A kind of method of heteroarylamine and amine reaction synthesis substituted heteroarylamine

Abstract

The invention discloses a method for synthesizing substituent miscellaneous aromatic amine through a reaction between miscellaneous aromatic amine and amine. Inorganic base serves as an accelerant. The miscellaneous aromatic amine and the amine are directly subjected to the de-ammonia gas alkylation reaction, N-substituent miscellaneous aromatic amine ramifications are obtained, the reaction temperature ranges from 130 DEG C to 200 DEG C, the reaction time ranges from 24 hours to 48 hours, and the by-product is ammonia gas. According to the technical scheme, the inorganic base serves as the accelerant, the amine low in price and easy to get serves as an alkylation reagent, under the solvent-free conditions of nitrogen protection and sealing, the miscellaneous aromatic amine and the amine are subjected to the de-ammonia gas N-alkylation reaction, and the N-substituent miscellaneous aromatic amine ramifications can be obtained through direct synthesizing. The reaction method is direct, conditions are simple, operation is easy, the by-product is ammonia gas, less pollution is caused, and the ammonia gas can be recycled.

Description

Technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a method for synthesizing substituted heteroarylamines by reacting heteroarylamines with amines. Background technique [0002] Almost all drugs contain at least one N atom and one C-N bond. Therefore, the construction of C-N bond and the synthesis of organic nitrogen compounds play a vital role in organic and drug synthesis. N-substituted heteroarylamine derivatives are also an important class of heterocyclic compounds, which are important intermediates in the synthesis of drugs and natural products. In traditional synthesis methods, Hofmann nitrogen-alkylation reaction and Gabriel method are common methods for synthesizing amine derivatives. However, Hofmann method uses excessive halogenated hydrocarbons, low selectivity, and multiple products which cause separation difficulties, and ammonium salts are produced. The Gabriel method is only suitable for the synthesis of pri...

AI Technical Summary

Problems solved by technology

In traditional synthetic methods, Hofmann nitrogen-alkylation reaction and Gabriel method are common methods for synthesizing amine derivatives. However, Hofmann method uses excess halogenated hydrocarbons, low selectivity, multiple products lead to separation difficulties, and ammonium salts are produced

The Gabriel method is only suitable for the synthesis of primary amines, and it uses a large amount of base and requires multi-step reactions to achieve low efficiency.

For the alkylation of heteroarylamines, the method of reacting with halogenated hydrocarbons has the problem of exocyclic N-alkylation and ring N-alkylation selectivity, and ring N-alkylation will give hetero Products with altered ring structures, resulting in low yields of target heteroaromatic ring derivatives

In addition, transition metal-catalyzed hydrogen-borrowing strategies have also been reported in recent years to achieve the alkylation of heteroarylamines, but these methods need to use expensive and highly toxic noble metal Ru, Rh, Ir catalysts and complex ligands, which not only increase In addition to the production cost, the presence of transition metal residues in the reaction may also make the product unsuitable for the synthesis of pharmaceutically active compounds

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