Synthesis method of o-bromo dipyridyl
By using the compound 2-acetyl-6-bromopyridine as raw material to generate intermediates and convert them into o-bromopyridine, the problems of harsh conditions of o-bromopyridine synthesis in the prior art are solved, and a simple, low-cost and high-yield synthesis route is achieved.
Patent Information
- Application Number
- CN202510705264.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-29
- Publication Date
- 2025-09-02
AI Technical Summary
The existing synthesis method of bipyridine of o-bromobile requires palladium catalysts and tin reagents, with harsh conditions and unstable yields.
The compound 2-acetyl-6-bromopyridine was used as raw material to form the intermediate 1-(2-(6-bromopyridine-2-yl)-2-oxyethyl)pyridine-1-onium iodide under the action of iodine and pyridine, and then reacted with acrolein diethanol and ammonium acetate in an organic solvent to convert it into the target compound o-bromopyridine.
It achieves short synthesis steps, low cost, mild reaction conditions and high yield, and is simple to post-process and is suitable for industrial production.
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Figure CN120574166A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing o-bromobipyridine. Background Art
[0002] The compound o-bromobipyridine is an important bipyridine compound and an important molecular building block. As a key intermediate, it is used in the synthesis of metal complexes in patent CN118620000A. The metal complex contains a tridentate ligand-metal-secondary amine structure and has good TADF performance. In patent CN118406092A, it is used for the synthesis of multidentate chelated nickel catalysts. The catalyst catalyzes alkyl radicals under visible light or ultraviolet light excitation to start free radical polymerization. The catalyst does not participate in the chain growth process and can effectively avoid the problem of reduced comonomer insertion rate caused by the steric effect of long-chain α-olefin comonomers. In patent EP1683804, it is used for the synthesis of novel platinum complexes. The platinum complex can be used as a material for light-emitting devices, has good luminescent properties and luminous efficiency, and can be used in various fields. In the prior art, the conventional synthesis route of the compound o-bromobipyridine requires the use of palladium catalysts and tin reagents, or requires the preparation of zinc reagents. The conditions are relatively harsh and the yield is unstable. Therefore, it is of great significance to develop new synthetic methods for o-bromobipyridine. Summary of the Invention
[0003] In view of the shortcomings of the synthesis methods of o-bromobipyridine in the prior art, the present invention aims to provide a synthesis method of o-bromobipyridine, which has the advantages of low cost, short steps, easy operation, relatively mild reaction conditions, low safety risks and ideal yield.
[0004] To achieve the above object, the present invention adopts the following technical solutions:
[0005] A method for synthesizing o-bromobipyridine is disclosed. The method uses the compound 2-acetyl-6-bromopyridine as a raw material, obtains the intermediate 1-(2-(6-bromopyridin-2-yl)-2-oxoethyl)pyridin-1-ium iodide under the action of iodine and pyridine, and then converts it into the target compound o-bromobipyridine. The synthetic route is as follows:
[0006]
[0007] Preferably, the synthesis method comprises the following steps:
[0008] (1) Compound 1, i.e., 2-acetyl-6-bromopyridine and iodine, is added to pyridine, heated to 60-100° C., and stirred for 1-3 hours. After the reaction is completed, the reaction solution is post-treated to obtain a crude product of compound 2, which does not require further purification;
[0009] (2) Compound 2 and acrolein diethyl acetal are added to an organic solvent I, and then ammonium acetate is added. The temperature is raised to 80-200°C and stirred for reaction for 2-10 hours. After the reaction is completed, the reaction solution is post-treated to obtain the target compound 3, namely o-bromobipyridine.
[0010] Preferably, in step (1),
[0011] The molar ratio of compound 1 to iodine is 1:1-2;
[0012] The mass volume ratio of compound 1 to pyridine is 1:5-40 g / mL.
[0013] Preferably, in step (1), the post-treatment process includes: after the reaction is completed, the reaction solution is cooled to room temperature, solids are precipitated, filtered, and the solids are collected to obtain a crude product of compound 2, and the crude product does not need to be further purified. Preferably, in step (2),
[0014] The molar ratio of compound 2 to acrolein diethyl acetal is 1:1-4;
[0015] The molar ratio of compound 2 to ammonium acetate is 1:2-7;
[0016] The mass volume ratio of compound 2 to organic solvent I is 1:5-40 g / mL.
[0017] Preferably, in step (2), the organic solvent I is selected from one or more of formic acid, acetic acid, or propionic acid. Preferably, in step (2), the post-treatment process comprises: after the reaction is completed, cooling the reaction solution to room temperature, adding the reaction solution to ice water, then adjusting the pH value to 5-7 with an alkaline aqueous solution, filtering, and collecting the solid to obtain the target compound 3, namely o-bromobipyridine.
[0018] Preferably, in step (2), the alkaline aqueous solution is selected from one or more of sodium bicarbonate solution, sodium carbonate solution, potassium carbonate solution, sodium hydroxide solution or potassium hydroxide solution.
[0019] Compared with the prior art, the beneficial technical effects of the present invention are:
[0020] The present invention provides a method for preparing o-bromobipyridine. Using the compound 2-acetyl-6-bromopyridine as a raw material, under the action of iodine and pyridine, an intermediate 1-(2-(6-bromopyridin-2-yl)-2-oxoethyl)pyridin-1-ium iodide is obtained, which is then converted into the target compound o-bromobipyridine. The synthesis method of the present invention has mild reaction conditions, simple post-processing and purification, and can achieve process scalability. Ultimately, the compound o-bromobipyridine is prepared in a short process, simple operation, low cost, and relatively mild reaction conditions. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] Figure 1 This is the H-NMR spectrum of o-bromobipyridine in Example 1. DETAILED DESCRIPTION
[0022] To further clarify the technical solutions and advantages of the embodiments of the present invention, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only a portion of the embodiments of the present invention, not all of them. Based on the described embodiments of the present invention, all other embodiments derived by persons of ordinary skill in the art without requiring creative effort are within the scope of protection of the present invention. Unless otherwise defined, technical or scientific terms used herein shall have the ordinary meanings understood by persons of ordinary skill in the field to which the present invention pertains.
[0023] Unless otherwise specified in the following examples, all reagents and materials used were commercially available.
[0024] The following examples synthesize o-bromobipyridine using compound 1 (2-acetyl-6-bromopyridine) as a raw material. Under the action of iodine and pyridine, intermediate 2 (1-(2-(6-bromopyridin-2-yl)-2-oxoethyl)pyridin-1-ium iodide) is obtained, which is then converted into the target compound 3 (o-bromobipyridine). The synthetic route is as follows:
[0025]
[0026] The technical solution of the present invention is further explained below through examples.
[0027] Example 1
[0028] In this example, the compound o-bromobipyridine is synthesized by the following steps:
[0029] (1) Compound 1, 2-acetyl-6-bromopyridine (200.00 g, 999.83 mmol, 1.00 eq) and iodine (253.76 g, 999.83 mmol, 1.00 eq), were added to pyridine (1.0 L), heated to 80°C, and stirred for 2 h. After the reaction was completed, the reaction solution was cooled to room temperature. Solids precipitated and were filtered and collected to obtain a crude product of compound 2 (weight 398.10 g, purity 97%, yield 95%). The crude product did not require further purification.
[0030] (2) Compound 2 (300.00 g, 740.68 mmol, 1.00 eq) and acrolein diethyl acetal (192.85 g, 1.48 mol, 2.00 eq) were added to acetic acid (2.0 L), and ammonium acetate (285.47 g, 3.70 mol, 5.00 eq) was added. The temperature was raised to 100°C and the mixture was stirred for 3 h. After the reaction was completed, the reaction solution was cooled to room temperature and added to ice water (1.0 L). The pH value was adjusted to 6 with 6 M sodium hydroxide aqueous solution, and the solid was collected by filtration to obtain the target compound 3, namely o-bromobipyridine (weight 168.20 g, purity 98%, yield 95%).
[0031] The H NMR spectrum of the obtained compound 3 (o-bromobipyridine) is as follows Figure 1 The characterization data are as follows: 1 H NMR (400MHz, CDCl3) δ8.67(d,J=4.7Hz,1H),8.40(t,J=7.9Hz,2H),7.83(td,J=7 .8,1.6Hz,1H),7.67(t,J=7.8Hz,1H),7.49(d,J=7.8Hz,1H),7.36–7.31(m,1H).
[0032] Examples 2-7
[0033] Examples 2-7 are the same as Example 1, except that the amount of acrolein diethyl acetal, the amount of ammonium acetate, organic solvent I, reaction temperature, and reaction time used in step (2) are adjusted, as shown in Table 1. The effects of various reaction conditions on the reaction yield in the synthesis of target compound 3 (o-bromobipyridine) were verified through Examples 1-7, and the results are shown in Table 1.
[0034] Table 1: Synthesis conditions and results of Examples and Comparative Examples
[0035]
[0036] Combined with Table 1, we can see that:
[0037] Comparing Examples 1-3, when the molar ratio of Compound 2 to acrolein diethyl acetal is 1.0:2.0, the reaction effect is already better.
[0038] Comparing Examples 1 and 4-5, when the molar ratio of compound 2 to ammonium acetate is 1.0:5.0, the reaction effect is already better.
[0039] Comparing Examples 1, 6-7, the reaction can be carried out in acetic acid, formic acid and propionic acid as solvents, among which acetic acid has a better effect as a solvent.
[0040] Comparing Examples 1, 8-9, when the reaction temperature is 100°C, the reaction effect has reached the best.
[0041] Comparing Examples 1 and 10-11, the reaction time is 2 hours, and the reaction effect has reached the best.
[0042] The above is a preferred embodiment of the present invention, but the present invention should not be limited to the contents disclosed in this embodiment. Therefore, any equivalent or modified implementations that do not depart from the spirit disclosed in the present invention fall within the scope of protection of the present invention.
Claims
1. A method for synthesizing o-bromobipyridine, characterized in that: The synthesis method uses the compound 2-acetyl-6-bromopyridine as a raw material, and under the action of iodine and pyridine, obtains the intermediate 1-(2-(6-bromopyridin-2-yl)-2-oxoethyl)pyridin-1-ium iodide, which is then converted into the target compound o-bromobipyridine. The synthesis route is as follows:
2. The method for synthesizing o-brominated bipyridine according to claim 1, wherein The synthesis method comprises the following steps: (1) Compound 1, i.e., 2-acetyl-6-bromopyridine and iodine, is added to pyridine, heated to 60-100° C., and stirred for 1-3 hours. After the reaction is completed, the reaction solution is post-treated to obtain a crude product of compound 2, which does not require further purification; (2) Compound 2 and acrolein diethyl acetal are added to an organic solvent I, and then ammonium acetate is added. The temperature is raised to 80-200°C and stirred for reaction for 2-10 hours. After the reaction is completed, the reaction solution is post-treated to obtain the target compound 3, namely o-bromobipyridine.
3. The method for synthesizing o-brominated bipyridine according to claim 2, wherein In the step (1), the molar ratio of compound 1 to iodine is 1:1-2; The mass volume ratio of compound 1 to pyridine is 1:5-40 g / mL.
4. The method for synthesizing o-brominated bipyridine according to claim 2, wherein In step (1), the post-treatment process includes: after the reaction is completed, the reaction solution is cooled to room temperature, solids are precipitated, filtered, and the solids are collected to obtain a crude product of compound 2, which does not require further purification.
5. The method for synthesizing o-brominated bipyridine according to claim 2, wherein In the step (2), the molar ratio of compound 2 to acrolein diethyl acetal is 1:1-4; The molar ratio of compound 2 to ammonium acetate is 1:2-7; The mass volume ratio of compound 2 to organic solvent I is 1:5-40 g / mL.
6. The method for synthesizing o-brominated bipyridine according to claim 2, wherein In the step (2), the organic solvent I is selected from one or more of formic acid, acetic acid or propionic acid.
7. The method for synthesizing o-brominated bipyridine according to claim 2, wherein In step (2), the post-treatment process includes: after the reaction is completed, cooling the reaction solution to room temperature, adding the reaction solution to ice water, adjusting the pH value to 5-7 with an alkaline aqueous solution, filtering, and collecting the solid to obtain the target compound 3, namely o-bromobipyridine.
8. The method for synthesizing o-brominated bipyridine according to claim 7, wherein In the step (2), the alkaline aqueous solution is selected from one or more of sodium bicarbonate solution, sodium carbonate solution, potassium carbonate solution, sodium hydroxide solution or potassium hydroxide solution.