Method for synthesizing alpha-amino ketone from ketone and imine

Abstract

The invention discloses a method for synthesizing alpha-amino ketone from ketone and imine, and belongs to the technical field of chemical organic synthesis. The method comprises the following steps: adding imine into an organic solvent, sufficiently dissolving so as to obtain an imine solution, further respectively adding ketone, a catalyst tetrabutyl ammonium iodide and an oxidant tert-butyl hydroperoxide into the solution, sealing up a tube opening, heating to be 130 DEG C, stirring for 3 hours, cooling down the system to be the room temperature after the reaction is ended, extracting by using dichloromethane and removing the solvent of on organic phase so as to obtain alpha-amino ketone. By adopting the method, defects in the conventional method for synthesizing alpha-amino ketone by electrophilic amination and nucleophilic amination are overcome, direct amination of alpha-position of a simple ketone compound such as acetone is achieved, a C-N bond is generated through oxidative coupling reaction between a N-H bond and a C-H bond at one step, and the alpha-position of a ketone substrate does not need to be prefunctionalized, so that the experiment steps are simple, the condition is gentle, the reagents are cheap, and the range of the substrate is wide; the method is applicable to industrial production.

Description

technical field [0001] The invention belongs to the technical field of chemical organic synthesis, and relates to a method for synthesizing α-aminoketone. Background technique [0002] α-Aminoketones are a class of organic molecules that are very important in the field of biology, such as cysteine ​​protease inhibitors ("J. Am. Chem. Soc." 1999, 121, 9907. ) are polymeric α -amino ketones. In addition, compounds such as α-amino ketones are still used to synthesize various heterocyclic structures ("J. Org. Chem." 1994, 59, 1589. "Tetrahedron Lett." 2003, 44, 5965. "Org. Lett." 2004 , 6, 843) and useful precursors of 1,2-diaminoalcohols ("Chem. Rev." 1996, 96, 835.). In terms of synthetic methods, the oxidative C-N bond coupling reaction between the nitrogen source N-H bond and the ketone α-position sp3 hybridized C-H bond is one-step construction of the C-N bond, which is the simplest and most effective method for the synthesis of α-amino ketones. However, such methods are...

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Problems solved by technology

In terms of synthetic methods, the oxidative C-N bond coupling reaction between the nitrogen source N-H bond and the ketone α-position sp3 hybridized C-H bond is one-step construction of the C-N bond, which is the simplest and most effective method for the synthesis of α-amino ketones. However, such methods are rarely reported

There are two traditional methods for synthesizing α-aminoketones: ① substitution reaction of α-haloketone / α-hydroxyketone with nucleophilic nitrogen source ("Org.Prep.Proced.Int." 1990, 22, 399. ), although this method is classic, its limitation is that it needs to pre-functionalize the α-position of the ketone before the amination reaction; 60, 8747. "Angew. Chem. Int. Ed." 2013, 52, 7080. "Chem. Rev." 2011, 111, 1637.), the key step of the electrophilic amination reaction is the formation of ketones under the action of metals Enol structure, so there are limitations for simple ketones such as acetone that are difficult to enolize

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