CN116987030B - Preparation method of pyridone ethanolamine salt - Google Patents
Preparation method of pyridone ethanolamine salt Download PDFInfo
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- CN116987030B CN116987030B CN202310969736.9A CN202310969736A CN116987030B CN 116987030 B CN116987030 B CN 116987030B CN 202310969736 A CN202310969736 A CN 202310969736A CN 116987030 B CN116987030 B CN 116987030B
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- LOEUPVXIWVJADW-UHFFFAOYSA-N 2-aminoethanol;1h-pyridin-2-one Chemical compound NCCO.O=C1C=CC=CN1 LOEUPVXIWVJADW-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title abstract description 28
- 239000003054 catalyst Substances 0.000 claims abstract description 60
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 36
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims abstract description 15
- YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 claims abstract description 11
- BAPJBEWLBFYGME-UHFFFAOYSA-N acrylic acid methyl ester Natural products COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000005863 Friedel-Crafts acylation reaction Methods 0.000 claims abstract description 7
- 238000007273 lactonization reaction Methods 0.000 claims abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 90
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- 238000003756 stirring Methods 0.000 claims description 26
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 20
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 18
- 239000012074 organic phase Substances 0.000 claims description 18
- 238000010438 heat treatment Methods 0.000 claims description 17
- 238000010992 reflux Methods 0.000 claims description 16
- 238000005406 washing Methods 0.000 claims description 16
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 14
- 238000001816 cooling Methods 0.000 claims description 13
- 238000001035 drying Methods 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 10
- 239000005457 ice water Substances 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 9
- -1 3,7,9,9-tetramethyl-2-decene-5-one Chemical compound 0.000 claims description 8
- 239000013078 crystal Substances 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 6
- 239000011261 inert gas Substances 0.000 claims description 6
- FZIBCCGGICGWBP-UHFFFAOYSA-N methyl 3-methylbut-2-enoate Chemical compound COC(=O)C=C(C)C FZIBCCGGICGWBP-UHFFFAOYSA-N 0.000 claims description 6
- 238000010025 steaming Methods 0.000 claims description 6
- 229960000583 acetic acid Drugs 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 239000012362 glacial acetic acid Substances 0.000 claims description 5
- 239000007791 liquid phase Substances 0.000 claims description 5
- 238000011068 loading method Methods 0.000 claims description 5
- 150000004702 methyl esters Chemical class 0.000 claims description 5
- 238000006386 neutralization reaction Methods 0.000 claims description 5
- 239000012044 organic layer Substances 0.000 claims description 5
- ZPSJGADGUYYRKE-UHFFFAOYSA-N 2H-pyran-2-one Chemical group O=C1C=CC=CO1 ZPSJGADGUYYRKE-UHFFFAOYSA-N 0.000 claims description 4
- 238000005805 hydroxylation reaction Methods 0.000 claims description 4
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 238000005755 formation reaction Methods 0.000 claims description 3
- 230000009471 action Effects 0.000 claims description 2
- 230000004913 activation Effects 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 239000010410 layer Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims description 2
- GGOZGYRTNQBSSA-UHFFFAOYSA-N pyridine-2,3-diol Chemical group OC1=CC=CN=C1O GGOZGYRTNQBSSA-UHFFFAOYSA-N 0.000 claims description 2
- 238000005185 salting out Methods 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims 1
- 239000012071 phase Substances 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 31
- 230000002195 synergetic effect Effects 0.000 abstract description 5
- 125000004122 cyclic group Chemical group 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 150000002443 hydroxylamines Chemical class 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 238000002390 rotary evaporation Methods 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 208000001840 Dandruff Diseases 0.000 description 4
- 229910052782 aluminium Inorganic materials 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 230000032798 delamination Effects 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000004064 recycling Methods 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000002453 shampoo Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000004645 aluminates Chemical class 0.000 description 1
- 229940047712 aluminum hydroxyphosphate Drugs 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SCKYRAXSEDYPSA-UHFFFAOYSA-N ciclopirox Chemical compound ON1C(=O)C=C(C)C=C1C1CCCCC1 SCKYRAXSEDYPSA-UHFFFAOYSA-N 0.000 description 1
- 229960003749 ciclopirox Drugs 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- ICAKDTKJOYSXGC-UHFFFAOYSA-K lanthanum(iii) chloride Chemical compound Cl[La](Cl)Cl ICAKDTKJOYSXGC-UHFFFAOYSA-K 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 1
- 229910001486 lithium perchlorate Inorganic materials 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- MPNNOLHYOHFJKL-UHFFFAOYSA-N peroxyphosphoric acid Chemical compound OOP(O)(O)=O MPNNOLHYOHFJKL-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 208000008742 seborrheic dermatitis Diseases 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/14—Phosphorus; Compounds thereof
- B01J27/16—Phosphorus; Compounds thereof containing oxygen, i.e. acids, anhydrides and their derivates with N, S, B or halogens without carriers or on carriers based on C, Si, Al or Zr; also salts of Si, Al and Zr
- B01J27/18—Phosphorus; Compounds thereof containing oxygen, i.e. acids, anhydrides and their derivates with N, S, B or halogens without carriers or on carriers based on C, Si, Al or Zr; also salts of Si, Al and Zr with metals other than Al or Zr
- B01J27/1802—Salts or mixtures of anhydrides with compounds of other metals than V, Nb, Ta, Cr, Mo, W, Mn, Tc, Re, e.g. phosphates, thiophosphates
- B01J27/1806—Salts or mixtures of anhydrides with compounds of other metals than V, Nb, Ta, Cr, Mo, W, Mn, Tc, Re, e.g. phosphates, thiophosphates with alkaline or alkaline earth metals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of pyridone ethanolamine salt, which takes 3, 3-dimethyl methyl acrylate and 3, 5-trimethyl hexanoyl chloride as main raw materials, and sequentially carries out Friedel-crafts acylation reaction, lactonization reaction, hydroxylamines and salification reaction to synthesize the pyridone ethanolamine salt, wherein a supported catalyst consisting of anhydrous aluminum trichloride, anhydrous polyaluminum chloride and hydroxyapatite carrier is selected as a catalyst for Friedel-crafts acylation, the yield of intermediates and the yield of the pyridone ethanolamine salt are improved through the synergistic effect of the supported catalyst and the catalyst, and the supported catalyst still has higher yield after repeated cyclic utilization.
Description
Technical field:
The invention relates to a preparation method of an anti-dandruff agent, in particular to a preparation method of pyridone ethanolamine salt.
The background technology is as follows:
Pyridone ethanolamine salt, which has the structure named as 1-hydroxy-4-methyl-6- (2, 4, trimethyl amyl) -2- (1H) -pyridone-2-amino ethoxide, is also called as ciclopirox and antidandruff agent OCT, has broad-spectrum sterilization effect on bacteria and fungi, is an anionic surfactant, can be compounded with other medicines, and plays a role in enhancing the efficacy. Due to its excellent bactericidal properties, it can play a very good role in terms of seborrheic dermatitis, and is also used in cosmetics. As the effective anti-dandruff component of the anti-dandruff shampoo, the anti-dandruff shampoo can be compounded with other components according to the proportion, and has more antibacterial effect.
The synthesis of pyridone ethanolamine salt generally comprises the steps of acylation reaction, cyclization reaction, hydroxylation reaction, cyclization reaction and the like, wherein the acylation reaction is carried out under the catalysis of Lewis acid, and the generally adopted Lewis acid catalyst is anhydrous aluminum chloride. Although anhydrous aluminum chloride has a good catalytic effect, the overall yield is still low; and aluminum chloride has the defects of difficult recycling and difficult post-treatment.
Patent CN112159352a discloses a preparation process of pyridone ethanolamine salt, which adopts a supported catalyst to carry out acylation reaction, the supported catalyst specifically comprises an active component and a carrier, the carrier is silica gel, and the active component comprises anhydrous aluminum chloride, anhydrous lanthanum chloride and anhydrous lithium perchlorate. The activity of the supported catalyst is 94.5-97.4%, and the activity can still reach 86.7-89.6% after five times of cyclic utilization. Thus, it can be seen that the activity and the product yield can be effectively improved by the synergistic effect of the supported catalysts.
The invention comprises the following steps:
the invention aims to provide a preparation method of pyridone ethanolamine salt, which aims to realize the use of a novel supported catalyst and ensure that the catalyst has higher product yield and catalyst recovery efficiency.
In order to achieve the above purpose, the present invention adopts the following technical scheme: the method is characterized in that 3, 3-dimethyl methyl acrylate and 3, 5-trimethyl hexanoyl chloride are used as main raw materials, and pyridone ethanolamine salt is synthesized through Friedel-crafts acylation reaction, lactonization reaction, hydroxylamines and salification reaction in sequence, wherein the Friedel-crafts acylation reaction adopts a supported catalyst.
Specifically, the technical scheme of the invention comprises the following steps:
(1) Under the action of a supported catalyst, carrying out reflux reaction on 3, 3-dimethyl methyl acrylate and 3, 5-trimethyl hexanoyl chloride to generate 3,7,9,9-tetramethyl-2-decene-5-keto acid methyl ester (intermediate a);
(2) Heating 3,7,9,9-tetramethyl-2-decene-5-ketoacid methyl ester obtained in the step (1) to carry out a lactonization reaction to form a pyrone ring, thus obtaining a product 4-methyl-6- (2, 4-trimethylpentyl) -2-pyrone (an intermediate b);
(3) Carrying out hydroxylation reaction on the 4-methyl-6- (2, 4-trimethylpentyl) -2-pyrone obtained in the step (2), wherein oxygen on the pyrone ring is substituted to form a hydroxypyridone ring, so as to obtain 1-hydroxy-4-methyl-6- (2, 4-trimethylpentyl) -2-pyridone (intermediate c); adding ethanolamine into a salting-out system to obtain a target product of 1-hydroxy-4-methyl-6- (2, 4-trimethyl-amyl) -2-pyridone ethanolamine salt;
the supported catalyst comprises anhydrous aluminum trichloride, anhydrous polyaluminium chloride and a carrier, wherein the carrier is porous hydroxyapatite, and the loading amount of active aluminum element is 7-10%.
By adopting the supported catalyst, the hydroxyapatite is used as a carrier in Friedel-crafts acylation reaction, so that the problem that aluminum trichloride is not easy to separate can be solved, the supported catalyst can be recycled, and the production cost is reduced; meanwhile, a certain amount of polyaluminium chloride is added into the catalyst, the polyaluminium chloride is used as a polymer-based solid acid catalyst, the catalyst itself has various active reaction sites and is an inorganic high polymer material composed of various complex aluminates and between AlCl 3 and Al (OH) 3, the species with different electronic structures can form a synergistic catalysis effect, and the polyaluminium chloride can improve the combination firmness of hydroxyapatite and aluminum trichloride and can ensure that extremely high catalysis effect is maintained during recycling.
Preferably, the preparation method of the supported catalyst comprises the following steps: under the protection of inert gas, stirring and dissolving carbon tetrachloride, anhydrous aluminum chloride and anhydrous polyaluminium chloride which are subjected to drying treatment; adding activated hydroxyapatite, stirring and refluxing for 8-24 hours, and filtering to obtain a solid initial product; and washing the solid initial product with carbon tetrachloride for 3-6 times, and drying with a vacuum dryer to obtain the supported catalyst.
Further, the weight ratio of the carbon tetrachloride to the anhydrous aluminum chloride to the anhydrous polyaluminum chloride to the hydroxyapatite is (10-15): (1-2): (0.2-0.6): (1.5-3).
Further, the hydroxyapatite is activated at an activation temperature of 600 to 900 ℃ for 2 to 6 hours.
Further, the particle size of the hydroxyapatite is 120 to 180 meshes.
Preferably, the specific method of the friedel-crafts acylation reaction of step (1) according to the present invention is as follows: adding a supported catalyst into dichloromethane, stirring in an ice water bath, dropwise adding 3, 5-trimethyl hexanoyl chloride, and cooling to 20-25 ℃ after the dropwise adding is finished. Slowly dripping 3, 3-dimethyl methyl acrylate, and carrying out reflux reaction for 8 hours at 40-50 ℃ to obtain a dark brown liquid phase system.
The system with complete reaction was slowly added dropwise to ice water under stirring, transferred to a separating funnel, allowed to stand for delamination, and the organic phase was removed. The upper aqueous phase was washed with dichloromethane in portions and the organic phases were combined. The organic layer was washed, dried and distilled to give 3,7,9,9-tetramethyl-2-decene-5-one acid methyl ester (intermediate a).
Further, the molar ratio of 3, 5-trimethylhexanoyl chloride to methyl 3, 3-dimethacrylate in the step (1) is 1: (1.1-1.5).
Further, the mass ratio of 3, 5-trimethyl hexanoyl chloride to the supported catalyst in the step (1) is 1: (2-3).
Further, in the step (1), the washing, drying and rotary steaming are respectively performed by washing with saturated NaHCO 3 and saturated NaCl, adding anhydrous magnesium sulfate for removing water, and filtering. The mixture is distilled by a rotary evaporator and is slowly heated to 100 ℃ to gradually remove dichloromethane solvent, 3-dimethyl methyl acrylate and 3, 5-trimethyl hexanoyl chloride.
Preferably, the specific method of the lactonization reaction of step (2) of the present invention is as follows: and (3) heating 3,7,9,9-tetramethyl-2-decene-5-methyl ketonate (intermediate a) obtained in the step (1) to 210-230 ℃ under the protection of inert gas, stirring and fully mixing to react for 24-36 hours, cooling to 20-25 ℃, adding dichloromethane, washing, drying and rotary evaporation respectively to obtain the product 4-methyl-6- (2, 4-trimethyl amyl) -2-pyrone (intermediate b).
Further, in the step (2), the washing, drying and rotary evaporation are respectively performed by using saturated NaHCO 3 and saturated NaCl, anhydrous magnesium sulfate is added for water removal, filtration is performed, and dichloromethane is removed by rotary evaporation at 20-30 ℃.
Preferably, the specific method of the hydroxylation and salification reaction in step (3) of the present invention is as follows: adding 4-methyl-6- (2, 4-trimethyl amyl) -2-pyrone (intermediate b), dichloromethane and water, adding sodium ethoxide, heating and stirring hydroxylamine hydrochloride, adding glacial acetic acid, heating and refluxing for 15-20 hours, cooling to room temperature, adding sodium hydroxide solution for neutralization, layering, taking an organic phase, extracting and combining aqueous layers by ethyl acetate, washing, drying and rotary steaming, adding ethanolamine, heating to 40-60 ℃, observing crystal formation, cooling and crystallizing, washing by ethyl acetate, and vacuum drying to obtain hydroxypyridone ethanolamine salt.
Further, the molar ratio of sodium ethoxide to 3, 5-trimethylhexanoyl chloride in step (1) is (1.5-2.5): the molar ratio of hydroxylamine hydrochloride to 3, 5-trimethylhexanoyl chloride in step (1) is (2.5-3.5): the molar ratio of the ethanolamine to the 3, 5-trimethylhexanoyl chloride in step (1) is (0.9-1.1): 1.
Compared with the prior art, the invention has the following beneficial effects:
The invention takes the activated hydroxyapatite as a carrier, adds aluminum trichloride and polyaluminium chloride as composite catalysts, improves the conversion rate of reaction raw materials and the yield of intermediates through the synergistic effect of the aluminum trichloride and the polyaluminium chloride, ensures that the catalyst still has good activity after repeated cyclic utilization.
The specific embodiment is as follows:
In order to make the purposes, technical solutions and advantages of the implementation of the present invention more clear, the technical solutions of the present invention are further described below by means of specific embodiments. Those skilled in the art should appreciate that the examples are only for aiding in understanding the technical contents and effects of the present invention and should not be construed as limiting the present invention.
Preparation example 1
A method for preparing a supported catalyst, comprising the steps of:
Under the protection of inert gas, weighing 150 mass parts of carbon tetrachloride, adding 20 mass parts of anhydrous aluminum chloride and 6 mass parts of anhydrous polyaluminium chloride, stirring and dissolving, and stirring and dissolving the dried carbon tetrachloride, the anhydrous aluminum chloride and the anhydrous polyaluminium chloride; weighing 30 parts by mass of 180-mesh hydroxyapatite, activating for 3 hours at 800 ℃, adding the hydroxyapatite cooled to room temperature into the solution, stirring and refluxing for 12 hours, and filtering to obtain a solid initial product; and washing the solid initial product with carbon tetrachloride for 4 times, and drying the solid initial product with a vacuum dryer to obtain the supported catalyst A.
Preparation example 2
A method for preparing a supported catalyst, comprising the steps of:
Under the protection of inert gas, weighing 120 mass parts of carbon tetrachloride, adding 12 mass parts of anhydrous aluminum chloride and 3 mass parts of anhydrous polyaluminium chloride, stirring and dissolving, and stirring and dissolving the dried carbon tetrachloride, the anhydrous aluminum chloride and the anhydrous polyaluminium chloride; weighing 20 parts by mass of 120-mesh hydroxyapatite, activating for 4 hours at 700 ℃, adding the hydroxyapatite cooled to room temperature into the solution, stirring and refluxing for 16 hours, and filtering to obtain a solid initial product; and washing the solid initial product with carbon tetrachloride for 3 times, and drying the solid initial product with a vacuum dryer to obtain the supported catalyst B.
Preparation example 3
A preparation method of a supported catalyst is based on preparation example 1, and the only difference is that anhydrous polyaluminium chloride is not added, so as to obtain a supported catalyst C.
Preparation example 4
The preparation method of the supported catalyst is based on preparation example 1, and the difference is that anhydrous polyaluminum chloride is not added, and the addition amount of the anhydrous polyaluminum chloride is increased from 20 parts by mass to 26 parts by mass, so as to obtain the supported catalyst D.
The aluminum loadings of the supported catalysts a to D obtained in preparation examples 1 to 4 were measured by a flame atomic absorption method and the measuring instrument was a flame atomic absorption spectrometer. The test results are shown in Table 1.
Table 1 aluminum loadings in each of the preparations
| Detection item | Aluminum loading |
| Preparation example 1 | 8.4％ |
| Preparation example 2 | 7.9％ |
| Preparation example 3 | 5.2％ |
| Preparation example 4 | 6.5％ |
As a comparison between preparation examples 1 and 4, it can be seen that the same quality of aluminum chloride was replaced with polyaluminum chloride in preparation example 1, and that aluminum chloride and hydroxy phosphate were better combined by using various functional bonds of polyaluminum chloride.
Example 1
A method for preparing pyridone ethanolamine salt, comprising the steps of:
(1) 500g of the supported catalyst A was added to 1L of methylene chloride, stirred in an ice-water bath, 176.5g (1 mol) of 3, 5-trimethylhexanoyl chloride was added dropwise, and the reaction mixture was allowed to return to room temperature after the completion of the dropwise addition. 148.2g (1.3 mol) of methyl 3, 3-dimethacrylate was slowly added dropwise thereto and reacted at 50℃for 8 hours under reflux to obtain a dark brown liquid phase system. The system with complete reaction was slowly added dropwise to ice water under stirring, transferred to a separating funnel, allowed to stand for delamination, and the organic phase was removed. The upper aqueous phase was washed with dichloromethane in portions and the organic phases were combined. The resulting organic layer was washed 3 times with saturated NaHCO 3 and 2 times with saturated NaCl, respectively, dehydrated and filtered by adding anhydrous magnesium sulfate, and the dichloromethane solvent, 3-dimethyl methyl acrylate and 3, 5-trimethyl hexanoyl chloride were gradually removed by spin-steaming to 100℃to give 3,7,9,9-tetramethyl-2-decen-5-one acid methyl ester (intermediate a).
(2) Under the protection of nitrogen, 3,7,9,9-tetramethyl-2-decene-5-methyl ketonate (intermediate a) is heated to 220 ℃, stirred and fully mixed for reaction for 30 hours, cooled to 25 ℃, 300mL of dichloromethane is added, the dichloromethane is respectively washed 3 times by saturated NaHCO3 and 2 times by saturated NaCl, anhydrous magnesium sulfate is added for dehydration and filtration, and the dichloromethane is removed by rotary evaporation at 20 ℃ to obtain the product 4-methyl-6- (2, 4-trimethyl amyl) -2-pyrone (intermediate b).
(3) 4-Methyl-6- (2, 4-trimethyl amyl) -2-pyrone (intermediate b), 500mL of dichloromethane and 10mL of water are stirred and mixed uniformly, 208.5g (3 mol) of hydroxylamine hydrochloride and 108g (2 mol) of sodium methoxide are added, stirring is continued, after heating to 40 ℃, 10g of glacial acetic acid is added, stirring is continued, heating and refluxing are carried out for 18 hours, 400mL of 0.1mol/LNaOH solution is added for neutralization, organic phases are separated, the aqueous phases are extracted and combined by ethyl acetate, the organic phases are washed with water for 2 times, dried and filtered by anhydrous magnesium sulfate, part of solvent is removed by reduced pressure rotary evaporation, 61g (1 mol) of ethanolamine is added, heating is carried out to 50 ℃, cooling crystallization is carried out after crystallization is carried out, cooling is carried out to 0 ℃, ethyl acetate is used for washing 3 times, and vacuum drying is carried out at 60 ℃ for 8 hours, thus obtaining pyridone ethanolamine salt.
Example 2
A method for preparing pyridone ethanolamine salt, comprising the steps of:
(1) 400g of supported catalyst A was added to 1L of methylene chloride, stirred in an ice-water bath, 176.5g (1 mol) of 3, 5-trimethylhexanoyl chloride was added dropwise, and the reaction mixture was allowed to return to room temperature after the completion of the dropwise addition. 159.6g (1.4 mol) of methyl 3, 3-dimethacrylate was slowly added dropwise thereto and reacted at 50℃under reflux for 12 hours to obtain a dark brown liquid phase system. The system with complete reaction was slowly added dropwise to ice water under stirring, transferred to a separating funnel, allowed to stand for delamination, and the organic phase was removed. The upper aqueous phase was washed with dichloromethane in portions and the organic phases were combined. The resulting organic layer was washed 3 times with saturated NaHCO 3 and 2 times with saturated NaCl, respectively, dehydrated and filtered by adding anhydrous magnesium sulfate, and the dichloromethane solvent, 3-dimethyl methyl acrylate and 3, 5-trimethyl hexanoyl chloride were gradually removed by spin-steaming to 100℃to give 3,7,9,9-tetramethyl-2-decen-5-one acid methyl ester (intermediate a).
(2) Under the protection of nitrogen, 3,7,9,9-tetramethyl-2-decene-5-methyl ketonate (intermediate a) is heated to 230 ℃, stirred and fully mixed for reaction for 24 hours, cooled to 20 ℃, 300mL of dichloromethane is added, the mixture is respectively washed 3 times by saturated NaHCO 3 and 2 times by saturated NaCl, anhydrous magnesium sulfate is added for dehydration and filtration, and the dichloromethane is removed by rotary evaporation at 20 ℃ to obtain the product 4-methyl-6- (2, 4-trimethyl amyl) -2-pyrone (intermediate b).
(3) 4-Methyl-6- (2, 4-trimethyl amyl) -2-pyrone (intermediate b), 500mL of dichloromethane and 10mL of water are stirred and mixed uniformly, 180.7g (2.6 mol) of hydroxylamine hydrochloride and 97.2g (1.8 mol) of sodium methoxide are added, stirring is continued, after heating to 40 ℃, 10g of glacial acetic acid is added, stirring is continued, heating and refluxing are carried out for 24 hours, 400mL of 0.1mol/LNaOH solution is added for neutralization, organic phases are separated, the aqueous phases are extracted and combined by ethyl acetate, the organic phases are washed 2 times by water, dried and filtered by anhydrous magnesium sulfate, part of solvent is removed by rotary evaporation under reduced pressure, 54.9g (0.9 mol) of ethanolamine is added, after the crystals are separated out, the crystals are cooled to 0 ℃ for cooling crystallization, the crystals are washed 3 times by ethyl acetate, and the pyridone ethanolamine salts are obtained after the crystals are dried at 50 ℃ under vacuum for 12 hours.
Example 3
A method for preparing pyridone ethanolamine salt, comprising the steps of:
(1) 400g of supported catalyst A was added to 1L of methylene chloride, stirred in an ice-water bath, 176.5g (1 mol) of 3, 5-trimethylhexanoyl chloride was added dropwise, and the reaction mixture was allowed to return to room temperature after the completion of the dropwise addition. 136.8g (1.2 mol) of methyl 3, 3-dimethacrylate was slowly added dropwise thereto and reacted at 40℃under reflux for 10 hours to obtain a dark brown liquid phase system. The system with complete reaction was slowly added dropwise to ice water under stirring, transferred to a separating funnel, allowed to stand for delamination, and the organic phase was removed. The upper aqueous phase was washed with dichloromethane in portions and the organic phases were combined. The organic layer was washed with saturated NaHCO3 and saturated NaCl for 3 times, and then dried over anhydrous magnesium sulfate, filtered, and distilled to 100℃to remove dichloromethane solvent, methyl 3, 3-dimethacrylate and 3, 5-trimethylhexanoyl chloride gradually to give 3,7,9,9-tetramethyl-2-decen-5-one acid methyl ester (intermediate a).
(2) Under the protection of nitrogen, 3,7,9,9-tetramethyl-2-decene-5-methyl ketonate (intermediate a) is heated to 210 ℃, stirred and fully mixed for reaction for 36 hours, cooled to 20 ℃, 300mL of dichloromethane is added, the mixture is respectively washed 3 times by saturated NaHCO 3 and 2 times by saturated NaCl, anhydrous magnesium sulfate is added for dehydration and filtration, and the dichloromethane is removed by rotary evaporation at 20 ℃ to obtain the product 4-methyl-6- (2, 4-trimethyl amyl) -2-pyrone (intermediate b).
(3) 4-Methyl-6- (2, 4-trimethyl amyl) -2-pyrone (intermediate b), 500mL of dichloromethane and 10mL of water are stirred and mixed uniformly, 222.4g (3.2 mol) of hydroxylamine hydrochloride and 118.8g (2.2 mol) of sodium methoxide are added, stirring is continued, after heating to 40 ℃, 10g of glacial acetic acid is added, stirring is continued, heating and refluxing are carried out for 24 hours, 400mL of 0.1mol/LNaOH solution is added for neutralization, organic phases are separated, the aqueous phases are extracted and combined by ethyl acetate, the organic phases are washed 2 times by water, dried and filtered by anhydrous magnesium sulfate, part of solvent is removed by rotary evaporation under reduced pressure, 67.1g (1.1 mol) of ethanolamine is added, cooling to 0 ℃ for cooling and crystallization after crystal precipitation is carried out, ethyl acetate is used for washing 3 times, and pyridone ethanolamine salt is obtained after vacuum drying at 50 ℃ for 12 hours.
Example 4
A process for preparing pyridone ethanolamine salt based on example 1, differing only in the use of the supported catalyst B of preparation example 2 in example 4.
Example 5
A process for preparing pyridone ethanolamine salt based on example 2, differing only in the use of the supported catalyst B of preparation example 2 in example 5.
Comparative example 1
A process for preparing pyridone ethanolamine salt based on example 1, differing only in that the supported catalyst C of preparation example 3 was used in comparative example 1.
Comparative example 2
A process for preparing pyridone ethanolamine salt, based on example 1, differs only in that the supported catalyst D of preparation example 4 is used in comparative example 2.
Comparative example 3
A process for preparing pyridone ethanolamine salt, based on example 1, was different only in that the supported catalyst C of production example 3 was used in comparative example 3 and the amount of the catalyst was adjusted to 800g.
Comparative example 4
A process for preparing pyridone ethanolamine salt, based on example 1, was distinguished only in that the supported catalyst D of production example 4 was used in comparative example 4 and the amount of the catalyst was adjusted to 650g.
Comparative example 5
A process for preparing pyridone ethanolamine salt, based on example 1, was distinguished only in that 210g of anhydrous aluminum chloride was directly added as a catalyst in comparative example 5.
Intermediate a, intermediate b, pyridone ethanolamine salt in examples 1 to 5 and comparative examples 1 to 5 were detected and calculated, and the intermediate a yield, intermediate b yield, pyridone ethanolamine salt yield were calculated, and the results are shown in table 2.
Table 2 intermediate yields and pyridone ethanolamine salt yields for each of the examples and comparative examples
| Detection item | Yield of intermediate a% | Intermediate b yield% | Yield of pyridone ethanolamine salt |
| Example 1 | 96.3 | 91.8 | 87.7 |
| Example 2 | 95.7 | 91.4 | 87.2 |
| Example 3 | 95.5 | 90.6 | 86.7 |
| Example 4 | 94.8 | 90.3 | 86.3 |
| Example 5 | 94.1 | 90.1 | 85.8 |
| Comparative example 1 | 88.6 | 84.6 | 80.9 |
| Comparative example 2 | 89.1 | 85.1 | 81.4 |
| Comparative example 3 | 90.9 | 86.9 | 83.1 |
| Comparative example 4 | 91.4 | 87.2 | 83.5 |
| Comparative example 5 | 82.7 | 79.1 | 75.6 |
As can be seen from Table 2, the yield of the intermediate a of examples 1-5 of the supported catalyst prepared by the present invention was 94.1-96.3%, which is significantly improved compared with 82.7% of the yield of the intermediate a by adding anhydrous aluminum chloride as a catalyst with the same weight of active aluminum. From example 1 and comparative examples 1 to 2, by adding polyaluminium chloride as an active component, active components of different species can be made to sufficiently exert synergistic effects; from example 1 and comparative examples 3 to 4, even if the amount of the anhydrous aluminum chloride supported catalyst is increased, the effect of polyaluminum chloride cannot be completely replaced.
The prepared supported catalyst was recycled, and the supported catalyst was recovered in step (1) in examples 1,4 and comparative examples 1,2 by the following recovery method: the aqueous phase obtained in the step (1) was washed with methylene chloride 3 times, acetone 2 times, isopropyl ether 2 times, and vacuum-dried at 90℃for 12 hours, and the supported catalyst was recovered and used 5 times in total. The yields of intermediate a in examples 1,4 and comparative examples 1,2 were tested, and the yields of the third and fifth times were calculated, and the results are shown in table 3.
TABLE 3 recovery yield results of Supported catalyst
As can be seen from Table 3, the supported catalyst of the present invention can improve the bonding firmness between hydroxyapatite and aluminum trichloride by adding polyaluminium chloride, and can ensure that an extremely high catalytic effect is maintained during recycling.
The present application is not limited to the above embodiment. The above embodiments are merely examples, and embodiments having substantially the same configuration and the same effects as those of the technical idea within the scope of the present application are included in the technical scope of the present application. Further, various modifications that can be made to the embodiments and other modes of combining some of the constituent elements in the embodiments, which are conceivable to those skilled in the art, are also included in the scope of the present application within the scope not departing from the gist of the present application.
Claims (8)
1. A method for preparing pyridone ethanolamine salt, comprising the steps of:
(1) Under the action of a supported catalyst, carrying out reflux reaction on 3, 3-dimethyl methyl acrylate and 3, 5-trimethyl hexanoyl chloride to generate 3,7,9,9-tetramethyl-2-decene-5-methyl ketonate;
(2) Heating 3,7,9,9-tetramethyl-2-decene-5-ketoacid methyl ester obtained in the step (1) to carry out a lactonization reaction to form a pyrone ring, thus obtaining a product 4-methyl-6- (2, 4-trimethylpentyl) -2-pyrone;
(3) Carrying out hydroxylation reaction on the 4-methyl-6- (2, 4-trimethyl amyl) -2-pyrone obtained in the step (2), wherein oxygen on the pyrone ring is substituted to form a hydroxypyridone ring, so as to obtain 1-hydroxy-4-methyl-6- (2, 4-trimethyl amyl) -2-pyridone; adding ethanolamine into a salting-out system to obtain a target product of 1-hydroxy-4-methyl-6- (2, 4-trimethyl-amyl) -2-pyridone ethanolamine salt;
The supported catalyst consists of anhydrous aluminum trichloride, anhydrous polyaluminium chloride and a carrier, wherein the carrier is activated hydroxyapatite, and the loading amount of active aluminum element is 7-10%.
2. The method according to claim 1, wherein the dried carbon tetrachloride, anhydrous aluminum chloride and anhydrous polyaluminum chloride are stirred and dissolved under the protection of inert gas; adding activated hydroxyapatite, stirring and refluxing for 8-24 hours, and filtering to obtain a solid initial product; and washing the solid initial product with carbon tetrachloride for 3-6 times, and drying with a vacuum dryer to obtain the supported catalyst.
3. The method according to claim 2, wherein the weight ratio of carbon tetrachloride, anhydrous aluminum chloride, anhydrous polyaluminum chloride, hydroxyapatite is (10-15): (1-2): (0.2-0.6): (1.5-3), wherein the hydroxyapatite is activated for 2-6 hours at an activation temperature of 600-900 ℃, and the particle size of the hydroxyapatite is 120-180 meshes.
4. The method according to claim 1, wherein the specific method of the friedel-crafts acylation reaction of step (1) is as follows: adding a supported catalyst into dichloromethane, stirring in an ice water bath, dropwise adding 3, 5-trimethyl hexanoyl chloride, cooling to 20-25 ℃ after the dropwise adding is finished, slowly dropwise adding 3, 3-dimethyl methyl acrylate, and carrying out reflux reaction for 8 hours at 40-50 ℃ to obtain a dark brown liquid phase system; slowly dripping the fully reacted system into ice water under stirring, transferring to a separating funnel, standing for layering, and taking out a lower organic phase; adding dichloromethane to the upper water phase in batches for washing, and combining organic phases; the obtained organic layer was washed, dried and distilled to obtain 3,7,9,9-tetramethyl-2-decene-5-one acid methyl ester.
5. The method of claim 4, wherein the molar ratio of 3, 5-trimethylhexanoyl chloride to methyl 3, 3-dimethacrylate in step (1) is 1: (1.1-1.5), the mass ratio of 3, 5-trimethyl hexanoyl chloride to the supported catalyst is 1: (2-3).
6. The process according to claim 4, wherein the lactonization of step (2) is carried out in the following manner: heating 3,7,9,9-tetramethyl-2-decene-5-methyl ketonate obtained in the step (1) to 210-230 ℃ under the protection of inert gas, stirring and fully mixing for reaction for 24-36 hours, cooling to 20-25 ℃, adding dichloromethane, washing, drying and rotary steaming respectively to obtain the product 4-methyl-6- (2, 4-trimethylpentyl) -2-pyrone.
7. The method according to claim 6, wherein the hydroxylamine and salt formation reaction in step (3) is carried out by the following steps: adding 4-methyl-6- (2, 4-trimethyl amyl) -2-pyrone, dichloromethane and water, adding sodium ethoxide, heating and stirring hydroxylamine hydrochloride, adding glacial acetic acid, heating and refluxing for 15-20 hours, cooling to room temperature, adding sodium hydroxide solution for neutralization, layering, taking an organic phase, extracting and combining a water layer by ethyl acetate, washing, drying and rotary steaming, adding ethanolamine, heating to 40-60 ℃, observing crystal formation, cooling and crystallizing, washing by ethyl acetate, and drying in vacuum to obtain hydroxypyridone ethanolamine salt.
8. The method according to claim 7, wherein: the molar ratio of sodium ethoxide to 3, 5-trimethylhexanoyl chloride in step (1) is (1.5-2.5): the molar ratio of hydroxylamine hydrochloride to 3, 5-trimethylhexanoyl chloride in step (1) is (2.5-3.5): the molar ratio of the ethanolamine to the 3, 5-trimethylhexanoyl chloride in step (1) is (0.9-1.1): 1.
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| GB1440975A (en) * | 1972-07-11 | 1976-06-30 | Hoechst Ag | Method and compositions for treating hair |
| CN103480401A (en) * | 2013-09-30 | 2014-01-01 | 江苏理工学院 | Preparation method of hydroxyapatite-supported aluminum trichloride catalyst |
| CN112159352A (en) * | 2020-10-23 | 2021-01-01 | 烟台东方化学有限公司 | Preparation process of pyridone ethanolamine salt |
| CN113024457A (en) * | 2021-03-25 | 2021-06-25 | 烟台东方化学有限公司 | Preparation process of sterilization environment-friendly pyridone ethanolamine salt |
| CN115124461A (en) * | 2021-03-27 | 2022-09-30 | 菏泽新东方日化科技有限公司 | Preparation process of antiseptic bacteriostatic pyridone ethanolamine salt |
| CN115784981A (en) * | 2022-12-19 | 2023-03-14 | 宿迁旭升化工有限公司 | Preparation process of piroctone olamine salt |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| GB1440975A (en) * | 1972-07-11 | 1976-06-30 | Hoechst Ag | Method and compositions for treating hair |
| CN103480401A (en) * | 2013-09-30 | 2014-01-01 | 江苏理工学院 | Preparation method of hydroxyapatite-supported aluminum trichloride catalyst |
| CN112159352A (en) * | 2020-10-23 | 2021-01-01 | 烟台东方化学有限公司 | Preparation process of pyridone ethanolamine salt |
| CN113024457A (en) * | 2021-03-25 | 2021-06-25 | 烟台东方化学有限公司 | Preparation process of sterilization environment-friendly pyridone ethanolamine salt |
| CN115124461A (en) * | 2021-03-27 | 2022-09-30 | 菏泽新东方日化科技有限公司 | Preparation process of antiseptic bacteriostatic pyridone ethanolamine salt |
| CN115784981A (en) * | 2022-12-19 | 2023-03-14 | 宿迁旭升化工有限公司 | Preparation process of piroctone olamine salt |
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