CN106279067B - A kind of preparation method of epoxiconazole intermediate and the preparation method of epoxiconazole - Google Patents
A kind of preparation method of epoxiconazole intermediate and the preparation method of epoxiconazole Download PDFInfo
- Publication number
- CN106279067B CN106279067B CN201610671263.4A CN201610671263A CN106279067B CN 106279067 B CN106279067 B CN 106279067B CN 201610671263 A CN201610671263 A CN 201610671263A CN 106279067 B CN106279067 B CN 106279067B
- Authority
- CN
- China
- Prior art keywords
- compound
- epoxiconazole
- preparation
- solvent
- alkali
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D301/00—Preparation of oxiranes
- C07D301/02—Synthesis of the oxirane ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/14—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by free hydroxyl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The present invention relates to a kind of preparation method of epoxiconazole intermediate and the preparation methods of epoxiconazole, using o-chloro benzyl chloride as raw material, react to obtain compound 4 with dimethyl sulphide or dimethyl sulfoxide, wherein the structural formula of compound 4 are as follows:；It is raw material with compound 4 and compound 2, reaction obtains epoxiconazole intermediate in the presence of alkali, wherein the structural formula of compound 2 are as follows:；The structural formula of epoxiconazole intermediate are as follows:
Description
Technical field
The present invention relates to a kind of preparation method of epoxiconazole intermediate and the preparation methods of epoxiconazole.
Background technique
Epoxiconazole, English common name: epoxiconazole is interior suction selectivity fungicide, the suppression of active constituent epoxiconazole
The synthesis of germ ergosterol processed hinders the formation of germ cell wall, and epoxiconazole molecule is to a kind of fungal enzyme (14-
Dencthylase) there is strength compatibility, compared with the fungicide being currently known, can more effectively inhibit germ fungal pathogens.Epoxiconazole
The chitinase activity that crop can be improved leads to the contraction of fungi haustorium, inhibits germ intrusion, this is epoxiconazole in all triazoles
Unique characteristic in class product.To the leaf on the crops such as banana, green onion garlic, celery, Kidney bean, melon, asparagus, peanut, beet
The diseases such as anthracnose, white rot on pinta, powdery mildew, rust and grape have good preventive effect.US5268517 uses lattice
There is safety and environmental protection, be unfavorable for advising greatly in formula reagent method, the technique to moisture and oxygen content requirement height in reaction process
Mould production, US20110295019 use Horner-Wadsworth-Emmons reaction method, and the raw material in the technique is not easy to close
At, and methyl nitrite is used during Material synthesis, steam is very easy to form explosive mixture, HWE with air
A large amount of phosphorus-containing wastewater is generated in reaction process, causes very big environmental pollution.
Summary of the invention
A kind of preparation for high, safety and environmental protection epoxiconazole intermediate that technical problem to be solved by the invention is to provide yields
The preparation method of method and epoxiconazole.
In order to solve the above-mentioned technical problem, the present invention adopts the following technical scheme:
It is an object of the present invention to provide a kind of preparation methods of epoxiconazole intermediate, include the following steps:
Step (1), using o-chloro benzyl chloride as raw material, react to obtain compound 4 with dimethyl sulphide or dimethyl sulfoxide, wherein
The structural formula of the compound 4 are as follows:
Step (2) with compound 4 and compound 2 is raw material, and reaction obtains compound 5 in the presence of alkali, as described
Epoxiconazole intermediate, wherein the structural formula of compound 2 are as follows:The knot of the epoxiconazole intermediate
Structure formula are as follows:
Preferably, in step (1), the temperature for carrying out the reaction is 30~120 DEG C, preferably 30~100 DEG C, into one
Preferably 30~50 DEG C, most preferably 35~45 DEG C of step.
Preferably, in step (1), the time for carrying out the reaction is 2~4 hours.
Preferably, in step (2), the alkali is selected from sodium carbonate, calcium hydroxide, sodium hydroxide, potassium hydroxide, amino
One of sodium, sodium hydride or a variety of mixed bases.
Preferably, in step (2), the compound 4 and the compound 2 are described in the presence of a solvent
Reaction, the solvent are molten selected from one of dimethyl sulfoxide, dimethyl sulphide, toluene, tetrahydrofuran or a variety of mixing
Agent.
Preferably, in step (2), the temperature for carrying out the reaction is 70~120 DEG C, preferably 70~100 DEG C, more excellent
Selection of land is 75~85 DEG C.
Preferably, in step (2), the time for carrying out the reaction is 1~3 hour.
Specifically, the epoxiconazole intermediate specific is the preparation method comprises the following steps: the o-chloro benzyl chloride is dissolved in described
In dimethyl sulphide or the dimethyl sulfoxide, reacted, after the reaction was completed stop heating, be cooled to 0~10 DEG C, then plus
Enter solvent, the compound 2, the alkali is added portionwise, is reacted, it is post-treated after the reaction was completed to obtain the fluorine
Ring azoles intermediate.
Specifically, the compound 2 is prepared via a method which to obtain: using the chloro- 1- of 2- to fluoro acetophenone as raw material,
Under the action of alkali and catalyst, in the presence of the solvent, reaction obtains the compound 2 at 60~150 DEG C.
Preferably, the alkali is potassium hydroxide and/or sodium hydroxide, and the catalyst is selected from sodium bromide, iodate
One of sodium, potassium bromide, potassium iodide are a variety of；The solvent is selected from water, dimethylformamide, dimethyl sulfoxide, alcohol
One of or it is a variety of.
Preferably, the reaction temperature is 90~110 DEG C.
Preferably, the time of the reaction is 4~6 hours.
Specifically, the compound 2 specific be the preparation method comprises the following steps: the chloro- 1- of 2- dissolves in a solvent fluoro acetophenone,
Alkali and catalyst is added, is reacted, when GC is detected without the chloro- 1- of 2- to fluoro acetophenone, stops heating, it is then post-treated to obtain
The compound 2.
It is a further object to provide a kind of preparation methods of epoxiconazole comprising following steps:
Step (1), by epoxiconazole intermediate in the presence of alkali, in the presence of the solvent, react to obtain with leaving group
Compound 6, wherein the structural formula of the compound 6 are as follows:
Step (2) reacts the compound 6 with triazole to obtain the epoxiconazole.
Preferably, in step (1), the leaving group is selected from sulfonyloxy methyl, to benzene methylsulfonyl and sulfonyloxy methyl
Or to one of halides of benzene methylsulfonyl or a variety of；The alkali is selected from triethylamine, pyridine or other organic bases；It is described
Solvent be selected from organic solvents such as methylene chloride, toluene or tetrahydrofurans.
Preferably, in step (2), the compound 6 and the triazole in the presence of the solvent, in the effect of alkali
Under reacted, the solvent be selected from dimethylformamide, N-Methyl pyrrolidone or dimethyl sulfoxide etc.；The alkali is
Selected from potassium carbonate, potassium hydroxide or sodium hydroxide.
Preferably, in step (2), the temperature for carrying out the reaction is 80~120 DEG C, more preferably 90~110 DEG C.
Specifically, the epoxiconazole specific be the preparation method comprises the following steps: epoxiconazole intermediate is dissolved in solvent, 5~
Leaving group and alkali are added at 15 DEG C, is reacted 0.5~1.5 hour at 10~35 DEG C, it is then post-treated to obtain compound 6,
In a solvent by the dissolution of compound 6, triazole and alkali is added, reacts 1~2 hour, it is then post-treated to obtain epoxiconazole.
Due to the implementation of above technical scheme, the invention has the following advantages over the prior art:
The present invention uses Corey epoxidation reaction method, which has raw material and be easy to get, and easy to operate, stereoselectivity is good,
The advantages that yield is high, and Atom economy is good, meets safety and environmental protection requirement, is suitble to industrialized production.
Specific embodiment
Synthetic route of the invention are as follows:
Technical scheme of the present invention will be further described combined with specific embodiments below, but the present invention should not necessarily be limited by this
A little embodiments, below the content be mass content.
Embodiment 1
25 g of compound 1 are dissolved in 50mL dimethyl sulfoxide, 15 grams of sodium hydroxides and 1 gram of potassium iodide are added, are warming up to
It 100 DEG C, reacts 5 hours, when GC detection is without compound 1, stops heating, be cooled to room temperature, ethyl acetate is added, successively use water,
5% sodium chloride solution and water washing, liquid separation is dry, and vacuum distillation removes ethyl acetate and obtains 21 g of compound 2, and purity >
95%, yield 95.5%.
Embodiment 2
25 grams of o-chloro benzyl chlorides are dissolved in 50mL dimethyl sulphide, are heated to 40 DEG C, reacts 3 hours, stops at such a temperature
It only heating, is cooled to 5 DEG C, then potassium hydroxide is added portionwise in the compound 2 that addition 50mL toluene and 21 grams of embodiments 1 obtain,
80 DEG C are heated to, the remaining dimethyl sulphide of collection system reacts 2 hours, when GC inspection does not measure compound 1, is cooled to room temperature, adds
Enter 50mL water, be layered, organic layer successively uses water, 5% sodium chloride solution and water washing, and dry, vacuum distillation obtains 40 grams of chemical combination
Object 5, purity > 92%, yield 93%.
Embodiment 3
25 grams of o-chloro benzyl chlorides are dissolved in 50mL dimethyl sulfoxide, are heated to 50 DEG C, are reacted 3 hours at such a temperature, are stopped
Heating, is cooled to 5 DEG C, compound 2 obtained in 21 grams of embodiments 1 is added, Sodamide is then added portionwise, is heated to 80 DEG C,
Reaction 2 hours is cooled to room temperature when GC inspection does not measure compound 1, and 50mL water, layering is added, and organic layer successively uses water, 5% chlorine
Change sodium solution and water washing, dry, vacuum distillation obtains 35 g of compound 5, purity > 91%, yield 80%.
Embodiment 4
25 grams of o-chloro benzyl chlorides are dissolved in 50mL dimethyl sulphide, are heated to 40 DEG C, reacts 3 hours, stops at such a temperature
It only heating, is cooled to 5 DEG C, then sodium hydroxide is added portionwise in the compound 2 that addition 50mL toluene and 21 grams of embodiments 1 obtain,
80 DEG C are heated to, the remaining dimethyl sulphide of collection system reacts 2 hours, when GC inspection does not measure compound 1, is cooled to room temperature, adds
Enter 50mL water, be layered, organic layer successively uses water, 5% sodium chloride solution and water washing, and dry, vacuum distillation obtains 32 grams of chemical combination
Object 5, purity > 92%, yield 72%.
Embodiment 5
Compound 5 obtained in 20 grams of embodiments 2 is dissolved in 50mL methylene chloride, at 10 DEG C, 8.5 grams of first are added
Base sulfonic acid chloride and 8 grams of triethylamines, are stirred at room temperature 1 hour, and 50mL water washing is added, and dry, vacuum distillation obtains crude Compound
6, it is dissolved in 50mL DMF, triazole and potassium carbonate is added, is warming up to 100 DEG C, react 2 hours, add at such a temperature
Enter 100mL ethyl acetate and 50mL water, liquid separation, organic layer successively uses water, 5% sodium chloride solution and water washing, and dry, decompression is steamed
It evaporates to obtain crude product, then obtains 20 grams of epoxiconazoles, purity > 98%, yield 85% with recrystallizing methanol.
Above-described embodiment is technical concepts and features to illustrate the invention, and its object is to allow be familiar with technique
People cans understand the content of the present invention and implement it accordingly, and it is not intended to limit the scope of the present invention, it is all according to the present invention
Equivalence changes or modification made by Spirit Essence should be all included within the scope of the present invention.
Claims (8)
1. a kind of preparation method of epoxiconazole, characterized by the following steps:
Step (1), using o-chloro benzyl chloride as raw material, react to obtain compound 4 with dimethyl sulphide, wherein the knot of the compound 4
Structure formula are as follows:；
Step (2) with compound 4 and compound 2 is raw material, and reaction obtains compound 5, the as fluorine in the presence of alkali
Ring azoles intermediate, wherein the structural formula of compound 2 are as follows:；The structural formula of the epoxiconazole intermediate
Are as follows:；The compound 2 is prepared via a method which to obtain: with the chloro- 1- of 2- to fluoro acetophenone
For raw material, under the action of alkali and catalyst, in the presence of the solvent, reaction obtains the compound 2 at 60 ~ 150 DEG C；
Step (3), by the epoxiconazole intermediate in the presence of alkali, it is in the presence of the solvent, anti-with leaving group reagent
It should obtain compound 6, wherein the structural formula of the compound 6 are as follows:；Wherein, L is sulfonyloxy methyl
Oxygroup；The leaving group reagent is one of halides of sulfonyloxy methyl or a variety of；
Step (4) reacts the compound 6 with triazole to obtain the epoxiconazole.
2. the preparation method of epoxiconazole according to claim 1, it is characterised in that: in step (1), carry out the reaction
Temperature be 30 ~ 120 DEG C.
3. the preparation method of epoxiconazole according to claim 1, it is characterised in that: the preparation chemical combination in step (2)
Alkali used in object 5 is one of sodium carbonate, calcium hydroxide, sodium hydroxide, potassium hydroxide, Sodamide, sodium hydride or a variety of
Mixed base.
4. the preparation method of epoxiconazole according to claim 1, it is characterised in that: in step (2), the compound 4
With the compound 2 is described in the presence of a solvent reacts, the solvent be dimethyl sulfoxide, dimethyl sulphide,
One of toluene, tetrahydrofuran or a variety of mixed solvents.
5. the preparation method of epoxiconazole according to claim 1, it is characterised in that: the preparation chemical combination in step (2)
The temperature of reaction when object 5 is 70 ~ 120 DEG C.
6. the preparation method of epoxiconazole according to claim 1, it is characterised in that: the preparation chemical combination in step (2)
For the alkali used when object 2 for potassium hydroxide and/or sodium hydroxide, the catalyst is sodium bromide, sodium iodide, bromination
One of potassium, potassium iodide are a variety of, and the solvent is one of water, dimethylformamide, dimethyl sulfoxide, alcohol or more
Kind.
7. the preparation method of epoxiconazole according to claim 1, it is characterised in that: in step (3), the alkali is three second
Amine, pyridine or other organic bases；The solvent is methylene chloride, toluene or tetrahydrofuran.
8. the preparation method of epoxiconazole according to claim 1, it is characterised in that: in step (4), the compound 6
In the presence of the solvent with the triazole, it is reacted in the presence of alkali, the solvent is dimethylformamide, N-
Methyl pyrrolidone or dimethyl sulfoxide；The alkali is selected from potassium carbonate, potassium hydroxide or sodium hydroxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610671263.4A CN106279067B (en) | 2016-08-16 | 2016-08-16 | A kind of preparation method of epoxiconazole intermediate and the preparation method of epoxiconazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610671263.4A CN106279067B (en) | 2016-08-16 | 2016-08-16 | A kind of preparation method of epoxiconazole intermediate and the preparation method of epoxiconazole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106279067A CN106279067A (en) | 2017-01-04 |
| CN106279067B true CN106279067B (en) | 2019-03-15 |
Family
ID=57671405
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610671263.4A Active CN106279067B (en) | 2016-08-16 | 2016-08-16 | A kind of preparation method of epoxiconazole intermediate and the preparation method of epoxiconazole |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106279067B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108164514B (en) * | 2018-03-02 | 2021-02-09 | 江苏七洲绿色化工股份有限公司 | Preparation method of epoxiconazole |
| CN110526906A (en) * | 2019-09-30 | 2019-12-03 | 江苏七洲绿色化工股份有限公司 | A kind of preparation method of epoxiconazole |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0515876A2 (en) * | 1991-05-31 | 1992-12-02 | BASF Aktiengesellschaft | Process for the preparation of cis-2-(1H-1,2,4-triazol-1-yl-methyl)2-(halophenyl)-3-(halophenyl)-oxirane |
| CN102378760A (en) * | 2009-02-05 | 2012-03-14 | 巴斯夫欧洲公司 | Method for producing hydroxymethyl diphenyloxiranes and corresponding 1-azolylmethyl-1,2-diphenyloxiranes |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005056548A1 (en) * | 2003-12-11 | 2005-06-23 | Cheminova A/S | Enantiomerically pure epoxiconazole and its use as crop protection agent |
-
2016
- 2016-08-16 CN CN201610671263.4A patent/CN106279067B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0515876A2 (en) * | 1991-05-31 | 1992-12-02 | BASF Aktiengesellschaft | Process for the preparation of cis-2-(1H-1,2,4-triazol-1-yl-methyl)2-(halophenyl)-3-(halophenyl)-oxirane |
| CN102378760A (en) * | 2009-02-05 | 2012-03-14 | 巴斯夫欧洲公司 | Method for producing hydroxymethyl diphenyloxiranes and corresponding 1-azolylmethyl-1,2-diphenyloxiranes |
Non-Patent Citations (1)
| Title |
|---|
| Regio- and Stereoselective Ring Opening of 2,3-Diaryl Oxiranes by LiBr/Amberlyst 15: A New Stereocontrolled Access to 1,2-Diaryl-2-bromo Alcohols;Arlette Solladie-Cavallo 等;《J. Org. Chem.》;20050201;第70卷;1605-1611 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106279067A (en) | 2017-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2867211T3 (en) | METHOD OF PREPARING MEDETOMIDINE WITH CHLORACETONE | |
| CN106278850B (en) | The synthetic method of the chloro- 1- acetylcyclopropanes of prothioconazoles intermediate 1- | |
| DK2847173T3 (en) | METHOD OF PRODUCING Medetomidine | |
| CN106279067B (en) | A kind of preparation method of epoxiconazole intermediate and the preparation method of epoxiconazole | |
| WO2009063487A3 (en) | An improved process for manufacture of epoxides, particularly epichlorohydrin | |
| CN101693649B (en) | Process for preparing 1.3.5-trimethoxybenzene | |
| CN108164514B (en) | Preparation method of epoxiconazole | |
| WO2012172121A1 (en) | Method for the preparation of medetomidine with chloroacetone | |
| CN106008183A (en) | Preparation methods for ephedrine or pseudoephedrine and for ephedrine or pseudoephedrine intermediate | |
| CN1685818A (en) | Simplified production technology of bisultap | |
| CN109942539A (en) | A kind of preparation method of the fluoro- 1,3- propane sultone of 2- | |
| CN114805051B (en) | Method for preparing 2, 4-dichlorobenzoic acid from propiconazole 4-H isomer | |
| CN104628559B (en) | Ozone oxidation method used for preparing halogenated acetic acid and esters of halogenated acetic acid | |
| CN104529924A (en) | Method for preparing 5-cyclopropyl-4-[2-methylthio-4-(trifluoromethyl)benzoyl] isoxazole | |
| CN107417643A (en) | A kind of synthesis technique of dyclonine hydrochloride | |
| CN107446590B (en) | Process for synthesizing fluorine-containing dicyclohexyl alkene liquid crystal at tail end | |
| CN103965092B (en) | A kind of bromo-N-of 2-that synthesizes is to the method for Methyl benzenesulfonyl base pyrroles | |
| CN109400541B (en) | Process for the preparation of cyproconazole from 1-chloro-2- (4-chlorophenyl) -3-methyl-4-penten-2-ol | |
| AU2003200192B2 (en) | Production method of an ether compound | |
| CN108299156A (en) | A kind of new synthetic method of luliconazole key chiral intermediate | |
| CN102898340A (en) | Synthesis method of S-substituted-anthranilate thioester derivatives | |
| CN107311873B (en) | Method for preparing 2, 6-dichloro-4-trifluoromethylaniline with 99% content | |
| CN106631736A (en) | Method for preparing 3,5-dichloro-2-pentanone | |
| CN114634492A (en) | Preparation method of lanoconazole | |
| CN105294391B (en) | Between benzyl dichloride synthesis technique |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |