CN115611806A - Preparation method of 4-trifluoromethyl-3-cyanopyridine - Google Patents
Preparation method of 4-trifluoromethyl-3-cyanopyridine Download PDFInfo
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- CN115611806A CN115611806A CN202211395719.0A CN202211395719A CN115611806A CN 115611806 A CN115611806 A CN 115611806A CN 202211395719 A CN202211395719 A CN 202211395719A CN 115611806 A CN115611806 A CN 115611806A
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- DHIRCRHQLUNYDS-UHFFFAOYSA-N 4-(trifluoromethyl)pyridine-3-carbonitrile Chemical compound FC(F)(F)C1=CC=NC=C1C#N DHIRCRHQLUNYDS-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims abstract description 41
- WRXXBTBGBXYHSG-UHFFFAOYSA-N 2,6-dichloro-4-(trifluoromethyl)pyridine-3-carbonitrile Chemical compound FC(F)(F)C1=CC(Cl)=NC(Cl)=C1C#N WRXXBTBGBXYHSG-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000003054 catalyst Substances 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 239000002253 acid Substances 0.000 claims abstract description 9
- 239000011230 binding agent Substances 0.000 claims abstract description 9
- 230000035484 reaction time Effects 0.000 claims abstract description 5
- 239000007858 starting material Substances 0.000 claims abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 66
- 238000006243 chemical reaction Methods 0.000 claims description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 20
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 17
- 239000012046 mixed solvent Substances 0.000 claims description 10
- 238000005984 hydrogenation reaction Methods 0.000 claims description 9
- 238000004821 distillation Methods 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- 239000012452 mother liquor Substances 0.000 claims description 8
- 238000005070 sampling Methods 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims 1
- 238000007086 side reaction Methods 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 230000000382 dechlorinating effect Effects 0.000 abstract 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000002994 raw material Substances 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- 238000001816 cooling Methods 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- OZECFIJVSAYAPH-UHFFFAOYSA-N ethyl-di(propan-2-yl)azanium;chloride Chemical compound Cl.CCN(C(C)C)C(C)C OZECFIJVSAYAPH-UHFFFAOYSA-N 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 3
- LMRJHNFECNKDKH-UHFFFAOYSA-N 4-(trifluoromethyl)nicotinic acid Chemical compound OC(=O)C1=CN=CC=C1C(F)(F)F LMRJHNFECNKDKH-UHFFFAOYSA-N 0.000 description 2
- 230000009849 deactivation Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- -1 trifluoromethyl aromatic compound Chemical class 0.000 description 2
- 239000003513 alkali Substances 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006467 substitution reaction Methods 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
- C07D213/85—Nitriles in position 3
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- Organic Chemistry (AREA)
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Abstract
The invention relates to the field of organic synthesis, in particular to a preparation method of 4-trifluoromethyl-3-cyanopyridine, which comprises the following steps: the method comprises the steps of dechlorinating 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine serving as a starting material and diisopropylethylamine serving as an acid-binding agent under the action of hydrogen and a catalyst to prepare the 4-trifluoromethyl-3-cyanopyridine. The method takes diisopropylethylamine as an acid-binding agent in the hydrodechlorination process, has the advantages of high selectivity, no side reaction, short reaction time, high product yield and purity, simple post-treatment and suitability for industrial production.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of 4-trifluoromethyl-3-cyanopyridine.
Background
4-trifluoromethyl-3-cyanopyridine is a useful synthetic intermediate, and 4-trifluoromethyl nicotinic acid can be synthesized through one-step alkaline hydrolysis reaction. The 4-trifluoromethyl nicotinic acid is a trifluoromethyl aromatic compound, has unique biological activity, can be used as a precursor substance for preparing other pesticides or medicines, and has important value.
At present, 2, 6-dichloro-3-cyano-4-trifluoromethylpyridine is used as a raw material to synthesize 3-cyano-4-trifluoromethylpyridine through hydrogenation catalytic reaction.
In patents CN101851193A, CN107286086A, CN108191749A and CN112110855A, triethylamine is used as an acid-binding agent in the hydrogenation catalytic reaction, but in practical studies, it is found that 2, 6-dichloro-3-cyano-4-trifluoromethylpyridine and triethylamine can react under the conditions of normal temperature and normal pressure, and the reaction formula is as follows:
therefore, triethylamine is used as an acid-binding agent, so that serious side reaction interference exists, the selectivity is poor, and the yield is low.
In patent CN108586328A and CN109232407A, inorganic base sodium carbonate is used as an acid-binding agent in the hydrogenation catalytic reaction, but sodium carbonate has poor solubility in a nonpolar solvent, and the effect is not obvious, and needs to be used in combination with solvents such as methanol or ethanol, but experiments prove that methanol or ethanol and 2, 6-dichloro-3-cyano-4-trifluoromethylpyridine can perform the following reactions:
therefore, sodium carbonate is used as an acid binding agent, methanol or ethanol is used as a solvent, and the synthesis of 3-cyano-4-trifluoromethyl pyridine also has more problems. And the sodium carbonate has relatively strong alkalinity and is easy to cause the hydrolysis of the 2, 6-dichloro-3-cyano-4-trifluoromethyl pyridine.
Disclosure of Invention
The invention aims to provide a preparation method of 4-trifluoromethyl-3-cyanopyridine, which has the advantages of short reaction time, high product yield and purity and simple post-treatment aiming at the problems in the prior art.
In order to achieve the purpose, the technical scheme of the invention is as follows: a preparation method of 4-trifluoromethyl-3-cyanopyridine comprises the following steps:
the method comprises the following steps of taking 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine as a starting material, diisopropylethylamine as an acid-binding agent, toluene and water as a mixed solvent, and reacting under the action of a catalyst and hydrogen to prepare the 4-trifluoromethyl-3-cyanopyridine by using a specific reaction formula as follows:
preferably, the preparation method comprises the following steps: adding 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine, diisopropylethylamine, toluene, water and a palladium carbon catalyst into a high-pressure reaction kettle, replacing nitrogen, filling hydrogen, heating, reacting, sampling, analyzing, adding water after the reaction is qualified, filtering to remove the catalyst, layering mother liquor, desolventizing an oil layer, and distilling under reduced pressure to obtain the 4-trifluoromethyl-3-cyanopyridine.
Preferably, the molar ratio of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine to diisopropylethylamine is 1. Preferably, the molar ratio of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine to diisopropylethylamine is 1.
Preferably, the mass ratio of the mixed solvent toluene to water is 45:1 to 3, the mass of the mixed solvent toluene and water is 1 to 10 times of the mass of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine. Preferably, the mass of the mixed solvent toluene and water is 1 to 5 times that of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine.
Preferably, the Pd content of the palladium carbon catalyst is 0.5-10%; the dosage of Pd/C is 0.05-10% of the mass of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine.
Preferably, the Pd content of the palladium carbon catalyst is 0.5-10%; the dosage of Pd/C is 0.05-5% of the mass of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine. Preferably, the dosage of Pd/C is 0.5-5% of the mass of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine.
Preferably, the pressure of hydrogen is from 0.1MPa to 10MPa.
Preferably, the pressure of hydrogen is 0.1MPa to 5MPa. Preferably, the pressure of hydrogen is 0.1MPa to 3MPa.
Preferably, the reaction temperature in the hydrogenation process is 20-120 ℃. Preferably, the reaction temperature in the hydrogenation process is 50-100 ℃.
Preferably, the hydrogenation reaction time is 1-10h. Preferably, the hydrogenation reaction time is 1-5h.
The beneficial effects of the invention are as follows: the invention provides a preparation method of 4-trifluoromethyl-3-cyanopyridine, which is a reaction system taking diisopropylethylamine as an acid-binding agent and toluene and water as mixed solvents. Diisopropylethylamine does not have side reaction with 2, 6-dichloro-3-cyano-4-trifluoromethylpyridine due to large steric hindrance, has moderate basicity, and can well form hydrochloride with generated hydrogen chloride. The diisopropylethylamine improves the selectivity and the reaction speed of the reaction, and improves the reaction yield, thereby reducing the production cost. After the diisopropylethylamine forms hydrochloride, the diisopropylethylamine can be regenerated by adding alkali to neutralize the hydrochloric acid and can be recycled and reused. Diisopropylethylamine is hardly dissolved in water, has good stability compared with triethylamine, hardly generates loss in the recovery process, and is suitable for industrial production. The mixed solvent system of toluene and water is used, so that the side reaction of alcohol substances and 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine is avoided, the post-reaction treatment process is simplified, and the reaction operation is optimized. The small amount of water mixed in the toluene can effectively dissolve the diisopropylethylamine hydrochloride generated in the reaction process, so that the diisopropylethylamine hydrochloride is dispersed in the reaction system in a liquid form, and the diisopropylethylamine hydrochloride is prevented from being separated out in a solid form. The precipitation of diisopropylethylamine hydrochloride encapsulates the palladium on carbon catalyst, resulting in catalyst deactivation. Therefore, compared with the single toluene or alcohol solvent, the mixed solvent system of toluene and water can effectively avoid the problem of palladium-carbon catalyst deactivation, and side reactions similar to the alcohol solvent can not occur. The method has the advantages of easily available raw materials, low cost, short steps, simplified process flow, high product content and yield, capability of greatly reducing the cost and improving the yield, and suitability for industrial production.
Drawings
FIG. 1 is a nuclear magnetic spectrum of 4-trifluoromethyl-3-cyanopyridine from example 1;
FIG. 2 is a 4-trifluoromethyl-3-cyanopyridine gas mass spectrum of example 1.
Detailed Description
Example 1
450g of toluene, 1.47g of 5% palladium carbon catalyst, 144.60g of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine, 155.08g of diisopropylethylamine and 10.0g of water are added into a high-pressure reaction kettle, hydrogen is replaced for three times, the pressure is increased to 0.5MPa, and the temperature is increased to 50-60 ℃ for reaction. Sampling and analyzing (GC) after reacting for 2 hours, and judging that the reaction is qualified when the content of the raw material is less than 0.3%;
after the reaction is finished, adding 300g of ice water, stirring for 10min, cooling to room temperature, and filtering to remove the palladium-carbon catalyst; separating the filtered mother liquor, wherein the upper layer is an oil phase, and the lower layer is a water phase;
the oil phase is distilled and desolventized at normal pressure, most of toluene solvent is removed, and then reduced pressure distillation is carried out, 101.20g of product is distilled out, the yield is 98.0%, and the content is 99%.
Nuclear magnetic data of 1 HNMR(400MHz，CDCl 3 ): 9.12 (s, 1H), 9.06 (d, J =5.12hz, 1h), 7.79 (d, J =5.12hz, 1h). The gas chromatography showed a product retention time of 6.044min, corresponding to a molecular weight of 172.1 (actual molecular weight of 172.11), from which the product was determined to be 4-trifluoromethyl-3-cyanopyridine.
Example 2
450g of toluene, 1.00g of 10 percent palladium carbon catalyst, 144.60g of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine, 155.08g of diisopropylethylamine and 10.0g of water are added into a high-pressure reaction kettle, hydrogen is replaced for three times, the pressure is increased to 0.5MPa, and the temperature is increased to 50-60 ℃ for reaction. Sampling and analyzing (GC) after reacting for 2 hours, and judging that the reaction is qualified when the content of the raw material is less than 0.3%;
after the reaction is finished, adding 300g of ice water, stirring for 10min, cooling to room temperature, and filtering to remove the palladium-carbon catalyst; separating the filtered mother liquor, wherein the upper layer is an oil phase and the lower layer is a water phase;
the oil phase is subjected to atmospheric distillation and desolventizing, most of toluene solvent is removed, and then the reduced pressure distillation is carried out, the distilled product is 100.17g, the yield is 97.0 percent, and the content is 99 percent.
Example 3
450g of toluene, 5.00g of 1% palladium-carbon catalyst, 144.60g of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine, 155.08g of diisopropylethylamine and 10.0g of water are added into a high-pressure reaction kettle, hydrogen is replaced for three times, the pressure is increased to 0.8MPa, and the temperature is increased to 60-70 ℃ for reaction. Sampling and analyzing (GC) after 4h of reaction, and judging that the reaction is qualified when the content of the raw material is less than 0.3%;
after the reaction is finished, adding 300g of ice water, stirring for 10min, cooling to room temperature, and filtering to remove the palladium-carbon catalyst; separating the filtered mother liquor, wherein the upper layer is an oil phase, and the lower layer is a water phase;
the oil phase is distilled and desolventized at normal pressure, most of toluene solvent is removed, and then reduced pressure distillation is carried out, 99.14g of product is distilled out, the yield is 96.0%, and the content is 99%.
Example 4
450g of toluene, 1.47g of 5% palladium carbon catalyst, 144.60g of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine, 155.08g of diisopropylethylamine and 10.0g of water are added into a high-pressure reaction kettle, hydrogen is replaced for three times, the pressure is increased to 2.0MPa, and the temperature is increased to 50 ℃ for reaction. Sampling and analyzing (GC) after reacting for 2 hours, and judging that the reaction is qualified when the content of the raw material is less than 0.3%;
after the reaction is finished, adding 300g of ice water, stirring for 10min, cooling to room temperature, and filtering to remove the palladium-carbon catalyst; separating the filtered mother liquor, wherein the upper layer is an oil phase, and the lower layer is a water phase;
the oil phase is distilled and desolventized at normal pressure, most of toluene solvent is removed, and then reduced pressure distillation is carried out, the distilled product is 100.17g, the yield is 97.0 percent, and the content is 99 percent.
Example 5
450g of toluene, 1.47g of 5% palladium carbon catalyst, 144.60g of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine, 155.08g of diisopropylethylamine and 10.0g of water are added into a high-pressure reaction kettle, hydrogen is replaced for three times, the pressure is increased to 0.5MPa, and the temperature is increased to 100 ℃ for reaction. Sampling and analyzing (GC) after reacting for 1.5h, and judging that the reaction is qualified when the content of the raw material is less than 0.3%;
after the reaction is finished, adding 300g of ice water, stirring for 10min, cooling to room temperature, and filtering to remove the palladium-carbon catalyst; separating the filtered mother liquor, wherein the upper layer is an oil phase, and the lower layer is a water phase;
the oil phase is distilled and desolventized at normal pressure, most of toluene solvent is removed, and then reduced pressure distillation is carried out, 95.00g of product is distilled out, the yield is 92.0%, and the content is 99%.
Example 6
450g of toluene, 1.47g of 5% palladium carbon catalyst, 144.60g of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine, 300.00g of diisopropylethylamine and 30.0g of water are added into a high-pressure reaction kettle, hydrogen is replaced for three times, the pressure is increased to 0.5MPa, and the temperature is increased to 50-60 ℃ for reaction. Sampling and analyzing (GC) after reacting for 2.5h, and judging that the reaction is qualified when the content of the raw material is less than 0.3%;
after the reaction is finished, adding 300g of ice water, stirring for 10min, cooling to room temperature, and filtering to remove the palladium-carbon catalyst; separating the filtered mother liquor, wherein the upper layer is an oil phase and the lower layer is a water phase;
the oil phase is distilled and desolventized at normal pressure, most of toluene solvent is removed, and then reduced pressure distillation is carried out, the distilled product is 100.17g, the yield is 97.0 percent, and the content is 99 percent.
The above description is only for the specific embodiments of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are also within the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (10)
1. A preparation method of 4-trifluoromethyl-3-cyanopyridine is characterized by comprising the following steps:
the method comprises the following steps of taking 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine as a starting material, diisopropylethylamine as an acid binding agent, and toluene and water as a mixed solvent, and reacting under the action of a catalyst and hydrogen to prepare the 4-trifluoromethyl-3-cyanopyridine, wherein the specific reaction formula is as follows:
2. the method of claim 1, wherein the method of making comprises: adding 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine, diisopropylethylamine, toluene, water and a palladium carbon catalyst into a high-pressure reaction kettle, introducing hydrogen after nitrogen replacement, heating for reaction, sampling and analyzing, adding water after the reaction is qualified, filtering to remove the catalyst, layering mother liquor, desolventizing an oil layer, and carrying out reduced pressure distillation to obtain the 4-trifluoromethyl-3-cyanopyridine.
3. The process according to claim 1, wherein the molar ratio of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine to diisopropylethylamine is 1 to 10.
4. The method according to claim 1, wherein the mass ratio of the mixed solvent toluene to water is 45:1 to 3, the mass of the mixed solvent toluene and water is 1 to 10 times of the mass of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine.
5. The method of claim 2, wherein the palladium on carbon catalyst is 0.5% to 10% Pd; the dosage of Pd/C is 0.05-10% of the mass of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine.
6. The method as claimed in claim 5, wherein the palladium on carbon catalyst Pd is present in an amount of 0.5% to 10%; the dosage of Pd/C is 0.05-5% of the mass of 2, 6-dichloro-3-cyano-4- (trifluoromethyl) pyridine.
7. The method of claim 2, wherein the pressure of the hydrogen gas is 0.1Mpa to 10Mpa.
8. The method of claim 7, wherein the pressure of the hydrogen gas is 0.1Mpa to 5Mpa.
9. The process of claim 2, wherein the reaction temperature during hydrogenation is in the range of 20 ℃ to 120 ℃.
10. The process of claim 2, wherein the hydrogenation reaction time is from 1 to 10 hours.
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| CN112110855A (en) * | 2020-09-25 | 2020-12-22 | 山东京博生物科技有限公司 | Method for preparing 3-cyano-4-trifluoromethylpyridine by using Ni-Fe/C bimetallic supported catalyst |
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| JP2002322152A (en) * | 2001-04-24 | 2002-11-08 | Koei Chem Co Ltd | Production method of cyanopyridines |
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