CN100532366C - Synthesis method of climbazole - Google Patents
Synthesis method of climbazole Download PDFInfo
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- CN100532366C CN100532366C CNB2007100206714A CN200710020671A CN100532366C CN 100532366 C CN100532366 C CN 100532366C CN B2007100206714 A CNB2007100206714 A CN B2007100206714A CN 200710020671 A CN200710020671 A CN 200710020671A CN 100532366 C CN100532366 C CN 100532366C
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- OWEGWHBOCFMBLP-UHFFFAOYSA-N 1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethylbutan-2-one Chemical compound C1=CN=CN1C(C(=O)C(C)(C)C)OC1=CC=C(Cl)C=C1 OWEGWHBOCFMBLP-UHFFFAOYSA-N 0.000 title claims abstract description 20
- 229960003344 climbazole Drugs 0.000 title claims abstract description 20
- 238000001308 synthesis method Methods 0.000 title 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 68
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 48
- 239000012074 organic phase Substances 0.000 claims abstract description 39
- 239000007788 liquid Substances 0.000 claims abstract description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000001816 cooling Methods 0.000 claims abstract description 13
- 239000003513 alkali Substances 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 238000005303 weighing Methods 0.000 claims abstract description 5
- 239000003054 catalyst Substances 0.000 claims abstract 2
- 238000003756 stirring Methods 0.000 claims description 44
- 230000018044 dehydration Effects 0.000 claims description 17
- 238000006297 dehydration reaction Methods 0.000 claims description 17
- 150000002460 imidazoles Chemical class 0.000 claims description 16
- 150000002576 ketones Chemical class 0.000 claims description 14
- 238000000967 suction filtration Methods 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 238000010189 synthetic method Methods 0.000 claims description 9
- 238000010792 warming Methods 0.000 claims description 6
- XXBDWLFCJWSEKW-UHFFFAOYSA-N dimethylbenzylamine Chemical compound CN(C)CC1=CC=CC=C1 XXBDWLFCJWSEKW-UHFFFAOYSA-N 0.000 claims description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 235000010755 mineral Nutrition 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- CMEWLCATCRTSGF-UHFFFAOYSA-N N,N-dimethyl-4-nitrosoaniline Chemical compound CN(C)C1=CC=C(N=O)C=C1 CMEWLCATCRTSGF-UHFFFAOYSA-N 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 238000011084 recovery Methods 0.000 claims description 2
- 241000143437 Aciculosporium take Species 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 239000002699 waste material Substances 0.000 abstract description 4
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 238000007710 freezing Methods 0.000 abstract description 2
- 230000008014 freezing Effects 0.000 abstract description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 abstract 9
- 238000000034 method Methods 0.000 abstract 3
- -1 chlorinated ether ketone Chemical class 0.000 abstract 2
- 239000005820 Prochloraz Substances 0.000 abstract 1
- 239000008346 aqueous phase Substances 0.000 abstract 1
- 238000001514 detection method Methods 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 238000002156 mixing Methods 0.000 abstract 1
- 238000000643 oven drying Methods 0.000 abstract 1
- 239000012071 phase Substances 0.000 abstract 1
- TVLSRXXIMLFWEO-UHFFFAOYSA-N prochloraz Chemical compound C1=CN=CN1C(=O)N(CCC)CCOC1=C(Cl)C=C(Cl)C=C1Cl TVLSRXXIMLFWEO-UHFFFAOYSA-N 0.000 abstract 1
- QXJKBPAVAHBARF-BETUJISGSA-N procymidone Chemical compound O=C([C@]1(C)C[C@@]1(C1=O)C)N1C1=CC(Cl)=CC(Cl)=C1 QXJKBPAVAHBARF-BETUJISGSA-N 0.000 abstract 1
- 238000004064 recycling Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 238000004659 sterilization and disinfection Methods 0.000 description 16
- 238000010992 reflux Methods 0.000 description 15
- 230000000630 rising effect Effects 0.000 description 15
- 235000011121 sodium hydroxide Nutrition 0.000 description 13
- 230000001954 sterilising effect Effects 0.000 description 11
- 230000002354 daily effect Effects 0.000 description 5
- 230000002147 killing effect Effects 0.000 description 5
- 208000001840 Dandruff Diseases 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 239000002453 shampoo Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000000645 desinfectant Substances 0.000 description 2
- 230000000249 desinfective effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000005541 medical transmission Effects 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000000344 soap Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 2
- 229940033663 thimerosal Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000028399 Critical Illness Diseases 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000002070 germicidal effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229940090668 parachlorophenol Drugs 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229940034610 toothpaste Drugs 0.000 description 1
- 239000000606 toothpaste Substances 0.000 description 1
- 229960003500 triclosan Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Aiming at the technical problems, the invention provides a method for synthesizing climbazole, which comprises the following steps: weighing chlorinated ether ketone, and adding alkali and imidazole into an organic solvent to obtain a system a; adding chlorinated ether ketone into the system a to obtain a system b; adding water into the system b, collecting the lower aqueous phase, and reserving an organic phase; adding water and hydrochloric acid to the organic phase, and collecting the upper organic phase; adding water and sodium hydroxide to the organic phase, adding water to the organic phase, and keeping the organic phase; recovering toluene from the organic phase at normal pressure, and collecting the residual liquid; freezing the rest liquid to 0 + -3 deg.C, filtering, and oven drying to obtain procymidone; mixing the water phases, cooling to below 25 ℃, adjusting the pH to 12-13 by using 30% liquid alkali, and recycling the catalyst for reuse. The process method for producing the prochloraz has the advantages of low imidazole consumption, production cost reduction, reduction of imidazole waste liquid discharge and environmental friendliness; after the method is applied, the product purity can be obviously improved through detection.
Description
One, technical field
The invention belongs to a kind of synthetic method of compound, particularly a kind of synthetic method of climbazole.
Two, background technology
Prior art: sterilization, thimerosal and sterilization, sterilization aerosol are to be specifically designed to human body.Fruit, vegetables, article and environment carry out degerming, the special daily chemical products of disinfectant, and to killing human body, food and environment germ and virus, the blocking-up infectious disease transmission has vital role.It is the product that recent people need in a hurry.Sterilant and washing composition are synergistic, and consistency is fine, can join sterilant in the washing composition, when cleaning; Play germ-resistant effect.When special occasions such as hospital, dining room clean, must add people's sterilant in the scavenging solution.Because people strengthen suddenly to sterilization, disinfectant consciousness in the recent period.Sterilization, thimerosal and sterilization, sterilization aerosol class daily chemical products have had great demand.The relevant expert of health and epidemic prevention department recommends to use Peracetic Acid, chloride sterilant (as 84 thimerosals), aqueous hydrogen peroxide solution, ozonize and uviolizing etc., and virus, germ are had preferable killing action, and its shortcoming is not have long-lasting.Be critically ill colony and place of flowabilities such as hospital, school, shop, public transport lacked and continue killing action.Recently exploitation be that efficient, wide spectrum, long-acting type disinfection solution and the disinfecting aerosol agent of main sterilization component has lasting killing action to germ, virus with sterilant such as triclosan, two para-chlorophenols, use separately or be used killing and suppressing all kinds of germs, virus, prevent that the infectious disease transmission effect is better with above-mentioned disinfection sanitizer.At present, to pathogenic agent further deeply under the prerequisite of understanding, also answer emphasis to strengthen all kinds of efficient, wide spectrums, long-acting type disinfection solution and disinfecting aerosol agent Products Development and production.Sterilization, sterilization are that daily product is used and the critical function that develops, and the disinfection function of daily product is generally realized by adding an amount of disinfection sanitizer.An ideal sterilant should possess following condition: the drug effect that, the microorganism of occurring in nature is had wide spectrum; Two, on a small quantity can be effectively; Three, excellent compatibility is arranged; Four, solvability, dispersed good does not influence the basic usefulness of product; Five, safe, nontoxic to human body, non-stimulated, can not produce allergy; Have no side effect.In fact, the sterilant that meets fully above-mentioned requirements seldom.Most use range are narrower.The used for cosmetic sanitas of China regulation has 66 kinds, be usually used in the daily chemical products only have ten surplus kind.Sterilization, the sanitas of at present domestic and international popular outbalance: climbazole, have another name called active climbazole, diazolones, English name: Climbazole, chemical name :-(4-chlorophenoxy)-3,3-dimethyl-1-(imidazoles-1-yl)-2-butanone, white or canescence crystal, fusing point: 95～97 ℃, be called as the efficient anti-dandruff and itching-relieving agent of the s-generation.Climbazole is the efficient germicide new product of German Bayer company exploitation listing in 1977, domesticly develops the beginning of the nineties in last century.Significant anti-dandruff and itching-relieving function of this product tool and excellent compatibility energy, shampoo with its preparation can not produce drawbacks such as precipitation, layering, variable color, skin irritation, has multiple anti-fungal property, to produce the human body dandruff main fungi---avette bud is embraced bacterium and is had unique effect, the white beads seedling that causes human oral cavity dental caries inflammation, periodontitis is also had obvious restraining effect.Become one of first-selected sterilant of cosmeticses of everyday use such as medium-to-high grade Ji hair-care shampoo, perfumed soap, medicated soap, medicated toothpaste and rinse liquid.Recommending working concentration in shampoo etc. is 0.5%～0.8%, dissolves in and uses in alcoholic solvent or the nonionogenic tenside, 70 ℃ of solvent temperatures.Climbazole is commonly used for the preparation of agricultural chemicals, personal care articles, 1-(4-chlorophenoxy)-3,3-dimethyl-1-(imidazoles-1-yl)-2-butanone belongs to s-generation dandruff sterilant, is made by cloroecther ketone and the reaction of excessive imidazoles usually, because of the imidazoles large usage quantity, cost an arm and a leg,, and produce a large amount of imidazoles waste liquids so synthetic cost is higher, do not meet the cleaner production requirement, big to environmental influence.
Three, summary of the invention
The present invention is directed to above-mentioned technical problem, provide a kind of production cost low, the product purity height, it is few to produce waste liquid, the synthetic method of eco-friendly climbazole.
Technical solution of the present invention is: a kind of synthetic method of climbazole, preparation process is: the cloroecther ketone that takes by weighing 1 molar part, in organic solvent, drop into organic bases or mineral alkali earlier as catalyzer, drop into imidazoles again, wherein the input amount of catalyzer and imidazoles is respectively 1～1.1 times of cloroecther ketone molfraction, 60～100 rev/mins are stirred intensification dehydration in 1～3 hour after 120 ℃, and 60～100 rev/mins of stirrings were cooled to 60 ℃ in 1～3 hour again, got reaction system a; Add the 1 molar part cloroecther ketone that takes by weighing in above-mentioned reaction system a, 60～100 rev/mins of stirrings are warming up to 110～120 ℃ and refluxed 3～6 hours, and 60～100 rev/mins of stirrings are cooled to 60 ± 5 ℃, get reaction system b; In reaction system b, add 10～16 molar part water,, collect lower floor's water, leave and take upper organic phase at 60 ℃ of standing demix; Upwards go on foot organic addition 10～16 molar part water and 0.1～0.2 molar part hydrochloric acid of leaving and taking, stir and be warming up to 60 ± 5 ℃ of standing demix, collect lower floor's water, leave and take upper organic phase; Upwards go on foot organic addition 10～16 molar part water and 0.2～0.3 molar part sodium hydroxide of leaving and taking, 60～100 rev/mins are stirred intensification 1～2 hour, refluxed 1～3 hour, 60 ± 5 ℃ of standing demix, upper organic phase adds 10～16 molar part water, 60 ± 5 ℃ of standing demix, 60 ℃ of standing demix are left and taken upper organic phase; The organic phase that the last step was left and taken stirs the dehydration in 1～3 hour that heats up for 60～100 rev/mins to 120 ℃ of normal pressures recovery toluene, leaves and takes remaining liq; To go up step 60～100 rev/mins of remaining liqs and stir 1～5 hour frozen cooling to 0 ± 3 ℃, suction filtration, oven dry, the product climbazole; The water of mixed collection, 60～100 rev/mins are stirred cooling 1～4 hour, are cooled to below 25 ℃, with 30% liquid adjusting PH with base to 12～13, behind the standing demix, divide sub-cloud water, reclaim the upper strata catalyzer and apply mechanically.Organic solvent is the toluene solution of toluene or mass percent 3～10% climbazoles.Organic bases is triethylamine, pyridine, N, N-dimethyl benzylamine, N, accelerine or N, N-Diethyl Aniline.The synthetic method of climbazole as claimed in claim 1 is characterized in that described mineral alkali is Na
2CO
3, NaHCO
3, NaOH or K
2CO
3The structural formula of climbazole is:
The beneficial effect that the present invention produces: use processing method of the present invention and produce climbazole, the imidazoles consumption is few, has reduced production cost, has reduced the discharging of imidazoles waste liquid, environmental friendliness; And behind utilization the present invention, product purity obviously improves as can be seen after testing.
Four, embodiment
Embodiment 1
In the 2000ml there-necked flask, throw toluene or mother liquor 900 grams, N, N-dimethyl benzylamine 260 grams, imidazoles 125 grams stir the dehydration that heats up to 120 ℃ of end, stir and are cooled to 60 ℃, throw cloroecther ketone 450 grams, stirred temperature rising reflux 4 hours, qualitative end, stirring is cooled to 60 ℃, adds water 400 grams, 60 ℃ of standing demix, lower floor's water is collected, and upper organic phase adds water 400 grams, and concentration is mass percent 30% hydrochloric acid 26 grams, 60 ℃ of standing demix, lower floor's water is collected, and upper organic phase adds water 400 grams, concentration is mass percent 30% liquid caustic soda 60 grams, stirs temperature rising reflux 1 hour, 60 ℃ of standing demix, upper organic phase adds water 400 grams, 60 ℃ of standing demix, and upper organic phase stirs the dehydration that heats up to 120 ℃, finish, normal pressure reclaims toluene 300 grams, stirs frozen cooling to 0 ℃, suction filtration, oven dry, get product 432 grams, yield 96%, content reaches 99%.
A collection of water stirs, and is cooled to below 25 ℃, and 30% liquid caustic soda is transferred PH=12-13, layering sub-cloud water, and the upper strata catalyzer is applied mechanically.
Yancheng City product quality supervision and testing institute assay:
| Sequence number | Test item | Unit | Technical requirements | Detected result | Individual event is judged |
| 1 | Content | ％ | ≥99.0 | 99.9 | Qualified |
| 2 | Para-chlorophenol | ％ | ≤0.1 | <0.1 | Qualified |
| 3 | Fusing point | ℃ | 96.0～98.0 | 97.2 | Qualified |
| 4 | Moisture | ％ | ≤0.5 | 0.1 | Qualified |
Embodiment 2
In the 2000ml there-necked flask, throw toluene or mother liquor 900 grams, N, accelerine 240 grams, imidazoles 125 grams stir the dehydration that heats up to 120 ℃ of end, stir and are cooled to 60 ℃, throw cloroecther ketone 450 grams, stirred temperature rising reflux 4 hours, qualitative end, stirring is cooled to 60 ℃, adds water 400 grams, 60 ℃ of standing demix, lower floor's water is collected, and upper organic phase adds water 400 grams, and concentration is mass percent 30% hydrochloric acid 26 grams, 60 ℃ of standing demix, lower floor's water is collected, and upper organic phase adds water 400 grams, concentration is mass percent 30% liquid caustic soda 60 grams, stirs temperature rising reflux 1 hour, 60 ℃ of standing demix, upper organic phase adds water 400 grams, 60 ℃ of standing demix, and upper organic phase stirs the dehydration that heats up to 120 ℃, finish, negative pressure reclaims toluene 300 grams, stirs frozen cooling to 0 ℃, suction filtration, oven dry, get product 418 grams, yield 93%, content reaches 99%.
A collection of water stirs, and is chilled to below 25 ℃, and 30% liquid caustic soda is transferred PH=12-13, layering sub-cloud water, and the upper strata catalyzer is applied mechanically.
Embodiment 3
Throw toluene 900 grams in the 2000ml there-necked flask, imidazoles 125 grams stir the temperature rising reflux dehydration to 120 ℃ of end, be cooled to 60 ℃, throw triethylamine 200 grams, cloroecther ketone 450 grams, stirred temperature rising reflux 6 hours, qualitative end is cooled to 60 ℃, add water 400 grams, 60 ℃ of layerings, lower floor's water is collected, organic addition water 400 grams, 30% hydrochloric acid, 26 grams, 60 ℃ of standing demix, lower floor's water is collected, organic addition water 400 grams, 30% liquid caustic soda, 60 grams, stirred temperature rising reflux 1 hour, 60 ℃ of standing demix, upper organic phase adds water 400 grams, 60 ℃ of standing demix, upper organic phase stirs the dehydration that heats up to 120 ℃, finishes, and negative pressure reclaims toluene 300 grams, stir frozen cooling to 0 ℃, suction filtration, oven dry gets product 427 grams, yield 95%, content 99%.
A collection of water stirs, and is chilled to below 25 ℃, and 30% liquid caustic soda is transferred PH=12-13, adds toluene 200 grams simultaneously, layering sub-cloud water, and upper organic phase rectifying is told catalyzer and is applied mechanically.
Embodiment 4
Throw toluene 900 grams in the 2000ml there-necked flask, imidazoles 125 grams stir the temperature rising reflux dehydration to 120 ℃ of end, be cooled to 60 ℃, throw sheet alkali 80 grams, the PTC50 gram, cloroecther ketone 450 grams stirred temperature rising reflux 10 hours, qualitative end, be cooled to 60 ℃, add water 400 grams, 60 ℃ of layerings, organic addition water 400 grams, 30% hydrochloric acid, 26 grams, 60 ℃ of standing demix, organic addition water 400 grams, 30% liquid caustic soda, 60 grams stirred temperature rising reflux 1 hour, 60 ℃ of standing demix, upper organic phase adds water 400 grams, 60 ℃ of standing demix, and upper organic phase stirs the dehydration that heats up to 120 ℃, finish, negative pressure reclaims toluene 300 grams, stirs frozen cooling to 0 ℃, suction filtration, oven dry, get product 405 grams, yield 90%, content 85%.
Embodiment 5
Throw toluene 900 grams in the 2000ml there-necked flask, imidazoles 125 grams stir the temperature rising reflux dehydration to 120 ℃ of end, be cooled to 60 ℃, throw sodium bicarbonate 120 grams, the PTC50 gram, cloroecther ketone 450 grams stirred temperature rising reflux 10 hours, qualitative end, be cooled to 60 ℃, add water 400 grams, 60 ℃ of layerings, organic addition water 400 grams, 30% hydrochloric acid, 26 grams, 60 ℃ of standing demix, organic addition water 400 grams, 30% liquid caustic soda, 60 grams stirred temperature rising reflux 1 hour, 60 ℃ of standing demix, upper organic phase adds water 400 grams, 60 ℃ of standing demix, and upper organic phase stirs the dehydration that heats up to 120 ℃, finish, negative pressure reclaims toluene 300 grams, stirs frozen cooling to 0 ℃, suction filtration, oven dry, get product 410 grams, yield 91%, content 85%.
Embodiment 6
In the 2000ml there-necked flask, throw toluene or suction filtration mother liquid obtained (composition mainly is the climbazole of toluene and about 3-10%) 900 grams, N, N-dimethyl benzylamine 260 grams, imidazoles 125 grams, 60-100 rev/min of stirring, dehydration was to 120 ℃ of end in intensification 1-3 hour, 60-100 rev/min is stirred cooling 1-3 hour to 60 ℃, throw cloroecther ketone 450 grams, 60-100 rev/min of stirring was warming up to 110-120 ℃ of backflow 3-6 hour, insulation finishes, stirring is cooled to 60 ± 5 ℃, add water 400 ± 100 grams, 60-100 rev/min of stirring is cooled to 60 ± 5 ℃ of standing demix, lower floor's water is collected (water 1), upper organic phase adds water 400 ± 100 grams, and 30% hydrochloric acid 25-30 gram stirs and is warming up to 60 ± 5 ℃ of standing demix, lower floor's water is collected (water 2), upper organic phase adds water 400 ± 100 grams, 30% liquid caustic soda 50-70 gram, and 60-100 rev/min is stirred intensification 1-2 hour, backflow 1-3 hour, 60 ± 5 ℃ of standing demix, upper organic phase add water 400 ± 100 grams, 60 ± 5 ℃ of standing demix, upper organic phase 60-100 rev/min is stirred intensification dehydration in 1-3 hour to 120 ℃, finish, normal pressure reclaims toluene 250-350 gram, and 60-100 rev/min of stirring was cooled to 0 ± 3 ℃ in freezing 1-5 hour, suction filtration, oven dry gets product 432 grams, yield 96%, content reaches 99%, mother liquid recycle.
Water 1 and water 2 mix, and 60-100 rev/min is stirred cooling 1-4 hour, is cooled to below 25 ℃, and 30% liquid caustic soda is transferred PH=12-13, layering sub-cloud water, and upper strata N, the N-dimethyl benzylamine is applied mechanically.
Comparative Examples 1
In the 2000ml there-necked flask, throw toluene 900 grams, cloroecther ketone 450 grams, imidazoles 250 grams, stirred temperature rising reflux 4 hours, qualitative end is cooled to 60 ℃, add water 500 grams, 60 ℃ of layering sub-cloud waters, upper organic phase adds water 400 grams, 30% hydrochloric acid, 26 grams, 60 ℃ of layering sub-cloud waters add water 400 grams, 30% liquid caustic soda, 60 grams stirred temperature rising reflux 1 hour, 60 ℃ of standing demix, upper organic phase adds water 400 grams, 60 ℃ of standing demix, upper organic phase stir the dehydration that heats up to 120 ℃, finish, negative pressure reclaims toluene 300 grams, stir frozen cooling to 0 ℃, suction filtration, oven dry, get product 405 grams, yield 95%.Content 95%.
Claims (3)
1. the synthetic method of a climbazole is characterized in that preparation process is:
A. take by weighing the cloroecther ketone of 1 molar part, in organic solvent, drop into organic bases or mineral alkali earlier as catalyzer, drop into imidazoles again, wherein the input amount of catalyzer and imidazoles is respectively 1～1.1 times of cloroecther ketone molfraction, 60～100 rev/mins are stirred intensification dehydration in 1～3 hour after 120 ℃, 60～100 rev/mins of stirrings were cooled to 60 ℃ in 1～3 hour again, got reaction system a, and described organic solvent is the toluene solution of toluene or mass percent 3～10% climbazoles;
B. add the 1 molar part cloroecther ketone that takes by weighing in above-mentioned reaction system a, 60～100 rev/mins of stirrings are warming up to 110～120 ℃ and refluxed 3～6 hours, and 60～100 rev/mins of stirrings are cooled to 60 ± 5 ℃, get reaction system b;
C. in reaction system b, add 10～16 molar part water,, collect lower floor's water, leave and take upper organic phase at 60 ℃ of standing demix;
D. upwards go on foot organic addition 10～16 molar part water and 0.1～0.2 molar part hydrochloric acid of leaving and taking, stir and be warming up to 60 ± 5 ℃ of standing demix, collect lower floor's water, leave and take upper organic phase;
E. organic addition 10～16 molar part water and 0.2～0.3 molar part sodium hydroxide of leaving and taking to steps d, 60～100 rev/mins are stirred intensification 1～2 hour, refluxed 1～3 hour, 60 ± 5 ℃ of standing demix, upper organic phase adds 10～16 molar part water, 60 ± 5 ℃ of standing demix, 60 ℃ of standing demix are left and taken upper organic phase;
F. the organic phase that step e is left and taken stirs dehydration in 1～3 hour to the 120 ℃ of normal pressures that heat up for 60～100 rev/mins and reclaims toluene, leaves and takes remaining liq;
G. will go up step 60～100 rev/mins of remaining liqs and stir 1～5 hour frozen cooling to 0 ± 3 ℃, suction filtration, oven dry, the product climbazole;
H. the water of mixed collection, 60～100 rev/mins are stirred cooling 1～4 hour, are cooled to below 25 ℃, with 30% liquid adjusting PH with base to 12～13, behind the standing demix, divide sub-cloud water, and recovery upper strata organic alkali catalyst is applied mechanically.
2. the synthetic method of climbazole as claimed in claim 1 is characterized in that described organic bases is triethylamine, pyridine, N, N-dimethyl benzylamine, N, accelerine or N, N-Diethyl Aniline.
3. the synthetic method of climbazole as claimed in claim 1 is characterized in that described mineral alkali is NaOH.
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| CNB2007100206714A CN100532366C (en) | 2007-03-20 | 2007-03-20 | Synthesis method of climbazole |
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| CN107739341A (en) * | 2017-10-31 | 2018-02-27 | 江苏绿叶农化有限公司 | A kind of preparation method of climbazole |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3812142A (en) * | 1971-02-05 | 1974-05-21 | Bayer Ag | Imidazolyl ketones |
| US4000299A (en) * | 1974-06-20 | 1976-12-28 | Bayer Aktiengesellschaft | 1-(Imidazol-1-yl)-1-[4-(4-chlorophenyl)phenoxy]-3,3-dimethylbutan-2-one, its salts and a process for their use |
| US4229580A (en) * | 1977-03-29 | 1980-10-21 | Bayer Aktiengesellschaft | Preparation of 1-azolyl-3,3-dimethyl-1-phenoxy-butan-2-ones |
-
2007
- 2007-03-20 CN CNB2007100206714A patent/CN100532366C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3812142A (en) * | 1971-02-05 | 1974-05-21 | Bayer Ag | Imidazolyl ketones |
| US4000299A (en) * | 1974-06-20 | 1976-12-28 | Bayer Aktiengesellschaft | 1-(Imidazol-1-yl)-1-[4-(4-chlorophenyl)phenoxy]-3,3-dimethylbutan-2-one, its salts and a process for their use |
| US4229580A (en) * | 1977-03-29 | 1980-10-21 | Bayer Aktiengesellschaft | Preparation of 1-azolyl-3,3-dimethyl-1-phenoxy-butan-2-ones |
Non-Patent Citations (1)
| Title |
|---|
| 活性甘宝素－新型高效去屑剂. 陆缵明等.上海轻工业，第4期. 1996 * |
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