CN104497080A - Abamectin ester compound and preparation method and application of abamectin ester compound - Google Patents
Abamectin ester compound and preparation method and application of abamectin ester compound Download PDFInfo
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Abstract
The invention relates to the technical field of insecticidal pesticides, and in particular relates to an abamectin ester compound and a preparation method and application of abamectin ester compound. The abamectin ester compound is prepared by chemically modifying abamectin. Compared with common abamectin products, the abamectin ester compound has the characteristics of being high in pesticide effect, long in lasting period, free of residue and free of environmental pollution, and also has the advantages of being fast to act and free of resistance; the abamectin ester compound is particularly extremely high in activities for lithocolletis ringoniella, leaf miner, various resistant aphids and other common pests, has stomach toxicity and touch out effect, and is reliable and stable in prevention and control effect under extremely low dose; compared with the common abamectin products, the abamectin ester compound has the advantages that the insecticidal activity of the abamectin ester compound is obviously improved, and the abamectin ester compound is suitable for popularization and application in pesticides-related fields.
Description
Technical field
The present invention relates to desinsection technical field of pesticide, particularly relate to Avrmectin ester compound and its production and use.
Background technology
Avrmectin (Avermectin, be called for short AVM) is a kind of agricultural or Veterinary Insecticides, miticide of being widely used, and primarily of Avermectin B1a and avermectin B1b mixing composition, wherein B1a is not less than 90%, B1b is no more than 5%., as antibiotic insecticide that is efficient, wide spectrum, there is low toxicity, efficient, highly to select, the advantage such as environmental protection and long residual effect, solve height poison that traditional agricultural chemicals exists, resistant gene pollutes and the problem such as environmental pollution.But along with the universal of Avrmectin in recent years and derived product thereof with promote, resistance is also more and more obvious, and the thermal destruction of Avrmectin own and photodegradation are very serious in addition, the lasting period is short, and compared to other chemical pesticides, its Dominant Facies is to decline.Therefore, need badly to research and produce there is better performance, and sterilant that cost lower more friendly to environment.
Summary of the invention
The object of the invention is, for prior art Problems existing, provide a kind of Avrmectin ester compound and its production and use.
The technical scheme that the present invention deals with problems is: a kind of Avrmectin ester compound, has structural formula shown in following formula I:
In formula, R is-OCCH
2ph or-OCCH
3; R
1for-CH
2cH
3or-CH
3; X-Y is-CH=CH-or-CH
2-CH (OH)-.
The preparation method of above-mentioned Avrmectin ester compound, comprises the steps:
(1) in the reactor, with organic solvent, Avrmectin is dissolved, obtain abamectin solution;
(2) step (1) gained solution is cooled to-25 DEG C ~-15 DEG C, add protective material, stir and drip protective material and acid binding agent at least 20 minutes later, controlling temperature of reaction is-25 ~-15 DEG C, dropwises rear continuation stirring reaction more than 15 minutes; Then, acid adding stops;
(3) step (2) gained material is cooled to-25 DEG C and adds acid binding agent, catalyzer, drip esterification part after fully stirring, controlling temperature of reaction is-25 DEG C ~-15 DEG C, continues stirring reaction more than 30 minutes; Then, add alkali and stop, stratification after being stirred well to few 30 minutes, then acid adding adjusts PH=7, stratification; Then by after freezing for gained organic phase 1 ~ 2 hour, then secondary clearing; Drying being separated the organic phase vacuum desolvation obtained after layering, obtaining C
5position is containing protecting group product;
(4) by step (3) products therefrom organic solvent dissolution, add methyl alcohol and catalyzer after being cooled to-5 DEG C, more at the uniform velocity add sodium borohydride, maintaining temperature of reaction is-5 DEG C ~ 5 DEG C, reacts more than 2 hours, then, in reaction solution, acid adding stops, and leaves standstill half an hour more than; Add adjusting PH with base=7 ~ 7.5, by freezing for separating obtained organic phase 1 ~ 2 hour after stratification, the drier organic phase of vacuum desolvation, obtain Avrmectin ester compound.
Prepare in the method for Avrmectin ester compound in the present invention, described organic solvent is preferably methylene dichloride; Described protective material is preferably allyl chlorocarbonate; Described acid binding agent is preferably Tetramethyl Ethylene Diamine; Described catalyzer is preferably Tetrabutyl amonium bromide or tetrakis triphenylphosphine palladium.
Prepare in the method for Avrmectin ester compound in the present invention, in described step (1), described organic solvent is methylene dichloride, and the mass ratio of Avrmectin and methylene dichloride is 1:6 to 1:5; In described step (2), described protective material is allyl chlorocarbonate, described acid binding agent is Tetramethyl Ethylene Diamine, and the mass ratio of Avrmectin and allyl chlorocarbonate is 7.4:1 to 8.2:1, and the mass ratio of Avrmectin and Tetramethyl Ethylene Diamine is 8:1 to 8.5:1; In described step (3), described acid binding agent is Tetramethyl Ethylene Diamine, and described catalyzer is Tetrabutyl amonium bromide; The mass ratio 4:1 to 8:1 of Avrmectin and Tetramethyl Ethylene Diamine, the mass ratio of Avrmectin and Tetrabutyl amonium bromide is 100:1 to 200:1, and the mass ratio of Avrmectin and esterification part is 6:1 to 11:1; In described step (4), described organic solvent is methylene dichloride, described catalyzer is tetrakis triphenylphosphine palladium, the mass ratio of Avrmectin and tetrakis triphenylphosphine palladium is 1000:1 to 1300:1, the mass ratio of Avrmectin and methyl alcohol is 2.1:1 to 1.6:1, and the mass ratio of Avrmectin and sodium borohydride is 19:1-26:1.
Prepare in the method for Avrmectin ester compound in the present invention, in described step (2), adding protectant mass ratio before and after in reaction is 7:3, and stopping institute's acid adding is phosphoric acid, and mass percent concentration is 2%; In described step (3), alkali added by termination reaction is sodium hydroxide solution, and mass percent concentration is 4%; Adjust PH=7 institute acid adding to be phosphoric acid, mass percent concentration is 2%; Described organic phase vacuum desolvation bake out temperature is 55 DEG C; In described step (4), termination reaction institute acid adding is acetic acid, and quality of acetic acid percentage concentration is 12%, and the mass ratio of Avrmectin and acetic acid is 1:1; Adjust pH=7 ~ 7.5 alkali used to be ammoniacal liquor, the mass percent concentration of ammoniacal liquor is 10%.
Prepare in the method for Avrmectin ester compound in the present invention, in described step (1), the mass ratio of Avrmectin and methylene dichloride is 1:5; In described step (2), temperature of reaction controls, at-20 DEG C, strictly to control temperature of reaction; In described step (4), control temperature of reaction and add sodium borohydride at 0 DEG C, speed can not be too fast, and preferably, adding the sodium borohydride time used is at least 10 minutes, adds.
Prepare in the present invention in the method for Avrmectin ester compound, in described step (4), after adjusting pH=7 ~ 7.5, add water or the saturated sodium chloride solution stratification again of 35 ~ 45 DEG C.
Prepare in the method for Avrmectin ester compound in the present invention, in described step (2), protective material and acid binding agent dropwise in rear continuation stirring reaction, and sampling detects, according to the timely feed supplement of reaction ratio.
Prepare in the method for Avrmectin ester compound in the present invention, in described step (3), gained C
5position is yellow or faint yellow containing protecting group product.
Prepare in the method for Avrmectin ester compound in the present invention, in described step (3), described esterification part is phenyllacetyl chloride, Acetyl Chloride 98Min..
Present invention also offers the purposes of Avrmectin ester compound, for in the agricultural chemicals such as sterilant, miticide or veterinary drug, preferably, described Avrmectin ester compound is as the activeconstituents of agricultural chemicals or auxiliary agent, preferably, as activeconstituents or the auxiliary agent of sterilant, compare with common Avrmectin product, insecticidal activity can be increased to more than 3 times.
Avrmectin ester compound prepared by the present invention is to C on Avrmectin basis
4-OH or C
4-OH and C
5-OH carries out the compound that chemical modification obtains simultaneously, compared with common Avrmectin product, has that drug effect is high, the lasting period is long, noresidue and nuisanceless feature, but also has instant effect and nonresistant advantage; Especially high to common insect pests activity such as the thin moth of inscription on ancient bronze objects, Liriomyza, various resistance aphids, existing stomach poison function has action of contace poison concurrently again, under low-down dosage, just there is very reliable and stable prevention effect, compare with common Avrmectin product, insecticidal activity significantly improves, and is suitable for applying in association area.
Accompanying drawing explanation
Fig. 1 is the HPLC quantitative analysis spectrogram of the embodiment of the present invention 1 gained Avrmectin ester compound product;
Fig. 2 is the nuclear-magnetism NMR spectrogram of the embodiment of the present invention 1 gained Avrmectin ester compound product.
Embodiment
In the present invention, the Avrmectin ester compound provided, has structural formula shown in following formula I:
In formula, R is phenylacetyl-OCCH
2ph or ethanoyl-OCCH
3; R
1for-CH
2cH
3or-CH
3; X-Y is-CH=CH-or-CH
2-CH (OH)-.
Because each C in Avrmectin molecule is active different, in the present invention, the method preparing Avrmectin ester compound performs following steps:
(1) in the reactor, with organic solvent, Avrmectin is dissolved, obtain abamectin solution;
(2) step (1) gained solution is cooled to-25 DEG C ~-15 DEG C, add protective material, stir and drip protective material and acid binding agent at least 20 minutes later, controlling temperature of reaction is-25 ~-15 DEG C, dropwises rear continuation stirring reaction more than 15 minutes; Then, acid adding stops;
(3) C
5protection: step (2) gained material is cooled to-25 DEG C and adds acid binding agent, catalyzer, drips esterification part after fully stirring, and controlling temperature of reaction is-25 DEG C ~-15 DEG C, continues stirring reaction more than 30 minutes; Then, add alkali and stop, stratification after being stirred well to few 30 minutes, then acid adding adjusts PH=7, stratification; Then by after freezing for gained organic phase 1 ~ 2 hour, then secondary clearing; Drying being separated the organic phase vacuum desolvation obtained after layering, obtaining C
5position is containing protecting group product;
(4) synthesizing ester compound make C
5deprotection: by step (3) products therefrom organic solvent dissolution, add methyl alcohol and catalyzer after being cooled to-5 DEG C, more at the uniform velocity add sodium borohydride, maintaining temperature of reaction is-5 DEG C ~ 5 DEG C, reacts more than 2 hours, then, in reaction solution, acid adding stops, and leaves standstill half an hour more than; Add adjusting PH with base=7 ~ 7.5, by freezing for separating obtained organic phase 1 ~ 2 hour after stratification, the drier organic phase of vacuum desolvation, obtain Avrmectin ester compound.
Prepare in the method for Avrmectin ester compound in the present invention, need the selection of solvent and dissolve each other between reagent involved by each step other side reactions do not occur, described organic solvent is preferably methylene dichloride; In the present invention, according to the protection needs of different positions C, described protective material is preferably allyl chlorocarbonate; Described acid binding agent is preferably Tetramethyl Ethylene Diamine; Described catalyzer is preferably Tetrabutyl amonium bromide or tetrakis triphenylphosphine palladium, preferably, for C
5reaction in guarded by location reaction and described step (3) is preferably Tetrabutyl amonium bromide, is preferably tetrakis triphenylphosphine palladium for the deprotection reaction in described step (4).
Prepare in the method for Avrmectin ester compound in the present invention, for enabling preparation each stage fully realize effect, in described step (1), described organic solvent is methylene dichloride, and the mass ratio of Avrmectin and methylene dichloride is 1:6 to 1:5; In described step (2), described protective material is allyl chlorocarbonate, described acid binding agent is Tetramethyl Ethylene Diamine, and the mass ratio of Avrmectin and allyl chlorocarbonate is 7.4:1 to 8.2:1, and the mass ratio of Avrmectin and Tetramethyl Ethylene Diamine is 8:1 to 8.5:1; In described step (3), described acid binding agent is Tetramethyl Ethylene Diamine, and described catalyzer is Tetrabutyl amonium bromide; The mass ratio 4:1 to 8:1 of Avrmectin and Tetramethyl Ethylene Diamine, the mass ratio of Avrmectin and Tetrabutyl amonium bromide is 100:1 to 200:1, and the mass ratio of Avrmectin and esterification part is 6:1 to 11:1; In described step (4), described organic solvent is methylene dichloride, described catalyzer is tetrakis triphenylphosphine palladium, the mass ratio of Avrmectin and tetrakis triphenylphosphine palladium is 1000:1 to 1300:1, the mass ratio of Avrmectin and methyl alcohol is 2.1:1 to 1.6:1, and the mass ratio of Avrmectin and sodium borohydride is 19:1-26:1.
Prepare in the method for Avrmectin ester compound in the present invention, for making each highly effective reaction step by step obtain target product, in described step (2), adding protectant mass ratio before and after in reaction is 7:3, stopping institute's acid adding is phosphoric acid, and mass percent concentration is 2%; In described step (3), alkali added by termination reaction is sodium hydroxide solution, and mass percent concentration is 4%; Adjust PH=7 institute acid adding to be phosphoric acid, mass percent concentration is 2%; Described organic phase vacuum desolvation bake out temperature is 55 DEG C; In described step (4), termination reaction institute acid adding is acetic acid, and quality of acetic acid percentage concentration is 12%, and the mass ratio of Avrmectin and acetic acid is 1:1; Adjust pH=7 ~ 7.5 alkali used to be ammoniacal liquor, the mass percent concentration of ammoniacal liquor is 10%.
Prepare in the method for Avrmectin ester compound in the present invention, for effectively controlling product and the speed of response of reaction, in described step (1), the mass ratio of Avrmectin and methylene dichloride is 1:5; In described step (2), temperature of reaction controls, at-20 DEG C, strictly to control temperature of reaction; In described step (4), control temperature of reaction and strengthen borane reducing agent sodium hydride at 0 DEG C, speed can not be too fast, and preferably, adding the sodium borohydride time used is at least 10 minutes.
Prepare in the method for Avrmectin ester compound in the present invention, for preventing that product needed for serious emulsification phenomena impair Multi-layer technology occurs in extraction process, in described step (4), after adjusting pH=7 ~ 7.5, add the warm water of 35 ~ 45 DEG C or add sodium chloride solution saturated on a small quantity stratification again, to make each phase layered high-efficient in solution and clear.
Prepare in the method for Avrmectin ester compound in the present invention, in described step (2), protective material and acid binding agent dropwise in rear continuation stirring reaction, and sampling detects, according to the timely feed supplement of reaction ratio.
Prepare in the method for Avrmectin ester compound in the present invention, in described step (3), gained C
5position is yellow or faint yellow containing protecting group product, then illustrate that reaction is qualified, can proceed subsequent step.
Prepare in the method for Avrmectin ester compound in the present invention, be efficiently obtained target product, in described step (3), described esterification part is preferably phenyllacetyl chloride, Acetyl Chloride 98Min..
Avrmectin ester compound prepared by the present invention adopts high performance liquid chromatograph (HPLC) and nuclear magnetic resonance spectroscopy (NMR) to carry out characterization.
In addition, present invention also offers the purposes of Avrmectin ester compound, in the agricultural chemicals such as sterilant, miticide or veterinary drug, preferably, described Avrmectin ester compound as the activeconstituents of agricultural chemicals or auxiliary agent, preferably, as activeconstituents or the auxiliary agent of sterilant.
Below in conjunction with specific embodiment, the present invention is further illustrated, but protection scope of the present invention is not limited to this.
The experimental technique used in following embodiment if no special instructions, is ordinary method.
Material used in following embodiment, reagent etc., if no special instructions, all can obtain from commercial channels.
Embodiment 1
Synthesize the Avrmectin ester compound as above shown in formula I, wherein, R is-OCCH
2ph, R
1for-CH
2cH
3, X-Y is-CH=CH-, i.e. HO-C
5-AVM-C
4-toluylic acid ester group Avrmectin B
1a(A is singly-bound, and 4,5 is the sequence number of carbon in compound structure), shown in the following formula II of structure:
The building-up reactions formula of formula II is as follows:
The preparation method of formula II is as follows:
(1) the Avermectin B1a fine powder of 40g 91.2% is dissolved in 200g organic solvent dichloromethane, until dissolve completely.
(2) step (1) gained abamectin solution is cooled to-15 DEG C, first add 3.5g allyl chlorocarbonate, stir after 20 minutes, drip 1.5g allyl chlorocarbonate and 4.8g tetramethyl-Edamine simultaneously, control temperature of reaction and be-15 DEG C, after dropwising, continue stirring reaction 15 minutes; Then stop with the phosphoric acid solution that mass percent concentration is 2%;
(3) step (2) is reacted last gained solution to continue to be cooled to-25 DEG C, add 8.7g Tetramethyl Ethylene Diamine and 0.35g Tetrabutyl amonium bromide, 6.5g phenyllacetyl chloride is dripped after abundant stirring, control temperature of reaction and be-25 DEG C, continue stirring reaction 30 minutes, then stop with sodium hydroxide solution, after layering, use phosphoric acid solution extracted organic phase, then will be separated the organic phase that obtains after layering in 55 DEG C of vacuum pull-up exsolution dryings; Wherein, the mass percent concentration of phosphoric acid solution is 2%, and the mass percent concentration of sodium hydroxide solution is 4%;
(4) the material methylene dichloride of step (3) being dried gained dissolves, be cooled to-5 DEG C, then in solution, 18.9g methyl alcohol is added, 0.034g tetrakis triphenylphosphine palladium, in 10 minutes slowly at the uniform velocity add 1.58g sodium borohydride, maintaining temperature of reaction is-5 DEG C ~ 5 DEG C, react 2 hours, question response is complete, the acetic acid solution termination reaction of 200g 12% is added in solution, pH of mixed=7 are regulated with the ammoniacal liquor that mass percent concentration is 10% after leaving standstill half an hour, by freezing for separating obtained organic phase 2 hours after stratification, the dry organic phase of vacuum desolvation again, obtain yellow product 37.85g, structure is as shown in formula II.
Adopt high performance liquid chromatograph (HPLC) and nuclear magnetic resonance spectroscopy (NMR) to carry out characterization to gained Avrmectin ester compound product, HPLC quantitative analysis, as shown in Fig. 1 and table 1, is 97.2% through liquid-phase chromatographic analysis content; As shown in Figure 2, by above-mentioned characterization, the present embodiment obtains the product as shown in formula II to nmr spectrum, and productive rate is 88.48%.
Embodiment 2
Synthesize the Avrmectin ester compound as above shown in formula I, wherein, R is-OCCH
3, R
1for-CH
2cH
3, X-Y is-CH=CH-, i.e. HO-C
5-AVM-C
4-acetate groups Avrmectin B
1a(A is singly-bound, and 4,5 is the sequence number of carbon in compound structure), shown in the following formula III of structure:
The building-up reactions formula of formula III is as follows:
The preparation method of formula III is as follows:
(1) the Avermectin B1a fine powder of 40g 94% is dissolved in 200g organic solvent dichloromethane, until dissolve completely.
(2) step (1) gained abamectin solution is cooled to-19 DEG C, first add 3.6g allyl chlorocarbonate, stir after 20 minutes, drip 1.6g allyl chlorocarbonate and 5g tetramethyl-Edamine simultaneously, control temperature of reaction and be-19 DEG C, after dropwising, continue stirring reaction 15 minutes; Then stop with the phosphoric acid solution that mass percent concentration is 2%;
(3) step (2) is reacted last gained solution to continue to be cooled to-25 DEG C, add 6.9g Tetramethyl Ethylene Diamine and 0.22g Tetrabutyl amonium bromide, 3.4g Acetyl Chloride 98Min. is dripped after abundant stirring, control temperature of reaction and be-20 DEG C, continue stirring reaction 30 minutes, then stop with sodium hydroxide solution, use phosphoric acid solution extracted organic phase after layering, the organic phase then separation obtained is in 55 DEG C of vacuum pull-up exsolution dryings; Wherein, the mass percent concentration of phosphoric acid solution is 2%, and the mass percent concentration of sodium hydroxide solution is 4%;
(4) the material methylene dichloride of step (3) being dried gained dissolves, be cooled to-5 DEG C, then in solution, 19.5g methyl alcohol is added, 0.034g tetrakis triphenylphosphine palladium, in 13 minutes slowly at the uniform velocity add 1.63g sodium borohydride, maintaining temperature of reaction is-5 DEG C ~ 5 DEG C, react 2 hours, question response is complete, the acetic acid solution termination reaction that 200g mass percent concentration is 12% is added in solution, pH of mixed=7 are regulated with the ammoniacal liquor that mass percent concentration is 10% after leaving standstill half an hour, by freezing for separating obtained organic phase 1 hour after stratification, the dry organic phase of vacuum desolvation again, obtain flaxen product 38.21g, structure is as shown in formula III.
High performance liquid chromatograph (HPLC) and nuclear magnetic resonance spectroscopy (NMR) is adopted to carry out characterization to gained Avrmectin ester compound product, wherein, HPLC quantitative analysis is as shown in table 1, is 98.15% through HPLC liquid-phase chromatographic analysis content; By above-mentioned characterization, the present embodiment obtains the product as shown in formula III, and productive rate is 92.62%.
Embodiment 3
Synthesize the Avrmectin ester compound as above shown in formula I, wherein, R is-OCCH
2ph, R
1for-CH
2cH
3, X-Y is-CH
2-CH (OH)-, i.e. HO-C
5-AVM-C
4-toluylic acid ester group Avrmectin B
2a(A is singly-bound, and 4,5 is the sequence number of carbon in compound structure), shown in the following formula IV of structure:
The building-up reactions formula of formula IV is as follows:
The preparation method of formula IV is as follows:
(1) by the Avrmectin B of 40g 92.8%
2afine powder is dissolved in 200g organic solvent dichloromethane, until dissolve completely.
(2) step (1) gained abamectin solution is cooled to-22 DEG C, first add 3.8g allyl chlorocarbonate, stir after 20 minutes, drip 1.6g allyl chlorocarbonate and 5g tetramethyl-Edamine simultaneously, control temperature of reaction and be-22 DEG C, after dropwising, continue stirring reaction 15 minutes; Then stop with the phosphoric acid solution that mass percent concentration is 2%;
(3) step (2) is reacted last gained solution to continue to be cooled to-25 DEG C, add 8.5g Tetramethyl Ethylene Diamine and 0.34g Tetrabutyl amonium bromide, 6.4g phenyllacetyl chloride is dripped after abundant stirring, control temperature of reaction and be-23 DEG C, continue stirring reaction 30 minutes, then stop with sodium hydroxide solution, use phosphoric acid solution extracted organic phase after layering, the organic phase then separation obtained is in 55 DEG C of vacuum pull-up exsolution dryings; Wherein, the mass percent concentration of phosphoric acid solution is 2%, and the mass percent concentration of sodium hydroxide solution is 4%;
(4) the material methylene dichloride of step (3) being dried gained dissolves, be cooled to-5 DEG C, then in solution, 18.6g methyl alcohol is added, 0.034g tetrakis triphenylphosphine palladium, in 11 minutes slowly at the uniform velocity add 1.6g sodium borohydride, maintaining temperature of reaction is-5 DEG C ~ 5 DEG C, react 2 hours, question response is complete, the acetic acid solution termination reaction that 200g mass percent concentration is 12% is added in solution, pH of mixed=7 are regulated with the ammoniacal liquor that mass percent concentration is 10% after leaving standstill half an hour, by freezing for separating obtained organic phase 1.5 hours after stratification, the dry organic phase of vacuum desolvation again, obtain yellow product 37.12g, structure is as shown in formula IV.
High performance liquid chromatograph (HPLC) and nuclear magnetic resonance spectroscopy (NMR) is adopted to carry out characterization to gained Avrmectin ester compound product, wherein, HPLC quantitative analysis is as shown in table 1, is 93.70% through HPLC liquid-phase chromatographic analysis content; By above-mentioned characterization, the present embodiment obtains the product as shown in formula IV, and productive rate is 82.42%.
Embodiment 4
Synthesize the Avrmectin ester compound as above shown in formula I, wherein, R is-OCCH
3, R
1for-CH
2cH
3, X-Y is-CH
2-CH (OH)-, i.e. HO-C
5-AVM-C
4-acetate groups Avrmectin B
2a(A is singly-bound, and 4,5 is the sequence number of carbon in compound structure), structure is as shown in the formula shown in (V):
The building-up reactions formula of formula (V) is as follows:
The preparation method of formula (V) is as follows:
(1) by the Avrmectin B of 40g 94.5%
2afine powder is dissolved in 200g organic solvent dichloromethane, until dissolve completely.
(2) step (1) gained abamectin solution is cooled to-17 DEG C, first add 3.6g allyl chlorocarbonate, stir after 20 minutes, drip 1.5g allyl chlorocarbonate and 6.7g tetramethyl-Edamine simultaneously, control temperature of reaction and be-17 DEG C, after dropwising, continue stirring reaction 15 minutes; Then stop with the phosphoric acid solution that mass percent concentration is 2%;
(3) step (2) is reacted last gained solution to continue to be cooled to-25 DEG C, add 5.5g Tetramethyl Ethylene Diamine and 0.21g Tetrabutyl amonium bromide, 3.8g Acetyl Chloride 98Min. is dripped after abundant stirring, control temperature of reaction and be-18 DEG C, continue stirring reaction 30 minutes, then stop with sodium hydroxide solution, use phosphoric acid solution extracted organic phase after layering, the organic phase then separation obtained is in 55 DEG C of vacuum pull-up exsolution dryings; Wherein, the mass percent concentration of phosphoric acid solution is 2%, and the mass percent concentration of sodium hydroxide solution is 4%;
(4) the material methylene dichloride of step (3) being dried gained dissolves, be cooled to-5 DEG C, then in solution, 24.8g methyl alcohol is added, 0.034g tetrakis triphenylphosphine palladium, in 15 minutes slowly at the uniform velocity add 2.1g sodium borohydride, maintaining temperature of reaction is-5 DEG C ~ 5 DEG C, react 2 hours, question response is complete, the acetic acid solution termination reaction that 200g mass percent concentration is 12% is added in solution, pH of mixed=7 are regulated with the ammoniacal liquor that mass percent concentration is 10% after leaving standstill half an hour, by freezing for separating obtained organic phase 2 hours after stratification, the dry organic phase of vacuum desolvation again, obtain flaxen product 36.98g, structure is such as formula shown in (V).
High performance liquid chromatograph (HPLC) and nuclear magnetic resonance spectroscopy (NMR) is adopted to carry out characterization to gained Avrmectin ester compound product, wherein, HPLC quantitative analysis is as shown in table 1, is 93.96% through HPLC liquid-phase chromatographic analysis content; By above-mentioned characterization, the present embodiment is obtained such as formula the product shown in (V), and productive rate is 87.77%.
Embodiment 5
Synthesize the Avrmectin ester compound as above shown in formula I, wherein, R is-OCCH
2ph, R
1for-CH
3, X-Y is-CH=CH-, shown in the following formula VI of structure:
The preparation method of formula VI is as follows:
(1) the Avermectin B1a fine powder of 40g 91.2% is dissolved in 200g organic solvent dichloromethane, until dissolve completely.
(2) step (1) gained abamectin solution is cooled to-15 DEG C, first add 3.1g allyl chlorocarbonate, stir after 20 minutes, drip 1.4g allyl chlorocarbonate and 4.2g tetramethyl-Edamine simultaneously, control temperature of reaction and be-15 DEG C, after dropwising, continue stirring reaction 15 minutes; Then stop with the phosphoric acid solution that mass percent concentration is 2%;
(3) step (2) is reacted last gained solution to continue to be cooled to-25 DEG C, add 8.1g Tetramethyl Ethylene Diamine and 0.31g Tetrabutyl amonium bromide, 6.0g phenyllacetyl chloride is dripped after abundant stirring, control temperature of reaction and be-25 DEG C, continue stirring reaction 30 minutes, then stop with sodium hydroxide solution, use phosphoric acid solution extracted organic phase after layering, the organic phase then separation obtained is in 55 DEG C of vacuum pull-up exsolution dryings; Wherein, the mass percent concentration of phosphoric acid solution is 2%, and the mass percent concentration of sodium hydroxide solution is 4%;
(4) the material methylene dichloride of step (3) being dried gained dissolves, be cooled to-5 DEG C, then in solution, 19.7g methyl alcohol is added, 0.029g tetrakis triphenylphosphine palladium, in 10 minutes slowly at the uniform velocity add 1.61g sodium borohydride, maintaining temperature of reaction is-5 DEG C ~ 5 DEG C, react 2 hours, question response is complete, the acetic acid solution termination reaction of 180g 12% is added in solution, pH of mixed=7 are regulated with the ammoniacal liquor that mass percent concentration is 10% after leaving standstill half an hour, by freezing for separating obtained organic phase 2 hours after stratification, the dry organic phase of vacuum desolvation again, obtain yellow product 35.95g, structure is as shown in formula II.
High performance liquid chromatograph (HPLC) and nuclear magnetic resonance spectroscopy (NMR) is adopted to carry out characterization to gained Avrmectin ester compound product, wherein, HPLC quantitative analysis is as shown in table 1, is 90.02% through HPLC liquid-phase chromatographic analysis content; By above-mentioned characterization, the present embodiment obtains the product as shown in formula III, and productive rate is 77.68%.
Embodiment 6
Synthesize the Avrmectin ester compound as above shown in formula I, wherein, R is-OCCH
3, R
1for-CH
3, X-Y is-CH=CH-, and structure is as shown in the formula shown in (VII):
The preparation method of formula (VII) is as follows:
(1) the Avermectin B1a fine powder of 40g 94% is dissolved in 210g organic solvent dichloromethane, until dissolve completely.
(2) step (1) gained abamectin solution is cooled to-19 DEG C, first add 3.6g allyl chlorocarbonate, stir after 20 minutes, drip 1.4g allyl chlorocarbonate and 4g tetramethyl-Edamine simultaneously, control temperature of reaction and be-19 DEG C, after dropwising, continue stirring reaction 15 minutes; Then stop with the phosphoric acid solution that mass percent concentration is 2%;
(3) step (2) is reacted last gained solution to continue to be cooled to-25 DEG C, add 5.9g Tetramethyl Ethylene Diamine and 0.22g Tetrabutyl amonium bromide, 2.9g Acetyl Chloride 98Min. is dripped after abundant stirring, control temperature of reaction and be-20 DEG C, continue stirring reaction 30 minutes, then stop with sodium hydroxide solution, use phosphoric acid solution extracted organic phase after layering, the organic phase then separation obtained is in 55 DEG C of vacuum pull-up exsolution dryings; Wherein, the mass percent concentration of phosphoric acid solution is 2%, and the mass percent concentration of sodium hydroxide solution is 4%;
(4) the material methylene dichloride of step (3) being dried gained dissolves, be cooled to-5 DEG C, then in solution, 16.5g methyl alcohol is added, 0.026g tetrakis triphenylphosphine palladium, in 13 minutes slowly at the uniform velocity add 1.49g sodium borohydride, maintaining temperature of reaction is-5 DEG C ~ 5 DEG C, react 2 hours, question response is complete, the acetic acid solution termination reaction that 194g mass percent concentration is 12% is added in solution, pH of mixed=7.1 are regulated with the ammoniacal liquor that mass percent concentration is 10% after leaving standstill half an hour, by freezing for separating obtained organic phase 1 hour after stratification, the dry organic phase of vacuum desolvation again, obtain flaxen product 35.35g, structure is as shown in formula III.
High performance liquid chromatograph (HPLC) and nuclear magnetic resonance spectroscopy (NMR) is adopted to carry out characterization to gained Avrmectin ester compound product, wherein, HPLC quantitative analysis is as shown in table 1, is 89.70% through HPLC liquid-phase chromatographic analysis content; By above-mentioned characterization, the present embodiment obtains the product as shown in formula III, and productive rate is 80.58%.
Embodiment 7
Synthesize the Avrmectin ester compound as above shown in formula I, wherein, R is-OCCH
2ph, R
1for-CH
3, X-Y is-CH
2-CH (OH)-, structure is as shown in the formula shown in (VIII):
The preparation method of formula (VIII) is as follows:
(1) the Avermectin B1a fine powder of 40g 92.8% is dissolved in 240g organic solvent dichloromethane, until dissolve completely.
(2) step (1) gained abamectin solution is cooled to-22 DEG C, first add 3.4g allyl chlorocarbonate, stir after 20 minutes, drip 1.4g allyl chlorocarbonate and 4.7g tetramethyl-Edamine simultaneously, control temperature of reaction and be-22 DEG C, after dropwising, continue stirring reaction 15 minutes; Then stop with the phosphoric acid solution that mass percent concentration is 2%;
(3) step (2) is reacted last gained solution to continue to be cooled to-25 DEG C, add 10g Tetramethyl Ethylene Diamine and 0.21g Tetrabutyl amonium bromide, 5.96g phenyllacetyl chloride is dripped after abundant stirring, control temperature of reaction and be-23 DEG C, continue stirring reaction 30 minutes, then stop with sodium hydroxide solution, use phosphoric acid solution extracted organic phase after layering, the organic phase then separation obtained is in 55 DEG C of vacuum pull-up exsolution dryings; Wherein, the mass percent concentration of phosphoric acid solution is 2%, and the mass percent concentration of sodium hydroxide solution is 4%;
(4) the material methylene dichloride of step (3) being dried gained dissolves, be cooled to-5 DEG C, then in solution, 25g methyl alcohol is added, 0.031g tetrakis triphenylphosphine palladium, in 10 minutes slowly at the uniform velocity add 1.54g sodium borohydride, maintaining temperature of reaction is-5 DEG C ~ 5 DEG C, react 2 hours, question response is complete, the acetic acid solution termination reaction that 196g mass percent concentration is 12% is added in solution, pH of mixed=7 are regulated with the ammoniacal liquor that mass percent concentration is 10% after leaving standstill half an hour, by freezing for separating obtained organic phase 1.5 hours after stratification, the dry organic phase of vacuum desolvation again, obtain yellow product 36.65g, structure is as shown in formula IV.
High performance liquid chromatograph (HPLC) and nuclear magnetic resonance spectroscopy (NMR) is adopted to carry out characterization to gained Avrmectin ester compound product, wherein, HPLC quantitative analysis is as shown in table 1, is 93.24% through HPLC liquid-phase chromatographic analysis content; By above-mentioned characterization, the present embodiment obtains the product as shown in formula III, and productive rate is 80.97%.
Embodiment 8
Synthesize the Avrmectin ester compound as above shown in formula I, wherein, R is-OCCH
3, R
1for-CH
3, X-Y is-CH
2-CH (OH)-, structure is as shown in the formula shown in (Ⅸ):
The preparation method of formula (Ⅸ) is as follows:
(1) the Avermectin B1a fine powder of 40g 94.5% is dissolved in 220g organic solvent dichloromethane, until dissolve completely.
(2) step (1) gained abamectin solution is cooled to-17 DEG C, first add 3.8g allyl chlorocarbonate, stir after 20 minutes, drip 1.6g allyl chlorocarbonate and 5g tetramethyl-Edamine simultaneously, control temperature of reaction and be-17 DEG C, after dropwising, continue stirring reaction 15 minutes; Then stop with the phosphoric acid solution that mass percent concentration is 2%;
(3) step (2) is reacted last gained solution to continue to be cooled to-25 DEG C, add 10g Tetramethyl Ethylene Diamine and 0.4g Tetrabutyl amonium bromide, 3.7g Acetyl Chloride 98Min. is dripped after abundant stirring, control temperature of reaction and be-18 DEG C, continue stirring reaction 30 minutes, then stop with sodium hydroxide solution, use phosphoric acid solution extracted organic phase after layering, the organic phase then separation obtained is in 55 DEG C of vacuum pull-up exsolution dryings; Wherein, the mass percent concentration of phosphoric acid solution is 2%, and the mass percent concentration of sodium hydroxide solution is 4%;
(4) the material methylene dichloride of step (3) being dried gained dissolves, be cooled to-5 DEG C, then in solution, 20.5g methyl alcohol is added, 0.04g tetrakis triphenylphosphine palladium, in 20 minutes slowly at the uniform velocity add 2.5g sodium borohydride, maintaining temperature of reaction is-5 DEG C ~ 5 DEG C, react 2 hours, question response is complete, the acetic acid solution termination reaction that 200g mass percent concentration is 12% is added in solution, pH of mixed=7 to 7.5 are regulated with the ammoniacal liquor that mass percent concentration is 10% after leaving standstill half an hour, by freezing for separating obtained organic phase 2 hours after stratification, the dry organic phase of vacuum desolvation again, obtain flaxen product 36.22g, structure is such as formula shown in (V).
High performance liquid chromatograph (HPLC) and nuclear magnetic resonance spectroscopy (NMR) is adopted to carry out characterization to gained Avrmectin ester compound product, wherein, HPLC quantitative analysis is as shown in table 1, is 91.78% through HPLC liquid-phase chromatographic analysis content; By above-mentioned characterization, the present embodiment obtains the product as shown in formula III, and productive rate is 83.92%.
Table 1
Application Example
Avrmectin ester compound prepared by the present invention as sterilant compared with common Avrmectin product, insecticidal activity can be increased to more than 3 times, obviously have that drug effect is high, the lasting period be long, noresidue and nuisanceless feature, but also there is instant effect and nonresistant advantage; Especially high to common insect pests activity such as the thin moth of inscription on ancient bronze objects, Liriomyza, various resistance aphids, existing stomach poison function has action of contace poison concurrently again, under low-down dosage, just there is very reliable and stable prevention effect, be described below in conjunction with embody rule example, but the present invention is not limited thereto.
Application examples 1
Avrmectin ester compound sampling obtained for the various embodiments described above is used as sterilant test respectively, with the thin moth 50 of the inscription on ancient bronze objects of equivalent only for experimental subjects, and contrast with existing abamectin insecticide, wherein, after all samples all prepares 1% missible oil, dilute 2000 times of uses.Insect death assay the results are shown in Table 2.
Table 2
Application examples 2
Avrmectin ester compound sampling obtained for the various embodiments described above is used as sterilant test respectively, with the aphid 50 of equivalent only for experimental subjects, and contrast with the existing abamectin insecticide emamectin benzoate for aphid and emamectin-benzoate, wherein, after all samples all prepares 1% missible oil, dilute 2000 times of uses.Insect death assay the results are shown in following table 3.
Table 3
Application examples 3
Avrmectin ester compound sampling obtained for the various embodiments described above is used as sterilant test respectively, with the Liriomyza 50 of equivalent only for experimental subjects, and contrast with existing abamectin insecticide, wherein, after all samples all prepares 1% missible oil, dilute 2000 times of uses.Insect death assay the results are shown in Table 4.
Table 4
The invention is not restricted to above-mentioned embodiment, those skilled in the art make to any apparent improvement of above-mentioned embodiment or change, all can not exceed the protection domain of design of the present invention and claims.
Claims (10)
1. an Avrmectin ester compound, has structural formula shown in following formula I:
In formula,
R is-OCCH
2ph or-OCCH
3;
R
1for-CH
2cH
3or-CH
3;
X-Y is-CH=CH-or-CH
2-CH (OH)-.
2. prepare a method for Avrmectin ester compound as claimed in claim 1, it is characterized in that, comprise the steps:
(1) in the reactor, with organic solvent, Avrmectin is dissolved, obtain abamectin solution;
(2) step (1) gained solution is cooled to-25 DEG C ~-15 DEG C, add protective material, stir and drip protective material and acid binding agent at least 20 minutes later, controlling temperature of reaction is-25 ~-15 DEG C, dropwises rear continuation stirring reaction more than 15 minutes;
(3) step (2) gained material is cooled to-25 DEG C and adds acid binding agent, catalyzer, drip esterification part after fully stirring, controlling temperature of reaction is-25 DEG C ~-15 DEG C, continues stirring reaction more than 30 minutes; Then, add alkali and stop, stratification after being stirred well to few 30 minutes, then acid adding adjusts PH=7, stratification; Then by after freezing for gained organic phase 1 ~ 2 hour, then secondary clearing; Organic phase vacuum desolvation layering obtained is dried, and obtains C
5position is containing protecting group product;
(4) by step (3) products therefrom organic solvent dissolution, add methyl alcohol and catalyzer after being cooled to-5 DEG C, more at the uniform velocity add sodium borohydride, maintaining temperature of reaction is-5 DEG C ~ 5 DEG C, reacts more than 2 hours, then, in reaction solution, acid adding stops, and leaves standstill half an hour more than; Add adjusting PH with base=7 ~ 7.5, by freezing for organic phase 1 ~ 2 hour after stratification, the drier organic phase of vacuum desolvation, obtain Avrmectin ester compound.
3. the method preparing Avrmectin ester compound according to claim 2, is characterized in that, described organic solvent is methylene dichloride; Described protective material is allyl chlorocarbonate; Described acid binding agent is Tetramethyl Ethylene Diamine; Described catalyzer is Tetrabutyl amonium bromide or tetrakis triphenylphosphine palladium.
4. the method preparing Avrmectin ester compound according to claim 2, is characterized in that, in described step (1), described organic solvent is methylene dichloride, and the mass ratio of Avrmectin and methylene dichloride is 1:6 to 1:5;
In described step (2), described protective material is allyl chlorocarbonate, described acid binding agent is Tetramethyl Ethylene Diamine, and the mass ratio of Avrmectin and allyl chlorocarbonate is 7.4:1 to 8.2:1, and the mass ratio of Avrmectin and Tetramethyl Ethylene Diamine is 8:1 to 8.5:1;
In described step (3), described acid binding agent is Tetramethyl Ethylene Diamine, and described catalyzer is Tetrabutyl amonium bromide; The mass ratio 4:1 to 8:1 of Avrmectin and Tetramethyl Ethylene Diamine, the mass ratio of Avrmectin and Tetrabutyl amonium bromide is 100:1 to 200:1, and the mass ratio of Avrmectin and esterification part is 6:1 to 11:1;
In described step (4), described organic solvent is methylene dichloride; Described catalyzer is tetrakis triphenylphosphine palladium, and the mass ratio of Avrmectin and tetrakis triphenylphosphine palladium is 1000:1 to 1300:1; The mass ratio of Avrmectin and methyl alcohol is 2.1:1 to 1.6:1, and the mass ratio of Avrmectin and sodium borohydride is 19:1-26:1.
5. the method preparing Avrmectin ester compound according to claim 2, is characterized in that, in described step (2), adding protectant mass ratio before and after in reaction is 7:3;
In described step (3), alkali added by termination reaction is sodium hydroxide solution, and mass percent concentration is 4%; Adjust PH=7 institute acid adding to be phosphoric acid, mass percent concentration is 2%; Described organic phase vacuum desolvation bake out temperature is 55 DEG C;
In described step (4), termination reaction institute acid adding is acetic acid, and quality of acetic acid percentage concentration is 12%, and the mass ratio of Avrmectin and acetic acid is 1:1; Adjust pH=7 ~ 7.5 alkali used to be ammoniacal liquor, the mass percent concentration of ammoniacal liquor is 10%.
6. the method preparing Avrmectin ester compound according to claim 2, is characterized in that, in described step (1), the mass ratio of Avrmectin and methylene dichloride is 1:5; In described step (2), temperature of reaction controls at-20 DEG C; In described step (4), control temperature of reaction and add sodium borohydride at 0 DEG C.
7. the method preparing Avrmectin ester compound according to claim 2, is characterized in that, in described step (4), after adjusting pH=7 ~ 7.5, adds water or the saturated nacl aqueous solution stratification again of 35 ~ 45 DEG C.
8. the method preparing Avrmectin ester compound according to claim 2, is characterized in that, in described step (3), gained C5 position is yellow or faint yellow containing protecting group product.
9. the method preparing Avrmectin ester compound according to claim 2, is characterized in that, in described step (3), described esterification part is phenyllacetyl chloride, Acetyl Chloride 98Min..
10. a purposes for Avrmectin ester compound as claimed in claim 1, is characterized in that: described Avrmectin ester compound is as the activeconstituents of agricultural chemicals or auxiliary agent.
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