CN101565406B - Preparation process for cyproconazole - Google Patents
Preparation process for cyproconazole Download PDFInfo
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- CN101565406B CN101565406B CN2009100313448A CN200910031344A CN101565406B CN 101565406 B CN101565406 B CN 101565406B CN 2009100313448 A CN2009100313448 A CN 2009100313448A CN 200910031344 A CN200910031344 A CN 200910031344A CN 101565406 B CN101565406 B CN 101565406B
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- cyproconazole
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- cyclopropyl
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- UFNOUKDBUJZYDE-UHFFFAOYSA-N 2-(4-chlorophenyl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol Chemical compound C1=NC=NN1CC(O)(C=1C=CC(Cl)=CC=1)C(C)C1CC1 UFNOUKDBUJZYDE-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 239000005757 Cyproconazole Substances 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000000047 product Substances 0.000 claims abstract description 12
- 239000012043 crude product Substances 0.000 claims abstract description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000005864 Sulphur Substances 0.000 claims abstract description 8
- 238000006735 epoxidation reaction Methods 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 6
- 238000001035 drying Methods 0.000 claims abstract description 5
- 239000003054 catalyst Substances 0.000 claims abstract description 3
- 238000001914 filtration Methods 0.000 claims abstract description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 25
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- 238000005516 engineering process Methods 0.000 claims description 11
- 150000003568 thioethers Chemical class 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 9
- 239000011707 mineral Substances 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000002798 polar solvent Substances 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 238000006482 condensation reaction Methods 0.000 claims description 6
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 claims description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 238000007670 refining Methods 0.000 claims description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 3
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 3
- -1 1-cyclopropyl ethyl Chemical group 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 abstract description 5
- 238000005406 washing Methods 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 abstract 2
- 239000003960 organic solvent Substances 0.000 abstract 2
- QKTOXOPFYCOLPV-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-(1-cyclopropylethyl)oxirane Chemical compound C1OC1(C=1C=CC(Cl)=CC=1)C(C)C1CC1 QKTOXOPFYCOLPV-UHFFFAOYSA-N 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000004807 desolvation Methods 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 150000007522 mineralic acids Chemical class 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 239000003899 bactericide agent Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000005451 methyl sulfates Chemical class 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 229930182558 Sterol Natural products 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 238000010977 unit operation Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention discloses a preparation process for high-purity cyproconazole, which comprises the following steps that: 1-(4-chlorphenyl)-2-cyclopropyl-1-acetone is taken as a raw material which performs an epoxidation reaction with a sulphur Fourier agent in a weak polarity organic solvent in the presence of alkali; the mixture is subjected to washing and desolvation to obtain 2-(4-chlorphenyl)-2-(1-cyclopropyl ethyl)epoxy ethane which is condensed and desolventized with 1,2,4-triazole in the presence of a catalyst to obtain a crude product; the crude product is directly dissolved into an organic solvent without processing, and the mixture reacts with inorganic acid by heating to generate salts of the cyproconazole; the salts of the cyproconazole are filtered and washed to obtain a salt; and the salt is dried and heated in a ceratin amount of water for deacidifying, and then the salt is subjected to filtration, washing and drying to obtain a finished product with high content and yield. The process is not only economical and environment-friendly, but also has the advantages of high purity and yield of the product, no need of recrystalization for a plurality of times, safe operation, convenience and the like.
Description
Technical field
The present invention relates to a kind of preparation technology of agricultural chemicals cyproconazole.
Background technology
Cyproconazole: (2RS, 3RS, )-2-(4-chloro-phenyl-)-3-cyclopropyl-1-(1H-1,2, the 4-triazol-1-yl) fourth-2-alcohol (hereinafter to be referred as I) is a kind of important triazole bactericidal agent, be sterol demethylation inhibitor, have prevention and therapeutic action, the foliar treatment and the seed that are used for important cash crop spray.
Its structural formula is:
Major impurity is in the synthetic cyproconazole: (2RS, 3RS, )-2-(4-chloro-phenyl-)-3-cyclopropyl-1-(1H-1,3, the 4-triazol-1-yl) fourth-2-alcohol (hereinafter to be referred as II), because (I) He (II) character is close, carrying out simple recrystallization with general solvent is difficult to separate, so general crude product purity has only about 70-80%, and the same viscosity with syrup is very big, be difficult to solidify.Because 1,2,1 bit substituent derivative just has fungicidal activity in the 4-triazole bactericidal agent, so we should control the generation of other position derivative in building-up process as far as possible, improves the quality of products the purpose that reduces production costs so that reach.
The synthesis technique of cyproconazole is U.S. Pat 4664696 (1987), German patent DE 3406993 (1984) and " modern agricultural chemicals " 2004 the 3rd the 4th phases of volume (author: all done comparatively detailed description trip south China), the consumption of but above-mentioned several pieces of documents sulphur Li Yede reagent when epoxidation reaction is all very big, contaminate environment not only, and yield is low, seems very uneconomical.A large amount of Anhydrous potassium carbonate catalysis have been used during condensation reaction, bring many troubles to aftertreatment, especially nearly all used silicagel column to carry out chromatographic separation during final refining, carry out the product that recrystallization has just obtained 95% above content with solvent again, so not only waste time and energy, and seriously having limited the industrial scale of this product, cost is high especially.
Summary of the invention
Technical problem to be solved by this invention is the defective that overcomes above-mentioned prior art, and the industrial preparation process of a kind of product purity height, yield height, cost is low and unit operation is more simple and safe cyproconazole is provided.
Technical conceive of the present invention is as follows: 1,2, and the 4-triazole has two kinds of isomer, 1H-1,2,4-triazole (hereinafter to be referred as IV) and 4H-1,2,4-triazole (hereinafter to be referred as V), wherein IV is comparatively stable, is main isomer; We select to have the generation that good optionally catalyzer is controlled II as far as possible in reaction process.We find when refining in the back, I and II can generate salt with many mineral acids and some organic acid, the salt less stable of II, and these two kinds of salt solubleness in some specific solvent has very big difference, the purpose that we utilize the nature difference of their salt to reach separation and purify just.
The concrete technical scheme that the present invention adopts is: the preparation technology of described cyproconazole comprises the steps:
(1) epoxidation reaction
Select for use in thioether, benzene, toluene or the hexanaphthene any for solvent, with 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone is raw material, with sulphur Li Yede reagent epoxidation reaction takes place in the presence of alkali, reaction is after wash and slough 2-(4-chloro-phenyl-)-2-(the 1-cyclopropyl ethyl) oxyethane that obtains behind the solvent;
Wherein: the configuration of sulphur Li Yede reagent is disposed in the presence of the trimethyl carbinol or isopropylcarbinol by thioether and methyl-sulfate and is formed, and the mol ratio of thioether and methyl-sulfate is 1.0～2.5: 1; The consumption of solvent is 1～4 times of 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone weight, and the mol ratio of sulphur Li Yede reagent and 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone is 1.0～3.6: 1; The mole proportioning of alkali and methyl-sulfate is 2.0～5.2: 1;
(2) condensation reaction
2-(4-chloro-phenyl-)-2-(1-cyclopropyl ethyl) oxyethane that step () is obtained is in polar solvent, controlled temperature is 70～120 ℃, in the presence of catalyzer with 1,2, the 4-triazole carries out condensation reaction, obtains the cyproconazole crude product after the reaction again after sloughing solvent;
Wherein: polar solvent is selected from N, dinethylformamide, N, in N-N,N-DIMETHYLACETAMIDE, N-Methyl pyrrolidone or the dimethyl sulfoxide (DMSO) any, the consumption of polar solvent are 2～5 times of weight of 2-(4-chloro-phenyl-)-2-(1-cyclopropyl ethyl) oxyethane; Catalyzer is selected from any one in potassium hydroxide, sodium hydroxide, sodium methylate or the sodium ethylate, and catalyst consumption is 0.05～0.3 times of 2-(4-chloro-phenyl-)-2-(1-cyclopropyl ethyl) oxyethane weight; 1,2, the consumption of 4-triazole is 1.0～3.5 molar equivalents of 2-(4-chloro-phenyl-)-2-(1-cyclopropyl ethyl) oxyethane;
(3) salify
The cyproconazole crude product that step (two) is obtained is dissolved in second solvent, and adds mineral acid, finally obtains the salt of cyproconazole;
Wherein: second solvent is selected from a kind of in methylene dichloride, ethylene dichloride or the chloroform, and the consumption of second solvent is 2～4 times of cyproconazole crude product weight; Mineral acid is selected from any in sulfuric acid, hydrochloric acid, phosphoric acid or the nitric acid, and the consumption of mineral acid is 1.0～3.0 molar equivalents of cyproconazole crude product;
(4) refining
The salt of the cyproconazole that step (three) is obtained adds depickling behind the water, and temperature is controlled at 40～90 ℃, at last after filtration, obtain the cyproconazole finished product after the drying.
Epoxidation reaction temperature is 10～50 ℃ in the above-mentioned steps (), and the reaction times can be 5～30 hours, and the preferred thioether of described solvent, described alkali are potassium hydroxide.
Polar solvent in the above-mentioned steps (two) is preferably N, dinethylformamide, and catalyzer is preferably potassium hydroxide.The time of condensation reaction can be 3～12 hours.Setting-up point is preferably 80～90 ℃.
The preferred hydrochloric acid of mineral acid in the above-mentioned steps (three), preferred ethylene dichloride of second solvent or chloroform; The temperature of salification process is 0～70 ℃, is preferably 50～65 ℃.Salt time can be 2～3 hours.
The weight of the water in the above-mentioned steps (four) is preferably 3～4 times of weight of the salt of cyproconazole.The depickling temperature is 40～90 ℃ in the step (four), and the time is 3～7 hours.
The invention has the beneficial effects as follows: the product purity height, content is more than 97% basically; The yield height, total molar yield about 80%; Product color is good, need not carry out silicagel column purifying, repeatedly recrystallization; Easy to operate and safe, environmental pollution is little, is more suitable for suitability for industrialized production.
Embodiment
The present invention is described further below in conjunction with specific embodiment, but the present invention should not only limit to these embodiment.
Embodiment one
In 500 milliliters of there-necked flasks, add thioether 250 grams, drip the 30 gram trimethyl carbinols, stir then, temperature is added dropwise to 50 gram methyl-sulfates in keeping below 35 ℃, finish, stirred 4 hours, add 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone 75 grams then, potassium hydroxide 50 grams are kept about 40 ℃ and were stirred 20 hours, and the sampling analysis raw material should be below 1%, reaction solution is poured in the cold water, stirring and dissolving is complete, static layering, and organic layer washs neutrality with suitable quantity of water, elder generation's normal pressure precipitation, low-boiling point material is taken off in decompression again, obtains about 2-(4-chloro-phenyl-)-2-(1-cyclopropyl ethyl) oxyethane 82 grams content 90% (chromatogram ration analysis, external standard method).
Above-mentioned 2-(4-chloro-phenyl-)-2-(1-cyclopropyl ethyl) oxyethane 82 grams are dissolved into 205 gram exsiccant N, in dinethylformamide (the being called for short DMF) solvent, add 1,2,4-triazole 32 grams, potassium hydroxide powder 7 grams are kept then about 85 ℃ and were stirred 4-5 hour, the sampling analysis raw material is below 3%, stop to stir, filter, then vacuum distillation recovered solvent, remaining object adds chloroform 200 grams, be heated to 50-55 ℃ of dissolving fully, keep the concentrated hydrochloric acid that this temperature drips 40 grams 35% then, dropwised in about 1 hour, stirred then 2 hours, cooling is filtered, the minimum of chloroform washing, drying obtains cyproconazole hydrochloride 92 grams.
Above-mentioned cyproconazole hydrochloride 88 grams add 330 gram distilled water, are heated to 80 ℃ then and stir 3 hours, and cooling is filtered, and filter cake washes neutrality with water, and 60 ℃ of vacuum-dryings obtain 82 gram cyproconazole finished products, white solid, content 97.5%.
Implementation column 2:
In 1000 milliliters of there-necked flasks, add thioether 375 grams, drip 30 gram isopropylcarbinols, stir then, temperature is added dropwise to 75 gram methyl-sulfates in keeping below 25 ℃, finishes, stirred 4 hours, add 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone 112 grams then, potassium hydroxide 80 grams are kept about 40 ℃ and were stirred 20 hours, the sampling analysis raw material should be below 1%, reaction solution is poured in the cold water, and stirring and dissolving is complete, static layering, organic layer washs neutrality with suitable quantity of water, elder generation's normal pressure precipitation, low-boiling point material is taken off in decompression again, obtains about 2-(4-chloro-phenyl-)-2-(1-cyclopropyl ethyl) oxyethane 126 grams, content 91.5% (GC, normalization method).
Above-mentioned 2-(4-chloro-phenyl-)-2-(1-cyclopropyl ethyl) oxyethane 126 grams are dissolved into 373 gram exsiccant N, in dinethylformamide (the being called for short DMF) solvent, add 1,2,4-triazole 49 grams, potassium hydroxide powder 7 grams are kept then about 90 ℃ and were stirred 4 hours, the sampling analysis raw material is below 3%, stop to stir, filter, then vacuum distillation recovered solvent, remaining object adds chloroform 335 grams, be heated to 50-55 ℃ of dissolving fully, keep the concentrated hydrochloric acid that this temperature drips 63 grams 35% then, dropwised in about 1 hour, stirred then 2 hours, cooling is filtered, the minimum of chloroform washing, drying obtains cyproconazole hydrochloride 140 grams.
Above-mentioned cyproconazole hydrochloride 140 grams add 560 gram distilled water, are heated to 85 ℃ then and stir 3 hours, and cooling is filtered, and filter cake washes neutrality with water, and 60 ℃ of vacuum-dryings obtain 125 gram cyproconazole finished products, white solid, content 97.2%.
Claims (7)
1. the preparation technology of cyproconazole is characterized in that: comprise the steps:
(1) epoxidation reaction
Select for use in thioether, benzene, toluene or the hexanaphthene any for solvent, with 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone is raw material, with sulphur Li Yede reagent epoxidation reaction takes place in the presence of alkali, reaction is after wash and slough 2-(4-chloro-phenyl-)-2-(the 1-cyclopropyl ethyl) oxyethane that obtains behind the solvent;
Wherein: the configuration of sulphur Li Yede reagent is disposed in the presence of the trimethyl carbinol or isopropylcarbinol by thioether and methyl-sulfate and is formed, and the mol ratio of thioether and methyl-sulfate is 1.0～2.5: 1; The consumption of solvent is 1～4 times of 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone weight, and the mol ratio of sulphur Li Yede reagent and 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone is 1.0～3.6: 1; The mole proportioning of alkali and methyl-sulfate is 2.0～5.2: 1;
(2) condensation reaction
2-(4-chloro-phenyl-)-2-(1-cyclopropyl ethyl) oxyethane that step () is obtained is in polar solvent, controlled temperature is 70～120 ℃, in the presence of catalyzer with 1,2, the 4-triazole carries out condensation reaction, and reaction is after obtain the cyproconazole crude product after sloughing solvent;
Wherein: polar solvent is selected from N, dinethylformamide, N, in N-N,N-DIMETHYLACETAMIDE, N-Methyl pyrrolidone or the dimethyl sulfoxide (DMSO) any, the consumption of polar solvent are 2～5 times of weight of 2-(4-chloro-phenyl-)-2-(1-cyclopropyl ethyl) oxyethane; Catalyzer is selected from any one in potassium hydroxide, sodium hydroxide, sodium methylate or the sodium ethylate, and catalyst consumption is 0.05～0.3 times of 2-(4-chloro-phenyl-)-2-(1-cyclopropyl ethyl) oxyethane weight; 1,2, the consumption of 4-triazole is 1.0～3.5 molar equivalents of 2-(4-chloro-phenyl-)-2-(1-cyclopropyl ethyl) oxyethane;
(3) salify
The cyproconazole crude product that step (two) is obtained is dissolved in second solvent, and adds mineral acid, finally obtains the salt of cyproconazole;
Wherein: second solvent is selected from a kind of in methylene dichloride, ethylene dichloride or the chloroform, and the consumption of second solvent is 2～4 times of cyproconazole crude product weight; Mineral acid is selected from any in sulfuric acid, hydrochloric acid, phosphoric acid or the nitric acid, and the consumption of mineral acid is 1.0～3.0 molar equivalents of cyproconazole crude product;
(4) refining
The salt of the cyproconazole that step (three) is obtained adds depickling behind the water, and temperature is controlled at 40～90 ℃, at last after filtration, obtain the cyproconazole finished product after the drying.
2. the preparation technology of cyproconazole according to claim 1 is characterized in that: epoxidation reaction temperature is 10～50 ℃ in the step (), and the preferred thioether of described solvent, described alkali are potassium hydroxide.
3. the preparation technology of cyproconazole according to claim 1, it is characterized in that: the polar solvent in the step (two) is preferably N, dinethylformamide, catalyzer is preferably potassium hydroxide.
4. the preparation technology of cyproconazole according to claim 1 is characterized in that: the preferred hydrochloric acid of mineral acid in the step (three), preferred ethylene dichloride of second solvent or chloroform; The temperature of salification process is 0～70 ℃.
5. the preparation technology of cyproconazole according to claim 1 is characterized in that: the weight of the water in the step (four) is preferably 3～4 times of weight of the salt of cyproconazole.
6. the preparation technology of cyproconazole according to claim 1 or 5, it is characterized in that: the depickling temperature is 40～90 ℃ in the step (four), and the time is 3～7 hours.
7. the preparation technology of cyproconazole according to claim 4, it is characterized in that: the temperature of step (three) salification process is 50～65 ℃.
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| US10981883B2 (en) * | 2013-01-09 | 2021-04-20 | BASF Agro B.V. | Process for the preparation of substituted oxiranes and triazoles |
| WO2021123935A1 (en) * | 2019-12-16 | 2021-06-24 | Coromandel International Limited | An improved process for preparation of an azole fungicide |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101798290B (en) * | 2010-04-02 | 2012-03-07 | 北京欧凯纳斯科技有限公司 | Method for synthesizing chiral cyproconazole |
| CN101857576B (en) * | 2010-06-18 | 2012-07-25 | 中国科学院上海有机化学研究所 | Method for preparing cyproconazole by cyclopropyl methyl ketone |
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