A kind of 3-acyl isoxazole compound and preparation method thereof

Abstract

The invention discloses a 3-acylisoxazole compound and a preparation method thereof. The 3-acylisoxazole compound has no substituents at positions 4 and 5, which facilitates subsequent functionalization according to application requirements, thereby expanding the The structural types of 3-acylisoxazole compounds have potential application value; a method for preparing 3-acylisoxazole compounds provided by the invention comprises ketone compounds, phenyl vinyl sulfone and tert-butyl nitrite. The ester is used as the reaction raw material, and the aqueous solution containing the surfactant is used as the reaction solvent to synthesize 3-acylisoxazole compounds through a two-step reaction. The reaction process does not require any metal catalyst, that is, it is synthesized in a mild and green reaction environment. The 3-acylisoxazole compounds are obtained, and the selectivity and yield of the products are high, and the ketone compounds have a wide range of applications and have a good prospect for amplification synthesis.

Description

technical field [0001] The invention relates to a 3-acylisoxazole compound and a preparation method thereof. Background technique [0002] Isoxazoles are a very important class of organic intermediates, and most of the compounds containing this structural fragment also have excellent biological activities, such as anti-tumor, anti-inflammatory, antibacterial and herbicidal. Isoxazole has a wide range of applications not only in medicine, but also in organic catalysis, fine synthesis and other fields. Therefore, in recent years, the research on the synthesis of isoxazoles at home and abroad is increasing, which is one of the current research hotspots. At present, there are also the following reports on the synthetic method of 3-acylisoxazole compounds, for example: [0003] (1) Fokin's group used chlorooxime as raw material, under the action of ruthenium catalyst and alkali, nitrogen oxides were generated in situ, and the isoxazoles were prepared by cycloaddition reaction w...

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Problems solved by technology

[0003] (1) The Fokin group used chloroxime as a raw material, under the action of ruthenium catalyst and alkali, produced nitrogen oxides in situ, and prepared isoxazole compounds by cycloaddition reaction with alkynes (see formula 2 Route a, Grecian, S.; Fokin, V.V.Angew.Chem.2008,120,8409), but the raw materials involved in this reaction need to be prepared in advance, the catalyst is expensive and easy to form isomers;

[0004] (2) Wang et al. used non-activated aromatic hydrocarbons as raw materials and potassium persulfate as an oxidant, and realized the synthesis of 3-acylisoxazole compounds through copper catalysis (see route b of formula 2, Wang, G.-W.; Cheng , M.-X.; Ma, R.-S.; Yang, S.-D.Chem.Commun.2015, 51, 6308), the disadvantage of this reaction is that the substrate is relatively limited, and the pyridine ring is indispensable. Poor reactivity of other aromatics;

[0005] (3) Horiuchi et al. reported that iron nitrate promoted the cycloaddition of acetophenone or acetone and alkyne to prepare 3-acyl isoxazole compounds (see route c of formula 2, Itoh, K.; Sakamaki, H.; Nakazat, N.; Horiuchi, A.; Horn, E.; Horiuchi, C.Synthesis, 2005, 3541), the disadvantage of this reaction is that the amount of ferric nitrate is large, and the types of ketones are limited; recently, Liu et al. reported that nitrous acid A similar reaction facilitated by tert-butyl ester (t-BuONO) (see scheme c of Equation 2, Dai, P.; Tan, X.; Luo, Q.; Yu, X.; Zhang, S.; Liu, F.; Zhang, W.Org.Lett.2019, 21, 5096), although the reaction has a wide range of substrates, the reaction solvent is more toxic;

[0007] It can be seen from the above background that there have been some reports on the synthesis of 3-acyl isoxazole compounds, but the methods reported in the literature are limited to the preparation of 3-acyl isoxazole compounds with substituent groups at positions 4 and 5.

The existence of these substituent groups affects the subsequent functionalization of 3-acylisoxazole compounds to a certain extent, and it is very difficult to selectively remove these substituent groups in the later stage; The 3-acylisoxazole compounds of the group are seldom reported

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