Synthetic method of alpha-deuterated carbonyl compound

Abstract

The invention belongs to the technical field of preparation of deuterated compounds, and particularly relates to a synthesis method of alpha-deuterated carbonyl compounds. Inorganic base barium oxide BaO or barium hydroxide Ba (OH) 2 is used as a catalyst, a deuterium supply reagent is used as a deuterium source, and deuteration of the alpha position of the carbonyl compound is efficiently completed. According to the method disclosed by the invention, the H / D conversion reaction can be carried out at the alpha position of carbonyl at high selectivity without influencing other positions, the applicable substrates are wide, and the target product can be obtained at high yield and high deuteration rate in both cyclic ketone and chain ketone reactions. For the reaction of nitrile compounds and sulfoxide compounds, the target product can be obtained with high yield and medium deuteration rate, and the method has the characteristics of simplicity, high efficiency and good regioselectivity.

Description

technical field [0001] The invention belongs to the technical field of preparation of deuterated compounds, in particular to a method for synthesizing α-deuterated carbonyl compounds. Background technique [0002] α-deuterated carbonyl compounds can be used for the study of organic chemical reaction mechanism, and can also synthesize deuterated biologically active molecules, prepare deuterated drugs, and even prepare deuterated reagents. As early as 1970, Maciel et al. (Ellis, P.; Maciel, G*.J.Am.Chem.Soc. 1970, 92, 5829) used the inorganic base potassium carbonate as a catalyst and heavy water as a source of deuterium, under reflux The deuterium reaction of the α-position of the ketone is carried out under the conditions of the ketone to synthesize the deuterated substrate, but the method must go through two reaction processes and each reaction time is as high as 24h to obtain a satisfactory high deuteration rate target product. The time is long and the operation is inconv...

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Problems solved by technology

As early as 1970, Maciel et al. (Ellis, P.; Maciel, G*. J. Am. Chem. Soc. 1970, 92, 5829) used the inorganic base potassium carbonate as a catalyst, and heavy water as a deuterium source. Under certain conditions, the deuteration reaction of the α position of the ketone is used to synthesize the deuterated substrate, but this method must go through two reaction processes and each reaction time is as high as 24h to obtain a satisfactory high deuterated rate target product. The time is long and the operation is inconvenient; after that, in 2004, the Berthelette group (Berthelette, C*.; Scheigetz, J.Label.Compd.Radiopharm.2004,47,891) utilized the organic base DBU as a catalyst, and also used heavy water as a deuterium source, Deuteration of aryl methyl ketones, but this method is only applicable to aryl methyl ketones, not applicable to other ketones, and good target products cannot be obtained for aryl methyl diketones

Chen's group (Zhan, M.; Xie, Y*.; Chen, Y*.; et al.J.Label.Compd.Radiopharm.2014,57,533) used pyridine as a base to catalyze the reaction. The post-treatment process of this method is cumbersome, and It also needs to go through two reaction processes, and the yield of the deuterated product of alkane ketone is only 40%.

Wasa group (Chang, Y.; Myers, T.; Wasa, M*. Adv. Synth. Catal. 2020, 362, 360) used Lewis acid B (C 6 f 5 ) 3 Catalysis, Lewis acid is expensive and unstable in the air, and it is usually operated in a glove box, which is inconvenient to use, and the selectivity of α-deuterated carbonyl compounds carried out by this method is poor. Only the target product with low deuteration rate and low yield can be obtained

The Beller group (Neubert, L.; Michalik, D.; Beller, M*.J.Am.Chem.Soc.2012,134,12239) uses transition metal ruthenium as a catalyst to catalyze the deuteration reaction of carbonyl compounds, and the catalyst is expensive. The post-processing is cumbersome, and finally only deuterium products with a medium-to-high deuterium rate and poor selectivity can be obtained

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