Background and overview[1]
1-Bromo-2-chloro-3-fluoro-4-iodobenzene is an iodobenzene derivative. It is a highly active compound. As a pharmaceutical intermediate, it is widely used in drug synthesis. However, the current synthesis of 1-bromo There are few literature reports on -2-chloro-3-fluoro-4-iodobenzene.
Structure
Preparation method[1]
A method for synthesizing 1-bromo-2-chloro-3-fluoro-4-iodobenzene that can be produced on a large scale with low energy consumption, few side reactions, high yield and high product purity. The technical solution includes the following steps:
① Mix 4-bromo-3-chloro-2-fluoroaniline and sulfuric acid, then heat up, reflux, and precipitate crystals;
②Add copper iodide and potassium iodide, and then add sodium nitrite aqueous solution dropwise;
③ Add sodium bisulfite aqueous solution dropwise, layer the layers, and extract the organic layer by distillation.
The reaction equation of the synthesis method is as follows:
The specific steps are as follows:
1) Add 4-bromo-3-chloro-2-fluoroaniline into the kettle, slowly add 30-80% sulfuric acid, 4-bromo-3-chloro-2-fluoroaniline and sulfuric acid at room temperature The molar ratio is 1:2.5-1:5, raise the temperature to reflux, stir to form salt for 1-2 hours, cool to 50-60℃, add copper iodide and 4-bromo-3-chloride -The molar ratio of 2-fluoroaniline and copper iodide is 1:0.02-1:0.08, add potassium iodide, the molar ratio of 4-bromo-3-chloro-2-fluoroaniline and potassium iodide is 1:1.2-1:1.5 , add 30% sodium nitrite aqueous solution dropwise, the molar ratio of 4-bromo-3-chloro-2-fluoroaniline and sodium nitrite is 1:1.1-1:1.4, after adding, keep warm and stir until no gas is released, stir 1 hour.
2) Add 20% sodium bisulfite aqueous solution dropwise to the reaction solution, stir for 1-2 hours, reduce the remaining potassium iodide, layer it to obtain a brown-red oil layer, and then rectify it to obtain a colorless liquid 1-bromo- 2-Chloro-3-fluoro-4-iodobenzene.
Main reference materials
[1] Synthesis method of CN201510202949.41-bromo-2-chloro-3-fluoro-4-iodobenzene
