3-acyl isoxazole compound and preparation method thereof

Abstract

The invention discloses a 3acyl isoxazole compound and a preparation method thereof. The No.4 and No.5 positions of the 3acyl isoxazole compound are free of substituent groups, and subsequent functionalization is facilitated according to use requirements, so that the structure type of the 3acyl isoxazole compound is expanded, and the 3acyl isoxazole compound has potential application value. According to the method for preparing the 3acyl isoxazole compound, the ketone compound, phenyl vinyl sulfone and tert-butyl nitrite are used as reaction raw materials; an aqueous solution containing a surfactant is used as a reaction solvent; the 3acyl isoxazole compound is synthesized through a two-step reaction; and no metal catalyst is needed in a reaction process, namely, the 3acyl isoxazole compound is synthesized in a mild and green reaction environment, the selectivity and yield of the product are very high, the application range of the ketone compound is wide. The method has a good amplified synthesis prospect.

Description

technical field [0001] The invention relates to a 3-acyl isoxazole compound and a preparation method thereof. Background technique [0002] Isoxazole compounds are a very important class of organic intermediates, and most of the compounds containing this structural fragment also have excellent biological activities, such as antitumor, anti-inflammatory, antibacterial and herbicidal. Isoxazoles are widely used 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 is increasing day by day at home and abroad, which is one of the current research hotspots. At present, there are also the following reports about the synthetic method of 3-acyl isoxazole compounds, for example: [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 react...

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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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