摘要
β-咔啉类化合物具有广泛的生物活性。为了探索高效合成此类化合物的方法,以3-乙酰氨基-4-苯基吡啶及其取代物(1a~1d)为原料,以钯催化C—H活化反应生成C—N键为关键步骤合成出9-乙酰基-β-咔啉类化合物(2a~2d),经水解得到目标产物β-咔啉类化合物(3a~3d),结构经1H NMR和MS(ESI)确证。通过对C—H活化反应关键步骤中催化剂的用量、溶剂和反应温度进行考察后发现:在反应规模为2.0 mmol时,醋酸钯为0.05 eq.,醋酸铜为1.10 eq.,二氧六环为10 mL,100℃反应12 h的最优条件下,9-乙酰基-β-咔啉类化合物(2a~2d)的收率为71%~94%。该反应存在取代基效应,含有斥电子基团,位阻较小的底物收率较高。
β-Carbolines are attributited with a wide range of biological activities.To explore efficient methods for synthesizing these compounds,9-acetyl-β-carboline compounds(2a~2d)were prepared from 3-acetamino-4-phenylpyridine and its derivatives(1a~1d)using palladium catalyzed C—H activation reaction combined with C—N bond generation as key steps,and the target productβ-carboline compounds(3a~3d)were subsequently obtained from the following hydrolysis,their structures were confirmed by 1H NMR and MS(ESI).After screening of the dosage of catalysts,solvents,and reaction temperature of the key C—H activation reaction,it was found that under the optimal conditions of 0.05 eq.palladium acetate,1.10 eq.copper acetate,10 mL dioxane,and 12 h reaction at 100℃,the yield of 9-acetyl-β-carboline compounds(2a~2d)was 71%~94%when the reactions were set up at 2.0 mmol scale.Substituent effect was observed in the reactions that substrates with electron repelling groups and low steric hindrance gave higher yield.
作者
钟铮
张灵帅
密霞
杨怀霞
ZHONG Zheng;ZHANG Lingshuai;MI Xia;YANG Huaixia(School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046,China)
出处
《合成化学》
2025年第8期577-582,共6页
Chinese Journal of Synthetic Chemistry
