CN109134563A - A kind of catalysis synthesizing technology of emamectin benzoate key intermediate - Google Patents
A kind of catalysis synthesizing technology of emamectin benzoate key intermediate Download PDFInfo
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- CN109134563A CN109134563A CN201810897060.6A CN201810897060A CN109134563A CN 109134563 A CN109134563 A CN 109134563A CN 201810897060 A CN201810897060 A CN 201810897060A CN 109134563 A CN109134563 A CN 109134563A
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- emamectin benzoate
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- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
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Abstract
The present invention relates to pesticide intermediate synthesis technical fields, a kind of catalysis synthesizing technology of emamectin benzoate key intermediate is specifically disclosed, the catalyst of the specific esterification of the process choice, that is triethylene diamine or tetramethyl ethylene diamin(e), a kind of method that can carry out the reaction of 5 hydroxy esterifications in a mild condition has been determined, this method has high selectivity to 5 hydroxyls, reaction effect is good, high income, processing is needed not move through after esterification can carry out the oxidation reaction of 4 " position hydroxyls in next step, acid binding agent can be recycled after reaction, it reduces environmental pollution, reduce production cost.
Description
Technical field
The present invention relates to pesticide intermediate synthesis technical fields, and in particular to a kind of emamectin benzoate key intermediate
Catalysis synthesizing technology.
Background technique
Emamectin-benzoate is as mature insecticide, and annual output is big, using extensive.Patent
US5362863 and US005288710 reports the synthetic method of methylamino avermectin, be using avermectin as raw material,
Esterification is carried out in 5 and 4 " position hydroxyls respectively and intermediate is made in oxidation reaction, then first ammonia is further prepared by intermediate
Base abamectin benzoate.And avermectin 5 have greater activity with 4 " position hydroxyls, therefore need to improve the selection of reaction
Property.Conventional production methods use under the conditions of low temperature (- 30~-20 DEG C), using tetramethylethylenediamine as acid binding agent, it is selective with
5 hydroxyls carry out esterification, and 4 " position hydroxyls are then oxidized to carbonyl again, this adds water to terminate reaction after reaction, tie up acid
Agent tetramethylethylenediamine water solubility is fabulous, drains with water, causes ammonia-nitrogen content in waste water high, and excessively high COD and ammonia nitrogen are useless
Water treatment system brings very big pressure.Therefore traditional sternness is faced with as the production technology of acid binding agent using tetramethylethylenediamine to choose
War.
In the prior art there are also using triethylamine, tri-n-butylamine etc. for acid binding agent, the inventors discovered that in triethylamine, tri-n-butylamine
When Deng for acid binding agent, no matter adjust reaction temperature or feed ratio, which can not carry out completely, and 5 with 4 " position hydroxyls
Selectivity is poor.
Summary of the invention
The problems such as high pollution in the prior art, low yield and poor selectivity, the present invention provides a kind of methylamino AVM hereinafter
The catalysis synthesizing technology of rhzomorph key intermediate, the technique selectively can carry out ester on 5 hydroxyls under mild conditions
Change reaction, high income is selective good.
To achieve the above object of the invention, present invention employs the following technical solutions:
A kind of catalysis synthesizing technology of emamectin benzoate key intermediate, is in acid binding agent and catalyst action
Under, raw material avermectin (II) is reacted in atent solvent with hydroxy protecting agent to be generated in the emamectin benzoate key
Mesosome (I)；
R1For methyl or ethyl；A-B is CH=CH or CH2-CH(OH)；
R2- X is hydroxy protecting agent, and wherein X is halogen；
Wherein the catalyst is any one in triethylene diamine and tetramethyl ethylene diamin(e) or two or more timess
The mixture of meaning ratio.
Preferably, the dosage of the catalyst is the 0.1~20% of raw material avermectin (II) molal quantity.
Preferably, the acid binding agent is in triethylamine, tripropyl amine (TPA), tri-n-butylamine, ethyl diisopropylamine and propyl diisopropylamine
Any one or two or more arbitrary proportions mixture.
It is further preferred that the dosage of the acid binding agent is 0.8~3.0 times of raw material avermectin (II) molal quantity.
The hydroxy protecting agent can for allyl chlorocarbonate, trim,ethylchlorosilane or t-Butyldimethylsilyl etc.,
But it is not limited to this, and the dosage of hydroxy protecting agent is 1.0~2.0 times of raw material avermectin (II) molal quantity.
Preferably, the atent solvent be methylene chloride, 1,2- dichloroethanes, sec-Butyl Acetate, isopropyl acetate or
1,4- dioxane.
Preferably, the reaction temperature is -30~30 DEG C, and the reaction time is 10min~60min.
The present invention also provides 4 " position method for oxidation of the emamectin benzoate key intermediate (I), i.e., urge aforementioned
It is combined to key intermediate (I) after reaction, without processing, the oxidation that 4 " positions are directly carried out in the reaction system is anti-
It answers, the step of specific oxidation reaction can refer to related report in the prior art.
Preferably, after the oxidation reaction, in the reaction system plus water, adjusting pH is acidity, further preferably 2~
3, it is extracted, is separated water phase and organic phase after extraction, organic phase obtains the intermediate that 4 " positions are oxidized to carbonyl after solvent is evaporated off,
Water phase tune pH is alkalinity, and further preferably >=11, the organic base and water stratification recycle after acid binding agent is separated drying
It applies, the extraction for reaction system can be recycled in the water phase separated.
Compared with the existing technology, the method for the present invention has the positive effect that:
1, by selecting catalyst, it is determined that one kind can carry out 5 hydroxy esterification reactions in a mild condition
Method, this method have high selectivity to 5 hydroxyls, and reaction speed is fast, high income.
2, processing is needed not move through after esterification can carry out the oxidation reaction of 4 " position hydroxyls in next step, simplify life
Production. art improves production efficiency.
3, also COD and ammonia nitrogen in waste water, the technique can be greatly reduced by recycling acid binding agent after oxidation reaction
It is environmentally protective, it overcomes acid binding agent in conventional production methods and fully enters waste water and cause waste water COD and ammonia nitrogen value high and be not easy
The drawbacks of processing, meets the developing direction of industry.
4, it can continue to apply after also recyclable acid binding agent and acid binding agent recycling after oxidation reaction, greatly reduce life
Produce cost, improve acid binding agent first use in conventional production methods can not recovery situation.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.
Embodiment 1
It takes 10g AVERMECTIN B1 (B1a content > 90%) to be dissolved in 40g methylene chloride at room temperature, 1.8g is added
The mixing of 2.8g triethylamine, 0.5g triethylene diamine and 2.0g methylene chloride is slowly added dropwise after allyl chlorocarbonate stirring 15min
Solution, about 10min add, and stir 10min after being added dropwise under room temperature, and end of reaction continues to aoxidize in next step anti-
It answers, 2.4g DMSO is added, 2.3g phenyl phosphate diacid chloride is slowly added dropwise in 2.3g triethylamine, and 5min is added dropwise, stirs at room temperature
Mix reaction 30min.20g water is added after reaction, the hydrochloric acid tune pH=2.5 stirring of 1mol/L, split-phase, organic phase concentration is added
Obtain 10.36g light yellow solid, yield 95%.
30% NaOH solution tune pH value > 11 are added in water layer, stand, split-phase.Upper layer is colorless and transparent triethylamine
3.58g, be added 0.5g piece alkali it is dry after obtain 3.4g, the rate of recovery 92%, the water phase of lower layer is reusable in oxidation reaction system
Extraction.
Embodiment 2
Avermectin B2 (B2a content > 90%) 10g is taken, is dissolved in 40g methylene chloride, 2.4g chlorine is added after dissolving completely
Allyl formate stirs the mixed solution that 3.8g tri-n-butylamine, 0.002g triethylene diamine are slowly added dropwise after 15min, 5min at room temperature
It being added dropwise, -25 DEG C of stirring 60min fully reactings after adding continue next step oxidation reaction, 2.5g DMSO is added,
2.4g phenyl phosphate diacid chloride is slowly added dropwise in 4.0g tri-n-butylamine, and 5min is added dropwise, and is stirred to react 30min at room temperature.Reaction knot
20g water is added after beam, the hydrochloric acid tune pH=3.0 of 1mol/L is added, stirs, split-phase, it is light yellow that organic phase is concentrated to get 10.54g
Solid, yield 97%.
30% NaOH solution tune pH value > 11 are added in water layer, stand, split-phase.Upper layer is lurid tri-n-butylamine 7.0g, is added
It is dry to enter 0.8g piece alkali, obtains 6.5g, the rate of recovery 90.2%.
Embodiment 3
AVERMECTIN B1 (B1a content > 90%) 10g is taken, is dissolved in 40g sec-Butyl Acetate, 1.9g is added after dissolving completely
1.5g ethyl diisopropylamine, 1.2g triethylamine and 0.4g tetramethyl is slowly added dropwise after stirring 15min at room temperature in allyl chlorocarbonate
The mixed solution of ethylene diamin(e), 5min are added dropwise, and stir 40min fully reacting after adding at 0 DEG C, continue next step oxygen
To change reaction, 2.4g DMSO is added, the 3ml dichloromethane solution of 1.8g solid phosgene is slowly added dropwise in 3.0g ethyl diisopropylamine,
5min is added dropwise, and is stirred to react 30min at room temperature.20g water is added after reaction, the hydrochloric acid tune pH=of 1mol/L is added
3.0, stirring, split-phase.Organic phase is concentrated to get 10.15g light yellow solid, yield 93%.
30% NaOH solution tune pH value > 11 are added in water layer, stand, split-phase.Upper layer is lurid ethyl diisopropylamine
5.6g, be added piece alkali it is dry 5.4g, the rate of recovery 94%.
Embodiment 4
It takes 10g AVERMECTIN B1 (B1a content > 90%) to be dissolved in 40g methylene chloride at room temperature, 1.8g is added
The triethylamine 0.95g recycled in embodiment 1, triethylene diamine 0.3g, tetramethyl is slowly added dropwise after allyl chlorocarbonate stirring 15min
The mixed solution of base ethylene diamin(e) 0.2g and 2.0g methylene chloride, about 10min add, and stir under room temperature after being added dropwise
10min, end of reaction continue next step oxidation reaction, 2.4g DMSO are added, (wherein 2.0g is to implement to 2.3g triethylamine
Recycled triethylamine in example 1,0.3g are newly to add triethylamine), 2.3g phenyl phosphate diacid chloride is slowly added dropwise, 6min is dripped
Finish, is stirred to react 30min at room temperature.20g water is added after reaction, the hydrochloric acid tune pH=2.1 stirring of 1mol/L is added, point
Phase, organic phase are concentrated to get 10.25g light yellow solid, yield 94%.
30% NaOH solution tune pH value > 11 are added in water layer, stand, split-phase.Upper layer is colorless and transparent triethylamine 3.6g,
3.38g, the rate of recovery 91.5% are obtained after the drying of 0.5g piece alkali is added.
Due to using one kettle way directly to carry out the oxidation reaction of 4 " position hydroxyls in above embodiments, not to key
The yield of intermediate (I) is detected, but the detection directly carried out to the yield of oxidation reaction product, oxidation reaction product
Yield can embody the yield of key intermediate (I), and under the premise of only key intermediate (I) obtains higher yields, oxidation is anti-
Product is answered just to have corresponding higher yield.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Made any modification, equivalent replacement or improvement etc., should all be included in the protection scope of the present invention within mind and principle.
Claims (10)
1. a kind of catalysis synthesizing technology of emamectin benzoate key intermediate, it is characterised in that: in acid binding agent and catalyst
Under effect, raw material avermectin (II) is reacted in atent solvent with hydroxy protecting agent generates the emamectin benzoate pass
Key intermediate (I)；
R1For methyl or ethyl；A-B is CH=CH or CH2-CH(OH)；
R2- X is hydroxy protecting agent, and wherein X is halogen；
Wherein the catalyst is the arbitrary proportion of any one or two kinds in triethylene diamine and tetramethyl ethylene diamin(e)
Mixture.
2. the catalysis synthesizing technology of emamectin benzoate key intermediate as described in claim 1, it is characterised in that: described
The dosage of catalyst is the 0.1~20% of raw material avermectin (II) molal quantity.
3. the catalysis synthesizing technology of emamectin benzoate key intermediate as described in claim 1, it is characterised in that: described
Acid binding agent be triethylamine, tripropyl amine (TPA), tri-n-butylamine, ethyl diisopropylamine and propyl diisopropylamine in any one or it is two or more
Arbitrary proportion mixture,.
4. the catalysis synthesizing technology of emamectin benzoate key intermediate as claimed in claim 3, it is characterised in that: described
The dosage of acid binding agent is 0.8~3.0 times of raw material avermectin (II) molal quantity.
5. the catalysis synthesizing technology of emamectin benzoate key intermediate as described in claim 1, it is characterised in that: described
Hydroxy protecting agent R2- X is allyl chlorocarbonate, trim,ethylchlorosilane or t-Butyldimethylsilyl.
The additional amount of the hydroxy protecting agent is 1.2~2.0 times of raw material avermectin (II) molal quantity.
6. the catalysis synthesizing technology of emamectin benzoate key intermediate as described in claim 1, it is characterised in that: described
Atent solvent be methylene chloride, 1,2- dichloroethanes, sec-Butyl Acetate, isopropyl acetate or 1,4- dioxane.
7. the catalysis synthesizing technology of emamectin benzoate key intermediate as described in claim 1, it is characterised in that: described
Reaction temperature be -30~30 DEG C, the reaction time be 10min~60min.
8. a kind of 4 " position method for oxidation of emamectin benzoate key intermediate, it is characterised in that: described in claim 1 anti-
After answering, oxidation reaction is directly carried out in the reaction system.
9. 4 " position method for oxidation of emamectin benzoate key intermediate as claimed in claim 8, it is characterised in that: oxidation
After reaction, in the reaction system plus water, adjusting pH is that acidity is extracted, and water phase and organic phase is separated, organic phase is evaporated off
The intermediate that 4 " positions are oxidized to carbonyl is obtained after solvent, water phase tune pH is the acid binding agent and water stratification after alkalinity, by organic base point
Recovery out.
10. 4 " position method for oxidation of emamectin benzoate key intermediate as claimed in claim 9, it is characterised in that: oxygen
Change after reaction, in the reaction system plus water, tune pH are extracted for 2~3, water phase and organic phase are separated, organic phase is steamed
Except after solvent 4 " positions are oxidized to the intermediate of carbonyl, after water phase tune pH is >=11, the acid binding agent and water stratification, by organic base
Separate recovery.
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| CN201810897060.6A CN109134563B (en) | 2018-08-08 | 2018-08-08 | Catalytic synthesis process of methylamino abamectin key intermediate |
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Cited By (2)
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| CN113354695A (en) * | 2021-05-26 | 2021-09-07 | 河北威远生物化工有限公司 | Continuous production process of emamectin benzoate B1/B2 |
| CN115109103A (en) * | 2022-07-27 | 2022-09-27 | 内蒙古新威远生物化工有限公司 | Synthetic method of emamectin benzoate |
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