Synthesis method of 2, 5-dibromopyridine

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of 2, 5-dibromopyridine, and the method comprises the following steps: (1) adding 2-aminopyridine and acetic anhydride into a four-neck flask, refluxing, and completely reacting by thin-layer chromatography tracking; (2) when the temperature of the reaction solution in the step (1) isreduced to 20-25 DEG C, dropwise adding liquid bromine, reacting for 2-3 hours at 45-55 DEG C after completion of the dropwise adding, adding water into the system until all solids are dissolved, dropwise adding a sodium hydroxide solution, continuously reacting for 30-40 minutes when a large amount of precipitate is generated, and carrying out suction filtration, drying and recrystallization to obtain 2-amino-5-bromopyridine; and (3) adding the 2-amino-5-bromopyridine into a hydrogen bromide solution, dropwise adding a sodium nitrate solution in the presence of a catalytic amount of cuprous bromide, controlling the temperature to be -5 to15 DEG C, and reacting for 2-5 hours to obtain the 2, 5-dibromopyridine. The method has the beneficial effects of mild reaction conditions, high yield, accessible raw materials, lower cost and fewer product byproducts, reduces the composite load of later separation, and has industrial prospects.

Description

technical field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a synthesis method of 2,5-dibromopyridine. Background technique

[0002] Pyridine and its derivatives are widely distributed in nature. Many plant components such as alkaloids contain pyridine ring compounds in their structures, which are the basis for the production of many important compounds, such as medicines, pesticides, dyes, surfactants, rubber additives, feed additives, food additives, adhesives, etc. Indispensable raw material in production. 2,5-Dibromopyridine is an important intermediate in organic synthesis, mainly used in pharmaceutical intermediates, organic synthesis, organic solvents, and can also be used in dye production, pesticide production and spices.

[0003] At present, the reported synthetic methods of 2,5-dibromopyridine have disadvantages such as low yield and long process route. Contents of the invention

[0004] The purpose o...

Examples

Embodiment 1

[0021] Add 18.82g (0.2mol) of 2-aminopyridine and 30.63g (0.3mol) of acetic anhydride to a 200ml four-port oil bath and raise the temperature to reflux, follow the reaction with thin-layer chromatography until the reaction is complete, and wait until the temperature of the reaction solution drops to 20-25 At ℃, slowly add 35.2g (0.22mol) of liquid bromine dropwise, and react at 50℃ for 2.5 hours after dropping. Add water to the system until the solid is completely dissolved, slowly add 80ml of 40% sodium hydroxide solution dropwise, a large amount of solid is formed, continue the reaction for 30 minutes, filter with suction, dry, and recrystallize with ethanol to obtain 2-amino-5-bromopyridine 14.1 g, yield 65% (molar yield).

[0022] Add 50ml48% hydrobromic acid solution in the 200ml there-necked flask equipped with stirrer and thermometer, 6.9g (0.048mol) cuprous bromide is dissolved in the hydrobromic acid solution, keep temperature 0 ℃ in ice-water bath and slowly add 6g (...

Embodiment 2

[0024] Add 18.82g (0.2mol) of 2-aminopyridine and 20.4g (0.2mol) of acetic anhydride to a 200ml four-port oil bath and raise the temperature to reflux, follow the reaction with thin-layer chromatography until the reaction is complete, and wait until the temperature of the reaction solution drops to 20-25 At ℃, slowly add 35.2g (0.22mol) of liquid bromine dropwise, and react at 55℃ for 2 hours after dropping. Add water to the system until the solid is completely dissolved, slowly add 80ml of 40% sodium hydroxide solution dropwise, a large amount of solid is formed, continue the reaction for 30 minutes, filter with suction, dry, and recrystallize with ethanol to obtain 2-amino-5-bromopyridine 12.98 g, yield 60% (molar yield).

[0025] Add 50ml of 48% hydrobromic acid solution to a 200ml three-necked flask equipped with a stirrer and a thermometer, dissolve 7.5g (0.052mol) of cuprous bromide in the hydrobromic acid solution, and slowly add 6g in an ice-water bath to maintain the ...

Embodiment 3

[0027] Add 18.82g (0.2mol) of 2-aminopyridine and 40.8g (0.4mol) of acetic anhydride to a 200ml four-port oil bath and raise the temperature to reflux, follow the reaction with thin-layer chromatography until the reaction is complete, and wait until the temperature of the reaction solution drops to 20-25 At ℃, slowly add 35.2g (0.22mol) of liquid bromine dropwise, and react at 45℃ for 3 hours after dropping. Add water to the system until the solid is completely dissolved, slowly add 80ml of 40% sodium hydroxide solution dropwise, a large amount of solid is formed, continue the reaction for 30 minutes, filter with suction, dry, and recrystallize with ethanol to obtain 2-amino-5-bromopyridine 12.5 g, yield 62% (molar yield).

[0028] Add 50ml48% hydrobromic acid solution in the 200ml there-necked flask equipped with agitator and thermometer, 8.6g (0.06mol) cuprous bromide is dissolved in the hydrobromic acid solution, and slowly add 6g ( 0.04mol) 2-amino-5-bromopyridine, keep t...

technical field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a synthesis method of 2,5-dibromopyridine. Background technique

[0002] Pyridine and its derivatives are widely distributed in nature. Many plant components such as alkaloids contain pyridine ring compounds in their structures, which are the basis for the production of many important compounds, such as medicines, pesticides, dyes, surfactants, rubber additives, feed additives, food additives, adhesives, etc. Indispensable raw material in production. 2,5-Dibromopyridine is an important intermediate in organic synthesis, mainly used in pharmaceutical intermediates, organic synthesis, organic solvents, and can also be used in dye production, pesticide production and spices.

[0003] At present, the reported synthetic methods of 2,5-dibromopyridine have disadvantages such as low yield and long process route. Contents of the invention

[0004] The purpose o...

Examples

Embodiment 1

[0021] Add 18.82g (0.2mol) of 2-aminopyridine and 30.63g (0.3mol) of acetic anhydride to a 200ml four-port oil bath and raise the temperature to reflux, follow the reaction with thin-layer chromatography until the reaction is complete, and wait until the temperature of the reaction solution drops to 20-25 At ℃, slowly add 35.2g (0.22mol) of liquid bromine dropwise, and react at 50℃ for 2.5 hours after dropping. Add water to the system until the solid is completely dissolved, slowly add 80ml of 40% sodium hydroxide solution dropwise, a large amount of solid is formed, continue the reaction for 30 minutes, filter with suction, dry, and recrystallize with ethanol to obtain 2-amino-5-bromopyridine 14.1 g, yield 65% (molar yield).

[0022] Add 50ml48% hydrobromic acid solution in the 200ml there-necked flask equipped with stirrer and thermometer, 6.9g (0.048mol) cuprous bromide is dissolved in the hydrobromic acid solution, keep temperature 0 ℃ in ice-water bath and slowly add 6g (...

Embodiment 2

[0024] Add 18.82g (0.2mol) of 2-aminopyridine and 20.4g (0.2mol) of acetic anhydride to a 200ml four-port oil bath and raise the temperature to reflux, follow the reaction with thin-layer chromatography until the reaction is complete, and wait until the temperature of the reaction solution drops to 20-25 At ℃, slowly add 35.2g (0.22mol) of liquid bromine dropwise, and react at 55℃ for 2 hours after dropping. Add water to the system until the solid is completely dissolved, slowly add 80ml of 40% sodium hydroxide solution dropwise, a large amount of solid is formed, continue the reaction for 30 minutes, filter with suction, dry, and recrystallize with ethanol to obtain 2-amino-5-bromopyridine 12.98 g, yield 60% (molar yield).

[0025] Add 50ml of 48% hydrobromic acid solution to a 200ml three-necked flask equipped with a stirrer and a thermometer, dissolve 7.5g (0.052mol) of cuprous bromide in the hydrobromic acid solution, and slowly add 6g in an ice-water bath to maintain the ...

Embodiment 3

[0027] Add 18.82g (0.2mol) of 2-aminopyridine and 40.8g (0.4mol) of acetic anhydride to a 200ml four-port oil bath and raise the temperature to reflux, follow the reaction with thin-layer chromatography until the reaction is complete, and wait until the temperature of the reaction solution drops to 20-25 At ℃, slowly add 35.2g (0.22mol) of liquid bromine dropwise, and react at 45℃ for 3 hours after dropping. Add water to the system until the solid is completely dissolved, slowly add 80ml of 40% sodium hydroxide solution dropwise, a large amount of solid is formed, continue the reaction for 30 minutes, filter with suction, dry, and recrystallize with ethanol to obtain 2-amino-5-bromopyridine 12.5 g, yield 62% (molar yield).

[0028] Add 50ml48% hydrobromic acid solution in the 200ml there-necked flask equipped with agitator and thermometer, 8.6g (0.06mol) cuprous bromide is dissolved in the hydrobromic acid solution, and slowly add 6g ( 0.04mol) 2-amino-5-bromopyridine, keep t...

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