Trifluoromethylation process for bromo-pyridine and derivatives thereof

Abstract

The invention belongs to the field of organic chemistry and relates to a trifluoromethylation process for bromo-pyridine and derivatives thereof. The process disclosed by the invention comprises the following steps: by taking a bromo-pyridine compound with a formula a structure as a raw material, performing trifluoromethylation under the action of a Maben reagent fluoro-S-( trifluoromethyl)-dibenzothiophene salt having a formula c structure, thereby obtaining the tirfluoromethylpyridine compound with a formula b structure. The structural formula is as shown in the specification. In the formula, X- is Bronst conjugate base, R is H or -CN or halogen or C1-C6 alkyl or C1-C6 alkoxy or -OH or -R1OH or COR2 or -CO2R3 or -CONR4 or -NR5R6; R1 is C1-C6 akyl; R2, R3 and R4 are identically or differently H or C1-C6 alkyl; and the R5 and R6 are identically or differently H or O or C1-C6 alkyl or C1-C6 alkoxy.

Description

technical field [0001] The invention belongs to the field of organic chemistry, in particular to the field of organic fluorine chemistry. Background technique [0002] In recent years, scientists have discovered in research that introducing trifluoromethyl into organic compound molecules can improve the lipophilicity of the compound, thereby improving the permeability to biological membranes and tissues and the electron attraction when reacting with living organisms. To achieve the purpose of enhancing the physiological activity of compounds, with the gradual deepening of research, trifluoromethyl compounds are more and more widely used in medicine, pesticides, chemical materials, etc., so it is urgent to develop low-cost, high-yield, suitable for industrialization. Trifluoromethylation process for production. [0003] Trifluoromethylpyridine compounds are common intermediates used in the synthesis of medicines, pesticides, and chemical materials, and can be prepared from h...

AI Technical Summary

Problems solved by technology

[0007] 1. [Ph 2 SCF 3 ] + [OTf] - The reagent needs to go through 5 steps of reaction to be synthesized, and the market price is relatively high;

[0008] 2. The iodine reagent is more expensive, and after replacing the iodopyridine with a bromopyridine compound, the reagent [Ph 2 SCF 3 ] + [OTf] - The trifluoromethylation reaction activity of the trifluoromethylation is very poor, resulting in the low yield of the fluorine spectrum

[0011] Although it is mentioned in this document that the yield of trifluoromethylation of bromopyridine and its derivatives is higher when this method is adopted, the experimental data disclosed in this document are all obtained under micro-tests. The review of the preparation process shows that the process cannot achieve the yield as in the literature when the production is carried out in tons, and the trifluoromethylation reagent used in the process needs to be prepared through 6 steps of reaction, and the market price is relatively high

[0012] In summary, the prior art methods are not suitable for the preparation of bromopyridine and its derivatives on a commercial scale, so an improved and commercially viable method is needed to solve the related problems in the prior art methods and make it suitable for mass production

Images