CN105968066B - The preparation method of benzoxazin ketone compound containing nitro - Google Patents
The preparation method of benzoxazin ketone compound containing nitro Download PDFInfo
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- C07—ORGANIC CHEMISTRY
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- 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
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Abstract
The present invention provides a kind of preparation methods of benzoxazin ketone compound containing nitro, preparation method provided by the invention passes through benzoxazin ketone compound, concentrated nitric acid and the solvent hybrid reaction that will have formula (I) structure, the benzoxazin ketone compound containing nitro with formula (II) structure is obtained, and makes the mixed solution of the solvent organic solvent and the concentrated sulfuric acid；So that the purity is high of the benzoxazin ketone compound containing nitro of preparation, and yield is improved, and the acid solution of end of reaction can also cover the bottom liquid for being used as reaction again, reduce the yield of waste liquid, while reducing the consumption of raw material.
Description
Technical field
The present invention relates to the field of chemical synthesis more particularly to a kind of preparation sides of the benzoxazin ketone compound containing nitro
Method.
Background technique
The synthesis of nitrogen-containing heterocycle compound is an important field of research, the benzoxazinone series especially containing nitro
Compound is important synthetic intermediate, can be used for the preparation of human administration and pesticide, for example, the fluoro- 6- nitro -2H-1 of 7-,
4- benzoxazine -3 (4H) -one can be used for the preparation of herbicide flumioxazin, flumioxazin structure are as follows:
And the fluoro- 6- nitro -2H-1 of 7- is prepared at present, the method for 4- benzoxazine -3 (4H) -one is main are as follows: by the fluoro- 2H- of 7-
Isosorbide-5-Nitrae-benzoxazine -3 (4H) -one carried out in the presence of the concentrated sulfuric acid and concentrated nitric acid nitrification be made, such as application No. is
201410219121 patent is exactly this method used, and still, the presently disclosed production method generates a large amount of spent acid, and
The color of the spent acid is very deep, can not recycle again, and environmental pressure is big, and obtained product purity is lower,
Summary of the invention
In view of this, technical problem to be solved by the present invention lies in provide a kind of benzoxazine ketone chemical combination containing nitro
The preparation method of object, the product purity that preparation method provided by the invention not only obtains is high, but also the waste liquid generated is few.
The present invention provides a kind of preparation methods of benzoxazin ketone compound containing nitro, comprising:
To have benzoxazin ketone compound, concentrated nitric acid and the solvent hybrid reaction of formula (I) structure, obtain with formula
(II) benzoxazin ketone compound containing nitro of structure, wherein the solvent is molten for the mixing of organic solvent and the concentrated sulfuric acid
Liquid；
Wherein, the Xn indicates to be connected with n X group on phenyl ring, and the X is halogen, hydroxyl, amido or C1~C20
Alkyl, the n are 0,1,2 or 3, and as n >=2, X is identical or different；
The R is the alkyl of C1~C10.
Preferably, the organic solvent is ethyl acetate, toluene, dimethylbenzene, methylene chloride, dimethyl sulfoxide, 1,2- bis-
One or more of chloroethanes, chloroform and tetrachloro-ethylene.
Preferably, the mass ratio of the organic solvent and the concentrated sulfuric acid is 1:(1~2.5).
Preferably, the temperature of the hybrid reaction is -5~10 DEG C.
Preferably, the mass concentration of the concentrated nitric acid is 55%~65%.
Preferably, the mass concentration of the concentrated sulfuric acid is 70%~85%.
Preferably, the X is the alkyl of halogen, hydroxyl, amido or C2~C10.
Preferably, the X be chlorine, bromine, hydroxyl, amido, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group,
Tert-butyl or n-pentyl.
Preferably, the R is methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, tert-butyl, n-pentyl, just
Hexyl or n-heptyl.
Preferably, the benzoxazin ketone compound containing nitro with formula (II) structure is formula (II-1), formula
(II-2), formula (II-3), formula (II-4), formula (II-5), formula (II-6), formula (II-7), formula (II-8), formula (II-9), formula (II-
10), formula (II-11), formula (II-12), formula (II-13), formula (II-14), formula (II-15), formula (II-16), formula (II-17), formula
(II-18), formula (II-19) or formula (II-20),
Compared with prior art, the present invention provides a kind of preparation method of benzoxazin ketone compound containing nitro,
Preparation method provided by the invention passes through the benzoxazin ketone compound that will have formula (I) structure, concentrated nitric acid and solvent mixing
Reaction, obtain the benzoxazin ketone compound containing nitro with formula (II) structure, and make the solvent organic solvent with
The mixed solution of the concentrated sulfuric acid；So that the purity is high of the benzoxazin ketone compound containing nitro of preparation, and yield also mentions
Gao Liao, and the acid solution of end of reaction can also cover the solvent for being used as reaction again, reduce the yield of waste liquid, reduce simultaneously
The consumption of raw material；The experimental results showed that the benzoxazine ketone chemical combination containing nitro of preparation method preparation provided by the invention
The purity of object is 97.8% or more, and yield is 97% or more.
Specific embodiment
The present invention provides a kind of preparation methods of benzoxazin ketone compound containing nitro, comprising:
To have benzoxazin ketone compound, concentrated nitric acid and the solvent hybrid reaction of formula (I) structure, obtain with formula
(II) benzoxazin ketone compound containing nitro of structure, wherein the solvent is molten for the mixing of organic solvent and the concentrated sulfuric acid
Liquid；
Wherein, the Xn indicates to be connected with n X group on phenyl ring, and the X is halogen, hydroxyl, amido or C1~C20
Alkyl, the n are 0,1,2 or 3, and as n >=2, X is identical or different；
The R is the alkyl of C1~C10.
According to the present invention, the present invention will have benzoxazin ketone compound, concentrated nitric acid and the solvent mixing of formula (I) structure
Reaction, obtains the benzoxazin ketone compound containing nitro with formula (II) structure；Wherein, the mass concentration of the concentrated nitric acid
Preferably 55wt%~65wt%, more preferably 60wt%~62wt%；In the solvent, the organic solvent and the dense sulphur
The mass ratio of acid is preferably 1:(1~2.5), more preferably 1:(1.5~2)；The organic solvent is preferably ethyl acetate, first
One or more of benzene, dimethylbenzene, methylene chloride, dimethyl sulfoxide, 1,2- dichloroethanes, chloroform and tetrachloro-ethylene,
More preferably ethyl acetate, toluene, dimethylbenzene, methylene chloride, dimethyl sulfoxide, 1,2- dichloroethanes, chloroform or tetrachloro
Ethylene；The mass concentration of the concentrated sulfuric acid is preferably 70wt%~85wt%, more preferably 75wt%~80wt%；The formula
(I) in the benzoxazin ketone compound of structure, the X is preferably the alkyl of halogen, hydroxyl, amido or C2~C10, more preferably
For chlorine, bromine, hydroxyl, amido, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, tert-butyl or n-pentyl；The R
Preferably methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, tert-butyl, n-pentyl, n-hexyl or n-heptyl；More
Body, the benzoxazin ketone compound containing nitro with formula (II) structure being prepared be preferably formula (II-1),
Formula (II-2), formula (II-3), formula (II-4), formula (II-5), formula (II-6), formula (II-7), formula (II-8), formula (II-9), formula
(II-10), formula (II-11), formula (II-12), formula (II-13), formula (II-14), formula (II-15), formula (II-16), formula (II-
17), formula (II-18), formula (II-19) or formula (II-20),
In the present invention, the benzoxazin ketone compound with formula (I) structure and the molar ratio of the concentrated nitric acid are excellent
It is selected as 1:(1.05~1.5), more preferably 1:(1.1~1.4), most preferably 1:(1.2~1.3)；The concentrated sulfuric acid with it is described
The mass ratio of benzoxazine compounds with formula (I) structure is (2~2.5): 1, more preferably (2.2~2.3): 1；It is described
The temperature of reaction is preferably -5~10 DEG C, more preferably 0~5 DEG C.
In the present invention, in order to keep reaction effect more preferable, the present invention preferably feeds in the following way, react and after
Processing: firstly, will have the benzoxazin ketone compound of formula (I) structure to mix with organic solvent, then in -5~10 DEG C of items
The concentrated sulfuric acid and concentrated nitric acid are sequentially added under part, obtains reaction solution, the reaction was continued under the conditions of -5~10 DEG C, obtains with formula (II)
The benzoxazin ketone compound containing nitro of structure；The time of the reaction is preferably 0.5~3 hour, more preferably 1~2
Hour；After completion of the reaction, reaction solution is quenched, the reaction solution being quenched, described be quenched with raw material is ice water；It is described when being quenched
The temperature of reaction solution is preferably 30 DEG C or less；After being quenched, by the reaction solution being quenched by vacuum distillation, organic solvent is recycled, so
Raffinate is cooled down afterwards, is centrifuged, obtains the benzoxazin ketone compound and spent acid containing nitro with formula (II) structure, is given up
Acid can be directly used for applying after being concentrated and filter by high temperature distillation.
The present invention provides a kind of preparation method of benzoxazin ketone compound containing nitro, preparations provided by the invention
Method passes through benzoxazin ketone compound, concentrated nitric acid and the solvent hybrid reaction that will have formula (I) structure, obtains with formula
(II) benzoxazin ketone compound containing nitro of structure, and keep the mixing of the solvent organic solvent and the concentrated sulfuric acid molten
Liquid；So that the purity is high of the benzoxazin ketone compound containing nitro of preparation, and yield also improves, and has reacted
Complete acid solution can also cover the solvent for being used as reaction again, reduce the yield of waste liquid, while reducing the consumption of raw material, no
It reduced by only cost, and be conducive to the protection of environment.
It is clearly and completely described below in conjunction with the technical solution of the embodiment of the present invention, it is clear that described implementation
Example is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, this field is common
Technical staff's every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.
Embodiment 1
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g7- is added, 30ml acetic acid second is added in 4- benzoxazine -3 (4H) -one
Ester, stirring a period of time adjust temperature to 0-10 DEG C, 80% content concentrated sulfuric acid 57g are slowly added dropwise, concentrated nitric acid is added dropwise at low temperature
It is dripped in 16.1g, 4h, insulation reaction 1h is then stirred under cryogenic conditions, pours into the burning for filling 150g ice water after reaction
In bottle, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa recycles organic solvent 55ml, so
Surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed afterwards, and drying obtains fluoro- 6- nitro -2H-1, the 4- benzo of white solid 7- and dislikes
Piperazine -3 (4H) -one, yield 97%, purity 98%.
Spent acid after reaction treatment is complete can be applied directly by the acid after high temperature distillation thickening filtration is used in next group.
Embodiment 2
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g7- is added, 30ml acetic acid second is added in 4- benzoxazine -3 (4H) -one
Ester, stirring a period of time adjust temperature to 0-10 DEG C, and it is 71% concentrated sulfuric acid 60 that batch content of recycling, which is slowly added dropwise, in low temperature
It is dripped in lower dropwise addition concentrated nitric acid 16.1g, 4h, insulation reaction 1h is then stirred under cryogenic conditions, pours into fill after reaction
In the flask of 150g ice water, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa, recycling has
Solvent 55ml, then surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed, and drying obtains the fluoro- 6- nitro-of white solid 7-
2H-1,4- benzoxazine -3 (4H) -one, yield 96.9%, purity 98%.
Spent acid after reaction treatment is complete can continue directly to apply to be used in down by the acid after high temperature distillation thickening filtration
A batch.
Embodiment 3
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g7- is added, 30ml dichloromethane is added in 4- benzoxazine -3 (4H) -one
Alkane, stirring a period of time adjust temperature to 0-10 DEG C, 80% concentrated sulfuric acid 55g are slowly added dropwise, concentrated nitric acid is added dropwise at low temperature
It is dripped in 16.1g, 4h, insulation reaction 1h is then stirred under cryogenic conditions, pours into the burning for filling 150g ice water after reaction
In bottle, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa recycles organic solvent 55ml, so
Surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed afterwards, and drying obtains fluoro- 6- nitro -2H-1, the 4- benzo of white solid 7- and dislikes
Piperazine -3 (4H) -one, yield 96.9%, purity 97.8%.
Spent acid after reaction treatment is complete can be applied directly by the acid after high temperature distillation thickening filtration is used in next group.
Embodiment 4
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g7- is added, 30ml diformazan is added in 4- benzoxazine -3 (4H) -one
Benzene, stirring a period of time adjust temperature to 0-10 DEG C, 75% concentrated sulfuric acid 60g are slowly added dropwise, concentrated nitric acid is added dropwise at low temperature
It is dripped in 16.1g, 4h, insulation reaction 1h is then stirred under cryogenic conditions, pours into the burning for filling 150g ice water after reaction
In bottle, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa recycles organic solvent 55ml, so
Surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed afterwards, and drying obtains fluoro- 6- nitro -2H-1, the 4- benzo of white solid 7- and dislikes
Piperazine -3 (4H) -one, yield 96.7%, purity 97.9%.
Spent acid after reaction treatment is complete can be applied directly by the acid after high temperature distillation thickening filtration is used in next group.
Embodiment 5
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g7- is added, 30ml dimethyl is added in 4- benzoxazine -3 (4H) -one
Sulfoxide, stirring a period of time adjust temperature to 0-10 DEG C, 80% concentrated sulfuric acid 55g are slowly added dropwise, concentrated nitric acid is added dropwise at low temperature
It is dripped in 16.1g, 4h, insulation reaction 1h is then stirred under cryogenic conditions, pours into the burning for filling 150g ice water after reaction
In bottle, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa recycles organic solvent 55ml, so
Surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed afterwards, and drying obtains fluoro- 6- nitro -2H-1, the 4- benzo of white solid 7- and dislikes
Piperazine -3 (4H) -one, yield 96.8%, purity 97.9%.
Spent acid after reaction treatment is complete can be applied directly by the acid after high temperature distillation thickening filtration is used in next group.
Embodiment 6
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g7- is added, 30ml toluene is added in 4- benzoxazine -3 (4H) -one,
Stirring a period of time adjusts temperature to 0-10 DEG C, 70% concentrated sulfuric acid 70g is slowly added dropwise, concentrated nitric acid 16.1g is added dropwise at low temperature,
It is dripped in 4h, insulation reaction 1h is then stirred under cryogenic conditions, is poured into the flask for filling 150g ice water after reaction, it will
Mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa, recycles organic solvent 55ml, then remaining
Material is cooled to 30 DEG C hereinafter, centrifugation, is washed, and drying obtains fluoro- 6- nitro -2H-1, the 4- benzoxazine -3 of white solid 7-
(4H) -one, yield 96.9%, purity 97.9%.
Spent acid after reaction treatment is complete can be applied directly by the acid after high temperature distillation thickening filtration is used in next group.
Embodiment 7
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g7- is added, bis- chloroethene of 30ml is added in 4- benzoxazine -3 (4H) -one
Alkane, stirring a period of time adjust temperature to 0-10 DEG C, 80% concentrated sulfuric acid 57ml are slowly added dropwise, concentrated nitric acid is added dropwise at low temperature
It is dripped in 16.1g, 4h, insulation reaction 1h is then stirred under cryogenic conditions, pours into the burning for filling 150g ice water after reaction
In bottle, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa recycles organic solvent 55ml, so
Surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed afterwards, and drying obtains fluoro- 6- nitro -2H-1, the 4- benzo of white solid 7- and dislikes
Piperazine -3 (4H) -one, yield 96.6%, purity 98.1%.
Spent acid after reaction treatment is complete can be applied directly by the acid after high temperature distillation thickening filtration is used in next group.
Embodiment 8
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g7- is added, tri- chloromethane of 30ml is added in 4- benzoxazine -3 (4H) -one
Alkane, stirring a period of time adjust temperature to 0-10 DEG C, 80% concentrated sulfuric acid 55g are slowly added dropwise, concentrated nitric acid is added dropwise at low temperature
It is dripped in 16.1g, 4h, insulation reaction 1h is then stirred under cryogenic conditions, pours into the burning for filling 150g ice water after reaction
In bottle, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa recycles organic solvent 55ml, so
Surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed afterwards, and drying obtains fluoro- 6- nitro -2H-1, the 4- benzo of white solid 7- and dislikes
Piperazine -3 (4H) -one, yield 96.8%, purity 97.8%.
Spent acid after reaction treatment is complete can be applied directly by the acid after high temperature distillation thickening filtration is used in next group.
Embodiment 9
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g7- is added, tetra- chloroethene of 30ml is added in 4- benzoxazine -3 (4H) -one
Alkene, stirring a period of time adjust temperature to 0-10 DEG C, 80% concentrated sulfuric acid 57g are slowly added dropwise, concentrated nitric acid is added dropwise at low temperature
It is dripped in 16.1g, 4h, insulation reaction 1h is then stirred under cryogenic conditions, pours into the burning for filling 150g ice water after reaction
In bottle, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa recycles organic solvent 55ml, so
Surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed afterwards, and drying obtains fluoro- 6- nitro -2H-1, the 4- benzo of white solid 7- and dislikes
Piperazine -3 (4H) -one, yield 96.7%, purity 98.1%.
Spent acid after reaction treatment is complete can directly be covered for next group by the acid after high temperature distillation thickening filtration.
Embodiment 10
In 250ml four-hole boiling flask, the chloro- 2H-1 of 20g7- is added, 30ml acetic acid second is added in 4- benzoxazine -3 (4H) -one
Ester, stirring a period of time adjust temperature to 0-10 DEG C, 80% concentrated sulfuric acid 57g are slowly added dropwise, concentrated nitric acid is added dropwise at low temperature
It is dripped in 14.8g, 4h, insulation reaction 1h is then stirred under cryogenic conditions, pours into the burning for filling 150g ice water after reaction
In bottle, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa recycles organic solvent 55ml, so
Surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed afterwards, and drying obtains fluoro- 6- nitro -2H-1, the 4- benzo of white solid 7- and dislikes
Piperazine -3 (4H) -one, yield 97.0%, purity 98.1%.
Spent acid after reaction treatment is complete can directly be covered for next group by the acid after high temperature distillation thickening filtration.
Embodiment 11
In 250ml four-hole boiling flask, -3 (4H) -one of 20g7- methyl -2H-1,4- benzoxazine is added,
30ml ethyl acetate is added, stirring a period of time adjusts temperature to 0-10 DEG C, the 80% content concentrated sulfuric acid is slowly added dropwise
Concentrated nitric acid 15.7g is added dropwise at low temperature, drips in 4h, insulation reaction 1h is then stirred under cryogenic conditions by 57g, and reaction terminates
It is poured into the flask for filling 150g ice water afterwards, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-
0.095MPa recycles organic solvent 55ml, and then surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed, and drying obtains white
Fluoro- -3 (4H) -one of 6- nitro -2H-1,4- benzoxazine of solid 7-, yield 97.2%, purity 98.0%.
Spent acid after reaction treatment is complete can be applied directly by the acid after high temperature distillation thickening filtration is used in next group.
Embodiment 12
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g5- is added, 30ml acetic acid second is added in 4- benzoxazine -3 (4H) -one
Ester, stirring a period of time adjust temperature to 0-10 DEG C, 80% content concentrated sulfuric acid 57g are slowly added dropwise, concentrated nitric acid is added dropwise at low temperature
It is dripped in 16.1g, 4h, insulation reaction 1h is then stirred under cryogenic conditions, pours into the burning for filling 150g ice water after reaction
In bottle, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa recycles organic solvent 55ml, so
Surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed afterwards, and drying obtains fluoro- 6- nitro -2H-1, the 4- benzo of white solid 7- and dislikes
Piperazine -3 (4H) -one, yield 96.9%, purity 98.0%.
Spent acid after reaction treatment is complete can be applied directly by the acid after high temperature distillation thickening filtration is used in next group.
Embodiment 13
In 250ml four-hole boiling flask, fluoro- -3 (4H) -one of 7- methyl -2H-1,4- benzoxazine of 20g5- is added, is added
30ml ethyl acetate, stirring a period of time adjust temperature to 0-10 DEG C, 80% content concentrated sulfuric acid 57g are slowly added dropwise, at low temperature
Concentrated nitric acid 14.8g is added dropwise, is dripped in 4h, insulation reaction 1h is then stirred under cryogenic conditions, pours into fill after reaction
In the flask of 150g ice water, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa, recycling has
Solvent 55ml, then surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed, and drying obtains the fluoro- 6- nitro-of white solid 7-
2H-1,4- benzoxazine -3 (4H) -one, yield 97.0%, purity 97.8%.
Spent acid after reaction treatment is complete can be applied directly by the acid after high temperature distillation thickening filtration is used in next group.
Embodiment 14
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g7- is added, 30ml acetic acid second is added in 4- benzoxazine -3 (4H) -one
Ester, stirring a period of time, adjust temperature to 0-10 DEG C, be slowly added dropwise embodiment 1 recycling apply 80% content concentrated sulfuric acid 50g and
Concentrated nitric acid 16.1g is added dropwise under low temperature, drips in 4h, insulation reaction 1h is then stirred under cryogenic conditions, instead by new 80% sulfuric acid 7g
It is poured into after answering in the flask for filling 150g ice water, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-
0.095MPa recycles organic solvent 55ml, and then surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed, and drying obtains white
Fluoro- -3 (4H) -one of 6- nitro -2H-1,4- benzoxazine of solid 7-, yield 96.9%, purity 97.9%.
Spent acid after reaction treatment is complete can also be applied directly by the acid after high temperature distillation thickening filtration is used in next group.
Comparative example 1
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g7-, 4- benzoxazine -3 (4H) -one, adjustment temperature to 0-10 is added
DEG C, 80% concentrated sulfuric acid 90g is slowly added dropwise, concentrated nitric acid 16.1g is added dropwise at low temperature, drips in 4h, is then stirred under cryogenic conditions
Insulation reaction 1h is mixed, is poured into the flask for filling 300g ice water after reaction, mixed liquor is poured into four-hole boiling flask and is subtracted
Pressure distillation, vacuum degree >=-0.095MPa recycle organic solvent 55ml, and then surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed
It washs, dries, obtain fluoro- -3 (4H) -one of 6- nitro -2H-1,4- benzoxazine of solid 7-, yield 93%, purity 95.6%.
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g7-, 4- benzoxazine -3 (4H) -one, adjustment temperature to 0-10 is added
DEG C, 80% concentrated sulfuric acid 80g and new 80% sulfuric acid 10g of 1 recovery of comparative example is slowly added dropwise, concentrated nitric acid is added dropwise at low temperature
It is dripped in 16.1g, 4h, insulation reaction 1h is then stirred under cryogenic conditions, pours into the burning for filling 300g ice water after reaction
In bottle, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa recycles organic solvent 55ml, so
Surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed afterwards, and drying obtains fluoro- 6- nitro -2H-1, the 4- benzoxazine -3 of solid 7-
(4H) -one, appearance are faint yellow, yield 85%, purity 94.0%., yield and content be substantially reduced compared with embodiment, quality
It does not reach requirement.
Comparative example 3
In 250ml four-hole boiling flask, the fluoro- 2H-1 of 20g7-, 4- benzoxazine -3 (4H) -one, adjustment temperature to 0-10 is added
DEG C, 80% concentrated sulfuric acid 80g and new 80% sulfuric acid 10g of 2 recovery of comparative example is slowly added dropwise, concentrated nitric acid is added dropwise at low temperature
It is dripped in 16.1g, 4h, insulation reaction 1h is then stirred under cryogenic conditions, pours into the burning for filling 300g ice water after reaction
In bottle, mixed liquor is poured into four-hole boiling flask and is evaporated under reduced pressure, vacuum degree >=-0.095MPa recycles organic solvent 55ml, so
Surplus material is cooled to 30 DEG C hereinafter, centrifugation, is washed afterwards, and drying obtains fluoro- 6- nitro -2H-1, the 4- benzo of dark yellow solid 7-
Oxazines -3 (4H) -one, yield 76%, purity 91%, quality condition substantially reduces, while economic index is poor, does not have work
Industry condition.
The above description of the embodiment is only used to help understand the method for the present invention and its core ideas.It should be pointed out that pair
For those skilled in the art, without departing from the principle of the present invention, the present invention can also be carried out
Some improvements and modifications, these improvements and modifications also fall within the scope of protection of the claims of the present invention.
Claims (2)
1. a kind of preparation method of the benzoxazin ketone compound containing nitro, comprising:
To have benzoxazin ketone compound, concentrated nitric acid and the solvent hybrid reaction of formula (I) structure, and obtain tying with formula (II)
The benzoxazin ketone compound and spent acid containing nitro of structure；
Wherein, the mass concentration of the concentrated nitric acid is 55%~65%；
The solvent is the mixed solution of organic solvent and the concentrated sulfuric acid；
The mass ratio of the organic solvent and the concentrated sulfuric acid is 1:(1~2.5)；
The mass concentration of the concentrated sulfuric acid is 70%~85%；
Spent acid can be directly used for applying after being concentrated and filter by high temperature distillation；
The benzoxazin ketone compound with formula (I) structure is formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula
(I-5), formula (I-6), formula (I-7), formula (I-8), formula (I-9) or formula (I-10),
The benzoxazin ketone compound containing nitro with formula (II) structure is formula (II-1), formula (II-2), formula (II-
3), formula (II-4), formula (II-5), formula (II-6), formula (II-7), formula (II-8), formula (II-9) or formula (II-10),
The organic solvent is ethyl acetate, toluene, dimethylbenzene, methylene chloride, dimethyl sulfoxide, 1,2- dichloroethanes, trichlorine
One or more of methane and tetrachloro-ethylene.
2. preparation method according to claim 1, which is characterized in that the temperature of the hybrid reaction is -5~10 DEG C.
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| US20140206663A1 (en) * | 2012-12-10 | 2014-07-24 | Jianfei Wang | Triazinone compounds |
| CN103965181A (en) * | 2014-05-22 | 2014-08-06 | 黑龙江大学 | Preparation method of flumioxazin |
| CN105566233A (en) * | 2015-12-31 | 2016-05-11 | 重庆威鹏药业有限公司 | Preparation method of erlotinib intermediate |
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| CN103965181A (en) * | 2014-05-22 | 2014-08-06 | 黑龙江大学 | Preparation method of flumioxazin |
| CN105566233A (en) * | 2015-12-31 | 2016-05-11 | 重庆威鹏药业有限公司 | Preparation method of erlotinib intermediate |
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| Synthesis of Novel 6-(2-aminopyrimidin-4-yl)benzoxazinones;Ch. Rajitha et al;《India Journal of Heterocyclic Chemistry》;20150331;第24卷;第325-328页尤其是第326页Scheme-1及右栏化合物3的制备 |
| 探索提高甲苯硝化反应中对硝基甲苯的收率;黄玲;《化工设计》;20110415;第21卷(第2期);第16-19页，尤其是第17页第2.2.4节 |
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