CN113788784A - Preparation method of 2-fluoro-3-trifluoromethylpyridine - Google Patents
Preparation method of 2-fluoro-3-trifluoromethylpyridine Download PDFInfo
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- CN113788784A CN113788784A CN202111086896.6A CN202111086896A CN113788784A CN 113788784 A CN113788784 A CN 113788784A CN 202111086896 A CN202111086896 A CN 202111086896A CN 113788784 A CN113788784 A CN 113788784A
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Abstract
The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of 2-fluoro-3-trifluoromethylpyridine. The method takes 2, 5-dichloro-3-trifluoromethylpyridine as a raw material, and the raw material is converted into the 2-fluoro-3-trifluoromethylpyridine through directional fluorination and selective hydrogenation reduction dechlorination. The 2, 5-dichloro-3-trifluoromethylpyridine is a derivative of a main byproduct obtained by over-chlorination in the production process of the 2, 3-dichloro-5-trifluoromethylpyridine, belongs to waste, so that the preparation process of the 2-fluoro-3-trifluoromethylpyridine has the advantages of easily available raw materials and low cost, and the reaction process has simple conditions and can realize the high-yield preparation of the 2, 3-dichloro-5-trifluoromethylpyridine.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of 2-fluoro-3-trifluoromethylpyridine.
Background
The information in this background section is only for enhancement of understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art that is already known to a person of ordinary skill in the art.
The 2-fluoro-3-trifluoromethylpyridine is an important chemical intermediate, and can be used for synthesizing herbicide flazasulfuron in the pesticide industry. At present, the scale production technology of the intermediate is relatively lack. The prior related production processes mainly comprise the following steps:
(1) 2-chloro-3-trifluoromethylpyridine was reacted with anhydrous hydrogen fluoride at 120 ℃ for 1 hour using 2, 4, 6-trimethylpyridine as a solvent to obtain 2-fluoro-3-trifluoromethylpyridine in a yield of 80%. The method has high yield, but the original 2-chloro-3-trifluoromethylpyridine is difficult to produce and has high price.
(2) 2-chloro-3-trifluoromethylpyridine and tetramethylammonium fluoride were reacted in DMF at room temperature for 24 hours to chromatographically obtain 2-fluoro-3-trifluoromethylpyridine almost quantitatively, but the problem of the method was the same as above.
(3) 2-chloro-3-trifluoromethylpyridine reacts with anhydrous hydrogen fluoride at 130 ℃, the pressure is near 8MPa, and the reaction time is 48 hours to obtain the 2-fluoro-3-trifluoromethylpyridine. Similar to the above process, the reaction conditions are severe.
(4) The method uses 3-trifluoromethyl pyridine as a raw material, and obtains 2-fluoro-3-trifluoromethyl pyridine in a chromatogram with 97% yield by reacting the 3-trifluoromethyl pyridine in acetonitrile for 1 hour under the action of silver difluoride at room temperature.
(5) 2-chloro-3-pyridinecarboxylic acid is used as a raw material, anhydrous hydrogen fluoride is used as a solvent, and the raw material reacts with sulfur tetrafluoride at 150 ℃ for 16 hours to obtain 2-fluoro-3-trifluoromethylpyridine with the yield of 37%. The method has low yield, high sulfur tetrafluoride price and low feasibility.
Therefore, although the prior art has various methods for producing the 2-fluoro-3-trifluoromethylpyridine, the problems of high raw material cost, difficult raw material acquisition, harsh reaction conditions and low yield generally exist, so that the method for preparing the 2-fluoro-3-trifluoromethylpyridine has important significance for providing the method which has the advantages of easily obtained raw materials, low cost, simple reaction conditions and high yield.
Disclosure of Invention
In order to solve the defects of the prior art, the invention provides a preparation method of 2-fluoro-3-trifluoromethylpyridine, which takes 2, 5-dichloro-3-trifluoromethylpyridine as a raw material and converts the raw material into the 2-fluoro-3-trifluoromethylpyridine through directional fluorination and selective hydrogenation reduction dechlorination. The 2, 5-dichloro-3-trifluoromethylpyridine is a derivative of a main byproduct obtained by over-chlorination in the production process of the 2, 3-dichloro-5-trifluoromethylpyridine, belongs to waste, so that the preparation process of the 2-fluoro-3-trifluoromethylpyridine has the advantages of easily available raw materials and low cost, and the reaction process has simple conditions and can realize the high-yield preparation of the 2, 3-dichloro-5-trifluoromethylpyridine.
The technical scheme is as follows:
a preparation method of 2-fluoro-3-trifluoromethylpyridine comprises the following steps:
(1)2, 5-dichloro-3-trifluoromethylpyridine and an anhydrous fluorinating reagent are subjected to selective fluorination reaction in an aprotic dipolar solvent to generate 2-fluoro-5-chloro-3-trifluoromethylpyridine;
(2) the 2-fluoro-5-chloro-3-trifluoromethylpyridine is subjected to selective catalytic hydrogenation reduction in lower aliphatic alcohol in the presence of an acid-binding agent to remove chlorine element, so as to obtain the 2-fluoro-3-trifluoromethylpyridine.
The reaction principle is as follows:
one or more embodiments of the present invention have at least the following advantageous effects:
(1) the 2, 5-dichloro-3-trifluoromethylpyridine is a derivative of a main byproduct obtained by over-chlorination in the production process of the 2, 3-dichloro-5-trifluoromethylpyridine, belongs to wastes, and the invention takes the 2, 5-dichloro-3-trifluoromethylpyridine as a raw material to be directionally converted into the 2-fluoro-3-trifluoromethylpyridine, so that the 2-fluoro-3-trifluoromethylpyridine has the advantages of easily obtained raw materials and low cost in the preparation process.
(2) The preparation method provided by the invention has the advantages of simple process, easiness in operation, contribution to industrial production, high product yield which can reach more than 90 percent and product purity which can reach more than 99 percent.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the invention and together with the description serve to explain the invention and not to limit the invention.
FIG. 1 is a gas mass spectrum of 2, 5-dichloro-3-trifluoromethylpyridine obtained in example 1;
FIG. 2 is a gas mass spectrum of 2-fluoro-5-chloro-3-trifluoromethylpyridine obtained in example 1;
FIG. 3 is a gas mass spectrum of 2-fluoro-3-trifluoromethylpyridine obtained in example 1.
Detailed Description
It is to be understood that the following detailed description is exemplary and is intended to provide further explanation of the invention as claimed. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.
As introduced in the background art, the method for producing 2-fluoro-3-trifluoromethylpyridine in the prior art generally has the problems of high raw material cost, difficult raw material acquisition, harsh reaction conditions and low yield.
In order to solve the technical problems, the invention provides a preparation method of 2-fluoro-3-trifluoromethylpyridine, which comprises the following steps:
(1)2, 5-dichloro-3-trifluoromethylpyridine and an anhydrous fluorinating reagent are subjected to selective fluorination reaction in an aprotic dipolar solvent to generate 2-fluoro-5-chloro-3-trifluoromethylpyridine;
(2) the 2-fluoro-5-chloro-3-trifluoromethylpyridine is subjected to selective catalytic hydrogenation reduction in lower aliphatic alcohol in the presence of an acid-binding agent to remove chlorine element, so as to obtain the 2-fluoro-3-trifluoromethylpyridine.
The 2, 5-dichloro-3-trifluoromethylpyridine is a derivative of a main byproduct obtained by over-chlorination in the production process of the 2, 3-dichloro-5-trifluoromethylpyridine, belongs to waste, and has no specific use value in production. The method takes 2, 5-dichloro-3-trifluoromethylpyridine as a raw material, and converts the raw material into the 2-fluoro-3-trifluoromethylpyridine through directional fluorination and selective hydrogenation reduction dechlorination, so that the 2, 5-dichloro-3-trifluoromethylpyridine can be effectively recycled, and the preparation process of the 2-fluoro-3-trifluoromethylpyridine has the advantages of easily obtained raw material and low cost while treating wastes.
In one or more embodiments of the present invention, the anhydrous fluorinating agent is a simple inorganic or organic fluoride containing fluoride ions, including but not limited to anhydrous alkali metal fluoride salts, anhydrous quaternary ammonium fluoride salts, anhydrous quaternary phosphonium fluoride salts, molecular adducts of anhydrous hydrogen fluoride and tertiary amines, molecular adducts of anhydrous hydrogen fluoride and pyridines, and the like;
further, the alkali metal salt is lithium, sodium, potassium, rubidium or cesium salt, preferably potassium salt; the quaternary ammonium salt is aliphatic chain and/or aromatic substituted quaternary ammonium salt, such as tetramethyl ammonium fluoride, tetraethyl ammonium fluoride, benzyl triethyl ammonium fluoride, didodecyl dimethyl ammonium fluoride, tetraphenyl ammonium fluoride, preferably tetramethyl ammonium fluoride; the quaternary phosphonium salt is aliphatic chain and/or aromatic substituted quaternary phosphonium salt, such as tetraphenyl phosphine fluoride, benzyl triethyl phosphine fluoride; the three substituents of the tertiary amine may be the same or different and are selected from the group consisting of aliphatic and aromatic, such as trimethylamine, triethylamine, dodecyldimethylamine, dodecylbenzylmethylamine, triphenylamine, preferably hydrogen fluoride-triethylamine (3: 1); the pyridine includes mono-or poly-substituted pyridine compounds, preferably hydrogen fluoride-pyridine (1: 1).
In one or more embodiments of the invention, the anhydrous fluorinating agent is used in an amount of 1.05 to 1.5 times the molar amount of 2, 5-dichloro-3-trifluoromethylpyridine.
In one or more embodiments of the present invention, the aprotic dipolar solvent includes:
chain ketones and cyclic ketones having 3 to 6 carbon atoms, preferably acetone;
or a chain nitrile, dinitrile or cyclic nitrile, dinitrile having 2 to 6 carbon atoms, preferably acetonitrile;
or chain or cyclic ethers, diethers of 3 to 6 carbon atoms, preferably tetrahydrofuran and dioxane;
or, a linear or cyclic amide of 3 to 6 carbon atoms, preferably N, N-dimethylformamide and N-methylpyrrolidone;
or, chain sulfones or sulfoxides and cyclic sulfones or sulfoxides of 2 to 4 carbon atoms, preferably dimethyl sulfoxide and sulfolane;
or one or two or more of morpholines with 3-6 carbon atoms, preferably N-formyl morpholine;
the amount of the aprotic dipolar solvent is 2-15 times of the mass of the 2, 5-dichloro-3-trifluoromethylpyridine.
Further, the aprotic dipolar solvent is an aprotic dipolar solvent having a high boiling point, and is preferably N, N-dimethylformamide, N-dimethylacetamide, sulfolane, N-methylpyrrolidone, or N-formylmorpholine.
In one or more embodiments of the present invention, the reaction in step (1) comprises a phase transfer catalyst, preferably quaternary ammonium salts and quaternary phosphonium salts, more preferably quaternary phosphonium salts, most preferably inexpensive and readily available quaternary phosphonium salts containing bromine or iodine with a molecular weight of 200-400, such as tetraphenylphosphonium bromide.
Further, the temperature of the selective fluorination reaction is 50-170 ℃, preferably 80-170 ℃, and the reaction time is 4-20 hours.
Further, after the selective fluorination reaction, the product is filtered, redundant salt is removed from the reaction solution, the solvent is distilled out under normal pressure or reduced pressure and is used repeatedly, water is added to directly carry out steam rectification to separate the intermediate 2-fluoro-5-chloro-3-trifluoromethylpyridine and the raw material 2, 5-dichloro-3-trifluoromethylpyridine, and the raw material is used repeatedly.
Further, the lower aliphatic alcohol in the step (2) is one or more of methanol, ethanol, propanol and isopropanol, preferably methanol and ethanol, and the amount of the lower aliphatic alcohol is 1-5 times of the mass of the 2, 5-dichloro-3-trifluoromethylpyridine.
Further, the acid-binding agent in step (2) comprises weak acid alkali metal or ammonium salt, tertiary amine, pyridine, and the weak acid alkali metal or ammonium salt includes but is not limited to sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium acetate, potassium acetate, ammonium carbonate, diammonium phosphate; tertiary amines include, but are not limited to, triethylamine, tripropylamine, dodecyldimethylamine, dodecylbenzylmethylamine, triphenylamine; pyridines include, but are not limited to, pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine; the acid-binding agent can be one or more than two; the dosage of the acid-binding agent is 1.05 to 1.5 times, preferably 1.2 to 1.3 times of the theoretical consumption molar weight according to the total reaction of the raw material 2-fluoro-5-chloro-3-trifluoromethyl pyridine.
In one or more embodiments of the present invention, the selective catalytic hydrogenation reduction process in step (2) is specifically: in the presence of an acid binding agent, 2-fluoro-5-chloro-3-trifluoromethylpyridine is catalyzed by a metal catalyst under certain hydrogen pressure to generate dechlorination reaction, or 2-fluoro-5-chloro-3-trifluoromethylpyridine is reacted with 1 to 8 times (preferably 3 to 5 times) of molar quantity of ammonium formate or alkali metal salt of formic acid, and chlorine atoms on the 2-fluoro-5-chloro-3-trifluoromethylpyridine are removed by catalytic reduction.
Further, the metal catalyst is one or more of nickel, palladium, platinum, iridium and ruthenium metal; palladium metal is preferred.
Further, the mass fraction of the added metal catalyst is 0.01-5 percent according to the weight of the 2-fluoro-5-chloro-3-trifluoromethylpyridine; preferably 0.01 to 1.0%.
Furthermore, one or more of nickel, palladium, platinum, iridium and ruthenium can be loaded on an inert substrate for use;
the inert substrate is a material which is inert and does not participate in catalytic hydrogenation reaction, such as active carbon, diatomite, ZSM-5 molecular sieve, magnesium oxide, titanium dioxide, alumina and the like;
the amount of the metal loaded on the inert substrate is 0.1 to 10 percent, preferably 3.0 to 7.0 percent, and more preferably 5 percent by weight;
furthermore, the water content of the catalyst formed by loading metal on the inert substrate is 1.0-70.0%;
further, the catalytic hydrogenation reduction reaction is carried out in a slurry bed reactor.
In one or more embodiments of the present invention, the reaction conditions for the catalytic hydrogenation reduction reaction are: the reaction temperature is 50-150 ℃, and the optimal temperature is 55-90 ℃; the reaction time is 6-16 hours;
the reaction pressure is 0.1MPa to 4.0MPa, preferably 0.1MPa to 2.0 MPa.
The process of the present invention is further explained below.
The preparation method of the 2-fluoro-3-trifluoromethylpyridine comprises the following steps:
(1)2, 5-dichloro-3-trifluoromethylpyridine reacts with a fluorinating reagent in an aprotic dipolar solvent to generate 2-fluoro-5-chloro-3-trifluoromethylpyridine, and the 2-fluoro-5-chloro-3-trifluoromethylpyridine is subjected to desolventizing and steam distillation purification;
(2) the 2-fluoro-5-chloro-3-trifluoromethylpyridine is subjected to catalytic hydrogenation reduction to remove chlorine element, so as to obtain the 2-fluoro-3-trifluoromethylpyridine, and after the reaction is finished, the 2-fluoro-3-trifluoromethylpyridine is filtered, desolventized, rectified and purified.
And (3) carrying out the reactions of the step (1) and the step (2) in the front and back steps, and carrying out normalized tracking by using a gas chromatograph.
In the step (1), the fluorination reagent is preferably added at a relatively low temperature, and the temperature can be raised for reflux in the later stage for accelerating the completion of the reaction.
In the step (2), the adopted metal catalyst is used and then applied again, the effect is still good, a new catalyst does not need to be additionally added generally, and the route avoids the poisoning effect of the substrate containing oxygen on the catalyst.
The reaction principle is as follows:
physical properties of 2-fluoro-3-trifluoromethylpyridine:
the molecular formula is as follows: c6H3F4N
Molecular weight: 165.09
Density: 1.355g/ml 25 deg.C
Boiling point: 113 deg.C
In order to make the technical solutions of the present invention more clearly understood by those skilled in the art, the technical solutions of the present invention will be described in detail below with reference to specific embodiments.
Example 1
A preparation method of 2-fluoro-3-trifluoromethylpyridine comprises the following steps:
(1) selective fluorination
21.82g (99 percent, 0.10mol) of 2, 5-dichloro-3-trifluoromethylpyridine, 100ml of anhydrous acetonitrile and 9.78g (0.105mol) of tetramethylammonium fluoride are added into a 500ml three-necked bottle at the room temperature of 20-30 ℃, stirred for 1 hour at the room temperature, gradually heated to 50 ℃, reacted for 2 hours, heated and refluxed for 4 hours, the reaction end point is determined by gas chromatography tracking test, filtered, a filter cake is washed, desolventized, 100ml of water is added into the reaction solution for steam rectification and purification, 18.95g of 2-fluoro-5-chloro-3-trifluoromethylpyridine is obtained, the content of the gas chromatography is 99.0 percent, the yield of the step is about 95 percent basically, and the product is colorless pungent transparent liquid.
(2) Catalytic hydrogenation
40.30g (99.0 percent, calculated as 0.2mol) of 2-fluoro-5-chloro-3-trifluoromethylpyridine, 41.5g (1.5 equivalent) of potassium carbonate, 240ml of isopropanol and 0.33g of palladium carbon are added into a 1000ml autoclave, about 300ml of the materials are subjected to vacuum replacement of hydrogen and pressurization to 2.0MPa, the hydrogen is added after the intermediate pressure is reduced, the reaction temperature is 55 ℃, the reaction is carried out for 12 hours, the temperature is reduced to room temperature, the sampling gas chromatography is followed, the reaction conversion rate is 98 percent, the product is 2-fluoro-3-trifluoromethylpyridine through gas chromatography, the salt and the catalyst are removed through filtration, the filter cake is washed with water to recover the catalyst, the filtrate is rectified and purified at normal pressure to obtain 31.35g, the content of the gas chromatography is 99 percent, and the product is colorless pungent and transparent liquid.
Example 2
A preparation method of 2-fluoro-3-trifluoromethylpyridine comprises the following steps:
(1) selective fluorination
21.82g (99 percent, 0.10mol) of 2, 5-dichloro-3-trifluoromethylpyridine, 300ml of acetone and 27.46g (0.105mol) of tetrabutylammonium fluoride are added into a 500ml three-necked bottle at the room temperature of 20-30 ℃, stirred for 1 hour at the room temperature, gradually heated to 50 ℃, reacted for 4 hours, the reaction endpoint is determined by a gas chromatography tracking test, filtered, a filter cake is washed, desolventized, 100ml of water is added into the reaction solution for steam rectification and purification, 19.18g of 2-fluoro-5-chloro-3-trifluoromethylpyridine is obtained, the content of the gas chromatography is 98.8.0 percent, the yield of the step is about 95 percent basically, and the product is colorless pungent transparent liquid.
(2) Catalytic hydrogenation
40.38g (98.80 percent, calculated as 0.2mol) of 2-fluoro-5-chloro-3-trifluoromethylpyridine is added into a 1000ml autoclave, 21.21g (1.05 equivalent) of triethylamine, 240ml of anhydrous methanol and 0.35g of palladium carbon are added, about 300ml of the materials are subjected to vacuum replacement of hydrogen and pressurization to 2.0MPa, the intermediate pressure is reduced and the hydrogen is added, the reaction temperature is 55 ℃, the reaction is carried out for 6 hours, the temperature is reduced to room temperature, the sampling gas chromatography is followed, the reaction conversion rate is 98.5 percent, the catalyst is recovered by filtration, the product is 2-fluoro-3-trifluoromethylpyridine by gas chromatography, the fraction temperature is concentrated to 90 ℃ by filtration under normal pressure, the steam distillation purification is carried out to obtain 31.22g, the gas chromatography content is 99 percent, the yield is 93.65 percent, and the product is colorless pungent transparent liquid.
Example 3
A preparation method of 2-fluoro-3-trifluoromethylpyridine comprises the following steps:
(1) selective fluorination
43.64g (99%, 0.20mol) of 2, 5-dichloro-3-trifluoromethylpyridine, 150ml of N, N-dimethylformamide, and 17.40g (0.30mol) of anhydrous potassium fluoride were put in a 500ml three-necked flask at 20 to 30 ℃ at room temperature, stirred at room temperature for 1 hour, gradually heating to 50 deg.C, heating and refluxing for 15 hr, determining reaction end point by gas chromatography tracking test, filtering, transferring into 1000ml three-necked bottle, adding 150ml of saturated ammonium chloride aqueous solution, stirring, adding 100ml of 1, extracting for three times by 2-dichloroethane, washing the dichloroethane phase once by saturated 100ml of ammonium chloride, drying by anhydrous sodium sulfate, and concentrating to obtain 37.90g of 2-fluoro-5-chloro-3-trifluoromethylpyridine, wherein the content of the gas chromatography is 99.0 percent, the yield of the step is about 95 percent basically, and the product is colorless pungent transparent liquid.
(2) Catalytic hydrogenation
40.31g (99.0 percent, calculated as 0.2mol) of 2-fluoro-5-chloro-3-trifluoromethylpyridine is added into a 1000ml autoclave, 41.5g (1.5 equivalent) of potassium carbonate, 200ml of absolute ethyl alcohol and 0.35g of palladium carbon are added, about 300ml of the materials are subjected to vacuum replacement of hydrogen and pressurization to 2.0MPa, the hydrogen is added after the intermediate pressure is reduced, the reaction temperature is 55 ℃, the reaction is carried out for 12 hours, the temperature is reduced to room temperature, the sampling gas chromatography is followed, the reaction conversion rate is 98.5 percent, the product is 2-fluoro-3-trifluoromethylpyridine by gas chromatography, the salt and the catalyst are filtered and removed, the catalyst is recovered by washing filter cakes with water, and the filtrate is rectified and purified at normal pressure to obtain 31.84g, the content of the gas chromatography is 99 percent, the yield is 97 percent, and the product is a colorless pungent transparent liquid.
Example 4
A preparation method of 2-fluoro-3-trifluoromethylpyridine comprises the following steps:
(1) selective fluorination
43.64g (99 percent, 0.20 mole) of 2, 5-dichloro-3-trifluoromethylpyridine, 150ml of sulfolane and 17.40g (0.30 mole) of anhydrous potassium fluoride are added into a 500ml three-necked flask at the room temperature of 20-30 ℃, stirred for 1 hour at the room temperature, gradually heated to 170 ℃, refluxed for 10 hours, subjected to gas chromatography tracking test to determine the reaction endpoint, filtered, transferred into a 1000ml three-necked flask, added with 150ml of saturated aqueous ammonium chloride solution, stirred, added with 100ml of 1, and extracted for three times with 2-dichloroethane, the dichloroethane phase is washed once with saturated 100ml of ammonium chloride, dried with anhydrous sodium sulfate and concentrated to obtain 37.30g of 2-fluoro-5-chloro-3-trifluoromethylpyridine with the gas chromatography content of 99.0 percent, the yield of the step is basically about 93.5 percent, and the product is a colorless pungent transparent liquid.
(2) Catalytic hydrogenation
40.30g (99.0 percent, calculated as 0.2mol) of 2-fluoro-5-chloro-3-trifluoromethylpyridine, 41.5g (1.5 equivalent) of potassium carbonate, 240ml of methanol and 2.0g of Raney nickel are added into a 1000ml autoclave, the hydrogen is replaced in vacuum and pressurized to 2.0MPa, the hydrogen is supplemented after the intermediate pressure is reduced, the reaction temperature is 55 ℃, the reaction is carried out for 16 hours, the temperature is reduced to room temperature, the sampling gas chromatography is followed, the reaction conversion rate is 98 percent, the product is 2-fluoro-3-trifluoromethylpyridine through gas chromatography, the salt and the catalyst are removed through filtration, the catalyst is recovered through washing filter cakes, the filtrate is rectified and purified at normal pressure to obtain 31.21g, the content of the gas chromatography is 99 percent, the yield is 96.5 percent, and the product is colorless transparent liquid with pungent smell.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A preparation method of 2-fluoro-3-trifluoromethylpyridine is characterized by comprising the following steps: comprises the following steps:
(1)2, 5-dichloro-3-trifluoromethylpyridine and an anhydrous fluorinating reagent are subjected to selective fluorination reaction in an aprotic dipolar solvent to generate 2-fluoro-5-chloro-3-trifluoromethylpyridine;
(2) the 2-fluoro-5-chloro-3-trifluoromethylpyridine is subjected to selective catalytic hydrogenation reduction in lower aliphatic alcohol in the presence of an acid-binding agent to remove chlorine element, so as to obtain the 2-fluoro-3-trifluoromethylpyridine.
2. The method of claim 1, wherein: the anhydrous fluorinating agent is a simple inorganic or organic fluoride containing fluoride ions, including but not limited to anhydrous alkali metal fluoride, anhydrous quaternary ammonium fluoride, anhydrous quaternary phosphonium fluoride, molecular adduct of anhydrous hydrogen fluoride and tertiary amine, molecular adduct of anhydrous hydrogen fluoride and pyridine substances;
further, the alkali metal salt is lithium, sodium, potassium, rubidium or cesium salt, preferably potassium salt; the quaternary ammonium salt is aliphatic chain and/or aromatic substituted quaternary ammonium salt, such as tetramethyl ammonium fluoride, tetraethyl ammonium fluoride, benzyl triethyl ammonium fluoride, didodecyl dimethyl ammonium fluoride, tetraphenyl ammonium fluoride, preferably tetramethyl ammonium fluoride; quaternary phosphonium salts are aliphatic chain and/or aromatic substituted quaternary phosphonium salts such as tetraphenylphosphonium fluoride, benzyltriethylphosphonium fluoride; the three substituents of the tertiary amine may be the same or different and are selected from the group consisting of aliphatic and aromatic, such as trimethylamine, triethylamine, dodecyldimethylamine, dodecylbenzylmethylamine, triphenylamine, preferably hydrogen fluoride-triethylamine (3: 1); pyridines include mono-or polysubstituted pyridines, preferably hydrogen fluoride-pyridine (1: 1);
preferably, the anhydrous fluorinating agent is used in an amount of 1.05 to 1.5 times the molar amount of 2, 5-dichloro-3-trifluoromethylpyridine.
3. The method of claim 1, wherein: the aprotic dipolar solvent includes:
chain ketones and cyclic ketones having 3 to 6 carbon atoms, preferably acetone;
or a chain nitrile, dinitrile or cyclic nitrile, dinitrile having 2 to 6 carbon atoms, preferably acetonitrile;
or chain or cyclic ethers, diethers of 3 to 6 carbon atoms, preferably tetrahydrofuran and dioxane;
or, a linear or cyclic amide of 3 to 6 carbon atoms, preferably N, N-dimethylformamide and N-methylpyrrolidone;
or, chain sulfones or sulfoxides and cyclic sulfones or sulfoxides of 2 to 4 carbon atoms, preferably dimethyl sulfoxide and sulfolane;
or one or two or more of morpholines with 3-6 carbon atoms, preferably N-formyl morpholine;
or the dosage of the aprotic dipolar solvent is 2-15 times of the mass of the 2, 5-dichloro-3-trifluoromethylpyridine;
preferably, the aprotic dipolar solvent is an aprotic dipolar solvent having a high boiling point, and more preferably N, N-dimethylformamide, N-dimethylacetamide, sulfolane, N-methylpyrrolidone, or N-formylmorpholine.
4. The method of claim 1, wherein: the reaction of step (1) comprises a phase transfer catalyst, preferably quaternary ammonium salts and quaternary phosphonium salts, more preferably quaternary phosphonium salts, most preferably inexpensive and readily available quaternary phosphonium salts containing bromine or iodine with a molecular weight of 200-400, such as tetraphenylphosphonium bromide.
5. The method of claim 1, wherein: the temperature of the selective fluorination reaction is 50-170 ℃, preferably 80-170 ℃, and the reaction time is 4-20 hours;
further, after the selective fluorination reaction, the product is filtered, redundant salt is removed from the reaction solution, the solvent is distilled out under normal pressure or reduced pressure and is used repeatedly, water is added to directly carry out steam rectification to separate the intermediate 2-fluoro-5-chloro-3-trifluoromethylpyridine and the raw material 2, 5-dichloro-3-trifluoromethylpyridine, and the raw material is used repeatedly.
6. The method of claim 1, wherein: the lower aliphatic alcohol in the step (2) is methanol, and the dosage of the lower aliphatic alcohol is 1-5 times of the mass of the 2, 5-dichloro-3-trifluoromethylpyridine;
or, the acid-binding agent in the step (2) comprises weak acid alkali metal or ammonium salt, tertiary amine and pyridine substances, wherein the weak acid alkali metal or ammonium salt comprises but is not limited to sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium acetate, potassium acetate, ammonium carbonate and diammonium phosphate; tertiary amines include, but are not limited to, triethylamine, tripropylamine, dodecyldimethylamine, dodecylbenzylmethylamine, triphenylamine; pyridines include, but are not limited to, pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine; the acid-binding agent can be one or two or more, and the dosage of the acid-binding agent is 1.05-1.5 times, preferably 1.2-1.3 times of the theoretical consumption molar weight according to the total reaction of the raw material 2-fluoro-5-chloro-3-trifluoromethylpyridine;
or, the selective catalytic hydrogenation reduction process in the step (2) is specifically as follows: in the presence of an acid binding agent, 2-fluoro-5-chloro-3-trifluoromethylpyridine is catalyzed by a metal catalyst under certain hydrogen pressure to generate dechlorination reaction, or 2-fluoro-5-chloro-3-trifluoromethylpyridine is reacted with 1 to 8 times (preferably 3 to 5 times) of molar quantity of ammonium formate or alkali metal salt of formic acid, and chlorine atoms on the 2-fluoro-5-chloro-3-trifluoromethylpyridine are removed by catalytic reduction.
7. The method of claim 6, wherein: the metal catalyst is one or more of nickel, palladium, platinum, iridium and ruthenium; preferably palladium metal;
further, the mass fraction of the added metal catalyst is 0.01-5 percent according to the weight of the 2-fluoro-5-chloro-3-trifluoromethylpyridine; preferably 0.01 to 1.0%.
8. The method of claim 7, wherein: one or more of metal nickel, palladium, platinum, iridium and ruthenium are loaded on an inert substrate for use;
further, the inert substrate is activated carbon, diatomite, a ZSM-5 molecular sieve, magnesium oxide, titanium dioxide or aluminum oxide.
9. The method of claim 8, wherein: the amount of the metal supported on the inert substrate is 0.1% to 10%, preferably 3.0% to 7.0%, and more preferably 5% by weight.
10. The method of claim 1, wherein: the reaction conditions of the catalytic hydrogenation reduction reaction are as follows: the reaction temperature is 50-150 ℃, and the optimal temperature is 55-90 ℃; the reaction time is 6-16 hours;
the reaction pressure is 0.1MPa to 4.0MPa, preferably 0.1MPa to 2.0 MPa.
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| CN112441966A (en) * | 2020-12-09 | 2021-03-05 | 山东省农药科学研究院 | Method for producing 2-chloro-3-trifluoromethylpyridine from 2,3, 6-trichloro-5-trifluoromethylpyridine |
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| CN112441966A (en) * | 2020-12-09 | 2021-03-05 | 山东省农药科学研究院 | Method for producing 2-chloro-3-trifluoromethylpyridine from 2,3, 6-trichloro-5-trifluoromethylpyridine |
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