Synthetic method of 2,3,4-trimethyl-6-bromopyridine

Abstract

The invention relates to the field of organic chemistry, in particular to a synthetic method of 2,3,4-trimethyl-6-bromopyridine. The method includes the following steps that diethyl malonate reacts with alkaline metal to generate salt, a toluene solution of 2,3-dimethyl-6- nitryl-4-chloropyridine is added dropwise to carry out condensation reaction, and then under the acid condition, decarboxylation is conducted to obtain 2,3,4-thimethyl-6-nitropyridine; 2,3,4-thimethyl-6-nitropyridine is catalyzed by Pd / C, methanol serves as solvent, hydrogenation reduction and filtration are conducted, filtrate is concentrated, and 2,3,4-thimethyl-6-aminopyridine is obtained; firstly, 2,3,4-thimethyl-6-aminopyridine reacts with acid to generate salt, cooling is conducted to make the temperature at 6-12 DEG C, liquid bromine is added dropwise, after liquid bromine is added, an aqueous solution of sodium nitrite is added dropwise, after the aqueous solution of sodium nitrite is added, the pH value of a solution is adjusted to be alkaline, and extraction, drying and concentration are conducted to obtain 2,3,4-thimethyl-6-bromopyridine. The synthetic method of 2,3,4-trimethyl-6-bromopyridine has the advantages that reaction conditions are mile, the yield is high, the raw materials are easy to obtain, the cost is low, the process path is short, and the synthetic method of 2,3,4-trimethyl-6-bromopyridine has industrial prospects.

Description

technical field

[0001] The invention relates to the field of organic chemistry, in particular to a synthesis method of 2,3,4-trimethyl-6-bromopyridine. 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. 2,3,4-Trimethyl-6-bromopyridine 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. Currently, the reported synthetic methods of 2,3,4-trimethyl-6-bromopyridine have disadvantages such as low yield and long process route. Contents of the invention

[0003] The probl...

Examples

Embodiment approach 1

[0012] Diethyl malonate reacts with sodium metal to form a salt, then adds dropwise a toluene solution of 2,3 dimethyl-6-nitro-4 chloropyridine for condensation reaction, and then decarboxylates under acidic conditions to obtain 2,3,4 - Trimethyl-6-nitropyridine; wherein the molar ratio of diethyl malonate, sodium metal, and 2,3 dimethyl-6-nitro-4-chloropyridine is 4.2:1.4:1.2.

[0013] 2,3,4-trimethyl-6-nitropyridine is catalyzed by Pd / C, methanol is used as a solvent, hydrogenation reduction, suction filtration, and the filtrate is concentrated to obtain 2,3,4-trimethyl-6-amino pyridine;

[0014] 2,3,4-Trimethyl-6-aminopyridine forms a salt with acid first, cools to -12°C, adds liquid bromine dropwise, and then adds sodium nitrite aqueous solution dropwise, after the dropwise addition, adjust the pH of the solution to be alkaline, Then extract, dry and concentrate to obtain 2,3,4-trimethyl-6-bromopyridine.

Embodiment approach 2

[0016] Diethyl malonate reacts with potassium metal to form a salt, then add dropwise a toluene solution of 2,3 dimethyl-6-nitro-5 chloropyridine for condensation reaction, and then decarboxylate under acidic conditions to obtain 2,3,4 - Trimethyl-6-nitropyridine; wherein the molar ratio of diethyl malonate, potassium metal, and 2,3 dimethyl-6-nitro-4-chloropyridine is 5.3:1.7:1.2.

[0017] 2,3,4-trimethyl-6-nitropyridine is catalyzed by Pd / C, methanol is used as a solvent, hydrogenation reduction, suction filtration, and the filtrate is concentrated to obtain 2,3,4-trimethyl-6-amino pyridine;

[0018] 2,3,4-Trimethyl-6-aminopyridine first forms a salt with acid, cools to 6°C, adds liquid bromine dropwise, and then adds sodium nitrite aqueous solution dropwise, adjusts the pH of the solution to be alkaline after the dropwise addition, and then Extraction, drying and concentration give 2,3,4-trimethyl-6-bromopyridine.

Embodiment approach 3

[0020] Diethyl malonate reacts with sodium metal to form a salt, then adds dropwise a toluene solution of 2,3 dimethyl-6-nitro-4 chloropyridine for condensation reaction, and then decarboxylates under acidic conditions to obtain 2,3,4 - Trimethyl-6-nitropyridine; wherein the molar ratio of diethyl malonate, sodium metal, and 2,3 dimethyl-6-nitro-4-chloropyridine is 4.8:1.5:1.2.

[0021] 2,3,4-trimethyl-6-nitropyridine is catalyzed by Pd / C, methanol is used as a solvent, hydrogenation reduction, suction filtration, and the filtrate is concentrated to obtain 2,3,4-trimethyl-6-amino pyridine;

[0022] 2,3,4-Trimethyl-6-aminopyridine first forms a salt with an acid, cools to -5°C, adds liquid bromine dropwise, and then adds sodium nitrite aqueous solution dropwise, and adjusts the pH of the solution to be alkaline after the dropwise addition. Then extract, dry and concentrate to obtain 2,3,4-trimethyl-6-bromopyridine.

technical field

[0001] The invention relates to the field of organic chemistry, in particular to a synthesis method of 2,3,4-trimethyl-6-bromopyridine. 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. 2,3,4-Trimethyl-6-bromopyridine 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. Currently, the reported synthetic methods of 2,3,4-trimethyl-6-bromopyridine have disadvantages such as low yield and long process route. Contents of the invention

[0003] The probl...

Examples

Embodiment approach 1

[0012] Diethyl malonate reacts with sodium metal to form a salt, then adds dropwise a toluene solution of 2,3 dimethyl-6-nitro-4 chloropyridine for condensation reaction, and then decarboxylates under acidic conditions to obtain 2,3,4 - Trimethyl-6-nitropyridine; wherein the molar ratio of diethyl malonate, sodium metal, and 2,3 dimethyl-6-nitro-4-chloropyridine is 4.2:1.4:1.2.

[0013] 2,3,4-trimethyl-6-nitropyridine is catalyzed by Pd / C, methanol is used as a solvent, hydrogenation reduction, suction filtration, and the filtrate is concentrated to obtain 2,3,4-trimethyl-6-amino pyridine;

[0014] 2,3,4-Trimethyl-6-aminopyridine forms a salt with acid first, cools to -12°C, adds liquid bromine dropwise, and then adds sodium nitrite aqueous solution dropwise, after the dropwise addition, adjust the pH of the solution to be alkaline, Then extract, dry and concentrate to obtain 2,3,4-trimethyl-6-bromopyridine.

Embodiment approach 2

[0016] Diethyl malonate reacts with potassium metal to form a salt, then add dropwise a toluene solution of 2,3 dimethyl-6-nitro-5 chloropyridine for condensation reaction, and then decarboxylate under acidic conditions to obtain 2,3,4 - Trimethyl-6-nitropyridine; wherein the molar ratio of diethyl malonate, potassium metal, and 2,3 dimethyl-6-nitro-4-chloropyridine is 5.3:1.7:1.2.

[0017] 2,3,4-trimethyl-6-nitropyridine is catalyzed by Pd / C, methanol is used as a solvent, hydrogenation reduction, suction filtration, and the filtrate is concentrated to obtain 2,3,4-trimethyl-6-amino pyridine;

[0018] 2,3,4-Trimethyl-6-aminopyridine first forms a salt with acid, cools to 6°C, adds liquid bromine dropwise, and then adds sodium nitrite aqueous solution dropwise, adjusts the pH of the solution to be alkaline after the dropwise addition, and then Extraction, drying and concentration give 2,3,4-trimethyl-6-bromopyridine.

Embodiment approach 3

[0020] Diethyl malonate reacts with sodium metal to form a salt, then adds dropwise a toluene solution of 2,3 dimethyl-6-nitro-4 chloropyridine for condensation reaction, and then decarboxylates under acidic conditions to obtain 2,3,4 - Trimethyl-6-nitropyridine; wherein the molar ratio of diethyl malonate, sodium metal, and 2,3 dimethyl-6-nitro-4-chloropyridine is 4.8:1.5:1.2.

[0021] 2,3,4-trimethyl-6-nitropyridine is catalyzed by Pd / C, methanol is used as a solvent, hydrogenation reduction, suction filtration, and the filtrate is concentrated to obtain 2,3,4-trimethyl-6-amino pyridine;

[0022] 2,3,4-Trimethyl-6-aminopyridine first forms a salt with an acid, cools to -5°C, adds liquid bromine dropwise, and then adds sodium nitrite aqueous solution dropwise, and adjusts the pH of the solution to be alkaline after the dropwise addition. Then extract, dry and concentrate to obtain 2,3,4-trimethyl-6-bromopyridine.