Background and overview[1]
Deuterium is a stable, non-radioactive isotope of hydrogen found in nature. Deuterated reagents are widely used in the study of reaction mechanisms. The synthesis of deuterated compounds is also an important research field in organic synthesis. Several deuterated entity compounds such as CTP-354, CTP-449, SD-254 and SD-809 have entered the clinical trial stage. Deuterated polymers are a type of organic materials with special functions and have important applications in biomedical imaging and genetic testing. Therefore, the synthesis of deuterated compounds has great practical significance. The traditional synthesis methods of deuterated compounds are: reduction of halogenated hydrocarbons with LiAlD4; reaction of Grignard reagent with heavy water; reaction of D2SO4 with amino acid compounds, etc. This type of synthesis method has shortcomings such as harsh reaction conditions, low yield, and poor deuteration selectivity. In recent years, the synthesis of deuterated compounds has been further developed. Use aniline hydrochloride to reflux in heavy water and synthesize deuterated aniline through D-H exchange reaction. Using Bu3SnD as deuterated reagent, deuterated pyrimidines and deuterated purines were synthesized. Under microwave conditions, aniline compounds react with heavy water in concentrated hydrochloric acid at 180°C to synthesize deuterated aniline compounds.
Preparation[2]
Preparation of deuterated aniline is as follows: add 10 mmol of aniline, 20 mL of heavy water and 20.3 mL of SOCl in the reaction bottle, and reflux for 24 hours. Cool to room temperature, TLC detects that the reaction is complete [Developing solvent: A=V (ethyl acetate): V (petroleum ether)=1:10], adjust to pH 7 with saturated sodium bicarbonate solution, and use ethyl acetate (3×20mL ) extraction, combined the organic layers, washed with saturated brine (2 × 15 mL), dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated and purified by silica gel column chromatography (eluent: A=1:20) to obtain deuterated aniline.
Main reference materials
[1] Synthesis of deuterated aniline compounds
[2] Regioselective Synthesis of Indoles via Rhodium-Catalyzed CH Activation Directed by an In-Situ Generated Redox-Neutral Group
