Synthetic method of succinimide type trifluoromethyl sulfuration reagent

Abstract

The invention belongs to the technical field of synthesis of organic compounds, and relates to a synthesis method of a succinimide type trifluoromethyl sulfide reagent. The CAS number of the reagent is 183267-04-1, and the structural formula of the reagent is shown in a formula (1) as described in the specification. According to the synthetic method of the succinimide type trifluoromethyl sulfide reagent, a nitrogen halogenated compound containing a succinimide structural framework, trifluoromethanesulfonate, nonafluorobutyl sulfonate, methanesulfonate and p-toluenesulfonate are used as reaction substrates and trifluoromethylthioester is used as a trifluoromethylthio source, for synthesis of the trifluoromethyl sulfuration reagent. According to the method, trifluoromethylthioester is taken as the trifluoromethylthio source, generates trifluoromethylthio negative ions under activation of fluorine negative ions, and conducts nucleophilic substitution on a reaction substrate, so the construction of a nitrogen-sulfur bond is realized, and the trifluoromethyl sulfuration reagent is obtained after separation and purification. According to the synthesis method of the trifluoromethyl sulfuration reagent, the raw materials are easy to prepare, the reaction reagent is low in price, the synthesis cost of the trifluoromethyl sulfuration reagent is remarkably reduced, and industrial production is facilitated; synthesis conditions are mild, and operation is simple and safe; and transition metal elements are not needed, and the method is green and environment-friendly.

Description

technical field

[0001] The invention belongs to the technical field of organic compound synthesis, and relates to a method for synthesizing a succinimide-type trifluoromethyl sulfide reagent. Background technique

[0002] Fluorine atoms play an important role in modern drug design and synthesis (Liu X, Xu C, Wang M, etal. Trifluoromethyltrimethylsilane: nucleophilic trifluoromethylation and beyond[J]. Chem Rev, 2015, 115(2):683-730.), According to statistics, 15% to 20% of modern drugs contain fluorine-containing groups (Hui R, Zhang S, Tan Z, et al. Research Progress of Trifluoromethylation with Sodium Trifluoromethanesulfinate[J]. Chin J OrgChem (Organic Chemistry), 2017, 37(12):3060-3075). The presence of fluorine-containing groups helps to increase the lipophilicity and metabolic stability of drug molecules (Yang B, Xu XH, Qing FL. Copper-mediated radical 1,2-bis(trifluoromethylation) of alkenes with sodium trifluoromethanesulfinate[J]. Org Lett, 2015, 17(8):1906-1909....

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