Institute of Pharmaceutical Chemistry and MTA-SZTE Stereochemistry Research Group, University of Szeged, H-6720 Szeged, Hungary.
Institute of Pharmaceutical Chemistry, Interdisciplinary Centre of Excellence, University of Szeged, H-6720 Szeged, Hungary.
Molecules. 2019 Oct 4;24(19):3578. doi: 10.3390/molecules24193578.
By direct coupling 7-azaindole and cyclic imines, such as 3,4-dihydroisoquinoline, 6,7-dihydrothieno[3,2-]pyridine, 3,4-dihydro-β-carboline, and 4,5-dihydro--benz[]azepine, new 3-substituted 7-azaindole derivatives have been synthesized. The reaction was extended to 4-azaindoles and 6-azaindoles, as electron-rich aromatic compounds. The lowest reactivity was observed in the case of C-3 substitution of 5-azaindole. In this case, the aza-Friedel-Crafts reaction took place by using 10 mol % of -toluenesulfonic acid (-TSA) as the catalyst. The role of the acid catalyst can be explained by the different pKa values of the azaindoles. All reactions were performed in solvent-free conditions by using both classical heating and microwave irradiation. In all cases, microwave heating proved to be more convenient to synthesize new C-3-substituted azaindole derivatives.
通过直接偶联 7-氮茚和环状亚胺，如 3,4-二氢异喹啉、6,7-二氢噻吩并[3,2-]吡啶、3,4-二氢-β-咔啉和 4,5-二氢--苯并[azepine]，合成了新的 3-取代的 7-氮茚衍生物。该反应扩展到了富电子芳香族化合物 4-氮茚和 6-氮茚。在 5-氮茚的 C-3 取代的情况下，反应活性最低。在这种情况下，通过使用 10 mol%的对甲苯磺酸（-TSA）作为催化剂，发生了氮杂-Friedel-Crafts 反应。酸催化剂的作用可以通过氮茚的不同 pKa 值来解释。所有反应都是在无溶剂条件下进行的，既使用了经典加热法，也使用了微波辐射法。在所有情况下，微波加热都被证明是合成新的 C-3-取代氮茚衍生物更方便的方法。
