Since its discovery, the Vilsmeier-Haack reaction has always been a subject of great interest to organic chemists and continues to attract considerable attention. It is a powerful tool for synthesis in organic chemistry. It is well known that inorganic acid halides react with disubstituted amides to form active complexes, halomethyl-eniminium salts, called Vilsmeier-Haack reagents. Due to its mild conditions, the commercial availability of the reagents and the better understanding of the mechanism, the Vilsmeier-Haack reagent was initially used to introduce formyl groups into activated aromatic and heteroatomic compounds and then it knows several uses in chlorination, chloroformylation , aromatization, cyclization,...etc . In recent years, the Vilsmeier Haack reagent has also found increasing application in the domino reactions of heteroatomic compounds. It is also important in various recent synthesis methodologies, using microwave chemistry. For years of research our laboratory interested in the development and functionalization of heterocyclic compounds such as aminopyridines, aminopyridopyrimidines, chromenopyrimidines,…etc with promising biological and pharmacological activities including some new concept of green chemistry ; as a part of our research, new heterocyclic systems were achieved in good yields via the Vilsmeier-Haack reaction starting from derivatives of 2-aminothiophene. All newly synthesized compounds were confirmed by ¹H NMR, ¹³C NMR analysis and some showed a positive biological activity.