A kind of method for preparing 1,4-dihydrooxazine

Abstract

The invention discloses a method for preparing 1,4-dihydrooxazine. An acyl diazo derivative and an acridine compound are taken as reaction substrates, AgOTf and Cu(OAc)2 are taken as reaction catalysts, NaHCO3 is used as an alkali, and the 1,4-dihydrooxazine is obtained through a ring addition reaction in an organic solvent. The method provided by the invention has the following characteristics that the reaction is more economical, functionalization in the later period is easier, reaction conditions are mild, the reaction can be carried out in the air, the use amount of the catalysts is small,post-treatment is simple and convenient, purification and large-scale industrial application of the product are facilitated, and one-step functionalization of commercial medicines is easier to carryout. Meanwhile, the raw materials such as the reactants, the catalysts and the like are cheap and easily available, the reaction composition is reasonable, a ligand is not needed, the atom economy ishigh, the reaction steps are few, and a relatively high yield can be obtained only by the one-step reaction, so that the method accords with requirements and directions of contemporary green chemistryand pharmaceutical chemistry and is suitable for screening high-activity 1,4-dihydrooxazine medicines, a gram-grade reaction can be well realized, and the method is suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to a method for preparing 1,4-dihydrooxazine, which belongs to the technical field of organic synthesis. Background technique [0002] 1,4-Dihydrooxazine is a ubiquitous core structure in many natural products, bioactive pharmaceuticals, and agrochemicals. Remarkably, 1,4-dihydrooxazine is often considered a privileged scaffold in medicinal chemistry for the discovery and optimization of new synthetic drug molecules. 1,4-Dihydrooxazine can also be used as a useful synthetic building block in the construction of heterocycles and as an additive in catalytic systems. At present, the method for preparing 1,4-dihydrooxazine has the disadvantages of harsh reaction conditions, cumbersome preparation of raw materials, large amount of raw materials, narrow substrate range, and low yield. E.g: [0003] (1) Siegfried et al. reported that aminoalkyne compounds were prepared by intramolecular nucleophilic addition and cyclization to 1,4-dih...

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Problems solved by technology

[0003] (1) Siegfried et al. reported that aminoalkyne compounds were prepared by intramolecular nucleophilic addition and cyclization to 1,4-dihydrooxazine, but the raw materials of aminoalkyne compounds required one or more steps of reaction to pre-prepare, so that the substrate narrow range and high preparation costs (cf.: Blechert, S., Angew. Chem. Int. Ed. 2005, 117 , 7972.);

[0004] (2) Urabe et al reported the preparation of 1,4-dihydrooxazine by intermolecular cycloaddition reaction between halogenated alkyne and hydroxylamine compound, but the reaction needs to be carried out at a higher temperature, and the reaction is not suitable for many Preparation of substituted oxazine rings (see: Urabe, H., J. Am. Chem. Soc. 2008, 130 , 1820.)

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