A method for the alkylation of copper-catalyzed n-heterocyclic aromatic compounds c(sp2)-h bond

Abstract

The invention discloses a copper catalyst N‑ Heterocyclic aromatic hydrocarbons C(sp 2 The method for the alkylation of )-H bond, the method process is as follows: under the presence of copper salt, N-F reagent, protonic acid and organic solvent, N‑ Heterocyclic aromatic compounds undergo alkylation reaction with naphthenic compounds or cyclic ether compounds, the reaction temperature is 20-60°C, and the reaction time is 3-20 h. After the reaction is completed, the reaction liquid is post-treated to obtain N ‑heteroaromatic derivatives. The present invention utilizes copper catalysis to realize N‑ The CDC reaction of heterocyclic aromatic compounds with cyclic ether compounds or cycloalkane compounds, this invention expands the applicable scope of substrates of the reaction, quinoline derivatives, pyridine derivatives, isoquinoline derivatives, benzoxazole derivatives Nitrogen-containing heteroaromatic compounds such as compounds and benzothiazole derivatives can be alkylated by this method.

Description

technical field [0001] The invention relates to a copper catalyzed N-heterocyclic aromatic compound C(sp 2 ) A method for the alkylation of the -H bond. Background technique [0002] N-heterocyclic aromatic compounds are an important class of natural compounds, which widely exist in the plant kingdom. Studies have shown that N-heterocyclic aromatic hydrocarbons have good biological activity, have remarkable effects in antibacterial, anti-inflammatory, anti-cancer, and anti-HIV viruses, and are widely used in the field of medicine. In recent years, the synthesis of alkyl-substituted heteroaromatic compounds has received extensive attention and some progress has been made. [0003] Prior to the present invention, existing N-heterocyclic aromatic hydrocarbons C(sp 2 )-H alkylation methods are mainly divided into the following two categories: [0004] (1) Cross-dehydrocoupling of N-heterocyclic aromatic hydrocarbons and ethers: K 2 S 2 o 8 , (NH 4 ) 2 S 2 o 8 , TBHP a...

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Problems solved by technology

[0004] (1) Cross-dehydrocoupling of N-heterocyclic aromatic hydrocarbons and ethers: K 2 S 2 o 8 , (NH 4 ) 2 S 2 o 8 , TBHP as an oxidant, but the required temperature is higher and the time is longer, such as literature: Synlett., 2016, 27, 1282; Chem Sci., 2017, 8, 4044; Eur.J.Org.Chem., 2015, 2015, 4973

[0005] (2) Cross dehydrogenation coupling of N-heterocyclic aromatic hydrocarbons and alkanes: PIFA / NaN 3 System, Sc(OTf) 3 or [Ir(ppy) 2 (dtbbpy)]PF 6 - Catalysis, etc., but the NaN used 3 High toxicity, expensive metal catalysts, such as literature: Org.Lett., 2009, 11, 1171; Angew.Chem., Int. Ed., 2013, 52, 3267; Angew.Chem., Int.Ed., 2017 ,56,12336.

However, the existing N-heteroaromatic hydrocarbons C(sp 2 The method of )-H alkylation is often only suitable for ether compounds with better activity, and there are very limited reports on the activation method of inert naphthenes

The existing methods still have defects such as expensive catalysts, high toxicity of reagents, high reaction temperature and insufficient substrate applicability.

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