Preparation method of 1,2,3-triazol-[1,5-a] quinoline compound

Abstract

The invention discloses a preparation method of a 1,2,3-triazol-[1,5-a] quinoline compound. The method comprises the steps of making substituted methyl quinoline react with an iodine simple substancein advance, adding a solid potassium phosphate trihydrate after the methyl quinoline disappears, and adding p-methyl benzene sulfonyl hydrazide for continuing a reaction to obtain the 1,2,3-triazol-[1,5-a] quinoline compound. The preparation method has the advantages that the adopted raw materials are cheap and easy to obtain, the operation method is simple, the reaction condition is mild, a one-pot approach can be adopted, the steps are short, the yield is up to 83%, and a feasible method is provided for industrial preparation of the compound.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a preparation method of 1,2,3-triazole-[1,5-a]quinoline compounds. Background technique [0002] 1,2,3-Triazoles and their derivatives are an extremely important class of triazine aromatic heterocyclic compounds. Because of its good anti-tumor, anti-fungal, anti-tuberculosis, anti-HIV virus and analgesic activities, it has been widely used in the fields of life science, material chemistry and medicine. [0003] Roy, B. et al. discovered a compound obtained by combining catechin epi, catechin, which has no antibacterial activity, and monocyclic lactam, which is inactive to bacteria, through the principle of drug splicing with triazole as the linking group. Shows moderate inhibitory activity against Escherichia coli. [RoyB,ChakrabortyA,Ghosh S K,BasakA.Design, synthesis and bioactivity of catechin / epicatechin and 2-azetidinone derived chimericmolecules[J].Bioorg.Med.Chem.Lett.,20...

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Problems solved by technology

[0012] (1) In 1974, Yasumitsu, Tamura et al reported the mixed reaction of 1-quinoline-1-ethanone oxime with O-2,4,6-trimethylbenzenesulfonyl hydroxylamine, and then mixed with PPA (polyphosphoric acid ) mixed reaction to obtain 4-substituted-1,2,3-triazole-quinoline derivatives, this reaction puts forward higher requirements for the laboratory preparation using this method, and the reagent PPA (polyphosphoric acid) used has Corrosive, thermal decomposition will produce highly toxic fumes, posing a threat to the safety of experimenters

[0013] (2) In 1999, Om and Prakash group developed a method for obtaining 3-methyl-1,2,3-triazol[1,5-a]quinoline from 2-(1-hydrazineethyl)quinoline , but the iodobenzene diacetate used will generate iodobenzene and remain in the product after reaction, and it is difficult to remove the iodobenzene and unreacted iodobenzene diacetate through conventional column chromatography, thus affecting the purity of the product. This method The 2-(1-hydrazineethyl)-quinoline used is not easy to obtain in industrial production, and the follow-up treatment of the reaction solution needs to evaporate the solvent in vacuum and then wash the remaining solid with ethane, and finally need to recrystallize in ethanol to obtain the product, The processing steps are cumbersome and more reagents are used, which is contrary to the concept of green chemistry and environmental protection

[0014] (3) In 2010, Ackermann et al. reported a method for the synthesis of 1,2,3-triazolophenanthrene by chemical reaction catalyzed by transition metal palladium. The reaction conditions are relatively complicated and transition metal palladium salts are required. And copper salts, metal reagents are expensive, and the presence of heavy metals in the reaction waste liquid will cause harm to the ecological environment and water body, the treatment is more troublesome, the reaction time is long, and the reaction needs to be 20 hours. At the same time, the reaction temperature is high and the safety is poor.

[0015] (4) In 2012, Avnish, Kumar et al. used 4-butyl-1-(2-iodophenyl)-1,2,3-triazole as raw material, and palladium acetate in alkaline environment, in DMF solvent 3-butyl-7-(4-butyl-1H-1,2,3-triazol-1-yl)-[1,2,3]triazolo[ 1,5-f]Phenanthridine, the reaction requires more reagents, and needs to complete the reaction in a nitrogen protection environment, the laboratory conditions are limited, the raw material 4-butyl-1-(2-iodophenyl)-1 , 2,3-triazole is not easy to obtain directly, it needs to be prepared in advance through other synthetic steps, and the palladium acetate catalyst used is more expensive, and the subsequent treatment of palladium ion waste liquid is more troublesome, which increases the synthesis cost, and the range of different substrates is not universal. Applicability, need to use different catalysts, bases and solvents according to different substrates

The reaction uses hydrazine hydrate reagent, which is corrosive, flammable and explosive, and belongs to safety control reagents, so it is inconvenient to use

At the same time, the raw material 2-benzoylpyridine is not a commercially available reagent and needs to be pre-prepared in advance

[0018] In summary, most of the methods reported in the literature currently use a multi-step synthesis strategy and a transition metal-catalyzed coupling synthesis strategy. The metal catalyst is expensive, the reaction conditions are harsh, the synthesis method is complex, consumes a large amount of solvents and reagents, and pollutes the environment.

At the same time, most of the raw materials used in the literature are not commercially available and need to be prepared in advance through a series of steps. The preparation process also requires the use of transition metals such as palladium and copper, explosive sodium azide and hydrazine hydrate, and highly toxic selenium dioxide. Wait

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