CN106317042B - A kind of synthetic method of the fluoro- 6- amino -4- of 7- (2- propargyls) -1,4- benzoxazines -3 (4H) -one derivative - Google Patents
A kind of synthetic method of the fluoro- 6- amino -4- of 7- (2- propargyls) -1,4- benzoxazines -3 (4H) -one derivative Download PDFInfo
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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Abstract
The present invention relates to organic synthesis fields, more particularly to a kind of fluoro- 6- amino -4- of 7- (2- propargyls) -1, the synthetic method of 4- benzoxazines -3 (4H) -one derivative, this method is with fluoro- 4- propinyls-Isosorbide-5-Nitrae-benzoxazine -3 (4H) -one and 3,4 of 6- amino -7-, 5,6- tetrahydrophthalic anhydride be raw material, under the catalytic action of organic acid and salt react to get；Wherein, the optimal selection of the catalyst is acetic acid and potassium acetate, and potassium acetate is cheap, with it is existing use piperidines to be reacted as catalyst compared with, using acetic acid and potassium acetate as catalyst, with the low significant advantage of production cost；And the yield of the reaction, up to 91% or more, for purity up to 99.5% or more, product purity and impurity standard meet relevant regulations.
Description
Technical field
The present invention relates to technical field of organic synthesis more particularly to a kind of 7- fluoro- 6- amino -4- (2- propargyls)-Isosorbide-5-Nitraes -
The synthetic method of benzoxazine -3 (4H) -one derivative.
Background technology
- benzoxazine -3 (4H) -one derivative of 7- fluoro- 6- amino -4- (2- propargyls)-Isosorbide-5-Nitrae, also known as flumioxazin
(speed is received) is a kind of IV-phenylphthalimide class herbicide absorbed for young shoot and blade, can effectively prevent and kill off 1 year
Raw broad leaved weed and grassy weed.Meanwhile the herbicide with efficient, low toxicity, highly selective strong and low environment because polluting
Feature, market prospects are very extensive.
There are main a few class methods for the synthesis of flumioxazin at present：
US4640707 discloses a kind of method preparing flumioxazin, and this method includes being not added with and urging using acetic acid as solvent
Agent, fluoro- 4- propinyls-Isosorbide-5-Nitrae-benzoxazine -3 (4H) -one of 6- amino -7- are reacted with 3,4,5,6- tetrahydrophthalic anhydride, to
To product flumioxazin, according to this patent prepare product purity is not high, existing market cannot be met to product purity
Requirement 99.2% or more；CN105061416A discloses a kind of method preparing flumioxazin, and this method includes with first
Benzene, dichloroethanes or methyl iso-butyl ketone (MIBK) are solvent, and the mixed of alkaline itrogenous organic substance or organic acid and itrogenous organic substance is added
Conjunction object is catalyst, and fluoro- 4- propinyls-Isosorbide-5-Nitrae-benzoxazine -3 (4H) -one of 6- amino -7- is dehydrated with 3,4,5,6- tetrahydrophthalic anhydride
Reaction prepares product flumioxazin.The catalyst of the patent report, especially preferred piperidines is control chemicals, using not
Convenient and price is high.
In summary：Existing method has the following disadvantages：1. product purity is low, fall short of specifications.2. the catalysis used
Agent especially piperidines belongs to easy toxogen material processed, and industrial applications are restricted and expensive.
In consideration of it, provide a kind of raw material be easy to get, the reaction of cheap catalyst, and ensure that product quality meets rule
The synthetic method of fixed flumioxazin is necessary.
Invention content
The object of the present invention is to provide a kind of 7- fluoro- 6- amino -4- (2- propargyls) -1,4- benzoxazines -3 (4H) -one
The synthetic method of derivative, specially：With fluoro- -3 (4H) -one of 4- propinyls -1,4- benzoxazines of 6- amino -7- and 3,4,5,
6- tetrahydrophthalic anhydride be raw material, under the catalytic action of organic acid and salt react to get.
The reaction mechanism mechanism of reaction is as follows：
Preferably, the salt is organic salt, and the organic salt is acetate or ammonium acetate；It is further preferred that the vinegar
Hydrochlorate is selected from least one of potassium acetate, cesium acetate, sodium acetate；Most preferably, the acetate is potassium acetate.
Alternatively, the salt is inorganic salts；Preferably, the inorganic salts are selected from potassium carbonate, cesium carbonate, potassium chloride, phosphoric acid hydrogen
It is one or more in dipotassium, potassium dihydrogen phosphate, potassium sulfate, potassium acid sulfate.
Preferably, the organic acid is one or more in acetic acid, propionic acid, butyric acid, trifluoroacetic acid, further preferably
For acetic acid.
As the most preferred scheme of the present invention, in the above method, the organic acid is acetic acid, and the salt is potassium acetate.
Preferably, in the above method, the molar ratio of organic acid and salt is 1:(0.01-5), further preferably 1：(0.05-
3)。
Preferably, in the above method, the fluoro- 4- propinyls of 6- amino -7--Isosorbide-5-Nitrae-benzoxazine -3 (4H) -one, 3,4,5,6-
Tetrahydrophthalic anhydride, the molar ratio of organic acid are 1:(0.95-1.3):(0.05-2).
Preferably, the reaction carries out in a solvent, and the solvent is selected from acetic acid, toluene, chloroform, hexamethylene, 1,2- bis-
It is one or more in chloroethanes, methyl iso-butyl ketone (MIBK).
It is further preferred that the reaction of the present invention is using toluene as solvent.
Preferably, the reaction carries out under the conditions of reflux dewatering.
The technical solution best as the present invention, the operation of above-mentioned reaction are specially：According to the fluoro- 4- propine of 6- amino -7-
Base -1,4- benzoxazines -3 (4H) -one, 3,4,5,6- tetrahydrophthalic anhydride, the molar ratio of acetic acid are 1:(0.95-1.3):(0.05-
2), the molar ratio of acetic acid and potassium acetate is 1:The ratio of (0.05-3) is reacted using toluene as solvent under the conditions of reflux dewatering,
To obtain the final product.
The synthetic method of the present invention further includes the steps that being post-processed to the system after reaction, and the post-processing is specific
For：After completion of the reaction, solvent is removed, obtained solid is beaten using organic solvent, it is dry to get product after filtering.
Preferably, the solvent that the mashing uses is one or more in ethyl acetate, ethyl alcohol, dichloromethane.Most
Preferably ethyl acetate.
The present invention reaction generate by-product be water, it is therefore desirable to during the reaction constantly remove generate water to
Reaction is promoted to be carried out towards positive reaction direction.But due to fluoro- -3 (4H) -one of 4- propinyls -1,4- benzoxazines of 6- amino -7- with
The particularity of 3,4,5,6- tetrahydrophthalic anhydride raw materials, under conditions of no catalyst, even if dividing aqueous solvent such as toluene, dichloro common
It is carried out in methane, reaction speed is very slow, greatly affected industrial production efficiency.Present inventors have unexpectedly found that with organic acid and salt
Reaction efficiency can be greatly improved as catalyst, shorten the reaction time, and side reaction is inhibited well in reaction, impurity life
At less.Further probe into its reaction mechanism, it may be possible to because by the combination of acid and salt, the PH of reaction environment can be adjusted
Value promotes reaction to be carried out towards main reaction.
The method for synthesizing flumioxazin is optimized in the present invention, and the method after optimization has following advantage：
(1) inorganic salt catalyst used is cheap, about 2000 yuan/ton, about with the price that uses in the prior art
50000 yuan/ton of piperidines compares (piperidines is controlled drug), has at low cost, the advantage that raw material is easy to get；
(2) reaction yield is up to 91% or more, and the purity of flumioxazin is up to 99.5% or more, product purity and miscellaneous
Matter specification meets the requirements.
On the basis of common knowledge of the art, above-mentioned each optimum condition can be combined with each other each preferably to get the present invention
Embodiment.
Specific implementation mode
The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention..The reagent referred in embodiment
Or raw material is known product, commercially available acquisition；The operation being related to is this field routine techniques behaviour unless otherwise specified
Make.
Embodiment 1
A kind of synthetic method of-benzoxazine -3 (4H) -one derivative of the fluoro- 6- amino -4- of 7- (2- propargyls)-Isosorbide-5-Nitrae, tool
Gymnastics conduct：
By the fluoro- 4- propinyls of the 6- amino -7- of 23.2g 95%-Isosorbide-5-Nitrae-benzoxazine -3 (4H) -one, 15.9g 3,4,5,
6- tetrahydrophthalic anhydride, 0.6g acetic acid, 1.96g potassium acetates are added in 100mL toluene solvants, react 6h, HPLC in 110 DEG C of reflux dewaterings
Reaction process is monitored, after the completion of reaction, solvent is sloughed in decompression, and gained filter cake is beaten using ethyl acetate, dry after filtering, is obtained
Flumioxazin 32.1g, purity 99.5%, yield 91%.Product confirms through NMR and LC-MS.
Embodiment 2
A kind of synthetic method of-benzoxazine -3 (4H) -one derivative of the fluoro- 6- amino -4- of 7- (2- propargyls)-Isosorbide-5-Nitrae, should
The operation of embodiment is differed only in embodiment 1：Potassium acetate is replaced with into sodium acetate.Reaction terminates, and obtains flumioxazin
31.8g, purity 99.2%, yield 90%.
Embodiment 3
A kind of synthetic method of-benzoxazine -3 (4H) -one derivative of the fluoro- 6- amino -4- of 7- (2- propargyls)-Isosorbide-5-Nitrae, should
The operation of embodiment is differed only in embodiment 1：Potassium acetate is replaced with into potassium carbonate.Reaction terminates, and obtains flumioxazin
31.7g, purity 99.5%, yield 90%.
Embodiment 4
A kind of synthetic method of-benzoxazine -3 (4H) -one derivative of the fluoro- 6- amino -4- of 7- (2- propargyls)-Isosorbide-5-Nitrae, should
The operation of embodiment is differed only in embodiment 1：Potassium acetate is replaced with into ammonium acetate.Reaction terminates, and obtains flumioxazin
31.6g, purity 99.5%, yield 89%.
Embodiment 5
A kind of synthetic method of-benzoxazine -3 (4H) -one derivative of the fluoro- 6- amino -4- of 7- (2- propargyls)-Isosorbide-5-Nitrae, should
The operation of embodiment is differed only in embodiment 1：Acetic acid is replaced with into propionic acid.Reaction terminates, and obtains flumioxazin 32.3g,
Purity 99.4%, yield 92%.
Embodiment 6
A kind of synthetic method of-benzoxazine -3 (4H) -one derivative of the fluoro- 6- amino -4- of 7- (2- propargyls)-Isosorbide-5-Nitrae, should
The operation of embodiment is differed only in embodiment 1：Toluene is replaced with into 1,2- dichloroethanes, reflux dewatering reaction, reaction knot
Beam obtains flumioxazin 32.0g, purity 99.7%, yield 91%.
Embodiment 7
A kind of synthetic method of-benzoxazine -3 (4H) -one derivative of the fluoro- 6- amino -4- of 7- (2- propargyls)-Isosorbide-5-Nitrae, should
The operation of embodiment is differed only in embodiment 1：The dosage of potassium acetate is 2.9g, and reaction terminates, and obtains flumioxazin
31.7g, purity 99.5%, yield 90%.
Embodiment 8
A kind of synthetic method of-benzoxazine -3 (4H) -one derivative of the fluoro- 6- amino -4- of 7- (2- propargyls)-Isosorbide-5-Nitrae, should
The operation of embodiment is differed only in embodiment 1：The dosage of potassium acetate is 0.05g, and reaction terminates, and obtains flumioxazin
31.8g, purity 99.4%, yield 90%.
Comparative example 1
The operation of the comparative example is differed only in embodiment 1：The dosage of potassium acetate is 3.5g, and reaction terminates, and obtains propine
Benfluralin 27.1g, purity 98.5%, yield 76%.
Comparative example 2
The operation of the comparative example is differed only in embodiment 1：The dosage of acetic acid is 0.02g, and the dosage of potassium acetate is
0.098g, reaction terminate, and obtain flumioxazin 19.9g, purity 97%, yield 55%.
Although above having used general explanation, specific implementation mode and experiment, the present invention is made to retouch in detail
It states, but on the basis of the present invention, it can be made some modifications or improvements, this is apparent to those skilled in the art
's.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, belong to claimed
Range.
Claims (9)
1. a kind of synthetic method of-benzoxazine -3 (4H) -one derivative of the fluoro- 6- amino -4- of 7- (2- propargyls)-Isosorbide-5-Nitrae, special
Sign is：With fluoro- 4- propinyls-Isosorbide-5-Nitrae-benzoxazine -3 (4H) -one and 3 of 6- amino -7-, 4,5,6- tetrahydrophthalic anhydride are raw material,
Under the catalytic action of organic acid and salt react to get；
The organic acid is selected from acetic acid or propionic acid；
The salt is selected from least one of potassium acetate, sodium acetate, potassium carbonate, cesium carbonate, ammonium acetate；
The structural formula of the fluoro- 6- amino -4- of 7- (2- propargyls) -1,4- benzoxazines -3 (4H) the -one derivative is as follows：
2. synthetic method according to claim 1, it is characterised in that：The molar ratio of the organic acid and salt is 1:(0.01-
5)。
3. synthetic method according to claim 2, it is characterised in that：The molar ratio of the organic acid and salt is 1：(0.05-
3)。
4. synthetic method according to claim 1, it is characterised in that：The fluoro- 4- propinyls -1,4- benzos of 6- amino -7- are disliked
Piperazine -3 (4H) -one, 3,4,5,6- tetrahydrophthalic anhydride, the molar ratio of organic acid are 1:(0.95-1.3):(0.05-2).
5. synthetic method according to claim 1, it is characterised in that：The reaction carries out in a solvent, the solvent choosing
From acetic acid, toluene, chloroform, hexamethylene, 1,2- dichloroethanes, methyl iso-butyl ketone (MIBK) it is one or more.
6. synthetic method according to claim 5, it is characterised in that：The solvent is selected from toluene.
7. synthetic method according to claim 1, it is characterised in that：According to the fluoro- 4- propinyls -1,4- benzene of 6- amino -7-
And oxazines -3 (4H) -one, 3,4,5,6- tetrahydrophthalic anhydride, the molar ratio of acetic acid are 1:(0.95-1.3):(0.05-2), acetic acid and vinegar
The molar ratio of sour potassium is 1:The ratio of (0.05-3), using toluene as solvent, under the conditions of reflux dewatering react to get.
8. according to any synthetic methods of claim 1-7, it is characterised in that：The reaction further includes being carried out to reaction solution
The step of post-processing, the post-processing are specially：After completion of the reaction, solvent is sloughed, gained filter cake is beaten using organic solvent,
Product is dried to obtain after filtering.
9. synthetic method according to claim 8, it is characterised in that：The organic solvent is selected from ethyl alcohol, ethyl acetate, two
It is one or more in chloromethanes.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0170191A2 (en) * | 1984-07-23 | 1986-02-05 | Sumitomo Chemical Company, Limited | Tetrahydrophtalimides, and their production and use |
| CN103965181A (en) * | 2014-05-22 | 2014-08-06 | 黑龙江大学 | Preparation method of flumioxazin |
| WO2014122674A1 (en) * | 2013-02-08 | 2014-08-14 | Rallis India Limited | Process for preparation of derivatives of tetrahydrophthalimide |
| CN105061416A (en) * | 2015-07-16 | 2015-11-18 | 北京颖泰嘉和生物科技股份有限公司 | Method for preparing flumioxazin |
| CN105837563A (en) * | 2016-04-25 | 2016-08-10 | 四川义结科技有限责任公司 | Production method of flumioxazin |
-
2016
- 2016-08-17 CN CN201610682770.8A patent/CN106317042B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0170191A2 (en) * | 1984-07-23 | 1986-02-05 | Sumitomo Chemical Company, Limited | Tetrahydrophtalimides, and their production and use |
| WO2014122674A1 (en) * | 2013-02-08 | 2014-08-14 | Rallis India Limited | Process for preparation of derivatives of tetrahydrophthalimide |
| CN103965181A (en) * | 2014-05-22 | 2014-08-06 | 黑龙江大学 | Preparation method of flumioxazin |
| CN105061416A (en) * | 2015-07-16 | 2015-11-18 | 北京颖泰嘉和生物科技股份有限公司 | Method for preparing flumioxazin |
| CN105837563A (en) * | 2016-04-25 | 2016-08-10 | 四川义结科技有限责任公司 | Production method of flumioxazin |
Non-Patent Citations (2)
| Title |
|---|
| Hydrolysis of N-phenylimide herbicide flumioxazin and its anilic acid derivative in aqueous solutions;Toshiyuki Katagi;《Journal of Pesticide Science》;20031231;第28卷(第1期);第44-50页 * |
| 新型除草剂丙炔氟草胺的合成研究;刘安昌，等;《世界农药》;20110430;第33卷(第2期);第27-29页 * |
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Denomination of invention: A synthetic method of 7-fluoro-6-amino-4 - (2-propargyl) - 1,4-benzoxazine-3 (4h) - one derivative Effective date of registration: 20210702 Granted publication date: 20181113 Pledgee: Agricultural Development Bank of China Baiyin branch business department Pledgor: Purpana (Beijing) Technologies Co.,Ltd. Registration number: Y2021990000573 |
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