CN105669535A - One-step synthesis method of 2-chloropyridine from N-pyridine oxide - Google Patents
One-step synthesis method of 2-chloropyridine from N-pyridine oxide Download PDFInfo
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- CN105669535A CN105669535A CN201610125367.5A CN201610125367A CN105669535A CN 105669535 A CN105669535 A CN 105669535A CN 201610125367 A CN201610125367 A CN 201610125367A CN 105669535 A CN105669535 A CN 105669535A
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- Prior art keywords
- chloropyridine
- pyridine oxide
- pyridine
- oxalyl chloride
- triethylamine
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- XHQWNZYGYHDHPQ-UHFFFAOYSA-N C=Nc1ccccn1 Chemical compound C=Nc1ccccn1 XHQWNZYGYHDHPQ-UHFFFAOYSA-N 0.000 description 1
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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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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention discloses a one-step synthesis method of 2-chloropyridine from N-pyridine oxide. The method comprises the following steps: 1) chlorination: adding N-pyridine oxide into a flask, adding dichloromethane, oxalyl chloride and triethylamine, and stirring to react under appropriate conditions; and 2) distillation: transferring the reaction mixture into a 500mL container, heating to 50-70 DEG C, carrying out reduced pressure distillation under the vacuum degree of 0.07-0.09 MPa to remove the dichloromethane, oxalyl chloride, triethylamine, pyridine and other raw materials and other byproducts, continuing heating to 90-95 DEG C, distilling under the vacuum degree of 0.07-0.09 MPa to obtain 2-chloropyridine, wherein the residual high-boiling fraction is a small amount of unreacted N-pyridine oxide. The method can be implemented by two steps, thereby reducing the reaction process and enhancing the yield. The oxalyl chloride and triethylamine are used as reaction reagents to react at low temperature under atmospheric pressure, so that the final 2-chloropyridine yield reaches 90%.
Description
Technical field
The invention belongs to chemosynthesis technical field, particularly to a kind of method of N-pyridine oxide one-step synthesis 2-chloropyridine.
Background technology
2-chloropyridine is an important chemical intermediate, is mainly used in the synthesis of medicine and pesticide, and some of which product is widely used in daily-use chemical industry and crop protection, and market prospect is very good. In medicine, 2-chloropyridine can produce hydryllin pheniramine (1) and antiarrhythmics disopyramide (2); On daily chemical products, 2-chloropyridine can produce a kind of antifungal PTO zinc salt (3); CPPU (4) can be produced in pesticide, it is the plant growth regulator of a kind of brand-new high activity, low toxicity, wide spectrum, its cell division activity having is 10-100 times of kinetins and zeatin, use before the florescence and can become seedless fruit by induced parthenocarpy, improve the percentage of fertile fruit of crop, florescence or when using after spending, it is possible to increase fruit, thus significantly improve yield and the fruit quality of crops.
Start people from 1891 and begin to explore the synthetic route of 2-chloropyridine, elapse through 100 years, the gradual perfection constantly improved with chemical theory along with experiment condition, having developed some new synthetic methods, these methods are divided into the chlorination of three kinds of (1) pyridine derivates according to the difference of raw material; (2) direct chlorination of pyridine; (3) other cyclisation method.
Route 1: produce for raw material with PA:
The synthesis of the raw material PA of route 1 is relatively difficult, and total recovery is not high.
Route 2: produce for raw material with 2 hydroxy pyrimidine:
The raw material sources of route 2 are relatively difficult equally and need to pass into phosgene, are unfavorable for the protection of personal safety and environment.
Route 3: synthesize for raw material direct chlorination with pyridine:
The technological requirement of route 3 is higher, and by-product is relatively more and once through yield is low.
Route 4: with pyridine for raw material through peroxidating, chlorination, also originally produced:
The raw material of route 4 is pyridine, and raw material is easy to get comparatively speaking, but the step of reaction is relatively more, and the yield causing entirety is relatively low.
Summary of the invention
In order to overcome the problems referred to above, a kind of method that it is an object of the invention to provide N-pyridine oxide one-step synthesis 2-chloropyridine,
Technical scheme is implemented as described below: a kind of method of N-pyridine oxide one-step synthesis 2-chloropyridine, concrete steps: 1) chlorination: N-pyridine oxide is joined in flask, add dichloromethane, oxalyl chloride and triethylamine stirring reaction under suitable conditions;
2) distillation: reactant mixture is moved in 500mL container, it is warming up to 50 DEG C-70 DEG C, decompression distillation is carried out when vacuum 0.07-0.09MPa, remove raw material and other by-products such as dichloromethane, oxalyl chloride, triethylamine, pyridine, it is continuously heating to 90-95 DEG C, vacuum is 0.07-0.09MPa, and the 2-chloropyridine that distillation obtains, remaining high boiling fraction is the N-pyridine oxide that a small amount of unreacted is complete.
Optimizing further, step 1) mole of medium-height grass acyl chlorides is 1.2-1.4:1 with the ratio of the mole of N-pyridine oxide.
Optimize further, step 1) in the mole of triethylamine be 1:1 with the mole of oxalyl chloride.
Optimize further, step 1) in the temperature of reaction control at 5 DEG C, along with the rising of temperature, the productivity of 2-chloropyridine presents a kind of trend being gradually reduced.
Optimize further, step 1) in time of reaction be 1 hour.
Optimize further, step 1) in the quality of dichloromethane be 2:1 with the mass ratio of N-pyridine oxide.
Compared with prior art, provide the benefit that: 1) the inventive method reaction need not move through N-aoxidize-2-chloropyridine as intermediate, N-pyridine oxide is generated through peroxidating from pyridine, N-pyridine oxide generates N-then through chlorination and aoxidizes-2-chloropyridine, reduction afterwards generates 2-chloropyridine, need three-step reaction, the method two step altogether, decrease course of reaction and improve yield; 2) reaction utilizes oxalyl chloride and triethylamine as reaction reagent, and reaction carries out under low-temperature atmosphere-pressure, and the productivity of final 2-chloropyridine reaches 90%.
Detailed description of the invention
Illustrated embodiment is to better present disclosure be illustrated, but is not that present disclosure is only limitted to illustrated embodiment.
Embodiment 1
The N-pyridine oxide of 95g is joined in flask, adds 190g dichloromethane, 155g oxalyl chloride and 123g triethylamine stirring reaction 1 hour when 5 DEG C; Being moved to by reactant in 500mL distillating still, carry out decompression distillation when temperature 65 DEG C, vacuum 0.07Mpa, after waiting until not have liquid to steam, continue to raise temperature to 90 DEG C, the material that vacuum 0.09Mpa steams is 2-chloropyridine. Remaining material is N-pyridine oxide. The content of 2-chloropyridine is 94.6% after testing, and productivity is 89.2%.
Embodiment 2
The N-pyridine oxide of 95g is joined in flask, adds 190g dichloromethane, 160g oxalyl chloride and 127g triethylamine stirring reaction 1.5 hours when 5 DEG C; Being moved to by reactant in 500mL distillating still, carry out decompression distillation when temperature 65 DEG C, vacuum 0.08Mpa, after waiting until not have liquid to steam, continue to raise temperature to 93 DEG C, the material that vacuum 0.09Mpa steams is 2-chloropyridine. Remaining material is N-pyridine oxide.The content of 2-chloropyridine is 95.6% after testing, and productivity is 89.9%.
Embodiment 3
The N-pyridine oxide of 95g is joined in flask, adds 190g dichloromethane, 160g oxalyl chloride and 130g triethylamine stirring reaction 1.5 hours when 10 DEG C; Being moved to by reactant in 500mL distillating still, at temperature 70 C, carry out decompression distillation when vacuum 0.07Mpa, after waiting until not have liquid to steam, continue to raise temperature to 90 DEG C, the material that vacuum 0.09Mpa steams is 2-chloropyridine. Remaining material is N-pyridine oxide. The content of 2-chloropyridine is 94.1% after testing, and productivity is 90.2%.
Embodiment 4
The N-pyridine oxide of 95g is joined in flask, adds 190g dichloromethane, 165g oxalyl chloride and 133g triethylamine stirring reaction 1 hour when 8 DEG C; Being moved to by reactant in 500mL distillating still, temperature 65 DEG C, carry out decompression distillation when vacuum 0.07Mpa, after waiting until not have liquid to steam, continue to raise temperature to 90 DEG C, the material that vacuum 0.09Mpa steams is 2-chloropyridine. Remaining material is N-pyridine oxide. The content of 2-chloropyridine is 94.8% after testing, and productivity is 90.1%.
Embodiment 5
The N-pyridine oxide of 95g is joined in flask, adds 190g dichloromethane, 155g oxalyl chloride and 123g triethylamine stirring reaction 1.5 hours when 10 DEG C; Being moved to by reactant in 500mL distillating still, at temperature 60 C, carry out decompression distillation when vacuum 0.07Mpa, after waiting until not have liquid to steam, continue to raise temperature to 90 DEG C, the material that vacuum 0.09Mpa steams is 2-chloropyridine. Remaining material is N-pyridine oxide. The content of 2-chloropyridine is 93.6% after testing, and productivity is 88.9%.
Embodiment 6
The N-pyridine oxide of 95g is joined in flask, adds 190g dichloromethane, 170g oxalyl chloride and 135g triethylamine stirring reaction 1 hour when 8 DEG C; Being moved to by reactant in 500mL distillating still, at temperature 70 C, carry out decompression distillation when vacuum 0.09Mpa, after waiting until not have liquid to steam, continue to raise temperature to 90 DEG C, the material that vacuum 0.09Mpa steams is 2-chloropyridine. Remaining material is N-pyridine oxide. The content of 2-chloropyridine is 94.6% after testing, and productivity is 89.9%.
Embodiment 7
The N-pyridine oxide of 95g is joined in flask, adds 190g dichloromethane, 175g oxalyl chloride and 140g triethylamine stirring reaction 1 hour when 5 DEG C; Being moved to by reactant in 500mL distillating still, at temperature 70 C, carry out decompression distillation when vacuum 0.07Mpa, after waiting until not have liquid to steam, continue to raise temperature to 90 DEG C, the material that vacuum 0.09Mpa steams is 2-chloropyridine. Remaining material is N-pyridine oxide. The content of 2-chloropyridine is 95.6% after testing, and productivity is 91.2%.
Embodiment 8
The N-pyridine oxide of 95g is joined in flask, adds 190g dichloromethane, 165g oxalyl chloride and 135g triethylamine stirring reaction 1.5 hours when 5 DEG C; Being moved to by reactant in 500mL distillating still, at temperature 60 C, carry out decompression distillation when vacuum 0.09Mpa, after waiting until not have liquid to steam, continue to raise temperature to 95 DEG C, the material that vacuum 0.09Mpa steams is 2-chloropyridine. Remaining material is N-pyridine oxide. The content of 2-chloropyridine is 96.6% after testing, and productivity is 91.1%.
Claims (6)
1. the method with N-pyridine oxide one-step synthesis 2-chloropyridine, it is characterised in that concrete steps: 1) chlorination: N-pyridine oxide is joined in flask, add dichloromethane, oxalyl chloride and triethylamine stirring reaction under suitable conditions;
2) distillation: reactant mixture is moved in 500mL container, it is warming up to 50 DEG C-70 DEG C, decompression distillation is carried out when vacuum 0.07-0.09MPa, remove raw material and other by-products such as dichloromethane, oxalyl chloride, triethylamine, pyridine, it is continuously heating to 90-95 DEG C, vacuum is 0.07-0.09MPa, and the 2-chloropyridine that distillation obtains, remaining high boiling fraction is the N-pyridine oxide that a small amount of unreacted is complete.
2. method according to claim 1, it is characterised in that described step 1) mole of medium-height grass acyl chlorides is 1.2-1.4:1 with the ratio of the mole of N-pyridine oxide.
3. method according to claim 1, it is characterised in that described step 1) in the mole of triethylamine and the mole of oxalyl chloride be 1:1.
4. method according to claim 1, it is characterised in that described step 1) in reaction temperature control at 5 DEG C.
5. method according to claim 1, it is characterised in that described step 1) in reaction time be 1 hour.
6. method according to claim 1, it is characterised in that described step 1) in the quality of dichloromethane and the mass ratio of N-pyridine oxide be 2:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610125367.5A CN105669535A (en) | 2016-03-04 | 2016-03-04 | One-step synthesis method of 2-chloropyridine from N-pyridine oxide |
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| CN201610125367.5A CN105669535A (en) | 2016-03-04 | 2016-03-04 | One-step synthesis method of 2-chloropyridine from N-pyridine oxide |
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| CN105669535A true CN105669535A (en) | 2016-06-15 |
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| CN201610125367.5A Pending CN105669535A (en) | 2016-03-04 | 2016-03-04 | One-step synthesis method of 2-chloropyridine from N-pyridine oxide |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20000051206A (en) * | 1999-01-19 | 2000-08-16 | 구광시 | A process for the preparation of 2-chloropyridine |
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2016
- 2016-03-04 CN CN201610125367.5A patent/CN105669535A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20000051206A (en) * | 1999-01-19 | 2000-08-16 | 구광시 | A process for the preparation of 2-chloropyridine |
Non-Patent Citations (3)
| Title |
|---|
| JAE-CHUL JUNG ET AL.: "PREPARATION OF 2-CHLOROPYRIDINE", 《SYNTHETIC COMMUNICATIONS》 * |
| 杨凤玲等: "草酰氯的合成及应用", 《杭州化工》 * |
| 王顺明等: "2-氯吡啶的合成研究", 《应用化工》 * |
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Application publication date: 20160615 |
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