CN104610136A - Synthetic method of 2-chloro-5-chloromethyl pyridine - Google Patents
Synthetic method of 2-chloro-5-chloromethyl pyridine Download PDFInfo
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- CN104610136A CN104610136A CN201410060990.8A CN201410060990A CN104610136A CN 104610136 A CN104610136 A CN 104610136A CN 201410060990 A CN201410060990 A CN 201410060990A CN 104610136 A CN104610136 A CN 104610136A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
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Abstract
The invention discloses a synthetic method of 2-chloro-5-chloromethyl pyridine. The synthetic method comprising the following steps: adding an organic solvent, an acid buffering agent solution and an initiator into 3-methylpyridine; adjusting the pH value of the solution in a range of 4-5; letting nitrogen in; elevating temperature to 80-100 DEG C while stirring; stopping letting nitrogen in, letting chlorine in and continuing elevating temperature for a reaction; stopping heating, shutting a chlorine injection vavle off, letting nitrogen in and bubbling to drive the chlorine off; desolventizing a reaction solution through underpressure distillation to obtain brown-red oily liquid; and purifying the brown-red oily liquid to obtain a finished product. According to the invention, a liquid phase chlorination method is adopted; raw materials are subjected to a reaction in liquid; meanwhile an acid buffering agent solution is added to adjust a pH value in a range of 4-5; and by-products are decreased, so that the yield of a target product can reach to about 90%.
Description
Technical field
The present invention relates to a kind of synthetic method of CCMP, belong to organic chemical synthesis field.
Background technology
CCMP (being called for short CCMP) is the important intermediate of the anabasine pesticide such as pesticide imidacloprid, acetamiprid, the pyridine of piperazine worm, can be used for preparing pharmaceuticals, agrochemicals and biotechnological formulation etc., particularly synthesizing efficient novel agrochemical haloxyfop, Provado and future are containing the vital intermediate of chloropyridines novel pesticide, that synthesizes with 2-chloro-5-trichloromethylpyridine contains chloropyridines new varieties of pesticides, is just obtaining manufacture and exploit energetically at present at home and abroad.
The route of current employing cyclization method synthesis CCMP mainly contains three, is benzylamine method, cyclopentadiene method, morpholine method respectively.
In the chlorination reaction of benzylamine method and morpholine method, there is chlorination inequality, easily form many chloros by product, separation difficulty, product purity is not ideal enough.
In cyclopentadiene method, ring-closure reaction generates CCMP, and avoid the many chloros by product produced in chloro process, product purity is higher, is the route that domestic most producer selects.But the chloro of cyclopentadiene method and cyclization process need use a large amount of DMF, and without effective recovery method, produce a large amount of waste water simultaneously, bring to environment and have a strong impact on.
The preparation method of 2-chloro-5-trichloromethylpyridine is disclosed in Chinese patent CN102452977A, 3-picoline is adopted to be raw material, under organic solvent and chlorine existent condition, cause through initiator, through a step liquid phase chlorination method Reactive Synthesis 2-chloro-5-trichloromethylpyridine, and carry out purification and obtain finished product.The 2-chloro-5-trichloromethylpyridine by-product object height obtained in this synthetic route, yield can only reach about 80%.
Summary of the invention
The object of the present invention is to provide a kind of synthetic method of CCMP.
The technical solution realizing the object of the invention is: a kind of synthetic method of CCMP, comprises the following steps: in 3-picoline, add organic solvent, acidic buffer agent solution and initiator, regulator solution pH value is at 4-5; Pass into nitrogen, stir and be warming up to 80-100, the logical nitrogen of DEG C stopping also passing into chlorine, continues temperature reaction; Stop heating, close chlorine sampling valve, pass into nitrogen, bubbling catches up with chlorine, after reaction solution underpressure distillation precipitation, obtains red-brown oily liquids, and finally purifying obtains finished product.
In above-mentioned steps, described organic solvent is oil of mirbane.
In above-mentioned steps, described acidic buffer agent solution is sodium dihydrogen phosphate.
In above-mentioned steps, described initiator is phosphorus trichloride.
In above-mentioned steps, described initiator add the 2%-5% that total amount is 3-picoline quality.
In above-mentioned steps, the add-on of described organic solvent is 3-4 times of 3-picoline quality.
In above-mentioned steps, the add-on of described buffer agent solution is 1-2 times of organic solvent volume.
In above-mentioned steps, described temperature of reaction is 120-160 DEG C, reaction times 12-20h.
Compared with prior art, the invention has the advantages that: adopt liquid phase chlorination method, raw material is reacted in the liquid state, add acidic buffer agent solution and adjust ph at 4-5 simultaneously, decrease the generation of by product, make the productive rate of target product reach about 90%.
Embodiment
Embodiment 1
In four-hole boiling flask, add 10g3-picoline, 30mL oil of mirbane and 45ml buffer agent solution, adopt dilute hydrochloric acid regulator solution pH value about 4, add 0.2g phosphorus trichloride simultaneously.Pass into nitrogen, induction stirring, be warming up to 80 DEG C, stop logical nitrogen and switch passing into chlorine, continue to be warming up to 120 DEG C, under constant temperature, chlorine blistering reaction 12h, stop heating, close chlorine sampling valve, pass into nitrogen, bubbling catches up with chlorine 1h.After reaction solution underpressure distillation precipitation, obtain red-brown oily liquids.High-vacuum fractionation purified product, collects overhead product.After chloroform extraction, combining extraction liquid, after decompression precipitation, obtain 18.9g pale yellow oily liquid body, the yield of product 2-chloro-5-trichloromethylpyridine is 89.6%.
Embodiment 2
In four-hole boiling flask, add 10g3-picoline, 25mL oil of mirbane and 25ml buffer agent solution, adopt dilute hydrochloric acid regulator solution pH value about 4.5, add 0.3g phosphorus trichloride simultaneously.Pass into nitrogen, induction stirring, be warming up to 100 DEG C, stop logical nitrogen and switch passing into chlorine, continue to be warming up to 140 DEG C, under constant temperature, chlorine blistering reaction 16h, stop heating, close chlorine sampling valve, pass into nitrogen, bubbling catches up with chlorine 1h.After reaction solution underpressure distillation precipitation, obtain red-brown oily liquids.High-vacuum fractionation purified product, collects overhead product.After chloroform extraction, combining extraction liquid, after decompression precipitation, obtain 19.4g pale yellow oily liquid body, the yield of product 2-chloro-5-trichloromethylpyridine is 91.3%.Embodiment 3
In four-hole boiling flask, add 10g3-picoline, 45mL oil of mirbane and 90ml buffer agent solution, adopt dilute hydrochloric acid regulator solution pH value about 5, add 0.5g phosphorus trichloride simultaneously.Pass into nitrogen, induction stirring, be warming up to 90 DEG C, stop logical nitrogen and switch passing into chlorine, continue to be warming up to 160 DEG C, under constant temperature, chlorine blistering reaction 20h, stop heating, close chlorine sampling valve, pass into nitrogen, bubbling catches up with chlorine 1h.After reaction solution underpressure distillation precipitation, obtain red-brown oily liquids.High-vacuum fractionation purified product, collects overhead product.After chloroform extraction, combining extraction liquid, after decompression precipitation, obtain 19.1g pale yellow oily liquid body, the yield of product 2-chloro-5-trichloromethylpyridine is 90.4%.
Claims (8)
1. a synthetic method for CCMP, is characterized in that comprising the following steps: in 3-picoline, add organic solvent, acidic buffer agent solution and initiator, regulator solution pH value is at 4-5; Pass into nitrogen, stir and be warming up to 80-100 DEG C, stop logical nitrogen and pass into chlorine, continuing temperature reaction; Stop heating, close chlorine sampling valve, pass into nitrogen, bubbling catches up with chlorine, after reaction solution underpressure distillation precipitation, obtains red-brown oily liquids, and finally purifying obtains finished product.
2. the synthetic method of CCMP according to claim 1, is characterized in that described organic solvent is oil of mirbane.
3. the synthetic method of CCMP according to claim 1, is characterized in that described acidic buffer agent solution is sodium dihydrogen phosphate.
4. the synthetic method of CCMP according to claim 1, is characterized in that described initiator is phosphorus trichloride.
5. the synthetic method of CCMP according to claim 1, what it is characterized in that described initiator adds the 2%-5% that total amount is 3-picoline quality.
6. the synthetic method of CCMP according to claim 1, is characterized in that the add-on of described organic solvent is 3-4 times of 3-picoline quality.
7. the synthetic method of CCMP according to claim 1, is characterized in that the add-on of described buffer agent solution is 1-2 times of organic solvent volume.
8. the synthetic method of CCMP according to claim 1, is characterized in that described temperature of reaction is 120-160 DEG C, reaction times 12-20h.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410060990.8A CN104610136B (en) | 2014-02-21 | 2014-02-21 | A kind of synthetic method of the trichloromethyl pyridine of 2 chlorine 5 |
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| CN201410060990.8A CN104610136B (en) | 2014-02-21 | 2014-02-21 | A kind of synthetic method of the trichloromethyl pyridine of 2 chlorine 5 |
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| CN104610136A true CN104610136A (en) | 2015-05-13 |
| CN104610136B CN104610136B (en) | 2017-07-14 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106187869A (en) * | 2016-07-28 | 2016-12-07 | 南京红太阳生物化学有限责任公司 | A kind of method of synthesis 2 chlorine 5 chloromethylpyridine |
| CN106380445A (en) * | 2015-07-28 | 2017-02-08 | 江苏吉华化工有限公司 | Method for preparing 2-chloro-5-chloromethylpyridine from 2-methylpyridine |
| CN106397308A (en) * | 2015-07-28 | 2017-02-15 | 江苏吉华化工有限公司 | Process for preparing 2-chloro-5-chloromethylpyridine from trimethylpyridine-phosphamide |
| CN107162962A (en) * | 2017-05-12 | 2017-09-15 | 江苏克胜作物科技有限公司 | The control method of the PMC dimer of 2 chlorine 5 |
| CN107628989A (en) * | 2017-10-26 | 2018-01-26 | 南京红太阳生物化学有限责任公司 | A kind of synthetic method of the PMC of 2 chlorine 5 |
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| US5198549A (en) * | 1990-05-19 | 1993-03-30 | Bayer Aktiengesellschaft | Side-chain chlorination of alkylated nitrogen heteroaromatics |
| CN1342648A (en) * | 2000-09-13 | 2002-04-03 | 中国科学院大连化学物理研究所 | Process for synthesizing 2-Cl-5-trifluoromethyl pyridine |
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| CN102452977A (en) * | 2010-10-28 | 2012-05-16 | 宁波大学 | Method for preparing 2-chloro-5-trichloromethylpyridine |
| CN102942518A (en) * | 2012-11-30 | 2013-02-27 | 江苏扬农化工股份有限公司 | Chlorination synthesis method of pyridine derivatives |
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2014
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| US5198549A (en) * | 1990-05-19 | 1993-03-30 | Bayer Aktiengesellschaft | Side-chain chlorination of alkylated nitrogen heteroaromatics |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106380445A (en) * | 2015-07-28 | 2017-02-08 | 江苏吉华化工有限公司 | Method for preparing 2-chloro-5-chloromethylpyridine from 2-methylpyridine |
| CN106397308A (en) * | 2015-07-28 | 2017-02-15 | 江苏吉华化工有限公司 | Process for preparing 2-chloro-5-chloromethylpyridine from trimethylpyridine-phosphamide |
| CN106187869A (en) * | 2016-07-28 | 2016-12-07 | 南京红太阳生物化学有限责任公司 | A kind of method of synthesis 2 chlorine 5 chloromethylpyridine |
| CN107162962A (en) * | 2017-05-12 | 2017-09-15 | 江苏克胜作物科技有限公司 | The control method of the PMC dimer of 2 chlorine 5 |
| CN107628989A (en) * | 2017-10-26 | 2018-01-26 | 南京红太阳生物化学有限责任公司 | A kind of synthetic method of the PMC of 2 chlorine 5 |
| CN107628989B (en) * | 2017-10-26 | 2020-07-24 | 南京红太阳生物化学有限责任公司 | Synthetic method of 2-chloro-5-chloromethylpyridine |
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| CN104610136B (en) | 2017-07-14 |
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