Beta-keto sulfone derivatives as well as preparation method and application thereof

Abstract

The invention discloses beta-keto sulfone derivatives as well as a preparation method and application thereof. The preparation method includes the following step: performing a reaction by using olefinazide and sulfonyl hydrazide as starting material, CuSO<4>.5H<2>O as a catalyst and water as a reaction solvent at 90 DEG C for 2-4 h. According to the method provided by the invention, the catalystCuSO<4>.5H<2>O is used in the reaction system, so that the reaction is effectively promoted, a self-coupling reaction of the sulfonyl hydrazide is inhibited, and the yield of the reaction is improved;meanwhile, the reaction reagents and catalyst used in the method are stable, cheap and easy to obtain, mass production is facilitated, and a novel effective way is provided for construction of the structures; the reaction solvent is water, and has the advantages of green economy and environmental protection; and in addition, results of activity experiments show that the product can inhibit 11 beta-hydroxysteroid dehydrogenase to a certain extent, so that the preparation method and the product have important application significance in the field of medicine.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a beta-carbonyl sulfone derivative and its preparation method and application. Background technique [0002] Sulfone is a very important class of sulfur-containing organic compounds. Due to its antibacterial, blood coagulation and other activities and medicinal value, it is widely used in the synthesis of organic synthesis and pharmaceutical intermediates. For example, penicillane sulfone drugs (sulbactam) are irreversible enzyme inhibitors, which act on β-lactamase and can competitively inhibit the activity of this enzyme, thereby producing antibacterial and bactericidal biological activities, especially for leprosy bacilli are particularly effective. Many functional groups in the β-carbonyl sulfone structure, such as carbonyl, active methylene, sulfone, etc., can react with many compounds and play a very important role in various chemical reactions in organic synth...

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Problems solved by technology

[0007] In 2012, Sreedhar et al first used terminal alkynes and sulfonyl chlorides to generate β-carbonyl sulfones under the action of catalysts (Sreedhar B and Rawat V.A regioselective catalyst-and additive-freesynthesis of β-ketosulfones from aryl acetylenes and sodium arenesulfones[J]. Synlett, 2012 (3): 413~417), this method directly adopts sulfonyl chloride as sulfonating reagent, shortens the reaction steps, reduces the reaction time, but sulfonyl chloride has pungent taste, and the productive rate of this reaction is not high

[0009] In 2013, Wei's research group improved the above reaction, using sulfonyl hydrazide with low toxicity, wide sources, and good chemical stability instead of sulfonyl chloride as raw material, and reported that sulfonyl hydrazide and olefins in Cu(OAc) 2 Under catalysis, β-carbonyl sulfones were synthesized by free radical reaction mechanism (Wei W, Liu C L, Yang D S, et al. Copper-catalyzed directoxysulfonylation of alkenes with dioxygen and sulfonylhydrazides leading to β-ketosulfones[J].Chem.Commun,2013 (49): 10239~10241), but the yield of the reaction is difficult to control, high and low, and the reaction time is too long

[0011] In 2008, Francesca G et al. found that β-carbonyl sulfone compounds can be converted from β-carbonyl sulfide oxidation (Francesca G, Ilaria N, Franca B, et al. Selective oxidation of sulfides tosulfoxides and sulfones using 30% aqueous hydrogen peroxide and silica-vanadia catalyst[J].J.Mol.Catal.A-Chem.2008(286):124~127), however, the raw material β-carbonyl sulfide of this reaction has the smell of rotten eggs, has certain toxicity and Not easy to synthesize

[0019] Yan-Shi Xiong et al recently found that β-carbonyl sulfone can be obtained by reacting aromatic alkynoic acid with sodium sulfonate (XiongY-S, Weng J, and Lu G. in water[J].Adv.Synth.Catal,2018,360(8):1611~1616), the reaction is mediated by manganese, using water as a solvent, the reaction conditions are mild and the reaction time is short, but This reaction yield is not high, and concrete reaction equation is as shown in formula 1-9:

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