A method of preparing beta-chloroalkenyl sulfone compounds from sulfonates and alkynes

Abstract

A method of preparing beta-chloroalkenyl sulfone compounds from sulfonates and alkynes is provided. The method includes directly synthesizing the beta-chloroalkenyl sulfone compounds from the sulfonates and the alkynes in a nitrogen or inert gas atmosphere by using an iron halogenide agent. The method adopts raw materials and the iron halogenide agent which are cheap, stable and easily available, and does not use ligands, acids, peroxides, microwave radiation, and other special reaction conditions. Pre-functionalization of a substrate is not needed. The method is mild in reaction conditions, simple in operation, short in reaction time and high in product selectivity, substrate applicability and yield, and has a potential application prospect in the fields of medicines, organic synthesis intermediates, and the like.

Description

【Technical field】 [0001] The invention relates to the fields of organic synthesis and chemical pharmacy, in particular to a method for synthesizing β-chlorene sulfone compounds from sulfinates and alkynes and compounds thereof. 【Background technique】 [0002] As an important organic drug raw material, sulfone compounds are mainly used in the production of important chemical intermediates of HIV-1 integrase inhibitors, amisulpride, dapsone, bilucaamide tablets, eletriptan and other drugs , while β-chlorosulfone compounds are important raw materials for modifying sulfone compounds, and β-chlorosulfone compounds are also important intermediates in organic synthesis. [0003] At present, there are a few literatures reporting the synthesis methods of β-chlorosulfone compounds. The synthetic method developed in recent years is to synthesize β-chloroalkene sulfone compounds by one-step method, such as the reaction of benzenesulfonyl chloride and phenylacetylene catalyzed by ferrou...

AI Technical Summary

Problems solved by technology

The synthetic method developed in recent years is to synthesize β-chloroalkene sulfone compounds by one-step method, such as the reaction of benzenesulfonyl chloride and phenylacetylene catalyzed by ferrous acetylacetonate reported in 2012, although this reaction controls the reaction reaction well. Formula configuration, but there are some disadvantages in this reaction, such as: the sensitivity of sulfonyl chloride to water, the need to add expensive ligands, long reaction time

In 2013, a reaction involving sulfonyl hydrazide was reported. The reaction provided a chlorine source by adding two equivalents of ferric chloride hexahydrate, but an additional double equivalent of TBHP was required as an oxidant. TBHP was explosive in the scale-up experiment and had a low yield. Rate

In 2014, the article reported that cuprous iodide was used as a catalyst to catalyze the reaction of sodium sulfinate and phenylacetylene, but an additional chlorine source must be added, and expensive phosphorus ligands need to be added. The low yield is also a place where the reaction needs to be improved.

The reaction yield is high, but the points for improvement are: 1. Two equivalents of ferric chloride hexahydrate are required to provide the chlorine source, so it does not meet the principle of atomic utilization; 2. TBHP needs to be used as the oxidant, although it is green, but It is limited in industrial application; 3. This condition is not applicable to intermediate alkynes, and is not applicable to aryl-substituted alkynes containing special groups (such as nitro, ester groups, etc.), and the types of chain alkynes need to be broadened

[0006] In 2014, Taniguchi's research group reported the reaction of sodium sulfinate and phenylacetylene using cuprous iodide as a catalyst, which requires additional addition of halogen sources (such as: KCl, KBr, etc.), addition of ligands, and low yield

However, the disadvantages of this reaction system are: 1. Need to add expensive phosphine ligands, the cost is too high; 2. The substrate applicability is relatively narrow, there are few types, and the yield is not high; 3. The reaction time is 18 hours, so the efficiency needs to be improved

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