CN110483411A - The preparation method of Fluoxastrobin based compound - Google Patents
The preparation method of Fluoxastrobin based compound Download PDFInfo
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- CN110483411A CN110483411A CN201810291282.3A CN201810291282A CN110483411A CN 110483411 A CN110483411 A CN 110483411A CN 201810291282 A CN201810291282 A CN 201810291282A CN 110483411 A CN110483411 A CN 110483411A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
Abstract
The present invention relates to the field of chemical synthesis, the preparation method of Fluoxastrobin based compound is disclosed, this method includes making to contain compound shown in formula (II) to be reacted as raw material,
Description
Technical field
The present invention relates to the field of chemical synthesis, and in particular to the preparation method of Fluoxastrobin based compound.
Background technique
Fluoxastrobin applies very extensive, the pin of global raw medicine as a kind of broad-spectrum germicide at present in agrochemical industry
Volume is sold just more than 1,000,000,000 dollars, has more literature method to report its synthetic method, is had in industrial production using more at present
For following two technique.
Technique 1:
This route is more classical, and document report is more.
It is disclosed in WO92/08703A using the halide of copper as catalyst, it is special in polar solvent in the presence of potassium carbonate
It is the synthetic method for preparing Fluoxastrobin in N,N-dimethylformamide according to reaction equation described in above-mentioned technique 1.US8124761B2 report
Road is in the presence of triethylene diamine, according to the method for the synthesis Fluoxastrobin of reaction equation described in above-mentioned technique 1.CN103265496A is disclosed
In the presence of azaheterocyclyl tertiary amines class compound, in the reaction dissolvents such as butyl acetate, closed according to reaction equation shown in above-mentioned technique 1
At the method for Fluoxastrobin.
Wherein the generally compound as shown in formula (c) of compound shown in formula (b) is made, such as following formula:
For example, patent WO92/08703A is disclosed in the presence of potassium acid sulfate, separating methanol synthesizes formula under the high temperature conditions
(b) compound shown in.US616291A is disclosed in the presence of acetic anhydride, under acid catalysis, the method for synthesis formula (b) compound.
It is disclosed in CN102070538A by compound shown in formula (c) and anhydride reaction, uses dimethyl suflfate for catalyst production
(b) method of compound shown in.CN103214423A is disclosed in the presence of dialkyl sulfate, depressurizes separating methanol preparation formula
(b) method of compound shown in.
CN101157657A also discloses another synthetic route, as shown in following formula technique 2, its main feature is that first by pyrimidine
Three ring, 2-Hydroxyphenyl Acetic Acid and o-hydroxy nitrile segment synthesis, then synthesizing methyl acrylate.
Technique 2:
Still it has been reported that the last separating methanol of compound shown in formula (d) obtains Fluoxastrobin, it is shown below:
However, what is obtained is all E formula configuration and Z formula when by method preparation formula (a) compound represented of above-mentioned document
The mixture of configuration.
For example the method referring to disclosed in CN101157657A obtains Z formula configuration about when synthesizing formula (a) compound represented
Account for 4% or so；Carry out preparation formula (a) compound represented according to CN103214423A and CN103265496A method, obtains Z formula structure
Type ratio accounts for about 5%；The compound referring to shown in CNl02070538A method synthesis formula (a) obtains Z formula configuration and accounts for about the left side 5-6%
It is right.
These E/Z mixtures, generally based on E formula configuration, Z formula configuration ratio is lower, about between 3-8%.
EP0382375 is more early disclosed when preparing methyl acrylate class product, is obtained the mixture of E/Z product, is configured as with E formula
It is main, while finding that E formula configuration activity is also high.Z formula configuration of compound exists as impurity.
These Z formula anomeric products are as impurity, general to be removed by post processing modes such as crystallizations in different phase, separation
Purification step is cumbersome.And wastage of material is caused in this way, it is also unfriendly to environment, not with the theory of current Green Chemistry
Symbol.
Summary of the invention
It is mostly the mixture of E/Z configuration, Z formula anomeric product conduct to overcome product when prior art preparation Fluoxastrobin
The problems such as wastage of material caused by impurity, separating-purifying complex steps, inventor's discovery can be by certain methods by formula
(a) the Z formula configuration of compound represented is converted to E formula configuration.
The present invention provides a kind of preparation methods of Fluoxastrobin based compound shown in formula (I), wherein this method includes making
It uses and contains compound shown in formula (II) and reacted as raw material,
Wherein, R is halogen, hydroxyl or 2- cyano-benzene oxygen.
The method of the invention is by converting an accepted way of doing sth (I) for compound shown in formula (II) under more mild reaction condition
Shown compound avoids complicated separating-purifying process and reduces the wave of raw material to obtain pure Fluoxastrobin based compound
Take, improves atom utilization.
Specific embodiment
The endpoint of disclosed range and any value are not limited to the accurate range or value herein, these ranges or
Value should be understood as comprising the value close to these ranges or value.For numberical range, between the endpoint value of each range, respectively
It can be combined with each other between the endpoint value of a range and individual point value, and individually between point value and obtain one or more
New numberical range, these numberical ranges should be considered as specific open herein.
The present invention provides a kind of preparation methods of Fluoxastrobin based compound shown in formula (I), wherein this method includes making
It uses and contains compound shown in formula (II) and reacted as raw material,
Wherein, R is halogen, hydroxyl or 2- cyano-benzene oxygen.
In the present invention, halogen can be fluorine, chlorine, bromine or iodine, preferably chlorine.
In the present invention, the reaction can carry out under strong illumination or under the conditions of high temperature (100-200 DEG C).It is preferred that
Ground, the reaction can carry out in the presence of diluent and acidic catalyst.
In the present invention, the acidic catalyst can be sulfuric acid, sodium bisulfate, potassium acid sulfate, methyl sulfate, sulfuric acid
Mono ethyl ester, dimethyl suflfate, methane sulfonic acid, ethylsulfonic acid, sulfamic acid, p-methyl benzenesulfonic acid, phosphoric acid, hydrochloric acid, trifluoroacetic acid, three
One of monoxone, dichloroacetic acid and monoxone are a variety of.Preferably, the acidic catalyst be sulfuric acid, methane sulfonic acid and
One of p-methyl benzenesulfonic acid is a variety of.Acidic catalyst used in the present invention can be commercial product.
In the present invention, the diluent can commonly use atent solvent to chemically react, such as can be selected from but not only limit
In acetonitrile, cyanophenyl, toluene, chlorobenzene, methanol, ethyl alcohol, methylene chloride, tetrahydrofuran, methyl tertiary butyl ether(MTBE), ether, 1,4- dioxy
Six rings, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), N-Methyl pyrrolidone, methyl acetate, ethyl acetate,
One of isopropyl acetate, n-butyl acetate and hexone are a variety of.Preferably, the diluent be acetonitrile,
One of DMF, methanol, hexone and n-butyl acetate are a variety of.Diluent used in the present invention can be city
Sell product.
In the present invention, the acidic catalyst and the molar ratio of the dosage of compound shown in formula (II) can be
(0.001-10): 1, specifically, for example, can for 0.002:1,0.005:1,0.008:1,0.01:1,0.02:1,0.05:1,
0.1:1,0.2:1,0.5:1,0.6:1,0.8:1,1:1,2:1,3:1,4:1,5:1,6:1,7:1,8:1,9:1,10:1 and these
The arbitrary value in range that any two in point value are constituted.Preferably, the acidic catalyst and chemical combination shown in formula (II)
The molar ratio of the dosage of object is (0.01-2): 1.Under normal circumstances, the acidity of acidic catalyst used is stronger, corresponding equal amount
Formula (II) shown in compound, the dosage of acidic catalyst is fewer, such as mole of compound shown in methane sulfonic acid and formula (II)
Than being preferably 0.05-0.5:1；The molar ratio of phosphoric acid and compound shown in formula (II) is preferably 0.5-2:1.
In the present invention, more mild reaction condition, faster reaction rate and higher yield in order to obtain, can
To suitably adjust reaction acidic catalyst and diluent used, the matching reached and synergy.Preferably,
When R is 2- cyano-benzene oxygen, and the acidic catalyst is selected from p-methyl benzenesulfonic acid and/or methane sulfonic acid, the diluent is preferred
Ground is selected from one of acetonitrile, N,N-dimethylformamide, n-butyl acetate or a variety of.
In the present invention, it is 20 DEG C of reflux temperatures to diluent that the condition of the reaction, which includes temperature,.It selects different
Diluent and acidic catalyst, it is desirable that reaction temperature it is different, general highly polar diluent and acid stronger catalyst can be with
It reacts at a lower temperature, opposite low pole diluent and acid weaker catalyst reaction temperatures are just higher.Such as with DMF
For diluent, methane sulfonic acid is catalyst, under room temperature, so that it may by (Z) -2- { 2- [6- (2- cyano-benzene oxygen) pyrimidine -
4- base oxygroup] phenyl } -3- methoxy-methyl acrylate is partially converted into (E) -2- { 2- [6- (2- cyano-benzene oxygen) pyrimidine -4-
Base oxygroup] phenyl } -3- methoxy-methyl acrylate (Fluoxastrobin) can be by 99% or more (Z) -2- { 2- at 80 DEG C or so
[6- (2- cyano-benzene oxygen) pyrimidine-4-yl oxygroup] phenyl } -3- methoxy-methyl acrylate is converted to Fluoxastrobin.
In the present invention, compound shown in formula (II), optional is contained in the raw material containing compound shown in formula (II)
Formula (I) shown in compound and optional impurity.In the present invention, the raw material containing compound shown in formula (II) can
Think the product or intermediate of above-mentioned technique 1 or technique 2, the mixture of E formula configuration and Z formula configuration, wherein mole of E formula configuration
Percentage can be 1%-98%, such as can be any two in 10%, 30%, 50%, 70%, 90% and these point values
The arbitrary value in range constituted；It can be compound shown in pure formula (II), i.e., simple E formula configuration of compound；It can also
To contain impurity, impurity described herein can be to generate in reaction raw materials o-hydroxy nitrile, dichloro pyrimidine, or reaction
By-product.
The method of the invention can relatively simplely by compound shown in formula (II) convert an accepted way of doing sth (I) shown in compound from
And obtain pure Fluoxastrobin based compound, avoid complicated cumbersome separating-purifying process while reducing the waste of raw material, it mentions
High atom utilization.The method of the invention is easy to operate, and reaction condition is milder, avoids cumbersome separating step, more
Conducive to industrialization production.
The present invention will be described in detail by way of examples below.
The conversion ratio of the configuration of compound of Z formula described in embodiment, surplus are the hydrogen ion fire configured by gas-chromatography
Flame detector detects.The gas-chromatography is the gas-chromatography of the model 6890GC of Aglient company production.
Examination of infrared spectrum in embodiment is using 27 Instrument measuring of Bruker TENSOP.
The following are raw materials used in embodiment:
(E/Z) -2- { 2- [6- (2- cyano-benzene oxygen) pyrimidine-4-yl oxygroup] phenyl } -3- methoxy-methyl acrylate is mixed
The product that object is above-mentioned technique 1 is closed, purchased from the safe fining Co., Ltd of Shangyu grain husk, wherein E formula configuration accounts for 95%, Z formula configuration and accounts for
5%.
(E/Z) -2- [2- (6- Chloropyrimide -4- base oxygroup) phenyl] -3- methoxy-methyl acrylate mixture is above-mentioned
The product of technique 1, wherein E formula configuration accounts for 90%, Z formula configuration and accounts for 10%.
(E/Z) -2- [2- (6- hydroxy pyrimidine -4- base oxygroup) phenyl] -3- methoxy-methyl acrylate mixture is technique 1
Product, wherein E formula configuration accounts for 92%, Z formula configuration and accounts for 8%.
(Z) -2- { 2- [6- (2- cyano-benzene oxygen) pyrimidine-4-yl oxygroup] phenyl } -3- methoxy-methyl acrylate is by purchasing
It is isolated by column chromatography method from safe fining Co., Ltd's (E/Z) mixture of Shangyu grain husk.
(Z) -2- [2- (6- Chloropyrimide -4- base oxygroup) phenyl] -3- methoxy-methyl acrylate substance is mixed by its (E/Z)
It is isolated by column chromatography method to close object.
(Z) -2- [2- (6- hydroxy pyrimidine -4- base oxygroup) phenyl] -3- methoxy-methyl acrylate substance is mixed by its (E/Z)
It is isolated by column chromatography method to close object.
P-methyl benzenesulfonic acid is the product purchased from Beijing chemical reagents corporation.
Methane sulfonic acid is the product purchased from Beijing chemical reagents corporation.
Ethyl Sulfate is the product purchased from Beijing chemical reagents corporation.
Dichloroacetic acid is the product purchased from Beijing chemical reagents corporation.
Embodiment 1
In 100ml reaction flask, 0.01mol (Z) -2- { 2- [6- (2- cyano-benzene oxygen) pyrimidine-4-yl oxygroup] benzene is added
Base } -3- methoxy-methyl acrylate (4.1g), 30ml DMF, 0.91g p-methyl benzenesulfonic acid is warming up to 80 DEG C, reacts 5 hours, take
Sample analysis stops reaction when conversion ratio reaches 99%, and removed under reduced pressure solvent recycles DMF, and 10ml ether is added, uses respectively
5ml is washed 2 times, is removed ether, is obtained 4.0g yellow solid, yield 97.6%.
By products therefrom carry out nuclear magnetic resonance spectroscopy test (1) and examination of infrared spectrum H-NMR.
The data of obtained nuclear magnetic resonance spectroscopy are as follows:
1H-NMR (500MHz, CDCl3, δ, ppm) and 3.64 (s, 3H), 3.75 (s, 3H), 6.42 (s, 1H), 7.22 (q, 1H),
7.29-7.43 (m, 5H), 7.49 (s, 1H), 7.65-7.78 (m, 2H), 8.40 (s, 1H).
Examination of infrared spectrum figure shows 820cm-1Locate the absorption peak strong without appearance, illustrate that products therefrom is all E formula configuration,
There is no Z formula configuration, as (E) -2- { 2- [6- (2- cyano-benzene oxygen) pyrimidine-4-yl oxygroup] phenyl } -3- methoxy acrylic acid
Methyl esters (Fluoxastrobin).
Embodiment 2
In 2000ml reaction flask, 1mol (2- { 2- [6- (2- cyano-benzene oxygen) pyrimidine-4-yl oxygroup] phenyl }-is added
(403g, wherein E formula configuration accounts for 95%, Z formula configuration and accounts for 5%) 3- methoxy-methyl acrylate, 1000ml acetonitrile, 9.6g methyl sulphur
Acid is warming up to reflux, reacts 6 hours, sampling analysis, when Z formula compound is less than 0.2%, stops reacting, removed under reduced pressure solvent,
Acetonitrile is recycled, with 1000ml ethyl acetate and 200ml water, layering takes organic phase, and it is solid to obtain 401g yellow for removed under reduced pressure solvent
Body, yield 99.5%.
By obtained solid carry out nuclear magnetic resonance spectroscopy test (1H-NMR) and examination of infrared spectrum, obtained nuclear magnetic resonance
Hydrogen spectrogram spectrum and 1 gained of embodiment1H-NMR data are consistent.It can thus be appreciated that is obtained is Fluoxastrobin.
Embodiment 3
In 100ml reaction flask, 0.01mol (Z) -2- [2- (6- Chloropyrimide -4- base oxygroup) phenyl] -3- methoxy is added
Base methyl acrylate (3.2g), 30ml acetonitrile, 0.96g methane sulfonic acid are warming up to 70 DEG C, react 8 hours, sampling analysis, when turning
When rate reaches 99%, stop reaction, 10ml ether is added in removed under reduced pressure solvent, is washed 2 times with 5ml respectively, sloughs ether and obtain
To 3.1g yellow solid, yield 96.9%.
By obtained solid carry out nuclear magnetic resonance spectroscopy test (1) and examination of infrared spectrum H-NMR.
The data of obtained nuclear magnetic resonance spectroscopy are as follows:
1H-NMR (500MHz, CDCl3, δ, ppm) and 3.64 (s, 3H), 3.75 (s, 3H), 6.78 (s, 1H), 7.17-7.42
(m, 4H), 7.45 (s, 1H), 8.40 (s, 1H).
Examination of infrared spectrum figure shows 820cm-1Locate the absorption peak strong without appearance, illustrate that products therefrom is all E formula configuration,
There is no Z formula configuration, as (E) -2- { 2- [6- Chloropyrimide -4- base oxygroup] phenyl } -3- methoxy-methyl acrylate.
Embodiment 4
In 2000ml reaction flask, 1mol 2- [2- (6- Chloropyrimide -4- base oxygroup) phenyl] -3- methoxy propyl is added
(320g, wherein E formula configuration accounts for 90%, Z formula configuration and accounts for 10%) e pioic acid methyl ester, 1000ml acetonitrile, and 96g methane sulfonic acid is warming up to
Reflux is reacted 6 hours, sampling analysis, when compound shown in Z formula is less than 0.2%, stops reaction, removed under reduced pressure solvent recycles second
Nitrile, with 1000ml ethyl acetate and 200ml water, layering takes organic phase, and removed under reduced pressure solvent obtains 319g yellow solid, yield
It is 99.7%.
By obtained solid carry out nuclear magnetic resonance spectroscopy test (1H-NMR) and examination of infrared spectrum, obtained nuclear magnetic resonance
Hydrogen spectrogram and infrared spectrogram are consistent with embodiment 3.It can thus be appreciated that is obtained is (E) -2- { 2- [6- Chloropyrimide -4- base oxygen
Base] phenyl } -3- methoxy-methyl acrylate.
Embodiment 5
In 100ml reaction flask, 0.01mol (Z) -2- [2- (6- hydroxy pyrimidine -4- base oxygroup) phenyl] -3- methoxy is added
Base methyl acrylate (4.2g), 50ml acetonitrile, 0.2g methane sulfonic acid are warming up to reflux, react 4 hours, sampling analysis works as conversion
When rate reaches 99%, stop reaction, removed under reduced pressure solvent recycles acetonitrile, and with 100ml ethyl acetate and 20ml water, layering has been taken
Machine phase, removed under reduced pressure solvent obtain 4.1g solid, yield 99.2%.
By obtained solid carry out nuclear magnetic resonance spectroscopy test (1) and examination of infrared spectrum H-NMR.
Examination of infrared spectrum figure shows 820cm-1Locate the absorption peak strong without appearance, illustrate that products therefrom is all E formula configuration,
There is no Z formula configuration, as (E) -2- { 2- [6- hydroxy pyrimidine -4- base oxygroup] phenyl } -3- methoxy-methyl acrylate.
Embodiment 6
In 2000ml reaction flask, 1mol 2- { 2- [6- hydroxy pyrimidine -4- base oxygroup] phenyl } -3- methoxy propyl is added
(403g, wherein E formula configuration accounts for 92%, Z formula configuration and accounts for 8%) e pioic acid methyl ester, 1000ml acetonitrile, and 20g methane sulfonic acid is warming up to back
Stream reacts 6 hours, sampling analysis, when Z formula compound is less than 0.2%, stops reaction, and removed under reduced pressure solvent recycles acetonitrile, uses
1000ml ethyl acetate and 200ml water, layering take organic phase, and removed under reduced pressure solvent obtains 401g yellow solid, and yield is
99.1%.
By obtained solid carry out nuclear magnetic resonance spectroscopy test (1) and examination of infrared spectrum H-NMR.
Obtained hydrogen nuclear magnetic resonance spectrogram spectrum and infrared spectrogram are consistent with embodiment 5.It can thus be appreciated that is obtained is
(E) -2- { 2- [6- hydroxy pyrimidine -4- base oxygroup] phenyl } -3- methoxy-methyl acrylate.
Embodiment 7
Fluoxastrobin is prepared according to method described in embodiment 1 is similar to, unlike, acidity used in embodiment 7 is urged
Agent is Ethyl Sulfate, and diluent is butyl acetate, finally obtains 3.6g yellow solid, yield 95.1%.
By obtained solid carry out nuclear magnetic resonance spectroscopy (1H-NMR) and examination of infrared spectrum, obtained nuclear magnetic resonance spectroscopy
Figure and infrared spectrogram are consistent with embodiment 1.It can thus be appreciated that is obtained is Fluoxastrobin.
Embodiment 8
Fluoxastrobin is prepared according to method described in embodiment 1 is similar to, unlike, acidity used in embodiment 8 is urged
Agent is potassium acid sulfate, diluent DMF, and reaction temperature 120 finally obtains 3.6g yellow solid, yield 81.8%.
By obtained solid carry out nuclear magnetic resonance spectroscopy (1H-NMR) and examination of infrared spectrum, obtained nuclear magnetic resonance spectroscopy
Figure and infrared spectrogram are consistent with embodiment 1.It can thus be appreciated that is obtained is Fluoxastrobin.
Embodiment 9
Fluoxastrobin is prepared according to method as described in example 2 is similar to, unlike, acidity used in embodiment 9 is urged
Agent is dichloroacetic acid, and diluent is acetonitrile, and reaction temperature 55 finally obtains 395g yellow solid, yield 95.8%.
By obtained solid carry out nuclear magnetic resonance spectroscopy (1H-NMR) and examination of infrared spectrum, obtained nuclear magnetic resonance spectroscopy
Figure and infrared spectrogram are consistent with embodiment 1.It can thus be appreciated that is obtained is Fluoxastrobin.
Embodiment 10
Fluoxastrobin is prepared according to method as described in example 2 is similar to, unlike, acidity used in embodiment 10 is urged
Agent is sulfuric acid, and diluent is isopropyl acetate, and reaction temperature is 110 DEG C, finally obtains 385g yellow solid, yield is
90.6%.
By obtained solid carry out nuclear magnetic resonance spectroscopy (1H-NMR) and examination of infrared spectrum, obtained nuclear magnetic resonance spectroscopy
Figure and infrared spectrogram are consistent with embodiment 1.It can thus be appreciated that is obtained is Fluoxastrobin.
The preferred embodiment of the present invention has been described above in detail, and still, the present invention is not limited thereto.In skill of the invention
In art conception range, can with various simple variants of the technical solution of the present invention are made, including each technical characteristic with it is any its
Its suitable method is combined, and it should also be regarded as the disclosure of the present invention for these simple variants and combination, is belonged to
Protection scope of the present invention.
Claims (8)
1. a kind of preparation method of Fluoxastrobin based compound shown in formula (I), which is characterized in that this method includes that use contains formula
(II) compound shown in is that raw material is reacted to obtain compound shown in formula (I),
Wherein, R is halogen, hydroxyl or 2- cyano-benzene oxygen.
2. according to the method described in claim 1, wherein, being carried out in the presence of the reaction is in diluent and acidic catalyst.
3. according to the method described in claim 2, wherein, the acidic catalyst rubs with the dosage of compound shown in formula (II)
You are than being (0.001-10): 1, preferably (0.01-2): 1.
4. according to the method in claim 2 or 3, wherein the acidic catalyst is selected from sulfuric acid, sodium bisulfate, hydrogen sulfate
Potassium, methyl sulfate, Ethyl Sulfate, dimethyl suflfate, methane sulfonic acid, ethylsulfonic acid, sulfamic acid, p-methyl benzenesulfonic acid, phosphorus
One of acid, hydrochloric acid, trifluoroacetic acid, trichloroacetic acid, dichloroacetic acid and monoxone are a variety of.
5. according to the method in claim 2 or 3, wherein the diluent be selected from acetonitrile, cyanophenyl, toluene, chlorobenzene, methanol,
Ethyl alcohol, methylene chloride, tetrahydrofuran, methyl tertiary butyl ether(MTBE), ether, 1,4- dioxane, N,N-dimethylformamide, dimethyl
In sulfoxide, N-Methyl pyrrolidone, methyl acetate, ethyl acetate, isopropyl acetate, n-butyl acetate and hexone
It is one or more.
6. according to the method in claim 2 or 3, wherein the condition of the reaction includes that temperature is 20 DEG C of extremely dilutions used
The reflux temperature of agent.
7. according to the method in claim 2 or 3, wherein when R be 2- cyano-benzene oxygen, the acidic catalyst be selected from pair
When toluenesulfonic acid and/or methane sulfonic acid, the diluent in acetonitrile, n,N-Dimethylformamide and n-butyl acetate one
Kind is a variety of.
8. method described in any one of -3 according to claim 1, wherein the raw material containing compound shown in formula (II)
Contain compound and optional impurity shown in compound shown in formula (II), optional formula (I).
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