MgO/SBA-15: A Synergistic Catalyst for the Enhanced Gewald Synthesis of 2-Aminothiophenes

The development of environmentally friendly synthetic methods has become a priority in organic chemistry. In this context, the synthesis of 2-aminothiophenes, bioactive compounds of pharmaceutical interest, remains an area of ​​active exploration. Conventional methods generally involve multi-step procedures and the use of harmful solvents. A simple and environmentally friendly protocol was developed for the synthesis of multi-substituted 2-aminothiophenes. The reaction uses a mixture of ketone derivatives, malonodinitrile, and elemental sulfur, in the presence of a small amount (2 wt%) of MgO/SBA-15 as a cocatalyst. The reactions were carried out at room temperature without solvent. The 2-aminothiophene derivatives were obtained in good yields ranging from 50% to 93% under mild conditions. The MgO/SBA-15 catalyst demonstrated remarkable catalytic efficiency, as well as good availability and excellent reusability. This protocol differs from previous methods that often required a two-step synthesis. The use of a solvent-free system and a recyclable catalyst contributes to reducing the ecological footprint of the process. The role of MgO/SBA-15 is crucial to promote the reaction efficiently under mild conditions. A one-pot, environmentally friendly, and efficient method has been developed for the first time for the synthesis of 2-aminothiophenes from acetophenone derivatives under solvent-free conditions. This protocol represents a significant advance in green chemistry and could be applied to other organic transformations.