A convenient ammonium chloride facilitated mild and efficient synthesis of Benzazepinoindole derivatives through a Pictet-Spengler reaction*

Abstract

Benzazepinoindoles are a promising class of compounds in the growing field of heterocyclic chemistry due to their intriguing pharmacological properties. The tetrahydro-benzazepinoindole scaffold, in particular, holds great promise as a versatile framework for drug discovery, especially in the development of antiproliferative and anti-inflammatory agents. In present work, we proposed the synthesis of tetrahydro-benzazepinoindoles starting from alkylated indole and benzaldehyde derivatives using NH₄Cl, and methanol as solvent. This approach is designed to achieve high efficiency and good to excellent yields, while accommodating diverse functional groups to enhance structural diversity. The scalability of this method was demonstrated through successful gram-scale reactions, highlighting its utility in practical applications. The synthesized compounds were characterized using advanced techniques, including ¹H NMR, ¹³C NMR, ¹⁹F NMR, DEPT-135, IR and mass spectrometry, confirming their structural integrity. This work provides a streamlined and reliable strategy for the synthesis of tetrahydro-benzazepinoindoles, contributing to advancements in synthetic methodology and paving the way for the development of novel bioactive molecules with significant therapeutic potential.