Method for preparing deuterated aldehyde through triazole carbene catalysis

Abstract

The invention provides a novel method for preparing deuterated aldehyde, which comprises the following step: by using deuterated methanol as a deuteration reagent, carrying out a hydrogen-deuterium exchange reaction on an aldehyde in the presence of a catalyst and alkali to obtain the deuterated aldehyde. According to the method, the deuterated methanol is used as the deuteration reagent, a triazole carbene salt is used as a catalyst precursor, deuteration of the aldehyde is effectively realized under the action of an alkali, and the deuteration rate of the aldehyde is as high as 98%. Moreover, the applicability of the reaction substrate is wide, deuteration of aryl aldehydes can be realized, deuteration of alkyl and alkenyl aldehydes can be realized, and medium to good deuteration rates can be obtained in the reactions. According to the metal-catalysis-free hydrogen-deuterium exchange reaction, hydrogen-deuterium exchange of the reaction is achieved through a manner of activating aldehyde with carbene, reaction steps are reduced, the atom economy is improved, and the applicability of a substrate is wide. Carbene is used as a catalyst, expensive precious metal does not need to be used as a catalyst, the reaction cost is reduced, and the reaction has very high economical efficiency and applicability.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for preparing deuterated aldehydes by triazole carbene catalysis. Background technique [0002] Deuterated compounds are an important class of substances, which can be used in reaction mechanism research, drug synthesis and pharmacokinetic research. For example, in 2017, the U.S. Food and Drug Administration (FDA) approved the world's first deuterated drug, AUSTEDOTM (deuterated tetrabenazine), which can be used to treat abnormal involuntary movements caused by Huntington's disease. This approval has greatly encouraged the research enthusiasm of synthetic chemists to develop new methods of deuteration. Aldehydes have a wide range of reactivity and are often used as the basic unit of reactions, and are widely used in the synthesis of drugs and natural products. By using deuterated aldehydes as reactants, deuterated drugs and natural products can be efficient...

AI Technical Summary

Problems solved by technology

[0006] Although aldehydes with high deuterium substitution rates can be obtained in traditional synthesis schemes, this scheme requires reactant doses or over-reacted doses of reactants, and the reaction steps are long and the by-products of the reaction are high, which increases environmental pollution and reduces atom economy. property, and the substrate applicability of the reaction is low, it is difficult to synthesize deuterated aldehydes for some complex substances

Although the hydrogen-deuterium exchange reaction catalyzed by transition metals can effectively improve the atom economy of the reactants, it needs to use expensive metal substances, which increases the cost of the reaction.

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