Synthesis method of 2-cyano-5-bromopyridine

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of 2-cyano-5-bromopyridine, which comprises the following steps: synthesizing 5-bromo-2-picolinic acid by using 2, 5-dibromopyridine as an initial raw material; synthesizing tert-butyl (5-bromopyridine-2-formyl) carbamic acid ester by virtue of a one-step method; the method comprises the following steps: synthesizing 5-bromo-2-pyridinecarboxamide; the method comprises the following steps: synthesizing 2-cyano-5-bromopyridine; compared with the prior art, the synthetic method of the 2-cyano-5-bromopyridine, disclosed by the invention, has the advantages of high safety, high yield, high purity of the obtained product, low cost and environmental friendliness.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for synthesizing 2-cyano-5-bromopyridine. Background Technology

[0002] The existing methods for synthesizing 2-cyano-5-bromopyridine mainly include the following two: The first method is the diazotization-cyanidation method using 5-bromo-2-aminopyridine as a raw material. This method requires first reacting 5-bromo-2-aminopyridine with sodium nitrite at a low temperature (0-5℃) to generate a diazonium salt, which is then reacted with a cyanide (such as cuprous cyanide or potassium cyanide) to introduce a cyano group. However, this method has significant drawbacks: the diazonium salt has poor stability, requiring strict control of low-temperature conditions, resulting in high operational risks; the use of highly toxic cyanides necessitates high requirements for equipment corrosion prevention, and the generated wastewater contains cyanide, leading to high environmental treatment costs, making it unsuitable for large-scale industrial production.

[0003] The second method is the direct cyanidation method using 2,5-dibromopyridine as a raw material: This method directly uses cyanides (such as zinc cyanide or potassium ferrocyanide) to react with 2,5-dibromopyridine in the presence of a catalyst (such as tetra(triphenylphosphine)palladium(0)). Although this method avoids the diazotization step, it still relies on highly toxic cyanides, and the catalysts are expensive, requiring harsh reaction conditions (high temperature and inert gas protection), which is detrimental to cost control and safe production. Summary of the Invention

[0004] This invention addresses the technical problems in the synthesis of 2-cyano-5-bromopyridine in the prior art, such as the use of highly toxic cyanide, high operational risks, and high costs, by providing a method for synthesizing 2-cyano-5-bromopyridine.

[0005] To achieve the above objectives, the technical solution adopted by this invention is as follows: a method for synthesizing 2-cyano-5-bromopyridine, comprising the following steps: Step 1: Under inert gas protection, 2,5-dibromopyridine is added to organic solvent 1, and methyl magnesium chloride is added dropwise at -60~-80℃. The mixture is stirred and reacted for 2-4 hours. Dry carbon dioxide is bubbled in, and the mixture is treated with acid to obtain 5-bromo-2-pyridinecarboxylic acid. Step 2: Add the 5-bromo-2-pyridinecarboxylic acid obtained in Step 1 to Organic Solvent 2, and add thionyl chloride dropwise while controlling the temperature at 0~10℃. After the addition is complete, raise the temperature to 35~45℃ and stir for 2-4 hours. Concentrate until no more distillate drips out, add Organic Solvent 2 until the material is completely dissolved, add triethylamine while controlling the temperature at 10~20℃, and add a solution of tert-butyl carbamate dropwise. After monitoring the completion of the reaction by thin-layer chromatography, extract, dry and concentrate to obtain tert-butyl (5-bromopyridine-2-carboxy) carbamate. Step three, remove the tert-butyloxycarbonyl protecting group by reacting the tert-butyl (5-bromopyridine-2-formyl) carbamate obtained in step two with an acidic solution at 15-25℃ for 2-4h to obtain 5-bromo-2-pyridinecarboxamide; Step four, dehydrate to generate cyano by stirring the 5-bromo-2-pyridinecarboxamide obtained in step three with a dehydrating agent in an organic solvent three at 80-100℃ for 6-8h to obtain the target product 2-cyano-5-bromopyridine.

[0006] As a preferred, the molar ratio of 2,5-dibromopyridine to methyl magnesium chloride in step one is 1:1.2; the organic solvent one is tetrahydrofuran; and the inert gas is nitrogen or argon.

[0007] As a preferred, the molar ratio of 5-bromo-2-pyridinecarboxylic acid to thionyl chloride to tert-butyl carbamate in step two is 1:1.10-1.30:1.01; and the organic solvent two is toluene.

[0008] As a preferred, the acidic solution in step three is hydrogen chloride ethyl acetate solution or a mixed solution of trifluoroacetic acid and dichloromethane with a volume ratio of 1:1.

[0009] As a preferred, the dehydrating agent in step four is phosphorus oxychloride, phosphorus pentoxide or thionyl chloride.

[0010] As a preferred, the molar ratio of 5-bromo-2-pyridinecarboxamide to the dehydrating agent in step four is 1:1.5-2.0.

[0011] As a preferred, the organic solvent three is toluene or chlorobenzene.

[0012] Compared with the prior art, the synthesis method of 2-cyano-5-bromopyridine has the advantages and positive effects that: (1) high safety: the present application avoids using highly toxic cyanide (such as potassium cyanide, cuprous cyanide), and uses tert-butyl carbamate (tert-butyloxycarbonyl amine) as the amino source, and then generates cyano by formamide dehydration, so that the toxicity of raw materials and intermediates is low, the operation risk is greatly reduced, and the safety production requirement is met; (2) high yield and high purity: the total yield of four steps is ≥64% (calculated based on 2,5-dibromopyridine), and the purity of the target product is ≥99%, which is higher than that of the existing diazotization-cyanation method (total yield about 50%) and direct cyanation method (total yield about 60%); (3) low cost: the raw materials 2,5-dibromopyridine and tert-butyl carbamate (tert-butyloxycarbonyl amine) are both industrial mass production products with low price; there is no special catalyst requirement and the organic solvent can be recycled (such as toluene recovery rate ≥80%), which further reduces the production cost; (4) Environmentally friendly: no cyanide-containing wastewater is generated during the reaction process, waste gas and waste liquid can be discharged in accordance with the standard through conventional environmental protection treatment process, the impact on the environment is small, and it conforms to the development trend of green chemical industry; (5) Simple operation: the reaction conditions are mild (no need for ultra-low temperature and ultra-high pressure), the steps are clear, the post-treatment is simple, and the large-scale industrial production is easy to realize; (6) Compared with using ammonia gas as the amino source, in the second step of the present application, tert-butyl carbamate is used as the amino source, the reaction control is more accurate (dropping solution of tert-butyl carbamate), the reaction process is mild, controllable, safe and uniform in heat release, the amide product is a single tert-butyl (5-bromopyridine-2-formyl) carbamate, which has high purity and high yield; because if ammonia gas is used in the second step of the present application, due to the uneven flow and diffusion of ammonia gas, the reaction process is violent (the reaction of ammonia gas with high-activity acyl chloride is a violent exothermic reaction, it is not easy to realize local heat dissipation by gas input, which may cause the reaction temperature to rise instantaneously, causing the solvent to boil violently, the material to splash, and even to overflow, which brings serious safety hazards), the amide product is a mixture of primary amide and over-acylated product, which has low yield and poor purity; (7) Compared with using ammonia water as the amino source, the present application also has the advantages of mild, controllable and safe reaction process and uniform heat release, and the obtained tert-butyl (5-bromopyridine-2-formyl) carbamate has high purity and high yield; because if ammonia water is used in the second step of the present application, the ammonia water contains a large amount of water, and the acyl chloride is extremely sensitive to water, the hydrolysis reaction rate of which is usually much faster than the aminolysis reaction with ammonia; this will cause the main reaction to become a hydrolysis reaction, and most of the expensive acyl chloride raw materials will react with water to generate useless 5-bromo-2-pyridine carboxylic acid; even if the ammonia water is slowly dropped, the water in it will immediately react with the acyl chloride to generate a large amount of heat and hydrogen chloride gas, causing local violent boiling, splashing and even overflow, which is very dangerous for experimental operation. BRIEF DESCRIPTION OF DRAWINGS

[0013] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed in the embodiment description will be briefly introduced as follows: Figure 1 It is a schematic diagram of the synthesis method of 2-cyano-5-bromo-pyridine. Figure 2 It is a purity detection result diagram of 2-cyano-5-bromo-pyridine obtained by using the present application. DETAILED DESCRIPTION

[0014] In order to more clearly understand the above-mentioned purposes, features and advantages of the present application, the present application will be further described below in combination with the drawings and embodiments.

[0015] Many specific details are set forth in the following description in order to provide a thorough understanding of the application. However, the application can be practiced according to other embodiments that can not be described in detail herein, and the application is not limited to the specific embodiments described in this specification.

[0016] Example 1 The following is a detailed description of the synthesis of 2-cyano-5-bromopyridine according to the method of Example 1, which comprises the following steps: Figure 1 The following is a detailed description of the synthesis of 2-cyano-5-bromopyridine according to the method of Example 1, which comprises the following steps: Step 1, under inert gas protection, the raw material 2,5-dibromopyridine is added to organic solvent 1, and methyl magnesium chloride is added dropwise at -60~ -80℃, stirring for 2-4h, blowing dry carbon dioxide, adjusting the acid to obtain 5-bromo-2-pyridine carboxylic acid; Step 2, 5-bromo-2-pyridine carboxylic acid obtained in step 1 is added to organic solvent 2, and thionyl chloride is added dropwise at 0~10℃, after addition, the temperature is raised to 35~45℃ and stirred for 2-4h, concentrated until no more distillate drops, added to organic solvent 2, the temperature is controlled at 10~20℃, added triethylamine and dropwise added t-butyl carbamate solution, after monitoring the reaction completion by thin layer chromatography, extracted, dried and concentrated to obtain t-butyl (5-bromopyridine-2-formyl) carbamate; Step 3, t-butyl (5-bromopyridine-2-formyl) carbamate obtained in step 2 is reacted with an acidic solution, stirring at 15-25℃ for 2-4h to remove the t-butoxycarbonyl protecting group to obtain 5-bromo-2-pyridine carboxamide; Step 4, 5-bromo-2-pyridine carboxamide obtained in step 3, dehydrating agent is added to organic solvent 3, stirring at 80-100℃ for 6-8h to dehydrate to generate cyano to obtain the target product 2-cyano-5-bromopyridine.

[0017] Step 1, synthesis of 5-bromo-2-pyridine carboxylic acid: 1. Experimental purpose: 2,5-dibromopyridine as raw material, through Grignard reaction / carboxylation reaction, to prepare intermediate 5-bromo-2-pyridine carboxylic acid.

[0018] 2. Main instruments and equipment: 500 mL three-necked flask, low-temperature constant temperature stirring bath, magnetic stirrer, constant pressure dropping funnel, thermometer, gas inlet tube, rotary evaporator and vacuum drying oven.

[0019] 3. Reagents and materials: 4. Experimental steps and phenomenon records: (1) Device setup and charging: Under nitrogen protection, a dry 500 mL three-necked flask was sequentially added with tetrahydrofuran (THF) (100 mL) and 2,5-dibromopyridine (23.6 g). The stirring was started and the solid was completely dissolved to obtain a colorless to light yellow clear solution. Cooling: The reaction bottle was placed in a low-temperature bath and slowly cooled to an internal temperature of -70°C (actual record: -68°C to -72°C). Dropwise addition of Grignard reagent: The THF solution of methyl magnesium chloride (40 mL, 3.0 M) was slowly added through a constant pressure dropping funnel. The dropwise addition speed was controlled to maintain the internal temperature at about -70°C. During the dropwise addition, the color of the reaction solution did not change significantly (recorded: remained clear).

[0020] 2,5-dibromopyridine + methyl magnesium chloride → 5-bromo-2-pyridyl magnesium chloride + bromomethane↑.

[0021] (2) Insulation reaction: After the dropwise addition was completed, the reaction was continuously stirred at -70°C for 2 hours. Thin layer chromatography (TLC) monitoring (developing agent: petroleum ether: ethyl acetate = 3:1, ultraviolet lamp 254 nm coloration) showed that the 2,5-dibromopyridine raw material point (Rf≈0.8) basically disappeared, and a new point was generated near the baseline (Rf≈0.1), which was preliminarily judged to be a Grignard salt. Carbon dioxide was introduced: Keeping the low temperature, dry carbon dioxide gas was introduced into the reaction solution for about 30 minutes. It was observed that the reaction solution gradually became a turbid suspension.

[0022] (3) Quenching and post-treatment: Keeping the internal temperature ≤-30°C, a pre-cooled dilute hydrochloric acid solution (100 mL) was slowly added for quenching. A large amount of bubbles were generated and the system gradually became clear. After the quenching was completed, the cold bath was removed and the temperature was naturally increased to room temperature (about 22°C).

[0023] After the introduction of carbon dioxide, 5-bromo-2-pyridyl magnesium chloride was acidified to obtain 5-bromo-2-pyridine carboxylic acid. 5-bromo-2-pyridyl magnesium chloride + carbon dioxide + hydrogen ion → 5-bromo-2-pyridine carboxylic acid + magnesium ion + chloride ion.

[0024] (4) Extraction and drying: The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate (100 mL × 3 times). The organic phase was washed with saturated brine (100 mL × 2 times). The organic phase was dried with anhydrous sodium sulfate for about 30 minutes.

[0025] (5) Concentration and product: The drying agent was removed by filtration and the filtrate was rotary evaporated under reduced pressure (water bath 60°C, vacuum degree 0.08 MPa) to remove the solvent. A white or white-like solid crude product was obtained.

[0026] 5. Product data: Appearance: white solid, Weight: 17.37 g, Yield calculation: (17.37 g / theoretical yield 20.2 g) x 100% = 86.0%, Melting point determination: 174-176 °C, Thin layer chromatography TLC purity: single major spot (petroleum ether: ethyl acetate = 1:1).

[0027] Experimental summary: The operation of this step was smooth, and temperature control was the key. The yield and purity of the product met the expectations and could be used for the next step reaction.

[0028] Step two, synthesis of tert-butyl (5-bromopyridine-2-formyl)carbamate: 1. Experimental purpose: Convert 5-bromo-2-pyridinecarboxylic acid into the corresponding N-Boc protected amide.

[0029] 2. Main instruments and equipment: (synchronous step one, low temperature bath is omitted).

[0030] 3. Reagents and materials: 4. Experimental steps and phenomenon records: (1) Acyl chloride: Add toluene (100 mL) and 5-bromo-2-pyridinecarboxylic acid (20.2 g) into a dry 500 mL reaction flask. Cool to 0-5°C with ice water bath, and slowly add thionyl chloride (8.7 mL). There is irritating gas (hydrogen chloride, sulfur dioxide) generated during the dropwise addition. After dropwise addition, remove the ice bath and warm to 40°C for 3 hours of stirring reaction. Thin layer chromatography TLC monitoring (petroleum ether: ethyl acetate = 1:1) shows that the acid point disappears and a new point is generated (Rf value is slightly higher).

[0031] 5-bromo-2-pyridinecarboxylic acid + thionyl chloride → 5-bromo-2-pyridinecarboxylic chloride + sulfur dioxide↑ + hydrogen chloride↑.

[0032] (2) Concentration to remove thionyl chloride: Concentrate the reaction liquid under reduced pressure until no obvious fraction is distilled out to obtain the acyl chloride crude product (oil). Amide: Add fresh toluene (100 mL) to dissolve the above oil. Control the temperature at 10-15°C with ice water bath, and then add triethylamine (14 mL) and then slowly dropwise add the solution of tert-butyl carbamate (11.83 g dissolved in 20 mL toluene). White smoke (triethylamine hydrochloride) is generated during the dropwise addition, and the system becomes turbid.

[0033] 5-bromo-2-pyridinecarboxylic chloride + triethylamine + tert-butyl carbamate → tert-butyl (5-bromopyridine-2-formyl)carbamate + triethylamine hydrochloride.

[0034] (3) Reaction monitoring: After the addition was complete, stirring was continued at 10-15℃ for 1 hour, followed by stirring at room temperature for 2 hours. HPLC monitoring showed that the peak area of ​​the starting material acyl chloride (or its corresponding acid) was <2%. Post-treatment: Water (100 mL) was added to the reaction solution to quench the reaction, and the mixture was stirred and separated. The aqueous phase was extracted with ethyl acetate (50 mL × 2). All organic phases were combined and washed successively with 1M dilute hydrochloric acid, saturated sodium bicarbonate solution, and saturated brine. The organic phases were dried over anhydrous sodium sulfate.

[0035] (4) Concentration and product yield: The filtrate was filtered and concentrated under reduced pressure to obtain a pale yellow viscous oily substance, which gradually solidified after standing at room temperature. Appearance: off-white solid, weight: 26.4 g, yield calculation: (26.4 g / theoretical yield 30.0 g) × 100% ≈ 88.0%, TLC / HPLC: showed that it was the main product with good purity.

[0036] (5) Experimental summary: The acyl chloride and amidation reactions were complete, and the post-processing steps were standard. The product state and yield met expectations.

[0037] Step 3, Synthesis of 5-bromo-2-pyridinecarboxamide (Boc deprotection): Key Procedure: 30.0 g (0.10 mol) of tert-butyl(5-bromopyridin-2-formyl)carbamate was dissolved in a small amount of ethyl acetate (10 mL), and dry hydrogen chloride gas was passed through at room temperature until saturation (approximately 0.4 mol). The system gradually became turbid, and a solid precipitated. Reaction Monitoring: Thin-layer chromatography (TLC) (petroleum ether:ethyl acetate = 1:1) showed the disappearance of the Boc protected product spot, and a new strongly polar spot (formamide hydrochloride) appeared near the origin. Post-treatment: After the reaction was complete, the mixture was filtered to obtain a white solid (hydrochloride). This solid was dissolved in water, and the pH was carefully adjusted to 8-9 with 5% sodium hydroxide solution, resulting in a large amount of white solid reprecipitating. The mixture was filtered, washed with water, and dried under vacuum at 50°C.

[0038] tert-butyl (5-bromopyridine-2-carboxylo) carbamate + hydrogen chloride → 5-bromo-2-pyridinecarboxamide hydrochloride + carbon dioxide↑ + isobutylene↑; 5-Bromo-2-pyridinecarboxamide hydrochloride + 5% sodium hydroxide solution → 5-Bromo-2-pyridinecarboxamide + sodium chloride + water.

[0039] Results: Product: 5-bromo-2-pyridinecarboxamide, Appearance: white crystalline powder, Weight: 19.0 g, Yield: 95.0%, Melting point: 219-221 °C.

[0040] Step 4, Synthesis of 2-cyano-5-bromopyridine (dehydration to nitrile): (1) Key Operations: 5-Bromo-2-pyridinecarboxamide (20.0 g, 0.10 mol) and toluene (100 mL) were added to a reaction flask, followed by the addition of phosphorus oxychloride (15.3 g, 0.10 mol) with stirring. The mixture was refluxed at 90 °C for 7 hours. Reaction Monitoring: High-performance liquid chromatography (HPLC) monitoring showed that the formamide peak area was <1%, with the main product peak appearing at a shorter retention time.

[0041] 5-Bromo-2-pyridinecarboxamide + phosphorus oxychloride → 2-cyano-5-bromopyridine + phosphoric acid + 3-hydrogen chloride↑.

[0042] (2) Key post-processing: Under good ventilation, slowly pour the cooled reaction solution into 200 g of vigorously stirred crushed ice / ice water. Carefully neutralize to pH 7-8 with 2 M sodium hydroxide solution. Extract with ethyl acetate, dry, and concentrate to obtain the crude product.

[0043] (3) Purification: The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 5:1).

[0044] (4) Results: Final product: 2-cyano-5-bromopyridine, Appearance: white needle-like crystals, Weight: 15.98 g, Yield: 89.8% (based on formamide), such as Figure 2 Purity (HPLC): 99.3%, Melting point: 129-131 °C, Overall yield of four steps (based on 2,5-dibromopyridine): 0.860 × 0.880 × 0.950 × 0.898 ≈ 64.6%.

[0045] Experimental Summary: This experiment successfully completed the four-step synthesis of 2-cyano-5-bromopyridine according to the established route.

[0046] Example 2 The difference between this embodiment and Example 1 is that in step two of this embodiment, 0.11 mol or 0.13 mol of thionyl chloride is used. Since the theoretical molar ratio of 5-bromo-2-pyridinecarboxylic acid to thionyl chloride participating in the reaction is 1:1, thionyl chloride is used in slight excess to ensure that the reaction proceeds completely.

[0047] Example 3 The difference between this embodiment and Example 1 is that in step three, the acidic solution is a mixture of trifluoroacetic acid and dichloromethane in a volume ratio of 1:1, yielding trifluoroacetate. This solid is dissolved in water, and the pH is carefully adjusted to 8-9 with a 5% sodium hydroxide solution, resulting in the re-precipitation of a large amount of white solid. The solution is then filtered, washed with water, and vacuum dried at 50°C.

[0048] tert-butyl (5-bromopyridine-2-carboxylic acid) carbamate + trifluoroacetic acid → trifluoroacetate + carbon dioxide↑ + isobutylene↑; Trifluoroacetate + 5% sodium hydroxide solution → 5-bromo-2-pyridinecarboxamide + sodium trifluoroacetate + water.

[0049] Example 4 The difference between this embodiment and Example 1 is that the dehydrating agent in step four is phosphorus pentoxide. The reaction formula is: 5-Bromo-2-pyridinecarboxamide + phosphorus pentoxide → 2-cyano-5-bromopyridine + 2-metaphophosphate.

[0050] Example 5 The difference between this embodiment and Example 1 is that the dehydrating agent in step four is thionyl chloride. The reaction formula is: 5-Bromo-2-pyridinecarboxamide + thionyl chloride → 2-cyano-5-bromopyridine + sulfur dioxide↑ + 2 hydrogen chloride↑.

[0051] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any other way. Any person skilled in the art may make changes or modifications to the above-disclosed technical content to create equivalent embodiments that can be applied to other fields. However, any simple modifications or equivalent changes made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the protection scope of the present invention.

Claims

1. A method for synthesizing 2-cyano-5-bromopyridine, characterized in that, Includes the following steps: Step 1: Under inert gas protection, 2,5-dibromopyridine is added to organic solvent 1, and methyl magnesium chloride is added dropwise at -60~-80℃. The mixture is stirred and reacted for 2-4 hours. Dry carbon dioxide is bubbled in, and the mixture is treated with acid to obtain 5-bromo-2-pyridinecarboxylic acid. Step 2: Add the 5-bromo-2-pyridinecarboxylic acid obtained in Step 1 to Organic Solvent 2, and add thionyl chloride dropwise while controlling the temperature at 0~10℃. After the addition is complete, raise the temperature to 35~45℃ and stir for 2-4 hours. Concentrate until no more distillate drips out, add Organic Solvent 2 until the material is completely dissolved, add triethylamine while controlling the temperature at 10~20℃, and add a solution of tert-butyl carbamate dropwise. After monitoring the completion of the reaction by thin-layer chromatography, extract, dry and concentrate to obtain tert-butyl (5-bromopyridine-2-carboxy) carbamate. Step 3: The tert-butyl (5-bromopyridine-2-carboxylic acid) carbamate obtained in Step 2 is reacted with an acidic solution and stirred at 15-25°C for 2-4 hours to remove the tert-butoxycarbonyl protecting group, yielding 5-bromo-2-pyridinecarboxamide. Step four: Add the 5-bromo-2-pyridine carboxamide obtained in step three and the dehydrating agent to organic solvent three, and stir the reaction at 80-100℃ for 6-8 hours to dehydrate and generate cyano group, thus obtaining the target product 2-cyano-5-bromopyridine.

2. The method for synthesizing 2-cyano-5-bromopyridine according to claim 1, characterized in that, In step one, the molar ratio of 2,5-dibromopyridine to methylmagnesium chloride is 1:1.2; the organic solvent is tetrahydrofuran; and the inert gas is nitrogen or argon.

3. The method for synthesizing 2-cyano-5-bromopyridine according to claim 1, characterized in that, In step two, the ratio of raw materials 5-bromo-2-pyridinecarboxylic acid: thionyl chloride: tert-butyl carbamate is 1:1.10~1.30:1.01 (molar ratio); the organic solvent is toluene.

4. The method for synthesizing 2-cyano-5-bromopyridine according to claim 1, characterized in that, The acidic solution mentioned in step three is an ethyl acetate solution of hydrogen chloride or a mixed solution of trifluoroacetic acid and dichloromethane in a volume ratio of 1:

1.

5. The method for synthesizing 2-cyano-5-bromopyridine according to claim 1, characterized in that, The dehydrating agent mentioned in step four is phosphorus oxychloride, phosphorus pentoxide, or thionyl chloride.

6. The method for synthesizing 2-cyano-5-bromopyridine according to claim 5, characterized in that, In step four, the molar ratio of 5-bromo-2-pyridinecarboxamide to the dehydrating agent is 1:1.5-2.

0.

7. The method for synthesizing 2-cyano-5-bromopyridine according to claim 6, characterized in that, The organic solvent is toluene or chlorobenzene.

Images