Regioselective Hydrogen Isotope Exchange Of Aromatic Aldehydes And Carboxylic Acids With Deuterium Oxide

Deuterium,as an isotope of hydrogen,had been widely used in the nuclear magnetic resonance analysis,reaction mechanism investigation and biological metabolism tracing.Besides,compared to traditional drugs and materials,the introduction of deuterium atom enhanced the metabolic stability of drugs and the durability of OLEDs,which promote the recent booming of deuterated drugs and materials.Aromatic aldehydes and carboxylic acids are vital intermediates of organic synthesis,which could be derived to various kinds of organic compounds including active pharmaceutical ingredients and organic materials.The thesis presented takes aromatic aldehydes and carbonyl acids as substrates,focus on the regioselective deuteration on their aromatic rings.In the first part,a detailed study was conducted on ortho-selective deuteration of aromatic aldehydes.Avoiding the meta-selection brought by conventional SEAr pathway,the ortho-selective deuteration of aromatic aldehydes was achieved by employing the C-H activation with deuterium oxide as deuterated resource.After a carefully scrutinization of reaction condition including type and equivalent of ligands,solvents,catalysts,additives as well as the reaction temperature and time,the optimized reaction afforded the ortho-deuterated model substrate with a deuterium-incorporation to 95%.With the optimal condition in hand,a series of aromatic aldehydes was exposed under the standard condition.The results showed most of substrates could be delivered with relatively good deuteration incorporation(75-95%)and excellent ortho-selectivity.Subsequent attempt focused on gram-scale preparation and second-round deuteration,which showed potential application in large scale preparation.Finally,a reversible concerted metallization-deprotonation mechanism was proposed,which was further supported by control experiments and a preliminary density-functional theory study.In the second part,a tentative study was conducted about regioselective deuteration of aromatic carboxylic acids.After a series optimization,three different protocol for regioselective deuteration had been established including:(1)a per-deuteration condition of benzoic acid catalyzed by Pt/C,affording all position of aromatic ring with deuterium-incorporation over 98%;(2)a selective ortho-deuteration condition of benzoic acid catalyzed by Pd(OAc)2,rendering the ortho-deuterated product with deuterium-incorporation over 96%leave other site intact;(3)a meta/para-deuteration condition of benzoic acid catalyzed by Cp*Ir(PMe3)Cl2,delivering the deuterium-incorporation of 90%for meta-position,88%for para-position,and a much lower 10%at ortho-sites.Besides,several gram-scale tests offered satisfactory results.