CN106946716B - Process for synthesizing benzalkonium chloride monomer - Google Patents
Process for synthesizing benzalkonium chloride monomer Download PDFInfo
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- CN106946716B CN106946716B CN201710182322.6A CN201710182322A CN106946716B CN 106946716 B CN106946716 B CN 106946716B CN 201710182322 A CN201710182322 A CN 201710182322A CN 106946716 B CN106946716 B CN 106946716B
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- ethyl acetate
- tertiary amine
- benzalkonium chloride
- benzyl chloride
- reaction kettle
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- 229960000686 benzalkonium chloride Drugs 0.000 title claims abstract description 50
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 title claims abstract description 50
- 239000000178 monomer Substances 0.000 title claims abstract description 36
- 238000000034 method Methods 0.000 title abstract description 10
- 230000002194 synthesizing effect Effects 0.000 title 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 162
- 238000006243 chemical reaction Methods 0.000 claims abstract description 64
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims abstract description 55
- 229940073608 benzyl chloride Drugs 0.000 claims abstract description 55
- 239000013078 crystal Substances 0.000 claims abstract description 49
- -1 alkyl dimethyl tertiary amine Chemical class 0.000 claims abstract description 30
- 239000012065 filter cake Substances 0.000 claims abstract description 26
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 22
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 22
- 239000000047 product Substances 0.000 claims abstract description 14
- 239000000498 cooling water Substances 0.000 claims abstract description 13
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- 238000002425 crystallisation Methods 0.000 claims abstract description 3
- 230000008025 crystallization Effects 0.000 claims abstract description 3
- 238000001035 drying Methods 0.000 claims abstract 2
- YWFWDNVOPHGWMX-UHFFFAOYSA-N n,n-dimethyldodecan-1-amine Chemical compound CCCCCCCCCCCCN(C)C YWFWDNVOPHGWMX-UHFFFAOYSA-N 0.000 claims description 22
- 150000003512 tertiary amines Chemical class 0.000 claims description 21
- 229910000831 Steel Inorganic materials 0.000 claims description 11
- 238000004140 cleaning Methods 0.000 claims description 11
- 230000006837 decompression Effects 0.000 claims description 11
- 238000009413 insulation Methods 0.000 claims description 11
- 239000010959 steel Substances 0.000 claims description 11
- 238000010792 warming Methods 0.000 claims description 11
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 238000000967 suction filtration Methods 0.000 claims 1
- 238000001914 filtration Methods 0.000 abstract description 13
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 239000012847 fine chemical Substances 0.000 abstract description 2
- 238000001953 recrystallisation Methods 0.000 abstract description 2
- 238000003756 stirring Methods 0.000 abstract description 2
- 238000001816 cooling Methods 0.000 abstract 1
- 239000011521 glass Substances 0.000 abstract 1
- 238000004321 preservation Methods 0.000 abstract 1
- 238000005086 pumping Methods 0.000 abstract 1
- 238000003828 vacuum filtration Methods 0.000 abstract 1
- 238000005406 washing Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 241000195493 Cryptophyta Species 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- PBLNBZIONSLZBU-UHFFFAOYSA-N 1-bromododecane Chemical compound CCCCCCCCCCCCBr PBLNBZIONSLZBU-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 230000001877 deodorizing effect Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- YXUPZGKORWTXID-UHFFFAOYSA-N domiphen Chemical compound CCCCCCCCCCCC[N+](C)(C)CCOC1=CC=CC=C1 YXUPZGKORWTXID-UHFFFAOYSA-N 0.000 description 1
- 229960000629 domiphen Drugs 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- OMEMQVZNTDHENJ-UHFFFAOYSA-N n-methyldodecan-1-amine Chemical compound CCCCCCCCCCCCNC OMEMQVZNTDHENJ-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
- C07C209/06—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms
- C07C209/12—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms with formation of quaternary ammonium compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/82—Purification; Separation; Stabilisation; Use of additives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of fine chemicals, in particular to a synthesis process of benzalkonium chloride monomer; the method specifically comprises the following steps: (1) respectively metering fatty alkyl dimethyl tertiary amine, benzyl chloride and ethyl acetate according to a formula; (2) putting ethyl acetate into a glass reaction kettle, pumping fatty alkyl dimethyl tertiary amine and benzyl chloride into a head tank respectively, starting a stirring device of the reaction kettle, and dripping the fatty alkyl dimethyl tertiary amine and the benzyl chloride into the reaction kettle in the same proportion at normal temperature; (3) heating the reaction kettle to 70-100 ℃, and carrying out heat preservation reaction for 7-10 hours; (4) starting circulating cooling water, and cooling the product to room temperature until crystals are completely separated out; (5) taking out the precipitated crystals, carrying out vacuum filtration, washing the crystals for 2-5 times by using ethyl acetate in the process of filtration, and keeping a filter cake; (6) and adding ethyl acetate into the filter cake for recrystallization, and drying after complete crystallization. The method has low production cost, and the prepared benzalkonium chloride has high purity.
Description
Technical field
The present invention relates to technology of fine chemicals, it is more particularly related to which a kind of benzalkonium chloride monomer closes
At technique.
Background technique
Benzalkonium chloride is a kind of cationic surfactant, also known as geramine, has wide spectrum, efficient sterilization algae removal energy
Power can efficiently control bacterium algae breeding and foundry loam growth in water, and have good sludge stripping effect and certain dispersion, seep
Effect thoroughly, at the same have it is certain deoil, deodorizing capability and corrosion inhibition, often do fungicide use in field of medicaments.
After the synthesis of benzalkonium chloride at present mostly uses dodecanol to synthesize dodecyl bromide, then react to obtain two with dimethylamine
Methyl dodecyl amine hydrogen bromide finally reacts to obtain benzalkonium chloride with benzyl chloride, and obtained benzalkonium chloride is mostly technical grade,
It is dfficult to apply to field of medicaments.Alkyl dimethylamine and benzyl chloride must be refined before the benzalkonium chloride preparation of pharmaceutical grade, the life
Production method process is complicated, and instrument and equipment requires height, and many medicinal benzalkonium chloride production companies can not prepare benzalkonium chloride,
Increase the cost of benzalkonium chloride medical product.
Summary of the invention
In order to solve above-mentioned technical problem in the prior art, the purpose of the present invention is to provide a kind of production cost is low
Benzalkonium chloride monomer synthesis technology.
In order to achieve the above-mentioned object of the invention, the invention adopts the following technical scheme:
A kind of benzalkonium chloride monomer synthesis technology, which comprises the steps of:
(1) fatty alkyl dimethyl tertiary amine, benzyl chloride and ethyl acetate are measured respectively by formula；
(2) ethyl acetate is put into 300L glassed steel reaction vessels, fatty alkyl dimethyl tertiary amine and benzyl chloride is distinguished
It is pumped into head tank, the agitating device of reaction kettle is opened, instills fatty alkyl dimethyl tertiary amine and benzyl chloride in proportion under room temperature
In reaction kettle；
(3) the steam-heated heating device of starting TCU control, is warming up to 70-100 DEG C for reaction kettle, insulation reaction 7-
10 hours；
(4) recirculated cooling water is opened, product is cooled to room temperature, until crystal is precipitated completely；
(5) crystal being precipitated is taken out, decompression filters, and divides 2-5 cleaning crystal with ethyl acetate during filtering, and retains filter
Cake；
(6) ethyl acetate is added in filter cake to be recrystallized, after crystallization is complete, crystal is under the conditions of -1.5Mpa, 60 DEG C
Constant weight is dried under vacuum to up to high-purity pharmaceutical grade benzalkonium chloride monomer.
Further, the molal weight of fatty alkyl dimethyl tertiary amine and benzyl chloride ratio is 1:1~1 in the step (1):
1.4。
Further, the fatty alkyl dimethyl tertiary amine in the step (1) is selected from Dodecyl Dimethyl Amine, 14
One of which in alkyl dimethyl tertiary amide, hexadecyldimethyl benzyl ammonium tertiary amine.
Further, in the step (2) additional amount of ethyl acetate fatty alkyl dimethyl tertiary amine can be completely dissolved
Subject to benzyl chloride.
Further, heating reaction unit described in the step (3) is the steam-heated collet of TCU control.
Further, in the step (5) ethyl acetate wash number in final crystal by fatty alkyl dimethyl uncle
Amine and benzyl chloride content are lower than subject to 0.005%.
Further, the additional amount of ethyl acetate is subject to and is completely dissolved filter cake in the step (6).
Further, the purity of acquired benzalkonium chloride monomer is greater than 99% in the step (6).
Compared with prior art, a kind of benzalkonium chloride monomer synthesis technology of the present invention has the advantages that.
For a kind of benzalkonium chloride monomer synthesis technology of the present invention compares traditional handicraft, benzalkonium chloride obtained is pure
Degree is high, impurity is few, and use is safe, can be effectively applied in field of medicaments.The present invention purifies benzene using the methods of recrystallization
Oronain is pricked, can be effectively reduced production cost, using the method energy that fatty alkyl dimethyl tertiary amine and benzyl chloride are added dropwise in proportion
Reaction efficiency and yield are enough improved, significant loss is avoided, further increases product cost；In addition, the invention is adopted
Benzalkonium chloride is produced with dodecyldimethylamine base tertiary amine, hexadecyldimethyl benzyl ammonium tertiary amine are raw material, it is tight raw material resources to be alleviated
, enrich the production ways of benzalkonium chloride.Benzalkonium chloride purity produced by the present invention is good, and precision is high, can by stable application in
Multiple fields.
Specific embodiment
A kind of benzalkonium chloride monomer synthesis technology of the present invention is done further below with reference to specific embodiment
It illustrates, to help those skilled in the art to have more complete, accurate and deep reason to inventive concept of the invention, technical solution
Solution.
Embodiment 1
A kind of benzalkonium chloride monomer synthesis technology, includes the following steps:
(1) Dodecyl Dimethyl Amine, benzyl chloride and ethyl acetate, the dimethyl are measured respectively by formula
The molal weight of base tertiary amine and benzyl chloride ratio is 1:1；
(2) ethyl acetate is put into 300L glassed steel reaction vessels, Dodecyl Dimethyl Amine and benzyl chloride is distinguished
It is pumped into head tank, the agitating device of reaction kettle is opened, instills Dodecyl Dimethyl Amine and benzyl chloride in proportion under room temperature
In reaction kettle；
(3) heat riser is opened, reaction kettle is warming up to 85 DEG C, insulation reaction 10 hours；
(4) recirculated cooling water is opened, product is cooled to room temperature, until crystal is precipitated completely；
(5) crystal being precipitated is taken out, decompression filters, and with 3 cleaning crystal of ethyl acetate point during filtering, retains filter
Cake；
(6) ethyl acetate is added in filter cake to be recrystallized, crystal is dried under vacuum under the conditions of -1.5Mpa, 60 DEG C
Constant weight is up to high-purity pharmaceutical grade benzalkonium chloride monomer.
Embodiment 2
A kind of benzalkonium chloride monomer synthesis technology, includes the following steps:
(1) dodecyldimethylamine base tertiary amine, benzyl chloride and ethyl acetate, the fatty alkyl diformazan are measured respectively by formula
The molal weight of base tertiary amine and benzyl chloride ratio is 1:1.2；
(2) ethyl acetate is put into 300L glassed steel reaction vessels, dodecyldimethylamine base tertiary amine and benzyl chloride is distinguished
It is pumped into head tank, the agitating device of reaction kettle is opened, instills dodecyldimethylamine base tertiary amine and benzyl chloride in proportion under room temperature
In reaction kettle；
(3) heat riser is opened, reaction kettle is warming up to 95 DEG C, insulation reaction 10 hours；
(4) recirculated cooling water is opened, product is cooled to room temperature, until crystal is precipitated completely；
(5) crystal being precipitated is taken out, decompression filters, and with 3 cleaning crystal of ethyl acetate point during filtering, retains filter
Cake；
(6) ethyl acetate is added in filter cake to be recrystallized, crystal is dried under vacuum under the conditions of -1.5Mpa, 60 DEG C
Constant weight is up to high-purity pharmaceutical grade benzalkonium chloride monomer.
Embodiment 3
A kind of benzalkonium chloride monomer synthesis technology, includes the following steps:
(1) hexadecyldimethyl benzyl ammonium tertiary amine, benzyl chloride and ethyl acetate, the etradecyldimethylamine are measured respectively by formula
The molal weight of base tertiary amine and benzyl chloride ratio is 1:1.3；
(2) ethyl acetate is put into 300L glassed steel reaction vessels, hexadecyldimethyl benzyl ammonium tertiary amine and benzyl chloride is distinguished
It is pumped into head tank, the agitating device of reaction kettle is opened, instills hexadecyldimethyl benzyl ammonium tertiary amine and benzyl chloride in proportion under room temperature
In reaction kettle；
(3) heat riser is opened, reaction kettle is warming up to 95 DEG C, insulation reaction 9 hours；
(4) recirculated cooling water is opened, product is cooled to room temperature, until crystal is precipitated completely；
(5) crystal being precipitated is taken out, decompression filters, and with 4 cleaning crystal of ethyl acetate point during filtering, retains filter
Cake；
(6) ethyl acetate is added in filter cake to be recrystallized, crystal is dried under vacuum under the conditions of -1.5Mpa, 60 DEG C
Constant weight is up to high-purity pharmaceutical grade benzalkonium chloride monomer.
Embodiment 4
A kind of benzalkonium chloride monomer synthesis technology, includes the following steps:
(1) Dodecyl Dimethyl Amine, benzyl chloride and ethyl acetate, the dimethyl are measured respectively by formula
The molal weight of base tertiary amine and benzyl chloride ratio is 1:1.1；
(2) ethyl acetate is put into 300L glassed steel reaction vessels, Dodecyl Dimethyl Amine and benzyl chloride is distinguished
It is pumped into head tank, the agitating device of reaction kettle is opened, instills Dodecyl Dimethyl Amine and benzyl chloride in proportion under room temperature
In reaction kettle；
(3) heat riser is opened, reaction kettle is warming up to 85 DEG C, insulation reaction 9 hours；
(4) recirculated cooling water is opened, product is cooled to room temperature, until crystal is precipitated completely；
(5) crystal being precipitated is taken out, decompression filters, and with 3 cleaning crystal of ethyl acetate point during filtering, retains filter
Cake；
(6) ethyl acetate is added in filter cake to be recrystallized, crystal is dried under vacuum under the conditions of -1.5Mpa, 60 DEG C
Constant weight is up to high-purity pharmaceutical grade benzalkonium chloride monomer.
Embodiment 5
A kind of benzalkonium chloride monomer synthesis technology, includes the following steps:
(1) Dodecyl Dimethyl Amine, benzyl chloride and ethyl acetate, the dimethyl are measured respectively by formula
The molal weight of base tertiary amine and benzyl chloride ratio is 1:1；
(2) ethyl acetate is put into 300L glassed steel reaction vessels, Dodecyl Dimethyl Amine and benzyl chloride is distinguished
It is pumped into head tank, the agitating device of reaction kettle is opened, instills Dodecyl Dimethyl Amine and benzyl chloride in proportion under room temperature
In reaction kettle；
(3) heat riser is opened, reaction kettle is warming up to 100 DEG C, insulation reaction 8 hours；
(4) recirculated cooling water is opened, product is cooled to room temperature, until crystal is precipitated completely；
(5) crystal being precipitated is taken out, decompression filters, and with 5 cleaning crystal of ethyl acetate point during filtering, retains filter
Cake；
(6) ethyl acetate is added in filter cake to be recrystallized, crystal is dried under vacuum under the conditions of -1.5Mpa, 60 DEG C
Constant weight is up to high-purity pharmaceutical grade benzalkonium chloride monomer.
Embodiment 6
A kind of benzalkonium chloride monomer synthesis technology, includes the following steps:
(1) dodecyldimethylamine base tertiary amine, benzyl chloride and ethyl acetate, the fatty alkyl diformazan are measured respectively by formula
The molal weight of base tertiary amine and benzyl chloride ratio is 1:1.4；
(2) ethyl acetate is put into 300L glassed steel reaction vessels, dodecyldimethylamine base tertiary amine and benzyl chloride is distinguished
It is pumped into head tank, the agitating device of reaction kettle is opened, instills dodecyldimethylamine base tertiary amine and benzyl chloride in proportion under room temperature
In reaction kettle；
(3) heat riser is opened, reaction kettle is warming up to 100 DEG C, insulation reaction 9 hours；
(4) recirculated cooling water is opened, product is cooled to room temperature, until crystal is precipitated completely；
(5) crystal being precipitated is taken out, decompression filters, and with 4 cleaning crystal of ethyl acetate point during filtering, retains filter
Cake；
(6) ethyl acetate is added in filter cake to be recrystallized, crystal is dried under vacuum under the conditions of -1.5Mpa, 60 DEG C
Constant weight is up to high-purity pharmaceutical grade benzalkonium chloride monomer.
Embodiment 7
A kind of benzalkonium chloride monomer synthesis technology, includes the following steps:
(1) dodecyldimethylamine base tertiary amine, benzyl chloride and ethyl acetate, the fatty alkyl diformazan are measured respectively by formula
The molal weight of base tertiary amine and benzyl chloride ratio is 1:1；
(2) ethyl acetate is put into 300L glassed steel reaction vessels, dodecyldimethylamine base tertiary amine and benzyl chloride is distinguished
It is pumped into head tank, the agitating device of reaction kettle is opened, instills dodecyldimethylamine base tertiary amine and benzyl chloride in proportion under room temperature
In reaction kettle；
(3) heat riser is opened, reaction kettle is warming up to 80 DEG C, insulation reaction 9 hours；
(4) recirculated cooling water is opened, product is cooled to room temperature, until crystal is precipitated completely；
(5) crystal being precipitated is taken out, decompression filters, and with 2 cleaning crystal of ethyl acetate point during filtering, retains filter
Cake；
(6) ethyl acetate is added in filter cake to be recrystallized, crystal is dried under vacuum under the conditions of -1.5Mpa, 60 DEG C
Constant weight is up to high-purity pharmaceutical grade benzalkonium chloride monomer.
Embodiment 8
A kind of benzalkonium chloride monomer synthesis technology, includes the following steps:
(1) hexadecyldimethyl benzyl ammonium tertiary amine, benzyl chloride and ethyl acetate, the etradecyldimethylamine are measured respectively by formula
The molal weight of base tertiary amine and benzyl chloride ratio is 1:1；
(2) ethyl acetate is put into 300L glassed steel reaction vessels, hexadecyldimethyl benzyl ammonium tertiary amine and benzyl chloride is distinguished
It is pumped into head tank, the agitating device of reaction kettle is opened, instills hexadecyldimethyl benzyl ammonium tertiary amine and benzyl chloride in proportion under room temperature
In reaction kettle；
(3) heat riser is opened, reaction kettle is warming up to 90 DEG C, insulation reaction 8.5 hours；
(4) recirculated cooling water is opened, product is cooled to room temperature, until crystal is precipitated completely；
(5) crystal being precipitated is taken out, decompression filters, and with 3 cleaning crystal of ethyl acetate point during filtering, retains filter
Cake；
(6) ethyl acetate is added in filter cake to be recrystallized, crystal is dried under vacuum under the conditions of -1.5Mpa, 60 DEG C
Constant weight is up to high-purity pharmaceutical grade benzalkonium chloride monomer.
Embodiment 9
A kind of benzalkonium chloride monomer synthesis technology, includes the following steps:
(1) hexadecyldimethyl benzyl ammonium tertiary amine, benzyl chloride and ethyl acetate, the etradecyldimethylamine are measured respectively by formula
The molal weight of base tertiary amine and benzyl chloride ratio is 1:1；
(2) ethyl acetate is put into 300L glassed steel reaction vessels, hexadecyldimethyl benzyl ammonium tertiary amine and benzyl chloride is distinguished
It is pumped into head tank, the agitating device of reaction kettle is opened, instills hexadecyldimethyl benzyl ammonium tertiary amine and benzyl chloride in proportion under room temperature
In reaction kettle；
(3) heat riser is opened, reaction kettle is warming up to 95 DEG C, keeps the temperature anti-9.5 hours；
(4) recirculated cooling water is opened, product is cooled to room temperature, until crystal is precipitated completely；
(5) crystal being precipitated is taken out, decompression filters, and with 5 cleaning crystal of ethyl acetate point during filtering, retains filter
Cake；
(6) ethyl acetate is added in filter cake to be recrystallized, crystal is dried under vacuum under the conditions of -1.5Mpa, 60 DEG C
Constant weight is up to high-purity pharmaceutical grade benzalkonium chloride monomer.
Comparative example 1
Domiphen is squeezed into destilling tower, is distilled 30 hours under reduced pressure atmosphere, after distillation, leads to cool brine
Freezing 5 hours, and centrifugation is stirred, later by material by filtering kettle, room temperature filtering obtains material A；Benzyl chloride is pumped into steaming again
Tower is evaporated, is distilled 4 hours in the environment of 60 DEG C, obtains material B；Material A is pumped into reaction kettle, then material B is pumped into head tank,
It is heated while stirring in the environment of 56-60 DEG C and instills material B in reaction kettle, insulation reaction 2 hours, be then turned on circulation
Cooling water is cooled to room temperature to get product.
The performance difference for the benzalkonium chloride that embodiment 1-9 and comparative example 1 are prepared is as shown in table 1.
Table 1
。
For the ordinary skill in the art, specific embodiment is only exemplarily described the present invention,
Obviously the present invention specific implementation is not subject to the restrictions described above, as long as use the inventive concept and technical scheme of the present invention into
The improvement of capable various unsubstantialities, or not improved the conception and technical scheme of the invention are directly applied to other occasions
, it is within the scope of the present invention.
Claims (5)
1. a kind of benzalkonium chloride monomer synthesis technology, which comprises the steps of:
(1) fatty alkyl dimethyl tertiary amine, benzyl chloride and ethyl acetate are measured respectively by formula, wherein fatty alkyl dimethyl
The molar ratio of tertiary amine and benzyl chloride is 1:1；；
(2) ethyl acetate is put into 300L glassed steel reaction vessels, fatty alkyl dimethyl tertiary amine and benzyl chloride is pumped respectively
Enter head tank, opens the agitating device of reaction kettle, instill fatty alkyl dimethyl tertiary amine and benzyl chloride instead in proportion under room temperature
It answers in kettle, wherein the additional amount of ethyl acetate, which is subject to, is completely dissolved fatty alkyl dimethyl tertiary amine and benzyl chloride；
(3) the steam-heated heating device of starting TCU control, is warming up to 70-100 DEG C for reaction kettle, insulation reaction 7-10 is small
When；
(4) recirculated cooling water is opened, product is cooled to room temperature, until crystal is precipitated completely；
(5) crystal being precipitated is taken out, decompression filters, and divides 2-5 cleaning crystal with ethyl acetate during suction filtration, retains filter cake；
(6) ethyl acetate is added in filter cake to be recrystallized, after crystallization is complete, crystal vacuum under the conditions of -1.5Mpa, 60 DEG C
To constant weight up to benzalkonium chloride monomer, purity is greater than 99% for drying, belongs to pharmaceutical grade benzalkonium chloride monomer.
2. benzalkonium chloride monomer synthesis technology as described in claim 1, which is characterized in that the fatty alkane in the step (1)
Base dimethyl tertiary amine is in Dodecyl Dimethyl Amine, dodecyldimethylamine base tertiary amine, hexadecyldimethyl benzyl ammonium tertiary amine
It is one of.
3. benzalkonium chloride monomer synthesis technology as described in claim 1, which is characterized in that add described in the step (3)
Thermal reaction apparatus is the steam-heated collet of TCU control.
4. benzalkonium chloride monomer synthesis technology as described in claim 1, which is characterized in that ethyl acetate in the step (5)
Wash number is subject to fatty alkyl dimethyl tertiary amine and benzyl chloride content in final crystal lower than 0.005%.
5. benzalkonium chloride monomer synthesis technology as described in claim 1, which is characterized in that ethyl acetate in the step (6)
Additional amount be subject to and be completely dissolved filter cake.
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| CN109553536B (en) * | 2017-09-27 | 2022-05-03 | 湖北葛店人福药用辅料有限责任公司 | Synthetic method of fatty alkyl dimethyl benzyl quaternary ammonium salt |
| CN109553539B (en) * | 2017-09-27 | 2022-05-03 | 湖北葛店人福药用辅料有限责任公司 | Preparation method of benzalkonium chloride |
| CN113861037B (en) * | 2021-09-24 | 2024-07-02 | 泰柯棕化(张家港)有限公司 | Production process of low-residue medicinal benzalkonium chloride |
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