CN106187876A - A kind of synthetic method of 2 chlorine apellagrins - Google Patents
A kind of synthetic method of 2 chlorine apellagrins Download PDFInfo
- Publication number
- CN106187876A CN106187876A CN201610551785.0A CN201610551785A CN106187876A CN 106187876 A CN106187876 A CN 106187876A CN 201610551785 A CN201610551785 A CN 201610551785A CN 106187876 A CN106187876 A CN 106187876A
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- Prior art keywords
- chloro
- chlorine apellagrin
- chloromethylpyridine
- synthetic method
- chlorine
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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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
- C07D213/807—Processes of preparation by oxidation of pyridines or condensed pyridines
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to the synthetic method of a kind of 2 chlorine apellagrins.The method, with 2 chlorine 3 chloromethylpyridine as raw material, with sodium nitrite/Organic Acid System as oxidant, obtains 2 chlorine apellagrins under the conditions of reaction temperature is 0～100 DEG C.Reaction condition of the present invention is gentle, with low cost, and 2 chlorine apellagrin yields are high, and raw materials used derives from pesticide imidacloprid by-product, has good Social benefit and economic benefit.
Description
Technical field
The invention belongs to organic synthesis field, be specifically related to the synthetic method of a kind of 2-chlorine apellagrin.
Background technology
In recent years, along with pesticide and the development of medicine, nicotinic acid sequence of chemical product are more and more concerned, and range of application is wide.
Wherein, 2-chlorine apellagrin, as important pesticide and medicine intermediate, mainly for the preparation of new and effective herbicide nicosulfuron, disappears
Scorching analgesic niflumic acid, pranoprofen and HIV Revertase inhibitor nevirapine.These products are not the most all for should
Ask.Therefore, the research to the preparation of 2-chlorine apellagrin and production technology is significant.
On the other hand, 2-vhloro-5-chloromethylpyridine is the key intermediate of synthetic pesticide imidacloprid, with 3-picoline is
During Material synthesis 2-vhloro-5-chloromethylpyridine, the isomer 2-chloro-3-chloromethyl pyrrole that meeting by-product market demand is the least
Pyridine.Prepare 2-chlorine apellagrin with the by-product 2-chloro-3-chloromethylpyridine of imidacloprid for raw material, be possible not only to cost-effective, simultaneously
Also make by-product 2-chloro-3-chloromethylpyridine be fully used, improve resource utilization, decrease the row of pollutant
Put.At present, less for the report of Material synthesis 2-chlorine apellagrin for thing with 2-chloro-3-picoline or its methyl chloride, as follows:
With 2-chloro-3-picoline as raw material, oxidized synthesis 2-chlorine apellagrin.The method mainly has nitration mixture oxidizing process
And potassium permanganate oxidation method (ES5011982).Nitration mixture oxidizing process requirement condition is harsh (190～210 DEG C), and equipment investment is big；High
Potassium manganate method yield relatively low (65%), used oxidant potassium permanganate is expensive, and produces substantial amounts of Mn-bearing waste water, makes
Become environmental pollution, be therefore not suitable for the production of 2-chlorine apellagrin.
2-chloro-3-trichloromethyl pyridine is obtained by the 2-chloro-3-further chlorination of chloromethylpyridine, patent US4504665 and
Patent JP58213760 utilizes 2-chloro-3-trichloromethyl pyridine to add pyrohydrolysis in 100% phosphoric acid to prepare 2-chlorine apellagrin, yield
About 80%.The method atom economy utilization ratio is low, and product yield is the highest, and acid consumption is big, and post processing is cumbersome.
Patent CN101602717A is with 2-chloro-3-chloromethylpyridine as raw material, through hydrolysis, hypochlorite oxidation two-step reaction
Obtain 2-chlorine apellagrin.The method has substantial amounts of waste water and salt to produce, unfavorable to industrialized production.
Summary of the invention
It is an object of the invention to overcome the deficiency that prior art severe reaction conditions, product yield are low, cost is high, it is provided that
A kind of method synthesizing 2-chlorine apellagrin.The method, with cheap sodium nitrite/acetate system as oxidant, has reaction condition temperature
With, technique is simple, and yield is high, the advantage of low cost.
The synthetic method of a kind of 2-chlorine apellagrin, the method is with 2-chloro-3-chloromethylpyridine as raw material, with sodium nitrite/vinegar
Acid system is oxidant, and under the conditions of reaction temperature is 0～100 DEG C, reaction prepares 2-chlorine apellagrin.
In certain embodiments: the mol ratio of sodium nitrite and 2-chloro-3-chloromethylpyridine is 1～5:1, acetic acid and 2-
The mol ratio of chloro-3-chloromethylpyridine is 1～5:1.
In some preferred embodiments: the mol ratio of sodium nitrite and 2-chloro-3-chloromethylpyridine is 2～3:1, acetic acid
The mol ratio of 3-chloromethylpyridine chloro-with 2-is 1～3:1.
In certain embodiments: reaction dissolvent is in dimethyl sulfoxide, dimethylformamide, acetone, ethanol and furan
Any one.
In some preferred embodiments: reaction dissolvent is dimethyl sulfoxide or dimethylformamide.
In technical solution of the present invention: the mass ratio of described solvent and 2-chloro-3-chloromethylpyridine is 2～4:1.
In certain embodiments: reaction temperature is 20～50 DEG C.
In some preferred embodiments: reaction temperature is 20～35 DEG C.
Beneficial effects of the present invention:
(1) raw material sources of the present invention produced by-product during producing pesticide imidacloprid, has saved cost, has subtracted
Lack the discharge of pollutant.
(2) present invention is with cheap sodium nitrite/acetate system as oxidant, low cost, and reaction condition is gentle, technique letter
Single, yield is high, overcomes the deficiencies in the prior art.
Detailed description of the invention
Below in conjunction with embodiment, the present invention will be further described, but protection scope of the present invention is not limited to this:
Embodiment 1
Equipped with in the 500ml four-hole boiling flask of mechanical agitation and drying tube, add 103.5g (1.5mol) sodium nitrite,
81g (0.5mol) 2-chloro-3-chloromethylpyridine, 45g (0.75mol) acetic acid and 200g dimethylformamide, start stirring, temperature control
20 DEG C of reactions, liquid chromatograph is monitored.Reaction 4h, 2-chloro-3-chloromethylpyridine converts completely, and reaction terminates.Decompression distills out
Major part solvent, adds water and washes away residual solvent and salt, filter to obtain yellow 2-chlorine apellagrin crude product, and methanol/water (V:V=2:1) is heavily tied
Brilliant, be dried and to obtain 71.6g white solid 2-chlorine apellagrin, purity 98.1%, yield 89.0%.
Embodiment 2
Equipped with in the 500ml four-hole boiling flask of mechanical agitation and drying tube, add 72.4g (1.05mol) sodium nitrite,
81g (0.5mol) 2-chloro-3-chloromethylpyridine, 45g (0.75mol) acetic acid and 162g dimethyl sulfoxide, start stirring, temperature control exists
30 DEG C of reactions, liquid chromatograph is monitored.Reaction 12h, 2-chloro-3-chloromethylpyridine converts completely, and reaction terminates.Decompression distills out big
Partial solvent, adds water and washes away residual solvent and salt, filters to obtain faint yellow 2-chlorine apellagrin crude product, and methanol/water (V:V=2:1) is heavily tied
Brilliant, be dried and to obtain 75.2g white solid 2-chlorine apellagrin, purity 98.5%, yield 94.0%.
Embodiment 3
Equipped with in the 500ml four-hole boiling flask of mechanical agitation and drying tube, add 86.2g (1.25mol) sodium nitrite,
81g (0.5mol) 2-chloro-3-chloromethylpyridine, 67.4g (1.1mol) acetic acid and 162g dimethyl sulfoxide, start stirring, temperature control
20 DEG C of reactions, liquid chromatograph is monitored.Reaction 8h, 2-chloro-3-chloromethylpyridine converts completely, and reaction terminates.Decompression distills out
Major part solvent, adds water and washes away residual solvent and salt, filters to obtain faint yellow 2-chlorine apellagrin crude product, methanol/water (V:V=2:1) weight
Crystallization, be dried to obtain 76.0g white solid 2-chlorine apellagrin, purity 98.6%, yield 95.1%.
Embodiment 4
Equipped with in the 500ml four-hole boiling flask of mechanical agitation and drying tube, add 72.4g (1.05mol) sodium nitrite,
81g (0.5mol) 2-chloro-3-chloromethylpyridine, 45g (0.75mol) acetic acid and 162g dimethyl sulfoxide, start stirring, temperature control exists
50 DEG C of reactions, liquid chromatograph is monitored.Reaction 3h, 2-chloro-3-chloromethylpyridine converts completely, and reaction terminates.Decompression distills out big
Partial solvent, adds water and washes away residual solvent and salt, filters to obtain yellow 2-chlorine apellagrin crude product, methanol/water (V:V=2:1) recrystallization,
It is dried to obtain 74.0g white solid 2-chlorine apellagrin, purity 98.0%, yield 92.0%.
Embodiment 5
Equipped with in the 500ml four-hole boiling flask of mechanical agitation and drying tube, add 72.4g (1.05mol) sodium nitrite,
81g (0.5mol) 2-chloro-3-chloromethylpyridine, 45g (0.75mol) acetic acid and 240g dimethylformamide, start stirring, temperature control
35 DEG C of reactions, liquid chromatograph is monitored.Reaction 4h, 2-chloro-3-chloromethylpyridine converts completely, and reaction terminates.Decompression distills out
Major part solvent, adds water and washes away residual solvent and salt, filter to obtain yellow 2-chlorine apellagrin crude product, and methanol/water (V:V=2:1) is heavily tied
Brilliant, be dried and to obtain 74.8g white solid 2-chlorine apellagrin, purity 98.3%, yield 93.4%.
Embodiment 6
Solvent, with embodiment 1, is only changed to ethanol by reaction condition, obtains 68.8g white solid 2-chlorine apellagrin, purity
78.3%, yield 68.3%.
Embodiment 7
Solvent, with embodiment 1, is only changed to acetone by reaction condition, obtains 66.4g white solid 2-chlorine apellagrin, purity
80.3%, yield 67.7%.
Embodiment 8
Reaction temperature, with embodiment 5, is only reduced to 10 DEG C by reaction condition, obtains 75.4g white solid 2-chlorine apellagrin,
Purity 76.3%, yield 73.9%.
Embodiment 9
Reaction temperature, with embodiment 5, is only reduced to 100 DEG C by reaction condition, obtains 74.6g white solid 2-chlorine cigarette
Acid, purity 80.3%, yield 76.0%.
Claims (8)
1. the synthetic method of a 2-chlorine apellagrin, it is characterised in that: the method is with 2-chloro-3-chloromethylpyridine as raw material, with Asia
Sodium nitrate/acetate system is oxidant, and under the conditions of reaction temperature is 0～100 DEG C, reaction prepares 2-chlorine apellagrin.
The synthetic method of 2-chlorine apellagrin the most according to claim 1, it is characterised in that: sodium nitrite and 2-chloro-3-chloromethane
The mol ratio of yl pyridines is 1～5:1, and the mol ratio of acetic acid and 2-chloro-3-chloromethylpyridine is 1～5:1.
The synthetic method of 2-chlorine apellagrin the most according to claim 2, it is characterised in that: sodium nitrite and 2-chloro-3-chloromethane
The mol ratio of yl pyridines is 2～3:1, and the mol ratio of acetic acid and 2-chloro-3-chloromethylpyridine is 1～3:1.
The synthetic method of 2-chlorine apellagrin the most according to claim 1, it is characterised in that: reaction dissolvent is sub-selected from dimethyl
Any one in sulfone, dimethylformamide, acetone, ethanol and furan.
The synthetic method of 2-chlorine apellagrin the most according to claim 4, it is characterised in that: reaction dissolvent be dimethyl sulfoxide or
Dimethylformamide.
6. according to the synthetic method of the 2-chlorine apellagrin described in claim 4 or 5, it is characterised in that: described solvent and the chloro-3-of 2-
The mass ratio of chloromethylpyridine is 2～4:1.
The synthetic method of 2-chlorine apellagrin the most according to claim 1, it is characterised in that: reaction temperature is 20～50 DEG C.
The synthetic method of 2-chlorine apellagrin the most according to claim 7, it is characterised in that: reaction temperature is 20～35 DEG C.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610551785.0A CN106187876A (en) | 2016-07-13 | 2016-07-13 | A kind of synthetic method of 2 chlorine apellagrins |
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| CN201610551785.0A CN106187876A (en) | 2016-07-13 | 2016-07-13 | A kind of synthetic method of 2 chlorine apellagrins |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110229098A (en) * | 2019-07-22 | 2019-09-13 | 潍坊新绿化工有限公司 | A kind of 2- chlorine apellagrin process for refining and purifying and drying process device |
| CN114062552A (en) * | 2021-11-16 | 2022-02-18 | 上海市农业科学院 | Method for detecting imidacloprid metabolite in plant-derived food |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4144238A (en) * | 1976-04-02 | 1979-03-13 | Lonza, Ltd. | Process for the production of pure white 2-chloronicotinic acid |
| CN101602717A (en) * | 2009-07-21 | 2009-12-16 | 南京第一农药集团有限公司 | A kind of method of Synthetic 2-chlorine apellagrin |
| CN101602714A (en) * | 2009-07-21 | 2009-12-16 | 南京第一农药集团有限公司 | A kind of novel method of Synthetic 2-chlorine apellagrin |
| CN104513198A (en) * | 2014-11-29 | 2015-04-15 | 南京红太阳生物化学有限责任公司 | 2-chloronicotinic acid synthetic method |
-
2016
- 2016-07-13 CN CN201610551785.0A patent/CN106187876A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4144238A (en) * | 1976-04-02 | 1979-03-13 | Lonza, Ltd. | Process for the production of pure white 2-chloronicotinic acid |
| CN101602717A (en) * | 2009-07-21 | 2009-12-16 | 南京第一农药集团有限公司 | A kind of method of Synthetic 2-chlorine apellagrin |
| CN101602714A (en) * | 2009-07-21 | 2009-12-16 | 南京第一农药集团有限公司 | A kind of novel method of Synthetic 2-chlorine apellagrin |
| CN104513198A (en) * | 2014-11-29 | 2015-04-15 | 南京红太阳生物化学有限责任公司 | 2-chloronicotinic acid synthetic method |
Non-Patent Citations (1)
| Title |
|---|
| 尹学琼等: ""由1－溴甲基萘制备1－萘甲酸"", 《精细石油化工》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110229098A (en) * | 2019-07-22 | 2019-09-13 | 潍坊新绿化工有限公司 | A kind of 2- chlorine apellagrin process for refining and purifying and drying process device |
| CN114062552A (en) * | 2021-11-16 | 2022-02-18 | 上海市农业科学院 | Method for detecting imidacloprid metabolite in plant-derived food |
| CN114062552B (en) * | 2021-11-16 | 2023-05-30 | 上海市农业科学院 | Method for detecting imidacloprid metabolites in plant-derived food |
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Effective date of registration: 20180522 Address after: 210047 No. 168 aromatics South Road, Nanjing chemical industry park, Jiangsu Applicant after: Nanjing Red Sun Biological Chemical Co., Ltd. Applicant after: Nanjing Redsun Co., Ltd. Address before: 210048 No. 168 aromatics South Road, Nanjing chemical industry park, Jiangsu Applicant before: Nanjing Red Sun Biological Chemical Co., Ltd. |
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