CN114591225B - Method for large-scale production of 2, 6-dibromo-4-methylpyridine - Google Patents

Method for large-scale production of 2, 6-dibromo-4-methylpyridine Download PDF

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CN114591225B
CN114591225B CN202210197836.XA CN202210197836A CN114591225B CN 114591225 B CN114591225 B CN 114591225B CN 202210197836 A CN202210197836 A CN 202210197836A CN 114591225 B CN114591225 B CN 114591225B
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methylpyridine
dibromo
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CN114591225A (en
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张如周
李迪
李伟杰
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Henan Alpha Pharmaceutical Technology Co ltd
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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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
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    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P70/00—Climate change mitigation technologies in the production process for final industrial or consumer products
    • Y02P70/50—Manufacturing or production processes characterised by the final manufactured product

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Abstract

The invention discloses a method for producing 2, 6-dibromo-4-methylpyridine in large scale, which is to carry out bromination reaction on 2, 6-dihydroxyl-4-methylpyridine and a brominating reagent under the catalysis of metal halide to prepare the 2, 6-dibromo-4-methylpyridine. Experiments prove that: the method has the advantages of mild reaction conditions, simple operation, low equipment requirement, easy purification treatment, high product yield, and capability of obtaining the target product with the HPLC purity of up to 99.5 percent through simple recrystallization treatment, and besides, the raw materials used in the method have low price, are simple and easy to obtain, have low production cost, and are very suitable for industrial production; in particular, the method is easy to realize the production scale of kilogram level to hundred kilogram level, and has very strong practical value for realizing the large-scale production of 2, 6-dibromo-4-methylpyridine.

Description

Method for large-scale production of 2, 6-dibromo-4-methylpyridine
Technical Field
The invention relates to a method for producing 2, 6-dibromo-4-methylpyridine in large scale, belonging to the technical field of organic synthesis.
Background
Pyridine and its derivatives are widely found in nature, and various pyridine derivatives have been studied for such use as chemical materials and organic intermediates, which are the basis of various important compounds, for example, as pesticides, fine chemical industries such as pharmaceuticals, polymers and textile industry pesticides (herbicides, acaricides, bird repellents, insect repellents), solvents, reagent intermediates, surfactants, binders, etc., and various pyridine derivatives have been studied for such use.
2, 6-dibromo-4-methylpyridineAs an intermediate, 2, 6-dibromo-4-methylpyridine is widely used in the fields of pharmaceutical engineering, photoelectric materials and the like, and in the pharmaceutical industry, 2, 6-dibromo-4-methylpyridine can be used as a pharmaceutical synthesis intermediate, such as: can be used for preparing 2-bromo-6-oxazinyl-4-methylpyridine; in addition, 2, 6-dibromo-4-methylpyridine is a heterocyclic organic compound,can also be used as photoelectric material.
Regarding the synthesis of 2, 6-dibromo-4-methylpyridine, at present, 2, 6-dihydroxy-4-methylpyridine is mainly taken as a raw material, and bromination reaction is carried out by using a brominating reagent to obtain 2, 6-dibromo-4-methylpyridine, for example: 2, 6-dihydroxy-4-methylpyridine reacts with liquid bromine under the catalysis of triphenylphosphine to prepare 2, 6-dibromo-4-methylpyridine; 2, 6-dihydroxy-4-methylpyridine and tetrabutylammonium bromide react in the presence of phosphorus pentoxide to prepare 2, 6-dibromo-4-methylpyridine; 2, 6-dihydroxy-4-methylpyridine reacts with hydrobromic acid acetic acid solution in the presence of concentrated sulfuric acid to prepare 2, 6-dibromo-4-methylpyridine; 2, 6-dihydroxy-4-methylpyridine is reacted with phosphorus oxybromide to produce 2, 6-dibromo-4-methylpyridine (see patent WO 2009/68652); 2, 6-dihydroxy-4-methylpyridine is reacted with phosphorus tribromide to produce 2, 6-dibromo-4-methylpyridine (see, e.g., "Synthesis, (12), 1665-1667;2000" and "Journal of the American Chemical Society,1947,69, p.1147-1148"), and the like.
However, the method of reacting 2, 6-dihydroxy-4-methylpyridine with liquid bromine, tetrabutylammonium bromide or hydrobromic acid acetic acid solution has the disadvantages of long reaction time (usually two days are needed), low yield (less than 35%), troublesome post-treatment, and capability of obtaining the target product with the purity higher than 95% through column chromatography, and cannot meet the requirement of large-scale production.
Although the reaction time of the method for reacting 2, 6-dihydroxy-4-methylpyridine with phosphorus oxybromide or phosphorus tribromide is short (about 6 hours), the post treatment is also troublesome, the product also needs to be purified by column chromatography, and the yield of the phosphorus oxybromide method is only 16%; in addition, the phosphorus tribromide process needs to be performed at a high temperature of 170 ℃; therefore, the two methods cannot meet the requirement of large-scale production.
The sandmeyer reaction is a reaction in which a diazonium functional group is substituted by halogen or cyano under the catalysis of cuprous salt, so that in theory, 4-methyl-2, 6-diaminopyridine can be prepared first, and then the 4-methyl-2, 6-diaminopyridine is subjected to the diazonium reaction and the sandmeyer reaction to obtain 2, 6-dibromo-4-methylpyridine. However, experiments show that the sandmeyer reaction has a large reaction system and troublesome post-treatment, and at present, 4-methyl pyridine is usually used as a starting material, sodium amide and tetrahydronaphthalene are firstly used for reflux reaction to generate 4-methyl-2, 6-diaminopyridine (see documents Tetrahedron Letters,2016,57 (3) and 333-336'), and the temperature required by the method is high and sodium amide is flammable and explosive. Therefore, the method cannot meet the requirement of large-scale production.
Disclosure of Invention
In view of the above problems of the prior art, it is an object of the present invention to provide a method for mass production of 2, 6-dibromo-4-methylpyridine.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a method for producing 2, 6-dibromo-4-methylpyridine in large scale comprises the step of carrying out bromination reaction on 2, 6-dihydroxyl-4-methylpyridine and a brominating reagent under the catalysis of metal halides to obtain the 2, 6-dibromo-4-methylpyridine.
In one embodiment, the metal halide is selected from one or more of aluminum chloride, copper bromide, and cuprous bromide, preferably copper bromide.
In one embodiment, the brominating reagent is one or more of N-bromosuccinimide (NBS), liquid bromine, 33% hydrobromic acid acetic acid solution, 48% hydrobromic acid aqueous solution, phosphorus tribromide, and trimethylbromosilane, preferably phosphorus tribromide or phosphorus tribromide, more preferably phosphorus tribromide.
An embodiment, the 2, 6-dihydroxy-4-methylpyridine: brominating reagent: the molar ratio of the metal halide is 1: (0.5-4.5): (0.1 to 1), preferably 1:1.5:0.2.
an embodiment, the method for the mass production of 2, 6-dibromo-4-methylpyridine, comprising the operations of:
adding a reaction solvent, 2, 6-dihydroxyl-4-methylpyridine, a brominating reagent and metal halide into a reaction vessel at room temperature, and then stirring and reacting at 50-140 ℃ (preferably 100-140 ℃ and preferably 120 ℃); and after the reaction is finished, carrying out post-treatment to obtain the 2, 6-dibromo-4-methylpyridine.
In a preferred embodiment, the reaction solvent is one or more of acetonitrile, tetrahydrofuran, carbon tetrachloride, 1, 2-dichloroethane, dimethyl sulfoxide, and ring Ding Feng, preferably acetonitrile.
In a preferred embodiment, the post-treatment is performed as follows:
cooling the reaction system to room temperature, pouring the reaction solution into ice water, regulating the pH value to be neutral by using alkali or alkali solution, filtering, drying a filter cake, and recrystallizing by using an organic solvent to obtain the 2, 6-dibromo-4-methylpyridine.
In a preferred embodiment, the organic solvent used for recrystallization is one or more of methanol, isopropanol, ethanol, ethyl acetate, dichloromethane, petroleum ether, n-heptane, n-hexane, methyl t-butyl ether, preferably petroleum ether.
Compared with the prior art, the invention has the following remarkable beneficial effects:
experiments prove that: the 2, 6-dihydroxyl-4-methylpyridine and a brominating reagent are subjected to bromination reaction under the catalysis of metal halide to prepare the 2, 6-dibromo-4-methylpyridine, so that the method has the advantages of mild reaction conditions, simplicity in operation, lower equipment requirements, easiness in purification treatment, high product yield (the molar yield can be up to 68.5%), capability of obtaining a target object with the HPLC purity up to 99.5% through simple recrystallization treatment, low price of raw materials, simplicity and easiness in obtaining, low production cost and suitability for industrial production; in particular, the method disclosed by the invention can break through the bottleneck of the existing method, is easy to realize the production scale of kilogram level to hundred kilograms level, has extremely high practical value for realizing the large-scale production of 2, 6-dibromo-4-methylpyridine, and has remarkable progress compared with the prior art.
Detailed Description
The technical scheme of the invention is further and fully described in the following by combining examples and comparative examples.
Comparative example 1
Triphenylphosphine (2.20 kg,1.0 eq) and acetonitrile (10L) are sequentially added into a high-low temperature jacketed reaction kettle at room temperature, after the addition, the temperature is reduced to about 0 ℃, then liquid bromine (1.28 kg,2.0 eq) is dripped into the reaction kettle, after the dripping is finished, the reaction is carried out for 30 minutes, yellow solid is separated out, then 2, 6-dihydroxyl-4-methylpyridine (0.5 kg,1.0 eq) is added into the mixture, the temperature is increased to 140 ℃ for two days, after the reaction is finished, the reaction liquid is slowly poured into ice water, dichloromethane is used for extraction, the organic phase obtained by extraction is dried by anhydrous sodium sulfate, filtration and concentration, and the obtained crude product is purified by column chromatography (leaching agent: petroleum ether/ethyl acetate=20:1), so that 0.33kg of 2, 6-dibromo-4-methylpyridine (white solid) can be obtained, the molar yield is 32.50%, and the GC purity is 96.2%.
Tested: 1 H NMR(CDCl 3 ,300Hz)δ7.47(s,2H),4.29(s,2H)； 13 C NMR(CDCl 3 ,75Hz)δ150.6,140.8,126.7,28.0。
comparative example 2
2, 6-dihydroxy-4-methylpyridine (0.5 kg,1.0 eq), phosphorus pentoxide (1.16 kg,2.05 eq), tetrabutylammonium bromide (2.84 kg,2.20 eq) and toluene (5L) were sequentially added into a high-low temperature jacketed reaction kettle at room temperature, the temperature was raised to reflux reaction, after the reaction was completed, the reaction solution was slowly poured into ice water, filtered, separated, the organic phase was washed with saturated saline solution, and then dried with anhydrous sodium sulfate, filtered and concentrated, and the obtained crude product was purified by column chromatography (eluent: petroleum ether/ethyl acetate=20:1), whereby 0.26kg of 2, 6-dibromo-4-methylpyridine (white solid) was obtained with a molar yield of 25.30% and GC purity of 97.0%.
Comparative example 3
2, 6-dihydroxy-4-methylpyridine (0.5 kg,1.0 eq), 48% hydrobromic acid acetic acid solution (10L) and concentrated sulfuric acid (3L) are sequentially added into a high-low temperature jacketed reaction kettle at room temperature, the temperature is raised to reflux reaction for two days, after the reaction is completed, the reaction solution is slowly poured into ice water, dichloromethane is used for extraction, an organic phase obtained by extraction is dried by anhydrous sodium sulfate, filtration and concentration, and the obtained crude product is purified by column chromatography (leaching agent: petroleum ether/ethyl acetate=20:1), so that 0.28kg of 2, 6-dibromo-4-methylpyridine (white solid) can be obtained, the molar yield is 27.35%, and the GC purity is 97.5%.
Comparative example 4
2, 6-dihydroxy-4-methylpyridine (0.50 kg,1.0 eq) and phosphorus tribromoxide (1.72 kg,1.50 eq) are added into a 50L high-low temperature jacketed reaction kettle at room temperature, the temperature is raised to 120 ℃ after the addition is finished, the reaction is carried out for 24 hours, the reaction is cooled to room temperature, the reaction is poured into 20L ice water, the pH is regulated to be neutral by 40% sodium hydroxide solution, white solid is separated out, filtration is carried out, a filter cake is recrystallized by petroleum ether, and 0.36kg of 2, 6-dibromo-4-methylpyridine (white solid) can be obtained, the molar yield is 35.80%, and the GC purity is 96.4%.
Comparative example 5
2, 6-dihydroxy-4-methylpyridine (0.50 kg,1.0 eq) and phosphorus tribromide (3.26 kg,3.00 eq) are added into a high-low temperature jacketed reaction kettle at room temperature, the temperature is raised to 120 ℃ for 24 hours after the reaction is completed, the reaction is cooled to room temperature, the reaction is poured into 10L ice water, the pH is regulated to be neutral by 40% sodium hydroxide solution, white solid is separated out, filtration and a filter cake is recrystallized by petroleum ether, so that 0.38kg of 2, 6-dibromo-4-methylpyridine (white solid) can be obtained, the molar yield is 38.20%, and the GC purity is 97.8%.
Example 1
2, 6-dihydroxy-4-methylpyridine (0.50 kg,1.0 eq), phosphorus tribromide (3.26 kg,3.00 eq), copper chloride (80 g,0.20 eq) were added to a high and low temperature jacketed reaction vessel containing 5L of acetonitrile at room temperature, the temperature was raised to 140 ℃ after the addition was completed, the reaction was cooled to room temperature, the reaction was poured into 10L of ice water, pH was adjusted to neutrality with 40% sodium hydroxide solution, white solid was precipitated, filtered, and the filter cake was recrystallized with petroleum ether to give 0.48kg of 2, 6-dibromo-4-methylpyridine (white solid) with a molar yield of 48.35% and a GC purity of 99.1%.
Example 2
At room temperature, 0.5kg of 2, 6-dihydroxy-4-methylpyridine (0.50 kg,1.0 eq), phosphorus tribromide (3.26 kg,3.00 eq), aluminum chloride (106.56 g,0.20 eq) were added into a high and low temperature jacketed reaction kettle containing 5L of acetonitrile, the temperature was raised to 140 ℃ for 24 hours, after the reaction was completed, the reaction was cooled to room temperature, poured into 10L of ice water, pH was adjusted to neutrality with 40% sodium hydroxide solution, white solid was precipitated, filtered and dried, and the filter cake was recrystallized with petroleum ether to obtain 0.50kg of 2, 6-dibromo-4-methylpyridine (white solid) with a molar yield of 50.20% and a GC purity of 99.1%.
Example 3
2, 6-dihydroxy-4-methylpyridine (0.50 kg,1.0 eq), phosphorus tribromide (3.26 kg,3.00 eq), copper bromide (178.50 g,0.20 eq) were added to a high and low temperature jacketed reaction kettle containing 5L of acetonitrile at room temperature, the temperature was raised to 140 ℃ after the addition was completed, the reaction was cooled to room temperature, the reaction was poured into 10L of ice water, the pH was adjusted to neutrality with 40% sodium hydroxide solution, white solid was precipitated, filtered and dried, and the filter cake was recrystallized with petroleum ether to give 0.66kg of 2, 6-dibromo-4-methylpyridine (white solid) with a molar yield of 65.80% and a GC purity of 99.2%.
Example 4
2, 6-dihydroxy-4-methylpyridine (0.50 kg,1.0 eq), phosphorus tribromide (1.63 kg,1.50 eq), copper bromide (178.50 g,0.20 eq) were added to a high and low temperature jacketed reaction kettle containing 5L of acetonitrile at room temperature, the temperature was raised to 140 ℃ after the addition was completed, the reaction was cooled to room temperature, the reaction was poured into 10L of ice water, the pH was adjusted to neutrality with 40% sodium hydroxide solution, a white solid was precipitated, filtered and dried, and the filter cake was recrystallized with petroleum ether to give 0.68kg of 2, 6-dibromo-4-methylpyridine (white solid) with a molar yield of 67.25% and a GC purity of 99.2%.
Example 5
At room temperature, 0.5kg of 2, 6-dihydroxy-4-methylpyridine (0.50 kg,1.0 eq), phosphorus tribromide (1.63 kg,1.50 eq), copper bromide (178.50 g,0.20 eq) were added into a high and low temperature jacketed reaction kettle containing 5L of acetonitrile, the temperature was raised to 120 ℃ for 24 hours, after the reaction was completed, the reaction was cooled to room temperature, poured into 10L of ice water, pH was adjusted to neutrality with 40% sodium hydroxide solution, white solid was precipitated, filtered and dried, and the filter cake was recrystallized with petroleum ether to obtain 0.65kg of 2, 6-dibromo-4-methylpyridine (white solid) with a molar yield of 64.87% and a GC purity of 99.4%.
Example 6
At room temperature, 2, 6-dihydroxy-4-methylpyridine (5 kg,1.0 eq) and copper bromide (1.79 kg,0.20 eq) were added into a high-low temperature jacketed reaction kettle containing 50L of acetonitrile, refrigeration was started, the internal temperature was cooled to 0 ℃, 16.3kg of phosphorus tribromide (1.50 eq) was slowly dropped into the reaction kettle, the addition was completed, the temperature was raised to 120 ℃ for 24 hours, after the reaction was completed, the reaction was cooled to room temperature, the reaction was poured into 50L of ice water, the pH was adjusted to neutrality with 40% sodium hydroxide solution, white solid was precipitated, filtered and dried, and the filter cake was recrystallized with petroleum ether to obtain 6.87kg of 2, 6-dibromo-4-methylpyridine (white solid) with a molar yield of 68.50% and GC purity of 99.5%.
From the above, it can be seen that the present invention can make 2, 6-dihydroxy-4-methylpyridine and brominating reagent undergo bromination reaction to obtain 2, 6-dibromo-4-methylpyridine under the catalysis of metal halide, and compared with the traditional solution method of liquid bromine, tetrabutylammonium bromide and hydrobromic acid acetic acid (see comparative examples 1-3), the reaction time is shorter (the reaction time is reduced from 2 days of comparative examples 1-3 to 24 hours of examples), the yield is high (the highest 32.5% of comparative examples 1-3 is improved to 68.50% of examples), the post-treatment operation is simple (the column chromatography of comparative examples 1-3 is improved to 99.5% of examples), and the purity of the obtained product is high (the highest 97.5% of comparative examples 1-3 is improved to 99.5% of examples); furthermore, comparing comparative examples 4-5 with examples, it can be seen that the presence of metal halides can effectively increase the molar yield of the reaction and the purity of the product; in particular, the method disclosed by the invention can break through the bottleneck of the existing method, is easy to realize the production scale of kilogram level to hundred kilogram level (see example 6), has very strong practical value for realizing the large-scale production of 2, 6-dibromo-4-methylpyridine, and has remarkable progress compared with the prior art.
Finally, it is pointed out here that: the above is only a part of the preferred embodiments of the present invention and should not be construed as limiting the scope of the present invention, and some insubstantial modifications and adaptations of the present invention based on the foregoing are within the scope of the present invention.

Claims (2)

1. A method for producing 2, 6-dibromo-4-methylpyridine on a large scale is characterized in that: the method comprises the steps of carrying out bromination reaction on 2, 6-dihydroxy-4-methylpyridine and a brominating reagent under the catalysis of metal halide to obtain 2, 6-dibromo-4-methylpyridine; the method comprises the following operations:
at room temperature, acetonitrile, 2, 6-dihydroxyl-4-methylpyridine, a brominating reagent and metal halide are added into a reaction vessel, and then stirred for reaction at 50-140 ℃; after the reaction is finished, cooling the reaction system to room temperature, pouring the reaction solution into ice water, adjusting the pH to be neutral by using alkali or alkali solution, filtering, drying a filter cake, and recrystallizing by using petroleum ether to obtain 2, 6-dibromo-4-methylpyridine;
the brominating reagent is phosphorus tribromide and the metal halide is copper bromide.
2. The method of claim 1, wherein: the 2, 6-dihydroxy-4-methylpyridine: brominating reagent: the molar ratio of the metal halide is 1: (0.5-4.5): (0.1-1).
CN202210197836.XA 2022-03-02 2022-03-02 Method for large-scale production of 2, 6-dibromo-4-methylpyridine Active CN114591225B (en)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5204478A (en) * 1992-08-20 1993-04-20 Warner-Lambert Company Process for the synthesis of 2,6-dichloro-5-fluoronicotinic acid and 2,6-dichloro-5-fluoronicotinoyl chloride
CN1756729A (en) * 2003-01-16 2006-04-05 通用电气公司 Bromination of hydroxyaromatic compounds and further conversion to dihydroxyaromatic compounds
CN101306968A (en) * 2008-06-30 2008-11-19 浙江工业大学 Process for synthesizing halogenated compounds by oxygenizing and halogenating reaction
CN102898360A (en) * 2012-11-12 2013-01-30 西华大学 Synthesis of 3, 5-dibromo-4-iodopyridine
CN103739614A (en) * 2013-12-31 2014-04-23 成都百裕科技制药有限公司 Hydrogenated pyridine derivative and preparation method thereof
CN112679420A (en) * 2020-12-27 2021-04-20 甘肃瀚聚药业有限公司 Preparation method of 2,5-dibromopyridine
CN113512000A (en) * 2021-04-29 2021-10-19 河南阿尔法医药科技有限公司 Method for large-scale production of 4 '-bromo-2, 2', 6 ', 2' -terpyridine

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5204478A (en) * 1992-08-20 1993-04-20 Warner-Lambert Company Process for the synthesis of 2,6-dichloro-5-fluoronicotinic acid and 2,6-dichloro-5-fluoronicotinoyl chloride
CN1756729A (en) * 2003-01-16 2006-04-05 通用电气公司 Bromination of hydroxyaromatic compounds and further conversion to dihydroxyaromatic compounds
CN101306968A (en) * 2008-06-30 2008-11-19 浙江工业大学 Process for synthesizing halogenated compounds by oxygenizing and halogenating reaction
CN102898360A (en) * 2012-11-12 2013-01-30 西华大学 Synthesis of 3, 5-dibromo-4-iodopyridine
CN103739614A (en) * 2013-12-31 2014-04-23 成都百裕科技制药有限公司 Hydrogenated pyridine derivative and preparation method thereof
CN112679420A (en) * 2020-12-27 2021-04-20 甘肃瀚聚药业有限公司 Preparation method of 2,5-dibromopyridine
CN113512000A (en) * 2021-04-29 2021-10-19 河南阿尔法医药科技有限公司 Method for large-scale production of 4 '-bromo-2, 2', 6 ', 2' -terpyridine

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Reza-Ali Fallahpour.An Efficient and Easy Route to Trimethyl Derivatives of 2,2’:6’,2’’-Terpyridine.《Synthesis》.2000,(第12期),第1665-1667页. *
刘鹰翔 等.《药物合成反应 新世纪第2版》.北京：中国中医药出版社,2017,第54页. *
卤代吡啶类化合物的合成及应用;张伟 等;《精细化工中间体》;第36卷(第4期);1-6 *

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