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CN104610155A - Preparation method for imazalil - Google Patents

Preparation method for imazalil Download PDF

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Publication number
CN104610155A
CN104610155A CN201510061742.XA CN201510061742A CN104610155A CN 104610155 A CN104610155 A CN 104610155A CN 201510061742 A CN201510061742 A CN 201510061742A CN 104610155 A CN104610155 A CN 104610155A
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Prior art keywords
imazalil
preparation
reaction
grams
ionic liquid
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CN201510061742.XA
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Chinese (zh)
Inventor
裴文
何建明
何甫长
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LINHAI LIMIN CHEMICALS CO Ltd
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LINHAI LIMIN CHEMICALS CO Ltd
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D233/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C07D233/60Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention discloses a preparation method for imazalil. The method is characterized by adding 2,4-dichloro-2'-chlorophenylethanol, imidazole, allyl chloride, sodium carbonate and ionic liquid in a reaction container, reacting for 1-10 hours at 10-100 DEG C, and carrying out posttreatment to obtain the imazalil, wherein the ionic liquid is 1-methyl-3-alkyl imidazole tetrafluoroborate. According to the method, the imazalil is prepared by using the 2,4-dichloro-2'-chlorophenylethanol, imidazole and allyl chloride and adopting a one-pot reaction technology in an ionic liquid reaction system. The technology is green chemical preparation technology which is simple to operate, energy saving and emission reducing, environmentally friendly and recyclable.

Description

A kind of preparation method of imazalil
Technical field
The present invention relates to a kind of novel processing step of imazalil.
Background technology
Imazalil is that imidazoles sterilant is inhaled in a kind of has a broad antifungal spectrum of exploitation in 1973 by Belgian Yang Sen company.Not only there is preventive effect to many fungal diseases of invasion and attack fruit, vegetables and ornamental crops, especially citrus, banana and other fruit sprayed, flood rotten (being mainly used in the storage of apple, banana, Cauliflower) that can prevent and treat the rear gourd, fruit and vegetable of results, and have high activity to Helminthosporium, fusarium, Septoria and drupe leaf rust etc., can be used for preventing and treating cereal disease and seed treatment.At present, the chemosynthesis bibliographical information of imazalil is little.Chemical name is 1-[2-(2,4 dichloro benzene base)-2-(2-allyloxy) ethyl]-1 H-imidazoles, and molecular weight is 297.2, and structural formula is:
The synthesis of imazalil mainly contains two lines.Route one is that carbonyl reduction becomes hydroxyl by the methyl bromide of 2,4 dichloro benzene ethyl ketone, and then the nitrogen-atoms of bromo methylene radical and imidazoles replaces, last and allyl bromide 98 alkylated reaction; Route two is that 1,3-dichlorobenzene and chloro-acetyl chloride react the chloro-2 '-chloroacetophenone of generation 2,4-bis-, and carbonyl reduction is hydroxyl, carries out the alkylation of nitrogen-atoms with imidazoles, finally carries out the alkylated reaction on Sauerstoffatom with chlorallylene again.Route one is more in the side reaction of this step of reduction reaction, affects reaction yield; The chemically reactive of route dimethyl chloride is lower, not easily carries out the alkylated reaction of nitrogen-atoms with imidazoles.The chloro-2 '-chloroacetophenone of reaction raw materials 2,4-bis-is relatively active in addition, stability is bad and to be not easy to use by suitability for industrialized production, and the condition preparing this raw material is harsh, expensive reagents, and has strong impulse smell, and toxicity is also very large.Because fungi produces resistance to multi-medicament, and have the trend day by day increased, antifungal drug research is subject to the attention of global medicine scholar day by day.The superiority that imidazoles and triazole compound show in clinical application, makes it have wide application prospect.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of novel syntheti c route of imazalil, and this preparation method adopts the chloro-2 '-chlorinated benzene ethanol of 2,4-bis-, imidazoles and chlorallylene to be raw material, in ionic liquid, adopts one pot reaction technology to prepare imazalil.
For solving above technical problem, the preparation method of imazalil of the present invention, adds 2 in reaction vessel, the chloro-2 '-chlorinated benzene ethanol of 4-bis-, imidazoles, chlorallylene, sodium carbonate and ionic liquid, at 10 ~ 100 DEG C of temperature, react 1 ~ 10 hour, obtain imazalil through aftertreatment;
Described ionic liquid is 1-methyl-3-alkylimidazolium tetrafluoroborate.
Reaction formula of the present invention is as follows:
Further, the molar ratio of described 2,4-bis-chloro-2 '-chlorinated benzene ethanol and imidazoles and chlorallylene is 1:1 ~ 1.5: 1 ~ 1.5.
Again further, the molar ratio of described 2,4-bis-chloro-2 '-chlorinated benzene ethanol and imidazoles and chlorallylene is 1:1.2: 1.2.
Further, the alkyl in described ionic liquid is C 1~ C 10alkyl.
Further, the weight consumption of described ionic liquid is 3 ~ 8 times of 2,4-bis-chloro-2 '-chlorinated benzene ethanol weight.
Further, the temperature of reaction of described method is 50 ~ 80 DEG C.
Further, the reaction times of described method is 3 ~ 5 hours.
Further, described aftertreatment is that reaction terminates rear temperature of reaction and drops to room temperature, adds the water with reaction system roughly same volume; Stratification, separates aqueous layer and organic layer; Aqueous layer extracted with diethyl ether, merges all organic layers, dry, steams solvent and obtains imazalil product.It is >=99% that gained imazalil analyzes content through HPLC, fusing point 50 ~ 52 DEG C.
The present invention utilizes the chloro-2 '-chlorinated benzene ethanol of 2,4-bis-, imidazoles and chlorallylene, in ionic liquid reaction system, adopts one pot reaction technology to prepare imazalil.This technology is easy and simple to handle, energy-saving and emission-reduction, environmental friendliness and the Green Chemistry technology of preparing of reusable edible.
Embodiment
With specific embodiment, technical scheme of the present invention is described below, but protection scope of the present invention is not limited thereto:
embodiment 1
In 500 milliliters of there-necked flasks, add 2 successively, the chloro-2 '-chlorinated benzene ethanol of 4-bis-22.6 grams (0.1 mole), imidazoles 8.2 grams (0.12 mole), chlorallylene 9.2 grams (0.12 mole), 21 grams, sodium carbonate (0.2 mole) and 1-methyl-3-butyl imidazole tetrafluoroborate ion liquid 113 grams, under 50 DEG C of conditions, react 5 hours.After reaction terminates, temperature of reaction drops to room temperature, adds 174 grams of water, stratification, separates aqueous layer and organic layer, and aqueous layer 100 milliliters of extracted with diethyl ether 3 times, merge all organic layers, and drying, boils off solvent, obtain imazalil product 17.8 grams, yield 60%.It is >=99% that HPLC analyzes content.Fusing point 51 ~ 52 DEG C.
embodiment 2
In 500 milliliters of there-necked flasks, add 2 successively, the chloro-2 '-chlorinated benzene ethanol of 4-bis-22.6 grams (0.1 mole), imidazoles 6.8 grams (0.1 mole), chlorallylene 7.7 grams (0.1 mole), 21 grams, sodium carbonate (0.2 mole) and 1-methyl-3-octylimidazole tetrafluoroborate ion liquid 69 grams, under 80 DEG C of conditions, react 10 hours.After reaction terminates, temperature of reaction drops to room temperature, adds 128 grams of water, stratification, separates aqueous layer and organic layer, and aqueous layer 100 milliliters of extracted with diethyl ether 3 times, merge all organic layers, and drying, boils off solvent, obtain imazalil product 17.5 grams, yield 59%.It is >=99% that HPLC analyzes content.Fusing point 51 ~ 52 DEG C.
embodiment 3
In 500 milliliters of there-necked flasks, add 2 successively, the chloro-2 '-chlorinated benzene ethanol of 4-bis-22.6 grams (0.1 mole), imidazoles 10.2 grams (0.15 mole), chlorallylene 9.2 grams (0.12 mole), 21 grams, sodium carbonate (0.2 mole) and 1-methyl-3-benzyl imidazole tetrafluoroborate ion liquid 180 grams, under 100 DEG C of conditions, react 1 hour.After reaction terminates, temperature of reaction drops to room temperature, adds 243 grams of water, stratification, separates aqueous layer and organic layer, and aqueous layer 100 milliliters of extracted with diethyl ether 3 times, merge all organic layers, and drying, boils off solvent, obtain imazalil product 18.1 grams, yield 61%.It is >=99% that HPLC analyzes content.Fusing point 51 ~ 52 DEG C.
embodiment 4
In 500 milliliters of there-necked flasks, add 2 successively, the chloro-2 '-chlorinated benzene ethanol of 4-bis-22.6 grams (0.1 mole), imidazoles 8.2 grams (0.12 mole), chlorallylene 9.2 grams (0.12 mole), 1-methyl-3-octylimidazole tetrafluoroborate ion liquid 163 grams is 7 by sodium carbonate regulation system pH value, under 80 DEG C of conditions, react 8 hours.After reaction terminates, temperature of reaction drops to room temperature, adds 224 grams of water, stratification, separates aqueous layer and organic layer, and aqueous layer 100 milliliters of extracted with diethyl ether 3 times, merge all organic layers, and drying, boils off solvent, obtain imazalil product 17.8 grams, yield 60%.It is >=99% that HPLC analyzes content.Fusing point 51 ~ 52 DEG C.
embodiment 5
In 500 milliliters of there-necked flasks, add 2 successively, the chloro-2 '-chlorinated benzene ethanol of 4-bis-22.6 grams (0.1 mole), imidazoles 8.2 grams (0.12 mole), chlorallylene 9.2 grams (0.12 mole), 21 grams, sodium carbonate (0.2 mole) and 1-methyl-3-hexyl imidazolium tetrafluoroborate ion liquid 136 grams, under 40 DEG C of conditions, react 3 hours.After reaction terminates, temperature of reaction drops to room temperature, adds 200 grams of water, stratification, separates aqueous layer and organic layer, and aqueous layer 100 milliliters of extracted with diethyl ether 3 times, merge all organic layers, and drying, boils off solvent, obtain imazalil product 17.8 grams, yield 60%.It is >=99% that HPLC analyzes content.Fusing point 51 ~ 53 DEG C.
embodiment 6
In 500 milliliters of there-necked flasks, add 2 successively, the chloro-2 '-chlorinated benzene ethanol of 4-bis-22.6 grams (0.1 mole), imidazoles 8.2 grams (0.12 mole), chlorallylene 9.2 grams (0.12 mole), 21 grams, sodium carbonate (0.2 mole) and 1-methyl-3-butyl imidazole tetrafluoroborate ion liquid 160 grams, under 50 DEG C of conditions, react 6 hours.After reaction terminates, temperature of reaction drops to room temperature, adds 221 grams of water, stratification, separates aqueous layer and organic layer, and solution layer 100 milliliters of extracted with diethyl ether 3 times, merge all organic layers, and drying, boils off solvent, obtain imazalil product 18.4 grams, yield 62%.It is >=99% that HPLC analyzes content.Fusing point 51 ~ 52 DEG C.
Above-mentioned embodiment is exemplary, being to better enable those skilled in the art understand the present invention, can not being interpreted as it is limiting the scope of the invention; As long as any equivalent change done by disclosed spirit or modification, all fall into the scope of protection of the invention.

Claims (8)

1. a preparation method for imazalil, is characterized in that in reaction vessel, add the chloro-2 '-chlorinated benzene ethanol of 2,4-bis-, imidazoles, chlorallylene, sodium carbonate and ionic liquid, at 10 ~ 100 DEG C of temperature, reacts 1 ~ 10 hour, obtains imazalil through aftertreatment;
Described ionic liquid is 1-methyl-3-alkylimidazolium tetrafluoroborate.
2. the preparation method of imazalil according to claim 1, is characterized in that the molar ratio of described 2,4-bis-chloro-2 '-chlorinated benzene ethanol and imidazoles and chlorallylene is 1:1 ~ 1.5: 1 ~ 1.5.
3. the preparation method of imazalil according to claim 1, is characterized in that the molar ratio of described 2,4-bis-chloro-2 '-chlorinated benzene ethanol and imidazoles and chlorallylene is 1:1.2: 1.2.
4. the preparation method of imazalil according to claim 1, is characterized in that the alkyl in described ionic liquid is C 1~ C 10alkyl.
5. the preparation method of the imazalil according to claim 1 or 4, is characterized in that the weight consumption of described ionic liquid is 3 ~ 8 times of 2,4-bis-chloro-2 '-chlorinated benzene ethanol weight.
6. the preparation method of imazalil according to claim 1, is characterized in that the temperature of reaction of described method is 50 ~ 80 DEG C.
7. the preparation method of imazalil according to claim 1, is characterized in that the reaction times of described method is 3 ~ 5 hours.
8. the preparation method of imazalil according to claim 1, is characterized in that described aftertreatment is that reaction terminates rear temperature of reaction and drops to room temperature, adds the water with reaction system roughly same volume; Stratification, separates aqueous layer and organic layer; Aqueous layer extracted with diethyl ether, merges organic layer, dry, steams solvent and obtains imazalil product.
CN201510061742.XA 2015-02-06 2015-02-06 Preparation method for imazalil Pending CN104610155A (en)

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104876873A (en) * 2015-05-22 2015-09-02 池州中瑞化工有限公司 Synthetic method of enilconazole
CN110437154A (en) * 2019-09-10 2019-11-12 武汉川泰科技有限公司 A kind of preparation method of enilconazole bulk pharmaceutical chemicals
CN110845416A (en) * 2019-11-19 2020-02-28 武汉回盛生物科技股份有限公司 O-allylation method of α -diaryl substituted ethanol
CN111187216A (en) * 2020-03-23 2020-05-22 徐州工业职业技术学院 Method for synthesizing imidazole ethanol by continuous method
CN111789120A (en) * 2020-07-29 2020-10-20 湖南省植物保护研究所 Bactericide imazalil ionic liquid, and preparation method and application thereof
CN115028586A (en) * 2022-06-27 2022-09-09 池州中瑞化工有限公司 Preparation method of chiral (S) -imazalil
CN115433132A (en) * 2022-10-20 2022-12-06 武汉回盛生物科技股份有限公司 A kind of enconazole crystal form, preparation method and application
CN116082245A (en) * 2022-12-26 2023-05-09 武汉工程大学 Enconazole crystal and preparation method and application thereof
CN116606255A (en) * 2023-05-18 2023-08-18 上海农帆生物科技有限公司 Preparation method of imazalil
CN118792003A (en) * 2024-09-14 2024-10-18 江苏斯瑞达材料技术股份有限公司 Polyurethane/epoxy resin thermosetting insulating adhesive and preparation method thereof

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CN101519403A (en) * 2009-04-08 2009-09-02 广东工业大学 Method for synthesis tioconazole

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104876873A (en) * 2015-05-22 2015-09-02 池州中瑞化工有限公司 Synthetic method of enilconazole
CN110437154A (en) * 2019-09-10 2019-11-12 武汉川泰科技有限公司 A kind of preparation method of enilconazole bulk pharmaceutical chemicals
CN110845416A (en) * 2019-11-19 2020-02-28 武汉回盛生物科技股份有限公司 O-allylation method of α -diaryl substituted ethanol
CN111187216A (en) * 2020-03-23 2020-05-22 徐州工业职业技术学院 Method for synthesizing imidazole ethanol by continuous method
CN111789120A (en) * 2020-07-29 2020-10-20 湖南省植物保护研究所 Bactericide imazalil ionic liquid, and preparation method and application thereof
CN111789120B (en) * 2020-07-29 2022-04-01 湖南省植物保护研究所 Bactericide imazalil ionic liquid, and preparation method and application thereof
CN115028586A (en) * 2022-06-27 2022-09-09 池州中瑞化工有限公司 Preparation method of chiral (S) -imazalil
CN115433132A (en) * 2022-10-20 2022-12-06 武汉回盛生物科技股份有限公司 A kind of enconazole crystal form, preparation method and application
CN116082245A (en) * 2022-12-26 2023-05-09 武汉工程大学 Enconazole crystal and preparation method and application thereof
CN116606255A (en) * 2023-05-18 2023-08-18 上海农帆生物科技有限公司 Preparation method of imazalil
CN118792003A (en) * 2024-09-14 2024-10-18 江苏斯瑞达材料技术股份有限公司 Polyurethane/epoxy resin thermosetting insulating adhesive and preparation method thereof
CN118792003B (en) * 2024-09-14 2025-02-11 江苏斯瑞达材料技术股份有限公司 Polyurethane/epoxy resin thermosetting insulating adhesive and preparation method thereof

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Application publication date: 20150513