A preparing method of deuterated aromatic compounds

Abstract

The invention belongs to the field of chemical synthesis, particularly a preparing method of deuterated aromatic compounds. The method includes subjecting an aryl halide, as an initial raw material, to a palladium catalyzed carbon-halogen bond reduction reaction in which deuterium anion participates at 60-100 DEG C under inert gas protection to synthesize a target compound, with deuterated sodiumformate being adopted as a deuterating agent, dimethyl sulfoxide being adopted as a solvent, metal palladium being adopted as a catalyst and organphosphorus being adopted as a ligand. The method is mild in condition, avoids the use of expensive deuterating agents as a solvent in a reaction process so that the production cost is reduced, and is suitable for large-scale production. The deuteration rate of the compounds reaches 98% or above, and the compounds can be applied in the field of organic optoelectronic materials, medicines, pesticides, and the like.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and in particular relates to a method for preparing deuterated aromatic compounds. Background technique [0002] Deuterium is a hydrogen isotope consisting of a neutron and a proton. Deuterated compounds are widely used in the fields of identification of organic matter such as life, environment and nuclear magnetic resonance. In 2017, the world's first deuterated drug, AUSTEDO, was approved for marketing by the US Food and Drug Administration (FDA), which marked FDA's recognition of the role of deuterium in drug design, which is different from that of ordinary hydrogen. This move will speed up the use of deuterium as a routine tool in the design of drug molecules. [0003] Aromatic compounds are the most common structure in drug molecules, and generally aromatic compounds are introduced into drug molecules through the reaction of functional groups on the aromatic ring. Therefore, it is very i...

AI Technical Summary

Problems solved by technology

At present, the reported method for synthesizing deuterated aromatic compounds has the following disadvantages: one, it needs to be prepared under high temperature and pressure or strong acid and strong alkali conditions, and its functional group compatibility is poor (Bull.Chem.Soc.Jpn.2011,1368-1370 ); Second, the use of deuterated reagents as solvents has high production costs (Org.Biomol.Chem., 2016, 14, 3091-3097); Third, the deuterated rate is generally low, generally only reaching 80%-95% , unable to meet the requirement of 98% deuteration rate in the field of drug research and development (Chem.Eur.J.2009,15,10397-10404)

In response to the above problems, the applicant has developed a high-efficiency deuteration method, but this method requires the use of tri-tert-butylphosphine, which is extremely sensitive to air, as a ligand, which is expensive and inconvenient to operate, thus limiting this method. The application value of the method (Org.Chem.Front.2015,2,1071-1075)

Images