A kind of β-carbonyl sulfone derivative and its preparation method and application

Abstract

The invention discloses a β-carbonyl sulfone derivative and a preparation method and application thereof. The preparation method comprises the following steps: using olefin azide and sulfonyl hydrazide as starting materials, using CuSO 4. 5H 2 O is a catalyst, water is a reaction solvent, the reaction temperature is 90 ° C, and the reaction time is 2-4 hours. The present invention uses catalyst CuSO in the reaction system 4. 5H 2 O, effectively promotes the reaction, inhibits the self-coupling reaction of sulfonyl hydrazide, and improves the yield of the reaction; at the same time, the reagents and catalysts used are stable, cheap and easy to obtain, which is convenient for mass production. The class structure provides a new and effective way; and the reaction solvent is water, which has the advantages of green economy and environmental protection. In addition, the results of the activity experiment show that the product can inhibit 11β-hydroxysteroid dehydrogenase to a certain extent, therefore, the preparation method and the product thereof have important application significance in the field of medicine.

Description

technical field [0001] The invention belongs to the field of organic synthesis, in particular to a β-carbonyl sulfone derivative, a preparation method and application thereof. Background technique [0002] Sulfones are a very important class of sulfur-containing organic compounds. They are widely used in organic synthesis and the synthesis of pharmaceutical intermediates due to their antibacterial, coagulation and other activities and medicinal value. For example, penicillane sulfone (sulbactam) is an irreversible enzyme inhibitor. It acts 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 structure of β-carbonyl sulfone, such as carbonyl, active methylene, sulfone, etc., can react with many compounds, participate in various chemical reactions in organic synthesis, and play a very important r...

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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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