CN107459495A - The benzoxazines 3 of 6 amido 2H of one kind 7 fluorine of synthesis 1,4（4H）The method of ketone - Google Patents
The benzoxazines 3 of 6 amido 2H of one kind 7 fluorine of synthesis 1,4（4H）The method of ketone Download PDFInfo
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- CN107459495A CN107459495A CN201710788345.1A CN201710788345A CN107459495A CN 107459495 A CN107459495 A CN 107459495A CN 201710788345 A CN201710788345 A CN 201710788345A CN 107459495 A CN107459495 A CN 107459495A
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- amidos
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- 238000000034 method Methods 0.000 title claims abstract description 23
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 14
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 14
- 125000003368 amide group Chemical group 0.000 title abstract 3
- 229910052731 fluorine Inorganic materials 0.000 title abstract 3
- 239000011737 fluorine Substances 0.000 title abstract 3
- 150000002576 ketones Chemical class 0.000 title abstract 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 title 1
- 150000005130 benzoxazines Chemical class 0.000 title 1
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 21
- 239000002994 raw material Substances 0.000 claims abstract description 17
- CEPCPXLLFXPZGW-UHFFFAOYSA-N 2,4-difluoroaniline Chemical class NC1=CC=C(F)C=C1F CEPCPXLLFXPZGW-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 11
- FOUWCSDKDDHKQP-UHFFFAOYSA-N flumioxazin Chemical compound FC1=CC=2OCC(=O)N(CC#C)C=2C=C1N(C1=O)C(=O)C2=C1CCCC2 FOUWCSDKDDHKQP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000006396 nitration reaction Methods 0.000 claims abstract description 10
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 5
- 238000010189 synthetic method Methods 0.000 claims abstract 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 27
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 18
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 18
- 239000011698 potassium fluoride Substances 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 239000000047 product Substances 0.000 claims description 13
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 12
- 239000000463 material Substances 0.000 claims description 9
- 229910017604 nitric acid Inorganic materials 0.000 claims description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 9
- 235000003270 potassium fluoride Nutrition 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 9
- 238000005070 sampling Methods 0.000 claims description 8
- 238000006266 etherification reaction Methods 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 238000011084 recovery Methods 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 239000012065 filter cake Substances 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 238000009413 insulation Methods 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 235000011181 potassium carbonates Nutrition 0.000 claims description 6
- 239000001103 potassium chloride Substances 0.000 claims description 6
- 235000011164 potassium chloride Nutrition 0.000 claims description 6
- 238000010792 warming Methods 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 3
- 238000006073 displacement reaction Methods 0.000 claims description 3
- -1 filtering Substances 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 3
- 239000012452 mother liquor Substances 0.000 claims description 3
- 230000000802 nitrating effect Effects 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 235000015320 potassium carbonate Nutrition 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 238000001256 steam distillation Methods 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 241000790917 Dioxys <bee> Species 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 238000001816 cooling Methods 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 abstract description 5
- 238000007086 side reaction Methods 0.000 abstract description 5
- 239000012535 impurity Substances 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 abstract 2
- CMLFRMDBDNHMRA-UHFFFAOYSA-N 2h-1,2-benzoxazine Chemical compound C1=CC=C2C=CNOC2=C1 CMLFRMDBDNHMRA-UHFFFAOYSA-N 0.000 abstract 1
- QRAOZQGIUIDZQZ-UHFFFAOYSA-N 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2N(C)CCOC2=CC=1B1OC(C)(C)C(C)(C)O1 QRAOZQGIUIDZQZ-UHFFFAOYSA-N 0.000 abstract 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 7
- 230000000977 initiatory effect Effects 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- 230000002363 herbicidal effect Effects 0.000 description 4
- 239000004009 herbicide Substances 0.000 description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000001546 nitrifying effect Effects 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- RJXOVESYJFXCGI-UHFFFAOYSA-N 2,4-difluoro-1-nitrobenzene Chemical class [O-][N+](=O)C1=CC=C(F)C=C1F RJXOVESYJFXCGI-UHFFFAOYSA-N 0.000 description 2
- 238000012271 agricultural production Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 239000004568 cement Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000003682 fluorination reaction Methods 0.000 description 2
- 238000003306 harvesting Methods 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- LOTKRQAVGJMPNV-UHFFFAOYSA-N 1-fluoro-2,4-dinitrobenzene Chemical class [O-][N+](=O)C1=CC=C(F)C([N+]([O-])=O)=C1 LOTKRQAVGJMPNV-UHFFFAOYSA-N 0.000 description 1
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 1
- SJTBRFHBXDZMPS-UHFFFAOYSA-N 3-fluorophenol Chemical compound OC1=CC=CC(F)=C1 SJTBRFHBXDZMPS-UHFFFAOYSA-N 0.000 description 1
- FBXGQDUVJBKEAJ-UHFFFAOYSA-N 4h-oxazin-3-one Chemical compound O=C1CC=CON1 FBXGQDUVJBKEAJ-UHFFFAOYSA-N 0.000 description 1
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- LWMAFJZTZAMNGG-UHFFFAOYSA-N Nc(cc(c(OC1)c2)NC1=O)c2F Chemical compound Nc(cc(c(OC1)c2)NC1=O)c2F LWMAFJZTZAMNGG-UHFFFAOYSA-N 0.000 description 1
- 238000010719 annulation reaction Methods 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 239000002420 orchard Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention discloses one kind synthesis 7 fluorine 6 amido 2H 1, the method of 4 benzoxazine 3 (4H) ketone, with 2,4 difluoroanilines are raw material, substituted by hydroxyl, be etherified, nitrified, hydrogenation reduction obtains (4H) ketone (flumioxazin intermediate) of 7 fluorine, 6 amido 2H Isosorbide-5-Nitraes benzoxazine 3.The synthetic method of the present invention, it is cheap and easy to get with 2,4 difluoroanilines for raw material, production cost is reduced to a certain extent；Intermediate 1, which needs not move through high-pressure hydrogenation reaction, to react cyclization with methyl chloroacetate, reduce the danger of reaction；Nitration reaction is easily-controllable, reduces side reaction, and impurity is few, improves yield；Catalyst for hydrogenation is recyclable, recycled, reduces cost；Other raw material is cheap and easy to get, and reaction is gentle, easy to operate, is advantageously implemented large-scale production.
Description
Technical field
The present invention relates to herbicide preparing technical field, is specially a kind of fluoro- 6- amidos -2H-1,4- Ben the Bing Evil of synthesis 7-
The method of piperazine -3 (4H) -one.
Background technology
Flumioxazin is the herbicide absorbed by young shoot and blade, and making soil treatment, can effectively to prevent and kill off 1 year raw broad-leaved miscellaneous
Grass and part grassy weed, it is degradable in the environment, to succession crop safety, it is suitable for the crop fields such as soybean, peanut, orchard
1 year raw broad leaved weed and part grassy weed are prevented and kill off, therefore the herbicide is widely used in terms of agricultural production, and have
Very big economic value.Fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7- is that wherein mesosome, chemical structural formula are as follows：
Flumioxazin is the wide variety of herbicide of agricultural production, fluoro- 6- amidos -2H-1, the 4- benzoxazines -3 of 7-
(4H) -one is wherein mesosome, and domestic technique has announced a variety of preparation technologies at present.Have and be with fluoro- 2, the 4- dinitro benzenes of 1,5- bis-
Initiation material, but such a mode is nitrified and controlled with fluorination reaction hardly possible, and impurity is high, and yield is low；In addition also have using use m fluorophenol as
Initiation material, but ehter bond easy fracture in nitrification aoxidizes, and side reaction is more, and iron cement processing is difficult caused by iron powder reducing；Also
With 2,4- difluoro nitrobenzenes for initiation material, but reaction difficult control when raw material is nitrified, and cyclization needs high-pressure hydrogenation, it is dangerous
Greatly, it is small that solvent alternative is hydrogenated with addition.Therefore a variety of synthetic routes for having announced, it is easy to accomplish industrialized production it is less.
It is domestic at present that prior art discloses on preparing fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7-
Process route mainly has several.
U.S. Patent Application No. is that US4803270 discloses a kind of method for synthesizing flumioxazin intermediate：With 1,5-
Two fluoro- 2,4- dinitro benzenes are initiation material, and intermediate is obtained by etherificate, hydrogenating reduction cyclization.Beneficial effects of the present invention
It is embodied in：It is few to react step number；But there is the shortcomings that certain in this method：First two steps are nitrified and fluorination reaction is difficult to control, and cause pair
Reaction is more, and yield is low, and impurity increases.
U.S. Patent Application No. is that US4792605 discloses a kind of method for synthesizing flumioxazin intermediate, between
Fluorophenol is initiation material, and by being etherified, nitrifying, iron powder reducing reacts to obtain intermediate.But the synthetic route ehter bond is nitrifying
When easy fracture, oxidation, side reaction is more, and yield is low, and iron cement caused by iron powder reducing is difficult to handle, pollution weight；Scale chemical industry
Industry production is difficult to.
Chinese Patent Application No. is that CN105837563A discloses a kind of method for synthesizing flumioxazin intermediate.Using
2,4- difluoro nitrobenzenes are initiation material, and by nitrifying, being etherified, hydrogenating reduction obtains；The route solvent reusable edible, starting
Raw material is cheap and easy to get, but this method has the shortcomings that certain：Phenyl ring contains nitro positioning complexity, easily generation when nitro is nitrified
Trinitro- product, difficult control is reacted, it is dangerous big；It is dangerous and cyclization needs high-pressure hydrogenation, and it is difficult selection to be hydrogenated with solvent,
Solubility is very low in Conventional solvents.
The content of the invention
It is an object of the invention to provide a kind of side of synthesis fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7-
Method, with 2,4- difluoroanilines for raw material, it is not necessary to hydrogenation can be cyclic, dangerous small, and nitration reaction is easily-controllable, and side reaction is few,
High income, to solve the problems mentioned in the above background technology.
To achieve the above object, the present invention provides following technical scheme：One kind synthesis fluoro- 6- amidos -2H-1,4- benzos of 7-
The method of oxazine -3 (4H) -one, with 2,4- difluoroanilines for raw material, is substituted by hydroxyl, is etherified, nitrified, hydrogenation reduction
Obtain fluoro- (4H) -one (flumioxazin intermediate) of 6- amidos -2H-1,4- benzoxazine -3 of 7-.
The further technical scheme of the present invention, comprises the following steps：
(1) hydroxyl substitutes
Putting into a certain amount of 2,4- difluoroanilines, water and potassium hydroxide successively into reactor, temperature is raised to 50 naturally~
80 degree, 60min is incubated after being added in 50-80 degree insulation about 4-5 hours, samples to 2,4- difluoroanilines and is less than 0.5%；Sampling is closed
After lattice, a certain amount of hydrochloric acid is added, side edged has intermediate 1 and water azeotropic to come out, heat temperature raising after stirring, with vapor
Distillation mode steams product；Distillation finishes, and intermediate 1 is treated to react in next step；
Wherein, the intermediate 1 is C6H6FNO, and product is C6H6FNO and potassium fluoride KF；C6H6FNO's and potassium fluoride KF
Mass ratio is 127: 58；
(2) etherification reaction
Put into C6H6FNO and potassium fluoride that a certain amount of DMF, potassium carbonate and step (1) obtain successively into reactor
KF, a certain amount of methyl chloroacetate is added dropwise, control is added dropwise at 2~3 hours, without obvious heat release；Add rear 50-80 DEG C of insulation reaction
4 hours, mixture gradually became yellow, and sampling raw material is less than 0.5%；Sylvite is filtered to remove after qualified, filtrate recovery DMF, is returned
Harvest complete, add a certain amount of methanol, be warming up to 60-70 degree, be incubated 30min, start to cool to 10~20 degree, in being filtrated to get
Mesosome 2；
Wherein, the intermediate 2 is C8H6FNO2, product C8H6FNO2, water H2O, potassium chloride (KCl), methanol CH3OH,
Carbon dioxide CO2；Its amount ratio is 334: 36: 149: 64: 88；
(3) nitration reaction
A certain amount of concentrated sulfuric acid is put into nitrating pot, temperature control is less than 50 DEG C.It is slowly added into and adds a certain amount of intermediate
2, stir 30min；Temperature of reaction kettle is controlled below 50 DEG C, and a certain amount of 70% nitric acid is added dropwise into mixture, and 60min is added dropwise
Left and right；It is added dropwise, the insulated and stirred 60min below 50 DEG C, sampling raw material ＜ 0.5% is qualified；Above-mentioned material is slowly added dropwise
Split-phase is quenched into the water head tank for filling water, stirring separates out solid, and filtering, filter cake is beaten 1 time with a certain amount of water, and is put into
A certain amount of sodium acid carbonate, filtering, filter cake dry to obtain intermediate 3.
Wherein, the intermediate 3 is C8H5FN2O4, product C8H5FN2O4With water H2O；Its amount ratio is 212: 18；
(4) hydrogenation reaction
By intermediate 3, quantitative DMF inputs hydrogenation kettle, weighed catalyst is put into, kettle is hydrogenated with nitrogen displacement, discharges oxygen,
Oxygen content ＜ 2.3%；80 DEG C are warming up to, is passed through hydrogen, pressure keeps 0.7MPa, 80-110 DEG C of reaction 120min；Reaction terminates,
70 DEG C are cooled to, obtains fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7-.
Preferably, in step (1), 2, the 4- difluoroanilines C6H5F2N, potassium hydroxide KOH and hydrochloric acid HCl quality
Than for 258: 112: 71.
Preferably, in step (2), the C6H6FNO of intermediate 1, potassium carbonate K2CO3 and the methyl chloroacetate
C3H5ClO2 mass ratio is 127: 138: 108.
Preferably, in step (3), the C of intermediate 28H6FNO2, nitric acid HNO3With sulfuric acid H2SO4Mass ratio be
167∶63∶98。
Preferably, in step (4), the C of intermediate 38H5FN2O4With hydrogen H2Mass ratio be 212: 2.
Preferably, in step (2), it is described be filtrated to get intermediate 2 after, mother liquor it is dry Methanol Recovery, can follow next time
Ring is standby.
Preferably, in step (1-4), hydroxyl substitution reaction, etherification reaction, the conversion ratio of nitration reaction and hydrogenation reaction
It is all higher than 99.5%.
Compared with prior art, the beneficial effects of the invention are as follows：
1st, the method for present invention synthesis fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7-, with 2,4- difluoroanilines
It is cheap and easy to get for raw material, production cost is reduced to a certain extent；
2nd, the present invention synthesis fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7- method, intermediate 1 without through
Cyclization can be reacted with methyl chloroacetate by crossing high pressure hydrogenation reaction, reduce the danger of reaction.
3rd, the method for present invention synthesis fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7-, etherificate annulation are adopted
It is cheap and easy to get with DMF solvent, and by simple precipitation can direct recovery, it is easy to operate.
4th, the method for present invention synthesis fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7-, nitration reaction is easily-controllable,
Side reaction is reduced, impurity is few, improves yield.
5th, the method for present invention synthesis fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7-, catalyst for hydrogenation
It is recyclable, recycled, reduce cost.
6th, the method for present invention synthesis fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7-, reaction step number is few, and
Each step process mild condition, safe, easy to operate, raw material is cheap and easy to get, and reaction is gentle, easy to operate, is advantageously implemented
Large-scale production.
Brief description of the drawings
Fig. 1 is the flumioxazin intermediate synthetic reaction equation of the present invention；
The hydroxyl that Fig. 2 is the present invention substitutes equation；
Fig. 3 is the etherification reaction equation of the present invention；
Fig. 4 is the nitration reaction equation of the present invention；
Fig. 5 is the hydrogenation reaction equation of the present invention.
Embodiment
Below in conjunction with the accompanying drawing in the embodiment of the present invention, the technical scheme in the embodiment of the present invention is carried out clear, complete
Site preparation describes, it is clear that described embodiment is only part of the embodiment of the present invention, rather than whole embodiments.It is based on
Embodiment in the present invention, those of ordinary skill in the art are obtained every other under the premise of creative work is not made
Embodiment, belong to the scope of protection of the invention.
Referring to Fig. 1, a kind of method of synthesis fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7-, with 2,4- bis-
Fluoroaniline is raw material, is substituted by hydroxyl, is etherified, nitrified, hydrogenation reduction obtains fluoro- 6- amidos -2H-1,4- Ben the Bing Evil of 7-
Piperazine -3 (4H) -one (flumioxazin intermediate).
The further technical scheme of the present invention, comprises the following steps：
(1) hydroxyl substitutes
Putting into a certain amount of 2,4- difluoroanilines, water and potassium hydroxide successively into reactor, temperature is raised to 50 naturally~
80 degree, 60min is incubated after being added in 50-80 degree insulation about 4-5 hours, samples to 2,4- difluoroanilines and is less than 0.5%；Sampling is closed
After lattice, a certain amount of hydrochloric acid is added, side edged has intermediate 1 and water azeotropic to come out, and is risen referring to Fig. 2, being heated after stirring
Temperature, product is steamed in a manner of steam distillation；Distillation finishes, and intermediate 1 is treated to react in next step；
Wherein, the intermediate 1 is C6H6FNO, and product is C6H6FNO and potassium fluoride KF；C6H6FNO's and potassium fluoride KF
Mass ratio is 127: 58；
Wherein, 2, the 4- difluoroanilines C6H5F2N, potassium hydroxide KOH and hydrochloric acid HCl mass ratio are 258: 112:
71；
(2) etherification reaction
Put into C6H6FNO and potassium fluoride that a certain amount of DMF, potassium carbonate and step (1) obtain successively into reactor
KF, a certain amount of methyl chloroacetate is added dropwise, control is added dropwise at 2~3 hours, without obvious heat release；Add rear 50-80 DEG C of insulation reaction
4 hours, mixture gradually became yellow, and sampling raw material is less than 0.5%；Sylvite is filtered to remove after qualified, filtrate recovery DMF, is returned
Harvest complete, add a certain amount of methanol, be warming up to 60-70 degree, be incubated 30min, start to cool to 10~20 degree, in being filtrated to get
Mesosome 2, refers to Fig. 3；After being filtrated to get intermediate 2, mother liquor it is dry Methanol Recovery, can next time circulation it is standby；
Wherein, the intermediate 2 is C8H6FNO2, product C8H6FNO2, water H2O, potassium chloride (KCl), methanol CH3OH,
Carbon dioxide CO2；Its amount ratio is 334: 36: 149: 64: 88；
Wherein, the C6H6FNO of intermediate 1, potassium carbonate K2CO3 and methyl chloroacetate C3H5ClO2 mass ratio are 127
∶138∶108；
(3) nitration reaction
A certain amount of concentrated sulfuric acid is put into nitrating pot, temperature control is less than 50 DEG C.It is slowly added into and adds a certain amount of intermediate
2, stir 30min；Temperature of reaction kettle is controlled below 50 DEG C, and a certain amount of 70% nitric acid is added dropwise into mixture, and 60min is added dropwise
Left and right；It is added dropwise, the insulated and stirred 60min below 50 DEG C, sampling raw material ＜ 0.5% is qualified；Above-mentioned material is slowly added dropwise
Split-phase is quenched into the water head tank for filling water, stirring separates out solid, and filtering, filter cake is beaten 1 time with a certain amount of water, and is put into
A certain amount of sodium acid carbonate, filtering, filter cake dry to obtain intermediate 3, refer to Fig. 4.
Wherein, the intermediate 3 is C8H5FN2O4, product C8H5FN2O4With water H2O；Its amount ratio is 212: 18；
Wherein, the C of intermediate 28H6FNO2, nitric acid HNO3With sulfuric acid H2SO4Mass ratio be 167: 63: 98；
(4) hydrogenation reaction
By intermediate 3, quantitative DMF inputs hydrogenation kettle, weighed catalyst is put into, kettle is hydrogenated with nitrogen displacement, discharges oxygen,
Oxygen content ＜ 2.3%；80 DEG C are warming up to, is passed through hydrogen, pressure keeps 0.7MPa, 80-110 DEG C of reaction 120min；Reaction terminates,
70 DEG C are cooled to, obtains fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7-；Referring to Fig. 5, wherein, the intermediate
3 C8H5FN2O4With hydrogen H2Mass ratio be 212: 2.
In step (1-4), hydroxyl substitution reaction, etherification reaction, the conversion ratio of nitration reaction and hydrogenation reaction are all higher than
99.5%.
The foregoing is only a preferred embodiment of the present invention, but protection scope of the present invention be not limited thereto,
Any one skilled in the art the invention discloses technical scope in, technique according to the invention scheme and its
Inventive concept is subject to equivalent substitution or change, should all be included within the scope of the present invention.
Claims (8)
1. the method for one kind synthesis fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7-, it is characterised in that with 2,4- bis-
Fluoroaniline is raw material, is substituted by hydroxyl, is etherified, nitrified, hydrogenation reduction obtains fluoro- 6- amidos -2H-1,4- Ben the Bing Evil of 7-
Piperazine -3 (4H) -one (flumioxazin intermediate).
2. the synthetic method of fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7- according to claim 1, it is special
Sign is：Synthetic method comprises the following steps：
(1) hydroxyl substitutes
Putting into a certain amount of 2,4- difluoroanilines, water and potassium hydroxide successively into reactor, temperature is raised to 50~80 degree naturally,
60min is incubated after being added in 50-80 degree insulation about 4-5 hours, samples to 2,4- difluoroanilines and is less than 0.5%；Sample it is qualified after,
A certain amount of hydrochloric acid is added, side edged has intermediate 1 and water azeotropic to come out, heat temperature raising after stirring, with steam distillation
Mode steams product；Distillation finishes, and intermediate 1 is treated to react in next step；
Wherein, the intermediate 1 is C6H6FNO, and product is C6H6FNO and potassium fluoride KF；C6H6FNO and potassium fluoride KF quality
Than for 127: 58；
(2) etherification reaction
Put into C6H6FNO and potassium fluoride KF that a certain amount of DMF, potassium carbonate and step (1) obtain successively into reactor, drip
Add a certain amount of methyl chloroacetate, control is added dropwise at 2~3 hours, without obvious heat release；It is small to add rear 50-80 DEG C of insulation reaction 4
When, mixture gradually becomes yellow, and sampling raw material is less than 0.5%；Sylvite is filtered to remove after qualified, filtrate recovery DMF, has been reclaimed
Finish, add a certain amount of methanol, be warming up to 60-70 degree, be incubated 30min, start to cool to 10~20 degree, be filtrated to get intermediate
2；
Wherein, the intermediate 2 is C8H6FNO2, product C8H6FNO2, water H2O, potassium chloride (KCl), methanol CH3OH, dioxy
Change carbon CO2；Its amount ratio is 334: 36: 149: 64: 88；
(3) nitration reaction
A certain amount of concentrated sulfuric acid is put into nitrating pot, temperature control is less than 50 DEG C.It is slowly added into and adds a certain amount of intermediate 2, stirs
Mix 30min；Temperature of reaction kettle is controlled below 50 DEG C, and a certain amount of 70% nitric acid is added dropwise into mixture, and it is left that 60min is added dropwise
It is right；It is added dropwise, the insulated and stirred 60min below 50 DEG C, sampling raw material ＜ 0.5% is qualified；Above-mentioned material is slowly added drop-wise to
Fill and split-phase is quenched in the water head tank of water, stirring separates out solid, filtering, and filter cake is beaten 1 time with a certain amount of water, and puts into one
Quantitative sodium acid carbonate, filtering, filter cake dry to obtain intermediate 3.
Wherein, the intermediate 3 is C8H5FN2O4, product C8H5FN2O4With water H2O；Its amount ratio is 212: 18；
(4) hydrogenation reaction
By intermediate 3, quantitative DMF inputs hydrogenation kettle, weighed catalyst is put into, kettle is hydrogenated with nitrogen displacement, discharges oxygen, it is oxygen-containing
Measure ＜ 2.3%；80 DEG C are warming up to, is passed through hydrogen, pressure keeps 0.7MPa, 80-110 DEG C of reaction 120min；Reaction terminates, cooling
To 70 DEG C, fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7- is obtained.
3. the synthetic method of fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7- according to claim 2, it is special
Sign is：In step (1), 2, the 4- difluoroanilines C6H5F2N, potassium hydroxide KOH and hydrochloric acid HCl mass ratio are 258:
112∶71。
4. the synthetic method of fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7- according to claim 2, it is special
Sign is：In step (2), the C6H6FNO of intermediate 1, potassium carbonate K2CO3 and methyl chloroacetate C3H5ClO2 quality
Than for 127: 138: 108.
5. the synthetic method of fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7- according to claim 2, it is special
Sign is：In step (3), the C of intermediate 28H6FNO2, nitric acid HNO3With sulfuric acid H2SO4Mass ratio be 167: 63: 98.
6. the synthetic method of fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7- according to claim 2, it is special
Sign is：In step (4), the C of intermediate 38H5FN2O4With hydrogen H2Mass ratio be 212: 2.
7. the synthetic method of fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7- according to claim 2, it is special
Sign is：In step (2), it is described be filtrated to get intermediate 2 after, mother liquor it is dry Methanol Recovery, can next time circulation it is standby.
8. the synthetic method of fluoro- (4H) -one of 6- amidos -2H-1,4- benzoxazine -3 of 7- according to claim 2, it is special
Sign is：In step (1-4), hydroxyl substitution reaction, etherification reaction, the conversion ratio of nitration reaction and hydrogenation reaction are all higher than
99.5%.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108976129A (en) * | 2018-08-16 | 2018-12-11 | 淮安国瑞化工有限公司 | A kind of fluoro- 2,4- 2,4-dinitrophenoxy of 2-(5-) acetic acid esters preparation method |
| CN113045557A (en) * | 2021-03-08 | 2021-06-29 | 宁夏一帆生物科技有限公司 | Production process of flumioxazin herbicide |
| CN113912561A (en) * | 2021-11-04 | 2022-01-11 | 京博农化科技有限公司 | Synthetic method of 6-amino-7-fluoro-2H-1, 4-benzoxazine-3 (4H) -ketone |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108976129A (en) * | 2018-08-16 | 2018-12-11 | 淮安国瑞化工有限公司 | A kind of fluoro- 2,4- 2,4-dinitrophenoxy of 2-(5-) acetic acid esters preparation method |
| CN108976129B (en) * | 2018-08-16 | 2022-10-28 | 安徽宁亿泰科技有限公司 | A kind of preparation method of 2-(5-fluoro-2,4-dinitrophenoxy) acetate |
| CN113045557A (en) * | 2021-03-08 | 2021-06-29 | 宁夏一帆生物科技有限公司 | Production process of flumioxazin herbicide |
| CN113912561A (en) * | 2021-11-04 | 2022-01-11 | 京博农化科技有限公司 | Synthetic method of 6-amino-7-fluoro-2H-1, 4-benzoxazine-3 (4H) -ketone |
| CN113912561B (en) * | 2021-11-04 | 2023-04-07 | 山东京博农化科技股份有限公司 | Synthetic method of 6-amino-7-fluoro-2H-1, 4-benzoxazine-3 (4H) -ketone |
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