CN107445851A - A kind of method that quaternary ammonium salt is continuously synthesized using micro-reaction device - Google Patents
A kind of method that quaternary ammonium salt is continuously synthesized using micro-reaction device Download PDFInfo
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- 238000006243 chemical reaction Methods 0.000 title claims abstract description 126
- 150000003242 quaternary ammonium salts Chemical class 0.000 title claims abstract description 34
- 238000000034 method Methods 0.000 title claims abstract description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 105
- -1 ammonium salt compound Chemical class 0.000 claims abstract description 25
- 150000001413 amino acids Chemical class 0.000 claims abstract description 16
- 150000008282 halocarbons Chemical class 0.000 claims abstract description 13
- 239000002253 acid Substances 0.000 claims abstract description 11
- 239000011230 binding agent Substances 0.000 claims abstract description 11
- 239000000463 material Substances 0.000 claims abstract description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 147
- 239000000243 solution Substances 0.000 claims description 104
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 40
- 239000007864 aqueous solution Substances 0.000 claims description 25
- 229920001343 polytetrafluoroethylene Polymers 0.000 claims description 24
- 239000004810 polytetrafluoroethylene Substances 0.000 claims description 24
- 239000007788 liquid Substances 0.000 claims description 19
- 238000000926 separation method Methods 0.000 claims description 13
- 239000008346 aqueous phase Substances 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052740 iodine Chemical group 0.000 claims description 2
- 239000011630 iodine Chemical group 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000000376 reactant Substances 0.000 abstract description 9
- 230000035484 reaction time Effects 0.000 abstract description 5
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 238000010438 heat treatment Methods 0.000 abstract description 2
- 239000003054 catalyst Substances 0.000 abstract 1
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 22
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 22
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 16
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 14
- 235000009518 sodium iodide Nutrition 0.000 description 12
- 238000001556 precipitation Methods 0.000 description 11
- 230000002421 anti-septic effect Effects 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 239000007791 liquid phase Substances 0.000 description 9
- 230000014759 maintenance of location Effects 0.000 description 8
- 150000004702 methyl esters Chemical class 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 7
- 230000003292 diminished effect Effects 0.000 description 7
- VAJVDSVGBWFCLW-UHFFFAOYSA-N 3-Phenyl-1-propanol Chemical compound OCCCC1=CC=CC=C1 VAJVDSVGBWFCLW-UHFFFAOYSA-N 0.000 description 6
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 6
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropyl alcohol Natural products CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 6
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 6
- 239000012266 salt solution Substances 0.000 description 6
- 238000007086 side reaction Methods 0.000 description 6
- CJGXMNONHNZEQQ-JTQLQIEISA-N ethyl (2s)-2-amino-3-phenylpropanoate Chemical compound CCOC(=O)[C@@H](N)CC1=CC=CC=C1 CJGXMNONHNZEQQ-JTQLQIEISA-N 0.000 description 5
- USYGMXDJUAQNGU-JTQLQIEISA-N methyl (2s)-2-amino-3-(4-methoxyphenyl)propanoate Chemical class COC(=O)[C@@H](N)CC1=CC=C(OC)C=C1 USYGMXDJUAQNGU-JTQLQIEISA-N 0.000 description 5
- ZQFRXVDPMWSCHZ-NSHDSACASA-N propyl (2s)-2-amino-3-phenylpropanoate Chemical compound CCCOC(=O)[C@@H](N)CC1=CC=CC=C1 ZQFRXVDPMWSCHZ-NSHDSACASA-N 0.000 description 5
- 150000002118 epoxides Chemical class 0.000 description 4
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 3
- ZRDJERPXCFOFCP-UHFFFAOYSA-N azane;iodic acid Chemical compound [NH4+].[O-]I(=O)=O ZRDJERPXCFOFCP-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- MAOYFMLUTBSVFC-QMMMGPOBSA-N C(C)OC([C@@H](NCCC)CCO)=O Chemical compound C(C)OC([C@@H](NCCC)CCO)=O MAOYFMLUTBSVFC-QMMMGPOBSA-N 0.000 description 2
- VDGWARYEOFDIAA-VIFPVBQESA-N C(CC)OC([C@@H](NCCC)CCO)=O Chemical compound C(CC)OC([C@@H](NCCC)CCO)=O VDGWARYEOFDIAA-VIFPVBQESA-N 0.000 description 2
- AGYKGLGUMGTNHK-UHFFFAOYSA-N C.[Br] Chemical compound C.[Br] AGYKGLGUMGTNHK-UHFFFAOYSA-N 0.000 description 2
- WVSBBCCXKUUWGB-ZETCQYMHSA-N COC([C@@H](NCCC)CCO)=O Chemical class COC([C@@H](NCCC)CCO)=O WVSBBCCXKUUWGB-ZETCQYMHSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000004902 Softening Agent Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- GRDSNVUGGUKPKE-NSHDSACASA-N ethyl (2s)-2-amino-3-(4-methoxyphenyl)propanoate Chemical compound CCOC(=O)[C@@H](N)CC1=CC=C(OC)C=C1 GRDSNVUGGUKPKE-NSHDSACASA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- PKAUVIXBZJUYRV-UHFFFAOYSA-N methane;hydroiodide Chemical compound C.I PKAUVIXBZJUYRV-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JYTNGEWJAZCVAN-UHFFFAOYSA-N 2-hexadecylbenzenesulfonic acid;sodium Chemical compound [Na].CCCCCCCCCCCCCCCCC1=CC=CC=C1S(O)(=O)=O JYTNGEWJAZCVAN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 229940107816 ammonium iodide Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005189 flocculation Methods 0.000 description 1
- 230000016615 flocculation Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000037048 polymerization activity Effects 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 239000003340 retarding agent Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000010801 sewage sludge Substances 0.000 description 1
- 238000004904 shortening Methods 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
- 238000001228 spectrum Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation 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 involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Plant Pathology (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of method that quaternary ammonium salt is continuously synthesized using micro-reaction device, and he is using amino acid derivativges, halogenated hydrocarbons as reactant, acid binding agent of the sodium hydroxide as reaction, is pumped into microreactor and is reacted in a manner of three feeding streams.Obtained product is the amino acid derived quarternary ammonium salt compound formed.Compared with prior art, the automaticity of the invention is high, and the material ratio of reactant, reaction temperature control are accurate, and the reaction time is short, and equipment, energy loss are low, easy to operate, and required manpower and materials greatly reduce.Simultaneously, above reaction is carried out using the invention, without using the reagent of catalyst, various complicated instruments and danger, heating is only needed with regard to reaction condition can be met, and solves the problem of localized heat release in course of reaction, realize that temperature is homogeneous, stably, can efficiently, obtain product in high quality.
Description
Technical field
The invention belongs to the field of chemical synthesis, and in particular to a kind of side that quaternary ammonium salt is continuously synthesized using micro-reaction device
Method.
Background technology
Organic quaternary ammonium salt is a kind of very extensive compound of purposes, and it does not allow in the status of industry, agricultural, pharmaceutical sector etc.
Despise.By taking phase transfer catalyst as an example, in phase-transfer-catalyzed reactions, quaternary ammonium salt can be formed with the nucleopilic reagent in aqueous phase from
Son is right, into organic phase, so as to accelerate reaction rate, reduces side reaction and improves yield.Industrially, organic quaternary ammonium salt conduct
Cationic surfactant, due to its excellent adsorptivity, emulsibility and thickening property, paid attention to by each industrial department, such as
Cetyl benzenesulfonic acid sodium.Acryloyloxyalkyl quaternaries cation monomer and acrylamide alkyl quaternaries cation
Monomer is due to at a relatively high polymerization activity, the higher polymer of easily prepared relative molecular weight, therefore flocculation is strong, in dirt
Sewage sludge process field is significant.And softening agent, antistatic additive are used as, it is mainly used in textile printing and dyeing industry, such
Softening agent and there are excellent soft, antistatic, sterilization, yellowing resistance energy.Dosage is few, and effect is good, and it is convenient to prepare, and compatibility is good,
With high cost performance.Answered in addition, organic quaternary ammonium salt has in dyeing retarding agents field, agriculture field, water treatment field etc.
With being a kind of highly important chemical products.
Antiseptic is also a big purposes of quaternary ammonium salt.Various types of quaternary ammonium salt antiseptics generally have powerful, wide spectrum
Antibacterial activity, and half-life period is longer.Research shows that low dose of quaternary ammonium salt antiseptic can reduce rapidly carefully in a short time
The viable count of bacterium.Also, because the more general aminated compounds of the toxicity of quaternary ammonium salt is low, thus as antiseptic quaternary ammonium salt sun from
Sub- monomer, its murder by poisoning to human body are small.Long chain macromolecule quaternary ammonium salt does not penetrate into human body skin, and this is also quaternary ammonium salt antiseptic
One of advantage.And with a large amount of uses of people, increasing bacterium generates drug resistance to general quaternary ammonium salt antiseptic,
In order to avoid this phenomenon, researcher has started the research of new quaternary ammonium salt antiseptic.In recent years, a derived from amino acid forms
The antiseptic of quarternary ammonium salt compound appear in the sight of people.Antibacterial effect of such antiseptic than general quaternary ammonium salt antiseptic
More preferably, and toxicity is smaller, so in the past few years, its research temperature more and more higher.
It is and less for the study on the synthesis of such amino acid derived quarternary ammonium salt compound formed.In current document report
In, only laboratory synthetic method, and the technique being combined to for industry is temporarily without report.Therefore, probe into a kind of achievable such
The method of quaternary ammonium salt industrialized production is necessary.In document report, the synthetic method of such compound is more numerous
Trivial, its step is as follows：The ethanol mixing of the amino acid of 1 equivalent, the para toluene sulfonamide of 1 equivalent and 1.2 equivalents, at 50 DEG C
At a temperature of react 48 hours, obtain amino-acid ester.After amino-acid ester is purified, be placed in seal pipe, add halogenated hydrocarbons with
And potassium carbonate, vacuumize, reacted 18 hours at a temperature of 90 DEG C, add ether, obtained precipitation is required product.
As can be seen that the season aminating reaction of second step has that some conventional methods are insoluble.1. it reacts
Condition it is more harsh, it is necessary in seal pipe vacuum reaction；2. the reaction time is longer；3. during the course of the reaction, ester group may break
Split；4. the mode of production is relative complex and does not have continuity；5. during the course of the reaction, the local PH of solution and local temperature be not
Easily accurate control, it is difficult to avoid the generation of side reaction, cause the quality decline of product.
In order to solve the above problems, we introduce microreactor to complete above-mentioned reaction.Skill is used as using miniflow field technology
Art is supported, using microreactor as reaction member, can accurately control the material ratio of reactant, the reaction time, reaction temperature with
And in course of reaction solution PH, so as to avoid the generation of the fracture of ester group and other side reactions, and can contract significantly
Short reaction time, lift the yield and quality of product.
Microreactor is a kind of consersion unit with micro-structural, is chemically reacted in microreactor, reactant
Scattered yardstick is in micron dimension, so having the change of hydrodynamics rule, the reinforcing of transmittance process, high safety and controllable
The characteristics of property is high.The synthesis of the amino acid derived quarternary ammonium salt compound formed, the flow velocity of reactant are carried out using micro-reaction device
It can accurately be controlled, be pumped into reactor by syringe pump and syringe, so that material is continuously reacted.And micro- anti-
Answer in device, built-in micro-structural system causes material to possess great heat exchange efficiency and mixing efficiency, realizes to reaction mass
Accurately mixed with required material ratio, at the same can accurate controlling reaction temperature, and the PH of solution can also be obtained
Even distribution.Local temperature is too high during the course of the reaction for this method for solving reported in document, and concentration of substrate is pockety
Shortcoming, this solves the problems, such as side reaction to a certain extent.Also, reactant due to serialization is put into, and micro- anti-
Answer reaction in device to enter without air, eliminate and vacuumize, remove numerous and diverse operation such as reaction solution.Therefore, carried out using microreactor
Season aminating reaction, the complexity of reaction can be reduced, realize continuous reaction, improve the concentration of yield and product.Instead
Greatly shortening between seasonable and a big advantage of the invention.Therefore, it is one ten to carry out season aminating reaction using microreactor
Divide preferable method.
The content of the invention
The technical problem to be solved in the present invention is to provide a kind of method that quaternary ammonium salt is continuously synthesized using micro-reaction device, with
The problems such as reactions steps existing for solution prior art are cumbersome, reaction temperature can not be controlled accurately and side reaction is inevitable.
In order to solve the above technical problems, the technical solution adopted by the present invention is as follows：
A kind of method that quaternary ammonium salt is continuously synthesized using micro-reaction device, it comprises the following steps：
Amino acid derivativges (I), halogenated hydrocarbons (II) and acid binding agent are pumped into the micro-mixer of micro-reaction device respectively simultaneously
In, it is pumped into the microreactor of micro-reaction device and is reacted after being sufficiently mixed, reaction solution liquid separation is collected after the completion of reaction, after
Processing obtains quaternary ammonium salt (III)；
Wherein,
R1For phenyl or 4- methoxyphenyls,
R2For methyl, ethyl or propyl group,
R3For methyl,
X is bromine or iodine.
These, it is preferred to before reaction, reaction solution is preheated to 80 DEG C.
These, it is preferred to after first mixing amino acid derivativges and acid binding agent, then gained mixed liquor and halogenated hydrocarbons existed
Mixed in micro-mixer.
Wherein, in above-mentioned preferred scheme, amino acid derivativges and acid binding agent are mixed using Y type blenders, institute
The micro-mixer stated is bayer blenders.
Wherein, the mol ratio of amino acid derivativges, halogenated hydrocarbons and acid binding agent is 1：3.2~3.5：2, preferably 1：3.3：2.
Wherein, described acid binding agent is sodium hydroxide.
Wherein, before micro-reaction device is pumped into, amino acid derivativges are configured to 35~50wt% toluene solution, halogen in advance
It is configured to 35~50wt% toluene solution in advance for hydrocarbon, acid binding agent is configured to the 18~25wt% aqueous solution in advance.
Wherein, in micro-reaction device, the first of the toluene solutions of amino acid derivativges, sodium hydrate aqueous solution and halogenated hydrocarbons
The velocity ratio of benzole soln is 1：0.5~0.75：1.7~2.2, preferable flow rate ratio is 1：0.7：2.0.
Wherein, in microreactor, the residence time is 8~16min, and reaction temperature is 90~99 DEG C；It is preferred that mode of heating
For oil bath.
Described post processing is：A layer aqueous phase will be removed after reaction solution liquid separation, taken out after adjusting pH to 4~6 with aqueous hydrochloric acid solution
Filter and be evaporated under reduced pressure, produce.
Wherein, described micro-reaction device includes the micro-mixer and microreactor being sequentially connected by connecting tube；Wherein,
The feeding mouth of micro-mixer is connected with 3 liquor inlet.
Wherein, described microreactor is coil pipe, and material is polytetrafluoroethylene (PTFE), internal diameter 1.0mm, volume is 15~
20mL；Wherein, in the microreactor, the flow velocity of the toluene solution of preferred amino acid derivative is 0.2~0.6mL/min, hydrogen
The flow velocity of aqueous solution of sodium oxide is 0.15~0.5mL/min, and the flow velocity of the toluene solution of halogenated hydrocarbons is 0.4~1.3mL/min.
Beneficial effect：
Compared with prior art, the invention provides a kind of method of continuous production antibacterial agent, the mistake of this method
Journey is easy, and reactant concentration, reaction temperature can be controlled accurately, while side reaction is preferably minimized.Also, this method is used,
Reaction time is greatly shortened, and reactant can be carried out continuously reaction, improve reaction efficiency, and obtained product qualities are also carried
Height, yield are up to more than 80%.
Brief description of the drawings
Fig. 1 is the structural representation of micro-reaction device used in the present invention.
Embodiment
The micro-reaction device that following examples are applicable including syringe, the Y types being connected with coil pipe as shown in figure 1, mix
Device, bayer blenders, microreactor, receiving flask.By high-precision thunder, not syringe pump, realization input microring array to reaction raw materials
In device and its equipment afterwards, so that reactant can realize serialization by each micro-reaction device, while control its anti-
Between seasonable.
Embodiment 1：
Take the toluene solution of 50g/100mL iodomethane, 20wt% sodium hydrate aqueous solutions and 40g/100mL phenylpropyl alcohol
The toluene solution of propylhomoserin methyl esters, respectively in inhalation syringe A, B, C, it is fixed on syringe pump.By syringe pump first by phenylalanine
The toluene solution of methyl esters is mixed with sodium hydrate aqueous solution by Y type blenders, and the mixed liquor of gained is preheated to 80 DEG C, then
Mixed with the toluene solution of iodomethane by bayer blenders, be pumped into microreactor and reacted.As microreactor
The specification of polytetrafluoroethylene (PTFE) coil pipe be 1mm/20mL.Phenyalanine methyl ester, sodium hydroxide, the mol ratio of iodomethane are 1:2:
3.3, velocity ratio 1:0.73:2.1, specific flow velocity is phenyalanine methyl ester 0.5mL/min, sodium hydroxide 0.365mL/min, iodine
Methane 1.05mL/min.Microreactor, which is placed in oil bath pan, controls temperature, and reaction temperature is maintained at into 90 DEG C, reacts retention time
For 10.5 minutes, i.e., after reaction starts 10.5 minutes, reaction solution is collected in receiving flask.After reaction finishes, by receiving flask
In reaction solution be transferred to separatory funnel, stand liquid separation, remove the aqueous phase of layer with 1:1 watery hydrochloric acid adjusts PH to 4~6, depressurizes
Filter, removes the sodium iodide of precipitation, obtains settled solution.Obtained solution is placed in Rotary Evaporators and is evaporated under reduced pressure, is taken out again
The sodium iodide of second of precipitation is filtered out, obtains the N of high-quality, N, N- trimethylphenylalanine methyl esters iodate ammonium salt solutions.Through height
Effect liquid phase chromatogram is analyzed, and in this secondary response, N, N, the yield of N- trimethylphenylalanine methyl esters ammonium iodides is 86.32%.
Embodiment 2
Take the toluene solution of 50g/100mL iodomethane, 20wt% sodium hydrate aqueous solutions and 40g/100mL phenylpropyl alcohol
The toluene solution of propylhomoserin ethyl ester, respectively in inhalation syringe A, B, C, it is fixed on syringe pump.By syringe pump first by phenylalanine
The toluene solution of ethyl ester is mixed with sodium hydrate aqueous solution by Y type blenders, and the mixed liquor of gained is preheated to 80 DEG C, then
Mixed with the toluene solution of iodomethane by bayer blenders, be pumped into microreactor and reacted.As microreactor
The specification of polytetrafluoroethylene (PTFE) coil pipe be 1mm/20mL.Phenylalanine ethyl ester, sodium hydroxide, the mol ratio of iodomethane are 1:2:
3.3, velocity ratio 1:0.68:1.98, specific flow velocity is phenylalanine ethyl ester 0.5mL/min, sodium hydroxide 0.34mL/min, iodine
Methane 0.99mL/min.Microreactor, which is placed in oil bath pan, controls temperature, and reaction temperature is maintained at into 90 DEG C, reacts retention time
For 11 minutes, i.e., after reaction starts 11 minutes, reaction solution is collected in receiving flask.After reaction finishes, by receiving flask
Reaction solution is transferred to separatory funnel, stands liquid separation, removes the aqueous phase of layer with 1:1 watery hydrochloric acid adjusts PH to 4~6, is filtered under diminished pressure, removes
The sodium iodide separated out is removed, obtains settled solution.Obtained solution is placed in Rotary Evaporators and is evaporated under reduced pressure, filters remove again
Second of sodium iodide separated out, obtains the N of high-quality, N, N- trimethylphenylalanine ethyl ester iodate ammonium salt solutions.Through efficient liquid phase
Chromatography, in this secondary response, N, N, the yield of N- trimethylphenylalanine ethyl ester ammonium iodides is 84.58%.
Embodiment 3
Take the toluene solution of 50g/100mL iodomethane, 20wt% sodium hydrate aqueous solutions and 40g/100mL phenylpropyl alcohol
The toluene solution of propylhomoserin propyl ester, respectively in inhalation syringe A, B, C, it is fixed on syringe pump.By syringe pump first by phenylalanine
The toluene solution of propyl ester is mixed with sodium hydrate aqueous solution by Y type blenders, and the mixed liquor of gained is preheated to 80 DEG C, then
Mixed with the toluene solution of iodomethane by bayer blenders, be pumped into microreactor and reacted.As microreactor
The specification of polytetrafluoroethylene (PTFE) coil pipe be 1mm/20mL.Phenylalanine propyl ester, sodium hydroxide, the mol ratio of iodomethane are 1:2:
3.3, velocity ratio 1:0.63:1.82, specific flow velocity is phenylalanine propyl ester 0.5mL/min, sodium hydroxide 0.315mL/min,
Iodomethane 0.91mL/min.Microreactor, which is placed in oil bath pan, controls temperature, and reaction temperature is maintained at into 90 DEG C, when reaction retains
Between be 11.5 minutes, i.e., reaction start 11.5 minutes after, reaction solution is collected in receiving flask.After reaction finishes, it will collect
Reaction solution in bottle is transferred to separatory funnel, stands liquid separation, removes the aqueous phase of layer with 1:1 watery hydrochloric acid adjusts PH to 4~6, decompression
Filtering, removes the sodium iodide of precipitation, obtains settled solution.Obtained solution is placed in Rotary Evaporators and is evaporated under reduced pressure, again
Filter and remove second of sodium iodide separated out, obtain the N of high-quality, N, N- trimethylphenylalanine propyl ester iodate ammonium salt solutions.Through
Efficient liquid phase chromatographic analysis, in this secondary response, N, N, the yield of N- trimethylphenylalanine propyl ester ammonium iodides is 83.49%.
Embodiment 4
Take the toluene solution of 50g/100mL bromomethane, 20wt% sodium hydrate aqueous solutions and 40g/100mL phenylpropyl alcohol
The toluene solution of propylhomoserin methyl esters, respectively in inhalation syringe A, B, C, it is fixed on syringe pump.By syringe pump first by phenylalanine
The toluene solution of methyl esters is mixed with sodium hydrate aqueous solution by Y type blenders, and the mixed liquor of gained is preheated to 80 DEG C, then
Mixed with the toluene solution of bromomethane by bayer blenders, be pumped into microreactor and reacted.As microreactor
The specification of polytetrafluoroethylene (PTFE) coil pipe be 1mm/20mL.Phenyalanine methyl ester, sodium hydroxide, the mol ratio of bromomethane are 1:2:
3.3, velocity ratio 1:0.73:1.39, specific flow velocity is phenyalanine methyl ester 0.5mL/min, sodium hydroxide 0.365mL/min,
Bromomethane 0.7mL/min.Microreactor, which is placed in oil bath pan, controls temperature, and reaction temperature is maintained at into 90 DEG C, when reaction retains
Between be 13 minutes, i.e., reaction start 13 minutes after, reaction solution is collected in receiving flask.After reaction finishes, by receiving flask
Reaction solution be transferred to separatory funnel, stand liquid separation, remove the aqueous phase of layer with 1:1 watery hydrochloric acid adjusts PH to 4~6, is filtered under diminished pressure,
The sodium bromide separated out is removed, obtains settled solution.Obtained solution is placed in Rotary Evaporators and is evaporated under reduced pressure, filters remove again
The sodium bromide of second of precipitation is removed, obtains the N of high-quality, N, N- trimethylphenylalanine methyl esters ammonium bromide solutions.Through efficient liquid
Analysis of hplc, in this secondary response, N, N, the yield of N- trimethylphenylalanine methyl esters ammonium bromides is 83.57%.
Embodiment 5
Take the toluene solution of 50g/100mL bromomethane, 20wt% sodium hydrate aqueous solutions and 40g/100mL phenylpropyl alcohol
The toluene solution of propylhomoserin ethyl ester, respectively in inhalation syringe A, B, C, it is fixed on syringe pump.By syringe pump first by phenylalanine
The toluene solution of ethyl ester is mixed with sodium hydrate aqueous solution by Y type blenders, and the mixed liquor of gained is preheated to 80 DEG C, then
Mixed with the toluene solution of bromomethane by bayer blenders, be pumped into microreactor and reacted.As microreactor
The specification of polytetrafluoroethylene (PTFE) coil pipe be 1mm/20mL.Phenylalanine ethyl ester, sodium hydroxide, the mol ratio of bromomethane are 1:2:
3.3, velocity ratio 1:0.68:1.24, specific flow velocity is phenylalanine ethyl ester 0.5mL/min, sodium hydroxide 0.34mL/min, bromine
Methane 0.62mL/min.Microreactor, which is placed in oil bath pan, controls temperature, and reaction temperature is maintained at into 90 DEG C, reacts retention time
For 13.5 minutes, i.e., after reaction starts 13.5 minutes, reaction solution is collected in receiving flask.After reaction finishes, by receiving flask
In reaction solution be transferred to separatory funnel, stand liquid separation, remove the aqueous phase of layer with 1:1 watery hydrochloric acid adjusts PH to 4~6, depressurizes
Filter, removes the sodium bromide of precipitation, obtains settled solution.Obtained solution is placed in Rotary Evaporators and is evaporated under reduced pressure, is taken out again
The sodium bromide of second of precipitation is filtered out, obtains the N of high-quality, N, N- trimethylphenylalanine ethyl ester ammonium bromide solutions.Through height
Effect liquid phase chromatogram is analyzed, and in this secondary response, N, N, the yield of N- trimethylphenylalanine ethyl ester ammonium bromides is 82.36%.
Embodiment 6
Take the toluene solution of 50g/100mL bromomethane, 20wt% sodium hydrate aqueous solutions and 40g/100mL phenylpropyl alcohol
The toluene solution of propylhomoserin propyl ester, respectively in inhalation syringe A, B, C, it is fixed on syringe pump.By syringe pump first by phenylalanine
The toluene solution of propyl ester is mixed with sodium hydrate aqueous solution by Y type blenders, and the mixed liquor of gained is preheated to 80 DEG C, then
Mixed with the toluene solution of bromomethane by bayer blenders, be pumped into microreactor and reacted.As microreactor
The specification of polytetrafluoroethylene (PTFE) coil pipe be 1mm/20mL.Phenylalanine propyl ester, sodium hydroxide, the mol ratio of bromomethane are 1:2:
3.3, velocity ratio 1:0.63:1.2, specific flow velocity is phenylalanine propyl ester 0.5mL/min, sodium hydroxide 0.315mL/min, bromine
Methane 0.6mL/min.Microreactor, which is placed in oil bath pan, controls temperature, and reaction temperature is maintained at into 90 DEG C, reacts retention time
For 14 minutes, i.e., after reaction starts 14 minutes, reaction solution is collected in receiving flask.After reaction finishes, by receiving flask
Reaction solution is transferred to separatory funnel, stands liquid separation, removes the aqueous phase of layer with 1:1 watery hydrochloric acid adjusts PH to 4~6, is filtered under diminished pressure, removes
The sodium bromide separated out is removed, obtains settled solution.Obtained solution is placed in Rotary Evaporators and is evaporated under reduced pressure, filters remove again
Second of sodium bromide separated out, obtains the N of high-quality, N, N- trimethylphenylalanine propyl ester ammonium bromide solutions.Through efficient liquid phase
Chromatography, in this secondary response, N, N, the yield of N- trimethylphenylalanine propyl ester ammonium bromides is 81.64%.
Embodiment 7
Take the toluene solution of 50g/100mL iodomethane, 20wt% sodium hydrate aqueous solutions and 40g/100mL to first
The toluene solution of epoxide phenyalanine methyl ester, respectively in inhalation syringe A, B, C, it is fixed on syringe pump.First will by syringe pump
The toluene solution of p-methoxyphenylalanine methyl esters is mixed with sodium hydrate aqueous solution by Y type blenders, and gained mixes
Close liquid and be preheated to 80 DEG C, then mixed with the toluene solution of iodomethane by bayer blenders, be pumped into microreactor and carry out
Reaction.Specification as the polytetrafluoroethylene (PTFE) coil pipe of microreactor is 1mm/20mL.P-methoxyphenylalanine methyl esters, hydroxide
Sodium, the mol ratio of iodomethane are 1:2:3.3, velocity ratio 1:0.63:1.8, specific flow velocity is p-methoxyphenylalanine methyl esters
0.5mL/min, sodium hydroxide 0.315mL/min, iodomethane 0.9mL/min.Microreactor, which is placed in oil bath pan, controls temperature, will
Reaction temperature is maintained at 90 DEG C, and reaction retention time is 11.5 minutes, i.e., after reaction starts 11.5 minutes, is received in receiving flask
Collect reaction solution.After reaction finishes, the reaction solution in receiving flask is transferred to separatory funnel, stands liquid separation, removes the aqueous phase of layer
With 1:1 watery hydrochloric acid adjusts PH to 4~6, is filtered under diminished pressure, removes the sodium iodide of precipitation, obtain settled solution.Obtained solution is put
It is evaporated under reduced pressure in Rotary Evaporators, filters remove second of sodium iodide separated out again, obtain the N of high-quality, N, N- front threes
Base p-methoxyphenylalanine methyl esters iodate ammonium salt solution.Through efficient liquid phase chromatographic analysis, in this secondary response, N, N, N- trimethyls pair
The yield of methoxyphenylalanine methyl esters ammonium iodide is 85.23%.
Embodiment 8
Take the toluene solution of 50g/100mL iodomethane, 20wt% sodium hydrate aqueous solutions and 40g/100mL to first
The toluene solution of epoxide phenylalanine ethyl ester, respectively in inhalation syringe A, B, C, it is fixed on syringe pump.First will by syringe pump
The toluene solution of p-methoxyphenylalanine ethyl ester is mixed with sodium hydrate aqueous solution by Y type blenders, and gained mixes
Close liquid and be preheated to 80 DEG C, then mixed with the toluene solution of iodomethane by bayer blenders, be pumped into microreactor and carry out
Reaction.Specification as the polytetrafluoroethylene (PTFE) coil pipe of microreactor is 1mm/20mL.P-methoxyphenylalanine ethyl ester, hydroxide
Sodium, the mol ratio of iodomethane are 1:2:3.3, velocity ratio 1:0.62:1.77, specific flow velocity is p-methoxyphenylalanine ethyl ester
0.5mL/min, sodium hydroxide 0.31mL/min, iodomethane 0.885mL/min.Microreactor, which is placed in oil bath pan, controls temperature,
Reaction temperature is maintained at 90 DEG C, reaction retention time is 12 minutes, i.e., after reaction starts 12 minutes, is collected in receiving flask
Reaction solution.After reaction finishes, the reaction solution in receiving flask is transferred to separatory funnel, stands liquid separation, the aqueous phase for removing layer is used
1:1 watery hydrochloric acid adjusts PH to 4~6, is filtered under diminished pressure, removes the sodium iodide of precipitation, obtain settled solution.Obtained solution is placed in
It is evaporated under reduced pressure in Rotary Evaporators, filters remove second of sodium iodide separated out again, obtain the N of high-quality, N, N- trimethyls
P-methoxyphenylalanine ethyl ester iodate ammonium salt solution.Through efficient liquid phase chromatographic analysis, in this secondary response, N, N, N- trimethyls are to first
The yield of epoxide phenylalanine ethyl ester ammonium iodide is 84.86%.
Embodiment 9
Take the toluene solution of 50g/100mL iodomethane, 20wt% sodium hydrate aqueous solutions and 40g/100mL to first
The toluene solution of epoxide phenylalanine propyl ester, respectively in inhalation syringe A, B, C, it is fixed on syringe pump.First will by syringe pump
The toluene solution of p-methoxyphenylalanine propyl ester is mixed with sodium hydrate aqueous solution by Y type blenders, and gained mixes
Close liquid and be preheated to 80 DEG C, then mixed with the toluene solution of iodomethane by bayer blenders, be pumped into microreactor and carry out
Reaction.Specification as the polytetrafluoroethylene (PTFE) coil pipe of microreactor is 1mm/20mL.P-methoxyphenylalanine propyl ester, hydroxide
Sodium, the mol ratio of iodomethane are 1:2:3.3, velocity ratio 1:0.56:1.59, specific flow velocity is p-methoxyphenylalanine propyl ester
0.5mL/min, sodium hydroxide 0.28mL/min, iodomethane 0.79mL/min.Microreactor, which is placed in oil bath pan, controls temperature, will
Reaction temperature is maintained at 90 DEG C, and reaction retention time is 13 minutes, i.e., after reaction starts 13 minutes, is collected in receiving flask anti-
Answer liquid.After reaction finishes, the reaction solution in receiving flask is transferred to separatory funnel, stands liquid separation, remove the aqueous phase of layer with 1:1
Watery hydrochloric acid adjusts PH to 4~6, is filtered under diminished pressure, removes the sodium iodide of precipitation, obtain settled solution.Obtained solution is placed in rotation
Turn to be evaporated under reduced pressure in evaporimeter, filter remove second of sodium iodide separated out again, obtain the N of high-quality, N, N- trimethyls pair
Methoxyphenylalanine propyl ester iodate ammonium salt solution.Through efficient liquid phase chromatographic analysis, in this secondary response, N, N, N- trimethyls are to methoxy
The yield of base phenylalanine propyl ester ammonium iodide is 84.02%.
Embodiment 10
Take the toluene solution of 50g/100mL bromomethane, 20wt% sodium hydrate aqueous solutions and 40g/100mL to first
The toluene solution of epoxide phenyalanine methyl ester, respectively in inhalation syringe A, B, C, it is fixed on syringe pump.First will by syringe pump
The toluene solution of p-methoxyphenylalanine methyl esters is mixed with sodium hydrate aqueous solution by Y type blenders, and gained mixes
Close liquid and be preheated to 80 DEG C, then mixed with the toluene solution of bromomethane by bayer blenders, be pumped into microreactor and carry out
Reaction.Specification as the polytetrafluoroethylene (PTFE) coil pipe of microreactor is 1mm/20mL.P-methoxyphenylalanine methyl esters, hydroxide
Sodium, the mol ratio of bromomethane are 1:2:3.3, velocity ratio 1:0.63:1.2, specific flow velocity is p-methoxyphenylalanine methyl esters
0.6mL/min, sodium hydroxide 0.378mL/min, bromomethane 0.72mL/min.Microreactor, which is placed in oil bath pan, controls temperature,
Reaction temperature is maintained at 90 DEG C, reaction retention time is 11.5 minutes, i.e., after reaction starts 11.5 minutes, in receiving flask
Collect reaction solution.After reaction finishes, the reaction solution in receiving flask is transferred to separatory funnel, stands liquid separation, removes the water of layer
Mutually with 1:1 watery hydrochloric acid adjusts PH to 4~6, is filtered under diminished pressure, removes the sodium bromide of precipitation, obtain settled solution.The solution that will be obtained
It is placed in Rotary Evaporators and is evaporated under reduced pressure, filters remove second of sodium bromide separated out again, obtain the N of high-quality, N, N- tri-
Methyl p-methoxyphenylalanine methyl esters ammonium bromide solution.Through efficient liquid phase chromatographic analysis, in this secondary response, N, N, N- trimethyls
The yield of p-methoxyphenylalanine methyl esters ammonium bromide is 85.96%.
Claims (9)
- A kind of 1. method that quaternary ammonium salt is continuously synthesized using micro-reaction device, it is characterised in that it comprises the following steps：Amino acid derivativges (I), halogenated hydrocarbons (II) and acid binding agent are pumped into the micro-mixer of micro-reaction device respectively simultaneously, filled Divide after mixing to be pumped into the microreactor of micro-reaction device and reacted, reaction solution is collected after the completion of reaction, it is post-treated to obtain Quaternary ammonium salt (III)；Wherein,R1For phenyl or 4- methoxyphenyls,R2For methyl, ethyl or propyl group,R3For methyl,X is bromine or iodine.
- 2. the method according to claim 1 that quaternary ammonium salt is continuously synthesized using micro-reaction device, it is characterised in that amino acid The mol ratio of derivative, halogenated hydrocarbons and acid binding agent is 1：3.2~3.5：2.
- 3. the method according to claim 1 that quaternary ammonium salt is continuously synthesized using micro-reaction device, it is characterised in that described Acid binding agent is sodium hydroxide.
- 4. the method according to claim 1 that quaternary ammonium salt is continuously synthesized using micro-reaction device, it is characterised in that be pumped into Before micro-reaction device, amino acid derivativges are configured to 35~50wt% toluene solution in advance, and halogenated hydrocarbons is configured to 35 in advance~ 50wt% toluene solution, acid binding agent are configured to the 18~25wt% aqueous solution in advance.
- 5. the method according to claim 4 that quaternary ammonium salt is continuously synthesized using micro-reaction device, it is characterised in that micro- anti- Answer in device, the velocity ratio of the toluene solution of the toluene solutions of amino acid derivativges, sodium hydrate aqueous solution and halogenated hydrocarbons is 1： 0.5~0.75：1.7~2.2.
- 6. the method according to claim 1 that quaternary ammonium salt is continuously synthesized using micro-reaction device, it is characterised in that micro- anti- Answer in device, the residence time is 8~16min, and reaction temperature is 90~99 DEG C.
- 7. the method according to claim 1 that quaternary ammonium salt is continuously synthesized using micro-reaction device, it is characterised in that described Post-process and be：A layer aqueous phase will be removed after reaction solution liquid separation, filters and is evaporated under reduced pressure after adjusting pH to 4~6, produce.
- 8. the method according to claim 1 that quaternary ammonium salt is continuously synthesized using micro-reaction device, it is characterised in that described Micro-reaction device includes the micro-mixer and microreactor being sequentially connected by connecting tube；Wherein, the feeding mouth of micro-mixer connects It is connected to 3 liquor inlet.
- 9. the method according to claim 1 that quaternary ammonium salt is continuously synthesized using micro-reaction device, it is characterised in that described Microreactor is coil pipe, and material is polytetrafluoroethylene (PTFE), and internal diameter 1.0mm, volume is 15~20mL.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108299250A (en) * | 2018-01-30 | 2018-07-20 | 江苏迪安化工有限公司 | The continuous preparation method of one inter-species di alkylamino group methylsulfonylphenylamine |
| CN109824755A (en) * | 2019-04-09 | 2019-05-31 | 湖南华腾制药有限公司 | N- tertbutyloxycarbonyl-L- leucyl-L-phenylalanine methyl esters production method |
| CN110694570A (en) * | 2019-10-11 | 2020-01-17 | 中国石油大学(北京) | Novel clear water agent tubule synthesis device and application thereof |
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| CN103588662A (en) * | 2013-11-06 | 2014-02-19 | 浙江大学 | Method for synthesis of betamipron in continuous-flow microreactor |
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| CN103588662A (en) * | 2013-11-06 | 2014-02-19 | 浙江大学 | Method for synthesis of betamipron in continuous-flow microreactor |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108299250A (en) * | 2018-01-30 | 2018-07-20 | 江苏迪安化工有限公司 | The continuous preparation method of one inter-species di alkylamino group methylsulfonylphenylamine |
| CN108299250B (en) * | 2018-01-30 | 2020-09-18 | 江苏迪安化工有限公司 | Continuous preparation method of m-dialkylaminomethylsulfonylanilide |
| CN109824755A (en) * | 2019-04-09 | 2019-05-31 | 湖南华腾制药有限公司 | N- tertbutyloxycarbonyl-L- leucyl-L-phenylalanine methyl esters production method |
| CN110694570A (en) * | 2019-10-11 | 2020-01-17 | 中国石油大学(北京) | Novel clear water agent tubule synthesis device and application thereof |
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