CN101805300B - Method for preparing chiral hexaconazole - Google Patents
Method for preparing chiral hexaconazole Download PDFInfo
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- CN101805300B CN101805300B CN2010101380334A CN201010138033A CN101805300B CN 101805300 B CN101805300 B CN 101805300B CN 2010101380334 A CN2010101380334 A CN 2010101380334A CN 201010138033 A CN201010138033 A CN 201010138033A CN 101805300 B CN101805300 B CN 101805300B
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Abstract
The invention provides a method for preparing chiral hexaconazole, comprising the following steps of: leading 1-(2, 4-dichlorophenyl)-1-pentanone and methylene triphenylphosphine to have ylide reaction, and generating 1-(2, 4-dichlorophenyl)-1-pentene; leading the 1-(2, 4-dichlorophenyl)-1-pentene and epoxidation reagent to have reaction under the action of transition metal catalyst, and generating epoxidation intermediate; and finally, carrying out ring opening between the epoxidation intermediate and 1, 2, 4-triazole, and obtaining (-)-hexaconazole. The chiral hexaconazole prepared by the method has high optical purity and the e. e% more than 80%; and furthermore, the total reaction yield is more than 75%, and is suitable for industrial production.
Description
Technical field
The present invention relates to the preparation method of the own azoles alcohol of a kind of agricultural chemicals, specifically, relate to a kind of novel method for preparing chiral hexaconazole.
Background technology
The optical activity agricultural chemicals is in the world one of active research direction to be compared in the chemistry of pesticide field at present.According to recent statistics, have 28% to be chipal compounds in the commercial agrochemicals; Surplus commercial 170 in kind of the chirality agricultural chemicals; Annual sales amount surpass 100,000,000 dollars have 30 surplus kind; Surpass 2,500 ten thousand dollars have 60 surplus kind; The chirality agricultural chemicals sales volume that wherein contains high reactivity chiral isomer composition surpasses 10,000,000,000 dollars, and the chirality agricultural chemicals annual sales amount of pure optically active isomer is near 3,000,000,000 dollars, and the chirality agricultural chemicals accounts for 35% of the global agricultural chemicals market share.
From the biological activity angle, the drug effect of optical activity agricultural chemicals and raceme preparation differs greatly, and the drug effect that has differs hundreds of times; From the environmental protection type agricultural angle, use the optical activity agricultural chemicals, can reduce dosage, alleviate toxicity and improve security, can satisfy the new demand that social development proposes agricultural chemicals; From the economic benefit angle, exploitation optical activity agricultural chemicals can conservation, reduces cost.
The synthesis of chiral medicine has chiral separation and the synthetic two kinds of means of asymmetry catalysis after the chemosynthesis usually.The former need consume the chiral separation agent of equivalent when synthetic drugs, in the medicine with several chiral centres is synthetic, its consumption will be doubled and redoubled.The latter only needs a spot of chiral catalyst, just can synthesize a large amount of chiral drugs, and pollutes for a short time, is that the green of compliance with environmental protection requirements is synthesized.Over nearly more than 30 years, along with the fast development of Organometallic Chemistry, chiral catalyst and asymmetric catalysis constantly make progress, and fine chemical products such as many chiral medicinals, agricultural chemicals and spices form scale prodn gradually.Because asymmetry catalysis is synthetic to have efficient, highly selective, by product is few, environmentally friendly and characteristics such as Atom economy, might become the main means of production of chirality agricultural chemicals future.
Own azoles alcohol is a kind of sterol demethylation suppressor factor that Britain ICI company develops, and is used to prevent and treat uncinula necator, Black Rotten, scab of apple, Powdery Mildew, coffee rust etc., just gets a good review with its mycocidal broad spectrum once listing.Own azoles alcohol is the triazole bactericidal agent that contains a chiral centre, and the compound method that adopts usually at present is: earlier with carbonyl epoxy method synthesizing epoxy midbody, and then with 1,2, the open loop of 4-triazole.The own azoles alcohol that this method obtains is racemic modification, and its reaction formula is as shown in Figure 1.
At present, mainly pure with the own azoles of use on the market with the sold-in of raceme.Yet show that after deliberation the drug effect of the single optical isomer of own azoles alcohol obviously is superior to racemic modification.According to bibliographical information (Yang Liping etc.; Three kinds of bioactive researchs of triazole bactericidal agent enantiomorph; Pesticide Science journal, 2002 the 4th the 2nd phases of volume), with HPLC (HPLC) the pure racemic modification of own azoles is split after; Enantiomorph is carried out biological activity determination respectively, and the result finds: the anti-microbial activity of (-)-own azoles alcohol is superior to (+)-own azoles alcohol.When drug concentration is 10 μ g/ml; When administration time is 72h; (-)-own azoles alcohol is the twice of (+)-own azoles alcohol to the bacteriostasis rate of tomato early blight bacterium and apple zonate spot bacterium, and when drug concentration was 2 μ g/ml, the anti-microbial activity obvious difference between two individual isomer increased; For Sclerotinia sclerotiorum; Effect is observed behind the 72h, and when drug concentration is 10 μ g/ml, the bacteriostasis rate of (+)-own azoles alcohol is 81.3%; And the bacteriostasis rate of (-)-own azoles alcohol is 100%; When drug concentration was 2 μ g/ml, the bacteriostasis rate of (+)-own azoles alcohol was 21.9%, and the bacteriostasis rate of (-)-own azoles alcohol then remains unchanged; In addition, also show same phenomenon for sugar beet leaf spot bacteria.
In sum, (-) of synthesis of optically active-own azoles alcohol can be enhanced product performance, and reduces dosage and the pollution that reduces ecotope.But, the method for the own azoles alcohol of the synthesis of chiral of having reported at present, route is complicated, and condition is harsh, and is with high costs, is not suitable for large-scale commercial prodn.
In order to address the above problem, the present invention adopts the asymmetry catalysis compound method to prepare chiral hexaconazole, obtains epoxy intermediate through transition metal-catalyzed two key asymmetric epoxidation reactions earlier, and then with 1,2, the open loop of 4-triazole, thus make (-)-own azoles alcohol.This method has efficiently, highly selective, by product is few, environmentally friendly and characteristics such as Atom economy, and simple to operate, yield is high, purity is high, is fit to suitability for industrialized production.
Summary of the invention
The object of the present invention is to provide a kind of method for preparing chiral hexaconazole, this method is on existing synthesis technique basis, introduces the asymmetry catalysis compound method, promptly through transition metal-catalyzed down, the asymmetric Epoxidation of alkene is realized.
The asymmetric epoxidation reaction of transition metal-catalyzed two keys has very consequence in chiral drug synthetic, and epoxidation reaction is the essential step of the suitability for industrialized production of own azoles alcohol sterilant.
In order to realize the object of the invention, the present invention provides a kind of method for preparing chiral hexaconazole, and it comprises the steps:
1) generates 1-(2,4 dichloro benzene base)-1-amylene (B) with 1-(2,4 dichloro benzene base)-1-pentanone (A) and the reaction of methylene tri phenyl phosphorus ylide;
2) under the effect of transition-metal catalyst, 1-(2,4 dichloro benzene base)-1-amylene (B) and epoxidation reagent reaction with above-mentioned generation generate epoxidation midbody (C);
3) epoxidation midbody (C) and 1,2, the open loop of 4-triazole generates (-)-own azoles alcohol (D).
Preparing method's of the present invention reaction formula is as shown in Figure 2.
Wherein, the mol ratio of 1-described in the step 1) (2,4 dichloro benzene base)-1-pentanone and methylene tri phenyl phosphorus ylide is 1: (1～3).
In reaction process, earlier 1-(2,4 dichloro benzene base)-1-pentanone is dissolved in organic solvent, maintain the temperature at-20～0 ℃, add methylene tri phenyl phosphorus ylide then, after finishing, be warmed up to room temperature, stirring reaction 4～12h under the room temperature.
Can in system, add water quencher reaction after reaction finishes, the mol ratio of 1-(2,4 dichloro benzene base)-1-pentanone and water is 1: (6～12).
Said organic solvent is preferably toluene, YLENE, benzene, THF (THF), dioxane or ether.
Said methylene tri phenyl phosphorus ylide is got final product according to the ordinary method preparation by triphenylphosphine monobromomethane and n-Butyl Lithium.
The mol ratio of 1-step 2) (2,4 dichloro benzene base)-1-amylene, transition-metal catalyst and epoxidation reagent is 1: (0.001～0.01): (1.5～3).
Earlier 1-(2,4 dichloro benzene base)-1-amylene and transition-metal catalyst are dissolved in the organic solvent, maintain the temperature at 0～10 ℃, add epoxidation reagent then, be warming up to 30～80 ℃, reaction 4～12h.
Said organic solvent is preferably toluene, YLENE, benzene, THF, dioxane, ether, N (DMF) or acetonitrile.
Said transition-metal catalyst is Cu, Fe, Ni, Co, Mn, Cr, Ti class catalyzer, and it can be preferably ferrocene, titanous chloride, tetraisopropoxy titanium or salen-Mn complex compound for forms such as metal-salt, complex compound or inner complexs.
Described epoxidation reagent is a superoxide, is preferably metachloroperbenzoic acid (mCPBA), tertbutanol peroxide or ozone.
The midbody of epoxidation described in the step 3) and 1,2, the mol ratio of 4-triazole are 1: (2～5).
In reaction process, epoxidation midbody elder generation and solid alkali and 1,2, the 4-triazole is dissolved in the organic solvent, and then adds phase-transfer catalyst, and control reaction temperature is 60～120 ℃.
The mol ratio of epoxidation midbody, solid alkali and phase-transfer catalyst is 1: (0.1～1.5): (5 * 10
-3～0.05).
Said organic solvent is preferably DMF, DMSO 99.8MIN. (DMSO) or N-Methyl pyrrolidone.
Said solid alkali comprises sodium hydroxide, Pottasium Hydroxide, salt of wormwood or sodium methylate.
Said phase-transfer catalyst comprises Tetrabutyl amonium bromide, benzyltriethylammoinium chloride or polyoxyethylene glycol.
Specifically, the method for preparing chiral hexaconazole of the present invention, it comprises the steps:
1) synthetic 1-(2,4 dichloro benzene base)-1-amylene (B)
With 1-(2; The 4-dichlorophenyl)-1-pentanone (A) is dissolved in the organic solvent, maintains the temperature at-20～0 ℃, in system, drips methylene tri phenyl phosphorus ylide; After dropwising; Slowly be warmed up to room temperature, stirring reaction 4～12h under the room temperature (gas chromatographic analysis raw material 1-(2,4 dichloro benzene base)-1-pentanone A content finishes less than reaction in 1% o'clock); The reaction back that finishes adds the shrend reaction of going out, and steaming desolventizes and obtains 1-(2,4 dichloro benzene base)-1-amylene (B) then;
2) synthesizing epoxy midbody (C)
With 1-(2; The 4-dichlorophenyl)-transition-metal catalyst of 1-amylene (B) and catalytic amount is dissolved in the organic solvent; Maintain the temperature at 0～10 ℃, in system, add epoxidation reagent, be warming up to 30～80 ℃; Reaction 4～12h (gas chromatographic analysis 1-(2,4 dichloro benzene base)-1-amylene disappearance afterreaction finishes); After reaction was accomplished, to neutral, organic phase was steamed and is desolventized not purified next step reaction, the solvent recuperation of directly being used for of the epoxidation midbody that obtains with the water stratification washing;
3) synthetic (-)-own azoles alcohol (D)
With epoxidation midbody, solid alkali and 1,2, the 4-triazole is dissolved in the organic solvent; In reaction system, add phase-transfer catalyst again, controlled temperature reacts at 60～120 ℃, and gas chromatographic analysis epoxidation midbody (C) content finishes less than reaction in 1% o'clock; Steaming desolventizes, and obtains (-)-own azoles alcohol bullion, and bullion obtains (-)-own azoles alcohol (D) behind recrystallization; HPLC purity＞95%, e.e%＞80%.
Said recrystallization is as recrystallization solvent with toluene, YLENE, methylene dichloride, chloroform or sherwood oil.
In addition, preparation method of the present invention in order further to improve the chiral selectivity of reaction, can also be in step 2) in system, add chiral ligand, and then react.Said chiral ligand comprises tartrate, isocamphol (DAIB), camphor sulfonamide and verivate thereof, 1-dinaphthol (BINOL), 2 part or porphyrin etc., and the mol ratio of chiral ligand and epoxidation midbody is (0.001～0.01): 1.
The inventive method is through the transition metal-catalyzed asymmetric epoxidation reaction of alkene down, and then the own azoles alcohol of synthesis of chiral, and its beneficial effect is:
1) the inventive method total recovery is high, yield＞75%; Product purity is high, purity＞95%; And the optical purity of product is high, e.e%＞80%;
2) the inventive method does not change the existing route of producing, and only need on the basis of existing production technique and equipment, simply adjust to get final product, and is easy and simple to handle, is fit to industrial production;
3) the used transition-metal catalyst of the inventive method can recycling, and the recovery＞95% provides cost savings to a certain extent;
4) though the production cost of the inventive method is slightly higher than the production cost of the own azoles alcohol of racemize; But the anti-microbial activity of (-) that generate-own azoles alcohol obviously is superior to the own azoles alcohol of racemize; The unit drug effect improves 40～50% than similar racemic modification, thereby can reduce dosage, reduces the pollution to environment.
Description of drawings
Fig. 1 is the synthesis technique of the own azoles alcohol of existing racemize;
Fig. 2 is the reaction formula of chiral hexaconazole according to the invention.
Embodiment
Following examples are used for further specifying the present invention, but do not limit the scope of the invention.
Embodiment 1
1) 1-(2,4 dichloro benzene base)-1-amylene (B) is synthetic
100mmol 1-(2,4 dichloro benzene base)-1-pentanone (23.1g) is dissolved in the pre-dried toluene, maintains the temperature at-20 ℃, in system, drip the toluene solution (concentration is 1mol/L) of 150mmol methylene tri phenyl phosphorus ylide (41.5g); After dropwising, slowly be warmed up to room temperature, stir 6h under the room temperature; Through gas chromatographic analysis raw material 1-(2; The 4-dichlorophenyl)-and 1-pentanone content finishes less than reaction in 1% o'clock, the reaction back adds 0.6mol in reaction system the shrend reaction of going out that finishes, and underpressure distillation obtains 21.7g 1-(2; The 4-dichlorophenyl)-and 1-amylene (B), yield 95%;
(2) epoxidation midbody (C) is synthetic
Tetraisopropoxy titanium (5 * 10 with 100mmol 1-(2,4 dichloro benzene base)-1-amylene (22.9g) and catalytic amount
-4Mol) be dissolved in DMF, maintain the temperature at 10 ℃, in system, add 150mmol tertbutanol peroxide (13.5g); Be warming up to 40 ℃ then, reaction 6h; Stopped reaction after gas chromatographic analysis 1-(2,4 dichloro benzene base)-1-amylene (B) disappears, reaction is washed with water to neutrality after accomplishing, and organic phase is steamed and is desolventized, and obtains epoxidation midbody (C), solvent recuperation; The epoxidation midbody (C) that obtains is not purified directly to be used for next step reaction;
(3) synthesizing of (-)-own azoles alcohol (D)
Get 100mmol epoxidation midbody (24.5g), 20mmol sodium hydroxide (0.8g) and 200mmol 1,2,4-triazole (13.8g) is dissolved in DMF, in system, adds 5 * 10 again
-4The mol Tetrabutyl amonium bromide; Control reaction temperature finishes less than reaction in 1% o'clock through gas chromatographic analysis epoxy intermediate (C) content at 60 ℃ then, and steaming desolventizes; Obtain (-)-own azoles alcohol bullion, bullion obtains 25.1g (-)-own azoles alcohol, yield 80% through the toluene recrystallization; HPLC purity 96.5%, e.e%:82%.
Embodiment 2
1) 1-(2,4 dichloro benzene base)-1-amylene (B) is synthetic
100mmol 1-(2,4 dichloro benzene base)-1-pentanone (23.1g) is dissolved in the pre-dried dioxane, maintains the temperature at-10 ℃, in system, drip the dioxane solution (concentration is 1mol/L) of 200mmol methylene tri phenyl phosphorus ylide (55.3g); After dropwising, slowly be warmed up to room temperature, stir 8h under the room temperature; Through gas chromatographic analysis raw material 1-(2; The 4-dichlorophenyl)-and 1-pentanone content finishes less than reaction in 1% o'clock, the reaction back adds 1mol in reaction system the shrend reaction of going out that finishes, and underpressure distillation obtains 21.3g 1-(2; The 4-dichlorophenyl)-and 1-amylene (B), yield 93.1%;
(2) epoxidation midbody (C) is synthetic
Salen-Mn complex compound (1 * 10 with 100mmol 1-(2,4 dichloro benzene base)-1-amylene (22.9g) and catalytic amount
-4Mol) be dissolved in toluene, maintain the temperature at 0 ℃, in system, add 150mmol mCPBA (25.9g); Be warming up to 50 ℃ then, reaction 8h; Stopped reaction after gas chromatographic analysis 1-(2,4 dichloro benzene base)-1-amylene (B) disappears, reaction is washed with water to neutrality after accomplishing, and organic phase is steamed and is desolventized, and obtains epoxidation midbody (C), solvent recuperation; The epoxidation midbody (C) that obtains is not purified directly to be used for next step reaction;
(3) synthesizing of (-)-own azoles alcohol (D)
Get 100mmol epoxidation midbody (24.5g), 100mmol Pottasium Hydroxide (5.6g) and 400mmol 1,2,4-triazole (27.6g) is dissolved in DMSO, in system, adds 1 * 10 again
-3The mol benzyltriethylammoinium chloride; Controlled temperature reacts under 100 ℃ then; Finish less than reaction in 1% o'clock through gas chromatographic analysis epoxy intermediate (C) content, steaming desolventizes, and obtains (-)-own azoles alcohol bullion; Bullion obtains 27.3g (-)-own azoles alcohol through the methylene dichloride recrystallization; Yield 87%, HPLC purity: 95.9%, e.e%:86%.
Embodiment 3
1) 1-(2,4 dichloro benzene base)-1-amylene (B) is synthetic
100mmol 1-(2,4 dichloro benzene base)-1-pentanone (23.1g) is dissolved among the pre-dried THF, maintains the temperature at 0 ℃, in system, drip the THF solution (concentration is 1mol/L) of 300mmol methylene tri phenyl phosphorus ylide (82.8g); After dropwising, slowly be warmed up to room temperature, stir 4h under the room temperature; Through gas chromatographic analysis raw material 1-(2; The 4-dichlorophenyl)-and 1-pentanone content finishes less than reaction in 1% o'clock, the reaction back adds 1.2mol in reaction system the shrend reaction of going out that finishes, and underpressure distillation obtains 22.3g 1-(2; The 4-dichlorophenyl)-and 1-amylene (B), yield 97.2%;
(2) epoxidation midbody (C) is synthetic
Titanous chloride (5 * 10 with 100mmol 1-(2,4 dichloro benzene base)-1-amylene (22.9g), catalytic amount
-4Mol) and 2 part (5 * 10
-4Mol) be dissolved in dioxane, maintain the temperature at 5 ℃, in system, feed ozone; Be warming up to 80 ℃ then, reaction 12h; Stopped reaction after gas chromatographic analysis 1-(2,4 dichloro benzene base)-1-amylene (B) disappears, reaction is washed with water to neutrality after accomplishing, and organic phase is steamed and is desolventized, and obtains epoxidation midbody (C), solvent recuperation; The epoxidation midbody (C) that obtains is not purified directly to be used for next step reaction;
(3) synthesizing of (-)-own azoles alcohol (D)
Get 100mmol epoxidation midbody (24.5g), 50mmol salt of wormwood (6.9g) and 500mmol 1,2,4-triazole (34.5g) is dissolved in N-Methyl pyrrolidone, in system, adds 3 * 10 again
-3The mol polyoxyethylene glycol; Controlled temperature reacts under 120 ℃ then; Finish less than reaction in 1% o'clock through gas chromatographic analysis epoxy intermediate (C) content, steaming desolventizes, and obtains (-)-own azoles alcohol bullion; Bullion obtains 26.7g (-)-own azoles alcohol through the sherwood oil recrystallization; Yield 85%, HPLC purity: 98%, e.e%:86%.
Embodiment 4
1) 1-(2,4 dichloro benzene base)-1-amylene (B) is synthetic
100mmol 1-(2,4 dichloro benzene base)-1-pentanone (23.1g) is dissolved in the pre-dried ether, maintains the temperature at-20 ℃, in system, drip the diethyl ether solution (concentration is 1mol/L) of 100mmol methylene tri phenyl phosphorus ylide (27.6g); After dropwising, slowly be warmed up to room temperature, stir 12h under the room temperature; Through gas chromatographic analysis raw material 1-(2; The 4-dichlorophenyl)-and 1-pentanone content finishes less than reaction in 1% o'clock, the reaction back adds 600mmol in reaction system the shrend reaction of going out that finishes, and underpressure distillation obtains 22g 1-(2; The 4-dichlorophenyl)-and 1-amylene (B), yield 96%;
(2) epoxidation midbody (C) is synthetic
Titanous chloride (1 * 10 with 100mmol 1-(2,4 dichloro benzene base)-1-amylene (22.9g), catalytic amount
-3Mol) and 1-dinaphthol (5 * 10
-4Mol) be dissolved in acetonitrile, maintain the temperature at 8 ℃, in system, add 150mmol tertbutanol peroxide (13.5g); Be warming up to 30 ℃ then, reaction 4h; Stopped reaction after gas chromatographic analysis 1-(2,4 dichloro benzene base)-1-amylene (B) disappears, reaction is washed with water to neutrality after accomplishing, and organic phase is steamed and is desolventized, and obtains epoxidation midbody (C), solvent recuperation; The epoxidation midbody (C) that obtains is not purified directly to be used for next step reaction;
(3) synthesizing of (-)-own azoles alcohol (D)
Get 100mmol epoxidation midbody (24.5g), 0.8mmol sodium methylate (5.5g) and 250mmol 1,2,4-triazole (17.3g) is dissolved in DMF, in system, adds 5 * 10 again
-3The mol Tetrabutyl amonium bromide; Controlled temperature reacts under 100 ℃ then; Finish less than reaction in 1% o'clock through gas chromatographic analysis epoxy intermediate (C) content, steaming desolventizes, and obtains (-)-own azoles alcohol bullion; Bullion obtains 25.7g (-)-own azoles alcohol through the chloroform recrystallization; Yield 82%, HPLC purity: 97%, e.e%:81%.
Though, the present invention has been done detailed description in the preceding text through generality explanation and specific embodiments, on basis of the present invention, can to some modifications of do or improvement, this will be apparent to those skilled in the art.Therefore, these modifications or the improvement on the basis of not departing from spirit of the present invention, made all belong to the scope that requirement of the present invention is protected.
Claims (10)
1. a method for preparing chiral hexaconazole is characterized in that, comprises the steps:
1) generates 1-(2,4 dichloro benzene base)-1-amylene with 1-(2,4 dichloro benzene base)-1-pentanone and the reaction of methylene tri phenyl phosphorus ylide;
2) under the effect of transition-metal catalyst, 1-(2,4 dichloro benzene base)-1-amylene and epoxidation reagent reaction with above-mentioned generation generate the epoxidation midbody, and said transition-metal catalyst is tetraisopropoxy titanium, salen-Mn complex compound or titanous chloride;
3) epoxidation midbody and 1,2, the open loop of 4-triazole generates (-)-own azoles alcohol.
2. preparation method according to claim 1 is characterized in that, the mol ratio of 1-described in the step 1) (2,4 dichloro benzene base)-1-pentanone and methylene tri phenyl phosphorus ylide is 1: (1～3).
3. preparation method according to claim 1 and 2 is characterized in that, elder generation is with 1-(2 in the step 1); The 4-dichlorophenyl)-the 1-pentanone is dissolved in organic solvent; Maintain the temperature at-20～0 ℃, add methylene tri phenyl phosphorus ylide then, after finishing; Be warmed up to room temperature, stirring reaction 4～12h under the room temperature.
4. preparation method according to claim 3 is characterized in that, in system, adds water quencher reaction after reaction finishes in the step 1); The mol ratio of 1-(2,4 dichloro benzene base)-1-pentanone and water is 1: (6～12).
5. preparation method according to claim 1 is characterized in that step 2) described in the mol ratio of 1-(2,4 dichloro benzene base)-1-amylene, transition-metal catalyst and epoxidation reagent be 1: (0.001～0.01): (1.5～3).
6. according to claim 1 or 5 described preparing methods, it is characterized in that step 2) middle earlier with 1-(2; The 4-dichlorophenyl)-1-amylene and transition-metal catalyst be dissolved in the organic solvent, maintains the temperature at 0～10 ℃, adds epoxidation reagent then; Be warming up to 30～80 ℃, reaction 4～12h.
7. preparation method according to claim 6 is characterized in that, said epoxidation reagent is a superoxide.
8. preparation method according to claim 1 is characterized in that, the midbody of epoxidation described in the step 3) and 1,2, and the mol ratio of 4-triazole is 1: (2～5).
9. according to claim 1 or 8 described preparing methods, it is characterized in that, in the step 3) in reaction process; Epoxidation midbody elder generation and solid alkali and 1,2, the 4-triazole is dissolved in the organic solvent; And then the adding phase-transfer catalyst, control reaction temperature is 60～120 ℃.
10. preparation method according to claim 9 is characterized in that, the mol ratio of epoxidation midbody, solid alkali and phase-transfer catalyst is 1 in the step 3): (0.1～1.5): (5 * 10
-3～0.05); Said solid alkali comprises sodium hydroxide, Pottasium Hydroxide, salt of wormwood or sodium methylate; Said phase-transfer catalyst comprises Tetrabutyl amonium bromide, benzyltriethylammoinium chloride or polyoxyethylene glycol.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0093526A2 (en) * | 1982-04-30 | 1983-11-09 | Imperial Chemical Industries Plc | Preparation of selected epoxides |
| EP0110536A2 (en) * | 1982-11-10 | 1984-06-13 | Imperial Chemical Industries Plc | Substituted alkenes and processes for their preparation |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0093526A2 (en) * | 1982-04-30 | 1983-11-09 | Imperial Chemical Industries Plc | Preparation of selected epoxides |
| EP0110536A2 (en) * | 1982-11-10 | 1984-06-13 | Imperial Chemical Industries Plc | Substituted alkenes and processes for their preparation |
Non-Patent Citations (1)
| Title |
|---|
| Torsten Spitzer, et. al.Enantiomer Separation of Fungicidal Triazolyl Alcohols by Normal Phase HPLC on Polysaccharide-Based Chiral Stationary Phases.《Chirality》.1999,第11卷(第3期),正文第195页至第200页. * |
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