CN112574125A - Method for improving conversion rate of azoxystrobin - Google Patents
Method for improving conversion rate of azoxystrobin Download PDFInfo
- Publication number
- CN112574125A CN112574125A CN202011392157.5A CN202011392157A CN112574125A CN 112574125 A CN112574125 A CN 112574125A CN 202011392157 A CN202011392157 A CN 202011392157A CN 112574125 A CN112574125 A CN 112574125A
- Authority
- CN
- China
- Prior art keywords
- azoxystrobin
- reaction
- filtering
- preparing
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000006243 chemical reaction Methods 0.000 title claims abstract description 61
- 239000005730 Azoxystrobin Substances 0.000 title claims abstract description 41
- WFDXOXNFNRHQEC-GHRIWEEISA-N azoxystrobin Chemical compound CO\C=C(\C(=O)OC)C1=CC=CC=C1OC1=CC(OC=2C(=CC=CC=2)C#N)=NC=N1 WFDXOXNFNRHQEC-GHRIWEEISA-N 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims abstract description 34
- 238000001914 filtration Methods 0.000 claims abstract description 41
- 238000001035 drying Methods 0.000 claims abstract description 26
- CHZCERSEMVWNHL-UHFFFAOYSA-N 2-hydroxybenzonitrile Chemical compound OC1=CC=CC=C1C#N CHZCERSEMVWNHL-UHFFFAOYSA-N 0.000 claims abstract description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000002994 raw material Substances 0.000 claims abstract description 16
- 238000005406 washing Methods 0.000 claims abstract description 16
- YRYZZSRRDCTETP-DHZHZOJOSA-N methyl (e)-2-[2-(6-chloropyrimidin-4-yl)oxyphenyl]-3-methoxyprop-2-enoate Chemical compound CO\C=C(\C(=O)OC)C1=CC=CC=C1OC1=CC(Cl)=NC=N1 YRYZZSRRDCTETP-DHZHZOJOSA-N 0.000 claims abstract description 14
- 238000002156 mixing Methods 0.000 claims abstract description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 12
- 238000001816 cooling Methods 0.000 claims abstract description 11
- -1 6-chloropyrimidin-4-yloxy Chemical group 0.000 claims abstract description 8
- BAPJBEWLBFYGME-UHFFFAOYSA-N acrylic acid methyl ester Natural products COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
- 239000013078 crystal Substances 0.000 claims abstract description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 claims abstract description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 22
- 239000000243 solution Substances 0.000 claims description 22
- 239000007864 aqueous solution Substances 0.000 claims description 21
- 238000010438 heat treatment Methods 0.000 claims description 20
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 claims description 14
- ACZGCWSMSTYWDQ-UHFFFAOYSA-N 3h-1-benzofuran-2-one Chemical compound C1=CC=C2OC(=O)CC2=C1 ACZGCWSMSTYWDQ-UHFFFAOYSA-N 0.000 claims description 12
- ORIHZIZPTZTNCU-YVMONPNESA-N salicylaldoxime Chemical compound O\N=C/C1=CC=CC=C1O ORIHZIZPTZTNCU-YVMONPNESA-N 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 10
- 239000007795 chemical reaction product Substances 0.000 claims description 10
- 239000000706 filtrate Substances 0.000 claims description 10
- 229910052751 metal Inorganic materials 0.000 claims description 10
- 239000002184 metal Substances 0.000 claims description 10
- 239000011259 mixed solution Substances 0.000 claims description 10
- 239000000047 product Substances 0.000 claims description 10
- 230000035484 reaction time Effects 0.000 claims description 10
- 229910052708 sodium Inorganic materials 0.000 claims description 10
- 239000011734 sodium Substances 0.000 claims description 10
- 229940017219 methyl propionate Drugs 0.000 claims description 9
- YDHPXCHZYXPZIS-VURMDHGXSA-N (3z)-3-(methoxymethylidene)-1-benzofuran-2-one Chemical compound C1=CC=C2C(=C/OC)/C(=O)OC2=C1 YDHPXCHZYXPZIS-VURMDHGXSA-N 0.000 claims description 8
- IUJAAIZKRJJZGQ-UHFFFAOYSA-N 2-(2-chlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1Cl IUJAAIZKRJJZGQ-UHFFFAOYSA-N 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 6
- XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 claims description 5
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 claims description 5
- 239000005751 Copper oxide Substances 0.000 claims description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 5
- 238000007259 addition reaction Methods 0.000 claims description 5
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 5
- 229910000431 copper oxide Inorganic materials 0.000 claims description 5
- 150000002148 esters Chemical group 0.000 claims description 5
- 230000001376 precipitating effect Effects 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
- 150000008065 acid anhydrides Chemical class 0.000 claims description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical class [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 claims description 4
- XXLKCUTUGWSJJO-UHFFFAOYSA-N (2-cyanophenyl) acetate Chemical compound CC(=O)OC1=CC=CC=C1C#N XXLKCUTUGWSJJO-UHFFFAOYSA-N 0.000 claims description 3
- NBVPQDYEDMAMFR-UHFFFAOYSA-N 3-methyl-3h-1-benzofuran-2-one Chemical compound C1=CC=C2C(C)C(=O)OC2=C1 NBVPQDYEDMAMFR-UHFFFAOYSA-N 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000004821 distillation Methods 0.000 abstract 1
- 238000001556 precipitation Methods 0.000 abstract 1
- 150000002825 nitriles Chemical class 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 241000221785 Erysiphales Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 241000233679 Peronosporaceae Species 0.000 description 1
- 229930182692 Strobilurin Natural products 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for improving the conversion rate of azoxystrobin, which comprises the following steps: preparing (E) -methyl 2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate; preparing o-hydroxybenzonitrile; reacting (E) -methyl 2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate, o-hydroxybenzonitrile, potassium carbonate and chlorosulfine in the ratio of 30: 35: 50: 1.1, mixing and dissolving in dimethylformamide to obtain a mixed product; the prepared mixed product is heated and kept warm, then filtered, and subjected to reduced pressure distillation, cooling, crystal precipitation, filtering washing and drying to prepare the azoxystrobin, and on the basis of the prior art, the synthesis of the azoxystrobin is improved, so that the yield of the azoxystrobin is effectively improved, the conversion rates of raw materials (E) -2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxy methyl acrylate and o-hydroxybenzonitrile of the azoxystrobin in the process of preparing the azoxystrobin are effectively improved, and the production benefit of the azoxystrobin is improved.
Description
Technical Field
The invention relates to the technical field of bactericide synthesis, in particular to a method for improving the conversion rate of azoxystrobin.
Background
Azoxystrobin is a strobilurin fungicide, has good activity on almost all fungal diseases such as powdery mildew, rust disease, glume blight, net blotch, downy mildew, rice blast and the like, and has the problems of low yield and harsh reaction conditions in the existing azoxystrobin synthesis method.
Disclosure of Invention
The invention provides a method for improving the conversion rate of azoxystrobin, aiming at solving the problems that the conversion rate of azoxystrobin is low and the reaction conditions are harsh in the prior art.
A method for increasing azoxystrobin conversion rate, comprising the following steps:
preparing (E) -methyl 2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate;
preparing o-hydroxybenzonitrile;
reacting (E) -methyl 2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate, o-hydroxybenzonitrile, potassium carbonate and chlorosulfine in the ratio of 30: 35: 50: 1.1, mixing and dissolving in dimethylformamide to obtain a mixed product;
heating and preserving heat of the prepared mixed product, filtering, distilling under reduced pressure, cooling, precipitating crystals, filtering, washing and drying to obtain the azoxystrobin.
Wherein the preparation of (E) -methyl 2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate comprises the following steps:
preparing benzofuran-2 (3H) -ketone by taking o-chlorophenylacetic acid as a raw material according to preset steps;
mixing benzofuran-2 (3H) -one with trimethyl orthoformate, heating, concentrating under reduced pressure, cooling, and filtering to obtain 3- (alpha-methoxy) methyl benzofuran-2 (3H) -one;
taking a methanol solution prepared by dissolving 3- (alpha-methoxy) methylene benzofuran-2 (3H) -ketone and metal sodium in methanol as raw materials, and preparing 3, 3-dimethoxy-2- (2-hydroxyphenyl) methyl propionate by ester exchange reaction and addition reaction of carbon-carbon double bonds under a preset process condition;
mixing 3, 3-dimethoxy-2- (2-hydroxyphenyl) methyl propionate and 4, 6-dichloropyrimidine, heating, filtering, washing, drying, filtering again, desolventizing, redissolving, filtering again, and drying again to obtain (E) -2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxy methyl acrylate.
Wherein the presetting step comprises the following steps:
preparing a sodium hydroxide aqueous solution;
putting o-chlorophenylacetic acid, a sodium hydroxide aqueous solution and copper oxide into a high-pressure kettle for reaction to prepare a reaction solution;
regulating the pH value of the reaction solution to 7 by using hydrochloric acid, filtering, drying, recovering, concentrating the filtrate, and adding toluene to prepare a mixed solution;
heating the mixed solution, and dropwise adding concentrated sulfuric acid until the reaction is completed to obtain a reaction product;
filtering the reaction product, washing the filtrate with saturated sodium bicarbonate water solution, drying with anhydrous magnesium sulfate, and desolventizing to obtain the benzofuran-2 (3H) -ketone.
Wherein the preset conditions are as follows: benzofuran-2 (3H) -one: trimethyl orthoformate: the molar ratio of acetic anhydride is 1: 2: 4, the reaction temperature is 100 ℃, and the reaction time is 12 h.
Wherein the predetermined process conditions are as follows: 3- (α -methoxy) methylenebenzofuran-2 (3H) -one: the molar ratio of the metal sodium is 1: 2, the reaction temperature is 0 ℃, and the reaction time is 1 h.
Wherein, the preparation of the o-hydroxybenzonitrile comprises the following steps:
taking salicylaldehyde as a raw material, and reacting the salicylaldehyde with a hydroxylamine hydrochloride aqueous solution to synthesize salicylaldoxime;
dehydrating and condensing salicylaldoxime and acid anhydride to obtain acetylsalicylonitrile;
acetylsalicylanitrile is hydrolyzed to synthesize o-hydroxybenzonitrile.
Wherein the concentration of the hydroxylamine hydrochloride aqueous solution is 20-60%.
Wherein the anhydride is acetic anhydride.
The invention has the beneficial effects that: on the basis of the prior art, the synthesis of the azoxystrobin is improved, so that the yield of the azoxystrobin is effectively improved, the conversion rates of raw materials (E) -2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxy methyl acrylate and o-hydroxybenzonitrile of the azoxystrobin in the process of preparing the azoxystrobin are effectively improved, and the production benefit of the azoxystrobin is improved.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a flow chart of the process steps of a method of the present invention for increasing azoxystrobin conversion.
FIG. 2 is a flow chart of the process steps for preparing (E) -methyl 2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate by the method for improving the conversion rate of azoxystrobin in the present invention.
FIG. 3 is a flow chart of the process steps for preparing benzofuran-2 (3H) -one according to a method of the present invention for increasing azoxystrobin conversion.
FIG. 4 is a flow chart of the process steps for preparing o-hydroxybenzonitrile by the method for improving the azoxystrobin conversion rate of the invention.
FIG. 5 is a flow chart of the process steps for preparing acetylsalicylic nitrile according to the method for increasing azoxystrobin conversion.
Detailed Description
Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout. The embodiments described below with reference to the drawings are illustrative and intended to be illustrative of the invention and are not to be construed as limiting the invention.
In the description of the present invention, it is to be understood that the terms "length", "width", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", and the like, indicate orientations or positional relationships based on the orientations or positional relationships illustrated in the drawings, and are used merely for convenience in describing the present invention and for simplicity in description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed in a particular orientation, and be operated, and thus, are not to be construed as limiting the present invention. Further, in the description of the present invention, "a plurality" means two or more unless specifically defined otherwise.
Referring to fig. 1 to 5, the present invention provides a technical solution:
a method for increasing azoxystrobin conversion rate, comprising the following steps:
s101, preparing (E) -methyl 2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate;
s102, preparing o-hydroxybenzonitrile;
s103 reacting (E) -methyl 2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate, o-hydroxybenzonitrile, potassium carbonate and chloroylidene ketone in a molar ratio of 30: 35: 50: 1.1, mixing and dissolving in dimethylformamide to obtain a mixed product;
s104, heating the prepared mixed product, preserving heat, filtering, distilling under reduced pressure, cooling, precipitating crystals, filtering, washing and drying to obtain the azoxystrobin.
Further, the preparation of (E) -methyl 2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate comprises the following steps:
s201, preparing benzofuran-2 (3H) -ketone by taking o-chlorophenylacetic acid as a raw material according to preset steps;
s202, mixing benzofuran-2 (3H) -one with trimethyl orthoformate, heating, concentrating under reduced pressure, cooling, and filtering under preset conditions to obtain 3- (alpha-methoxy) methylene benzofuran-2 (3H) -one;
s203, using a methanol solution prepared by dissolving 3- (alpha-methoxy) methyl benzofuran-2 (3H) -ketone and metal sodium in methanol as a raw material, and preparing methyl 3, 3-dimethoxy-2- (2-hydroxyphenyl) propionate through an ester exchange reaction and an addition reaction of carbon-carbon double bonds under a preset process condition;
s204, mixing 3, 3-dimethoxy-2- (2-hydroxyphenyl) methyl propionate and 4, 6-dichloropyrimidine, heating, filtering, washing, drying, filtering again, desolventizing, redissolving, filtering again, and drying again to obtain (E) -2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxy methyl acrylate.
Further, the presetting step comprises the following steps:
s301, preparing a sodium hydroxide aqueous solution;
s302, putting o-chlorophenylacetic acid, a sodium hydroxide aqueous solution and copper oxide into a high-pressure kettle for reaction to prepare a reaction solution;
s303, adjusting the pH value of the reaction solution to 7 by using hydrochloric acid, filtering, drying, recovering, concentrating the filtrate, and adding toluene to prepare a mixed solution;
s304, heating the mixed solution, and dropwise adding concentrated sulfuric acid until the reaction is completed to obtain a reaction product;
s305, filtering the reaction product, washing the filtrate with saturated aqueous sodium bicarbonate solution, drying with anhydrous magnesium sulfate, and desolventizing to obtain the benzofuran-2 (3H) -one.
Further, the preset conditions are as follows: benzofuran-2 (3H) -one: trimethyl orthoformate: the molar ratio of acetic anhydride is 1: 2: 4, the reaction temperature is 100 ℃, and the reaction time is 12 h.
Further, the predetermined process conditions are as follows: 3- (α -methoxy) methylenebenzofuran-2 (3H) -one: the molar ratio of the metal sodium is 1: 2, the reaction temperature is 0 ℃, and the reaction time is 1 h.
Further, the preparation of the o-hydroxybenzonitrile comprises the following steps:
s401, reacting salicylaldehyde serving as a raw material with a hydroxylamine hydrochloride aqueous solution to synthesize salicylaldoxime;
s402, dehydrating and condensing salicylaldoxime and acid anhydride to obtain acetylsalicylonitrile;
s403 hydrolyzes acetylsalicylic nitrile to synthesize o-hydroxybenzonitrile.
Further, the concentration of the hydroxylamine hydrochloride aqueous solution is 20-60%.
Further, the acid anhydride is acetic anhydride.
Further, the dehydration condensation comprises the following steps:
s501, adding acetic anhydride accounting for 110-160% of the total weight of the hydroxylamine hydrochloride aqueous solution into salicylaldoxime;
and S502, reacting for 2-5 hours at a preset temperature, and desolventizing to obtain the acetylsalicylic nitrile.
Further, the preset temperature is 120-160 ℃.
Specific example 1:
preparing a sodium hydroxide aqueous solution, putting o-chlorophenylacetic acid, the sodium hydroxide aqueous solution and copper oxide into an autoclave for reaction to prepare a reaction solution, adjusting the pH value of the reaction solution to 7 by using hydrochloric acid, filtering, drying, recovering, concentrating the filtrate, and then adding toluene to prepare a mixed solution; heating the mixed solution, and dropwise adding concentrated sulfuric acid until the reaction is completed to obtain a reaction product; filtering the reaction product, washing the filtrate with saturated sodium bicarbonate water solution, drying with anhydrous magnesium sulfate, and desolventizing to obtain benzofuran-2 (3H) -one; reacting benzofuran-2 (3H) -one: trimethyl orthoformate: acetic anhydride is added according to a molar ratio of 1: 2: 4, reacting under the reaction condition that the reaction temperature is 100 ℃ and the reaction time is 12 hours, and obtaining the 3- (alpha-methoxy) methylene benzofuran-2 (3H) -ketone after heating, decompression, concentration, cooling and filtration; using a methanol solution prepared by dissolving 3- (alpha-methoxy) methylene benzofuran-2 (3H) -one and metal sodium in methanol as raw materials, wherein the ratio of 3- (alpha-methoxy) methylene benzofuran-2 (3H) -one: the molar ratio of the metal sodium is 1: 2, preparing 3, 3-dimethoxy-2- (2-hydroxyphenyl) methyl propionate by ester exchange reaction and addition reaction of carbon-carbon double bonds under the conditions that the reaction temperature is 0 ℃ and the reaction time is 1 h; mixing 3, 3-dimethoxy-2- (2-hydroxyphenyl) methyl propionate and 4, 6-dichloropyrimidine, heating, filtering, washing, drying, filtering again, desolventizing, redissolving, filtering again, and drying again to obtain (E) -2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxy methyl acrylate; salicylaldehyde is taken as a raw material and reacts with 20 percent of hydroxylamine hydrochloride aqueous solution to synthesize salicylaldoxime; adding acetic anhydride accounting for 110% of the total weight of the hydroxylamine hydrochloride aqueous solution into salicylaldoxime, reacting for 2 hours at 120 ℃, and desolventizing to obtain acetylsalicylic nitrile; hydrolyzing acetylsalicylanitrile to synthesize o-hydroxybenzonitrile, methyl (E) -2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate, o-hydroxybenzonitrile, potassium carbonate and chloroylidene ketone as 30: 35: 50: 1.1, mixing and dissolving in dimethylformamide to obtain a mixed product; heating and preserving heat of the prepared mixed product, filtering, distilling under reduced pressure, cooling, precipitating crystals, filtering, washing and drying to obtain the azoxystrobin.
Specific example 2:
preparing a sodium hydroxide aqueous solution, putting o-chlorophenylacetic acid, the sodium hydroxide aqueous solution and copper oxide into an autoclave for reaction to prepare a reaction solution, adjusting the pH value of the reaction solution to 7 by using hydrochloric acid, filtering, drying, recovering, concentrating the filtrate, and then adding toluene to prepare a mixed solution; heating the mixed solution, and dropwise adding concentrated sulfuric acid until the reaction is completed to obtain a reaction product; filtering the reaction product, washing the filtrate with saturated sodium bicarbonate water solution, drying with anhydrous magnesium sulfate, and desolventizing to obtain benzofuran-2 (3H) -one; reacting benzofuran-2 (3H) -one: trimethyl orthoformate: acetic anhydride is added according to a molar ratio of 1: 2: 4, reacting under the reaction condition that the reaction temperature is 100 ℃ and the reaction time is 12 hours, and obtaining the 3- (alpha-methoxy) methylene benzofuran-2 (3H) -ketone after heating, decompression, concentration, cooling and filtration; using a methanol solution prepared by dissolving 3- (alpha-methoxy) methylene benzofuran-2 (3H) -one and metal sodium in methanol as raw materials, wherein the ratio of 3- (alpha-methoxy) methylene benzofuran-2 (3H) -one: the molar ratio of the metal sodium is 1: 2, preparing 3, 3-dimethoxy-2- (2-hydroxyphenyl) methyl propionate by ester exchange reaction and addition reaction of carbon-carbon double bonds under the conditions that the reaction temperature is 0 ℃ and the reaction time is 1 h; mixing 3, 3-dimethoxy-2- (2-hydroxyphenyl) methyl propionate and 4, 6-dichloropyrimidine, heating, filtering, washing, drying, filtering again, desolventizing, redissolving, filtering again, and drying again to obtain (E) -2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxy methyl acrylate; salicylaldehyde is taken as a raw material and reacts with 20 percent of hydroxylamine hydrochloride aqueous solution to synthesize salicylaldoxime; adding acetic anhydride accounting for 160 percent of the total weight of the hydroxylamine hydrochloride aqueous solution into salicylaldoxime, reacting for 5 hours at 160 ℃, and desolventizing to obtain acetylsalicylic nitrile; hydrolyzing acetylsalicylanitrile to synthesize o-hydroxybenzonitrile, methyl (E) -2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate, o-hydroxybenzonitrile, potassium carbonate and chloroylidene ketone as 30: 35: 50: 1.1, mixing and dissolving in dimethylformamide to obtain a mixed product; heating and preserving heat of the prepared mixed product, filtering, distilling under reduced pressure, cooling, precipitating crystals, filtering, washing and drying to obtain the azoxystrobin.
By contrast, the yield of example 2 is higher, and the preferred reaction conditions can be selected.
According to the invention, on the basis of the prior art, the synthesis of the azoxystrobin is improved, so that the yield of the azoxystrobin is effectively improved, the conversion rates of raw materials (E) -2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxy methyl acrylate and o-hydroxybenzonitrile of the azoxystrobin in the process of preparing the azoxystrobin are effectively improved, and the production benefit of the azoxystrobin is improved.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (8)
1. A method for improving the conversion rate of azoxystrobin is characterized by comprising the following steps:
preparing (E) -methyl 2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate;
preparing o-hydroxybenzonitrile;
reacting (E) -methyl 2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate, o-hydroxybenzonitrile, potassium carbonate and chlorosulfine in the ratio of 30: 35: 50: 1.1, mixing and dissolving in dimethylformamide to obtain a mixed product;
heating and preserving heat of the prepared mixed product, filtering, distilling under reduced pressure, cooling, precipitating crystals, filtering, washing and drying to obtain the azoxystrobin.
2. The method for improving azoxystrobin conversion rate according to claim 1, wherein the preparation of methyl (E) -2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxyacrylate comprises the following steps:
preparing benzofuran-2 (3H) -ketone by taking o-chlorophenylacetic acid as a raw material according to preset steps;
mixing benzofuran-2 (3H) -one with trimethyl orthoformate, heating, concentrating under reduced pressure, cooling, and filtering to obtain 3- (alpha-methoxy) methyl benzofuran-2 (3H) -one;
taking a methanol solution prepared by dissolving 3- (alpha-methoxy) methylene benzofuran-2 (3H) -ketone and metal sodium in methanol as raw materials, and preparing 3, 3-dimethoxy-2- (2-hydroxyphenyl) methyl propionate by ester exchange reaction and addition reaction of carbon-carbon double bonds under a preset process condition;
mixing 3, 3-dimethoxy-2- (2-hydroxyphenyl) methyl propionate and 4, 6-dichloropyrimidine, heating, filtering, washing, drying, filtering again, desolventizing, redissolving, filtering again, and drying again to obtain (E) -2- [2- (6-chloropyrimidin-4-yloxy) phenyl ] -3-methoxy methyl acrylate.
3. The method of claim 2, wherein the pre-set step comprises the steps of:
preparing a sodium hydroxide aqueous solution;
putting o-chlorophenylacetic acid, a sodium hydroxide aqueous solution and copper oxide into a high-pressure kettle for reaction to prepare a reaction solution;
regulating the pH value of the reaction solution to 7 by using hydrochloric acid, filtering, drying, recovering, concentrating the filtrate, and adding toluene to prepare a mixed solution;
heating the mixed solution, and dropwise adding concentrated sulfuric acid until the reaction is completed to obtain a reaction product;
filtering the reaction product, washing the filtrate with saturated sodium bicarbonate water solution, drying with anhydrous magnesium sulfate, and desolventizing to obtain the benzofuran-2 (3H) -ketone.
4. The method for improving azoxystrobin conversion rate according to claim 2, wherein the preset conditions are as follows: benzofuran-2 (3H) -one: trimethyl orthoformate: the molar ratio of acetic anhydride is 1: 2: 4, the reaction temperature is 100 ℃, and the reaction time is 12 h.
5. The method of claim 2, wherein the predetermined process conditions are: 3- (α -methoxy) methylenebenzofuran-2 (3H) -one: the molar ratio of the metal sodium is 1: 2, the reaction temperature is 0 ℃, and the reaction time is 1 h.
6. The method for improving azoxystrobin conversion rate according to claim 1, wherein the preparation of o-hydroxybenzonitrile comprises the following steps:
taking salicylaldehyde as a raw material, and reacting the salicylaldehyde with a hydroxylamine hydrochloride aqueous solution to synthesize salicylaldoxime;
dehydrating and condensing salicylaldoxime and acid anhydride to obtain acetylsalicylonitrile;
acetylsalicylanitrile is hydrolyzed to synthesize o-hydroxybenzonitrile.
7. The method for improving azoxystrobin conversion rate according to claim 6, wherein the concentration of the hydroxylamine hydrochloride aqueous solution is 20-60%.
8. The method of claim 7, wherein the anhydride is acetic anhydride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011392157.5A CN112574125A (en) | 2020-12-01 | 2020-12-01 | Method for improving conversion rate of azoxystrobin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011392157.5A CN112574125A (en) | 2020-12-01 | 2020-12-01 | Method for improving conversion rate of azoxystrobin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112574125A true CN112574125A (en) | 2021-03-30 |
Family
ID=75126760
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011392157.5A Pending CN112574125A (en) | 2020-12-01 | 2020-12-01 | Method for improving conversion rate of azoxystrobin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112574125A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113424822A (en) * | 2021-06-30 | 2021-09-24 | 安徽广信农化股份有限公司 | Azoxystrobin emulsion and preparation method thereof |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1219537A (en) * | 1990-11-16 | 1999-06-16 | 曾尼卡有限公司 | Process for preparing benzofuranone derivatives |
| CN1228086A (en) * | 1996-08-19 | 1999-09-08 | 曾尼卡有限公司 | Process for preparation of pyrimidine compounds |
| CN102241651A (en) * | 2011-05-25 | 2011-11-16 | 江苏七洲绿色化工股份有限公司 | Preparation method of azoxystrobin intermediate |
| CN102417498A (en) * | 2011-08-24 | 2012-04-18 | 重庆紫光化工股份有限公司 | Synthetic method of 3-(alpha-methoxy)methylene benzofuran-2(3H)-one |
| CN104230822A (en) * | 2014-09-16 | 2014-12-24 | 重庆紫光国际化工有限责任公司 | Method for synthesizing azoxystrobin |
| CN106336388A (en) * | 2016-07-27 | 2017-01-18 | 重庆紫光国际化工有限责任公司 | Synthetic method of benzofuran-2(3H)-one |
| CN107235920A (en) * | 2017-07-29 | 2017-10-10 | 江苏绿叶农化有限公司 | A kind of synthetic method of Fluoxastrobin |
| CN107698520A (en) * | 2017-10-31 | 2018-02-16 | 江苏绿叶农化有限公司 | A kind of preparation method of Fluoxastrobin |
| CN109651263A (en) * | 2019-01-24 | 2019-04-19 | 安徽广信农化股份有限公司 | A kind of synthetic method of Fluoxastrobin |
-
2020
- 2020-12-01 CN CN202011392157.5A patent/CN112574125A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1219537A (en) * | 1990-11-16 | 1999-06-16 | 曾尼卡有限公司 | Process for preparing benzofuranone derivatives |
| CN1228086A (en) * | 1996-08-19 | 1999-09-08 | 曾尼卡有限公司 | Process for preparation of pyrimidine compounds |
| CN102241651A (en) * | 2011-05-25 | 2011-11-16 | 江苏七洲绿色化工股份有限公司 | Preparation method of azoxystrobin intermediate |
| CN102417498A (en) * | 2011-08-24 | 2012-04-18 | 重庆紫光化工股份有限公司 | Synthetic method of 3-(alpha-methoxy)methylene benzofuran-2(3H)-one |
| CN104230822A (en) * | 2014-09-16 | 2014-12-24 | 重庆紫光国际化工有限责任公司 | Method for synthesizing azoxystrobin |
| CN106336388A (en) * | 2016-07-27 | 2017-01-18 | 重庆紫光国际化工有限责任公司 | Synthetic method of benzofuran-2(3H)-one |
| CN107235920A (en) * | 2017-07-29 | 2017-10-10 | 江苏绿叶农化有限公司 | A kind of synthetic method of Fluoxastrobin |
| CN107698520A (en) * | 2017-10-31 | 2018-02-16 | 江苏绿叶农化有限公司 | A kind of preparation method of Fluoxastrobin |
| CN109651263A (en) * | 2019-01-24 | 2019-04-19 | 安徽广信农化股份有限公司 | A kind of synthetic method of Fluoxastrobin |
Non-Patent Citations (4)
| Title |
|---|
| SHUAI-SHUAI LI等: "Iridium(III)-Catalyzed Tandem [3 + 2] Annulation: Synthesis of Spirocyclic Phosphoramide Derivatives", 《ORG. LETT.》 * |
| XIANG ZHANG等: "Design, Synthesis, and Antifungal Activities of New -Methoxyacrylate Analogues", 《J. CHIN. CHEM. SOC》 * |
| 董捷等: "嘧菌酯的合成", 《精细化工中间体》 * |
| 钏永明等: "(E)-2-[ 2-(6-氯嘧啶-4-基氧基)苯基] -3-甲氧基丙烯酸甲酯的合成工艺改进", 《合成化学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113424822A (en) * | 2021-06-30 | 2021-09-24 | 安徽广信农化股份有限公司 | Azoxystrobin emulsion and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101941963A (en) | Synthesis method of erdosteine | |
| CN105061373A (en) | Synthesis method of dapagliflozin isomer impurity | |
| US9332762B2 (en) | Method for preparing amicarbazone | |
| CN112574125A (en) | Method for improving conversion rate of azoxystrobin | |
| CN111807990B (en) | Intermediate for preparing trifloxystrobin and synthetic method thereof | |
| CN108440409B (en) | Green and efficient preparation method of rebamipide | |
| CN110407685A (en) | The preparation method of o-methyl-benzene fluoroacetic acid | |
| CN109912531B (en) | Preparation method of high-purity febuxostat | |
| CN101671309B (en) | Synthesis method of 6-ethyl-4-hydroxyl-5-fluorine-2-cloro pyridine ammonium salt | |
| CN101857544B (en) | Synthesis method of herbicide 2, 4-dichlorphenoxyacetic acid | |
| JPS6222740A (en) | Isolation of p-hydroxybenzaldehyde | |
| CN106187940A (en) | A kind of one kettle way prepares the method for Febustat | |
| CN112574111A (en) | Preparation method of pyrazole herbicide intermediate 1-methyl-5 hydroxypyrazole | |
| CN101250191B (en) | Method for preparing 2-phenylamino-6-dibutylamino-3-methyl fluorane | |
| CN107892676A (en) | The preparation method of Cefdinir active thioester | |
| CN109438214A (en) | The preparation method of the bromo- 2,4 difluorobenzene formic acid of high-purity 5- | |
| WO2019178947A1 (en) | Preparation method for azoxystrobin and intermediate thereof | |
| CN114213308A (en) | Method for synthesizing atorvastatin ester by using continuous flow tubular reactor | |
| CN108033892A (en) | A kind of preparation method of N- alkyl iminodiacetics acid | |
| CN105461691A (en) | Preparation method of azelnidipine | |
| CN106167453B (en) | A kind of preparation method of 2,4 dichlorophenoxyacetic acid methyl esters | |
| CN110128347A (en) | A kind of synthetic method of 1- methyl-1 H- indazole -6- formic acid | |
| CN111039845A (en) | Preparation method of 4-fluoro-7-bromoisatin | |
| CN110357773A (en) | The synthesis of 3- chloro-4-hydroxyl benzoic acid | |
| CN109776448B (en) | Preparation method of febuxostat crystal form A |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210330 |
|
| RJ01 | Rejection of invention patent application after publication |