CN101659637A - Preparation method of 2-chloro-3-cyanopyridine - Google Patents
Preparation method of 2-chloro-3-cyanopyridine Download PDFInfo
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- CN101659637A CN101659637A CN200910152436A CN200910152436A CN101659637A CN 101659637 A CN101659637 A CN 101659637A CN 200910152436 A CN200910152436 A CN 200910152436A CN 200910152436 A CN200910152436 A CN 200910152436A CN 101659637 A CN101659637 A CN 101659637A
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- cyanopyridine
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- trichloromethyl
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Abstract
The invention provides a preparation method of 2-chloro-3-cyanopyridine, which comprises the steps of: dissolving 3-cyanopyridine-N-oxide and bis(trichloromethyl)carbonate in an organic solvent, dropwise adding organic alkali at the temperature of minus 5 to 40 DEG C, heating to 30 to 75 DEG C for reaction after the dropwise adding; and after reaction, separating and purifying the reaction liquid,thus obtaining the 2-chloro-3-cyanopyridine. Compared with the prior art, the preparation method of 2-chloro-3-cyanopyridine has the beneficial effects that (1) the bis(trichloromethyl)carbonate is asafer chlorinating reagent and used for synthesizing 2-chloro-3-cyanopyridine, which can avoid the generation of highly polluting wastes such as sulfur dioxide, phosphoric waste water and the like, and has little influence on environment; and (2) the preparation method of 2-chloro-3-cyanopyridine has simple technique, relatively mild reaction condition and high chlorination yield.
Description
(1) technical field
The present invention relates to a kind of preparation method of 2-chloro-3-cyanopyridine.
(2) background technology
2-chloro-3-cyanopyridine is important medicine and pesticide intermediate, with it is that raw material can the synthesizing anti-AIDS pharmaceutical nevirapine, anti-depression medicine Midanping, agricultural chemicals such as the medicine of numerous excellent propertys such as non-steroidal anti-inflammatory analgesics niflumic acid and pharynx sulfometuron-methyl, diflufenican can also be as domestic animal feed additive to improve its output.
The synthetic route of existing 2-chloro-3-cyanopyridine has a lot, and wherein route is a raw material with the N-oxide compound (N-oxo-3-cyanopyridine) of 3-cyanopyridine, reacts with chlorination reagent.Used chlorination reagent is thionyl chloride, SULPHURYL CHLORIDE, phosphorus oxychloride, phosphorus pentachloride etc., mainly have the following disadvantages: (1) use thionyl chloride, when SULPHURYL CHLORIDE is done chlorination reagent, can suppress the generation of 2-chloro-5-cyanopyridine, but generated by product 2-hydroxyl-3-cyanopyridine, the yield of product has only 45%, and a large amount of asphyxiant sulfur dioxide gas are emitted in reaction, are difficult to handle (JP8-3018847); (2) use phosphorus oxychloride, when phosphorus pentachloride is done chlorination reagent, it uses consumption is more than 6 times of feed molar amount, has produced a large amount of reluctant phosphorous refuse and spent acid, contaminate environment, be difficult to reach environmental protection requirement (JP59-144759, CN101117332A).In the face of domestic strict day by day environmental regulation, be necessary to develop new alternative method, reduce the environmental pollution when producing 2-chloro-3-cyanopyridine.
(3) summary of the invention
In order to solve the above-mentioned defective of existing Synthetic 2-technical existence of chloro-3-cyanopyridine, the invention provides a kind of preparation method of 2-chloro-3-cyanopyridine, with two (trichloromethyl) carbonic ether as chlorination reagent, N-oxide compound reaction with the 3-cyanopyridine, to improve the chlorination yield, reduce influence to environment.
The technical solution used in the present invention is:
A kind of preparation method of 2-chloro-3-cyanopyridine, described method comprises: 3-cyanopyridine N-oxide compound and two (trichloromethyl) carbonic ether are dissolved in the organic solvent, dripping organic bases in-5～40 ℃ (can directly drip, also can drip after the organic solvent dissolution dilution), be warming up to 30～75 ℃ after dropwising and react, reaction finishes afterreaction liquid and obtains described 2-chloro-3-cyanopyridine through separation and purification; Described organic solvent is one of following: chloroform, ethylene dichloride, methylene dichloride, tetrahydrofuran (THF), 1,4-dioxane, sherwood oil, normal hexane, hexanaphthene, normal heptane, butanone; Described organic bases is one of following: triethylamine, Tri-n-Propylamine, tri-n-butylamine, methylphenylamine, N, dinethylformamide, N,N-dimethylacetamide, pyridine; The ratio of described 3-cyanopyridine N-oxide compound, two (trichloromethyl) carbonic ether, organic bases amount of substance is 1: 0.5～10: 0.5～10.
It is as follows to the present invention relates to reaction formula:
Described separation and purification can be carried out according to this area ordinary method, specifically can be as follows: after the reaction end, and washing and alkali cleaning successively, water is removed in layering, organic addition activated carbon reflux decolour, cooling is filtered, and distillating recovering solvent gets 2-chloro-3-cyanopyridine.
Described organic solvent quality consumption is 2～20 times of 3-cyanopyridine N-oxide mass, is preferably 5～10 times.
The ratio of described 3-cyanopyridine N-oxide compound, two (trichloromethyl) carbonic ether, organic bases amount of substance is preferably 1: 1.0～and 3.5: 1.0～3.5.
Preferably, described temperature of reaction is 45～60 ℃, 2～8 hours reaction times.
Described organic bases is preferably triethylamine or Tri-n-Propylamine.
Preferably, described organic solvent is a sherwood oil, and its quality consumption is 5～10 times of 3-cyanopyridine N-oxide mass.
Preferably, 10～25 ℃ of described organic bases dropping temperatures, 1～2 hour dropping time.
Concrete, described method is as follows: 3-cyanopyridine N-oxide compound and two (trichloromethyl) carbonic ether are dissolved in the sherwood oil, in the Tri-n-Propylamine of 10～25 ℃ of droppings with petroleum ether dissolution, be warming up to 45～60 ℃ after dropwising and reacted 2～8 hours, reaction finishes afterreaction liquid and obtains described 2-chloro-3-cyanopyridine through separation and purification; The ratio of described 3-cyanopyridine N-oxide compound, two (trichloromethyl) carbonic ether, organic bases amount of substance is 1: 1.0～3.5: 1.0～3.5; Described sherwood oil total mass consumption is 5～10 times of 3-cyanopyridine N-oxide mass.
Can utilize liquid chromatography to detect the chlorizate content in the present invention's reaction with the monitoring reaction process.
The present invention compared with prior art, its beneficial effect is embodied in:
(1) two (trichloromethyl) carbonic ether is a kind of chlorination reagent of safety, can avoid the generation of sulfurous gas, the contour polluting waste of phosphorus-containing wastewater with its Synthetic 2-chloro-3-cyanopyridine, and is little to environmental influence.
(2) technology is simple, and the existing relatively method of reaction conditions is gentle, chlorination yield height.
(4) embodiment
The present invention is described further below in conjunction with specific embodiment, but protection scope of the present invention is not limited in this:
Embodiment 1:
Thermometer is housed respectively on the exsiccant there-necked flask, and constant pressure funnel and is filled with the drying tube of calcium chloride, and escaping gas absorbs with aqueous sodium hydroxide solution.With 2.4g (0.02mol) 3-cyanopyridine N-oxide compound, two (trichloromethyl) carbonic ethers (3.0g) that its molar weight is 0.5 times are dissolved in the 20mL ethylene dichloride, triethylamine (1.0g) with 0.5 times of its molar weight under-5 ℃ slowly drips with about 1mL ethylene dichloride dilution back, about 30min dropwises, and is warming up to 60 ℃ of reaction 4h then.Reaction is cooled to room temperature after finishing, water and 10% sodium carbonate solution washing successively, and organic addition activated carbon, the decolouring in 30 minutes that refluxes, cooling is filtered, and gets the filtrate distillating recovering solvent, obtains 2-chloro-3-cyanopyridine, and yield is 20%.
Embodiment 2～4:
The difference of embodiment 2～4 is the mol ratio of 3-cyanopyridine N-oxide compound, two (trichloromethyl) carbonic ether and triethylamine, and other are identical with embodiment 1.The results are shown in following table:
| Embodiment | Three's mol ratio | The yield (%) of 2-chloro-3-cyanopyridine |
| ??2 | ??1∶2∶2 | ??40 |
| ??3 | ??1∶3.5∶3.5 | ??65 |
| ??4 | ??1∶10∶10 | ??66 |
Embodiment 5～11:
The difference of embodiment 5～11 is solvent.And the mole dosage of two (trichloromethyl carbonates) and triethylamine all is 3.5 times of N-oxide compound of 3-cyanopyridine among the embodiment 5～11, and other are identical with embodiment 1.The results are shown in following table:
| Embodiment | Solvent | The yield (%) of 2-chloro-3-cyanopyridine |
| ??5 | Chloroform | ??50 |
| ??6 | Tetrahydrofuran (THF) | ??15 |
| ??7 | 1, the 4-dioxane | ??25 |
| ??8 | Hexanaphthene | ??51 |
| ??9 | Normal heptane | ??56 |
| ??10 | Sherwood oil | ??77 |
| ??11 | Butanone | ??20 |
Embodiment 12～15:
The difference of embodiment 12～15 is catalyzer.The mole dosage of wherein two (trichloromethyl) carbonic ethers and catalyzer all is 3.5 times of N-oxide compound of 3-cyanopyridine, and solvent is a sherwood oil, and other are identical with embodiment 1.The results are shown in following table:
| Embodiment | Catalyzer | The yield (%) of 2-chloro-3-cyanopyridine |
| ??12 | Tri-n-Propylamine | ??76 |
| ??13 | Tri-n-butylamine | ??71 |
| ??14 | Pyridine | ??36 |
| ??15 | ??DMF | ??10 |
Annotate: DMF is N, dinethylformamide
Embodiment 16～30:
The difference of embodiment 16～30 is dropping temperature and temperature of reaction.The mole dosage of wherein two (trichloromethyl) carbonic ethers and Tri-n-Propylamine all is 3.5 times of N-oxide compound of 3-cyanopyridine, and solvent is a sherwood oil, and other are identical with embodiment 1.The results are shown in following table:
| Embodiment | Dropping temperature ℃ | Temperature of reaction ℃ | The yield (%) of 2-chloro-3-cyanopyridine |
| ??16 | ??-5 | ??30 | ??15 |
| ??17 | ??-5 | ??45 | ??49 |
| ??18 | ??-5 | ??60 | ??52 |
| ??19 | ??-5 | ??75 | ??41 |
| ??20 | ??10 | ??30 | ??50 |
| ??21 | ??10 | ??45 | ??80 |
| ????22 | ????10 | ????60 | ????86 |
| ????23 | ????10 | ????75 | ????62 |
| ????24 | ????25 | ????30 | ????50 |
| ????25 | ????25 | ????45 | ????75 |
| ????26 | ????25 | ????60 | ????85 |
| ????27 | ????25 | ????75 | ????68 |
| ????28 | ????40 | ????45 | ????35 |
| ????29 | ????40 | ????60 | ????45 |
| ????30 | ????40 | ????75 | ????40 |
Claims (8)
1. the preparation method of a 2-chloro-3-cyanopyridine, described method comprises: 3-cyanopyridine N-oxide compound and two (trichloromethyl) carbonic ether are dissolved in the organic solvent, drip organic bases in-5～40 ℃, be warming up to 30～75 ℃ after dropwising and react, reaction finishes afterreaction liquid and obtains described 2-chloro-3-cyanopyridine through separation and purification; Described organic solvent is one of following: chloroform, ethylene dichloride, methylene dichloride, tetrahydrofuran (THF), 1,4-dioxane, sherwood oil, normal hexane, hexanaphthene, normal heptane, butanone; Described organic bases is one of following: triethylamine, Tri-n-Propylamine, tri-n-butylamine, methylphenylamine, N, dinethylformamide, N,N-dimethylacetamide, pyridine; The ratio of described 3-cyanopyridine N-oxide compound, two (trichloromethyl) carbonic ether, organic bases amount of substance is 1: 0.5～10: 0.5～10.
2. the method for claim 1 is characterized in that described organic solvent quality consumption is 2～20 times of 3-cyanopyridine N-oxide mass.
3. the method for claim 1 is characterized in that the ratio of described 3-cyanopyridine N-oxide compound, two (trichloromethyl) carbonic ether, organic bases amount of substance is 1: 1.0～3.5: 1.0～3.5.
4. the method for claim 1 is characterized in that described temperature of reaction is 45～60 ℃, 2～8 hours reaction times.
5. the method for claim 1 is characterized in that described organic bases is triethylamine or Tri-n-Propylamine.
6. the method for claim 1 is characterized in that described organic solvent is a sherwood oil, and the quality consumption is 5～10 times of 3-cyanopyridine N-oxide mass.
7. the method for claim 1 is characterized in that described organic bases dropping temperature is 10～25 ℃, 1～2 hour dropping time.
8. the method for claim 1, it is characterized in that described method is as follows: 3-cyanopyridine N-oxide compound and two (trichloromethyl) carbonic ether are dissolved in the sherwood oil, in the Tri-n-Propylamine of 10～25 ℃ of droppings with petroleum ether dissolution, be warming up to 45～60 ℃ after dropwising and reacted 2～8 hours, reaction finishes afterreaction liquid and obtains described 2-chloro-3-cyanopyridine through separation and purification; The ratio of described 3-cyanopyridine N-oxide compound, two (trichloromethyl) carbonic ether, organic bases amount of substance is 1: 1.0～3.5: 1.0～3.5; Described sherwood oil total mass consumption is 5～10 times of 3-cyanopyridine N-oxide mass.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101941943A (en) * | 2010-09-07 | 2011-01-12 | 浙江工业大学 | Synthesis method of 2-chlorine-3-cyanopyridine |
| CN109369519A (en) * | 2018-10-23 | 2019-02-22 | 浙江大学 | A kind of environment-friendly preparation method thereof of the chloro- nicotinonitrile of 2- |
| CN109369521A (en) * | 2018-10-23 | 2019-02-22 | 浙江大学 | A kind of environment-friendly preparation method thereof of 2- chloroquinoline |
-
2009
- 2009-09-08 CN CN200910152436A patent/CN101659637A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101941943A (en) * | 2010-09-07 | 2011-01-12 | 浙江工业大学 | Synthesis method of 2-chlorine-3-cyanopyridine |
| CN109369519A (en) * | 2018-10-23 | 2019-02-22 | 浙江大学 | A kind of environment-friendly preparation method thereof of the chloro- nicotinonitrile of 2- |
| CN109369521A (en) * | 2018-10-23 | 2019-02-22 | 浙江大学 | A kind of environment-friendly preparation method thereof of 2- chloroquinoline |
| CN109369519B (en) * | 2018-10-23 | 2021-05-04 | 浙江大学 | Green preparation method of 2-chloro-3-cyanopyridine |
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Open date: 20100303 |