Department of Organic Chemistry, Faculty of Chemistry, Voronezh State University, Universitetskaya Sq. 1, 394018 Voronezh, Russia.
Moscow Center of Fundamental and Applied Mathematics, Leninskie Gory Str., 1, 119234 Moscow, Russia.
Molecules. 2022 Dec 12;27(24):8800. doi: 10.3390/molecules27248800.
N-Arylmaleimides are universal substrates for the synthesis of various heterocyclic compounds with a wide spectrum of biological activity. However, their reactions with thioacetamides have not been comprehensively studied. We studied the reactions of thioacetamide with N-arylmaleimides under various conditions. We established for the first time that three types of products: epithiopyrrolo[3,4-c]pyridines, pyrrolo[3,4-c]pyridines and 3,3'-thiobis(1-arylpyrrolidine-2,5-diones) can be obtained in different conditions. In all cases, two maleimide molecules are involved in the reaction. 3,3'-Thiobis(1-arylpyrrolidine-2,5-diones) are the major products when the reaction is conducted at boiling in acetic acid. When thioacetamide and N-arylmaleimide are kept in dioxane at 50 °C, epithiopyrrolo[3,4-c]pyridines can be isolated, which, when heated in dioxane, in acetic acid or in methanol in the presence of catalytic amounts of sodium methoxide, are converted into pyrrolo[3,4-c]pyridines by eliminating hydrogen sulfide. The reaction of thioacetamide and N-arylmaleimide in dioxane at boiling temperature with the portioned addition of N-arylmaleimide leads predominantly to the formation of pyrrolo[3,4-c]pyridines. The reaction of thioacetamide with N-alkylmaleimides under all the above conditions leads predominantly to the formation of the corresponding sulfides. The structure of the compounds obtained was characterized by a set of spectral analysis methods and X-ray diffraction (XRD) data.
N-芳基马来酰亚胺是合成具有广泛生物活性的各种杂环化合物的通用底物。然而，它们与硫代乙酰胺的反应尚未得到全面研究。我们在各种条件下研究了硫代乙酰胺与 N-芳基马来酰亚胺的反应。我们首次建立了三种类型的产物：噻吩并吡咯[3,4-c]吡啶、吡咯并[3,4-c]吡啶和 3,3'-二硫代双(1-芳基吡咯烷-2,5-二酮)，它们可以在不同条件下获得。在所有情况下，两个马来酰亚胺分子都参与了反应。当在乙酸中回流时，3,3'-二硫代双(1-芳基吡咯烷-2,5-二酮)是主要产物。当硫代乙酰胺和 N-芳基马来酰亚胺在二氧六环中于 50°C 保持时，可以分离出噻吩并吡咯[3,4-c]吡啶，当在二氧六环、乙酸或甲醇中并在催化量的甲醇钠存在下加热时，通过消除硫化氢转化为吡咯并[3,4-c]吡啶。在二氧六环中回流温度下，分批加入 N-芳基马来酰亚胺，硫代乙酰胺与 N-芳基马来酰亚胺的反应主要生成吡咯并[3,4-c]吡啶。在上述所有条件下，硫代乙酰胺与 N-烷基马来酰亚胺的反应主要生成相应的硫醚。通过一系列光谱分析方法和 X 射线衍射 (XRD) 数据对所得到的化合物的结构进行了表征。
