CN101723905B - Synthesis method of 2-(2-(6-(2-cyano phenoxyl) pyridine-4-oxygroup) phenyl) methyl acetate - Google Patents
Synthesis method of 2-(2-(6-(2-cyano phenoxyl) pyridine-4-oxygroup) phenyl) methyl acetate Download PDFInfo
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- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 title claims abstract description 31
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 title claims abstract description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims abstract description 30
- 238000001308 synthesis method Methods 0.000 title abstract 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 71
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 54
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229910000027 potassium carbonate Inorganic materials 0.000 claims abstract description 18
- 238000010992 reflux Methods 0.000 claims abstract description 17
- 239000012065 filter cake Substances 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000000706 filtrate Substances 0.000 claims abstract description 10
- 238000001914 filtration Methods 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 239000000047 product Substances 0.000 claims abstract description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
- 229910052760 oxygen Inorganic materials 0.000 claims description 27
- 239000001301 oxygen Substances 0.000 claims description 27
- 239000002994 raw material Substances 0.000 claims description 24
- 235000011181 potassium carbonates Nutrition 0.000 claims description 20
- 238000001035 drying Methods 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- CHZCERSEMVWNHL-UHFFFAOYSA-N 2-hydroxybenzonitrile Chemical compound OC1=CC=CC=C1C#N CHZCERSEMVWNHL-UHFFFAOYSA-N 0.000 claims description 14
- 238000010907 mechanical stirring Methods 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 9
- 238000010189 synthetic method Methods 0.000 claims description 6
- 230000006837 decompression Effects 0.000 claims description 3
- 238000010612 desalination reaction Methods 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 239000013067 intermediate product Substances 0.000 abstract description 14
- 238000001816 cooling Methods 0.000 abstract 2
- TZJVIARHKFQXNT-UHFFFAOYSA-N 4,6-dichloropyridine Chemical compound ClC1=C=C(Cl)N=C[CH]1 TZJVIARHKFQXNT-UHFFFAOYSA-N 0.000 abstract 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 abstract 1
- 238000011033 desalting Methods 0.000 abstract 1
- -1 salicyl methyl acetate Chemical compound 0.000 abstract 1
- 238000004817 gas chromatography Methods 0.000 description 12
- 238000012544 monitoring process Methods 0.000 description 12
- BVBSGGBDFJUSIH-UHFFFAOYSA-N Methyl (2-hydroxyphenyl)acetate Chemical class COC(=O)CC1=CC=CC=C1O BVBSGGBDFJUSIH-UHFFFAOYSA-N 0.000 description 9
- XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 7
- ZLWLTDZLUVBSRJ-UHFFFAOYSA-K chembl2360149 Chemical compound [Na+].[Na+].[Na+].O=C1C(N=NC=2C=CC(=CC=2)S([O-])(=O)=O)=C(C(=O)[O-])NN1C1=CC=C(S([O-])(=O)=O)C=C1 ZLWLTDZLUVBSRJ-UHFFFAOYSA-K 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 238000009413 insulation Methods 0.000 description 6
- 239000012452 mother liquor Substances 0.000 description 6
- 238000011084 recovery Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000000967 suction filtration Methods 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 5
- 239000005730 Azoxystrobin Substances 0.000 description 3
- 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 description 3
- 238000000034 method Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 241000235349 Ascomycota Species 0.000 description 1
- 241000221198 Basidiomycota Species 0.000 description 1
- 241000221785 Erysiphales Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000896238 Oidium Species 0.000 description 1
- 241000233654 Oomycetes Species 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000010903 husk 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
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
Abstract
The invention relates to a synthesis method of 2-(2-(6-(2-cyano phenoxyl) pyridine-4-oxygroup) phenyl) methyl acetate. The synthesis method comprises the following steps of: adopting 4,6-dichloro pyridine, salicyl methyl acetate and anhydrous potassium carbonate to react for 2 to 6h at 20 to 100 DEG C in DMF solvent, filtering and desalting after the reaction is finished to obtain a DMF solution of an intermediate product 2-(2-(6-cloro pyridine-4-oxygroup)phenyl) methyl acetate; reacting salicyl carbonitrile with anhydrous potassium carbonate for 1 to 3h at 104 to 110 DEG C in a toluene system, refluxing to separate generated water, cooling to 50 to 100 DEG C, dripping the DMF solution prepared by the reaction in the last step, reacting for 1 to 9h at 50 to 100 DEG C, cooling to the room temperature, filtering, eluting a filter cake by using the DMF solution, and removing the filter cake; and desolventizing the filtrate and recrystallizing methanol to obtain the target product. The purity of the 2-(2-(6-(2-cyano phenoxyl) pyridine-4-oxygroup) phenyl) methyl acetate is 93 to 95 percent, and the yield coefficient thereof is 73 to 79 percent.
Description
Technical field
The present invention relates to the synthetic method of the important intermediate of agriculture new and effective sterilant Azoxystrobin.
Background technology
Azoxystrobin is new and effective, wide spectrum, systemic fungicide, can be used for cauline leaf spraying, seed treatment, also can carry out scholar's earth and handle.It is to nearly all Eumycetes (Ascomycetes, Basidiomycetes, Oomycete and imperfect fungi) disease, as withered lame, the net blotch of Powdery Mildew, rust, grain husk, oidium, rice blast etc. good activity is arranged all, and does not have cross resistance with at present existing sterilant.Be used for cereal, paddy rice, grape, potato, vegetables, fruit tree and other crop, to these crop safeties.And 2-(2-(6-(2-cyano-benzene oxygen) pyrimidine-4-oxygen base) phenyl) methyl acetate is the synthetic very important intermediate of Azoxystrobin.Operational path in the past (Chinese patent CN 101157657A) is: 4, and 2-(6-chloropyrimide-4-oxygen base) cyanobenzene is made in 6-dichloro pyrimidine and salicylonitrile reaction earlier, and then makes with the reaction of o-hydroxy phenylacetic acid methyl esters.The temperature required height of this method, long reaction time, by product is many, and yield is relatively low.
Summary of the invention
At the defective that prior art exists, the present invention aims to provide improving one's methods of a kind of Synthetic 2-(2-(6-(2-cyano-benzene oxygen) pyrimidine-4-oxygen base) phenyl) methyl acetate.This method reaction times is short, temperature is low, yield is high.
Technical scheme of the present invention is: at first adopt 4,6-dichloro pyrimidine and o-hydroxy phenylacetic acid methyl esters, Anhydrous potassium carbonate are at DMF (N, dinethylformamide, down with) hybrid reaction in the solvent, filtering separation obtains the DMF solution of 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate; Again salicylonitrile, Anhydrous potassium carbonate reflux water-dividing in toluene system is prepared phenol sylvite, drip the intermediate that the first step obtains, reacting by heating obtains final product.Reaction equation is:
The concrete operations step is:
(1) intermediate 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate is synthetic:
Raw materials used proportioning:
4,1.0 moles of 6-dichloro pyrimidines
1.0 moles of o-hydroxy phenylacetic acid methyl esters
1.0～3.0 moles of Anhydrous potassium carbonates
DMF 600ml
Step is: under the drying nitrogen protection; in the reaction flask that mechanical stirring, condenser are housed, add above-mentioned raw materials in proportion; under 20～100 ℃, react 2～6h, obtain the DMF solution of intermediate 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate behind the complete filtration of the reaction desalination.Treat next step reaction usefulness.
(2) 2-(2-(6-(2-cyano-benzene oxygen) pyrimidine-4-oxygen base) phenyl) methyl acetate is synthetic:
With raw material 4, the 6-dichloro pyrimidine is 1.0 moles of meters with the first step reaction scale, and this step reaction raw materials consumption is as follows:
0.9 mole of salicylonitrile
1.0～3.0 moles of Anhydrous potassium carbonates
Toluene 500～700ml
Processing step is: under the drying nitrogen protection; in the reaction flask that mechanical stirring, condenser are housed, add salicylonitrile, toluene and Anhydrous potassium carbonate in proportion successively; heat temperature raising; 104～110 ℃ of following reflux water-dividings; be cooled to 50～100 ℃ after dividing water to finish; drip the DMF solution of intermediate product 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate of previous step reaction, 50～100 ℃ of reaction 1～9h.
This step also can operate like this: after dividing water intact, steam the toluene that removes in the reaction solution, be cooled to 50～100 ℃, add DMF, drip the DMF solution of previous step reaction, 50～100 ℃ of reaction 1～9h.The DMF dosage: every mole of intermediate 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate is 400～500ml.
(3) handle and make with extra care: above-mentioned reaction system is reduced to room temperature, filters, and filter cake DMF drip washing discards filter cake.The filtrate decompression distillation removes solvent, gets target product with recrystallizing methanol; Purity 85～95%, yield 73～79%.
Synthetic method of the present invention is compared with the synthetic method of prior art, have significant advantage and be the reaction times short, temperature is low, yield is high, cost is cheap relatively and workable.
The present invention is described in further detail below in conjunction with specific embodiment.
Embodiment
Embodiment 1
Under the drying nitrogen protection; in the reaction flask that mechanical stirring, condenser are housed, add 4,6 dichloro pyrimidines (76g, 98%; 0.5mol), o-hydroxy phenylacetic acid methyl esters (84.8g; 98%, 0.5mol), DMF 300ml stirring and dissolving, add Anhydrous potassium carbonate (125.4g; 99%; 0.9mol), being heated to 50 ℃ of reaction 2.5h, gas-chromatography monitoring raw material reaction is intact.Reduce to room temperature, filter, filtrate (the DMF solution of intermediate product 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate) is stand-by.
Under the drying nitrogen protection, in four-hole bottle, add salicylonitrile (57g, 94% successively; 0.45mol), toluene 300ml, Anhydrous potassium carbonate (75.3g; 99%, 0.81mol) heat temperature raising, reflux water-dividing; reflux temperature is 104-110 ℃; after dividing water intact, be cooled to below 100 ℃, drip the DMF solution of the intermediate product of previous step reaction gained; 90-100 ℃ of insulation reaction 3h, gas-chromatography monitoring raw material reaction is intact.
Reduce to room temperature, suction filtration with 100ml DMF drip washing filter cake, adds the 125ml recrystallizing methanol behind the mother liquor concentrating under reduced pressure, filter yellow crystals 145.5g, purity 93%, total recovery 75%.
Embodiment 2
Under the drying nitrogen protection, in the reaction flask that mechanical stirring, condenser are housed, add 4,6 dichloro pyrimidine (76g; 98%; 0.5mol), the o-hydroxy phenylacetic acid methyl esters (84.8g, 98%, 0.5mol), N; dinethylformamide DMF 300ml stirring and dissolving; the adding Carbon Dioxide (125.4g, 99%, 0.9mol); be heated to 50 ℃ of reaction 2.5h, gas-chromatography monitoring raw material reaction is intact.Reduce to room temperature, filter, filtrate (the DMF solution of intermediate product 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate) is stand-by.
Under the drying nitrogen protection, in four-hole bottle, add salicylonitrile (57g, 94% successively; 0.45mol), toluene 300ml, Anhydrous potassium carbonate (75.3g, 99%, 0.81mol) heat temperature raising; reflux water-dividing; reflux temperature is 104-110 ℃, and after branch water was intact, normal pressure steamed and removes toluene; add 200mlDMF; drip the DMF solution of the intermediate product of previous step reaction gained, 90-100 ℃ of insulation reaction 1h, gas-chromatography monitoring raw material reaction is intact.
Reduce to room temperature, suction filtration with 100ml DMF drip washing filter cake, adds the 125ml recrystallizing methanol behind the mother liquor precipitation, filter yellow crystals 150.1g, purity 95%, total recovery 79%.
Embodiment 3
Under the drying nitrogen protection, in the reaction flask that mechanical stirring, condenser are housed, add 4,6 dichloro pyrimidine (30.4g; 98%; 0.2mol), the o-hydroxy phenylacetic acid methyl esters (33.9g, 98%, 0.2mol), N; dinethylformamide DMF 120ml stirring and dissolving; the adding Anhydrous potassium carbonate (33.5g, 99%, 0.24mol); be heated to 50 ℃ of reaction 5h, gas-chromatography monitoring raw material reaction is intact.Reduce to room temperature, filter, filtrate (the DMF solution of intermediate product 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate) is stand-by.
Under the drying nitrogen protection, in four-hole bottle, add salicylonitrile (22.8g, 94% successively; 0.18mol), toluene 120ml, Anhydrous potassium carbonate (30.7g; 99%, 0.32mol) heat temperature raising, reflux water-dividing; reflux temperature is 104-110 ℃; after dividing water intact, be cooled to below 100 ℃, drip the DMF solution of the intermediate product of previous step reaction gained; 70-80 ℃ of insulation reaction 5h, gas-chromatography monitoring raw material reaction is intact.
Reduce to room temperature, suction filtration, 60ml DMF drip washing adds the 50ml recrystallizing methanol behind the mother liquor precipitation, filter yellow crystals 57.1g, purity 93%, total recovery 73.5%.
Embodiment 4
Under the drying nitrogen protection, in the reaction flask that mechanical stirring, condenser are housed, add 4,6 dichloro pyrimidine (30.4g; 98%; 0.2mol), the o-hydroxy phenylacetic acid methyl esters (33.9g, 98%, 0.2mol), N; dinethylformamide 120ml stirring and dissolving; the adding Anhydrous potassium carbonate (33.5g, 99%, 0.24mol); be heated to 50 ℃ of reaction 5h, gas-chromatography monitoring raw material reaction is intact.Reduce to room temperature, filter, filtrate (the DMF solution of intermediate product 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate) is stand-by.
Under the drying nitrogen protection, in four-hole bottle, add salicylonitrile (22.8g, 94% successively; 0.18mol), toluene 120ml, Anhydrous potassium carbonate (30.7g, 99%, 0.32mol) heat temperature raising; reflux water-dividing, reflux temperature are 104-110 ℃, divide the intact back of water normal pressure to steam and remove toluene; add 80ml N; dinethylformamide DMF is cooled to below 100 ℃, the DMF solution of the intermediate product of step gained in the dropping; 90-100 ℃ of insulation reaction 1h, gas-chromatography monitoring raw material reaction is intact.
Reduce to room temperature, suction filtration, 60ml DMF drip washing filter cake adds the 50ml recrystallizing methanol behind the mother liquor precipitation, filter yellow crystals 57.5g, purity 94.2%, total recovery 75%.
Embodiment 5
Under the drying nitrogen protection, in the reaction flask that mechanical stirring, condenser are housed, add 4,6 dichloro pyrimidine (30.4g; 98%; 0.2mol), the o-hydroxy phenylacetic acid methyl esters (33.9g, 98%, 0.2mol), N; dinethylformamide DMF 120ml stirring and dissolving; the adding Anhydrous potassium carbonate (33.5g, 99%, 0.24mol); be heated to 85 ℃ of reaction 1h, gas-chromatography monitoring raw material reaction is complete.Reduce to room temperature, filter, filtrate (the DMF solution of intermediate product 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate) is standby.
Under the drying nitrogen protection, in four-hole bottle, add salicylonitrile (22.8g, 94% successively; 0.18mol), toluene 120ml, Anhydrous potassium carbonate (30.7g; 99%, 0.32mol) heat temperature raising, reflux water-dividing; reflux temperature is 104-110 ℃; after dividing water intact, be cooled to below 100 ℃, drip the DMF solution of the intermediate product of previous step reaction gained; 50 ℃ of insulation reaction 9h, gas-chromatography monitoring raw material reaction is intact.
Reduce to room temperature, suction filtration with 60ml DMF drip washing, adds the 50ml recrystallizing methanol behind the mother liquor precipitation, filter yellow crystals 62.0g, purity 85%, total recovery 73.0%.
Embodiment 6
Under the drying nitrogen protection, in the reaction flask that mechanical stirring, condenser are housed, add 4,6 dichloro pyrimidine (30.4g; 98%; 0.2mol), the o-hydroxy phenylacetic acid methyl esters (33.9g, 98%, 0.2mol), N; dinethylformamide DMF 120ml stirring and dissolving; the adding Anhydrous potassium carbonate (83.6g, 99%, 0.6mol); 20 ℃ of reaction 6h, gas-chromatography monitoring raw material reaction is intact.Filter, filtrate (the DMF solution of intermediate product 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate) is standby.
Under the drying nitrogen protection, in four-hole bottle, add salicylonitrile (22.8g, 94% successively; 0.18mol), toluene 120ml, Anhydrous potassium carbonate (30.7g; 99%, 0.32mol) heat temperature raising, reflux water-dividing; reflux temperature is 104-110 ℃; after dividing water intact, be cooled to below 100 ℃, drip the DMF solution of the intermediate product of previous step reaction gained; 90-100 ℃ of insulation reaction 3h, gas-chromatography monitoring raw material reaction is intact.
Reduce to room temperature, suction filtration, 60ml DMF drip washing filter cake adds the 50ml recrystallizing methanol behind the mother liquor precipitation, filter yellow crystals 55.1g, purity 95%, total recovery 72.5%.
Claims (2)
1.2-the synthetic method of (2-(6-(2-cyano-benzene oxygen) pyrimidine-4-oxygen base) phenyl) methyl acetate is characterized in that processing step is:
(1) intermediate 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate is synthetic:
Raw materials used proportioning:
Step is: under the drying nitrogen protection, in the reaction flask that mechanical stirring, condenser are housed, add above-mentioned raw materials in proportion, under 20～100 ℃, reaction 2～6h, obtain the DMF solution of intermediate 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate behind the filtration desalination, stand-by;
(2) 2-(2-(6-(2-cyano-benzene oxygen) pyrimidine-4-oxygen base) phenyl) methyl acetate is synthetic:
More than go on foot reaction scale with raw material 4, the 6-dichloro pyrimidine is 1.0 moles of meters, and this step reaction raw materials consumption is as follows:
0.9 mole of salicylonitrile
1.0～3.0 moles of Anhydrous potassium carbonates
Toluene 500～700ml
Processing step is: under the drying nitrogen protection, in the reaction flask that mechanical stirring, condenser are housed, add salicylonitrile, toluene and Anhydrous potassium carbonate in proportion successively, heat temperature raising, 104～110 ℃ of reactions down, reflux water-dividing, divide water to finish and be cooled to 50～100 ℃, drip the DMF solution of 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate of previous step reaction gained, 50～100 ℃ of reaction 1～9h;
(3) handle and make with extra care: above-mentioned reaction system is reduced to room temperature, filters, and filter cake DMF drip washing discards filter cake; The filtrate decompression distillation removes solvent, gets target product with recrystallizing methanol.
2.2-the synthetic method of (2-(6-(2-cyano-benzene oxygen) pyrimidine-4-oxygen base) phenyl) methyl acetate is characterized in that processing step is:
(1) intermediate 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate is synthetic:
Raw materials used proportioning:
Step is: under the drying nitrogen protection, in the reaction flask that mechanical stirring, condenser are housed, add above-mentioned raw materials in proportion, under 20～100 ℃, reaction 2～6h, obtain the DMF solution of intermediate 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate behind the filtration desalination, stand-by;
(2) 2-(2-(6-(2-cyano-benzene oxygen) pyrimidine-4-oxygen base) phenyl) methyl acetate is synthetic:
More than go on foot reaction scale with raw material 4, the 6-dichloro pyrimidine is 1.0 moles of meters, and this step reaction raw materials consumption is as follows:
0.9 mole of salicylonitrile
1.0～3.0 moles of Anhydrous potassium carbonates
Toluene 500～700ml
Processing step is: under the drying nitrogen protection, in the reaction flask that mechanical stirring, condenser are housed, add salicylonitrile, toluene and Anhydrous potassium carbonate in proportion successively, heat temperature raising, 104～110 ℃ of reactions down, reflux water-dividing is after branch water is finished, steam and remove toluene, add DMF, drip the DMF solution of 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate of previous step reaction gained, 50～100 ℃ of reaction 1～9h; The DMF dosage: every mole of 2-(2-(6-chloropyrimide-4-oxygen base) phenyl) methyl acetate is 400～500ml;
(3) handle and make with extra care: above-mentioned reaction system is reduced to room temperature, filters, and filter cake DMF drip washing discards filter cake; The filtrate decompression distillation removes solvent, gets target product with recrystallizing methanol.
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| CN102952085A (en) * | 2012-11-20 | 2013-03-06 | 大连九信生物化工科技有限公司 | Synthesis method of 2-(2-(6-(2-cyanophenoxy) pyrimidin-4-oxy) phenyl) methyl acetate |
| CN104387329A (en) * | 2014-10-27 | 2015-03-04 | 河北临港化工有限公司 | Method for synthesizing intermediate methyl 2-(2-(6-chloropyrimidine-4-yl-oxo)phenyl) acetate |
| CN106083735B (en) * | 2016-06-03 | 2018-09-21 | 安徽广信农化股份有限公司 | A kind of synthesis technology of azoxystrobin intermediate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1234794A (en) * | 1996-10-28 | 1999-11-10 | 曾尼卡有限公司 | Process for preparing (E)-methyl 2-[2-(6-(2-cyanophenoxy)-pyrimidin-4-yloxy) phenyl]-3-methoxypropenoate in the absence of cooper (salt) and of N, N-dimethylformamide |
| CN1511144A (en) * | 2001-06-13 | 2004-07-07 | Process for preparation of azoxystrobin and analogues thereof | |
| CN101157657A (en) * | 2007-10-24 | 2008-04-09 | 北京颖新泰康科技有限公司 | Method for preparing azoxystrobin and its analogue |
-
2009
- 2009-11-25 CN CN2009102201945A patent/CN101723905B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1234794A (en) * | 1996-10-28 | 1999-11-10 | 曾尼卡有限公司 | Process for preparing (E)-methyl 2-[2-(6-(2-cyanophenoxy)-pyrimidin-4-yloxy) phenyl]-3-methoxypropenoate in the absence of cooper (salt) and of N, N-dimethylformamide |
| CN1511144A (en) * | 2001-06-13 | 2004-07-07 | Process for preparation of azoxystrobin and analogues thereof | |
| CN101157657A (en) * | 2007-10-24 | 2008-04-09 | 北京颖新泰康科技有限公司 | Method for preparing azoxystrobin and its analogue |
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