Background and overview[1]
In the field of organic chemistry, pyridine structural modules are widely found in synthetic drugs, natural products and functional materials, and are especially common in pharmaceutical compounds containing heterocyclic or fused rings. Therefore, the development of such compounds plays a very important role in the design and synthesis of drugs and their intermediates. The traditional synthesis method of pyridine compounds mainly involves the condensation reaction of carbonyl compounds, but this method has some limitations, such as poor substrate scalability. In recent years, in order to improve the limitations of such methods, many researchers have developed a variety of preparation processes for pyridine compounds. 2-(4-nitrophenyl)pyridine can be used as a pharmaceutical synthesis intermediate.
Preparation[1]
The preparation of 2-(4-nitrophenyl)pyridine can be achieved with high yields by using acid halide compounds and amine compounds as reaction substrates, under the synergistic action of suitable catalysts, ligands, bases and auxiliaries. The pyridine drug intermediate compound substituted at the 2-position is obtained with high efficiency, and has good industrial application prospects and value.
At room temperature, add 100mmol p-nitrobenzoyl chloride, 150mmol n-butylamine, 10mmol copper (II) ethyl acetoacetate, 8mmol ligand L1, 150mmol dimethylaminopyridine and 40 mmol silver acetate, stir and heat up to 80°C, and continue stirring at this temperature for 10 hours. After the reaction is completed, the reaction system is naturally cooled to room temperature, fully washed with deionized water, separated into layers, and the upper organic phase is taken, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the resulting residue is separated by silica gel column chromatography. The deliquidated mixture was a mixture of n-butanol and ethyl acetate, with a volume ratio of 1:4, to obtain compound 2-(4-nitrophenyl)pyridine of formula (I) with a yield of 95.8%.
1H-NMR (400MHz, CDCl3) δ: 8.76-8.70 (m, 1H), 8.35-8.25 (m, 2H), 8.23-8.15 (m, 2H), 7.88-7.74 (m, 2H), 7.35 (ddd, J=6.7, 4.8, 2.2Hz, 1H).
MSm/z: 201.06(M+1,100).
Main reference materials
[1]CN201510021195.2 A synthesis method of 2-substituted pyridine drug intermediate compounds
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