CN102146072A - Method for preparing isoprothiolane - Google Patents
Method for preparing isoprothiolane Download PDFInfo
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- CN102146072A CN102146072A CN2011100569038A CN201110056903A CN102146072A CN 102146072 A CN102146072 A CN 102146072A CN 2011100569038 A CN2011100569038 A CN 2011100569038A CN 201110056903 A CN201110056903 A CN 201110056903A CN 102146072 A CN102146072 A CN 102146072A
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Abstract
The invention provides a method for preparing isoprothiolane. The method comprises the following steps of: uniformly mixing diisopropyl malonate, carbon disulfide and alkaline aqueous solution, adding dichloroethane and a catalyst, and after the reaction is finished, cooling and purifying to obtain the isoprothiolane, wherein the catalyst is alkylpyridinium chloride. The isoprothiolane synthesized by the invention has the purity of over 95 percent, and the synthetic yield in a pilot plant test is over 90 percent; in addition, the method for preparing the isoprothiolane has the advantages of greatly shortening process time and reducing production cost.
Description
Technical field
The invention belongs to pesticide field, relate in particular to a kind of preparation method of isoprothiolane.
Background technology
Isoprothiolane has another name called isoprothiolane, Fujione, and chemical name is 1,3-dithiolane-2-subunit Diisopropyl malonate, two (1-methylethyl)-1,3-dithiolane-2-subunit malonic ester.Isoprothiolane in research and development in 1969, is more stable to light, heat, to the heterocyclic nitrogen-group fungicide of people, animal low toxicity by Japanese agricultural chemicals company.Its principal feature: the one, have high selectivity, lower reason dosage can demonstrate good fungistatic effect to Pyricularia oryzae, and the dosage raising also demonstrates the inhibition effect to the culm rot bacterium; The 2nd, have interior absorption, plant accumulates on leaf texture after absorbing, and is easier to concentrate cob and branch stalk; The 3rd, the lasting period is long, and resistance of rainwater washing against; The 4th, paddy rice neck pest there is special efficacy, the effect of rice leaf pest also is higher than Kitazine, all effective to rice seedling pest and culm rot, big area is used also can doublely control planthopper, leafhopper, and plant-growth is had regulating effect.
Domestic each producer is all by adopting Diisopropyl malonate and dithiocarbonic anhydride, sodium hydroxide reaction to make sodium salt earlier, again with ethylene dichloride and the synthetic isoprothiolane of sodium salt back flow reaction at present.But in the back flow reaction process, because inorganic sodium salt causes sodium salt and ethylene dichloride to be difficult to full contact with organically the ethylene dichloride consistency is relatively poor, cause the rate of utilization of raw material lower on the one hand, cost is higher; Cause synthesis yield lower (about 60%) on the other hand.Be the raising synthesis yield in the prior art, thereby prolong reflux time, cause the synthesis technique time longer again.And, directly adopt the synthetic isoprothiolane first product purity that obtains of sodium salt and ethylene dichloride relatively low, second-rate, product appearance is reddish-brown, and has unpleasant stink.
In organic synthesis, the common speed of heterogeneous organic reaction is very slow, and yield is low; If but use water-soluble inorganic salt, with the little organic solvent dissolution organism of polarity, and add the quaternary ammonium salt or the quaternary alkylphosphonium salt of (0.05mol is following) on a small quantity, reaction then is easy to carry out, this class reaction is phase-transfer catalysis (Phase transfer is called for short PT) reaction.Wherein, can impel and improve speed of response and, be called phase-transfer catalyst at the salt of two alternate transfer negative ions.Generally have the reaction of phase-transfer catalysis, all have the aqueous solution and organic solvent two-phase, reaction of ionic type thing often dissolves in water, is insoluble to organic phase, and organic substrates then dissolves among the organic solvent.When not having phase-transfer catalyst, two-phase is isolated mutually, and several reactants can't contact, and reaction is carried out very slowly.The existence of phase-transfer catalyst can combine with the ion institute of aqueous phase, and utilize self affinity to organic solvent, in organic phase, impels reaction to take place the reactant transfer of aqueous phase.
For example, the method of the synthetic isoprothiolane of a kind of phase transfer catalysis process is disclosed in the prior art, generate sodium salt by Diisopropyl malonate, dithiocarbonic anhydride, sodium hydroxide reaction, sodium salt and ethylene dichloride reaction in the presence of quaternary ammonium salt phase transfer catalyst then, thereby preparation isoprothiolane.By adopting quaternary ammonium salt, can improve the building-up reactions transformation efficiency in this method, but it is still lower to adopt this method to prepare the synthesis yield of isoprothiolane, only reaches 77% as catalyzer; Therefore further improve synthesis yield as need, still need prolong reflux time, adopt this method still to fail to realize suitability for industrialized production.
Summary of the invention
The invention solves that the isoprothiolane synthesis yield that exists in the prior art is lower, the process time is long and the cost technical problems of high.
The invention provides a kind of preparation method of isoprothiolane, comprise earlier Diisopropyl malonate, dithiocarbonic anhydride and alkaline aqueous solution being mixed, add ethylene dichloride and catalyzer again, the reaction postcooling is purified and is obtained described isoprothiolane; Wherein, described catalyzer is the kelene yl pyridines.
The preparation method of isoprothiolane provided by the invention compared with prior art has the following advantages:
(1) adopt the purity of preparation method's synthetic isoprothiolane of the present invention to be higher than 95%, the pilot scale synthesis yield is up to more than 90%;
(2) the back flow reaction required time is shorter among the preparation method provided by the invention, therefore can shorten the process time greatly;
(3) preparation method provided by the invention effectively reduces the consumption of Diisopropyl malonate and ethylene dichloride, thereby reduces production costs.
Embodiment
The invention provides a kind of preparation method of isoprothiolane, comprise earlier Diisopropyl malonate, dithiocarbonic anhydride and alkaline aqueous solution being mixed, add ethylene dichloride and catalyzer again, the reaction postcooling is purified and is obtained described isoprothiolane; Wherein, described catalyzer is the kelene yl pyridines.
Preparation method provided by the invention is with Diisopropyl malonate (C
9H
16O
4), dithiocarbonic anhydride (CS
2), alkaline aqueous solution and ethylene dichloride (ClCH
2CH
2Cl) be raw material, by the synthetic described isoprothiolane of phase transfer catalysis process.Wherein alkaline aqueous solution is example with the aqueous sodium hydroxide solution, and described reaction mechanism is as follows:
As those skilled in the art's common practise, described isoprothiolane synthesize not using that synthesis yield only is about 60% under the condition of catalyzer.Therefore pass through to use various catalyzer in the prior art, thereby improve synthesis yield.For example, the available technology adopting quaternary ammonium salt is as phase-transfer catalyst, but its synthesis yield only reaches 78%.The present inventor finds, adopts the kelene yl pyridines as catalyzer, can effectively improve the transformation efficiency of phase-transfer-catalyzed reactions, makes and adopts preparation method provided by the invention to prepare the pilot scale combined coefficient of isoprothiolane up to more than 90%.
Particularly, phase-transfer catalyst of the present invention is the kelene yl pyridines, and its structural formula is
Wherein: R is the alkyl of carbonatoms 1 ~ 16.Under the preferable case, described kelene yl pyridines is selected from any one in chlorination-1-picoline, chlorination-1-ethylpyridine, chlorination-1-butyl-pyridinium, chlorination-1-dodecyl pyridine, the chlorination-kelene yl pyridines such as 1-cetyl pyridinium.More preferably under the situation, described kelene yl pyridines is selected from any one in chlorination-1-butyl-pyridinium, the chlorination-1-dodecyl pyridine.
Among the present invention, catalyst consumption need not too much, under the preferable case, is benchmark with the Diisopropyl malonate of 1mol, and described catalyst consumption is 5-50g.More preferably under the situation, be benchmark with the Diisopropyl malonate of 1mol, described catalyst consumption is 10-30g.
Preparation in accordance with the present invention, the preparation method of described isoprothiolane specifically may further comprise the steps: add Diisopropyl malonate, dithiocarbonic anhydride in the reactor that electronic stirring, thermometer, reflux exchanger, dropping bath are housed, whipped state drips alkaline aqueous solution solution down, drips off the back and continues to stir; Add ethylene dichloride and catalyzer then, after the back flow reaction, standing demix also takes off a layer organic phase, removes ethylene dichloride, pulverizes behind the crystallisation by cooling, obtains lurid described isoprothiolane.
Among the present invention,, can effectively improve the transformation efficiency of reaction by adopting the kelene yl pyridines as catalyzer.Under the preferable case, also can further regulate the rational proportion of each reaction raw materials among the present invention, thereby make building-up reactions more abundant, improve the rate of utilization of each raw material.Particularly, the mol ratio of Diisopropyl malonate, dithiocarbonic anhydride, ethylene dichloride and alkaline aqueous solution is 1:1.1:2:4.5.Among the present invention,, thereby effectively reduce the consumption of Diisopropyl malonate and ethylene dichloride by the consumption of rational proportion raw material.For example, the Diisopropyl malonate consumption can be reduced to below the 0.727t/t from 1.03t/t of the prior art, and the consumption of ethylene dichloride can be reduced to below the 0.6t/t from 1.3t/t of the prior art.
Among the present invention, the aqueous solution of the various alkaline matters that described alkaline aqueous solution is used always for those skilled in the art for example is the aqueous solution of sodium hydroxide and/or potassium hydroxide.More preferably under the situation, the alkaline matter sodium hydroxide in the described alkaline aqueous solution and/or the mol ratio of potassium hydroxide and water are 2:1.
Preparation in accordance with the present invention after Diisopropyl malonate, dithiocarbonic anhydride mix, drips alkaline aqueous solution, drips off the back and continues to stir, and obtains sodium salt after stirring is finished shown in preceding reaction mechanism.Temperature when dripping alkaline aqueous solution in the reactor is 25-45 ℃, and dripping off the time of continuing to stir in the back is 5-60min.
Preparation in accordance with the present invention adds ethylene dichloride and catalyzer again in reactor, under the catalyzer existence condition, ethylene dichloride and sodium salt back flow reaction obtain described isoprothiolane.Under the preferable case, the back flow reaction temperature is 60-90 ℃.Reflux time is 1-3h.Therefore among the present invention, reflux time is shorter, can shorten the process time greatly, and process time of 20h of the prior art is foreshortened in the 8h.
Preparation in accordance with the present invention after back flow reaction is finished, with the reaction system standing demix, is taken off a layer organic phase.Remove wherein unreacted ethylene dichloride completely then, pulverize behind the crystallisation by cooling, obtain described isoprothiolane.Wherein, the step that removes ethylene dichloride, crystallisation by cooling is conventionally known to one of skill in the art, repeats no more among the present invention.
Below in conjunction with embodiment and Comparative Examples the present invention is further explained explanation, raw materials usedly in embodiment and the Comparative Examples all is commercially available.
Embodiment 1
In the reactor that electronic stirring, thermometer, reflux exchanger, dropping bath are housed, add 1mol Diisopropyl malonate, 1.1mol dithiocarbonic anhydride, start stirring, drip 4.5mol aqueous sodium hydroxide solution (mol ratio of sodium hydroxide and water is 2:1) down at 30 ℃; Keep in the reactor temperature-resistantly after dripping off, continue to stir 30min.From dropping bath, add the 2mol ethylene dichloride then, add 10g catalyzer chlorination-1-dodecyl pyridine again, 70 ℃ of following back flow reaction 1h.After reaction is finished, standing demix.Take off a layer organic phase and remove ethylene dichloride.Cooling is pulverized after the product crystallization, obtains lurid isoprothiolane sample, is designated as S1.To the S1 calculating of weighing, obtaining this isoprothiolane sample purity is 95.8%, and synthesis yield is 91.5%.
Embodiment 2
In the reactor that electronic stirring, thermometer, reflux exchanger, dropping bath are housed, add 1mol Diisopropyl malonate, 1.1mol dithiocarbonic anhydride, start stirring, drip 4.5mol potassium hydroxide aqueous solution (mol ratio of potassium hydroxide and water is 2:1) down at 35 ℃; Keep in the reactor temperature-resistantly after dripping off, continue to stir 35min.From dropping bath, add the 2mol ethylene dichloride then, add 15g catalyzer chlorination-1-butyl-pyridinium again, 75 ℃ of following back flow reaction 1.5h.After reaction is finished, standing demix.Take off a layer organic phase and remove ethylene dichloride.Cooling is pulverized after the product crystallization, obtains lurid isoprothiolane sample, is designated as S2.To the S2 calculating of weighing, obtaining this isoprothiolane sample purity is 96.2%, and synthesis yield is 92.1%.
Embodiment 3
In the reactor that electronic stirring, thermometer, reflux exchanger, dropping bath are housed, add 1mol Diisopropyl malonate, 1.1mol dithiocarbonic anhydride, start stirring, drip 4.5mol alkaline aqueous solution (in the alkaline aqueous solution, the mol ratio of sodium hydroxide, potassium hydroxide and water is 1:1:1) down at 40 ℃; Keep in the reactor temperature-resistantly after dripping off, continue to stir 45min.From dropping bath, add the 2mol ethylene dichloride then, add 20g catalyzer chlorination-1-cetyl pyridinium again, 80 ℃ of following back flow reaction 2h.After reaction is finished, standing demix.Take off a layer organic phase and remove ethylene dichloride.Cooling is pulverized after the product crystallization, obtains lurid isoprothiolane sample, is designated as S3.To the S3 calculating of weighing, obtaining this isoprothiolane sample purity is 96.0%, and synthesis yield is 91.3%.
Embodiment 4
In the reactor that electronic stirring, thermometer, reflux exchanger, dropping bath are housed, add 1mol Diisopropyl malonate, 1.1mol dithiocarbonic anhydride, start stirring, drip 4.5mol aqueous sodium hydroxide solution (mol ratio of sodium hydroxide and water is 2:1) down at 45 ℃; Keep in the reactor temperature-resistantly after dripping off, continue to stir 50min.From dropping bath, add the 2mol ethylene dichloride then, add 15g catalyzer chlorination-1-ethylpyridine again, 80 ℃ of following back flow reaction 2h.After reaction is finished, standing demix.Take off a layer organic phase and remove ethylene dichloride.Cooling is pulverized after the product crystallization, obtains lurid isoprothiolane sample, is designated as S4.To the S4 calculating of weighing, obtaining this isoprothiolane sample purity is 96.1%, and synthesis yield is 92.0%.
Comparative Examples 1
In the reactor that electronic stirring, thermometer, reflux exchanger, dropping bath are housed, add 1mol Diisopropyl malonate, 1.1mol dithiocarbonic anhydride, start stirring, drip 4.5mol aqueous sodium hydroxide solution (mol ratio of sodium hydroxide and water is 2:1) down at 30 ℃; Keep in the reactor temperature-resistantly after dripping off, continue to stir 30min.From dropping bath, add 2mol ethylene dichloride, 70 ℃ of following back flow reaction 15h then.After reaction is finished, standing demix.Take off a layer organic phase and remove ethylene dichloride.Cooling is pulverized after the product crystallization, obtains lurid isoprothiolane sample, is designated as DS1.To the DS1 calculating of weighing, obtaining this isoprothiolane sample purity is 87.5%, and synthesis yield is 64.9%.
Comparative Examples 2
In the reactor that electronic stirring, thermometer, reflux exchanger, dropping bath are housed, add 1mol Diisopropyl malonate, 1.1mol dithiocarbonic anhydride, start stirring, drip 4.5mol aqueous sodium hydroxide solution (mol ratio of sodium hydroxide and water is 2:1) down at 30 ℃; Keep in the reactor temperature-resistantly after dripping off, continue to stir 30min.From dropping bath, add the 2mol ethylene dichloride then, add 10g catalyzer tetrabutylammonium chloride again, 70 ℃ of following back flow reaction 4h.After reaction is finished, standing demix.Take off a layer organic phase and remove ethylene dichloride.Cooling is pulverized after the product crystallization, obtains lurid isoprothiolane sample, is designated as DS2.To the DS2 calculating of weighing, obtaining this isoprothiolane sample purity is 93.3%, and synthesis yield is 75.8%.
Result by the foregoing description 1-4 and Comparative Examples 1-2 more as can be seen, by adopting the kelene yl pyridines as catalyzer, the purity of the isoprothiolane for preparing is higher than 95% among the preparation method provided by the invention, the pilot scale synthesis yield is up to more than 90%.And reflux time is lacked (1-3h) among the preparation method provided by the invention, and therefore the required process time shortens greatly.In addition, by the consumption (mol ratio of Diisopropyl malonate, dithiocarbonic anhydride, ethylene dichloride and alkaline aqueous solution is 1:1.1:2:4.5) of rational proportion raw material, each raw material can be fully used among the present invention, reduce cost.
Claims (10)
1. the preparation method of an isoprothiolane comprises earlier Diisopropyl malonate, dithiocarbonic anhydride and alkaline aqueous solution being mixed, and adds ethylene dichloride and catalyzer again, and the reaction postcooling is purified and obtained described isoprothiolane; It is characterized in that described catalyzer is the kelene yl pyridines.
2. preparation method according to claim 1 is characterized in that: described kelene yl pyridines structural formula is:
Wherein, R is the alkyl of carbonatoms 1-16.
3. preparation method according to claim 2 is characterized in that: selected kelene yl pyridines is selected from any one in chlorination-1-picoline, chlorination-1-ethylpyridine, chlorination-1-butyl-pyridinium, chlorination-1-dodecyl pyridine, the chlorination-kelene yl pyridines such as 1-cetyl pyridinium.
4. preparation method according to claim 3 is characterized in that: described kelene yl pyridines is selected from any one in chlorination-1-butyl-pyridinium, the chlorination-1-dodecyl pyridine.
5. preparation method according to claim 1 and 2 is characterized in that: the Diisopropyl malonate with 1mol is a benchmark, and described catalyst consumption is 5-50g.
6. preparation method according to claim 1, it is characterized in that: in the reactor that electronic stirring, thermometer, reflux exchanger, dropping bath are housed, add Diisopropyl malonate, dithiocarbonic anhydride, whipped state drips alkaline aqueous solution down, drips off the back and continues to stir; Add ethylene dichloride and catalyzer then, after the back flow reaction, standing demix also takes off a layer organic phase, removes ethylene dichloride, pulverizes behind the crystallisation by cooling, obtains described isoprothiolane.
7. according to claim 1 or 6 described preparation methods, it is characterized in that: the mol ratio of Diisopropyl malonate, dithiocarbonic anhydride, ethylene dichloride and alkaline aqueous solution is 1:1.1:2:4.5.
8. according to claim 1 or 6 described preparation methods, it is characterized in that: described alkaline aqueous solution is the aqueous solution of sodium hydroxide and/or potassium hydroxide; In the described alkaline aqueous solution, the mol ratio of sodium hydroxide and/or potassium hydroxide and water is 2:1.
9. preparation method according to claim 6 is characterized in that: the temperature when dripping alkaline aqueous solution in the reactor is 25-45 ℃, and dripping off the time of continuing to stir in the back is 5-60min.
10. preparation method according to claim 6 is characterized in that: the back flow reaction temperature is 60-90 ℃, and reflux time is 1-3h.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113960307A (en) * | 2021-10-15 | 2022-01-21 | 北京勤邦生物技术有限公司 | Test strip for detecting isoprothiolane and preparation method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3876663A (en) * | 1971-02-02 | 1975-04-08 | Nihon Nohyako Kabushiki Kaisha | Process for the manufacture of cyclic mercaptals |
-
2011
- 2011-03-10 CN CN 201110056903 patent/CN102146072B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3876663A (en) * | 1971-02-02 | 1975-04-08 | Nihon Nohyako Kabushiki Kaisha | Process for the manufacture of cyclic mercaptals |
Non-Patent Citations (2)
| Title |
|---|
| 李继睿等: "稻瘟灵生产合成工艺新技术", 《农药》 * |
| 梁百能等: "相转移催化法合成稻瘟灵", 《湖南化工》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113960307A (en) * | 2021-10-15 | 2022-01-21 | 北京勤邦生物技术有限公司 | Test strip for detecting isoprothiolane and preparation method and application thereof |
| CN113960307B (en) * | 2021-10-15 | 2023-07-07 | 北京勤邦科技股份有限公司 | Test strip for detecting isoprothiolane and preparation method and application thereof |
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