CN109836334A - A method of continuously preparing cyclopropylamine - Google Patents
A method of continuously preparing cyclopropylamine Download PDFInfo
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- CN109836334A CN109836334A CN201910113412.9A CN201910113412A CN109836334A CN 109836334 A CN109836334 A CN 109836334A CN 201910113412 A CN201910113412 A CN 201910113412A CN 109836334 A CN109836334 A CN 109836334A
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- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 238000000034 method Methods 0.000 title claims abstract description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 45
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 229910001868 water Inorganic materials 0.000 claims abstract description 24
- AWQVKAURKXXOCG-UHFFFAOYSA-N n-cyclopropylformamide Chemical compound O=CNC1CC1 AWQVKAURKXXOCG-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000002360 preparation method Methods 0.000 claims abstract description 17
- 239000005708 Sodium hypochlorite Substances 0.000 claims abstract description 14
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000000463 material Substances 0.000 claims abstract description 8
- 238000002156 mixing Methods 0.000 claims description 7
- SUUDTPGCUKBECW-UHFFFAOYSA-N n-propylformamide Chemical compound CCCNC=O SUUDTPGCUKBECW-UHFFFAOYSA-N 0.000 claims description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
- 238000010348 incorporation Methods 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 238000012824 chemical production Methods 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 57
- 235000011121 sodium hydroxide Nutrition 0.000 description 13
- 239000006185 dispersion Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 238000006462 rearrangement reaction Methods 0.000 description 5
- 238000007086 side reaction Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 238000005352 clarification Methods 0.000 description 4
- 238000004817 gas chromatography Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 3
- 230000008707 rearrangement Effects 0.000 description 3
- 150000007945 N-acyl ureas Chemical class 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- XUBOMFCQGDBHNK-JTQLQIEISA-N (S)-gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCN[C@@H](C)C1 XUBOMFCQGDBHNK-JTQLQIEISA-N 0.000 description 1
- BZSXEZOLBIJVQK-UHFFFAOYSA-N 2-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1C(O)=O BZSXEZOLBIJVQK-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- -1 cyclopropyl formyl amine Chemical class 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229940124307 fluoroquinolone Drugs 0.000 description 1
- 229960003923 gatifloxacin Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- JKQOBWVOAYFWKG-UHFFFAOYSA-N molybdenum trioxide Chemical compound O=[Mo](=O)=O JKQOBWVOAYFWKG-UHFFFAOYSA-N 0.000 description 1
- 239000004476 plant protection product Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses the methods that the one kind for belonging to chemical production technical field continuously prepares cyclopropylamine.Specifically includes the following steps: cyclopropyl formamide is dissolved in water by (1), preparation obtains solution A；(2) sodium hypochlorite, sodium hydroxide and water are mixed, preparation obtains solution B；(3) solution A and solution B are continuously passed through micro-mixer and are mixed to get reaction liquid C, reaction liquid C enters tubular reactor reaction；(4) rectification step (3) resulting material, obtains cyclopropylamine.The present invention only needs a step pyroreaction, so that it may which by the isolated cyclopropylamine of rectifier unit, and cyclopropylamine yield reaches 94% or more, high-efficiency and economic, solves the problems such as process in prior art is cumbersome, production efficiency is low, product is unstable.
Description
Technical field
The invention belongs to chemical production technical field, in particular to a kind of method for continuously preparing cyclopropylamine.
Background technique
Cyclopropylamine is the essential intermediates of fluoroquinolone antibacterial agents such as production Ciprofloxacin, gatifloxacin, simultaneously
Cyclopropylamine applies also for the synthesis of plant protection product, feed addictive.Cyclopropylamine is very widely used, as is produced from downstream
The exploitation and application of product have very big market prospects in drug and organic synthesis field.
Hoffmann rearrangement reaction is to synthesize the final step reaction of cyclopropylamine technique.Although having now been developed many as tetrem
The improved conditions such as lead plumbate, N- bromo-succinimide, hypervalent iodine reagent are used for Hoffmann rearrangement reaction, but based on economic factor
Consider, industrially still mainly using sodium hydroxide and reaction reagent of the sodium hypochlorite as Hoffmann rearrangement.Under the conditions of this kind
There are more side reactions for Hoffmann rearrangement reaction, such as the hydrolysis of carboxylic acid amides, excessive oxidation and formation acylureas.In order to inhibit these
Side reaction, industrial Hoffmann rearrangement reaction are usually carried out with complicated multistep processes, greatly limit production efficiency and production capacity.
In order to reduce the hydrolysis of raw material cyclopropyl formamide, the way in patent document such as US3711549 is first low
Cyclopropyl formamide solution is slowly added dropwise under the conditions of warm (< 5 DEG C) into liquor natrii hypochloritis, reaction a period of time, hydrogen is then added
Sodium oxide molybdena (solid or solution) is simultaneously gradually warmed up that the reaction was continued.Since reaction intermediate isocyanates is in the presence of anti-with sodium hydroxide
The main reaction answered and the side reaction reacted with raw material, product need to be added enough alkali before heating to inhibit acylureas
It generates.Since there are the side reaction of excessive oxidation, sodium hypochlorite is usually advisable with slightly excessive, further reduced anti-under low temperature
Answer rate.The above batch technology exist in the actual operation process temperature be difficult to control, process is cumbersome, production efficiency is low, product
A series of stubborn problems such as unstable, have increased considerably the energy and material consumption of production process.
In order to solve the normal problem of the above batch technology, continuous processing can be passed through by having some patent document propositions
To complete the Hoffmann rearrangement of cyclopropyl formamide.Patent CN1498884A describes a kind of continuous processing of two stages reaction: ring
After propyl formamide solution is mixed with the solution containing sodium hypochlorite and sodium hydroxide, by the first reaction zone (30~55 DEG C), pass through
It detects reactant concentration and controls two strands of feedstock ratios, guarantee the largely reaction (> 90%) of cyclopropyl formamide.Mixed liquor is passed through
The reaction was continued for two reaction zones (60~150 DEG C), and final mixed liquor is supplied to rectifying column, and tower top obtains cyclopropylamine.This kind of continuous processing
The reaction condition for having references to batch technology is divided to low temperature and high temperature two stages of reaction, and there is no effectively simplified reaction process, and
And cyclopropylamine yield is relatively low (85%).Patent CN108129330A describes another continuous processing: containing cyclopropyl formamide, secondary
The mixed liquor of sodium chlorate and sodium hydroxide is directly entered rectifying column continuation instead after passing through low temperature (- 15~30 DEG C) tubular reactor
It answers.This kind of technique has bigger requirement to the distillation ability of rectifying column, needs there are two rectifying column cooperations to reach satisfactory
Separating effect, and rectifying column in reaction can have apparent back-mixing, the more difficult effective control of reaction process.Although process above
By cyclopropyl formamide Hoffmann rearrangement process continuous, but the low-temp reaction stage that there are still reaction rates is slow, the reaction time is long,
The problems such as relatively high for equipment requirement, and the reinforcing without really realizing reaction process.
Summary of the invention
The purpose of the present invention is to provide a kind of method for continuously preparing cyclopropylamine, specific technical solution is as follows:
It is a kind of continuously prepare cyclopropylamine method the following steps are included:
(1) cyclopropyl formamide is dissolved in water, preparation obtains solution A；
(2) sodium hypochlorite, sodium hydroxide and water are mixed, preparation obtains solution B；
(3) solution A and solution B are continuously passed through micro-mixer and are mixed to get reaction liquid C, reaction liquid C enters pipe reaction
Device reaction；
(4) rectification step (3) resulting material, obtains cyclopropylamine.
The mass fraction of step (1) the solution A middle ring propyl formamide is 20~50%, and the preparation temperature of solution A is 30-
70℃；Preferably, the mass fraction of step (1) solution A middle ring propyl formamide is 20-30%, and the preparation temperature of solution A is 40-
60℃。
The raising of the solubility with temperature of cyclopropyl formamide has biggish promotion, and ring under conditions of being added without acid or alkali
Propyl formamide solution has extraordinary thermal stability, and present invention selection configures cyclopropyl formyl amine aqueous solution at relatively high temperatures,
It can obtain the solution A of higher concentration.
In step (2) solution B, the molar ratio of sodium hypochlorite and sodium hydroxide is 1:(2~3), hypochlorous acid in solution B
The molar concentration of sodium is 0.5~6mol/L, preferably 0.5~3.5mol/L；Temperature is prepared as 10~50 DEG C, preferably 10~40
℃。
The volume flow ratio that step (3) solution A and solution B are continuously passed through micro-mixer is 1:(1~5).
The initial molar ratio of sodium hypochlorite, cyclopropyl formamide and sodium hydroxide is (0.96 in step (3) reaction liquid C
~1.1): 1:(1.8~3.3)；Preferably, sodium hypochlorite in step (3) reaction liquid C, cyclopropyl formamide and sodium hydroxide just
Beginning molar ratio is (0.98~1.05): 1:(2.1~2.4)；Sodium hypochlorite, cyclopropyl formamide and hydroxide in the reaction liquid C
The initial molar ratio of sodium refers to that solution A and solution B are quickly uniformly mixed in micro-mixer, each component does not participate in rubbing of reacting also
That ratio.
Micro-mixer is micro passage reaction, film dispersion microreactor or Microtraps hole reactor in the step (3).
Tubular reactor is temperature control coil pipe etc. in the step (3).
Mixing temperature in step (3) micro-mixer is 20~90 DEG C, preferably 40~90 DEG C；Incorporation time is
0.1~1s.
Reaction temperature in step (3) tubular reactor is 50~100 DEG C, the reaction liquid C residence time is 0.5~
60min；Preferably, the reaction temperature in step (3) tubular reactor be 80~90 DEG C, the reaction liquid C residence time be 3~
8min。
The invention has the benefit that
(1) under alkaline condition, temperature is higher, and cyclopropyl formamide hydrolysis rate is faster, and there are low-temp reaction ranks for the prior art
Section is the hydrolysis in order to reduce cyclopropyl formamide；The present invention carries out Hoffmann rearrangement reaction by cyclopropyl formamide and prepares cyclopropyl
Amine, reaction process do not need the low-temp reaction stage then, and reaction solution is directly reacted under the high temperature conditions；In reaction process, ring
The basic hydrolysis of propyl formamide and the chlorination of cyclopropyl formamide are a parallel reactions, and inventor, which tests, finds chlorine in step reaction
The activation energy for changing reaction is higher than the activation energy of hydrolysis, improves the progress that temperature is more advantageous to chlorination reaction, therefore this hair
Bright pyroreaction has no more hydrolytic side reactions and occurs.
(2) in the present invention, after cyclopropyl formamide is efficiently mixed with sodium hypochlorite and sodium hydroxide, it is only necessary to which a step high temperature is anti-
It answers, so that it may which by the isolated cyclopropylamine of rectifier unit, and cyclopropylamine yield reaches 94% or more.The method of the present invention process letter
Single, continuous operation, feasibility are strong；It is low, energy saving refrigerated module, equipment investment are not needed；Pyroreaction, reaction time is short, produces
It is high-efficient；Product yield is high, quality is stablized；Efficiently solve that the existing batch process process of cyclopropylamine is cumbersome, production efficiency
Low, the problems such as product is unstable, realize the process intensification for preparing cyclopropylamine.
Detailed description of the invention
Fig. 1 is the process flow chart that the present invention continuously prepares cyclopropylamine.
Specific embodiment
The present invention provides a kind of methods for continuously preparing cyclopropylamine, with reference to the accompanying drawings and examples to the present invention do into
The explanation of one step.
Microreactor of the present invention is micro passage reaction or patent ZL00105779.0, ZL200510012114.9
Described in microreactor, mixed with providing be able to achieve between two fluids efficient, moment reaches uniform reaction environment；This
Inventing the micro-mixer not only includes micro passage reaction, film dispersion microreactor or Microtraps hole reactor, other are able to achieve
The device quickly mixed can also be used for the present invention.
Water of the present invention is preferably deionized water, distilled water, pure water etc..
Embodiment 1
Cyclopropylamine is continuously prepared according to technique as shown in Figure 1:
(1) it prepares solution A: 75g water being added into 22g cyclopropyl formamide, it is molten under 40 DEG C of water-bath temperature controls and stirring
Clearly, then with water it is settled to 100mL, preparation obtains cyclopropyl formamide solution density close to 1 solution A；
(2) it prepares solution B: under 10~20 DEG C of water-bath temperature controls and stirring, slowly 23.5g sodium hydrate solid being added
In the liquor natrii hypochloritis for being 10.1% to 186g available chlorine content and a small amount of water, dissolved clarification is added, then is settled to 160mL with water,
Preparation obtains solution B；
(3) step (1) acquired solution A and step (2) acquired solution B are connected respectively with the flow of 5mL/min and 8mL/min
Continuous to be passed through in micro-reactor apparatus, micro-reactor apparatus is mainly made of 40 DEG C of Microtraps hole reactors and 90 DEG C of temperature control coil pipes；Two strands molten
Liquid realizes quick mixing in the reactor of Microtraps hole, obtains reaction liquid C, and the residence time is about in the reactor of Microtraps hole for reaction liquid C
For 0.3s, wherein solution A is dispersed phase, and solution B is continuous phase；Following reaction liquid C is passed directly into temperature control coil pipe, the residence time
For 4min.
(4) enter rectifier unit from the material that coil pipe comes out, final separation obtains cyclopropyl amine product；Pass through gas-chromatography point
It is 95.5% that analysis and mass balance, which obtain cyclopropylamine yield,.
Embodiment 2
Cyclopropylamine is continuously prepared according to technique as shown in Figure 1:
(1) it prepares solution A: 70g water being added into 25g cyclopropyl formamide, it is molten under 40 DEG C of water-bath temperature controls and stirring
Clearly, then with water it is settled to 100mL, preparation obtains solution A；
(2) it prepares solution B: under 10~20 DEG C of water-bath temperature controls and stirring, slowly 25.9g sodium hydrate solid being added
In the liquor natrii hypochloritis for being 12.5% to 175g available chlorine content and a small amount of water, dissolved clarification is added, then is settled to 200mL with water,
Preparation obtains solution B；
(3) by step (1) acquired solution A and step (2) acquired solution B respectively with the flow of 5mL/min and 10mL/min
It is continuously passed through in micro-reactor apparatus, micro-reactor apparatus is mainly made of 40 DEG C of film dispersion microreactors and 80 DEG C of temperature control coil pipes；Two
Stock solution realizes quickly mixing in film dispersion microreactor, obtains reaction liquid C, and reaction liquid C is stopped in film dispersion microreactor
Staying the time is about 0.2s, and wherein solution A is dispersed phase, and solution B is continuous phase；Following reaction liquid C is passed directly into temperature control coil pipe,
Residence time is 6min.
(4) enter rectifier unit from the material that coil pipe comes out, final separation obtains cyclopropyl amine product；Pass through gas-chromatography point
It is 94.0% that analysis and mass balance, which obtain cyclopropylamine yield,.
Embodiment 3
Cyclopropylamine is continuously prepared according to technique as shown in Figure 1:
(1) it prepares solution A: 68g water being added into 30g cyclopropyl formamide, it is molten under 50 DEG C of water-bath temperature controls and stirring
Clearly, then with water it is settled to 100mL, preparation obtains solution A；
(2) it prepares solution B: under 20~30 DEG C of water-bath temperature controls and stirring, slowly 36.7g sodium hydrate solid being added
In the liquor natrii hypochloritis for being 12.5% to 216g available chlorine content and a small amount of water, dissolved clarification is added, then is settled to 250mL with water,
Preparation obtains solution B；
(3) by step (1) acquired solution A and step (2) acquired solution B respectively with the stream of 5mL/min and 12.5mL/min
Amount is continuously passed through in micro-reactor apparatus, and micro-reactor apparatus is mainly made of 60 DEG C of film dispersion microreactors and 70 DEG C of temperature control coil pipes；
Two strands of solution realize quickly mixing in film dispersion microreactor, obtain reaction liquid C, reaction liquid C is in film dispersion microreactor
Residence time is about 0.2s, and wherein solution A is dispersed phase, and solution B is continuous phase；Following reaction liquid C is passed directly into temperature control coil pipe
It is interior, residence time 15min.
(4) enter rectifier unit from the material that coil pipe comes out, final separation obtains cyclopropyl amine product；Pass through gas-chromatography point
It is 94.2% that analysis and mass balance, which obtain cyclopropylamine yield,.
Embodiment 4
Cyclopropylamine is continuously prepared according to technique as shown in Figure 1:
(1) it prepares solution A: 700g water being added into 250g cyclopropyl formamide, it is molten under 40 DEG C of water-bath temperature controls and stirring
Clearly, then with water it is settled to 1L, preparation obtains solution A；
(2) it prepares solution B: under 10~20 DEG C of water-bath temperature controls and stirring, slowly 259g sodium hydrate solid being added
In the liquor natrii hypochloritis for being 12% to 1.8kg available chlorine content and a small amount of water, dissolved clarification is added, then is settled to 1.8L with water, matches
Solution B is made；
(3) by step (1) acquired solution A and step (2) acquired solution B respectively with the flow of 50mL/min and 90mL/min
It is passed through in micro-reactor apparatus, micro-reactor apparatus is mainly made of 60 DEG C of microreactors and 90 DEG C of temperature control coil pipes；Utilize patent ZL
Microreactor structure shown in 200510012114.9: containing 10 parallel channels, is dispersion with 50 microns of stainless steel microfiltration membranes
Medium.Two strands of solution realize quick mixing in microreactor, obtain reaction liquid C, reaction liquid C residence time in microreactor
About 0.6s, wherein solution A is dispersed phase, and solution B is continuous phase；Following reaction liquid C is passed directly into temperature control coil pipe, when stop
Between be 5min.
(4) enter rectifier unit from the material that coil pipe comes out, final separation obtains cyclopropyl amine product；Pass through gas-chromatography point
It is 96.0% that analysis and mass balance, which obtain cyclopropylamine yield,.
Claims (10)
1. a method of continuously prepare cyclopropylamine, which comprises the following steps:
(1) cyclopropyl formamide is dissolved in water, preparation obtains solution A；
(2) sodium hypochlorite, sodium hydroxide and water are mixed, preparation obtains solution B；
(3) solution A and solution B are continuously passed through micro-mixer and are mixed to get reaction liquid C, it is anti-that reaction liquid C enters tubular reactor
It answers；
(4) rectification step (3) resulting material, obtains cyclopropylamine.
2. the method according to claim 1, wherein the quality of the step (1) solution A middle ring propyl formamide point
Number is 20~50%, and the preparation temperature of solution A is 30-70 DEG C.
3. the method according to claim 1, wherein the quality of the step (1) solution A middle ring propyl formamide point
Number is 20-30%, and the preparation temperature of solution A is 40-60 DEG C.
4. the method according to claim 1, wherein in the step (2) solution B, sodium hypochlorite and hydroxide
The molar ratio of sodium is 1:(2~3), the molar concentration of sodium hypochlorite is 0.5~6mol/L in solution B, and preparing temperature is 10~50
℃。
5. the method according to claim 1, wherein the step (3) solution A and solution B are continuously passed through micro- mix
The volume flow ratio of clutch is 1:(1~5).
6. the method according to claim 1, wherein sodium hypochlorite, cyclopropyl first in the step (3) reaction liquid C
The initial molar ratio of amide and sodium hydroxide is (0.96~1.1): 1:(1.8~3.3).
7. the method according to claim 1, wherein in the step (3) micro-mixer be micro passage reaction,
Film disperses microreactor or Microtraps hole reactor.
8. the method according to claim 1, wherein the mixing temperature in the step (3) micro-mixer is 20
~90 DEG C, incorporation time is 0.1~1s.
9. the method according to claim 1, wherein the reaction temperature in the step (3) tubular reactor is
50~100 DEG C, the reaction liquid C residence time is 0.5~60min.
10. the method according to claim 1, wherein the reaction temperature in the step (3) tubular reactor is
80~90 DEG C, the reaction liquid C residence time is 3~8min.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112473612A (en) * | 2020-11-10 | 2021-03-12 | 中国平煤神马能源化工集团有限责任公司 | Novel continuous flow coupling reactor for rapid strong exothermic reaction |
| CN113149896A (en) * | 2021-03-09 | 2021-07-23 | 利尔化学股份有限公司 | Preparation method of 3-aminopyridine |
| CN117229232A (en) * | 2023-11-13 | 2023-12-15 | 深圳智微通科技有限公司 | Method for preparing 2,2-dimorpholinodiethyl ether by continuous flow |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5728873A (en) * | 1995-06-30 | 1998-03-17 | Huels Aktiengesellschaft | Process for the preparation of cyclopropanamine |
| CN1736577A (en) * | 2005-07-08 | 2006-02-22 | 清华大学 | Multi-channeled micro-structured reactor |
| CN108129330A (en) * | 2017-12-30 | 2018-06-08 | 浙江沙星科技有限公司 | A kind of cyclopropylamine continuous production system and production method |
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| CN112473612A (en) * | 2020-11-10 | 2021-03-12 | 中国平煤神马能源化工集团有限责任公司 | Novel continuous flow coupling reactor for rapid strong exothermic reaction |
| CN113149896A (en) * | 2021-03-09 | 2021-07-23 | 利尔化学股份有限公司 | Preparation method of 3-aminopyridine |
| CN117229232A (en) * | 2023-11-13 | 2023-12-15 | 深圳智微通科技有限公司 | Method for preparing 2,2-dimorpholinodiethyl ether by continuous flow |
| CN117229232B (en) * | 2023-11-13 | 2024-02-23 | 深圳智微通科技有限公司 | Method for preparing 2,2-dimorpholinodiethyl ether by continuous flow |
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