Preparation method of 2-methyl-3-bromopyridine

Abstract

The invention belongs to the field of organic synthesis and particularly relates to a preparation method of 2-methyl-3-bromopyridine. The preparation method includes the following steps that 1, diethyl malonate reacts with alkali metal to generate salt, then a methylbenzene solution of 2-chlorine-3-nitropyridine is added dropwise to be conducted a condensation reaction, and the 2-methyl-3-nitropyridine is obtained through decarboxylation under an acidic condition; 2, under the catalysis of Pd / C, methanol serves as a solvent, a hydrogenation reduction and suction filtration are conducted on the 2-methyl-3-nitropyridine, filtered liquid is condensed, and 2-methyl-3-aminopyridine is obtained; 3, the 2-methyl-3-aminopyridine reacts with acid to generate salt, the cooling is conducted to enable the temperature to be in -10 DEG C-0 DEG C, bromine is added dropwise, after the addition, then a sodium nitrite solution is added dropwise, after addition, pH of the solution is adjusted to be alkaline, then extracting, drying and concentration are conducted, and the 2-methyl-3-bromopyridine is obtained. The preparation method of the 2-methyl-3-bromopyridine has the advantages that the reaction condition is moderate, the operation is easy, the post-processing is simple, enlarged production is easy, and the preparation method is very suitable for industrial production; the catalysis effect is good, and the reaction yield ratio is high; the price of the raw material is low, and the production cost is low.

Description

technical field

[0001] The invention belongs to the field of organic synthesis, and in particular relates to a preparation method of 2-methyl-3-bromopyridine. Background technique

[0002] 2-Methyl-3-bromopyridine is an important intermediate, mainly used as pharmaceutical intermediates, organic synthesis intermediates, organic solvents, and also used in the production of dyes, spices and pesticides.

[0003] At present, the main synthetic route of 2-methyl-3-bromopyridine is to use 2-methylpyridine as raw material, react with liquid bromine under the catalysis of Lewis acid, and its products are 3-bromo-2-methylpyridine and 5- A mixture of bromo-2-picoline, and 3-bromo-2-picoline and 5-bromo-2-picoline are difficult to separate. The shortcoming of this method is: the consumption of aluminum trichloride is big, and catalytic effect is poor; Bromine can carry out bromination in multiple positions, and by-product is many, and product yield is low; The boiling point of gained ...

Examples

Embodiment 1

[0019] (1) Preparation of 2-methyl-3-nitropyridine: Heat a mixture of diethyl malonate (80ml, 0.5mol) and sodium (2.53g, 0.11mol) in an oil bath to 90°C, stir for 1h, After heating up to 120°C and stirring for 45 min, it was cooled to room temperature. A toluene solution of 2-chloro-3-nitropyridine (15.6 g, 0.1 mol) was added dropwise. After the addition was complete, the reaction solution was heated to 110° C. for 1.5 h, cooled to room temperature and stirred for 15 h. The solvent was evaporated under reduced pressure, 6N hydrochloric acid (100ml) was added, the temperature was raised to reflux for 3.5h and then cooled to room temperature. Adjust the pH to alkaline with saturated sodium carbonate solution, extract with ethyl acetate, combine the base phases, dry over anhydrous sodium sulfate, and concentrate by suction filtration to obtain 2-methyl-3-nitropyridine with a molar yield of 92%. .

[0020] (2) Preparation of 2-methyl-3-aminopyridine: Dissolve 2-methyl-3-nitropyr...

Embodiment 2

[0023] (1) Preparation of 2-methyl-3-nitropyridine: Heat a mixture of diethyl malonate (80ml, 0.5mol) and sodium (2.76g, 0.12mol) in an oil bath to 90°C, stir for 1h, After heating up to 120°C and stirring for 45 min, it was cooled to room temperature. A toluene solution of 2-chloro-3-nitropyridine (15.6 g, 0.1 mol) was added dropwise. After the addition was complete, the reaction solution was heated to 110° C. for 1.5 h, cooled to room temperature and stirred for 15 h. The solvent was evaporated under reduced pressure, 6N hydrochloric acid (100ml) was added, the temperature was raised to reflux for 3.5h and then cooled to room temperature. Adjust the pH to alkaline with saturated sodium carbonate solution, extract with ethyl acetate, combine the base phases, dry over anhydrous sodium sulfate, and concentrate by suction filtration to obtain 2-methyl-3-nitropyridine with a molar yield of 95%. .

[0024] (2) Preparation of 2-methyl-3-aminopyridine: Dissolve 2-methyl-3-nitropyr...

Embodiment 3

[0027] (1) Preparation of 2-methyl-3-nitropyridine: Heat a mixture of diethyl malonate (80ml, 0.5mol) and sodium (2.99g, 0.13mol) in an oil bath to 90°C, stir for 1h, After heating up to 120°C and stirring for 45 min, it was cooled to room temperature. A toluene solution of 2-chloro-3-nitropyridine (15.6 g, 0.1 mol) was added dropwise. After the addition was complete, the reaction solution was heated to 110° C. for 1.5 h, cooled to room temperature and stirred for 15 h. The solvent was evaporated under reduced pressure, 6N hydrochloric acid (100ml) was added, the temperature was raised to reflux for 3.5h and then cooled to room temperature. Adjust the pH to alkaline with saturated sodium carbonate solution, extract with ethyl acetate, combine the base phases, dry over anhydrous sodium sulfate, and concentrate by suction filtration to obtain 2-methyl-3-nitropyridine with a molar yield of 95%. .

[0028] (2) Preparation of 2-methyl-3-aminopyridine: Dissolve 2-methyl-3-nitropyr...

technical field

[0001] The invention belongs to the field of organic synthesis, and in particular relates to a preparation method of 2-methyl-3-bromopyridine. Background technique

[0002] 2-Methyl-3-bromopyridine is an important intermediate, mainly used as pharmaceutical intermediates, organic synthesis intermediates, organic solvents, and also used in the production of dyes, spices and pesticides.

[0003] At present, the main synthetic route of 2-methyl-3-bromopyridine is to use 2-methylpyridine as raw material, react with liquid bromine under the catalysis of Lewis acid, and its products are 3-bromo-2-methylpyridine and 5- A mixture of bromo-2-picoline, and 3-bromo-2-picoline and 5-bromo-2-picoline are difficult to separate. The shortcoming of this method is: the consumption of aluminum trichloride is big, and catalytic effect is poor; Bromine can carry out bromination in multiple positions, and by-product is many, and product yield is low; The boiling point of gained ...

Examples

Embodiment 1

[0019] (1) Preparation of 2-methyl-3-nitropyridine: Heat a mixture of diethyl malonate (80ml, 0.5mol) and sodium (2.53g, 0.11mol) in an oil bath to 90°C, stir for 1h, After heating up to 120°C and stirring for 45 min, it was cooled to room temperature. A toluene solution of 2-chloro-3-nitropyridine (15.6 g, 0.1 mol) was added dropwise. After the addition was complete, the reaction solution was heated to 110° C. for 1.5 h, cooled to room temperature and stirred for 15 h. The solvent was evaporated under reduced pressure, 6N hydrochloric acid (100ml) was added, the temperature was raised to reflux for 3.5h and then cooled to room temperature. Adjust the pH to alkaline with saturated sodium carbonate solution, extract with ethyl acetate, combine the base phases, dry over anhydrous sodium sulfate, and concentrate by suction filtration to obtain 2-methyl-3-nitropyridine with a molar yield of 92%. .

[0020] (2) Preparation of 2-methyl-3-aminopyridine: Dissolve 2-methyl-3-nitropyr...

Embodiment 2

[0023] (1) Preparation of 2-methyl-3-nitropyridine: Heat a mixture of diethyl malonate (80ml, 0.5mol) and sodium (2.76g, 0.12mol) in an oil bath to 90°C, stir for 1h, After heating up to 120°C and stirring for 45 min, it was cooled to room temperature. A toluene solution of 2-chloro-3-nitropyridine (15.6 g, 0.1 mol) was added dropwise. After the addition was complete, the reaction solution was heated to 110° C. for 1.5 h, cooled to room temperature and stirred for 15 h. The solvent was evaporated under reduced pressure, 6N hydrochloric acid (100ml) was added, the temperature was raised to reflux for 3.5h and then cooled to room temperature. Adjust the pH to alkaline with saturated sodium carbonate solution, extract with ethyl acetate, combine the base phases, dry over anhydrous sodium sulfate, and concentrate by suction filtration to obtain 2-methyl-3-nitropyridine with a molar yield of 95%. .

[0024] (2) Preparation of 2-methyl-3-aminopyridine: Dissolve 2-methyl-3-nitropyr...

Embodiment 3

[0027] (1) Preparation of 2-methyl-3-nitropyridine: Heat a mixture of diethyl malonate (80ml, 0.5mol) and sodium (2.99g, 0.13mol) in an oil bath to 90°C, stir for 1h, After heating up to 120°C and stirring for 45 min, it was cooled to room temperature. A toluene solution of 2-chloro-3-nitropyridine (15.6 g, 0.1 mol) was added dropwise. After the addition was complete, the reaction solution was heated to 110° C. for 1.5 h, cooled to room temperature and stirred for 15 h. The solvent was evaporated under reduced pressure, 6N hydrochloric acid (100ml) was added, the temperature was raised to reflux for 3.5h and then cooled to room temperature. Adjust the pH to alkaline with saturated sodium carbonate solution, extract with ethyl acetate, combine the base phases, dry over anhydrous sodium sulfate, and concentrate by suction filtration to obtain 2-methyl-3-nitropyridine with a molar yield of 95%. .

[0028] (2) Preparation of 2-methyl-3-aminopyridine: Dissolve 2-methyl-3-nitropyr...

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