CN109503506A - A kind of intermediate production method of flumioxazin - Google Patents
A kind of intermediate production method of flumioxazin Download PDFInfo
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- CN109503506A CN109503506A CN201811449172.1A CN201811449172A CN109503506A CN 109503506 A CN109503506 A CN 109503506A CN 201811449172 A CN201811449172 A CN 201811449172A CN 109503506 A CN109503506 A CN 109503506A
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- flumioxazin
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- potassium hydroxide
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- 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
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of intermediate production methods of flumioxazin, it is characterized in that, with 2,4- difluoroaniline, propargyl chloride, hydroxyl ethyl acetate and potassium hydroxide are primary raw material, the fluoro- 2H-1 of important intermediate N- propinyl -7- that flumioxazin is made is reacted through one-step method, 4- benzoxazine -3- (4H) ketone, the beneficial effects of the present invention are: avoiding carrying out etherification reaction using methyl chloroacetate or methyl bromoacetate, methyl chloroacetate or methyl bromoacetate need chlorination or bromination to obtain, expensive starting materials, it is not easy to obtain, pollutes environment；The reduction of latter one nitro hydrogenation is reduced using 2,4- difluoroaniline simultaneously or double nitro intermediates, hydrogenating reduction also belong to high-risk technique, and double nitros are even more that risk is larger, improve the safety of technique；It is reacted around propynylated below, there are two amino, are selectively affected, while added cost；Etherificate and propynylated progress one-step synthesis method simplify technique, reduce costs.
Description
Technical field
The present invention relates to a kind of herbicide, the intermediate production method of specifically a kind of flumioxazin.
Background technique
Flumioxazin is the widely applied herbicide of agricultural production, and domestic technique has announced a variety of preparation processes at present.
Have with fluoro- 2, the 4- dinitrobenzene of 1,5- bis- for starting material and 2,4- difluoro nitrobenzene is starting material, but such mode later period
More step hydrogenating reductions have the appearance of dinitro intermediate, and security risk is larger, and impurity is high；The propynylated of later period can there are two amino
With selection, cause yield low, impurity is high；The synthetic route announced all carries out ether using methyl chloroacetate or methyl bromoacetate
Change reaction, methyl chloroacetate or methyl bromoacetate need chlorination or bromination to obtain, and expensive starting materials are not easy to obtain, and pollute environment；Simultaneously
Using the more step nitro hydrogenation reduction of 2,4- difluoro nitrobenzene or double nitro intermediates, hydrogenating reduction also belongs to high-risk technique, double
Nitro is even more that risk is larger, improves the safety of technique；Propynylated to react below, there are two amino, and selectivity is by shadow
It rings, while added cost；Etherificate and propynylated progress one-step synthesis method simplify technique, reduce costs.
It is domestic at present prior art discloses about the process route for preparing flumioxazin mainly include the following types:
US4803270 discloses a kind of method for synthesizing flumioxazin intermediate: with fluoro- 2, the 4- dinitrobenzene of 1,5- bis-
For starting material, by being etherified, add hydrogen, nitrification plus hydrogen, is propynylated, then reacting to obtain target product with tetrahydrophthalic anhydride.The present invention
Have the beneficial effect that: reaction step number it is few；But this method has some disadvantages: intermediate is di-nitrated product, unstable,
Etherification reaction is carried out using methyl chloroacetate or methyl bromoacetate, methyl chloroacetate or methyl bromoacetate need chlorination or bromination to obtain
It arrives, expensive starting materials are not easy to obtain, and pollute environment；Propynylated to react below, there are two amino, are selectively affected, while at
This increasing.
Patent CN105837563A discloses a kind of method for synthesizing flumioxazin.It is using 2,4- difluoro nitrobenzene
Beginning raw material by nitrification, etherificate, hydrogenating reduction, nitrification, reduction, then reacts to obtain target production with propargyl chloride and flumioxazin
Object；The route solvent is Ke Xunhuanliyong, and starting material is cheap and easy to get, but this method has some disadvantages: phenyl ring contains nitro
Nitro positioning is complicated when being nitrified, trinitro- product easily generated, reacts difficult control, and risk is big；Use methyl chloroacetate or bromine
Methyl acetate carries out etherification reaction, and methyl chloroacetate or methyl bromoacetate need chlorination or bromination to obtain, and expensive starting materials are not easy
, pollute environment；Propynylated to react below, there are two amino, are selectively affected, while added cost.
Summary of the invention
The purpose of the present invention is to provide a kind of intermediate production methods of flumioxazin, to solve above-mentioned background technique
The problem of middle proposition.
To achieve the above object, the invention provides the following technical scheme:
A kind of intermediate production method of flumioxazin, it is characterised in that with 2,4- difluoroaniline, propargyl chloride, hydroxyl second
Acetoacetic ester and potassium hydroxide are primary raw material, and the important intermediate N- propinyl -7- that flumioxazin is made is reacted through one-step method
Fluoro- 2H-1,4- benzoxazine -3- (4H) ketone.
As a further solution of the present invention: its synthetic method the following steps are included:
S1, etherification reaction
2,4- difluoroaniline and potassium hydroxide are put into reaction kettle, solvent uses polar solvent (such as DMF, DMSO, DMI
Deng), temperature control starts that hydroxyl ethyl acetate is added dropwise in 80-150 degree, while having ethyl alcohol to generate and producing (can be with tiny structure),
It is added dropwise, keeps the temperature 1 hour, for use；
Reaction equation is as follows:
The molar ratio of 2,4- difluoroanilines, potassium hydroxide and hydroxyl ethyl acetate is 1: 2.1: 1；
S2, propynylated reaction
Propargyl chloride is added dropwise in the solution that step reaction obtains upwards, controls reaction temperature 0-80 degree, time for adding is according to reaction
Temperature adjust, be added dropwise and keep the temperature 1 hour, start filtering generate salt potassium chloride and potassium fluoride, mother liquor negative pressure recycling design,
Obtain the important intermediate N- propinyl fluoro- 2H-1 of -7- that crystalline solid is flumioxazin, 4- benzoxazine -3- (4H) ketone；
Reaction equation is as follows:
The molar ratio of the fluoro- 2H-1 of 7-, 4- benzoxazine -3- (4H) ketone and propargyl chloride is 1: 0.995；
As further scheme of the invention: the reaction condition in step S1 is to guarantee the initial reaction in reaction kettle
Temperature is 80-150 DEG C, under conditions of potassium hydroxide excessive (molar ratio is greater than 1), solvent using polar solvent (such as DMF,
DMSO, DMI etc.), temperature control starts that hydroxyl ethyl acetate is added dropwise in 80-150 degree, while having ethyl alcohol to generate and produce (can be with
Tiny structure), it is added dropwise, keeps the temperature 1 hour, for use；Potassium hydroxide is added in S2
As further scheme of the invention: the reaction condition in step S2 is potassium hydroxide and sodium hydroxide mixing
Using or be used alone.
As further scheme of the invention: sodium hydroxide is added in the solution that step reaction obtains upwards, chlorine third is added dropwise again
Alkynes controls reaction temperature 0-80 degree, and time for adding adjusts according to reaction temperature, is added dropwise and keeps the temperature 1 hour, starts filtering and produces
Raw salt potassium chloride and potassium fluoride, mother liquor negative pressure recycling design obtain the important intermediate N- propine that crystalline solid is flumioxazin
The fluoro- 2H-1 of base -7-, 4- benzoxazine -3- (4H) ketone；
Compared with prior art, the beneficial effects of the present invention are: avoiding carrying out using methyl chloroacetate or methyl bromoacetate
Etherification reaction, methyl chloroacetate or methyl bromoacetate need chlorination or bromination to obtain, and expensive starting materials are not easy to obtain, and pollute environment；Together
When using 2,4- difluoroaniline reduce latter one nitro hydrogenation reduction or double nitro intermediates, hydrogenating reduction also belong to high-risk work
Skill, double nitros are even more that risk is larger, improve the safety of technique；It is reacted around propynylated below, there are two amino, selections
Property is affected, while added cost；Etherificate and propynylated progress one-step synthesis method simplify technique, reduce costs.
Synthetic route of the invention avoids carrying out etherification reaction, monoxone first using methyl chloroacetate or methyl bromoacetate
Ester or methyl bromoacetate need chlorination or bromination to obtain, and expensive starting materials are not easy to obtain, and pollute environment；2,4- difluorobenzene is used simultaneously
Amine reduces the reduction of latter one nitro hydrogenation or double nitro intermediates, hydrogenating reduction also belong to high-risk technique, and double nitros are even more wind
Danger is larger, improves the safety of technique；It is reacted around propynylated below, there are two amino, are selectively affected, simultaneously
Added cost；Etherificate and propynylated progress one-step synthesis method simplify technique, reduce costs.
Detailed description of the invention
Fig. 1 is a kind of intermediate production method synthetic route chart of flumioxazin.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment shall fall within the protection scope of the present invention.
Referring to Fig. 1, in the embodiment of the present invention, a kind of intermediate production method of flumioxazin includes the following steps.
S1, etherification reaction
1 mole of 2,4- difluoroaniline and 2 molar potassium hydroxides are put into reaction kettle, solvent uses polar solvent (such as
DMF, DMSO, DMI etc.), temperature control starts that 1 hydroxy ethyl acetate is added dropwise in 80-150 degree, while having ethyl alcohol to generate simultaneously
It produces (can be with tiny structure), is added dropwise, keep the temperature 1 hour, for use；
Reaction equation is as follows:
The molar ratio of 2,4- difluoroanilines, potassium hydroxide and hydroxyl ethyl acetate is 1: 2.1: 1；
S2, propynylated reaction
1 mole of propargyl chloride is added dropwise in the obtained solution of step reaction upwards, controls reaction temperature 0-80 degree, time for adding according to
Reaction temperature is adjusted, and is added dropwise and is kept the temperature 1 hour, and salt potassium chloride and potassium fluoride that filtering generates, the recycling of mother liquor negative pressure are started
Solvent obtains the important intermediate N- propinyl fluoro- 2H-1 of -7- that crystalline solid is flumioxazin, 4- benzoxazine -3- (4H) ketone；
Reaction equation is as follows:
The molar ratio of the fluoro- 2H-1 of 7-, 4- benzoxazine -3- (4H) ketone and propargyl chloride is 1: 0.995；
It is obvious to a person skilled in the art that invention is not limited to the details of the above exemplary embodiments, Er Qie
In the case where without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, the present embodiments are to be considered as illustrative and not restrictive, and the scope of the present invention is by appended power
Benefit requires rather than above description limits, it is intended that all by what is fallen within the meaning and scope of the equivalent elements of the claims
Variation is included within the present invention.Any reference signs in the claims should not be construed as limiting the involved claims.
In addition, it should be understood that although this specification is described in terms of embodiments, but not each embodiment is only wrapped
Containing an independent technical solution, this description of the specification is merely for the sake of clarity, and those skilled in the art should
It considers the specification as a whole, the technical solutions in the various embodiments may also be suitably combined, forms those skilled in the art
The other embodiments being understood that.
Claims (5)
1. a kind of intermediate production method of flumioxazin, which is characterized in that with 2,4- difluoroaniline, propargyl chloride, hydroxyl second
Acetoacetic ester and potassium hydroxide are primary raw material, and the important intermediate N- propinyl -7- that flumioxazin is made is reacted through one-step method
Fluoro- 2H-1,4- benzoxazine -3- (4H) ketone.
2. a kind of intermediate production method of flumioxazin according to claim 1, which is characterized in that including following step
It is rapid:
S1, etherification reaction
2,4- difluoroaniline and potassium hydroxide are put into reaction kettle, solvent uses polar solvent (such as DMF, DMSO, DMI),
Temperature control starts that hydroxyl ethyl acetate is added dropwise in 80-150 degree, while having ethyl alcohol to generate and producing (can be with tiny structure), is added dropwise
It finishes, keeps the temperature 1 hour, for use；
Reaction equation is as follows:
The molar ratio of 2,4- difluoroanilines, potassium hydroxide and hydroxyl ethyl acetate is 1: 2.1: 1；
S2, propynylated reaction
Propargyl chloride is added dropwise in the solution that step reaction obtains upwards, controls reaction temperature 0-80 degree, time for adding is according to reaction temperature
It adjusts, is added dropwise and keeps the temperature 1 hour, start salt potassium chloride and potassium fluoride that filtering generates, mother liquor negative pressure recycling design must be tied
Crystal is the important intermediate N- propinyl fluoro- 2H-1 of -7- of flumioxazin, 4- benzoxazine -3- (4H) ketone；
Reaction equation is as follows:
The molar ratio of the fluoro- 2H-1 of 7-, 4- benzoxazine -3- (4H) ketone and propargyl chloride is 1: 0.995.
3. a kind of intermediate production method of flumioxazin according to claim 2, which is characterized in that in step S1
Reaction condition is to guarantee that the initial reaction temperature in reaction kettle is 80-150 DEG C, is sufficiently turned under the conditions of twice of potassium hydroxide
The fluoro- 2H-1 of 7- is turned to, 4- benzoxazine -3- (4H) ketone can be converted sufficiently in this way.
4. a kind of intermediate production method of flumioxazin according to claim 2, which is characterized in that in step S2
Reaction condition is, reaction temperature is 0-80 DEG C, and time for adding is subject to temperature and is controlled, while utilizing excessive potassium hydroxide in S1
As acid binding agent, comprehensive utilization is played, while this step does not have other positions tournament selection, improves the yield of product.
5. a kind of intermediate production method of flumioxazin according to claim 2, which is characterized in that step S1 and S2
Reaction can be completed in same reaction kettle, accomplish that two steps merge the purpose of reaction, used solvent is consistent.
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| CN201811449172.1A CN109503506A (en) | 2018-11-21 | 2018-11-21 | A kind of intermediate production method of flumioxazin |
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| CN201811449172.1A CN109503506A (en) | 2018-11-21 | 2018-11-21 | A kind of intermediate production method of flumioxazin |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112742333A (en) * | 2021-02-05 | 2021-05-04 | 内蒙古世杰化工有限公司 | Etherification device is used in flumioxazin production |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140200140A1 (en) * | 2013-12-30 | 2014-07-17 | Sumitomo Chemical Company, Limited | Method of controlling pests |
| CN105272973A (en) * | 2014-06-10 | 2016-01-27 | 华中师范大学 | Pyrimidine diketone compounds containing benzoxazine ring and application thereof |
| CN106317042A (en) * | 2016-08-17 | 2017-01-11 | 帕潘纳(北京)科技有限公司 | Synthesis method of 7-fluorine-6-amino-4-(2-propargyl)-1,4-benzoxazine-3(4H)-ketone derivative |
| CN107459464A (en) * | 2017-08-23 | 2017-12-12 | 连云港世杰农化有限公司 | One kind synthesis 2（The nitro-phenoxy of 5 fluorine 2）The method of methyl acetate |
| CN107629043A (en) * | 2017-09-26 | 2018-01-26 | 连云港世杰农化有限公司 | A kind of synthetic method of flumioxazin |
-
2018
- 2018-11-21 CN CN201811449172.1A patent/CN109503506A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140200140A1 (en) * | 2013-12-30 | 2014-07-17 | Sumitomo Chemical Company, Limited | Method of controlling pests |
| CN105272973A (en) * | 2014-06-10 | 2016-01-27 | 华中师范大学 | Pyrimidine diketone compounds containing benzoxazine ring and application thereof |
| CN106317042A (en) * | 2016-08-17 | 2017-01-11 | 帕潘纳(北京)科技有限公司 | Synthesis method of 7-fluorine-6-amino-4-(2-propargyl)-1,4-benzoxazine-3(4H)-ketone derivative |
| CN107459464A (en) * | 2017-08-23 | 2017-12-12 | 连云港世杰农化有限公司 | One kind synthesis 2（The nitro-phenoxy of 5 fluorine 2）The method of methyl acetate |
| CN107629043A (en) * | 2017-09-26 | 2018-01-26 | 连云港世杰农化有限公司 | A kind of synthetic method of flumioxazin |
Non-Patent Citations (2)
| Title |
|---|
| CHUN-LI SU，等: "Using gene expression database to uncover biology functions of 1,4-disubstituted 1,2,3-triazole analogues synthesized via a copper (I)-catalyzed reaction", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
| 刘安昌，等: "新型除草剂丙炔氟草胺的合成研究", 《世界农药》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112742333A (en) * | 2021-02-05 | 2021-05-04 | 内蒙古世杰化工有限公司 | Etherification device is used in flumioxazin production |
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