method of amine ethylated piperazine, and relates to the technical field of preparation of aminoethyl piperazine. Mixing a piperazine compound, a chlorination reagent and a soluble piperazine compound solvent, and carrying out chlorination reaction to obtain chlorinated piperazine hydrochloride; the piperazine compound comprises 2-hydroxyethyl piperazine or N, N' -di (2-hydroxyethyl) piperazine; mixing the chloropiperazine hydrochloride, organic amine and water, and carrying out substitution reaction to obtain amine ethylated piperazine; the organic amine comprises methylamine, ethylamine and propylamine. The preparation method provided by the invention has the advantages of high product yield, high purity, simple operation, wide sources of reaction raw materials and low production cost, and is suitable for industrial production.

Description

Aminoethylated piperazine and preparation method thereof
Technical Field
The invention relates to the technical field of carbon dioxide capture, and particularly relates to a preparation method of amine ethylated piperazine.
Background
Industrial production using fossil fuels as a main energy source emits a large amount of flue gas rich in carbon dioxide, which is a main greenhouse gas causing global warming, every year, so how to reduce the emission of carbon dioxide to reduce its atmospheric concentration is a common problem facing the present human society. Meanwhile, carbon dioxide is a cheap, easily-obtained, non-combustible, non-toxic, harmless and renewable carbon resource, and can be catalytically converted into chemical raw materials and fine chemicals comprising carboxylic acid, urea, carbonate/polycarbonate, carbamate, oxazolinone, quinazolinedione, methanol, formic acid, formamide and the like by constructing chemical bonds such as C-C, C-N, C-O and methods such as hydrogenation reduction and the like. Therefore, from the perspective of environmental protection and resource utilization, the method has very important research value and ecological benefit for capturing and separating carbon dioxide from flue waste gas discharged from industry, is an effective way for solving relevant environmental problems, and can provide material basis for resource utilization.
Chinese patent CN102596362A discloses that aminoethylpiperazine containing multistage amines can be used for capturing carbon dioxide. The documents R.N.Zaguulin, Z.M Baimetov, Journal of general Chemistry, USSR,1991,61, 889-containing 894 disclose the preparation of N- (2-ethylamino-ethyl) -piperazine starting from 2-aminoethyl-piperazine and ethyl chloride by base-promoted nucleophilic substitution; however, the yield of the product prepared by this method is only 14%, and the yield is low.
Disclosure of Invention
In view of the above, the present invention is directed to an aminoethylated piperazine and a preparation method thereof. The preparation method provided by the invention has high product yield.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a preparation method of amine ethylated piperazine, which comprises the following steps:
mixing a piperazine compound, a chlorination reagent and a soluble piperazine compound solvent, and carrying out chlorination reaction to obtain chlorinated piperazine hydrochloride; the piperazine compounds comprise 2-hydroxyethyl piperazine or N, N' -bis (2-hydroxyethyl) piperazine;
mixing the chloropiperazine hydrochloride, organic amine and water, and carrying out substitution reaction to obtain amine ethylated piperazine; the organic amine comprises methylamine, ethylamine and propylamine.
Preferably, the chlorinating agent preferably comprises one or more of thionyl chloride, phosphorus oxychloride and methanesulfonyl chloride.
Preferably, the molar ratio of the piperazine compound to the chlorinating agent is 1: 1.5 to 5.
Preferably, the temperature of the chlorination reaction is 25-80 ℃, and the time is 4-24 h.
Preferably, the molar ratio of the chloropiperazine hydrochloride to the organic amine is 1: 5 to 30.
Preferably, the temperature of the substitution reaction is 50-80 ℃, and the time is 8-16 h.
The invention provides a preparation method of amine ethylated piperazine, which comprises the following steps: mixing a piperazine compound, a chlorination reagent and a soluble piperazine compound solvent, and carrying out chlorination reaction to obtain chlorinated piperazine hydrochloride; the piperazine compound comprises 2-hydroxyethyl piperazine or N, N' -di (2-hydroxyethyl) piperazine; mixing the chloropiperazine hydrochloride, organic amine and water for substitution reaction to obtain amine ethylated piperazine; the organic amine comprises methylamine, ethylamine and propylamine. The preparation method provided by the invention has the advantages of high product yield, high purity, simple operation, wide sources of reaction raw materials and low production cost, and is suitable for industrial production.
Detailed Description
The invention provides a preparation method of amine ethylated piperazine, which comprises the following steps:
mixing a piperazine compound, a chlorination reagent and a soluble piperazine compound solvent, and carrying out chlorination reaction to obtain chlorinated piperazine hydrochloride; the piperazine compound comprises 2-hydroxyethyl piperazine or N, N' -di (2-hydroxyethyl) piperazine;
mixing the chloropiperazine hydrochloride, organic amine and water, and carrying out substitution reaction to obtain amine ethylated piperazine; the organic amine comprises methylamine, ethylamine and propylamine.
Mixing a piperazine compound, a chlorination reagent and a soluble piperazine compound solvent, and carrying out chlorination reaction to obtain chlorinated piperazine hydrochloride; the piperazine compound comprises 2-hydroxyethyl piperazine or N, N' -di (2-hydroxyethyl) piperazine.
In the present invention, the chlorinating agent preferably comprises one or more of thionyl chloride, phosphorus oxychloride and methanesulfonyl chloride. In the present invention, the molar ratio of the piperazine-based compound to the chlorinating agent is preferably 1: 1.5 to 5, more preferably 1: 2 to 3. In the present invention, the soluble piperazine compound solvent is preferably a chloroalkane solvent, and more preferably includes dichloromethane; the dosage of the soluble piperazine compound solvent is not specially limited, and the raw materials can be dissolved; in the embodiment of the present invention, the ratio of the amount of the substance of the piperazine-based compound to the volume of the soluble piperazine-based compound solvent is preferably 24 mmol: 35 mL. In the invention, the mixing mode is that the piperazine compound is dissolved in the soluble piperazine compound solvent, and then the chlorination reagent is dripped; the stirring speed is preferably 400-700 r/min, and more preferably 500-600 r/min; the dropping speed is not specially limited, and the dropping can be carried out at a constant speed; in the embodiment of the invention, the dripping speed is preferably 13-14 mmol/min; the dropwise addition is preferably carried out using a constant pressure dropping funnel.
In the invention, the temperature of the chlorination reaction is preferably 25-80 ℃, and more preferably 35-65 ℃; the chlorination reaction time is preferably 4-24 hours, and more preferably 8-12 hours; the chlorination reaction is preferably carried out under oil bath conditions; in the chlorination reaction process, hydroxyl in the 2-hydroxyethyl piperazine is replaced by chlorine to generate 2-chloroethyl piperazine hydrochloride, or two hydroxyl in the N, N '-bis (2-hydroxyethyl) piperazine are replaced by chlorine to generate the N, N' -bis (2-chloroethyl) piperazine hydrochloride.
After the chlorination reaction, the invention preferably further comprises the step of cooling the system of the chlorination reaction to room temperature and then carrying out suction filtration to obtain the chloropiperazine hydrochloride. The cooling method of the present invention is not particularly limited, and a cooling method known to those skilled in the art may be used. In the present invention, the suction filtration is preferably performed by a water pump.
After the chloropiperazine hydrochloride is obtained, mixing the chloropiperazine hydrochloride, organic amine and water for substitution reaction to obtain the amine ethylated piperazine; the organic amine comprises methylamine, ethylamine and propylamine.
In the present invention, the molar ratio of the chloropiperazine hydrochloride to the organic amine is preferably 1: 5-30, more preferably 1: 10-25, most preferably 1: 15 to 20. In the present invention, the order of mixing is preferably to dissolve the organic amine in water to obtain an amine solution; mixing the obtained amine solution with chloropiperazine hydrochloride; the concentration of the amine solution is preferably 20-45 wt%, and more preferably 30-40 wt%. In the present invention, the mixing method is preferably stirring mixing, and the speed and time of stirring mixing are not particularly limited in the present invention, and the raw materials may be uniformly mixed.
In the invention, the temperature of the substitution reaction is preferably 50-80 ℃, and more preferably 60-70 ℃; the time of the substitution reaction is preferably 8-16 h, and more preferably 10-12 h; the substitution reaction is preferably carried out in an autoclave. In the invention, the chloropiperazine hydrochloride reacts with organic amine to generate amine ethylated piperazine in the substitution reaction process.
After the substitution reaction, the method preferably further comprises the steps of cooling the system of the substitution reaction to room temperature, adding a first alkaline reagent under the stirring condition, mixing for 20-60 min, then standing for layering, adding a second alkaline reagent into the obtained aqueous organic phase (upper layer) under the stirring condition, and mixingAnd standing for layering for the second time after 0.5-2 hours, extracting the obtained aqueous organic phase (upper layer), drying the obtained organic phase, and concentrating to constant weight to obtain the aminoethyl piperazine. In the present invention, the cooling is preferably performed by soaking in an ice-water bath. In the invention, the stirring speed is preferably 800-1200 r/min, and more preferably 1000-1100 r/min. In the present invention, the first and second alkaline agents independently preferably comprise Na 2 CO 3 、K 2 CO 3 NaOH or KOH; the first alkaline reagent and the second alkaline reagent are used in the form of alkaline reagent solid or alkaline reagent aqueous solution, and the concentration of the alkaline reagent aqueous solution is preferably 40-60 wt%; the first alkaline reagent is used for removing HCl generated in the reaction; the first alkaline reagent is preferably added in 4-5 times, and the molar ratio of the chloropiperazine hydrochloride to the first alkaline reagent is preferably 1: 5-15, more preferably 1: 10-12; the second alkaline reagent is preferably added in 3-4 times, and the molar ratio of the chloropiperazine hydrochloride to the second alkaline reagent is preferably 1: 4-10, more preferably 1: 5-8; the first alkaline agent and the second alkaline agent are added in portions in order to prevent the alkaline agent from dissolving a large amount of heat to cause bumping of the solution. In the present invention, the first standing layer and the second standing layer are preferably performed in a separatory funnel. In the present invention, the extractant for extraction preferably includes dichloromethane or chloroform; the amount of the extractant used in the present invention is not particularly limited, and the amount of the extractant known to those skilled in the art can be used; in the embodiment of the present invention, the ratio of the amount of the substance of the chloropiperazine hydrochloride to the volume of the extracting agent is preferably 24 mmol: 15mL, and the number of times of extraction is preferably 3-4. In the present invention, the drying means is preferably drying with a drying agent, and the drying agent is preferably anhydrous sodium sulfate. In the present invention, the concentration is preferably performed by distillation under reduced pressure; the reduced pressure distillation is preferably carried out using a rotary evaporator.
In the present invention, the aminoethylated piperazine has the structure shown in formula I:
Figure BDA0003164305960000041
in the formula I, R 2 Is hydrogen or
Figure BDA0003164305960000042
The R is 1 And R 3 Independently is C1-C3 alkyl, R 4 Is hydrogen.
In the invention, the C1-C3 alkyl is methyl, ethyl, n-propyl or isopropyl.
In the present invention, when R is 1 When being methyl, R 2 Hydrogen; when R is 1 When being ethyl, R 2 Hydrogen; when R is 1 When n-propyl, R 2 Hydrogen; when R is 1 When it is isopropyl, R 2 Hydrogen.
In the present invention, when R is 1 Methyl, R 3 When being methyl, R 4 Hydrogen; when R is 1 Methyl, R 3 When it is ethyl, R 4 Hydrogen; when R is 1 Methyl, R 3 When n-propyl, R 4 Hydrogen; when R is 1 Methyl, R 3 When it is isopropyl, R 4 Hydrogen.
The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It should be apparent that the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
Synthesis of N- (2-methylaminoethyl) -piperazine
Figure BDA0003164305960000051
Step 1: dissolving 240mmol of 2-hydroxyethyl piperazine in 350mL of dichloromethane in a 500mL single-neck bottle, stirring for 10min at room temperature under 600r/min, dropwise adding 400mmol of thionyl chloride into the solution at a constant speed by using a constant-pressure dropping funnel under an ice water bath, after dropwise adding within 30min, transferring the single-neck bottle to a 40 ℃ oil bath for reflux reaction for 12h, then removing the single-neck bottle from the oil bath, cooling to room temperature, and performing suction filtration to constant weight by using a water pump to obtain an intermediate 2-chloroethyl piperazine hydrochloride.
Step 2: transferring all the 2-chloroethyl piperazine hydrochloride obtained in the step 1 into a 500mL high-pressure reaction kettle, adding 260mL of 40 wt% methylamine aqueous solution, sealing, and reacting for 12h under the conditions of 60 ℃ oil bath and 800r/min stirring speed; soaking the autoclave in an ice-water bath for 1h, transferring the reaction mixed solution into a 1L beaker cooled by the ice-water bath, adding 80g of NaOH in 4 batches under the magnetic stirring condition of 1000r/min, stirring for 20min, transferring the mixed solution into a 500mL separating funnel for standing, discharging the milky water phase at the lower layer, pouring the light yellow aqueous organic phase at the upper layer into 200mL NaOH solution with the concentration of 50 wt% cooled by the ice-water bath, stirring for 20min at room temperature, transferring into the 500mL separating funnel for standing and layering again, discharging the water phase at the lower layer, extracting the dark yellow aqueous organic phase at the upper layer for 2 times by using dichloromethane, wherein the volume of dichloromethane used for single extraction is 200mL, and after the dichloromethane phases are combined, anhydrous Na is used for anhydrous Na 2 SO 4 Drying overnight, removing the solvent dichloromethane by using a rotary evaporator, and then distilling under reduced pressure by using an oil pump to constant weight to obtain the N- (2-methylaminoethyl) -piperazine (the boiling point of which under the pressure of 1mm Hg is 82-86 ℃, the total molar yield of the two steps is 45% and the purity is 99%). Nuclear magnetic characterization data: 1 HNMR(400MHz,CDCl 3 )δ＝2.39-2.45(m,9H),2.64(t,J＝4.0Hz,2H),2.85(t,J＝3.2Hz,4H)。
example 2
Synthesis of N- (2-ethylamino ethyl) -piperazine
Figure BDA0003164305960000061
Step 1: dissolving 240mmol of 2-hydroxyethyl piperazine in 350mL of dichloromethane in a 500mL single-neck bottle, stirring for 10min at room temperature under 600r/min, dropwise adding 400mmol of thionyl chloride into the solution at a constant speed by using a constant-pressure dropping funnel under an ice water bath, after dropwise adding within 30min, immediately transferring the single-neck bottle to an oil bath at 40 ℃ for reflux reaction for 12h, removing the single-neck bottle from the oil bath, cooling to room temperature, and performing suction filtration by using a water pump to constant weight to obtain an intermediate 2-chloroethyl piperazine hydrochloride.
Step 2: transferring all the 2-chloroethylpiperazine hydrochloride obtained in the step 1 into a 500mL high-pressure reaction kettle, adding 260mL of 30 wt% ethylamine aqueous solution, sealing, reacting for 12h under the conditions of 60 ℃ oil bath and 800r/min stirring speed, soaking the high-pressure kettle for 1h in an ice water bath, transferring the reaction mixed solution into a 1L beaker cooled by the ice water bath, adding 80g of NaOH in 4 batches under the condition of 1000r/min magnetic stirring, stirring for 20min, transferring all the mixed solution into a 500mL separating funnel for standing, discharging the lower milky aqueous phase, pouring the upper pale yellow aqueous organic phase into 200mL of 50 wt% NaOH solution cooled by the ice water bath, stirring the mixed solution at the room temperature for 20min, transferring into the 500mL separating funnel for standing and layering again, discharging the lower aqueous phase, extracting the upper deep yellow aqueous organic phase with dichloromethane for 2 times, the volume of dichloromethane used for single extraction is 200mL, and anhydrous Na is used after dichloromethane phases are combined 2 SO 4 Drying overnight, removing solvent dichloromethane by using a rotary evaporator, and then distilling under reduced pressure by using an oil pump until the weight is constant to obtain the N- (2-ethylamino ethyl) -piperazine (the boiling point is 91-94 ℃ under the pressure of 1mm Hg, the total molar yield of the two steps is 51%, and the purity is 99%). Nuclear magnetic characterization data: 1 H NMR(400MHz,CDCl 3 )δ＝2.86(t,J＝5.2Hz,4H),2.61-2.70(m,4H),2.40-2.47(m,6H),1.10(t,J＝7.2Hz,3H)。
example 3
Synthesis of N- (2-N-propylaminoethyl) -piperazine
Figure BDA0003164305960000071
Step 1: in a 500mL single-neck flask, 240mmol of 2-hydroxyethylpiperazine was dissolved in 350mL of dichloromethane and stirred at 600r/min at room temperature for 10 min. 400mmol of thionyl chloride is dropwise added into the solution at a constant speed by a constant-pressure dropping funnel in an ice water bath, and the dropwise addition is finished within 30 min. And then transferring the single-neck bottle to an oil bath at 40 ℃ for reflux reaction for 12 hours, removing the single-neck bottle from the oil bath, cooling to room temperature, and performing suction filtration by using a water pump until the weight is constant to obtain the intermediate 2-chloroethyl piperazine hydrochloride.
Step 2: transferring all the chloroethyl piperazine hydrochloride obtained in the step 1 into a 500mL high-pressure reaction kettle, then adding 260mL of a 30 wt% n-propylamine aqueous solution, sealing, reacting for 12h under the conditions of 60 ℃ oil bath and 800r/min stirring speed, soaking the high-pressure kettle for 1h in an ice water bath, transferring the reaction mixed solution into a 1L beaker cooled by the ice water bath, adding 80g of NaOH in 4 batches under the condition of 1000r/min magnetic stirring, stirring for 20min, transferring all the mixed solution into a 500mL separating funnel for standing, discharging the milky water phase at the lower layer, pouring the light yellow water-containing organic phase at the upper layer into 200mL of a 50 wt% NaOH solution cooled by the ice water bath, stirring for 20min at the temperature of the mixed solution, transferring into the 500mL separating funnel for standing and separating the layers again, discharging the water phase at the lower layer, extracting the deep yellow water-containing organic phase at the upper layer for 2 times by using dichloromethane, the volume of dichloromethane used for single extraction is 200mL, and anhydrous Na is used after dichloromethane phases are combined 2 SO 4 Drying overnight, removing the solvent dichloromethane by using a rotary evaporator, and then distilling under reduced pressure by using an oil pump to constant weight to obtain the N- (2-N-propylaminoethyl) -piperazine (the boiling point of which under the pressure of 1mm Hg is 99-105 ℃, the total molar yield of the two steps is 61% and the purity is 99%). Nuclear magnetic characterization data: 1 H NMR(400MHz,CDCl 3 )δ＝2.86(t,J＝3.2Hz,4H),2.69(t,J＝4.4Hz,2H),2.56(t,J＝4.8Hz,2H),2.40-2.47(m,6H),2.86(sextet,J＝4.8Hz,2H),0.90(t,J＝5.2Hz,3H)。
example 4
Synthesis of N, N' -di (2-methylaminoethyl) -piperazine
Figure BDA0003164305960000081
Step 1: dissolving 240mmol of N, N '-bis (2-hydroxyethyl) piperazine in 350mL of dichloromethane in a 500mL single-neck bottle, magnetically stirring at the speed of 600r/min for 10min, dropwise adding 600mmol of thionyl chloride into the solution at a constant speed by a constant-pressure dropping funnel at room temperature, after dropwise adding within 30min, immediately transferring the single-neck bottle to a 40 ℃ oil bath for reflux reaction for 12h, removing the single-neck bottle from the oil bath, cooling to room temperature, and performing suction filtration by a water pump to constant weight to obtain an intermediate N, N' -bis (2-chloroethyl) piperazine hydrochloride.
Step 2: transferring all the N, N' -bis (2-chloroethyl) piperazine hydrochloride obtained in the step 1 into a 500mL high-pressure reaction kettle, adding 260mL methylamine aqueous solution with the concentration of 40 wt%, sealing, reacting for 12h under the conditions of 60 ℃ oil bath and 800r/min stirring speed, soaking the autoclave for 1h in ice water bath, transferring the reaction mixed solution into a 1L beaker cooled by ice water bath, adding 80g NaOH in 4 batches under the condition of 1000r/min magnetic stirring, stirring for 20min, transferring all the mixed solution into a 500mL separating funnel for standing, discharging the milky water phase of the lower layer, pouring the light yellow aqueous organic phase of the upper layer into 200mL NaOH solution with the concentration of 50 wt% cooled by ice water bath, stirring for 20min at the room temperature, transferring into the 500mL separating funnel for standing and layering again, discharging the aqueous phase of the lower layer, extracting the deep yellow aqueous organic phase of the upper layer with dichloromethane for 2 times, the volume of dichloromethane used for single extraction is 200mL, and anhydrous Na is used after dichloromethane phases are combined 2 SO 4 Drying overnight, removing solvent dichloromethane by using a rotary evaporator, and then distilling under reduced pressure to constant weight to obtain N, N' -bis (2-methylaminoethyl) -piperazine (the boiling point of which is 102-108 ℃ under the pressure of 1mm Hg, the total molar yield of the two steps is 37%, and the purity is 99%). Nuclear magnetic characterization data: 1 HNMR(400MHz,CDCl 3 )δ＝2.42-2.48(m,20H),2.64(t,J＝6.0Hz,4H)。
example 5
Synthesis of N, N' -di (2-ethylamino ethyl) -piperazine
Figure BDA0003164305960000082
Step 1: dissolving 240mmol of N, N '-bis (2-hydroxyethyl) piperazine in 350mL of dichloromethane in a 500mL single-neck bottle, magnetically stirring at the speed of 600r/min for 10min, dropwise adding 600mmol of thionyl chloride into the solution at a constant speed by a constant-pressure dropping funnel at room temperature, after dropwise adding within 30min, immediately transferring the single-neck bottle into an oil bath at 40 ℃ for reflux reaction for 12h, removing the single-neck bottle out of the oil bath, cooling to room temperature, and performing suction filtration by a water pump to constant weight to obtain an intermediate N, N' -bis (2-chloroethyl) piperazine hydrochloride.
And 2, step: transferring all the N, N' -bis (2-chloroethyl) piperazine hydrochloride obtained in the step 1 into a 500mL high-pressure reaction kettle, adding 260mL of 30 wt% aqueous solution of ethylamine, sealing, reacting for 12h under the conditions of 60 ℃ oil bath and 800r/min stirring speed, soaking the autoclave for 1h in ice water bath, transferring the reaction mixed solution into a 1L beaker cooled by ice water bath, adding 80g of NaOH in 4 batches under the condition of 1000r/min magnetic stirring, stirring for 20min, transferring all the mixed solution into a 500mL separating funnel for standing, discharging the lower milky water phase, pouring the upper light yellow aqueous organic phase into 200mL of 50 wt% NaOH solution cooled by ice water bath, stirring the mixed solution for 20min at the temperature, transferring into the 500mL separating funnel for standing and layering again, discharging the lower aqueous phase, extracting the upper deep yellow aqueous organic phase with dichloromethane for 2 times, the volume of dichloromethane used for single extraction is 200mL, and anhydrous Na is used after dichloromethane phases are combined 2 SO 4 Drying overnight, removing solvent dichloromethane by using a rotary evaporator, and then distilling under reduced pressure to constant weight to obtain N, N' -bis (2-ethylamino ethyl) -piperazine (the boiling point of which is 122-125 ℃ under the pressure of 1mm Hg, the total molar yield of the two steps is 41%, and the purity is 99%). Nuclear magnetic characterization data: 1 HNMR(400MHz,CDCl 3 )δ＝2.63-2.70(m,8H),2.46-2.48(m,10H),1.09(t,J＝4.8Hz,6H)。
example 6
Synthesis of N, N' -di (2-N-propylaminoethyl) -piperazine
Figure BDA0003164305960000091
Step 1: dissolving 240mmol of N, N '-bis (2-hydroxyethyl) piperazine in 350mL of dichloromethane in a 500mL single-neck bottle, magnetically stirring at the speed of 600r/min for 10min, dropwise adding 600mmol of thionyl chloride into the solution at a constant speed by a constant-pressure dropping funnel at room temperature, after dropwise adding within 30min, immediately transferring the single-neck bottle to a 40 ℃ oil bath for reflux reaction for 12h, removing the single-neck bottle from the oil bath, cooling to room temperature, and performing suction filtration by a water pump to constant weight to obtain an intermediate N, N' -bis (2-chloroethyl) piperazine hydrochloride.
Step 2: transferring all the N, N' -bis (2-chloroethyl) piperazine hydrochloride obtained in the step 1 into a 500mL high-pressure reaction kettle, then adding 260mL of 40 wt% N-propylamine aqueous solution, sealing, reacting for 12h under the conditions of 60 ℃ oil bath and 800r/min stirring speed, soaking the autoclave for 1h in an ice water bath, transferring the reaction mixed solution into a 1L beaker cooled by the ice water bath, adding 80g of NaOH in 4 batches under the condition of 1000r/min magnetic stirring, stirring for 20min, transferring all the mixed solution into a 500mL separating funnel for standing, discharging a lower milky aqueous phase, pouring an upper light yellow aqueous organic phase into 200mL of 50 wt% NaOH solution cooled by the ice water bath, stirring for 20min at the room temperature, transferring into the 500mL separating funnel for standing and layering again, discharging a lower aqueous phase, extracting the upper deep yellow aqueous organic phase with dichloromethane for 2 times, the volume of dichloromethane used for single extraction is 200mL, and anhydrous Na is used after dichloromethane phases are combined 2 SO 4 Drying overnight, removing solvent dichloromethane by using a rotary evaporator, and then distilling under reduced pressure to constant weight to obtain N, N' -bis (2-N-propylaminoethyl) -piperazine (the boiling point of which under the pressure of 1mm Hg is 145-149 ℃, the total molar yield of the two steps is 43%, and the purity is 99%). Nuclear magnetic characterization data: 1 H NMR(400MHz,CDCl 3 )δ＝2.68(t,J＝6.4Hz,4H),2.55(t,J＝7.2Hz,4H),2.45-2.48(m,10H),2.86(sextet,J＝7.6Hz,4H),0.90(t,J＝7.2Hz,6H)。
the foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims (4)

1. The preparation method of the amine ethylated piperazine is characterized by comprising the following steps:
mixing a piperazine compound, a chlorination reagent and a solvent of a soluble piperazine compound, and carrying out chlorination reaction to obtain chlorinated piperazine hydrochloride; the piperazine compound is selected from 2-hydroxyethyl piperazine or N, N' -di (2-hydroxyethyl) piperazine;
mixing the chloropiperazine hydrochloride, organic amine and water for substitution reaction to obtain amine ethylated piperazine; the organic amine is selected from methylamine, ethylamine and propylamine;
the temperature of the substitution reaction is 50-80 ℃; the mol ratio of the chloropiperazine hydrochloride to the organic amine is 1: 5-30; the time of the substitution reaction is 8-16 h.
2. The preparation method according to claim 1, wherein the chlorinating agent is one or more selected from thionyl chloride, phosphorus oxychloride and methanesulfonyl chloride.
3. The production method according to claim 1 or 2, wherein the molar ratio of the piperazine-based compound to the chlorinating agent is 1: 1.5 to 5.
4. The preparation method according to claim 1 or 2, characterized in that the temperature of the chlorination reaction is 25-80 ℃ and the time is 4-24 h.
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